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Sample records for challenge induces ifng

  1. Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

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    Nilesh Dharajiya

    Full Text Available According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1, Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1 Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2 Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation.

  2. Selective inhibition of IFNG-induced autophagy by Mir155- and Mir31-responsive WNT5A and SHH signaling.

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    Holla, Sahana; Kurowska-Stolarska, Mariola; Bayry, Jagadeesh; Balaji, Kithiganahalli Narayanaswamy

    2014-02-01

    Autophagy is one of the major immune mechanisms engaged to clear intracellular infectious agents. However, several pathogens have evolved strategies to evade autophagy. Here, we demonstrated that Mycobacteria, Shigella, and Listeria but not Klebsiella, Staphylococcus, and Escherichia inhibit IFNG-induced autophagy in macrophages by evoking selective and robust activation of WNT and SHH pathways via MTOR. Utilization of gain- or loss-of-function analyses as well as mir155-null macrophages emphasized the role of MTOR-responsive epigenetic modifications in the induction of Mir155 and Mir31. Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. Altogether, these results established a role for new host factors and inhibitory mechanisms employed by the pathogens to limit autophagy, which could be targeted for therapeutic interventions.

  3. IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

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    Sampaio Elizabeth P

    2007-04-01

    Full Text Available Abstract Background Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL and also the influence of this SNP in the secretion of IFN-γ in vitro. Methods Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR. Leishmania-induced IFN-γ production on peripheral blood mononuclear cell (PBMC culture supernatants was assessed by ELISA. Results There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers. Conclusion Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.

  4. Distinct Methylation of IFNG in the Gut

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    Gonsky, Rivkah; Deem, Richard L; Targan, Stephan R.

    2009-01-01

    Mucosal expression of proinflammatory cytokines plays a pivotal role in inflammatory bowel disease (IBD) pathogenesis. Epigenetic remodeling of chromatin via DNA methylation regulates gene expression. In this study, IFNG DNA methylation was analyzed within the mucosal compartment in both normal and IBD populations and compared to its peripheral counterparts. Overall IFNG methylation (across eight CpG sites) was significantly lower in lamina propria (LP) T cells compared to peripheral blood (P...

  5. Identification of biomarkers of response to IFNg during endotoxin tolerance: application to septic shock.

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    Florence Allantaz-Frager

    Full Text Available The rapid development in septic patients of features of marked immunosuppression associated with increased risk of nosocomial infections and mortality represents the rational for the initiation of immune targeted treatments in sepsis. However, as there is no clinical sign of immune dysfunctions, the current challenge is to develop biomarkers that will help clinicians identify the patients that would benefit from immunotherapy and monitor its efficacy. Using an in vitro model of endotoxin tolerance (ET, a pivotal feature of sepsis-induced immunosuppression in monocytes, we identified using gene expression profiling by microarray a panel of transcripts associated with the development of ET which expression was restored after immunostimulation with interferon-gamma (IFN-γ. These results were confirmed by qRT-PCR. Importantly, this short-list of markers was further evaluated in patients. Of these transcripts, six (TNFAIP6, FCN1, CXCL10, GBP1, CXCL5 and PID1 were differentially expressed in septic patients' blood compared to healthy blood upon ex vivo LPS stimulation and were restored by IFN-γ. In this study, by combining a microarray approach in an in vitro model and a validation in clinical samples, we identified a panel of six new transcripts that could be used for the identification of septic patients eligible for IFNg therapy. Along with the previously identified markers TNFa, IL10 and HLA-DRA, the potential value of these markers should now be evaluated in a larger cohort of patients. Upon favorable results, they could serve as stratification tools prior to immunostimulatory treatment and to monitor drug efficacy.

  6. Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi.

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    Guilmot, Aline; Bosse, Julie; Carlier, Yves; Truyens, Carine

    2013-01-01

    We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8(+) T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the ability of the parasite to trigger IFN-g synthesis by NK cells in vitro. We here extended our knowledge on NK cell activation by the parasite. We compared the ability of T. cruzi to activate cord blood and adult NK cells from healthy individuals. Twenty-four hours co-culture of cord blood mononuclear cells with T. cruzi trypomastigotes and IL-15 induced high accumulation of IFN-g transcripts and IFN-g release. TNF-a, but not IL-10, was also produced. This was associated with up-regulation of CD69 and CD54, and down-regulation of CD62L on NK cells. The CD56(bright) NK cell subset was the major IFN-g responding subset (up to 70% IFN-g-positive cells), while CD56(dim) NK cells produced IFN-g to a lesser extent. The response points to a synergy between parasites and IL-15. The neonatal response, observed in all newborns, remained however slightly inferior to that of adults. Activation of IL-15-sensitized cord blood NK cells by the parasite required contacts with live/intact parasites. In addition, it depended on the engagement of TLR-2 and 4 and involved IL-12 and cross-talk with monocytes but not with myeloid dendritic cells, as shown by the use of neutralizing antibodies and cell depletion. This work highlights the ability of T. cruzi to trigger a robust IFN-g response by IL-15-sensitized human neonatal NK cells and the important role of monocytes in it, which might perhaps partially compensate for the neonatal defects of DCs. It suggests that monocyte- and IL-12- dependent IFN-g release by NK cells is a potentially important innate immune response pathway allowing T. cruzi to favour a type 1 immune response in neonates.

  7. Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi.

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    Aline Guilmot

    Full Text Available We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8(+ T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the ability of the parasite to trigger IFN-g synthesis by NK cells in vitro. We here extended our knowledge on NK cell activation by the parasite. We compared the ability of T. cruzi to activate cord blood and adult NK cells from healthy individuals. Twenty-four hours co-culture of cord blood mononuclear cells with T. cruzi trypomastigotes and IL-15 induced high accumulation of IFN-g transcripts and IFN-g release. TNF-a, but not IL-10, was also produced. This was associated with up-regulation of CD69 and CD54, and down-regulation of CD62L on NK cells. The CD56(bright NK cell subset was the major IFN-g responding subset (up to 70% IFN-g-positive cells, while CD56(dim NK cells produced IFN-g to a lesser extent. The response points to a synergy between parasites and IL-15. The neonatal response, observed in all newborns, remained however slightly inferior to that of adults. Activation of IL-15-sensitized cord blood NK cells by the parasite required contacts with live/intact parasites. In addition, it depended on the engagement of TLR-2 and 4 and involved IL-12 and cross-talk with monocytes but not with myeloid dendritic cells, as shown by the use of neutralizing antibodies and cell depletion. This work highlights the ability of T. cruzi to trigger a robust IFN-g response by IL-15-sensitized human neonatal NK cells and the important role of monocytes in it, which might perhaps partially compensate for the neonatal defects of DCs. It suggests that monocyte- and IL-12- dependent IFN-g release by NK cells is a potentially important innate immune response pathway allowing T. cruzi to favour a type 1 immune response in neonates.

  8. Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-γ memory in human CD4(+) T lymphocytes.

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    Dong, Jun; Chang, Hyun-Dong; Ivascu, Claudia; Qian, Yu; Rezai, Soheila; Okhrimenko, Anna; Cosmi, Lorenzo; Maggi, Laura; Eckhardt, Florian; Wu, Peihua; Sieper, Joachim; Alexander, Tobias; Annunziato, Francesco; Gossen, Manfred; Li, Jun; Radbruch, Andreas; Thiel, Andreas

    2013-03-01

    Cytokine memory for IFN-γ production by effector/memory Th1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory Th1 cells characterized by stable effector functions, we identified a T-cell-specific methylation pattern at the IFNG promoter and CNS-1 in ex vivo effector/memory Th1 cells, and investigated methylation dynamics of these regions during the development of effector/memory Th1 cells. During Th1 differentiation, demethylation occurred at both the promoter and CNS-1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN-γ capture assay, we found early IFN-γ-producing cells from 2-day differentiating cultures acquired "permissive" levels of demethylation and developed into effector/memory Th1 cells undergoing progressive demethylation at the IFNG promoter and CNS-1 when induced by IL-12. Methylation levels of these regions in effector/memory Th1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN-γ-producers, coincident with recruitment of effector/memory Th1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL-12 signaling potentiates the stable functional IFN-γ memory in effector/memory Th1 cells characterized by hypomethylation at the IFNG promoter and CNS-1.

  9. La proteína asociada a SLAM (SAP regula la expresión de IFN-g en lepra The SLAM-associated protein (SAP regulates IFN-g expression in leprosy

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    María F. Quiroga

    2004-10-01

    Full Text Available La inmunidad protectora contra Mycobacterium leprae requiere IFN-g. Los pacientes con lepra tuberculoide producen localmente citoquinas Th1, mientras que los pacientes lepromatosos producen citoquinas Th2. La molécula linfocitaria activadora de señales (SLAM y la proteína asociada a SLAM (SAP participan en la diferenciación celular que conduce a producción de patrones específicos de citoquinas. A fin de investigar la vía SLAM/SAP en la infección por M. leprae, determinamos expresión de ARN mensajero (ARNm de SAP, IFN-g y SLAM en pacientes con lepra. Observamos que la expresión de SLAM correlacionó en forma directa con la expresión de IFN-g, mientras que la expresión de SAP correlacionó inversamente con la expresión de ambas proteínas. Así, nuestros resultados indican que SAP interferiría con las respuestas de citoquinas Th1 mientras que SLAM contribuiría con la respuesta Th1 en lepra, señalando a la vía SLAM/SAP como potencial blanco modulador de citoquinas en enfermedades con respuestas Th2 disfuncionales.Tuberculoid leprosy patients locally produce Th1 cytokines, while lepromatous patients produce Th2 cytokines. Signaling lymphocytic activation molecule (SLAM and the SLAM-associated protein (SAP participate in the differentiation process that leads to the production of specific patterns of cytokines by activated T cells. To investigate the SLAM/SAP pathway in M. leprae infection, we determined the expression of SAP, IFN-g and SLAM RNA messenger in leprosy patients. We found a direct correlation of SLAM expression with IFN-g expression, whereas the expression of SAP was inversely correlated with the expression of both SLAM and IFN-g. Therefore, our data indicate that SAP might interfere with Th1 cytokine responses while SLAM expression may contribute to Th1 responses in leprosy. This study further suggests that the SLAM/SAP pathway might be a focal point for therapeutic modulation of T cell cytokine responses in diseases

  10. Amiodarone-Induced Thyrotoxic Thyroiditis: A Diagnostic and Therapeutic Challenge

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    Umang Barvalia

    2014-01-01

    Full Text Available Amiodarone is an iodine-based, potent antiarrhythmic drug bearing a structural resemblance to thyroxine (T4. It is known to produce thyroid abnormalities ranging from abnormal thyroid function testing to overt hypothyroidism or hyperthyroidism. These adverse effects may occur in patients with or without preexisting thyroid disease. Amiodarone-induced thyrotoxicosis (AIT is a clinically recognized condition commonly due to iodine-induced excessive synthesis of thyroid, also known as type 1 AIT. In rare instances, AIT is caused by amiodarone-induced inflammation of thyroid tissue, resulting in release of preformed thyroid hormones and a hyperthyroid state, known as type 2 AIT. Distinguishing between the two states is important, as both conditions have different treatment implications; however, a mixed presentation is not uncommon, posing diagnostic and treatment challenges. We describe a case of a patient with amiodarone-induced type 2 hyperthyroidism and review the current literature on the best practices for diagnostic and treatment approaches.

  11. 60 Tear IFN-G is Increased After Sublingual Immunotherapy in Allergic Conjunctivitis Patients and Correlates With Clinical Improvement

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    Aguilar-Velazquez, Gustavo; Santacruz, Concepcion; Hernandez, Pedro M.; Chavez, Raul; Ayala-Balboa, Julio; Estrada-Parra, Sergio; Perez-Tapia, Mayra; Jiménez-Martínez, Maria C.

    2012-01-01

    Background Despite success of sublingual immunotherapy (SLIT) in the treatment of allergy diseases, more research is needed related to ocular allergy. Thus, the aim of this work was to analyze the ocular microenvironment provided by tear cytokines in allergic conjunctivitis (AC) patients treated with SLIT and to correlate tear and serum cytokines with ocular findings. Methods 19 AC-patients were included in this study. AC diagnosis was based on a clinical history and full ophthalmologic examination according to the diagnosis standards of the American Academy of Ophthalmology. Routine immunological studies were performed to corroborate allergic status Negative coproparasitoscopic results were documented. This study was approved by Scientific and Ethics Committees if Institute of Ophthalmology “Conde de la Valenciana,” Mexico City an all subjects gave their informed consent to obtain samples. Tear and serum samples were collected to determine cytokines IL2, IL-4, IL-5, IFN-g, TNF-a, IL-10 by cytometric bead arrays (CBA), following manufacturer's instructions. Results After 6 months of treatment with SLIT we observed significant higher IFN-g concentration, without significant changes in IL2, IL4, IL5, TNFa or IL10. We observed significant clinical improvement since 3 months of treatment and it was maintained until the end of 6 months. Clinical improvement correlated with IFN-g concentration. Conclusions Clinical outcome in AC-patients treated with SLIT could be tear IFN-g dependent.

  12. Thalidomide protects mice against LPS-induced shock

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    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  13. Chronic radiation-induced dermatitis: challenges and solutions

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    Spałek M

    2016-12-01

    Full Text Available Mateusz Spałek Department of Radiotherapy I, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Abstract: Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF. RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and

  14. Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections.

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    Stappers, M H T; Thys, Y; Oosting, M; Plantinga, T S; Ioana, M; Reimnitz, P; Mouton, J W; Netea, M G; Joosten, L A B; Gyssens, I C

    2014-12-01

    Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.

  15. Risk model incorporating donor IL6 and IFNG genotype and gastrointestinal GVHD can discriminate patients at high risk of steroid refractory acute GVHD.

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    Alam, N; Xu, W; Atenafu, E G; Uhm, J; Seftel, M; Gupta, V; Kuruvilla, J; Lipton, J H; Messner, H A; Kim, D D H

    2015-05-01

    Steroid refractory acute GVHD (SR aGVHD) is associated with high morbidity and mortality. This study attempted to generate a risk model for SR aGVHD using 259 single nucleotide polymorphisms (SNPs) in 53 genes of recipients and donors. A total of 268 patients with aGVHD who were treated with systemic steroids were included. Patients were randomly divided into training (n=180) and validation sets (n=88). Clinical risk factors were also evaluated. In the training set, 85 (47.2%) developed SR aGVHD. Gastrointestinal involvement (Prs1800797; P=6.2 × 10(-4)) and IFNG (rs2069727; P=4.4 × 10(-4)) were significant risk factors. Scores were assigned to the above risk factors. Patients were divided into low (score 0, n=74) vs high risk (scores 1-3; n=106) in risk model. Higher incidence of SR aGVHD was noted in the high risk (61.3%) vs the low-risk group (27%; Prs1800797) and IFNG (rs2069727) along with gastrointestinal involvement of aGVHD.

  16. Laser-Induced Breakdown Spectroscopy: Fundamentals, Applications, and Challenges

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    Anabitarte, F.; Cobo, A.; J. M. Lopez-Higuera

    2012-01-01

    Laser-induced breakdown spectroscopy (LIBS) is a technique that provides an accurate in situ quantitative chemical analysis and, thanks to the developments in new spectral processing algorithms in the last decade, has achieved a promising performance as a quantitative chemical analyzer at the atomic level. These possibilities along with the fact that little or no sample preparation is necessary have expanded the application fields of LIBS. In this paper, we review the state of the ar...

  17. Induced pluripotent stem cells: Challenges and opportunities for cancer immunotherapy

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    Patty eSachamitr

    2014-04-01

    Full Text Available Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumour associated antigens (TAA are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focussed on the administration of autologous monocyte-derived dendritic cells (moDC pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumour infiltrating lymphocytes (TIL as a source of TAA-specific cytotoxic T cells (CTL. Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross-present exogenous TAA to the CD8+ T cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS cells as well as minor subsets of DC with therapeutic potential, including CD141+XCR1+ DC, capable of cross-presenting TAA to naïve CD8+ T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.

  18. Ipilimumab-Induced Enteritis without Colitis: A New Challenge

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    Marcus Messmer

    2016-11-01

    Full Text Available Introduction: Ipilimumab is an immune checkpoint inhibitor targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA4, approved to treat metastatic melanoma. It was the first therapy shown to prolong survival in a large, randomized clinical trial. However, immune-related adverse events are common and can be severe. Enterocolitis is a common adverse event with ipilimumab, but enteritis without colitis has not been previously described. Case Report: An 83-year-old man presented to our hospital with grade 3 diarrhea for 5 days. One month prior, he had started treatment with ipilimumab for metastatic melanoma. On presentation, he was found to have severe electrolyte disturbances, including hyponatremia, hypokalemia, and acute kidney injury. Causes of infectious diarrhea were excluded, and he was treated with corticosteroids for presumed ipilimumab-associated enterocolitis. However, colonoscopy revealed normal mucosa, both grossly and on pathology of random biopsies. Steroids were weaned but his symptoms recurred. He then underwent upper endoscopy with enteroscopy. Biopsy of the duodenum was notable for acute inflammation, villous blunting, and other changes consistent with ipilimumab-associated injury. He was restarted on high-dose steroids and his symptoms resolved. Discussion: Ipilimumab-induced enteritis is a serious and potentially life-threatening immune related adverse event that warrants prompt recognition and aggressive management. As in cases of ipilimumab-associated enterocolitis, steroids are an effective therapy. Enteritis without colitis should be suspected in patients on ipilimumab who present with severe diarrhea but have a normal colonoscopy.

  19. Recombinant proteins from Gallibacterium anatis induces partial protection against heterologous challenge in egg-laying hens

    DEFF Research Database (Denmark)

    Pors, Susanne Elisabeth; Skjerning, Ragnhild Bager; Flachs, Esben M.

    2016-01-01

    after challenge. All birds were euthanized and subjected to a post mortem procedure including scoring of lesions and sampling for bacterial growth. Moreover, ELISA assays were used to quantify antigen-specific IgG titers in serum. The results showed that all three proteins induced protection against...

  20. Induced mutations in yeast cell populations adapting to an unforeseen challenge.

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    Moore, Lindsay S; Wei, Wu; Stolovicki, Elad; Benbenishty, Tamar; Wilkening, Stefan; Steinmetz, Lars M; Braun, Erez; David, Lior

    2014-01-01

    The modern evolutionary synthesis assumes that mutations occur at random, independently of the environment in which they confer an advantage. However, there are indications that cells facing challenging conditions can adapt rapidly, utilizing processes beyond selection of pre-existing genetic variation. Here, we show that a strong regulatory challenge can induce mutations in many independent yeast cells, in the absence of general mutagenesis. Whole genome sequencing of cell lineages reveals a repertoire of independent mutations within a single lineage that arose only after the cells were exposed to the challenging environment, while other cells in the same lineage adapted without any mutation in their genomes. Thus, our experiments uncovered multiple alternative routes for heritable adaptation that were all induced in the same lineage during a short time period. Our results demonstrate the existence of adaptation mechanisms beyond random mutation, suggesting a tight connection between physiological and genetic processes.

  1. IL-2 AND IFN-g, BUT NOT IL-4 SECRETION BY PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC ARE RELATED TO CD4+ T CELLS AND CLINICAL STATUS IN BRAZILIAN HIV-1-INFECTED SUBJECTS

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    Marisa A. HONG

    1998-11-01

    Full Text Available It has been reported that production of IL-2 and IFN-g, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divisão de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV- infected patients and normal subjects, were detected. The patients with CD4+ T cell counts g production compared to controls. Patients with higher counts of CD4+ T cells (either between 200-500 or >500 cells/mm3 also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-g release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells >500 cells/mm3 showed increased levels of IL-2 and IFN-g, than individuals with CD4+ T cells g production at advanced HIV disease. IL-4 production was not affected during HIV infection. Taken together, these findings suggest that the cytokine profile might be influenced by the HIV infection rather than the cause of disease progression.

  2. Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

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    Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

    2016-05-01

    We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.

  3. Diet-induced obesity attenuates cytokine production following an immune challenge

    OpenAIRE

    2014-01-01

    Obesity increases susceptibility for numerous diseases and neurological disorders including cardiovascular disease, metabolic syndrome, and dementia. One factor that may contribute to the increased risk for these conditions is the development of chronic inflammation. The current study evaluated whether diet-induced obesity (DIO) affects cognitive performance by increasing neuroinflammation and prolonging the behavioral and inflammatory response to an immune challenge. Adult male C57BL/6J mice...

  4. Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer

    Directory of Open Access Journals (Sweden)

    Williamson Anna-Lise

    2003-01-01

    Full Text Available Abstract Background The failure of specific types of human papillomaviruses (HPV to raise effective immune responses may be important in the pathogenesis of cervical cancer, the second most common cancer in South African women. Polymorphisms of a number of cytokine genes have been implicated in inducing susceptibility or resistance to cancers caused by infectious agents owing to their role in determining host immune response. Polymorphisms of IL-10 and IFN-γ genes are believed to influence the expression and/or secretion levels of their respective cytokines. Methods and Results In this study, women with histologically proven cancer of the cervix (n = 458 and hospital-based controls (n = 587 were investigated for bi-allelic -1082 (A/G polymorphisms of IL-10 and the bi-allelic +874(A/T polymorphisms of IFN-γ. In addition, the distributions of the allelic frequencies were stratified in both the African and mixed race population groups of South Africa. We found striking differences in the allele distribution of IFN-γ (X2 = 0.02 among the two ethnic groups. A significant increase in the allele distribution of the IFN-γ AA genotype was found in the African group compared to the mixed population group (OR, 0.5; 95% CI, 0.2–1.0. For IL-10 there were no significant allelic differences between the two South African ethnic groups. Furthermore, when the ethnic groups were combined the IL-10 allelic frequencies in the combined South African data were similar to those observed in an Oriental population from Southern China and in an Italian population. However, the allele frequencies of the IFN-γ genotype among the two South African ethnic groups were different when compared to an Italian Caucasoid group. While crude analysis of these data showed both statistically significantly increased and diminished risks of cervical cancer among high producers of INF-γ and low producers of IL-10 respectively, these associations were no longer significant when the

  5. Triptolide Attenuates Endotoxin- and Staphylococcal Exotoxin-Induced T-Cell Proliferation and Production of Cytokines and Chemokines

    Science.gov (United States)

    2005-02-01

    interferon gamma (IFNg) are pivotal mediators in superantigen-induced toxic shock.[2,7,10,13] Both TNFa and IL-1 have potent immunostimulating...and the Swiss-Dutch J5 Immunoglob- ulin Study Group. Prognostic values of tumor necrosis factor/cachectin, interferon- alpha, and interferon - gamma in

  6. Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects

    DEFF Research Database (Denmark)

    Ihlemann, Nikolaj; Rask-Madsen, Christian; Perner, Anders;

    2003-01-01

    cofactor of eNOS. Therefore, we examined whether an acute supplement of BH4 could restore endothelial dysfunction induced by an oral glucose challenge. Healthy subjects were examined in 53 experiments. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies were obtained......An oral glucose challenge causes transient impairment of endothelial function, probably because of increased oxidative stress. During oxidative stress, endothelial nitric oxide (NO) synthase (eNOS) becomes uncoupled because of decreased bioavailability of tetrahydrobiopterin (BH4), an essential...... (n = 10) and SNP (n = 8). On different days (6R)-5,6,7,8-tetrahydro-l-biopterin dihydrochloride (6R-BH4; n = 10), the active cofactor of eNOS or its stereoisomer (6S)-5,6,7,8-tetrahydro-l-biopterin sulfate (6S-BH4; n = 10), which is inactive as a cofactor, was added 10 min (500 microg/min) before...

  7. Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducing myo-inositol biosynthesis.

    Science.gov (United States)

    Gardell, Alison M; Yang, Jun; Sacchi, Romina; Fangue, Nann A; Hammock, Bruce D; Kültz, Dietmar

    2013-12-15

    This study aimed to determine the regulation of the de novo myo-inositol biosynthetic (MIB) pathway in Mozambique tilapia (Oreochromis mossambicus) brain following acute (25 ppt) and chronic (30, 60 and 90 ppt) salinity acclimations. The MIB pathway plays an important role in accumulating the compatible osmolyte, myo-inositol, in cells in response to hyperosmotic challenge and consists of two enzymes, myo-inositol phosphate synthase and inositol monophosphatase. In tilapia brain, MIB enzyme transcriptional regulation was found to robustly increase in a time (acute acclimation) or dose (chronic acclimation) dependent manner. Blood plasma osmolality and Na(+) and Cl(-) concentrations were also measured and significantly increased in response to both acute and chronic salinity challenges. Interestingly, highly significant positive correlations were found between MIB enzyme mRNA and blood plasma osmolality in both acute and chronic salinity acclimations. Additionally, a mass spectrometry assay was established and used to quantify total myo-inositol concentration in tilapia brain, which closely mirrored the hyperosmotic MIB pathway induction. Thus, myo-inositol is a major compatible osmolyte that is accumulated in brain cells when exposed to acute and chronic hyperosmotic challenge. These data show that the MIB pathway is highly induced in response to environmental salinity challenge in tilapia brain and that this induction is likely prompted by increases in blood plasma osmolality. Because the MIB pathway uses glucose-6-phosphate as a substrate and large amounts of myo-inositol are being synthesized, our data also illustrate that the MIB pathway likely contributes to the high energetic demand posed by salinity challenge.

  8. Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges

    Indian Academy of Sciences (India)

    Zi-Bing Jin; Satoshi Okamoto; Michiko Mandai; Masayo Takahashi

    2009-12-01

    Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are the prodominant causes of human blindness in the world; however, these diseases are difficult to treat. Currently, knowledge on the mechanisms of these diseases is still very limited and no radical drugs are available. Induced pluripotent stem (iPS) cells are an innovative technology that turns somatic cells into embryonic stem (ES)-like cells with pluripotent potential via the exogenous expression of several key genes. It can be used as an unlimited source for cell differentiation or tissue engineering, either of which is a promising therapy for human degenerative diseases. Induced pluripotent cells are both an unlimited source for retinal regeneration and an expectant tool for pharmaprojects and developmental or disease modelling. In this review, we try to summarize the advancement of iPS-based technologies and the potential utility for retinal degenerative diseases. We also discuss the challenges of using this technology in the retinology field.

  9. Re-challenge with Etanercept in patients with Etanercept-induced Neutropenia.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-08-05

    TNF blockers have rarely been associated with haematological complications; however, there are scattered case reports of marked neutropenia with their use and necessitating in their withdrawal. We would like to report a series of five patients who developed neutropenia with etanercept use; however, all these patients were re-challenged with etanercept with a mean follow up of 30 months. These patients developed neutropenia within 2 months of starting etanercept. Two patients were eventually taken off etanercept; one of them needed switching to a different form of TNF blockers, and the second patient is in clinical remission with low-dose corticosteroids. All our patients continued to have mild-moderate degree of neutropenia; however, they are being monitored very closely and they are enjoying complete disease remission. It was interesting to note that none of our patients had increased infections during the re-challenge phase, even though they had grade 2 to grade 4 neutropenia. We have re-challenged these patients without any clinical complications, revealing that patients with mild to moderate neutropenia can be safely exposed to TNF blockers as long as they are monitored with regular cell count checks. Although largely noted to be clinically insignificant in our patient series, the potential of drug-induced neutropenia in causing higher rate of infections do exist. Careful clinical and hematologic monitoring is the best way to recognize this adverse event.

  10. Sweat-inducing physiological challenges do not result in acute changes in hair cortisol concentrations.

    Science.gov (United States)

    Grass, Juliane; Kirschbaum, Clemens; Miller, Robert; Gao, Wei; Steudte-Schmiedgen, Susann; Stalder, Tobias

    2015-03-01

    Hair cortisol concentrations (HCC) are assumed to provide a stable, integrative marker of long-term systemic cortisol secretion. However, contrary to this assumption, some recent observations have raised the possibility that HCC may be subject to acute influences, potentially related to cortisol incorporation from sweat. Here, we provide a first detailed in vivo investigation of this possibility comprising two independent experimental studies: study I (N=42) used a treadmill challenge to induce sweating together with systemic cortisol reactivity while in study II (N=52) a sauna bathing challenge induced sweating without systemic cortisol changes. In both studies, repeated assessments of HCC, salivary cortisol, cortisol in sweat and individuals' sweating rate (single assessment) were conducted on the experimental day and at a next-day follow-up. Results across the two studies consistently revealed that HCC were not altered by the acute interventions. Further, HCC were found to be unrelated to acute salivary cortisol reactivity, sweat cortisol levels, sweating rate or the time of examination. In line with previous data, cortisol levels in sweat were strongly related to total salivary cortisol output across the examined periods. The present results oppose recent case report data by showing that single sweat-inducing interventions do not result in acute changes in HCC. Our data also tentatively speak against the notion that cortisol in sweat may be a dominant source of HCC. Further, our findings also indicate that HCC are not subject to diurnal variation. This research provides further support for hair cortisol analysis as a marker of integrated long-term systemic cortisol secretion.

  11. Induced Pluripotent Stem Cell-derived Cardiomyocytes: Cardiac Applications, Opportunities and Challenges.

    Science.gov (United States)

    Moreau, Adrien; Boutjdir, Mohamed; Chahine, Mohamed

    2017-03-28

    Chronic diseases are the primary cause of mortality worldwide, accounting for 67% of deaths. One of the major challenges in developing new treatments is the lack of understanding of the exact underlying biological and molecular mechanisms. Chronic cardiovascular diseases are the single most common cause of death worldwide, and sudden deaths due to cardiac arrhythmias account for approximately 50% of all such cases. Traditional genetic screening for genes involved in cardiac disorders is laborious and frequently fails to detect the mutation that explains or causes the disorder. However, when mutations are identified, human induced pluripotent stem cells (hiPSCs) derived from affected patients make it possible to address fundamental research questions directly relevant to human health. As such, hiPSC technology has recently been used to model human diseases and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) thus offer a unique opportunity to investigate potential disease-causing genetic variants in their natural environment. The purpose of this review is to present the current state of knowledge regarding hiPSC-CMs, including their potential, limitations, and challenges and to discuss future prospects.

  12. Prevalence of Exercise-Induced Bronchospasm by laboratory exercise challenge among Ragunan Sport School athletes

    Directory of Open Access Journals (Sweden)

    Ignatio Rika

    2008-03-01

    Full Text Available Exercise-induced bronchospasm (EIB is a common condition among adolescent athletes. There has been no study examining the prevalence of EIB among adolescent athletes in Indonesia. This study aimed to get the prevalence of EIB among Ragunan Sport School athletes by laboratory exercise challenge. Subjects performed static cycle ergometer exercise (Monark, Sweden to reach minimal workload of 90% maximal heart rate. Force expiratory ventilation (FEV₁ was examined by spirometry (Minato AS-PAL, Japan at minute 0, 5, 10 and 20 post exercise. The EIB was defined as a decline of FEV₁ as much as 10% or more from baseline value. Room temperature and humidity were 28°C-31°C and 74%-82% respectively. There were 168 athletes from 12 sport types who participated in this study. Among them, 23 athletes (13.7% were EIB positive. The highest percentage of EIB was in taekwondo (54.5%. Sixteen athletes with EIB (70% were from less asthmogenic sports. Athletes with EIB consisted of 17 (17.5% females and 6 (8.4% males. In conclusion, the prevalence of EIB among adolescent athletes was moderately high, and was more prevalent in female. More over, laboratory exercise challenge could elicit EIB in less asthmogenic sport. (Med J Indones 2008; 17: 33-6Keywords: adolescent athlete, asthmogenic sports

  13. Mutant Brucella abortus membrane fusogenic protein induces protection against challenge infection in mice.

    Science.gov (United States)

    de Souza Filho, Job Alves; de Paulo Martins, Vicente; Campos, Priscila Carneiro; Alves-Silva, Juliana; Santos, Nathalia V; de Oliveira, Fernanda Souza; Menezes, Gustavo B; Azevedo, Vasco; Cravero, Silvio Lorenzo; Oliveira, Sergio Costa

    2015-04-01

    Brucella species can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understand this host-pathogen interplay. Here, we evaluated the role of the Brucella membrane fusogenic protein (Mfp) and outer membrane protein 19 (Omp19) in bacterial pathogenesis. In this study, we showed that B. abortus Δmfp::kan and Δomp19::kan deletion mutant strains have reduced persistence in vivo in C57BL/6 and interferon regulatory factor 1 (IRF-1) knockout (KO) mice. Additionally, 24 h after macrophage infection with a Δmfp::kan or Δomp19::kan strain expressing green fluorescent protein (GFP) approximately 80% or 65% of Brucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP-1, respectively, whereas around 60% of BCVs containing wild-type S2308 were found in LAMP-1-negative compartments. B. abortus Δomp19::kan was attenuated in vivo but had a residual virulence in C57BL/6 and IRF-1 KO mice, whereas the Δmfp::kan strain had a lower virulence in these same mouse models. Furthermore, Δmfp::kan and Δomp19::kan strains were used as live vaccines. Challenge experiments revealed that in C57BL/6 and IRF-1 KO mice, the Δmfp::kan strain induced greater protection than the vaccine RB51 and protection similar that of vaccine S19. However, a Δomp19::kan strain induced protection similar to that of RB51. Thus, these results demonstrate that Brucella Mfp and Omp19 are critical for full bacterial virulence and that the Δmfp::kan mutant may serve as a potential vaccine candidate in future studies.

  14. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Yu Fen Samantha Seah

    2015-12-01

    Full Text Available Embryonic stem cells (ESCs are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases.

  15. Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

    Science.gov (United States)

    Yi, E S; Lee, H; Suh, Y K; Tang, W; Qi, M; Yin, S; Remick, D G; Ulich, T R

    1996-10-01

    Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.

  16. A DNA vaccine directed against a rainbow trout rhabdovirus induces early protection against a nodavirus challenge in turbot

    DEFF Research Database (Denmark)

    Sommerset, I.; Lorenzen, Ellen; Lorenzen, Niels;

    2003-01-01

    A DNA vaccine encoding the envelope glycoprotein from a fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), has previously been shown to induce both early and long time protection against the virus in rainbow trout. Challenge experiments have revealed that the immunity established shortly...... after vaccination is cross-protective against heterologous fish rhabdoviruses. In this study, we show that the DNA vaccine encoding the VHSV glycoprotein also induces early protection against a non-enveloped, positive-sense RNA vir-us belonging to the Nodavirus family, the Atlantic halibut nodavirus...... (AHNV). In a vaccine. efficacy test using juvenile turbot as model fish, the fish injected with the VHSV vaccine were completely protected against a nodavirus challenge performed 8 days post vaccination, while the cumulative mortality in the control group reached 54%. A DNA vaccine carrying the gene...

  17. Prospects and challenges for practical application of rhizobacteria-mediated induced systemic resistance

    NARCIS (Netherlands)

    Loon, L.C. van; Bakker, P.A.H.M.; Pieterse, C.M.J.

    2002-01-01

    Selected strains of plant growth-promoting rhizobacteria are able to induce a systemic resistance (ISR) in plants, which is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). The generally non-specific character of induced resistance constitutes an increase in the level o

  18. Exertional-induced bronchoconstriction: Comparison between cardiopulmonary exercise test and methacholine challenging test

    Directory of Open Access Journals (Sweden)

    Mostafa Ghanei

    2015-01-01

    Full Text Available Introduction: Exertional-induced bronchoconstriction is a condition in which the physical activity causes constriction of airways in patients with airway hyper- responsiveness. In this study, we tried to study and evaluate any relationship between the findings of cardiopulmonary exercise testing (CPET and the response to methacholine challenge test (MCT in patients with dyspnea after activity. Materials and Methods: Thirty patients with complaints of dyspnea following activity referred to "Lung Clinic" of Baqiyatallah Hospital but not suffering from asthma were entered into the study. The subjects were excluded from the study if: Suffering from any other pulmonary diseases, smoking more than 1 cigarette a week in the last year, having a history of smoking more than 10 packets of cigarettes/year, having respiratory infection in the past 4 weeks, having abnormal chest X-ray or electrocardiogram, and cannot discontinue the use of medicines interfering with bronchial provocation. Baseline spirometry was performed for all the patients, and the values of forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, and FEV/FVC were recorded. The MCT and then the CPET were performed on all patients. Results: The mean VO 2 (volume oxygen in patients with positive methacholine test (20.45 mL/kg/min was significantly lower than patients with negative MCT (28.69 mL/kg/min (P = 0.000. Respiratory rates per minute (RR and minute ventilation in the group with positive MCT (38.85 and 1.636 L were significantly lower than the group with negative methacholine test (46.78 and 2.114 L (P < 0.05. Also, the O 2 pulse rate in the group with negative methacholine test (116.27 mL/beat was significantly higher than the group with positive methacholine test (84.26 mL/beat (P < 0.001. Conclusion: Pulmonary response to exercise in patients with positive methacholine test is insufficient. The dead space ventilation in these patients has increased. Also, dynamic

  19. Challenge assay: A functional biomarker for exposure-induced DNA repair deficiency and for risk of cancer.

    Science.gov (United States)

    Au, William W; Giri, Ashok K; Ruchirawat, Mathuros

    2010-01-01

    A variety of biomarkers have been used to monitor exposed populations to determine potential health hazards from their exposure to environmental toxic agents. However, the majority of these biomarkers have been focused onto the identification of biological damage from the exposure. Therefore, there is a need to develop functional biomarkers that can identify exposure-induced functional deficiencies. More importantly, these deficiencies should be positioned along pathways that are responsible for the development of specific diseases. One of such pathways belongs to the extensive and complex DNA-repair machinery. The machinery thus becomes a large target for damage from environmental toxic agents. The hypothesis is that damage to any component of a repair pathway will interfere with the pathway-specific repair activities. Therefore, when cells from exposed populations are challenged with a DNA-damaging agent in vitro, the in vivo exposure-induced repair deficiency will be dramatically amplified and the deficiency will be detectable in a challenge assay as increased chromosome aberrations, micronuclei or un-repaired DNA strand breaks. The challenge assay has been used in different laboratories to show that a variety of exposed populations (with exposure to air pollutants, arsenic, benzene, butadiene, cigarette smoke, incense smoke, lead, mercury, pesticides, uranium or xylene but not to low concentrations of air pollutants or butadiene) expressed abnormal challenge response. The predicted health consequences of some of these studies have also been validated. Therefore, the challenge assay is a useful functional biomarker for population studies. Details of the challenge assay and its application will be presented in this review.

