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Sample records for app-dependent proinflammatory signaling

  1. Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation

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    Halleskog Carina

    2012-05-01

    Full Text Available Abstract Background WNT-5A signaling in the central nervous system is important for morphogenesis, neurogenesis and establishment of functional connectivity; the source of WNT-5A and its importance for cellular communication in the adult brain, however, are mainly unknown. We have previously investigated the inflammatory effects of WNT/β-catenin signaling in microglia in Alzheimer's disease. WNT-5A, however, generally recruits β-catenin-independent signaling. Thus, we aim here to characterize the role of WNT-5A and downstream signaling pathways for the inflammatory transformation of the brain's macrophages, the microglia. Methods Mouse brain sections were used for immunohistochemistry. Primary isolated microglia and astrocytes were employed to characterize the WNT-induced inflammatory transformation and underlying intracellular signaling pathways by immunoblotting, quantitative mRNA analysis, proliferation and invasion assays. Further, measurements of G protein activation by [γ-35 S]GTP binding, examination of calcium fluxes and cyclic AMP production were used to define intracellular signaling pathways. Results Astrocytes in the adult mouse brain express high levels of WNT-5A, which could serve as a novel astroglia-microglia communication pathway. The WNT-5A-induced proinflammatory microglia response is characterized by increased expression of inducible nitric oxide synthase, cyclooxygenase-2, cytokines, chemokines, enhanced invasive capacity and proliferation. Mapping of intracellular transduction pathways reveals that WNT-5A activates heterotrimeric Gi/o proteins to reduce cyclic AMP levels and to activate a Gi/o protein/phospholipase C/calcium-dependent protein kinase/extracellular signal-regulated kinase 1/2 (ERK1/2 axis. We show further that WNT-5A-induced ERK1/2 signaling is responsible for distinct aspects of the proinflammatory transformation, such as matrix metalloprotease 9/13 expression, invasion and proliferation. Conclusions

  2. Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation.

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    Radtke, Simone; Wüller, Stefan; Yang, Xiang-ping; Lippok, Barbara E; Mütze, Barbara; Mais, Christine; de Leur, Hildegard Schmitz-Van; Bode, Johannes G; Gaestel, Matthias; Heinrich, Peter C; Behrmann, Iris; Schaper, Fred; Hermanns, Heike M

    2010-03-15

    The inflammatory response involves a complex interplay of different cytokines which act in an auto- or paracrine manner to induce the so-called acute phase response. Cytokines are known to crosstalk on multiple levels, for instance by regulating the mRNA stability of targeted cytokines through activation of the p38-MAPK pathway. In our study we discovered a new mechanism that answers the long-standing question how pro-inflammatory cytokines and environmental stress restrict immediate signalling of interleukin (IL)-6-type cytokines. We show that p38, activated by IL-1beta, TNFalpha or environmental stress, impairs IL-6-induced JAK/STAT signalling through phosphorylation of the common cytokine receptor subunit gp130 and its subsequent internalisation and degradation. We identify MK2 as the kinase that phosphorylates serine 782 in the cytoplasmic part of gp130. Consequently, inhibition of p38 or MK2, deletion of MK2 or mutation of crucial amino acids within the MK2 target site or the di-leucine internalisation motif blocks receptor depletion and restores IL-6-dependent STAT activation as well as gene induction. Hence, a novel negative crosstalk mechanism for cytokine signalling is described, where cytokine receptor turnover is regulated in trans by pro-inflammatory cytokines and stress stimuli to coordinate the inflammatory response.

  3. Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

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    Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

    2012-01-01

    Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur. PMID:22276186

  4. Inhibitors of MyD88-dependent proinflammatory cytokine production identified utilizing a novel RNA interference screening approach.

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    John S Cho

    2009-09-01

    Full Text Available The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha. How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses.

  5. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    LENUS (Irish Health Repository)

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  6. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

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    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  7. Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.

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    Amaral, Maria E; Barbuio, Raquel; Milanski, Marciane; Romanatto, Talita; Barbosa, Helena C; Nadruz, Wilson; Bertolo, Manoel B; Boschero, Antonio C; Saad, Mario J A; Franchini, Kleber G; Velloso, Licio A

    2006-07-01

    Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.

  8. ROS detoxification and proinflammatory cytokines are linked by p38 MAPK signaling in a model of mature astrocyte activation.

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    Adrian Nahirnyj

    Full Text Available Astrocytes are the most abundant glial cell in the retinal nerve fiber layer (NFL and optic nerve head (ONH, and perform essential roles in maintaining retinal ganglion cell (RGC detoxification and homeostasis. Mature astrocytes are relatively quiescent, but rapidly undergo a phenotypic switch in response to insult, characterized by upregulation of intermediate filament proteins, loss of glutamate buffering, secretion of pro-inflammatory cytokines, and increased antioxidant production. These changes result in both positive and negative influences on RGCs. However, the mechanism regulating these responses is still unclear, and pharmacologic strategies to modulate select aspects of this switch have not been thoroughly explored. Here we describe a system for rapid culture of mature astrocytes from the adult rat retina that remain relatively quiescent, but respond robustly when challenged with oxidative damage, a key pathogenic stress associated with inner retinal injury. When primary astrocytes were exposed to reactive oxygen species (ROS we consistently observed characteristic changes in activation markers, along with increased expression of detoxifying genes, and secretion of proinflammatory cytokines. This in vitro model was then used for a pilot chemical screen to target specific aspects of this switch. Increased activity of p38α and β Mitogen Activated Protein Kinases (MAPKs were identified as a necessary signal regulating expression of MnSOD, and heme oxygenase 1 (HO-1, with consequent changes in ROS-mediated injury. Additionally, multiplex cytokine profiling detected p38 MAPK-dependent secretion of IL-6, MCP-1, and MIP-2α, which are proinflammatory signals recently implicated in damage to the inner retina. These data provide a mechanism to link increased oxidative stress to proinflammatory signaling by astrocytes, and establish this assay as a useful model to further dissect factors regulating the reactive switch.

  9. The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia

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    Mousumi Ghosh

    2015-01-01

    Full Text Available Cyclic AMP is an important intracellular regulator of microglial cell homeostasis and its negative perturbation through proinflammatory signaling results in microglial cell activation. Though cytokines, TNF-α and IL-1β, decrease intracellular cyclic AMP, the mechanism by which this occurs is poorly understood. The current study examined which signaling pathways are responsible for decreasing cyclic AMP in microglia following TNF-α stimulation and sought to identify the role cyclic AMP plays in regulating these pathways. In EOC2 microglia, TNF-α produced a dramatic reduction in cyclic AMP and increased cyclic AMP-dependent PDE activity that could be antagonized by Rolipram, myristoylated-PKI, PD98059, or JSH-23, implicating a role for PDE4, PKA, MEK, and NF-κB in this regulation. Following TNF-α there were significant increases in iNOS and COX-2 immunoreactivity, phosphorylated ERK1/2 and NF-κB-p65, IκB degradation, and NF-κB p65 nuclear translocation, which were reduced in the presence of high levels of cyclic AMP, indicating that reductions in cyclic AMP during cytokine stimulation are important for removing its inhibitory action on NF-κB activation and subsequent proinflammatory gene expression. Further elucidation of the signaling crosstalk involved in decreasing cyclic AMP in response to inflammatory signals may provide novel therapeutic targets for modulating microglial cell activation during neurological injury and disease.

  10. PSFC: a Pathway Signal Flow Calculator App for Cytoscape [version 2; referees: 2 approved

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    Lilit Nersisyan

    2017-04-01

    Full Text Available Cell signaling pathways are sequences of biochemical reactions that propagate an input signal, such as a hormone binding to a cell-surface receptor, into the cell to trigger a reactive process. Assessment of pathway activities is crucial for determining which pathways play roles in disease versus normal conditions. To date various pathway flow/perturbation assessment tools are available, however they are constrained to specific algorithms and specific data types. There are no accepted standards for evaluation of pathway activities or simulation of flow propagation events in pathways, and the results of different software are difficult to compare. Here we present Pathway Signal Flow Calculator (PSFC, a Cytoscape app for calculation of a pathway signal flow based on the pathway topology and node input data. The app provides a rich framework for customization of different signal flow algorithms to allow users to apply various approaches within a single computational framework.

  11. CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2.

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    Roy J Soberman

    Full Text Available The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(-/- mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1 infection. CD200R1(-/- peritoneal macrophages demonstrated a 70-75% decrease in the generation of IL-6 and CCL5 (Rantes in response to the TLR2 agonist Pam(2CSK(4 and to HSV-1. CD200R1(-/- macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(-/- mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(-/- mice and CD200R1(-/- fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in "licensing" pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.

  12. Epidermal Growth Factor Receptor Signaling Enhances the Proinflammatory Effects of Staphylococcus aureus Gamma-Toxin on the Mucosa.

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    Gillman, Aaron N; Breshears, Laura M; Kistler, Charles K; Finnegan, Patrick M; Torres, Victor J; Schlievert, Patrick M; Peterson, Marnie L

    2017-06-28

    Staphylococcus aureus ( S. aureus ) produces many different exotoxins including the gamma-toxins, HlgAB and HlgCB. Gamma-toxins form pores in both leukocyte and erythrocyte membranes, resulting in cell lysis. The genes encoding gamma-toxins are present in most strains of S. aureus, and are commonly expressed in clinical isolates recovered from menstrual Toxic Shock Syndrome (mTSS) patients. This study set out to investigate the cytotoxic and proinflammatory effects of gamma-toxins on vaginal epithelial surfaces. We found that both HlgAB and HlgCB were cytotoxic to cultured human vaginal epithelial cells (HVECs) and induced cytokine production at sub-cytotoxic doses. Cytokine production induced by gamma-toxin treatment of HVECs was found to involve epidermal growth factor receptor (EGFR) signaling and mediated by shedding of EGFR ligands from the cell surface. The gamma-toxin subunits displayed differential binding to HVECs (HlgA 93%, HlgB 97% and HlgC 28%) with both components (HlgAB or HlgCB) required for maximum detectable binding and significant stimulation of cytokine production. In studies using full thickness ex vivo porcine vaginal mucosa, HlgAB or HlgCB stimulated a dose-dependent cytokine response, which was reduced significantly by inhibition of EGFR signaling. The effects of gamma-toxins on porcine vaginal tissue and cultured HVECs were validated using ex vivo human ectocervical tissue. Collectively, these studies have identified the EGFR-signaling pathway as a key component in gamma-toxin-induced proinflammatory changes at epithelial surfaces and highlight a potential therapeutic target to diminish toxigenic effects of S. aureus infections.

  13. Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms

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    Vladan P. Čokić

    2015-01-01

    Full Text Available The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34+ cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs.

  14. TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

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    Zheng, Shasha; Hedl, Matija; Abraham, Clara

    2015-02-15

    Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

  15. Anthocyanin prevents CD40-activated proinflammatory signaling in endothelial cells by regulating cholesterol distribution.

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    Xia, Min; Ling, Wenhua; Zhu, Huilian; Wang, Qing; Ma, Jing; Hou, Mengjun; Tang, Zhihong; Li, Lan; Ye, Qinyuan

    2007-03-01

    Intracellular tumor necrosis factor receptor-associated factors (TRAFs) translocation to lipid rafts is a key element in CD40-induced signaling. The purpose of this study was to investigate the influence of anthocyanin on CD40-mediated proinflammatory events in human endothelial cells and the underlying possible molecular mechanism. Treatment of endothelial cells with anthocyanin prevented from CD40-induced proinflammatory status, measured by production of IL-6, IL-8, and monocyte chemoattractant protein-1 through inhibiting CD40-induced nuclear factor-kappaB (NF-kappaB) activation. TRAF-2 played pivotal role in CD40-NF-kappaB pathway as TRAF-2 small interference RNA (siRNA) diminished CD40-induced NF-kappaB activation and inflammation. TRAF-2 overexpression increased CD40-mediated NF-kappaB activation. Moreover, TRAF-2 almost totally recruited to lipid rafts after stimulation by CD40 ligand and depletion of cholesterol diminished CD40-mediated NF-kappaB activation. Exposure to anthocyanin not only interrupted TRAF-2 recruitment to lipid rafts but also decreased cholesterol content in Triton X-100 insoluble lipid rafts. However, anthocyanin did not influence the interaction between CD40 ligand and CD40 receptor. Our findings suggest that anthocyanin protects from CD40-induced proinflammatory signaling by preventing TRAF-2 translocation to lipid rafts through regulation of cholesterol distribution, which thereby may represent a mechanism that would explain the anti-inflammatory response of anthocyanin.

  16. HP1330 Contributes to Streptococcus suis Virulence by Inducing Toll-Like Receptor 2- and ERK1/2-Dependent Pro-inflammatory Responses and Influencing In Vivo S. suis Loads

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    Qiang Zhang

    2017-07-01

    Full Text Available Streptococcus suis 2 (SS2 has evolved into a highly invasive pathogen responsible for two large-scale outbreaks of streptococcal toxic shock-like syndrome (STSLS in China. Excessive inflammation stimulated by SS2 is considered a hallmark of STSLS, even it also plays important roles in other clinical symptoms of SS2-related disease, including meningitis, septicemia, and sudden death. However, the mechanism of SS2-caused excessive inflammation remains poorly understood. Here, a novel pro-inflammatory protein was identified (HP1330, which could induce robust expression of pro-inflammatory cytokines (TNF-α, MCP-1, and IL-1β in RAW264.7 macrophages. To evaluate the role of HP1330 in SS2 virulence, an hp1330-deletion mutant (Δhp1330 was constructed. In vitro, hp1330 disruption led to a decreased pro-inflammatory ability of SS2 in RAW 264.7 macrophages. In vivo, Δhp1330 showed reduced lethality, pro-inflammatory activity, and bacterial loads in mice. To further elucidate the mechanism of HP1330-induced pro-inflammatory cytokine production, antibody blocking and gene-deletion experiments with macrophages were performed. The results revealed that the pro-inflammatory activity of HP1330 depended on the recognition of toll-like receptor 2 (TLR2. Furthermore, a specific inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2 pathways could significantly decrease HP1330-induced pro-inflammatory cytokine production, and western blot analysis showed that HP1330 could induce activation of the ERK1/2 pathway. Taken together, our findings demonstrate that HP1330 contributes to SS2 virulence by inducing TLR2- and ERK1/2-dependent pro-inflammatory cytokine production and influencing in vivo bacterial loads, implying that HP1330 may be associated with STSLS caused by SS2.

  17. The Effects of Peripheral and Central High Insulin on Brain Insulin Signaling and Amyloid-β in Young and Old APP/PS1 Mice.

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    Stanley, Molly; Macauley, Shannon L; Caesar, Emily E; Koscal, Lauren J; Moritz, Will; Robinson, Grace O; Roh, Joseph; Keyser, Jennifer; Jiang, Hong; Holtzman, David M

    2016-11-16

    Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP swe /PS1 dE9 transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections

  18. Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

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    Shaw, Jillian L; Chang, Karen T

    2013-01-01

    Post-mortem brains from Down syndrome (DS) and Alzheimer's disease (AD) patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1), but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP), which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

  19. Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

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    Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

    2017-12-01

    Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

  20. Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

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    Jillian L Shaw

    Full Text Available Post-mortem brains from Down syndrome (DS and Alzheimer's disease (AD patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1, but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP, which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

  1. Histone Deacetylase 7 Promotes Toll-like Receptor 4-dependent Proinflammatory Gene Expression in Macrophages*

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    Shakespear, Melanie R.; Hohenhaus, Daniel M.; Kelly, Greg M.; Kamal, Nabilah A.; Gupta, Praveer; Labzin, Larisa I.; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A.; Reid, Robert C.; Irvine, Katharine M.; Fairlie, David P.; Sweet, Matthew J.

    2013-01-01

    Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target. PMID:23853092

  2. Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory gene expression in macrophages.

    Science.gov (United States)

    Shakespear, Melanie R; Hohenhaus, Daniel M; Kelly, Greg M; Kamal, Nabilah A; Gupta, Praveer; Labzin, Larisa I; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A; Reid, Robert C; Irvine, Katharine M; Fairlie, David P; Sweet, Matthew J

    2013-08-30

    Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target.

  3. Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

    Science.gov (United States)

    Zhang, Baochun; Crankshaw, Will; Nesemeier, Ryan; Patel, Jay; Nweze, Ikenna; Lakshmanan, Jaganathan; Harbrecht, Brian G

    2015-02-01

    Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Assessing the usability of Shazam mobile app

    Science.gov (United States)

    Hussain, Azham; Mkpojiogu, Emmanuel O. C.; Almazini, Hassan; Almazini, Hussein

    2017-10-01

    Like searching for a "needle" in a "haystack", suppose that there is a large set of signals (finite sequences of numbers) fs1; s2; s3; g, and a special signal q that may or may not be in the collection. How can the signals be found in the collection that is similar, or identical to q, and how can this be done quickly? A solution to this question is the basis of the Shazam smart phone app, where a listener captures a short excerpt of a recorded song with the smart phone's microphone, and in a matter of moments the app reports the name of the song and the artist. Here, the "needle" is the excerpt, and the "haystack" is a vast corpus of popular music. The Shazam algorithm is powered by Fourier analysis. This paper presents a report on a usability evaluation of Amazon Shazam app. The researchers present the outcome based on a task-based evaluation that involved 15 users of different level of experience who performed 5 tasks using the Shazam mobile app. Post-test questionnaire was used to capture users' perceptions about the app. The results demonstrate that most of the participants were satisfied with services provided by the app.

  5. Patterns, Attitudes, and Dependence toward WhatsApp among College Students

    Directory of Open Access Journals (Sweden)

    Harshavardhan Sampath

    2017-01-01

    Full Text Available Background: WhatsApp (WA, a free cross-platform smartphone application has revolutionized social communication over the virtual world. It enables information sharing, both personal and professional, individually and across social groups. Despite these positive changes, there have been concerns about excessive WA use, especially among college students, resulting in the neglect of important social and academic commitments. However, there is lack of quality research on WA use in this vulnerable population. Aims: The aim of this study is to understand the patterns and attitudes toward WA use and measure the level of dependence among college students. Materials and Methods: In a sample of 150 undergraduate medical college students who provided informed consent, comprehensive questionnaires were administered to assess the patterns, attitudes, and dependence toward WA use. Results: WA was the most common social media platform used (70% which eclipsed the time spend on other apps (Facebook, Twitter, etc. While half of the students spent 1–2 h/day, a significant minority (10.67% spent almost 6–7 h/day on WA. Nearly 12% (n = 18 of students qualified for WA dependence. There were no significant differences in patterns of WA use between students with or without WA dependence. Students with WA dependence had significantly lesser negative attitudes toward its use compared to the rest. Scores on all dimensions of WA addiction, namely, salience, mood modification, tolerance, withdrawal, conflict, and relapse were significantly higher in students with WA dependence. Conclusion: WA dependence is an emerging behavioral addiction among college students. With no specific pattern of use to distinguish dependent users, it is difficult to recognize this problem. Changing the attitudes towards WA use by creating awareness about it's addictive potential, monitoring and restricting the use of mobile phones especially during class hours, encouraging face to face

  6. Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer's disease.

    Science.gov (United States)

    Bukhari, Hassan; Glotzbach, Annika; Kolbe, Katharina; Leonhardt, Gregor; Loosse, Christina; Müller, Thorsten

    2017-09-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus. As a consequence nuclear -potentially toxic- structures emerge, which were recently found to a high extent in human AD tissue and thus, may contribute to neurodegeneration. Relevant for the signaling machinery are modifications at the very C-terminal end of the precursor protein, the APP intracellular domain (AICD). In this review we update the knowledge on mechanisms on AICD referring to our 2008 article: The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-Relevance for Alzheimer's disease (T. Muller, et al., 2008). We summarize how AICD is generated and degraded, we describe its intramolecular motifs, translational modifications, and how those as well as APP dimerization influence AICD generation and function. Moreover, we resume the AICD interactome and elucidate AICDs involvement in nuclear signaling, transcriptional regulation, cell death, DNA repair and cell cycle re-entry and we give insights in its physiological function. Results are summarized in the comprehensive poster "The world of AICD". Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The Pro-inflammatory Effects of Glucocorticoids in the Brain

    Science.gov (United States)

    Duque, Erica de Almeida; Munhoz, Carolina Demarchi

    2016-01-01

    Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

  8. Angry Apps: The Impact of Network Timer Selection on Power Consumption, Signalling Load, and Web QoE

    Directory of Open Access Journals (Sweden)

    Christian Schwartz

    2013-01-01

    Full Text Available The popularity of smartphones and mobile applications has experienced a considerable growth during the recent years, and this growth is expected to continue in the future. Since smartphones have only very limited energy resources, battery efficiency is one of the determining factors for a good user experience. Therefore, some smartphones tear down connectionsto the mobile network soon after a completed data transmission to reduce the power consumption of their transmission unit. However, frequent connection reestablishments caused by apps which send or receive small amounts of data often lead to a heavy signalling load within the mobile network. One of the major contributions of this paper is the investigation of the resulting tradeoff between energy consumption at the smartphone and the generated signalling traffic in the mobile network. We explain that this tradeoff can be controlled by the connection release timeout and study the impact of this parameter for a number of popular apps that cover a wide range of traffic characteristics in terms of bandwidth requirements and resulting signalling traffic. Finally, we study the impact of the timer settings on Quality of Experience (QoE for web traffic. This is an important aspect since connection establishments not only lead to signalling traffic but also increase the load time of web pages.

  9. Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity

    DEFF Research Database (Denmark)

    Rusu, Patricia; Jansen, Anna; Soba, Peter

    2007-01-01

    . Specifically, axonal transport defects have been reported in AD animal models, including mice and flies that overexpress APP and tau. Here we demonstrate that the APP-induced traffic jam of vesicles in peripheral nerves of Drosophila melanogaster larvae depends on the four residues NPTY motif in the APP...... neurotransmission at the neuromuscular junction in transgenic larvae that express human APP. Consistent with the observation that these larvae do not show any obvious movement deficits, we found no changes in basal synaptic transmission. However, short-term synaptic plasticity was affected by overexpression of APP...

  10. Necroptotic cells release find-me signal and are engulfed without proinflammatory cytokine production.

    Science.gov (United States)

    Wang, Qiang; Ju, Xiaoli; Zhou, Yang; Chen, Keping

    2015-11-01

    Necroptosis is a form of caspase-independent programmed cell death which is mediated by the RIP1-RIP3 complex. Although phagocytosis of apoptotic cells has been extensively investigated, how necroptotic cells are engulfed has remained elusive. Here, we investigated how necroptotic cells attracted and were engulfed by macrophages. We found that necroptotic cells induced the migration of THP-1 cells in a transwell migration assay. Further analysis showed that ATP released from necroptotic cells acted as a find-me signal that induced the migration of THP-1 cells. We also found that Annexin V blocked phagocytosis of necroptotic cells by macrophages. Furthermore, necroptotic cells were shown to be silently cleared by macrophages without any proinflammatory cytokine production. These data uncover an evolutionarily conserved mechanism of the find-me signal in different types of cell death and immunological consequences between apoptotic and necroptotic cells during phagocytosis.

  11. Palmitoylated APP Forms Dimers, Cleaved by BACE1.

    Directory of Open Access Journals (Sweden)

    Raja Bhattacharyya

    Full Text Available A major rate-limiting step for Aβ generation and deposition in Alzheimer's disease brains is BACE1-mediated cleavage (β-cleavage of the amyloid precursor protein (APP. We previously reported that APP undergoes palmitoylation at two cysteine residues (Cys186 and Cys187 in the E1-ectodomain. 8-10% of total APP is palmitoylated in vitro and in vivo. Palmitoylated APP (palAPP shows greater preference for β-cleavage than total APP in detergent resistant lipid rafts. Protein palmitoylation is known to promote protein dimerization. Since dimerization of APP at its E1-ectodomain results in elevated BACE1-mediated cleavage of APP, we have now investigated whether palmitoylation of APP affects its dimerization and whether this leads to elevated β-cleavage of the protein. Here we report that over 90% of palAPP is dimerized while only ~20% of total APP forms dimers. PalAPP-dimers are predominantly cis-oriented while total APP dimerizes in both cis- and trans-orientation. PalAPP forms dimers 4.5-times more efficiently than total APP. Overexpression of the palmitoylating enzymes DHHC7 and DHHC21 that increase palAPP levels and Aβ release, also increased APP dimerization in cells. Conversely, inhibition of APP palmitoylation by pharmacological inhibitors reduced APP-dimerization in coimmunoprecipitation and FLIM/FRET assays. Finally, in vitro BACE1-activity assays demonstrate that palmitoylation-dependent dimerization of APP promotes β-cleavage of APP in lipid-rich detergent resistant cell membranes (DRMs, when compared to total APP. Most importantly, generation of sAPPβ-sAPPβ dimers is dependent on APP-palmitoylation while total sAPPβ generation is not. Since BACE1 shows preference for palAPP dimers over total APP, palAPP dimers may serve as novel targets for effective β-cleavage inhibitors of APP as opposed to BACE1 inhibitors.

  12. Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-κB signaling in cultured astrocytes

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Hussein, Mohamed Hamed; Kato, Shin; Suzuki, Satoshi; Ito, Tetsuya; Togari, Hajime; Asai, Kiyofumi

    2009-01-01

    Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor-α and interferon-γ, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-κB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-κB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-κB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.

  13. A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.

    Directory of Open Access Journals (Sweden)

    April M Weissmiller

    Full Text Available Clues to Alzheimer disease (AD pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP and its processing has emerged and considerable interest has been directed at the hypothesis that Aβ peptides induce changes central to pathogenesis. Accordingly, molecules that reduce the levels of Aβ peptides have been discovered such as γ-secretase inhibitors (GSIs and modulators (GSMs. GSIs and GSMs reduce Aβ levels through very different mechanisms. However, GSIs, but not GSMs, markedly increase the levels of APP CTFs that are increasingly viewed as disrupting neuronal function. Here, we evaluated the effects of GSIs and GSMs on a number of neuronal phenotypes possibly relevant to their use in treatment of AD. We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF, suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with respect to anti-amyloid treatments, even an APP-specific GSI may have deleterious effects and GSMs may serve as a better alternative.

  14. Absorption and fluorescence spectroscopic characterization of BLUF domain of AppA from Rhodobacter sphaeroides

    Science.gov (United States)

    Zirak, P.; Penzkofer, A.; Schiereis, T.; Hegemann, P.; Jung, A.; Schlichting, I.

    2005-08-01

    The BLUF domain of the transcriptional anti-repressor protein AppA from the non-sulfur anoxyphototrophic purple bacterium Rhodobacter sphaeroides was characterized by absorption and emission spectroscopy. The BLUF domain constructs AppA 148 (consisting of amino-acid residues 1-148) and AppA 126 (amino-acid residues 1-126) are investigated. The cofactor of the investigated domains is found to consist of a mixture of the flavins riboflavin, FMN, and FAD. The dark-adapted domains exist in two different active receptor conformations (receptor states) with different sub-nanosecond fluorescence lifetimes (BLUF r,f and BLUF r,sl) and a small non-interacting conformation (BLUF nc). The active receptor conformations are transformed to putative signalling states (BLUF s,f and BLUF s,sl) of low fluorescence efficiency and picosecond fluorescence lifetime by blue-light excitation (light-adapted domains). In the dark at room temperature both signalling states recover back to the initial receptor states with a time constant of about 17 min. A quantum yield of signalling state formation of about 25% was determined by intensity dependent transmission measurements. A photo-cycle scheme is presented including photo-induced charge transfer complex formation, charge recombination, and protein binding pocket reorganisation.

  15. Absorption and fluorescence spectroscopic characterization of BLUF domain of AppA from Rhodobacter sphaeroides

    International Nuclear Information System (INIS)

    Zirak, P.; Penzkofer, A.; Schiereis, T.; Hegemann, P.; Jung, A.; Schlichting, I.

    2005-01-01

    The BLUF domain of the transcriptional anti-repressor protein AppA from the non-sulfur anoxyphototrophic purple bacterium Rhodobacter sphaeroides was characterized by absorption and emission spectroscopy. The BLUF domain constructs AppA 148 (consisting of amino-acid residues 1-148) and AppA 126 (amino-acid residues 1-126) are investigated. The cofactor of the investigated domains is found to consist of a mixture of the flavins riboflavin, FMN, and FAD. The dark-adapted domains exist in two different active receptor conformations (receptor states) with different sub-nanosecond fluorescence lifetimes (BLUF r,f and BLUF r,sl ) and a small non-interacting conformation (BLUF nc ). The active receptor conformations are transformed to putative signalling states (BLUF s,f and BLUF s,sl ) of low fluorescence efficiency and picosecond fluorescence lifetime by blue-light excitation (light-adapted domains). In the dark at room temperature both signalling states recover back to the initial receptor states with a time constant of about 17 min. A quantum yield of signalling state formation of about 25% was determined by intensity dependent transmission measurements. A photo-cycle scheme is presented including photo-induced charge transfer complex formation, charge recombination, and protein binding pocket reorganisation

  16. Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory signaling in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Irina N Baranova

    Full Text Available Serum amyloid A (SAA is an acute phase protein with cytokine-like and chemotactic properties, that is markedly up-regulated during various inflammatory conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B scavenger receptors, SR-BI and CD36, have been identified as SAA receptors. This study provides new evidence that SR-BII, splice variant of SR-BI, could function as an SAA receptor mediating its uptake and pro-inflammatory signaling. The uptake of Alexa Fluor488 SAA was markedly (~3 fold increased in hSR-BII-expressing HeLa cells when compared with mock-transfected cells. The levels of SAA-induced interleukin-8 secretion by hSR-BII-expressing HEK293 cells were also significantly (~3-3.5 fold higher than those detected in control cells. Moderately enhanced levels of phosphorylation of all three mitogen-activated protein kinases, ERK1/2, and p38 and JNK, were observed in hSR-BII-expressing cells following SAA stimulation when compared with control wild type cells. Transgenic mice with pLiv-11-directed liver/kidney overexpression of hSR-BI or hSR-BII were used to assess the in vivo role of each receptor in SAA-induced pro-inflammatory response in these organs. Six hours after intraperitoneal SAA injection both groups of transgenic mice demonstrated markedly higher (~2-5-fold expression levels of inflammatory mediators in the liver and kidney compared to wild type mice. Histological examinations of hepatic and renal tissue from SAA-treated mice revealed moderate level of damage in the liver of both transgenic but not in the wild type mice. Activities of plasma transaminases, biomarkers of liver injury, were also moderately higher in hSR-B transgenic mice when compared to wild type mice. Our findings identify hSR-BII as a functional SAA receptor that mediates SAA uptake and contributes to its pro-inflammatory signaling via the MAPKs-mediated signaling pathways.

  17. Photo dynamics of BLUF domain mutant H44R of AppA from Rhodobacter sphaeroides

    International Nuclear Information System (INIS)

    Zirak, P.; Penzkofer, A.; Hegemann, P.; Mathes, T.

    2007-01-01

    The photo-cycle dynamics of the H44R mutant of the BLUF domain of the transcriptional anti-repressor protein AppA (AppA-H44R) from the non-sulfur anoxyphototropic purple bacterium Rhodobacter sphaeroides is studied in order to gain information on the involvement of His44 in the photo-cyclic mechanism of the AppA BLUF domain and to add information to the involved processes. The amino acid residue histidine at position 44 is replaced by arginine. A 12 nm red-shifted signalling state is formed upon blue-light excitation, while in wild-type AppA (AppA-wt) the red-shift is 16 nm. The recovery to the receptor dark state is approximately a factor of 2.5 faster (τ rec ∼ 6.5 min) than the recovery of the wild-type counterpart. Extended light exposure of the mutant causes photo-degradation of flavin (mainly free flavin conversion to lumichrome and re-equilibration between free and non-covalently bound flavin) and protein aggregation (showing up as light scattering). No photo-degradation was observed for AppA-wt. The quantum efficiency of signalling-state formation determined by intensity dependent absorption measurements is found to be φ s ∼ 0.3 (for AppA-wt: φ s ∼ 0.24). A two-component single-exponential fluorescence relaxation was observed, which is interpreted as fast fluorescence quenching to an equilibrium value by photo-induced electron transfer followed by slower fluorescence decay due to charge recombination. Based on the experimental findings, an extended photo-cycle model for BLUF domains is proposed

  18. Photo dynamics of BLUF domain mutant H44R of AppA from Rhodobacter sphaeroides

    Science.gov (United States)

    Zirak, P.; Penzkofer, A.; Hegemann, P.; Mathes, T.

    2007-05-01

    The photo-cycle dynamics of the H44R mutant of the BLUF domain of the transcriptional anti-repressor protein AppA (AppA-H44R) from the non-sulfur anoxyphototropic purple bacterium Rhodobacter sphaeroides is studied in order to gain information on the involvement of His44 in the photo-cyclic mechanism of the AppA BLUF domain and to add information to the involved processes. The amino acid residue histidine at position 44 is replaced by arginine. A 12 nm red-shifted signalling state is formed upon blue-light excitation, while in wild-type AppA (AppA-wt) the red-shift is 16 nm. The recovery to the receptor dark state is approximately a factor of 2.5 faster ( τrec ≈ 6.5 min) than the recovery of the wild-type counterpart. Extended light exposure of the mutant causes photo-degradation of flavin (mainly free flavin conversion to lumichrome and re-equilibration between free and non-covalently bound flavin) and protein aggregation (showing up as light scattering). No photo-degradation was observed for AppA-wt. The quantum efficiency of signalling-state formation determined by intensity dependent absorption measurements is found to be ϕs ≈ 0.3 (for AppA-wt: ϕs ≈ 0.24). A two-component single-exponential fluorescence relaxation was observed, which is interpreted as fast fluorescence quenching to an equilibrium value by photo-induced electron transfer followed by slower fluorescence decay due to charge recombination. Based on the experimental findings, an extended photo-cycle model for BLUF domains is proposed.

  19. Particles from wood smoke and traffic induce differential pro-inflammatory response patterns in co-cultures

    International Nuclear Information System (INIS)

    Kocbach, Anette; Herseth, Jan Inge; Lag, Marit; Refsnes, Magne; Schwarze, Per E.

    2008-01-01

    The inflammatory potential of particles from wood smoke and traffic has not been well elucidated. In this study, a contact co-culture of monocytes and pneumocytes was exposed to 10-40 μg/cm 2 of particles from wood smoke and traffic for 12, 40 and 64 h to determine their influence on pro-inflammatory cytokine release (TNF-α, IL-1, IL-6, IL-8) and viability. To investigate the role of organic constituents in cytokine release the response to particles, their organic extracts and the washed particles were compared. Antagonists were used to investigate source-dependent differences in intercellular signalling (TNF-α, IL-1). The cytotoxicity was low after exposure to particles from both sources. However, wood smoke, and to a lesser degree traffic-derived particles, induced a reduction in cell number, which was associated with the organic fraction. The release of pro-inflammatory cytokines was similar for both sources after 12 h, but traffic induced a greater release than wood smoke particles with increasing exposure time. The organic fraction accounted for the majority of the cytokine release induced by wood smoke, whereas the washed traffic particles induced a stronger response than the corresponding organic extract. TNF-α and IL-1 antagonists reduced the release of IL-8 induced by particles from both sources. In contrast, the IL-6 release was only reduced by the IL-1 antagonist during exposure to traffic-derived particles. In summary, particles from wood smoke and traffic induced differential pro-inflammatory response patterns with respect to cytokine release and cell number. Moreover, the influence of the organic particle fraction and intercellular signalling on the pro-inflammatory response seemed to be source-dependent

  20. Selective deletion of apolipoprotein E in astrocytes ameliorates the spatial learning and memory deficits in Alzheimer's disease (APP/PS1) mice by inhibiting TGF-β/Smad2/STAT3 signaling.

    Science.gov (United States)

    Zheng, Jin-Yu; Sun, Jian; Ji, Chun-Mei; Shen, Lin; Chen, Zhong-Jun; Xie, Peng; Sun, Yuan-Zhao; Yu, Ru-Tong

    2017-06-01

    Astrocytes and apolipoprotein E (apoE) play critical roles in cognitive function, not only under physiological conditions but also in some pathological situations, particularly in the pathological progression of Alzheimer's disease (AD). The regulatory mechanisms underlying the effect of apoE, derived from astrocytes, on cognitive deficits during AD pathology development are unclear. In this study, we generated amyloid precursor protein/apoE knockout (APP/apoE KO ) and APP/glial fibrillary acidic protein (GFAP)-apoE KO mice (the AD mice model used in this study was based on the APP-familial Alzheimer disease overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function. To explore the mechanism, we investigated the amyloidogenic process related transforming growth factor β/mothers against decapentaplegic homolog 2/signal transducer and activator of transcription 3 (TGF-β/Smad2/STAT3) signaling pathway and further confirmed by administering TGF-β-overexpression adeno-associated virus (specific to astrocytes) to APP/GFAP-apoE KO mice and TGF-β-inhibition adeno-associated virus (specific to astrocytes) to APP/WT mice. Whole body deletion of apoE significantly ameliorated the spatial learning and memory impairment, reduced amyloid β-protein production and inhibited astrogliosis in APP/apoE KO mice, as well as specific deletion apoE in astrocytes in APP/GFAP-apoE KO mice. Moreover, amyloid β-protein accumulation was increased due to promotion of amyloidogenesis of APP, and astrogliosis was upregulated by activation of TGF-β/Smad2/STAT3 signaling. Furthermore, the overexpression of TGF-β in astrocytes in APP/GFAP-apoE KO mice abrogated the effects of apoE knockout. In contrast, repression of TGF-β in astrocytes of APP/WT mice exerted a therapeutic effect similar to apoE knockout. These data suggested that apoE derived from astrocytes contributes to the risk of AD through TGF-β/Smad2/STAT3 signaling activation

  1. Role of Glycogen Synthase Kinase-3β in APP Hyperphosphorylation Induced by NMDA Stimulation in Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Xanthi Antoniou

    2010-01-01

    Full Text Available The phosphorylation of Amyloid Precursor Protein (APP at Thr668 plays a key role in APP metabolism that is highly relevant to AD. The c-Jun-N-terminal kinase (JNK, glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (Cdk5 can all be responsible for this phosphorylation. These kinases are activated by excitotoxic stimuli fundamental hallmarks of AD. The exposure of cortical neurons to a high dose of NMDA (100 μM for 30’-45’ led to an increase of P-APP Thr668. During NMDA stimulation APP hyperphosphorylation has to be assigned to GSK-3β activity, since addition of L803-mts, a substrate competitive inhibitor of GSK-3β reduced APP phosphorylation induced by NMDA. On the contrary, inhibition of JNK and Cdk5 with D-JNKI1 and Roscovitine respectively did not prevent NMDA-induced P-APP increase. These data show a tight connection, in excitotoxic conditions, between APP metabolism and the GSK-3β signaling pathway.

  2. Alteration in cellular viability, pro-inflammatory cytokines and nitric oxide production in nephrotoxicity generation by Amphotericin B: involvement of PKA pathway signaling.

    Science.gov (United States)

    França, F D; Ferreira, A F; Lara, R C; Rossoni, J V; Costa, D C; Moraes, K C M; Tagliati, C A; Chaves, M M

    2014-12-01

    Amphotericin B is one of the most effective antifungal agents; however, its use is often limited owing to adverse effects, especially nephrotoxicity. The purpose of this study was to evaluate the effect of inhibiting the PKA signaling pathway in nephrotoxicity using Amphotericin B from the assessment of cell viability, pro-inflammatory cytokines and nitric oxide (NO) production in LLC-PK1 and MDCK cell lines. Amphotericin B proved to be cytotoxic for both cell lines, as assessed by the mitochondrial enzyme activity (MTT) assay; caused DNA fragmentation, determined by flow cytometry using the propidium iodide (PI) dye; and activated the PKA pathway (western blot assay). In MDCK cells, the inhibition of the PKA signaling pathway (using the H89 inhibitor) caused a significant reduction in DNA fragmentation. In both cells lines the production of interleukin-6 (IL)-6 proved to be a dependent PKA pathway, whereas tumor necrosis factor-alpha (TNF-α) was not influenced by the inhibition of the PKA pathway. The NO production was increased when cells were pre-incubated with H89 followed by Amphotericin B, and this production produced a dependent PKA pathway in LLC-PK1 and MDCK cells lines. Therefore, considering the present study's results as a whole, it can be concluded that the inhibition of the PKA signaling pathway can aid in reducing the degree of nephrotoxicity caused by Amphotericin B. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Absorption and fluorescence spectroscopic characterization of BLUF domain of AppA from Rhodobacter sphaeroides

    Energy Technology Data Exchange (ETDEWEB)

    Zirak, P. [Institut II - Experimentelle und Angewandte Physik, Universitaet Regensburg, Universitaetstrasse 31, D-93053 Regensburg (Germany); Penzkofer, A. [Institut II - Experimentelle und Angewandte Physik, Universitaet Regensburg, Universitaetstrasse 31, D-93053 Regensburg (Germany)], E-mail: alfons.penzkofer@physik.uni-regensburg.de; Schiereis, T. [Institut fuer Biologie, Experimentelle Biophysik, Humboldt-Universitaet zu Berlin, Invalidenstrasse 42, D-10115 Berlin (Germany); Hegemann, P. [Institut fuer Biologie, Experimentelle Biophysik, Humboldt-Universitaet zu Berlin, Invalidenstrasse 42, D-10115 Berlin (Germany); Jung, A. [Max-Planck-Institut fuer medizinische Forschung, Abteilung Biomolekulare Mechanismen, Jahnstrasse 29, D-69120 Heidelberg (Germany); Schlichting, I. [Max-Planck-Institut fuer medizinische Forschung, Abteilung Biomolekulare Mechanismen, Jahnstrasse 29, D-69120 Heidelberg (Germany)

    2005-08-08

    The BLUF domain of the transcriptional anti-repressor protein AppA from the non-sulfur anoxyphototrophic purple bacterium Rhodobacter sphaeroides was characterized by absorption and emission spectroscopy. The BLUF domain constructs AppA{sub 148} (consisting of amino-acid residues 1-148) and AppA{sub 126} (amino-acid residues 1-126) are investigated. The cofactor of the investigated domains is found to consist of a mixture of the flavins riboflavin, FMN, and FAD. The dark-adapted domains exist in two different active receptor conformations (receptor states) with different sub-nanosecond fluorescence lifetimes (BLUF{sub r,f} and BLUF{sub r,sl}) and a small non-interacting conformation (BLUF{sub nc}). The active receptor conformations are transformed to putative signalling states (BLUF{sub s,f} and BLUF{sub s,sl}) of low fluorescence efficiency and picosecond fluorescence lifetime by blue-light excitation (light-adapted domains). In the dark at room temperature both signalling states recover back to the initial receptor states with a time constant of about 17 min. A quantum yield of signalling state formation of about 25% was determined by intensity dependent transmission measurements. A photo-cycle scheme is presented including photo-induced charge transfer complex formation, charge recombination, and protein binding pocket reorganisation.

  4. β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.

    Science.gov (United States)

    Lin, Rui; Choi, Yeon Ho; Zidar, David A; Walker, Julia K L

    2018-06-01

    Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4 + T-helper cell type 2 (Th2) cells are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of β-arrestin (β-arr)-2 and that CD4 + T cells from these mice displayed significantly reduced CCL22-mediated chemotaxis. Because CCL22-mediated activation of CCR4 plays a role in Th2 cell regulation in asthmatic inflammation, we hypothesized that CCR4-mediated migration of CD4 + Th2 cells to the lung in asthma may use β-arr-dependent signaling. To test this hypothesis, we assessed the effect of various signaling inhibitors on CCL22-induced chemotaxis using in vitro-polarized primary CD4 + Th2 cells from β-arr2-knockout and wild-type mice. Our results show, for the first time, that CCL22-induced, CCR4-mediated Th2 cell chemotaxis is dependent, in part, on a β-arr2-dependent signaling pathway. In addition, we show that this chemotactic signaling mechanism involves activation of P-p38 and Rho-associated protein kinase. These findings point to a proinflammatory role for β-arr2-dependent signaling and support β-arr2 as a novel therapeutic target in asthma.

  5. Photo dynamics of BLUF domain mutant H44R of AppA from Rhodobacter sphaeroides

    Energy Technology Data Exchange (ETDEWEB)

    Zirak, P. [Institut II - Experimentelle und Angewandte Physik, Universitaet Regensburg, Universitaetstrasse 31, D-93053 Regensburg (Germany); Penzkofer, A. [Institut II - Experimentelle und Angewandte Physik, Universitaet Regensburg, Universitaetstrasse 31, D-93053 Regensburg (Germany)], E-mail: alfons.penzkofer@physik.uni-regensburg.de; Hegemann, P.; Mathes, T. [Institut fuer Biologie, Experimentelle Biophysik, Humboldt-Universitaet zu Berlin, Invalidenstr. 42, D-10115 Berlin (Germany)

    2007-05-21

    The photo-cycle dynamics of the H44R mutant of the BLUF domain of the transcriptional anti-repressor protein AppA (AppA-H44R) from the non-sulfur anoxyphototropic purple bacterium Rhodobacter sphaeroides is studied in order to gain information on the involvement of His44 in the photo-cyclic mechanism of the AppA BLUF domain and to add information to the involved processes. The amino acid residue histidine at position 44 is replaced by arginine. A 12 nm red-shifted signalling state is formed upon blue-light excitation, while in wild-type AppA (AppA-wt) the red-shift is 16 nm. The recovery to the receptor dark state is approximately a factor of 2.5 faster ({tau}{sub rec} {approx} 6.5 min) than the recovery of the wild-type counterpart. Extended light exposure of the mutant causes photo-degradation of flavin (mainly free flavin conversion to lumichrome and re-equilibration between free and non-covalently bound flavin) and protein aggregation (showing up as light scattering). No photo-degradation was observed for AppA-wt. The quantum efficiency of signalling-state formation determined by intensity dependent absorption measurements is found to be {phi}{sub s} {approx} 0.3 (for AppA-wt: {phi}{sub s} {approx} 0.24). A two-component single-exponential fluorescence relaxation was observed, which is interpreted as fast fluorescence quenching to an equilibrium value by photo-induced electron transfer followed by slower fluorescence decay due to charge recombination. Based on the experimental findings, an extended photo-cycle model for BLUF domains is proposed.

  6. Embelin and its derivatives unravel the signaling, proinflammatory and antiatherogenic properties of GPR84 receptor.

    Science.gov (United States)

    Gaidarov, Ibragim; Anthony, Todd; Gatlin, Joel; Chen, Xiaohua; Mills, David; Solomon, Michelle; Han, Sangdon; Semple, Graeme; Unett, David J

    2018-05-01

    GPR84 is an orphan G-protein coupled receptor, expressed on monocytes, macrophages and neutrophils and is significantly upregulated by inflammatory stimuli. The physiological role of GPR84 remains largely unknown. Medium chain fatty acids (MCFA) activate the receptor and have been proposed to be its endogenous ligands, although the high concentrations of MCFAs required for receptor activation generally exceed normal physiological levels. We identified the natural product embelin as a highly potent and selective surrogate GPR84 agonist (originally disclosed in patent application WO2007027661A2, 2007) and synthesized close structural analogs with widely varying receptor activities. These tools were used to perform a comprehensive study of GPR84 signaling and function in recombinant cells and in primary human macrophages and neutrophils. Activation of recombinant GPR84 by embelin in HEK293 cells results in G i/o as well as G12/13-Rho signaling. In human macrophages, GPR84 initiates PTX sensitive Erk1/2 and Akt phosphorylation, PI-3 kinase activation, calcium flux, and release of prostaglandin E2. In addition, GPR84 signaling in macrophages elicits G i Gβγ-mediated augmentation of intracellular cAMP, rather than the decrease expected from G iα engagement. GPR84 activation drives human neutrophil chemotaxis and primes them for amplification of oxidative burst induced by FMLP and C5A. Loss of GPR84 is associated with attenuated LPS-induced release of proinflammatory mediators IL-6, KC-GROα, VEGF, MIP-2 and NGAL from peritoneal exudates. While initiating numerous proinflammatory activities in macrophages and neutrophils, GPR84 also possesses GPR109A-like antiatherosclerotic properties in macrophages. Macrophage receptor activation leads to upregulation of cholesterol transporters ABCA1 and ABCG1 and stimulates reverse cholesterol transport. These data suggest that GPR84 may be a target of therapeutic value and that distinct modes of receptor modulation (inhibition vs

  7. Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway.

    Science.gov (United States)

    Mizuno, Katsuhiko; Fukami, Tatsuki; Toyoda, Yasuyuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2010-10-23

    Oral antifungal terbinafine has been reported to cause liver injury with inflammatory responses in a small percentage of patients. However the underlying mechanism remains unknown. To examine the inflammatory reactions, we investigated whether terbinafine and other antifungal drugs increase the release of pro-inflammatory cytokines using human monocytic cells. Dose- and time-dependent changes in the mRNA expression levels and the release of interleukin (IL)-8 and tumor necrosis factor (TNF)α from human monocytic THP-1 and HL-60 cells with antifungal drugs were measured. Effects of terbinafine on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK)1/2 were investigated. The release of IL-8 and TNFα from THP-1 and HL-60 cells was significantly increased by treatment with terbinafine but not by fluconazole, suggesting that terbinafine can stimulate monocytes and increase the pro-inflammatory cytokine release. Terbinafine also significantly increased the phosphorylation of ERK1/2 and p38 MAP kinase in THP-1 cells. Pretreatment with a MAP kinase/ERK kinase (MEK)1/2 inhibitor U0126 significantly suppressed the increase of IL-8 and TNFα levels by terbinafine treatment in THP-1 cells, but p38 MAPK inhibitor SB203580 did not. These results suggested that an ERK1/2 pathway plays an important role in the release of IL-8 and TNFα in THP-1 cells treated with terbinafine. The release of inflammatory mediators by terbinafine might be one of the mechanisms underlying immune-mediated liver injury. This in vitro method may be useful to predict adverse inflammatory reactions that lead to drug-induced liver injury. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. NF-κB dependent and independent mechanisms of quartz-induced proinflammatory activation of lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Schins Roel PF

    2010-05-01

    Full Text Available Abstract In the initiation and progression of pulmonary inflammation, macrophages have classically been considered as a crucial cell type. However, evidence for the role of epithelial type II cells in pulmonary inflammation has been accumulating. In the current study, a combined in vivo and in vitro approach has been employed to investigate the mechanisms of quartz-induced proinflammatory activation of lung epithelial cells. In vivo, enhanced expression of the inflammation- and oxidative stress-related genes HO-1 and iNOS was found on the mRNA level in rat lungs after instillation with DQ12 respirable quartz. Activation of the classical NF-κB pathway in macrophages and type II pneumocytes was indicated by enhanced immunostaining of phospho-IκBα in these specific lung cell types. In vitro, the direct, particle-mediated effect on proinflammatory signalling in a rat lung epithelial (RLE cell line was compared to the indirect, macrophage product-mediated effect. Treatment with quartz particles induced HO-1 and COX-2 mRNA expression in RLE cells in an NF-κB independent manner. Supernatant from quartz-treated macrophages rapidly activated the NF-κB signalling pathway in RLE cells and markedly induced iNOS mRNA expression up to 2000-fold compared to non-treated control cells. Neutralisation of TNFα and IL-1β in macrophage supernatant did not reduce its ability to elicit NF-κB activation of RLE cells. In addition the effect was not modified by depletion or supplementation of intracellular glutathione. The results from the current work suggest that although both oxidative stress and NF-κB are likely involved in the inflammatory effects of toxic respirable particles, these phenomena can operate independently on the cellular level. This might have consequences for in vitro particle hazard testing, since by focusing on NF-κB signalling one might neglect alternative inflammatory pathways.

  9. Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling.

    Science.gov (United States)

    Coates, Philip J; Rundle, Jana K; Lorimore, Sally A; Wright, Eric G

    2008-01-15

    In addition to the directly mutagenic effects of energy deposition in DNA, ionizing radiation is associated with a variety of untargeted and delayed effects that result in ongoing bone marrow damage. Delayed effects are genotype dependent with CBA/Ca mice, but not C57BL/6 mice, susceptible to the induction of damage and also radiation-induced acute myeloid leukemia. Because macrophages are a potential source of ongoing damaging signals, we have determined their gene expression profiles and we show that bone marrow-derived macrophages show widely different intrinsic expression patterns. The profiles classify macrophages derived from CBA/Ca mice as M1-like (pro-inflammatory) and those from C57BL/6 mice as M2-like (anti-inflammatory); measurements of NOS2 and arginase activity in normal bone marrow macrophages confirm these findings. After irradiation in vivo, but not in vitro, C57BL/6 macrophages show a reduction in NOS2 and an increase in arginase activities, indicating a further M2 response, whereas CBA/Ca macrophages retain an M1 phenotype. Activation of specific signal transducer and activator of transcription signaling pathways in irradiated hemopoietic tissues supports these observations. The data indicate that macrophage activation is not a direct effect of radiation but a tissue response, secondary to the initial radiation exposure, and have important implications for understanding genotype-dependent responses and the mechanisms of the hemotoxic and leukemogenic consequences of radiation exposure.

  10. Modulation of Cartilage Degradation Biomarkers Reflect the Activation and Inhibition of Pro-Inflammatory Cytokine Signaling in an Ex Vivo Model of Bovine Cartilage

    DEFF Research Database (Denmark)

    Kjelgaard-Petersen, Cecilie Freja; Sharma, Neha; Kayed, Ashref

    2017-01-01

    -inflammatory treatments for inflammatory arthritis. The aim of this study was to investigate the effect of small molecule inhibitors targeting 4 main pro-inflammatory signaling pathways (p38, Syk, IκBα, and STAT) on Oncostatin M (OSM) and Tumor Necrosis Factor α (TNFα) stimulated cartilage....

  11. Pro iOS Geo building apps with location based services

    CERN Document Server

    Andreucci, Giacomo

    2013-01-01

    Deepen your app development skills with Pro iOS Geo. This book shows you how to use geolocation-based tools to enhance the iOS apps you develop. Author Giacomo Andreucci describes different ways to integrate geo services, depending on the kind of app you're looking to develop: a web app, a hybrid app, or a native app. You'll discover how to use the Google Maps API features to integrate powerful geo capabilities in your apps with a little effort. You'll learn how to: Design geographic features for your apps while respecting usability criteria Design touristic geo apps Use HTML5 and the Google M

  12. App Inventor

    CERN Document Server

    Wolber, David; Spertus, Ellen; Looney, Liz

    2011-01-01

    Yes, you can create your own apps for Android phones-and it's easy to do. This extraordinary book introduces App Inventor for Android, a powerful visual tool that lets anyone build apps for Android-based devices. Learn the basics of App Inventor with step-by-step instructions for more than a dozen fun projects, such as creating location-aware apps, data storage, and apps that include decision-making logic. The second half of the book features an Inventor's manual to help you understand the fundamentals of app building and computer science. App Inventor makes an excellent textbook for beginne

  13. Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells

    Directory of Open Access Journals (Sweden)

    Sutinen Elina M

    2012-08-01

    Full Text Available Abstract Background Alzheimer’s disease (AD involves increased accumulation of amyloid-β (Aβ plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18 in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress. Methods We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP and its processing products, its cleaving enzymes, involved in amyloidogenic processing of APP, and markers of apoptosis. Results IL-18 increased protein levels of the β-site APP-cleaving enzyme BACE-1, the N-terminal fragment of presenilin-1 and slightly presenilin enhancer 2, both of which are members of the γ-secretase complex, as well as Fe65, which is a binding protein of the C-terminus of APP and one regulator for GSK-3β. IL-18 also increased APP expression and phosphorylation, which preceded increased BACE-1 levels. Further, IL-18 altered APP processing, increasing Aβ40 production in particular, which was inhibited by IL-18 binding protein. Increased levels of soluble APPβ were detected in culture medium after the IL-18 exposure. IL-18 also increased anti-apoptotic bcl-xL levels, which likely counteracted the minor increase of the pro-apoptotic caspase-3. Lactate dehydrogenase activity in culture medium was unaffected. Conclusions The IL-18 induction of BACE-1, APP processing, and Aβ is likely to be

  14. A conceptual framework for technology-enabled and technology-dependent user behavior toward device mesh and mesh app

    Directory of Open Access Journals (Sweden)

    Ming-Hsiung Hsiao

    2018-06-01

    Full Text Available The device mesh and mesh app revealed by Gartner as the future strategic technology trend are able to predict people's need from their historic data, then provides the needed services or service innovation to support their activity engagement. However, many theories have identified that it is the motivation, rather than technology, that drives people to engage in activities or tasks. For this reason, this study builds a conceptual framework by integrating the extant logic and theories to explore how future technology would generate benefits for people. It integrates task-technology fit (TTF model and motivation theory (mainly expectancy-value theory to explain such technology user behavior. It also points out the difference between technology-enabled and technology-dependent user behavior and concludes that too much emphasis on the role of technology with too little attention on motivation would distort technology user behavior, and the role of technology as well. Keywords: Device mesh, Mesh app, Expectancy-value theory, Task-technology fit (TTF, Technology-enabled user, Technology-dependent user

  15. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    Directory of Open Access Journals (Sweden)

    Steven Moore

    2015-05-01

    Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

  16. APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

    Science.gov (United States)

    Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J

    2015-05-05

    Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

    OpenAIRE

    Hye Joo Kim; Seong Hwan Kim; Jung-Mi Yun

    2012-01-01

    Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-?B signaling pathway. In this...

  18. IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK

    Directory of Open Access Journals (Sweden)

    Karsten Schmidt

    2017-01-01

    Full Text Available The pathology of inclusion body myositis (IBM involves an inflammatory response and β-amyloid deposits in muscle fibres. It is believed that MAP kinases such as the ERK signalling pathway mediate the inflammatory signalling in cells. Further, there is evidence that autophagic activity plays a crucial role in the pathogenesis of IBM. Using a well established in vitro model of IBM, the autophagic pathway, MAP kinases, and accumulation of β-amyloid were examined. We demonstrate that stimulation of muscle cells with IL-1β and IFN-γ led to an increased phosphorylation of ERK. The ERK inhibitor PD98059 diminished the expression of proinflammatory markers as well as the accumulation of β-amyloid. In addition, IL-1β and IFN-γ led to an increase of autophagic activity, upregulation of APP, and subsequent accumulation of β-sheet aggregates. Taken together, the data demonstrate that the ERK pathway contributes to formation of β-amyloid and regulation of autophagic activity in muscle cells exposed to proinflammatory cell stress. This suggests that ERK serves as an important mediator between inflammatory mechanisms and protein deposition in skeletal muscle and is a crucial element of the pathology of IBM.

  19. Diet and Physical Activity Apps: Perceived Effectiveness by App Users

    Science.gov (United States)

    Egelandsdal, Bjørg; Amdam, Gro V; Almli, Valerie L; Oostindjer, Marije

    2016-01-01

    Background Diet and physical activity apps are two types of health apps that aim to promote healthy eating and energy expenditure through monitoring of dietary intake and physical activity. No clear evidence showing the effectiveness of using these apps to promote healthy eating and physical activity has been previously reported. Objective This study aimed to identify how diet and physical activity (PA) apps affected their users. It also investigated if using apps was associated with changes in diet and PA. Methods First, 3 semi-structured focus group discussions concerning app usability were conducted (15 app users and 8 nonusers; mean age 24.2 years, SD 6.4), including outcome measures such as motivations, experiences, opinions, and adherence. Results from the discussions were used to develop a questionnaire. The questionnaire, which contained questions about behavior changes, app usage, perceived effectiveness, and opinions of app usability, was answered by 500 Norwegians, with a mean age of 25.8 years (SD 5.1). Results App users found diet and PA apps effective in promoting healthy eating and exercising. These apps affected their actions, health consciousness, and self-education about nutrition and PA; and were also a part of their social lives. Over half of the users perceived that apps were effective in assisting them to eat healthily and to exercise more. Diet apps were more effective when they were frequently used and over a long period of time, compared to infrequent or short-term use (P=.01 and P=.02, respectively). Users who used diet and PA apps, perceived apps as more effective than users who only used one type of app (all Pusers were better at maintaining diet and PA behaviors than nonusers (all P<.05). Young adults found apps fun to use, but sometimes time consuming. They wanted apps to be designed to meet their personal expectations. Conclusions App usage influenced action, consciousness, self-education about nutrition and PA, and social life. It

  20. Designing apps for success developing consistent app design practices

    CERN Document Server

    David, Matthew

    2014-01-01

    In 2007, Apple released the iPhone. With this release came tools as revolutionary as the internet was to businesses and individuals back in the mid- and late-nineties: Apps. Much like websites drove (and still drive) business, so too do apps drive sales, efficiencies and communication between people. But also like web design and development, in its early years and iterations, guidelines and best practices for apps are few and far between.Designing Apps for Success provides web/app designers and developers with consistent app design practices that result in timely, appropriate, and efficiently

  1. A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells

    International Nuclear Information System (INIS)

    Schnabl, Bernd; Brandl, Katharina; Fink, Marina; Gross, Philipp; Taura, Kojiro; Gaebele, Erwin; Hellerbrand, Claus; Falk, Werner

    2008-01-01

    Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. In injured liver they are the main extracellular matrix protein producing cell type and further perpetuate hepatic injury by secretion of pro-inflammatory mediators. Since LPS-mediated signaling through toll-like receptor 4 (TLR4) has been identified as key fibrogenic signal in HSCs we aimed to test TLR4 as potential target of therapy via ligand-binding soluble receptors. Incubation of human HSCs with a fusion protein between the extracellular domain of TLR4 and MD2 which binds LPS inhibited LPS-induced NFκB and JNK activation. TLR4/MD2 abolished LPS-induced secretion of IL-6, IL-8, MCP1, and RANTES in HSCs. In addition, TLR4/MD2 fused to human IgG-Fc neutralized LPS activity. Since TLR4 mutant mice are resistant to liver fibrosis, the TLR4/MD2 soluble receptor might represent a new therapeutic molecule for liver fibrogenesis in vivo

  2. Apps for Mathematics Learning: A Review of "Educational" Apps from the iTunes App Store

    Science.gov (United States)

    Highfield, Kate; Goodwin, Kristy

    2013-01-01

    Increasingly iPads™ are being used in schools and prior-to-school settings, with a plethora of Apps available for mathematics learning. Despite the growing number of Apps available in the iTunes App Store, there has been limited systematic analysis of the pedagogic design of Apps designed for mathematics learning. This paper describes a content…

  3. mHealthApps: A Repository and Database of Mobile Health Apps.

    Science.gov (United States)

    Xu, Wenlong; Liu, Yin

    2015-03-18

    The market of mobile health (mHealth) apps has rapidly evolved in the past decade. With more than 100,000 mHealth apps currently available, there is no centralized resource that collects information on these health-related apps for researchers in this field to effectively evaluate the strength and weakness of these apps. The objective of this study was to create a centralized mHealth app repository. We expect the analysis of information in this repository to provide insights for future mHealth research developments. We focused on apps from the two most established app stores, the Apple App Store and the Google Play Store. We extracted detailed information of each health-related app from these two app stores via our python crawling program, and then stored the information in both a user-friendly array format and a standard JavaScript Object Notation (JSON) format. We have developed a centralized resource that provides detailed information of more than 60,000 health-related apps from the Apple App Store and the Google Play Store. Using this information resource, we analyzed thousands of apps systematically and provide an overview of the trends for mHealth apps. This unique database allows the meta-analysis of health-related apps and provides guidance for research designs of future apps in the mHealth field.

  4. APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

    Directory of Open Access Journals (Sweden)

    Hilla Fogel

    2014-06-01

    Full Text Available Accumulation of amyloid-β peptides (Aβ, the proteolytic products of the amyloid precursor protein (APP, induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease.

  5. Bee Venom Inhibits Porphyromonas gingivalis Lipopolysaccharides-Induced Pro-Inflammatory Cytokines through Suppression of NF-κB and AP-1 Signaling Pathways.

    Science.gov (United States)

    Kim, Woon-Hae; An, Hyun-Jin; Kim, Jung-Yeon; Gwon, Mi-Gyeong; Gu, Hyemin; Park, Jae-Bok; Sung, Woo Jung; Kwon, Yong-Chul; Park, Kyung-Duck; Han, Sang Mi; Park, Kwan-Kyu

    2016-11-10

    Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis ( P. gingivalis ), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine for various diseases. Previous studies have demonstrated the anti-inflammatory, anti-bacterial effects of BV. However, a direct role and cellular mechanism of BV on periodontitis-like human keratinocytes have not been explored. Therefore, we investigated the anti-inflammatory mechanism of BV against P. gingivalis LPS (PgLPS)-induced HaCaT human keratinocyte cell line. The anti-inflammatory effect of BV was demonstrated by various molecular biological methods. The results showed that PgLPS increased the expression of Toll-like receptor (TLR)-4 and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and interferon (IFN)-γ. In addition, PgLPS induced activation of the signaling pathways of inflammatory cytokines-related transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). BV effectively inhibited those pro-inflammatory cytokines through suppression of NF-κB and AP-1 signaling pathways. These results suggest that administration of BV attenuates PgLPS-induced inflammatory responses. Furthermore, BV may be a useful treatment to anti-inflammatory therapy for periodontitis.