  20. Chemically induced Salmonella enteritidis ghosts as a novel vaccine candidate against virulent challenge in a rat model.

    Science.gov (United States)

    Vinod, Nagarajan; Oh, Sung; Kim, Seongdae; Choi, Chang Won; Kim, Sei Chang; Jung, Cheong-Hwan

    2014-05-30

    Salmonella enteritidis ghosts (SEGs), non-living empty bacterial cell envelopes were generated by using the minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH) and investigated as a vaccine candidate in rats. To determine the immunogenicity and protective efficacy of SEG vaccine, rats were divided into four groups: group A (non-vaccinated control), group B (orally vaccinated), group C (intramuscularly vaccinated) and group D (intramuscularly vaccinated with complete Freund's adjuvant). Vaccination of rats with SEGs induced significant immune responses before and after virulent challenge. Rats vaccinated with SEGs showed significant increases in serum IgG antibodies after challenging with virulent S. enteritidis on week 8 and week 10 (P<0.01). During the vaccination period, groups B, C and D showed significantly higher serum bactericidal activity (SBA) compared to group A (P<0.01). Most importantly, bacterial loads in vaccinated groups were significantly lower than in the non-vaccinated group (P<0.01). In conclusion, these results show that the chemically induced SEGs as a vaccine candidate against virulent challenge.

  1. Pyrosequencing analysis of Salinomycin and Eimeria spp. challenge-induced changes in broiler cecal microbial communities

    Science.gov (United States)

    Eimeria spp. invade and damage the intestinal cell lining of broilers, resulting in cell necrosis and secondary bacterial infections. The current work investigates the effect of anticoccidial agents, salinomycin in combination with roxarsone, and Eimeria challenge on the composition of broiler ceca...

  2. Recombinant proteins from Gallibacterium anatis induces partial protection against heterologous challenge in egg-laying hens

    DEFF Research Database (Denmark)

    Pors, Susanne Elisabeth; Skjerning, Ragnhild Bager; Flachs, Esben M.;

    2016-01-01

    are urgently required. The aim of the present study was to evaluate the cross-protective capacity of three recombinant proteins recently identified as potential vaccine candidates; GtxA-N, GtxA-C, and FlfA, in an in vivo challenge model. Nine groups of birds were immunized twice with each protein, respectively...

  3. Side effects induced by the acute levodopa challenge in Parkinson’s Disease and atypical parkinsonisms

    Science.gov (United States)

    Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

    2017-01-01

    Introduction Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. Methods We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Results Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40–13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Conclusions Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD. PMID:28207803

  4. Could an experimental dengue virus infection fail to induce solid immunity against homologous viral challenge in non-human primates?

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Lazo, Laura; Marcos, Ernesto; Martín, Jorge; Suzarte, Edith; Castro, Jorge; Romero, Yaremis; Guillén, Gerardo; Hermida, Lisset

    2016-02-01

    There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate. Some authors have tried to explain this contradiction by hypothesizing that protection rates in non-human primates (NHPs) are associated with a lack of post-challenge anamnestic immune responses. Here, we studied the protection and anamnestic response patterns after homologous challenge in NHPs previously infected with DENV-2. Two immunization schemes were used, varying the viral doses and the intervals between them. Animals developed immunity against DENV-2 that provided full protection against reinfection with a homologous virus. However, all monkeys showed a significant increase in antiviral and neutralizing antibody titers after challenge. Our results suggest that sterilizing immunity could not be induced by infection with the virus despite the lack of detectable viremia in some animals in which an increase in antibody titer was observed. For this reason, we propose that the lack of an anamnestic neutralizing antibody response after challenge, as suggested by some authors, should be carefully reviewed as a criterion for evaluating the functionality of vaccine candidates.

  5. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    Science.gov (United States)

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

  6. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  7. Methotrexate-induced necrolysis in tumoral-stage mycosis fungoides: a challenging diagnosis.

    Science.gov (United States)

    Mna, Amira Ben; Souissi, Asmahene; Halouani, Slim; El Euch, Dalenda; Zahani, Alia; Kchir, Nidham; Zaraa, Ines; Mokni, Mourad

    2016-01-01

    Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous infusions of methotrexate. Since then, few cases of methotrexate-induced skin ulcers in patients with mycosis fungoides have been published. We report an additional patient with erythrodermic mycosis fungoides who developed cutaneous ulcerations as a sole manifestation of methotrexate toxicity.

  8. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  9. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Science.gov (United States)

    Hird, Thomas R; Grassly, Nicholas C

    2012-01-01

    Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  10. Management of phenytoin induced gingival enlargement associated with cerebral palsy: A challenge to the clinician

    Directory of Open Access Journals (Sweden)

    Anupama Shriram Rao

    2013-01-01

    Full Text Available Phenytoin, which is the drug of choice for treatment of grandmal, psychomotor seizures associated with cerebral palsy, has serious side effect like gingival enlargement. Drug induced gingival enlargement is not only esthetically disfiguring but often impairs speech, mastication, nutrition and plaque control measures. In addition, poor oral hygiene, lack of motor coordination and muscular limitations in mentally disabled individuals results in increased susceptibility to periodontal disease. The present case report unfolds a complex nature of the management of phenytoin induced gingival enlargement, secondarily complicated by inflammation, and in the cerebral palsy patient. A supportive team work of periodontist, neurophysician, and general anesthetist plays a significant role in maintaining the quality of life in mentally disabled patient.

  11. Management of phenytoin induced gingival enlargement associated with cerebral palsy: A challenge to the clinician

    OpenAIRE

    Anupama Shriram Rao; Amit K Walvekar; Rao, Subramaniam M; Biju Thomas

    2013-01-01

    Phenytoin, which is the drug of choice for treatment of grandmal, psychomotor seizures associated with cerebral palsy, has serious side effect like gingival enlargement. Drug induced gingival enlargement is not only esthetically disfiguring but often impairs speech, mastication, nutrition and plaque control measures. In addition, poor oral hygiene, lack of motor coordination and muscular limitations in mentally disabled individuals results in increased susceptibility to periodontal disease. T...

  12. Disulfiram-induced de novo convulsions without alcohol challenge: Case series and review of literature

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    Ranganath Ramarao Kulkarni

    2015-01-01

    Full Text Available Seizure induction by disulfiram (DSF an adverse effect of therapeutic dosages of DSF is less understood. In our prospective case series of eight subjects with alcohol dependence a temporal, dose-dependent, and reversible epileptogenic potential due to DSF was noted. Mean duration of onset of first seizure was 2.13 ± 1.13 weeks after initiation of DSF therapy (125-500 mg/day with no other detectable causes of seizures. Presence of alcohol withdrawal seizures (50%, DSF-induced hypertension (HTN (37.5%, psychosis (12.5% were noted, that may suggest common neurobiological underpinnings like dopamine-beta-hydroxylase inhibition. Various types of DSF-induced generalized seizures (tonic-clonic, 62.5%; myoclonic and tonic-clonic, 25%; myoclonic, 12.5% were effectively managed by halving initial DSF dose (37.5% even after cessation of antiepileptics, or stopping DSF (37.5%. Presence of alcohol withdrawal seizures, DSF-induced HTN/psychosis during DSF therapy may be early risk factors for dose-dependent and reversible adverse effect of DSF therapy - seizure induction, emphasizing caution.

  13. Disulfiram-Induced De Novo Convulsions without Alcohol Challenge: Case Series and Review of Literature.

    Science.gov (United States)

    Kulkarni, Ranganath Ramarao; Bairy, Bhavya K

    2015-01-01

    Seizure induction by disulfiram (DSF) an adverse effect of therapeutic dosages of DSF is less understood. In our prospective case series of eight subjects with alcohol dependence a temporal, dose-dependent, and reversible epileptogenic potential due to DSF was noted. Mean duration of onset of first seizure was 2.13 ± 1.13 weeks after initiation of DSF therapy (125-500 mg/day) with no other detectable causes of seizures. Presence of alcohol withdrawal seizures (50%), DSF-induced hypertension (HTN) (37.5%), psychosis (12.5%) were noted, that may suggest common neurobiological underpinnings like dopamine-beta-hydroxylase inhibition. Various types of DSF-induced generalized seizures (tonic-clonic, 62.5%; myoclonic and tonic-clonic, 25%; myoclonic, 12.5%) were effectively managed by halving initial DSF dose (37.5%) even after cessation of antiepileptics, or stopping DSF (37.5%). Presence of alcohol withdrawal seizures, DSF-induced HTN/psychosis during DSF therapy may be early risk factors for dose-dependent and reversible adverse effect of DSF therapy - seizure induction, emphasizing caution.

  14. Proteomic profile of hemolymph and detection of induced antimicrobial peptides in response to microbial challenge in Diatraea saccharalis (Lepidoptera: Crambidae).

    Science.gov (United States)

    Rocha, Iara Fernanda; Maller, Alexandre; de Cássia Garcia Simão, Rita; Kadowaki, Marina Kimiko; Angeli Alves, Luis Francisco; Huergo, Luciano Fernandes; da Conceição Silva, José Luis

    2016-04-29

    Insects are organisms extremely well adapted to diverse habitats, primarily due to their innate immune system, which provides them with a range of cellular and humoral responses against microorganisms. Lepidoptera hemolymph proteins involved in humoral responses are well known; however, there is a lack of knowledge about the sugarcane borer Diatraea saccharalis. In this present work, the hemolymph proteins of this pest insect were studied by applying proteomic methodologies. Two-dimensional electrophoresis (2-DE) gels of proteins extracted from naive larvae and larvae challenged with Escherichia coli (ATCC 11224) and Bacillus subtilis (ATCC 6623) showed an average of 300 spots, and 92 of these spots corresponded in all three 2-DE gels. Forty-one spots were excised and digested with trypsin and analyzed using mass spectrometry. After analysis, 10 proteins were identified, including some proteins of the immune system: β-defensin-like protein, Turandot A-like protein, attacin-like protein, peptidoglycan recognition protein and cyclophilin-like protein. Nine proteins were present in both experimental conditions; however, β-defensin-like protein was present only in hemolymph challenged by B. subtilis. Notably, attacin-like protein was strongly induced by challenge with E. coli, suggesting an immune response against the infection. However, antimicrobial activity was observed in the test zone of microbial growth inhibition of B. subtilis solely with the hemolymph extract of the larvae challenged with B. subtilis. We made for the first time a proteomic profile of the hemolymph of D. saccharalis in which it was possible to identify the presence of important proteins involved in the immune response.

  15. Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.

    Directory of Open Access Journals (Sweden)

    Noam Cohen

    Full Text Available Mice are exceedingly sensitive to intra-peritoneal (IP challenge with some virulent pneumococci (LD50 = 1 bacterium. To investigate how peripheral contact with bacterial capsular polysaccharide (PS antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1 The PS co-localized with MHC molecules on the BMDC surface; 2 PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3 Type-specific resistance to lethal IP challenge was manifested only after day 5; 4 Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5 Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6 Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.

  16. Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.

    Science.gov (United States)

    Cohen, Noam; Margalit, Raanan; Pevsner-Fischer, Meirav; Yona, Simon; Jung, Steffen; Eisenbach, Lea; Cohen, Irun R

    2012-01-01

    Mice are exceedingly sensitive to intra-peritoneal (IP) challenge with some virulent pneumococci (LD50 = 1 bacterium). To investigate how peripheral contact with bacterial capsular polysaccharide (PS) antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC) of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP) and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1) The PS co-localized with MHC molecules on the BMDC surface; 2) PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3) Type-specific resistance to lethal IP challenge was manifested only after day 5; 4) Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5) Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6) Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.

  17. Optimal strategies for virtual screening of induced-fit and flexible target in the 2015 D3R Grand Challenge

    Science.gov (United States)

    Ye, Zhaofeng; Baumgartner, Matthew P.; Wingert, Bentley M.; Camacho, Carlos J.

    2016-09-01

    Induced fit or protein flexibility can make a given structure less useful for docking and/or scoring. The 2015 Drug Design Data Resource (D3R) Grand Challenge provided a unique opportunity to prospectively test optimal strategies for virtual screening in these type of targets: heat shock protein 90 (HSP90), a protein with multiple ligand-induced binding modes; and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a kinase with a large flexible pocket. Using previously known co-crystal structures, we tested predictions from methods that keep the receptor structure fixed and used (a) multiple receptor/ligand co-crystals as binding templates for minimization or docking ("close"), (b) methods that align or dock to a single receptor ("cross"), and (c) a hybrid approach that chose from multiple bound ligands as initial templates for minimization to a single receptor ("min-cross"). Pose prediction using our "close" models resulted in average ligand RMSDs of 0.32 and 1.6 Å for HSP90 and MAP4K4, respectively, the most accurate models of the community-wide challenge. On the other hand, affinity ranking using our "cross" methods performed well overall despite the fact that a fixed receptor cannot model ligand-induced structural changes,. In addition, "close" methods that leverage the co-crystals of the different binding modes of HSP90 also predicted the best affinity ranking. Our studies suggest that analysis of changes on the receptor structure upon ligand binding can help select an optimal virtual screening strategy.

  18. Expression analysis of chitinase upon challenge inoculation to Alternaria wounding and defense inducers in Brassica juncea

    Directory of Open Access Journals (Sweden)

    Sandhya Rawat

    2017-03-01

    Full Text Available Chitinases are the hydrolytic enzymes which belong to the pathogenesis-related (PR protein family and play an important role not only in plant defense but also in various abiotic stresses. However, only a limited number of chitinase genes have been characterised in B. juncea. In this study, we have characterised B. juncea class IV chitinase gene (accession no EF586206 in response to fungal infection, salicylic acid (SA, jasmonic acid (JA treatments and wounding. Gene expression studies revealed that the transcript levels of Bjchitinase (BjChp gene increases significantly both in local and distal tissues after Alternaria infection. Bjchitinase gene was also induced by jasmonic acid and wounding but moderately by salicylic acid. A 2.5 kb class IV chitinase promoter of this gene was isolated from B. juncea by Genome walking (accession no KF055403.1. In-silico analysis of this promoter revealed a number of conserved cis-regulatory elements related to defense, wounding and signalling molecules like SA, and JA. For validation, chitinase promoter was fused to the GUS gene, and the resultant construct was then introduced into Arabidopsis plants. Histochemical analysis of T2 transgenic Arabidopsis plants showed that higher GUS activity in leaves after fungal infection, wounding and JA treatment but weakly by SA. GUS activity was seen in meristematic tissues, young leaves, seeds and siliques. Finally investigation has led to the identification of a pathogen-inducible, developmentally regulated and organ-specific promoter. Present study revealed that Bjchitinase (BjChp promoter is induced during biotic and environmental stress and it can be used in developing finely tuned transgenics.

  19. Mathematical models of blast induced TBI: current status, challenges and prospects

    Directory of Open Access Journals (Sweden)

    Raj K Gupta

    2013-05-01

    Full Text Available Blast induced traumatic brain injury (TBI has become a signature wound of recent military activities and is the leading cause of death and long-term disability among U.S. soldiers. The current limited understanding of brain injury mechanisms impedes the development of protection, diagnostic and treatment strategies. We believe mathematical models of blast wave brain injury biomechanics and neurobiology, complemented with in vitro and in vivo experimental studies, will enable a better understanding of injury mechanisms and accelerate the development of both protective and treatment strategies. The goal of this paper is to review the current state of the art in mathematical and computational modeling of blast induced TBI, identify research gaps and recommend future developments. A brief overview of blast wave physics, injury biomechanics and the neurobiology of brain injury is used as a foundation for a more detailed discussion of multiscale mathematical models of primary biomechanics and secondary injury and repair mechanisms. The paper also presents a discussion of model development strategies, experimental approaches to generate benchmark data for model validation and potential applications of the model for prevention and protection against blast wave TBI.

  20. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Science.gov (United States)

    Singh, Shailbala; Yang, Guojun; Schluns, Kimberly S; Anthony, Scott M; Sastry, K Jagannadha

    2014-01-01

    Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  1. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    Full Text Available Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer for harnessing the adjuvant potential of natural killer T (NKT cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  2. Agrochemical-induced stress in stingless bees: peculiarities, underlying basis, and challenges.

    Science.gov (United States)

    Lima, M A P; Martins, G F; Oliveira, E E; Guedes, R N C

    2016-10-01

    The toxicological stress induced by pesticides, particularly neonicotinoid insecticides, and its consequences in bees has been the focus of much recent attention, particularly for honey bees. However, the emphasis on honey bees and neonicotinoids has led to neglect of the relevance of stingless bees, the prevailing pollinators of natural and agricultural tropical ecosystems, and of other agrochemicals, including other pesticides and even leaf fertilizers. Consequently, studies focusing on agrochemical effects on stingless bees are sparse, usually limited to histopathological studies, and lack a holistic assessment of the effects of these compounds on physiology and behavior. Such effects have consequences for individual and colony fitness and are likely to affect both the stingless bee populations and the associated community, thereby producing a hierarchy of consequences thus far overlooked. Herein, we review the current literature on stingless bee-agrochemical interactions and discuss the underlying mechanisms involved in reported stress symptoms, as well as the potential consequences based on the peculiarities of these pollinators.

  3. Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

    Institute of Scientific and Technical Information of China (English)

    Raúl J Andrade; Mercedes Robles; Alejandra Fernández-Casta(n)er; Susana López-Ortega; M Carmen López-Vega; M Isabel Lucena

    2007-01-01

    Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and postcommercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice.To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be finetuned as further information is collected.

  4. Heat killed multi-serotype Shigella immunogens induced humoral immunity and protection against heterologous challenge in rabbit model.

    Science.gov (United States)

    Nag, Dhrubajyoti; Sinha, Ritam; Mitra, Soma; Barman, Soumik; Takeda, Yoshifumi; Shinoda, Sumio; Chakrabarti, M K; Koley, Hemanta

    2015-11-01

    Recently we have shown the homologous protective efficacy of heat killed multi-serotype Shigella (HKMS) immunogens in a guinea pig colitis model. In our present study, we have advanced our research by immunizing rabbits with a reduced number of oral doses and evaluating the host's adaptive immune responses. The duration of immunogenicity and subsequently protective efficacy was determined against wild type heterologous Shigella strains in a rabbit luminal model. After three successive oral immunizations with HKMS immunogens, serum and lymphocyte supernatant antibody titer against the heterologous shigellae were reciprocally increased and remained at an elevated level up to 180 days. Serogroup and serotype specific O-antigen of lipopolysaccharide and immunogenic proteins of heterologous challenge strains were detected by immunoblot assay. Up-regulation of IL-12p35, IFN-γ and IL-10 mRNA expression was detected in immunized rabbit peripheral blood mononuclear cells (PBMC) after stimulation with HKMS in vitro. HKMS-specific plasma cell response was confirmed by production of a relatively higher level of HKMS-specific IgG in immunized PBMC supernatant compared to control group. Furthermore, the immunized groups of rabbits exhibited complete protection against wild type heterologous shigellae challenge. Thus HKMS immunogens induced humoral and Th1-mediated adaptive immunity and provided complete protection in a rabbit model. These immunogens could be a broad spectrum non-living vaccine candidate for human use in the near future.

  5. Recent Advances in NSAIDs-Induced Enteropathy Therapeutics: New Options, New Challenges

    Directory of Open Access Journals (Sweden)

    Yun Jeong Lim

    2013-01-01

    Full Text Available The injurious effects of NSAIDs on the small intestine were not fully appreciated until the widespread use of capsule endoscopy. It is estimated that over two-thirds of regular NSAID users develop injury in the small intestinal injuries and that these injuries are more common than gastroduodenal mucosal injuries. Recently, chronic low-dose aspirin consumption was found to be associated with injury to the lower gut and to be a significant contributing factor in small bowel ulceration, hemorrhage, and strictures. The ability of aspirin and NSAIDs to inhibit the activities of cyclooxygenase (COX contributes to the cytotoxicity of these drugs in the gastrointestinal tract. However, many studies found that, in the small intestine, COX-independent mechanisms are the main contributors to NSAID cytotoxicity. Bile and Gram-negative bacteria are important factors in the pathogenesis of NSAID enteropathy. Here, we focus on a promising strategy to prevent NSAID-induced small intestine injury. Selective COX-2 inhibitors, prostaglandin derivatives, mucoprotective drugs, phosphatidylcholine-NSAIDs, and probiotics have potential protective effects on NSAID enteropathy.

  6. Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

    Directory of Open Access Journals (Sweden)

    Siobhan F Clarke

    Full Text Available Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac(+, with metabolic improvement achieved in DIO mice in receipt of vancomycin. However, two phases of weight gain were observed with effects most marked early in the intervention phase. Here, we compare the gut microbial populations at the early relative to the late stages of intervention using a high throughput sequencing-based analysis to understand the temporal relationship between the gut microbiota and obesity. This reveals several differences in microbiota composition over the intervening period. Vancomycin dramatically altered the gut microbiota composition, relative to controls, at the early stages of intervention after which time some recovery was evident. It was also revealed that Bac(+ treatment initially resulted in the presence of significantly higher proportions of Peptococcaceae and significantly lower proportions of Rikenellaceae and Porphyromonadaceae relative to the gut microbiota of L. salivarius UCC118 bacteriocin negative (Bac(- administered controls. These differences were no longer evident at the later time. The results highlight the resilience of the gut microbiota and suggest that interventions may need to be monitored and continually adjusted to ensure sustained modification of the gut microbiota.

  7. Vaccination with Enzymatically Cleaved GPI-Anchored Proteins from Schistosoma mansoni Induces Protection against Challenge Infection

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    Vicente P. Martins

    2012-01-01

    Full Text Available The flatworm Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, a debilitating disease that occurs throughout the developing world. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control schistosomiasis is through immunization with an antischistosomiasis vaccine combined with drug treatment. In the search for potential vaccine candidates, numerous tegument antigens have been assessed. As the major interface between parasite and mammalian host, the tegument plays crucial roles in the establishment and further course of schistosomiasis. Herein, we evaluated the potential of a GPI fraction, containing representative molecules located on the outer surface of adult worms, as vaccine candidate. Immunization of mice with GPI-anchored proteins induced a mixed Th1/Th2 type of immune response with production of IFN-γ and TNF-α, and low levels of IL-5 into the supernatant of splenocyte cultures. The protection engendered by this vaccination protocol was confirmed by 42% reduction in worm burden, 45% reduction in eggs per gram of hepatic tissue, 29% reduction in the number of granulomas per area, and 53% reduction in the granuloma fibrosis. Taken together, the data herein support the potential of surface-exposed GPI-anchored antigens from the S. mansoni tegument as vaccine candidate.

  8. Induced pluripotent stem cell (iPS) technology: promises and challenges

    Institute of Scientific and Technical Information of China (English)

    MIGUELA Esteban; GAN Yi; QIN DaJiang; PEI DuanQing

    2009-01-01

    In 2006,an article published in Cell by Shinya Yamanaka took by surprise the stem cell research community.By performing systematic retroviral transduction of factors enriched in embryonic stem (ES) cells,the authors demonstrated the reprogramming of mouse fibroblasts into an ES cell-like state.These cells,baptized iPS (induced pluripotent stem) cells,were immediately recognized as a ground-breaking discovery.Subsequently,the same authors and other groups reported a similar achievement with human fibroblasts.Two years later,the number of top quality papers on iPS is astonishing,and interest in the scientific community has risen to a fever pitch.But although iPS has the potential to revolutionize Regenerative Medicine,important questions still remain unanswered.Work from multiple laboratories worldwide including ours is focused on deciphering the molecular mechanisms of iPS,and trying to improve the technique to make it suitable for the clinic.In this review article we briefly discuss the past,present and future of iPS,with emphasis on urgent issues to be solved.

  9. rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

    Science.gov (United States)

    Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

    2014-09-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.

  10. Predator-induced physiological responses in tadpoles challenged with herbicide pollution

    Institute of Scientific and Technical Information of China (English)

    Pablo BURRACO; Lidia Jiménez DUARTE; Ivan GOMEZ-MESTRE

    2013-01-01

    Predators induce plastic responses in multiple prey taxa,ranging from morphological to behavioral or physiological changes.In amphibians,tadpoles activate plastic responses to reduce predation risk by reducing their activity rate and altering their morphology,specifically tail depth and pigmentation.Furthermore,there is now evidence that tadpoles' defenses are modified when predators combine with other stressful factors such as pollutants or competitors,but our knowledge on the physiological responses underlying these responses is still scarce.Here we study physiological responses in Pelobates cultripes tadpoles exposed to a natural predator (larvae of the aquatic beetle Dytiscus circumflexus),non-lethal concentrations of herbicide (glyphosate,0.5 mg/L and 1.0 mg/L) or both factors combined.We measured corticosterone levels,standard metabolic rate,oxidative damage (TBARS) and activity of antioxidant enzymes,and immune response (via leukocyte count).Tadpoles reduced their corticosterone concentration by ca.24% in the presence of predator cues,whereas corticosterone did not change in the presence of glyphosate.Two enzymes involved in antioxidant response also decreased in the presence of predators (14.7% and 13.2% respectively) but not to glyphosate.Herbicide,however,increased the number of neutrophils and reduced that of lymphocytes,and had an interaction effect with predator presence.Standard metabolic rate did not vary across treatments in our experiment.Thus we show a marked physiological response to the presence of predators but little evidence for interaction between predators and low levels of herbicide.Multiple assessment of the physiological state of animals is important to understand the basis and consequences of phenotypic plasticity.

  11. Predator-induced physiological responses in tadpoles challenged with herbicide pollution

    Directory of Open Access Journals (Sweden)

    Pablo BURRACO, Lidia Jiménez DUARTE, Ivan GOMEZ-MESTRE

    2013-08-01

    Full Text Available Predators induce plastic responses in multiple prey taxa, ranging from morphological to behavioral or physiological changes. In amphibians, tadpoles activate plastic responses to reduce predation risk by reducing their activity rate and altering their morphology, specifically tail depth and pigmentation. Furthermore, there is now evidence that tadpoles’ defenses are modified when predators combine with other stressful factors such as pollutants or competitors, but our knowledge on the physiological responses underlying these responses is still scarce. Here we study physiological responses in Pelobates cultripes tadpoles exposed to a natural predator (larvae of the aquatic beetle Dytiscus circumflexus, non-lethal concentrations of herbicide (glyphosate, 0.5 mg/L and 1.0 mg/L or both factors combined. We measured corticosterone levels, standard metabolic rate, oxidative damage (TBARS and activity of antioxidant enzymes, and immune response (via leukocyte count. Tadpoles reduced their corticosterone concentration by ca. 24% in the presence of predator cues, whereas corticosterone did not change in the presence of glyphosate. Two enzymes involved in antioxidant response also decreased in the presence of predators (14.7% and 13.2% respectively but not to glyphosate. Herbicide, however, increased the number of neutrophils and reduced that of lymphocytes, and had an interaction effect with predator presence. Standard metabolic rate did not vary across treatments in our experiment. Thus we show a marked physiological response to the presence of predators but little evidence for interaction between predators and low levels of herbicide. Multiple assessment of the physiological state of animals is important to understand the basis and consequences of phenotypic plasticity [Current Zoology 59 (4: 475–484, 2013].

  12. Progress and Future Challenges of Human Induced Pluripotents Stem Cell in Regenerative Medicine

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    Anna Meiliana

    2011-08-01

    Full Text Available BACKGROUND: Less than a decade ago the prospect for reprogramming the human somatic cell looked bleak at best. It seemed that the only methods at our disposal for the generation of human isogenic pluripotent cells would have to involve somatic cell nuclear transfer (SCNT. Shinya Yamanaka in August 2006 in his publication (Cell promised to change everything by showing that it was apparently very simple to revert the phenotype of a differentiated cell to a pluripotent one by overexpressing four transcription factors in murine fibroblasts. CONTENT: Mouse and human somatic cells can be genetically reprogrammed into induced pluripotent stem cells (iPSCs by the expression of a defined set of factors (Oct4, Sox2, c-Myc, and Klf4, as well as Nanog and LIN28. iPSCs could be generated from mouse and human fibroblasts as well as from mouse liver, stomach, pancreatic, neural stem cells, and keratinocytes. Similarity of iPSCs and embryonic stem cells (ESCs has been demonstrated in their morphology, global expression profiles, epigenetic status, as well as in vitro and in vivo differentiation potential for both mouse and human cells. Many techniques for human iPSCs (hiPSCs derivation have been developed in recent years, utilizing different starting cell types, vector delivery systems, and culture conditions. A refined or perfected combination of these techniques might prove to be the key to generating clinically applicable hiPSCs. SUMMARY: iPSCs are a revolutionary tool for generating in vitro models of human diseases and may help us to understand the molecular basis of epigenetic reprogramming. Progress of the last four years has been truly amazing, almost verging on science fiction, but if we can learn to produce such cells cheaply and easily, and control their differentiation, our efforts to understand and fight disease will become more accessible, controllable and tailored. Ability to safely and efficiently derive hiPSCs may be of decisive importance to

  13. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

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    Fadel Elie

    2011-09-01

    Full Text Available Abstract Background Involvement of inflammation in pulmonary hypertension (PH has previously been demonstrated and recently, immune-modulating dendritic cells (DCs infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS, as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT, monocrotaline-exposure/pneumonectomy (MCT/PE. Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature

  14. Effect of smoking on the levels of TNF-α and IFN-g in sera and BALF in patients with chronic obstructive pulmonary disease%吸烟对慢性阻塞性肺疾病患者血清及肺泡灌洗液中肿瘤坏死因子-α及干扰素-γ的影响

    Institute of Scientific and Technical Information of China (English)

    张念; 徐清; 陈菁; 杨硕; 刘梦琳; 聂红; 孙洁民

    2012-01-01

    Objective To investigate the effects of smoking on the levels of TNF-a and IFN-g in sera and BALF in patients with chronic obstructive pulmonary disease (COPD). Methods Patients enrolled were divided into 4 groups; normal control group, non-smoking COPD group, smoking COPD group, and smoking cessation COPD group. Levels of TNF-a and IFN-g in sera and BALF in all the patients were determined. Results Levels of TNF-a and IFN-g in sera and BALF in patients with COPD in acute and stable periods were higher than those in normal control group (P < 0.05). Levels of TNF-a and IFN-g in BALF in acute and stable periods in smoking COPD group were significantly higher than those in non-smoking COPD group and smoking cessation COPD group (P < 0.05). Conclusions Patients with COPD present enhanced systemic and airway inflammation mediated by TNF-a and IFN-g in both acute and stable phases. Smoking COPD patients present significantly enhanced airway inflammation, which seems be lowered after smoking cessation.%目的:评价吸烟对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者急性期、稳定期血清及肺泡灌洗液中肿瘤坏死因子-α(TNF-α)及干扰素-γ(IFN-γ)的影响.方法:分别测定正常对照组、非吸烟COPD组、持续吸烟COPD组及戒烟COPD组患者急性期、稳定期血清及肺泡灌洗液中TNF-α及IFN-γ的水平,并对各组血清及肺泡灌洗液中TNF-α及IFN-γ水平分别进行比较.结果:COPD患者无论在急性期还是稳定期,肺泡灌洗液中TNF-α水平较正常对照组高(P<0.05).其中,持续吸烟的COPD患者肺泡灌洗液中TNF-α水平较非吸烟COPD组及戒烟COPD组高(P<0.05).急性期及稳定期COPD患者血清中TNF-α水平较正常组高(P<0.05).急性期及稳定期COPD患者血清及肺泡灌洗液中IFN-γ水平均较正常组高(P<0.05).其中,持续吸烟的COPD患者肺泡灌洗液中IFN-γ水平较非吸烟COPD及戒烟COPD患者均高(P<0.05).结论:COPD

  15. Initiating rain water harvest technology for climate change induced drought resilient agriculture: scopes and challenges in Bangladesh

    Directory of Open Access Journals (Sweden)

    Hasan Muhammad Abdullah

    2015-12-01

    Full Text Available Bangladesh is primarily an agrarian economy. Agriculture is the single largest producing sector of the economy since it comprises about 18.6% of the country's GDP and employs around 45% of the total labor force. The performance of this sector has an overwhelming impact on major macroeconomic indicators like employment generation, poverty alleviation, human resource development and food security. The agriculture sector is extremely vulnerable to disaster and climate induced risks. Climate change is anticipated to aggravate the frequency and intensity of extreme weather events in Bangladesh. Drought is one of the major setbacks for the agriculture and its development. Therefore, disaster and climatic risk, especially drought management in agriculture is a major challenge for Bangladesh in achieving sustainable agricultural development. There are some regions in Bangladesh where every steps of agriculture from field preparation to ripening of crops dependents on rainfall. Consequently, drought affects annually 2.5 million ha in kharif (wet season and 1.2 million ha in dry season. Water is a natural resource with spatial scarcity and availability. Additionally, Cross-country anthropogenic activities caused a severe negative impact on water resources and eco-systems of Bangladesh in the recent years. The rivers and cannels dry up during the dry season and make the people completely dependent on groundwater (Abdullah, 2015. Accordingly the contribution of groundwater as a source of irrigation has increased and surface water has declined. It is now inevitable to look for alternate water source for agriculture. Water harvest technologies (WHTs can play an important role in this regard. WHTs can provide an additional source of water for crop production at the most critical stages of the growing season, thereby increasing yields and food security. The study is consists of drought scenario analysis, GIS based drought mapping and systematic literature

  16. A randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on pruritus induced by histamine, and cowhage challenge in healthy volunteers.

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    Rachel A Gibson

    Full Text Available BACKGROUND: Transient receptor potential vanilloid type 1 (TRPV1 is a non-selective cation channel widely expressed in skin tissues, and peripheral sensory nerve fibres. Activation of TRPV1 releases neuropeptides; the resulting neurogenic inflammation is believed to contribute to the development of pruritus. A TRPV1 antagonist has the potential to perform as an anti-pruritic agent. SB705498 is a TRPV1 antagonist that has demonstrated in vitro activity against cloned TRPV1 human receptors and when orally administered has demonstrated pharmacodynamic activity in animal models and clinical studies. OBJECTIVES: To select a topical dose of SB705498 using the TRPV1 agonist capsaicin; to confirm engagement of the TRPV1 antagonistic action of SB705498 and assess whether the dose selected has an effect on itch induced by two challenge agents. METHODS: A clinical study was conducted in 16 healthy volunteers to assess the effects of 3 doses of SB705498 on skin flare induced by capsaicin. Subjects with a robust capsaicin response were chosen to determine if the selected topical formulation of SB705498 had an effect on challenge agent induced itch. RESULTS: Following capsaicin challenge the greatest average reduction in area of flare was seen for the 3% formulation. This dose was selected for further investigation. Itch intensity induced by two challenge agents (cowhage and histamine was assessed on the Computerised Visual Analogue Scale. The difference in average itch intensity (Weighted Mean Over 15 Mins between the 3% dose of SB705498 and placebo for the cowhage challenge was -0.64, whilst the histamine challenge showed on average a -4.65 point change. CONCLUSIONS: The 3% topical formulation of SB705498 cream was clinically well tolerated and had target specific pharmacodynamic activity. However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo. SB705498 is unlikely to be of symptomatic

  17. DNA vaccination with a gene encoding Toxoplasma gondii Rhoptry Protein 17 induces partial protective immunity against lethal challenge in mice

    Directory of Open Access Journals (Sweden)

    Wang Hai-Long

    2016-01-01

    Full Text Available Toxoplasma gondii is an obligate intracellular apicomplexan parasite that affects humans and various vertebrate livestock and causes serious economic losses. To develop an effective vaccine against T. gondii infection, we constructed a DNA vaccine encoding the T. gondii rhoptry protein 17 (TgROP17 and evaluated its immune protective efficacy against acute T. gondii infection in mice. The DNA vaccine (p3×Flag-CMV-14-ROP17 was intramuscularly injected to BALB/c mice and the immune responses of the vaccinated mice were determined. Compared to control mice treated with empty vector or PBS, mice immunized with the ROP17 vaccine showed a relatively high level of specific anti-T. gondii antibodies, and a mixed IgG1/IgG2a response with predominance of IgG2a production. The immunized mice also displayed a specific lymphocyte proliferative response, a Th1-type cellular immune response with production of IFN-γ and interleukin-2, and increased number of CD8+ T cells. Immunization with the ROP17 DNA significantly prolonged the survival time (15.6 ± 5.4 days, P < 0.05 of mice after challenge infection with the virulent T. gondii RH strain (Type I, compared with the control groups which died within 8 days. Therefore, our data suggest that DNA vaccination with TgROP17 triggers significant humoral and cellular responses and induces effective protection in mice against acute T. gondii infection, indicating that TgROP17 is a promising vaccine candidate against acute toxoplasmosis.

  18. Immunization of African Indigenous Pigs with Attenuated Genotype I African Swine Fever Virus OURT88/3 Induces Protection Against Challenge with Virulent Strains of Genotype I.

    Science.gov (United States)

    Mulumba-Mfumu, L K; Goatley, L C; Saegerman, C; Takamatsu, H-H; Dixon, L K

    2016-10-01

    The attenuated African swine fever virus genotype I strain OURT88/3 has previously been shown to induce protection of European breeds of domestic pigs against challenge with virulent isolates. To determine whether protective immune responses could also be induced in indigenous breeds of pigs from the Kinshassa region in Democratic Republic of Congo, we immunized a group of eight pigs with OURT88/3 strain and challenged the pigs 3 weeks later with virulent genotype I strain OURT88/1. Four of the pigs were protected against challenge. Three of the eight pigs died from African swine fever virus and a fourth from an unknown cause. The remaining four pigs all survived challenge with a recent virulent genotype I strain from the Democratic Republic of Congo, DRC 085/10. Control groups of non-immune pigs challenged with OURT88/1 or DRC 085/10 developed signs of acute ASFV as expected and had high levels of virus genome in blood.

  19. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism

    NARCIS (Netherlands)

    Duivenvoorde, L.P.M.; Schothorst, van E.M.; Derous, D.; Stelt, van der I.; Masania, J.; Rabbani, N.; Thornalley, P.J.; Keijer, J.

    2015-01-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-in

  20. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Science.gov (United States)

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  1. Immersion exposure of rainbow trout (Oncorhynchus mykiss) fry to wildtype Flavobacterium psychrophilum induces no mortality, but protects against later intraperitoneal challenge

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Brudeseth, B.E.; Wiklund, T.

    2010-01-01

    in high titres of non-attenuated isolates of F. psychrophilum, was able to induce immunity to a subsequent ip challenge. Immersion in live bacteria for 30 or 50 min caused no mortality and protected a major fraction of the fry against challenges 26 and 47 days later with RPS values of 88.2 and 60......Flavobacterium psychrophilum, the causative agent of RTFS or rainbow trout fry syndrome, causes high mortality among hatchery reared rainbow trout (Oncorhynchus mykiss) fry in Europe and the USA. Despite several attempts, no efficient vaccines have yet been developed, the main obstacle being...... that the fry have to be vaccinated very early, i.e. around 0.2–0.5 g, where RTFS usually starts to give problems in the fish farms. Consequently, only oral or bath vaccines are relevant. Immersion of fry in inactivated or attenuated bacteria has resulted in RPS values of less than 50%. However, the results...

  2. Vaccination with recombinant adenoviruses expressing the peste des petits ruminants virus F or H proteins overcomes viral immunosuppression and induces protective immunity against PPRV challenge in sheep.

    Science.gov (United States)

    Rojas, José M; Moreno, Héctor; Valcárcel, Félix; Peña, Lourdes; Sevilla, Noemí; Martín, Verónica

    2014-01-01

    Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV). Two recombinant replication-defective human adenoviruses serotype 5 (Ad5) expressing either the highly immunogenic fusion protein (F) or hemagglutinin protein (H) from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses. Thus, neutralizing antibodies were detected in sera from immunized sheep. In addition, we detected a significant antigen specific T-cell response in vaccinated sheep against two different PPRV strains, indicating that the vaccine induced heterologous T cell responses. Importantly, no clinical signs and undetectable virus shedding were observed after virulent PPRV challenge in vaccinated sheep. These vaccines also overcame the T cell immunosuppression induced by PPRV in control animals. The results indicate that these adenovirus constructs could be a promising alternative to current vaccine strategies for the development of PPRV DIVA vaccines.

  3. Rhizobacteria-mediated induced systemic resistance (ISR) in Arabidopsis is not associated with a direct effect on expression of known defense-related genes but stimulates the expression of the jasmonate-inducible gene Atvsp upon challenge.

    Science.gov (United States)

    van Wees, S C; Luijendijk, M; Smoorenburg, I; van Loon, L C; Pieterse, C M

    1999-11-01

    Selected strains of nonpathogenic rhizobacteria from the genus Pseudomonas are capable of eliciting broad-spectrum induced systemic resistance (ISR) in plants that is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). In Arabidopsis, the ISR pathway functions independently of salicylic acid (SA) but requires responsiveness to jasmonate and ethylene. Here, we demonstrate that known defense-related genes, i.e. the SA-responsive genes PR-1, PR-2, and PR-5, the ethylene-inducible gene Hel, the ethylene- and jasmonate-responsive genes ChiB and Pdf1.2, and the jasmonate-inducible genes Atvsp, Lox1, Lox2, Pall, and Pin2, are neither induced locally in the roots nor systemically in the leaves upon induction of ISR by Pseudomonas fluorescens WCS417r. In contrast, plants infected with the virulent leaf pathogen Pseudomonas syringae pv. tomato (Pst) or expressing SAR induced by preinfecting lower leaves with the avirulent pathogen Pst(avrRpt2) exhibit elevated expression levels of most of the defense-related genes studied. Upon challenge inoculation with Pst, PR gene transcripts accumulated to a higher level in SAR-expressing plants than in control-treated and ISR-expressing plants, indicating that SAR involves potentiation of SA-responsive PR gene expression. In contrast, pathogen challenge of ISR-expressing plants led to an enhanced level of Atvsp transcript accumulation. The otherjasmonate-responsive defense-related genes studied were not potentiated during ISR, indicating that ISR is associated with the potentiation of specific jasmonate-responsive genes.

  4. Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice

    Science.gov (United States)

    Li, Wenfang; Ye, Ling; Carrion, Ricardo; Mohan, Gopi S.; Nunneley, Jerritt; Staples, Hilary; Ticer, Anysha; Patterson, Jean L.; Compans, Richard W.; Yang, Chinglai

    2015-01-01

    In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed “antigenic subversion.” To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection. PMID:25877553

  5. Protection Induced in Broiler Chickens following Drinking-Water Delivery of Live Infectious Laryngotracheitis Vaccines against Subsequent Challenge with Recombinant Field Virus.

    Science.gov (United States)

    Korsa, Mesula G; Browning, Glenn F; Coppo, Mauricio J C; Legione, Alistair R; Gilkerson, James R; Noormohammadi, Amir H; Vaz, Paola K; Lee, Sang-Won; Devlin, Joanne M; Hartley, Carol A

    2015-01-01

    Infectious laryngotracheitis virus (ILTV) causes acute upper respiratory tract disease in chickens. Attenuated live ILTV vaccines are often used to help control disease, but these vaccines have well documented limitations, including retention of residual virulence, incomplete protection, transmission of vaccine virus to unvaccinated birds and reversion to high levels of virulence following bird-to-bird passage. Recently, two novel ILTV field strains (class 8 and 9 ILTV viruses) emerged in Australia due to natural recombination between two genotypically distinct commercial ILTV vaccines. These recombinant field strains became dominant field strains in important poultry producing areas. In Victoria, Australia, the recombinant class 9 virus largely displaced the previously predominant class 2 ILTV strain. The ability of ILTV vaccines to protect against challenge with the novel class 9 ILTV strain has not been studied. Here, the protection induced by direct (drinking-water) and indirect (contact) exposure to four different ILTV vaccines against challenge with class 9 ILTV in commercial broilers was studied. The vaccines significantly reduced, but did not prevent, challenge virus replication in vaccinated chickens. Only one vaccine significantly reduced the severity of tracheal pathology after direct drinking-water vaccination. The results indicate that the current vaccines can be used to help control class 9 ILTV, but also indicate that these vaccines have limitations that should be considered when designing and implementing disease control programs.

  6. Enhanced mucosal immunoglobulin A response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide.

    Science.gov (United States)

    Cubillos, Carolina; de la Torre, Beatriz G; Jakab, Annamaria; Clementi, Giorgia; Borrás, Eva; Bárcena, Juan; Andreu, David; Sobrino, Francisco; Blanco, Esther

    2008-07-01

    The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptide-immunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.

  7. Evaluation of lincomycin in drinking water for treatment of induced porcine proliferative enteropathy using a Swine challenge model.

    Science.gov (United States)

    Bradford, James R; Winkelman, Nathan L; Moreira, Frederico P; Elfring, Gregory D

    2004-01-01

    A single-location, challenge-model study was conducted to evaluate the effectiveness of lincomycin against porcine proliferative enteropathy when administered through the drinking water at 125 and 250 mg/gallon. The primary variables of interest were pig removal rate, diarrhea scores, demeanor scores, and abdominal appearance scores. Ancillary performance variables examined included average daily feed intake, average daily gain, and feed per gain. After a 3-day acclimation period, pigs were challenged on 2 consecutive days with a mucosal homogenate containing a total dose of 1.4 x 10(9) cells of Lawsonia intracellularis. Five days later, when porcine proliferative enteropathy was well established, drinking water medicated with 125 mg (L125) or 250 mg (L250) lincomycin/gallon was provided to two groups of pigs for 10 days. Pigs were observed for 13 days following the treatment period. A third group of pigs served as controls and received unmedicated drinking water throughout the study. The L250 group experienced a significantly lower (P < .05) pig removal rate than the control group over the 23-day observation period. Additionally, for every primary variable, the L250 group experienced a significantly decreased (P < .01) number of abnormal days compared with the control group. The L125 group showed a significant reduction (P < .05) in abnormal demeanor and abnormal abdominal appearance scores compared with controls.

  8. Eimeria maxima microneme protein 2 delivered as DNA vaccine and recombinant protein induces immunity against experimental homogenous challenge.

    Science.gov (United States)

    Huang, Jingwei; Zhang, Zhenchao; Li, Menghui; Song, Xiaokai; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

    2015-10-01

    E. maxima is one of the seven species of Eimeria that infects chicken. Until now, only a few antigenic genes of E. maxima have been reported. In the present study, the immune protective effects against E. maxima challenge of recombinant protein and DNA vaccine encoding EmMIC2 were evaluated. Two-week-old chickens were randomly divided into five groups. The experimental group of chickens was immunized with 100 μg DNA vaccine pVAX1-MIC2 or 200 μg rEmMIC2 protein while the control group of chickens was injected with pVAX1 plasmid or sterile PBS. The results showed that the anti-EmMIC2 antibody titers of both rEmMIC2 protein and pVAX1-MIC2 groups were significantly higher as compared to PBS and pVAX1 control (Precombinant protein and the DNA vaccine could obviously alleviate jejunum lesions, body weight loss, increase oocyst, decrease ratio and provide ACIs of more than 165. All the above results suggested that immunization with EmMIC2 was effective in imparting partial protection against E. maxima challenge and it could be an effective antigen candidate for the development of new vaccines against E. maxima.

  9. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

    Directory of Open Access Journals (Sweden)

    Franklin R Toapanta

    2016-06-01

    Full Text Available A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD- 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h and/or microbiological (S. Typhi bacteremia endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD- was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml of TD volunteers during disease days and increase in plasmablasts (PB during the recovery phase (>day 14. Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21 and gut homing (integrin α4β7 molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

  10. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease

    Science.gov (United States)

    Toapanta, Franklin R.; Bernal, Paula J.; Fresnay, Stephanie; Magder, Laurence S.; Darton, Thomas C.; Jones, Claire; Waddington, Claire S.; Blohmke, Christoph J.; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.; Sztein, Marcelo B.

    2016-01-01

    A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6–9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans. PMID:27300136

  11. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

    Science.gov (United States)

    Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Magder, Laurence S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

    2016-06-01

    A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

  12. Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs.

    Science.gov (United States)

    Wex, Eva; Bouyssou, Thierry

    2015-01-01

    Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known.

  13. Bacillus subtilis PB6 improves intestinal health of broiler chickens challenged with Clostridium perfringens-induced necrotic enteritis.

    Science.gov (United States)

    Jayaraman, Sathishkumar; Thangavel, Gokila; Kurian, Hannah; Mani, Ravichandran; Mukkalil, Rajalekshmi; Chirakkal, Haridasan

    2013-02-01

    Necrotic enteritis (NE) is an enterotoxemic disease caused by Clostridium perfringens that results in significant economic losses, averaging damage of $0.05 per bird. The present study investigated the influence of a dietary supplement, Bacillus subtilis PB6, on performance, intestinal health, and gut integrity against C. perfringens-induced NE in broiler birds. Bacillus subtilis PB6 (ATCC-PTA 6737) is a natural strain isolated from healthy chicken gut that has been shown in in vitro to produce antimicrobial substances with broad activity against various strains of Campylobacter and Clostridium species. The animal study was conducted on broiler chickens (Cobb 400) for the period of 35 d using a completely randomized design. The experimental design included 3 treatments groups. Each treatment group contained 6 replicates, 3 male and 3 female, with 12 birds in each replicate. The 3 treatment groups were an uninfected control, an infected control, and an infected group supplemented with B. subtilis PB6 at 500 g/t of feed, containing 5 × 10(11) cfu/kg. Necrotic enteritis was induced in the broiler birds via oral inoculation of 30,000 oocysts of mixed strains of Eimeria species on d 14 followed by C. perfringens (10(8) cfu/mL) on d 19 through 21 of trial. The birds were analyzed for BW gain, mortality, feed conversion ratio (FCR), intestinal lesion score, intestinal C. perfringens counts, and villus histomorphometry. The infected control group showed markedly thickened mucosa, hemorrhages, intestinal lesions, and ballooning of intestine. The supplementation of B. subtilis PB6 reduced the FCR (P < 0.05) and intestinal C. perfringens counts significantly (P < 0.05) compared with the infected control group. It was also observed that B. subtilis PB6 improved villi length by 10.88 and 30.46% (P < 0.05) compared with uninfected and infected control groups, respectively. The group supplemented with B. subtilis PB6 significantly (P < 0.05) increased the villi length to crypt

  14. Effects of dietary threonine supplementation on immune challenge induced by swine Pseudorabies live vaccine in weaned pigs.

    Science.gov (United States)

    Mao, Xiangbing; Lai, Xiang; Yu, Bing; He, Jun; Yu, Jie; Zheng, Ping; Tian, Gang; Zhang, Keying; Chen, Daiwen

    2014-01-01

    The present study was conducted to determine whether dietary threonine supplementation can improve immunity of weaned pigs challenged by swine Pseudorabies live vaccine (SPLV). Thirty crossbred piglets weaned at 21 days of age were randomly assigned to three groups receiving diets containing true ileal digestible threonine (TIDT) at 0.74, 0.89 and 1.11% for 14 days. On day 8, all pigs were injected intramuscularly with SPLV or sterile 0.9% NaCl solution. SPLV injection enhanced serum IgA, IgM, IgG, IFN-γ, IL-1β, TNF-α and IL-10 concentrations (p dietary TIDT levels enhanced serum IgG (p dietary TIDT levels and SPLV injection (p dietary TIDT levels attenuated the increase of the serum IFN-γ concentration, and the increase of the relative mRNA abundance of TLR3, TLR7 and TLR9 in the different tissues (p dietary threonine supplementation could improve the immune status of weaned pigs injected with SPLV by down-regulating the expression of TLR3, TLR7 and TLR9 in tissues, and thus regulating T-helper cytokine secretion.

  15. The recombinant Lactococcus lactis oral vaccine induces protection against C. difficile spore challenge in a mouse model.

    Science.gov (United States)

    Guo, Shanguang; Yan, Weiwei; McDonough, Sean P; Lin, Nengfeng; Wu, Katherine J; He, Hongxuan; Xiang, Hua; Yang, Maosheng; Moreira, Maira Aparecida S; Chang, Yung-Fu

    2015-03-24

    Clostridium difficile infection (CDI) causes nosocomial antibiotic-associated diarrhea and colitis in the developed world. Two potent cytotoxins, toxin A (TcdA) and toxin B (TcdB) are the virulence factors of this disease and can be a good vaccine candidate against CDI. In the present study, we genetically engineered Lactococcus lactis to express the nontoxic, recombinant fragments derived from TcdA and TcdB C-terminal receptor binding domains (Tcd-AC and Tcd-BC) as an oral vaccine candidate. The immunogenicity of the genetically engineered L. lactis oral vaccine delivery system (animal groups LAC and LBC or the combination of both, LACBC) was compared with the recombinant TcdA and TcdB C-terminal receptor binding domain proteins (animal groups PAC and PBC or the combination of both, PACBC), which were expressed and purified from E. coli. After the C. difficile challenge, the control groups received PBS or engineered L. lactis with empty vector, showed severe diarrhea symptoms and died within 2-3 days. However, both the oral vaccine and recombinant protein vaccine groups had significantly lower mortalities, body weight decreases and histopathologic lesions than the control sham-vaccine groups (pvaccinated animals produced higher titers of both IgG and IgA than the control groups (pvaccine against CDI.

  16. Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges.

    Science.gov (United States)

    Mathews, Stephanie; Xu, Mingjiang; Wang, Hua; Bertola, Adeline; Gao, Bin

    2014-05-15

    Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

  17. Predictive validity of a MK-801-induced cognitive impairment model in mice: implications on the potential limitations and challenges of modeling cognitive impairment associated with schizophrenia preclinically.

    Science.gov (United States)

    Brown, Jordan W; Rueter, Lynne E; Zhang, Min

    2014-03-03

    Cognitive impairment associated with schizophrenia (CIAS) is a major and disabling symptom domain of the disease that is generally unresponsive to current pharmacotherapies. Critically important to the discovery of novel therapeutics for CIAS is the utilization of preclinical models with robust predictive validity. We investigated the predictive validity of MK-801-induced memory impairments in mouse inhibitory avoidance (MK-IA) as a preclinical model for CIAS by investigating compounds that have been tested in humans, including antipsychotics, sodium channel blocker mood stabilizers, and putative cognitive enhancers. The atypical antipsychotic clozapine, as well as risperidone and olanzapine (see Brown et al., 2013), had no effect on MK-801-induced memory impairments. For sodium channel blockers, carbamazepine significantly attenuated memory impairments induced by MK-801, whereas lamotrigine had no effect. Nicotine, donepezil, modafinil, and xanomeline all significantly attenuated MK-801-induced memory impairments, but the magnitude of effects and the dose-responses observed varied across compounds. Clinically, only acute administration of nicotine has demonstrated consistent positive effects on CIAS, while inconsistent results have been reported for lamotrigine, donepezil, and modafinil; atypical antipsychotics produce only moderate improvements at best. A positive clinical signal has been observed with xanomeline, but only in a small pilot trial. The results presented here suggest that the MK-IA model lacks robust predictive validity for CIAS as the model is likely permissive and may indicate false positive signals for compounds and mechanisms that lack clear clinical efficacy for CIAS. Our findings also highlight the potential limitations and challenges of using NMDA receptor antagonists in rodents to model CIAS.

  18. The bovine viral diarrhea virus E2 protein formulated with a novel adjuvant induces strong, balanced immune responses and provides protection from viral challenge in cattle.

    Science.gov (United States)

    Snider, Marlene; Garg, Ravendra; Brownlie, Robert; van den Hurk, Jan V; van Drunen Littel-van den Hurk, Sylvia

    2014-11-28

    Bovine viral diarrhea virus (BVDV) is still one of the most serious pathogens in cattle, meriting the development of improved vaccines. Recently, we developed a new adjuvant consisting of poly[di(sodium carboxylatoethylphenoxy)]-phosphazene (PCEP), either CpG ODN or poly(I:C), and an immune defense regulator (IDR) peptide. As this adjuvant has been shown to mediate the induction of robust, balanced immune responses, it was evaluated in an E2 subunit vaccine against BVDV in lambs and calves. The BVDV type 2 E2 protein was produced at high levels in a mammalian expression system and purified. When formulated with either CpG ODN or poly(I:C), together with IDR and PCEP, the E2 protein elicited high antibody titers and production of IFN-γ secreting cells in lambs. As the immune responses were stronger when poly(I:C) was used, the E2 protein with poly(I:C), IDR and PCEP was subsequently tested in cattle. Robust virus neutralizing antibodies as well as cell-mediated immune responses, including CD8(+) cytotoxic T cell (CTL) responses, were induced. The fact that CTL responses were demonstrated in calves vaccinated with an E2 protein subunit vaccine indicates that this adjuvant formulation promotes cross-presentation. Furthermore, upon challenge with a high dose of virulent BVDV-2, the vaccinated calves showed almost no temperature response, weight loss, leukopenia or virus replication, in contrast to the control animals, which had severe clinical disease. These data suggest that this E2 subunit formulation induces significant protection from BVDV-2 challenge, and thus is a promising BVDV vaccine candidate; in addition, the adjuvant platform has applications in bovine vaccines in general.

  19. Effects of Syzygium aromaticum-derived triterpenes on postprandial blood glucose in streptozotocin-induced diabetic rats following carbohydrate challenge.

    Directory of Open Access Journals (Sweden)

    Andile Khathi

    Full Text Available PURPOSE: Recent reports suggest that the hypoglycaemic effects of the triterpenes involve inhibition of glucose transport in the small intestine. Therefore, the effects of Syzygium spp-derived triterpenes oleanolic acid (OA and maslinic acid (MA were evaluated on carbohydrate hydrolyzing enzymes in STZ-induced diabetic rats and consequences on postprandial hyperglycaemia after carbohydrate loading. METHODS: We determined using Western blot analysis the expressions of α-amylase and α-glucosidase and glucose transporters SGLT1 and GLUT2 in the small intestine intestines isolated from diabetic rats treated with OA/MA for 5 weeks. In vitro assays were used to assess the inhibitory activities of OA and MA against α-amylase, α-glucosidase and sucrase. RESULTS: OA and MA ameliorated postprandial hyperglycemia in carbohydrate loaded diabetic rats as indicated by the significantly small glucose area under the curve (AUC in treated diabetic animals compared with that in untreated diabetic rats. Western blotting showed that OA and MA treatment not only down-regulated the increase of SGLT1 and GLUT2 expressions in the small intestine of STZ-induced diabetic rats, but also inhibited small intestine α-amylase, sucrase and α-glucosidase activity. IC50 values of OA against α-amylase (3.60 ± 0.18 mmol/L, α-glucosidase (12.40 ± 0.11 mmol/L and sucrase (11.50 ± 0.13 mmol/L did not significantly differ from those of OA and acarbose. CONCLUSIONS: The results of suggest that OA and MA may be used as potential supplements for treating postprandial hyperglycemia. NOVELTY OF THE WORK: The present observations indicate that besides improving glucose homeostasis in diabetes, OA and MA suppress postprandial hyperglycaemia mediated in part via inhibition of carbohydrate hydrolysis and reduction of glucose transporters in the gastrointestinal tract. Inhibition of α-glucosidase and α-amylase can significantly decrease the postprandial hyperglycaemia after a mixed

  20. A single immunization with HA DNA vaccine by electroporation induces early protection against H5N1 avian influenza virus challenge in mice

    Directory of Open Access Journals (Sweden)

    Chen Jianjun

    2009-02-01

    Full Text Available Abstract Background Developing vaccines for the prevention of human infection by H5N1 influenza viruses is an urgent task. DNA vaccines are a novel alternative to conventional vaccines and should contribute to the prophylaxis of emerging H5N1 virus. In this study, we assessed whether a single immunization with plasmid DNA expressing H5N1 hemagglutinin (HA could provide early protection against lethal challenge in a mouse model. Methods Mice were immunized once with HA DNA at 3, 5, 7 days before a lethal challenge. The survival rate, virus titer in the lungs and change of body weight were assayed to evaluate the protective abilities of the vaccine. To test the humoral immune response induced by HA DNA, serum samples were collected through the eye canthus of mice on various days after immunization and examined for specific antibodies by ELISA and an HI assay. Splenocytes were isolated after the immunization to determine the antigen-specific T-cell response by the ELISPOT assay. Results Challenge experiments revealed that a single immunization of H5N1 virus HA DNA is effective in early protection against lethal homologous virus. Immunological analysis showed that an antigen-specific antibody and T-cell response could be elicited in mice shortly after the immunization. The protective abilities were correlated with the amount of injected DNA and the length of time after vaccination. Conclusion A single immunization of 100 μg H5 HA DNA vaccine combined with electroporation was able to provide early protection in mice against homologous virus infection.

  1. A preliminary study of the effects of individual response to challenge tests and stress induced by humans on learning performance of weaned piglets (Sus scrofa).

    Science.gov (United States)

    Brajon, Sophie; Laforest, Jean-Paul; Schmitt, Océane; Devillers, Nicolas

    2016-08-01

    This study investigated whether individual behavioural characteristics of piglets and stress induced by experience with humans can influence learning performance. After weaning, piglets received a chronic experience with humans to modulate their emotional state: rough (ROU), gentle (GEN), or minimal (MIN) experience. Simultaneously, they were trained on a discrimination task. Afterward, their behaviour during challenge tests was assessed. The first learning step of the task involved associating a positive sound cue with a response (approach a trough) and success of piglets depended mostly on motivation to seek for reward. Although the experience with humans did not have direct effect, the degree of fear of handler, measured based on their reactivity to a human approach test, was related to motivation to seek rewards and learning speed of this first step in stressed ROU piglets, but not in MIN and GEN piglets. In contrast, the second learning step was more cognitively challenging, since it involved discrimination learning, including negative cues during which piglets had to learn to avoid the trough. Locomotion activity, measured during an open-field test, was associated with performance of the discrimination learning. To conclude, fearfulness towards humans and locomotion activity are linked with learning performance in relation to task complexity, highlighting the necessity to take into account these factors in animal research and management.

  2. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  3. Immunization with Individual Proteins of the Lrp/AsnC Family Induces Protection Against Brucella melitensis 16M Challenges in Mice

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    Xinhui eWang

    2015-10-01

    Full Text Available Brucellosis is one of the most common zoonoses worldwide. Subunit vaccines are promising for the prevention of human brucellosis. In our previous protective antigen screening studies, we identified a new protective antigen, BMEI0357, which belongs to the Lrp/asnC protein family, a conserved transcriptional regulator in bacteria that is absent in eukaryotes. In the present study, the Brucella genome annotation was screened and a total of 6 proteins were identified as members of the Lrp/AsnC family. Lrp/AsnC proteins have 2 domains that are conserved among the family members. However, sequence similarities between these proteins ranged from 9% to 50%, indicating high sequence heterogeneity. To test whether proteins of this family have similar characteristics, all 6 proteins were cloned and expressed in Escherichia coli. The recombinant proteins were purified and their protective efficacy was evaluated in BALB/c mice challenged with Brucella melitensis 16M. The results show that all 6 Lrp/AsnC proteins could induce a protective immune response against Brucella melitensis 16M. Antibodies against the Lrp/AsnC proteins were detected in the immunized mice. However, levels of antibodies against these proteins were relatively variable in human brucellosis sera. Taken together, our results show that these 6 proteins of the Lrp/AsnC family in Brucella could induce protective immune responses in mice.

  4. Vaccination with recombinant adenoviruses expressing the peste des petits ruminants virus F or H proteins overcomes viral immunosuppression and induces protective immunity against PPRV challenge in sheep.

    Directory of Open Access Journals (Sweden)

    José M Rojas

    Full Text Available Peste des petits ruminants (PPR is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV. Two recombinant replication-defective human adenoviruses serotype 5 (Ad5 expressing either the highly immunogenic fusion protein (F or hemagglutinin protein (H from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses. Thus, neutralizing antibodies were detected in sera from immunized sheep. In addition, we detected a significant antigen specific T-cell response in vaccinated sheep against two different PPRV strains, indicating that the vaccine induced heterologous T cell responses. Importantly, no clinical signs and undetectable virus shedding were observed after virulent PPRV challenge in vaccinated sheep. These vaccines also overcame the T cell immunosuppression induced by PPRV in control animals. The results indicate that these adenovirus constructs could be a promising alternative to current vaccine strategies for the development of PPRV DIVA vaccines.

  5. Two outer membrane lipoproteins from Histophilus somni are immunogenic in rabbits and sheep and induce protection against bacterial challenge in mice.

    Science.gov (United States)

    Guzmán-Brambila, Carolina; Rojas-Mayorquín, Argelia E; Flores-Samaniego, Beatriz; Ortuño-Sahagún, Daniel

    2012-11-01

    Histophilus somni is an economically important pathogen of cattle and other ruminants and is considered one of the key components of the bovine respiratory disease (BRD) complex, the leading cause of economic loss in the livestock industry. BRD is a multifactorial syndrome, in which a triad of agents, including bacteria, viruses, and predisposing factors or "stressors," combines to induce disease. Although vaccines against H. somni have been used for many decades, traditional bacterins have failed to demonstrate effective protection in vaccinated animals. Hence, the BRD complex continues to produce strong adverse effects on the health and well-being of stock and feeder cattle. The generation of recombinant proteins may facilitate the development of more effective vaccines against H. somni, which could confer better protection against BRD. In the present study, primers were designed to amplify, clone, express, and purify two recombinant lipoproteins from H. somni, p31 (Plp4) and p40 (LppB), which are structural proteins of the outer bacterial membrane. The results presented here demonstrate, to our knowledge for the first time, that when formulated, an experimental vaccine enriched with these two recombinant lipoproteins generates high antibody titers in rabbits and sheep and exerts a protective effect in mice against septicemia induced by H. somni bacterial challenge.

  6. Transcutaneous immunization with toxin-coregulated pilin A induces protective immunity against Vibrio cholerae O1 El Tor challenge in mice.

    Science.gov (United States)

    Rollenhagen, Julianne E; Kalsy, Anuj; Cerda, Francisca; John, Manohar; Harris, Jason B; Larocque, Regina C; Qadri, Firdausi; Calderwood, Stephen B; Taylor, Ronald K; Ryan, Edward T

    2006-10-01

    Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], 50 mug) on days 0, 19, and 40. Mice immunized with TcpA alone did not develop anti-TcpA responses. Mice that received transcutaneously applied TcpA and CT developed prominent anti-TcpA immunoglobulin G (IgG) serum responses but minimal anti-TcpA IgA. Transcutaneous immunization with CT induced prominent IgG and IgA anti-CT serum responses. In an infant mouse model, offspring born to dams transcutaneously immunized either with TcpA and CT or with CT alone were challenged with 10(6) CFU (one 50% lethal dose) wild-type V. cholerae O1 El Tor strain N16961. At 48 h, mice born to females transcutaneously immunized with CT alone had 36% +/- 10% (mean +/- standard error of the mean) survival, while mice born to females transcutaneously immunized with TcpA and CT had 69% +/- 6% survival (P < 0.001). Our results suggest that transcutaneous immunization with TcpA and an immunoadjuvant induces protective anti-TcpA immune responses. Anti-TcpA responses may contribute to an optimal cholera vaccine.

  7. Aspects of T Cell-Mediated Immunity Induced in Mice by a DNA Vaccine Based on the Dengue-NS1 Antigen after Challenge by the Intracerebral Route

    Science.gov (United States)

    Oliveira, Edson R. A.; Gonçalves, Antônio J. S.; Costa, Simone M.; Azevedo, Adriana S.; Mantuano-Barradas, Marcio; Nogueira, Ana Cristina M. A.

    2016-01-01

    Dengue disease has emerged as a major public health issue across tropical and subtropical countries. Infections caused by dengue virus (DENV) can evolve to life-threatening forms, resulting in about 20,000 deaths every year worldwide. Several animal models have been described concerning pre-clinical stages in vaccine development against dengue, each of them presenting limitations and advantages. Among these models, a traditional approach is the inoculation of a mouse-brain adapted DENV variant in immunocompetent animals by the intracerebral (i.c.) route. Despite the historical usage and relevance of this model for vaccine testing, little is known about the mechanisms by which the protection is developed upon vaccination. To cover this topic, a DNA vaccine based on the DENV non-structural protein 1 (pcTPANS1) was considered and investigations were focused on the induced T cell-mediated immunity against i.c.-DENV infection. Immunophenotyping assays by flow cytometry revealed that immunization with pcTPANS1 promotes a sustained T cell activation in spleen of i.c.-infected mice. Moreover, we found that the downregulation of CD45RB on T cells, as an indicator of cell activation, correlated with absence of morbidity upon virus challenge. Adoptive transfer procedures supported by CFSE-labeled cell tracking showed that NS1-specific T cells induced by vaccination, proliferate and migrate to peripheral organs of infected mice, such as the liver. Additionally, in late stages of infection (from the 7th day onwards), vaccinated mice also presented reduced levels of circulating IFN-γ and IL-12p70 in comparison to non-vaccinated animals. In conclusion, this work presented new aspects about the T cell-mediated immunity concerning DNA vaccination with pcTPANS1 and the i.c. infection model. These insights can be explored in further studies of anti-dengue vaccine efficacy. PMID:27631083

  8. Brucella abortus Omp19 recombinant protein subcutaneously co-delivered with an antigen enhances antigen-specific T helper 1 memory responses and induces protection against parasite challenge.

    Science.gov (United States)

    Coria, Lorena M; Ibañez, Andrés E; Pasquevich, Karina A; Cobiello, Paula L González; Frank, Fernanda M; Giambartolomei, Guillermo H; Cassataro, Juliana

    2016-01-20

    The discovery of effective adjuvants for many vaccines especially those with limited commercial appeal, such as vaccines to poverty-related diseases, is required. In this work, we demonstrated that subcutaneous co-administration of mice with the outer membrane protein U-Omp19 from Brucella spp. plus OVA as antigen (Ag) increases Ag-specific T cell proliferation and T helper (Th) 1 immune responses in vitro and in vivo. U-Omp19 treated dendritic cells promote IFN-γ production by specific CD4(+) T cells and increases T cell proliferation. U-Omp19 co-administration induces the production of Ag specific effector memory T cell populations (CD4(+) CD44(high) CD62L(low) T cells). Finally, subcutaneous co-administration of U-Omp19 with Trypanosoma cruzi Ags confers protection against virulent parasite challenge, reducing parasitemia and weight loss while increasing mice survival. These results indicate that the bacterial protein U-Omp19 when delivered subcutaneously could be a suitable component of vaccine formulations against infectious diseases requiring Th1 immune responses.

  9. IFNB1/interferon-ß-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Ejlerskov, Patrick; Liu, Yawei

    2013-01-01

    differs significantly from type I IFNs, can induce autophagy, no such function for any type I IFN has been reported. We show here that IFNB1 induces autophagy in MCF-7, MDAMB231 and SKBR3 breast cancer cells by measuring the turnover of two autophagic markers, MAP1LC3B/LC3 and SQSTM1/p62. The induction......IFNB1/interferon (IFN)-ß belongs to the type I IFNs and exerts potent antiproliferative, proapoptotic, antiangiogenic and immunemodulatory functions. Despite the beneficial effects of IFNB1 in experimental breast cancers, clinical translation has been disappointing, possibly due to induction...... of survival pathways leading to treatment resistance. Defects in autophagy, a conserved cellular degradation pathway, are implicated in numerous cancer diseases. Autophagy is induced in response to cancer therapies and can contribute to treatment resistance. While the type II IFN, IFNG, which in many aspects...

  10. Uncertain translation, uncertain benefit and uncertain risk: ethical challenges facing first-in-human trials of induced pluripotent stem (ips) cells.

    Science.gov (United States)

    Fung, Ronald K F; Kerridge, Ian H

    2013-02-01

    The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes.

  11. Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo.

    Science.gov (United States)

    Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M; Werling, Dirk

    2015-11-17

    Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a "proof of concept" vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage.

  12. Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.