  6. Collagen-derived N-acetylated proline-glycine-proline upregulates the expression of pro-inflammatory cytokines and extracellular matrix proteases in nucleus pulposus cells via the NF-κB and MAPK signaling pathways.

    Science.gov (United States)

    Feng, Chencheng; He, Jinyue; Zhang, Yang; Lan, Minghong; Yang, Minghui; Liu, Huan; Huang, Bo; Pan, Yong; Zhou, Yue

    2017-07-01

    N-acetylated proline-glycine-proline (N-Ac-PGP) is a chemokine involved in inflammatory diseases and is found to accumulate in degenerative discs. N-Ac-PGP has been demonstrated to have a pro-inflammatory effect on human cartilage endplate stem cells. However, the effect of N-Ac-PGP on human intervertebral disc cells, especially nucleus pulposus (NP) cells, remains unknown. The purpose of this study was to investigate the effect of N-Ac-PGP on the expression of pro-inflammatory factors and extracellular matrix (ECM) proteases in NP cells and the molecular mechanism underlying this effect. Therefore, Milliplex assays were used to detect the levels of various inflammatory cytokines in conditioned culture medium of NP cells treated with N-Ac-PGP, including interleukin-1β (IL-1β), IL-6, IL-17, tumor necrosis factor-α (TNF-α) and C-C motif ligand 2 (CCL2). RT-qPCR was also used to determine the expression of pro-inflammatory cytokines and ECM proteases in the NP cells treated with N-Ac-PGP. Moreover, the role of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in mediating the effect of N-Ac-PGP on the phenotype of NP cells was investigated using specific signaling inhibitors. Milliplex assays showed that NP cells treated with N-Ac-PGP (10 and 100 µg/ml) secreted higher levels of IL-1β, IL-6, IL-17, TNF-α and CCL2 compared with the control. RT-qPCR assays showed that NP cells treated with N-Ac-PGP (100 µg/ml) had markedly upregulated expression of matrix metalloproteinase 3 (MMP3), MMP13, a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4), ADAMTS5, IL-6, CCL-2, CCL-5 and C-X-C motif chemokine ligand 10 (CXCL10). Moreover, N-Ac-PGP was shown to activate the MAPK and NF-κB signaling pathways in NP cells. MAPK and NF-κB signaling inhibitors suppressed the upregulation of proteases and pro-inflammatory cytokines in NP cells treated with N-Ac-PGP. In conclusion, N-Ac-PGP induces the

  7. Lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes with diabetic nephropathy depending on the stage of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    2012-06-01

    Full Text Available Aim: to study the role and relationship of lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes mellitus (DM2 with diabetic nephropathy (DN, depending on the stage of chronic kidney disease (CKD. Materials and Methods: a total of 240 patients with type 2 diabetes in the early stages of DN and CKD were studied. Results: in patients with type 2 diabetes development of DN was associated with an increased level of proinflammatory cytokines and lipid abnormalities (hypertriglyceridemia. We found a negative correlation between the level of triglycerides (TG and glomerular filtration rate (GFR (r = -0,43 and a direct correlation between the level of IL-6 and TG (r = 0,48. Conclusions: increased levels of proinflammatory cytokines and triglycerides increase the risk of development and progression of DN and CKD.

  8. Pro-inflammatory signaling by IL-10 and IL-22: bad habit stirred up by interferons ?

    Directory of Open Access Journals (Sweden)

    Heiko eMühl

    2013-02-01

    Full Text Available Interleukin (IL-10 and IL-22 are key members of the IL-10 cytokine family that share characteristic properties such as defined structural features, usage of IL-10R2 as one receptor chain, and activation of signal transducer and activator of transcription (STAT-3 as dominant signaling mode. IL-10, formerly known as cytokine synthesis inhibitory factor, is key to deactivation of monocytes/macrophages and dendritic cells. Accordingly, pre-clinical studies document its anti-inflammatory capacity. However, the outcome of clinical trials assessing the therapeutic potential of IL-10 in prototypic inflammatory disorders has been disappointing. In contrast to IL-10, IL-22 acts primarily on non-leukocytic cells, in particular epithelial cells of intestine, skin, liver, and lung. STAT3-driven proliferation, anti-apoptosis, and anti-microbial tissue protection is regarded a principal function of IL-22 at host/environment interfaces. In this hypothesis article, hidden/underappreciated pro-inflammatory characteristics of IL-10 and IL-22 are outlined and related to cellular priming by type I interferon. It is tempting to speculate that an inherent inflammatory potential of IL-10 and IL-22 confines their usage in tissue protective therapy and beyond that determines in some patients efficacy of type I interferon treatment.

  9. App Inventor for Android Build Your Own Apps - No Experience Required!

    CERN Document Server

    Tyler, Jason

    2011-01-01

    Create Android mobile apps, no programming required! Even with limited programming experience, you can easily learn to create apps for the Android platform with this complete guide to App Inventor for Android. App Inventor for Android is a visual language that relies on simple programming blocks that users can drag and drop to create apps. This handy book gives you a series of fully worked-out apps, complete with their programming blocks, which you can customize for your own use or use as a starting point for creating the next killer app. And it's all without writing a single line of code. Don

  10. User Experience of Cognitive Behavioral Therapy Apps for Depression: An Analysis of App Functionality and User Reviews.

    Science.gov (United States)

    Stawarz, Katarzyna; Preist, Chris; Tallon, Debbie; Wiles, Nicola; Coyle, David

    2018-06-06

    health and well-being. Users, including health professionals, valued and used apps that incorporated both core cognitive behavioral therapy and non-cognitive behavioral therapy elements, but concerns were also expressed regarding the unsupervised use of apps. Positivity was seen as important to engagement, for example, in the context of automatic thoughts, users expressed a preference to capture not just negative but also positive ones. Privacy, security, and trust were crucial to the user experience. Cognitive behavioral therapy apps for depression need to improve with respect to incorporating evidence-based cognitive behavioral therapy elements. Equally, a positive user experience is dependent on other design factors, including consideration of varying contexts of use. App designers should be able to clearly identify the therapeutic basis of their apps, but they should also draw on evidence-based strategies to support a positive and engaging user experience. The most effective apps are likely to strike a balance between evidence-based cognitive behavioral therapy strategies and evidence-based design strategies, including the possibility of eclectic therapeutic techniques. ©Katarzyna Stawarz, Chris Preist, Debbie Tallon, Nicola Wiles, David Coyle. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.06.2018.

  11. Detecting android malicious apps and categorizing benign apps with ensemble of classifiers

    KAUST Repository

    Wang, Wei

    2017-01-17

    Android platform has dominated the markets of smart mobile devices in recent years. The number of Android applications (apps) has seen a massive surge. Unsurprisingly, Android platform has also become the primary target of attackers. The management of the explosively expansive app markets has thus become an important issue. On the one hand, it requires effectively detecting malicious applications (malapps) in order to keep the malapps out of the app market. On the other hand, it needs to automatically categorize a big number of benign apps so as to ease the management, such as correcting an app’s category falsely designated by the app developer. In this work, we propose a framework to effectively and efficiently manage a big app market in terms of detecting malapps and categorizing benign apps. We extract 11 types of static features from each app to characterize the behaviors of the app, and employ the ensemble of multiple classifiers, namely, Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naive Bayes (NB), Classification and Regression Tree (CART) and Random Forest (RF), to detect malapps and to categorize benign apps. An alarm will be triggered if an app is identified as malicious. Otherwise, the benign app will be identified as a specific category. We evaluate the framework on a large app set consisting of 107,327 benign apps as well as 8,701 malapps. The experimental results show that our method achieves the accuracy of 99.39% in the detection of malapps and achieves the best accuracy of 82.93% in the categorization of benign apps.

  12. Facebook apps for smoking cessation: a review of content and adherence to evidence-based guidelines.

    Science.gov (United States)

    Jacobs, Megan A; Cobb, Caroline O; Abroms, Lorien; Graham, Amanda L

    2014-09-09

    Facebook is the most popular social network site, with over 1 billion users globally. There are millions of apps available within Facebook, many of which address health and health behavior change. Facebook may represent a promising channel to reach smokers with cessation interventions via apps. To date, there have been no published reports about Facebook apps for smoking cessation. The purpose of this study was to review the features and functionality of Facebook apps for smoking cessation and to determine the extent to which they adhere to evidence-based guidelines for tobacco dependence treatment. In August 2013, we searched Facebook and three top Internet search engines using smoking cessation keywords to identify relevant Facebook apps. Resultant apps were screened for eligibility (smoking cessation-related, English language, and functioning). Eligible apps were reviewed by 2 independent coders using a standardized coding scheme. Coding included content features (interactive, informational, and social) and adherence to an established 20-item index (possible score 0-40) derived from the US Public Health Service's Clinical Practice Guidelines for Treating Tobacco Use and Dependence. We screened 22 apps for eligibility; of these, 12 underwent full coding. Only 9 apps were available on Facebook. Facebook apps fell into three broad categories: public pledge to quit (n=3), quit-date-based calculator/tracker (n=4), or a multicomponent quit smoking program (n=2). All apps incorporated interactive, informational, and social features except for two quit-date-based calculator/trackers apps (lacked informational component). All apps allowed app-related posting within Facebook (ie, on self/other Facebook profile), and four had a within-app "community" feature to enable app users to communicate with each other. Adherence index summary scores among Facebook apps were low overall (mean 15.1, SD 7.8, range 7-30), with multicomponent apps scoring the highest. There are few

  13. Smartphone apps for snoring.

    Science.gov (United States)

    Camacho, M; Robertson, M; Abdullatif, J; Certal, V; Kram, Y A; Ruoff, C M; Brietzke, S E; Capasso, R

    2015-10-01

    To identify and systematically evaluate user-friendly smartphone snoring apps. The Apple iTunes app store was searched for snoring apps that allow recording and playback. Snoring apps were downloaded, evaluated and rated independently by four authors. Two patients underwent polysomnography, and the data were compared with simultaneous snoring app recordings, and one patient used the snoring app at home. Of 126 snoring apps, 13 met the inclusion and exclusion criteria. The most critical app feature was the ability to graphically display the snoring events. The Quit Snoring app received the highest overall rating. When this app's recordings were compared with in-laboratory polysomnography data, app snoring sensitivities ranged from 64 to 96 per cent, and snoring positive predictive values ranged from 93 to 96 per cent. A chronic snorer used the app nightly for one month and tracked medical interventions. Snoring decreased from 200 to 10 snores per hour, and bed partner snoring complaint scores decreased from 9 to 2 (on a 0-10 scale). Select smartphone apps are user-friendly for recording and playing back snoring sounds. Preliminary comparison of more than 1500 individual snores demonstrates the potential clinical utility of such apps; however, further validation testing is recommended.

  14. Best Android Apps

    CERN Document Server

    Hendrickson, Mike

    2010-01-01

    You can choose from thousands of apps to make your Android device do just about anything you can think of -- and probably a few things you'd never imagine. There are so many Android apps available, in fact, that it's been difficult to find the best of the bunch -- until now. Best Android Apps leads you beyond the titles in Android Market's "Top Paid" and "Top Free" bins to showcase apps that will truly delight, empower, and entertain you. The authors have tested and handpicked more than 200 apps and games, each listed with a description and details highlighting the app's valuable tips and sp

  15. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  16. Selecting "App"ealing and "App"ropriate Book Apps for Beginning Readers

    Science.gov (United States)

    Cahill, Maria; McGill-Franzen, Anne

    2013-01-01

    Beginning with a brief rationale for selecting quality digital picture book apps for beginning readers, the authors describe the elements of digital picture books and provide a brief review of the instructional benefits of digital picture book use for beginning readers. They then present a detailed taxonomy for selecting quality picture book apps.…

  17. Enabling Psychiatrists to be Mobile Phone App Developers: Insights Into App Development Methodologies.

    Science.gov (United States)

    Zhang, Melvyn Wb; Tsang, Tammy; Cheow, Enquan; Ho, Cyrus Sh; Yeong, Ng Beng; Ho, Roger Cm

    2014-11-11

    The use of mobile phones, and specifically smartphones, in the last decade has become more and more prevalent. The latest mobile phones are equipped with comprehensive features that can be used in health care, such as providing rapid access to up-to-date evidence-based information, provision of instant communications, and improvements in organization. The estimated number of health care apps for mobile phones is increasing tremendously, but previous research has highlighted the lack of critical appraisal of new apps. This lack of appraisal of apps has largely been due to the lack of clinicians with technical knowledge of how to create an evidence-based app. We discuss two freely available methodologies for developing Web-based mobile phone apps: a website builder and an app builder. With these, users can program not just a Web-based app, but also integrate multimedia features within their app, without needing to know any programming language. We present techniques for creating a mobile Web-based app using two well-established online mobile app websites. We illustrate how to integrate text-based content within the app, as well as integration of interactive videos and rich site summary (RSS) feed information. We will also briefly discuss how to integrate a simple questionnaire survey into the mobile-based app. A questionnaire survey was administered to students to collate their perceptions towards the app. These two methodologies for developing apps have been used to convert an online electronic psychiatry textbook into two Web-based mobile phone apps for medical students rotating through psychiatry in Singapore. Since the inception of our mobile Web-based app, a total of 21,991 unique users have used the mobile app and online portal provided by WordPress, and another 717 users have accessed the app via a Web-based link. The user perspective survey results (n=185) showed that a high proportion of students valued the textbook and objective structured clinical

  18. Identification of Users for a Smoking Cessation Mobile App: Quantitative Study.

    Science.gov (United States)

    Chevalking, S K Leon; Ben Allouch, Somaya; Brusse-Keizer, Marjolein; Postel, Marloes G; Pieterse, Marcel E

    2018-04-09

    The number of mobile apps that support smoking cessation is growing, indicating the potential of the mobile phone as a means to support cessation. Knowledge about the potential end users for cessation apps results in suggestions to target potential user groups in a dissemination strategy, leading to a possible increase in the satisfaction and adherence of cessation apps. This study aimed to characterize potential end users for a specific mobile health (mHealth) smoking cessation app. A quantitative study was conducted among 955 Dutch smokers and ex-smokers. The respondents were primarily recruited from addiction care facilities and hospitals through Web-based media via websites and forums. The respondents were surveyed on their demographics, smoking behavior, and personal innovativeness. The intention to use and the attitude toward a cessation app were determined on a 5-point Likert scale. To study the association between the characteristics and intention to use and attitude, univariate and multivariate ordinal logistic regression analyses were performed. The multivariate ordinal logistic regression showed that the number of previous quit attempts (odds ratio [OR] 4.1, 95% CI 2.4-7.0, and OR 3.5, 95% CI 2.0-5.9) and the score on the Fagerstrom Test of Nicotine Dependence (OR 0.8, 95% CI 0.8-0.9, and OR 0.8, 95% CI 0.8-0.9) positively correlates with the intention to use a cessation app and the attitude toward cessation apps, respectively. Personal innovativeness also positively correlates with the intention to use (OR 0.3, 95% CI 0.2-0.4) and the attitude towards (OR 0.2, 95% CI 0.1-0.4) a cessation app. No associations between demographics and the intention to use or the attitude toward using a cessation app were observed. This study is among the first to show that demographic characteristics such as age and level of education are not associated with the intention to use and the attitude toward using a cessation app when characteristics related specifically to the

  19. Android apps security

    CERN Document Server

    Gunasekera, Sheran

    2012-01-01

    Android Apps Security provides guiding principles for how to best design and develop Android apps with security in mind. It explores concepts that can be used to secure apps and how developers can use and incorporate these security features into their apps. This book will provide developers with the information they need to design useful, high-performing, and secure apps that expose end-users to as little risk as possible.  Overview of Android OS versions, features, architecture and security.  Detailed examination of areas where attacks on applications can take place and what controls should b

  20. Calsyntenin-1 shelters APP from proteolytic processing during anterograde axonal transport

    Directory of Open Access Journals (Sweden)

    Martin Steuble

    2012-06-01

    Endocytosis of amyloid-β precursor protein (APP is thought to represent the major source of substrate for the production of the amyloidogenic Aβ peptide by the β-secretase BACE1. The irreversible nature of proteolytic cleavage implies the existence of an efficient replenishment route for APP from its sites of synthesis to the cell surface. We recently found that APP exits the trans-Golgi network in intimate association with calsyntenin-1, a transmembrane cargo-docking protein for Kinesin-1-mediated vesicular transport. Here we characterized the function of calsyntenin-1 in neuronal APP transport using selective immunoisolation of intracellular trafficking organelles, immunocytochemistry, live-imaging, and RNAi. We found that APP is co-transported with calsyntenin-1 along axons to early endosomes in the central region of growth cones in carriers that exclude the α-secretase ADAM10. Intriguingly, calsyntenin-1/APP organelles contained BACE1, suggesting premature cleavage of APP along its anterograde path. However, we found that APP contained in calsyntenin-1/APP organelles was stable. We further analyzed vesicular trafficking of APP in cultured hippocampal neurons, in which calsyntenin-1 was reduced by RNAi. We found a markedly increased co-localization of APP and ADAM10 in axons and growth cones, along with increased proteolytic processing of APP and Aβ secretion in these neurons. This suggested that the reduced capacity for calsyntenin-1-dependent APP transport resulted in mis-sorting of APP into additional axonal carriers and, therefore, the premature encounter of unprotected APP with its ectodomain proteases. In combination, our results characterize calsyntenin-1/APP organelles as carriers for sheltered anterograde axonal transport of APP.

  1. Google App Inventor

    CERN Document Server

    Roberts, Ralph

    2011-01-01

    This book is written in the Beginner's Guide format that takes the reader through a series of steps to build exciting apps using Google's App Inventor. This book is perfect for people with little or no experience, not just Android developers. No matter your level of experience, you will find plenty of information that you can use to create powerful apps, apps that can be published on Android Market and other places.

  2. Hypnosis: There’s an App for that. A systematic review of hypnosis apps

    Science.gov (United States)

    Sucala, Madalina; Schnur, Julie B.; Glazier, Kimberly; Miller, Sarah J.; Green, Joseph P.; Montgomery, Guy H.

    2013-01-01

    The study systematically reviews the hypnosis apps available via iTunes that were compatible with iPhone or iPad. Of 1455 apps identified on iTunes, 407 met inclusion criteria and were further reviewed. Most common hypnosis app targets were: weight loss (23%), boosting self-esteem (20%), and relaxation/stress reduction (19%). 83% of apps delivered hypnosis via audio track, and 37% allowed tailoring. Less than 14% of apps reported disclaimers. None of the apps reported having been tested for efficacy, and none reported being evidence-based. Although apps have the potential to enhance hypnosis delivery, it seems as though technology has raced ahead of the supporting science. Recommendations from clinical researchers and policy makers are needed to inform responsible hypnosis app development and use. PMID:23957263

  3. APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone.

    Directory of Open Access Journals (Sweden)

    Melanie Laßek

    2016-04-01

    Full Text Available The hallmarks of Alzheimer's disease (AD are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network.

  4. Effect of growth conditions on expression of the acid phosphatase (cyx-appA) operon and the appY gene, which encodes a transcriptional activator of Escherichia coli

    DEFF Research Database (Denmark)

    Brøndsted, Lone; Atlung, Tove

    1996-01-01

    The expression and transcriptional regulation of the Escherichia coli cyx-appA operon and the appY gene has been investigated during different environmental conditions using single copy transcriptional lacZ fusions. The cyx-appA operon encodes acid phosphatase and a putative cytochrome oxidase...... of the cyx-appA operon. The nitrate repression was partially dependent on NarL. A high expression of the operon was obtained in glucose medium supplemented with formate, where E.coli obtains energy by fermentation. The formate induction was independent of the fhlA gene product. The results presented...... in this paper indicate a clear difference in the regulation of the cyx-appA operon compared to the cyd operon, encoding the cytochrome d oxidase complex. The results suggest that cytochrome x oxidase has a function at even more oxygen limiting conditions than cytochrome d oxidase. The expression of the app...

  5. A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration.

    Science.gov (United States)

    Lee, C A; Silva, M; Siber, A M; Kelly, A J; Galyov, E; McCormick, B A

    2000-10-24

    In response to Salmonella typhimurium, the intestinal epithelium generates an intense inflammatory response consisting largely of polymorphonuclear leukocytes (neutrophils, PMN) migrating toward and ultimately across the epithelial monolayer into the intestinal lumen. It has been shown that bacterial-epithelial cell interactions elicit the production of inflammatory regulators that promote transepithelial PMN migration. Although S. typhimurium can enter intestinal epithelial cells, bacterial internalization is not required for the signaling mechanisms that induce PMN movement. Here, we sought to determine which S. typhimurium factors and intestinal epithelial signaling pathways elicit the production of PMN chemoattractants by enterocytes. Our results suggest that S. typhimurium activates a protein kinase C-dependent signal transduction pathway that orchestrates transepithelial PMN movement. We show that the type III effector protein, SipA, is not only necessary but is sufficient to induce this proinflammatory response in epithelial cells. Our results force us to reconsider the long-held view that Salmonella effector proteins must be directly delivered into host cells from bacterial cells.

  6. On cryptographic security of end-to-end encrypted connections in WhatsApp and Telegram messengers

    Directory of Open Access Journals (Sweden)

    Sergey V. Zapechnikov

    2017-11-01

    Full Text Available The aim of this work is to analyze the available possibilities for improving secure messaging with end-to-end connections under conditions of external violator actions and distrusted service provider. We made a comparative analysis of cryptographic security mechanisms for two widely used messengers: Telegram and WhatsApp. It was found that Telegram is based on MTProto protocol, while WhatsApp is based on the alternative Signal protocol. We examine the specific features of messengers implementation associated with random number generation on the most popular Android mobile platform. It was shown that Signal has better security properties. It is used in several other popular messengers such as TextSecure, RedPhone, GoogleAllo, FacebookMessenger, Signal along with WhatsApp. A number of possible attacks on both messengers were analyzed in details. In particular, we demonstrate that the metadata are poorly protected in both messengers. Metadata security may be one of the goals for further studies.

  7. Governance mechanisms for healthcare apps

    DEFF Research Database (Denmark)

    Manikas, Konstantinos; Hansen, Klaus Marius; Kyng, Morten

    2014-01-01

    The introduction of the `app store' concept has challenged the way software is distributed and marketed: developers have easier access to customers, while customers have easy access to innovative applications. Apps today are increasingly focusing on more "mission-critical" areas like healthcare...... with the Apple AppStore counting more than 40,000 apps under the category "health & fitness". This rapid development of healthcare apps increases the necessity of governance as, currently, healthcare apps are not thoroughly governed. The U.S. Food and Drug Administration and the European Commission only have...... policies for apps that are medical devices.In this paper, we approach the problem of how to govern healthcare and medical apps by addressing the risks the use of these apps pose, while at the same time inviting for development of new apps. To do so we (i) analyze four cases of healthcare app governance...

  8. ApkCombiner: Combining Multiple Android Apps to Support Inter-App Analysis

    OpenAIRE

    Li , Li; Bartel , Alexandre; Bissyandé , Tegawendé ,; Klein , Jacques; Traon , Yves ,

    2015-01-01

    Part 8: Mobile and Cloud Services Security; International audience; Android apps are made of components which can leak information between one another using the ICC mechanism. With the growing momentum of Android, a number of research contributions have led to tools for the intra-app analysis of Android apps. Unfortunately, these state-of-the-art approaches, and the associated tools, have long left out the security flaws that arise across the boundaries of single apps, in the interaction betw...

  9. Apps of Steel: Are Exercise Apps Providing Consumers with Realistic Expectations?: A Content Analysis of Exercise Apps for Presence of Behavior Change Theory

    Science.gov (United States)

    Cowan, Logan T.; Van Wagenen, Sarah A.; Brown, Brittany A.; Hedin, Riley J.; Seino-Stephan, Yukiko; Hall, P. Cougar; West, Joshua H.

    2013-01-01

    Objective. To quantify the presence of health behavior theory constructs in iPhone apps targeting physical activity. Methods. This study used a content analysis of 127 apps from Apple's (App Store) "Health & Fitness" category. Coders downloaded the apps and then used an established theory-based instrument to rate each app's inclusion of…

  10. easyHealthApps: e-Health Apps dynamic generation for smartphones & tablets.

    Science.gov (United States)

    Paschou, Mersini; Sakkopoulos, Evangelos; Tsakalidis, Athanasios

    2013-06-01

    Mobile phones and especially smartphones have been embraced by a rapidly increasing number of people worldwide and this trend is expected to evolve even more in the years to come. There are numerous smartphone Apps that record critical medical data in an effort to solve a particular health issue each time. We studied such applications and not surprisingly, we have found that development and design effort is often repeated. Software patterns have been detected to exist, however re-usability has not been enforced. This leads to lost programming manpower and to increased probability of repeating bugs in Apps. Moreover, at the moment smartphone e-Health Apps demand time, effort and costs for development. Unfortunately even simple data recording Apps are practically impossible to be produced by multiple health domain users who are not developers. In this work, we propose, design and implement a simple and integrated solution which gives healthcare professionals and researchers the ability to create their own data intensive smartphone applications, independent of the desired healthcare domain. The proposed approach applies efficient software techniques that hide development from the users and enable App creation through a simple Web User Interface. The Apps produced are in native format and it is possible to dynamically receive m-Health business logic and the chosen UI. Evaluation of the proposed solution has shown that the generated Apps are functionally and UI equivalent to human-coded Apps according to a number of comparison parameters. Furthermore, e-Health professionals show particular interest in developing Apps on their own for a particular domain they focus on.

  11. Anxiety: There is an app for that. A systematic review of anxiety apps.

    Science.gov (United States)

    Sucala, Madalina; Cuijpers, Pim; Muench, Frederick; Cardoș, Roxana; Soflau, Radu; Dobrean, Anca; Achimas-Cadariu, Patriciu; David, Daniel

    2017-06-01

    Smartphones and mobile devices have become ubiquitous, and with the rapid advance of technology, the number of health applications (apps) that are available for consumers on these devices is constantly growing. In particular, there has been a recent proliferation of anxiety apps. However, there has been no review of the quality or content of these anxiety apps and little is known about their purpose, the features they contain, and their empirical support. The goal of this systematic review was to assess the commercially available anxiety apps. A list of anxiety apps was collected in January 2017, using the Power Search function of iTunes and Google Play. Of 5,078 identified apps, 52 met our inclusion criteria (i.e., being defined as an anxiety/worry relief app, and offering psychological techniques aimed primarily at reducing anxiety) and were further reviewed. The majority (67.3%) of the currently available anxiety apps were found to lack the involvement of health care professionals in their development, and very few (3.8%) of them have been rigorously tested. At the moment, although anxiety apps have the potential to enhance access to mental health care, there is a marked discrepancy between the wealth of commercially available apps, and the paucity of data regarding their efficacy and effectiveness. Although the great promise of apps is their ability to increasing access to evidence-based mental health, the field is not quite there yet and the full potential of apps for treating anxiety has yet to be exploited. © 2017 Wiley Periodicals, Inc.

  12. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    François Huaux

    Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

  13. Downregulation of PI3K/Akt/mTOR signaling pathway in curcumin-induced autophagy in APP/PS1 double transgenic mice.

    Science.gov (United States)

    Wang, Chen; Zhang, Xiong; Teng, Zhipeng; Zhang, Tong; Li, Yu

    2014-10-05

    Autophagy is a lysosomal degradation pathway, which is essential for cell survival, proliferation, differentiation and homeostasis. It is well known that beta-amyloid (Aβ) aggregation is one of key characteristics for Alzheimer's disease (AD), which triggers a complex pathological cascade, leading to neurodegeneration. Recent studies have shown that Aβ peptide is generated from amyloid β precursor protein (APP) during autophagic turnover of APP-rich organelles by autophagy. Aβ generation during normal autophagy is subsequently degraded by lysosomes. Curcumin, a nature plant extraction, has been reported to inhibit the generation and deposition of Aβ; however, the underlying mechanisms are not fully understood yet. In the present study, we reported that curcumin treatment not only attenuated cognitive impairment detected by Morris water maze test, but also inhibited the generation of Aβ investigated by immunohistochemistry in APP/PS1 double transgenic AD mice. Moreover, curcumin induced autophagy in the mice, evidenced by LC3 immunofluorescence analysis and western blot assays on LC3. Furthermore, we found that curcumin significantly decreased the expression of Phosphatidylinositol 3-Kinase (PI3K), phosphorylated Akt and rapamycin (mTOR) at protein levels, respectively. Taken together, our data suggests that curcumin inhibits Aβ generation and induces of autophagy by downregulating PI3K/Akt/mTOR signaling pathway, and further shows a neuroprotective effect. Meanwhile curcumin might be a candidate neuroprotective agent for AD patients treatment by inducing autophagy. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Plausibility of Menstrual Cycle Apps Claiming to Support Conception.

    Science.gov (United States)

    Freis, Alexander; Freundl-Schütt, Tanja; Wallwiener, Lisa-Maria; Baur, Sigfried; Strowitzki, Thomas; Freundl, Günter; Frank-Herrmann, Petra

    2018-01-01

    /30 points, myNFP 20/30 points, Lily 19/30 points, and OvuView 11/30 points. We concluded that the available cycle apps vary according to their underlying scientific quality and clear rating criteria have been suggested. Three of the tested apps were judged to be eligible for further study. The scientific evaluation of cycle apps depends on good prospective studies undertaken by independent investigators who are free of commercial bias.

  15. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: jzvereb@gmail.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: ipuray@mdanderson.org [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: fesus@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences (Hungary); Balajthy, Zoltán, E-mail: balajthy@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

    2014-08-08

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  16. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    International Nuclear Information System (INIS)

    Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán

    2014-01-01

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  17. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  18. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    International Nuclear Information System (INIS)

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-01-01

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics

  19. A novel synthetic derivative of melatonin, 5-hydroxy-2’-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation

    International Nuclear Information System (INIS)

    Shim, Do-Wan; Shin, Hee Jae; Han, Ji-Won; Ji, Young-Eun; Jang, Cheol-Hun; Koppula, Sushruta; Kang, Tae-Bong; Lee, Kwang-Ho

    2015-01-01

    Melatonin is substantially reported to possess anti-inflammatory properties. In the present study, we synthesized a novel melatonin derivative, 5-hydroxy-2′-isobutyl-streptochlorin (HIS), which displayed superior anti-inflammatory properties to its parent compound. Further, we explored its underlying mechanisms in cellular and experimental animal models. Lipopolysaccharide was used to induce in vitro inflammatory responses in RAW 264.7 macrophages. LPS-primed macrophages were pulsed with biologically unrelated toxic molecules to evaluate the role of HIS on inflammasome activation. In vivo verifications were carried out using acute lung injury (ALI) and Escherichia coli-induced septic shock mouse models. HIS inhibited the production of proinflammatory mediators and cytokines such as nitric oxide, cyclooxygenase 2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages. HIS suppressed the infiltration of immune cells into the lung and the production of pro-inflammatory cytokines such as IL-6 and TNF-α in broncho-alveolar lavage fluid in the ALI mouse model. Mechanistic studies revealed that the inhibitory effects of HIS were mediated through the regulation of the TIR domain-containing, adaptor-inducing, interferon-β (TRIF)-dependent signaling pathway from toll-like receptors. Further, HIS attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation independent of mitochondrial ROS production. Furthermore, HIS suppressed IL-1β, IL-6 and interferon-β production in peritoneal lavage in the Escherichia coli-induced sepsis mouse model. In conclusion, HIS exerted potent anti-inflammatory effects via the regulation of TRIF-dependent signaling and inflammasome activation. Notably, the superior anti-inflammatory properties of this derivative compared with its parent compound could be a promising lead for treating various inflammatory-mediated diseases. - Highlights: • Νovel compound, 5-hydroxy-2′-isobutyl-streptochlorin (HIS) was

  20. A novel synthetic derivative of melatonin, 5-hydroxy-2’-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Do-Wan [Department of Biotechnology, Research Institute of Inflammatory Disease, Konkuk University, Chungju (Korea, Republic of); Shin, Hee Jae [Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science & Technology, Ansan (Korea, Republic of); Han, Ji-Won; Ji, Young-Eun; Jang, Cheol-Hun; Koppula, Sushruta; Kang, Tae-Bong [Department of Biotechnology, Research Institute of Inflammatory Disease, Konkuk University, Chungju (Korea, Republic of); Lee, Kwang-Ho, E-mail: kwangho@kku.ac.kr [Department of Biotechnology, Research Institute of Inflammatory Disease, Konkuk University, Chungju (Korea, Republic of)

    2015-04-15

    Melatonin is substantially reported to possess anti-inflammatory properties. In the present study, we synthesized a novel melatonin derivative, 5-hydroxy-2′-isobutyl-streptochlorin (HIS), which displayed superior anti-inflammatory properties to its parent compound. Further, we explored its underlying mechanisms in cellular and experimental animal models. Lipopolysaccharide was used to induce in vitro inflammatory responses in RAW 264.7 macrophages. LPS-primed macrophages were pulsed with biologically unrelated toxic molecules to evaluate the role of HIS on inflammasome activation. In vivo verifications were carried out using acute lung injury (ALI) and Escherichia coli-induced septic shock mouse models. HIS inhibited the production of proinflammatory mediators and cytokines such as nitric oxide, cyclooxygenase 2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages. HIS suppressed the infiltration of immune cells into the lung and the production of pro-inflammatory cytokines such as IL-6 and TNF-α in broncho-alveolar lavage fluid in the ALI mouse model. Mechanistic studies revealed that the inhibitory effects of HIS were mediated through the regulation of the TIR domain-containing, adaptor-inducing, interferon-β (TRIF)-dependent signaling pathway from toll-like receptors. Further, HIS attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation independent of mitochondrial ROS production. Furthermore, HIS suppressed IL-1β, IL-6 and interferon-β production in peritoneal lavage in the Escherichia coli-induced sepsis mouse model. In conclusion, HIS exerted potent anti-inflammatory effects via the regulation of TRIF-dependent signaling and inflammasome activation. Notably, the superior anti-inflammatory properties of this derivative compared with its parent compound could be a promising lead for treating various inflammatory-mediated diseases. - Highlights: • Νovel compound, 5-hydroxy-2′-isobutyl-streptochlorin (HIS) was

  1. A Guide to Help Consumers Choose Apps and Avoid App Overload

    Science.gov (United States)

    Schuster, Ellen; Zimmerman, Lynda

    2014-01-01

    Mobile technology has transformed the way consumers access and use information. The exponential growth of mobile apps makes finding suitable, easy-to-use nutrition and health-related apps challenging. A guide for consumers helps them ask important questions before downloading apps. The guide can be adapted for other Extension disciplines.

  2. Mobile Phone Apps to Improve Medication Adherence: A Systematic Stepwise Process to Identify High-Quality Apps.

    Science.gov (United States)

    Santo, Karla; Richtering, Sarah S; Chalmers, John; Thiagalingam, Aravinda; Chow, Clara K; Redfern, Julie

    2016-12-02

    There are a growing number of mobile phone apps available to support people in taking their medications and to improve medication adherence. However, little is known about how these apps differ in terms of features, quality, and effectiveness. We aimed to systematically review the medication reminder apps available in the Australian iTunes store and Google Play to assess their features and their quality in order to identify high-quality apps. This review was conducted in a similar manner to a systematic review by using a stepwise approach that included (1) a search strategy; (2) eligibility assessment; (3) app selection process through an initial screening of all retrieved apps and full app review of the included apps; (4) data extraction using a predefined set of features considered important or desirable in medication reminder apps; (5) analysis by classifying the apps as basic and advanced medication reminder apps and scoring and ranking them; and (6) a quality assessment by using the Mobile App Rating Scale (MARS), a reliable tool to assess mobile health apps. We identified 272 medication reminder apps, of which 152 were found only in Google Play, 87 only in iTunes, and 33 in both app stores. Apps found in Google Play had more customer reviews, higher star ratings, and lower cost compared with apps in iTunes. Only 109 apps were available for free and 124 were recently updated in 2015 or 2016. Overall, the median number of features per app was 3.0 (interquartile range 4.0) and only 18 apps had ≥9 of the 17 desirable features. The most common features were flexible scheduling that was present in 56.3% (153/272) of the included apps, medication tracking history in 54.8% (149/272), snooze option in 34.9% (95/272), and visual aids in 32.4% (88/272). We classified 54.8% (149/272) of the included apps as advanced medication reminder apps and 45.2% (123/272) as basic medication reminder apps. The advanced apps had a higher number of features per app compared with the

  3. Mobile Apps for Suicide Prevention: Review of Virtual Stores and Literature.

    Science.gov (United States)

    de la Torre, Isabel; Castillo, Gema; Arambarri, Jon; López-Coronado, Miguel; Franco, Manuel A

    2017-10-10

    The best manner to prevent suicide is to recognize suicidal signs and signals, and know how to respond to them. We aim to study the existing mobile apps for suicide prevention in the literature and the most commonly used virtual stores. Two reviews were carried out. The first was done by searching the most commonly used commercial app stores, which are iTunes and Google Play. The second was a review of mobile health (mHealth) apps in published articles within the last 10 years in the following 7 scientific databases: Science Direct, Medline, PsycINFO, Embase, The Cochrane Library, IEEE Xplore, and Google Scholar. A total of 124 apps related to suicide were found in the cited virtual stores but only 20 apps were specifically designed for suicide prevention. All apps were free and most were designed for Android. Furthermore, 6 relevant papers were found in the indicated scientific databases; in these studies, some real experiences with physicians, caregivers, and families were described. The importance of these people in suicide prevention was indicated. The number of apps regarding suicide prevention is small, and there was little information available from literature searches, indicating that technology-based suicide prevention remains understudied. Many of the apps provided no interactive features. It is important to verify the accuracy of the results of different apps that are available on iOS and Android. The confidence generated by these apps can benefit end users, either by improving their health monitoring or simply to verify their body condition. ©Isabel de la Torre, Gema Castillo, Jon Arambarri, Miguel López-Coronado, Manuel A Franco. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 10.10.2017.

  4. The World of Orthodontic apps.

    Directory of Open Access Journals (Sweden)

    Gaurav Gupta

    2017-01-01

    Full Text Available The usage of the portable electronic devices such as the smartphones and handheld tablets has increased over the years, and this is true in the health-care industry also. This is because of the development of various patient management softwares. The use of apps to manage, educate, and inform patient is not uncommon among orthodontists nowadays. The aim of this article was to review the various apps available on the Google Play Store and iOS Apple Store for orthodontists and patients. Four smartphones using orthodontically relevant keywords such as orthodontics, orthodontists, and braces were searched and reviewed in detail. Out of the 354 orthodontically relevant apps available in both Android and Apple operating systems, the apps could be categorized as orthodontist-related apps or patient-related apps. Under these categories they could be further classified as practice managements apps, patient education apps, model analysis apps, tooth material calculators, patient reminder apps, etc.

  5. Patterns, Attitudes, and Dependence toward WhatsApp among College Students

    OpenAIRE

    Harshavardhan Sampath; Sai Kalyani; Geeta Soohinda; Sanjiba Dutta

    2017-01-01

    Background: WhatsApp (WA), a free cross-platform smartphone application has revolutionized social communication over the virtual world. It enables information sharing, both personal and professional, individually and across social groups. Despite these positive changes, there have been concerns about excessive WA use, especially among college students, resulting in the neglect of important social and academic commitments. However, there is lack of quality research on WA use in this vulnerable...

  6. Apps Developed by Academics

    Science.gov (United States)

    Shing, Sophia; Yuan, Benjamin

    2016-01-01

    In the days of the digital Wild West, developers from all backgrounds have joined in the gold rush trying to profit from the almost unbridled spending of well-to-do parents on educational products. In 2016, the Apple App Store had over 80,000 educational apps. The proliferation of educational apps has happened at a furious pace and more apps are…

  7. Gamification in Stress Management Apps: A Critical App Review

    Science.gov (United States)

    Christmann, Corinna A; Bleser, Gabriele

    2017-01-01

    Background In today’s society, stress is more and more often a cause of disease. This makes stress management an important target of behavior change programs. Gamification has been suggested as one way to support health behavior change. However, it remains unclear to which extend available gamification techniques are integrated in stress management apps, and if their occurrence is linked to the use of elements from behavior change theory. Objective The aim of this study was to investigate the use of gamification techniques in stress management apps and the cooccurrence of these techniques with evidence-based stress management methods and behavior change techniques. Methods A total of 62 stress management apps from the Google Play Store were reviewed on their inclusion of 17 gamification techniques, 15 stress management methods, and 26 behavior change techniques. For this purpose, an extended taxonomy of gamification techniques was constructed and applied by 2 trained, independent raters. Results Interrater-reliability was high, with agreement coefficient (AC)=.97. Results show an average of 0.5 gamification techniques for the tested apps and reveal no correlations between the use of gamification techniques and behavior change techniques (r=.17, P=.20), or stress management methods (r=.14, P=.26). Conclusions This leads to the conclusion that designers of stress management apps do not use gamification techniques to influence the user’s behaviors and reactions. Moreover, app designers do not exploit the potential of combining gamification techniques with behavior change theory. PMID:28592397

  8. Behavioral functionality of mobile apps in health interventions: a systematic review of the literature.

    Science.gov (United States)

    Payne, Hannah E; Lister, Cameron; West, Joshua H; Bernhardt, Jay M

    2015-02-26

    Several thousand mobile phone apps are available to download to mobile phones for health and fitness. Mobile phones may provide a unique means of administering health interventions to populations. The purpose of this systematic review was to systematically search and describe the literature on mobile apps used in health behavior interventions, describe the behavioral features and focus of health apps, and to evaluate the potential of apps to disseminate health behavior interventions. We conducted a review of the literature in September 2014 using key search terms in several relevant scientific journal databases. Only English articles pertaining to health interventions using mobile phone apps were included in the final sample. The 24 studies identified for this review were primarily feasibility and pilot studies of mobile apps with small sample sizes. All studies were informed by behavioral theories or strategies, with self-monitoring as the most common construct. Acceptability of mobile phone apps was high among mobile phone users. The lack of large sample studies using mobile phone apps may signal a need for additional studies on the potential use of mobile apps to assist individuals in changing their health behaviors. Of these studies, there is early evidence that apps are well received by users. Based on available research, mobile apps may be considered a feasible and acceptable means of administering health interventions, but a greater number of studies and more rigorous research and evaluations are needed to determine efficacy and establish evidence for best practices.

  9. App Savvy Turning Ideas into iPad and iPhone Apps Customers Really Want

    CERN Document Server

    Yarmosh, Ken

    2010-01-01

    How can you make your iPad or iPhone app stand out in the highly competitive App Store? While many books simply explore the technical aspects of iPad and iPhone app design and development, App Savvy also focuses on the business, product, and marketing elements critical to pursuing, completing, and selling your app -- the ingredients for turning a great idea into a genuinely successful product. Whether you're a designer, developer, entrepreneur, or just someone with a unique idea, App Savvy explains every step in the process, with guidelines for planning a solid concept, engaging customers ea

  10. App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile Medical Apps.

    Science.gov (United States)

    Lewis, Thomas Lorchan; Wyatt, Jeremy C

    2015-08-19

    One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research.

  11. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    International Nuclear Information System (INIS)

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P.

    2014-01-01

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes

  12. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada); Klegeris, Andis [Department of Biology, University of British Columbia Okanagan, Kelowna, BC (Canada); Little, Jonathan P., E-mail: jonathan.little@ubc.ca [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada)

    2014-03-28

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

  13. LYATK1 potently inhibits LPS-mediated pro-inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Feng [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China); Liu, Yuan [Department of Ophthalmology, Nanjing First Hospital, Nanjing Medical University, Nanjing (China); Wang, Xiujuan; Kong, Wei [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China); Zhao, Feng, E-mail: taixingzhaofeng163@163.com [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China)

    2016-01-29

    Lipopolysaccharide (LPS)-primed monocytes/macrophages produce pro-inflammatory cytokines, which could lead to endotoxin shock. TGF-β-activated kinase1 (TAK1) activation is involved in the process. In the current study, we studied the potential effect of a selective TAK1 inhibitor, LYTAK1, on LPS-stimulated response both in vitro and in vivo. We demonstrated that LYTAK1 inhibited LPS-induced mRNA expression and production of several pro-inflammatory cytokines [interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)] in RAW 264.7 macrophages. LYTAK1's activity was almost nullified with TAK1 shRNA-knockdown. Meanwhile, in both primary mouse bone marrow derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs), LPS-induced pro-inflammatory cytokine production was again attenuated with LYTAK1 co-treatment. Molecularly, LYTAK1 dramatically inhibited LPS-induced TAK1-nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (Erk, Jnk and p38) activation in RAW 264.7 cells, mouse BMDMs and human PBMCs. In vivo, oral administration of LYTAK1 inhibited LPS-induced activation of TAK1-NFκB-p38 in ex-vivo cultured PBMCs, and cytokine production and endotoxin shock in mice. Together, these results demonstrate that LYTAK1 inhibits LPS-induced production of several pro-inflammatory cytokines and endotoxin shock probably through blocking TAK1-regulated signalings. - Highlights: • LYTAK1 inhibits LPS-induced pro-inflammatory cytokine production in RAW 264.7 cells. • The effect by LYTAK1 is more potent than other known TAK1 inhibitors. • LYTAK1 inhibits LPS-induced cytokine production in primary macrophages/monocytes. • LYTAK1 inhibits LPS-induced TAK1-NFκB and MAPK activation in macrophages/monocytes. • LYTAK1 gavage inhibits LPS-induced endotoxin shock and cytokine production in mice.

  14. LYATK1 potently inhibits LPS-mediated pro-inflammatory response

    International Nuclear Information System (INIS)

    Xi, Feng; Liu, Yuan; Wang, Xiujuan; Kong, Wei; Zhao, Feng

    2016-01-01

    Lipopolysaccharide (LPS)-primed monocytes/macrophages produce pro-inflammatory cytokines, which could lead to endotoxin shock. TGF-β-activated kinase1 (TAK1) activation is involved in the process. In the current study, we studied the potential effect of a selective TAK1 inhibitor, LYTAK1, on LPS-stimulated response both in vitro and in vivo. We demonstrated that LYTAK1 inhibited LPS-induced mRNA expression and production of several pro-inflammatory cytokines [interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)] in RAW 264.7 macrophages. LYTAK1's activity was almost nullified with TAK1 shRNA-knockdown. Meanwhile, in both primary mouse bone marrow derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs), LPS-induced pro-inflammatory cytokine production was again attenuated with LYTAK1 co-treatment. Molecularly, LYTAK1 dramatically inhibited LPS-induced TAK1-nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (Erk, Jnk and p38) activation in RAW 264.7 cells, mouse BMDMs and human PBMCs. In vivo, oral administration of LYTAK1 inhibited LPS-induced activation of TAK1-NFκB-p38 in ex-vivo cultured PBMCs, and cytokine production and endotoxin shock in mice. Together, these results demonstrate that LYTAK1 inhibits LPS-induced production of several pro-inflammatory cytokines and endotoxin shock probably through blocking TAK1-regulated signalings. - Highlights: • LYTAK1 inhibits LPS-induced pro-inflammatory cytokine production in RAW 264.7 cells. • The effect by LYTAK1 is more potent than other known TAK1 inhibitors. • LYTAK1 inhibits LPS-induced cytokine production in primary macrophages/monocytes. • LYTAK1 inhibits LPS-induced TAK1-NFκB and MAPK activation in macrophages/monocytes. • LYTAK1 gavage inhibits LPS-induced endotoxin shock and cytokine production in mice.

  15. Attention and Cognitive Bias Modification Apps: Review of the Literature and of Commercially Available Apps

    Science.gov (United States)

    Ying, JiangBo; Song, Guo; Fung, Daniel SS; Smith, Helen

    2018-01-01

    Background Automatic processes, such as attentional biases or interpretative biases, have been purported to be responsible for several psychiatric disorders. Recent reviews have highlighted that cognitive biases may be modifiable. Advances in eHealth and mHealth have been harnessed for the delivery of cognitive bias modification. While several studies have evaluated mHealth-based bias modification intervention, no review, to our knowledge, has synthesized the evidence for it. In addition, no review has looked at commercial apps and their functionalities and methods of bias modification. A review is essential in determining whether scientifically validated apps are available commercially and the proportion of commercial apps that have been evaluated scientifically. Objective The objective of this review was primarily to determine the proportion of attention or cognitive bias modification apps that have been evaluated scientifically and secondarily to determine whether the scientifically evaluated apps were commercially available. We also sought to identify commercially available bias modification apps and determine the functionalities of these apps, the methods used for attention or cognitive bias modification, and whether these apps had been evaluated scientifically. Methods To identify apps in the published literature, we searched PubMed, MEDLINE, PsycINFO, and Scopus for studies published from 2000 to April 17, 2018. The search terms used were “attention bias” OR “cognitive bias” AND “smartphone” OR “smartphone application” OR “smartphone app” OR “mobile phones” OR “mobile application” OR mobile app” OR “personal digital assistant.” To identify commercial apps, we conducted a manual cross-sectional search between September 15 and 25, 2017 in the Apple iTunes and Google Play app stores. The search terms used to identify the apps were “attention bias” and “cognitive bias.” We also conducted a manual search on the apps with

  16. Developing smartphone apps for behavioural studies: The AlcoRisk app case study.

    Science.gov (United States)

    Smith, Anthony; de Salas, Kristy; Lewis, Ian; Schüz, Benjamin

    2017-08-01

    Smartphone apps have emerged as valuable research tools to sample human behaviours at their time of occurrence within natural environments. Human behaviour sampling methods, such as Ecological Momentary Assessment (EMA), aim to facilitate research that is situated in ecologically valid real world environments rather than laboratory environments. Researchers have trialled a range of EMA smartphone apps to sample human behaviours such as dieting, physical activity and smoking. Software development processes for EMA smartphones apps, however, are not widely documented with little guidance provided for the integration of complex multidisciplinary behavioural and technical fields. In this paper, the AlcoRisk app for studying alcohol consumption and risk taking tendencies is presented alongside a software development process that integrates these multidisciplinary fields. The software development process consists of three stages including requirements analysis, feature and interface design followed by app implementation. Results from a preliminary feasibility study support the efficacy of the AlcoRisk app's software development process. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Gamification in Stress Management Apps: A Critical App Review.

    Science.gov (United States)

    Hoffmann, Alexandra; Christmann, Corinna A; Bleser, Gabriele

    2017-06-07

    In today's society, stress is more and more often a cause of disease. This makes stress management an important target of behavior change programs. Gamification has been suggested as one way to support health behavior change. However, it remains unclear to which extend available gamification techniques are integrated in stress management apps, and if their occurrence is linked to the use of elements from behavior change theory. The aim of this study was to investigate the use of gamification techniques in stress management apps and the cooccurrence of these techniques with evidence-based stress management methods and behavior change techniques. A total of 62 stress management apps from the Google Play Store were reviewed on their inclusion of 17 gamification techniques, 15 stress management methods, and 26 behavior change techniques. For this purpose, an extended taxonomy of gamification techniques was constructed and applied by 2 trained, independent raters. Interrater-reliability was high, with agreement coefficient (AC)=.97. Results show an average of 0.5 gamification techniques for the tested apps and reveal no correlations between the use of gamification techniques and behavior change techniques (r=.17, P=.20), or stress management methods (r=.14, P=.26). This leads to the conclusion that designers of stress management apps do not use gamification techniques to influence the user's behaviors and reactions. Moreover, app designers do not exploit the potential of combining gamification techniques with behavior change theory. ©Alexandra Hoffmann, Corinna A Christmann, Gabriele Bleser. Originally published in JMIR Serious Games (http://games.jmir.org), 07.06.2017.

  18. Integrated approach reveals diet, APOE genotype and sex affect immune response in APP mice.

    Science.gov (United States)

    Nam, Kyong Nyon; Wolfe, Cody M; Fitz, Nicholas F; Letronne, Florent; Castranio, Emilie L; Mounier, Anais; Schug, Jonathan; Lefterov, Iliya; Koldamova, Radosveta

    2018-01-01

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice. To identify differentially expressed genes and gene-networks correlated to diet, APOE isoform and sex, we performed RNA sequencing and applied Weighted Gene Co-expression Network Analysis. We determined that the immune response network with major hubs Tyrobp/DAP12, Csf1r, Tlr2, C1qc and Laptm5 correlated significantly and positively to the phenotype of female APP/E4-HFD mice. Correspondingly, we found that in female APP/E4-HFD mice, microglia coverage around plaques, particularly of larger size, was significantly reduced. This suggests altered containment of the plaque growth and sex-dependent vulnerability in response to diet. The results of our study show concurrent impact of diet, APOE isoform and sex on the brain transcriptome and AD-like phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The Cytoscape app article collection

    NARCIS (Netherlands)

    Pico, Alexander R.; Bader, Gary D.; Demchak, Barry; Guitart Pla, Oriol; Hull, Timothy; Longabaugh, William; Lopes, Christian; Lotia, Samad; Molenaar, Piet; Montojo, Jason; Morris, John H.; Ono, Keiichiro; Schwikowski, Benno; Welker, David; Ideker, Trey

    2014-01-01

    As a network visualization and analysis platform, Cytoscape relies on apps to provide domain-specific features and functions. There are many resources available to support Cytoscape app development and distribution, including the Cytoscape App Store and an online "cookbook" for app developers. This

  20. Cannabis Mobile Apps: A Content Analysis.

    Science.gov (United States)

    Ramo, Danielle E; Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

    2015-08-12

    Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. The Apple and Google Play app stores were searched using the terms "cannabis" and "marijuana." Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated "17+" years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated "high maturity" (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Cannabis apps are generally free and highly rated. Apps were most often informational (facts, strain classification), or recreational (games), likely

  1. Pro Android Apps Performance Optimization

    CERN Document Server

    Guihot, Hervé

    2012-01-01

    Today's Android apps developers are often running into the need to refine, improve and optimize their apps performances. As more complex apps can be created, it is even more important for developers to deal with this critical issue. Android allows developers to write apps using Java, C or a combination of both with the Android SDK and the Android NDK. Pro Android Apps Performance Optimization reveals how to fine-tune your Android apps, making them more stable and faster. In this book, you'll learn the following: * How to optimize your Java code with the SDK, but also how to write and optimize

  2. APP processing and the APP-KPI domain involvement in the amyloid cascade.

    Science.gov (United States)

    Menéndez-González, M; Pérez-Pinera, P; Martínez-Rivera, M; Calatayud, M T; Blázquez Menes, B

    2005-01-01

    Alternative APP mRNA splicing can generate isoforms of APP containing a Kunitz protease inhibitor (KPI) domain. KPI is one of the main serine protease inhibitors. Protein and mRNA KPI(+)APP levels are elevated in Alzheimer's disease (AD) brain and are associated with increased amyloid beta deposition. In the last years increasing evidence on multiple points in the amyloid cascade where KPI(+)APP is involved has been accumulated, admitting an outstanding position in the pathogenesis of AD to the KPI domain. This review focuses on the APP processing, the molecular activity of KPI and its physiological and pathological roles and the KPI involvement in the amyloid cascade through the nerve growth factor, the lipoprotein receptor-related protein, the tumor necrosis factor-alpha converting enzyme and the Notch1 protein.

  3. Best iPhone Apps

    CERN Document Server

    Biersdorfer, J

    2010-01-01

    With over 250,000 apps to choose from in Apple's App Store, you can make your iPhone or iPod Touch do just about anything you can imagine -- and almost certainly a few things you would never think of. While it's not hard to find apps, it is frustratingly difficult to find the the best ones. That's where this new edition of Best iPhone Apps comes in. New York Times technology columnist J.D. Biersdorfer has stress-tested hundreds of the App Store's mini-programs and hand-picked more than 200 standouts to help you get work done, play games, stay connected with friends, explore a new city, get i

  4. Smartphone use in neurosurgery? APP-solutely!

    Science.gov (United States)

    Zaki, Michael; Drazin, Doniel

    2014-01-01

    A number of smartphone medical apps have recently emerged that may be helpful for the neurosurgical patient, practitioner, and trainee. This study aims to review the current neurosurgery-focused apps available for the iPhone, iPad, and Android platforms as of December 2013. Two of the most popular smartphone app stores (Apple Store and Android Google Play Store) were surveyed for neurosurgery-focused apps in December 2013. Search results were categorized based on their description page. Data were collected on price, rating, app release date, target audience, and medical professional involvement in app design. A review of the top apps in each category was performed. The search resulted in 111 unique apps, divided into these 7 categories: 16 (14%) clinical tools, 17 (15%) conference adjunct, 27 (24%) education, 18 (16%) literature, 15 (14%) marketing, 10 (9%) patient information, and 8 (7%) reference. The average cost of paid apps was $23.06 (range: $0.99-89.99). Out of the 111 apps, 71 (64%) were free, 48 (43%) had reviews, and 14 (13%) had more than 10 reviews. Seventy-three (66%) apps showed evidence of medical professional involvement. The number of apps being released every year has been increasing since 2009. There are a number of neurosurgery-themed apps available to all audiences. There was a lack of patient information apps for nonspinal procedures. Most apps did not have enough reviews to evaluate their quality. There was also a lack of oversight to validate the accuracy of medical information provided in these apps.

  5. HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Grace Lui

    Full Text Available We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1 / Receptor-for-Advanced-Glycation-End-products (RAGE signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB.A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80; age-and-sex matched asymptomatic individuals (tested for latent TB were used for comparison (n = 45. Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan for cytokine induction ex vivo.In active PTB, plasma IL-8/CXCL8 [median(IQR, 6.0(3.6-15.1 vs 3.6(3.6-3.6 pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001, severity-score (rs +0.317, P = 0.004, and fever and hospitalization durations (rs +0.407, P<0.001. IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021 and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012 concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold. Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1 and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034. Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α when combined with lipoarabinomannan.In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important

  6. Cannabis Mobile Apps: A Content Analysis

    Science.gov (United States)

    Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

    2015-01-01

    Background Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. Objective We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. Methods The Apple and Google Play app stores were searched using the terms “cannabis” and “marijuana.” Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Results Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated “17+” years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated “high maturity” (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Conclusions Cannabis apps are generally free and highly rated. Apps were most often informational

  7. Mobile apps in cardiology: review.

    Science.gov (United States)

    Martínez-Pérez, Borja; de la Torre-Díez, Isabel; López-Coronado, Miguel; Herreros-González, Jesús

    2013-07-24

    Cardiovascular diseases are the deadliest diseases worldwide, with 17.3 million deaths in 2008 alone. Among them, heart-related deaths are of the utmost relevance; a fact easily proven by the 7.25 million deaths caused by ischemic heart disease alone in that year. The latest advances in smartphones and mHealth have been used in the creation of thousands of medical apps related to cardiology, which can help to reduce these mortality rates. The aim of this paper is to study the literature on mobile systems and applications currently available, as well as the existing apps related to cardiology from the leading app stores and to then classify the results to see what is available and what is missing, focusing particularly on commercial apps. Two reviews have been developed. One is a literature review of mobile systems and applications, retrieved from several databases and systems such as Scopus, PubMed, IEEE Xplore, and Web of Knowledge. The other is a review of mobile apps in the leading app stores, Google play for Android and Apple's App Store for iOS. Search queries up to May 2013 located 406 papers and 710 apps related to cardiology and heart disease. The most researched section in the literature associated with cardiology is related to mobile heart (and vital signs) monitoring systems and the methods involved in the classification of heart signs in order to detect abnormal functions. Other systems with a significant number of papers are mobile cardiac rehabilitation systems, blood pressure measurement, and systems for the detection of heart failure. The majority of apps for cardiology are heart monitors and medical calculators. Other categories with a high number of apps are those for ECG education and interpretation, cardiology news and journals, blood pressure tracking, heart rate monitoring using an external device, and CPR instruction. There are very few guides on cardiac rehabilitation and apps for the management of the cardiac condition, and there were no

  8. MILD CHOLESTEROL DEPLETION REDUCES AMYLOID-β PRODUCTION BY IMPAIRING APP TRAFFICKING TO THE CELL SURFACE

    Science.gov (United States)

    Guardia-Laguarta, Cristina; Coma, Mireia; Pera, Marta; Clarimón, Jordi; Sereno, Lidia; Agulló, José M.; Molina-Porcel, Laura; Gallardo, Eduard; Deng, Amy; Berezovska, Oksana; Hyman, Bradley T.; Blesa, Rafael; Gómez-Isla, Teresa; Lleó, Alberto

    2009-01-01

    It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and γ-secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Aβ40 and Aβ42 in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol-dependent decrease in the APP C-terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)-based technique to study APP-Presenilin 1 (PS1) interactions and lipid rafts in intact cells. Our data indicate that cholesterol depletion reduces association of APP into lipid rafts and disrupts APP-PS1 interaction. Taken together, our results suggest that mild membrane cholesterol reduction impacts the cleavage of APP upstream of γ-secretase and appears to be mediated by changes in APP trafficking and partitioning into lipid rafts. PMID:19457132

  9. Mobile medical apps for patient education: a graded review of available dermatology apps.

    Science.gov (United States)

    Masud, Aisha; Shafi, Shahram; Rao, Babar K

    2018-02-01

    The utilization of mobile applications (apps) as educational resources for patients highlights the need for an objective method of evaluating the quality of health care-related mobile apps. In this study, a quantified rubric was developed to objectively grade publicly available dermatology mobile apps with the primary focus of patient education. The rubric included 5 criteria thought to be most important in evaluating the adequacy of these apps in relaying health information to patients: educational objectives, content, accuracy, design, and conflict of interest. A 4-point scale was applied to each criterion. The use of this objective rubric could have implications in the evaluation and recommendation of mobile health care apps as a vital educational resource for patients.

  10. Health Apps and How to Market Them

    OpenAIRE

    Hillenbrand, Susanna

    2016-01-01

    In future health apps may become as popular as mobile games and retail shopping apps. Some consumers even think that health app usage is more valuable than making or receiving calls. This multibillion industry of mobile software applications and especially health apps is relatively new. The main research topic was how to market health apps globally. Health apps like fitness, weight loss and wellness apps are new trend in apps business. Healthcare apps are divided into health- and medical apps...

  11. Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

    Directory of Open Access Journals (Sweden)

    Lukas P. Feilen

    2017-05-01

    Full Text Available Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs. The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

  12. Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

    Science.gov (United States)

    Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

    2017-01-01

    Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

  13. Mobile Videoconferencing Apps for Telemedicine.

    Science.gov (United States)

    Zhang, Kai; Liu, Wei-Li; Locatis, Craig; Ackerman, Michael

    2016-01-01

    The quality and performance of several videoconferencing applications (apps) tested on iOS (Apple, Cupertino, CA) and Android (Google, Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G), and fourth-generation (4G) cellular networks are described. The tests were done to determine how well apps perform compared with videoconferencing software installed on computers or with more traditional videoconferencing using dedicated hardware. The rationale for app assessment and the testing methodology are described. Findings are discussed in relation to operating system platform (iOS or Android) for which the apps were designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network, and apps interact, and it is impossible to discuss videoconferencing experienced on mobile devices in relation to one of these factors without referencing the others. Apps for mobile devices can vary significantly from other videoconferencing software or hardware. App performance increased over the testing period due to improvements in network infrastructure and how apps manage bandwidth.

  14. Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation

    Science.gov (United States)

    Rosas-Ballina, Mauricio; Ferrer, Sergio Valdés; Dancho, Meghan; Ochani, Mahendar; Katz, David; Cheng, Kai Fan; Olofsson, Peder S.; Chavan, Sangeeta S.; Al-Abed, Yousef; Tracey, Kevin J.; Pavlov, Valentin A.

    2014-01-01

    Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer’s disease and schizophrenia. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The anti-inflammatory efficacy of xanomeline was retained for at least 20h, associated with alterations in splenic lymphocyte, and dendritic cell proportions, and decreased splenocyte responsiveness to endotoxin. These results highlight an important role of the M1 mAChR in a neural circuitry to spleen in which brain cholinergic activation lowers peripheral pro-inflammatory cytokines to levels favoring survival. The therapeutic efficacy of xanomeline was also manifested by significantly improved survival in preclinical settings of severe sepsis. These findings are of interest for strategizing novel therapeutic approaches in inflammatory diseases. PMID:25063706

  15. Interrater Reliability of mHealth App Rating Measures: Analysis of Top Depression and Smoking Cessation Apps.

    Science.gov (United States)

    Powell, Adam C; Torous, John; Chan, Steven; Raynor, Geoffrey Stephen; Shwarts, Erik; Shanahan, Meghan; Landman, Adam B

    2016-02-10

    There are over 165,000 mHealth apps currently available to patients, but few have undergone an external quality review. Furthermore, no standardized review method exists, and little has been done to examine the consistency of the evaluation systems themselves. We sought to determine which measures for evaluating the quality of mHealth apps have the greatest interrater reliability. We identified 22 measures for evaluating the quality of apps from the literature. A panel of 6 reviewers reviewed the top 10 depression apps and 10 smoking cessation apps from the Apple iTunes App Store on these measures. Krippendorff's alpha was calculated for each of the measures and reported by app category and in aggregate. The measure for interactiveness and feedback was found to have the greatest overall interrater reliability (alpha=.69). Presence of password protection (alpha=.65), whether the app was uploaded by a health care agency (alpha=.63), the number of consumer ratings (alpha=.59), and several other measures had moderate interrater reliability (alphas>.5). There was the least agreement over whether apps had errors or performance issues (alpha=.15), stated advertising policies (alpha=.16), and were easy to use (alpha=.18). There were substantial differences in the interrater reliabilities of a number of measures when they were applied to depression versus smoking apps. We found wide variation in the interrater reliability of measures used to evaluate apps, and some measures are more robust across categories of apps than others. The measures with the highest degree of interrater reliability tended to be those that involved the least rater discretion. Clinical quality measures such as effectiveness, ease of use, and performance had relatively poor interrater reliability. Subsequent research is needed to determine consistent means for evaluating the performance of apps. Patients and clinicians should consider conducting their own assessments of apps, in conjunction with

  16. Social anxiety apps: a systematic review and assessment of app descriptors across mobile store platforms.

    Science.gov (United States)

    Alyami, Mohsen; Giri, Bachan; Alyami, Hussain; Sundram, Frederick

    2017-08-01

    The aim of this systematic review is twofold: (1) to characterise the purpose and description of available social anxiety apps and (2) to review the evidence on the effectiveness of social anxiety apps. A search was conducted on three major mobile platforms: Apple iTunes, Google Play and Windows Store. Apps were included if they addressed social anxiety and used an English language interface. A systematic review of the literature from MEDLINE, EMBASE, PsycINFO, Cochrane, Scopus and Web of Science to identify evidence-based evaluations of social anxiety apps was also undertaken. Of the 1154 apps identified, 38 apps met the inclusion criteria: iTunes (n=18), Google Play (n=16) and Windows Store (n=4). Over 60% of apps were exclusively focused on social anxiety, while the remainder targeted social anxiety and related conditions. Most developers did not provide information on their organisational affiliations or their content source. Most apps used multimedia while 17 apps used text only. Finally, although the systematic review of the literature identified 94 articles, none of which met inclusion criteria. Social anxiety apps have the potential to overcome barriers to accessing treatment; however, none of the apps identified have had studies on their effectiveness published. As the evidence base is lacking, it is therefore not currently possible to recommend their use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Medication Adherence Apps: Review and Content Analysis.

    Science.gov (United States)

    Ahmed, Imran; Ahmad, Niall Safir; Ali, Shahnaz; Ali, Shair; George, Anju; Saleem Danish, Hiba; Uppal, Encarl; Soo, James; Mobasheri, Mohammad H; King, Dominic; Cox, Benita; Darzi, Ara

    2018-03-16

    Medication adherence is an expensive and damaging problem for patients and health care providers. Patients adhere to only 50% of drugs prescribed for chronic diseases in developed nations. Digital health has paved the way for innovative smartphone solutions to tackle this challenge. However, despite numerous apps available claiming to improve adherence, a thorough review of adherence apps has not been carried out to date. The aims of this study were to (1) review medication adherence apps available in app repositories in terms of their evidence base, medical professional involvement in development, and strategies used to facilitate behavior change and improve adherence and (2) provide a system of classification for these apps. In April 2015, relevant medication adherence apps were identified by searching the Apple App Store and the Google Play Store using a combination of relevant search terms. Data extracted included app store source, app price, documentation of health care professional (HCP) involvement during app development, and evidence base for each respective app. Free apps were downloaded to explore the strategies used to promote medication adherence. Testing involved a standardized medication regimen of three reminders over a 4-hour period. Nonadherence features designed to enhance user experience were also documented. The app repository search identified a total of 5881 apps. Of these, 805 fulfilled the inclusion criteria initially and were tested. Furthermore, 681 apps were further analyzed for data extraction. Of these, 420 apps were free for testing, 58 were inaccessible and 203 required payment. Of the 420 free apps, 57 apps were developed with HCP involvement and an evidence base was identified in only 4 apps. Of the paid apps, 9 apps had HCP involvement, 1 app had a documented evidence base, and 1 app had both. In addition, 18 inaccessible apps were produced with HCP involvement, whereas 2 apps had a documented evidence base. The 420 free apps were

  18. MedAd-AppQ: A quality assessment tool for medication adherence apps on iOS and android platforms.

    Science.gov (United States)

    Ali, Eskinder Eshetu; Teo, Amanda Kai Sin; Goh, Sherlyn Xue Lin; Chew, Lita; Yap, Kevin Yi-Lwern

    2018-02-02

    With the recent proliferation of smartphone medication adherence applications (apps), it is increasingly more difficult for patients and clinicians to identify the most useful app. To develop a quality assessment tool for medication adherence apps, and evaluate the quality of such apps from the major app stores. In this study, a Medication Adherence App Quality assessment tool (MedAd-AppQ) was developed and two evaluators independently assessed apps that fulfilled the following criteria: availability in English, had at least a medication reminder feature, non-specific to certain disease conditions (generic apps), free of technical malfunctions and availability on both the iPhone Operating System (iOS) and Android platforms. Descriptive statistics, Mann-Whitney U test, Pearson product moment correlation and Spearman rank-order correlation were used for statistical analysis. MedAd-AppQ was designed to have 24 items (total 43 points) categorized under three sections: content reliability (11 points), feature usefulness (29 points) and feature convenience (3 points). The three sections of MedAd-AppQ were found to have inter-rater correlation coefficients of 0.801 (p-value apps (27 iOS and 25 Android), quality scores ranged between 7/43 (16.3%) and 28/43 (65.1%). There was no significant difference between the quality scores of the Android and iOS versions. None of the apps had features for self-management of side effects. Only two apps in each platform provided disease-related and/or medication information. MedAd-AppQ can be used to reliably assess the quality of adherence apps. Clinicians can use the tool in selecting apps for use by patients. Developers of adherence apps should consider features that provide therapy-related information and help patients in medications and side-effects management. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Attention-dependent modulation of cortical taste circuits revealed by Granger causality with signal-dependent noise.

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    Qiang Luo

    2013-10-01

    Full Text Available We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention.

  20. Programming Google App Engine

    CERN Document Server

    Sanderson, Dan

    2010-01-01

    As one of today's cloud computing services, Google App Engine does more than provide access to a large system of servers. It also offers you a simple model for building applications that scale automatically to accommodate millions of users. With Programming Google App Engine, you'll get expert practical guidance that will help you make the best use of this powerful platform. Google engineer Dan Sanderson shows you how to design your applications for scalability, including ways to perform common development tasks using App Engine's APIs and scalable services. You'll learn about App Engine's a

  1. Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase

    Science.gov (United States)

    Kim, Ji Min; Lee, Eun Kyeong; Kim, Dae Hyun; Yu, Byung Pal

    2010-01-01

    Advanced glycation endproducts (AGE) are oxidative products formed from the reaction between carbohydrates and a free amino group of proteins that are provoked by reactive species (RS). It is also known that AGE enhance the generation of RS and that the binding of AGE to a specific AGE receptor (RAGE) induces the activation of the redox-sensitive, pro-inflammatory transcription factor, nuclear factor-kappa B (NF-ĸB). In this current study, we investigated the anti-oxidative effects of short-term kaempferol supplementation on the age-related formation of AGE and the binding activity of RAGE in aged rat kidney. We further investigated the suppressive action of kaempferol against AGE's ability to stimulate activation of pro-inflammatory NF-ĸB and its molecular mechanisms. For this study, we utilized young (6 months old), old (24 months old), and kaempferol-fed (2 and 4 mg/kg/day for 10 days) old rats. In addition, for the molecular work, the rat endothelial cell line, YPEN-1 was used. The results show that AGE and RAGE were increased during aging and that these increases were blunted by kaempferol. In addition, dietary kaempferol reduced age-related increases in NF-κB activity and NF-ĸB-dependant pro-inflammatory gene activity. The most significant new finding from this study is that kaempferol supplementation prevented age-related NF-κB activation by suppressing AGE-induced nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Taken together, our results demonstrated that dietary kaempferol exerts its anti-oxidative and anti-inflammatory actions by modulating the age-related NF-κB signaling cascade and its pro-inflammatory genes by suppressing AGE-induced NADPH oxidase activation. Based on these data, dietary kaempferol is proposed as a possible anti-AGE agent that may have the potential for use in anti-inflammation therapies. PMID:20431987

  2. Shigella dysenteriae infection activates proinflammatory response through β-catenin/NF-κB signaling pathway.

    Directory of Open Access Journals (Sweden)

    Ashidha Gopal

    Full Text Available Shigella dysenteriae (S.dysenteriae the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of β-catenin and NF-κB regulates proinflammatory cytokines TNF-α and IL-8 by modulating GSK-3β activity during S.dysenteriae infection in rat ileal loop model. Here we demonstrated that S.dysenteriae infection stimulate β-catenin degradation which in turn decreased the association between NF-κB and β-catenin. Also, we showed that S.dysenteriae infection increased GSK-3β kinase activity which in turn phosphorylates β-catenin for its degradation by ubiquitination and upregulates IL-8 through NF-κB activation thereby leading to inflammation. Thus these findings revealed the role of β-catenin/ NF-κB and GSK-3β in modulating the inflammatory response during bacterial infection and also showed that β-catenin acts as a critical regulator of inflammation.

  3. The fitness of apps: a theory-based examination of mobile fitness app usage over 5 months

    Science.gov (United States)

    Kim, Jinsook

    2017-01-01

    Background There are thousands of fitness-related smartphone applications (“apps”) available for free and purchase, but there is uncertainty if these apps help individuals achieve and maintain personal fitness. Technology usage attrition is also a concern among research studies on health technologies. Methods Usage of three fitness apps was examined over 5 months to assess adherence and effectiveness. Initially, 64 participants downloaded three free apps available on Android and iOS and 47 remained in the study until posttest. With a one group pre-posttest design and checkpoints at months 1, 3, and 5, exercise and exercise with fitness apps were examined in the framework of the Theory of Planned Behavior (TPB) using a validated survey. Apps were selected based on their function from the Functional Triad. Perceived fitness was also measured. T-tests, sign tests, Fisher’s exact tests, and linear and logistic regression were used to compare pre to posttests and users to non-users of the apps. Results Forty-seven participants completed both pre and posttests. Individual item scores indicated no significant change pre to posttest except for decreases observed in usefulness of using apps for exercise (attitude) (−0.78, Papps (subjective norm) (−1.02, Papps (perceived behavioral control) (−1.29, Papps over the next 2 weeks (behavioral intention) (Papps (−1.72, Papps (−2.56, Papp users (n=32) to non-users (n=15), there was only a significant difference in subscale total scores at posttest for attitude toward exercising using apps, which was significantly more favorable among users than non-users (32.3 vs. 27.6, PApp usage and effectiveness appears to have a connection to usefulness (attitude) and to perceived difficulties of exercising using apps (perceived behavioral control). Exercise and exercise using apps are not influenced by peer influence (subjective norm). Intention to exercise using these particular apps decreased (behavioral intention). Those who

  4. An Android Communication App Forensic Taxonomy.

    Science.gov (United States)

    Azfar, Abdullah; Choo, Kim-Kwang Raymond; Liu, Lin

    2016-09-01

    Due to the popularity of Android devices and applications (apps), Android forensics is one of the most studied topics within mobile forensics. Communication apps, such as instant messaging and Voice over IP (VoIP), are one popular app category used by mobile device users, including criminals. Therefore, a taxonomy outlining artifacts of forensic interest involving the use of Android communication apps will facilitate the timely collection and analysis of evidentiary materials from such apps. In this paper, 30 popular Android communication apps were examined, where a logical extraction of the Android phone images was collected using XRY, a widely used mobile forensic tool. Various information of forensic interest, such as contact lists and chronology of messages, was recovered. Based on the findings, a two-dimensional taxonomy of the forensic artifacts of the communication apps is proposed, with the app categories in one dimension and the classes of artifacts in the other dimension. Finally, the artifacts identified in the study of the 30 communication apps are summarized using the taxonomy. It is expected that the proposed taxonomy and the forensic findings in this paper will assist forensic investigations involving Android communication apps. © 2016 American Academy of Forensic Sciences.

  5. Browser App Approach: Can It Be an Answer to the Challenges in Cross-Platform App Development?

    Directory of Open Access Journals (Sweden)

    Minh Q. Huynh

    2017-02-01

    Full Text Available Aim/Purpose: As smartphones proliferate, many different platforms begin to emerge. The challenge to developers as well as IS educators and students is how to learn the skills to design and develop apps to run on cross-platforms. Background: For developers, the purpose of this paper is to describe an alternative to the complex native app development. For IS educators and students, the paper provides a feasible way to learn and develop fully functional mobile apps without technical burdens. Methodology: The methods used in the development of browser-based apps is prototyping. Our proposed approach is browser-based, supports cross-platforms, uses open-source standards, and takes advantage of “write-once-and-run-anywhere” (WORA concept. Contribution: The paper illustrates the application of the browser-based approach to create a series of browser apps without high learning curve. Findings: The results show the potentials for using browser app approach to teach as well as to create new apps. Recommendations for Practitioners\t: Our proposed browser app development approach and example would be useful to mobile app developers/IS educators and non-technical students because the source code as well as documentations in this project are available for downloading. Future Research: For further work, we discuss the use of hybrid development framework to enhance browser apps.

  6. Cholesterol-dependent energy transfer between fluorescent proteins-insights into protein proximity of APP and BACE1 in different membranes in Niemann-Pick type C disease cells.

    Science.gov (United States)

    von Einem, Bjoern; Weber, Petra; Wagner, Michael; Malnar, Martina; Kosicek, Marko; Hecimovic, Silva; Arnim, Christine A F von; Schneckenburger, Herbert

    2012-11-26

    Förster resonance energy transfer (FRET) -based techniques have recently been applied to study the interactions between β-site APP-cleaving enzyme-GFP (BACE1-GFP) and amyloid precursor protein-mRFP (APP-mRFP) in U373 glioblastoma cells. In this context, the role of APP-BACE1 proximity in Alzheimer's disease (AD) pathogenesis has been discussed. FRET was found to depend on intracellular cholesterol levels and associated alterations in membrane stiffness. Here, NPC1 null cells (CHO-NPC1-/-), exhibiting increased cholesterol levels and disturbed cholesterol transport similar to that observed in Niemann-Pick type C disease (NPC), were used to analyze the influence of altered cholesterol levels on APP-BACE1 proximity. Fluorescence lifetime measurements of whole CHO-wild type (WT) and CHO-NPC1-/- cells (EPI-illumination microscopy), as well as their plasma membranes (total internal reflection fluorescence microscopy, TIRFM), were performed. Additionally, generalized polarization (GP) measurements of CHO-WT and CHO-NPC1-/- cells incubated with the fluorescence marker laurdan were performed to determine membrane stiffness of plasma- and intracellular-membranes. CHO-NPC1-/- cells showed higher membrane stiffness at intracellular- but not plasma-membranes, equivalent to cholesterol accumulation in late endosomes/lysosomes. Along with higher membrane stiffness, the FRET efficiency between BACE1-GFP and APP-mRFP was reduced at intracellular membranes, but not within the plasma membrane of CHO-NPC1-/-. Our data show that FRET combined with TIRF is a powerful technique to determine protein proximity and membrane fluidity in cellular models of neurodegenerative diseases.

  7. The CJOrtho app: A mobile clinical and educational tool for orthopedics.

    Science.gov (United States)

    Reina, N; Cognault, J; Ollivier, M; Dagneaux, L; Gauci, M-O; Pailhé, R

    2018-04-11

    The need for modern patient evaluation tools continues to grow. A dependable and reproducible assessment provides objective follow-up and increases the validity of collected data. This is where mobile apps come into play, as they provide a link between surgeons and patients. They also open the possibility of interacting with other healthcare staff to exchange common scientific reference systems and databases. The CJOrtho app provides fast access to 65 classification systems in orthopedics or trauma surgery, 20 clinical outcome scores and a digital goniometer. The development of free mobile apps is an opportunity for education and better follow-up, while meeting the demands of patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Hye Joo Kim

    2012-01-01

    Full Text Available Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria, and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this study, we analyzed the effects of fisetin on proinflammatory cytokine secretion and epigenetic regulation, in human monocytes cultured under hyperglycemic conditions. Human monocytic (THP-1 cells were cultured under control (14.5 mmol/L mannitol, normoglycemic (NG, 5.5 mmol/L glucose, or hyperglycemic (HG, 20 mmol/L glucose conditions, in the absence or presence of fisetin. Fisetin was added (3–10 μM for 48 h. While the HG condition significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α release from THP-1 cells, fisetin suppressed NF-κB activity and cytokine release. Fisetin treatment also significantly reduced CBP/p300 gene expression, as well as the levels of acetylation and HAT activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore propose that fisetin supplementation be considered for diabetes prevention.

  9. Transplantation of Human Menstrual Blood-Derived Mesenchymal Stem Cells Alleviates Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Yongjia Zhao

    2018-04-01

    Full Text Available Extracellular β-amyloid (Aβ plaques and neurofibrillary tangles (NFTs are the pathological hallmarks of Alzheimer’s disease (AD. Mesenchymal stem cells (MSCs have shown therapeutic efficacy in many neurodegenerative diseases, including AD. Human menstrual blood-derived stem cells (MenSCs are a novel source of MSCs advantageous for their higher proliferation rate and because they are easy to obtain without ethical concerns. Although MenSCs have exhibited therapeutic efficacy in some diseases, their effects on AD remain elusive. In the present study, we showed that intracerebral transplantation of MenSCs dramatically improved the spatial learning and memory of APP/PS1 mice. In addition, MenSCs significantly ameliorated amyloid plaques and reduced tau hyperphosphorylation in APP/PS1 mice. Remarkably, we also found that intracerebral transplantation of MenSCs markedly increased several Aβ degrading enzymes and modulated a panel of proinflammatory cytokines associated with an altered microglial phenotype, suggesting an Aβ degrading and anti-inflammatory impact of MenSCs in the brains of APP/PS1 mice. In conclusion, these findings suggest that MenSCs are a promising therapeutic candidate for AD.

  10. Cre-mediated stress affects sirtuin expression levels, peroxisome biogenesis and metabolism, antioxidant and proinflammatory signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yu Xiao

    Full Text Available Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function in a tissue-specific manner. To analyze phenotypic alterations related to Cre-expression, we have used AMH-Cre-transgenic mice as a model system. Different Cre expression levels were obtained by investigation of C57BL/6J wild type as well as heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself in Sertoli cells already has led to oxidative stress and lipid peroxidation (4-HNE lysine adducts, inducing PPARα/γ, peroxisome proliferation and alterations of peroxisome biogenesis (PEX5, PEX13 and PEX14 as well as metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase. In addition to the strong catalase increase, a NRF2- and FOXO3-mediated antioxidative response (HMOX1 of the endoplasmic reticulum and mitochondrial SOD2 and a NF-κB activation were noted. TGFβ1 and proinflammatory cytokines like IL1, IL6 and TNFα were upregulated and stress-related signaling pathways were induced. Sertoli cell mRNA-microarray analysis revealed an increase of TNFR2-signaling components. 53BP1 recruitment and expression levels for DNA repair genes as well as for p53 were elevated and the ones for related sirtuin deacetylases affected (SIRT 1, 3-7 in Sertoli cells. Under chronic Cre-mediated DNA damage conditions a strong downregulation of Sirt1 was observed, suggesting that the decrease of this important coordinator between DNA repair and metabolic signaling might induce the repression release of major transcription factors regulating metabolic and cytokine-mediated stress pathways. Indeed, caspase-3 was activated and increased germ cell apoptosis was observed, suggesting paracrine effects. In conclusion, the observed wide stress-induced effects and metabolic alterations suggest that it is essential to use the correct control animals (Cre/Wt with matched Cre expression levels to differentiate between Cre-mediated and specific gene-knock out

  11. Cre-Mediated Stress Affects Sirtuin Expression Levels, Peroxisome Biogenesis and Metabolism, Antioxidant and Proinflammatory Signaling Pathways

    Science.gov (United States)

    Xiao, Yu; Karnati, Srikanth; Qian, Guofeng; Nenicu, Anca; Fan, Wei; Tchatalbachev, Svetlin; Höland, Anita; Hossain, Hamid; Guillou, Florian; Lüers, Georg H.; Baumgart-Vogt, Eveline

    2012-01-01

    Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function in a tissue-specific manner. To analyze phenotypic alterations related to Cre-expression, we have used AMH-Cre-transgenic mice as a model system. Different Cre expression levels were obtained by investigation of C57BL/6J wild type as well as heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself in Sertoli cells already has led to oxidative stress and lipid peroxidation (4-HNE lysine adducts), inducing PPARα/γ, peroxisome proliferation and alterations of peroxisome biogenesis (PEX5, PEX13 and PEX14) as well as metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase). In addition to the strong catalase increase, a NRF2- and FOXO3-mediated antioxidative response (HMOX1 of the endoplasmic reticulum and mitochondrial SOD2) and a NF-κB activation were noted. TGFβ1 and proinflammatory cytokines like IL1, IL6 and TNFα were upregulated and stress-related signaling pathways were induced. Sertoli cell mRNA-microarray analysis revealed an increase of TNFR2-signaling components. 53BP1 recruitment and expression levels for DNA repair genes as well as for p53 were elevated and the ones for related sirtuin deacetylases affected (SIRT 1, 3-7) in Sertoli cells. Under chronic Cre-mediated DNA damage conditions a strong downregulation of Sirt1 was observed, suggesting that the decrease of this important coordinator between DNA repair and metabolic signaling might induce the repression release of major transcription factors regulating metabolic and cytokine-mediated stress pathways. Indeed, caspase-3 was activated and increased germ cell apoptosis was observed, suggesting paracrine effects. In conclusion, the observed wide stress-induced effects and metabolic alterations suggest that it is essential to use the correct control animals (Cre/Wt) with matched Cre expression levels to differentiate between Cre-mediated and specific gene-knock out

  12. Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ana Cecilia Machado Diaz

    2012-01-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA in samples of synovial fluid from patients with RA and osteoarthritis (OA. The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

  13. The kunitz protease inhibitor form of the amyloid precursor protein (KPI/APP) inhibits the proneuropeptide processing enzyme prohormone thiol protease (PTP). Colocalization of KPI/APP and PTP in secretory vesicles.

    Science.gov (United States)

    Hook, V Y; Sei, C; Yasothornsrikul, S; Toneff, T; Kang, Y H; Efthimiopoulos, S; Robakis, N K; Van Nostrand, W

    1999-01-29

    Proteolytic processing of proenkephalin and proneuropeptides is required for the production of active neurotransmitters and peptide hormones. Variations in the extent of proenkephalin processing in vivo suggest involvement of endogenous protease inhibitors. This study demonstrates that "protease nexin 2 (PN2)," the secreted form of the kunitz protease inhibitor (KPI) of the amyloid precursor protein (APP), potently inhibited the proenkephalin processing enzyme known as prohormone thiol protease (PTP), with a Ki,app of 400 nM. Moreover, PTP and PN2 formed SDS-stable complexes that are typical of kunitz protease inhibitor interactions with target proteases. In vivo, KPI/APP (120 kDa), as well as a truncated form of KPI/APP that resembles PN2 in apparent molecular mass (110 kDa), were colocalized with PTP and (Met)enkephalin in secretory vesicles of adrenal medulla (chromaffin granules). KPI/APP (110-120 kDa) was also detected in pituitary secretory vesicles that contain PTP. In chromaffin cells, calcium-dependent secretion of KPI/APP with PTP and (Met)enkephalin demonstrated the colocalization of these components in functional secretory vesicles. These results suggest a role for KPI/APP inhibition of PTP in regulated secretory vesicles. In addition, these results are the first to identify an endogenous protease target of KPI/APP, which is developmentally regulated in aging and Alzheimer's disease.

  14. Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Md Rashedunnabi Akanda

    2018-02-01

    Full Text Available Globally, gastric ulcer is a vital health hazard for a human. Rabdosia inflexa (RI has been used in traditional medicine for inflammatory diseases. The present study aimed to investigate the protective effect and related molecular mechanism of RI using lipopolysaccharide (LPS-induced inflammation in RAW 246.7 cells and HCl/EtOH-induced gastric ulcer in mice. We applied 3-(4,5-dimethyl-thiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, nitric oxide (NO, reactive oxygen species (ROS, histopathology, malondialdehyde (MDA, quantitative real-time polymerase chain reaction (qPCR, immunohistochemistry (IHC, and Western blot analyses to evaluate the protective role of RI. Study revealed that RI effectively attenuated LPS-promoted NO and ROS production in RAW 246.7 cells. In addition, RI mitigated gastric oxidative stress by inhibiting lipid peroxidation, elevating NO, and decreasing gastric inflammation. RI significantly halted elevated gene expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, inducible nitric oxide synthetase (iNOS, and cyclooxygenase-2 (COX-2 in gastric tissue. Likewise, RI markedly attenuated the mitogen-activated protein kinases (MAPKs phosphorylation, COX-2 expression, phosphorylation and degradation of inhibitor kappa B (IκBα and activation of nuclear factor kappa B (NF-κB. Thus, experimental findings suggested that the anti-inflammatory and gastroprotective activities of RI might contribute to regulating pro-inflammatory cytokines and MAPK/NF-κB signaling pathways.

  15. Induction of TLR-2 and TLR-5 expression by Helicobacter pylori switches cagPAI-dependent signalling leading to the secretion of IL-8 and TNF-α.

    Directory of Open Access Journals (Sweden)

    Suneesh Kumar Pachathundikandi

    2011-05-01

    Full Text Available Helicobacter pylori is the causative agent for developing gastritis, gastric ulcer, and even gastric cancer. Virulent strains carry the cag pathogenicity island (cagPAI encoding a type-IV secretion system (T4SS for injecting the CagA protein. However, mechanisms of sensing this pathogen through Toll-like receptors (TLRs and downstream signalling pathways in the development of different pathologies are widely unclear. Here, we explored the involvement of TLR-2 and TLR-5 in THP-1 cells and HEK293 cell lines (stably transfected with TLR-2 or TLR-5 during infection with wild-type H. pylori and isogenic cagPAI mutants. H. pylori triggered enhanced TLR-2 and TLR-5 expression in THP-1, HEK293-TLR2 and HEK293-TLR5 cells, but not in the HEK293 control. In addition, IL-8 and TNF-α cytokine secretion in THP-1 cells was induced in a cagPAI-dependent manner. Furthermore, we show that HEK293 cells are not competent for the uptake of T4SS-delivered CagA, and are therefore ideally suited for studying TLR signalling in the absence of T4SS functions. HEK293 control cells, which do not induce TLR-2 and TLR-5 expression during infection, only secreted cytokines in small amounts, in agreement with T4SS functions being absent. In contrast, HEK293-TLR2 and HEK293-TLR5 cells were highly competent for inducing the secretion of IL-8 and TNF-α cytokines in a cagPAI-independent manner, suggesting that the expression of TLR-2 or TLR-5 has profoundly changed the capability to trigger pro-inflammatory signalling upon infection. Using phospho-specific antibodies and luciferase reporter assays, we further demonstrate that H. pylori induces IRAK-1 and IκB phosphorylation in a TLR-dependent manner, and this was required for activation of transcription factor NF-κB. Finally, NF-κB activation in HEK293-TLR2 and HEK293-TLR5 cells was confirmed by expressing p65-GFP which was translocated from the cytoplasm into the nucleus. These data indicate that H. pylori-induced expression

  16. Role of Inflammatory Signaling in the Differential Effects of Saturated and Poly-unsaturated Fatty Acids on Peripheral Circadian Clocks

    Directory of Open Access Journals (Sweden)

    Sam-Moon Kim

    2016-05-01

    Full Text Available Inflammatory signaling may play a role in high-fat diet (HFD-related circadian clock disturbances that contribute to systemic metabolic dysregulation. Therefore, palmitate, the prevalent proinflammatory saturated fatty acid (SFA in HFD and the anti-inflammatory, poly-unsaturated fatty acid (PUFA, docosahexaenoic acid (DHA, were analyzed for effects on circadian timekeeping and inflammatory responses in peripheral clocks. Prolonged palmitate, but not DHA, exposure increased the period of fibroblast Bmal1-dLuc rhythms. Acute palmitate treatment produced phase shifts of the Bmal1-dLuc rhythm that were larger in amplitude as compared to DHA. These phase-shifting effects were time-dependent and contemporaneous with rhythmic changes in palmitate-induced inflammatory responses. Fibroblast and differentiated adipocyte clocks exhibited cell-specific differences in the time-dependent nature of palmitate-induced shifts and inflammation. DHA and other inhibitors of inflammatory signaling (AICAR, cardamonin repressed palmitate-induced proinflammatory responses and phase shifts of the fibroblast clock, suggesting that SFA-mediated inflammatory signaling may feed back to modulate circadian timekeeping in peripheral clocks.

  17. Your Life in Web Apps

    CERN Document Server

    Turnbull, Giles

    2008-01-01

    What is a web app? It's software that you use right in your web browser. Rather than installing an application on your computer, you visit a web site and sign up as a new user of its software. Instead of storing your files on your own hard disk, the web app stores them for you, online. Is it possible to switch entirely to web apps? To run nothing but a browser for an entire day? In this PDF we'll take you through one day in the life of a web apps-only user and chronicle the pros and cons of living by browser. And if the idea of switching, fully or partially, to web apps sounds appealing to

  18. Detection Of Malware Collusion With Static Dependence Analysis On Inter-App Communication

    Science.gov (United States)

    2016-12-08

    app permission leakage.” IEEE Transactions on Software Engineering, 2015 [4]. Bugiel, Sven, Lucas Davi, Alexandra Dmitrienko, Thomas Fischer , Ahmad...Dmitrienko, Thomas Fischer , and Ahmad-Reza Sadeghi. “Xmandroid: A new android evolution to mitigate privilege escalation attacks.”, Technical Report...Technical report, Department of Computer Science, University of Maryland, College Park, 2009. [12]. Gordon, Michael I., Deokhwan Kim, Jeff H. Perkins

  19. β-asarone improves learning and memory and reduces Acetyl Cholinesterase and Beta-amyloid 42 levels in APP/PS1 transgenic mice by regulating Beclin-1-dependent autophagy.

    Science.gov (United States)

    Deng, Minzhen; Huang, Liping; Ning, Baile; Wang, Nanbu; Zhang, Qinxin; Zhu, Caixia; Fang, Yongqi

    2016-12-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, and studies have suggested that β-asarone has pharmacological effects on beta-amyloid (Aβ) injected in the rat hippocampus. However, the effect of β-asarone on autophagy in the APP/PS1 transgenic mouse is unreported. APP/PS1 transgenic mice were randomly divided into six groups (n=10/group): an untreated group, an Aricept-treated group, a 3-MA-treated group, a rapamycin-treated group, an LY294002-treated group, a β-asarone-treated group. The control group consisted of wild-type C57BL/6 mice. All treatments were administered to the mice for 30 days. Spatial learning and memory were assessed by water maze, passive avoidance, and step-down tests. AChE and Aβ 42 levels in the hippocampus were determined by ELISA. p-Akt, p-mTOR, and LC3B expression were detected by flow cytometry. The expression of p-Akt, p-mTOR, Beclin-1, and p62 proteins was assessed by western blot. Changes in autophagy were viewed using a transmission electron microscope. APP and Beclin-1 mRNA levels were measured by Real-Time PCR. The learning and memory of APP/PS1 transgenic mice were improved significantly after β-asarone treatment compared with the untreated group. In addition, β-asarone treatment reduced AChE and Aβ 42 levels, increased p-mTOR and p62 expression, decreased p-Akt, Beclin-1, and LC3B expression, decreased the number of autophagosomes and reduced APP mRNA and Beclin-1 mRNA levels compared with the untreated group. That is, β-asarone treatment can improve the learning and memory abilities of APP/PS1 transgenic mouse by inhibiting Beclin-1-dependent autophagy via the PI3K/Akt/mTOR pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model.

    Science.gov (United States)

    Liao, Fan; Zhang, Tony J; Mahan, Thomas E; Jiang, Hong; Holtzman, David M

    2015-07-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sleep-wake cycle in both humans and mice; ISF Aβ is higher during wakefulness and lower during sleep. Intracerebroventricular infusion of orexin increased wakefulness and ISF Aβ levels, and chronic sleep deprivation significantly increased Aβ plaque formation in amyloid precursor protein transgenic (APP) mice. Growth hormone-releasing hormone (GHRH) is a well-documented sleep regulatory substance which promotes non-rapid eye movement sleep. GHRHR(lit/lit) mice that lack functional GHRH receptor have shorter sleep duration and longer wakefulness during light periods. The current study was undertaken to determine whether manipulating sleep by interfering with GHRH signaling affects brain ISF Aβ levels in APPswe/PS1ΔE9 (PS1APP) transgenic mice that overexpress mutant forms of APP and PSEN1 that cause autosomal dominant AD. We found that intraperitoneal injection of GHRH at dark onset increased sleep and decreased ISF Aβ and that delivery of a GHRH antagonist via reverse-microdialysis suppressed sleep and increased ISF Aβ. The diurnal fluctuation of ISF Aβ in PS1APP/GHRHR(lit/lit) mice was significantly smaller than that in PS1APP/GHRHR(lit/+) mice. However despite decreased sleep in GHRHR deficient mice, this was not associated with an increase in Aβ accumulation later in life. One of several possibilities for the finding is the fact that GHRHR deficient mice have GHRH-dependent but sleep-independent factors which protect against Aβ deposition. Copyright © 2014

  1. Keep Using My Health Apps: Discover Users' Perception of Health and Fitness Apps with the UTAUT2 Model.

    Science.gov (United States)

    Yuan, Shupei; Ma, Wenjuan; Kanthawala, Shaheen; Peng, Wei

    2015-09-01

    Health and fitness applications (apps) are one of the major app categories in the current mobile app market. Few studies have examined this area from the users' perspective. This study adopted the Extended Unified Theory of Acceptance and Use of Technology (UTAUT2) Model to examine the predictors of the users' intention to adopt health and fitness apps. A survey (n=317) was conducted with college-aged smartphone users at a Midwestern university in the United States. Performance expectancy, hedonic motivations, price value, and habit were significant predictors of users' intention of continued usage of health and fitness apps. However, effort expectancy, social influence, and facilitating conditions were not found to predict users' intention of continued usage of health and fitness apps. This study extends the UTATU2 Model to the mobile apps domain and provides health professions, app designers, and marketers with the insights of user experience in terms of continuously using health and fitness apps.

  2. From analogue to apps--developing an app to prepare children for medical imaging procedures.

    Science.gov (United States)

    Williams, Gigi; Greene, Siobhan

    2015-01-01

    The Royal Children's Hospital (RCH) in Melbourne has launched a world-first app for children that will help reduce anxiety and the need for anesthesia during medical imaging procedures. The free, game-based app, "Okee in Medical Imaging", helps children aged from four to eight years to prepare for all medical imaging procedures--X-ray, CT, MRI, ultrasound, nuclear medicine, and fluoroscopy. The app is designed to reduce anticipatory fear of imaging procedures, while helping to ensure that children attend imaging appointments equipped with the skills required for efficient and effective scans to be performed. This paper describes how the app was developed.

  3. Citrix XenApp performance essentials

    CERN Document Server

    Dentella, Luca

    2013-01-01

    A practical hands-on tutorial including multiple examples on application management using Citrix XenApp 6.5.Citrix XenApp Performance Essentials is intended for IT architects and system administrators who work with Citrix XenApp and who need an agile, practical guide to tune and optimize the performance.

  4. Peripheral Injection of SB203580 Inhibits the Inflammatory-Dependent Synthesis of Proinflammatory Cytokines in the Hypothalamus

    Directory of Open Access Journals (Sweden)

    Andrzej P. Herman

    2014-01-01

    Full Text Available The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL- 1β, IL-6, and tumor necrosis factor (TNF α in the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS (400 ng/kg over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK, which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFα synthesis. Intravenous injection of SB203580 successfully inhibited (P<0.01 synthesis of IL-1β and reduced (P<0.01 the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P<0.01 gene expression of TNFα but its effect was not observed at the level of TNFα protein synthesis. SB203580 also reduced (P<0.01 LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.

  5. Google Apps zijn leuk

    NARCIS (Netherlands)

    den Hollander, Franciscus

    Het bericht dat de Rijksuniversiteit Groningen overgaat op de mailvoorziening en agenda van Google Apps for Education bracht een golf van publiciteit teweeg. Mediaberichten naar aanleiding van de overgang naar Google Apps.

  6. Motor impulsivity in APP-SWE mice: a model of Alzheimer's disease.

    Science.gov (United States)

    Adriani, Walter; Ognibene, Elisa; Heuland, Emilie; Ghirardi, Orlando; Caprioli, Antonio; Laviola, Giovanni

    2006-09-01

    Among transgenic mouse models of Alzheimer's disease, APP-SWE mice have been shown to develop beta-amyloid plaques and to exhibit progressive impairment of cognitive function. Human Alzheimer's disease, however, also includes secondary clinical manifestations, spanning from hyperactivity to agitation. The aim of this study was a better characterization of motor impulsivity in APP-SWE mice, observed at 12 months of age, when levels of soluble beta-amyloid are elevated and beta-amyloid neuritic plaques start to appear. Mice were tested for spatial learning abilities in the Morris water maze (seven daily sessions, four trials per day). The distance traveled to reach the hidden platform showed a learning curve in both groups. This profile, however, was somewhat delayed in APP-SWE mice, thus confirming slightly impaired spatial capacities. To evaluate motor impulsivity, animals were trained to nose-poke for a food reward, which was delivered after a waiting interval that increased over days (15-60 s). Further nose-poking during this signaled waiting interval resulted in food-reward loss and electric-shock punishment. APP-SWE mice received an increased quantity of punishment and were able to earn fewer food rewards, suggesting inability to wait already at the lowest delay. After the animals were killed, prefrontal cortex samples were assessed for neurochemical parameters. Serotonin turnover was elevated in the prefrontal cortex of APP-SWE mice compared with controls. The results clearly confirm cognitive deficits, and are consistent with the hypothesis of reduced behavioral-inhibition abilities. Together with recent findings, APP-SWE mice emerge as a suitable animal model, characterized by a number of specific behavioral alterations, resembling primary and secondary symptoms of human Alzheimer's disease.

  7. ''Are Chemistry Educational Apps Useful?''--A Quantitative Study with Three In-House Apps

    Science.gov (United States)

    Ping, Grace Lee Yuan; Lok, Chang; Yeat, Tan Wei; Cherynn, Tan Jie Ying; Tan, Emelyn Sue Qing

    2018-01-01

    Three internally developed mobile apps, "3D Sym Op", "SM2 Chem" and "ARMolVis," available for free on both the Apple App Store and Google Play Store were evaluated in seven studies. Each study was a systematic process of Pre-Test, In-lecture App Demo, App Assisted Interactive Tutorials (AAITs) and/or Independent App…

  8. There's an App for that!

    Science.gov (United States)

    Dutton, Gail

    2011-01-01

    Important as training the sales force is, mobile training apps are being used for much more. Visual Eyes Inc., for example, has developed training apps for the U.S. military's combat medical teams that detail specific medical procedures, such as controlling hemorrhaging. Other apps, developed for corporations and government agencies, pass along…

  9. The Rise and Need for Mobile Apps for Maternal and Child Health Care in China: Survey Based on App Markets.

    Science.gov (United States)

    Zhang, Puhong; Dong, Le; Chen, Huan; Chai, Yanling; Liu, Jianbo

    2018-06-08

    Mobile health services are thriving in the field of maternal and child health in China due to expansions in the field of electronic health and the introduction of the two-child policy. There are numerous maternal and child health apps in computer stores, but the exact number of apps, number of downloads, and features of these apps is not known. This study aimed to explore the use of maternal and child health apps in Android and iOS app stores and to describe the key functional features of the most popular apps, with the purpose of providing insight into further research and development of maternal and child health mobile health products. The researchers conducted a search in the 3 most popular Android app stores (Tencent MyApp, Baidu Mobile Assistant, and 360 Mobile Assistant) and the iTunes App Store in China. All apps regarding family planning (contraception and preparing for pregnancy), pregnancy and perinatal care, neonatal care and health, and development for children under 6 years were included in the initial analysis. Maternal and child health mobile apps with predominant features of product marketing, children's songs, animation, or games were excluded from the study. The 50 most frequently used apps in each of the Android stores as well as the iTunes store (a total of 78 deduplicated apps) were selected and downloaded for an in-depth analysis. A total of 5276 Android apps and 877 iOS apps developed for maternal and child health care were identified. Of the 78 most frequently used apps, 43 (55%) apps focused on one stage of MCH care, mainly targeting child care (25 apps) and before pregnancy care (11 apps), whereas 35 (45%) of the apps covered 2 or more stages, most of which (32 apps) included both pregnancy and child care services. The app features that were commonly adopted by the popular apps were health education, communication, health status self-monitoring, a diary, reminders, and counseling. Within the app feature of "health status self

  10. Controlling Your "App"etite: How Diet and Nutrition-Related Mobile Apps Lead to Behavior Change.

    Science.gov (United States)

    West, Joshua H; Belvedere, Lindsay M; Andreasen, Rebecca; Frandsen, Christine; Hall, P Cougar; Crookston, Benjamin T

    2017-07-10

    In recent years, obesity has become a serious public health crisis in the United States. Although the problem of obesity is being addressed through a variety of strategies, the use of mobile apps is a relatively new development that could prove useful in helping people to develop healthy dietary habits. Though such apps might lead to health behavior change, especially when relevant behavior change theory constructs are integrated into them, the mechanisms by which these apps facilitate behavior change are largely unknown. The purpose of this study was to identify which behavior change mechanisms are associated with the use of diet- and nutrition-related health apps and whether the use of diet- and nutrition-related apps is associated with health behavior change. A cross-sectional survey was administered to a total of 217 participants. Participants responded to questions on demographics, use of diet and nutrition apps in the past 6 months, engagement and likability of apps, and changes in the participant's dietary behaviors. Regression analysis was used to identify factors associated with reported changes in theory and separately for reported changes in actual behavior, after controlling for potential confounding variables. The majority of study participants agreed or strongly agreed with statements regarding app use increasing their motivation to eat a healthy diet, improving their self-efficacy, and increasing their desire to set and achieve health diet goals. Additionally, majority of participants strongly agreed that using diet/nutrition apps led to changes in their behavior, namely increases in actual goal setting to eat a healthy diet (58.5%, 127/217), increases in their frequency of eating healthy foods (57.6%, 125/217), and increases in their consistency of eating healthy foods (54.4%, 118/217). Participants also responded favorably to questions related to engagement and likability of diet/nutrition apps. A number of predictors were also positively

  11. Design for children's apps

    OpenAIRE

    MORANTE BONET, MIRIAM; Costa Ferrer, María; Rodríguez Calatayud, María Nuria

    2017-01-01

    Are children under 2 years old exposed to apps? Which ones? How often? What kind of apps would be best suited for small children based on their physical and cognitive development, the evolution of their play patterns and their ability to interact with mobile devices? How to design apps as appropriate as possible for children under 2 years old? These are some of the main questions that are answered through the research presented in this publication. An investigation that demonstra...

  12. The Business of iPhone and iPad App Development Making and Marketing Apps That Succeed

    CERN Document Server

    Wooldridge, Dave

    2011-01-01

    The phenomenal success of the iPhone, iPad and the iPod touch has ushered in a "gold rush" for developers, but with well over 300,000 apps in the highly competitive App Store, it has become increasingly difficult for new apps to stand out in the crowd. Achieving consumer awareness and sales longevity for your iOS app requires a lot of organization and some strategic planning. Updated and expanded for iOS 4, this bestselling book will show you how to incorporate marketing and business savvy into every aspect of the design and development process, giving your app the best possible chance of

  13. Driver feedback mobile APP

    Energy Technology Data Exchange (ETDEWEB)

    Soriguera Marti, F.; Miralles Miquel, E.

    2016-07-01

    This paper faces the human factor in driving and its consequences for road safety. It presents the concepts behind the development of a smartphone app capable of evaluating drivers’ performance. The app provides feedback to the driver in terms of a grade (between 0 and 10) depending on the aggressiveness and risks taken while driving. These are computed from the cumulative probability distribution function of the jerks (i.e. the time derivative of acceleration), which are measured using the smartphones’ accelerometer. Different driving contexts (e.g. urban, freeway, congestion, etc.) are identified applying cluster analysis to the measurements, and treated independently. Using regression analysis, the aggressiveness indicator is related to the drivers' safety records and to the probability of having an accident, through the standard DBQ - Driving Behavior Questionnaire. Results from a very limited pilot test show a strong correlation between the 99th percentile of the jerk measurements and the DBQ results. A linear model is fitted. This allows quantifying the safe driving behavior only from smartphone measurements. Finally, this indicator is translated into a normalized grade and feedback to the driver. This feedback will challenge the driver to train and to improve his performance. The phone will be blocked while driving and will incorporate mechanisms to prevent bad practices, like competition in aggressive driving. The app is intended to contribute to the improvement of road safety, one of the major public health problems, by tackling the human factor which is the trigger of the vast majority of traffic accidents. Making explicit and quantifying risky behaviors is the first step towards a safer driving. (Author)

  14. ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity

    Directory of Open Access Journals (Sweden)

    Bu Guojun

    2007-07-01

    Full Text Available Abstract Background The generation of the amyloid-β peptide (Aβ through the proteolytic processing of the amyloid precursor protein (APP is a central event in the pathogenesis of Alzheimer's disease (AD. Recent studies highlight APP endocytosis and localization to lipid rafts as important events favoring amyloidogenic processing. However, the precise mechanisms underlying these events are poorly understood. ApoER2 is a member of the low density lipoprotein receptor (LDL-R family exhibiting slow endocytosis rate and a significant association with lipid rafts. Despite the important neurophysiological roles described for ApoER2, little is known regarding how ApoER2 regulates APP trafficking and processing. Results Here, we demonstrate that ApoER2 physically interacts and co-localizes with APP. Remarkably, we found that ApoER2 increases cell surface APP levels and APP association with lipid rafts. The increase of cell surface APP requires the presence of ApoER2 cytoplasmic domain and is a result of decreased APP internalization rate. Unexpectedly, ApoER2 expression correlated with a significant increase in Aβ production and reduced levels of APP-CTFs. The increased Aβ production was dependent on the integrity of the NPxY endocytosis motif of ApoER2. We also found that expression of ApoER2 increased APP association with lipid rafts and increased γ-secretase activity, both of which might contribute to increased Aβ production. Conclusion These findings show that ApoER2 negatively affects APP internalization. However, ApoER2 expression stimulates Aβ production by shifting the proportion of APP from the non-rafts to the raft membrane domains, thereby promoting β-secretase and γ-secretase mediated amyloidogenic processing and also by incrementing the activity of γ-secretase.

  15. A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis.

    Science.gov (United States)

    Zhuang, Yuan; Cheng, Ping; Liu, Xiao-fei; Peng, Liu-sheng; Li, Bo-sheng; Wang, Ting-ting; Chen, Na; Li, Wen-hua; Shi, Yun; Chen, Weisan; Pang, Ken C; Zeng, Ming; Mao, Xu-hu; Yang, Shi-ming; Guo, Hong; Guo, Gang; Liu, Tao; Zuo, Qian-fei; Yang, Hui-jie; Yang, Liu-yang; Mao, Fang-yuan; Lv, Yi-pin; Zou, Quan-ming

    2015-09-01

    Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Image restoration by Wiener filtering in the presence of signal-dependent noise.

    Science.gov (United States)

    Kondo, K; Ichioka, Y; Suzuki, T

    1977-09-01

    An optimum filter to restore the degraded image due to blurring and the signal-dependent noise is obtained on the basis of the theory of Wiener filtering. Computer simulations of image restoration using signal-dependent noise models are carried out. It becomes clear that the optimum filter, which makes use of a priori information on the signal-dependent nature of the noise and the spectral density of the signal and the noise showing significant spatial correlation, is potentially advantageous.

  17. Amazing Android Apps For Dummies

    CERN Document Server

    Begun, Daniel A

    2011-01-01

    Find the Android apps that are right for you so you can have fun and get more done!The popularity of Android apps is exploding and this handy guide helps you sort through the thousands of available applications so you can find the ones that are ideal for you. You'll explore a variety of apps in the areas of entertainment, finance, health, food, music, news, weather, photography, reference, dining out, social networking, sports, travel, and more. Author Daniel Begun helps you navigate through this enormous-and potentially overwhelming-array of Android apps.Holds your hand through the oftentimes

  18. The Potential of Mobile Apps for Improving Asthma Self-Management: A Review of Publicly Available and Well-Adopted Asthma Apps

    Science.gov (United States)

    Tinschert, Peter; Jakob, Robert; Barata, Filipe; Kramer, Jan-Niklas

    2017-01-01

    Background Effective disease self-management lowers asthma’s burden of disease for both individual patients and health care systems. In principle, mobile health (mHealth) apps could enable effective asthma self-management interventions that improve a patient’s quality of life while simultaneously reducing the overall treatment costs for health care systems. However, prior reviews in this field have found that mHealth apps for asthma lack clinical evaluation and are often not based on medical guidelines. Yet, beyond the missing evidence for clinical efficacy, little is known about the potential apps might have for improving asthma self-management. Objective The aim of this study was to assess the potential of publicly available and well-adopted mHealth apps for improving asthma self-management. Methods The Apple App store and Google Play store were systematically searched for asthma apps. In total, 523 apps were identified, of which 38 apps matched the selection criteria to be included in the review. Four requirements of app potential were investigated: app functions, potential to change behavior (by means of a behavior change technique taxonomy), potential to promote app use (by means of a gamification components taxonomy), and app quality (by means of the Mobile Application Rating Scale [MARS]). Results The most commonly implemented functions in the 38 reviewed asthma apps were tracking (30/38, 79%) and information (26/38, 68%) functions, followed by assessment (20/38, 53%) and notification (18/38, 47%) functions. On average, the reviewed apps applied 7.12 of 26 available behavior change techniques (standard deviation [SD]=4.46) and 4.89 of 31 available gamification components (SD=4.21). Average app quality was acceptable (mean=3.17/5, SD=0.58), whereas subjective app quality lied between poor and acceptable (mean=2.65/5, SD=0.87). Additionally, the sum scores of all review frameworks were significantly correlated (lowest correlation: r36=.33, P=.04 between

  19. Neurodegeneration in Alzheimer Disease: Role of Amyloid Precursor Protein and Presenilin 1 Intracellular Signaling

    Directory of Open Access Journals (Sweden)

    Mario Nizzari

    2012-01-01

    Full Text Available Alzheimer disease (AD is a heterogeneous neurodegenerative disorder characterized by (1 progressive loss of synapses and neurons, (2 intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3 amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP and presenilin 1 and 2 (PS1 and PS2. The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

  20. Office 2010 Web Apps For Dummies

    CERN Document Server

    Weverka, Peter

    2010-01-01

    Enhance your Microsoft Office 2010 experience with Office 2010 Web Apps!. Office Web Apps complement Office, making it easy to access and edit files from anywhere. It also simplifies collaboration with those who don't have Microsoft Office on their computers. This helpful book shows you the optimum ways you can use Office Web Apps to save time and streamline your work. Veteran For Dummies author Peter Weverka begins with an introduction to Office Web Apps and then goes on to clearly explain how Office Web Apps provide you with easier, faster, more flexible ways to get things done.: Walks you t

  1. The Potential of Mobile Apps for Improving Asthma Self-Management: A Review of Publicly Available and Well-Adopted Asthma Apps.

    Science.gov (United States)

    Tinschert, Peter; Jakob, Robert; Barata, Filipe; Kramer, Jan-Niklas; Kowatsch, Tobias

    2017-08-02

    Effective disease self-management lowers asthma's burden of disease for both individual patients and health care systems. In principle, mobile health (mHealth) apps could enable effective asthma self-management interventions that improve a patient's quality of life while simultaneously reducing the overall treatment costs for health care systems. However, prior reviews in this field have found that mHealth apps for asthma lack clinical evaluation and are often not based on medical guidelines. Yet, beyond the missing evidence for clinical efficacy, little is known about the potential apps might have for improving asthma self-management. The aim of this study was to assess the potential of publicly available and well-adopted mHealth apps for improving asthma self-management. The Apple App store and Google Play store were systematically searched for asthma apps. In total, 523 apps were identified, of which 38 apps matched the selection criteria to be included in the review. Four requirements of app potential were investigated: app functions, potential to change behavior (by means of a behavior change technique taxonomy), potential to promote app use (by means of a gamification components taxonomy), and app quality (by means of the Mobile Application Rating Scale [MARS]). The most commonly implemented functions in the 38 reviewed asthma apps were tracking (30/38, 79%) and information (26/38, 68%) functions, followed by assessment (20/38, 53%) and notification (18/38, 47%) functions. On average, the reviewed apps applied 7.12 of 26 available behavior change techniques (standard deviation [SD]=4.46) and 4.89 of 31 available gamification components (SD=4.21). Average app quality was acceptable (mean=3.17/5, SD=0.58), whereas subjective app quality lied between poor and acceptable (mean=2.65/5, SD=0.87). Additionally, the sum scores of all review frameworks were significantly correlated (lowest correlation: r 36 =.33, P=.04 between number of functions and gamification

  2. Nitric oxide signaling depends on biotin in Jurkat human lymphoma cells.

    Science.gov (United States)

    Rodriguez-Melendez, Rocio; Zempleni, Janos

    2009-03-01

    Biotin affects gene expression through a diverse array of cell signaling pathways. Previous studies provided evidence that cGMP-dependent signaling also depends on biotin, but the mechanistic sequence of cGMP regulation by biotin is unknown. Here we tested the hypothesis that the effects of biotin in cGMP-dependent cell signaling are mediated by nitric oxide (NO). Human lymphoid (Jurkat) cells were cultured in media containing deficient (0.025 nmol/L), physiological (0.25 nmol/L), and pharmacological (10 nmol/L) concentrations of biotin for 5 wk. Both levels of intracellular biotin and NO exhibited a dose-dependent relationship in regard to biotin concentrations in culture media. Effects of biotin on NO levels were disrupted by the NO synthase (NOS) inhibitor N-monomethyl-arginine. Biotin-dependent production of NO was linked with biotin-dependent expression of endothelial and neuronal NOS, but not inducible NOS. Previous studies revealed that NO is an activator of guanylate cyclase. Consistent with these previous observations, biotin-dependent generation of NO increased the abundance of cGMP in Jurkat cells. Finally, the biotin-dependent generation of cGMP increased protein kinase G activity. Collectively, the results of this study are consistent with the hypothesis that biotin-dependent cGMP signaling in human lymphoid cells is mediated by NO.

  3. Evaluating Apps for Learning and Teaching

    Directory of Open Access Journals (Sweden)

    Diana Renee D Jonas-Dwyer

    2012-03-01

    Full Text Available A growing number of educators and students are adopting mobile devices and using applications (apps. There are often no formal guidelines to assist with evaluating apps. A review of the literature was conducted to determine relevant criteria that could be applied to evaluating apps. Relevant examples are included where appropriate. Evaluation criteria are offered to assist educators and students with determining the suitability of apps.

  4. Suppressive Effect on Lipopolysaccharide-Induced Proinflammatory Mediators by Citrus aurantium L. in Macrophage RAW 264.7 Cells via NF-κB Signal Pathway

    Directory of Open Access Journals (Sweden)

    Sang-Rim Kang

    2011-01-01

    Full Text Available Citrus fruits have been used as an edible fruit and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are used widely in traditional herbal medicine in Korea, as they are believed to contain bioactive components exerting anti-inflammatory activity. This study examined whether the crude methanol extract of Citrus aurantium L. (CME has a suppressive effect on inducible enzymes and proinflammatory cytokines by inhibiting the NF-κB pathway in LPS-stimulated macrophage RAW 264.7 cells. The cells were pretreated with the indicated concentrations of CME (5, 10, 20, and 50 μg/mL and then treated with LPS (1 μg/mL. The results showed that CME (10, 20, and 50 μg/mL inhibited the LPS- (1 μg/mL induced mRNA and protein expression of iNOS in macrophage Raw 264.7 cells. In addition, the expression of COX-2 was inhibited at the mRNA and protein levels by CME in a dose-dependent manner. The mRNA expression of proinflammatory cytokines, such as TNF-α and IL-6, were markedly reduced by CME (10, 20, and 50 μg/mL. Moreover, CME clearly suppressed the nuclear translocation of the NF-κB p65 subunits, which was correlated with its inhibitory effect on I-κB phosphorylation. These results suggest that CME has anti-inflammatory properties by modulating the expression of COX-2, iNOS, and proinflammatory cytokines, such as TNF-α and IL-6, in macrophage RAW 264.7 cells via the NF-κB pathway.

  5. Large-Scale Analysis of Auditory Segregation Behavior Crowdsourced via a Smartphone App.

    Science.gov (United States)

    Teki, Sundeep; Kumar, Sukhbinder; Griffiths, Timothy D

    2016-01-01

    The human auditory system is adept at detecting sound sources of interest from a complex mixture of several other simultaneous sounds. The ability to selectively attend to the speech of one speaker whilst ignoring other speakers and background noise is of vital biological significance-the capacity to make sense of complex 'auditory scenes' is significantly impaired in aging populations as well as those with hearing loss. We investigated this problem by designing a synthetic signal, termed the 'stochastic figure-ground' stimulus that captures essential aspects of complex sounds in the natural environment. Previously, we showed that under controlled laboratory conditions, young listeners sampled from the university subject pool (n = 10) performed very well in detecting targets embedded in the stochastic figure-ground signal. Here, we presented a modified version of this cocktail party paradigm as a 'game' featured in a smartphone app (The Great Brain Experiment) and obtained data from a large population with diverse demographical patterns (n = 5148). Despite differences in paradigms and experimental settings, the observed target-detection performance by users of the app was robust and consistent with our previous results from the psychophysical study. Our results highlight the potential use of smartphone apps in capturing robust large-scale auditory behavioral data from normal healthy volunteers, which can also be extended to study auditory deficits in clinical populations with hearing impairments and central auditory disorders.

  6. Large-Scale Analysis of Auditory Segregation Behavior Crowdsourced via a Smartphone App.

    Directory of Open Access Journals (Sweden)

    Sundeep Teki

    Full Text Available The human auditory system is adept at detecting sound sources of interest from a complex mixture of several other simultaneous sounds. The ability to selectively attend to the speech of one speaker whilst ignoring other speakers and background noise is of vital biological significance-the capacity to make sense of complex 'auditory scenes' is significantly impaired in aging populations as well as those with hearing loss. We investigated this problem by designing a synthetic signal, termed the 'stochastic figure-ground' stimulus that captures essential aspects of complex sounds in the natural environment. Previously, we showed that under controlled laboratory conditions, young listeners sampled from the university subject pool (n = 10 performed very well in detecting targets embedded in the stochastic figure-ground signal. Here, we presented a modified version of this cocktail party paradigm as a 'game' featured in a smartphone app (The Great Brain Experiment and obtained data from a large population with diverse demographical patterns (n = 5148. Despite differences in paradigms and experimental settings, the observed target-detection performance by users of the app was robust and consistent with our previous results from the psychophysical study. Our results highlight the potential use of smartphone apps in capturing robust large-scale auditory behavioral data from normal healthy volunteers, which can also be extended to study auditory deficits in clinical populations with hearing impairments and central auditory disorders.

  7. Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines.

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    Brown, D M; Wilson, M R; MacNee, W; Stone, V; Donaldson, K

    2001-09-15

    Studies into the effects of ultrafine particles in the lung have shown adverse effects considered to be due in part to the particle size. Air pollution particles (PM(10)) are associated with exacerbations of respiratory disease and deaths from cardiovascular causes in epidemiological studies and the ultrafine fraction of PM(10) has been hypothesized to play an important role. The aim of the present study was to investigate proinflammatory responses to various sizes of polystyrene particles as a simple model of particles of varying size including ultrafine. In the animal model, we demonstrated that there was a significantly greater neutrophil influx into the rat lung after instillation of 64-nm polystyrene particles compared with 202- and 535-nm particles and this was mirrored in other parameters of lung inflammation, such as increased protein and lactate dehydrogenase in bronchoalveolar lavage. When surface area instilled was plotted against inflammation, these two variables were directly proportional and the line passed through zero. This suggests that surface area drives inflammation in the short term and that ultrafine particles cause a greater inflammatory response because of the greater surface area they possess. In vitro, we measured the changes in intracellular calcium concentration in mono mac 6 cells in view of the potential role of calcium as a signaling molecule. Calcium changes after particle exposure may be important in leading to proinflammatory gene expression such as chemokines. We demonstrated that only ultrafine polystyrene particles induced a significant increase in cytosolic calcium ion concentration. Experiments using dichlorofluorescin diacetate demonstrated greater oxidant activity of the ultrafine particles, which may explain their activity in these assays. There were significant increases in IL-8 gene expression in A549 epithelial cells after treatment with the ultrafine particles but not particles of other sizes. These findings suggest

  8. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease.

    Science.gov (United States)

    Thomas, Karen E; Sapone, Anna; Fasano, Alessio; Vogel, Stefanie N

    2006-02-15

    Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of CD. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with CD.

  9. Development of a Rating Tool for Mobile Cancer Apps: Information Analysis and Formal and Content-Related Evaluation of Selected Cancer Apps.

    Science.gov (United States)

    Böhme, Cathleen; von Osthoff, Marc Baron; Frey, Katrin; Hübner, Jutta

    2017-08-17

    Mobile apps are offered in large numbers and have different qualities. The aim of this article was to develop a rating tool based on formal and content-related criteria for the assessment of cancer apps and to test its applicability on apps. After a thorough analysis of the literature, we developed a specific rating tool for cancer apps based on the MARS (mobile app rating system) and a rating tool for cancer websites. This instrument was applied to apps freely available in stores and focusing on some cancer topic. Ten apps were rated on the basis of 22 criteria. Sixty percent of the apps (6/10) were rated poor and insufficient. The rating by different scientists was homogenous. The good apps had reliable sources were regularly updated and had a concrete intent/purpose in their app description. In contrast, the apps that were rated poor had no distinction of scientific content and advertisement. In some cases, there was no imprint to identify the provider. As apps of poor quality can give misinformation and lead to wrong treatment decisions, efforts have to be made to increase usage of high-quality apps. Certification would help cancer patients to identify reliable apps, yet acceptance of a certification system must be backed up.

  10. TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Griffiths Gareth

    2009-07-01

    Full Text Available Abstract Background Phosphatidylcholine (PC is a major lipid of the gastrointestinal mucus layer. We recently showed that mucus from patients suffering from ulcerative colitis has low levels of PC. Clinical studies reveal that the therapeutic addition of PC to the colonic mucus using slow release preparations is beneficial. The positive role of PC in this disease is still unclear; however, we have recently shown that PC has an intrinsic anti-inflammatory property. It could be demonstrated that the exogenous application of PC inhibits membrane-dependent actin assembly and TNF-α-induced nuclear NF-κB activation. We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties. Methods PC species with different fatty acid side chains were applied to differentiated and non-differentiated Caco-2 cells treated with TNF-α to induce a pro-inflammatory response. We analysed TNF-α-induced NF-κB-activation via the transient expression of a NF-κB-luciferase reporter system. Pro-inflammatory gene transcription was detected with the help of a quantitative real time (RT-PCR analysis. We assessed the binding of TNF-α to its receptor by FACS and analysed lipid rafts by isolating detergent resistant membranes (DRMs. Results The exogenous addition of all PC species tested significantly inhibited TNF-α-induced pro-inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF-α and MMP-1 were significantly reduced after PC pre-treatment for at least two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB inhibitor SN 50 and was not due to a reduced binding of TNF-α to its receptor or a decreased surface expression of TNF-α receptors. PC was also effective when applied to the apical side of polarised Caco-2 cultures if cells were stimulated from the basolateral side. PC treatment changed the compartmentation of the TNF-α-receptors 1 and 2 to DRMs. Conclusion PC

  11. The Business of iPhone App Development

    CERN Document Server

    Wooldridge, Dave

    2010-01-01

    The phenomenal success of the iPhone and the iPod touch has ushered in a "gold rush" for developers, but with well over 100,000 apps in the highly competitive App Store, it has become increasingly difficult for new apps to stand out in the crowd. Achieving consumer awareness and sales longevity for your iPhone app requires a lot of organization and some strategic planning. This book will show you how to incorporate marketing and business savvy into every aspect of the design and development process, giving your app the best possible chance of succeeding in the App Store. The Business

  12. Detection of App Collusion Potential Using Logic Programming

    OpenAIRE

    Blasco, Jorge; Chen, Thomas M.; Muttik, Igor; Roggenbach, Markus

    2017-01-01

    Android is designed with a number of built-in security features such as app sandboxing and permission-based access controls. Android supports multiple communication methods for apps to cooperate. This creates a security risk of app collusion. For instance, a sandboxed app with permission to access sensitive data might leak that data to another sandboxed app with access to the internet. In this paper, we present a method to detect potential collusion between apps. First, we extract from apps a...