    Science.gov (United States)

    Peters, S E; Paterson, G K; Bandularatne, E S D; Northen, H C; Pleasance, S; Willers, C; Wang, J; Foote, A K; Constantino-Casas, F; Scase, T J; Blacklaws, B A; Bryant, C E; Mastroeni, P; Charles, I G; Maskell, D J

    2010-01-01

    In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4(+) and CD8(+) T cells and B lymphocytes in the spleen and reduced infiltration by CD11b(+) cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.

  13. Protective immunity induced by irradiated third-stage larvae of the filaria Acanthocheilonema viteae is directed against challenge third-stage larvae before molting.

    Science.gov (United States)

    Bleiss, W; Oberländer, U; Hartmann, S; Adam, R; Marko, A; Schönemeyer, A; Lucius, R

    2002-04-01

    Jirds (Meriones unguiculatus) were vaccinated with irradiated L3 third-stage larvae (L3) of Acanthocheilonema viteae, and the time required for killing of the challenge L3 was determined. The number of parasites recovered from vaccinated jirds was reduced to about 10% of the control values on the second day after challenge infection and later on. Histological studies revealed an eosinophil-rich infiltrate containing macrophages, neutrophils, and mast cells in the vicinity of the L3 on day 2 after challenge and destruction of the worms by day 4 after challenge. Ultrastructural studies confirmed these data and showed that eosinophils, macrophages, and mast cells were close to the L3 on day 2 after challenge. Flattening of the eosinophils onto the surface of the worms, degranulation of electron-dense material, and rupture of the L3 surface was observed on day 4 after challenge, followed by invasion of the inner of the worms by phagocytic cells. These data show that immune attack against the challenge L3 in vaccinated jirds is initiated between the first and the second day after challenge and that killing occurs around the fourth day after challenge, before the worms undergo their first molt.

  14. Sensitization to and Challenge with Gliadin Induce Pancreatitis and Extrapancreatic Inflammation in HLA-DQ8 Mice: An Animal Model of Type 1 Autoimmune Pancreatitis

    Science.gov (United States)

    Moon, Sung-Hoon; Kim, Jihun; Kim, Mi-Young; Park, Do Hyun; Song, Tae Jun; Kim, Sun A; Lee, Sang Soo; Seo, Dong Wan; Lee, Sung Koo; Kim, Myung-Hwan

    2016-01-01

    Background/Aims The aim of this study was to establish a pathogenetic mechanism of pancreatitis in celiac disease and IgG4-related disease using gluten-sensitive human leukocyte antigen (HLA)-DQ8 transgenic mice. Methods Transgenic mice expressing HLA-DQ8 genes were utilized. Control mice were not sensitized but were fed gliadin-free rice cereal. Experimental groups consisted of gliadin-sensitized and gliadin-challenged mice; nonsensitized mice with cerulein hyperstimulation; and gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation. Results Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation showed significant inflammatory cell infiltrates, fibrosis and acinar atrophy compared with the control mice and the other experimental groups. The immunohistochemical analysis showed greater IgG1-positive plasma cells in the inflammatory infiltrates of gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation compared with the control mice and the other experimental groups. Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation or gliadin-sensitized and gliadin-challenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs. Conclusions Gliadin-sensitization and cerulein hyperstimulation of gluten-sensitive HLA-DQ8 transgenic mice resulted in pancreatitis and extrapancreatic inflammation. This animal model suggests that chronic gliadin ingestion in a susceptible individual with the HLA-DQ8 molecule may be associated with pancreatitis and extrapancreatic inflammation. PMID:27114422

  15. Challenged Pragmatism

    DEFF Research Database (Denmark)

    Christoffersen, Lisbet; Vinding, Niels Valdemar

    2013-01-01

    of religious faith have made religious claims and thereby challenged a secular understanding of the Danish labour market. This raises the question of the extent to which the religion of the individual can be accepted in the general public sphere. At the same time, religious ethos organisations have argued...

  16. Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

    Science.gov (United States)

    Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

    2015-06-01

    A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h) and/or microbiological (S. Typhi bacteremia) endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-). Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD-) were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h). Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.

  17. Mobility Challenges

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part of th...... mobilities. In particular the article discusses 1) the physical city, its infrastructures and technological hardware/software, 2) policies and planning strategies for urban mobility and 3) the lived everyday life in the city and the region.......This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part...... of the so-called ‘mobility turn’ within social science. The perspective is illustrative for the research efforts at the Centre for Mobility and Urban Studies (C-MUS), Aalborg University. The article presents the contours of a theoretical perspective meeting the challenges to research into contemporary urban...

  18. Rhizobacteria-mediated induced systemic resistance (ISR) in Arabidopsis is not associated with a direct effect on expression of known defense-related genes but stimulates the expression of the jasmonate-inducible gene Atvsp upon challenge

    NARCIS (Netherlands)

    Wees, A.C.M. van; Luijendijk, M.; Smoorenburg, I.; Loon, L.C. van; Pieterse, C.M.J.

    1999-01-01

    Selected strains of nonpathogenic rhizobacteria from the genus Pseudomonas are capable of eliciting broadspectrum induced systemic resistance (ISR) in plants that is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). In Arabidopsis, the ISR pathway functions independently

  19. Prevention of tri-nitrobenzene of sulfonic acid-induced colitis in chicken by using extract of Aloe vera

    Directory of Open Access Journals (Sweden)

    Motamed Elsayed Mahmoud

    Full Text Available Aim: Aloe vera, species of succulent plant in the genus Aloe, has multiple clinical activities and used routinely to accelerate wound healing. The present study was designed to investigate the anti-inflammatory effect of Aloe vera extracts (AVE in vitro and in vivo. Materials and Methods: The effect of crude AVE on inducible nitric oxide production by LPS/IFNg-stimulated cultured macrophages was evaluated. The therapeutic effect of administering crude Aloe vera extracts (100 mg/kg b.w. on the development of tri-nitrobenzene of sulfonic acid (TNBS-induced colitis (40 mg/kg b. w. in chicken was also investigated. Chicken is a valuable model for this purpose because it showed preference to bitter taste of Aloe vera. Diverse clinical pictures of the colitis including weight loss, diarrhea and histopathological changes were evaluated. Results: Nitrite production by LPS/IFNg-stimulated macrophages was maximally reduced by adding of AVE (100 μg/ml. This result suggests a direct inhibitory effect of AVE on the inflammatory cells. Chicks treated orally with AVE showed improvement of the histological signs with no inflammatory cell infiltrates and reduction of myeloperoxidase (MPO activities when compared with colitis control group. AVE pretreatment ameliorated significantly the clinical and histopathological severity of the TNBS-induced colitis; decreased body weight loss and diarrhea and increased survival. Conclusion: It was concluded that oral administration of AVE represents a valuable therapeutic approach for the treatment of colitis in chicken. [Vet. World 2012; 5(8.000: 469-476

  20. Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges.

    Science.gov (United States)

    Man, Mao-Qiang; Hatano, Yutaka; Lee, Seung H; Man, Mona; Chang, Sandra; Feingold, Kenneth R; Leung, Donald Y M; Holleran, Walter; Uchida, Yoshikazu; Elias, Peter M

    2008-01-01

    Atopic dermatitis (AD) is a chronic dermatosis bearing clinical, histological, and immunologic similarities to chronic allergic contact dermatitis (ACD). AD shows a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels, a permeability barrier abnormality, and Staphylococcus aureus colonization. Repeated hapten challenges reportedly produce a Th2-like hypersensitivity reaction (Th2-like HR). Here, 9-10 challenges with oxazolone (Ox) to hairless mice also produced a chronic Th2-like HR. Permeability barrier function and expression of differentiation proteins, filaggrin, loricrin, and involucrin, became abnormal. CRTH-positive Th2-dominant inflammatory infiltrate, with increased IL-4 expression, and a large increase in serum IgE levels were observed. The barrier abnormality was associated with decreased stratum corneum (SC) ceramide content and impaired lamellar body secretion, resulting in abnormal lamellar membranes, as in human AD. Furthermore, as in human AD, epidermal serine protease activity in SC increased and expression of two lamellar body-derived antimicrobial peptides, CRAMP and mBD3, declined after Ox challenges, paralleling the decrease of their human homologues in AD. Thus, multiple Ox challenges to normal murine skin produce a chronic Th2-like HR, with multiple features of human AD. Because of its reproducibility, predictability, and low cost, this model could prove useful for evaluating both pathogenic mechanisms and potential therapies for AD.

  1. Challenging Identities

    DEFF Research Database (Denmark)

    Keydar, Ceglar; Marin, Manuela; Janik, Allan;

    , cultural, and political practices. Notions of national identity and national politics are challenged by European integration, as well as by increasing demographic heterogeneity due to migration, and migrants experience conflicts of identification stemming from clashes between cultural heritage...... and the cultures of the new habitat. European horizons—frames of mind, historical memories, and expectations at the level of groups or communities, at the national level, and at the general European level—are at odds. Analyzing a series of issues in European countries from Turkey to Spain and from Scandinavia...

  2. Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

    Directory of Open Access Journals (Sweden)

    Franklin R Toapanta

    2015-06-01

    Full Text Available A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD- 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h and/or microbiological (S. Typhi bacteremia endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-. Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD- were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h. Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.

  3. Data Challenges

    CERN Multimedia

    McCubbin, N A

    Some two years ago we planned a series of Data Challenges starting at the end of 2001. At the time, that seemed to be comfortingly far in the future... Well, as the saying goes, doesn't time fly when you are having fun! ATLAS Computing is now deep in the throes of getting the first Data Challenge (DC0) up and running. One of the main aims of DC0 is to have a software 'release' in which we can generate full physics events, track all particles through the detector, simulate the detector response, reconstruct the event, and study it, with appropriate data storage en route. As all software is "always 95% ready" (!), we have been able to do most of this, more or less, for some time. But DC0 forces us to have everything working, together, at the same time: a reality check. DC0 should finish early next year, and it will be followed almost immediately afterwards by DC1 (DC0 was foreseen as the 'check' for DC1). DC1 will last into the middle of 2002, and has two major goals. The first is generation, simulation, and r...

  4. Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge

    Directory of Open Access Journals (Sweden)

    Bernard eArulanandam

    2011-12-01

    Full Text Available We have shown that immunization with soluble recombinant (r chlamydial protease-like activity factor (rCPAF and a T helper (Th 1 type adjuvant can induce significantly enhanced bacterial clearance and protection against Chlamydia–induced pathological sequelae in the genital tract. In this study, we investigated the use of bone marrow derived dendritic cells (BMDCs pulsed ex vivo with rCPAF+CpG in an adoptive subcutaneous immunization for the ability to induce protective immunity against genital chlamydial infection. We found that BMDCs pulsed with rCPAF+CpG efficiently up-regulated the expression of activation markers CD86, CD80, CD40 and major histocompatibility complex class II (MHC II, and secreted interleukin-12, but not IL-10 and IL-4. Mice adoptively immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs produced elevated levels of antigen-specific IFN- and enhanced IgG1 and IgG2a antibodies. Moreover, mice immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs exhibited significantly reduced genital Chlamydia shedding, accelerated resolution of infection, and reduced oviduct pathology when compared to infected mock-immunized animals. These results suggest that adoptive subcutaneous immunization with ex vivo rCPAF-pulsed BMDCs is an effective approach, comparable to that induced by UV-EB-BMDCs, for inducing robust anti-Chlamydia immunity.

  5. SPS Challenges

    CERN Document Server

    Chapochnikova, Elena

    2008-01-01

    In future the SPS should be able to transfer to the LHC the beam produced by a completely new pre-injector chain and required by the LHC for different upgrade scenarios. The issues related to this extremely challenging task are presented together with some possible ways of overcoming the problems that arise. Besides an increase in injection energy provided by PS2, these measures can include both an SPS vacuum chamber upgrade against the e-cloud and operation with larger longitudinal emittance for beam stability. As a result the power plant of the SPS RF system must be doubled. The SPS upgrade will also need the improvement or replacement of many other machine elements.

  6. Measuring Regional and District Variations in the Incidence of Pregnancy-induced Hypertension (PIH) in Ghana : Challenges, Opportunities and Implications for Maternal and Newborn Health Policy and Programs

    NARCIS (Netherlands)

    Antwi, Edward; Klipstein-Grobusch, Kerstin; Asare, Gloria Quansah; Koram, Kwadwo A; Grobbee, Diederick; Agyepong, Irene Akua

    2016-01-01

    OBJECTIVES: The objectives were to assess the quality of health management information system (HMIS) data needed for assessment of local area variation in pregnancy induced hypertension (PIH) incidence and to describe district and regional variations in PIH incidence. METHODS: A retrospective review

  7. Reduction of porcine circovirus type 2 (PCV2 viremia by a reformulated inactivated chimeric PCV1-2 vaccine-induced humoral and cellular immunity after experimental PCV2 challenge

    Directory of Open Access Journals (Sweden)

    Seo Hwi

    2012-10-01

    Full Text Available Abstract Background The objective of the present study was to elucidate the humoral and cellular immune response mechanisms by which a reformulated inactivated chimeric PCV1-2 vaccine reduces the PCV2 viremia. Forty PCV2 seronegative 3-week-old pigs were randomly divided into the following four groups: vaccinated challenged (T01, vaccinated non-challenged (T02, non-vaccinated challenged (T03, and non-vaccinated non-challenged (T04 animals. The pigs in groups T01 and T02 were immunized with a reformulated inactivated chimeric PCV1-2 vaccine (Fostera™ PCV; Pfizer Animal Health administered as a 2.0 ml dose at 21 days of age. At 35 days of age (0 days post-challenge, the pigs in groups T01 and T03 were inoculated intranasally with 2 ml each of PCV2b. Results A reduction of PCV2 viremia coincided with the appearance of both PCV2-specific neutralizing antibodies (NA and interferon-γ-secreting cells (IFN-γ-SCs in the vaccinated animals. However, the presence of anti-PCV2 IgG antibodies did not correlate with the reduction of PCV2 viremia. Lymphocyte subset analysis indicated that the numbers of CD3+ and CD4+ cells increased in vaccinated animals but the numbers of CD4+ cells decreased transiently in non-vaccinated animals. The observation of a delayed type hypersensitivity response in only the vaccinated animals also supports a CD4+ cell-associated protective cellular immune response induced by the reformulated inactivated chimeric PCV1-2 vaccine. Conclusions The induction of PCV2-specific NA and IFN-γ-SCs, and CD4+ cells by the reformulated inactivated chimeric PCV1-2 vaccine is the important protective immune response leading to reduction of the PCV2 viremia and control of the PCV2 infection. To our knowledge this is the first demonstration of protective humoral and cellular immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine and its effect on reduction of PCV2 viremia by vaccination.

  8. Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge.

    Directory of Open Access Journals (Sweden)

    Freek Cox

    Full Text Available There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV adjuvated with the saponin-based adjuvant Matrix-M (MM can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

  9. Scrapheap Challenge

    CERN Document Server

    2004-01-01

    Three British guys at CERN recently took a break from work to try their hand at Scrapheap Challenge. Shown on Channel 4 in the UK, it is a show where two teams must construct a machine for a specific task using only the junk they can scavenge from the scrap yard around them. And they have just 10 hours to build their contraption before it is put to the test. The first round, aired 19 September, pitted a team of three women, from the British Army's Royal Electrical and Mechanical Engineers, against the CERN guys - the Up 'n Atoms: Ali Day, David McFarlane and James Ridewood. Each team, with the help of an appointed expert, had the task of making a giant, 3-metre self-propelled "bowling ball", to roll down a 50 metre bowling alley at skittles 4 metres high. The Up 'n Atoms' contraption featured a small car with a huge wheel on its back. Once up to speed, slamming on the brakes caused the wheel to roll over and take the car with it. On their very last run they managed to take out seven pins. Luckily, though, ...

  10. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    Science.gov (United States)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  11. Induced systemic resistance and symbiotic performance of peanut plants challenged with fungal pathogens and co-inoculated with the biocontrol agent Bacillus sp. CHEP5 and Bradyrhizobium sp. SEMIA6144.

    Science.gov (United States)

    Figueredo, María Soledad; Tonelli, María Laura; Ibáñez, Fernando; Morla, Federico; Cerioni, Guillermo; Del Carmen Tordable, María; Fabra, Adriana

    2017-04-01

    Synergism between beneficial rhizobacteria and fungal pathogens is poorly understood. Therefore, evaluation of co-inoculation of bacteria that promote plant growth by different mechanisms in pathogen challenged plants would contribute to increase the knowledge about how plants manage interactions with different microorganisms. The goals of this work were a) to elucidate, in greenhouse experiments, the effect of co-inoculation of peanut with Bradyrhizobium sp. SEMIA6144 and the biocontrol agent Bacillus sp. CHEP5 on growth and symbiotic performance of Sclerotium rolfsii challenged plants, and b) to evaluate field performance of these bacteria in co-inoculated peanut plants. The capacity of Bacillus sp. CHEP5 to induce systemic resistance against S. rolfsii was not affected by the inoculation of Bradyrhizobium sp. SEMIA6144. This microsymbiont, protected peanut plants from the S. rolfsii detrimental effect, reducing the stem wilt incidence. However, disease incidence in plants inoculated with the isogenic mutant Bradyrhizobium sp. SEMIA6144 V2 (unable to produce Nod factors) was as high as in pathogen challenged plants. Therefore, Bradyrhizobium sp. SEMIA6144 Nod factors play a role in the systemic resistance against S. rolfsii. Bacillus sp. CHEP5 enhanced Bradyrhizobium sp. SEMIA6144 root surface colonization and improved its symbiotic behavior, even in S. rolfsii challenged plants. Results of field trials confirmed the Bacillus sp. CHEP5 ability to protect against fungal pathogens and to improve the yield of extra-large peanut seeds from 2.15% (in Río Cuarto) to 16.69% (in Las Vertientes), indicating that co-inoculation of beneficial rhizobacteria could be a useful strategy for the peanut production under sustainable agriculture system.

  12. An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques.

    Science.gov (United States)

    Fernandez, Stefan; Thomas, Stephen J; De La Barrera, Rafael; Im-Erbsin, Rawiwan; Jarman, Richard G; Baras, Benoît; Toussaint, Jean-François; Mossman, Sally; Innis, Bruce L; Schmidt, Alexander; Malice, Marie-Pierre; Festraets, Pascale; Warter, Lucile; Putnak, J Robert; Eckels, Kenneth H

    2015-04-01

    The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques. One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes. Most of the formulations tested prevented viremia after challenge, with the dengue serotype 1 and 2 virus strains administered at 40 and 32 weeks post-dose 2, respectively. This study shows that inactivated dengue vaccines, when formulated with alum or an Adjuvant System, are candidates for further development.

  13. Regulatory challenges

    Energy Technology Data Exchange (ETDEWEB)

    Austvik, Ole Gunnar

    2003-07-01

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for

  14. Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines.

    Science.gov (United States)

    Olleros, Maria L; Martin, Maria L; Vesin, Dominique; Fotio, Agathe L; Santiago-Raber, Marie-Laure; Rubbia-Brandt, Laura; Spahr, Laurent; Hadengue, Antoine; Garcia, Irene

    2008-10-01

    Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS.

  15. Outer membrane vesicles from flagellin-deficient Salmonella enterica serovar Typhimurium induce cross-reactive immunity and provide cross-protection against heterologous Salmonella challenge

    Science.gov (United States)

    Liu, Qiong; Liu, Qing; Yi, Jie; Liang, Kang; Hu, Bo; Zhang, Xiangmin; Curtiss, Roy; Kong, Qingke

    2016-01-01

    Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infection of multiple serotypes Salmonella. In this study, a flagellin-deficient S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein profiles and cryo-electron microscopy revealed that there were no significant differences between the wild-type and mutant OMVs, with the exception of a large amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non-flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong mucosal antibody responses in mice when administered via the intranasal route in addition to provoking higher cross-reactive immune responses against OMPs isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and intraperitoneal immunization with the non-flagellin OMVs provided efficient protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our results indicate that the flagellin-deficient OMVs may represent a new vaccine platform that could be exploited to facilitate the production of a broadly protective vaccine. PMID:27698383

  16. Vesicular stomatitis virus replicon expressing the VP2 outer capsid protein of bluetongue virus serotype 8 induces complete protection of sheep against challenge infection.

    Science.gov (United States)

    Kochinger, Stefanie; Renevey, Nathalie; Hofmann, Martin A; Zimmer, Gert

    2014-06-13

    Bluetongue virus (BTV) is an arthropod-borne pathogen that causes an often fatal, hemorrhagic disease in ruminants. Different BTV serotypes occur throughout many temperate and tropical regions of the world. In 2006, BTV serotype 8 (BTV-8) emerged in Central and Northern Europe for the first time. Although this outbreak was eventually controlled using inactivated virus vaccines, the epidemic caused significant economic losses not only from the disease in livestock but also from trade restrictions. To date, BTV vaccines that allow simple serological discrimination of infected and vaccinated animals (DIVA) have not been approved for use in livestock. In this study, we generated recombinant RNA replicon particles based on single-cycle vesicular stomatitis virus (VSV) vectors. Immunization of sheep with infectious VSV replicon particles expressing the outer capsid VP2 protein of BTV-8 resulted in induction of BTV-8 serotype-specific neutralizing antibodies. After challenge with a virulent BTV-8 strain, the vaccinated animals neither developed signs of disease nor showed viremia. In contrast, immunization of sheep with recombinant VP5 - the second outer capsid protein of BTV - did not confer protection. Discrimination of infected from vaccinated animals was readily achieved using an ELISA for detection of antibodies against the VP7 antigen. These data indicate that VSV replicon particles potentially represent a safe and efficacious vaccine platform with which to control future outbreaks by BTV-8 or other serotypes, especially in previously non-endemic regions where discrimination between vaccinated and infected animals is crucial.

  17. CHALLENGES IN MAINTAINING EMOTION REGULATION IN A SLEEP AND ENERGY DEPRIVED STATE INDUCED BY THE 4800KM ULTRA-ENDURANCE BICYCLE RACE; THE RACE ACROSS AMERICA (RAAM

    Directory of Open Access Journals (Sweden)

    Ian M. Lahart

    2013-09-01

    Full Text Available Multiday ultra-endurance races present athletes with a significant number of physiological and psychological challenges. We examined emotions, the perceived functionality (optimal-dysfunctional of emotions, strategies to regulate emotions, sleep quality, and energy intake-expenditure in a four-man team participating in the Race Across AMerica (RAAM; a 4856km continuous cycle race. Cyclists reported experiencing an optimal emotional state for less than 50% of total competition, with emotional states differing significantly between each cyclist over time. Coupled with this emotional disturbance, each cyclist experienced progressively worsening sleep deprivation and daily negative energy balances throughout the RAAM. Cyclists managed less than one hour of continuous sleep per sleep episode, high sleep latency and high percentage moving time. Of note, actual sleep and sleep efficiency were better maintained during longer rest periods, highlighting the importance of a race strategy that seeks to optimise the balance between average cycling velocity and sleep time. Our data suggests that future RAAM cyclists and crew should: 1 identify beliefs on the perceived functionality of emotions in relation to best (functional-optimal and worst (dysfunctional performance as the starting point to intervention work; 2 create a plan for support sufficient sleep and recovery; 3 create nutritional strategies that maintain energy intake and thus reduce energy deficits; and 4 prepare for the deleterious effects of sleep deprivation so that they are able to appropriately respond to unexpected stressors and foster functional working interpersonal relationships

  18. Attenuated Salmonella typhimurium delivering DNA vaccine encoding duck enteritis virus UL24 induced systemic and mucosal immune responses and conferred good protection against challenge

    Directory of Open Access Journals (Sweden)

    Yu Xia

    2012-07-01

    Full Text Available Abstract Orally delivered DNA vaccines against duck enteritis virus (DEV were developed using live attenuated Salmonella typhimurium (SL7207 as a carrier and Escherichia coli heat labile enterotoxin B subunit (LTB as a mucosal adjuvant. DNA vaccine plasmids pVAX-UL24 and pVAX-LTB-UL24 were constructed and transformed into attenuated Salmonella typhimurium SL7207 resulting SL7207 (pVAX-UL24 and SL7207 (pVAX-LTB-UL24 respectively. After ducklings were orally inoculated with SL7207 (pVAX-UL24 or SL7207 (pVAX-LTB-UL24, the anti-DEV mucosal and systemic immune responses were recorded. To identify the optimum dose that confers maximum protection, we used different doses of the candidate vaccine SL7207 (pVAX-LTB-UL24 during oral immunization. The strongest mucosal and systemic immune responses developed in the SL7207 (pVAX-LTB-UL24 (1011 CFU immunized group. Accordingly, oral immunization of ducklings with SL7207 (pVAX-LTB-UL24 showed superior efficacy of protection (60-80% against a lethal DEV challenge (1000 LD50, compared with the limited survival rate (40% of ducklings immunized with SL7207 (pVAX-UL24. Our study suggests that the SL7207 (pVAX-LTB-UL24 can be a candidate DEV vaccine.

  19. Responses of three very large inducible GTPases to bacterial and white spot syndrome virus challenges in the giant fresh water prawn Macrobrachium rosenbergii.

    Science.gov (United States)

    Huang, Ying; Jin, Min; Yin, Shaowu; Ding, Zhengfeng; Wang, Wen; Ren, Qian

    2016-04-01

    Interferons (IFNs) are cytokines secreted by cells in response to invasion by pathogens, such as viruses, bacteria, parasites, or tumor cells. Very large inducible GTPases (VLIG) are the latest IFN-inducible GTPase family to be discovered and are the largest known GTPases of any species. However, VLIG proteins from invertebrates have yet to be characterized. In this study, three forms of VLIGs designated as MrVLIG1, MrVLIG2, and MrVLIG3 were cloned from the giant fresh water prawn Macrobrachium rosenbergii. MrVLIG1 has a 5445 bp open reading frame (ORF) encoding an 1814-amino acid protein. The complete nucleotide sequence of MrVLIG2 cDNA is 7055 bp long consisting of a 5757 bp ORF encoding a protein with 1918 amino acids. The full length of the MrVLIG3 gene consists of 5511 bp with a 3909 bp ORF encoding a peptide with 1302 amino acids. BLASTP and phylogenetic tree analyses showed that the three MrVLIGs are clustered into one subgroup and, together with other vertebrate VLIGs, into a branch. Tissue distribution analysis indicated that the mRNAs of the three MrVLIGs were widely expressed in almost all detected tissues, including the hemocytes, heart, hepatopancreas, gills, stomach, and intestine, with the highest expression in the hepatopancreas. They were also detected in the intestine but with relatively low expression levels. Quantitative real-time RT-PCR analysis showed that the mRNA transcripts of the MrVLIGs in the hepatopancreas were significantly expressed at various time points after infection with Vibrio parahaemolyticus and white spot syndrome virus. In summary, the three isoforms of VLIG genes participate in the innate immune response of the shrimps to bacterial and viral infections.

  20. Effects of Slow-stroke Back Massage on Chemotherapy-induced Nausea and Vomiting in the Pediatrics with Acute Leukemia: a Challenge of Controlling Symptoms

    Directory of Open Access Journals (Sweden)

    Mojtaba Miladinia

    2015-12-01

    Full Text Available Introduction Nausea and vomiting are the most common side effects of chemotherapy in the pediatrics with cancer which affect their quality of life. Use of some methods of complementary medicine in leukemia patients is problematic. Because, leukemia patients are at risk of infection and bleeding, therefore the use of acupressure, acupuncture, and deep massage can be risky in these patients. Slow- stroke back massage is applied on the surface of body, so does not have complications. No study has addressed the effect of massage therapy on chemotherapy-induced nausea and vomiting in pediatrics with acute leukemia in the world.  Material and methods This study was a two-group randomized controlled trial (RCT, double blind and repeated measures design. In this RCT, 45 school age children with acute leukemia were placed in the massage and control groups. Before start of the study, at the day of chemotherapy administration (day 1th, only nausea and vomiting were measured. Then during 6 days next (day 2 through 7, the intervention group received 5-minutes Super Smash Bros. Melee (SSBM, immediately before start of each session of chemotherapy. Nausea was measured during chemotherapy, 0.5 h and 3 h after each session of chemotherapy in the two groups. Also vomiting was recorded during 24 h after each session of chemotherapy. Repeated measures ANOVA, Chi-square, and t-test were used for analysis. Results Most of pediatrics were male (58.13%, and suffered from Acute myeloid leukemia (AML (81.7%. The repeated measure analysis showed that in the intervention group, the SSBM reduced progressive mean of nausea severity and frequency of vomit over time. While, this side effects have slightly increased over time in the control group. Conclusion The results of this study are suggesting that SSBM, as a non-pharmacologic, easy and safe method, is effective in controlling Chemotherapy-induced nausea and vomiting (CINV in the pediatrics with acute leukemia.

  1. Modulatory effect of cilostazol on tramadol-induced behavioral and neurochemical alterations in rats challenged across the forced swim despair test

    Directory of Open Access Journals (Sweden)

    Noha M. Gamil

    2016-06-01

    Full Text Available Pain-associated depression is encountered clinically in some cases such as cancer, chronic neuropathy, and after operations. Tramadol is an opioid analgesic drug that may modulate monoaminergic neurotransmission by inhibition of noradrenaline and serotonin reuptake that may contribute to its antidepressant-like effects. Clinically, tramadol is used either alone or in combination with other NSAIDs in the treatment of cases associated with pain and depression, e.g. low back pain, spinal cord injury, and post-operative pain management. However, tramadol monotherapy as an antidepressant is impeded by severe adverse effects including seizures and serotonin syndrome. Interestingly, phosphodiesterase-III inhibitors demonstrated novel promising antidepressant effects. Among which, cilostazol was reported to attenuate depression in post-stroke cases, geriatrics and patients undergoing carotid artery stenting. Therefore, this study was carried out to investigate the possible antidepressant-like effects of tramadol and/or cilostazol on the behavioral level in experimental animals, and to examine the neurochemical and biochemical effects of tramadol, cilostazol and their combination in rats, in order to explore the probable mechanisms of action underlying their effects. To achieve our target, male albino mice and rats were randomly allocated into five groups and administered either vehicle for control, fluoxetine (20 mg/kg, p.o., tramadol HCl (20 mg/kg, p.o., cilostazol (100 mg/kg, p.o., or combination of both tramadol and cilostazol. At day 14, mice and rats were challenged in the tail suspension test and forced swim test, respectively. Rats were sacrificed and brains were isolated for determination of brain monoamines, MDA, NO, SOD, and TNF-α. The current results showed that concurrent administration of cilostazol to tramadol-treated animals modulated depression on the behavioral level, and showed ameliorative neurochemical and biochemical effects

  2. Constitutive, but Not Challenge-Induced, Interleukin-10 Production Is Robust in Acute Pre-Pubescent Protein and Energy Deficits: New Support for the Tolerance Hypothesis of Malnutrition-Associated Immune Depression Based on Cytokine Production in vivo

    Directory of Open Access Journals (Sweden)

    Bill Woodward

    2011-01-01

    Full Text Available The tolerance model of acute (i.e., wasting pre-pubescent protein and energy deficits proposes that the immune depression characteristic of these pathologies reflects an intact anti-inflammatory form of immune competence that reduces the risk of autoimmune reactions to catabolically released self antigens. A cornerstone of this proposition is the finding that constitutive (first-tier interleukin(IL-10 production is sustained even into the advanced stages of acute malnutrition. The IL-10 response to inflammatory challenge constitutes a second tier of anti-inflammatory regulation and was the focus of this investigation. Weanling mice consumed a complete diet ad libitum, a low-protein diet ad libitum (mimicking incipient kwashiorkor, or the complete diet in restricted daily quantities (mimicking marasmus, and their second-tier IL-10 production was determined both in vitro and in vivo using lipopolysaccharide (LPS and anti-CD3 as stimulants of innate and adaptive defences, respectively. Both early (3 days and advanced (14 days stages of wasting pathology were examined and three main outcomes emerged. First, classic in vitro systems are unreliable for discerning cytokine production in vivo. Secondly, in diverse forms of acute malnutrition declining challenge-induced IL-10 production may provide an early sign that anti-inflammatory control over immune competence is failing. Thirdly, and most fundamentally, the investigation provides new support for the tolerance model of malnutrition-associated inflammatory immune depression.

  3. GC-MS and NMR analysis of the bioactive compounds from the crude extracts of Waltheria indica and the histopathological changes induced in albino rats challenged with Naja nigricollis venom

    Directory of Open Access Journals (Sweden)

    Philip Ilani

    2016-05-01

    Full Text Available Objective: To develop a characteristic fingerprint of the different chemical compounds of plant by gas chromatography-mass spectrometer (GC-MS and nuclear magnetic resonance (NMR analysis and assess the effect of the crude extract on histological changes induced in Naja nigricollis (N. nigricollis envenomed albino rats. Methods: The coarsely powdered Waltheria indica (W. indica whole plant material was extracted using 70% methanol. GC-MS analysis was carried out using a Shimadzu GC-MS QP 2010 plus system of gas chromatography interfaced to a mass spectrometer. The identification of components was based on National Institute of Standard and Technology-08 and Willey-8 libraries. Hydrogen-NMR spectra of the extracts was performed using Bruker Biospin Avance 400-MHz NMR spectrophotometer with a 5 mm broad inverse probe head, equipped with shielded z-gradient accessories and C-13 NMR hetero-nuclear single quantum correction was carried out using the Brucker’s standard pulse library. The efficacy of the crude extract of W. indica whole plant was tested and the lesions induced in the liver, brain and kidney of albino rats challenged with N. nigricollis were analyzed by light microscopy. Results: The identification of the bioactive compounds from W. indica by GC-MS analysis revealed 41 peaks. A total of 38 compounds were identified with majority having important pharmacological activities that included anti-microbial, anti-cancer, anti-oxidant antiinflammatory, anti-allergenic, anti-ageing, anti-arthritic, larvicidal, anti-convulsant and herbicidal activities. C-13 and hydrogen-NMR analysis of W. indica elucidated key bioactive compounds in the whole plant that were consistent with the classes of bioactive compounds detected by GC-MS analysis. The efficacy of the crude extract of W. indica whole plant in ameliorating histopathological lesions induced in the liver, brain and kidney of albino rats challenged with N. nigricollis venom revealed the

  4. GC-MS and NMR analysis of the bioactive compounds from the crude extracts ofWaltheria indica and the histopathological changes induced in albino rats challenged withNaja nigricollis venom

    Institute of Scientific and Technical Information of China (English)

    Philip Ilani; Nicholas Ajodo; Folashade Adewusi; Samirat Yakubu; Victor Yakubu Cosmos; Ache Eunice; Atonila Kayode Ezekiel; Oshiedu Sarah; Emmanuel Amlabu

    2016-01-01

    Objective:To develop a characteristic fingerprint of the different chemical compounds of plant by gas chromatography-mass spectrometer (GC-MS) and nuclear magnetic resonance (NMR) analysis and assess the effect of the crude extract on histological changes induced inNaja nigricollis(N. nigricollis)envenomed albino rats. Methods: The coarsely powderedWaltheria indica (W. indica) whole plant material was extracted using 70% methanol.GC-MS analysis was carried out using a ShimadzuGC-MS QP 2010 plus system of gas chromatography interfaced to a mass spectrometer. The identification of components was based on National Institute of Standard and Technology-08 and Willey-8 libraries. Hydrogen-NMR spectra of the extracts was performed using Bruker Biospin Avance 400-MHzNMR spectrophotometer with a 5 mm broad inverse probe head, equipped with shielded z-gradient accessories andC-13 NMR hetero-nuclear single quantum correction was carried out using the Brucker’s standard pulse library. The efficacy of the crude extract ofW. indica whole plant was tested and the lesions induced in the liver, brain and kidney of albino rats challenged withN. nigricollis were analyzed by light microscopy. Results:The identification of the bioactive compounds fromW. indica byGC-MS analysis revealed 41 peaks. A total of 38 compounds were identified with majority having important pharmacological activities that included anti-microbial, anti-cancer, anti-oxidant anti-inflammatory, anti-allergenic, anti-ageing, anti-arthritic, larvicidal, anti-convulsant and herbicidal activities.C-13 and hydrogen-NMR analysis ofW. indica elucidated key bioactive compounds in the whole plant that were consistent with the classes of bioactive compounds detected byGC-MS analysis. The efficacy of the crude extract ofW. indica whole plant in ameliorating histopathological lesions induced in the liver, brain and kidney of albino rats challenged withN. nigricollis venom revealed the abrogation of tissue degeneration when

  5. Factors regulated by interferon gamma and hypoxia-inducible factor 1A contribute to responses that protect mice from Coccidioides immitis infection

    Directory of Open Access Journals (Sweden)

    Woelk Christopher H

    2012-09-01

    Full Text Available Abstract Background Coccidioidomycosis results from airborne infections caused by either Coccidioides immitis or C. posadasii. Both are pathogenic fungi that live in desert soil in the New World and can infect normal hosts, but most infections are self-limited. Disseminated infections occur in approximately 5% of cases and may prove fatal. Mouse models of the disease have identified strains that are resistant (e.g. DBA/2 or susceptible (e.g. C57BL/6 to these pathogens. However, the genetic and immunological basis for this difference has not been fully characterized. Results Microarray technology was used to identify genes that were differentially expressed in lung tissue between resistant DBA/2 and sensitive C57BL/6 mice after infection with C. immitis. Differentially expressed genes were mapped onto biological pathways, gene ontologies, and protein interaction networks, which revealed that innate immune responses mediated by Type II interferon (i.e., IFNG and the signal transducer and activator of transcription 1 (STAT1 contribute to the resistant phenotype. In addition, upregulation of hypoxia inducible factor 1A (HIF1A, possibly as part of a larger inflammatory response mediated by tumor necrosis factor alpha (TNFA, may also contribute to resistance. Microarray gene expression was confirmed by real-time quantitative PCR for a subset of 12 genes, which revealed that IFNG HIF1A and TNFA, among others, were significantly differentially expressed between the two strains at day 14 post-infection. Conclusion These results confirm the finding that DBA/2 mice express more Type II interferon and interferon stimulated genes than genetically susceptible strains and suggest that differential expression of HIF1A may also play a role in protection.