  13. Building Android Apps with HTML, CSS, and JavaScript Making Native Apps with Standards-Based Web Tools

    CERN Document Server

    Stark, Jonathan

    2012-01-01

    It's true: if you know HTML, CSS, and JavaScript, you already have the tools you need to develop Android applications. Now updated for HTML5, the second edition of this hands-on guide shows you how to use open source web standards to design and build apps that can be adapted for any Android device. You'll learn how to create an Android-friendly web app on the platform of your choice, and then use Adobe's free PhoneGap framework to convert it to a native Android app. Discover why device-agnostic mobile apps are the wave of the future, and start building apps that offer greater flexibility and

  14. Public health guidelines for physical activity: is there an app for that? A review of android and apple app stores.

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    Knight, Emily; Stuckey, Melanie I; Prapavessis, Harry; Petrella, Robert J

    2015-05-21

    Physical activity participation is an important behavior for modifying lifestyle-related disease risk. Mobile health apps for chronic disease management and prevention are being developed at a rapid rate. However, it is unclear whether these apps are evidence-based. Current public health recommendations for physical activity participation for adults highlight the importance of engaging in 150 minutes weekly of purposeful exercise, and muscle strengthening activities on at least 2 days of the week. The aims of the present review were to (1) identify available evidence-based physical activity apps, and (2) identify technological features that could be leveraged to improve health outcomes. iTunes and Google Play mobile app stores were searched using keyword and category searching during a single day (February 18, 2014) for physical activity apps available in English. The description pages of eligible apps were reviewed by 4 independent reviewers for evidence-based content, technological, and descriptive features. An a priori subset of apps was downloaded for further review (n=6 affiliated with a non-commercial agency; n=10 top rated; n=10 random selection), and developers were contacted for information regarding evidence-informed content. The initial search yielded 2400 apps, of which 379 apps (n=206 iTunes; n=173 Google Play) were eligible. Primary results demonstrated no apps (n=0) adhering to evidence-based guidelines for aerobic physical activity, and 7 out of 379 implementing evidence-based guidelines for resistance training physical activity. Technological features of apps included social networking (n=207), pairing with a peripheral health device (n=61), and measuring additional health parameters (n=139). Secondary results revealed 1 app that referenced physical activity guidelines (150 minutes/weekly of exercise), and demonstrated that apps were based on various physical activity reports (n=4) or personal expertise (n=2). The present study demonstrated a

  15. Apps seeking theories: results of a study on the use of health behavior change theories in cancer survivorship mobile apps.

    Science.gov (United States)

    Vollmer Dahlke, Deborah; Fair, Kayla; Hong, Y Alicia; Beaudoin, Christopher E; Pulczinski, Jairus; Ory, Marcia G

    2015-03-27

    Thousands of mobile health apps are now available for use on mobile phones for a variety of uses and conditions, including cancer survivorship. Many of these apps appear to deliver health behavior interventions but may fail to consider design considerations based in human computer interface and health behavior change theories. This study is designed to assess the presence of and manner in which health behavior change and health communication theories are applied in mobile phone cancer survivorship apps. The research team selected a set of criteria-based health apps for mobile phones and assessed each app using qualitative coding methods to assess the application of health behavior change and communication theories. Each app was assessed using a coding derived from the taxonomy of 26 health behavior change techniques by Abraham and Michie with a few important changes based on the characteristics of mHealth apps that are specific to information processing and human computer interaction such as control theory and feedback systems. A total of 68 mobile phone apps and games built on the iOS and Android platforms were coded, with 65 being unique. Using a Cohen's kappa analysis statistic, the inter-rater reliability for the iOS apps was 86.1 (Papps, 77.4 (Papps were consistently higher than those of the Android platform apps. For personalization and tailoring, 67% of the iOS apps (24/36) had these elements as compared to 38% of the Android apps (12/32). In the area of prompting for intention formation, 67% of the iOS apps (34/36) indicated these elements as compared to 16% (5/32) of the Android apps. Mobile apps are rapidly emerging as a way to deliver health behavior change interventions that can be tailored or personalized for individuals. As these apps and games continue to evolve and include interactive and adaptive sensors and other forms of dynamic feedback, their content and interventional elements need to be grounded in human computer interface design and health

  16. Windows 8 app projects XAML and C#

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    Vermeir, Nico

    2013-01-01

    Become a leading Windows 8 app developer by using Windows 8 App Projects - XAML and C# Edition to learn techniques, tools, and ideas to create successful, 5-star apps. Windows 8 App Projects - XAML and C# Edition shows you the nuts and bolts of the Windows 8 development ecosystem. Then, through a series of example driven chapters, you'll discover how to leverage the platform's unique features. With each project, you'll be one step closer to building full-featured, responsive, and well designed apps that feel like they're a part of the operating system. Windows 8 App Projects - XAML and C# Edit

  17. Using Google App Engine

    CERN Document Server

    Severance, Charles

    2009-01-01

    Build exciting, scalable web applications quickly and confidently using Google App Engine and this book, even if you have little or no experience in programming or web development. App Engine is perhaps the most appealing web technology to appear in the last year, providing an easy-to-use application framework with basic web tools. While Google's own tutorial assumes significant experience, Using Google App Engine will help anyone get started with this platform. By the end of this book, you'll know how to build complete, interactive applications and deploy them to the cloud using the same s

  18. Cell biology apps for Apple devices.

    Science.gov (United States)

    Stark, Louisa A

    2012-01-01

    Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app on a five-point scale (1 star = lowest; 5 stars = highest) for educational and production values; I also provide an overall score.

  19. Apps in therapy: occupational therapists' use and opinions.

    Science.gov (United States)

    Seifert, Anna M; Stotz, Nicole; Metz, Alexia E

    2017-11-01

    To gather information on occupational therapy practitioners' use and opinions of apps, an online survey was distributed to occupational therapy practitioners licensed in the state of Ohio. The survey sought information regarding clinical populations and skill areas for which apps are used, potential barriers to use of apps and preferred apps/app features. OTs working in medical and education-based settings and with clients of all ages responded to the survey. Over half (53%) reported not using apps in therapy, with "not having access to the technology at work" being the leading reason endorsed. Of practitioners who did report using apps, the majority used them with ≤25% of their case load and primarily used tablets to do so. Clinicians indicated that they use apps for a wide variety of reasons, including to promote skill building and to support the therapeutic process. Preferred features included the ability to grade difficulty up/down, multiple uses and accurate feedback. Recommendations from peers were the most commonly reported way respondents found new apps. The results suggest that occupational therapy practitioners employ clinical reasoning when implementing apps in therapy. Possible ways to improve access to apps for therapists who would like to implement them are discussed. Implications for Rehabilitation Many occupational therapy practitioners are using apps with at least a portion of their caseloads. Therapists select apps based on peer recommendations, most commonly selecting those which promote skill building and support the therapeutic process. More therapists might make use of apps if potential barriers were reduced or eliminated, including availability of technology in the clinical practice setting, therapist training and education, therapist input into app development and an enhanced evidence base.

  20. Apps and eating disorders: A systematic clinical appraisal.

    Science.gov (United States)

    Fairburn, Christopher G; Rothwell, Emily R

    2015-11-01

    Smartphone applications (apps) are proliferating and health-related apps are particularly popular. The aim of this study was to identify, characterize, and evaluate the clinical utility of apps designed either for people with eating disorders or for eating disorder professionals. A search of the major app stores identified 805 potentially relevant apps, of which 39 were primarily designed for people with eating disorders and five for professionals. The apps for people with eating disorders had four main functions. Most common was the provision of advice, the quality of which ranged from sound to potentially harmful. Five apps included self-assessment tools but only two used methods that would generally be viewed as reliable. Four apps had the self-monitoring of eating habits as a major feature. Entering information into these apps could be accomplished with varying degrees of ease, but viewing it was more difficult. One app allowed the transfer of information between patients and clinicians. The enthusiasm for apps outstrips the evidence supporting their use. Given their popularity, it is suggested that clinicians evaluate app use as part of routine assessment. The clinical utility of the existing apps is not clear. Some are capable of tracking key features over time, but none has the functions required for analytic self-monitoring as in cognitive behavioral treatments. The full potential of apps has yet to be realized. Specialized apps could be designed to augment various forms of treatment, and there is the possibility that they could deliver an entire personalized intervention. © 2015 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc.

  1. Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice.

    Science.gov (United States)

    Leroy, Karelle; Ando, Kunie; Laporte, Vincent; Dedecker, Robert; Suain, Valérie; Authelet, Michèle; Héraud, Céline; Pierrot, Nathalie; Yilmaz, Zehra; Octave, Jean-Noël; Brion, Jean-Pierre

    2012-12-01

    Lack of tau expression has been reported to protect against excitotoxicity and to prevent memory deficits in mice expressing mutant amyloid precursor protein (APP) identified in familial Alzheimer disease. In APP mice, mutant presenilin 1 (PS1) enhances generation of Aβ42 and inhibits cell survival pathways. It is unknown whether the deficient phenotype induced by concomitant expression of mutant PS1 is rescued by absence of tau. In this study, we have analyzed the effect of tau deletion in mice expressing mutant APP and PS1. Although APP/PS1/tau(+/+) mice had a reduced survival, developed spatial memory deficits at 6 months and motor impairments at 12 months, these deficits were rescued in APP/PS1/tau(-/-) mice. Neuronal loss and synaptic loss in APP/PS1/tau(+/+) mice were rescued in the APP/PS1/tau(-/-) mice. The amyloid plaque burden was decreased by roughly 50% in the cortex and the spinal cord of the APP/PS1/tau(-/-) mice. The levels of soluble and insoluble Aβ40 and Aβ42, and the Aβ42/Aβ40 ratio were reduced in APP/PS1/tau(-/-) mice. Levels of phosphorylated APP, of β-C-terminal fragments (CTFs), and of β-secretase 1 (BACE1) were also reduced, suggesting that β-secretase cleavage of APP was reduced in APP/PS1/tau(-/-) mice. Our results indicate that tau deletion had a protective effect against amyloid induced toxicity even in the presence of mutant PS1 and reduced the production of Aβ. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Smartphone Apps for Measuring Human Health and Climate Change Co-Benefits: A Comparison and Quality Rating of Available Apps.

    Science.gov (United States)

    Sullivan, Rachel K; Marsh, Samantha; Halvarsson, Jakob; Holdsworth, Michelle; Waterlander, Wilma; Poelman, Maartje P; Salmond, Jennifer Ann; Christian, Hayley; Koh, Lenny Sc; Cade, Janet E; Spence, John C; Woodward, Alistair; Maddison, Ralph

    2016-12-19

    Climate change and the burden of noncommunicable diseases are major global challenges. Opportunities exist to investigate health and climate change co-benefits through a shift from motorized to active transport (walking and cycling) and a shift in dietary patterns away from a globalized diet to reduced consumption of meat and energy dense foods. Given the ubiquitous use and proliferation of smartphone apps, an opportunity exists to use this technology to capture individual travel and dietary behavior and the associated impact on the environment and health. The objective of the study is to identify, describe the features, and rate the quality of existing smartphone apps which capture personal travel and dietary behavior and simultaneously estimate the carbon cost and potential health consequences of these actions. The Google Play and Apple App Stores were searched between October 19 and November 6, 2015, and a secondary Google search using the apps filter was conducted between August 8 and September 18, 2016. Eligible apps were required to estimate the carbon cost of personal behaviors with the potential to include features to maximize health outcomes. The quality of included apps was assessed by 2 researchers using the Mobile Application Rating Scale (MARS). Out of 7213 results, 40 apps were identified and rated. Multiple travel-related apps were identified, however no apps solely focused on the carbon impact or health consequences of dietary behavior. None of the rated apps provided sufficient information on the health consequences of travel and dietary behavior. Some apps included features to maximize participant engagement and encourage behavior change towards reduced greenhouse gas emissions. Most apps were rated as acceptable quality as determined by the MARS; 1 was of poor quality and 10 apps were of good quality. Interrater reliability of the 2 evaluators was excellent (ICC=0.94, 95% CI 0.87-0.97). Existing apps capturing travel and dietary behavior and the

  3. Apps and eating disorders: A systematic clinical appraisal

    OpenAIRE

    Fairburn, Christopher G.; Rothwell, Emily R.

    2015-01-01

    ABSTRACT Objective Smartphone applications (apps) are proliferating and health?related apps are particularly popular. The aim of this study was to identify, characterize, and evaluate the clinical utility of apps designed either for people with eating disorders or for eating disorder professionals. Method A search of the major app stores identified 805 potentially relevant apps, of which 39 were primarily designed for people with eating disorders and five for professionals. Results The apps f...

  4. Factors influencing healthcare provider respondent fatigue answering a globally administered in-app survey

    Directory of Open Access Journals (Sweden)

    Vikas N. O’Reilly-Shah

    2017-09-01

    Full Text Available Background Respondent fatigue, also known as survey fatigue, is a common problem in the collection of survey data. Factors that are known to influence respondent fatigue include survey length, survey topic, question complexity, and open-ended question type. There is a great deal of interest in understanding the drivers of physician survey responsiveness due to the value of information received from these practitioners. With the recent explosion of mobile smartphone technology, it has been possible to obtain survey data from users of mobile applications (apps on a question-by-question basis. The author obtained basic demographic survey data as well as survey data related to an anesthesiology-specific drug called sugammadex and leveraged nonresponse rates to examine factors that influenced respondent fatigue. Methods Primary data were collected between December 2015 and February 2017. Surveys and in-app analytics were collected from global users of a mobile anesthesia calculator app. Key independent variables were user country, healthcare provider role, rating of importance of the app to personal practice, length of time in practice, and frequency of app use. Key dependent variable was the metric of respondent fatigue. Results Provider role and World Bank country income level were predictive of the rate of respondent fatigue for this in-app survey. Importance of the app to the provider and length of time in practice were moderately associated with fatigue. Frequency of app use was not associated. This study focused on a survey with a topic closely related to the subject area of the app. Respondent fatigue rates will likely change dramatically if the topic does not align closely. Discussion Although apps may serve as powerful platforms for data collection, responses rates to in-app surveys may differ on the basis of important respondent characteristics. Studies should be carefully designed to mitigate fatigue as well as powered with the

  5. Circadian wheel running behavior is altered in an APP/E4 mouse model of late onset Alzheimer's disease.

    Science.gov (United States)

    Boggs, Katelyn N; Kakalec, Peter A; Smith, Meghann L; Howell, Stefanie N; Flinn, Jane M

    2017-12-01

    Circadian rhythms are altered in several diseases associated with aging, one of which is Alzheimer's disease (AD). One example of a circadian rhythm is the rest-activity cycle, which can be measured in mice by monitoring their wheel-running. The present study sought to investigate differences in light phase/dark phase activity between a mouse model of late onset AD (APP/E4) and control (C57Bl6J) mice, in both the pre-plaque and post-plaques stages of the disease. To assess activity level, 24-h wheel running behavior was monitored at six months (pre-plaque) and twelve months (post-plaque) for a period of nine days. The following measures were analyzed: counts (wheel rotations) during the dark phase, counts during the light phase, hour of activity onset, and hour of activity offset. Key findings indicate that activity onset is delayed in APP/E4 mice at six and twelve months, and activity profiles for APP/E4 and C57Bl6J mice differ during the light and dark phase in such a way that APP/E4 mice run less in the early hours of the dark phase and more in the later hours of the dark phase compared to C57Bl6J mice. These findings imply that rest-activity cycle is altered in the pre-plaque stages of AD in APP/E4 mice, as they show impairments as early as six months of age. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Who are mobile app users from healthy lifestyle websites? Analysis of patterns of app use and user characteristics.

    Science.gov (United States)

    Elavsky, Steriani; Smahel, David; Machackova, Hana

    2017-12-01

    The use of online communities and websites for health information has proliferated along with the use of mobile apps for managing health behaviors such as diet and exercise. The scarce evidence available to date suggests that users of these websites and apps differ in significant ways from non-users but most data come from US- and UK-based populations. In this study, we recruited users of nutrition, weight management, and fitness-oriented websites in the Czech Republic to better understand who uses mobile apps and who does not, including user sociodemographic and psychological profiles. Respondents aged 13-39 provided information on app use through an online survey (n = 669; M age = 24.06, SD = 5.23; 84% female). Among users interested in health topics, respondents using apps for managing nutrition, weight, and fitness (n = 403, 60%) were more often female, reported more frequent smartphone use, and more expert phone skills. In logistic regression models, controlling for sociodemographics, web, and phone activity, mHealth app use was predicted by levels of excessive exercise (OR 1.346, 95% CI 1.061-1.707, p users, we found differences in types of apps used by gender, age, and weight status. Controlling for sociodemographics and web and phone use, drive for thinness predicted the frequency of use of apps for healthy eating (β = 0.14, p user characteristics of mHealth app users from nutrition, weight management, and fitness websites, helping inform subsequent design of mHealth apps and mobile intervention strategies.

  7. Mobile Apps for Educational Purposes.

    Science.gov (United States)

    Pilcher, Jobeth

    With the growing number of mobile resources, nurse educators and professional development practitioners have the opportunity to harness mobile applications as a tool for their education toolbox. Yet, the overwhelming availability of choices can lead to questions, such as the following: How do we locate apps without spending huge amounts of our valuable time? How do we know which apps to choose? How can we evaluate apps? This article is aimed at addressing these questions.

  8. Tetrahydroxystilbene glucoside modulates amyloid precursor protein processing via activation of AKT-GSK3β pathway in cells and in APP/PS1 transgenic mice.

    Science.gov (United States)

    Yin, Xiaomin; Chen, Chen; Xu, Ting; Li, Lin; Zhang, Lan

    2018-01-01

    Alternative splicing of amyloid precursor protein (APP) exon 7 generates the isoforms containing a Kunitz protease inhibitor (KPI) domain. APP-KPI levels in the brain are correlated with amyloid beta (Aβ) production. Here, we determined the effect of Tetrahydroxystilbene glucoside (TSG) on the AKT-GSK3β pathway. We found GSK3β increased APP-KPI inclusion level and interacted with the splicing factor ASF. TSG was intragastrically administered to 5-month-old APP/PS1 transgenic mice for 12 months. We found that the activated the AKT-GSK3β signaling pathway suppressed APP-KPI inclusion. Moreover, TSG treatment attenuated amyloid deposition in APP/PS1 mice. This study demonstrates the neuroprotective effect of TSG on APP expression, suggesting that TSG may be beneficial for AD prevention and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Review of Cadw Mobile App [application

    Directory of Open Access Journals (Sweden)

    Miriam Rothenberg

    2017-06-01

    Full Text Available The Welsh Government's historic environment service, Cadw (Welsh: 'to keep, protect', released a mobile app in early 2016 so that members of the public can learn about and plan visits to heritage sites cared for by Cadw. With more than one hundred archaeological sites available for browsing, conveniently ordered by spatial proximity to the user, and with a clean and accessible user-interface, the app effectively showcases the richness and distinctive character of Wales's archaeological record. The app is free and available to download for both iOS and Android devices (from Apple's App Store and the Google Play Store, and is also well signposted on Cadw's website. This article is a review of the Cadw mobile app.

  10. Apps ændrer din hverdag: Apps to change your life

    OpenAIRE

    Thorsen, Kasper Emil; Jensen, Anders Mandrup; Andersen, Kristian Coff Schang

    2014-01-01

    This paper examines the problem that apps that intend to improve our health, are not effective in regards to making people exercise, whereas games and other entertainment apps made primarily for pastime easily catches the attention of most. To investigate the cause of this issue, we made use of material presented by Nir Eyal, Charles Duhigg, B. J. Fogg, Cass R. Sunstein and Richard H. Thaler. Based on the knowledge obtained through the theories of the aforementioned theorists, we have selecte...

  11. MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol.

    Science.gov (United States)

    Santo, Karla; Chow, Clara K; Thiagalingam, Aravinda; Rogers, Kris; Chalmers, John; Redfern, Julie

    2017-10-08

    The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums. ACTRN12616000661471; Pre-results.

  12. Tie2 signaling cooperates with TNF to promote the pro-inflammatory activation of human macrophages independently of macrophage functional phenotype.

    Science.gov (United States)

    García, Samuel; Krausz, Sarah; Ambarus, Carmen A; Fernández, Beatriz Malvar; Hartkamp, Linda M; van Es, Inge E; Hamann, Jörg; Baeten, Dominique L; Tak, Paul P; Reedquist, Kris A

    2014-01-01

    Angiopoietin (Ang) -1 and -2 and their receptor Tie2 play critical roles in regulating angiogenic processes during development, homeostasis, tumorigenesis, inflammation and tissue repair. Tie2 signaling is best characterized in endothelial cells, but a subset of human and murine circulating monocytes/macrophages essential to solid tumor formation express Tie2 and display immunosuppressive properties consistent with M2 macrophage polarization. However, we have recently shown that Tie2 is strongly activated in pro-inflammatory macrophages present in rheumatoid arthritis patient synovial tissue. Here we examined the relationship between Tie2 expression and function during human macrophage polarization. Tie2 expression was observed under all polarization conditions, but was highest in IFN-γ and IL-10 -differentiated macrophages. While TNF enhanced expression of a common restricted set of genes involved in angiogenesis and inflammation in GM-CSF, IFN-γ and IL-10 -differentiated macrophages, expression of multiple chemokines and cytokines, including CXCL3, CXCL5, CXCL8, IL6, and IL12B was further augmented in the presence of Ang-1 and Ang-2, via Tie2 activation of JAK/STAT signaling. Conditioned medium from macrophages stimulated with Ang-1 or Ang-2 in combination with TNF, sustained monocyte recruitment. Our findings suggest a general role for Tie2 in cooperatively promoting the inflammatory activation of macrophages, independently of polarization conditions.

  13. Popular weight-management apps: Their use and quality

    Directory of Open Access Journals (Sweden)

    Juliana Chen

    2015-09-01

    Conclusions: While greater popularity of apps was associated with higher quality, the overall quality of commercial dietary weight-management apps remains suboptimal. Popular weight-management apps are useful for self-monitoring, however are lacking in the recognised behavioural change techniques that may facilitate changes in health behaviours. With the majority of these apps designed for self-directed management, strategies to improve the rigour of these apps are warranted and commercial app developers could benefit from collaboration with behavioural researchers.

  14. Smartphone apps for orthopaedic sports medicine - a smart move?

    Science.gov (United States)

    Wong, Seng Juong; Robertson, Greg A; Connor, Katie L; Brady, Richard R; Wood, Alexander M

    2015-01-01

    With the advent of smartphones together with their downloadable applications (apps), there is increasing opportunities for doctors, including orthopaedic sports surgeons, to integrate such technology into clinical practice. However, the clinical reliability of these medical apps remains questionable. We reviewed available apps themed specifically towards Orthopaedic Sports Medicine and related conditions and assessed the level of medical professional involvement in their design and content, along with a review of these apps. The most popular smartphone app stores (Android, Apple, Blackberry, Windows, Samsung, Nokia) were searched for Orthopaedic Sports medicine themed apps, using the search terms; Orthopaedic Sports Medicine, Orthopaedics, Sports medicine, Knee Injury, Shoulder Injury, Anterior Cruciate Ligament Tear, Medial Collateral Ligament Tear, Rotator Cuff Tear, Meniscal Tear, Tennis Elbow. All English language apps related to orthopaedic sports medicine were included. A total of 76 individual Orthopaedic Sports Medicine themed apps were identified. According to app store classifications, there were 45 (59 %) medical themed apps, 28 (37 %) health and fitness themed apps, 1 (1 %) business app, 1 (1 %) reference app and 1 (1 %) sports app. Forty-nine (64 %) apps were available for download free of charge. For those that charged access, the prices ranged from £0.69 to £69.99. Only 51 % of sports medicine apps had customer satisfaction ratings and 39 % had named medical professional involvement in their development or content. We found the majority of Orthopaedic Sports Medicine apps had no named medical professional involvement, raising concerns over their content and evidence-base. We recommend increased regulation of such apps to improve the accountability of app content.

  15. Creating Innovative Student Projects with App Smashing

    Science.gov (United States)

    Young, Donna

    2014-01-01

    The potential for using various apps to improve student learning is tremendous. Yet, despite the iPad's possibilities, apps are often limited in their functionality. No one has created that magical, one-size-fits-all app that accomplishes all of the tasks that you had in mind. Luckily, there is an answer to this common problem: app smashing.…

  16. Redefining Cheminformatics with Intuitive Collaborative Mobile Apps

    Science.gov (United States)

    Clark, Alex M; Ekins, Sean; Williams, Antony J

    2012-01-01

    Abstract The proliferation of mobile devices such as smartphones and tablet computers has recently been extended to include a growing ecosystem of increasingly sophisticated chemistry software packages, commonly known as apps. The capabilities that these apps can offer to the practicing chemist are approaching those of conventional desktop-based software, but apps tend to be focused on a relatively small range of tasks. To overcome this, chemistry apps must be able to seamlessly transfer data to other apps, and through the network to other devices, as well as to other platforms, such as desktops and servers, using documented file formats and protocols whenever possible. This article describes the development and state of the art with regard to chemistry-aware apps that make use of facile data interchange, and some of the scenarios in which these apps can be inserted into a chemical information workflow to increase productivity. A selection of contemporary apps is used to demonstrate their relevance to pharmaceutical research. Mobile apps represent a novel approach for delivery of cheminformatics tools to chemists and other scientists, and indications suggest that mobile devices represent a disruptive technology for drug discovery, as they have been to many other industries. PMID:23198002

  17. Neuron-astrocyte signaling is preserved in the aging brain.

    Science.gov (United States)

    Gómez-Gonzalo, Marta; Martin-Fernandez, Mario; Martínez-Murillo, Ricardo; Mederos, Sara; Hernández-Vivanco, Alicia; Jamison, Stephanie; Fernandez, Ana P; Serrano, Julia; Calero, Pilar; Futch, Hunter S; Corpas, Rubén; Sanfeliu, Coral; Perea, Gertrudis; Araque, Alfonso

    2017-04-01

    Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca 2+ elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca 2+ signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP 3 R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca 2+ signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca 2+ physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580. © 2017 Wiley

  18. Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages.

    Science.gov (United States)

    Zhong, Ta-Ying; Arancibia, Sergio; Born, Raimundo; Tampe, Ricardo; Villar, Javiera; Del Campo, Miguel; Manubens, Augusto; Becker, María Inés

    2016-06-01

    Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5 Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages. Copyright © 2016 by The American Association of

  19. Sleep apps and behavioral constructs: A content analysis

    Directory of Open Access Journals (Sweden)

    Diana S. Grigsby-Toussaint

    2017-06-01

    Full Text Available Although sleep apps are among the most popular commercially available health apps, little is known about how well these apps are grounded in behavioral theory. Three-hundred and sixty-nine apps were initially identified using the term “sleep” from the Google play store and Apple iTunes in September 2015. The final sample consisted of 35 apps that met the following inclusion criteria: 1 Stand-alone functionality; 2 Sleep tracker or monitor apps ranked by 100+ users; 3 Sleep Alarm apps ranked by 1000+ users; and 4 English language. A coding instrument was developed to assess the presence of 19 theoretical constructs. All 35 apps were downloaded and coded. The inter-rater reliability between coders was 0.996. A “1” was assigned if a construct was present in the app and “0” if it was not. Mean scores were calculated across all apps, and comparisons were made between total scores and app ratings using R. The mean behavior construct scores (BCS across all apps was 34% (5% - 84%. Behavioral constructs for realistic goal setting (86%, time management (77%, and self-monitoring (66% were most common. Although a positive association was observed between BCS and user ratings, this was not found to be statistically significant (p > 0.05. The mean persuasive technology score was 42% (20% to 80%, with higher scores for paid compared to free apps (p < 0.05. While the overall behavior construct scores were low, an opportunity exists to develop or modify existing apps to support sustainable sleep hygiene practices.

  20. Phenylbutyric acid rescues endoplasmic reticulum stress-induced suppression of APP proteolysis and prevents apoptosis in neuronal cells.

    Directory of Open Access Journals (Sweden)

    Jesse C Wiley

    Full Text Available BACKGROUND: The familial and sporadic forms of Alzheimer's disease (AD have an identical pathology with a severe disparity in the time of onset [1]. The pathological similarity suggests that epigenetic processes may phenocopy the Familial Alzheimer's disease (FAD mutations within sporadic AD. Numerous groups have demonstrated that FAD mutations in presenilin result in 'loss of function' of gamma-secretase mediated APP cleavage [2], [3], [4], [5]. Accordingly, ER stress is prominent within the pathologically impacted brain regions in AD patients [6] and is reported to inhibit APP trafficking through the secretory pathway [7], [8]. As the maturation of APP and the cleaving secretases requires trafficking through the secretory pathway [9], [10], [11], we hypothesized that ER stress may block trafficking requisite for normal levels of APP cleavage and that the small molecular chaperone 4-phenylbutyrate (PBA may rescue the proteolytic deficit. METHODOLOGY/PRINCIPAL FINDINGS: The APP-Gal4VP16/Gal4-reporter screen was stably incorporated into neuroblastoma cells in order to assay gamma-secretase mediated APP proteolysis under normal and pharmacologically induced ER stress conditions. Three unrelated pharmacological agents (tunicamycin, thapsigargin and brefeldin A all repressed APP proteolysis in parallel with activation of unfolded protein response (UPR signaling-a biochemical marker of ER stress. Co-treatment of the gamma-secretase reporter cells with PBA blocked the repressive effects of tunicamycin and thapsigargin upon APP proteolysis, UPR activation, and apoptosis. In unstressed cells, PBA stimulated gamma-secretase mediated cleavage of APP by 8-10 fold, in the absence of any significant effects upon amyloid production, by promoting APP trafficking through the secretory pathway and the stimulation of the non-pathogenic alpha/gamma-cleavage. CONCLUSIONS/SIGNIFICANCE: ER stress represses gamma-secretase mediated APP proteolysis, which replicates

  1. Apps for Ancient Civilizations

    Science.gov (United States)

    Thompson, Stephanie

    2011-01-01

    This project incorporates technology and a historical emphasis on science drawn from ancient civilizations to promote a greater understanding of conceptual science. In the Apps for Ancient Civilizations project, students investigate an ancient culture to discover how people might have used science and math smartphone apps to make their lives…

  2. Mobile Phone Apps for Smoking Cessation: Quality and Usability Among Smokers With Psychosis.

    Science.gov (United States)

    Ferron, Joelle C; Brunette, Mary F; Geiger, Pamela; Marsch, Lisa A; Adachi-Mejia, Anna M; Bartels, Stephen J

    2017-03-03

    Smoking is one of the top preventable causes of mortality in people with psychotic disorders such as schizophrenia. Cessation treatment improves abstinence outcomes, but access is a barrier. Mobile phone apps are one way to increase access to cessation treatment; however, whether they are usable by people with psychotic disorders, who often have special learning needs, is not known. Researchers reviewed 100 randomly selected apps for smoking cessation to rate them based on US guidelines for nicotine addiction treatment and to categorize them based on app functions. We aimed to test the usability and usefulness of the top-rated apps in 21 smokers with psychotic disorders. We identified 766 smoking cessation apps and randomly selected 100 for review. Two independent reviewers rated each app with the Adherence Index to US Clinical Practice Guideline for Treating Tobacco Use and Dependence. Then, smokers with psychotic disorders evaluated the top 9 apps within a usability testing protocol. We analyzed quantitative results using descriptive statistics and t tests. Qualitative data were open-coded and analyzed for themes. Regarding adherence to practice guidelines, most of the randomly sampled smoking cessation apps scored poorly-66% rated lower than 10 out of 100 on the Adherence Index (Mean 11.47, SD 11.8). Regarding usability, three common usability problems emerged: text-dense content, abstract symbols on the homepage, and subtle directions to edit features. In order for apps to be effective and usable for this population, developers should utilize a balance of text and simple design that facilitate ease of navigation and content comprehension that will help people learn quit smoking skills. ©Joelle C Ferron, Mary F Brunette, Pamela Geiger, Lisa A Marsch, Anna M Adachi-Mejia, Stephen J Bartels. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 03.03.2017.

  3. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  4. Assuring SS7 dependability: A robustness characterization of signaling network elements

    Science.gov (United States)

    Karmarkar, Vikram V.

    1994-04-01

    Current and evolving telecommunication services will rely on signaling network performance and reliability properties to build competitive call and connection control mechanisms under increasing demands on flexibility without compromising on quality. The dimensions of signaling dependability most often evaluated are the Rate of Call Loss and End-to-End Route Unavailability. A third dimension of dependability that captures the concern about large or catastrophic failures can be termed Network Robustness. This paper is concerned with the dependability aspects of the evolving Signaling System No. 7 (SS7) networks and attempts to strike a balance between the probabilistic and deterministic measures that must be evaluated to accomplish a risk-trend assessment to drive architecture decisions. Starting with high-level network dependability objectives and field experience with SS7 in the U.S., potential areas of growing stringency in network element (NE) dependability are identified to improve against current measures of SS7 network quality, as per-call signaling interactions increase. A sensitivity analysis is presented to highlight the impact due to imperfect coverage of duplex network component or element failures (i.e., correlated failures), to assist in the setting of requirements on NE robustness. A benefit analysis, covering several dimensions of dependability, is used to generate the domain of solutions available to the network architect in terms of network and network element fault tolerance that may be specified to meet the desired signaling quality goals.

  5. HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TNF alpha receptor associated factor 2.

    Directory of Open Access Journals (Sweden)

    Giorgio Mangino

    Full Text Available BACKGROUND: HIV-1 Nef is a virulence factor that plays multiple roles during HIV replication. Recently, it has been described that Nef intersects the CD40 signalling in macrophages, leading to modification in the pattern of secreted factors that appear able to recruit, activate and render T lymphocytes susceptible to HIV infection. The engagement of CD40 by CD40L induces the activation of different signalling cascades that require the recruitment of specific tumor necrosis factor receptor-associated factors (i.e. TRAFs. We hypothesized that TRAFs might be involved in the rapid activation of NF-κB, MAPKs and IRF-3 that were previously described in Nef-treated macrophages to induce the synthesis and secretion of proinflammatory cytokines, chemokines and IFNβ to activate STAT1, -2 and -3. METHODOLOGY/PRINCIPAL FINDINGS: Searching for possible TRAF binding sites on Nef, we found a TRAF2 consensus binding site in the AQEEEE sequence encompassing the conserved four-glutamate acidic cluster. Here we show that all the signalling effects we observed in Nef treated macrophages depend on the integrity of the acidic cluster. In addition, Nef was able to interact in vitro with TRAF2, but not TRAF6, and this interaction involved the acidic cluster. Finally silencing experiments in THP-1 monocytic cells indicate that both TRAF2 and, surprisingly, TRAF6 are required for the Nef-induced tyrosine phosphorylation of STAT1 and STAT2. CONCLUSIONS: Results reported here revealed TRAF2 as a new possible cellular interactor of Nef and highlighted that in monocytes/macrophages this viral protein is able to manipulate both the TRAF/NF-κB and TRAF/IRF-3 signalling axes, thereby inducing the synthesis of proinflammatory cytokines and chemokines as well as IFNβ.

  6. The Top Chinese Mobile Health Apps: A Systematic Investigation.

    Science.gov (United States)

    Hsu, Jeffrey; Liu, Di; Yu, Ya Min; Zhao, Hui Tong; Chen, Zhi Rou; Li, Jiao; Chen, Wei

    2016-08-29

    China's mHealth market is on track to become a global leader by industry size. The Chinese mobile app market and health care system have peculiarities that distinguish them from other app markets. To date, Chinese mHealth apps have not been systematically investigated. The objective of this study was to provide an overview of Chinese mHealth apps as of December 2015. We identified and investigated the most downloaded apps from the iOS and Android platforms. For each app, we analyzed and recorded its main service offered, mHealth initiative, disease and specialty focus, app cost, target user, Web app availability, and emphasis on information security. Standard descriptive statistics were used. A total of 234 apps met the inclusion criteria and were investigated. The apps targeting nonhealth care professionals focused on providing telemedicine and appointment-making services. The apps targeting health care professionals focused on education and peer reviewed articles. The most common disease-specific apps focused primarily on diabetes, hypertension, and hepatitis management. Most apps were free and available on both iOS and Android platforms. The primary mHealth initiatives targeted by the apps reflect Chinese patients' demand for access to medical care. Disease-specific apps are also representative of disease prevalence in China. Government press releases suggest that new policies on the horizon may shift the industry.

  7. Consumer Mobile Apps for Potential Drug-Drug Interaction Check: Systematic Review and Content Analysis Using the Mobile App Rating Scale (MARS).

    Science.gov (United States)

    Kim, Ben Yb; Sharafoddini, Anis; Tran, Nam; Wen, Emily Y; Lee, Joon

    2018-03-28

    General consumers can now easily access drug information and quickly check for potential drug-drug interactions (PDDIs) through mobile health (mHealth) apps. With aging population in Canada, more people have chronic diseases and comorbidities leading to increasing numbers of medications. The use of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and empowerment. The aim of this study was to review the characteristics and quality of publicly available mHealth apps that check for PDDIs. Apple App Store and Google Play were searched to identify apps with PDDI functionality. The apps' general and feature characteristics were extracted. The Mobile App Rating Scale (MARS) was used to assess the quality. A total of 23 apps were included for the review-12 from Apple App Store and 11 from Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD. The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS scores for the apps from Google Play and Apple App Store were not statistically different (P=.84). The information dimension was associated with the highest score (3.63), whereas the engagement dimension resulted in the lowest score (2.75). The total number of features per app, average rating, and price were significantly associated with the total MARS score. Some apps provided accurate and comprehensive information about potential adverse drug effects from PDDIs. Given the potentially severe consequences of incorrect drug information, there is a need for oversight to eliminate low quality and potentially harmful apps. Because managing PDDIs is complex in the absence of complete information, secondary features such as medication reminder, refill reminder, medication history tracking, and pill identification could help enhance the effectiveness of PDDI apps. ©Ben YB Kim, Anis Sharafoddini, Nam Tran, Emily Y Wen, Joon Lee. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.03.2018.

  8. Planet App: Kids' Book Apps Are Everywhere. But Are They Any Good?

    Science.gov (United States)

    Bird, Elizabeth

    2011-01-01

    A proper picture book app lets a parent and child read, listen to, or explore a book in a fun and interactive manner. Typical options offered in these apps include turning off the sound (so that a parent or child can read on their own), changing from one language to another, and small interactive features, such as making the characters move. To…

  9. Oceanographic data at your fingertips: the SOCIB App for smartphones

    Science.gov (United States)

    Lora, Sebastian; Sebastian, Kristian; Troupin, Charles; Pau Beltran, Joan; Frontera, Biel; Gómara, Sonia; Tintoré, Joaquín

    2015-04-01

    The Balearic Islands Coastal Ocean Observing and Forecasting System (SOCIB, http://www.socib.es), is a multi-platform Marine Research Infrastructure that generates data from nearshore to the open sea in the Western Mediterranean Sea. In line with SOCIB principles of discoverable, freely available and standardized data, an application (App) for smartphones has been designed, with the objective of providing an easy access to all the data managed by SOCIB in real-time: underwater gliders, drifters, profiling buoys, research vessel, HF Radar and numerical model outputs (hydrodynamics and waves). The Data Centre, responsible for the aquisition, processing and visualisation of all SOCIB data, developed a REpresentational State Transfer (REST) application programming interface (API) called "DataDiscovery" (http://apps.socib.es/DataDiscovery/). This API is made up of RESTful web services that provide information on : platforms, instruments, deployments of instruments. It also provides the data themselves. In this way, it is possible to integrate SOCIB data in third-party applications, developed either by the Data Center or externally. The existence of a single point for the data distribution not only allows for an efficient management but also makes easier the concepts and data access for external developers, who are not necessarily familiar with the concepts and tools related to oceanographic or atmospheric data. The SOCIB App for Android (https://play.google.com/store/apps/details?id=com.socib) uses that API as a "data backend", in such a way that it is straightforward to manage which information is shown by the application, without having to modify and upload it again. The only pieces of information that do not depend on the services are the App "Sections" and "Screens", but the content displayed in each of them is obtained through requests to the web services. The API is not used only for the smartphone app: presently, most of SOCIB applications for data visualisation

  10. Apps for Radiation Oncology. A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    J.J. Calero

    2017-02-01

    Full Text Available Introduction: Software applications executed on a smart-phone or mobile device (“Apps” are increasingly used by oncologists in their daily work. A comprehensive critical review was conducted on Apps specifically designed for Radiation Oncology, which aims to provide scientific support for these tools and to guide users in choosing the most suited to their needs. Material and methods: A systematic search was conducted in mobile platforms, iOS and Android, returning 157 Apps. Excluding those whose purpose did not match the scope of the study, 31 Apps were methodically analyzed by the following items: Objective Features, List of Functionalities, Consistency in Outcomes and Usability. Results: Apps are presented in groups of features, as Dose Calculators (7 Apps, Clinical Calculators (4, Tools for Staging (7, Multipurpose (7 and Others (6. Each App is presented with the list of attributes and a brief comment. A short summary is provided at the end of each group. Discussion and Recommendations: There are numerous Apps with useful tools at the disposal of radiation oncologists. The most advisable Apps do not match the more expensive. Three all-in-one apps seem advisable above all: RadOnc Reference (in English, Easy Oncology (in German and iOncoR (in Spanish. Others recommendations are suggested for specific tasks: dose calculators, treatment-decision and staging.

  11. Stromal Adipocyte Enhancer-binding Protein (AEBP1) Promotes Mammary Epithelial Cell Hyperplasia via Proinflammatory and Hedgehog Signaling*

    Science.gov (United States)

    Holloway, Ryan W.; Bogachev, Oleg; Bharadwaj, Alamelu G.; McCluskey, Greg D.; Majdalawieh, Amin F.; Zhang, Lei; Ro, Hyo-Sung

    2012-01-01

    Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1TG) mice, and the onset of ductal hyperplasia was accelerated in AEBP1TG mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1TG bone marrow cells into non-transgenic (AEBP1NT) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1TG mammary macrophages and epithelium. Shh expression was induced in AEBP1TG macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1TG mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1TG peritoneal macrophages. The conditioned AEBP1TG macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1TG macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis. PMID:22995915

  12. Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling.

    Science.gov (United States)

    Holloway, Ryan W; Bogachev, Oleg; Bharadwaj, Alamelu G; McCluskey, Greg D; Majdalawieh, Amin F; Zhang, Lei; Ro, Hyo-Sung

    2012-11-09

    Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1(TG)) mice, and the onset of ductal hyperplasia was accelerated in AEBP1(TG) mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1(TG) bone marrow cells into non-transgenic (AEBP1(NT)) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1(TG) mammary macrophages and epithelium. Shh expression was induced in AEBP1(TG) macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1(TG) mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1(TG) peritoneal macrophages. The conditioned AEBP1(TG) macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1(TG) macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis.

  13. Sencha Architect app development

    CERN Document Server

    Groner, Loiane

    2013-01-01

    A standard tutorial-based approach for using Sencha Architect to develop applications in Ext JS and Sencha Touch.Sencha Architect App Development is for Ext JS and Sencha Touch developers that are looking to improve their productivity by using Sencha Architect for app development. Basic knowledge of Ext JS and Sencha Touch is required.

  14. A review of mobile apps for epilepsy self-management.

    Science.gov (United States)

    Escoffery, Cam; McGee, Robin; Bidwell, Jonathan; Sims, Christopher; Thropp, Eliana Kovitch; Frazier, Cherise; Mynatt, Elizabeth D

    2018-04-01

    Mobile health app developers increasingly are interested in supporting the daily self-care of people with chronic conditions. The purpose of this study was to review mobile applications (apps) to promote epilepsy self-management. It investigates the following: 1) the available mobile apps for epilepsy, 2) how these apps support patient education and self-management (SM), and 3) their usefulness in supporting management of epilepsy. We conducted the review in Fall 2017 and assessed apps on the Apple App Store that related to the terms "epilepsy" and "seizure". Inclusion criteria included apps (adult and pediatric) that, as follows, were: 1) developed for patients or the community; 2) made available in English, and 3) less than $5.00. Exclusion criteria included apps that were designed for dissemination of publications, focused on healthcare providers, or were available in other languages. The search resulted in 149 apps, of which 20 met the selection criteria. A team reviewed each app in terms of three sets of criteria: 1) epilepsy-specific descriptions and SM categories employed by the apps and 2) Mobile App Rating Scale (MARS) subdomain scores for reviewing engagement, functionality, esthetics, and information; and 3) behavioral change techniques. Most apps were for adults and free. Common SM domains for the apps were treatment, seizure tracking, response, and safety. A number of epilepsy apps existed, but many offered similar functionalities and incorporated few SM domains. The findings underline the need for mobile apps to cover broader domains of SM and behavioral change techniques and to be evaluated for outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Building Web Apps for Google TV

    CERN Document Server

    Ferrate, Andres; Lee, Daniels; Ohye, Maile; Carff, Paul; Shen, Shawn; Hines, Steven

    2011-01-01

    By integrating the Web with traditional TV, Google TV offers developers an important new channel for content. But creating apps for Google TV requires learning some new skills-in fact, what you may already know about mobile or desktop web apps isn't entirely applicable. Building Web Apps for Google TV will help you make the transition to Google TV as you learn the tools and techniques necessary to build sophisticated web apps for this platform. This book shows you how Google TV works, how it fits into the web ecosystem, and what the opportunities are for delivering rich content to millions o

  16. Long-time treatment by low-dose N-acetyl-L-cysteine enhances proinflammatory cytokine expressions in LPS-stimulated macrophages.

    Directory of Open Access Journals (Sweden)

    Tomokazu Ohnishi

    Full Text Available N-acetyl-L-cysteine is known to act as a reactive oxygen species scavenger and used in clinical applications. Previous reports have shown that high-dose N-acetyl-L-cysteine treatment inhibits the expression of proinflammatory cytokines in activated macrophages. Here, we have found that long-time N-acetyl-L-cysteine treatment at low-concentration increases phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, which are essential for the induction of proinflammatory cytokines including interleukin 1β and interleukin 6 in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, long-time N-acetyl-L-cysteine treatment decreases expressions of protein phosphatases, catalytic subunit of protein phosphatase-2A and dual specificity phosphatase 1. On the other hand, we have found that short-time N-acetyl-L-cysteine treatment at low dose increases p53 expression, which inhibits expressions of proinflammatory cytokines. These observations suggest that long-time low-dose N-acetyl-L-cysteine treatment increases expressions of proinflammatory cytokines through enhancement of kinase phosphorylation.

  17. Mobile Apps for Self-Injury: A Content Analysis.

    Science.gov (United States)

    Vieira, Aaron M; Lewis, Stephen P

    2018-05-01

    A growing body of research points to the salience of the Internet and mobile material among individuals who self-injure. However, to date, no research has investigated the mobile apps related to nonsuicidal self-injury (NSSI). Such information would clarify which apps may be useful for those who self-injure while highlighting whether app-related content warrants improvement. The current study examined the content and usability of NSSI apps available on the two largest app-related platforms (Google Play and iTunes). Using content analysis, apps were examined regarding their content (e.g., presence of NSSI myths and types of coping strategies) as well as usability (e.g., app performance). Results indicate that NSSI apps have varied content, with few developed by, or affiliated with, a trusted source (e.g., university). NSSI apps tend to not propagate NSSI myths that vary with respect to the quality of coping strategies offered. They also tend to be rated favorably in terms of their usability. Overall, the present findings add to the NSSI literature and highlight several implications and avenues for future work, which are discussed.

  18. A Novel Approach for Designing Mobile Native Apps

    Directory of Open Access Journals (Sweden)

    Sasmita Pani

    2017-01-01

    Full Text Available Mobile devices are differed from desktop based systems in terms of particular execution environment, constrained resources, and high mobility requirement. To overcome these shortcomings, various agile based methodologies are developed for native mobile applications such as Mobile-D, Scrum etc. These agile techniques are based on various phases and these phases begin from exploring, initializing and implementing the mobile apps. But these techniques are not focusing on elaborating design model for mobile native apps. The aim of the paper is to provide a layered approach or layered model for design of mobile native apps which can be used as a framework for developing mobile native apps. Any mobile native app developer can use this sequential approach or design model for design and development of mobile native apps. This design model gives a standard or framework, based on which generic native mobile apps can be designed and developed. This paper also shows an empirical analysis among the web app design models with the proposed design model for mobile native app development.

  19. Forensic Taxonomy of Android Social Apps.

    Science.gov (United States)

    Azfar, Abdullah; Choo, Kim-Kwang Raymond; Liu, Lin

    2017-03-01

    An Android social app taxonomy incorporating artifacts that are of forensic interest will enable users and forensic investigators to identify the personally identifiable information (PII) stored by the apps. In this study, 30 popular Android social apps were examined. Artifacts of forensic interest (e.g., contacts lists, chronology of messages, and timestamp of an added contact) were recovered. In addition, images were located, and Facebook token strings used to tie account identities and gain access to information entered into Facebook by a user were identified. Based on the findings, a two-dimensional taxonomy of the forensic artifacts of the social apps is proposed. A comparative summary of existing forensic taxonomies of different categories of Android apps, designed to facilitate timely collection and analysis of evidentiary materials from Android devices, is presented. © 2016 American Academy of Forensic Sciences.

  20. The best 100 free apps for libraries

    CERN Document Server

    Hahn, Jim

    2013-01-01

    Librarian Jim Hahn has carefully culled the over 500,000 available apps down to the 100 that are the absolute best for day-in, day-out library services. The guide covers apps from both Apple and Android devices, including tablets. This guide is intended as an introduction for those with little or no app experience and for those wanting to know more about app uses for information access.

  1. Mobile Apps for Librarians

    Science.gov (United States)

    Power, June L.

    2013-01-01

    In an increasing mobile environment, library and reading-related activities often take place on a phone or tablet device. Not only does this mean that library Web sites must keep mobile navigability in mind, but also develop and utilize apps that allow patrons to interact with information and with libraries. While apps do not serve every purpose,…

  2. Popularity Modeling for Mobile Apps: A Sequential Approach.

    Science.gov (United States)

    Zhu, Hengshu; Liu, Chuanren; Ge, Yong; Xiong, Hui; Chen, Enhong

    2015-07-01

    The popularity information in App stores, such as chart rankings, user ratings, and user reviews, provides an unprecedented opportunity to understand user experiences with mobile Apps, learn the process of adoption of mobile Apps, and thus enables better mobile App services. While the importance of popularity information is well recognized in the literature, the use of the popularity information for mobile App services is still fragmented and under-explored. To this end, in this paper, we propose a sequential approach based on hidden Markov model (HMM) for modeling the popularity information of mobile Apps toward mobile App services. Specifically, we first propose a popularity based HMM (PHMM) to model the sequences of the heterogeneous popularity observations of mobile Apps. Then, we introduce a bipartite based method to precluster the popularity observations. This can help to learn the parameters and initial values of the PHMM efficiently. Furthermore, we demonstrate that the PHMM is a general model and can be applicable for various mobile App services, such as trend based App recommendation, rating and review spam detection, and ranking fraud detection. Finally, we validate our approach on two real-world data sets collected from the Apple Appstore. Experimental results clearly validate both the effectiveness and efficiency of the proposed popularity modeling approach.

  3. Mobile app reading speed test.

    Science.gov (United States)

    Kingsnorth, Alec; Wolffsohn, James S

    2015-04-01

    To validate the accuracy and repeatability of a mobile app reading speed test compared with the traditional paper version. Twenty-one subjects wearing their full refractive correction glasses read 14 sentences of decreasing print size between 1.0 and -0.1 logMAR, each consisting of 14 words (Radner reading speed test) at 40 cm with a paper-based chart and twice on iPad charts. Time duration was recorded with a stop watch for the paper chart and on the App itself for the mobile chart allowing critical print size (CPS) and optimal reading speed (ORS) to be derived objectively. The ORS was higher for the mobile app charts (194±29 wpm; 195±25 wpm) compared with the paper chart (166±20 wpm; F=57.000, pmobile app charts (0.17±0.20 logMAR; 0.18±0.17 logMAR) compared with the paper chart (0.25±0.17 logMAR; F=5.406, p=0.009). The mobile app test had a mean difference repeatability of 0.30±22.5 wpm, r=0.917 for ORS, and a CPS of 0.0±0.2 logMAR, r=0.769. Repeatability of the app reading speed test is as good (ORS) or better (CPS) than previous studies on the paper test. While the results are not interchangeable with paper-based charts, mobile app tablet-based tests of reading speed are reliable and rapid to perform, with the potential to capture functional visual ability in research studies and clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Creating iPhone Apps with Cocoa Touch

    CERN Document Server

    Hockenberry, Craig

    2010-01-01

    Creating iPhone Apps with Cocoa Touch: The Mini Missing Manual walks you through developing your first iPhone App and introduces you to your programming environments and tools: Cocoa Touch, Interface Builder, Xcode, and the Objective-C programming language. If you're a Java or C developer, this eBook is your fast track to App development. This eBook is adapted from parts of iPhone App Development: The Missing Manual.

  5. APP transgenic mice for modelling behavioral and psychological symptoms of dementia (BPSD)

    Science.gov (United States)

    Lalonde, R.; Fukuchi, K.; Strazielle, C.

    2012-01-01

    The discovery of gene mutations responsible for autosomal dominant Alzheimer's disease has enabled researchers to reproduce in transgenic mice several hallmarks of this disorder, notably Aβ accumulation, though in most cases without neurofibrillary tangles. Mice expressing mutated and wild-type APP as well as C-terminal fragments of APP exhibit variations in exploratory activity reminiscent of behavioral and psychological symptoms of Alzeimer dementia (BPSD). In particular, open-field, spontaneous alternation, and elevated plus-maze tasks as well as aggression are modified in several APP transgenic mice relative to non-transgenic controls. However, depending on the precise murine models, changes in open-field and elevated plus-maze exploration occur in either direction, either increased or decreased relative to controls. It remains to be determined which neurotransmitter changes are responsible for this variability, in particular with respect to GABA, 5HT, and dopamine. PMID:22373961

  6. Human resistin stimulates the pro-inflammatory cytokines TNF-α and IL-12 in macrophages by NF-κB-dependent pathway

    International Nuclear Information System (INIS)

    Silswal, Nirupama; Singh, Anil K.; Aruna, Battu; Mukhopadhyay, Sangita; Ghosh, Sudip; Ehtesham, Nasreen Z.

    2005-01-01

    Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-α and IL-12, similar to that obtained using 5 μg/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-κB transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-α in U937 cells by hResistin was markedly reduced in the presence of either dominant negative IκBα plasmid or PDTC, a pharmacological inhibitor of NF-κB. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications

  7. Spatial Navigation in Complex and Radial Mazes in APP23 Animals and Neurotrophin Signaling as a Biological Marker of Early Impairment

    Science.gov (United States)

    Hellweg, Rainer; Huber, Roman; Kuhl, Alexander; Riepe, Matthias W.; Lohmann, Peter

    2006-01-01

    Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease(AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse…

  8. Signaling induced by hop/STI-1 depends on endocytosis

    International Nuclear Information System (INIS)

    Americo, Tatiana A.; Chiarini, Luciana B.; Linden, Rafael

    2007-01-01

    The co-chaperone hop/STI-1 is a ligand of the cell surface prion protein (PrP C ), and their interaction leads to signaling and biological effects. Among these, hop/STI-1 induces proliferation of A172 glioblastoma cells, dependent on both PrP C and activation of the Erk pathway. We tested whether clathrin-mediated endocytosis affects signaling induced by hop/STI-1. Both hyperosmolarity induced by sucrose and monodansyl-cadaverine blocked Erk activity induced by hop/STI-1, without affecting the high basal Akt activity typical of A172. The endocytosis inhibitors also affected the sub-cellular distribution of phosphorylated Erk, consistent with blockade of the latter's activity. The data indicate that signaling induced by hop/STI-1 depends on endocytosis. These findings are consistent with a role of sub-cellular trafficking in signal transduction following engagement by PrP C by ligands such as hop/STI-1, and may help help unravel both the functions of the prion protein, as well as possible loss-of-function components of prion diseases

  9. CSS for Windows 8 app development

    CERN Document Server

    Foster, Jeremy

    2013-01-01

    CSS for Windows 8 App Development is your learning guide for CSS - the language of great Windows 8-style apps. Learn the built-in styles that make the built-in controls shine, how to define them, and how to use CSS to give your custom app assets that beautiful Modern UI style. CSS (Cascading Style Sheets) is the clear standard for styling web applications, and with HTML, CSS, and JavaScript now powering apps on Windows 8, it's the clear standard there as well. CSS is a powerful styling and layout language that greatly simplifies the selection of page elements and their visual display, layout,

  10. iOS app development for dummies

    CERN Document Server

    Feiler, Jesse

    2014-01-01

    If you've got incredible iOS ideas, get this book and bring them to life! iOS 7 represents the most significant update to Apple's mobile operating system since the first iPhone was released, and even the most seasoned app developers are looking for information on how to take advantage of the latest iOS 7 features in their app designs. That's where iOS App Development For Dummies comes in! Whether you're a programming hobbyist wanting to build an app for fun or a professional developer looking to expand into the iOS market, this book will walk you through the fundamentals of building a univer

  11. Composite Social Network for Predicting Mobile Apps Installation

    Science.gov (United States)

    2011-06-02

    Social network tools (such as the Facebook app and the Twitter app) can observe users’ online friendship network . In this work, our key idea is...the friendship network from phones by collecting data from social networking apps such as the Facebook and Twitter apps. We summarize all the networks ...ar X iv :1 10 6. 03 59 v1 [ cs .S I] 2 J un 2 01 1 Composite Social Network for Predicting Mobile Apps Installation Wei Pan

  12. Cuisine Ireland 'APP'

    OpenAIRE

    Seberry, Dermot

    2014-01-01

    Description Cuisine Ireland contains 15 samplerecipes from renowned Irish chef and author Dermot Seberry. Taking you to the heart of ancient Ireland, from the most northern beauty of the Mourne & Cooley peninsula along the magnificent east coastline and across to the Boyne Valley, the focus of this app is on the very best the region has to offer food tourists and local chefs. This app was developed as a companion piece to Dermot’s new book “Ireland, A Culinary Journey of the North East”. T...

  13. Analyzing Android Browser Apps for file:// Vulnerabilities

    OpenAIRE

    Wu, Daoyuan; Chang, Rocky K. C.

    2014-01-01

    Securing browsers in mobile devices is very challenging, because these browser apps usually provide browsing services to other apps in the same device. A malicious app installed in a device can potentially obtain sensitive information through a browser app. In this paper, we identify four types of attacks in Android, collectively known as FileCross, that exploits the vulnerable file:// to obtain users' private files, such as cookies, bookmarks, and browsing histories. We design an automated s...

  14. Chitosan drives anti-inflammatory macrophage polarisation and pro-inflammatory dendritic cell stimulation

    Directory of Open Access Journals (Sweden)

    MI Oliveira

    2012-07-01

    Full Text Available Macrophages and dendritic cells (DC share the same precursor and play key roles in immunity. Modulation of their behaviour to achieve an optimal host response towards an implanted device is still a challenge. Here we compare the differentiation process and polarisation of these related cell populations and show that they exhibit different responses to chitosan (Ch, with human monocyte-derived macrophages polarising towards an anti-inflammatory phenotype while their DC counterparts display pro-inflammatory features. Macrophages and DC, whose interactions with biomaterials are frequently analysed using fully differentiated cells, were cultured directly on Ch films, rather than exposed to the polymer after complete differentiation. Ch was the sole stimulating factor and activated both macrophages and DC, without leading to significant T cell proliferation. After 10 d on Ch, macrophages significantly down-regulated expression of pro-inflammatory markers, CD86 and MHCII. Production of pro-inflammatory cytokines, particularly TNF-α, decreased with time for cells cultured on Ch, while anti-inflammatory IL-10 and TGF-β1, significantly increased. Altogether, these results suggest an M2c polarisation. Also, macrophage matrix metalloproteinase activity was augmented and cell motility was stimulated by Ch. Conversely, DC significantly enhanced CD86 expression, reduced IL-10 secretion and increased TNF-α and IL-1β levels. Our findings indicate that cells with a common precursor may display different responses, when challenged by the same biomaterial. Moreover, they help to further comprehend macrophage/DC interactions with Ch and the balance between pro- and anti-inflammatory signals associated with implant biomaterials. We propose that an overall pro-inflammatory reaction may hide the expression of anti-inflammatory cytokines, likely relevant for tissue repair/regeneration.

  15. Linear motif atlas for phosphorylation-dependent signaling

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Jensen, LJ; Diella, F

    2008-01-01

    bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14-3-3]. The atlas reveals new aspects of signaling...

  16. Just a fad? Gamification in health and fitness apps.

    Science.gov (United States)

    Lister, Cameron; West, Joshua H; Cannon, Ben; Sax, Tyler; Brodegard, David

    2014-08-04

    Gamification has been a predominant focus of the health app industry in recent years. However, to our knowledge, there has yet to be a review of gamification elements in relation to health behavior constructs, or insight into the true proliferation of gamification in health apps. The objective of this study was to identify the extent to which gamification is used in health apps, and analyze gamification of health and fitness apps as a potential component of influence on a consumer's health behavior. An analysis of health and fitness apps related to physical activity and diet was conducted among apps in the Apple App Store in the winter of 2014. This analysis reviewed a sample of 132 apps for the 10 effective game elements, the 6 core components of health gamification, and 13 core health behavior constructs. A regression analysis was conducted in order to measure the correlation between health behavior constructs, gamification components, and effective game elements. This review of the most popular apps showed widespread use of gamification principles, but low adherence to any professional guidelines or industry standard. Regression analysis showed that game elements were associated with gamification (Pgamification (Pgamification was only associated with composite motivational behavior scores (Pgamification use in health and fitness apps, and the potential to impact health behavior. The results show that use of gamification in health and fitness apps has become immensely popular, as evidenced by the number of apps found in the Apple App Store containing at least some components of gamification. This shows a lack of integrating important elements of behavioral theory from the app industry, which can potentially impact the efficacy of gamification apps to change behavior. Apps represent a very promising, burgeoning market and landscape in which to disseminate health behavior change interventions. Initial results show an abundant use of gamification in health and

  17. Evaluating the Dietary and Nutritional Apps in the Google Play Store.

    Science.gov (United States)

    Schumer, Harleigh; Amadi, Chioma; Joshi, Ashish

    2018-01-01

    The objective of this study was to evaluate the features of diet and nutrition apps available in the Google Play Store. A search was conducted in August 2017 using the Google Play Store database to identify apps related to diet and nutrition. Terms entered into the app search engine included 'diet apps' and 'nutrition apps'. The first 50 apps resulting from each search term was assessed. Duplicates were removed, and a comparative analysis was performed on the remaining diet and nutrition apps. A total of 86 diet and nutrition apps were identified. One hundred percent (n = 86) of the apps retrieved were freely available. More than half of the apps were applicable to a target user group of all ages (94%, n = 81). Stratified analysis across unique diet and nutrition apps (total, n = 72) showed a higher average rating for the diet apps (4.4) in comparison to that for the nutrition apps (4.3). Diet apps were more likely to be recently updated than the nutrition apps (72% vs. 66%), and diet apps were more likely to feature app purchase than nutrition apps (36% vs. 19%). The average rating was slightly higher for diet apps not featuring in-app purchases, but ratings were similar for the nutrition apps. A centralized resource is needed that can provide information on health-related apps to allow for systematic evaluation of their effectiveness. Further research needs to examine improved methods of designing app-store platforms and presenting the available apps to properly guide users in app selection.

  18. Mindfulness-Based Symptom and Stress Management Apps for Adults With Chronic Lung Disease: Systematic Search in App Stores.