  6. Thank You, Challenges!

    Institute of Scientific and Technical Information of China (English)

    陈晨; 陈传光

    2016-01-01

    A person may meet many challenges in his or her life.Some people think challenges are terrible.But I think they’re great.And I want to say,"Thank you,challenges!"For some people,it’s hard to face the challenges because they are afraid of failing in the end.However,it’s necessary for a person to face the challenges.Challenges are good to~①you.

  7. Foreign Body Induced Neuralgia: A Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    S. Padmashree

    2013-01-01

    Full Text Available Neuropathic pain is caused by neural injury or painful states associated with either peripheral or central nerve injury. One of the aetiologies of this type of pain is iatrogenic trauma. This case highlights the features of peripheral neuropathic pain caused by foreign body left in the mental foramen following a previous surgical procedure. The foreign body was detected on routine radiographic evaluation. Once the foreign body was removed by surgical intervention, the pain resolved. This stresses the importance of routine radiographic evaluation in proper diagnosis and treatment planning in the management of neuropathic pain. This paper also sheds light on the role of iatrogenic mechanical cause of peripheral neuropathic pain and warrants a tough degree of caution on the part of oral clinicians.

  8. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway.

    Science.gov (United States)

    Petecchia, Loredana; Sabatini, Federica; Usai, Cesare; Caci, Emanuela; Varesio, Luigi; Rossi, Giovanni A

    2012-08-01

    Epithelial barrier permeability is altered in inflammatory respiratory disorders by a variety of noxious agents through modifications of the epithelial cell structure that possibly involve tight junction (TJ) organization. To evaluate in vitro whether pro-inflammatory cytokines involved in the pathogenesis of respiratory disorders could alter TJ organization and epithelial barrier integrity, and to characterize the signal transduction pathway involved Calu-3 airway epithelial cells were exposed to TNF-a, IL-4 and IFN-g to assess changes in: (a) TJ assembly, that is, occludin and zonula occludens (ZO)-1 expression and localization, evaluated by confocal microscopy; (b) apoptotic activity, quantified using terminal transferase deoxyuridine triphosphate nick-end labeling staining; (c) epithelial barrier integrity, detected as transmembrane electrical resistance and expressed as G(T) values; (d) epidermal growth factor receptor (EGFR)-dependent mitogenactivated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinases (ERK)1/2 phosphorylation, assessed by western blotting. Exposure to cytokines for 48 h induced a noticeable downregulation of the TJ transmembrane proteins. The degree ZO-1 and occludin colocalization was 62±2% in control cultures and significantly decreased in the presence of TNF-a (47±3%), IL-4 (43±1%) and INF-g (35±3%). Although no apoptosis induction was detected following exposure to cytokines, changes in the epithelial barrier integrity were observed, with a significant enhancement in paracellular conductance. G(T) values were, respectively, 1.030±0.0, 1.300±0.04, 1.260±0.020 and 2.220±0.015 (mS/cm²)1000 in control cultures and in those exposed to TNF-a, IFN-g and IL-4. The involvement of EGFR-dependent MAPK/ERK1/2 signaling pathway in cytokine-induced damage was demonstrated by a significant increase in threonine/tyrosine phosphorylation of ERK1/2, already detectable after 5 min incubation. All these cytokine-induced changes were

  9. Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yang, E-mail: yangshi_xz@126.com; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

    2015-05-22

    Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation.

  10. 78 FR 49296 - Centennial Challenges 2014 Sample Return Robot Challenge

    Science.gov (United States)

    2013-08-13

    ... SPACE ADMINISTRATION Centennial Challenges 2014 Sample Return Robot Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Sample Return Robot... Robot Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  11. Fine-tuning synthesis of Yersinia pestis LcrV from runaway-like replication balanced-lethal plasmid in a Salmonella enterica serovar typhimurium vaccine induces protection against a lethal Y. pestis challenge in mice.

    Science.gov (United States)

    Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M; Branger, Christine G; Tinge, Steven A; Curtiss, Roy

    2010-06-01

    A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal DeltaasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain chi9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/P(cro)) (P(R)), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC P(BAD) c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of beta-lactamase, and cloned into pYA4534 under the control of the P(trc) promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain chi9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route.

  12. National Drug IQ Challenge

    Science.gov (United States)

    ... Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2016 National Drug IQ Challenge ... Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2015 National Drug IQ Challenge ...

  13. The Backpack Design Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    Something as simple as carrying books to school can be an interesting design challenge for students. It's an old problem that gets reinvented from time to time. In this article, the author discusses a backpack design challenge in which teachers work with students to design another way to carry books to school. The challenge started by trying to…

  14. Climate challenges, vulnerabilities, and food security

    OpenAIRE

    Margaret C. Nelson; Ingram, Scott E.; Dugmore, Andrew J.; Streeter, Richard; Matthew A. Peeples; McGovern, Thomas H.; Hegmon, Michelle; Arneborg, Jette; Keith W. Kintigh; Brewington, Seth; Spielmann, Katherine A.; Simpson, Ian A; Strawhacker, Colleen; Comeau, Laura E. L.; Torvinen, Andrea

    2015-01-01

    Climate-induced disasters are impacting human well-being in ever-increasing ways. Disaster research and management recognize and emphasize the need to reduce vulnerabilities, although extant policy is not in line with this realization. This paper assesses the extent to which vulnerability to food shortage, as a result of social, demographic, and resource conditions at times of climatic challenge, correlates with subsequent declines in social and food security. Extreme climate challenges are i...

  15. Generation of colonies of induced trophoblast cells during standard reprogramming of porcine fibroblasts to induced pluripotent stem cells.

    Science.gov (United States)

    Ezashi, Toshihiko; Matsuyama, Haruyo; Telugu, Bhanu Prakash V L; Roberts, R Michael

    2011-10-01

    During reprogramming of porcine mesenchymal cells with a four-factor (POU5F1/SOX2/KLF4/MYC) mixture of vectors, a fraction of the colonies had an atypical phenotype and arose earlier than the recognizable porcine induced pluripotent stem (iPS) cell colonies. Within days after each passage, patches of cells with an epithelial phenotype formed raised domes, particularly under 20% O(2) conditions. Relative to gene expression of the iPS cells, there was up-regulation of genes for transcription factors associated with trophoblast (TR) lineage emergence, e.g., GATA2, PPARG, MSX2, DLX3, HAND1, GCM1, CDX2, ID2, ELF5, TCFAP2C, and TEAD4 and for genes required for synthesis of products more typical of differentiated TR, such as steroids (HSD17B1, CYP11A1, and STAR), pregnancy-associated glycoproteins (PAG6), and select cytokines (IFND, IFNG, and IL1B). Although POU5F1 was down-regulated relative to that in iPS cells, it was not silenced in the induced TR (iTR) cells over continued passage. Like iPS cells, iTR cells did not senesce on extended passage and displayed high telomerase activity. Upon xenografting into immunodeficient mice, iTR cells formed nonhemorrhagic teratomas composed largely of layers of epithelium expressing TR markers. When cultured under conditions that promoted embryoid body formation, iTR cells formed floating spheres consisting of a single epithelial sheet whose cells were tethered laterally by desmosome-like structures. In conclusion, reprogramming of porcine fibroblasts to iPS cells generates, as a by-product, colonies composed of self-renewing populations of TR cells, possibly containing TR stem cells.

  16. Indirect airway challenges

    NARCIS (Netherlands)

    Joos, GF; O'Connor, B; Anderson, SD; Chung, F; Cockcroft, DW; Dahlen, B; DiMaria, G; Foresi, A; Hargreave, FE; Holgate, ST; Inman, M; Lotvall, J; Magnussen, H; Polosa, R; Postma, DS; Riedler, J

    2003-01-01

    Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Di

  17. Science Challenge Day

    Science.gov (United States)

    Siegel, Deborah

    2013-01-01

    Science fairs can be good motivators, but as extracurricular activities, they leave some students behind. However, by staging a Science Challenge Day at school, educators can involve all students in doing everything from choosing activities to judging projects. This article presents a model for running a successful Science Challenge Day. The…

  18. Challenge and Change

    Science.gov (United States)

    Mehaffy, George L.

    2012-01-01

    In the past twenty years, various industries have been forever altered by technology: newspapers, book publishing, the photography business, and many more. Higher education too faces unprecedented challenges primarily driven by rapid changes in technology. To meet these challenges and adapt to these changes, new models are needed. Six challenges…

  19. Big Data Challenges

    Directory of Open Access Journals (Sweden)

    Alexandru Adrian TOLE

    2013-10-01

    Full Text Available The amount of data that is traveling across the internet today, not only that is large, but is complex as well. Companies, institutions, healthcare system etc., all of them use piles of data which are further used for creating reports in order to ensure continuity regarding the services that they have to offer. The process behind the results that these entities requests represents a challenge for software developers and companies that provide IT infrastructure. The challenge is how to manipulate an impressive volume of data that has to be securely delivered through the internet and reach its destination intact. This paper treats the challenges that Big Data creates.

  20. Challenges of serious games

    Directory of Open Access Journals (Sweden)

    B. Fernández-Manjón

    2015-11-01

    Full Text Available Although educational games have revealed to be a very effective focus in diverse situations, their use in education is still very limited. In this paper we analyse the main challenges concerning educational games that, from our perspective, have to be approached so that the use of this kind of games can be widespread. These challenges are classified in three main dimensions: socio-cultural, educational and technological. Once the challenges are identified, some possible measures are suggested to address or reduce these problems so that the use of educational games may be widespread.

  1. Community Challenge Grantees

    Data.gov (United States)

    Department of Housing and Urban Development — HUD's Community Challenge Grants aim to reform and reduce barriers to achieving affordable, economically vital and sustainable communities. The funds are awarded to...

  2. Better Buildings Challenge Overview

    Energy Technology Data Exchange (ETDEWEB)

    None

    2011-06-01

    The Better Buildings Challenge is a national leadership initiative calling on corporate chief executive officers, university presidents, and state and local leaders to make a significant commitment to building energy efficiency.

  3. Big data challenges

    DEFF Research Database (Denmark)

    Bachlechner, Daniel; Leimbach, Timo

    2016-01-01

    Although reports on big data success stories have been accumulating in the media, most organizations dealing with high-volume, high-velocity and high-variety information assets still face challenges. Only a thorough understanding of these challenges puts organizations into a position in which...... they can make an informed decision for or against big data, and, if the decision is positive, overcome the challenges smoothly. The combination of a series of interviews with leading experts from enterprises, associations and research institutions, and focused literature reviews allowed not only...... framework are also relevant. For large enterprises and startups specialized in big data, it is typically easier to overcome the challenges than it is for other enterprises and public administration bodies....

  4. Brazil World Cup Challenges

    Directory of Open Access Journals (Sweden)

    MANSUR, R.

    2012-12-01

    Full Text Available Overcoming the productivity challenge is the main benefit of the 2014 World Cup for Brazilian people. The sustainable development of our cultural tourism industry will catapult the new middle class growing up rate.

  5. The Electric Car Challenge.

    Science.gov (United States)

    Diehl, Brian E.

    1997-01-01

    Describes the Electric Car Challenge during which students applied methods of construction to build lightweight, strong vehicles that were powered by electricity. The activity required problem solving, sheet metal work, electricity, design, and construction skills. (JOW)

  6. A challenging read

    Directory of Open Access Journals (Sweden)

    Cathy Foley

    2004-11-01

    Full Text Available Andrei Mourachkine uses his new book to argue that superconductivity could be achieved at room temperature and, while his thesis may rest on some unconfirmed evidence, it does challenge preconceptions, says Cathy Foley.

  7. MDP challenges from a software provider's perspective

    Science.gov (United States)

    Ohara, Shuichiro

    2014-10-01

    This industry faces new challenges every day. It gets tougher as process nodes shrink and the data complexity and volume increase. We are a mask data preparation (MDP) software provider, and have been providing MDP systems to mask shops since 1990. As the industry has, MDP software providers also have been facing new challenges over time, and the challenges get tougher as process nodes shrink and the data complexity and volume increase. We discuss such MDP challenges and solutions in this paper from a MDP software provider's perspective. The data volume continuously increases, and it is caused by shrinking the process node. In addition, resolution enhancement techniques (RET) such as optical proximity correction (OPC) and inverse lithography technique (ILT) induce data complexity, and it contributes considerably to the increase in data volume. The growth of data volume and complexity brings challenges to MDP system, such as the computing speed, shot count, and mask process correction (MPC). New tools (especially mask writers) also bring new challenges. Variable-shaped E-beam (VSB) mask writers demand fracturing less slivers and lower figure counts for CD accuracy and write time requirements respectively. Now multibeam mask writers are under development and will definitely bring new challenges.

  8. 78 FR 19742 - Centennial Challenges: 2014 Night Rover Challenge

    Science.gov (United States)

    2013-04-02

    ... Rover Challenge purse is $1,500,000 (one million five hundred thousand U.S. dollars). Prizes will be... SPACE ADMINISTRATION Centennial Challenges: 2014 Night Rover Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Night Rover Challenge....

  9. Antibodies specific for hypervariable regions 3 to 5 of the feline immunodeficiency virus envelope glycoprotein are not solely responsible for vaccine-induced acceleration of challenge infection in cats

    NARCIS (Netherlands)

    W. Huisman (Willem); E.J.A. Schrauwen (Eefje); S.D. Pas (Suzan); J.A. Karlas (Jos); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2004-01-01

    textabstractIn a previous vaccination study in cats, the authors reported on accelerated feline immunodeficiency virus (FIV) replication upon challenge in animals vaccinated with a candidate envelope subunit vaccine. Plasma transfer studies as well as antibody profiles in vaccinated cats indicated a

  10. Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

    Directory of Open Access Journals (Sweden)

    Morawetz R.A.

    1998-01-01

    Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

  11. Challenges in obesity research

    Directory of Open Access Journals (Sweden)

    Andreu Palou

    2013-09-01

    Full Text Available Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  12. Challenges in obesity research.

    Science.gov (United States)

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  13. Radiogenomics - current status, challenges and future directions

    DEFF Research Database (Denmark)

    Andreassen, Christian Nicolaj; Schack, Line Meinertz Hybel; Laursen, Louise Vagner;

    2016-01-01

    . These strategies include 'big data approaches' and collaborative research within international consortia. Furthermore, research that combines the study of radiation-induced gene expression and genome-wide SNP genotype may discover genetic alterations that regulate the biological response to ionizing radiation...... to side effects after radiotherapy. Despite this, certain fundamental challenges still relate to genomic approaches. Based on the latest insights into complex trait genetics and molecular genetics, we provide an analysis of these challenges and propose putative strategies to further advance the field...

  14. Quantum Randi Challenge

    CERN Document Server

    Vongehr, Sascha

    2012-01-01

    Violations of Bell type inequalities in quantum experiments disprove all relativistic micro causal, classically real models. Desperate attempts at saving classicality retreated to claiming what Shimony calls a conspiracy. It is time to embrace the quantum paradigm instead of being stuck in defending it against positions on par with the belief in divinely planted fossils. However, different from 'quantum-magic' pseudoscience, there is resistance against quantum mechanics among scientific literate audiences, and it is growing. The Quantum Randi Challenge is designed to help scientists and educators discredit local realistic models and related attacks against quantum physics. Its 'Randi-type' properties are ensured via a simple computer game that can be made attractive and understandable to lay people. We introduce the general concept of a 'James Randi type' challenge as a tool for science outreach aimed against the spread of pseudoscience. This is a challenge which, according to the laws of nature as known to s...

  15. Challenges facing production grids

    Energy Technology Data Exchange (ETDEWEB)

    Pordes, Ruth; /Fermilab

    2007-06-01

    Today's global communities of users expect quality of service from distributed Grid systems equivalent to that their local data centers. This must be coupled to ubiquitous access to the ensemble of processing and storage resources across multiple Grid infrastructures. We are still facing significant challenges in meeting these expectations, especially in the underlying security, a sustainable and successful economic model, and smoothing the boundaries between administrative and technical domains. Using the Open Science Grid as an example, I examine the status and challenges of Grids operating in production today.

  16. Banff Challenge 2

    CERN Document Server

    Junk, Thomas R

    2011-01-01

    Experimental particle physics collaborations constantly seek newer and better ideas for improving the sensitivity of their searches for new particles and phenomena. Statistical techniques are the last step in interpreting the results of an experiment; they are used to make discoveries (hypothesis testing), and to measure parameters (point estimation). They are also used in the first step - experiment and analysis design. Banff Challenge 2 asks participants to test their methods of disco vering hidden signals in simulated datasets and of measuring the properties of these signals. The Challenge problems are described, and the performances of the submitted entries is summarized, for datasets with and without simulated signals present.

  17. The Dirty Water Challenge

    Science.gov (United States)

    Walker, Mark; Kremer, Angelika; Schluter, Kirsten

    2007-01-01

    "The Dirty Water Challenge" is a fun activity that teaches children about their environment in an engaging and practical way. Inquiry is embedded within the practical--students have to design, plan, and then build their own design of water filter. Students are exposed to important concepts from a variety of scientific disciplines, including how…

  18. Challenges of Retrenchment.

    Science.gov (United States)

    Mingle, James R.; And Others

    The retrenchment experiences of a variety of institutions--large and small, public and private--are described and evaluated using an extensive spectrum of case studies sponsored by the Southern Regional Education Board. Part One discusses challenges of retrenchment (James R. Mingle) and strategies for the 1980s (David W. Breneman). Part Two,…

  19. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Experience in many parts of the developing world has shown thatfood fortification offers a cost-effective and sustainable solution to the problem of micronutrient malnutrition. Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs, governments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy. On the other hand, formidable challenges still remain in many countries in Asia, constraining the widespread adoption of this strategy. The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making. The government faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort. Industry faces the challenge of adapting its production system to the requirements of fortification in order that they can contribute to social objectives while pursuing their economic objectives. The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification, as these players in turn face the challenges that confront them.

  20. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    RODOLFOF.FLORENTINO

    2001-01-01

    Experience in many parts of the developing world has shown that food fortification offers a costeffective and sustainable solution to the problem of micronutrient malnutrition.Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs,govenments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy.On the other hand,formidable challenges still remain in many countries in Asia,constraining the widespread adoption of this strategy,The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making,The governent faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort.Industry faces the challenge of adapting its production system to the requirements of fortification in oreder that they can contribute to social bojectives while pursuing their economic objectives,The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification,as these players in turn face the challenges that confront them.

  1. The Moon Challenge

    Science.gov (United States)

    Fitzsimmons, Pat; Leddy, Diana; Johnson, Lindy; Biggam, Sue; Locke, Suzan

    2013-01-01

    This article describes a first-grade research project that incorporates trade books and challenges misconceptions. Educators see the power of their students' wonder at work in their classrooms on a daily basis. This wonder must be nourished by students' own experiences--observing the moon on a crystal clear night--as well as by having…

  2. Challenges in data science

    DEFF Research Database (Denmark)

    Carbone, Anna; Jensen, M.; Sato, Aki-Hiro

    2016-01-01

    The ability to process and manage large data volumes has been proven to be not enough to tackle the current challenges presented by "Big Data". Deep insight is required for understanding interactions among connected systems, space- and time-dependent heterogeneous data structures. Emergence...

  3. Challenges of CE

    NARCIS (Netherlands)

    Verhagen, Wim J.C.; Stjepandić, Josip; Wognum, Nel

    2015-01-01

    Despite a long pedigree and many positive reports on its use and benefits, concurrent engineering (CE) and its associated research (sub)domains still experience significant development. In this final chapter, a socio-technical framework is applied to classify and analyze challenges identified as

  4. Asia's new challenges

    DEFF Research Database (Denmark)

    Brach, Juliana; Vang, Jan

    2012-01-01

    Asian countries are currently undergoing significant changes with respect to their role in and interaction with the international economy. Despite their heterogeneity, Asian countries share the common aim to upgrade capacities, skills and capabilities. This paper aims at unpacking the challenges...

  5. Kayak Design Challenge

    Science.gov (United States)

    Wood, Anson

    2011-01-01

    Living in the Adirondack Park and being an avid outdoorsman has often resulted in the author's love of the outdoors working its way into class projects. In 2010, the author gave a group of 25 students in grades 9-12 a challenge that required them to design and construct a prototype inexpensive, lightweight kayak for backpackers and fisherman. In…

  6. Challenging the Boundaries

    DEFF Research Database (Denmark)

    Nørgaard, Nina

    2004-01-01

    To many people, challenging the boundaries between the traditional disciplines in foreign language studies means doing cultural studies. The aim of this article is to pull in a different direction by suggesting how the interface between linguistics and literature may be another fertile field...

  7. The blind hens’ challenge

    DEFF Research Database (Denmark)

    Sandøe, Peter; Hocking, Paul M.; Forkman, Björn

    2014-01-01

    repellent, yet 'welfare-only' positions appear to be committed to endorsing this possibility if it produces welfare gains. We call this the 'Blind Hens' Challenge'. In this paper, we argue that there are both empirical and theoretical reasons why even those adopting 'welfare-only' views should be concerned...

  8. Hopes and Challenges

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China tops the medal tally again at the Asian Games but still faces challenges in some events The curtain of the 16th Asian Games has fallen, but the 15 days of exciting competitions will be recorded in the history of the Games.

  9. Ecommerce: Ongoing Challenges

    Directory of Open Access Journals (Sweden)

    Derek Mohammed

    2010-08-01

    Full Text Available This paper examines some of the challenges of online marketing, including the importance of adding online marketing to corporation budgets. A review of the pros and cons of social networking on the Internet, when used as a marketing tool by companies is presented. In addition, new forms of Internet shoppers and new niches for companies are identified

  10. Electric Vehicle Battery Challenge

    Science.gov (United States)

    Roman, Harry T.

    2014-01-01

    A serious drawback to electric vehicles [batteries only] is the idle time needed to recharge their batteries. In this challenge, students can develop ideas and concepts for battery change-out at automotive service stations. Such a capability would extend the range of electric vehicles.

  11. MALL: The Pedagogical Challenges

    Science.gov (United States)

    Burston, Jack

    2014-01-01

    In this paper the development of mobile-assisted language learning (MALL) over the past 20 years is reviewed with a particular focus on the pedagogical challenges facing its exploitation. Following a consideration of the definition of mobile learning, the paper describes the dominant mobile technologies upon which MALL applications have been…

  12. Anthropocene Age Wicked Challenges

    DEFF Research Database (Denmark)

    Edgeman, Rick; Wu, Zhaohui

    2015-01-01

    Grand global challenges, including wicked human caused or influenced ones key to sustainability, characterize the Anthropocene Age. Among these are climate change driven by increased methane and CO2 in the atmosphere; consequent global warming and increasing intensity and incidence of extreme...

  13. India's Higher Education Challenges

    Science.gov (United States)

    Altbach, Philip G.

    2014-01-01

    India, with the world's second largest higher education system and a rapidly growing economy as one of the BRIC nations, faces significant challenges in building both capacity and excellence in higher education. India's higher education system is characterized by "islands of excellence in a sea of mediocrity." The mainstream universities…

  14. 81 FR 54853 - Notice of Centennial Challenges Space Robotics Challenge

    Science.gov (United States)

    2016-08-17

    ... Space Robotics Challenge AGENCY: National Aeronautics and Space Administration (NASA). NOTICE: (16-056). ACTION: Notice of Centennial Challenges Space Robotics Challenge. SUMMARY: This notice is issued in accordance with 51 U.S.C. 20144(c). The Space Robotics Challenge is open and teams that wish to compete...

  15. 77 FR 70835 - Centennial Challenges 2013 Sample Return Robot Challenge

    Science.gov (United States)

    2012-11-27

    ... SPACE ADMINISTRATION Centennial Challenges 2013 Sample Return Robot Challenge AGENCY: National... in accordance with 51 U.S.C. 20144(c). The 2013 Sample Return Robot Challenge is scheduled and teams... Robot Challenge is a prize competition designed to encourage development of new technologies...

  16. 76 FR 56819 - Centennial Challenges 2012 Sample Return Robot Challenge

    Science.gov (United States)

    2011-09-14

    ... SPACE ADMINISTRATION Centennial Challenges 2012 Sample Return Robot Challenge AGENCY: National... 42 U.S.C. 2451(314)(d). The 2012 Sample Return Robot Challenge is scheduled and teams that wish to... technologies of interest and value to NASA and the nation. The 2012 Sample Return Robot Challenge is a...

  17. Red wine asthma: a controlled challenge study.

    Science.gov (United States)

    Dahl, R; Henriksen, J M; Harving, H

    1986-12-01

    Drinking red wine may provoke bronchospasm in subjects with asthma. In order to reveal some of the possible agents involved in this reaction, 18 patients with a history of red wine-induced asthma were studied. They received, in a double-blind fashion, red wine with low sulfur dioxide (SO2) and high amine, high SO2 and high amine and low SO2 and low amine content. In each challenge, the wine was administered in stepwise increasing quantities until a total of 385 ml or a fall in peak expiratory flow of greater than 15% was reached. Nine subjects demonstrated a significant fall in peak flow in one or more challenges. In all cases the most severe reaction was observed after the wine with high SO2 content. The study suggests that SO2 is the most important factor in red wine-induced asthma. It is recommended that wine labels provide information on the SO2 content.

  18. Targeted therapy of renal cell carcinoma: synergistic activity of cG250-TNF and IFNg.

    NARCIS (Netherlands)

    Bauer, S.; Oosterwijk-Wakka, J.C.; Adrian, N.; Oosterwijk, E.; Fischer, E.; Wuest, T.; Stenner, F.; Perani, A.; Cohen, L.; Knuth, A.; Divgi, C.; Jager, D.; Scott, A.M.; Ritter, G.; Old, L.J.; Renner, C.

    2009-01-01

    Immunotherapeutic targeting of G250/Carbonic anhydrase IX (CA-IX) represents a promising strategy for treatment of renal cell carcinoma (RCC). The well characterized human-mouse chimeric G250 (cG250) antibody has been shown in human studies to specifically enrich in CA-IX positive tumors and was cho

  19. Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

    Science.gov (United States)

    Kitamura, Yoshiaki; Nakagawa, Hideyuki; Fujii, Tatsuya; Sakoda, Takema; Enomoto, Tadao; Mizuguchi, Hiroyuki; Fukui, Hiroyuki; Takeda, Noriaki

    2015-11-01

    In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.

  20. Mathematical olympiad challenges

    CERN Document Server

    Andreescu, Titu

    2000-01-01

    Mathematical Olympiad Challenges is a rich collection of problems put together by two experienced and well-known professors and coaches of the U.S. International Mathematical Olympiad Team. Hundreds of beautiful, challenging, and instructive problems from algebra, geometry, trigonometry, combinatorics, and number theory were selected from numerous mathematical competitions and journals. An important feature of the work is the comprehensive background material provided with each grouping of problems. The problems are clustered by topic into self-contained sections with solutions provided separately. All sections start with an essay discussing basic facts and one or two representative examples. A list of carefully chosen problems follows and the reader is invited to take them on. Additionally, historical insights and asides are presented to stimulate further inquiry. The emphasis throughout is on encouraging readers to move away from routine exercises and memorized algorithms toward creative solutions to open-e...

  1. Perishable Inventory Challenges

    DEFF Research Database (Denmark)

    Damgaard, Cecilie Maria; Nguyen, Vivi Thuy; Hvolby, Hans-Henrik

    2012-01-01

    The paper investigates how inventory control of perishable items is managed and line up some possible options of improvement. This includes a review of relevant literature dealing with the challenges of determining ordering policies for perishable products and a study of how the current procedure...... in the retail supply chains. The goal is to find and evaluate the parameters which affect the decision making process, when finding the optimal order quantity and order time. The paper takes a starting point in the retail industry but links to other industries.......The paper investigates how inventory control of perishable items is managed and line up some possible options of improvement. This includes a review of relevant literature dealing with the challenges of determining ordering policies for perishable products and a study of how the current procedures...

  2. GREEN BUILDING CHALLENGE 2005

    OpenAIRE

    López de Asiaín, Jaime; Alvarez-Ude, Luis

    2005-01-01

    Green Building Challenge 2005 forma part d'un projecte de cooperació entre diferents països (més de 20 en l'actualitat) que té per objectiu el desenvolupament d'una metodologia d'avaluació del comportament ecològic dels edificis i els resultats se presentaran en una conferència internacional a celebrar a Tòquio (Japó) a la finals de l'any 2005: Sustainable Building 2005. Green Building Challenge 2005 forma parte de un proyecto de cooperación entre distintos países (más de 20 en la actualid...

  3. Challenges in sexual medicine

    DEFF Research Database (Denmark)

    Cellek, Selim; Giraldi, Annamaria

    2012-01-01

    The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have...... placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain...... several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field...

  4. The challenge of conceiving

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Jørgensen, Ulrik

    2011-01-01

    different or even not very well established ideas of what might be a good design result. We present two mutually supportive approaches to problem identification that we have developed, applied and refined. The first is providing an approach to map the arenas of development that influence the context......One of the big challenges in the CDIO approach to engineering education is the first part focusing on conceiving problems to be handled and eventually solved. Traditional engineering education has been dominated by its focus on technical disciplines emphasising their individual tool box of problem...... the perspective of engineering design challenges where the need for problem identification is obvious to avoid the pitfall to reproduce and piecemeal engineer already existing product or service concepts. Problem identification is not a simple desk research task as it often involves a multitude of actors having...

  5. Challenges in Request Management

    DEFF Research Database (Denmark)

    Sommer, Anita Friis

    2014-01-01

    Request management (RQM) is a new term used for managing customer requests for new products. It is the counterpart to typical product development processes, which has no direct customer involvement. It is essential to manage customer requests in a structured and efficient way to obtain...... profitability. This research study seeks to investigate the challenges of RQM in practice. Existing demand chain management literature is used as a basis for developing a RQM framework. RQM is investigated through an explorative research design in a dyadic B2B case study including a global industrial company...... and its customers. The study provides an insight into a new area of supply chain management, including the process activity flow and challenges involved across the process. Furthermore, the method is dyadic including the customer in the case study, which is rare in related research....

  6. Diagnostic Challenges at SNS

    CERN Document Server

    Plum, M A

    2003-01-01

    The Spallation Neutron Source now being built in Oak Ridge, Tennessee, USA, accelerates an H- ion beam to 1000 MeV with an average power of 1.4 MW. The H- beam is then stripped to H+, compressed in a storage ring to a pulse length of 695 ns, and then directed onto a mercury neutron spallation target. Most of the acceleration is accomplished with superconducting rf cavities. The presence of these cavities, the high average beam power, and the large range of beam intensity in the storage ring, provide unique challenges to the beam diagnostics systems. In this talk we will discuss these challenges and some of our solutions, including the laser profile monitor system, the residual gas ionization profile monitors, and network attached devices. Measurements performed using prototype instrumentation will also be presented.

  7. Challenges to Resistance Welding

    DEFF Research Database (Denmark)

    Song, Quanfeng

    This report originates from the compulsory defense during my Ph.D. study at the Technical University of Denmark. Resistance welding is an old and well-proven technology. Yet the emergence of more and more new materials, new designs, invention off new joining techniques, and more stringent...... requirement in quality have imposed challenges to the resistance welding. More some research and development have to be done to adapt the old technology to the manufacturing industry of the 21st century. In the 1st part of the report, the challenging factors to the resistance welding are reviewed. Numerical...... simulation of resistance welding has been under development for many years. Yet it is no easy to make simulation results reliable and accurate because of the complexity of resistance welding process. In the 2nd part of the report numerical modeling of resistance welding is reviewed, some critical factors...

  8. Supernova Photometric Classification Challenge

    CERN Document Server

    Kessler, Richard; Jha, Saurabh; Kuhlmann, Stephen

    2010-01-01

    We have publicly released a blinded mix of simulated SNe, with types (Ia, Ib, Ic, II) selected in proportion to their expected rate. The simulation is realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point spread function and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). We challenge scientists to run their classification algorithms and report a type for each SN. A spectroscopically confirmed subset is provided for training. The goals of this challenge are to (1) learn the relative strengths and weaknesses of the different classification algorithms, (2) use the results to improve classification algorithms, and (3) understand what spectroscopically confirmed sub-...

  9. Ireland's Competitiveness Challenge 2011

    OpenAIRE

    2012-01-01

    The NCC publishes two annual competitiveness reports. Ireland's Competitiveness Challenge focuses on the national competitiveness issues of most importance to the enterprise sector and identifies policy recommendations required to address these issues. The report focuses on pursuing policies to improve competitiveness, particularly those to reduce the cost base for enterprise, to enhance the performance of the entire education system, and to deliver meaningful public sector reform. Ireland's ...

  10. South China Sea Challenge

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    China's attempts to solve disputes with ASEAN over the South China Sea help regional peace China's marine economy and security are currently faced with new challenges, requiring careful handling, especially in disputes with ASEAN countries and in promoting common development of the South China Sea. The outcome of how this is dealt with could undoubtedly pave the way for solutions to other oceanic disputes. The South China Sea is located south of

  11. Managing the Fukushima Challenge

    OpenAIRE

    Suzuki, Atsuyuki

    2014-01-01

    The Fukushima Daiichi accident raises a fundamental question: Can science and technology prevent the inevitability of serious accidents, especially those with low probabilities and high consequences? This question reminds us of a longstanding challenge with the trans-sciences, originally addressed by Alvin Weinberg well before the Three Mile Island and Chernobyl accidents. This article, revisiting Weinberg's issue, aims at gaining insights from the accident with a special emphasis on the soci...

  12. Gaddafi's Death Poses Challenges

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The death of Muammar Gaddafi marks a new era for Libya.It also poses a huge challenge for Libyan authorities dealing with tribal conflicts.He Wenping,a researcher with the Institute of West-Asian and African Studies at the Chinese Academy of Social Sciences,believes that Libya is in danger of falling into a period of internal strife and tribal conflict.

  13. Terabit Wireless Communication Challenges

    Science.gov (United States)

    Hwu, Shian U.

    2012-01-01

    This presentation briefly discusses a research effort on Terabit Wireless communication systems for possible space applications. Recently, terahertz (THz) technology (300-3000 GHz frequency) has attracted a great deal of interest from academia and industry. This is due to a number of interesting features of THz waves, including the nearly unlimited bandwidths available, and the non-ionizing radiation nature which does not damage human tissues and DNA with minimum health threat. Also, as millimeter-wave communication systems mature, the focus of research is, naturally, moving to the THz range. Many scientists regard THz as the last great frontier of the electromagnetic spectrum, but finding new applications outside the traditional niches of radio astronomy, Earth and planetary remote sensing, and molecular spectroscopy particularly in biomedical imaging and wireless communications has been relatively slow. Radiologists find this area of study so attractive because t-rays are non-ionizing, which suggests no harm is done to tissue or DNA. They also offer the possibility of performing spectroscopic measurements over a very wide frequency range, and can even capture signatures from liquids and solids. According to Shannon theory, the broad bandwidth of the THz frequency bands can be used for terabit-per-second (Tb/s) wireless communication systems. This enables several new applications, such as cell phones with 360 degrees autostereoscopic displays, optic-fiber replacement, and wireless Tb/s file transferring. Although THz technology could satisfy the demand for an extremely high data rate, a number of technical challenges need to be overcome before its development. This presentation provides an overview the state-of-the- art in THz wireless communication and the technical challenges for an emerging application in Terabit wireless systems. The main issue for THz wave propagation is the high atmospheric attenuation, which is dominated by water vapor absorption in the THz

  14. Bioinformatics Challenge Days

    Science.gov (United States)

    2013-12-30

    concentrations 3. Genome Assembly for the Clinic: Performing de novo assembly from clinical samples with an emphasis on pathogen identification 4...The Illumina Genome Analyzer II was used. The sample contained 1.4 Gbp of data. DE NOVO GENETIC ASSEMBLY (BCD1, 2) The same datasets were used...Challenge (BCD1) 21   From Metagenomic Sample to Useful Visual (BCD1, 2) 21   De Novo Genetic Assembly (BCD1, 2) 22   Identifying Markers of Genetic

  15. CHALLENGES FOR FOREIGN TEACHERS

    Institute of Scientific and Technical Information of China (English)

    DengJing

    2004-01-01

    The learner differences and contrasts between the two cultures involved are important aspects that influence foreign language teaching and learning. The foreign teacher as an outsider of the learner's native culture, inevitably faces quite a few challenges. With the focus on the self-esteem, character types, and motivation of the learner, the paper analyses how these factors influence the foreign teacher's teaching. Relevant solutions are also proposed.