    Science.gov (United States)

    Owens, Otis L; Beer, Jenay M; Reyes, Ligia I; Gallerani, David G; Myhren-Bennett, Amanda R; McDonnell, Karen K

    2018-05-15

    Up to 70% of lung cancer survivors are affected by chronic obstructive pulmonary disease (COPD), a common, debilitating, comorbid disease. Lung cancer and COPD are both characterized by symptoms such as breathlessness, fatigue, and psychological distress. These distressing chronic symptoms are exacerbated by stress and detract from an individual's quality of life. The aim of this study was to identify and evaluate evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a COPD or lung cancer history (ie, chronic lung disease). For this review, an interdisciplinary research team used 19 keyword combinations in the search engines of Google and iOS app stores in May 2017. Evaluations were conducted on the apps' (1) content, (2) usability heuristics, (3) grade-level readability, and (4) cultural sensitivity. The search resulted in 768 apps (508 in iOS and 260 in Google stores). A total of 9 apps met the inclusion criteria and received further evaluation. Only 1 app had below an eighth-grade reading level; the ninth one did not have enough text to calculate a readability score. None of the 9 apps met the cultural sensitivity evaluation criteria. This systematic review identified critical design flaws that may affect the ease of using the apps in this study. Few mobile apps promote mindfulness-based strategies among adults with chronic lung disease (ie, COPD or lung cancer or both), but those that exist, overall, do not meet the latest scientific evidence. Recommendations include more stringent regulation of health-related apps, use of evidence-based frameworks and participatory design processes, following evidence-based usability practices, use of culturally sensitive language and images, and ensuring that content is written in plain language. ©Otis L Owens, Jenay M Beer, Ligia I Reyes, David G Gallerani, Amanda R Myhren-Bennett, Karen K McDonnell. Originally published in JMIR Mhealth and Uhealth (http

  19. Angular dependence of Auger signals from a GaAs (111) surface

    International Nuclear Information System (INIS)

    Barnard, W.O.

    1984-03-01

    This dissertation is concerned with the angular dependence of the L 3 M 4 M 4 1067 eV Ga and L 3 M 4 M 4 1228 eV As Auger electron signals from a (111) GaAs surface, using a system which is equipped with a cylindrical mirror analyser. Following a detailed discussion of the Auger process, a review is given of angular effects in the emission excitation and detection of Auger signals. Present theories are discussed and an empirical theory is developed to test the experimental results obtained in this study. The experimental procedures and equipment used are presented. It was found that the Auger signals show a strong variation with the angle of rotation about the normal of a GaAs surface. Furthermore, the nature of the angular spectra of the Ga and As signals are interchanged when the electron beam incident surface is changed from (111) to (111). The main features of the angular variation of the quasi-elastic backscattered signal is reflected in the corresponding Ga and As Auger angular spectra. The angular dependence of the quasi-elastic backscattered signal can be explained semi-quantitatively in terms of the empirical theory. Theoretical arguments are presented which suggest that the Auger signals should show an angular dependence similar to the quasi-elastic backscattered signal. Evidence was found that geometric screening-off of underlying atoms by surface and near surface atoms influence the Auger yield

  20. Attention Deficit Hyperactivity Disorder: Is There an App for That? Suitability Assessment of Apps for Children and Young People With ADHD.

    Science.gov (United States)

    Powell, Lauren; Parker, Jack; Robertson, Naomi; Harpin, Valerie

    2017-10-04

    Attention-deficit/hyperactivity disorder (ADHD) is a complex highly comorbid disorder, which can have a huge impact on those with ADHD, their family, and the community around them. ADHD is currently managed using pharmacological and nonpharmacological interventions. However, with advances in technology and an increase in the use of mobile apps, managing ADHD can be augmented using apps specifically designed for this population. However, little is known regarding the suitability and usability of currently available apps. The aim of this study was to explore the suitability of the top 10 listed apps for children and young people with ADHD and clinicians who work with them. It is hypothesized that mobile apps designed for this population could be more suitably designed for this population. The top 10 listed apps that are specifically targeted toward children and young people with ADHD in the United Kingdom were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 5 clinicians who specialize in treating this population and 5 children and young people with ADHD themselves, to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable for this population. Five themes emerged from clinician and young people interviews: the accessibility of the technology, the importance of relating to apps, addressing ADHD symptoms and related difficulties, age appropriateness, and app interaction. Three additional themes emerged from the clinician interviews alone: monitoring symptoms, side effects and app effect on relationships, and the impact of common comorbid conditions. The characteristics of the apps did not appear to match well with the views of our sample. These findings suggest that the apps may not be suitable in meeting the complex needs associated with this condition. Further research is required to explore the value of apps for children and young people with ADHD and

  1. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK.

    Directory of Open Access Journals (Sweden)

    Steve Pedrini

    2005-01-01

    Full Text Available Statins are widely used cholesterol-lowering drugs that act by inhibiting HMGCoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent evidence suggests that statin use may be associated with a decreased risk for Alzheimer disease, although the mechanisms underlying this apparent risk reduction are poorly understood. One popular hypothesis for statin action is related to the drugs' ability to activate alpha-secretase-type shedding of the alpha-secretase-cleaved soluble Alzheimer amyloid precursor protein ectodomain (sAPP(alpha. Statins also inhibit the isoprenoid pathway, thereby modulating the activities of the Rho family of small GTPases-Rho A, B, and C-as well as the activities of Rac and cdc42. Rho proteins, in turn, exert many of their effects via Rho-associated protein kinases (ROCKs. Several cell-surface molecules are substrates for activated alpha-secretase-type ectodomain shedding, and regulation of shedding typically occurs via activation of protein kinase C or extracellular-signal-regulated protein kinases, or via inactivation of protein phosphatase 1 or 2A. However, the possibility that these enzymes play a role in statin-stimulated shedding has been excluded, leading us to investigate whether the Rho/ROCK1 protein phosphorylation pathway might be involved.We found that both atorvastatin and simvastatin stimulated sAPP(alpha shedding from a neuroblastoma cell line via a subcellular mechanism apparently located upstream of endocytosis. A farnesyl transferase inhibitor also increased sAPP(alpha shedding, as did a dominant negative form of ROCK1. Most conclusively, a constitutively active ROCK1 molecule inhibited statin-stimulated sAPP(alpha shedding.Together, these data suggest that statins exert their effects on shedding of sAPP(alpha from cultured cells, at least in part, by modulation of the isoprenoid pathway and ROCK1.

  2. Security Concerns in Android mHealth Apps

    OpenAIRE

    He, Dongjing; Naveed, Muhammad; Gunter, Carl A.; Nahrstedt, Klara

    2014-01-01

    Mobile Health (mHealth) applications lie outside of regulatory protection such as HIPAA, which requires a baseline of privacy and security protections appropriate to sensitive medical data. However, mHealth apps, particularly those in the app stores for iOS and Android, are increasingly handling sensitive data for both professionals and patients. This paper presents a series of three studies of the mHealth apps in Google Play that show that mHealth apps make widespread use of unsecured Intern...

  3. Turnover of amyloid precursor protein family members determines their nuclear signaling capability.

    Science.gov (United States)

    Gersbacher, Manuel T; Goodger, Zoë V; Trutzel, Annette; Bundschuh, Diana; Nitsch, Roger M; Konietzko, Uwe

    2013-01-01

    The amyloid precursor protein (APP) as well as its homologues, APP-like protein 1 and 2 (APLP1 and APLP2), are cleaved by α-, β-, and γ-secretases, resulting in the release of their intracellular domains (ICDs). We have shown that the APP intracellular domain (AICD) is transported to the nucleus by Fe65 where they jointly bind the histone acetyltransferase Tip60 and localize to spherical nuclear complexes (AFT complexes), which are thought to be sites of transcription. We have now analyzed the subcellular localization and turnover of the APP family members. Similarly to AICD, the ICD of APLP2 localizes to spherical nuclear complexes together with Fe65 and Tip60. In contrast, the ICD of APLP1, despite binding to Fe65, does not translocate to the nucleus. In addition, APLP1 predominantly localizes to the plasma membrane, whereas APP and APLP2 are detected in vesicular structures. APLP1 also demonstrates a much slower turnover of the full-length protein compared to APP and APLP2. We further show that the ICDs of all APP family members are degraded by the proteasome and that the N-terminal amino acids of ICDs determine ICD degradation rate. Together, our results suggest that different nuclear signaling capabilities of APP family members are due to different rates of full-length protein processing and ICD proteasomal degradation. Our results provide evidence in support of a common nuclear signaling function for APP and APLP2 that is absent in APLP1, but suggest that APLP1 has a regulatory role in the nuclear translocation of APP family ICDs due to the sequestration of Fe65.

  4. Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

    Science.gov (United States)

    Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

    2016-01-01

    Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

  5. Instant Citrix XenApp

    CERN Document Server

    Mallett, Andrew

    2013-01-01

    Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks. This book is a great tool to quickly learn and explore the features offered by XenApp 6.5.Windows system administrators who want a quick lesson on how to install and configure XenApp.

  6. Adherence to evidence-based guidelines among diabetes self-management apps.

    Science.gov (United States)

    Breland, Jessica Y; Yeh, Vivian M; Yu, Jessica

    2013-09-01

    Smartphone apps can provide real-time, interactive self-management aid to individuals with diabetes. It is currently unclear whether existing diabetes self-management apps follow evidence-based guidelines. The purpose of this study was to evaluate the extent to which existing diabetes self-management apps address the seven self-management behaviors recommended by the American Association of Diabetes Educators (the AADE7™). The term "diabetes" identified relevant self-management apps via the Apple App Store search engine in March 2012. Ratings were based on app descriptions and downloads. Chi-square analyses assessed differences in apps based on developer type. Apps promoted a median of two AADE7™ skills. Overall reliability between description and download ratings was good (kappa = .66). Reliability of individual skills was variable (kappa = .25 to .91). Most diabetes apps do not conform to evidence-based recommendations, and future app reviews would benefit from testing app performance. Future apps may also benefit from theory-based designs.

  7. iPad apps for orthopedic surgeons.

    Science.gov (United States)

    Franko, Orrin I; Bhola, Siddharth

    2011-12-01

    The development and distribution of mobile applications, or apps, designed for medical professionals and patients is quickly expanding, and within this group are apps designed specifically for orthopedic use. Currently, the most popular mobile apps are sponsored by private companies and focus on delivering device-specific information. If this trend toward the use of privately funded educational materials continues, regulations may need to be established to ensure that the information provided is accurate, honest, and supported by peer-reviewed literature. It will likely be the responsibility of the orthopedic community to ensure that the development and use of these apps has appropriate oversight and validation as they are incorporated into clinical practice and training. Copyright © 2011, SLACK Incorporated.

  8. Angiopoietin-like protein 2 induces proinflammatory responses in peritoneal cells

    Energy Technology Data Exchange (ETDEWEB)

    Umikawa, Masato, E-mail: umikawa@med.u-ryukyu.ac.jp [Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa (Japan); Umikawa, Asako; Asato, Tsuyoshi; Takei, Kimiko [Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa (Japan); Matsuzaki, Goro [Department of Tropical Infectious Diseases, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa (Japan); Kariya, Ken-ichi [Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa (Japan); Zhang, Cheng Cheng, E-mail: alec.zhang@utsouthwestern.edu [Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX (United States)

    2015-11-13

    Monocytes and macrophages are important effectors and regulators of inflammation, and both their differentiation and activation are regulated strictly in response to environmental cues. Angiopoietin-like protein 2 (Angptl2) is a multifaceted protein, displaying many physiological and pathological functions in inflammation, angiogenesis, hematopoiesis, and tumor development. Although recent studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation caused by Angptl2 remain unclear. The purpose of the present study was to elucidate the role of Angptl2 in inflammation by understanding the effects of Angptl2 on monocytes/macrophages. We showed that Angptl2 directly activates resident murine peritoneal monocytes and macrophages and induces a drastic upregulation of the transcription of several inflammatory genes including nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, and several proinflammatory cytokine genes such as interleukin (IL)-1β, IL-6, TNFα, and CSF2, along with activation of ERK, JNK, p38, and nuclear factor kappa B signaling pathways. Concordantly, proinflammatory cytokines IL-1β, IL-6, TNFα, and GM-CSF, were rapidly elevated from murine peritoneal monocytes and macrophages. These results demonstrate a novel role for Angptl2 in inflammation via the direct activation of peritoneal monocytes and macrophages. - Highlights: • Angptl2 directly activates resident murine peritoneal monocytes and macrophages. • Angptl2 induces a drastic upregulation of expression of inflammatory genes. • Angptl2 induces activation of ERK, JNK, p38, and nuclear factor kappa B signaling pathways. • Angptl2 does not activate bone marrow derived macrophages or macrophage cell lines.

  9. L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Xiang-Zhu Xie

    2016-01-01

    Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

  10. Android app development for dummies

    CERN Document Server

    Burton, Michael

    2015-01-01

    The updated edition of the bestselling guide to Android app development If you have ambitions to build an Android app, this hands-on guide gives you everything you need to dig into the development process and turn your great idea into a reality! In this new edition of Android App Development For Dummies, you'll find easy-to-follow access to the latest programming techniques that take advantage of the new features of the Android operating system. Plus, two programs are provided: a simple program to get you started and an intermediate program that uses more advanced aspects of the Android plat

  11. Interaction between Ebola Virus Glycoprotein and Host Toll-Like Receptor 4 Leads to Induction of Proinflammatory Cytokines and SOCS1 ▿ †

    OpenAIRE

    Okumura, Atsushi; Pitha, Paula M.; Yoshimura, Akihiko; Harty, Ronald N.

    2009-01-01

    Ebola virus initially targets monocytes and macrophages, which can lead to the release of proinflammatory cytokines and chemokines. These inflammatory cytokines are thought to contribute to the development of circulatory shock seen in fatal Ebola virus infections. Here we report that host Toll-like receptor 4 (TLR4) is a sensor for Ebola virus glycoprotein (GP) on virus-like particles (VLPs) and that resultant TLR4 signaling pathways lead to the production of proinflammatory cytokines and sup...

  12. Signal-dependent independent component analysis by tunable mother wavelets

    International Nuclear Information System (INIS)

    Seo, Kyung Ho

    2006-02-01

    The objective of this study is to improve the standard independent component analysis when applied to real-world signals. Independent component analysis starts from the assumption that signals from different physical sources are statistically independent. But real-world signals such as EEG, ECG, MEG, and fMRI signals are not statistically independent perfectly. By definition, standard independent component analysis algorithms are not able to estimate statistically dependent sources, that is, when the assumption of independence does not hold. Therefore before independent component analysis, some preprocessing stage is needed. This paper started from simple intuition that wavelet transformed source signals by 'well-tuned' mother wavelet will be simplified sufficiently, and then the source separation will show better results. By the correlation coefficient method, the tuning process between source signal and tunable mother wavelet was executed. Gamma component of raw EEG signal was set to target signal, and wavelet transform was executed by tuned mother wavelet and standard mother wavelets. Simulation results by these wavelets was shown

  13. Mobile Apps for Weight Management: A Scoping Review.

    Science.gov (United States)

    Rivera, Jordan; McPherson, Amy; Hamilton, Jill; Birken, Catherine; Coons, Michael; Iyer, Sindoora; Agarwal, Arnav; Lalloo, Chitra; Stinson, Jennifer

    2016-07-26

    Obesity remains a major public health concern. Mobile apps for weight loss/management are found to be effective for improving health outcomes in adults and adolescents, and are pursued as a cost-effective and scalable intervention for combating overweight and obesity. In recent years, the commercial market for 'weight loss apps' has expanded at rapid pace, yet little is known regarding the evidence-based quality of these tools for weight control. To characterize the inclusion of evidence-based strategies, health care expert involvement, and scientific evaluation of commercial mobile apps for weight loss/management. An electronic search was conducted between July 2014 and July 2015 of the official app stores for four major mobile operating systems. Three raters independently identified apps with a stated goal of weight loss/management, as well as weight loss/management apps targeted to pediatric users. All discrepancies regarding selection were resolved through discussion with a fourth rater. Metadata from all included apps were abstracted into a standard assessment criteria form and the evidence-based strategies, health care expert involvement, and scientific evaluation of included apps was assessed. Evidence-based strategies included: self-monitoring, goal-setting, physical activity support, healthy eating support, weight and/or health assessment, personalized feedback, motivational strategies, and social support. A total of 393 apps were included in this review. Self-monitoring was most common (139/393, 35.3%), followed by physical activity support (108/393, 27.5%), weight assessment (100/393, 25.4%), healthy eating support (91/393, 23.2%), goal-setting (84/393, 21.4%), motivational strategies (28/393, 7.1%), social support (21/393, 5.3%), and personalized feedback (7/393, 1.8%). Of apps, 0.8% (3/393) underwent scientific evaluation and 0.3% (1/393) reported health care expert involvement. No apps were comprehensive in the assessment criteria, with the majority

  14. Capitalizing on App Development Tools and Technologies

    Science.gov (United States)

    Luterbach, Kenneth J.; Hubbell, Kenneth R.

    2015-01-01

    Instructional developers and others creating apps must choose from a wide variety of app development tools and technologies. Some app development tools have incorporated visual programming features, which enable some drag and drop coding and contextual programming. While those features help novices begin programming with greater ease, questions…

  15. Smartphone apps for spinal surgery: is technology good or evil?

    Science.gov (United States)

    Robertson, Greg A J; Wong, Seng Juong; Brady, Richard R; Subramanian, Ashok S

    2016-05-01

    The increased utilization of smartphones together with their downloadable applications (apps) provides opportunity for doctors, including spinal surgeons, to integrate such technology into clinical practice. However, the clinical reliability of the medical app sector remains questionable. We reviewed available apps themed specifically towards spinal surgery and related conditions and assessed the level of medical professional involvement in their design and content. The most popular smartphone app stores (Android, Apple, Blackberry, Windows, Samsung, Nokia) were searched for spinal surgery-themed apps, using the disease terms Spinal Surgery, Back Surgery, Spine, Disc Prolapse, Sciatica, Radiculopathy, Spinal Stenosis, Scoliosis, Spinal Fracture and Spondylolisthesis. A total of 78 individual spinal surgery themed apps were identified, of which there were six duplicates (N = 72). According to app store classifications, there were 57 (79 %) medical themed apps, 11 (15 %) health and fitness themed apps, 1 (1 %) business and 3 (4 %) education themed apps. Forty-five (63 %) apps were available for download free of charge. For those that charged access, the prices ranged from £0.62 to £47.99. Only 44 % of spinal surgery apps had customer satisfaction ratings and 56 % had named medical professional involvement in their development or content. This is the first study to specifically address the characteristics of apps related to spinal surgery. We found that nearly half of spinal surgery apps had no named medical professional involvement, raising concerns over app content and evidence base for their use. We recommend increased regulation of spinal surgical apps to improve the accountability of app content.

  16. Security Concerns in Android mHealth Apps.

    Science.gov (United States)

    He, Dongjing; Naveed, Muhammad; Gunter, Carl A; Nahrstedt, Klara

    2014-01-01

    Mobile Health (mHealth) applications lie outside of regulatory protection such as HIPAA, which requires a baseline of privacy and security protections appropriate to sensitive medical data. However, mHealth apps, particularly those in the app stores for iOS and Android, are increasingly handling sensitive data for both professionals and patients. This paper presents a series of three studies of the mHealth apps in Google Play that show that mHealth apps make widespread use of unsecured Internet communications and third party servers. Both of these practices would be considered problematic under HIPAA, suggesting that increased use of mHealth apps could lead to less secure treatment of health data unless mHealth vendors make improvements in the way they communicate and store data.

  17. Structure-Based Design and Synthesis of a Small Molecule that Exhibits Anti-inflammatory Activity by Inhibition of MyD88-mediated Signaling to Bacterial Toxin Exposure.

    Science.gov (United States)

    Alam, Shahabuddin; Javor, Sacha; Degardin, Melissa; Ajami, Dariush; Rebek, Mitra; Kissner, Teri L; Waag, David M; Rebek, Julius; Saikh, Kamal U

    2015-08-01

    Both Gram-positive and Gram-negative pathogens or pathogen-derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88-mediated pro-inflammatory cellular immunity for host defense. However, dysregulated MyD88-mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB-loop structure of MyD88 was capable of inhibiting pro-inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non-polar cyclohexane linker which strongly inhibited the production of pro-inflammatory cytokines in human primary cells to SEB (IC50 1-50 μm) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC50 10-200 μm). Consistent with cytokine inhibition, in a ligand-induced cell-based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS-induced MyD88-mediated NF-kB-dependent expression of reporter activity (IC50 10-30 μm). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro-inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin-induced inflated pro-inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic. © 2014 John Wiley & Sons A/S.

  18. Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α.

    LENUS (Irish Health Repository)

    Afonina, Inna S

    2011-10-21

    Granzyme B is a cytotoxic lymphocyte-derived protease that plays a central role in promoting apoptosis of virus-infected target cells, through direct proteolysis and activation of constituents of the cell death machinery. However, previous studies have also implicated granzymes A and B in the production of proinflammatory cytokines, via a mechanism that remains undefined. Here we show that IL-1α is a substrate for granzyme B and that proteolysis potently enhanced the biological activity of this cytokine in vitro as well as in vivo. Consistent with this, compared with full-length IL-1α, granzyme B-processed IL-1α exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1α within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1α processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine.

  19. Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release

    Directory of Open Access Journals (Sweden)

    Claudia Weber

    2015-01-01

    Insulin solutions displayed cytotoxic and pro-inflammatory potential caused by phenol or m-cresol. We speculate that during insulin pump therapy phenol and m-cresol might induce cell death and inflammatory reactions at the infusion site in vivo. Inflammation is perpetuated by release of MCP-1 by activated monocytic cells leading to enhanced recruitment of inflammatory cells. To minimize acute skin complications caused by phenol/m-cresol accumulation, a frequent change of infusion sets and rotation of the infusion site is recommended.

  20. Quality Assessment of Medical Apps that Target Medication-Related Problems.

    Science.gov (United States)

    Loy, John Shiguang; Ali, Eskinder Eshetu; Yap, Kevin Yi-Lwern

    2016-10-01

    The advent of smartphones has enabled a plethora of medical apps for disease management. As of 2012, there are 40,000 health care-related mobile apps available in the market. Since most of these medical apps do not go through any stringent quality assessment, there is a risk of consumers being misinformed or misled by unreliable information. In this regard, apps that target medication-related problems (MRPs) are not an exception. There is little information on what constitutes quality in apps that target MRPs and how good the existing apps are. To develop a quality assessment tool for evaluating apps that target MRPs and assess the quality of such apps available in the major mobile app stores (iTunes and Google Play). The top 100 free and paid apps in the medical categories of iTunes and Google Play stores (total of 400 apps) were screened for inclusion in the final analysis. English language apps that targeted MRPs were downloaded on test devices to evaluate their quality. Apps intended for clinicians, patients, or both were eligible for evaluation. The quality assessment tool consisted of 4 sections (appropriateness, reliability, usability, privacy), which determined the overall quality of the apps. Apps that fulfilled the inclusion criteria were classified based on the presence of any 1 or more of the 5 features considered important for apps targeting MRPs (monitoring, interaction checker, dose calculator, medication information, medication record). Descriptive statistics and Mann-Whitney tests were used for analysis. Final analysis was based on 59 apps that fulfilled the study inclusion criteria. Apps with interaction checker (66.9%) and monitoring features (54.8%) had the highest and lowest overall qualities. Paid apps generally scored higher for usability than free apps (P = 0.006) but lower for privacy (P = 0.003). Half of the interaction checker apps were unable to detect interactions with herbal medications. Blood pressure and heart rate monitoring apps

  1. Emergency Preparedness and Disaster Response: There's An App for That.

    Science.gov (United States)

    Bachmann, Daniel J; Jamison, Nathan K; Martin, Andrew; Delgado, Jose; Kman, Nicholas E

    2015-10-01

    Smartphone applications (or apps) are becoming increasingly popular with emergency responders and health care providers, as well as the public as a whole. There are thousands of medical apps available for Smartphones and tablet computers, with more added each day. These include apps to view textbooks, guidelines, medication databases, medical calculators, and radiology images. Hypothesis/Problem With an ever expanding catalog of apps that relate to disaster medicine, it is hard for both the lay public and responders to know where to turn for effective Smartphone apps. A systematic review of these apps was conducted. A search of the Apple iTunes store (Version 12; Apple Inc.; Cupertino, California USA) was performed using the following terms obtained from the PubMed Medical Subject Headings Database: Emergency Preparedness, Emergency Responders, Disaster, Disaster Planning, Disaster Medicine, Bioterrorism, Chemical Terrorism, Hazardous Materials (HazMat), and the Federal Emergency Management Agency (FEMA). After excluding any unrelated apps, a working list of apps was formed and categorized based on topics. Apps were grouped based on applicability to responders, the lay public, or regional preparedness, and were then ranked based on iTunes user reviews, value, relevance to audience, and user interface. This search revealed 683 applications and was narrowed to 219 based on relevance to the field. After grouping the apps as described above, and subsequently ranking them, the highest quality apps were determined from each group. The Community Emergency Response Teams and FEMA had the best apps for National Disaster Medical System responders. The Centers for Disease Control and Prevention (CDC) had high-quality apps for emergency responders in a variety of fields. The National Library of Medicine's Wireless Information System for Emergency Responders (WISER) app was an excellent app for HazMat responders. The American Red Cross had the most useful apps for natural

  2. Cell-Cell Contact Area Affects Notch Signaling and Notch-Dependent Patterning.

    Science.gov (United States)

    Shaya, Oren; Binshtok, Udi; Hersch, Micha; Rivkin, Dmitri; Weinreb, Sheila; Amir-Zilberstein, Liat; Khamaisi, Bassma; Oppenheim, Olya; Desai, Ravi A; Goodyear, Richard J; Richardson, Guy P; Chen, Christopher S; Sprinzak, David

    2017-03-13

    During development, cells undergo dramatic changes in their morphology. By affecting contact geometry, these morphological changes could influence cellular communication. However, it has remained unclear whether and how signaling depends on contact geometry. This question is particularly relevant for Notch signaling, which coordinates neighboring cell fates through direct cell-cell signaling. Using micropatterning with a receptor trans-endocytosis assay, we show that signaling between pairs of cells correlates with their contact area. This relationship extends across contact diameters ranging from micrometers to tens of micrometers. Mathematical modeling predicts that dependence of signaling on contact area can bias cellular differentiation in Notch-mediated lateral inhibition processes, such that smaller cells are more likely to differentiate into signal-producing cells. Consistent with this prediction, analysis of developing chick inner ear revealed that ligand-producing hair cell precursors have smaller apical footprints than non-hair cells. Together, these results highlight the influence of cell morphology on fate determination processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Just a Fad? Gamification in Health and Fitness Apps

    Science.gov (United States)

    2014-01-01

    Background Gamification has been a predominant focus of the health app industry in recent years. However, to our knowledge, there has yet to be a review of gamification elements in relation to health behavior constructs, or insight into the true proliferation of gamification in health apps. Objective The objective of this study was to identify the extent to which gamification is used in health apps, and analyze gamification of health and fitness apps as a potential component of influence on a consumer’s health behavior. Methods An analysis of health and fitness apps related to physical activity and diet was conducted among apps in the Apple App Store in the winter of 2014. This analysis reviewed a sample of 132 apps for the 10 effective game elements, the 6 core components of health gamification, and 13 core health behavior constructs. A regression analysis was conducted in order to measure the correlation between health behavior constructs, gamification components, and effective game elements. Results This review of the most popular apps showed widespread use of gamification principles, but low adherence to any professional guidelines or industry standard. Regression analysis showed that game elements were associated with gamification (P<.001). Behavioral theory was associated with gamification (P<.05), but not game elements, and upon further analysis gamification was only associated with composite motivational behavior scores (P<.001), and not capacity or opportunity/trigger. Conclusions This research, to our knowledge, represents the first comprehensive review of gamification use in health and fitness apps, and the potential to impact health behavior. The results show that use of gamification in health and fitness apps has become immensely popular, as evidenced by the number of apps found in the Apple App Store containing at least some components of gamification. This shows a lack of integrating important elements of behavioral theory from the app industry

  4. Commercially available mobile phone headache diary apps: a systematic review.

    Science.gov (United States)

    Hundert, Amos S; Huguet, Anna; McGrath, Patrick J; Stinson, Jennifer N; Wheaton, Mike

    2014-08-19

    Headache diaries are often used by headache sufferers to self-monitor headaches. With advances in mobile technology, mobile electronic diary apps are becoming increasingly common. This review aims to identify and evaluate all commercially available mobile headache diary apps for the two most popular mobile phone platforms, iOS and Android. The authors developed a priori a set of 7 criteria that define an ideal headache diary app intended to help headache sufferers better understand and manage their headaches, while providing relevant data to health professionals. The app criteria were intended as minimum requirements for an acceptable headache diary app that could be prescribed by health care professionals. Each app was evaluated and scored against each criterion. Of the 38 apps identified, none of the apps met all 7 app criteria. The 3 highest scoring apps, meeting 5 of the app criteria, were iHeadache (developed by Better QOL), ecoHeadache (developed by ecoTouchMedia), and Headache Diary Pro (developed by Froggyware). Only 18% of the apps were created with scientific or clinical headache expertise and none of the apps reported on psychometric properties. Despite the growing market and demand, there is a concerning lack of scientific expertise and evidence base associated with headache diary apps.

  5. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells.

    Science.gov (United States)

    Park, Hyo-Hyun; Lee, Soyoung; Son, Hee-Young; Park, Seung-Bin; Kim, Mi-Sun; Choi, Eun-Ju; Singh, Thoudam S K; Ha, Jeoung-Hee; Lee, Maan-Gee; Kim, Jung-Eun; Hyun, Myung Chul; Kwon, Taeg Kyu; Kim, Yeo Hyang; Kim, Sang-Hyun

    2008-10-01

    Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation. Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. The pharmacological actions of these flavonoids suggest their potential activity for treatment of allergic inflammatory diseases through the down-regulation of mast cell activation.

  6. Review and Evaluation of Mindfulness-Based iPhone Apps.

    Science.gov (United States)

    Mani, Madhavan; Kavanagh, David J; Hides, Leanne; Stoyanov, Stoyan R

    2015-08-19

    There is growing evidence for the positive impact of mindfulness on wellbeing. Mindfulness-based mobile apps may have potential as an alternative delivery medium for training. While there are hundreds of such apps, there is little information on their quality. This study aimed to conduct a systematic review of mindfulness-based iPhone mobile apps and to evaluate their quality using a recently-developed expert rating scale, the Mobile Application Rating Scale (MARS). It also aimed to describe features of selected high-quality mindfulness apps. A search for "mindfulness" was conducted in iTunes and Google Apps Marketplace. Apps that provided mindfulness training and education were included. Those containing only reminders, timers or guided meditation tracks were excluded. An expert rater reviewed and rated app quality using the MARS engagement, functionality, visual aesthetics, information quality and subjective quality subscales. A second rater provided MARS ratings on 30% of the apps for inter-rater reliability purposes. The "mindfulness" search identified 700 apps. However, 94 were duplicates, 6 were not accessible and 40 were not in English. Of the remaining 560, 23 apps met inclusion criteria and were reviewed. The median MARS score was 3.2 (out of 5.0), which exceeded the minimum acceptable score (3.0). The Headspace app had the highest average score (4.0), followed by Smiling Mind (3.7), iMindfulness (3.5) and Mindfulness Daily (3.5). There was a high level of inter-rater reliability between the two MARS raters. Though many apps claim to be mindfulness-related, most were guided meditation apps, timers, or reminders. Very few had high ratings on the MARS subscales of visual aesthetics, engagement, functionality or information quality. Little evidence is available on the efficacy of the apps in developing mindfulness.

  7. Hippocampal network oscillations in APP/APLP2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Xiaomin Zhang

    Full Text Available The physiological function of amyloid precursor protein (APP and its two homologues APP-like protein 1 (APLP1 and 2 (APLP2 is largely unknown. Previous work suggests that lack of APP or APLP2 impairs synaptic plasticity and spatial learning. There is, however, almost no data on the role of APP or APLP at the network level which forms a critical interface between cellular functions and behavior. We have therefore investigated memory-related synaptic and network functions in hippocampal slices from three lines of transgenic mice: APPsα-KI (mice expressing extracellular fragment of APP, corresponding to the secreted APPsα ectodomain, APLP2-KO, and combined APPsα-KI/APLP2-KO (APPsα-DM for "double mutants". We analyzed two prominent patterns of network activity, gamma oscillations and sharp-wave ripple complexes (SPW-R. Both patterns were generally preserved in all strains. We find, however, a significantly reduced frequency of gamma oscillations in CA3 of APLP2-KO mice in comparison to APPsα-KI and WT mice. Network activity, basic synaptic transmission and short-term plasticity were unaltered in the combined mutants (APPsα-DM which showed, however, reduced long-term potentiation (LTP. Together, our data indicate that APLP2 and the intracellular domain of APP are not essential for coherent activity patterns in the hippocampus, but have subtle effects on synaptic plasticity and fine-tuning of network oscillations.

  8. An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor Uncoordinated-5C-induced Signaling That Merges with Amyloid β Precursor Protein Signaling.

    Science.gov (United States)

    Hashimoto, Yuichi; Toyama, Yuka; Kusakari, Shinya; Nawa, Mikiro; Matsuoka, Masaaki

    2016-06-03

    A missense mutation (T835M) in the uncoordinated-5C (UNC5C) netrin receptor gene increases the risk of late-onset Alzheimer disease (AD) and also the vulnerability of neurons harboring the mutation to various insults. The molecular mechanisms underlying T835M-UNC5C-induced death remain to be elucidated. In this study, we show that overexpression of wild-type UNC5C causes low-grade death, which is intensified by an AD-linked mutation T835M. An AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1, inhibit this death. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of death-associated protein kinase 1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid β precursor protein (APP). Notably, netrin1 also binds to APP and partially inhibits the death-signaling cascade, induced by APP. These results may provide new insight into the amyloid β-independent pathomechanism of AD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. The Not-So-Global Blood Oxygen Level-Dependent Signal.

    Science.gov (United States)

    Billings, Jacob; Keilholz, Shella

    2018-04-01

    Global signal regression is a controversial processing step for resting-state functional magnetic resonance imaging, partly because the source of the global blood oxygen level-dependent (BOLD) signal remains unclear. On the one hand, nuisance factors such as motion can readily introduce coherent BOLD changes across the whole brain. On the other hand, the global signal has been linked to neural activity and vigilance levels, suggesting that it contains important neurophysiological information and should not be discarded. Any widespread pattern of coordinated activity is likely to contribute appreciably to the global signal. Such patterns may include large-scale quasiperiodic spatiotemporal patterns, known also to be tied to performance on vigilance tasks. This uncertainty surrounding the separability of the global BOLD signal from concurrent neurological processes motivated an examination of the global BOLD signal's spatial distribution. The results clarify that although the global signal collects information from all tissue classes, a diverse subset of the BOLD signal's independent components contribute the most to the global signal. Further, the timing of each network's contribution to the global signal is not consistent across volunteers, confirming the independence of a constituent process that comprises the global signal.

  10. WhatsApp in Clinical Practice: A Literature Review.

    Science.gov (United States)

    Mars, Maurice; Scott, Richard E

    2016-01-01

    Several spontaneous telemedicine services using WhatsApp Messenger have started in South Africa raising issues of confidentiality, data security and storage, record keeping and reporting. This study reviewed the literature on WhatsApp in clinical practice, to determine how it is used, and users' satisfaction. Pubmed, Scopus, Science Direct and IEE Expert databases were searched using the search term WhatsApp and Google Scholar using the terms WhatsApp Telemedicine and WhatsApp mHealth. Thirty-two papers covering 17 disciplines were relevant with the most papers, 12, from India. Seventeen papers reported the use of WhatsApp Groups within departments, 14 of which were surgery related disciplines. Groups improved communication and advice given on patient management. Confidentiality was mentioned in 19 papers and consent in five. Data security was partially addressed in 11 papers with little understanding of how data are transmitted and stored. Telemedicine services outside of departmental groups were reported in seven papers and covered emergency triage in maxillofacial, plastic, neuro and general surgery, and cardiology and telestroke. WhatsApp is seen to be a simple, cheap and effective means of communication within the clinical health sector and its use will grow. Users have paid little attention to confidentiality, consent and data security. Guidelines for using WhatsApp for telemedicine are required including downloading. WhatsApp messages to computer for integration with electronic medical records.

  11. Security Concerns in Android mHealth Apps

    Science.gov (United States)

    He, Dongjing; Naveed, Muhammad; Gunter, Carl A.; Nahrstedt, Klara

    2014-01-01

    Mobile Health (mHealth) applications lie outside of regulatory protection such as HIPAA, which requires a baseline of privacy and security protections appropriate to sensitive medical data. However, mHealth apps, particularly those in the app stores for iOS and Android, are increasingly handling sensitive data for both professionals and patients. This paper presents a series of three studies of the mHealth apps in Google Play that show that mHealth apps make widespread use of unsecured Internet communications and third party servers. Both of these practices would be considered problematic under HIPAA, suggesting that increased use of mHealth apps could lead to less secure treatment of health data unless mHealth vendors make improvements in the way they communicate and store data. PMID:25954370

  12. App Use in Psychiatric Education: A Medical Student Survey.

    Science.gov (United States)

    Lau, Cecilia; Kolli, Venkata

    2017-02-01

    The objective of the study is to understand and appraise app use by medical students during their clerkships. Following Creighton University IRB approval, a voluntary and anonymous paper-based, 15-question survey was distributed to third-year medical students. Data were analyzed using Microsoft Excel. Of 112 medical students available, 76.7% (86) participated in the survey. All participants owned a smartphone or tablet with 84.9% using Apple iOS, followed by 12.8% using Android platform. Students reported using the fewest number of apps during surgery, psychiatry, and obstetrics and gynecology clerkships. The largest number of apps were used during the internal medicine rotation (70.3%). The three most popular apps were Epocrates, UpToDate, and UWorld. The most common uses for these apps were as references during the clerkship, followed by improving knowledge, and test taking. Perceived major benefits included accessibility (96% of student respondents) and interactivity (39.5%). Common apps used during the psychiatry clerkship included UpToDate (71%), Epocrates (51%), and Medscape (43%). Despite less frequent app use during their psychiatry clerkship, 90% felt there was a utility for educational apps in psychiatric education. Consistent with the previous literature on medical students preferring educational apps, students suggest developers focus on question bank-type apps, followed by clinical support-focused and self-directed case-based learning apps for psychiatry clerkship learning. Educators should factor these modes of educational delivery into future educational app development. This survey shows a high degree of smartphone and tablet use among medical students, and they attest to mobile phone app utility in psychiatric education.

  13. Medical apps in endocrine diseases - hide and seek.

    Science.gov (United States)

    Albrecht, Urs-Vito; von Jan, Ute

    2014-04-01

    Quantitative review and categorization of available endocrinology related mobile apps for the iOS platform (Apple®) and outline of search strategies to identify appropriate mobile apps for this field. A total of 80 endocrinology related search terms were collected and grouped into 8 main categories covering different areas of endocrinology. These terms were then used to perform comprehensive searches in three categories of Apple's app store, namely 'Medicine', 'Health and Fitness', and 'Reference'. Altogether, matches were found for only 33 of the 80 collected endocrinology related search terms; the majority of matches were found in the medical category, followed by matches for the health and fitness (27/33), and reference (16/33) categories. Restricting the search to these categories significantly helped in discriminating between health related apps and those having another purpose. The distribution of apps per category roughly matches what one can expect considering available data for incidence and prevalence of corresponding endocrinological conditions. Apps matching terms belonging to the spectrum of glucose homeostasis disorders are the most common. For conditions where patients do not have to constantly monitor their condition, apps tend to have a reference or educational character, while for conditions that require a high level of involvement from patients, there are proportionally more apps for self-management. With a single exception, the identified apps had not undergone regulation, and information about the data sources, professional backgrounds, and reliability of the content and integrated information sources was rare. While applying a good search strategy is important for finding apps for endocrinology related problems, users also need to consider whether the app they have found respects all necessary criteria regarding reliability, privacy and data protection before they place their trust in it.

  14. Anti-Inflammatory Action of an Antimicrobial Model Peptide That Suppresses the TRIF-Dependent Signaling Pathway via Inhibition of Toll-Like Receptor 4 Endocytosis in Lipopolysaccharide-Stimulated Macrophages.

    Directory of Open Access Journals (Sweden)

    Do-Wan Shim

    Full Text Available Antimicrobial peptides (AMPs, also called host defense peptides, particularly those with amphipathic helical structures, are emerging as target molecules for therapeutic development due to their immunomodulatory properties. Although the antimicrobial activity of AMPs is known to be exerted primarily by permeation of the bacterial membrane, the mechanism underlying its anti-inflammatory activity remains to be elucidated. We report potent anti-inflammatory activity of WALK11.3, an antimicrobial model peptide with an amphipathic helical conformation, in lipopolysaccharide (LPS-stimulated RAW264.7 cells. This peptide inhibited the expression of inflammatory mediators, including nitric oxide, COX-2, IL-1β, IL-6, INF-β, and TNF-α. Although WALK11.3 did not exert a major effect on all downstream signaling in the MyD88-dependent pathway, toll-like receptor 4 (TLR4- mediated pro-inflammatory signals were markedly attenuated in the TRIF-dependent pathway due to inhibition of the phosphorylation of STAT1 by attenuation of IRF3 phosphorylation. WALK11.3 specifically inhibited the endocytosis of TLR4, which is essential for triggering TRIF-mediated signaling in macrophage cells. Hence, we suggest that specific interference with TLR4 endocytosis could be one of the major modes of the anti-inflammatory action of AMPs. Our designed WALK11 peptides, which possess both antimicrobial and anti-inflammatory activities, may be promising molecules for the development of therapies for infectious inflammation.

  15. CERN Apps meet in a forum

    CERN Multimedia

    Antonella Del Rosso

    2013-01-01

    In the fast-evolving world of mobile apps, creativity and usability are key words. For the time being, the number of CERN apps is quite limited but the situation could quickly change. An information-sharing forum set up by the IT Department is a starting point to channel your creativity with the help of experts, best practices and useful guidelines.   The CAPPS (CERN Apps) Forum was set up about a year ago. Its members come from various departments and meet every two or three months to update each other on the apps that are in preparation, share the latest news on the available software, discuss best practices and so on. “The Forum is open to anybody wanting to develop apps at CERN,” explains David Foster, Deputy Department Head and initiator of the CAPPS Forum. “Developers, communication experts and IT infrastructure experts meet and discuss various topics, from branding-related issues to coding and implementation solutions. The aim is to go forward in a coherent way...

  16. Be smart: Download the app!

    CERN Multimedia

    Katarina Anthony

    2013-01-01

    What’s the closest snack point to the CLIC test facility? How do you get from your current location to SM18? How do you enter the CERN Open Days photo contest? Finding out is simple: there’s an app for that!   The CERN Open Days app is your personal guide to the Laboratory. Developed by expert volunteers from the IT Department, the app provides comprehensive practical information on CERN transport, shops, snack points and toilet facilities along with detailed location information and event timetables. You can also favourite the sites, activities and lectures you plan to see, and tick them off as you go along. More information here.

  17. Photo Apps -

    Data.gov (United States)

    Department of Transportation — Images of various facilities used as a tool to eliminate travel time and for immediate access to concerned areas. App thumbnails images 4 per row and allows the user...

  18. Airport Surface Access and Mobile Apps

    Directory of Open Access Journals (Sweden)

    Luis Martin-Domingo

    2015-02-01

    Full Text Available Purpose: Airport Surface Access faces two main opposite issues: (1 cars, being the main transport mode, contribute to the increasing level of congestion and pollution of cities; and (2 simultaneously, parking fees are one important source of airports commercial revenue, creating a dilemma for airports when facing the problem. Following the recent trend of air passengers travelling with Smartphone (78% in 2013, the purpose of this paper is to monitor the adoption of mobile Applications (Apps by airports and to analyze if the information and functions provided in those Apps can help to overcome the above two issues. Design/methodology/approach: 31 iPhone App of some of the largest European airports were evaluated in the lab using the evaluation model of Destinations Mobile Applications (Scolari and Fernández-Cavia 2014 adapted for for the Airport Surface Access on Airport Apps Findings and Originality/value: The Apps evaluated provided a very limited functionality to help passengers to plan and book their trips to/from the airports on public transports and gave high priority to parking information and services. Originality/value: Although Airport Surface Access has been a widely researched, the originality of this paper is the analysis of airport mobile Apps as a potential tool for airports to deal with the surface airport access problems.Access, Airports, Mobile Internet, Commercial Revenues

  19. Apps for Hearing Science and Care.

    Science.gov (United States)

    Paglialonga, Alessia; Tognola, Gabriella; Pinciroli, Francesco

    2015-09-01

    Our research aims at the identification and assessment of applications (referred to as apps) in the hearing health care domain. This research forum article presents an overview of the current availability, affordability, and variety of hearing-related apps. The available apps were reviewed by searching on the leading platforms (iOS, Android, Windows Phone stores) using the keywords hearing, audiology, audio, auditory, speech, language, tinnitus, hearing loss, hearing aid, hearing sys tem, cochlear implant, implantable device, auditory training, hearing rehabilitation, and assistive technology/tool/device. O n the bas is of the offered services, apps were classified into 4 application domains: (a) screening and assessment, (b) intervention and rehabilitation, (c) education and information, and (d) assistive tools. A large variety of apps are available in the hearing health care domain. These cover a wide range of services for people with hearing or communication problems as well as for hearing professionals, families, or informal caregivers. This evolution can potentially bring along considerable advantages and improved outcomes in the field of hearing health care. Nevertheless, potential risks and threats (e.g., safety, quality, effectiveness, privacy, and regulation) should not be overlooked. Significant research—particularly in terms of assessment and guidance—is still needed for the informed, aware, and safe adoption of hearing-related apps by patients and professionals.

  20. A phonology-free mobile communication app.

    Science.gov (United States)

    Kondapalli, Ananya; Zhang, Lee R; Patel, Shreya; Han, Xiao; Kim, Hee Jin; Li, Xintong; Altschuler, Eric L

    2016-11-01

    Aphasia - loss of comprehension or expression of language - is a devastating functional sequela of stroke. There are as yet no effective methods for rehabilitation of aphasia. An assistive device that allows aphasia patients to communicate and interact at speeds approaching real time is urgently needed. Behavioral and linguistic studies of aphasia patients show that they retain normal thinking processes and most aspects of language. They lack only phonology: the ability to translate (input) and/or output sounds (or written words) such as "ta-ble" into the image of a four-legged object with a top at which one works or eats. We have made a phonology-free communication mobile app that may be useful for patients with aphasia and other communication disorders. Particular innovations of our app include calling Google Images as a "subroutine" to allow a near-infinite number of choices (e.g. food or clothing items) for patients without having to make countless images, and by the use of animation for words, phrases or concepts that cannot be represented by a single image. We have tested our app successfully in one patient. The app may be of great benefit to patients with aphasia and other communication disorders. Implications for Rehabilitation We have made a phonology-free mobile communication app. This app may facilitate communication for patients with aphasia and other communication disorders.

  1. A Framework to Assist Health Professionals in Recommending High-Quality Apps for Supporting Chronic Disease Self-Management: Illustrative Assessment of Type 2 Diabetes Apps.

    Science.gov (United States)

    Hale, Kelli; Capra, Sandra; Bauer, Judith

    2015-09-14

    This paper presents an approach to assist health professionals in recommending high quality apps for supporting chronic disease self-management. Most app reviews focus on popularity, aesthetics, functionality, usability, and information quality. There is no doubt these factors are important in selecting trustworthy apps which are appealing to users, but behavioral theory may be also be useful in matching the apps to user needs. The framework developed aims to be methodologically sound, capable of selecting popular apps which include content covered by evidence-based programs, consistent with behavioral theory, as well as a patient-centered approach for matching apps to patients' individual needs. A single disease-type 2 diabetes-was selected to illustrate how the framework can be applied as this was deemed to represent the types of strategies used in many chronic diseases. A systematic approach based on behavioral theory and recommendations from best practice guidelines was developed for matching apps to patients' needs. In March 2014, a series of search strategies was used to identify top-rated iPhone and Android health apps, representing 29 topics from five categories of type 2 diabetes self-management strategies. The topics were chosen from published international guidelines for the management of diabetes. The senior author (KH) assessed the most popular apps found that addressed these topics using the Behavioral Theory Content Survey (BTS), which is based on traditional behavioral theory. A tool to assist decision making when using apps was developed and trialed with health professionals for ease of use and understanding. A total of 14 apps were assessed representing all five topic categories of self-management. Total theoretical scores (BTS scores) were less than 50 on a 100-point scale for all apps. Each app scored less than 50% of the total possible BTS score for all four behavioral theories and for most of the 20 behavioral strategies; however, apps scored

  2. Alterations of cAMP-dependent signaling in dystrophic skeletal muscle

    Directory of Open Access Journals (Sweden)

    Rüdiger eRudolf

    2013-10-01

    Full Text Available Autonomic regulation processes in striated muscles are largely mediated by cAMP/PKA-signaling. In order to achieve specificity of signaling its spatial-temporal compartmentation plays a critical role. We discuss here how specificity of cAMP/PKA-signaling can be achieved in skeletal muscle by spatio-temporal compartmentation. While a microdomain containing PKA type I in the region of the neuromuscular junction is important for post-synaptic, activity-dependent stabilization of the nicotinic acetylcholine receptor, PKA type I and II microdomains in the sarcomeric part of skeletal muscle are likely to play different roles, including the regulation of muscle homeostasis. These microdomains are due to specific A-kinase anchoring proteins, like rapsyn and myospryn. Importantly, recent evidence indicates that compartmentation of the cAMP/PKA-dependent signaling pathway and pharmacological activation of cAMP production are aberrant in different skeletal muscles disorders. Thus, we discuss here their potential as targets for palliative treatment of certain forms of dystrophy and myasthenia. Under physiological conditions, the neuropeptide, α-calcitonin-related peptide, as well as beta-adrenergic agonists are the most-mentioned natural triggers for activating cAMP/PKA signaling in skeletal muscle. While the precise domains and functions of these first messengers are still under investigation, agonists of β2-adrenoceptors clearly exhibit anabolic activity under normal conditions and reduce protein degradation during atrophic periods. Past and recent studies suggest direct sympathetic innervation of skeletal muscle fibers. In summary, the organization and roles of cAMP-dependent signaling in skeletal muscle are increasingly understood, revealing crucial functions in processes like nerve-muscle interaction and muscle trophicity.

  3. Instant EdgeSight for XenApp

    CERN Document Server

    Hasan, Vaqar

    2013-01-01

    Filled with practical, step-by-step instructions and clear explanations for the most important and useful tasks. Instant EdgeSight for XenApp is a practical, hands-on guide that contains instruction-based examples from basic to advanced level topics. Instant EdgeSight for XenApp will serve as an excellent source of information for Citrix XenApp professionals and novices alike. It is assumed that readers have experience working with Citrix products and have some sort of familiarity with monitoring.

  4. Application of low-cost methodologies for mobile phone app development.

    Science.gov (United States)

    Zhang, Melvyn; Cheow, Enquan; Ho, Cyrus Sh; Ng, Beng Yeong; Ho, Roger; Cheok, Christopher Cheng Soon

    2014-12-09

    The usage of mobile phones and mobile phone apps in the recent decade has indeed become more prevalent. Previous research has highlighted a method of using just the Internet browser and a text editor to create an app, but this does not eliminate the challenges faced by clinicians. More recently, two methodologies of app development have been shared, but there has not been any disclosures pertaining to the costs involved. In addition, limitations such as the distribution and dissemination of the apps have not been addressed. The aims of this research article are to: (1) highlight a low-cost methodology that clinicians without technical knowledge could use to develop educational apps; (2) clarify the respective costs involved in the process of development; (3) illustrate how limitations pertaining to dissemination could be addressed; and (4) to report initial utilization data of the apps and to share initial users' self-rated perception of the apps. In this study, we will present two techniques of how to create a mobile app using two of the well-established online mobile app building websites. The costs of development are specified and the methodology of dissemination of the apps will be shared. The application of the low-cost methodologies in the creation of the "Mastering Psychiatry" app for undergraduates and "Déjà vu" app for postgraduates will be discussed. A questionnaire survey has been administered to undergraduate students collating their perceptions towards the app. For the Mastering Psychiatry app, a cumulative total of 722 users have used the mobile app since inception, based on our analytics. For the Déjà vu app, there has been a cumulative total of 154 downloads since inception. The utilization data demonstrated the receptiveness towards these apps, and this is reinforced by the positive perceptions undergraduate students (n=185) had towards the low-cost self-developed apps. This is one of the few studies that have demonstrated the low

  5. Sound level measurements using smartphone "apps": Useful or inaccurate?

    Directory of Open Access Journals (Sweden)

    Daniel R Nast

    2014-01-01

    Full Text Available Many recreational activities are accompanied by loud concurrent sounds and decisions regarding the hearing hazards associated with these activities depend on accurate sound measurements. Sound level meters (SLMs are designed for this purpose, but these are technical instruments that are not typically available in recreational settings and require training to use properly. Mobile technology has made such sound level measurements more feasible for even inexperienced users. Here, we assessed the accuracy of sound level measurements made using five mobile phone applications or "apps" on an Apple iPhone 4S, one of the most widely used mobile phones. Accuracy was assessed by comparing application-based measurements to measurements made using a calibrated SLM. Whereas most apps erred by reporting higher sound levels, one application measured levels within 5 dB of a calibrated SLM across all frequencies tested.

  6. Installing the ARL Phrase Book Android Application and Configuring its Dependencies

    Science.gov (United States)

    2015-02-01

    application contains several third - party applications, which add additional steps to the installation process. Due to these dependencies, the installation...military terms, additional Dari terms, etc.) were added to the Phrase Book app. In addition, third - party apps (e.g., Carnegie Mellon University’s...Phrase Book app uses 2 third - party apps from the Google Play Store, Google’s app store. The Google Play Store is accessible by clicking on the white

  7. Leakiness and Creepiness in App Space: User Perceptions of Privacy and Mobile App Use

    DEFF Research Database (Denmark)

    Shklovski, Irina; Mainwaring, Scott; Skúladóttir, Halla Hrund

    2014-01-01

    Mobile devices are playing an increasingly intimate role in everyday life. However, users can be surprised when in- formed of the data collection and distribution activities of apps they install. We report on two studies of smartphone users in western European countries, in which users were confr...... to important underlying issues, even when users continue using apps they find creepy....

  8. Pro-smoking apps: where, how and who are most at risk.

    Science.gov (United States)

    BinDhim, Nasser F; Freeman, Becky; Trevena, Lyndal

    2015-03-01

    Pro-smoking applications (app) provide information about brands of tobacco products, where to buy them, and encourage their use. It is unclear in which countries these apps are being downloaded, or whether app stores play a role in promoting or regulating these apps, particularly those that appear to target children. The lifetime popularity of 107 pro-smoking apps was investigated, using a third-party app metrics service that aggregates data from app stores about app download popularity by country. Apps were deemed popular if at any time in their lifespan they achieved a top 25 ranking overall across all apps, or a top 25 ranking in any particular category of apps, such as 'educational games'. Fifty-eight pro-smoking apps reached 'popularity' status in Apple and Android stores in one or more of 49 countries, particularly Italy, Egypt, Germany, Belgium and the USA. The daily downloads in each country ranged from approximately 2000 to 80 000. The Apple store featured five of the pro-smoking apps in various categories, and two apps were featured by the Android market. Two pro-smoking apps in the Apple store were extremely popular in the 'Educational Games' and 'Kids' Games' categories. Pro-smoking apps were popular in many countries. Most apps were assigned to entertainment and games categories, with some apps specifically targeting children through placement in categories directed at children. App stores that feature pro-smoking apps may be in violation of tobacco control laws. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Beyond Native Apps: Web Technologies to the Rescue! (Keynote)

    NARCIS (Netherlands)

    Malavolta, Ivano

    2016-01-01

    As of today, mobile software development teams can follow a number of different development and distribution strategies, ranging from native apps, to mobile web apps, hybrid apps, and the recently emerging progressive web apps. This talk provides a state-of-the-art overview of the development

  10. Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid

    Directory of Open Access Journals (Sweden)

    Zadeh Mojgan

    2012-03-01

    Full Text Available Abstract Background The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA, may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. Methods To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031. Results Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56, and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction. Conclusions These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.

  11. The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli.

    Science.gov (United States)

    Qiao, Huan; Liu, Yan; Veach, Ruth A; Wylezinski, Lukasz; Hawiger, Jacek

    2014-08-08

    A hallmark of inflammation, increased vascular permeability, is induced in endothelial cells by multiple agonists through stimulus-coupled assembly of the CARMA3 signalosome, which contains the adaptor protein BCL10. Previously, we reported that BCL10 in immune cells is targeted by the "death" adaptor CRADD/RAIDD (CRADD), which negatively regulates nuclear factor κB (NFκB)-dependent cytokine and chemokine expression in T cells (Lin, Q., Liu, Y., Moore, D. J., Elizer, S. K., Veach, R. A., Hawiger, J., and Ruley, H. E. (2012) J. Immunol. 188, 2493-2497). This novel anti-inflammatory CRADD-BCL10 axis prompted us to analyze CRADD expression and its potential anti-inflammatory action in non-immune cells. We focused our study on microvascular endothelial cells because they play a key role in inflammation. We found that CRADD-deficient murine endothelial cells display heightened BCL10-mediated expression of the pleotropic proinflammatory cytokine IL-6 and chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) in response to LPS and thrombin. Moreover, these agonists also induce significantly increased permeability in cradd(-/-), as compared with cradd(+/+), primary murine endothelial cells. CRADD-deficient cells displayed more F-actin polymerization with concomitant disruption of adherens junctions. In turn, increasing intracellular CRADD by delivery of a novel recombinant cell-penetrating CRADD protein (CP-CRADD) restored endothelial barrier function and suppressed the induction of IL-6 and MCP-1 evoked by LPS and thrombin. Likewise, CP-CRADD enhanced barrier function in CRADD-sufficient endothelial cells. These results indicate that depletion of endogenous CRADD compromises endothelial barrier function in response to inflammatory signals. Thus, we define a novel function for CRADD in endothelial cells as an inducible suppressor of BCL10, a key mediator of responses to proinflammatory agonists. © 2014 by The American Society for Biochemistry and Molecular Biology

  12. Development of a Mobile App for Family Planning Providers.

    Science.gov (United States)

    Halsall, Viannella; Rogers, Jennifer; Witt, Jacki; Song, Sejun; Nguyen, Hoang Duc Huy; Kelly, Patricia

    To provide an overview of lessons learned during the development process of an app for iOS and Android based on national recommendations for providing quality family planning services. After a review of existing apps was conducted to determine whether an app of clinical recommendations for family planning existed, a team of clinicians, training specialists, and app developers created a resource app by first drafting a comprehensive content map. A prototype of the app was then pilot tested using smart tablets by a volunteer convenience sample of women's healthcare professionals. Outcomes measured included usability, acceptability, download analytics, and satisfaction by clinicians as reported through an investigator-developed tool. Sixty-nine professionals tested a prototype of the app, and completed a user satisfaction tool. Overall, user feedback was positive, and a zoom function was added to the final version as a result of the pilot test. Within 3 months of being publicly available, the app was downloaded 677 times, with 97% of downloads occurring on smart phones, 76% downloads occurring on iOS devices, and 24% on Android devices. This trend persisted throughout the following 3 months. Clinicians with an interest in developing an app should consider a team approach to development, pilot test the app prior to wider distribution, and develop a web-based version of the app to be used by clinicians who are unable to access smart devices in their practice setting.

  13. PoliticAPP: Towards a Categorization of Mobile Apps in Political Communication

    Directory of Open Access Journals (Sweden)

    Pablo VÁZQUEZ SANDE

    2016-06-01

    Full Text Available This article is an analyze of all mobile apps that are available in the field of Spanish political communication, with the aim to develop a pioneering categorization of these platforms according to various criteria as promoters, aims pursued or areas of performance. It includes also a critical review from which it is concluded that these app reproduce classic communication patterns with the voters. That means that the implementation of these channels seems to have been due more to political marketing than to boost democratic participation or to introduce an horizontal outline of a new relationship between politicians and citizens.

  14. ADHD: Is There an App for That? A Suitability Assessment of Apps for the Parents of Children and Young People With ADHD.

    Science.gov (United States)

    Powell, Lauren; Parker, Jack; Harpin, Valerie

    2017-10-13

    Attention-deficit hyperactivity disorder (ADHD) is a highly comorbid disorder that can impact significantly on the individual and their family. ADHD is managed via pharmacological and nonpharmacological interventions. Parents also gain support from parent support groups, which may include chat rooms, as well as face-to-face meetings. With the growth of technology use over recent years, parents have access to more resources that ever before. A number of mobile apps have been developed to help parents manage ADHD in their children and young people. Unfortunately many of these apps are not evidence-based, and little is known of their suitability for the parents or whether they are helpful in ADHD management. The aim of this study was to explore the (1) parents' views of the suitability of the top ten listed apps for parents of children and young people with ADHD and (2) the views of clinicians that work with them on the suitability and value of the apps. The top 10 listed apps specifically targeted toward the parents of children and young people with ADHD were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 7 parents of children or young people with ADHD and 6 clinicians who specialize in working with this population to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable and valuable for this population. Four themes emerged from clinician and parent interviews: (1) the importance of relating to the app, (2) apps that address ADHD-related difficulties, (3) how the apps can affect family relationships, and (4) apps as an educational tool. Two additional themes emerged from the clinician interviews alone: monitoring ADHD symptoms and that apps should be practical. Parents also identified an additional theme: the importance of the technology. Overall, the characteristics of the current top 10 listed apps did not appear to match well to the views of our

  15. Signal restoration for NMR imaging using time-dependent gradients

    International Nuclear Information System (INIS)

    Frahm, J.; Haenicke, W.

    1984-01-01

    NMR imaging experiments that employ linear but time-dependent gradients for encoding spatial information in the time-domain signals result in distorted images when treated with conventional image reconstruction techniques. It is shown here that the phase and amplitude distortions can be entirely removed if the timeshape of the gradient is known. The method proposed is of great theoretical and experimental simplicity. It consists of a retransformation of the measured time-domain signal and corresponds to synchronisation of the signal sampling with the time-development of the gradient field strength. The procedure complements other treatments of periodically oscillating gradients in NMR imaging. (author)

  16. Characteristics, Quality and Contribution to Signal Detection of Spontaneous Reports of Adverse Drug Reactions Via the WEB-RADR Mobile Application: A Descriptive Cross-Sectional Study.

    Science.gov (United States)

    Oosterhuis, Ingrid; Taavola, Henric; Tregunno, Philip M; Mas, Petar; Gama, Sara; Newbould, Victoria; Caster, Ola; Härmark, Linda

    2018-05-14

    Spontaneous reporting of suspected adverse drug reactions is key for efficient post-marketing safety surveillance. To increase usability and accessibility of reporting tools, the Web-Recognising Adverse Drug Reactions (WEB-RADR) consortium developed a smartphone application (app) based on a simplified reporting form. The objective of this study was to evaluate the characteristics, quality and contribution to signals of reports submitted via the WEB-RADR app. The app was launched in the UK, the Netherlands and Croatia between July 2015 and May 2016. Spontaneous reports submitted until September 2016 with a single reporter were included. For each country, app reports and reports received through conventional means in the same time period were compared to identify characteristic features. A random subset of reports was assessed for clinical quality and completeness. The contribution to signal detection was assessed by a descriptive analysis. Higher proportions of app reports were submitted by patients in the UK (28 vs. 18%) and Croatia (32 vs. 7%); both p < 0.01. In the Netherlands, the difference was small (60 vs. 57%; p = 0.5). The proportion of female patients and the median patient ages in app reports submitted by patients were similar to the reference. The proportion of reports of at least moderate quality was high in both samples (app: 78-85%, reference: 78-98%), for all countries. App reports contributed to detecting eight potential safety signals at the national level, four of which were eventually signalled. The WEB-RADR app offers a new route of spontaneous reporting that shows promise in attracting reports from patients and that could become an important tool in the future. Patient demographics are similar to conventional routes, report quality is sufficient despite a simplified reporting form, and app reports show potential in contributing to signal detection.

  17. Enhancing Pharmacy Student Learning and Perceptions of Medical Apps

    OpenAIRE

    Rodis, Jennifer; Aungst, Timothy Dy; Brown, Nicole V; Cui, Yan; Tam, Leonard

    2016-01-01

    Background The use of mobile apps in health care is growing. Current and future practitioners must be equipped with the skills to navigate and utilize apps in patient care, yet few strategies exist for training health care professional students on the usage of apps. Objective To characterize first-year pharmacy student use of medical apps, evaluate first-year pharmacy student's perception of skills in finding, evaluating, and using medical apps before and after a focused learning experience, ...

  18. BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods.

    Directory of Open Access Journals (Sweden)

    Krzysztof J Gorgolewski

    2017-03-01

    Full Text Available The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS. The portability of these applications (BIDS Apps is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

  19. Apps and Mobile Support Services in Canadian Academic Medical Libraries

    Directory of Open Access Journals (Sweden)

    Tess Grynoch

    2016-12-01

    Full Text Available Objective: To examine how Canadian academic medical libraries are supporting mobile apps, what apps are currently being provided by these libraries, and what types of promotion are being used. Methods: A survey of the library websites for the 17 medical schools in Canada was completed. For each library website surveyed, the medical apps listed on the website, any services mentioned through this medium, and any type of app promotion events were noted. When Facebook and Twitter accounts were evident, the tweets were searched and the past two years of Facebook posts scanned for mention of medical apps or mobile services/events. Results: All seventeen academic medical libraries had lists of mobile medical apps with a large range in the number of medical relevant apps (average=31, median= 23. A total of 275 different apps were noted and the apps covered a wide range of subjects. Five of the 14 Facebook accounts scanned had posts about medical apps in the past two years while 11 of the 15 Twitter accounts had tweets about medical apps. Social media was only one of the many promotional methods noted. Outside of the app lists and mobile resources guides, Canadian academic medical libraries are providing workshops, presentations, and drop-in sessions for mobile medical apps. Conclusion: While librarians cannot simply compare mobile services and resources between academic medical libraries without factoring in a number of other circumstances, librarians can learn from mobile resources strategies employed at other libraries, such as using research guides to increase medical app literacy.

  20. Digital age and the public eHealth perspective: Prevailing health app use among Austrian Internet users.

    Science.gov (United States)

    Naszay, Marlene; Stockinger, Andreas; Jungwirth, David; Haluza, Daniela

    2017-12-19

    New technological developments affect almost every sector of our daily lives including the healthcare sector. Successful adoption and sustainable integration of eHealth and telemedicine in Public Health strategies (also known as Public eHealth) depend on knowledge and constant evaluation of consumers' needs, proficiencies, and preferences. We therefore assessed how the general Austrian population perceived innovative Public eHealth solutions. The online survey on 562 Austrian adults (58.9% females) collected self-reported data on current and expected use of smartphone-based health applications (apps) of digital natives (35 years and younger) and digital immigrants (aged 35+). In total, 26.7% (95% CI 23.0-30.4) of participants already used health apps, especially lifestyle-associated apps for monitoring exercise habits and nutritional habits. We found substantial digital age group differences; compared to digital immigrants digital natives were more likely to use mobile devices and health apps. Health apps have the potential to improve community health and prevent lifestyle diseases cost-effectively and efficiently, and thus build an important pillar of Public eHealth. With regard to aging societies, healthcare providers could take advantage of consumer-oriented health apps by assessing individual needs of specific target groups such as elderly people.

  1. High Glucose Promotes Aβ Production by Inhibiting APP Degradation

    Science.gov (United States)

    Zhang, Shuting; Song, Weihong

    2013-01-01

    Abnormal deposition of neuriticplaques is the uniqueneuropathological hallmark of Alzheimer’s disease (AD).Amyloid β protein (Aβ), the major component of plaques, is generated from sequential cleavage of amyloidβ precursor protein (APP) by β-secretase and γ-secretase complex. Patients with diabetes mellitus (DM), characterized by chronic hyperglycemia,have increased risk of AD development.However, the role of high blood glucose in APP processing and Aβ generation remains elusive. In this study, we investigated the effect of high glucose on APP metabolism and Aβ generation in cultured human cells. We found that high glucose treatment significantly increased APP protein level in both neuronal-like and non-neuronal cells, and promoted Aβ generation. Furthermore, we found that high glucose-induced increase of APP level was not due to enhancement of APP gene transcription but resulted from inhibition of APP protein degradation. Taken together, our data indicated that hyperglycemia could promote AD pathogenesis by inhibiting APP degradation and enhancing Aβ production. More importantly, the elevation of APP level and Aβ generation by high glucose was caused by reduction of APP turnover rate.Thus,our study provides a molecular mechanism of increased risk of developing AD in patients withDMand suggests thatglycemic control might be potentially beneficial for reducing the incidence of AD in diabetic patients and delaying the AD progression. PMID:23894546

  2. Apps: a new medium for non-fiction innovation

    OpenAIRE

    Allen, Catherine

    2015-01-01

    Apps are now a dominant content medium: in the US people spend more time on apps than they do watching TV. Non-fiction content is being avidly consumed on mobile devices, but in a completely different way to the book model. This article explores three strands of potential that the app medium holds for non-fiction content, putting forward the case that apps have the power to further weave non-fiction into the fabric of society and life.

  3. Ghera: A Repository of Android App Vulnerability Benchmarks

    OpenAIRE

    Mitra, Joydeep; Ranganath, Venkatesh-Prasad

    2017-01-01

    Security of mobile apps affects the security of their users. This has fueled the development of techniques to automatically detect vulnerabilities in mobile apps and help developers secure their apps; specifically, in the context of Android platform due to openness and ubiquitousness of the platform. Despite a slew of research efforts in this space, there is no comprehensive repository of up-to-date and lean benchmarks that contain most of the known Android app vulnerabilities and, consequent...

  4. Research on the Application of GSR and ECG in the Usability Testing of an Aggregation Reading App

    Directory of Open Access Journals (Sweden)

    Sha Liu

    2016-09-01

    Full Text Available Usability testing is a very important step in improving App design and development. The traditional usability testing methods are based on users'expressions and behaviors, which hardly show users' emotional experience and cognitive load in real time. The introduction of an electrophysiological technique can make up for the deficiency of the traditional usability testing methods. In this study, a usability testing was carried out with the old and the new version of an App software. The behavior and the subjective evaluation of the participants were recorded, and their GSR and ECG signals were collected. Then, 14 physiological characteristics, such as GSR-Mean, LF, HF, LF/HF, etc., were extracted from the GSR and ECG signals. These characteristics were analyzed, and a significance test of difference of the two versions was made. This research indicated that there is a certain application value of GSR and HRV in usability testing and evaluation of an App product. But the meanings of the physiological characteristics must be explained in combination with the behavior and subjective evaluation of users. The result can prove that physiological characteristics have obvious advantages in real-time monitoring users' emotional changes, which can be helpful to find the usability problems of the product.

  5. Storybook app creation demystified a cast study

    CERN Document Server

    Friedlander, Amy

    2013-01-01

    This case study explains how Wasabi Productions created its first app, Lazy Larry Lizard, and provides insight into the development of soon-to-be-released app, Gorilla Band. Inside, you will find notes on how storybook apps are produced from start to finish, including costs, production process, people, technology, pricing, release cycle, marketing and more. You will also find insights on technology, storyboard development and pricing.

  6. Creating mobile apps with Appcelerator Titanium

    CERN Document Server

    Brousseau, Christian

    2013-01-01

    Creating Mobile Apps with Appcelerator Titanium provides a hands-on approach and working examples on creating apps and games as well as embedding them onto a social networking website. Developers can then move on from there to develop their own applications based on the ones they have developed throughout the course of this book.""Creating Mobile Apps with Appcelerator Titanium"" is for developers who have experience with modern languages and development environments. Also, if you are familiar with the concepts of Object-oriented Programming (OOP), reusable components, AJAX closures, and so on

  7. Host transcription factors in the immediate pro-inflammatory response to the parasitic mite Psoroptes ovis.

    Directory of Open Access Journals (Sweden)

    Stewart T G Burgess

    Full Text Available BACKGROUND: Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. RESULTS: Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. CONCLUSIONS: Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.

  8. EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

    Science.gov (United States)

    Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

    2016-12-01

    The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Apps: a new medium for non-fiction innovation

    Directory of Open Access Journals (Sweden)

    Catherine Allen

    2015-07-01

    Full Text Available Apps are now a dominant content medium: in the US people spend more time on apps than they do watching TV. Non-fiction content is being avidly consumed on mobile devices, but in a completely different way to the book model. This article explores three strands of potential that the app medium holds for non-fiction content, putting forward the case that apps have the power to further weave non-fiction into the fabric of society and life.

  10. ‘Gamification’ for Health Behaviour Change in Smartphone Apps

    Directory of Open Access Journals (Sweden)

    Elizabeth Ann Edwards

    2015-09-01

    Full Text Available Background: Gamification techniques are showing promise in promoting healthy behaviours and delivering health promotion advice, however, their use in Mobile-Health is relatively new. Gamification involves using ‘gaming’ elements such as badges, leader boards, health-related challenges, rewards, ability to ‘level up’ and use of avatars to motivate and engage people to change health behavior. Gamification techniques may also overlap with validated health behaviour change techniques (BCTs, however, few apps appear to apply the techniques systematically or to define the BCTs they include. Aim: We aimed a to assess the number apps that incorporate gamification to modify health behaviors, b to examine the BCT repertoire and combinations used in these apps c to consider associations with user satisfaction. Methods: English-language health apps that contain gamification techniques were identified through a systematic search of the official Apple and Google Play store and the NHS health apps library. Top rated free and paid Medical, Health & Wellness, Health & Fitness apps as defined by Apple and Google Play stores were searched. Apps were coded for BCTs according to the Michie et al. taxonomy. The taxonomy comprises 16 categories and 93 individual BCTs. BCT coding was conducted by two trained researchers (EE, JL who scored independently and then cross-checked for discrepancies. BCT numbers, user ratings and app pricing were compared. We explored the association between number of BCTs per app, user and NHS libraries’ ratings and price. We also investigated, which of the 16 BCT categories and the individual 93 BCTs and their combinations were most commonly used. Results: 1,680 Medical, Health & Wellness or Health & Fitness Apps were reviewed and seventy containing gamification techniques were identified. The mean number of BCTs used was 12.5 (range 1-24. There was no correlation between number of BCTs, customer ratings, NHS library app rating or

  11. Towards a Framework for Evaluating Mobile Mental Health Apps.

    Science.gov (United States)

    Chan, Steven; Torous, John; Hinton, Ladson; Yellowlees, Peter

    2015-12-01

    Mobile phones are ubiquitous in society and owned by a majority of psychiatric patients, including those with severe mental illness. Their versatility as a platform can extend mental health services in the areas of communication, self-monitoring, self-management, diagnosis, and treatment. However, the efficacy and reliability of publicly available applications (apps) have yet to be demonstrated. Numerous articles have noted the need for rigorous evaluation of the efficacy and clinical utility of smartphone apps, which are largely unregulated. Professional clinical organizations do not provide guidelines for evaluating mobile apps. Guidelines and frameworks are needed to evaluate medical apps. Numerous frameworks and evaluation criteria exist from the engineering and informatics literature, as well as interdisciplinary organizations in similar fields such as telemedicine and healthcare informatics. We propose criteria for both patients and providers to use in assessing not just smartphone apps, but also wearable devices and smartwatch apps for mental health. Apps can be evaluated by their usefulness, usability, and integration and infrastructure. Apps can be categorized by their usability in one or more stages of a mental health provider's workflow. Ultimately, leadership is needed to develop a framework for describing apps, and guidelines are needed for both patients and mental health providers.

  12. Quality of Smartphone Apps Related to Alcohol Use Disorder.

    Science.gov (United States)

    Penzenstadler, Louise; Chatton, Anne; Van Singer, Mathias; Khazaal, Yasser

    2016-01-01

    Apps for smartphones are opening an important range of opportunities for improving the care of people with alcohol use disorders (AUDs). This study aimed to evaluate the quality of English language apps for AUDs and to compare paid and free apps. The keywords 'alcohol', 'alcohol addiction', 'alcohol help' and 'stop drinking' were entered into the iTunes Store search engine. Apps were evaluated using a standardized assessment designed to rate the quality of apps in terms of accountability, interactivity, self-help score and evidence-based content. The Brief DISCERN score and the criteria of the 'Health on the Net' label were also used as content quality indicators. Of the 137 unique apps identified, 52 met the inclusion criteria. Overall, the content quality and self-help scores of these AUD apps were poor. The main quality indicators were not linked to payment status. Multiple linear regressions showed that the Brief DISCERN score significantly predicted content quality. Poor content quality and self-help scores of AUD smartphone apps underline the gap between their potential promises and the overall quality of available products in stores. The quality indicators used in the present study may be used for further app developments. © 2016 S. Karger AG, Basel.

  13. Enhancing Pharmacy Student Learning and Perceptions of Medical Apps.

    Science.gov (United States)

    Rodis, Jennifer; Aungst, Timothy Dy; Brown, Nicole V; Cui, Yan; Tam, Leonard

    2016-05-12

    The use of mobile apps in health care is growing. Current and future practitioners must be equipped with the skills to navigate and utilize apps in patient care, yet few strategies exist for training health care professional students on the usage of apps. To characterize first-year pharmacy student use of medical apps, evaluate first-year pharmacy student's perception of skills in finding, evaluating, and using medical apps before and after a focused learning experience, and assess student satisfaction and areas for improvement regarding the learning experience. Students listened to a recorded, Web-based lecture on finding, evaluating, and using mobile apps in patient care. A 2-hour, interactive workshop was conducted during which students were led by an instructor through a discussion on strategies for finding and using apps in health care. The students practiced evaluating 6 different health care-related apps. Surveys were conducted before and after the focused learning experience to assess students' perceptions of medical apps and current use and perspectives on satisfaction with the learning experience and role of technology in health care. This educational intervention is the first described formal, interactive method to educate student pharmacists on medical apps. With a 99% response rate, surveys conducted before and after the learning experience displayed perceived improvement in student skills related to finding (52/119, 44% before vs 114/120, 95% after), evaluating (18/119, 15% before vs 112/120, 93% after), and using medical apps in patient care (31/119, 26% before vs 108/120, 90% after) and the health sciences classroom (38/119, 32% before vs 104/120, 87% after). Students described satisfaction with the educational experience and agreed that it should be repeated in subsequent years (89/120, 74% agreed or strongly agreed). Most students surveyed possessed portable electronic devices (107/119, 90% mobile phone) and agreed with the concept of medical apps

  14. Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

    DEFF Research Database (Denmark)

    Karlsen, Allan Ertman; Heding, P E; Frobøse, H

    2004-01-01

    The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback reg...... regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown....

  15. Smart apps for the smart plastic surgeon

    Directory of Open Access Journals (Sweden)

    Aniketh Venkataram

    2015-01-01

    Full Text Available Smartphones have the ability to benefit plastic surgeons in all aspects of patient care and education. With the sheer number of applications available and more being created everyday, it is easy to miss out on apps which could be of great relevance. Moreover, the range of android applications available has not been extensively discussed in the literature. To this end, we have compiled an exhaustive list of android smartphone applications, which we feel can help our day to day functioning. The apps have been extensively reviewed and neatly described along with all their potential uses. In addition, we have made an effort to highlight ′non-medical′ or efficiency apps which can improve departmental functioning. These apps have not been described in prior articles, and their functionality might not be known to all. We believe that the technology savvy plastic surgeon can make maximum use of these apps to his benefit.

  16. Uptake of an Incentive-Based mHealth App: Process Evaluation of the Carrot Rewards App

    Science.gov (United States)

    Oh, Paul; Alter, David; Leahey, Tricia; Kwan, Matthew; Faulkner, Guy

    2017-01-01

    Background Behavioral economics has stimulated renewed interest in financial health incentives worldwide. The Carrot Rewards app was developed as part of a public-private partnership to reward Canadians with loyalty points (eg, movies and groceries) for downloading the app, referring friends, and completing an average of 1 to 2 educational health quizzes per week (“micro-learning”), with long-term objectives of increasing health knowledge and encouraging healthy behaviors. Objective The main objective of this study was to evaluate uptake of a loyalty points-based mHealth app during the exclusive 3-month launch period in British Columbia (BC), Canada. The secondary aims were to describe the health and sociodemographic characteristics of users, as well as participation levels (eg, proportion of quizzes completed and friends referred). Methods The app was promoted via loyalty program email campaigns (1.64 million emails). Number of downloads and registrations (users enter age, gender, and valid BC postal code to register) were collected. Additional sociodemographics were inferred by linking postal codes with census data at the local health area (LHA) level. Health risk assessments were also deployed. Participation levels were collected over 3 months and descriptive data were presented. Results In 3 months, 67,464 individuals downloaded the app; in its first week, Carrot Rewards was the most downloaded health app in Canada. Among valid users (n=57,885; at least one quiz completed), the majority were female (62.96%; 36,446/57,885) and aged 18 to 34 years (54.34%; 31,459/57,885). More than half of the users (52.40%; 30,332/57,885) resided in LHAs where the median personal income was below the provincial average (Can $28,765). Furthermore, 64.42% (37,291/57,885) of users lived in metropolitan (ie, urban) LHAs, compared with 56.17% of the general BC population. The most prevalent risk factors were “not” meeting physical activity guidelines (72.70%; 31

  17. Caspase activation increases beta-amyloid generation independently of caspase cleavage of the beta-amyloid precursor protein (APP).

    Science.gov (United States)

    Tesco, Giuseppina; Koh, Young Ho; Tanzi, Rudolph E

    2003-11-14

    The amyloid precursor protein (APP) undergoes "alternative" proteolysis mediated by caspases. Three major caspase recognition sites have been identified in the APP, i.e. one at the C terminus (Asp720) and two at the N terminus (Asp197 and Asp219). Caspase cleavage at Asp720 has been suggested as leading to increased production of Abeta. Thus, we set out to determine which putative caspase sites in APP, if any, are cleaved in Chinese hamster ovary cell lines concurrently with the increased Abeta production that occurs during apoptosis. We found that cleavage at Asp720 occurred concurrently with caspase 3 activation and the increased production of total secreted Abeta and Abeta1-42 in association with staurosporine- and etoposide-induced apoptosis. To investigate the contribution of caspase cleavage of APP to Abeta generation, we expressed an APP mutant truncated at Asp720 that mimics APP caspase cleavage at the C-terminal site. This did not increase Abeta generation but, in contrast, dramatically decreased Abeta production in Chinese hamster ovary cells. Furthermore, the ablation of caspase-dependent cleavage at Asp720, Asp197, and Asp219 (by site-directed mutagenesis) did not prevent enhanced Abeta production following etoposide-induced apoptosis. These findings indicate that the enhanced Abeta generation associated with apoptosis does not require cleavage of APP at its C-terminal (Asp720) and/or N-terminal caspase sites.

  18. Targeted On-Demand Team Performance App Development

    Science.gov (United States)

    2018-02-01

    management protocols and set up file management using encryption and a secure server. Complete 10 Customize Data Collection App Modify CareAssess App to...greater team morale. An App that serves to build relationships around the management of emergency medicine cases over time, could stimulate the... Management 4. Casualty Care 5. Trauma Care 6. Critical Care 7. Trauma Management 8. High Performing Teams 9. Team Characteristics 10. Team Composition

  19. Smartphone-apps som nyt psykiatrisk behandlingstiltag

    DEFF Research Database (Denmark)

    Dalum, Anette Ellegaard; Arnfred, Sidse

    2014-01-01

    The number of smartphone apps for people with mental health issues is undergoing a dramatical growth in these years. We review the available literature on the topic, discuss opportunities and theoretical considerations using smartphone apps in psychiatric treatment and provide an overview...

  20. Cyclophilin D deficiency rescues Aβ-impaired PKA/CREB signaling and alleviates synaptic degeneration.

    Science.gov (United States)

    Du, Heng; Guo, Lan; Wu, Xiaoping; Sosunov, Alexander A; McKhann, Guy M; Chen, John Xi; Yan, Shirley ShiDu

    2014-12-01

    The coexistence of neuronal mitochondrial pathology and synaptic dysfunction is an early pathological feature of Alzheimer's disease (AD). Cyclophilin D (CypD), an integral part of mitochondrial permeability transition pore (mPTP), is involved in amyloid beta (Aβ)-instigated mitochondrial dysfunction. Blockade of CypD prevents Aβ-induced mitochondrial malfunction and the consequent cognitive impairments. Here, we showed the elimination of reactive oxygen species (ROS) by antioxidants probucol or superoxide dismutase (SOD)/catalase blocks Aβ-mediated inactivation of protein kinase A (PKA)/cAMP regulatory-element-binding (CREB) signal transduction pathway and loss of synapse, suggesting the detrimental effects of oxidative stress on neuronal PKA/CREB activity. Notably, neurons lacking CypD significantly attenuate Aβ-induced ROS. Consequently, CypD-deficient neurons are resistant to Aβ-disrupted PKA/CREB signaling by increased PKA activity, phosphorylation of PKA catalytic subunit (PKA C), and CREB. In parallel, lack of CypD protects neurons from Aβ-induced loss of synapses and synaptic dysfunction. Furthermore, compared to the mAPP mice, CypD-deficient mAPP mice reveal less inactivation of PKA-CREB activity and increased synaptic density, attenuate abnormalities in dendritic spine maturation, and improve spontaneous synaptic activity. These findings provide new insights into a mechanism in the crosstalk between the CypD-dependent mitochondrial oxidative stress and signaling cascade, leading to synaptic injury, functioning through the PKA/CREB signal transduction pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Popular Nutrition-Related Mobile Apps: A Feature Assessment.

    Science.gov (United States)

    Franco, Rodrigo Zenun; Fallaize, Rosalind; Lovegrove, Julie A; Hwang, Faustina

    2016-08-01

    A key challenge in human nutrition is the assessment of usual food intake. This is of particular interest given recent proposals of eHealth personalized interventions. The adoption of mobile phones has created an opportunity for assessing and improving nutrient intake as they can be used for digitalizing dietary assessments and providing feedback. In the last few years, hundreds of nutrition-related mobile apps have been launched and installed by millions of users. This study aims to analyze the main features of the most popular nutrition apps and to compare their strategies and technologies for dietary assessment and user feedback. Apps were selected from the two largest online stores of the most popular mobile operating systems-the Google Play Store for Android and the iTunes App Store for iOS-based on popularity as measured by the number of installs and reviews. The keywords used in the search were as follows: calorie(s), diet, diet tracker, dietician, dietitian, eating, fit, fitness, food, food diary, food tracker, health, lose weight, nutrition, nutritionist, weight, weight loss, weight management, weight watcher, and ww calculator. The inclusion criteria were as follows: English language, minimum number of installs (1 million for Google Play Store) or reviews (7500 for iTunes App Store), relation to nutrition (ie, diet monitoring or recommendation), and independence from any device (eg, wearable) or subscription. A total of 13 apps were classified as popular for inclusion in the analysis. Nine apps offered prospective recording of food intake using a food diary feature. Food selection was available via text search or barcode scanner technologies. Portion size selection was only textual (ie, without images or icons). All nine of these apps were also capable of collecting physical activity (PA) information using self-report, the global positioning system (GPS), or wearable integrations. Their outputs focused predominantly on energy balance between dietary

  2. Thylakoid redox signals are integrated into organellar-gene-expression-dependent retrograde signalling in the prors1-1 mutant

    Directory of Open Access Journals (Sweden)

    Luca eTadini

    2012-12-01

    Full Text Available Perturbations in organellar gene expression (OGE and the thylakoid redox state (TRS activate retrograde signalling pathways that adaptively modify nuclear gene expression (NGE, according to developmental and metabolic needs. The prors1-1 mutation in Arabidopsis down-regulates the expression of the nuclear gene Prolyl-tRNA Synthetase1 (PRORS1 which acts in both plastids and mitochondria, thereby impairing protein synthesis in both organelles and triggering OGE-dependent retrograde signalling. Because the mutation also affects thylakoid electron transport, TRS-dependent signals may likewise have an impact on the changes in NGE observed in this genotype. In this study, we have investigated whether signals related to TRS are actually integrated into the OGE-dependent retrograde signalling pathway. To this end, the chaos mutation (for chlorophyll a/b binding protein harvesting-organelle specific, which shows a partial loss of PSII antennae proteins and thus a reduction in PSII light absorption capability, was introduced into the prors1-1 mutant background. The resulting double mutant displayed a prors1-1-like reduction in plastid translation rate and a chaos-like decrease in PSII antenna size, whereas the hyper-reduction of the thylakoid electron transport chain, caused by the prors1-1 mutation, was alleviated, as determined by monitoring chlorophyll (Chl fluorescence and thylakoid phosphorylation. Interestingly, a substantial fraction of the nucleus-encoded photosynthesis genes down-regulated in the prors1-1 mutant are expressed at nearly wild-type rates in prors1-1 chaos leaves, and this recovery is reflected in the steady-state levels of their protein products in the chloroplast. We therefore conclude that signals related to photosynthetic electron transport and TRS, and indirectly to carbohydrate metabolism and energy balance, are indeed fed into the OGE-dependent retrograde pathway to modulate NGE and adjust the abundance of chloroplast proteins.

  3. Health Behavior Theory in Popular Calorie Counting Apps: A Content Analysis

    OpenAIRE

    Davis, Siena F; Ellsworth, Marisa A; Payne, Hannah E; Hall, Shelby M; West, Joshua H; Nordhagen, Amber L

    2016-01-01

    Background Although the Health & Fitness category of the Apple App Store features hundreds of calorie counting apps, the extent to which popular calorie counting apps include health behavior theory is unknown. Objective This study evaluates the presence of health behavior theory in calorie counting apps. Methods Data for this study came from an extensive content analysis of the 10 most popular calorie counting apps in the Health & Fitness category of the Apple App Store. Results Each app was ...

  4. Direct to Consumer Mobile Teledermatology Apps: An Exploratory Study

    OpenAIRE

    Kochmann, Matthias; Locatis, Craig

    2016-01-01

    Background: Since 2012, “Direct to Consumer” mobile teledermatology apps have become more available, relinquishing many data collection tasks normally done by healthcare professionals directly to patients. Introduction: To determine user friendliness, diagnostic quality, and service of commercially available mobile teledermatology apps. Materials and Methods: All mobile teledermatology apps available at the Apple App Store were reviewed. The two most popular mobile teledermatol...

  5. Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

    Science.gov (United States)

    Grimm, Marcus O. W.; Grösgen, Sven; Rothhaar, Tatjana L.; Burg, Verena K.; Hundsdörfer, Benjamin; Haupenthal, Viola J.; Friess, Petra; Müller, Ulrike; Fassbender, Klaus; Riemenschneider, Matthias; Grimm, Heike S.; Hartmann, Tobias

    2011-01-01

    Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology. PMID:21660213

  6. Safe Sex Messages Within Dating and Entertainment Smartphone Apps: A Review.

    Science.gov (United States)

    Huang, Evelyn Tzu-Yen; Williams, Henrietta; Hocking, Jane S; Lim, Megan Sc

    2016-11-08

    Smartphone apps provide a new platform for entertainment, information distribution, and health promotion activities, as well as for dating and casual sexual encounters. Previous research has shown high acceptability of sexual health interventions via smartphone apps; however, sexual health promotion apps were infrequently downloaded and underused. Integrating sexual health promotion into established apps might be a more effective method. The objective of our study was to critically review popular sex-related apps and dating apps, in order to ascertain whether they contain any sexual health content. Part 1: In January 2015, we used the term "sexual" to search for free apps in the Apple iTunes store and Android Google Play store, and categorized the sexual health content of the 137 apps identified. Part 2: We used the term "dating" to search for free geosocial-networking apps in the Apple iTunes and Android Google Play stores. The apps were downloaded to test functionality and to determine whether they included sexual health content. Part 1: Of the 137 apps identified, 15 (11.0%) had sexual health content and 15 (11.0%) contained messages about sexual assault or violence. The majority of the apps did not contain any sexual health content. Part 2: We reviewed 60 dating apps: 44 (73%) targeting heterosexual users, 9 (15%) targeting men who have sex with men (MSM), 3 (5%) targeting lesbian women, and 4 (7%) for group dating. Only 9 dating apps contained sexual health content, of which 7 targeted MSM. The majority of sex-related apps and dating apps contained no sexual health content that could educate users about and remind them of their sexual risks. Sexual health practitioners and public health departments will need to work with app developers to promote sexual health within existing popular apps. For those apps that already contain sexual health messages, further study to investigate the effectiveness of the content is needed. ©Evelyn Tzu-Yen Huang, Henrietta

  7. A parental perspective on apps for young children

    NARCIS (Netherlands)

    Broekman, F.L.; Piotrowski, J.T.; Beentjes, H.W.J.; Valkenburg, P.M.

    2016-01-01

    Touchscreen applications (apps) for young children have seen increasingly high rates of growth with more than a hundred thousand now available apps. As with other media, parents play a key role in young children’s app selection and use. However, to date, we know very little about how parents select

  8. Car App's Persuasive Design Principles and Behavior Change

    Science.gov (United States)

    Zhang, Chao; Wan, Lili; Min, Daihwan

    2016-01-01

    The emphasis of this study lies in behavior change after using car apps that assist users in using their vehicles and establishing a process for examining the interrelationship between car app's persuasive characteristics and behavior change. A categorizing method was developed and 697 car apps were investigated and classified into eight…

  9. App Reviews: Breaking the User and Developer Language Barrier

    KAUST Repository

    Hoon, Leonard

    2015-10-22

    Apple, Google and third party developers offer apps across over twenty categories for various smart mobile devices. Offered exclusively through the App Store and Google Play, each app allows users to review the app and their experience with it. Current literature offers a general statistical picture of these reviews, and a broad overview of the nature of discontent of apps. However, we do not yet have a good framework to classify user reviews against known software quality attributes like performance or usability. In order to close this gap, in this paper, we develop an ontology encompassing software attributes derived from software quality models. This decomposes into approximately five thousand words that users employ to review apps. By identifying a consistent set of vocabulary that users communicate with, we can sanitise large datasets to extract stakeholder actionable information from reviews. The findings offered in this paper assists future app review analysis by bridging end-user communication and software engineering vocabulary.

  10. App Reviews: Breaking the User and Developer Language Barrier

    KAUST Repository

    Hoon, Leonard; Rodriguez-Garcia, Miguel Angel; Vasa, Rajesh; Valencia-Garcí a, Rafael; Schneider, Jean-Guy

    2015-01-01

    Apple, Google and third party developers offer apps across over twenty categories for various smart mobile devices. Offered exclusively through the App Store and Google Play, each app allows users to review the app and their experience with it. Current literature offers a general statistical picture of these reviews, and a broad overview of the nature of discontent of apps. However, we do not yet have a good framework to classify user reviews against known software quality attributes like performance or usability. In order to close this gap, in this paper, we develop an ontology encompassing software attributes derived from software quality models. This decomposes into approximately five thousand words that users employ to review apps. By identifying a consistent set of vocabulary that users communicate with, we can sanitise large datasets to extract stakeholder actionable information from reviews. The findings offered in this paper assists future app review analysis by bridging end-user communication and software engineering vocabulary.

  11. Mobile Apps in Oncology: A Survey on Health Care Professionals' Attitude Toward Telemedicine, mHealth, and Oncological Apps.

    Science.gov (United States)

    Kessel, Kerstin A; Vogel, Marco Me; Schmidt-Graf, Friederike; Combs, Stephanie E

    2016-11-24

    Mobile apps are an evolving trend in the medical field. To date, few apps in an oncological context exist. The aim was to analyze the attitude of health care professionals (HCPs) toward telemedicine, mHealth, and mobile apps in the field of oncology. We developed and conducted an online survey with 24 questions evaluating HCPs' general attitude toward telemedicine and patients using medical mobile apps. Specific questions on the possible functionality for patients and the resulting advantages and disadvantages for both the patients' and HCPs' daily clinical routine were evaluated. A total of 108 HCPs completed the survey. In all, 88.9% (96/108) considered telemedicine useful and 84.3% (91/108) supported the idea of an oncological app complementing classical treatment. Automatic reminders, timetables, and assessment of side effects and quality of life during therapy were rated as the most important functions. In contrast, uncertainty regarding medical responsibility and data privacy were reasons mostly named by critics. Most (64.8%, 70/108) were in favor of an alert function due to data input needing further clarification, and 94% (66/70) were willing to contact the patient after a critical alert. In all, 93.5% (101/108) supported the idea of using the collected data for scientific research. Moreover, 75.0% (81/108) believed establishing a mobile app could be beneficial for the providing hospital. A majority of HCPs are in favor of telemedicine and the use of oncological apps by patients. Assessing side effects can lead to quicker response and thus lower inconvenience for patients. Clinical data, such as life quality and treatment satisfaction, could be used to evaluate and improve the therapy workflow. Eventually, a mobile app would enhance the patients' relationship to their treating department because they are in permanent contact. ©Kerstin A Kessel, Marco ME Vogel, Friederike Schmidt-Graf, Stephanie E Combs. Originally published in the Journal of Medical

  12. Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus.

    Science.gov (United States)

    Torres, Manuel; Jimenez, Sebastian; Sanchez-Varo, Raquel; Navarro, Victoria; Trujillo-Estrada, Laura; Sanchez-Mejias, Elisabeth; Carmona, Irene; Davila, Jose Carlos; Vizuete, Marisa; Gutierrez, Antonia; Vitorica, Javier

    2012-11-22

    Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor extent, proteasomal activity could be

  13. Women's experiences with using a smartphone app (the Pregnant+ app) to manage gestational diabetes mellitus in a randomised controlled trial.

    Science.gov (United States)

    Skar, Jeanette B; Garnweidner-Holme, Lisa M; Lukasse, Mirjam; Terragni, Laura

    2018-03-01

    The purpose of this study was to explore the experiences of women with gestational diabetes mellitus (GDM) with controlling their blood glucose values and receiving health and nutrition information using a smartphone app (the Pregnant+ app). The study utilised the interpretative phenomenological analysis method. Semi-structured interviews were conducted with 17 participants among those participating to the randomised controlled trial. The women experienced sorrow and disappointment when they were diagnosed with GDM, but they all went through a process of learning to self-manage their condition that was strongly motivated by theirdesire to care for their unborn babies. The women found that the app increased their confidence in their self management of GDM and their motivation for behavioural change. For some women, the app contributed to feelings offrustration or obsession. In addition, some technological problems and a lack of support from health-care professionals limited several women from using the app. The findings suggest that asmartphone app may have potential for supporting women with GDM, particularly in their blood glucose management. However, it also highlights some of the potential challenges of using mHealth technologies. The findings indicate that a closer collaboration between health-care professionals and patients is of great importance in the implementation of apps for women with GDM. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. There is an app for that! The current state of mobile applications (apps) for DSM-5 obsessive-compulsive disorder, posttraumatic stress disorder, anxiety and mood disorders.

    Science.gov (United States)

    Van Ameringen, Michael; Turna, Jasmine; Khalesi, Zahra; Pullia, Katrina; Patterson, Beth

    2017-06-01

    Mental health apps are viewed as a promising modality to extend the reach of mental health care beyond the clinic. They do so by providing a means of assessment, tracking, and treatment through a smartphone. Given that nearly 2/3 of the American population owns a smartphone, mental health apps offer the possibility of overcoming treatment barriers such as geographic location or financial barriers. Unfortunately, the excitement surrounding mental health apps may be premature as the current supporting literature regarding their efficacy is limited. The app marketplace is littered with apps claiming to treat or assess symptoms, but even those created by reputable organizations or those incorporating components of evidence-based treatments have not yet been validated in terms of their efficacy. This review aims to provide a comprehensive review of the current state of the mental health app literature by examining published reports of apps designed for DSM-5 anxiety and mood disorders, OCD, and PTSD. The breadth of apps reviewed includes those oriented around assessment, symptom tracking, and treatment as well as "multipurpose" apps, which incorporate several of these components. This review will also present some of the most popular mental health apps which may have clinical utility and could be prescribed to clients. While we discuss many potential benefits of mental health apps, we focus on a number of issues that the current state of the app literature presents. Overall there is a significant disconnect between app developers, the scientific community and health care, leaving the utility of existing apps questionable. © 2017 Wiley Periodicals, Inc.

  15. Athletic Training Education: There's an App for That

    Science.gov (United States)

    Keeley, Kim; Potteiger, Kelly; Brown, Christopher D.

    2015-01-01

    Context: Mobile applications (apps) are growing in popularity due to the increased use of smartphones. Many available apps are educational in nature and may provide both students and educators freedom for learning to occur outside of the typical classroom environment. Objective: To provide a description of relevant apps along with a brief synopsis…

  16. Medical apps in endocrine diseases – hide and seek

    Science.gov (United States)

    von Jan, Ute

    2014-01-01

    Objectives: Quantitative review and categorization of available endocrinology related mobile apps for the iOS platform (Apple®) and outline of search strategies to identify appropriate mobile apps for this field. Methods: A total of 80 endocrinology related search terms were collected and grouped into 8 main categories covering different areas of endocrinology. These terms were then used to perform comprehensive searches in three categories of Apple’s app store, namely ‘Medicine’, ‘Health and Fitness’, and ‘Reference’. Results: Altogether, matches were found for only 33 of the 80 collected endocrinology related search terms; the majority of matches were found in the medical category, followed by matches for the health and fitness (27/33), and reference (16/33) categories. Restricting the search to these categories significantly helped in discriminating between health related apps and those having another purpose. The distribution of apps per category roughly matches what one can expect considering available data for incidence and prevalence of corresponding endocrinological conditions. Apps matching terms belonging to the spectrum of glucose homeostasis disorders are the most common. For conditions where patients do not have to constantly monitor their condition, apps tend to have a reference or educational character, while for conditions that require a high level of involvement from patients, there are proportionally more apps for self-management. With a single exception, the identified apps had not undergone regulation, and information about the data sources, professional backgrounds, and reliability of the content and integrated information sources was rare. Conclusions: While applying a good search strategy is important for finding apps for endocrinology related problems, users also need to consider whether the app they have found respects all necessary criteria regarding reliability, privacy and data protection before they place their trust in

  17. Game Bola Tangkis Berbasis Android Menggunakan App Inventor

    Directory of Open Access Journals (Sweden)

    Mhd Arief Hasan

    2017-11-01

    Full Text Available AbstrakBerkembangnya teknologi yang berbasis mobile sekarang ini sudah sangat maju dan sering dipakai untuk dunia Information Technology (IT, bisnis, pendidikan dan media pembelajaran. Teknologi handphone yang saat ini berkembang pesat salah satunya adalah sistem operasi Android mobile (Android OS. Android adalah sistem operasi berbasis Linux yang dirancang untuk perangkat mobile layar sentuh yang memungkinkan perangkat lunak bebas dimodifikasi dan didistribusikan oleh pembuat perangkat, operator nirkabel dan pengembang aplikasi. Salah satu editor dalam pemrograman android adalah APP Inventor .App Inventor merupakan aplikasi web sumber terbuka yang awalnya dikembangkan oleh Google, dan saat ini dikelola oleh Massachusetts Institute of Technology (MIT. App Inventor memungkinkan pengguna baru untuk memprogram komputer untuk menciptakan aplikasi perangkat lunak bagi sistem operasi Android.  Dengan adanya kemudahan dalam pembuatan program yang disediakan oleh App Inventor yang tidak diharuskan lagi untuk menuliskan koding. Semua fasilitas itu bisa digunakan dengan menggunakan klik drag menggunakan blog diagram. Maka peneliti mengambil kasus game bola tangkis dalam penelitian ini. Kata kunci : Game Bola Tangkis, Android, App Inventor AbstractThe development of mobile-based technology is now very advanced and often used for the world of Information Technology (IT, business, education and learning media. Mobile technology is currently growing rapidly one of them is the Android mobile operating system (Android OS. Android is a Linux-based operating system designed for touch-screen mobile devices that allows free software to be modified and distributed by device makers, wireless carriers and app developers. One of the editors in android programming is APP Inventor. Appper Inventor is an open source web application originally developed by Google, and is currently managed by the Massachusetts Institute of Technology (MIT. App Inventor allows new users

  18. 15 CFR 740.7 - Computers (APP).

    Science.gov (United States)

    2010-01-01

    ... 4A003. (2) Technology and software. License Exception APP authorizes exports of technology and software... License Exception. (2) Access and release restrictions—(i)Computers and software. Computers and software... software eligible for License Exception APP may not be reexported or transferred (in country) without prior...

  19. Low Quality of Free Coaching Apps With Respect to the American College of Sports Medicine Guidelines: A Review of Current Mobile Apps.

    Science.gov (United States)

    Modave, François; Bian, Jiang; Leavitt, Trevor; Bromwell, Jennifer; Harris Iii, Charles; Vincent, Heather

    2015-07-24

    Low physical activity level is a significant contributor to chronic disease, weight dysregulation, and mortality. Nearly 70% of the American population is overweight, and 35% is obese. Obesity costs an estimated US$ 147 billion annually in health care, and as many as 95 million years of life. Although poor nutritional habits remain the major culprit, lack of physical activity significantly contributes to the obesity epidemic and related lifestyle diseases. Over the past 10 years, mobile devices have become ubiquitous, and there is an ever-increasing number of mobile apps that are being developed to facilitate physical activity, particularly for active people. However, no systematic assessment has been performed about their quality with respect to following the parameters of sound fitness principles and scientific evidence, or suitability for a variety of fitness levels. The aim of this paper is to fill this gap and assess the quality of mobile coaching apps on iOS mobile devices. A set of 30 popular mobile apps pertaining to physical activity programming was identified and reviewed on an iPhone device. These apps met the inclusion criteria and provided specific prescriptive fitness and exercise programming content. The content of these apps was compared against the current guidelines and fitness principles established by the American College of Sports Medicine (ACSM). A weighted scoring method based on the recommendations of the ACSM was developed to generate subscores for quality of programming content for aerobic (0-6 scale), resistance (0-6 scale), and flexibility (0-2 scale) components using the frequency, intensity, time, and type (FITT) principle. An overall score (0-14 scale) was generated from the subscores to represent the overall quality of a fitness coaching app. Only 3 apps scored above 50% on the aerobic component (mean 0.7514, SD 1.2150, maximum 4.1636), 4 scored above 50% on the resistance/strength component (mean 1.4525, SD 1.2101, maximum 4

  20. Cloning and Expression of Phytase appA Gene from Shigella sp. CD2 in Pichia pastoris and Comparison of Properties with Recombinant Enzyme Expressed in E. coli.

    Directory of Open Access Journals (Sweden)

    Moushree Pal Roy

    Full Text Available The phytase gene appAS was isolated from Shigella sp. CD2 genomic library. The 3.8 kb DNA fragment contained 1299 bp open reading frame encoding 432 amino acid protein (AppAS with 22 amino acid signal peptide at N-terminal and three sites of N-glycosylation. AppAS contained the active site RHGXRXP and HDTN sequence motifs, which are conserved among histidine acid phosphatases. It showed maximum identity with phytase AppA of Escherichia coli and Citrobacter braakii. The appAS was expressed in Pichia pastoris and E. coli to produce recombinant phytase rAppAP and rAppAE, respectively. Purified glycosylated rAppAP and nonglycosylated rAppAE had specific activity of 967 and 2982 U mg(-1, respectively. Both had pH optima of 5.5 and temperature optima of 60°C. Compared with rAppAE, rAppAP was 13 and 17% less active at pH 3.5 and 7.5 and 11 and 18% less active at temperature 37 and 50°C, respectively; however, it was more active at higher incubation temperatures. Thermotolerance of rAppAP was 33% greater at 60°C and 24% greater at 70°C, when compared with rAppAE. Both the recombinant enzymes showed high specificity to phytate and resistance to trypsin. To our knowledge, this is the first report on cloning and expression of phytase from Shigella sp.

  1. Cloning and Expression of Phytase appA Gene from Shigella sp. CD2 in Pichia pastoris and Comparison of Properties with Recombinant Enzyme Expressed in E. coli.

    Science.gov (United States)

    Pal Roy, Moushree; Mazumdar, Deepika; Dutta, Subhabrata; Saha, Shyama Prasad; Ghosh, Shilpi

    2016-01-01

    The phytase gene appAS was isolated from Shigella sp. CD2 genomic library. The 3.8 kb DNA fragment contained 1299 bp open reading frame encoding 432 amino acid protein (AppAS) with 22 amino acid signal peptide at N-terminal and three sites of N-glycosylation. AppAS contained the active site RHGXRXP and HDTN sequence motifs, which are conserved among histidine acid phosphatases. It showed maximum identity with phytase AppA of Escherichia coli and Citrobacter braakii. The appAS was expressed in Pichia pastoris and E. coli to produce recombinant phytase rAppAP and rAppAE, respectively. Purified glycosylated rAppAP and nonglycosylated rAppAE had specific activity of 967 and 2982 U mg(-1), respectively. Both had pH optima of 5.5 and temperature optima of 60°C. Compared with rAppAE, rAppAP was 13 and 17% less active at pH 3.5 and 7.5 and 11 and 18% less active at temperature 37 and 50°C, respectively; however, it was more active at higher incubation temperatures. Thermotolerance of rAppAP was 33% greater at 60°C and 24% greater at 70°C, when compared with rAppAE. Both the recombinant enzymes showed high specificity to phytate and resistance to trypsin. To our knowledge, this is the first report on cloning and expression of phytase from Shigella sp.

  2. Structural features of the KPI domain control APP dimerization, trafficking, and processing.

    Science.gov (United States)

    Ben Khalifa, Naouel; Tyteca, Donatienne; Marinangeli, Claudia; Depuydt, Mathieu; Collet, Jean-François; Courtoy, Pierre J; Renauld, Jean-Christophe; Constantinescu, Stefan; Octave, Jean-Noël; Kienlen-Campard, Pascal

    2012-02-01

    The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.

  3. The Anatomy of Virtual Manipulative Apps: Using Grounded Theory to Conceptualize and Evaluate Educational Apps that Contain Virtual Manipulatives

    OpenAIRE

    Boyer-Thurgood, Jennifer M.

    2017-01-01

    This exploratory qualitative study used grounded theory to investigate the anatomy of educational apps that contain virtual manipulatives. For this study 100 virtual manipulatives within educational apps designed for the iPad were observed by the researcher in order to expand the explanations of and build theory about virtual manipulatives within apps. Affordance theory was used to frame all six phases of the study in which the researcher identified virtual manipulatives situated within educa...

  4. Gene array analysis of PD-1H overexpressing monocytes reveals a pro-inflammatory profile

    Directory of Open Access Journals (Sweden)

    Preeti Bharaj

    2018-02-01

    Full Text Available We have previously reported that overexpression of Programmed Death -1 Homolog (PD-1H in human monocytes leads to activation and spontaneous secretion of multiple pro inflammatory cytokines. Here we evaluate changes in monocytes gene expression after enforced PD-1H expression by gene array. The results show that there are significant alterations in 51 potential candidate genes that relate to immune response, cell adhesion and metabolism. Genes corresponding to pro-inflammatory cytokines showed the highest upregulation, 7, 3.2, 3.0, 5.8, 4.4 and 3.1 fold upregulation of TNF-α, IL-1 β, IFN-α, γ, λ and IL-27 relative to vector control. The data are in agreement with cytometric bead array analysis showing induction of proinflammatory cytokines, IL-6, IL-1β and TNF-α by PD-1H. Other genes related to inflammation, include transglutaminase 2 (TG2, NF-κB (p65 and p50 and toll like receptors (TLR 3 and 4 were upregulated 5, 4.5 and 2.5 fold, respectively. Gene set enrichment analysis (GSEA also revealed that signaling pathways related to inflammatory response, such as NFκB, AT1R, PYK2, MAPK, RELA, TNFR1, MTOR and proteasomal degradation, were significantly upregulated in response to PD-1H overexpression. We validated the results utilizing a standard inflammatory sepsis model in humanized BLT mice, finding that PD-1H expression was highly correlated with proinflammatory cytokine production. We therefore conclude that PD-1H functions to enhance monocyte activation and the induction of a pro-inflammatory gene expression profile.

  5. iPad Apps That Promote Mathematical Knowledge? "Yes, They Exist!"

    Science.gov (United States)

    Larkin, Kevin

    2014-01-01

    Having trouble finding the right app? In this article, Kevin Larkin discusses the difficulties teachers encounter when searching the App Store for high quality, appropriate apps that support students' mathematical learning. Kevin provides a useful link to a collection of over 100 app reviews.

  6. Using the Modern Technology That Is the "App"

    Science.gov (United States)

    Bernardelli, Alessio

    2013-01-01

    A few years ago, the sight of the letters APP would have made teachers in England think of the Assessing Pupils' Progress assessment approach introduced by the government. Now, when they see those same letters they mostly think about smartphone and tablet applications, shortened to "apps." With the thousands of apps available in the…

  7. HMGB1-RAGE pathway drives peroxynitrite signaling-induced IBD-like inflammation in murine nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Varun Chandrashekaran

    2017-10-01

    Full Text Available Recent clinical studies found a strong association of colonic inflammation and Inflammatory bowel disease (IBD-like phenotype with NonAlcoholic Fatty liver Disease (NAFLD yet the mechanisms remain unknown. The present study identifies high mobility group box 1 (HMGB1 as a key mediator of intestinal inflammation in NAFLD and outlines a detailed redox signaling mechanism for such a pathway. NAFLD mice showed liver damage and release of elevated HMGB1 in systemic circulation and increased intestinal tyrosine nitration that was dependent on NADPH oxidase. Intestines from NAFLD mice showed higher Toll like receptor 4 (TLR4 activation and proinflammatory cytokine release, an outcome strongly dependent on the existence of NAFLD pathology and NADPH oxidase. Mechanistically intestinal epithelial cells showed the HMGB1 activation of TLR-4 was both NADPH oxidase and peroxynitrite dependent with the latter being formed by the activation of NADPH oxidase. Proinflammatory cytokine production was significantly blocked by the specific peroxynitrite scavenger phenyl boronic acid (FBA, AKT inhibition and NADPH oxidase inhibitor Apocynin suggesting NADPH oxidase-dependent peroxynitrite is a key mediator in TLR-4 activation and cytokine release via an AKT dependent pathway. Studies to ascertain the mechanism of HMGB1-mediated NADPH oxidase activation showed a distinct role of Receptor for advanced glycation end products (RAGE as the use of inhibitors targeted against RAGE or use of deformed HMGB1 protein prevented NADPH oxidase activation, peroxynitrite formation, TLR4 activation and finally cytokine release. Thus, in conclusion the present study identifies a novel role of HMGB1 mediated inflammatory pathway that is RAGE and redox signaling dependent and helps promote ectopic intestinal inflammation in NAFLD.

  8. Proinflammatory effect of sodium 4-phenylbutyrate in deltaF508-cystic fibrosis transmembrane conductance regulator lung epithelial cells: involvement of extracellular signal-regulated protein kinase 1/2 and c-Jun-NH2-terminal kinase signaling.

    Science.gov (United States)

    Roque, Telma; Boncoeur, Emilie; Saint-Criq, Vinciane; Bonvin, Elise; Clement, Annick; Tabary, Olivier; Jacquot, Jacky

    2008-09-01

    Sodium 4-phenylbutyrate (4-PBA) has attracted a great deal of attention in cystic fibrosis (CF) pathology due to its capacity to traffic DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR) to the cell membrane and restore CFTR chloride function at the plasma membrane of CF lung cells in vitro and in vivo. Using two different DeltaF508-CFTR lung epithelial cell lines (CFBE41o- and IB3-1 cells, characterized with DeltaF508-homozygous and heterozygous genotype, respectively) in vitro, 4-PBA induced an increase of proinflammatory cytokine interleukin (IL)-8 production in a concentration-dependent manner. This 4-PBA-induced IL-8 production was associated with a strong reduction of proteasome and nuclear factor-kappaB transcriptional activities in the two DeltaF508-CFTR lung cells either in a resting state or after tumor necrosis factor-alpha stimulation. In contrast, a strong increase of activator protein-1 transcriptional activity was observed. The inhibition of extracellular signal-regulated protein kinase 1/2 (ERK1/2) by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126) and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) and c-Jun-NH(2)-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) by anthra[1,9-cd] pyrazol-6 (2H)-one (SP600125), respectively, was associated with a reduction (2-3.5-fold) of IL-8 production in both DeltaF508-CFTR lung cell lines treated with 4-PBA. No significant change of IL-8 production was observed after an inhibition of p38 MAPK with 4-[4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-2-yl] phenol (SB202190). Therefore, we suggest that inhibition of both ERK1/2 and JNK signaling may be a means to strongly reduce 4-PBA-induced IL-8 production in combination with 4-PBA treatment to restore CFTR Cl(-) channel function in lung epithelial cells of patients with CF.

  9. Photoperiod- and Triiodothyronine-dependent Regulation of Reproductive Neuropeptides, Proinflammatory Cytokines, and Peripheral Physiology in Siberian Hamsters (Phodopus sungorus).

    Science.gov (United States)

    Banks, Ruth; Delibegovic, Mirela; Stevenson, Tyler J

    2016-06-01

    Seasonal trade-offs in reproduction and immunity are ubiquitous in nature. The mechanisms that govern transitions across seasonal physiological states appear to involve reciprocal switches in the local synthesis of thyroid hormone. In long-day (LD) summer-like conditions, increased hypothalamic triiodothyronine (T3) stimulates gonadal development. Alternatively, short-day (SD) winter-like conditions increase peripheral leukocytes and enhance multiple aspects of immune function. These data indicate that the localized effects of T3 in the hypothalamus and leukocytes are photoperiod dependent. We tested the hypothesis that increased peripheral T3 in SD conditions would increase aspects of reproductive physiology and inhibit immune function, whereas T3 injections in LD conditions would facilitate aspects of immune function (i.e., leukocytes). In addition, we also examined whether T3 regulates hypothalamic neuropeptide expression as well as hypothalamic and splenic proinflammatory cytokine expression. Adult male Siberian hamsters were maintained in LD (15L:9D) or transferred to SD (9L:15D) for 8 weeks. A subset of LD and SD hamsters was treated daily with 5 µg T3 for 2 weeks. LD and SD controls were injected with saline. Daily T3 administration in SD hamsters (SD+T3) resulted in a rapid and substantial decrease in peripheral leukocyte concentrations and stimulated gonadal development. T3 treatment in LD (LD+T3) had no effect on testicular volumes but significantly increased leukocyte concentrations. Molecular analyses revealed that T3 stimulated interleukin 1β messenger RNA (mRNA) expression in the spleen and inhibited RFamide Related Peptide-3 mRNA expression in the hypothalamus. Moreover, there was a photoperiod-dependent decrease in splenic tumor necrosis factor-α mRNA expression. These findings reveal that T3 has tissue-specific and photoperiod-dependent regulation of seasonal rhythms in reproduction and immune function. © 2016 The Author(s).

  10. Gebruikersdata bij abonnementen in app stores

    NARCIS (Netherlands)

    Roosendaal, A.P.C.; Nieuwenhuis, O.A.

    2013-01-01

    Kranten en tijdschriften bieden tegenwoordig vaak, naast de papieren edities, digitale abonnementen aan. De content wordt in dat geval via een app gelezen op een mobiele device, zoals een smartphone of tablet. Om abonnementen in deze vorm aan te kunnen bieden is het bouwen van een app noodzakelijk.

  11. Cool Apps: Productivity at Your Fingertips

    Science.gov (United States)

    Flaherty, Bill

    2013-01-01

    In addition to listing apps and their value, this article focuses on ways people can be more productive by adopting certain workflows in several ways. Apps listed herein include those useful in calendaring, printing, photo-editing, image-recognition, image scanning, electronic signatures, and making and sharing lists and notes.

  12. Enhancing Application Performance Using Mini-Apps: Comparison of Hybrid Parallel Programming Paradigms

    Science.gov (United States)

    Lawson, Gary; Sosonkina, Masha; Baurle, Robert; Hammond, Dana

    2017-01-01

    In many fields, real-world applications for High Performance Computing have already been developed. For these applications to stay up-to-date, new parallel strategies must be explored to yield the best performance; however, restructuring or modifying a real-world application may be daunting depending on the size of the code. In this case, a mini-app may be employed to quickly explore such options without modifying the entire code. In this work, several mini-apps have been created to enhance a real-world application performance, namely the VULCAN code for complex flow analysis developed at the NASA Langley Research Center. These mini-apps explore hybrid parallel programming paradigms with Message Passing Interface (MPI) for distributed memory access and either Shared MPI (SMPI) or OpenMP for shared memory accesses. Performance testing shows that MPI+SMPI yields the best execution performance, while requiring the largest number of code changes. A maximum speedup of 23 was measured for MPI+SMPI, but only 11 was measured for MPI+OpenMP.

  13. Users’ Adoption of Mental Health Apps: Examining the Impact of Information Cues

    Science.gov (United States)

    Huang, Hsiao-Ying

    2017-01-01

    Background Numerous mental health apps have been developed and made available to users on the current app market. Users may find it difficult and overwhelming to select apps from the hundreds of choices that are available in the app marketplace. Clarifying what information cues may impact a user’s selection and adoption of mental health apps is now a critical and pressing issue. Objective The aim of this study was to investigate the impact of information cues on users’ adoption of anxiety apps using observational data from the Android app market. Methods A systematic search of anxiety apps was conducted on the Android app store by using keywords search. The title and metadata information of a total of 274 apps that met our criteria were collected and analyzed. Three trained researchers recorded the app rankings from the search results page on different dates and Web browsers. Results Our results show that ratings (r=.56, Papp prices have significant negative correlations with installs (r=−.36). The results also reveal that lower-priced apps have higher ratings (r=−.23, Papp permission requests (r=.18, P=.002) from the device. For app titles, we found that apps with titles related to symptoms have significantly lower installs than apps with titles that are not related to symptoms (Papps by analyzing observational data. As the first of its kind, we found impactful indicators for mental health app adoptions. We also discovered a labeling effect of app titles that could hinder mental health app adoptions and which may provide insight for future designs of mental health apps and their search mechanisms. PMID:28659256

  14. Pro-smoking apps for smartphones: the latest vehicle for the tobacco industry?

    Science.gov (United States)

    BinDhim, Nasser F; Freeman, Becky; Trevena, Lyndal

    2014-01-01

    Smartphone use is growing exponentially and will soon become the only mobile phone handset for about 6 billion users. Smartphones are ideal marketing targets as consumers can be reached anytime, anywhere. Smartphone application (app) stores are global shops that sell apps to users all around the world. Although smartphone stores have a wide collection of health-related apps they also have a wide set of harmful apps. In this study, the availability of 'pro-smoking' apps in two of the largest smartphone app stores (Apple App store and Android Market) was examined. In February 2012, we searched the Apple App Store and Android Market for pro-smoking apps, using the keywords Smoke, Cigarette, Cigar, Smoking and Tobacco. We excluded apps that were not tobacco-related and then assessed the tobacco-related apps against our inclusion criteria. 107 pro-smoking apps were identified and classified into six categories based on functionality.42 of these apps were from the Android Market and downloaded by over 6 million users. Some apps have explicit images of cigarette brands. Tobacco products are being promoted in the new 'smartphone app' medium which has global reach, a huge consumer base of various age groups and underdeveloped regulation. The paper also provides two examples of app store responses to country-specific laws and regulations that could be used to control the harmful contents in the app stores for individual countries.

  15. Reading apps for children: Readability from the design perspective

    Science.gov (United States)

    Mohammed, Wasan Abdulwahab; Husni, Husniza

    2017-10-01

    Electronic reading for young children opens new avenues especially with the advance of modern reading devices. The readability of mobile learning applications has received extensive attention by the designers and developers. The reason for such concern is due to its importance in determining usability related issues especially in the design context for children. In many cases, children find it difficult to interact with mobile reading apps. This is because apps for reading and for entertainment require different features. As such, this study sets out three objectives: 1) to evaluate five reading apps for young children from design perspectives; 2) to examine the readability for current existing mobile apps for reading and 3) to propose and evaluate mobile apps UI guideline for readability. Readability indices, observation and interview were conducted on 6 - 8 years old students. The obtained result showed that certain reading apps provide better reading experience for children than others. Some of the reasons are mostly related to the design characteristics embedded within the app. In addition, the use of animation was found to stimulate children reading experience as it is believed to offer the interactivity elements to gain their interest and willingness to read. These findings are believed to provide the recommendations and insights for designers of reading apps for children.

  16. iOS app development portable genius

    CERN Document Server

    Wentk, Richard

    2012-01-01

    The essential skills and technologies needed for iOS development in one handy guide! The unprecedented popularity of iOS devices, such as the iPhone, iPad, and iPod touch, has led to a development boom. If you’re eager to become part of the action, then this is the book for you! Packed with must-have information on iOS development, this handy guide covers Objective-C, Xcode, Frameworks, and sound design principles and explains how to upload an app to the app store and integrate apps with the latest advances that Apple offers developers. The featured tips and tricks will get you up and ru

  17. Pro JavaScript for web apps

    CERN Document Server

    Freeman, Adam

    2012-01-01

    JavaScript is the engine behind every web app, and a solid knowledge of it is essential for all modern web developers. Pro JavaScript for Web Apps gives you all of the information that you need to create professional, optimized, and efficient JavaScript applications that will run across all devices. It takes you through all aspects of modern JavaScript application creation, showing you how to combine JavaScript with the new features of HTML5 and CSS3 to make the most of the new web technologies. The focus of the book is on creating professional web applications, ensuring that your app provides

  18. Engineering stories? A narratological approach to children's book apps

    Directory of Open Access Journals (Sweden)

    Hadassah Stichnothe

    2014-01-01

    Full Text Available With the rise of smartphones and tablet pcs, children's book apps have emerged as a new type of children's media. While some of them are based on popular children's books such as Mo Willems’ Pigeon books or Beatrix Potter's Peter Rabbit, others were specifically designed as apps. This paper focuses on examining book apps under the aspects of implied user strategies and narrative structure. Using a narratological framework that also takes into account the unique characteristics of the medium, a terminology for the analysis of book apps will be sketched out. Furthermore, an exemplary analysis of iOS books apps for pre- and grade school children comes to the conclusion that, far from offering the child users room for individual creativity, a large number of apps rather train their users in following prescribed paths of reading.

  19. Building Android Apps with HTML, CSS, and JavaScript

    CERN Document Server

    Stark, Jonathan

    2010-01-01

    If you know HTML, CSS, and JavaScript, you already have the tools you need to develop Android applications. This hands-on book shows you how to use these open source web standards to design and build apps that can be adapted for any Android device -- without having to use Java. You'll learn how to create an Android-friendly web app on the platform of your choice, and then convert it to a native Android app with the free PhoneGap framework. Discover why device-agnostic mobile apps are the wave of the future, and start building apps that offer greater flexibility and a broader reach. Learn the

  20. Instant Passbook app development for iOS how-to

    CERN Document Server

    Moon, Keith D

    2013-01-01

    Filled with practical, step-by-step instructions and clear explanations for the most important and useful tasks. A step-by-step guide, focusing on simple projects to help you create a Passbook app for iOS 6.Instant Passbook App Development for iOS 6 How-to is for registered Apple iOS developers, experienced in building an app using Objective-C and Xcode, looking to add Passbook functionality to their app. You will need to have an understanding of the JSON format, REST APIs, and a server-side language like Ruby. Familiarity with executing commands via the Terminal app is expected for the exerci

  1. mHealth App for Cannabis Users: Satisfaction and Perceived Usefulness.

    Science.gov (United States)

    Monney, Grégoire; Penzenstadler, Louise; Dupraz, Olivia; Etter, Jean-François; Khazaal, Yasser

    2015-01-01

    The aim of this study was to describe the characteristics of cannabis users and their levels of satisfaction with Stop-cannabis, an app intended for cannabis users who want to stop or reduce their cannabis use or prevent relapse. A cross-sectional online survey was administered to users of Stop-cannabis, a French-language app for iOS and Android devices. All app users were invited to participate in the survey via a message sent to the app. For hundred and eighty-two users answered the survey. The app was used daily by 348 of the participants (around 70%). More than 80% of participants (397) considered the app to have helped them "a little" or "a lot" to stop or reduce cannabis consumption. Most of the users' suggestions were related to the number or the quality of the messages sent by, or displayed in, the app. This pilot study supports the feasibility of such an app and its perceived usefulness. A self-selection bias, however, limits the conclusions of the study. The efficacy of the app should be evaluated in a randomized controlled trial.

  2. mHealth App for Cannabis Users: Satisfaction and Perceived Usefulness

    Directory of Open Access Journals (Sweden)

    gregoire eMonney

    2015-08-01

    Full Text Available Objective: The aim of this study was to describe the characteristics of cannabis users and their levels of satisfaction with Stop-cannabis, an app intended for cannabis users who want to stop or reduce their cannabis use or prevent relapse. Methods: A cross-sectional online survey was administered to users of Stop-cannabis, a French-language app for iOS and Android devices. All app users were invited to participate in the survey via a message sent to the app. Results: For hundred and eighty-two users answered the survey. The app was used daily by 348 of the participants (around 70%. More than 80% of participants (397 considered the app to have helped them a little or a lot to stop or reduce cannabis consumption. Most of the users’ suggestions were related to the number or the quality of the messages sent by, or displayed in, the app.Conclusion: This pilot study supports the feasibility of such an app and its perceived usefulness. A self-selection bias however limits the conclusions of the study. The efficacy of the app should be evaluated in a randomized controlled trial.