  16. Cleanroom laboratory challenge overcome.

    Science.gov (United States)

    Quinn, Ronan

    2010-10-01

    Ronan Quinn, managing director of interior construction specialist Ardmac, describes the challenges of building and fitting out a new cleanroom laboratory for blood and bone marrow therapeutic treatment at Our Lady's Children's Hospital Crumlin in Dublin. The "state-of-the-art" facility, which fully complies with the recent EU Directive concerning human tissues and cells, has been well received by the client and end-users alike, but, as he explains, there were many obstacles to overcome during its completion.

  17. EDMS implementation challenge.

    Science.gov (United States)

    De La Torre, Marta

    2002-08-01

    The challenges faced by facilities wishing to implement an electronic medical record system are complex and overwhelming. Issues such as customer acceptance, basic computer skills, and a thorough understanding of how the new system will impact work processes must be considered and acted upon. Acceptance and active support are necessary from Senior Administration and key departments to enable this project to achieve measurable success. This article details one hospital's "journey" through design and successful implementation of an electronic medical record system.

  18. ATLAS Data Challenge 1

    CERN Document Server

    DC1 TaskForce

    2003-01-01

    The ATLAS Collaboration at CERN is preparing for the data taking and analysis at LHC that will start in 2007. Therefore, in 2002 a series of Data Challenges (DC's) was started whose goals are the validation of the Computing Model, of the complete software suite, of the data model, and to ensure the correctness of the technical choices to be made. A major feature of the first Data Challenge (DC1) was the preparation and the deployment of the software required for the production of large event samples for the High Level Trigger and Physics communities, and the production of those large data samples as a worldwide distributed activity. It should be noted that it was not an option to "run everything at CERN" even if we had wanted to; the resources were not available at CERN to carry out the production on a reasonable time-scale. We were therefore faced with the great challenge of organising and then carrying out this large-scale production at a significant number of sites around the world. However, the benefits o...

  19. IDEOLOGICALLY CHALLENGING ENTERTAINMENT (ICE

    Directory of Open Access Journals (Sweden)

    Dana Lori Chalmers

    2015-09-01

    Full Text Available Ideologically Challenging Entertainment (ICE is entertainment that challenges ‘us vs. them’ ideologies associated with radicalization, violent conflict and terrorism. ICE presents multiple perspectives on a conflict through mainstream entertainment. This article introduces the theoretical underpinnings of ICE, the first ICE production and the audience responses to it. The first ICE production was Two Merchants: The Merchant of Venice adapted to challenge ideologies of the Arab-Israeli Conflict. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views. Each performance included two versions of the adaptation: a Jewish dominated society with an Arab Muslim minority, contrasted with an Arab Muslim dominated society and a Jewish minority. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views to become more tolerant of differences away from ideological radicalization. Of audience members who did not initially agree with the premise of the production, 40% reconsidered their ideological views, indicating increased tolerance, greater awareness of and desire to change their own prejudices. In addition, 86% of the audience expressed their intention to discuss the production with others, thereby encouraging critical engagement with, and broader dissemination of the message. These outcomes suggest that high quality entertainment – as defined by audience responses to it - can become a powerful tool in the struggle against radicalised ideologies.

  20. DNA Vaccine Encoding HPV16 Oncogenes E6 and E7 Induces Potent Cell-mediated and Humoral Immunity Which Protects in Tumor Challenge and Drives E7-expressing Skin Graft Rejection

    Science.gov (United States)

    Chandra, Janin; Dutton, Julie L.; Li, Bo; Woo, Wai-Ping; Xu, Yan; Tolley, Lynn K.; Yong, Michelle; Wells, James W.; R. Leggatt, Graham; Finlayson, Neil

    2017-01-01

    We have previously shown that a novel DNA vaccine technology of codon optimization and the addition of ubiquitin sequences enhanced immunogenicity of a herpes simplex virus 2 polynucleotide vaccine in mice, and induced cell-mediated immunity when administered in humans at relatively low doses of naked DNA. We here show that a new polynucleotide vaccine using the same technology and encoding a fusion protein of the E6 and E7 oncogenes of high-risk human papillomavirus type 16 (HPV16) is immunogenic in mice. This vaccine induces long-lasting humoral and cell-mediated immunity and protects mice from establishment of HPV16-E7-expressing tumors. In addition, it suppresses growth of readily established tumors and shows enhanced efficacy when combined with immune checkpoint blockade targeted at PD-L1. This vaccine also facilitates rejection of HPV16-E7-expressing skin grafts that demonstrate epidermal hyperplasia with characteristics of cervical and vulvar intraepithelial neoplasia. Clinical studies evaluating the efficacy of this vaccine in patients with HPV16+ premalignancies are planned. PMID:28166181

  1. Nanotechnology: Opportunities and Challenges

    Science.gov (United States)

    Meyyappan, Meyya

    2003-01-01

    Nanotechnology seeks to exploit novel physical, chemical, biological, mechanical, electrical, and other properties, which arise primarily due to the nanoscale nature of certain materials. A key example is carbon nanotubes (CNTs) which exhibit unique electrical and extraordinary mechanical properties and offer remarkable potential for revolutionary applications in electronics devices, computing, and data storage technology, sensors, composites, nanoelectromechanical systems (NEMS), and as tip in scanning probe microscopy (SPM) for imaging and nanolithography. Thus the CNT synthesis, characterization, and applications touch upon all disciplines of science and engineering. This presentation will provide an overview and progress report on this and other major research candidates in Nanotechnology and address opportunities and challenges ahead.

  2. Challenging the Innovation Paradigm

    CERN Document Server

    Sveiby, Karl Erik; Segercrantz, Beata

    2012-01-01

    Innovation is almost always seen as a "good thing". Challenging the Innovation Paradigm is a critical analysis of the innovation frenzy and contemporary innovation research. The one-sided focus on desirable effects of innovation misses many opportunities to reduce the undesirable consequences. Authors in this book show how systemic effects outside the innovating firms reduce the net benefits of innovation for individual employees, customers, as well as for society as a whole - also the innovators' own organizations. This book analyzes the dominant discourses that construct and recons

  3. Challenges in pharmacogenetics.

    Science.gov (United States)

    Cascorbi, Ingolf; Bruhn, Oliver; Werk, Anneke N

    2013-05-01

    The attempt to optimize drug treatment of patients by using evidenced-based medicine considering individual physiological and disease-related conditions is standard of modern medicine. Pharmacogenetics (PGx) has contributed to individualization considering hereditary genetic information; however, increasingly, pharmacogenomics is becoming essential, particularly in relation to modern oncology. New technologies such as next-generation sequencing and rapid development of computational and information sciences will help to better elucidate the consequences of genetic variation, considering also epigenetics and gene-environmental interactions and their translation into clinically relevant individual phenotypes. This review highlights the current challenging and most promising examples of PGx.

  4. Semantic Web Evaluation Challenge

    CERN Document Server

    2014-01-01

    This book constitutes the thoroughly refereed post conference proceedings of the first edition of the Semantic Web Evaluation Challenge, SemWebEval 2014, co-located with the 11th Extended Semantic Web conference, held in Anissaras, Crete, Greece, in May 2014. This book includes the descriptions of all methods and tools that competed at SemWebEval 2014, together with a detailed description of the tasks, evaluation procedures and datasets. The contributions are grouped in three areas: semantic publishing (sempub), concept-level sentiment analysis (ssa), and linked-data enabled recommender systems (recsys).

  5. Induction of Golli-MBP Expression in CNS Macrophages During Acute LPS-Induced CNS Inflammation and Experimental Autoimmune Encephalomyelitis (EAE

    Directory of Open Access Journals (Sweden)

    Tracey L. Papenfuss

    2007-01-01

    Full Text Available Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP as a candidate molecule enriched in peripheral macrophages. In situ hybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE–induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extending in vitro observations to in vivo biology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment.

  6. Proteomics Technologies and Challenges

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.

  7. ATLAS Data Challenge 1

    CERN Document Server

    Poulard, G

    2003-01-01

    In 2002 the ATLAS experiment started a series of Data Challenges (DC) of which the goals are the validation of the Computing Model, of the complete software suite, of the data model, and to ensure the correctness of the technical choices to be made. A major feature of the first Data Challenge (DC1) was the preparation and the deployment of the software required for the production of large event samples for the High Level Trigger (HLT) and physics communities, and the production of those samples as a world-wide distributed activity. The first phase of DC1 was run during summer 2002, and involved 39 institutes in 18 countries. More than 10 million physics events and 30 million single particle events were fully simulated. Over a period of about 40 calendar days 71000 CPU-days were used producing 30 Tbytes of data in about 35000 partitions. In the second phase the next processing step was performed with the participation of 56 institutes in 21 countries (~ 4000 processors used in parallel). The basic elements of ...

  8. Safeguards by Design Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Alwin, Jennifer Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-13

    The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA’s limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

  9. Résultats challenge

    CERN Multimedia

    Club de pétanque

    2015-01-01

    C'est avec un temps magnifique que se disputait pour la deuxième année le Challenge de notre cher ami Patrick DURAND le jeudi 30 juillet 2015. Vingt-six personnes formées en doublettes s'affrontaient pour trois parties .Après des parties très serrées le juge arbitre Claude JOUVE épaulé par Alain PHILIPONA déclarait  vainqueur l'imbattable Claude MACARI suivi de très près par Eric DARMEDRU et à la troisième place Christian JOUVE. La première féminine était Mireille ROCHE. La soirée se clôturait par une succulente paëlla préparée par Jennifer et sa maman Sylvie JOUVE. Rendez-vous à tous pour le jeudi 27 août 2015 pour le challenge Jean-Claude FROT Nos concours sont ouverts à tous les amateurs de pétanque.

  10. Challenge Based Innovation gala

    CERN Document Server

    CERN. Geneva; Utriainen, Tuuli Maria; Toivonen, Harri; Nordberg, Markus

    2014-01-01

    Challenge Based Innovation gala   There’s a new experiment starting in CERN called IdeaLab where we work together with detector R&D researchers to help them to bridge their knowledge into a more human, societally oriented context. Currently we are located in B153, but will move our activities to a new facility next to the Globe in May 2014. One of our first pilot projects is a 5 month course CBI (Challenge Based Innovation) where two multidisciplinary student teams join forces with Edusafe & TALENT projects at CERN. Their goal is to discover what kind of tools for learning could be created in collaboration with the two groups. After months of user interviews and low resolution prototyping they are ready to share the results with us in the form of an afternoon gala. We warmly welcome you to join us to see the students' results and experience the prototypes they have conceived. The event is in three parts, you are welcome to visit all of them,...

  11. Rising to the Challenge

    Directory of Open Access Journals (Sweden)

    Xiaoping Li

    2015-06-01

    Full Text Available Writing is recognized as a vital skill in education and the workplace; students in the United States finishing K-12 schooling are expected to be competent writers. Yet, the Nation’s Report Card found that U.S. high school graduates coming into the workforce are particularly deficient in writing skills. Teachers serve as a crucial link in the move to improve literacy skills of K-12 students; however, teachers themselves are underprepared to be writers and writing teachers. Therefore, there is an urgent need to improve teachers’ writing skills and skills of teaching writing to improve K-12 students’ writing skills in the United States. This qualitative study examined the process-based writing project experienced by 22 practicing teachers through their reflective practices in a graduate capstone class. In particular, this study explored the challenges the teachers faced and the lessons they learned through the recursive phases of writing: planning, drafting, revising, editing, conferring, and publishing. The triangulation of the researchers’ field notes, teachers’ daily reflections, and informal interviews between the instructor and the teachers indicated that the challenges the teachers faced and the lesson they learned through the process-based writing project were phase specific. On the completion of the writing project, the participating teachers (a developed a deep understanding of process-based writing; (b learned new skills of planning, drafting, revising, editing, and sharing; and (c were more confident as writers themselves and as writing teachers for their students.

  12. Review - China's Environmental Challenges

    Directory of Open Access Journals (Sweden)

    Bill Bleisch

    2013-12-01

    Full Text Available Review of: Judith Shapiro. 2012. China's Environmental Challenges. Cambridge: UK and Malden, MA: Polity Press. Judith Shapiro's latest ambitious work picks up the story of modern China's checkered relationship with the environment at approximately the point where her previous study, Mao's War Against Nature (2001, left off. This latest book sets out to address questions of grave importance to China and to the world. The litany of challenges – poisonous water and toxic air, scarcity of water and other resources, deforestation, soil erosion, loss of biodiversity – seem nearly insurmountable, despite evidence of considerable attention from the Chinese government and from China's public, and despite the rocket-like rise of China's economic power and political influence in the world. Shapiro adds to this list the growing problems with lapses in environmental justice, both within China and passed on to its neighbours and to the countries with which it trades. Not only do growing environmental problems affect China's ability to achieve the government's stated goals of a 'harmonious society' with 'moderate prosperity for all,' but these problems, and the ways that ...

  13. Therapeutic challenges of urosepsis.

    Science.gov (United States)

    Wagenlehner, F M E; Pilatz, A; Naber, K G; Weidner, W

    2008-10-01

    Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community or nosocomial acquired urinary tract infection (UTI). The underlying UTI is almost exclusively a complicated one with involvement of parenchymatous urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The treatment of urosepsis comprises four major aspects: Early goal directed therapy, early optimal pharmacodynamic exposure to antimicrobials, early control of the complicating factor in the urinary tract and specific sepsis therapy. Following these prerequisites there appear two major challenges that need to be addressed: Firstly, time from admission to therapy is critical; the shorter the time to effective treatment, the higher the success rate. This aspect has to become incorporated into the organisational process. Secondly, adequate initial antibiotic therapy has to be insured. This goal implies however, a wide array of measures to ensure rational antibiotic policy. Both challenges are best targeted if an interdisciplinary approach at any level of the process is established, encompassing urologists, intensive care specialists, radiologists, microbiologists and clinical pharmacologists working tightly together at any time.

  14. The ALICE Data Challenges

    Institute of Scientific and Technical Information of China (English)

    J.P.Baud; W.Carena; 等

    2001-01-01

    Since 1998,the ALICE experiment and the CERN/IT division have jointly executed several large-scale high throughput distributed computing exercises:the ALICE data challenges.The goals of these regular exercises are to test hardware and software components of the data acqusition and computing systems in realistic conditions and to execute an early integration of the overall ALICE computing infrastructure.This paper reports on the third ALICE Data Challenge (ADC III) that has been performed at CERN from January to March 2001.The data used during the ADC Ⅲ are simulated physics raw data of the ALICE TPC,produced with the ALICE simulation program AliRoot.The data acquisition was based on the ALICE online framework called the ALICE Data Acquisition Test Environment (DATE) system.The data after event building,were then formatted with the ROOT I/O package and a data catalogue based on MySQl was established.The Mass Storage System used during ADC III is CASTOR.Different software tools have been used to monitor the performances,DATE has demonstrated performances of more than 500 MByte/s.An aggregate data throughput of 85 MByte/s was sutained in CASTOR over several days.The total collected data amounts to 100 TBytes in 100.00 files.

  15. Synergistic effect of interferon-gamma and tumor necrosis factor-alpha on coxsackievirus and adenovirus receptor expression: an explanation of cell sloughing during testicular inflammation in mice.

    Science.gov (United States)

    Gao, Ying; Lui, Wing-Yee

    2014-03-01

    Coxsackievirus and adenovirus receptor (CAR) is a junction molecule that expresses on Sertoli and germ cells. It mediates Sertoli-germ cell adhesion and facilitates migration of preleptotene/leptotene spermatocytes across the blood-testis barrier, suggesting that CAR-based cell adhesion and migration are crucial for spermatogenesis. Interferon-gamma (IFNG) and tumor necrosis factor alpha (TNF) are two major cytokines that are elevated during testicular inflammation and cause reduced fertility. We investigated the mechanism by which IFNG and TNF exert their disruptive effects on testicular cell adhesion. We have demonstrated that combined treatment with IFNG and TNF (IFNG+TNF) exerts a synergistic effect by downregulating CAR mRNA and protein levels. Immunofluorescence staining revealed that IFNG+TNF treatment effectively removes CAR from the site of cell-cell contact. Using inhibitor and co-immunoprecipitation, we confirmed that IFNG+TNF mediates CAR protein degradation via ubiquitin-proteasome and NFKB pathways. Blockage of ubiquitin-proteasome pathway significantly inhibits CAR degradation, as indicated by the reappearance of CAR at the site of cell-cell contact. Additionally, IFNG+TNF reduces CAR mRNA via transcriptional regulation. Mutational studies have shown that IFNG+TNF-induced CAR repression is achieved by suppression of the basal transcription. Electrophoretic mobility shift assay and chromatin immunoprecipitation assays further confirmed that IFNG+TNF treament not only inhibits binding of the basal transcription factors but also promotes binding of NFKB subunits and Sp1 (negative regulators) to the CAR promoter region. Taken together, IFNG+TNF treatment significantly downregulates CAR expression, which provides an explanation of how cell sloughing in the epithelium mediates, by loss of CAR-based cell adhesion, during testicular inflammation.

  16. Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls. Cytokine profiles in nickel-sensitive individuals with nickel allergy-related hand eczema before and after nickel challenge

    DEFF Research Database (Denmark)

    Borg, L; Christensen, J M; Kristiansen, J

    2000-01-01

    Exposure to nickel is a major cause of allergic contact dermatitis which is considered to be an inflammatory response induced by antigen-specific T cells. Here we describe the in vitro analysis of the nickel-specific T-cell-derived cytokine response of peripheral blood mononuclear cells from 35...... was somewhat of a surprise, since previous studies have suggested a Th1 response in nickel-mediated allergic contact dermatitis. Subsequently, the nickel-allergic individuals were randomized to experimental exposure to nickel or vehicle in a double-blind design. A daily 10-min exposure of one finger to 10 ppm...... nickel solution for 1 week followed by 100 ppm for an additional week evoked a clinical response of hand eczema in the nickel-exposed group. Blood samples were drawn on days 7 and 14 after the start of this exposure to occupationally relevant concentrations of nickel. No statistically significant...

  17. Simulating hypoxia-induced acidic environment in cancer cells facilitates mobilization and redox-cycling of genomic copper by daidzein leading to pro-oxidant cell death: implications for the sensitization of resistant hypoxic cancer cells to therapeutic challenges.

    Science.gov (United States)

    Ullah, Mohammad F; Ahmad, Aamir; Bhat, Showket H; Khan, Husain Y; Zubair, Haseeb; Sarkar, Fazlul H; Hadi, Sheikh M

    2016-04-01

    This study was conducted to investigate the mechanism of action involved in the anti-cancer activity of daidzein and identification of cancer specific micro-environment as therapeutic target of this secondary metabolite derived from soy. Our data indicated that daidzein induces cellular DNA breakage, anti-proliferative effects and apoptosis in a concentration-dependent manner. We demonstrated that such a daidzein-induced anti-cancer action involves a copper-dependant pathway in which endogenous copper is mobilized by daidzein and redox-cycled to generate reactive oxygen species which act as an upstream signal leading to pro-oxidant cell death. Further in the context of hypoxia being a resistant factor against standard therapies and that an effect secondary to hypoxia is the intracellular acidification, we show that the anticancer activity of daidzein is modulated positively in acidic pH but copper-specific chelator is still able to inhibit daidzein activity. Moreover, an experimental setup of hypoxia mimic (cobalt chloride) revealed an enhanced sensitivity of cancer cells to the cytotoxic effects of daidzein which was neutralized in the presence of neocuproine. The findings support a paradigm shift from the conventional antioxidant property of dietary isoflavones to molecules capable of initiating a pro-oxidant signaling mediated by reactive oxygen species. Further, the clinical relevance of such an action mechanism in cancer chemoprevention is also proposed. This study identified endogenous copper as a molecular target and acidic pH as a modulating factor for the therapeutic activity of daidzein against cancer. The evidence presented highlights the potential of dietary agents as adjuvants to standard therapeutic regimens.

  18. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  19. Offshore northern Europe, the challenges

    Energy Technology Data Exchange (ETDEWEB)

    Bergseth, S. [Statoil, Stavenger (Norway)

    1996-12-31

    This paper relates to challenges of the offshore activity in the North Sea. It is appropriate to address these challenges in the context of generating values through efficient management of resources, markets, safety and technology, as the challenges lie therein. The petroleum industry is built to turn natural resources into market value, assuring broad benefits to stake holders and shareholders. In the following, the challenges facing the industry the industry offshore Northern Europe is examined on this background

  20. WCET Tool Challenge 2011: Report

    DEFF Research Database (Denmark)

    Bonenfant, Armelle; Cassé, Hugues; Bünte, Sven;

    2011-01-01

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC’11) defined two k...

  1. The Global Energy Challenge

    DEFF Research Database (Denmark)

    Connolly, David

    2011-01-01

    This report gives a brief overview of the global energy challenge and subsequently outlines how and where renewable energy could be developed to solve these issues. The report does not go into a lot of detail on these issues and hence, it is meant as an overview only. The report begins by outlining...... the causes of global climate change, concluding that energy-related emissions are the primary contributors to the problem. As a result, global energy production is analysed in more detail, discussing how it has evolved over the last 30 years and also, how it is expected to evolve in the coming 30 years....... Afterwards, the security of the world’s energy supply is investigated and it becomes clear that there is both an inevitable shortage of fossil fuels and a dangerous separation of supply and demand. The final topic discussed is renewable energy, since it is one sustainable solution to the global energy...

  2. Energy Challenges for ICT

    DEFF Research Database (Denmark)

    Fagas, Giorgos; Gallagher, John Patrick; Gammaitoni, Luca

    2017-01-01

    The energy consumption from the expanding use of information and communications technology (ICT) is unsustainable with present drivers, and it will impact heavily on the future climate change. However, ICT devices have the potential to contribute significantly to the reduction of CO2 emission...... the energy sustainability of ICT and capture the full potential of ICT in resource efficiency, a multidisciplinary ICT-energy community needs to be brought together covering devices, microarchitectures, ultra large-scale integration (ULSI), high-performance computing (HPC), energy harvesting, energy storage......, system design, embedded systems, efficient electronics, static analysis, and computation. In this chapter, we introduce challenges and opportunities in this emerging field and a common framework to strive towards energy-sustainable ICT....

  3. A specific nanomanufacturing challenge

    Science.gov (United States)

    Kelly, M. J.; Dean, M. C.

    2016-03-01

    For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO® brick scaled down by a factor of 10 n for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts.

  4. The challenge of implementation

    DEFF Research Database (Denmark)

    Andersen, Karen Heide Hauge

    2015-01-01

    Reaching the students in innovation and entrepreneurship courses is hard, when the courses are a requirement but not included in the main project of the curriculum. It is a major paradox for lecturers, who have never participated in and cannot see the relevance of such course, to implement...... these concepts in daily teaching, as it is strongly encouraged by policy makers and educations. This paper aims to discuss how lecturers experience the challenge of teaching their own discipline while being imposed to embrace and promote innovation and entrepreneurship teaching. Through a single study case...... of the paper: which factors influence the degree of implementation of innovation and entrepreneurship in the individual lecturers’ daily teaching? The paper questions the common approach taken by higher educational institutions whereby lecturers are urged to teach innovation and entrepreneurship with minor...

  5. EOSDIS Customer Support Challenges

    Science.gov (United States)

    Moses, J. F.; Boquist, C. L.

    2006-05-01

    The Earth Observation System Data and Information System (EOSDIS) is a large, complex data system currently supporting over 18 operational NASA satellite missions including the flagship EOS missions: Terra, Aqua, and Aura. The observations collected by these missions are kept at geographically distributed data centers. EOSDIS manages over four petabytes of data accessed by over 200,000 distinct users last year. The data centers distributed more than 37 million Earth science data products during 2005 to a diverse customer community. An important goal for these data centers is to provide an adequate service at a uniform level for the user community to ensure we get the most benefit from our investment in space resources. This paper discusses the challenges, the ways the data centers coordinate among themselves to provide service, and recent results of measuring customer satisfaction with this service.

  6. Challenges in plastics recycling

    DEFF Research Database (Denmark)

    Pivnenko, Kostyantyn; Jakobsen, L. G.; Eriksen, Marie Kampmann

    2015-01-01

    Recycling of waste plastics still remains a challenging area in the waste management sector. The current and potential goals proposed on EU or regional levels are difficult to achieve, and even to partially fullfil them the improvements in collection and sorting should be considerable. A study...... was undertaken to investigate the factors affecting quality in plastics recycling. The preliminary results showed factors primarily influencing quality of plastics recycling to be polymer cross contamination, presence of additives, non-polymer impurities, and polymer degradation. Deprivation of plastics quality......, with respect to recycling, has been shown to happen throughout the plastics value chain, but steps where improvements may happen have been preliminary identified. Example of Cr in plastic samples analysed showed potential spreading and accumulation of chemicals ending up in the waste plastics. In order...

  7. Multicore Programming Challenges

    Science.gov (United States)

    Perrone, Michael

    The computer industry is facing fundamental challenges that are driving a major change in the design of computer processors. Due to restrictions imposed by quantum physics, one historical path to higher computer processor performance - by increased clock frequency - has come to an end. Increasing clock frequency now leads to power consumption costs that are too high to justify. As a result, we have seen in recent years that the processor frequencies have peaked and are receding from their high point. At the same time, competitive market conditions are giving business advantage to those companies that can field new streaming applications, handle larger data sets, and update their models to market conditions faster. The desire for newer, faster and larger is driving continued demand for higher computer performance.

  8. Ayurveda research: Ontological challenges

    Directory of Open Access Journals (Sweden)

    Jayakrishna Nayak

    2012-01-01

    Full Text Available Collaborative research involving Ayurveda and the current sciences is undoubtedly an imperative and is emerging as an exciting horizon, particularly in basic sciences. Some work in this direction is already going on and outcomes are awaited with bated breath. For instance the ′ASIIA (A Science Initiative In Ayurveda′ projects of Dept of Science and Technology, Govt of India, which include studies such as Ayurvedic Prakriti and Genetics. Further intense and sustained collaborative research needs to overcome a subtle and fundamental challenge-the ontologic divide between Ayurveda and all the current sciences. Ontology, fundamentally, means existence; elaborated, ontology is a particular perspective of an object of existence and the vocabulary developed to share that perspective. The same object of existence is susceptible to several ontologies. Ayurveda and modern biomedical as well as other sciences belong to different ontologies, and as such, collaborative research cannot be carried out at required levels until a mutually acceptable vocabulary is developed.

  9. Polyhydroxyalkanoates, challenges and opportunities.

    Science.gov (United States)

    Wang, Ying; Yin, Jin; Chen, Guo-Qiang

    2014-12-01

    Microbial polyhydroxyalkanoates (PHA) have been developed as biodegradable plastics for the past many years. However, PHA still have only a very limited market. Because of the availability of large amount of shale gas, petroleum will not raise dramatically in price, this situation makes PHA less competitive compared with low cost petroleum based plastics. Therefore, two strategies have been adopted to meet this challenge: first, the development of a super PHA production strain combined with advanced fermentation processes to produce PHA at a low cost; second, the construction of functional PHA production strains with technology to control the precise structures of PHA molecules, this will allow the resulting PHA with high value added applications. The recent systems and synthetic biology approaches allow the above two strategies to be implemented. In the not so distant future, the new technology will allow PHA to be produced with a competitive price compared with petroleum-based plastics.

  10. Ayurveda research: Ontological challenges.

    Science.gov (United States)

    Nayak, Jayakrishna

    2012-01-01

    Collaborative research involving Ayurveda and the current sciences is undoubtedly an imperative and is emerging as an exciting horizon, particularly in basic sciences. Some work in this direction is already going on and outcomes are awaited with bated breath. For instance the 'ASIIA (A Science Initiative In Ayurveda)' projects of Dept of Science and Technology, Govt of India, which include studies such as Ayurvedic Prakriti and Genetics. Further intense and sustained collaborative research needs to overcome a subtle and fundamental challenge-the ontologic divide between Ayurveda and all the current sciences. Ontology, fundamentally, means existence; elaborated, ontology is a particular perspective of an object of existence and the vocabulary developed to share that perspective. The same object of existence is susceptible to several ontologies. Ayurveda and modern biomedical as well as other sciences belong to different ontologies, and as such, collaborative research cannot be carried out at required levels until a mutually acceptable vocabulary is developed.

  11. New challenges in gas

    Energy Technology Data Exchange (ETDEWEB)

    Mandil, C. [Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France); Chabrelie, M.F. [Cedigaz, 92 - Rueil Malmaison (France); Streicher, C. [Prosernat, 92 - Paris la Defense (France)] [and others

    2003-07-01

    New developments in the area of gas treatment will be to a large extent driven by the need to find appropriate solutions to the fundamental need of sustainable development. New gas treatment processes are developed with the aim to minimise contaminant emissions and meet most stringent environmental specifications. A new major challenge for the industry will be to implement new cost effective technologies for reducing CO{sub 2} emissions. Industry has also to minimise its costs, and therefore, in order to ensure at the same time a better protection of the environment and a better safety, it is necessary to innovate. The purpose of this seminar is precisely to identify better the innovations which are required in the area of gas treatment. These proceedings comprise 8 papers and a summary of the contributions to a round-table discussion dealing with the options for CO{sub 2} capture and sequestration. The presentations treat of: the future prospects for the gas industry (M.F. Chabrelie, Cedigaz); the solutions for offshore gas treatment (C. Streicher, Prosernat); gas treatment with membranes (H. Meyer, GTI); the Axens Multibed{sub TM} technology for natural gas treatment (G. Jochem, Axens); the potentials and applications for the Propure co-current contactors (F.P. Nilsen, ProPure); the production of very-sour and super-sour large gas reserves: the new challenges (F. Lallemand, TotalFinaElf); Hybrisol, a new gas treatment process for sour natural gases (F. Lecomte, IFP); and the conception and building of large acid-gas removal units (J. Castel, Technip-Coflexip). (J.S.)

  12. Challenges and perspectives in quantitative NMR.

    Science.gov (United States)

    Giraudeau, Patrick

    2017-01-01

    This perspective article summarizes, from the author's point of view at the beginning of 2016, the major challenges and perspectives in the field of quantitative NMR. The key concepts in quantitative NMR are first summarized; then, the most recent evolutions in terms of resolution and sensitivity are discussed, as well as some potential future research directions in this field. A particular focus is made on methodologies capable of boosting the resolution and sensitivity of quantitative NMR, which could open application perspectives in fields where the sample complexity and the analyte concentrations are particularly challenging. These include multi-dimensional quantitative NMR and hyperpolarization techniques such as para-hydrogen-induced polarization or dynamic nuclear polarization. Because quantitative NMR cannot be dissociated from the key concepts of analytical chemistry, i.e. trueness and precision, the methodological developments are systematically described together with their level of analytical performance. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Musculoskeletal challenges of osteoporosis.

    Science.gov (United States)

    Sinaki, M

    1998-06-01

    Reduction in the biomechanical competence of the axial skeleton can result in challenging complications. Osteoporosis consists of a heterogeneous group of syndromes in which bone mass per unit volume is reduced in otherwise normal bone, which results in more fragile bone. The geriatric population has an increased risk for debilitating postural changes because of several factors. The two most apparent factors are involutional loss of functional muscle motor units and the greater prevalence of osteoporosis in this population. Obviously, the main objective of rehabilitation is to prevent fractures rather than to treat the complications. These complications can vary from "silent" compression fractures of vertebral bodies, to sacral insufficiency fractures, to "breath-taking" fractures of the spine or femoral neck. The exponential loss of bone at the postmenopausal stage is not accompanied by an incremental loss of muscle strength. The loss of muscle strength follows a more gradual course and is not affected significantly by a sudden hormonal decline, as is the case with bone loss. This muscle loss may contribute to osteoporosis-related skeletal disfigurations. In men and women, the combination of aging and reduction of physical activity can affect musculoskeletal health, and contribute to the development of bone fragility. The parallel decline in muscle mass and bone mass with age is more than a coincidence, and inactivity may explain some of the bone loss previously associated with aging per se. Kyphotic postural change is the most physically disfiguring and psychologically damaging effect of osteoporosis and can contribute to an increment in vertebral fractures and the risk of falling. Axial skeletal fractures, such as fracture of the sacral alae (sacral insufficiency fracture) and pubic rami, may not be found until radiographic changes are detected. Management of chronic pain should include not only improvement of muscle strength and posture but also, at times

  14. Challenges in Mathematical Cognition

    Directory of Open Access Journals (Sweden)

    Lara Alcock

    2016-04-01

    Full Text Available This paper reports on a collaborative exercise designed to generate a coherent agenda for research on mathematical cognition. Following an established method, the exercise brought together 16 mathematical cognition researchers from across the fields of mathematics education, psychology and neuroscience. These participants engaged in a process in which they generated an initial list of research questions with the potential to significantly advance understanding of mathematical cognition, winnowed this list to a smaller set of priority questions, and refined the eventual questions to meet criteria related to clarity, specificity and practicability. The resulting list comprises 26 questions divided into six broad topic areas: elucidating the nature of mathematical thinking, mapping predictors and processes of competence development, charting developmental trajectories and their interactions, fostering conceptual understanding and procedural skill, designing effective interventions, and developing valid and reliable measures. In presenting these questions in this paper, we intend to support greater coherence in both investigation and reporting, to build a stronger base of information for consideration by policymakers, and to encourage researchers to take a consilient approach to addressing important challenges in mathematical cognition.

  15. Challenges in organ transplantation.

    Science.gov (United States)

    Beyar, Rafael

    2011-04-01

    Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty.

  16. Ribosomal Antibiotics: Contemporary Challenges

    Directory of Open Access Journals (Sweden)

    Tamar Auerbach-Nevo

    2016-06-01

    Full Text Available Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.

  17. Challenges in Piaget's legacy.

    Science.gov (United States)

    Bibace, Roger

    2013-03-01

    The publication of After Piaget (Martí and Rodríguez 2012) hopefully triggers a new effort to understand the richness of the efforts of that major psychologist of the 20th century. Piaget was consistently concerned with part/whole relationships throughout his life. He addressed this issue philosophically, epistemologically, and psychologically. Conceptually Piaget struggled with the issue of continuity/discontinuity in development and changed his mind about how to reconcile the discontinuities of stages with his concept of development. I also attribute his variability to the implications of his important work on perception, and to his willingness to get involved in widespread concrete applications of his approach to education including the education of children with special needs; his center for genetic epistemology, and his interest in psychoanalysis. Benefiting from all the authors of After Piaget, I want to point out that Piaget has identified many major issues that will continue to constitute challenges to psychology in this century. These include specifying terms such as 'development;' methodological issues such as sampling both quantitatively in one culture and across cultures; comprehensive inclusion of the psychological processes covered by introductory textbooks in psychology; and conceptual issues such as the relationships among all these parts within a whole. I make a distinction between an 'issue' and a 'problem'--problems have solutions; while issues refer to controversies in science generally as well as in psychology that have persisted for centuries.

  18. Challenges in Astronomy Education

    Science.gov (United States)

    De Greve, Jean-Pierre

    2010-11-01

    Astronomy is an attractive subject for education. It deals with fascination of the unknown and the unreachable, yet is uses tools, concepts and insights from various fundamental sciences such as mathematics, physics, chemistry, biology. Because of this it can be well used for introducing sciences to young people and to raise their interest in further studies in that direction. It is also an interesting subject for teaching as its different aspects (observation techniques, theory, data sampling and analysis, modelling,?) offer various didactical approaches towards different levels of pupils, students and different backgrounds. And it gives great opportunities to teach and demonstrate the essence of scientific research, through tutorials and projects. In this paper we discuss some of the challenges education in general, and astronomy in particular, faces in the coming decades, given the major geophysical and technological changes that can be deducted from our present knowledge. This defines a general, but very important background in terms of educational needs at various levels, and in geographical distribution of future efforts of the astronomical community. Special emphasis will be given to creative approaches to teaching, to strategies that are successful (such as the use of tutorials with element from computer games), and to initiatives complementary to the regular educational system. The programs developed by the IAU will be briefly highlighted.