  3. Large-Scale Analysis of Framework-Specific Exceptions in Android Apps

    OpenAIRE

    Fan, Lingling; Su, Ting; Chen, Sen; Meng, Guozhu; Liu, Yang; Xu, Lihua; Pu, Geguang; Su, Zhendong

    2018-01-01

    Mobile apps have become ubiquitous. For app developers, it is a key priority to ensure their apps' correctness and reliability. However, many apps still suffer from occasional to frequent crashes, weakening their competitive edge. Large-scale, deep analyses of the characteristics of real-world app crashes can provide useful insights to guide developers, or help improve testing and analysis tools. However, such studies do not exist -- this paper fills this gap. Over a four-month long effort, w...

  4. Automation support for mobile app quality assurance - a tool landscape

    OpenAIRE

    Braun, Susanne; Elberzhager, Frank; Holl, Konstantin

    2017-01-01

    Competitive pressure in app stores, as well as direct and transparent feedback of app store reviews have resulted in an increased demand for outstanding app quality and user experience. At the same time, reduced time-to-market, decreased budgets and time available for quality assurance, and careful user experience design have to be considered. In response, an enormous market for mobile app quality and user experience measurement tools has grown around the mobile app store ecosystems. Develope...

  5. Negative blood oxygen level dependent signals during speech comprehension.

    Science.gov (United States)

    Rodriguez Moreno, Diana; Schiff, Nicholas D; Hirsch, Joy

    2015-05-01

    Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.

  6. Social gaming on the Spotify app platform

    OpenAIRE

    Jönsson, Martin

    2013-01-01

    Spotify wants to explore the possibilities of social gaming within their desktop client. Thanks to their Spotify Apps API it is possible to build applications that integrate with the Spotify library while using modern web technologies. This thesis work consists of exploring what is possible using the Spotify App API and the most modern web technologies available. The main theme and goal of the Spotify App is to engage users in a social context. Creating a quiz application, which users can pla...

  7. Using GeoMapApp in the Classroom

    Science.gov (United States)

    Goodwillie, A. M.

    2017-12-01

    The GeoMapApp tool has been updated with enhanced functionality that is useful in the classroom. Hosted as a service of the IEDA Facility at Columbia University, GeoMapApp (http://www.geomapapp.org) is a free resource that integrates a wide range of research-grade geoscience data in one intuitive map-based interface. It includes earthquake and volcano data, geological maps, plate tectonic data sets, and a high-resolution topography/bathymetry base map. Users can also import and analyse their own data files. Layering and transparency capabilities allow users to compare multiple data sets at once. The GeoMapApp interface presents data in its proper geospatial context, helping students more easily gain insight and understanding from the data. Simple tools for data manipulation allow students to analyse the data in different ways such as generating profiles and producing visualisations for reports. The new Save Session capability is designed to assist in the classroom: The educator saves a pre-loaded state of GeoMapApp. When shared with the class, the saved session file allows students to open GeoMapApp with exactly the same data sets loaded and the same display parameters chosen thus freeing up valuable time in which students can explore the data. In this presentation, activities related to plate tectonics will be highlighted. One activity helps students investigate plate boundaries by exploring earthquake and volcano locations. Another requires students to calculate the rate of seafloor spreading using crustal age data in various ocean basins. A third uses the GeoMapApp layering technique to explore the influence of geological forces in shaping the landscape. Educators report that using GeoMapApp in the classroom lowers the barriers to data accessibility for students; fosters an increased sense of data "ownership" - GeoMapApp presents the same data in the same tool used by researchers; allows engagement with authentic geoscience data; promotes STEM skills and

  8. Mobile Health in Oncology: A Patient Survey About App-Assisted Cancer Care.

    Science.gov (United States)

    Kessel, Kerstin Anne; Vogel, Marco Me; Kessel, Carmen; Bier, Henning; Biedermann, Tilo; Friess, Helmut; Herschbach, Peter; von Eisenhart-Rothe, Rüdiger; Meyer, Bernhard; Kiechle, Marion; Keller, Ulrich; Peschel, Christian; Schmid, Roland M; Combs, Stephanie E

    2017-06-14

    showed a significant but mild relationship between age and app use (P=.03, r=-.12), favoring younger age; male gender correlated as well (P=.04; r=-.11). The results show that the introduction of mobile apps needs to follow different strategies depending on the patients' attitude. Age and gender seem to be the strongest predictive factors. For oncology patients, our survey showed that about half of the patients were willing to send data via an app supporting their treatment. In the future, clinical data such as quality of life and treatment satisfaction recorded by mobile health (mHealth) devices could be used to evaluate and improve therapy workflow. Furthermore, apps could support classical visits, document adverse effects, and remind patients of treatment dates or drug intake. ©Kerstin Anne Kessel, Marco ME Vogel, Carmen Kessel, Henning Bier, Tilo Biedermann, Helmut Friess, Peter Herschbach, Rüdiger von Eisenhart-Rothe, Bernhard Meyer, Marion Kiechle, Ulrich Keller, Christian Peschel, Roland M Schmid, Stephanie E Combs. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 14.06.2017.

  9. The Impact of Mobile Apps on Alcohol Use Disorder: A Systematic Review Protocol.

    Science.gov (United States)

    Sawares, Antoine Sa; Shen, Nelson; Xue, Yunlin; Abi-Jaoude, Alexxa; Wiljer, David

    2017-04-04

    Alcohol use disorder (AUD) is among the most prevalent mental disorders worldwide and is associated with a diverse range of physical and psychological comorbidities. Despite various types of treatment, there are many barriers to accessing treatment (ie, stigma, cost, accessibility of service, etc). Mobile apps have the potential to overcome these barriers and provide support to those who need it. The purpose of this systematic review is to assess the effectiveness of mobile apps in reducing alcohol consumption for individuals with AUD and understand the psychological outcomes of using the apps (ie, client empowerment, self-efficacy, etc). The search strategy was applied to 7 health sciences and interdisciplinary databases. Two reviewers will independently assess all titles and abstracts for relevance and then full texts of relevant articles for eligibility. To be included, the article must be a quantitative evaluation of clinical outcomes using the intervention and the intervention must be a consumer-facing app focused on supporting individuals with AUD. Two reviewers will independently extract data from all eligible articles using a standardized extraction worksheet and will independently assess the study quality. A meta-analysis will be conducted if appropriate. Depending on outcomes reported, pooled risk ratios or standardized mean differences will be calculated and reported in the review. The search strategy yielded 699 unique citations. Of those, 63 (9.0%, 63/699) articles were assessed as relevant for full-text review. The full-text reviews are currently underway and the final review is projected to be completed in the summer of 2017. There is potential for mobile apps to support individuals with AUD to reduce their alcohol consumption. This review will be the first to assess the effectiveness of AUD mobile apps and client experiences using the apps. ©Antoine SA Sawares, Nelson Shen, Yunlin Xue, Alexxa Abi-Jaoude, David Wiljer. Originally published in JMIR

  10. mHealth in Urology: A Review of Experts’ Involvement in App Development

    Science.gov (United States)

    Pereira-Azevedo, Nuno; Carrasquinho, Eduardo; Cardoso de Oliveira, Eduardo; Cavadas, Vitor; Osório, Luís; Fraga, Avelino; Castelo-Branco, Miguel; Roobol, Monique J.

    2015-01-01

    Introduction Smartphones are increasingly playing a role in healthcare and previous studies assessing medical applications (apps) have raised concerns about lack of expert involvement and low content accuracy. However, there are no such studies in Urology. We reviewed Urology apps with the aim of assessing the level of participation of healthcare professionals (HCP) and scientific Urology associations in their development. Material and Methods A systematic search was performed on PubMed, Apple's App Store and Google's Play Store, for Urology apps, available in English. Apps were reviewed by three graders to determine the app’s platform, target customer, developer, app type, app category, price and the participation of a HCP or a scientific Urology association in the development. Results The search yielded 372 apps, of which 150 were specific for Urology. A fifth of all apps had no HCP involvement (20.7%) and only a third had been developed with a scientific Urology association (34.7%). The lowest percentage of HCP (13.4%) and urological association (1.9%) involvement was in apps designed for the general population. Furthermore, there was no contribution from an Urology society in "Electronic Medical Record" nor in "Patient Information" apps. A limitation of the study is that only Android and iOS apps were reviewed. Conclusions Despite the increasing Mobile Health (mHealth) market, this is the first study that demonstrates the lack of expert participation in the design of Urology apps, particularly in apps designed for the general public. Until clear regulation is enforced, the urological community should help regulate app development. Maintaining a register of certified apps or issuing an official scientific seal of approval could improve overall app quality. We propose that urologists become stakeholders in mHealth, shaping future app design and promoting peer-review app validation. PMID:25984916

  11. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

    DEFF Research Database (Denmark)

    Batth, Tanveer S; Papetti, Moreno; Pfeiffer, Anamarija

    2018-01-01

    Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2...... of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates...

  12. Consumer Mobile Health Apps: Current State, Barriers, and Future Directions.

    Science.gov (United States)

    Kao, Cheng-Kai; Liebovitz, David M

    2017-05-01

    This paper discusses the current state, barriers, and future directions of consumer-facing applications (apps). There are currently more than 165,000 mobile health apps publicly available in major app stores, the vast majority of which are designed for patients. The top 2 categories are wellness management and disease management apps, whereas other categories include self-diagnosis, medication reminder, and electronic patient portal apps. Apps specific to physical medicine and rehabilitation also are reviewed. These apps have the potential to provide low-cost, around-the-clock access to high-quality, evidence-based health information to end users on a global scale. However, they have not yet lived up to their potential due to multiple barriers, including lack of regulatory oversight, limited evidence-based literature, and concerns of privacy and security. The future directions may consist of improving data integration into the health care system, an interoperable app platform allowing access to electronic health record data, cloud-based personal health record across health care networks, and increasing app prescription by health care providers. For consumer mobile health apps to fully contribute value to health care delivery and chronic disease management, all stakeholders within the ecosystem must collaborate to overcome the significant barriers. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  13. Cell Size and Growth Rate Are Modulated by TORC2-Dependent Signals.

    Science.gov (United States)

    Lucena, Rafael; Alcaide-Gavilán, Maria; Schubert, Katherine; He, Maybo; Domnauer, Matthew G; Marquer, Catherine; Klose, Christian; Surma, Michal A; Kellogg, Douglas R

    2018-01-22

    The size of all cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrient availability, but the underlying mechanisms are unknown. Here, we show that nutrients modulate cell size and growth rate via the TORC2 signaling network in budding yeast. An important function of the TORC2 network is to modulate synthesis of ceramide lipids, which play roles in signaling. TORC2-dependent control of ceramide signaling strongly influences both cell size and growth rate. Thus, cells that cannot make ceramides fail to modulate their growth rate or size in response to changes in nutrients. PP2A associated with the Rts1 regulatory subunit (PP2A Rts1 ) is embedded in a feedback loop that controls TORC2 signaling and helps set the level of TORC2 signaling to match nutrient availability. Together, the data suggest a model in which growth rate and cell size are mechanistically linked by ceramide-dependent signals arising from the TORC2 network. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. App Development Paradigms for Instructional Developers

    Science.gov (United States)

    Luterbach, Kenneth J.; Hubbell, Kenneth R.

    2015-01-01

    To create instructional apps for desktop, laptop and mobile devices, developers must select a development tool. Tool selection is critical and complicated by the large number and variety of app development tools. One important criterion to consider is the type of development environment, which may primarily be visual or symbolic. Those distinct…

  15. Smartphone Applications - Idea sourcing, and app development: Implications for firms

    Directory of Open Access Journals (Sweden)

    Debbie Vigar-Ellis

    2014-05-01

    Full Text Available With the dramatic increase in smartphone usage and the consequent increase in applications (apps for these smartphones, organisations are constantly looking for new apps to offer customers as well as employees.  Information Systems (IS departments of organisations have traditionally been tasked with the acquisition and/or development of such information technologies within organisations.  This research aimed to determine from IS managers, the smartphone app usage in firms, the sources of app ideas and the locations for app development.  It also investigated various aspects of the success or otherwise of the development process.  Results indicate that while most ideas for apps currently come from IS and marketing departments within the organisation, and development of apps is also done mainly within the organisation , these development strategies are not necessarily the most effective.  Managerial implications are discussed.

  16. Ultraviolet Radiation and the Slug Transcription Factor Induce Proinflammatory and Immunomodulatory Mediator Expression in Melanocytes

    Directory of Open Access Journals (Sweden)

    Stephanie H. Shirley

    2012-01-01

    Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  17. Validation of EncephalApp, Smartphone-Based Stroop Test, for the Diagnosis of Covert Hepatic Encephalopathy.

    Science.gov (United States)

    Bajaj, Jasmohan S; Heuman, Douglas M; Sterling, Richard K; Sanyal, Arun J; Siddiqui, Muhammad; Matherly, Scott; Luketic, Velimir; Stravitz, R Todd; Fuchs, Michael; Thacker, Leroy R; Gilles, HoChong; White, Melanie B; Unser, Ariel; Hovermale, James; Gavis, Edith; Noble, Nicole A; Wade, James B

    2015-10-01

    Detection of covert hepatic encephalopathy (CHE) is difficult, but point-of-care testing could increase rates of diagnosis. We aimed to validate the ability of the smartphone app EncephalApp, a streamlined version of Stroop App, to detect CHE. We evaluated face validity, test-retest reliability, and external validity. Patients with cirrhosis (n = 167; 38% with overt HE [OHE]; mean age, 55 years; mean Model for End-Stage Liver Disease score, 12) and controls (n = 114) were each given a paper and pencil cognitive battery (standard) along with EncephalApp. EncephalApp has Off and On states; results measured were OffTime, OnTime, OffTime+OnTime, and number of runs required to complete 5 off and on runs. Thirty-six patients with cirrhosis underwent driving simulation tests, and EncephalApp results were correlated with results. Test-retest reliability was analyzed in a subgroup of patients. The test was performed before and after transjugular intrahepatic portosystemic shunt placement, and before and after correction for hyponatremia, to determine external validity. All patients with cirrhosis performed worse on paper and pencil and EncephalApp tests than controls. Patients with cirrhosis and OHE performed worse than those without OHE. Age-dependent EncephalApp cutoffs (younger or older than 45 years) were set. An OffTime+OnTime value of >190 seconds identified all patients with CHE with an area under the receiver operator characteristic value of 0.91; the area under the receiver operator characteristic value was 0.88 for diagnosis of CHE in those without OHE. EncephalApp times correlated with crashes and illegal turns in driving simulation tests. Test-retest reliability was high (intraclass coefficient, 0.83) among 30 patients retested 1-3 months apart. OffTime+OnTime increased significantly (206 vs 255 seconds, P = .007) among 10 patients retested 33 ± 7 days after transjugular intrahepatic portosystemic shunt placement. OffTime+OnTime decreased significantly (242 vs

  18. A systematic review of quality assessment methods for smartphone health apps.

    Science.gov (United States)

    BinDhim, Nasser F; Hawkey, Alexandra; Trevena, Lyndal

    2015-02-01

    There are large numbers of health-related applications (apps) available in various app stores for many smartphone devices. Consequently, increasing numbers of articles are attempting to evaluate the content and the quality of health-related smartphone apps for specific health conditions. The aim of this article is to describe and summarize the methodologies used to determine the quality of health-related apps targeting health consumers and to propose a set of criteria for evaluating the quality of smartphone health-related apps. In 2013, literature searches were performed using Medline and CINAHL, and we included all articles that had the aim of assessing the quality of health-related smartphone apps. The assessment method used in these studies was summarized and scored using a set of quality criteria developed for this study. From 606 articles generated by the search, only 10 met the inclusion criteria. Based on our quality criteria, the mean score was 5.05 out of 8 (range, 2-7). Eighty percent of the studies did not identify the app store country in which the apps were found. Forty percent of the studies did not clearly mention whether they only had assessed the app description or had downloaded the app content for evaluation. Sixty percent of the studies did not provide a list of the apps they had evaluated. Overall, we identified six evaluation methodologies used to assess the quality of health-related apps described in RESULTS. This article provides a summary of currently used methods for assessing the quality of smartphone health-related apps and proposes a set of criteria to enable future studies to consistently review health-related app quality in a standardized manner.

  19. Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering

    Directory of Open Access Journals (Sweden)

    Sudhir H. Ranganath

    2016-06-01

    Full Text Available Mesenchymal stromal cells (MSCs are promising therapeutic candidates given their potent immunomodulatory and anti-inflammatory secretome. However, controlling the MSC secretome post-transplantation is considered a major challenge that hinders their clinical efficacy. To address this, we used a microparticle-based engineering approach to non-genetically modulate pro-inflammatory pathways in human MSCs (hMSCs under simulated inflammatory conditions. Here we show that microparticles loaded with TPCA-1, a small-molecule NF-κB inhibitor, when delivered to hMSCs can attenuate secretion of pro-inflammatory factors for at least 6 days in vitro. Conditioned medium (CM derived from TPCA-1-loaded hMSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts, compared with CM from untreated or TPCA-1-preconditioned hMSCs. Thus, we provide a broadly applicable bioengineering solution to facilitate intracellular sustained release of agents that modulate signaling. We propose that this approach could be harnessed to improve control over MSC secretome post-transplantation, especially to prevent adverse remodeling post-myocardial infarction.

  20. Health App Use Among US Mobile Phone Owners: A National Survey.

    Science.gov (United States)

    Krebs, Paul; Duncan, Dustin T

    2015-11-04

    Mobile phone health apps may now seem to be ubiquitous, yet much remains unknown with regard to their usage. Information is limited with regard to important metrics, including the percentage of the population that uses health apps, reasons for adoption/nonadoption, and reasons for noncontinuance of use. The purpose of this study was to examine health app use among mobile phone owners in the United States. We conducted a cross-sectional survey of 1604 mobile phone users throughout the United States. The 36-item survey assessed sociodemographic characteristics, history of and reasons for health app use/nonuse, perceived effectiveness of health apps, reasons for stopping use, and general health status. A little over half (934/1604, 58.23%) of mobile phone users had downloaded a health-related mobile app. Fitness and nutrition were the most common categories of health apps used, with most respondents using them at least daily. Common reasons for not having downloaded apps were lack of interest, cost, and concern about apps collecting their data. Individuals more likely to use health apps tended to be younger, have higher incomes, be more educated, be Latino/Hispanic, and have a body mass index (BMI) in the obese range (all Psafety was quite high, and most felt that the apps had improved their health. About half of the respondents (427/934, 45.7%) had stopped using some health apps, primarily due to high data entry burden, loss of interest, and hidden costs. These findings suggest that while many individuals use health apps, a substantial proportion of the population does not, and that even among those who use health apps, many stop using them. These data suggest that app developers need to better address consumer concerns, such as cost and high data entry burden, and that clinical trials are necessary to test the efficacy of health apps to broaden their appeal and adoption.

  1. A novel immune-to-CNS communication pathway: cells of the meninges surrounding the spinal cord CSF space produce proinflammatory cytokines in response to an inflammatory stimulus.

    Science.gov (United States)

    Wieseler-Frank, Julie; Jekich, Brian M; Mahoney, John H; Bland, Sondra T; Maier, Steven F; Watkins, Linda R

    2007-07-01

    Pain is enhanced in response to elevations of proinflammatory cytokines in spinal cerebrospinal fluid (CSF), following either intrathecal injection of these cytokines or intrathecal immune challenge with HIV-1 gp120 that induces cytokine release. Spinal cord glia have been assumed to be the source of endogenous proinflammatory cytokines that enhance pain. However, assuming that spinal cord glia are the sole source of CSF cytokines may be an underestimate, as the cellular composition of the meninges surrounding the spinal cord CSF space includes several cell types known to produce proinflammatory cytokines. The present experiments provide the first investigation of the immunocompetent nature of the spinal cord meninges. Here, we explore whether rat meninges are responsive to intrathecal gp120. These studies demonstrate that: (a) intrathecal gp120 upregulates meningeal gene expression of proinflammatory signals, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin 6 (IL-6), and inducible nitric oxide synthase (iNOS), and (b) intrathecal gp120 induces meningeal release of TNF-alpha, IL-1beta, and IL-6. In addition, stimulation of isolated meninges in vitro with gp120 induced the release of TNF-alpha and IL-1beta, indicating that the resident cells of the meninges are able to respond without immune cell recruitment. Taken together, these data document that the meninges are responsive to immunogenic stimuli in the CSF and that the meninges may be a source of immune products detected in CSF. The ability of the meninges to release to proinflammatory signals suggests a potential role in the modulation of pain.

  2. N(6)-(2-Hydroxyethyl)adenosine in the Medicinal Mushroom Cordyceps cicadae Attenuates Lipopolysaccharide-Stimulated Pro-inflammatory Responses by Suppressing TLR4-Mediated NF-κB Signaling Pathways.

    Science.gov (United States)

    Lu, Meng-Ying; Chen, Chin-Chu; Lee, Li-Ya; Lin, Ting-Wei; Kuo, Chia-Feng

    2015-10-23

    Natural products play an important role in promoting health with relation to the prevention of chronic inflammation. N(6)-(2-Hydroxyethyl)adenosine (HEA), a physiologically active compound in the medicinal mushroom Cordyceps cicadae, has been identified as a Ca(2+) antagonist and shown to control circulation and possess sedative activity in pharmacological tests. The fruiting body of C. cicadae has been widely applied in Chinese medicine. However, neither the anti-inflammatory activities of HEA nor the fruiting bodies of C. cicadae have been carefully examined. In this study, we first cultured the fruiting bodies of C. cicadae and then investigated the anti-inflammatory activities of water and methanol extracts of wild and artificially cultured C. cicadae fruiting bodies. Next, we determined the amount of three bioactive compounds, adenosine, cordycepin, and HEA, in the extracts and evaluated their synergistic anti-inflammatory effects. Moreover, the possible mechanism involved in anti-inflammatory action of HEA isolated from C. cicadae was investigated. The results indicate that cordycepin is more potent than adenosine and HEA in suppressing the lipopolysaccharide (LPS)-stimulated release of pro-inflammatory cytokines by RAW 264.7 macrophages; however, no synergistic effect was observed with these three compounds. HEA attenuated the LPS-induced pro-inflammatory responses by suppressing the toll-like receptor (TLR)4-mediated nuclear factor-κB (NF-κB) signaling pathway. This result will support the use of HEA as an anti-inflammatory agent and C. cicadae fruiting bodies as an anti-inflammatory mushroom.

  3. Popular NREL-Developed Transportation Mobile App Launches on Android

    Science.gov (United States)

    Platform | News | NREL Popular NREL-Developed Transportation Mobile App Launches on Android Platform Popular NREL-Developed Transportation Mobile App Launches on Android Platform May 23, 2017 More since the new Android version of the Alternative Fueling Station Locator App launched last week. The U.S

  4. Locking it down: The privacy and security of mobile medication apps.

    Science.gov (United States)

    Grindrod, Kelly; Boersema, Jonathan; Waked, Khrystine; Smith, Vivian; Yang, Jilan; Gebotys, Catherine

    2017-01-01

    To explore the privacy and security of free medication applications (apps) available to Canadian consumers. The authors searched the Canadian iTunes store for iOS apps and the Canadian Google Play store for Android apps related to medication use and management. Using an Apple iPad Air 2 and a Google Nexus 7 tablet, 2 reviewers generated a list of apps that met the following inclusion criteria: free, available in English, intended for consumer use and related to medication management. Using a standard data collection form, 2 reviewers independently coded each app for the presence/absence of passwords, the storage of personal health information, a privacy statement, encryption, remote wipe and third-party sharing. A Cohen's Kappa statistic was used to measure interrater agreement. Of the 184 apps evaluated, 70.1% had no password protection or sign-in system. Personal information, including name, date of birth and gender, was requested by 41.8% (77/184) of apps. Contact information, such as address, phone number and email, was requested by 25% (46/184) of apps. Finally, personal health information, other than medication name, was requested by 89.1% (164/184) of apps. Only 34.2% (63/184) of apps had a privacy policy in place. Most free medication apps offer very limited authentication and privacy protocols. As a result, the onus currently falls on patients to input information in these apps selectively and to be aware of the potential privacy issues. Until more secure systems are built, health care practitioners cannot fully support patients wanting to use such apps.

  5. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

    Directory of Open Access Journals (Sweden)

    BA Walter

    2016-07-01

    Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

  6. An AICD-based functional screen to identify APP metabolism regulators

    Directory of Open Access Journals (Sweden)

    Lee Jeremy C

    2007-08-01

    Full Text Available Abstract Background A central event in Alzheimer's disease (AD is the regulated intramembraneous proteolysis of the β-amyloid precursor protein (APP, to generate the β-amyloid (Aβ peptide and the APP intracellular domain (AICD. Aβ is the major component of amyloid plaques and AICD displays transcriptional activation properties. We have taken advantage of AICD transactivation properties to develop a genetic screen to identify regulators of APP metabolism. This screen relies on an APP-Gal4 fusion protein, which upon normal proteolysis, produces AICD-Gal4. Production of AICD-Gal4 induces Gal4-UAS driven luciferase expression. Therefore, when regulators of APP metabolism are modulated, luciferase expression is altered. Results To validate this experimental approach we modulated α-, β-, and γ-secretase levels and activities. Changes in AICD-Gal4 levels as measured by Western blot analysis were strongly and significantly correlated to the observed changes in AICD-Gal4 mediated luciferase activity. To determine if a known regulator of APP trafficking/maturation and Presenilin1 endoproteolysis could be detected using the AICD-Gal4 mediated luciferase assay, we knocked-down Ubiquilin 1 and observed decreased luciferase activity. We confirmed that Ubiquilin 1 modulated AICD-Gal4 levels by Western blot analysis and also observed that Ubiquilin 1 modulated total APP levels, the ratio of mature to immature APP, as well as PS1 endoproteolysis. Conclusion Taken together, we have shown that this screen can identify known APP metabolism regulators that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. We demonstrate for the first time that Ubiquilin 1 regulates APP metabolism in the human neuroblastoma cell line, SH-SY5Y.

  7. Fra app'ernes planet til klasserummet

    DEFF Research Database (Denmark)

    Falkesgaard Slot, Marie; Gissel, Stig Toke; Lorentzen, Rasmus Fink

    2013-01-01

    Artiklen udpeger en række kategorier og begreber, som læreren kan anvende i sit arbejde med at analysere og vurdere hvilke handle- og betydningsmuligheder, der er indbygget i hhv. funktionelle, didaktiske og semantiske apps. Med afsæt i disse begreber gives praksisnære bud på, hvordan apps på for...

  8. DMPD: Post-transcriptional regulation of proinflammatory proteins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15075353 Post-transcriptional regulation of proinflammatory proteins. Anderson P, P...l) (.csml) Show Post-transcriptional regulation of proinflammatory proteins. PubmedID 15075353 Title Post-tr...anscriptional regulation of proinflammatory proteins. Authors Anderson P, Phillip

  9. Incorporation of Mobile Application (App) Measures Into the Diagnosis of Smartphone Addiction.

    Science.gov (United States)

    Lin, Yu-Hsuan; Lin, Po-Hsien; Chiang, Chih-Lin; Lee, Yang-Han; Yang, Cheryl C H; Kuo, Terry B J; Lin, Sheng-Hsuan

    2017-07-01

    Global smartphone expansion has brought about unprecedented addictive behaviors. The current diagnosis of smartphone addiction is based solely on information from clinical interview. This study aimed to incorporate application (app)-recorded data into psychiatric criteria for the diagnosis of smartphone addiction and to examine the predictive ability of the app-recorded data for the diagnosis of smartphone addiction. Smartphone use data of 79 college students were recorded by a newly developed app for 1 month between December 1, 2013, and May 31, 2014. For each participant, psychiatrists made a diagnosis for smartphone addiction based on 2 approaches: (1) only diagnostic interview (standard diagnosis) and (2) both diagnostic interview and app-recorded data (app-incorporated diagnosis). The app-incorporated diagnosis was further used to build app-incorporated diagnostic criteria. In addition, the app-recorded data were pooled as a score to predict smartphone addiction diagnosis. When app-incorporated diagnosis was used as a gold standard for 12 candidate criteria, 7 criteria showed significant accuracy (area under receiver operating characteristic curve [AUC] > 0.7) and were constructed as app-incorporated diagnostic criteria, which demonstrated remarkable accuracy (92.4%) for app-incorporated diagnosis. In addition, both frequency and duration of daily smartphone use significantly predicted app-incorporated diagnosis (AUC = 0.70 for frequency; AUC = 0.72 for duration). The combination of duration, frequency, and frequency trend for 1 month can accurately predict smartphone addiction diagnosis (AUC = 0.79 for app-incorporated diagnosis; AUC = 0.71 for standard diagnosis). The app-incorporated diagnosis, combining both psychiatric interview and app-recorded data, demonstrated substantial accuracy for smartphone addiction diagnosis. In addition, the app-recorded data performed as an accurate screening tool for app-incorporated diagnosis. © Copyright 2017 Physicians

  10. An Evidence-based Forensic Taxonomy of Windows Phone Dating Apps.

    Science.gov (United States)

    Cahyani, Niken Dwi Wahyu; Choo, Kim-Kwang Raymond; Ab Rahman, Nurul Hidayah; Ashman, Helen

    2018-05-21

    Advances in technologies including development of smartphone features have contributed to the growth of mobile applications, including dating apps. However, online dating services can be misused. To support law enforcement investigations, a forensic taxonomy that provides a systematic classification of forensic artifacts from Windows Phone 8 (WP8) dating apps is presented in this study. The taxonomy has three categories, namely: Apps Categories, Artifacts Categories, and Data Partition Categories. This taxonomy is built based on the findings from a case study of 28 mobile dating apps, using mobile forensic tools. The dating app taxonomy can be used to inform future studies of dating and related apps, such as those from Android and iOS platforms. © 2018 American Academy of Forensic Sciences.

  11. The Hierarchy of Proinflammatory Cytokines in Ocular Inflammation.

    Science.gov (United States)

    Da Cunha, A P; Zhang, Q; Prentiss, M; Wu, X Q; Kainz, V; Xu, Y Y; Vrouvlianis, J; Li, H; Rangaswamy, N; Leehy, B; McGee, T L; Bell, C L; Bigelow, C E; Kansara, V; Medley, Q; Huang, Q; Wu, H Y

    2018-04-01

    The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1β (IL-1β), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation. We delivered adeno-associated virus (AAV) vectors expressing IL-1β, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function. We found that IL-1β had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1β resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1β was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1β was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1β in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1β alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1β or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects. Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1β is the most pathogenic when it is continuously expressed in the eye.

  12. Influence of a Character-Based App on Children's Learning of Nutritional Information: Should Apps Be Served with a Side of Media Characters?

    Science.gov (United States)

    Putnam, Marisa M; Richmond, Elana M; Brunick, Kaitlin L; Wright, Charlotte A; Calvert, Sandra L

    2018-04-01

    Childhood obesity is a health issue in the United States, associated with marketing practices in which media characters are often used to sell unhealthy products. This study examined exposure to a socially contingent touch-screen gaming app, which replied immediately, reliably, and accurately to children's actions. Children's recall of nutritional content and their liking of the character were assessed. Four- and five-year-old children (N = 114) received no-exposure, single-exposure, or repeated-exposure to a character-based iPad app rewarding healthy and penalizing unhealthy behaviors. Children reported how much they liked the character and recalled healthy and unhealthy items from the app. An ordinary least squares regression was conducted on how much children liked the character by condition. Poisson regressions were conducted on the number of items recalled by condition alone, and in an interacted model of treatment condition by liking the character. Children liked the character more in the repeated app-exposure condition than in the control group (P = 0.018). Children in the repeated and single app-exposure conditions recalled more healthy (P < 0.001) and unhealthy (P < 0.001) items than the control group. Within treatment conditions, liking the character increased recall of healthy items in the single app-exposure compared to the repeated app-exposure condition (P = 0.005). Results revealed that repeated exposure increased children's learning of nutritional information and liking of the character. The results contribute to our understanding of how to deliver effective nutrition information to young children in a new venue, a gaming app.

  13. Appreneur secrets to success in the app store

    CERN Document Server

    Pierce, Taylor

    2013-01-01

    You are interested in making an app. You have read all of the stories of successful developers and appreneurs. You are determined to get a piece of the pie. The world of apps is the fastest growing market in the world today, and it is here to stay. The best part is you can get in on it! Now what if I told you that without the knowledge contained in this book the odds of you making a profit are slim to none? What if I also told you that you probably wouldn't break even? There is more to apps than most people think. The average person assumes that if they make an app, they will instantly become

  14. Smartphone apps for calculating insulin dose: a systematic assessment.

    Science.gov (United States)

    Huckvale, Kit; Adomaviciute, Samanta; Prieto, José Tomás; Leow, Melvin Khee-Shing; Car, Josip

    2015-05-06

    Medical apps are widely available, increasingly used by patients and clinicians, and are being actively promoted for use in routine care. However, there is little systematic evidence exploring possible risks associated with apps intended for patient use. Because self-medication errors are a recognized source of avoidable harm, apps that affect medication use, such as dose calculators, deserve particular scrutiny. We explored the accuracy and clinical suitability of apps for calculating medication doses, focusing on insulin calculators for patients with diabetes as a representative use for a prevalent long-term condition. We performed a systematic assessment of all English-language rapid/short-acting insulin dose calculators available for iOS and Android. Searches identified 46 calculators that performed simple mathematical operations using planned carbohydrate intake and measured blood glucose. While 59% (n = 27/46) of apps included a clinical disclaimer, only 30% (n = 14/46) documented the calculation formula. 91% (n = 42/46) lacked numeric input validation, 59% (n = 27/46) allowed calculation when one or more values were missing, 48% (n = 22/46) used ambiguous terminology, 9% (n = 4/46) did not use adequate numeric precision and 4% (n = 2/46) did not store parameters faithfully. 67% (n = 31/46) of apps carried a risk of inappropriate output dose recommendation that either violated basic clinical assumptions (48%, n = 22/46) or did not match a stated formula (14%, n = 3/21) or correctly update in response to changing user inputs (37%, n = 17/46). Only one app, for iOS, was issue-free according to our criteria. No significant differences were observed in issue prevalence by payment model or platform. The majority of insulin dose calculator apps provide no protection against, and may actively contribute to, incorrect or inappropriate dose recommendations that put current users at risk of both catastrophic overdose and more

  15. Popular Mobile Phone Apps for Diet and Weight Loss: A Content Analysis.

    Science.gov (United States)

    Zaidan, Sarah; Roehrer, Erin

    2016-07-11

    A review of the literature has revealed that the rates of overweight and obesity have been increasing in Australia over the last two decades and that wellness mobile phone apps play a significant role in monitoring and managing individuals' weight. Although mobile phone app markets (iTunes and Google Play) list thousands of mobile phone health apps, it is not always clear whether those apps are supported by credible sources. Likewise, despite the prevailing use of mobile phone apps to aid with weight management, the usability features of these apps are not well characterized. The research explored how usability taxonomy could inform the popularity of downloaded, socially focused wellness mobile phone apps, in particular weight loss and diet apps. The aim of the study was to investigate the Australian mobile phone app stores (iTunes and Google Play) in order to examine the usability features of the most popular (ie, most downloaded) wellness apps. The design of this study comprises 3 main stages: stage 1, identifying apps; stage 2, development of weight loss and diet evaluation framework; and stage 3, application of the evaluation framework. Each stage includes specific data collection, analysis tools, and techniques. The study has resulted in the development of a justified evaluation framework for weight loss and diet mobile phone apps. Applying the evaluation framework to the identified apps has shown that the most downloaded iTunes and Google Play apps are not necessarily the most usable or effective. In addition, the research found that search algorithms for iTunes and Google Play are biased toward apps' titles and keywords that do not accurately define the real functionality of the app. Moreover, the study has also analyzed the apps' user reviews, which served as justification for the developed evaluation framework. The analysis has shown that ease of use, reminder, bar code scanning, motivation, usable for all, and synchronization are significant attributes

  16. Mobile health apps in Sweden: what do physicians recommend?

    Science.gov (United States)

    Zhang, Yiping; Koch, Sabine

    2015-01-01

    Currently over 50,000 mobile health apps are available worldwide. In general, they are considered as innovations potentially delivering benefits to patients. Physicians are considered as potential channels to disseminate these innovations to patients. However, physicians' behavior in this regard has not been studied. To capture physicians' attitudes towards recommending health apps to patients and to describe factors influencing physicians' behavior, taking the specifics of an early adopter country, Sweden, into account. Diffusion of Innovation theory, the Health App Maturity Model and the Six Hurdles Model were used to construct a web-based survey that was answered by 44 Swedish physicians. Survey results were followed up with 2 individual interviews. Descriptive statistics were used for quantitative data analysis and recursive abstraction for qualitative data analysis. Only a small group of physicians currently recommend mobile health apps to their patients. However, most physicians have a positive attitude and perceive improvement of patients' self-management ability as main benefit of health apps. Main perceived weaknesses include the lack of evidence-based content and lack of multi-language support. Regulation of health apps under the Medical Device Directive is asked for to assure quality and patient safety. Innovators and early adopters play an important role in the diffusion of mobile health apps. Interpersonal communication is seen as the most effective way for physicians gaining information and also motivates them to recommend mobile health apps to their patients. Physicians' knowledge about certified websites to ensure quality is however low.

  17. A qualitative study of user perceptions of mobile health apps

    Directory of Open Access Journals (Sweden)

    Wei Peng

    2016-11-01

    Full Text Available Abstract Background Mobile apps for health exist in large numbers today, but oftentimes, consumers do not continue to use them after a brief period of initial usage, are averse toward using them at all, or are unaware that such apps even exist. The purpose of our study was to examine and qualitatively determine the design and content elements of health apps that facilitate or impede usage from the users’ perceptive. Methods In 2014, six focus groups and five individual interviews were conducted in the Midwest region of the U.S. with a mixture of 44 smartphone owners of various social economic status. The participants were asked about their general and health specific mobile app usage. They were then shown specific features of exemplar health apps and prompted to discuss their perceptions. The focus groups and interviews were audio recorded, transcribed verbatim, and coded using the software NVivo. Results Inductive thematic analysis was adopted to analyze the data and nine themes were identified: 1 barriers to adoption of health apps, 2 barriers to continued use of health apps, 3 motivators, 4 information and personalized guidance, 5 tracking for awareness and progress, 6 credibility, 7 goal setting, 8 reminders, and 9 sharing personal information. The themes were mapped to theories for interpretation of the results. Conclusions This qualitative research with a diverse pool of participants extended previous research on challenges and opportunities of health apps. The findings provide researchers, app designers, and health care providers insights on how to develop and evaluate health apps from the users’ perspective.

  18. A qualitative study of user perceptions of mobile health apps.

    Science.gov (United States)

    Peng, Wei; Kanthawala, Shaheen; Yuan, Shupei; Hussain, Syed Ali

    2016-11-14

    Mobile apps for health exist in large numbers today, but oftentimes, consumers do not continue to use them after a brief period of initial usage, are averse toward using them at all, or are unaware that such apps even exist. The purpose of our study was to examine and qualitatively determine the design and content elements of health apps that facilitate or impede usage from the users' perceptive. In 2014, six focus groups and five individual interviews were conducted in the Midwest region of the U.S. with a mixture of 44 smartphone owners of various social economic status. The participants were asked about their general and health specific mobile app usage. They were then shown specific features of exemplar health apps and prompted to discuss their perceptions. The focus groups and interviews were audio recorded, transcribed verbatim, and coded using the software NVivo. Inductive thematic analysis was adopted to analyze the data and nine themes were identified: 1) barriers to adoption of health apps, 2) barriers to continued use of health apps, 3) motivators, 4) information and personalized guidance, 5) tracking for awareness and progress, 6) credibility, 7) goal setting, 8) reminders, and 9) sharing personal information. The themes were mapped to theories for interpretation of the results. This qualitative research with a diverse pool of participants extended previous research on challenges and opportunities of health apps. The findings provide researchers, app designers, and health care providers insights on how to develop and evaluate health apps from the users' perspective.

  19. Photoperiodic Regulation of Behavioral Responsiveness to Proinflammatory Cytokines

    OpenAIRE

    Wen, Jarvi C.; Prendergast, Brian J.

    2007-01-01

    Symptoms of bacterial infection include decreases in body mass (cachexia), induction of depressive-like hedonic tone (anhedonia), decreases in food intake (anorexia), and increases in body temperature (fever). Recognition of bacteria by the innate immune system triggers the release of proinflammatory cytokines which induce these sickness behaviors via central and peripheral substrates. In Siberian hamsters, exposure to short day lengths decreases both the production of proinflammatory cytokin...

  20. Android arcade game app a real world project : case study approach

    CERN Document Server

    DiMarzio, Jerome

    2012-01-01

    Apress, the leading Android books publisher, continues to provide you with very hands-on, practical books for teaching and showing app developers how to build and design apps, including game apps, that can be built and deployed in the various Android app stores out there. Android Arcade Game App:  A Real World Project - Case Study Approach is no different in that it walks you through creating an arcade style Prison Break game app-top to bottom-for an Android smartphone or tablet.  This book teaches you the unique characteristics and challenges of creating an Arcade style game And it provides y

  1. Building cross-platform apps using Titanium, Alloy, and Appcelerator cloud services

    CERN Document Server

    Saunders, Aaron

    2014-01-01

    Skip Objective-C and Java to get your app to market faster, using the skills you already have Building Cross-Platform Apps using Titanium, Alloy, and Appcelerator Cloud Services shows you how to build cross-platform iOS and Android apps without learning Objective-C or Java. With detailed guidance given toward using the Titanium Mobile Platform and Appcelerator Cloud Services, you will quickly develop the skills to build real, native apps- not web apps-using existing HTML, CSS, and JavaScript know-how. This guide takes you step-by-step through the creation of a photo-sharing app that leverages

  2. Apps for asthma self-management: a systematic assessment of content and tools

    Directory of Open Access Journals (Sweden)

    Huckvale Kit

    2012-11-01

    Full Text Available Abstract Background Apps have been enthusiastically adopted by the general public. They are increasingly recognized by policy-makers as a potential medium for supporting self-management of long-term conditions. We assessed the degree to which current smartphone and tablet apps for people with asthma offer content and tools of appropriate quality to support asthma self-management. Methods We adapted systematic review methodology to the assessment of apps. We identified English-language asthma apps for all ages through a systematic search of official app stores. We systematically assessed app content using criteria derived from international guidelines and systematic review of strategies for asthma self-management. We covered three domains: comprehensiveness of asthma information, consistency of advice with evidence and compliance with health information best practice principles. Results We identified 103 apps for asthma in English, of which 56 were sources of information about the condition and 47 provided tools for the management of asthma. No apps offered both types of functionality. Only three information apps approached our definition of comprehensiveness of information about asthma. No apps provided advice on lay management of acute asthma that included details of appropriate reliever medication use. In 32 of 72 instances, apps made unequivocal recommendations about strategies for asthma control or prophylaxis that were unsupported by current evidence. Although 90% of apps stated a clear purpose, compliance with other best practice principles for health information was variable. Contact details were located for 55%, funding source for 18% and confidentiality policy for 17%. Conclusions No apps for people with asthma combined reliable, comprehensive information about the condition with supportive tools for self-management. Healthcare professionals considering recommending apps to patients as part of asthma self-management should exercise

  3. Exploiting Proximity-Based Mobile Apps for Large-Scale Location Privacy Probing

    Directory of Open Access Journals (Sweden)

    Shuang Zhao

    2018-01-01

    Full Text Available Proximity-based apps have been changing the way people interact with each other in the physical world. To help people extend their social networks, proximity-based nearby-stranger (NS apps that encourage people to make friends with nearby strangers have gained popularity recently. As another typical type of proximity-based apps, some ridesharing (RS apps allowing drivers to search nearby passengers and get their ridesharing requests also become popular due to their contribution to economy and emission reduction. In this paper, we concentrate on the location privacy of proximity-based mobile apps. By analyzing the communication mechanism, we find that many apps of this type are vulnerable to large-scale location spoofing attack (LLSA. We accordingly propose three approaches to performing LLSA. To evaluate the threat of LLSA posed to proximity-based mobile apps, we perform real-world case studies against an NS app named Weibo and an RS app called Didi. The results show that our approaches can effectively and automatically collect a huge volume of users’ locations or travel records, thereby demonstrating the severity of LLSA. We apply the LLSA approaches against nine popular proximity-based apps with millions of installations to evaluate the defense strength. We finally suggest possible countermeasures for the proposed attacks.

  4. How Can iPad Apps Enrich Postgraduate Psychology Research?

    Science.gov (United States)

    Kucirkova, Natalia

    2014-01-01

    In this short Opinion piece, I outline how iPad apps can facilitate theory development, data collection, data representation and dissemination of postgraduate psychology research. I reflect on how apps supported my own postgraduate research practice and how one particular app--Our Story--enriched the individual stages of my research enquiry. I…

  5. Behavior change techniques in popular alcohol reduction apps: content analysis.

    Science.gov (United States)

    Crane, David; Garnett, Claire; Brown, James; West, Robert; Michie, Susan

    2015-05-14

    Mobile phone apps have the potential to reduce excessive alcohol consumption cost-effectively. Although hundreds of alcohol-related apps are available, there is little information about the behavior change techniques (BCTs) they contain, or the extent to which they are based on evidence or theory and how this relates to their popularity and user ratings. Our aim was to assess the proportion of popular alcohol-related apps available in the United Kingdom that focus on alcohol reduction, identify the BCTs they contain, and explore whether BCTs or the mention of theory or evidence is associated with app popularity and user ratings. We searched the iTunes and Google Play stores with the terms "alcohol" and "drink", and the first 800 results were classified into alcohol reduction, entertainment, or blood alcohol content measurement. Of those classified as alcohol reduction, all free apps and the top 10 paid apps were coded for BCTs and for reference to evidence or theory. Measures of popularity and user ratings were extracted. Of the 800 apps identified, 662 were unique. Of these, 13.7% (91/662) were classified as alcohol reduction (95% CI 11.3-16.6), 53.9% (357/662) entertainment (95% CI 50.1-57.7), 18.9% (125/662) blood alcohol content measurement (95% CI 16.1-22.0) and 13.4% (89/662) other (95% CI 11.1-16.3). The 51 free alcohol reduction apps and the top 10 paid apps contained a mean of 3.6 BCTs (SD 3.4), with approximately 12% (7/61) not including any BCTs. The BCTs used most often were "facilitate self-recording" (54%, 33/61), "provide information on consequences of excessive alcohol use and drinking cessation" (43%, 26/61), "provide feedback on performance" (41%, 25/61), "give options for additional and later support" (25%, 15/61) and "offer/direct towards appropriate written materials" (23%, 14/61). These apps also rarely included any of the 22 BCTs frequently used in other health behavior change interventions (mean 2.46, SD 2.06). Evidence was mentioned by 16

  6. Changes in the Levels of Pro-Inflammatory Cytokines in Patients with Generalized Periodontitis and Hypertension, Depending on the Method of Treatment

    Directory of Open Access Journals (Sweden)

    T. Vicharenko

    2017-12-01

    Full Text Available Inflammatory mediators have an important role in the pathogenesis of periodontal disease. One of the leading mediators of the initiation of the pathological process is interleukin-1 (IL-1 – an endogenous pyrogen, a lymphocyte-activating factor. Numerous pro-inflammatory effects of interleukin-1β (IL-1β occur in synergy with tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6, effects on hematopoiesis, participates in nonspecific anti-infective defense. The objective of the study is to determine levels of interleukin-6 and tumor necrosis factor alpha (TNF-α in patients with hypertension II stage and generalized periodontitis of the II degree depending on the treatment method. There were examined 30 patients with hypertension of the II stage and with generalized periodontitis of the II degree. Patients’ age ranged from 35 to 54 years. These patients were divided into two groups. The control group included 10 patients without general somatic pathology and with healthy periodontitis of the same age.  The result of the analysis of tumor necrosis factor alpha (TNF-α in patients in the first group before the treatment was 10.69±2.33 pg/ml. After the treatment this indicator was 6.97±1.57 pg/ml (p>0.1 in patients of the first group. In patients of the second group the tumor necrosis factor alpha (TNF-α was 9.49±2.2 pg/ml; after the treatment according to the offered scheme this figure decreased up to 2.77±0.9 pg/ml (p0.1. In the second group, before the treatment the level of  interleukin-6 was 9.65±2.41 pg/ml; after the treatment according to the offered scheme it was 2.62±0.5 pg/ml (p<0.01. In the control group the interleukin-6 level was 2.24±0.51 pg/ml. Analyzing the obtained results after the treatment in both groups we can conclude: after the treatment of generalized periodontitis of the II degree in patients with hypertension of the II stage, indices of pro-inflammatory cytokines decreased and ranged in normal limits; in

  7. Proinflammatory cytokine levels in patients with conversion disorder.

    Science.gov (United States)

    Tiyekli, Utkan; Calıyurt, Okan; Tiyekli, Nimet Dilek

    2013-06-01

    It was aimed to evaluate the relationship between proinflammatory cytokine levels and conversion disorder both commonly known as stress regulated. Baseline proinflammatory cytokine levels-[Tumour necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6)]-were evaluated with enzyme-linked immunosorbent assay in 35 conversion disorder patients and 30 healthy controls. Possible changes in proinflammatory cytokine levels were evaluated again, after their acute phase in conversion disorder patients. Statistically significant decreased serum TNF-α levels were obtained in acute phase of conversion disorder. Those levels increased after acute conversion phase. There were no statistically significant difference observed between groups in serum IL-1β and (IL-6) levels. Stress associated with conversion disorder may suppress immune function in acute conversion phase and may have diagnostic and therapeutic value.

  8. Moving Phones Tick Slower: Creating an Android App to Demonstrate Time Dilation

    Science.gov (United States)

    Underwood, Bret; Zhai, Yunxiao

    2016-05-01

    Smartphones and tablets are packed with sensors that allow us to take experimental data, essentially making them mobile physics labs. Apps exist that make it easy to capture and analyze data from these sensors, allowing users to study diverse phenomena such as free fall acceleration, the speed of sound, radioactivity, and many others. Commonly, the use of apps in the physics classroom focuses on existing apps rather than on the creation of apps themselves. This is for a good reason-writing an app usually requires advanced knowledge of programming languages and experience with app design. These skills are generally regarded as beyond the typical physics student. However, there are app development environments, such as MIT App Inventor 2 for Android, which make the process of creating an app and utilizing the sensors much more accessible to students. Putting the ability to create and configure apps within the reach of students can also help integrate computation into the curriculum. In this article, we discuss our creation of an Android app, Time Dilation Calculator, done as part of a senior undergraduate capstone project, which uses App Inventor and a mobile device's global positioning system (GPS) receiver to calculate the time dilation effect of special relativity.

  9. Smartphones in ecology and evolution: a guide for the app-rehensive.

    Science.gov (United States)

    Teacher, Amber G F; Griffiths, David J; Hodgson, David J; Inger, Richard

    2013-12-01

    Smartphones and their apps (application software) are now used by millions of people worldwide and represent a powerful combination of sensors, information transfer, and computing power that deserves better exploitation by ecological and evolutionary researchers. We outline the development process for research apps, provide contrasting case studies for two new research apps, and scan the research horizon to suggest how apps can contribute to the rapid collection, interpretation, and dissemination of data in ecology and evolutionary biology. We emphasize that the usefulness of an app relies heavily on the development process, recommend that app developers are engaged with the process at the earliest possible stage, and commend efforts to create open-source software scaffolds on which customized apps can be built by nonexperts. We conclude that smartphones and their apps could replace many traditional handheld sensors, calculators, and data storage devices in ecological and evolutionary research. We identify their potential use in the high-throughput collection, analysis, and storage of complex ecological information.

  10. Commercially Available Smartphone Apps to Support Postoperative Pain Self-Management: Scoping Review.

    Science.gov (United States)

    Lalloo, Chitra; Shah, Ushma; Birnie, Kathryn A; Davies-Chalmers, Cleo; Rivera, Jordan; Stinson, Jennifer; Campbell, Fiona

    2017-10-23

    Recently, the use of smartphones to deliver health-related content has experienced rapid growth, with more than 165,000 mobile health (mHealth) apps currently available in the digital marketplace. With 3 out of 4 Canadians currently owning a smartphone, mHealth apps offer opportunities to deliver accessible health-related knowledge and support. Many individuals experience pain after surgery, which can negatively impact their health-related quality of life, including sleep, emotional, and social functioning. Smartphone apps that provide remote real-time monitoring and symptom management have the potential to improve self-management skills in patients experiencing postoperative pain. Increased confidence and practice of self-management skills could contribute to decreased postoperative pain and reduce risk of developing persistent pain. Published reviews of general pain self-management apps demonstrate a lack of evidence-based content, theoretical grounding, and health care professional involvement. However, no review to date has focused on the app marketplace specific for individuals with postoperative pain. The aim of this study was to characterize and critically appraise the content and functionality of commercially available postoperative pain self-management apps. An electronic search and extraction was conducted between December 2016 and March 2017 of the official Canadian app stores for the three major smartphone operating systems (iPhone operating system [iOS], Android, and Windows). Stores were searched separately using predetermined search terms. Two authors screened apps based on information provided in the public app description. Metadata from all included apps were abstracted into a standard spreadsheet. Two authors verified the data with reference to the apps and downloaded apps themselves. The content and functionality of each app as it pertained to postoperative pain self-management was rated. A total of 10 apps met the inclusion criteria. All

  11. Geosocial-Networking App Usage Patterns of Gay, Bisexual, and Other Men Who Have Sex With Men: Survey Among Users of Grindr, A Mobile Dating App.

    Science.gov (United States)

    Goedel, William C; Duncan, Dustin T

    2015-01-01

    Geosocial-networking apps like Grindr have been used increasingly among men who have sex with men (MSM) to meet anonymous partners. These mobile dating apps employ global positioning system technology to facilitate connections with other users based on their current location. These new technologies have generated quicker and easier modes for men who have sex with men to meet potential partners based on attraction and physical proximity. The aim of this study is to describe geosocial-networking app use and recent sexual behaviors of MSM in the Atlanta metropolitan statistical area. Our sample was recruited from Grindr, the most commonly used of these mobile apps among MSM, using broadcast advertising. Advertisements were displayed over the course of a 72-hour period and participants were directed to a Web-based survey. In total, 604 men clicked through the advertisement, and 92 users completed the survey. One-third (38.0%) of the men reported using these mobile apps to meet new sexual partners, and one-fifth (18.5%) used them to "kill time" when bored. Men reporting currently being in a relationship were less likely to report using these mobile apps to meet other MSM to date or to find a boyfriend or romantic partner, but more likely to report using these mobile apps to meet other MSM to have sex, X (2) 24=12.1, P=.016. Respondents had current accounts on 3.11 mobile apps (SD 1.84) on average, with Grindr being the most common (100%), followed by Scruff (52.5%), and Jack'd (45.7%). Most men were most active in the late night (40.2%), and on weekdays (64.1%). Each day, on average, men reported opening these mobile apps 8.38 times (SD 8.10) and spent 1.31 hours (SD 1.15) on these mobile apps. The age respondents began using these mobile apps was associated with the age at their first instance of insertive anal sex (r80=.527, Pmobile apps and spend significant time on them. For these reasons, HIV prevention interventions could be delivered on these mobile apps.

  12. Web-based hybrid mobile apps: state of the practice and research opportunities

    NARCIS (Netherlands)

    Malavolta, Ivano

    2016-01-01

    This paper describes the contents of a tutorial on web-based hybrid mobile apps. Nowadays millions of mobile apps are downloaded and used all over the world. Mobile apps are distributed via different app stores like Google Play Store, the Apple App Store, the Windows Phone Store. One of the most

  13. Using Mobile App Development Tools to Build a GIS Application

    Science.gov (United States)

    Mital, A.; Catchen, M.; Mital, K.

    2014-12-01

    Our group designed and built working web, android, and IOS applications using different mapping libraries as bases on which to overlay fire data from NASA. The group originally planned to make app versions for Google Maps, Leaflet, and OpenLayers. However, because the Leaflet library did not properly load on Android, the group focused efforts on the other two mapping libraries. For Google Maps, the group first designed a UI for the web app and made a working version of the app. After updating the source of fire data to one which also provided historical fire data, the design had to be modified to include the extra data. After completing a working version of the web app, the group used webview in android, a built in resource which allowed porting the web app to android without rewriting the code for android. Upon completing this, the group found Apple IOS devices had a similar capability, and so decided to add an IOS app to the project using a function similar to webview. Alongside this effort, the group began implementing an OpenLayers fire map using a simpler UI. This web app was completed fairly quickly relative to Google Maps; however, it did not include functionality such as satellite imagery or searchable locations. The group finished the project with a working android version of the Google Maps based app supporting API levels 14-19 and an OpenLayers based app supporting API levels 8-19, as well as a Google Maps based IOS app supporting both old and new screen formats. This project was implemented by high school and college students under an SGT Inc. STEM internship program

  14. Mobile telephone apps in mental health practice: uses, opportunities and challenges

    OpenAIRE

    Marley, Justin; Farooq, Saeed

    2015-01-01

    Smartphones are used by patients and clinicians alike. Vast numbers of software applications (apps) run on smartphones and carry out useful functions. Clinician- and patient-oriented mental health apps have been developed. In this article, we provide an overview of apps that are relevant for mental health. We look at clinician-oriented apps that support assessment, diagnosis and treatment as well as patient-oriented apps that support education and self-management. We conclude by looking at th...

  15. English Language Teaching Apps: Positioning Parents and Young Learners

    Science.gov (United States)

    Chik, Alice

    2014-01-01

    Since the introduction of iPads in 2010, the sales of tablet computers and mobile applications (apps) have grown exponentially. iPads and other tablets are marketed as learning tools, and many apps target learners as young as six months old. This article reports on a research project examining the unique features of English learning apps based on…

  16. An Evidence-Based Forensic Taxonomy of Windows Phone Communication Apps.

    Science.gov (United States)

    Cahyani, Niken Dwi Wahyu; Martini, Ben; Choo, Kim-Kwang Raymond; Ab Rahman, Nurul Hidayah; Ashman, Helen

    2018-05-01

    Communication apps can be an important source of evidence in a forensic investigation (e.g., in the investigation of a drug trafficking or terrorism case where the communications apps were used by the accused persons during the transactions or planning activities). This study presents the first evidence-based forensic taxonomy of Windows Phone communication apps, using an existing two-dimensional Android forensic taxonomy as a baseline. Specifically, 30 Windows Phone communication apps, including Instant Messaging (IM) and Voice over IP (VoIP) apps, are examined. Artifacts extracted using physical acquisition are analyzed, and seven digital evidence objects of forensic interest are identified, namely: Call Log, Chats, Contacts, Locations, Installed Applications, SMSs and User Accounts. Findings from this study would help to facilitate timely and effective forensic investigations involving Windows Phone communication apps. © 2017 American Academy of Forensic Sciences.

  17. The Quality and Accuracy of Mobile Apps to Prevent Driving After Drinking Alcohol.

    Science.gov (United States)

    Wilson, Hollie; Stoyanov, Stoyan R; Gandabhai, Shailen; Baldwin, Alexander

    2016-08-08

    Driving after the consumption of alcohol represents a significant problem globally. Individual prevention countermeasures such as personalized mobile app aimed at preventing such behavior are widespread, but there is little research on their accuracy and evidence base. There has been no known assessment investigating the quality of such apps. This study aimed to determine the quality and accuracy of apps for drink driving prevention by conducting a review and evaluation of relevant mobile apps. A systematic app search was conducted following PRISMA guidelines. App quality was assessed using the Mobile App Rating Scale (MARS). Apps providing blood alcohol calculators (hereafter "calculators") were reviewed against current alcohol advice for accuracy. A total of 58 apps (30 iOS and 28 Android) met inclusion criteria and were included in the final analysis. Drink driving prevention apps had significantly lower engagement and overall quality scores than alcohol management apps. Most calculators provided conservative blood alcohol content (BAC) time until sober calculations. None of the apps had been evaluated to determine their efficacy in changing either drinking or driving behaviors. This novel study demonstrates that most drink driving prevention apps are not engaging and lack accuracy. They could be improved by increasing engagement features, such as gamification. Further research should examine the context and motivations for using apps to prevent driving after drinking in at-risk populations. Development of drink driving prevention apps should incorporate evidence-based information and guidance, lacking in current apps.

  18. Interpolis SlimOpWeg-programma : de AutoModus-app : vragenlijstonderzoek naar het effect van een app om smartphonegebruik in de auto te verminderen.

    NARCIS (Netherlands)

    Groot-Mesken, J. de Wijnen, W. Stelling-Konczak, A. & Commandeur, J.J.F.

    2017-01-01

    Interpolis SlimOpWeg programme: the AutoModus app; Survey into the effect of an app on reducing smartphone use while driving a car. Within the programme SlimOpWeg the Dutch insurance company Interpolis had a smartphone app developed. The purpose of this ‘AutoModus app’ is to help young drivers to

  19. Specialized Binary Analysis for Vetting Android APPS Using GUI Logic

    Science.gov (United States)

    2016-04-01

    user expectation of what the app is doing. These techniques enable security analysts to quickly vet any given Android app even if the source code is...Malware Detection for Android applications, Binary Analysis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF PAGES 19a...of what the app is doing. These techniques enable security analysts to quickly vet any given Android app even if the source code is unavailable. These

  20. Schistosome tegumental ecto-apyrase (SmATPDase1 degrades exogenous pro-inflammatory and pro-thrombotic nucleotides

    Directory of Open Access Journals (Sweden)

    Akram A. Da’dara

    2014-03-01

    Full Text Available Schistosomes are parasitic worms that can survive in the hostile environment of the human bloodstream where they appear refractory to both immune elimination and thrombus formation. We hypothesize that parasite migration in the bloodstream can stress the vascular endothelium causing this tissue to release chemicals alerting responsive host cells to the stress. Such chemicals are called damage associated molecular patterns (DAMPs and among the most potent is the proinflammatory mediator, adenosine triphosphate (ATP. Furthermore, the ATP derivative ADP is a pro-thrombotic molecule that acts as a strong activator of platelets. Schistosomes are reported to possess at their host interactive tegumental surface a series of enzymes that could, like their homologs in mammals, degrade extracellular ATP and ADP. These are alkaline phosphatase (SmAP, phosphodiesterase (SmNPP-5 and ATP diphosphohydrolase (SmATPDase1. In this work we employ RNAi to knock down expression of the genes encoding these enzymes in the intravascular life stages of the parasite. We then compare the abilities of these parasites to degrade exogenously added ATP and ADP. We find that only SmATPDase1-suppressed parasites are significantly impaired in their ability to degrade these nucleotides. Suppression of SmAP or SmNPP-5 does not appreciably affect the worms’ ability to catabolize ATP or ADP. These findings are confirmed by the functional characterization of the enzymatically active, full-length recombinant SmATPDase1 expressed in CHO-S cells. The enzyme is a true apyrase; SmATPDase1 degrades ATP and ADP in a cation dependent manner. Optimal activity is seen at alkaline pH. The Km of SmATPDase1 for ATP is 0.4 ± 0.02 mM and for ADP, 0.252 ± 0.02 mM. The results confirm the role of tegumental SmATPDase1 in the degradation of the exogenous pro-inflammatory and pro-thrombotic nucleotides ATP and ADP by live intravascular stages of the parasite. By degrading host inflammatory signals

  1. Autism Children’s App using PECS

    Directory of Open Access Journals (Sweden)

    Nareena Soomro

    2018-01-01

    Full Text Available Since autistic children suffers from learning disabilities and communication barriers, this research aim to design, develop and evaluate an Android based mobile application (app providing better learning environment with inclusion of graphical representation in a cost effective manner. This research evaluate various supporting technologies and finds Picture Exchange Communication System (PECS to be better choice for integrating with the app. Evaluation results reveal that the inclusion of PECS helped the children suffering from Autistic Spectrum Disorder (ASD to better communicate with others. The study included autistic children who do not speak, who are unintelligible and who are minimally effective communicators with their present communication system. The evolution results showed encouraging impacts of the Autism App in supporting autistic children to adapt to normal life and improve the standard of their life.

  2. Single amino acid change in STING leads to constitutive active signaling.

    Directory of Open Access Journals (Sweden)

    Eric D Tang

    Full Text Available The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

  3. Single amino acid change in STING leads to constitutive active signaling.

    Science.gov (United States)

    Tang, Eric D; Wang, Cun-Yu

    2015-01-01

    The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS) activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

  4. TLR2−/− Mice Display Decreased Severity of Giardiasis via Enhanced Proinflammatory Cytokines Production Dependent on AKT Signal Pathway

    Directory of Open Access Journals (Sweden)

    Xin Li

    2017-09-01

    the promotion of proinflammatory cytokines production. For the first time, our results demonstrated that TLR2 played a negative role in host defense against Giardia.

  5. Cisplatin ototoxicity involves cytokines and STAT6 signaling network

    Institute of Scientific and Technical Information of China (English)

    Hyung-Jin Kim; Jeong-Dug Sul; Channy Park; Sang-Young Chung; Sung-Kyun Moon; David J Lim; Hong-Seob So; Raekil Park; Gi-Su Oh; Jeong-Han Lee; Ah-Ra Lyu; Hye-Min Ji; Sang-Heon Lee; Jeho Song; Sung-Joo Park; Yong-Ouk You

    2011-01-01

    We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type,WT) and STAT4-/-,but not in STAT6-/- mice. Moreover,the expression levels of the protein and mRNA of proinflammatory cytokines,including TNF-α,IL-1β,and IL-6,were markedly increased in the serum and cochlea of WT and STAT4+,but not STAT6-/- mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6-/- mice were intact after treatment with cisplatin,whereas those from WT and STAT4-/- mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells,and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.

  6. Expert Involvement and Adherence to Medical Evidence in Medical Mobile Phone Apps

    DEFF Research Database (Denmark)

    Subhi, Yousif; Bube, Sarah Hjartbro; Rolskov Bojsen, Signe

    2015-01-01

    BACKGROUND: Both clinicians and patients use medical mobile phone apps. Anyone can publish medical apps, which leads to contents with variable quality that may have a serious impact on human lives. We herein provide an overview of the prevalence of expert involvement in app development and whether...... or not app contents adhere to current medical evidence. OBJECTIVE: To systematically review studies evaluating expert involvement or adherence of app content to medical evidence in medical mobile phone apps. METHODS: We systematically searched 3 databases (PubMed, The Cochrane Library, and EMBASE......), and included studies evaluating expert involvement or adherence of app content to medical evidence in medical mobile phone apps. Two authors performed data extraction independently. Qualitative analysis of the included studies was performed. RESULTS: Based on inclusion criteria, 52 studies were included...

  7. Differential interaction of Apolipoprotein-E isoforms with insulin receptors modulates brain insulin signaling in mutant human amyloid precursor protein transgenic mice.

    Science.gov (United States)

    Chan, Elizabeth S; Chen, Christopher; Cole, Gregory M; Wong, Boon-Seng

    2015-09-08

    It is unclear how human apolipoprotein E4 (ApoE4) increases the risk for Alzheimer's disease (AD). Although Aβ levels can lead to insulin signaling impairment, these experiments were done in the absence of human ApoE. To examine ApoE role, we crossed the human ApoE-targeted replacement mice with mutant human amyloid precursor protein (APP) mice. In 26 week old mice with lower Aβ levels, the expression and phosphorylation of insulin signaling proteins remained comparable among APP, ApoE3xAPP and ApoE4xAPP mouse brains. When the mice aged to 78 weeks, these proteins were markedly reduced in APP and ApoE4xAPP mouse brains. While Aβ can bind to insulin receptor, how ApoE isoforms modulate this interaction remains unknown. Here, we showed that ApoE3 had greater association with insulin receptor as compared to ApoE4, regardless of Aβ42 concentration. In contrast, ApoE4 bound more Aβ42 with increasing peptide levels. Using primary hippocampal neurons, we showed that ApoE3 and ApoE4 neurons are equally sensitive to physiological levels of insulin. However, in the presence of Aβ42, insulin failed to elicit a downstream response only in ApoE4 hippocampal neurons. Taken together, our data show that ApoE genotypes can modulate this Aβ-mediated insulin signaling impairment.

  8. Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia.

    Science.gov (United States)

    Wei, Li; Tokizane, Kyohei; Konishi, Hiroyuki; Yu, Hua-Rong; Kiyama, Hiroshi

    2017-10-03

    Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood. We used endogenous, natural, and surrogate agonists for GPR84 (capric acid, embelin, and 6-OAU, respectively) and examined their effect on mouse primary cultured microglia in vitro. 6-n-Octylaminouracil (6-OAU), embelin, and capric acid rapidly induced membrane ruffling and motility in cultured microglia obtained from C57BL/6 mice, although these agonists failed to promote microglial pro-inflammatory cytokine expression. Concomitantly, 6-OAU suppressed forskolin-induced increase of cAMP in cultured microglia. Pertussis toxin, an inhibitor of Gi-coupled signaling, completely suppressed 6-OAU-induced microglial membrane ruffling and motility. In contrast, no 6-OAU-induced microglial membrane ruffling and motility was observed in microglia from DBA/2 mice, a mouse strain that does not express functional GPR84 protein due to endogenous nonsense mutation of the GPR84 gene. GPR84 mediated signaling causes microglial motility and membrane ruffling but does not promote pro-inflammatory responses. As GPR84 is a known receptor for medium-chain fatty acids, those released from damaged brain cells may be involved in the enhancement of microglial motility through GPR84 after neuronal injury.

  9. Security Recommendations for mHealth Apps: Elaboration of a Developer's Guide.

    Science.gov (United States)

    Morera, Enrique Pérez; de la Torre Díez, Isabel; Garcia-Zapirain, Begoña; López-Coronado, Miguel; Arambarri, Jon

    2016-06-01

    Being the third fastest-growing app category behind games and utilities, mHealth apps are changing the healthcare model, as medicine today involves the data they compile and analyse, information known as Big Data. However, the majority of apps are lacking in security when gathering and dealing with the information, which becomes a serious problem. This article presents a guide regarding security solution, intended to be of great use for developers of mHealth apps. In August 2015 current mobile health apps were sought out in virtual stores such as Android Google Play, Apple iTunes App Store etc., in order to classify them in terms of usefulness. After this search, the most widespread weaknesses in the field of security in the development of these mobile apps were examined, based on sources such as the "OWASP Mobile Security Project, the initiative recently launched by the Office of Civil Rights (OCR), and other articles of scientific interest. An informative, elemental guide has been created for the development of mHealth apps. It includes information about elements of security and its implementation on different levels for all types of mobile health apps based on the data that each app manipulates, the associated calculated risk as a result of the likelihood of occurrence and the threat level resulting from its vulnerabilities - high level (apps for monitoring, diagnosis, treatment and care) from 6 ≤ 9, medium level (calculator, localizer and alarm) from 3 ≤ 6 and low level (informative and educational apps) from 0 ≤ 3. The guide aims to guarantee and facilitate security measures in the development of mobile health applications by programmers unconnected to the ITC and professional health areas.

  10. Content Analysis of Diet-Related Mobile Apps: A Self-Regulation Perspective.

    Science.gov (United States)

    Zahry, Nagwan R; Cheng, Ying; Peng, Wei

    2016-10-01

    Diet-related mobile apps hold promise in helping individuals self-regulate their eating behaviors. Nevertheless, little is known about the extent to which diet-related mobile apps incorporate the established behavior change theories and evidence-based practices that promote dietary self-regulation. Guided by the self-regulation aspect of Bandura's social cognitive theory and the Dietary Guidelines for Americans 2010 of the U.S. Department of Agriculture, this study conducts a content analysis of diet-related mobile apps for iPhone (N = 400). In terms of the adherence to the self-regulation aspect of the social cognitive theory, results show that although 72.5% of the apps incorporate at least one theoretical construct, few apps tap all three processes of self-regulation (i.e., self-observation/monitoring, judgment process, and self-reaction). Additionally, outcome expectation is manifested in a majority of the diet-related apps. In terms of the Dietary Guidelines for Americans 2010, while the diet-related apps equally emphasize setting goals for calorie intake or nutrient consumption, more apps feature nutrient tracking than calorie tracking. Implications and limitations are discussed.

  11. Android Apps for Absolute Beginners

    CERN Document Server

    Jackson, Wallace

    2011-01-01

    Anybody can start building simple apps for the Android platform, and this book will show you how! Android Apps for Absolute Beginners takes you through the process of getting your first Android applications up and running using plain English and practical examples. It cuts through the fog of jargon and mystery that surrounds Android application development, and gives you simple, step-by-step instructions to get you started.* Teaches Android application development in language anyone can understand, giving you the best possible start in Android development * Provides simple, step-by-step exampl

  12. Functional relevance of protein glycosylation to the pro-inflammatory effects of extracellular matrix metalloproteinase inducer (EMMPRIN) on monocytes/macrophages.

    Science.gov (United States)

    Ge, Heng; Yuan, Wei; Liu, Jidong; He, Qing; Ding, Song; Pu, Jun; He, Ben

    2015-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) is an important pro-inflammatory protein involved in the cellular functions of monocytes/macrophages. We have hypothesized that high-level heterogeneousness of protein glycosylation of EMMPRIN may have functional relevance to its biological effects and affect the inflammatory activity of monocytes/macrophages. The glycosylation patterns of EMMPRIN expressed by monocytes/macrophages (THP-1 cells) in response to different extracellular stimuli were observed, and the structures of different glycosylation forms were identified. After the purification of highly- and less-glycosylated proteins respectively, the impacts of different glycosylation forms on the pro-inflammatory effects of EMMPRIN were examined in various aspects, such as cell adhesion to endothelial cells, cell migrations, cytokine expression, and activation of inflammatory signalling pathway. 1) It was mainly the highly-glycosylated form of EMMPRIN (HG-EMMPRIN) that increased after being exposed to inflammatory signals (PMA and H2O2). 2) Glycosylation of EMMPRIN in monocytes/macrophages led to N-linked-glycans being added to the protein, with the HG form containing complex-type glycans and the less-glycosylated form (LG) the simple type. 3) Only the HG-EMMPRIN but not the LG-EMMPRIN exhibited pro-inflammatory effects and stimulated inflammatory activities of the monocytes/macrophages (i.e., activation of ERK1/2 and NF-κB pathway, enhanced monocyte-endothelium adhesion, cell migration and matrix metalloproteinase -9 expression). Post-transcriptional glycosylation represents an important mechanism that determines the biological effects of EMMPRIN in monocytes/macrophages. Glycosylation of EMMPRIN may serve as a potential target for regulating the inflammatory activities of monocytes/macrophages.

  13. Functional relevance of protein glycosylation to the pro-inflammatory effects of extracellular matrix metalloproteinase inducer (EMMPRIN on monocytes/macrophages.

    Directory of Open Access Journals (Sweden)

    Heng Ge

    Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN is an important pro-inflammatory protein involved in the cellular functions of monocytes/macrophages. We have hypothesized that high-level heterogeneousness of protein glycosylation of EMMPRIN may have functional relevance to its biological effects and affect the inflammatory activity of monocytes/macrophages.The glycosylation patterns of EMMPRIN expressed by monocytes/macrophages (THP-1 cells in response to different extracellular stimuli were observed, and the structures of different glycosylation forms were identified. After the purification of highly- and less-glycosylated proteins respectively, the impacts of different glycosylation forms on the pro-inflammatory effects of EMMPRIN were examined in various aspects, such as cell adhesion to endothelial cells, cell migrations, cytokine expression, and activation of inflammatory signalling pathway.1 It was mainly the highly-glycosylated form of EMMPRIN (HG-EMMPRIN that increased after being exposed to inflammatory signals (PMA and H2O2. 2 Glycosylation of EMMPRIN in monocytes/macrophages led to N-linked-glycans being added to the protein, with the HG form containing complex-type glycans and the less-glycosylated form (LG the simple type. 3 Only the HG-EMMPRIN but not the LG-EMMPRIN exhibited pro-inflammatory effects and stimulated inflammatory activities of the monocytes/macrophages (i.e., activation of ERK1/2 and NF-κB pathway, enhanced monocyte-endothelium adhesion, cell migration and matrix metalloproteinase -9 expression.Post-transcriptional glycosylation represents an important mechanism that determines the biological effects of EMMPRIN in monocytes/macrophages. Glycosylation of EMMPRIN may serve as a potential target for regulating the inflammatory activities of monocytes/macrophages.

  14. The App Squad: SLJ's Advisors Weigh in on Kids' Book Apps

    Science.gov (United States)

    Ishizuka, Kathy

    2011-01-01

    In this article, "School Library Journal's" ("SLJ") advisors talk about book apps for kids. They discuss what they like, what one should look for in discerning the best for kids and teens, and where this all might be headed.

  15. Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model.

    Science.gov (United States)

    Borkowski, Julia; Li, Li; Steinmann, Ulrike; Quednau, Natascha; Stump-Guthier, Carolin; Weiss, Christel; Findeisen, Peter; Gretz, Norbert; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

    2014-09-13

    The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6

  16. NRF2 Signaling Negatively Regulates Phorbol-12-Myristate-13-Acetate (PMA-Induced Differentiation of Human Monocytic U937 Cells into Pro-Inflammatory Macrophages.

    Directory of Open Access Journals (Sweden)

    Min-Gu Song

    Full Text Available Blood monocytes are recruited to injured tissue sites and differentiate into macrophages, which protect against pathogens and repair damaged tissues. Reactive oxygen species (ROS are known to be an important contributor to monocytes' differentiation and macrophages' function. NF-E2-related factor 2 (NRF2, a transcription factor regulating cellular redox homeostasis, is known to be a critical modulator of inflammatory responses. We herein investigated the role of NRF2 in macrophage differentiation using the human monocytic U937 cell line and phorbol-12-myristate-13-acetate (PMA. In U937 cells with NRF2 silencing, PMA-stimulated cell adherence was significantly facilitated when compared to control U937 cells. Both transcript and protein levels for pro-inflammatory cytokines, including interleukine-1β (IL-1β, IL-6, and tumor necrosis factor-α (TNFα were highly elevated in PMA-stimulated NRF2-silenced U937 compared to the control. In addition, PMA-inducible secretion of monocyte chemotactic protein 1 (MCP-1 was significantly high in NRF2-silenced U937. As an underlying mechanism, we showed that NRF2-knockdown U937 retained high levels of cellular ROS and endoplasmic reticulum (ER stress markers expression; and subsequently, PMA-stimulated levels of Ca2+ and PKCα were greater in NRF2-knockdown U937 cells, which caused enhanced nuclear accumulation of nuclear factor-ҡB (NFҡB p50 and extracellular signal-regulated kinase (ERK-1/2 phosphorylation. Whereas the treatment of NRF2-silenced U937 cells with pharmacological inhibitors of NFҡB or ERK1/2 largely blocked PMA-induced IL-1β and IL-6 expression, indicating that these pathways are associated with cell differentiation. Taken together, our results suggest that the NRF2 system functions to suppress PMA-stimulated U937 cell differentiation into pro-inflammatory macrophages and provide evidence that the ROS-PKCα-ERK-NFҡB axis is involved in PMA-facilitated differentiation of NRF2-silenced U937

  17. Knoflook remt App

    NARCIS (Netherlands)

    Mul, M.F.; Becker, P.M.; Peet-Schwering, van der C.M.C.; Wikselaar, van P.G.; Wisselink, H.J.; Stockhofe, N.

    2011-01-01

    De Animal Sciences Group van Wageningen UR heeft in opdracht van biologische varkenshouders onderzocht of het mogelijk is om in plaats van antibiotica, knoflook te gebruiken voor de bestrijding van longontsteking door de bacterie Actinobacillus pleuropneumoniae (App). Uit de resultaten blijkt dat

  18. Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.

    Science.gov (United States)

    Yang, Lichao; Guo, Han; Li, Ying; Meng, Xianglan; Yan, Lu; Dan Zhang; Wu, Sangang; Zhou, Hao; Peng, Lu; Xie, Qiang; Jin, Xin

    2016-10-10

    The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.

  19. Smartphone apps to support hospital prescribing and pharmacology education: a review of current provision.

    Science.gov (United States)

    Haffey, Faye; Brady, Richard R W; Maxwell, Simon

    2014-01-01

    Junior doctors write the majority of hospital prescriptions but many indicate they feel underprepared to assume this responsibility and around 10% of prescriptions contain errors. Medical smartphone apps are now widely used in clinical practice and present an opportunity to provide support to inexperienced prescribers. This study assesses the contemporary range of smartphone apps with prescribing or related content. Six smartphone app stores were searched for apps aimed at the healthcare professional with drug, pharmacology or prescribing content. Three hundred and six apps were identified. 34% appeared to be for use within the clinical environment in order to aid prescribing, 14% out with the clinical setting and 51% of apps were deemed appropriate for both clinical and non-clinical use. Apps with drug reference material, such as textbooks, manuals or medical apps with drug information were the commonest apps found (51%), followed by apps offering drug or infusion rate dose calculation (26%). 68% of apps charged for download, with a mean price of £14.25 per app and a range of £0.62-101.90. A diverse range of pharmacology-themed apps are available and there is further potential for the development of contemporary apps to improve prescribing performance. Personalized app stores may help universities/healthcare organizations offer high quality apps to students to aid in pharmacology education. Users of prescribing apps must be aware of the lack of information regarding the medical expertise of app developers. This will enable them to make informed choices about the use of such apps in their clinical practice. © 2013 The British Pharmacological Society.

  20. Usability Pitfalls of Diabetes mHealth Apps for the Elderly

    Directory of Open Access Journals (Sweden)

    Maša Isaković

    2016-01-01

    Full Text Available Diabetes mellitus has high prevalence in the ageing population and is often accompanied by other comorbidities, such as Alzheimer’s disease, and general disabilities, such as poor eyesight. These comorbidities have redefined ways in which patients use mHealth apps, including diabetes apps. The latter have proven benefits for monitoring blood glucose levels and insulin tracking in the general population. In this paper, we analyse a diabetes monitoring app DeStress Assistant (DeSA, which was developed as a part of an EU project and tested in a hospital setting. Due to the increasing number of older adults, we wanted to ensure the app was suitable for that demographic. Based on a number of supervised tests, we show that the app, which was developed with the help of workshops and feedback from tech-savvy patients and clinicians, is difficult to use by elderly users. We demonstrate that with a small number of changes it is possible to raise the usability of the app in a number of categories. We summarise the lessons learned in the discussion. Our findings demonstrate that special care needs to be taken when developing mHealth apps for the elderly population.

  1. Free smoking cessation mobile apps available in Australia: a quality review and content analysis.

    Science.gov (United States)

    Thornton, Louise; Quinn, Catherine; Birrell, Louise; Guillaumier, Ashleigh; Shaw, Brad; Forbes, Erin; Deady, Mark; Kay-Lambkin, Frances

    2017-12-01

    This review aimed to identify free, high-quality, smoking cessation mobile applications (apps) that adhere to Australian smoking cessation treatment guidelines. A systematic search of smoking cessation apps was conducted using Google. The technical quality of relevant apps was rated using the Mobile Application Rating Scale. The content of apps identified as high quality was assessed for adherence to smoking cessation treatment guidelines. 112 relevant apps were identified. The majority were of poor technical quality and only six 'high-quality' apps were identified. These apps adhered to Australian treatment guidelines in part. The efficacy of two apps had been previously evaluated. In lieu of more substantial research in this area, it is suggested that the high-quality apps identified in this review may be more likely than other available apps to encourage smoking cessation. Implications for public health: Smoking cessation apps have the potential to address many barriers that prevent smoking cessation support being provided; however few high-quality smoking cessation apps are currently available in Australia, very few have been evaluated and the app market is extremely volatile. More research to evaluate smoking cessation apps, and sustained funding for evidence-based apps, is needed. © 2017 The Authors.

  2. Hyaluronan signaling during ozone-induced lung injury requires TLR4, MyD88, and TIRAP.

    Directory of Open Access Journals (Sweden)

    Zhuowei Li

    Full Text Available Ozone exposure is associated with exacerbation of reactive airways disease. We have previously reported that the damage-associated molecular pattern, hyaluronan, is required for the complete biological response to ambient ozone and that hyaluronan fragments signal through toll-like receptor 4 (TLR4. In this study, we further investigated the role of TLR4 adaptors in ozone-induced airway hyperresponsiveness (AHR and the direct response to hyaluronan fragments (HA. Using a murine model of AHR, C57BL/6J, TLR4-/-, MyD88-/-, and TIRAP-/- mice were characterized for AHR after exposure to either ozone (1 ppm × 3 h or HA fragments. Animals were characterized for AHR with methacholine challenge, cellular inflammation, lung injury, and production of pro-inflammatory cytokines. Ozone-exposed C57BL/6J mice developed cellular inflammation, lung injury, pro-inflammatory cytokines, and AHR, while mice deficient in TLR4, MyD88 or TIRAP demonstrated both reduced AHR and reduced levels of pro-inflammatory cytokines including TNFα, IL-1β, MCP-1, IL-6 and KC. The level of hyaluronan was increased after inhalation of ozone in each strain of mice. Direct challenge of mice to hyaluronan resulted in AHR in C57BL/6J mice, but not in TLR4-/-, MyD88-/-, or TIRAP-/- mice. HA-induced cytokine production in wild-type mice was significantly reduced in TLR4-/-, MyD88-/-, or TIRAP-/- mice. In conclusion, our findings support that ozone-induced airway hyperresponsiveness is dependent on the HA-TLR4-MyD88-TIRAP signaling pathway.

  3. Evaluation of diagnostic thresholds dependability for tribologic signals received in the environment disturbed by vibroacoustic and functional signals

    Directory of Open Access Journals (Sweden)

    Lindstedt Paweł

    2015-12-01

    Full Text Available Determination of dependable diagnostic thresholds for tribologic signals received e.g. from antifriction bearings (in particular for insufficient number of measurements, only 4÷5 is a really difficult task due to complexity of working environment where such bearings are operated. Typical working environment for such objects must take account for operation time under various working conditions and accompanying (and disturbing signals, e.g. vibroacoustic ones. The sought assessment of the relationship between diagnostic signals and environmental noise can be determined from convolution of both diagnostic and environments signals that make up the complete set of received information. The convolution of these two series of signals can be obtained from an algorithm based on the Cauchy product. Then one has to find the coherence factor and the square of amplitude gain for the set of diagnostic signals with reference to various sets of signals received from environment, which makes it possible to evaluate cohesion of the investigated series of signals, thus their suitability to determine diagnostic threshold for tribologic signals intended for the analysis.

  4. Leptin regulates the pro-inflammatory response in human epidermal keratinocytes.

    Science.gov (United States)

    Lee, Moonyoung; Lee, Eunyoung; Jin, Sun Hee; Ahn, Sungjin; Kim, Sae On; Kim, Jungmin; Choi, Dalwoong; Lim, Kyung-Min; Lee, Seung-Taek; Noh, Minsoo

    2018-05-01

    The role of leptin in cutaneous wound healing process has been suggested in genetically obese mouse studies. However, the molecular and cellular effects of leptin on human epidermal keratinocytes are still unclear. In this study, the whole-genome-scale microarray analysis was performed to elucidate the effect of leptin on epidermal keratinocyte functions. In the leptin-treated normal human keratinocytes (NHKs), we identified the 151 upregulated and 53 downregulated differentially expressed genes (DEGs). The gene ontology (GO) enrichment analysis with the leptin-induced DEGs suggests that leptin regulates NHKs to promote pro-inflammatory responses, extracellular matrix organization, and angiogenesis. Among the DEGs, the protein expression of IL-8, MMP-1, fibronectin, and S100A7, which play roles in which is important in the regulation of cutaneous inflammation, was confirmed in the leptin-treated NHKs. The upregulation of the leptin-induced proteins is mainly regulated by the STAT3 signaling pathway in NHKs. Among the downregulated DEGs, the protein expression of nucleosome assembly-associated centromere protein A (CENPA) and CENPM was confirmed in the leptin-treated NHKs. However, the expression of CENPA and CENPM was not coupled with those of other chromosome passenger complex like Aurora A kinase, INCENP, and survivin. In cell growth kinetics analysis, leptin had no significant effect on the cell growth curves of NHKs in the normal growth factor-enriched condition. Therefore, leptin-dependent downregulation of CENPA and CENPM in NHKs may not be directly associated with mitotic regulation during inflammation.

  5. Interactivity in Educational Apps for Young Children: A Multimodal Analysis

    Science.gov (United States)

    Blitz-Raith, Alexandra H.; Liu, Jianxin

    2017-01-01

    Interactivity is an important indicator of an educational app's reception. Since most educational apps are multimodal, it justifies a methodological initiative to understand meaningful involvement of multimodality in enacting and even amplifying interactivity in an educational app. Yet research so far has largely concentrated on algorithm…

  6. Proinflammatory Cytokine Responses in Extra-Respiratory Tissues During Severe Influenza

    NARCIS (Netherlands)

    Short, Kirsty R; Veeris, Rebecca; Leijten, Lonneke M; van den Brand, Judith M; Jong, Victor L; Stittelaar, Koert J; Osterhaus, Ab D M E|info:eu-repo/dai/nl/074960172; Andeweg, Arno C; van Riel, Debby

    2017-01-01

    Severe influenza is often associated with disease manifestations outside the respiratory tract. While proinflammatory cytokines can be detected in the lungs and blood of infected patients, the role of extra-respiratory organs in the production of proinflammatory cytokines is unknown. Here, we show

  7. Proinflammatory Cytokine Responses in Extra-Respiratory Tissues during Severe Influenza

    NARCIS (Netherlands)

    Short, Kirsty R.; Veeris, Rebecca; Leijten, Lonneke M.; van den Brand, Judith M A; Jong, Victor L.; Stittelaar, Koert; Osterhaus, Ab D.M.E.; Andeweg, Arno C; Van Riel, Debby

    2017-01-01

    Severe influenza is often associated with disease manifestations outside the respiratory tract. While proinflammatory cytokines can be detected in the lungs and blood of infected patients, the role of extra-respiratory organs in the production of proinflammatory cytokines is unknown. Here, we show

  8. A Pilot Comparison of a Smartphone App With or Without 2-Way Messaging Among Chronic Pain Patients: Who Benefits From a Pain App?

    Science.gov (United States)

    Jamison, Robert N; Jurcik, Dylan C; Edwards, Robert R; Huang, Chuan-Chin; Ross, Edgar L

    2017-08-01

    The overall aim of this study was to determine the effect of introducing a smartphone pain application (app), for both Android and iPhone devices that enables chronic pain patients to assess, monitor, and communicate their status to their providers. This study recruited 105 chronic pain patients to use a smartphone pain app and half of the patients (N=52) had 2-way messaging available through the app. All patients completed baseline measures and were asked to record their progress every day for 3 months, with the opportunity to continue for 6 months. All participants were supplied a Fitbit to track daily activity. Summary line graphs were posted to each of the patients' electronic medical records and physicians were notified of their patient's progress. Ninety patients successfully downloaded the pain app. Average age of the participants was 47.1 (range, 18 to 72), 63.8% were female and 32.3% reported multiple pain sites. Adequate validity and reliability was found between the daily assessments and standardized questionnaires (r=0.50) and in repeated daily measures (pain, r=0.69; sleep, r=0.83). The app was found to be easily introduced and well tolerated. Those patients assigned to the 2-way messaging condition on average tended to use the app more and submit more daily assessments (95.6 vs. 71.6 entries), but differences between groups were not significant. Pain-app satisfaction ratings overall were high. This study highlights some of the challenges and benefits in utilizing smartphone apps to manage chronic pain patients, and provides insight into those individuals who might benefit from mHealth technology.

  9. Behaviour Change Techniques embedded in health and lifestyle apps: coding and analysis.

    Directory of Open Access Journals (Sweden)

    Gaston Antezana

    2015-09-01

    Full Text Available Background There is evidence showing that commercially available health and lifestyle apps can be used as co-adjuvants to clinical interventions and for the prevention of chronic and non-communicable diseases. This can be particularly significant to support and improve wellbeing of young people given their familiarity with these resources. However it is important to understand the content and consistency of Behaviour Change Techniques (BCT’s embedded in the apps to maximise their potential benefits. Objectives This study explores the BCT content of a selected list of health and lifestyle tracking apps in three behavioural dimensions: physical activity, sleep and diet. We identified BCT commonalities within and between categories to detect the most frequently used and arguably more effective techniques in the context of wellbeing and promotion of health behaviours. Methods Apps were selected by using keywords and by reviewing the “health and fitness” category of GooglePlay (477 apps. The selection criteria included free apps (even if they also offered paid versions and being common to GooglePlay and AppStore. A background review of each app was also completed. Selected apps were classified according to user ratings in GooglePlay (apps with less that 4+ star ratings were disregarded. The top ten apps in each category were selected, making it a total of 30 for the analysis. Three coders used the apps for two months and were trained to use a comprehensive 93 items taxonomy (BCTv1 to complete the analysis. Results Strong BCT similarities were found across all three categories, suggesting a consistent basic content composition. Out of all 93 BCTS’s 8 were identified as being present in at least 50% of the apps. 6 of these BCT’s are concentrated in categories “1. Goals and Planning” and “2. Feedback and Monitoring”. BCT “Social support (unspecified” was coded for in 63% of the apps, as it was present through different features in

  10. Apps and Adolescents: A Systematic Review of Adolescents' Use of Mobile Phone and Tablet Apps That Support Personal Management of Their Chronic or Long-Term Physical Conditions.

    Science.gov (United States)

    Majeed-Ariss, Rabiya; Baildam, Eileen; Campbell, Malcolm; Chieng, Alice; Fallon, Debbie; Hall, Andrew; McDonagh, Janet E; Stones, Simon R; Thomson, Wendy; Swallow, Veronica

    2015-12-23

    The prevalence of physical chronic or long-term conditions in adolescents aged 10-24 years is rising. Mobile phone and tablet mobile technologies featuring software program apps are widely used by these adolescents and their healthy peers for social networking or gaming. Apps are also used in health care to support personal condition management and they have considerable potential in this context. There is a growing body of literature on app use in health contexts, thereby making a systematic review of their effectiveness very timely. To systematically review the literature on the effectiveness of mobile apps designed to support adolescents' management of their physical chronic or long-term conditions. We conducted a review of the English-language literature published since 2003 in five relevant bibliographical databases using key search terms. Two independent reviewers screened titles and abstracts using data extraction and quality assessment tools. The search returned 1120 hits. Of the 19 eligible full-text papers, four met our review criteria, reporting one pilot randomized controlled trial and three pretest/post-test studies. Samples ranged from 4 to 18 participants, with a combined sample of 46 participants. The apps reported were targeted at type 1 diabetes, asthma, and cancer. Two papers provided data for calculating effect size. Heterogeneity in terms of study design, reported outcomes, follow-up times, participants' ages, and health conditions prevented meta-analyses. There was variation in whether adolescents received guidance in using the app or were solely responsible for navigating the app. Three studies reported some level of patient involvement in app design, development, and/or evaluation. Health professional involvement in the modelling stages of apps was reported in all studies, although it was not always clear whether specific clinical (as opposed to academic) expertise in working with adolescents was represented. The dearth of studies and the

  11. BPcontrol. A Mobile App to Monitor Hypertensive Patients.

    Science.gov (United States)

    Carrera, Adrian; Pifarré, Marc; Vilaplana, Jordi; Cuadrado, Josep; Solsona, Sara; Mateo, Jordi; Solsona, Francesc

    2016-12-07

    Hypertension or high blood pressure is on the rise. Not only does it affect the elderly but is also increasingly spreading to younger sectors of the population. Treating this condition involves exhaustive monitoring of patients. The current mobile health services can be improved to perform this task more effectively. To develop a useful, user-friendly, robust and efficient app, to monitor hypertensive patients and adapted to the particular requirements of hypertension. This work presents BPcontrol, an Android and iOS app that allows hypertensive patients to communicate with their health-care centers, thus facilitating monitoring and diagnosis. Usability, robustness and efficiency factors for BPcontrol were evaluated for different devices and operating systems (Android, iOS and system-aware). Furthermore, its features were compared with other similar apps in the literature. BPcontrol is robust and user-friendly. The respective start-up efficiency of the Android and iOS versions of BPcontrol were 2.4 and 8.8 times faster than a system-aware app. Similar values were obtained for the communication efficiency (7.25 and 11.75 times faster for the Android and iOS respectively). When comparing plotting performance, BPcontrol was on average 2.25 times faster in the Android case. Most of the apps in the literature have no communication with a server, thus making it impossible to compare their performance with BPcontrol. Its optimal design and the good behavior of its facilities make BPcontrol a very promising mobile app for monitoring hypertensive patients.

  12. The Analysis Of Smartphone Apps In Geomatics Education

    Science.gov (United States)

    Teo, T.-A.; Wu, H.-M.; Shih, T.-Y.; Tsai, F.

    2014-04-01

    Geomatics is a discipline of collecting, processing and analysing geospatial data. Data collection is a core process of geomatics which usually adopt precise equipment to measure geospatial data. With the development of technology, a smartphone in this present era is not simply for communication; several low cost measurement devices such as Global Positioning System (GPS), gyro and camera are assembled in a smartphone. Although the devices assembled in a smartphone could not meet the needs of accuracy requirement for many geomatics applications, millions of mobile applications (Apps) can be downloaded and installed from Google Play and Apple Store freely, and a variety of sensors can be chosen for user. Considering that the popularity and convenience of a smartphone, and assuming that the accuracy of those collected data is acceptable for learning purposes, it is expected that a smartphone can be employed in geomatics for hand-on education. For example, Vespucci OSM Editor is an App to edit the OpenStreetMap on Android. The user may have the hand-on experience on GPS positioning, web services and mapping via Vespucci OSM Editor. The aim of this paper is to collect and analyze different Apps for geomatics education. The Apps are classified into four categories, namely, surveying, remote sensing, GPS and Geographic Information System (GIS). In this paper, more than 20 free Apps are collected and analysed for different hand-on studies in geomatics education. Finally, all the related Apps are listed on a website for updating.

  13. Consumer behaviour in Apple's App Store

    OpenAIRE

    Ayalew, Romel

    2011-01-01

    Mobile applications stores such as Apple’s App Store and Google’s Android Market revolutionized the distribution of applications for mobile devices. However, with thousands of application submissions, limited testing resources and the lack of an effective filtering mechanism, application stores suffer from information overload and a risk of releasing poor quality applications that could create confusion to consumers and may seriously affect the App store markets. Thus concern has been raised ...

  14. Using apps for learning across the curriculum a literacy-based framework and guide

    CERN Document Server

    Beach, Richard

    2014-01-01

    How can apps be used to foster learning with literacy across the curriculum? This book offers both a theoretical framework for considering app affordances and practical ways to use apps to build students' disciplinary literacies and to foster a wide range of literacy practices.Using Apps for Learning Across the Curriculumpresents a wide range of different apps and also assesses their value features methods for and apps related to planning instruction and assessing student learning identifies favorite apps whose affordances are most likely to foster certain disciplinary literacies includes reso

  15. Clinicians' perspective on an app for patient self-monitoring in eating disorder treatment

    DEFF Research Database (Denmark)

    Lindgreen, Pil; Clausen, Loa; Lomborg, Kirsten

    2018-01-01

    Objective: The Recovery Record smartphone app is a self-monitoring tool for individuals recovering from eating disorders. Oppositely to traditional pen-and-paper meal diaries, the app allows for in-app patient–clinician linkage enabling clinicians to access patient app data anytime. The aim of our...... with challenges associated with the app, for example, an added work load and potential harm to the patient–clinician collaboration. Thus, prior to adopting the app, we encourage clinicians and managements to discuss the objectives, advantages and disadvantages of adopting the app, and outline specific guidelines...

  16. Mobile Apps for Teaching Intubation: Scoping Review and Critical Analysis in eLearning.

    Science.gov (United States)

    Matava, Clyde; Leo, Anne-Marie; Alam, Fahad

    2017-09-05

    Airway management is a core skill in anesthesia ensuring adequate oxygenation and delivery of inhalational agents for the patient. The goals of this study were to critically evaluate the quality of airway management apps and target revised Bloom's Taxonomy cognitive levels. An electronic search using the keywords "airway" and "airway management" was conducted in May 2015 across the App Store, Google Play, BlackBerry World, and Windows Store. Apps were included in the study if their content was related to airway management. App content and characteristics were extracted into a standard form and evaluated. A total of 65 apps met the inclusion criteria, and 73% (47/65) of apps were developed by companies or industry. Anesthesiology trainees were the target audience in only 20% (13/65) of apps. Bag mask ventilation and laryngeal mask airways were covered in only 20% (13/65) of apps. Only 2 apps were supported in the scientific literature. For Bloom's Taxonomy, 37% (24/65) of apps targeted knowledge, 5% (3/65) comprehension, 22% (14/65) application, 28% (18/65) analysis, 9% (6/65) evaluation, and 0% synthesis. Multivariate analysis identified cost of apps, size of apps (MB), and apps targeting trainees and paramedics to be associated with higher levels of cognitive processing of revised Bloom's Taxonomy. Apps developed for teaching intubation target lower levels of cognitive processing and are largely not validated by research. Cost, app size, and targeted user are associated with higher cognitive levels. Trainees and all users should be aware of the paucity of the published evidence behind the efficacy of some of these apps. ©Clyde Matava, Anne-Marie Leo, Fahad Alam. Originally published in JMIR Medical Education (http://mededu.jmir.org), 05.09.2017.

  17. How Do Infant Feeding Apps in China Measure Up? A Content Quality Assessment.

    Science.gov (United States)

    Zhao, Jing; Freeman, Becky; Li, Mu

    2017-12-06

    Globally, with the popularization of mobile phones, the number of health-related mobile phone apps has skyrocketed to 259,000 in 2016. In the digital era, people are accessing health information through their fingertips. In China, there are several apps that claim to provide infant feeding and nutrition guidance. However, the quality of information in those apps has not been extensively assessed. We aimed to assess the quality of Chinese infant feeding apps using comprehensive quality assessment criteria and to explore Chinese mothers' perceptions on apps' quality and usability. We searched for free-to-download Chinese infant feeding apps in the iTunes and Android App Stores. We conducted a comprehensive assessment of the accountability, scientific basis, accuracy of information relevant to infant feeding, advertising policy, and functionality and carried out a preliminary screening of infant formula advertisements in the apps. In addition, we also conducted exploratory qualitative research through semistructured interviews with Chinese mothers in Shanghai to elicit their views about the quality of apps. A total of 4925 apps were screened, and 26 apps that met the selection criteria were evaluated. All 26 apps were developed by commercial entities, and the majority of them were rated poorly. The highest total score was 62.2 (out of approximately 100) and the lowest was 16.7. In the four quality domains assessed, none of them fulfilled all the accountability criteria. Three out of 26 apps provided information covering the three practices from the World Health Organization's infant feeding recommendations. Only one app described its advertising policy in its terms of usage. The most common app functionality was a built-in social forum (19/26). Provision of a website link was the least common functionality (2/26). A total of 20 out of 26 apps promoted infant formula banner advertisements on their homepages. In addition, 12 apps included both e-commerce stores and

  18. Behavior change techniques in top-ranked mobile apps for physical activity.

    Science.gov (United States)

    Conroy, David E; Yang, Chih-Hsiang; Maher, Jaclyn P

    2014-06-01

    Mobile applications (apps) have potential for helping people increase their physical activity, but little is known about the behavior change techniques marketed in these apps. The aim of this study was to characterize the behavior change techniques represented in online descriptions of top-ranked apps for physical activity. Top-ranked apps (n=167) were identified on August 28, 2013, and coded using the Coventry, Aberdeen and London-Revised (CALO-RE) taxonomy of behavior change techniques during the following month. Analyses were conducted during 2013. Most descriptions of apps incorporated fewer than four behavior change techniques. The most common techniques involved providing instruction on how to perform exercises, modeling how to perform exercises, providing feedback on performance, goal-setting for physical activity, and planning social support/change. A latent class analysis revealed the existence of two types of apps, educational and motivational, based on their configurations of behavior change techniques. Behavior change techniques are not widely marketed in contemporary physical activity apps. Based on the available descriptions and functions of the observed techniques in contemporary health behavior theories, people may need multiple apps to initiate and maintain behavior change. This audit provides a starting point for scientists, developers, clinicians, and consumers to evaluate and enhance apps in this market. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Developing a Mobile App for Prevention and Treatment of Pressure Injuries.

    Science.gov (United States)

    Salomé, Geraldo Magela; Ferreira, Lydia Masako

    2018-02-01

    This descriptive study describes the planning and development of a mobile application (app) for prevention and treatment of pressure injuries for use by providers in a university research center. The app delineates risk factors for pressure injury development, provides an evaluation of the wound, recommends wound cleansing procedures, performs pressure injury staging, and recommends treatment interventions. A mobile app was developed using a contextualized instructional design, which involves a constructivist proposal and planning, developing, and applying specific didactic situations, thus incorporating mechanisms that favor contextualization. A literature search was conducted to identify relevant studies for the construction of the mobile app. The development process involved the selection of app tools, definition of the navigation structure, and planning of the environment configuration. The environment for downloading the app software on the Internet and installing it on the mobile device was created. The literature search yielded 18 articles, 2 books, and 1 master's degree thesis. A mobile app was created with an easy-to-use graphic interface. The app stores the patient's demographic characteristics and provides an evaluation of his/her wound, a list of risk factors for pressure injury development, wound cleansing procedures, and treatment interventions. The developed app may be useful in clinical practice, helping to prevent pressure injuries and promote select nursing interventions for the treatment of patients with pressure injury.

  20. Cleaning up That Mess: A Framework for Classifying Educational Apps

    Science.gov (United States)

    Cherner, Todd; Dix , Judy; Lee, Corey

    2014-01-01

    As tablet technologies continue to evolve, the emergence of educational applications (apps) is impacting the work of teacher educators. Beyond online lists of best apps for education and recommendations from colleagues, teacher educators have few resources available to support their teaching of how to select educational apps. In response, this…

  1. Educational Behavior Apps and Wearable Devices: Current Research and Prospects

    Science.gov (United States)

    Lowe, Heather

    2016-01-01

    Dartmouth and MIT have developed educational behavior apps and wearable devices that collect contiguous streams of data from student users. Given the consent of the user, the app collects information about a student's physical activity, sleep patterns, and location to form conjectures about social and academic behavior. These apps have the…

  2. App use, physical activity and healthy lifestyle: a cross sectional study.

    Science.gov (United States)

    Dallinga, Joan Martine; Mennes, Matthijs; Alpay, Laurence; Bijwaard, Harmen; Baart de la Faille-Deutekom, Marije

    2015-08-28

    Physical inactivity is a growing public health concern. Use of mobile applications (apps) may be a powerful tool to encourage physical activity and a healthy lifestyle. For instance, apps may be used in the preparation of a running event. However, there is little evidence for the relationship between app use and change in physical activity and health in recreational runners. The aim of this study was to determine the relationship between the use of apps and changes in physical activity, health and lifestyle behaviour, and self-image of short and long distance runners. A cross sectional study was designed. A random selection of 15,000 runners (of 54,000 participants) of a 16 and 6.4 km recreational run (Dam tot Damloop) in the Netherlands was invited to participate in an online survey two days after the run. Anthropometrics, app use, activity level, preparation for running event, running physical activity (RPA), health and lifestyle, and self-image were addressed. A chi-squared test was conducted to analyse differences between app users and non-app users in baseline characteristics as well as in RPA, healthy lifestyle and perceived health. In addition, a multivariate logistic regression analysis was performed to determine if app use could predict RPA, perceived health and lifestyle, and self-image. Of the 15,000 invited runners, 28% responded. For both distances, app use was positively related to RPA and feeling healthier (p motivating others to participate in running, and losing weight (p < 0.01). Furthermore, for 16 km runners app use was positively related to eating healthier, feeling more energetic and reporting a higher chance to maintain sport behaviour (p < 0.05). These results suggest that use of mobile apps has a beneficial role in the preparation of a running event, as it promotes health and physical activity. Further research is now needed to determine a causal relationship between app use and physical and health related behaviour.

  3. Mental Health Mobile Apps for Preadolescents and Adolescents: A Systematic Review.

    Science.gov (United States)

    Grist, Rebecca; Porter, Joanna; Stallard, Paul

    2017-05-25

    There are an increasing number of mobile apps available for adolescents with mental health problems and an increasing interest in assimilating mobile health (mHealth) into mental health services. Despite the growing number of apps available, the evidence base for their efficacy is unclear. This review aimed to systematically appraise the available research evidence on the efficacy and acceptability of mobile apps for mental health in children and adolescents younger than 18 years. The following were systematically searched for relevant publications between January 2008 and July 2016: APA PsychNet, ACM Digital Library, Cochrane Library, Community Care Inform-Children, EMBASE, Google Scholar, PubMed, Scopus, Social Policy and Practice, Web of Science, Journal of Medical Internet Research, Cyberpsychology, Behavior and Social Networking, and OpenGrey. Abstracts were included if they described mental health apps (targeting depression, bipolar disorder, anxiety disorders, self-harm, suicide prevention, conduct disorder, eating disorders and body image issues, schizophrenia, psychosis, and insomnia) for mobile devices and for use by adolescents younger than 18 years. A total of 24 publications met the inclusion criteria. These described 15 apps, two of which were available to download. Two small randomized trials and one case study failed to demonstrate a significant effect of three apps on intended mental health outcomes. Articles that analyzed the content of six apps for children and adolescents that were available to download established that none had undergone any research evaluation. Feasibility outcomes suggest acceptability of apps was good and app usage was moderate. Overall, there is currently insufficient research evidence to support the effectiveness of apps for children, preadolescents, and adolescents with mental health problems. Given the number and pace at which mHealth apps are being released on app stores, methodologically robust research studies

  4. Pro-inflammatory capacity of classically activated monocytes relates positively to muscle mass and strength.

    Science.gov (United States)

    Beenakker, Karel G M; Westendorp, Rudi G J; de Craen, Anton J M; Slagboom, Pieternella E; van Heemst, Diana; Maier, Andrea B

    2013-08-01

    In mice, monocytes that exhibit a pro-inflammatory profile enter muscle tissue after muscle injury and are crucial for clearance of necrotic tissue and stimulation of muscle progenitor cell proliferation and differentiation. The aim of this study was to test if pro-inflammatory capacity of classically activated (M1) monocytes relates to muscle mass and strength in humans. This study included 191 male and 195 female subjects (mean age 64.2 years (SD 6.4) and 61.9 ± 6.4, respectively) of the Leiden Longevity Study. Pro-inflammatory capacity of M1 monocytes was assessed by ex vivo stimulation of whole blood with Toll-like receptor (TLR) 4 agonist lipopolysaccharide (LPS) and TLR-2/1 agonist tripalmitoyl-S-glycerylcysteine (Pam₃Cys-SK₄), both M1 phenotype activators. Cytokines that stimulate M1 monocyte response (IFN-γ and GM-CSF) as well as cytokines that are secreted by M1 monocytes (IL-6, TNF-α, IL-12, and IL-1β) were measured. Analyses were adjusted for age, height, and body fat mass. Upon stimulation with LPS, the cytokine production capacity of INF-γ, GM-CSF, and TNF-α was significantly positively associated with lean body mass, appendicular lean mass and handgrip strength in men, but not in women. Upon stimulation with Pam₃Cys-SK₄, IL-6; TNF-α; and Il-1β were significantly positively associated with lean body mass and appendicular lean in women, but not in men. Taken together, this study shows that higher pro-inflammatory capacity of M1 monocytes upon stimulation is associated with muscle characteristics and sex dependent. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

  5. Stability of the Filter Equation for a Time-Dependent Signal on Rd

    International Nuclear Information System (INIS)

    Stannat, Wilhelm

    2005-01-01

    Stability of the pathwise filter equation for a time-dependent signal process induced by a d-dimensional stochastic differential equation and a linear observation is studied, using a variational approach. A lower bound for the rate of stability is identified in terms of the mass-gap of a parabolic ground state transform associated with the generator of the signal process and the square of the observation. The lower bound can be easily calculated a priori and provides hints on how precisely to measure the signal in order to reach a certain rate of stability. Ergodicity of the signal process is not needed

  6. Will HTML5 Kill the Native App?

    Science.gov (United States)

    Fredette, Michelle

    2013-01-01

    For colleges and universities today, the question is no longer whether to develop a campus app or not. Instead, the debate has shifted to the best--and most cost-efficient--way to make campus applications accessible to the myriad devices and operating systems out there. Schools have a few options: They can develop multiple native app versions;…

  7. Global Outreach of a Locally-Developed Mobile Phone App for Undergraduate Psychiatry Education.

    Science.gov (United States)

    Zhang, Melvyn Wb; Cheok, Christopher Cs; Ho, Roger Cm

    2015-06-08

    Over the past decade, there have been massive developments in both Web-based and mobile phone technologies. Mobile phones are well accepted by students, trainees, and doctors. A review of the current literature has identified the following specialties that have used mobile phones in education: pediatrics, ophthalmology, nephrology, plastic surgery, orthopedics, pharmacology, and urology. However, to date, there are no published papers examining the application of the latest mobile phone technologies for psychiatry education internationally. The main objectives of this study are (1) to determine the feasibility and receptiveness of a locally-developed psychiatry mobile phone app and user perspectives (both quantitative and qualitative) towards it, and (2) to determine the receptiveness of a locally-developed app for psychiatry education internationally. A Web-based app that contained textbook contents, videos, and quizzes was developed using HTML5 technologies in 2012. Native apps were subsequently developed in 2013. Information about the apps was disseminated locally to Singaporean medical students, but the respective native apps were made available on the app stores. A user perspective survey was conducted locally to determine student's perception of the app. From the inception of the app until the time of preparation of this manuscript, there have been a cumulative total of 28,500 unique visits of the responsive HTML5 Web-based mobile phone app. There have been a cumulative total of 2200 downloads of the Mastering Psychiatry app from the Apple app store and 7000 downloads of the same app from the Android app store. The initial user perspective survey conducted locally highlighted that approximately a total of 95.2% (177/186) of students felt that having a psychiatry mobile phone app was deemed to be useful. Further chi-squared analysis demonstrated that there was a significant difference between males and females in their perception of having textbook contents in

  8. User Preferences for Content, Features, and Style for an App to Reduce Harmful Drinking in Young Adults: Analysis of User Feedback in App Stores and Focus Group Interviews.

    Science.gov (United States)

    Milward, Joanna; Khadjesari, Zarnie; Fincham-Campbell, Stephanie; Deluca, Paolo; Watson, Rod; Drummond, Colin

    2016-05-24

    Electronic screening and brief intervention (eSBI) is effective in reducing weekly alcohol consumption when delivered by a computer. Mobile phone apps demonstrate promise in delivering eSBI; however, few have been designed with an evidence-based and user-informed approach. This study aims to explore from a user perspective, preferences for content, appearance, and operational features to inform the design of a mobile phone app for reducing quantity and frequency of drinking in young adults engaged in harmful drinking (18-30 year olds). Phase 1 included a review of user reviews of available mobile phone apps that support a reduction in alcohol consumption. Apps were identified on iTunes and Google Play and were categorized into alcohol reduction support, entertainment, blood alcohol content measurement (BAC), or other. eSBI apps with ≥18 user reviews were subject to a content analysis, which coded praise, criticism, and recommendations for app content, functionality, and esthetics. Phase 2 included four focus groups with young adults drinking at harmful levels and residing in South London to explore their views on existing eSBI apps and preferences for future content, functionality, and appearance. Detailed thematic analysis of the data was undertaken. In Phase 1, of the 1584 apps extracted, 201 were categorized as alcohol reduction, 154 as BAC calculators, 509 as entertainment, and 720 as other. We classified 32 apps as eSBI apps. Four apps had ≥18 user reviews: Change for Life Drinks Tracker, Drinksmeter, Drinkaware, and Alcohol Units Calculator. The highest proportion of content praises were for information and feedback provided in the apps (12/27, 44%), followed by praise for the monitoring features (5/27, 19%). Many (8/12, 67%) criticisms were for the drinking diary; all of these were related to difficulty entering drinks. Over half (18/32, 56%) of functionality criticisms were descriptions of software bugs, and over half of those (10/18, 56%) were for app

  9. TControl: A mobile app to follow up tobacco-quitting patients.

    Science.gov (United States)

    Pifarré, Marc; Carrera, Adrián; Vilaplana, Jordi; Cuadrado, Josep; Solsona, Sara; Abella, Francesc; Solsona, Francesc; Alves, Rui

    2017-04-01

    Tobacco smoking is a major risk factor for a wide range of respiratory and circulatory diseases in active and passive smokers. Well-designed campaigns are raising awareness to the problem and an increasing number of smokers seeks medical assistance to quit their habit. In this context, there is the need to develop mHealth Apps that assist and manage large smoke quitting programs in efficient and economic ways. Our main objective is to develop an efficient and free mHealth app that facilitates the management of, and assistance to, people who want to quit smoking. As secondary objectives, our research also aims at estimating the economic effect of deploying that App in the public health system. Using JAVA and XML we develop and deploy a new free mHealth App for Android, called TControl (Tobacco-quitting Control). We deploy the App at the Tobacco Unit of the Santa Maria Hospital in Lleida and determine its stability by following the crashes of the App. We also use a survey to test usability of the app and differences in aptitude for using the App in a sample of 31 patients. Finally, we use mathematical models to estimate the economic effect of deploying TControl in the Catalan public health system. TControl keeps track of the smoke-quitting users, tracking their status, interpreting it, and offering advice and psychological support messages. The App also provides a bidirectional communication channel between patients and clinicians via mobile text messages. Additionally, registered patients have the option to interchange experiences with each other by chat. The App was found to be stable and to have high performances during startup and message sending. Our results suggest that age and gender have no statistically significant effect on patient aptitude for using TControl. Finally, we estimate that TControl could reduce costs for the Catalan public health system (CPHS) by up to € 400M in 10 years. TControl is a stable and well behaved App, typically operating near

  10. Medical applications: a database and characterization of apps in Apple iOS and Android platforms.

    Science.gov (United States)

    Seabrook, Heather J; Stromer, Julie N; Shevkenek, Cole; Bharwani, Aleem; de Grood, Jill; Ghali, William A

    2014-08-27

    Medical applications (apps) for smart phones and tablet computers are growing in number and are commonly used in healthcare. In this context, there is a need for a diverse community of app users, medical researchers, and app developers to better understand the app landscape. In mid-2012, we undertook an environmental scan and classification of the medical app landscape in the two dominant platforms by searching the medical category of the Apple iTunes and Google Play app download sites. We identified target audiences, functions, costs and content themes using app descriptions and captured these data in a database. We only included apps released or updated between October 1, 2011 and May 31, 2012, with a primary "medical" app store categorization, in English, that contained health or medical content. Our sample of Android apps was limited to the most popular apps in the medical category. Our final sample of Apple iOS (n = 4561) and Android (n = 293) apps illustrate a diverse medical app landscape. The proportion of Apple iOS apps for the public (35%) and for physicians (36%) is similar. Few Apple iOS apps specifically target nurses (3%). Within the Android apps, those targeting the public dominated in our sample (51%). The distribution of app functions is similar in both platforms with reference being the most common function. Most app functions and content themes vary considerably by target audience. Social media apps are more common for patients and the public, while conference apps target physicians. We characterized existing medical apps and illustrated their diversity in terms of target audience, main functions, cost and healthcare topic. The resulting app database is a resource for app users, app developers and health informatics researchers.

  11. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

    Science.gov (United States)

    Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

    2017-01-01

    Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. . Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. How Do Infant Feeding Apps in China Measure Up? A Content Quality Assessment

    Science.gov (United States)

    Freeman, Becky; Li, Mu

    2017-01-01

    Background Globally, with the popularization of mobile phones, the number of health-related mobile phone apps has skyrocketed to 259,000 in 2016. In the digital era, people are accessing health information through their fingertips. In China, there are several apps that claim to provide infant feeding and nutrition guidance. However, the quality of information in those apps has not been extensively assessed. Objective We aimed to assess the quality of Chinese infant feeding apps using comprehensive quality assessment criteria and to explore Chinese mothers’ perceptions on apps’ quality and usability. Methods We searched for free-to-download Chinese infant feeding apps in the iTunes and Android App Stores. We conducted a comprehensive assessment of the accountability, scientific basis, accuracy of information relevant to infant feeding, advertising policy, and functionality and carried out a preliminary screening of infant formula advertisements in the apps. In addition, we also conducted exploratory qualitative research through semistructured interviews with Chinese mothers in Shanghai to elicit their views about the quality of apps. Results A total of 4925 apps were screened, and 26 apps that met the selection criteria were evaluated. All 26 apps were developed by commercial entities, and the majority of them were rated poorly. The highest total score was 62.2 (out of approximately 100) and the lowest was 16.7. In the four quality domains assessed, none of them fulfilled all the accountability criteria. Three out of 26 apps provided information covering the three practices from the World Health Organization’s infant feeding recommendations. Only one app described its advertising policy in its terms of usage. The most common app functionality was a built-in social forum (19/26). Provision of a website link was the least common functionality (2/26). A total of 20 out of 26 apps promoted infant formula banner advertisements on their homepages. In addition, 12

  13. E-Books and E-Book Apps: Considerations for Beginning Readers

    Science.gov (United States)

    Bates, Celeste C.; Klein, Adria; Schubert, Barbara; McGee, Lea; Anderson, Nancy; Dorn, Linda; McClure, Erin; Ross, Rachael Huber

    2017-01-01

    This article highlights considerations for teachers when selecting and using e-books and e-book applications (apps) with beginning readers during guided and independent reading. A framework for examining e-books and e-book apps is suggested, and several apps and related digital features are described. The article also includes an overview of…

  14. Mobile medical and health apps: state of the art, concerns, regulatory control and certification

    Science.gov (United States)

    Boulos, Maged N. Kamel; Brewer, Ann C.; Karimkhani, Chante; Buller, David B.; Dellavalle, Robert P.

    2014-01-01

    This paper examines the state of the art in mobile clinical and health-related apps. A 2012 estimate puts the number of health-related apps at no fewer than 40,000, as healthcare professionals and consumers continue to express concerns about the quality of many apps, calling for some form of app regulatory control or certification to be put in place. We describe the range of apps on offer as of 2013, and then present a brief survey of evaluation studies of medical and health-related apps that have been conducted to date, covering a range of clinical disciplines and topics. Our survey includes studies that highlighted risks, negative issues and worrying deficiencies in existing apps. We discuss the concept of ‘apps as a medical device’ and the relevant regulatory controls that apply in USA and Europe, offering examples of apps that have been formally approved using these mechanisms. We describe the online Health Apps Library run by the National Health Service in England and the calls for a vetted medical and health app store. We discuss the ingredients for successful apps beyond the rather narrow definition of ‘apps as a medical device’. These ingredients cover app content quality, usability, the need to match apps to consumers’ general and health literacy levels, device connectivity standards (for apps that connect to glucometers, blood pressure monitors, etc.), as well as app security and user privacy. ‘Happtique Health App Certification Program’ (HACP), a voluntary app certification scheme, successfully captures most of these desiderata, but is solely focused on apps targeting the US market. HACP, while very welcome, is in ways reminiscent of the early days of the Web, when many “similar” quality benchmarking tools and codes of conduct for information publishers were proposed to appraise and rate online medical and health information. It is probably impossible to rate and police every app on offer today, much like in those early days of the Web

  15. Developing multiplatform apps : using hybrid solutions

    OpenAIRE

    Kristbergsson, Ellert

    2015-01-01

    The aim of this thesis is to describe the process of developing multiplatform apps for mobile phones by discussing and comparing the different methods of developing apps for all platforms. The purpose is to ease decision making of smaller companies that are starting to develop their own product for smartphones. The paper analyses tools based on the Cordova framework and the Qt framework. The difference between how the frameworks deliver the code to the machine, Cordova compiles JavaScript...

  16. Detecting android malicious apps and categorizing benign apps with ensemble of classifiers

    KAUST Repository

    Wang, Wei; Li, Yuanyuan; Wang, Xing; Liu, Jiqiang; Zhang, Xiangliang

    2017-01-01

    Android platform has dominated the markets of smart mobile devices in recent years. The number of Android applications (apps) has seen a massive surge. Unsurprisingly, Android platform has also become the primary target of attackers. The management

  17. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

    International Nuclear Information System (INIS)

    Fukumoto, Yasunori; Kuki, Kazumasa; Morii, Mariko; Miura, Takahito; Honda, Takuya; Ishibashi, Kenichi; Hasegawa, Hitomi; Kubota, Sho; Ide, Yudai; Yamaguchi, Noritaka; Nakayama, Yuji; Yamaguchi, Naoto

    2014-01-01

    Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint

  18. Calcium-Dependent Protein Kinases in Phytohormone Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Wuwu Xu

    2017-11-01

    Full Text Available Calcium-dependent protein kinases (CPKs/CDPKs are Ca2+-sensors that decode Ca2+ signals into specific physiological responses. Research has reported that CDPKs constitute a large multigene family in various plant species, and play diverse roles in plant growth, development, and stress responses. Although numerous CDPKs have been exhaustively studied, and many of them have been found to be involved in plant hormone biosynthesis and response mechanisms, a comprehensive overview of the manner in which CDPKs participate in phytohormone signaling pathways, regulating nearly all aspects of plant growth, has not yet been undertaken. In this article, we reviewed the structure of CDPKs and the mechanism of their subcellular localization. Some CDPKs were elucidated to influence the intracellular localization of their substrates. Since little work has been done on the interaction between CDPKs and cytokinin signaling pathways, or on newly defined phytohormones such as brassinosteroids, strigolactones and salicylic acid, this paper mainly focused on discussing the integral associations between CDPKs and five plant hormones: auxins, gibberellins, ethylene, jasmonates, and abscisic acid. A perspective on future work is provided at the end.

  19. Dynamic trafficking of STAT5 depends on an unconventional nuclear localization signal

    Science.gov (United States)

    Shin, Ha Youn; Reich, Nancy C.

    2013-01-01

    Summary Signal transducer and activator of transcription 5 (STAT5) is crucial for physiological processes that include hematopoiesis, liver metabolism and mammary gland development. However, aberrant continual activity of STAT5 has been causally linked to human leukemias and solid tumor formation. As a regulated transcription factor, precise cellular localization of STAT5 is essential. Conventional nuclear localization signals consist of short stretches of basic amino acids. In this study, we provide evidence that STAT5 nuclear import is dependent on an unconventional nuclear localization signal that functions within the conformation of an extensive coiled-coil domain. Both in vitro binding and in vivo functional assays reveal that STAT5 nuclear import is mediated by the importin-α3/β1 system independently of STAT5 activation by tyrosine phosphorylation. The integrity of the coiled-coil domain is essential for STAT5 transcriptional induction of the β-casein gene following prolactin stimulation as well as its ability to synergize with the glucocorticoid receptor. The glucocorticoid receptor accumulates in the nucleus in response to prolactin and this nuclear import is dependent on STAT5 nuclear import. STAT5 continually shuttles in and out of the nucleus and live cell imaging demonstrates that STAT5 nuclear export is mediated by both chromosome region maintenance 1 (Crm1)-dependent and Crm1-independent pathways. A Crm1-dependent nuclear export signal was identified within the STAT5 N-terminus. These findings provide insight into the fundamental mechanisms that regulate STAT5 nuclear trafficking and cooperation with the glucocorticoid receptor and provide a basis for clinical intervention of STAT5 function in disease. PMID:23704351

  20. Developing A mobile App for the Rehabilitation of Ankle Sprains

    Directory of Open Access Journals (Sweden)

    Suzanne McDonough

    2015-10-01

    Full Text Available Background: Musculoskeletal injuries are common and costly. Ankle sprains are one of the most common such injuries, carrying significant risk of persistent disabling symptoms. Rehabilitation has been shown to be more effective than standard conservative approaches for musculoskeletal injuries. The use of a mobile app to present rehabilitation guidance may offer a more accessible, engaging and effective solution to ankle sprain rehabilitation. Several existing apps target the prevention and rehabilitation of ankle sprains, however evaluation details are limited. Aim: To develop a mobile phone app that provides interactive, personalised and tailored rehabilitation for people following ankle sprains. Method(s: In order to build requirements and produce content for the app (entitled ReApp 2, relevant literature was reviewed and behaviour change strategies identified from the Behaviour Change Taxonomy (BCT developed by Michie et al (2013. A flexible and team orientated methodology called Agile was used to refine the technical specification and implemented software using feedback from technical experts (n=5 and clinicians (n=6. Technical experts consisted of participants with at least five years of experience in ICT or a related discipline. These technical experts completed the System Usability Scale (SUS to rate the usability of the software. The SUS is a widely used usability survey, which provides a single overall score for each participant. These scores can be used to provide comparison between user groups and other software. The clinicians consisted of five physiotherapists and one sport and exercise consultant, all of whom had at least five years of experience in providing rehabilitation treatment for ankle injuries. These clinicians also completed a questionnaire and gave qualitative feedback on the clinical appropriateness of the app. Results: The identified BCTs were prioritised according to clinical importance, technical complexity and time