  19. Osteomyelitis: a current challenge

    Directory of Open Access Journals (Sweden)

    Luciana Souza Jorge

    2010-06-01

    Full Text Available Over the last 30 years, the pathogenesis of osteomyelitis has almost been totally elucidated, and many factors responsible for the persistence of this infection have been identified. Numerous antimicrobial agents with distinct spectrums of action, pharmacokinetics, and pharmacodynamics have been used in its treatment. Surgical techniques, including muscle grafts, the Ilizarov technique, and antibiotic bone cements, have been applied. However, bone infections are still a challenge. Despite the importance of isolation and identification of microorganisms to determine the antimicrobial treatment of bone infections, there are few systematic national studies about the etiological profile of these diseases. This article describes the current knowledge of osteomyelitis and summarizes published national data based on the experience of different Orthopedic and Traumatology Services. In general, S. aureus was described as an important etiological agent; however, the difference in design of national studies makes a comparison between the prevalence of bone infection, the associated risk factors, and the different therapeutic approaches difficult. In conclusion, effort is necessary in order to stimulate systematic national studies in different Orthopedics and Traumatology Services to obtain a better consensus on preventive measures and therapies of bone infections.

  20. VISIR: Experiences and Challenges

    Directory of Open Access Journals (Sweden)

    Mohamed Tawfik

    2012-02-01

    Full Text Available It is of crucial importance the integration of practical sessions in engineering curricula owing to their significant role in understanding engineering concepts and scientific phenomena. However, the lack of practical sessions due to the high costs of the equipment and the unavailability of instructors has caused a significant declination in experimentation in engineering education. Remote laboratories have tackled this issues providing online reusable and shared workbenches unconstrained by neither geographical nor time considerations. Thereby, they have extremely proliferated among universities and integrated into engineering curricula over the last decade. This contribution compiles diverse experiences based on the deployment of the remote laboratory, Virtual Instrument Systems in Reality (VISIR, on the practices of undergraduate engineering grades at various universities within the VISIR community. It aims to show the impact of its usage on engineering education concerning the assessments of students and teachers as well. In addition, the paper address the next challenges and future works carried out at several universities within the VISIR community.

  1. 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.

  2. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-12-01

    Full Text Available ABSTRACT IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  3. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-10-01

    Full Text Available IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  4. Aquagenic urticaria: diagnostic and management challenges

    Directory of Open Access Journals (Sweden)

    Rothbaum R

    2016-11-01

    Full Text Available Robert Rothbaum, Jean S McGee Department of Dermatology, Boston University School of Medicine, Boston, MA, USA Abstract: Aquagenic urticaria (AU is a rare inducible form of physical urticaria, which occurs in response to cutaneous exposure to water, including sweat and tears. Patients present with characteristic 1–3 mm folliculocentric wheals with surrounding 1–3 cm erythematous flares within 20–30 minutes following skin contact with water. In rare cases, there are concomitant systemic symptoms, such as wheezing or shortness of breath. The pathogenesis of AU is poorly understood at this time, and it appears to be mediated in both a histamine-dependent and independent manner. Diagnosis is based on eliciting a thorough clinical history combined with a water challenge test. Some patients may need to undergo further testing to exclude other physical urticarias. Rarely, multiple physical urticarias can be present in one patient, which can complicate diagnosis and treatment. Currently, the first-line therapy for AU is an oral administration of nonsedating, second-generation H1 antihistamines, but many patients may require further interventions to have adequate symptomatic control. In this review, we discuss the diagnostic and management challenges of AU. We review the key diagnostic features that differentiate AU from other physical urticarias. We additionally describe a therapeutic ladder for the treatment of AU and the rationale supporting these treatments. Keywords: aquagenic urticaria, physical urticaria, inducible urticaria, diagnosis, management

  5. Challenging High-Ability Students

    Science.gov (United States)

    Scager, Karin; Akkerman, Sanne F.; Pilot, Albert; Wubbels, Theo

    2014-01-01

    The existing literature on indicators of an optimal learning environment for high-ability students frequently discusses the concept of challenge. It is, however, not clear what, precisely, constitutes appropriate challenge for these students. In this study, the authors examined an undergraduate honours course, Advanced Cell Biology, which has…

  6. Organizational leadership: meeting the challenge.

    Science.gov (United States)

    Hart, A L

    1994-06-01

    Leadership can be learned. Knowledge of leadership theories can serve as basis for developing skills and techniques. Style, trait, and transformational leadership can be applied in both health care institutions and professional associations. Organizational leadership is challenging, but those challenges can help individual nurses grow in the leadership skills that will continue to be demanded in the ever changing healthcare arena.

  7. Statistics Poster Challenge for Schools

    Science.gov (United States)

    Payne, Brad; Freeman, Jenny; Stillman, Eleanor

    2013-01-01

    The analysis and interpretation of data are important life skills. A poster challenge for schoolchildren provides an innovative outlet for these skills and demonstrates their relevance to daily life. We discuss our Statistics Poster Challenge and the lessons we have learned.

  8. Challenging high-ability students

    NARCIS (Netherlands)

    Scager, Karin; Akkerman, Sanne F.; Pilot, Albert; Wubbels, Theo; Hafd Onderwijsadvies en training; Leerstoel Vermunt; Faculteit Sociale Wetenschappen; LS Wubbels; Education and Learning: Development in Interaction

    2014-01-01

    The existing literature on indicators of an optimal learning environment for high-ability students frequently discusses the concept of challenge. It is, however, not clear what, precisely, constitutes appropriate challenge for these students. In this study, the authors examined an undergraduate hono

  9. IT Challenges for Space Medicine

    Science.gov (United States)

    Johnson-Throop, Kathy

    2010-01-01

    This viewgraph presentation reviews the various Information Technology challenges for aerospace medicine. The contents include: 1) Space Medicine Activities; 2) Private Medical Information; 3) Lifetime Surveillance of Astronaut Health; 4) Mission Medical Support; 5) Data Repositories for Research; 6) Data Input and Output; 7) Finding Data/Information; 8) Summary of Challenges; and 9) Solutions and questions.

  10. Challenges Facing Group Work Online

    Science.gov (United States)

    Chang, Bo; Kang, Haijun

    2016-01-01

    Online group work can be complicated because of its asynchronous characteristics and lack of physical presence, and its requirements for skills in handling technology, human relationships, and content-related tasks. This study focuses on the administrative, logistical and relationship-related challenges in online group work. Challenges in areas…

  11. Interior Design: Challenges and Solutions.

    Science.gov (United States)

    School Planning and Management, 1999

    1999-01-01

    Presents solutions to architectural challenges in school interior design; these solutions made the indoor environments more conducive and attractive for learning. Addresses four challenges: making a long corridor look less like a tunnel; maintaining tradition and minimizing cost in a new athletic facility; designing a kindergarten that is secure…

  12. Radioecological challenges for mining

    Energy Technology Data Exchange (ETDEWEB)

    Vesterbacka, P.; Ikaeheimonen, T.K.; Solatie, D. [Radiation and Nuclear Safety Authority (Finland)

    2014-07-01

    In Finland, mining became popular in the mid-1990's when the mining amendments to the law made the mining activities easier for foreign companies. Also the price of the minerals rose and mining in Finland became economically profitable. Expanding mining industry brought new challenges to radiation safety aspect since radioactive substances occur in nearly all minerals. In Finnish soil and bedrock the average crystal abundance of uranium and thorium are 2.8 ppm and 10 ppm, respectively. It cannot be predicted beforehand how radionuclides behave in the mining processes which why they need to be taken into account in mining activities. Radiation and Nuclear Safety Authority (STUK) has given a national guide ST 12.1 based on the Finnish Radiation Act. The guide sets the limits for radiation doses to the public also from mining activities. In general, no measures to limit the radiation exposure are needed, if the dose from the operation liable to cause exposure to natural radiation is no greater than 0.1 mSv per year above the natural background radiation dose. If the exposure of the public may be higher than 0.1 mSv per year, the responsible party must provide STUK a plan describing the measures by which the radiation exposure is to be kept as low as is reasonably achievable. In that case the mining company responsible company has to make a radiological baseline study. The baseline study must focus on the environment that the mining activities may impact. The study describes the occurrence of natural radioactivity in the environment before any mining activities are started. The baseline study lasts usually for two to three years in natural circumstances. Based on the baseline study measurements, detailed information of the existing levels of radioactivity in the environment can be attained. Once the mining activities begin, it is important that the limits are set for the wastewater discharges to the environment and environmental surveillance in the vicinity of

  13. Histamine and tryptase in nasal lavage fluid after allergen challenge

    DEFF Research Database (Denmark)

    Jacobi, H H; Skov, P S; Poulsen, L K

    1999-01-01

    BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine......, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing...... and a significant increase in the levels of histamine and tryptase. The challenge of subjects not allergic to pollen produced no such response. Azelastine and cetirizine significantly reduced allergen-induced sneezing and the associated increase in histamine and tryptase levels. No significant differences were...

  14. 76 FR 41526 - Centennial Challenges 2011 Strong Tether Challenge

    Science.gov (United States)

    2011-07-14

    ... register. Centennial Challenges is a program of prize competitions to stimulate innovation in technologies...,000 (two million U.S. dollars). Incremental prizes will be offered for entries that meet...

  15. Oral food challenges in children

    Directory of Open Access Journals (Sweden)

    Hye Yung Yum

    2011-01-01

    Full Text Available Many patients assume that allergic reactions against foods are responsible for triggering or worsening their allergic symptoms. Therefore, it is important to identify patients who would benefit from an elimination diet, while avoiding unnecessary dietary restrictions. The diagnosis of food allergy depends on the thorough review of the patients's medical history, results of supplemented trials of dietary elimination, and in vivo and in vitro tests for measuring specific IgE levels. However, in some cases the reliability of such procedures is suboptimal. Oral food challenges are procedures employed for making an accurate diagnosis of immediate and occasionally delayed adverse reactions to foods. The timing and type of the challenge, preparation of patients, foods to be tested, and dosing schedule should be determined on the basis of the patient's history, age, and experience. Although double-blind, placebo-controlled food challenges(DBPCFC are used to establish definitively if a food is the cause of adverse reactions, they are time-consuming, expensive and troublesome for physician and patients. In practice, An open challenge controlled by trained personnel is sufficient especially in infants and young children. The interpretation of the results and follow-up after a challenge are also important. Since theses challenges are relatively safe and informative, controlled oral food challenges could become the measure of choice in children.

  16. Managing nut-induced anaphylaxis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Lomas JM

    2015-10-01

    Full Text Available Jeanne M Lomas, Kirsi M Järvinen Division of Pediatric Allergy and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Abstract: The prevalence of peanut and tree nut allergy in the USA has increased, especially in the pediatric population. Nut allergy remains the leading cause of fatal anaphylactic reactions. Management of anaphylaxis includes not only treatment of symptoms during a reaction, but strict dietary avoidance and education on potential situations, which may place the patient at high risk for accidental exposure. Cross-reactivity between various nuts along with various cross-contamination sources should be discussed with all nut-allergic individuals. Exciting research continues to emerge on other potential treatments for patients allergic to nuts, including allergen immunotherapy. Results of such interventions have been encouraging, though further studies are needed regarding safety and long-term outcomes before these can be applied to clinical practice. Keywords: peanut, tree nut, anaphylaxis, cross-reactivity, avoidance, immunotherapy

  17. The Leadership Challenge Activities Book

    CERN Document Server

    Kouzes, James M; Biech, Elaine

    2010-01-01

    ACTIVE Learning for Exemplary Leaders. The best leaders are the best learners. This evidence-based truth has been a foundational principle of The Leadership Challenge since it was first published nearly twenty-five years ago. In this new work, bestselling Leadership Challenge authors Jim Kouzes and Barry Posner team up with experiential learning expert Elaine Biech to bring today's leaders over 100 engaging activities designed to expand and accelerate their leadership development efforts. Grounded in The Five Practices of Exemplary Leadership® model, The Leadership Challenge Activities Book in

  18. Energy challenges. A European answer

    Energy Technology Data Exchange (ETDEWEB)

    Berge, Hans ten [EURELECTRIC, Brussels (Belgium)

    2013-02-01

    The European electricity sector is facing four main challenges: a very challenging investment climate, relatively low electricity demand, the continued expansion of electricity from subsidised renewable energy sources, and the unexpected weakness of the EU Emissions Trading System (ETS). EURELECTRIC's answers to these challenges revolve around a more consistent framework with the ETS as the key driver of decarbonisation, the integration of renewables into the market and a less distortive approach to their development, a renewed focus on energy infrastructure as a means of completing the internal energy market, and an improved strategy for RD and D.

  19. Challenges in aerospace medicine education.

    Science.gov (United States)

    Grenon, S Marlene; Saary, Joan

    2011-11-01

    Aerospace medicine training and research represents a dream for many and a challenge for most. In Canada, although some opportunities exist for the pursuit of education and research in the aerospace medicine field, they are limited despite the importance of this field for enabling safe human space exploration. In this commentary, we aim to identify some of the challenges facing individuals wishing to get involved in the field as well as the causal factors for these challenges. We also explore strategies to mitigate against these.

  20. Challenge of COPD: Getting Tested

    Science.gov (United States)

    ... please turn JavaScript on. Feature: The Challenge of COPD Getting Tested Past Issues / Fall 2014 Table of Contents Getting Tested Everyone at risk for COPD who has cough, sputum production, or shortness of ...

  1. Wildland Fire Sensors Challenge Webinar

    Science.gov (United States)

    This challenge seeks a field-ready prototype system capable of measuring constituents of smoke, including particulates, carbon monoxide, ozone, and carbon dioxide, over the wide range of levels expected during wildland fires.

  2. The Challenge to Affirmative Action

    Science.gov (United States)

    McGinnis, James W.

    1978-01-01

    The Bakke case is the latest and most serious challenge to the constitutionality of voluntary affirmative action programs. If Bakke is upheld, it could virtually wipe out efforts to include minorities in most professional schools and some government employment. (Author)

  3. Refugee status determination: three challenges

    Directory of Open Access Journals (Sweden)

    Martin Jones

    2009-04-01

    Full Text Available Refugee status determination (RSD, which is vital to the protection of so many asylum seekers worldwide, is at best an imperfect, haphazard and challenging process. It merits greater attention and appropriate reform.

  4. Japanese Management: An American Challenge.

    Science.gov (United States)

    Rehder, Robert R.

    1979-01-01

    In contrast to the American system of management, Japanese management motivates its employees by challenging them with high goals and by providing inhouse training and development opportunities to meet their self-fulfillment needs. (Author/LD)

  5. Challenges in Designing Mechatronic Systems

    DEFF Research Database (Denmark)

    Torry-Smith, Jonas; Qamar, Ahsan; Achiche, Sofiane

    2013-01-01

    Development of mechatronic products is traditionally carried out by several design experts from different design domains. Performing development of mechatronic products is thus greatly challenging. In order to tackle this, the critical challenges in mechatronics have to be well understood and well...... supported through applicable methods and tools. This paper aims at identifying the major challenges, by conducting a systematic and thorough survey of the most relevant research work in mechatronic design. Solutions proposed in literature are assessed and illustrated through a case study in order...... to investigate if the challenges can be handled appropriately by the methods, tools, and mindsets suggested by the mechatronic community. Using a real world mechatronics case, the paper identifies the areas where further research is required, by showing a clear connection between the actual problems faced during...

  6. Challenges to Nordic Police Research

    DEFF Research Database (Denmark)

    Holmberg, Lars

    2015-01-01

    The paper will cover three main points: A short description of published police research in the Nordic countries; a somewhat longer discussion of the nature of, and challenges to, Nordic police research and, finally, a critique of the homeliness of research.......The paper will cover three main points: A short description of published police research in the Nordic countries; a somewhat longer discussion of the nature of, and challenges to, Nordic police research and, finally, a critique of the homeliness of research....

  7. Effect of folate deficiency on experimental colitis in mice induced by dextran sodium sulfate%叶酸缺乏对葡聚糖硫酸钠诱导的小鼠实验性结肠炎的影响

    Institute of Scientific and Technical Information of China (English)

    马玉萍; 肖锐; 方维丽; 李海东; 刘文天

    2015-01-01

    Objective To investigate whether folate deficiency cause high expression level of interferon gamma (IFN-γ) resulted from IFN-γ gene ( IFNG) hypomethylation and then promote the pathogenesis and development of ulcerative colitis (UC ) in a dextran sulfate sodium (DSS )-induced experimental colitis model in mice .Methods A total of 24 female BALB/c mice were divided into four groups ,six mice in each group , including folate deficient/DSS+ group , standard diet/DSS+ group , standard diet/DSS - group and folate deficient/DSS- group .At the beginning of the sixth week since fed , the mice of model groups were treated with 5% DSS to establish experimental colitis .By the end of the sixth week ,disease activity index (DAI) of colitis and histological changes were evaluated .The folate level of peripheral blood serum of mice were detected by enzyme-linked immunosorbent assay (ELISA ) . The expression of IFN-γ in colonic mucosa of mice was examined by immunohistochemistry . The methylation level of CpG island in the promoter region of IFNG was determined by methylation specific polymerase chain reaction (MSP) .The t test was used for measurement data .Chi square test was performed for comparison between groups of count data . Spearman correlation analysis was used for correlation analysis .Results The folate levels of peripheral blood serum of folate deficiency/DSS+ group and folate deficiency/DSS- group ((2 .70 ± 0 .19) and (2 .80 ± 0 .25)μg/L) were significantly lower than those of standard diet/DSS+ group and standard diet/DSS- group ((13 .62 ± 0 .38 ) and (13 .52 ± 0 .77)μg/L ,t= -63 .33、32 .27 ,both P< 0 .05) ,resepectively .The expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group and standard diet/DSS+ group were significantly higher than those of folate deficiency/DSS- group and standard diet/DSS- group (χ2 = 22 .18 ,P< 0 .05 ) . And the expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group was also higher than that of

  8. Challenges in implementing and maintaining osteoporosis therapy

    Directory of Open Access Journals (Sweden)

    Modi A

    2014-08-01

    Full Text Available Ankita Modi,1 Shiva Sajjan,1 Sampada Gandhi2 1Center for Observational and Real-World Evidence, Merck & Co., Inc., Whitehouse Station, NJ, USA; 2School of Public Health, Rutgers University, Piscataway, NJ, USA Abstract: In the United States, an estimated 19% of older men and 30% of older women are at elevated risk of osteoporotic fracture and considered to be eligible for treatment. The burden of osteoporosis is similar in Europe and is projected to rise worldwide, with aging populations and increasing fracture rates accompanying urbanization. Notwithstanding its high prevalence, osteoporosis is often underdiagnosed and undertreated. Moreover, even when the diagnosis is made and the decision is taken to treat, there are remaining challenges in implementing therapy for osteoporosis. Several patient populations are particularly challenging for clinicians to treat and require further study with regard to osteoporosis therapy. These include the very elderly, who face challenges relating to adherence; men, in whom osteoporosis remains under-recognized; patients with glucocorticoid-induced osteoporosis or renal impairment, who are at increased risk of fracture; patients with preexisting gastrointestinal problems who cannot tolerate existing orally administered osteoporosis therapies; and high-risk patients who show inadequate response to therapy. Moreover, poor adherence and poor persistence with osteoporosis medications are common and result in an increased risk of fracture, higher medical costs, and increased hospitalizations. Once the decision to institute therapy is made, patient education about osteoporosis and fracture risk should be provided. This is particularly important for men, who may not be aware that osteoporosis can be a concern. Secondary prevention programs, including fracture liaison services and bone therapy groups, can help to improve adherence to therapy. Further study is needed to guide the treatment of men, the very elderly

  9. Nasal PMN response to repeated challenge with endotoxin in healthy volunteers**

    Science.gov (United States)

    Abstract Rationale: We have employed nasal challenge with Iipopolysaccharid (lPS) followed by nasal lavage (NU to experimentally induce and examine upper airway inflammation in human volunteers.It is unclear however whether adaptation within individuals occurs following repeated ...

  10. Stable isotope views on ecosystem function: challenging or challenged?

    Science.gov (United States)

    Resco, Víctor; Querejeta, José I.; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C.; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A.; Torres-Cañabate, Patricia; Valladares, Fernando

    2010-01-01

    Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Úbeda, 18–22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes. PMID:20015858

  11. Challenges and counter challenges in HIV/AIDS

    Institute of Scientific and Technical Information of China (English)

    Qingsheng Li; Charles Wood

    2010-01-01

    @@ Since the beginning of the HIV/AIDS pandemic, there has been significant progress in combating the virus.In addition to identifying HIV,1 scientists have developed an array of antiretroviral drugs and successfully converted the once deadly disease into a treatable and chronic condition.2 Nevertheless, this battle is far from over and HIV still outsmarts humans in multiple ways and poses tremendous challenges. Within this context, the Chinese Medical Journal has timely published this special issue on HIV/AIDS, highlighting the ongoing challenges posed by HIV and potential solutions to these problems.

  12. ESTUARINE AND COASTAL CHALLENGES IN CHINA

    Institute of Scientific and Technical Information of China (English)

    陈吉余; 陈沈良

    2002-01-01

    Estuaries and coasts are conjunctions of four spheres (atmosphere, lithosphere, hydrosphere and biosphere) and important matter and energy convergence/divergence zones, where developed economy, dense population and highly intensive exploitation induce adverse environmental changes and serious destruction of resources, which have great impacts on coastal sustainable development, especially as the highly intensive development in river basins has direct and pronounced effects on estuaries and their adjacent coasts. In the new century, China's estuaries and coast are faced with four main challenges: sharp decrease of sediment discharge into the sea, rapid increase of pollution matter into the sea, loss of coastal wetland, and the impacts of global sea level rise on the coastallowlands of China. Therefore, it is undoubtedly very important and urgent to carry out studies on estuarine and coastal environmental changes, in order to resolve the issue of national sustainable development, especially that of rational use of coastal zone resources. ``

  13. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Directory of Open Access Journals (Sweden)

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  14. Challenges in diagnostic accuracy studies in primary care : the fecal calprotectin example

    NARCIS (Netherlands)

    Holtman, Gea A.; Lisman-van Leeuwen, Yvonne; Kollen, Boudewijn J.; Escher, Johanna C.; Kindermann, Angelika; van Rheenen, Patrick F.; Berger, Marjolein Y.

    2013-01-01

    Background: Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodological implications of ou

  15. Challenges in diagnostic accuracy studies in primary care: The fecal calprotectin example

    NARCIS (Netherlands)

    G.A. Holtman (Gea A); Y. van Leeuwen (Yvonne); B.J. Kollen (Boudewijn ); J.C. Escher (Johanna); A. Kindermann; P.F.V. Rheenen (Patrick F Van); M.Y. Berger (Marjolein)

    2013-01-01

    textabstractAbstract. Background: Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodologi

  16. Ecological Challenges for Closed Systems

    Science.gov (United States)

    Nelson, Mark; Dempster, William; Allen, John P.

    2012-07-01

    Closed ecological systems are desirable for a number of purposes. In space life support systems, material closure allows precious life-supporting resources to be kept inside and recycled. Closure in small biospheric systems facilitates detailed measurement of global ecological processes and biogeochemical cycles. Closed testbeds facilitate research topics which require isolation from the outside (e.g. genetically modified organisms; radioisotopes) so their ecological interactions and fluxes can be studied separate from interactions with the outside environment. But to achieve and maintain closure entails solving complex ecological challenges. These challenges include being able to handle faster cycling rates and accentuated daily and seasonal fluxes of critical life elements such as carbon dioxide, oxygen, water, macro- and mico-nutrients. The problems of achieving sustainability in closed systems for life support include how to handle atmospheric dynamics including trace gases, producing a complete human diet and recycling nutrients and maintaining soil fertility, the sustaining of healthy air and water and preventing the loss of crucial elements from active circulation. In biospheric facilities the challenge is also to produce analogues to natural biomes and ecosystems, studying processes of self-organization and adaptation in systems that allow specification or determination of state variables and cycles which may be followed through all interactions from atmosphere to soils. Other challenges include the dynamics and genetics of small populations, the psychological challenges for small isolated human groups and measures and options which may be necessary to ensure long-term operation of closed ecological systems.

  17. Aquagenic urticaria: diagnostic and management challenges

    Science.gov (United States)

    Rothbaum, Robert; McGee, Jean S

    2016-01-01

    Aquagenic urticaria (AU) is a rare inducible form of physical urticaria, which occurs in response to cutaneous exposure to water, including sweat and tears. Patients present with characteristic 1–3 mm folliculocentric wheals with surrounding 1–3 cm erythematous flares within 20–30 minutes following skin contact with water. In rare cases, there are concomitant systemic symptoms, such as wheezing or shortness of breath. The pathogenesis of AU is poorly understood at this time, and it appears to be mediated in both a histamine-dependent and independent manner. Diagnosis is based on eliciting a thorough clinical history combined with a water challenge test. Some patients may need to undergo further testing to exclude other physical urticarias. Rarely, multiple physical urticarias can be present in one patient, which can complicate diagnosis and treatment. Currently, the first-line therapy for AU is an oral administration of nonsedating, second-generation H1 antihistamines, but many patients may require further interventions to have adequate symptomatic control. In this review, we discuss the diagnostic and management challenges of AU. We review the key diagnostic features that differentiate AU from other physical urticarias. We additionally describe a therapeutic ladder for the treatment of AU and the rationale supporting these treatments. PMID:27942227

  18. Wheat induced urticaria

    Directory of Open Access Journals (Sweden)

    Uppal Monica

    2004-09-01

    Full Text Available Wheat is widely consumed all over India in various forms - flour, daliya, maida, suji and wheat bran. Very few cases of wheat induced urticaria have been reported. This may be due to unusual features of wheat related hypersensitivity. A 35 year old female presented to us with history of chronic urticaria and angioedema. History revealed correlation between wheat intake and urticaria episodes. Prick testing was done with wheat antigen in the standard series and derivatives of raw wheat. Normal saline and histamine were used as controls. Prick testing was positive. Oral challenge induced urticaria within half an hour. This report discusses clinical features of wheat related hypersensitivity.

  19. Immune responses induced by a Leishmania (Leishmania amazonensis recombinant antigen in mice and lymphocytes from vaccinated subjects

    Directory of Open Access Journals (Sweden)

    Ana Paula FERNANDES

    1997-03-01

    Full Text Available In the search for Leishmania recombinant antigens that can be used as a vaccine against American Cutaneous Leishmaniasis, we identified a Leishmania (Leishmania amazonensis recombinant protein of 33 kD (Larp33 which is recognized by antibodies and peripheral blood leukocytes (PBL from subjects vaccinated with Leishvacin ®, Larp33 was expressed in Escherichia coli after cloning of a 2,2 kb Sau3A digested genomic fragment of L. (L. amazonensis into the pDS56-6 His vector. Immunoblotting analysis indicated that Larp33 corresponds to an approximately 40-kD native protein expressed in promastigotes of L.(L. amazonensis and L. (Viannia braziliensis. Northern blots of total RNA also demonstrated that the gene coding for this protein is expressed in promastigotes of the major lineages of Leishmania causing American Cutaneous Leishmaniasis. Larp33 induced partial protection in susceptible mouse strains (BALB/c and C57BL/10 against L. (L. amazonensis after vaccination using Bacille Calmette-Guerin (BCG as adjuvant. In vitro stimulation of splenocytes from BALB/c protected mice with Larp33 elicited the secretion of IL-2 and IFN-g, suggesting that a Th1 cell-mediated protective response is associated with the resistance observed in these mice. As revealed by its immunogenic and antigenic properties, this novel recombinant antigen is a suitable candidate to compose a vaccine against cutaneous leishmaniasisA resposta imune induzida por uma proteína recombinante de Leishmania (Leishmania amazonensis de 33 kD (Larp33 foi avaliada em linfócitos de indivíduos vacinados com a Leishvacin® e em camundongos através de vacinação. Larp33 foi expressa em Escherichia coli após clonagem de um fragmento genômico de L. (L. amazonensis de 2,2 kb no vetor pDS56-6His. Larp33 foi reconhecida por anticorpos IgG presentes no soro de indivíduos vacinados com Leishvacin® e induziu proliferação em linfócitos desses indivíduos em níveis comparáveis ao ant

  20. Seismological challenges for stellar structure

    CERN Document Server

    Christensen-Dalsgaard, J

    2010-01-01

    Helioseismology has provided very detailed information about the solar interior, and extensive data on a large number of stars, although at less detail, are promised by the ongoing and upcoming asteroseismic projects. In the solar case there remain serious challenges in understanding the inferred solar structure, particularly in the light of the revised determinations of the solar surface composition. Also, a secure understanding of the origins of solar rotation as inferred from helioseismology, both in the radiative interior and in the convection zone, is still missing. In the stellar case challenges are certain to appear as the data allow more detailed inferences of the properties of stellar cores. Large remaining uncertainties in modelling concerns the properties of convective cores and other processes that may cause mixing. As a result of developing asteroseismic signatures addressing these and other issues, we can look forward to a highly challenging, and hence exciting, era of stellar astrophysics.

  1. Pediatric Sedation: A Global Challenge

    Directory of Open Access Journals (Sweden)

    David Gozal

    2010-01-01

    Full Text Available Pediatric sedation is a challenge which spans all continents and has grown to encompass specialties outside of anesthesia, radiology and emergency medicine. All sedatives are not universally available and local and national regulations often limit the sedation practice to specific agents and those with specific credentials. Some specialties have established certification and credentials for sedation delivery whereas most have not. Some of the relevant sedation guidelines and recommendations of specialty organizations worldwide will be explored. The challenge facing sedation care providers moving forward in the 21st century will be to determine how to apply the local, regional and national guidelines to the individual sedation practices. A greater challenge, perhaps impossible, will be to determine whether the sedation community can come together worldwide to develop standards, guidelines and recommendations for safe sedation practice.

  2. Challenges in future linear colliders

    CERN Document Server

    Chattopadhyay, S

    2002-01-01

    For decades, electron-positron colliders have been complementing proton-proton colliders. But the circular LEP, the largest e/sup -/e /sup +/ collider, represented an energy limit beyond which energy losses to synchrotron radiation necessitate moving to e/sup -/e/sup + / linear colliders (LCs), thereby raising new challenges for accelerator builders. Japanese-American, German, and European collaborations have presented options for the "Future Linear Collider " (FLC). Key accelerator issues for any FLC option are the achievement of high enough energy and luminosity. Damping rings, taking advantage of the phenomenon of synchrotron radiation, have been developed as the means for decreasing beam size, which is crucial for ensuring a sufficiently high rate of particle-particle collisions. Related challenges are alignment and stability in an environment where even minute ground motion can disrupt performance, and the ability to monitor beam size. The technical challenges exist within a wider context of socioeconomi...

  3. Higgs Machine Learning Challenge 2014

    CERN Multimedia

    Olivier, A-P; Bourdarios, C ; LAL / Orsay; Goldfarb, S ; University of Michigan

    2014-01-01

    High Energy Physics (HEP) has been using Machine Learning (ML) techniques such as boosted decision trees (paper) and neural nets since the 90s. These techniques are now routinely used for difficult tasks such as the Higgs boson search. Nevertheless, formal connections between the two research fields are rather scarce, with some exceptions such as the AppStat group at LAL, founded in 2006. In collaboration with INRIA, AppStat promotes interdisciplinary research on machine learning, computational statistics, and high-energy particle and astroparticle physics. We are now exploring new ways to improve the cross-fertilization of the two fields by setting up a data challenge, following the footsteps of, among others, the astrophysics community (dark matter and galaxy zoo challenges) and neurobiology (connectomics and decoding the human brain). The organization committee consists of ATLAS physicists and machine learning researchers. The Challenge will run from Monday 12th to September 2014.

  4. Interleukin-12 and protective immunity to schistosomes

    Directory of Open Access Journals (Sweden)

    Mountford A.P.

    1998-01-01

    Full Text Available The attenuated vaccine against Schistosoma mansoni induces Th1-mediated protective immunity and we have sought to identify a role for IL-12 in this model. Elevated levels of IL-12 (p40 mRNA were detected in the lymph nodes (LN and the lungs of vaccinated mice, whilst treatment of vaccinated mice with anti-IL-12 antibodies decreased the ratio of IFNg:IL-4 secreted by in vitro-cultured LN cells. However, there was only marginal abrogation of the level of resistance in these mice. Soluble antigens from the lung-stage of the parasite (SLAP appeared to be efficient stimulators of IFNg and IL-12 secretion. These antigens when used to immunise mice in conjunction with IL-12 as an adjuvant, elicited a polarised Th1 response with abundant IFNg secretion but no IL-4. This immunisation regime also induced significant protection against reinfection, whereas inoculation of mice with SLAP alone did not. The induction of a dominant Th1 response using SLAP + IL-12 probably operates via IFNg production by natural killer (NK cells stimulated by IL-12, since in vivo ablation of NK cells using anti-NK1.1 antibody reduced CD4+-dependent IFNg production from cultured LN cells by over 97%. Nevertheless, in mice with a genetic disruption of the IFNg receptor, administration of SLAP + IL-12 induced levels of IFNg equal to those in wild-type mice, thus showing that in this model IL-12 can directly prime T cells independent of IFNg. Clearly, IL-12 has a critical role in protective immunity to schistosomes and it may aid the development of an effective vaccine against this disease

  5. The Challenge of Prejudice: Counsellors' Talk about Challenging Clients' Prejudices

    Science.gov (United States)

    Spong, Sheila J.

    2012-01-01

    This paper considers the implications for training and practice of counsellors' responses to the notion of challenging clients' prejudices. It explores tensions in counselling discourse between social responsibility, responsibility to the client and responsibility for one's self as counsellor. Three focus groups of counsellors were asked whether a…

  6. Success of Breast Cancer Startup Challenge Inspires Second Challenge | Poster

    Science.gov (United States)

    By Thomas Stackhouse, Joseph Conrad, and Michele Newton, Contributing Writers, and Rosemarie Truman, Guest Writer Sixty-one teams have been accepted into, and are now competing in, the Neuro Startup Challenge, a new collaboration established by the National Institutes of Health (NIH) with The Center for Advancing Innovation (CAI) and Heritage Provider Network, Inc.

  7. Challenges in anaesthesia for elderly

    DEFF Research Database (Denmark)

    Strøm, Camilla; Rasmussen, L S

    2014-01-01

    The segment of elderly individuals comprises a growing proportion of the global population. Health care systems and health care providers worldwide need to understand the specific challenges related to treatment of this heterogeneous patient population. The process of ageing is complex and under ...... of the challenges, when dealing with the aged surgical population with emphasis on postoperative cognitive changes....... of treatment of an elderly patient is not necessarily to increase human longevity regardless of the consequences, but to increase active longevity free from disability and functional dependence. For older people, deterioration in function can be devastating and is often precipitated by a stressful event...

  8. The challenges of big data.

    Science.gov (United States)

    Mardis, Elaine R

    2016-05-01

    The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest.

  9. Understanding the LHC Controls Challenges

    CERN Document Server

    Van den Eynden, M

    2000-01-01

    The analysis, design and construction of the LHC control system is a complex problem which will challenge CERN's capability to provide a modern controls infrastructure fulfilling the stringent operational requirements of this machine. The first part of this talk will review the present LHC project context in which several controls initiatives have already been taken. The second part will try to highlight the important technical aspects and engineering steps involved in the process of defining a control system architecture. The importance of understanding the major LHC operational challenges will be stressed along with some practical proposals and examples on how to conduct such activity with all stakeholders.

  10. Vitreous substitutes: challenges and directions

    Institute of Scientific and Technical Information of China (English)

    Qian-Ying; Gao; Yue; Fu; Yan-Nian; Hui

    2015-01-01

    The natural vitreous body has a fine structure and complex functions. The imitation of the natural vitreous body by vitreous substitutes is a challenging work for both researchers and ophthalmologists. Gases, silicone oil, heavy silicone oil and hydrogels, particularly the former two vitreous substitutes are clinically widely used with certain complications. Those, however, are not real artificial vitreous due to lack of structure and function like the natural vitreous body. This article reviews the situations, challenges, and future directions in the development of vitreous substitutes, particularly the experimental and clinical use of a new artificial foldable capsular vitreous body.

  11. The challenges of big data

    Science.gov (United States)

    2016-01-01

    ABSTRACT The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest. PMID:27147249

  12. Grand Challenges of Enterprise Integration

    Energy Technology Data Exchange (ETDEWEB)

    Brosey, W.D; Neal, R.E.; Marks, D.

    2001-04-01

    Enterprise Integration connects and combines people, processes, systems, and technologies to ensure that the right people and the right processes have the right information and the right resources at the right time. A consensus roadmap for Technologies for Enterprise Integration was created as part of an industry/government/academia partnership in the Integrated Manufacturing Technology Initiative (IMTI). Two of the grand challenges identified by the roadmapping effort will be addressed here--Customer Responsive Enterprises and Totally Connected Enterprises. Each of these challenges is briefly discussed as to the current state of industry and the future vision as developed in the roadmap.

  13. Authenticity and its Contemporary Challenges

    DEFF Research Database (Denmark)

    Bork Petersen, Franziska

    2013-01-01

    In this thesis I investigate what ‘authenticity’ means in a contemporary popular context and how it is used in the staging of bodies. Furthermore, I analyse works of dance and fashion from the past fifteen years with a focus on their strategies of challenging the notion of ‘bodily authenticity...... and by a depiction of 'working hard'. But various techniques also mask the hard work, for example by showing a participant ‘having fun’ performing it. Contemporary works of dance and fashion challenge the problematic implications in the notion of ‘bodily authenticity’. I analyse three strategies of undermining...

  14. Dengue vaccine development: strategies and challenges.

    Science.gov (United States)

    Ramakrishnan, Lakshmy; Pillai, Madhavan Radhakrishna; Nair, Radhakrishnan R

    2015-03-01

    Infection with dengue virus may result in dengue fever or a more severe outcome, such as dengue hemorrhagic syndrome/shock. Dengue virus infection poses a threat to endemic regions for four reasons: the presence of four serotypes, each with the ability to cause a similar disease outcome, including fatality; difficulties related to vector control; the lack of specific treatment; and the nonavailability of a suitable vaccine. Vaccine development is considered challenging due to the severity of the disease observed in individuals who have acquired dengue-specific immunity, either passively or actively. Therefore, the presence of vaccine-induced immunity against a particular serotype may prime an individual to severe disease on exposure to dengue virus. Vaccine development strategies include live attenuated vaccines, chimeric, DNA-based, subunit, and inactivated vaccines. Each of the candidates is in various stages of preclinical and clinical development. Issues pertaining to selection pressures, viral interaction, and safety still need to be evaluated in order to induce a complete protective immune response against all four serotypes. This review highlights the various strategies that have been employed in vaccine development, and identifies the obstacles to producing a safe and effective vaccine.

  15. They rose to the challenge!

    CERN Multimedia

    Anaïs Schaeffer

    2015-01-01

    The Challenge-Based Innovation programme is a Masters-level initiative developed at CERN in collaboration with many universities around the world. The first programme saw 45 students take part, and their final results were presented at an official "gala" held on 26 February.   On 26 February, after their official presentations, the six CBI teams presented their prototypes to the public in the IdeaSquare building.   As part of the IdeaSquare project, the Challenge-Based Innovation (CBI) programme is based on a very pragmatic question: can the tools and results produced by basic research (like that being carried out at CERN) be used to solve societal problems? If so, how? To answer this question, 45 students from very different professional and cultural backgrounds formed six teams, each with a specific societal challenge to solve (see here). Over a six-month period – from September 2014 to February 2015 – the six teams worked on the challenge in o...

  16. Bioanalysis: challenges and solutions seminar.

    Science.gov (United States)

    Roberts, Andrew

    2011-09-01

    Industry challenges and solutions for bioanalysis were top of the agenda for the Spring Seminar organized by Quotient Bioresearch in Munich, Germany. The seminar was attended by representatives from pharmaceutical and biotechnology organisations across Europe and featured debates and panel discussions from leading industry speakers on new techniques and hot topics, including the latest industry guidelines.

  17. Toxaphene: a challenging analytical problem

    NARCIS (Netherlands)

    Geus, de H.J.; Wester, P.G.; Schelvis, A.; Boer, de J.; Brinkman, U.A.Th.

    2000-01-01

    The analysis of toxaphene, a highly complex mixture of chlorinated bornanes, bornenes and camphenes, is a challenging problem, especially as individual congeners are present at trace levels in biota and other relevant samples. The complicated nomenclature of the compounds of interest is briefly disc

  18. Kids Camping Takes the Challenge.

    Science.gov (United States)

    James, Vickie L.; Hohnbaum, Claudia

    2002-01-01

    A Wisconsin Girl Scout camp integrated The Healthy Kids Challenge into its program. The camp evaluated policies related to meals, snacks, physical activities, team building, and self-esteem. Staff inservice training resulted in healthier meals on the same budget and developed ownership of the program. Campers and families had opportunities to…

  19. Challenges to 5G standardization

    DEFF Research Database (Denmark)

    Mihovska, Albena D.; Prasad, Ramjee

    2013-01-01

    Interoperable, ubiquitous and dynamic are key objectives for fifth-generation (5G) communication systems and applications. These characteristics are also at the core of the main challenges that researchers, manufacturers, regulators and standardization bodies face when designing targeted strategies...... for the successful deployment of 5G enabling technologies....

  20. Efficient audio power amplification - challenges

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Michael A.E.

    2005-07-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where extensive research and development are needed is covered. (au)

  1. Conceptual challenges for internalising externalities

    DEFF Research Database (Denmark)

    Miguel, Brandão; Weidema, Bo Pedersen

    2013-01-01

    We analyse a number of different externalities to identify conceptual challenges for the practical implementation of their internalisation. Three issues were identified: i) The balance between compensation and technology change and the respective effects on the nominal and real GDP; ii) The relev...

  2. Challenges in Measuring Teachers' Knowledge

    Science.gov (United States)

    Fauskanger, Janne

    2015-01-01

    Mathematical knowledge for teaching (MKT) measures have been widely adopted by researchers. Critics have debated the value of such measures and questioned the type of knowledge that these access. This article reports on a study where the challenges in measuring teachers' knowledge were illuminated through investigating relationships between the…

  3. The Concrete and Pavement Challenge

    Science.gov (United States)

    Roman, Harry T.

    2012-01-01

    The modern world is characterized by the extensive use of concrete and asphalt pavement. Periodically, these materials are replaced and the old materials disposed of. In this challenge, students will be asked to develop ways to reuse the old materials. It is important for students to understand how concrete and asphalt are made and applied, as…

  4. Fostering Reflection through Challenging Practica

    Science.gov (United States)

    Nickel, Jodi; Sutherby, Linda; Garrow-Oliver, Susan

    2010-01-01

    This article describes challenging practicum situations that provided three early childhood education students with leadership opportunities to promote best practices in child care centers. Using excerpts from student journals and meetings, the article documents students' initial discouragement at practices observed, inspiration through…

  5. Climate Change: Meeting the Challenge

    Science.gov (United States)

    Chance, Paul; Heward, William L.

    2010-01-01

    In "Climate Change: Meeting the Challenge," we conclude the special section by assuming that you have been persuaded by Thompson's paper or other evidence that global warming is real and poses a threat that must be dealt with, and that for now the only way to deal with it is by changing behavior. Then we ask what you, as behavior analysts, can do…

  6. Challenges in a Physics Course

    DEFF Research Database (Denmark)

    Hernández, Carola Hernández; Ravn, Ole; Forero Shelton, Antonio Manu

    2014-01-01

    This article identifies and analyses some of the challenges that arose in a development process of changing from a content-based teaching environment to a student-centred environment in an undergraduate physics course for medicine and biology students at Universidad de los Andes. Through the use...

  7. The Challenge of Affirmative Action.

    Science.gov (United States)

    Pang, Valerie Ooka; Strom, David; Young, Russell L.

    1997-01-01

    Explores the challenges of using affirmative action programs when competing groups of underrepresented people vie for limited school resources. The case study of a San Francisco (California) high school illustrates the difficulties of balancing competing goals when affirming diversity and addressing patterns of discrimination conflict with equal…

  8. Accountability: new challenges, new forms

    NARCIS (Netherlands)

    C. van Woerkum; N. Aarts

    2012-01-01

    The general call for more accountability, affecting all western institutions, has reached the communication professionals as well. How can they cope with this new challenge? The danger is that they focus mainly on outcomes, so on performative accountability, whereas decisional accountability, meanin

  9. A Water-Service Challenge

    Science.gov (United States)

    Roman, Harry T.

    2011-01-01

    It is important to let students see the value of mathematics in design--and how mathematics lends perspective to problem solving. In this article, the author describes a water-service challenge which enables students to design a water utility system that uses surface runoff into an open reservoir as the potable water source. This challenge…

  10. Authenticity and its Contemporary Challenges

    DEFF Research Database (Denmark)

    Bork Petersen, Franziska

    2013-01-01

    In this thesis I investigate what ‘authenticity’ means in a contemporary popular context and how it is used in the staging of bodies. Furthermore, I analyse works of dance and fashion from the past fifteen years with a focus on their strategies of challenging the notion of ‘bodily authenticity’. ...

  11. Chinese adoption: practices and challenges.

    Science.gov (United States)

    Lihua, H

    2001-01-01

    The majority of children in China who are the subject of protective services are either abandoned or disabled. Recent reform efforts in China's child welfare practices have focused on the importance of providing safe, permanent families for children in lieu of long-term institutional care. Although challenges still exist, adoption and foster care are increasingly being seen as viable alternatives for these children.

  12. Challenging Sexual Harassment on Campus

    Science.gov (United States)

    Baker, Nancy V.

    2010-01-01

    More than thirty years ago, an administrative assistant at Cornell University first challenged her university's indifference to her boss's sexually predatory behavior. While she did not prevail, her case sparked a movement. Litigation, news stories, and government guidelines defining sexual harassment followed. And universities responded: policies…

  13. NASA Space Rocket Logistics Challenges

    Science.gov (United States)

    Neeley, James R.; Jones, James V.; Watson, Michael D.; Bramon, Christopher J.; Inman, Sharon K.; Tuttle, Loraine

    2014-01-01

    The Space Launch System (SLS) is the new NASA heavy lift launch vehicle and is scheduled for its first mission in 2017. The goal of the first mission, which will be uncrewed, is to demonstrate the integrated system performance of the SLS rocket and spacecraft before a crewed flight in 2021. SLS has many of the same logistics challenges as any other large scale program. Common logistics concerns for SLS include integration of discreet programs geographically separated, multiple prime contractors with distinct and different goals, schedule pressures and funding constraints. However, SLS also faces unique challenges. The new program is a confluence of new hardware and heritage, with heritage hardware constituting seventy-five percent of the program. This unique approach to design makes logistics concerns such as commonality especially problematic. Additionally, a very low manifest rate of one flight every four years makes logistics comparatively expensive. That, along with the SLS architecture being developed using a block upgrade evolutionary approach, exacerbates long-range planning for supportability considerations. These common and unique logistics challenges must be clearly identified and tackled to allow SLS to have a successful program. This paper will address the common and unique challenges facing the SLS programs, along with the analysis and decisions the NASA Logistics engineers are making to mitigate the threats posed by each.

  14. The Electric Power Exhibit Challenge

    Science.gov (United States)

    Roman, Harry T.

    2012-01-01

    A design challenge is all about planning first and understanding the problem before diving in and looking frantically for a solution. Any experienced engineer or designer will tell one to think first and plan the steps before acting. An experienced carpenter friend of the author always said to "take many measurements and cut once." There is great…

  15. Turbulent Dissipation Challenge -- Problem Description

    CERN Document Server

    Parashar, Tulasi N; Wicks, Robert; Karimabadi, Homa; Chandran, S Peter Gary Benjamin; Matthaeus, William H

    2014-01-01

    The goal of this document is to present a detailed description of the goals, simulation setup and diagnostics for the Turbulent Dissipation Challenge $($http://arxiv.org/abs/1303.0204$)$ as discussed in the Solar Heliospheric and INterplanetary Environment $($SHINE$)$ 2013 workshop, American Geophysical Union Fall Meeting 2013 and the accompanying antenna meeting in Berkeley.

  16. IPTV: Challenges and Future Directions

    NARCIS (Netherlands)

    Bonastre, O.M.; Montpetit, M.J.; Cesar Garcia, P.S.

    2011-01-01

    The move to IP Protocol Television (IPTV) has challenged the traditional television industry by opening the Internet to high quality real time television content delivery. Thus it has provided an enabling set of key technologies to understand and foster further innovations in the multimedia landscap

  17. Challenges in Business System Integration

    NARCIS (Netherlands)

    Hvolby, H.H.; Trienekens, J.H.

    2010-01-01

    Four main frameworks for intercompany relationships (SCOR, CPFR, ISA95 and OAG) are discussed and compared. The link between the frameworks and different supply chain integration applications such as ERP, CRM and VMI are pictured. Finally the state-of-the-art, future state and challenges of the supp

  18. CHALLENGES FACING THE ESP PRACTITIONER

    Directory of Open Access Journals (Sweden)

    SIMION MINODORA OTILIA

    2015-12-01

    Full Text Available The ESP teacher has to face certain challenges in his profession: One of the biggest challenges of the ESP teacher is the fact that he/she lacks the necessary knowledge of the subject to teach Business English, for instance, some researchers believing that such courses should be taught by subject teachers. The task of teaching ESP by ESL teachers is not an easy one. Dudley- Evans and St. John pointed out its complexity, identifying five key roles of the ESP practitioner: teacher, course designer and materials provider, collaborator, researcher and evaluator and this is probably the biggest challenge of the profession. The ESP practitioner has also to be aware of the fact that using a foreign language for workplace or study purposes requires not only linguistic proficiency and knowledge but also knowledge of work –related and disciplinary concepts.Last but not least, another challenge for the ESP practitioner is the use of technology in class, a valuable tool for helping with traditional forms of teaching and for creating new forms of communicating.Thus, the ESP practitioner has many things in common with the teacher of general English: he has to be familiar with linguistic development and teaching theories ,he has to be aware of contemporary ideas related to his position and role and he has to become familiar with the new technologies which can be used to improve his methodology.However,his role is more complex than that of a General English teacher.

  19. The Challenges of Becoming Agile

    DEFF Research Database (Denmark)

    Ovesen, Nis; Dowlen, Chris

    2012-01-01

    During the last decade agile methods have been a vast success in the domain of software development. This paper investigates whether these methods can be successfully transferred to the domain of physical product development in order to address the fundamental challenges of increased marked speed...

  20. The Challenge of Urban Policy

    Science.gov (United States)

    Glaeser, Edward L.

    2012-01-01

    Urbanization almost invariably accompanies development, and the cities of India and China are experiencing spectacular increases in population. The concentration of millions of people in a small mass creates challenges for public policy, especially in the areas of basic infrastructure, public health, traffic congestion, and often law enforcement…

  1. The WCET Tool Challenge 2011

    DEFF Research Database (Denmark)

    Hanxleden, Reinhard von; Holsti, Niklas; Lisper, Björn;

    of problems to be solved by the Challenge participants with their tools, WCET problems, which ask for bounds on the execution time, and ow-analysis problems, which ask for bounds on the number of times certain parts of the code can be executed. The benchmarks to be used in WCC'11 were debie1, Papa...

  2. Climate change challenges for SEA

    DEFF Research Database (Denmark)

    Larsen, Sanne Vammen

    This paper takes a theoretical perspective on the challenges that climate changes pose for SEA. The theoretical framework used is the sociologist Ulrich Beck’s theory of risk society and the aspects that characterise this society. Climate change is viewed as a risk, and the theory is used to derive...

  3. Self Efficacy: Operationalizing Challenge Education.

    Science.gov (United States)

    McGowan, Michael L.

    1986-01-01

    Examines self-efficacy theory and how it can be utilized in describing participant change in adventure/challenge programs. Explores connection between personal experience and how people view ability to function in world around them. Discusses Bandura's theory and interaction of sources of information: performance accomplishment, vicarious…

  4. Challenges of Integrated Water Resources Management in Indonesia

    OpenAIRE

    Mohamad Ali Fulazzaky

    2014-01-01

    The increased demands for water and land in Indonesia as a consequence of the population growth and economic development has reportedly have been accelerated from the year to year. The spatial and temporal variability of human induced hydrological changes in a river basin could affect quality and quantity of water. The challenge is that integrated water resources management (IWRM) should cope with complex issues of water in order to maximize the resultant economic and social welfare in an eq...

  5. An All-School Library Challenge

    Science.gov (United States)

    Quirk, Connie

    2005-01-01

    The library media center is hosting an all-school team challenge, designed to celebrate reading and library skills. Students could choose from the contest categories like "Lord of the Rings", "Harry Potter", Author Facts Challenge and Opening Lines Challenge for the competition and those students who read more challenging books show their…

  6. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity.C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys. At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a global transcriptional variations in kidney tissues, (b morphological changes in the kidneys, (c changes in white and red blood cell count as well as blood levels of urea, and (d changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months.Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these

  7. Challenges and opportunities in nanomanufacturing

    Science.gov (United States)

    Cooper, Khershed P.; Wachter, Ralph F.

    2011-10-01

    Nanomanufacturing is the fabrication of materials and components with nanoscale features and resolution and their integration into useful engineered systems. Through the precise control of materials and processes at the nanoscale, new features, functional capabilities, and properties, controlled by physics at the nanoscale, may be realized. The challenges for nanomanufacturing are achieving the desired functionality, product quality, process repeatability, production scalability and cost affordability. The ONR Manufacturing Science Program is meeting these challenges though basic research in nano-scale direct digital manufacturing, massively parallel nanoscale processing, and high-throughput (e.g., roll-to-roll) nanofabrication that encourages system-level integration. These concepts along with research examples will be described.

  8. Terahertz applications: trends and challenges

    Science.gov (United States)

    Robin, Thierry; Bouye, Clementine; Cochard, Jacques

    2014-03-01

    The objective of our work [1] was to determine the opportunities and challenges for Terahertz application development for the next years with a focus on systems: for homeland security and for Non Destructive Testing (NDT). Terahertz radiation has unique abilities and has been the subject of extensive research for many years. Proven concepts have emerged for numerous applications including Industrial NDT, Security, Health, Telecommunications, etc. Nevertheless, there has been no widely deployed application and Businesses based on THz technologies are still in their infancy. Some technological, market and industrial barriers are still to be broken. We summarize the final analysis and data: study of the technology trends and major bottlenecks per application segment, main challenges to be addressed in the next years, key opportunities for THz technologies based on market needs and requirements.

  9. Present challenges in hadrontherapy techniques

    Science.gov (United States)

    Amaldi, U.; Braccini, S.

    2011-07-01

    Hadrontherapy is a high-precision technique in cancer radiation therapy, which allows obtaining a superior conformal treatment with respect to photons used in conventional radiation therapy. To reach this ambitious goal without reducing the patient throughput needed in a hospital-based environment, the physical and radiobiological properties of charged hadrons, protons and carbon ions in particular, have to be exploited at best, making use of the most modern technologies issued from research in nuclear and particle physics. In the present days, we are assisting to a continuous technological challenge, leading to the conception and to the development of innovative methods and instruments. In this paper, the most relevant challenges in dose delivery systems, gantries, imaging, quality assurance and particle accelerators are reviewed.

  10. Heparin Characterization: Challenges and Solutions

    Science.gov (United States)

    Jones, Christopher J.; Beni, Szabolcs; Limtiaco, John F. K.; Langeslay, Derek J.; Larive, Cynthia K.

    2011-07-01

    Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size polydispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.

  11. Challenges for Success in Startups

    Science.gov (United States)

    Spitzer, Richard

    2000-03-01

    The basic challenges to a startup company such as IME have stemmed from the need to balance the business world's goal of fast entry into the market place with the necessity for a solid foundation in technology. Our technology base is broad - indeed it has the makings of a new industry - and the lure of quick commercial success in a specific application could easily make IME vulnerable to the R&D might of giant international companies. The essential challenges for success play out in business/technology decision tradeoffs: (i) preserving equity and viability while keeping R&D momentum and establishing intellectual property, (ii) attracting investors while maintaining focus on long-range goals, and (iii) developing a complete team while protecting capital resources. This balancing act keeps the company agile and resilient, qualities that large corporations could emulate with profit.

  12. Challenges in Complex Systems Science

    CERN Document Server

    Miguel, Maxi San; Kertesz, Janos; Kaski, Kimmo; Díaz-Guilera, Albert; MacKay, Robert S; Loreto, Vittorio; Erdi, Peter; Helbing, Dirk

    2012-01-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneou...

  13. Challenges in pediatric endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Vikas Mittal

    2014-01-01

    Full Text Available We performed endothelial keratoplasty (EK in three eyes of two siblings (2.5 years, male and 3.5 years, female with congenital hereditary endothelial dystrophy (CHED and report the intraoperative and postoperative difficulties. Repeated iris prolapse, apprehension of crystalline lens touch due to positive vitreous pressure, and need for frequent air injections to attach the graft were intraoperative challenges in all three eyes. These were addressed by use of Sheet′s glide instead of Busin′s glide during graft insertion and suturing of main and side ports before air injection. One eye had graft dislocation on second postoperative day due to eye rubbing by the child. Graft was repositioned with air and a venting incision was created. Postoperative examination required repeated general anesthesia. Corneal edema resolved completely in all three eyes. Present case series highlights the possible intraoperative and postoperative challenges and their solutions in pediatric EK for CHED.

  14. Smart textiles: Challenges and opportunities

    Science.gov (United States)

    Cherenack, Kunigunde; van Pieterson, Liesbeth

    2012-11-01

    Smart textiles research represents a new model for generating creative and novel solutions for integrating electronics into unusual environments and will result in new discoveries that push the boundaries of science forward. A key driver for smart textiles research is the fact that both textile and electronics fabrication processes are capable of functionalizing large-area surfaces at very high speeds. In this article we review the history of smart textiles development, introducing the main trends and technological challenges faced in this field. Then, we identify key challenges that are the focus of ongoing research. We then proceed to discuss fundamentals of smart textiles: textile fabrication methods and textile interconnect lines, textile sensor, and output device components and integration of commercial components into textile architectures. Next we discuss representative smart textile systems and finally provide our outlook over the field and a prediction for the future.

  15. Antibiotic resistance: An ethical challenge.

    Science.gov (United States)

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper.

  16. Grand challenges for biological engineering.

    Science.gov (United States)

    Yoon, Jeong-Yeol; Riley, Mark R

    2009-09-22

    Biological engineering will play a significant role in solving many of the world's problems in medicine, agriculture, and the environment. Recently the U.S. National Academy of Engineering (NAE) released a document "Grand Challenges in Engineering," covering broad realms of human concern from sustainability, health, vulnerability and the joy of living. Biological engineers, having tools and techniques at the interface between living and non-living entities, will play a prominent role in forging a better future. The 2010 Institute of Biological Engineering (IBE) conference in Cambridge, MA, USA will address, in part, the roles of biological engineering in solving the challenges presented by the NAE. This letter presents a brief outline of how biological engineers are working to solve these large scale and integrated problems of our society.

  17. Grand challenges for biological engineering

    Directory of Open Access Journals (Sweden)

    Riley Mark R

    2009-09-01

    Full Text Available Abstract Biological engineering will play a significant role in solving many of the world's problems in medicine, agriculture, and the environment. Recently the U.S. National Academy of Engineering (NAE released a document "Grand Challenges in Engineering," covering broad realms of human concern from sustainability, health, vulnerability and the joy of living. Biological engineers, having tools and techniques at the interface between living and non-living entities, will play a prominent role in forging a better future. The 2010 Institute of Biological Engineering (IBE conference in Cambridge, MA, USA will address, in part, the roles of biological engineering in solving the challenges presented by the NAE. This letter presents a brief outline of how biological engineers are working to solve these large scale and integrated problems of our society.

  18. Challenges for Research on Intelligence

    Directory of Open Access Journals (Sweden)

    Earl Hunt

    2013-10-01

    Full Text Available After 100 years of research, the definition of the field is still inadequate. The biggest challenge we see is moving away from a de-factor definition of intelligence in terms of test scores, but at the same time making clear what the boundaries of the field are. We then present four challenges for the field, two within a biological and two within a social context. These revolve around the issues of the malleability of intelligence and its display in everyday life, outside of a formal testing context. We conclude that developments in cognitive neuroscience and increases in the feasibility of monitoring behavior outside of the context of a testing session offer considerable hope for expansion of our both the biological and social aspects of individual differences in cognition.

  19. Challenges of evaluating multilevel interventions.

    Science.gov (United States)

    Nastasi, Bonnie K; Hitchcock, John

    2009-06-01

    This article uses the Comprehensive Mixed-Methods Participatory Evaluation (CMMPE; Nastasi and Hitchcock Transforming school mental health services: Population-based approaches to promoting the competency and wellness of children, Thousand Oaks, CA: Corwin Press with National Association of School Psychologists 2008; Nastasi et al. School-based mental health services: creating comprehensive and culturally specific programs. Washington, DC: American Psychological Association 2004) model as a framework for addressing the multiplicity of evaluation decisions and complex nature of questions related to program success in multilevel interventions. CMMPE defines program success in terms of acceptability, integrity, social or cultural validity, outcomes (impact), sustainability and institutionalization, thus broadening the traditional notions of program outcomes. The authors use CMMPE and an example of a community-based multilevel sexual risk prevention program with multiple outcomes to discuss challenges of evaluating multilevel interventions. The sexual risk program exemplifies what Schensul and Trickett (this issue) characterize as multilevel intervention-multilevel evaluation (M-M), with both intervention and evaluation at community, health practitioner, and patient levels. The illustration provides the context for considering several challenges related to M-M designs: feasibility of randomized controlled trials within community-based multilevel intervention; acceptability and social or cultural validity of evaluation procedures; implementer, recipient, and contextual variations in program success; interactions among levels of the intervention; unanticipated changes or conditions; multiple indicators of program success; engaging multiple stakeholders in a participatory process; and evaluating sustainability and institutionalization. The complexity of multilevel intervention and evaluation designs challenges traditional notions of evaluation research and experimental

  20. Challenges in sharing information effectively

    DEFF Research Database (Denmark)

    Sonnenwald, Diane H.

    2006-01-01

    were not recognized; implications of relevant information were not shared; differences in the role and expression of emotions when sharing information was not understood; and, the need to reestablish trust was not recognized. Conclusion. The challenges in information sharing identified here may extend...... to other high stress, unique and complex situations, such as natural disasters. Recommendations for more effective information behaviour techniques in dynamic group work situations are presented....

  1. Feature Selection: Algorithms and Challenges

    Institute of Scientific and Technical Information of China (English)

    Xindong Wu; Yanglan Gan; Hao Wang; Xuegang Hu

    2006-01-01

    Feature selection is an active area in data mining research and development. It consists of efforts and contributions from a wide variety of communities, including statistics, machine learning, and pattern recognition. The diversity, on one hand, equips us with many methods and tools. On the other hand, the profusion of options causes confusion. This paper reviews various feature selection methods and identifies research challenges that are at the forefront of this exciting area.

  2. Diagnostic challenges in celiac disease

    Directory of Open Access Journals (Sweden)

    M Haghighat

    2014-04-01

    Full Text Available   1-The most important challenge in diagnosis of celiac disease is not- performing the diagnostic tests in suspected persons. Because of multi-organ damage and multiple manifestations of disease, diagnosis of celiac disease may be delayed. It seems general physicians should be awared about uncommon presentations of disease and indications of celiac tests 2-The second most important challenge is in patients with suspected disease but negative serologic tests. In these cases evaluating of HLA can be useful. 3- The third challenge is in cases with positive serologic tests but negative histopathological findings. There may be false positive serologic response or consumption of gluten before testing. We recommend introduction of gluten for at least 3 mo and re- endoscopy and if diagnosis is equivocal HLA-typing  for DQ8 and  DQ2 should be done. 4-The forth challenge is about performing endoscopy. Based on guideline from ESPGHAN if there are typical clinical manifestations of celiac disease, Anti-TTG more than ten times UPN , positive Anti-EMA and HLA DQ2, performing endoscopy may not be necessary, but many physicians don’t agree with this idea. 5-In people who are genetically predisposed to celiac disease antibody levels may be fluctuating thus endoscopy with biopsy should be done in these patients. 6-In children lower than 2years, Anti- TTG and Anti –EMA have low sensitivity. we recommend Anti-TTG and Anti-DGP in these patients. 7-Resolution of symptoms after gluten free diet is not necessarily a feature of celiac disease. This condition may be seen in patients with IBS or non-celiac gluten sensitivity.  

  3. Diagnostic Challenges in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Mahmood Haghighat

    2014-04-01

    Full Text Available 1. The most important challenge in diagnosis of celiac disease is not-performing the diagnostic tests in suspected persons. Because of multi-organ damage and multiple manifestations of disease, diagnosis of celiac disease may be delayed. It seems general physicians should be aware about uncommon presentations of disease and indications of celiac tests. 2. The second most important challenge is in patients with suspected disease but negative serologic tests. In these cases evaluating of HLA can be useful. 3. The third challenge is in cases with positive serologic tests but negative histopathological findings. There may be false positive serologic response or consumption of gluten before testing. We recommend introduction of gluten for at least 3 mo and re- endoscopy and if diagnosis is equivocal HLA-typing for DQ8 and DQ2 should be done. 4. The forth challenge is about performing endoscopy. Based on guideline from ESPGHAN if there are typical clinical manifestations of celiac disease, Anti-TTG more than ten times UPN, positive Anti-EMA and HLA DQ2, performing endoscopy may not be necessary, but many physicians don’t agree with this idea. 5. In people who are genetically predisposed to celiac disease antibody levels may be fluctuating thus endoscopy with biopsy should be done in these patients. 6. In children lower than 2years, Anti- TTG and Anti –EMA have low sensitivity. we recommend Anti-TTG and Anti-DGP in these patients. 7. Resolution of symptoms after gluten free diet is not necessarily a feature of celiac disease. This condition may be seen in patients with IBS or non-celiac gluten sensitivity.

  4. The challenges of managing migration

    Energy Technology Data Exchange (ETDEWEB)

    Tacoli, Cecilia

    2005-10-15

    Migration and urbanisation are driven by economic growth and social change, but also by deepening inequalities. Managing migration should not be equated with curbing it, as this inevitably reduces migrants' rights. But managing population movement whilst respecting the rights of migrants and nonmigrants, supporting the contribution of migration to poverty reduction and economic growth in sending and receiving areas and reducing the human and material costs of movement means that fundamental challenges need to be addressed.

  5. The ambiguous challenge of intranets

    DEFF Research Database (Denmark)

    Thommesen, Jacob

    2003-01-01

    media, email and the web, partly in the perspective of media richness theory, partly compared with philosophical discussions of classical media. The fourth chapter presents an intranet in a global company, in which problems and challenges related to ambiguity have proven significant.......In this thesis I shall present the argument that intranets increase the role of ambiguity – confrontation between contradicting frames of interpretation – in organisational communication by encouraging processes across organisational borders. In the first chapter I discuss philosophical aspects...

  6. The Challenge of the bespoke

    DEFF Research Database (Denmark)

    Tamke, Martin; Quinn, Gregory; Evers, Henrik Leander

    2014-01-01

    The Dermoid project, a series of three plywood grid shells, navigates at the interface between parametrically designed architectural spaces and the efficiency and resourcefulness of the simulations that are necessary in order to build them. It highlights the increasingly common challenges...... and conflicts which occur in building practice ranging from design to fabrication and highlights approaches that facilitate implementation in multiple scales of material, element and structure....

  7. Challenges to sustainable risk management

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Ariel C., Aurora, Ashish, Hall, Dennis E.,

    2004-08-09

    This paper summarizes the intermediate lessons learned from the analyses of the risk management problems in three technological endeavors. These problems are: the absence of a structure for rewarding successful project risk management; the need for an ever-more accurate economic measure of risk; and the difficulty of transferring risks to contract-bound independent outsourcing entity. This paper also describes recent advancement towards providing answers to these challenges and future research endeavors in this field.

  8. Challenges for Contextualizing Language Learning

    DEFF Research Database (Denmark)

    Eskildsen, Søren; Rehm, Matthias

    2013-01-01

    To help facilitate language learning for immigrants or foreigners arriving to another culture and language, we propose a context-aware mobile application. To expand on the known elements like location, activity, time and identity, we investigate the challenges on including cultural awareness...... to ensure a better experience-based learning. We present methods used to collect information about everyday activities collected by immigrants or foreigners. This information will help structuring language learning assignments presented through the context-aware mobile application....

  9. Asia Confronts Its Inflation Challenge

    Institute of Scientific and Technical Information of China (English)

    Gerard Lyons

    2011-01-01

    @@ Asia is finally waking up to its inflation challenge.Recent weeks have seen a further round of monetary tighten-ing, with a succession of central banks raising interest rates, or taking other measures to put a cap on rising prices.India, in particular, has taken tougher action than before, with a large rate hike, whilst others such as China have again pushed up reserve requirements.

  10. Paraganglioma: a potentially challenging tumor.

    Science.gov (United States)

    Trombetta, Mark; Silverman, Jan; Colonias, Athanasios; Lee, Vincent; Mohanty, Alok; Parda, David

    2008-03-01

    Paragangliomas are usually low-grade neoplasms with a benign natural history. While the treatment of paraganglioma has historically been controversial, surgery and radiotherapy have become standardized as therapies of choice for primary therapy. More recently, stereotactic radiosurgery has been used effectively against this rare tumor. The development of metastatic disease in patients with paraganglioma is an unusual and challenging event. This case report and review describes the specific features of this disease and the multiple therapeutic options.

  11. Challenges and Advances in Nanotoxicology

    Directory of Open Access Journals (Sweden)

    Robert L. Tanguay

    2014-08-01

    Full Text Available This Special Issue of Nanomaterials examines the potential for engineered nanomaterials to negatively impact biological systems and highlights some advances in evaluating key areas of their hazard potential. Nanomaterial science is evolving rapidly with the generation of more complex nanostructures with exciting potential applications. Keeping modern toxicology abreast of this innovation to the point that it guides a safer nanotechnology presents an equally exciting and eminently worthwhile challenge. [...

  12. Challenges of Big Data Analysis.

    Science.gov (United States)

    Fan, Jianqing; Han, Fang; Liu, Han

    2014-06-01

    Big Data bring new opportunities to modern society and challenges to data scientists. On one hand, Big Data hold great promises for discovering subtle population patterns and heterogeneities that are not possible with small-scale data. On the other hand, the massive sample size and high dimensionality of Big Data introduce unique computational and statistical challenges, including scalability and storage bottleneck, noise accumulation, spurious correlation, incidental endogeneity, and measurement errors. These challenges are distinguished and require new computational and statistical paradigm. This article gives overviews on the salient features of Big Data and how these features impact on paradigm change on statistical and computational methods as well as computing architectures. We also provide various new perspectives on the Big Data analysis and computation. In particular, we emphasize on the viability of the sparsest solution in high-confidence set and point out that exogeneous assumptions in most statistical methods for Big Data can not be validated due to incidental endogeneity. They can lead to wrong statistical inferences and consequently wrong scientific conclusions.

  13. Challenges when introducing electronic exam

    Directory of Open Access Journals (Sweden)

    Matti Kuikka

    2014-10-01

    Full Text Available Time pressures often necessitate the use of more efficient exam tools, such as electronic exams (e-exams, instead of traditional paper exams. However, teachers may face challenges when introducing e-exams in a higher education context. This paper describes what kinds of challenges teachers may face when introducing e-exams, based on experiences in Turku University of Applied Sciences (TUAS where e-exams have been used since 2012. For this research, the authors used their personal experiences as administrators and teachers of current e-systems used for e-exams in universities in Turku, Finland. Quantitative data were collected by survey from teachers in TUAS (the case study. The learning management systems, Moodle, Optima and ViLLE, and dedicated e-examination systems, Soft Tutor and Tenttis, were also compared to clarify what kind of features are available in order to ease teachers’ work with examinations. The results identified various challenges during e-exam introduction in TUAS. The paper also provides a list of essential services or features for teachers to ease the introduction of e-exams. Among the analysed systems, ViLLE supported most of the required features, and can be used for both learning management and e-examination systems, providing teachers with one single system, which was found to be important to teachers. The key service found by this paper is ‘support for teachers’, which is in line with previous studies.

  14. Challenges in complex systems science

    Science.gov (United States)

    San Miguel, M.; Johnson, J. H.; Kertesz, J.; Kaski, K.; Díaz-Guilera, A.; MacKay, R. S.; Loreto, V.; Érdi, P.; Helbing, D.

    2012-11-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneous databases; moving from data to dynamical models, going beyond correlations to cause-effect relationships, understanding the relationship between simple and comprehensive models with appropriate choices of variables, ensemble modeling and data assimilation, modeling systems of systems of systems with many levels between micro and macro; and formulating new approaches to prediction, forecasting, and risk, especially in systems that can reflect on and change their behaviour in response to predictions, and systems whose apparently predictable behaviour is disrupted by apparently unpredictable rare or extreme events. These challenges are part of the FuturICT agenda.

  15. CHALLENGES IN CROSS CULTURAL ADVERTISING

    Directory of Open Access Journals (Sweden)

    Yuni Retnowati

    2015-10-01

    Full Text Available At first, marketing practitioners and academics consider standardized approaches to marketing and advertising strategies in globalization, and then some studies proved that the standardization of advertising across culture is not valid. Therefore, cross cultural advertising takes local culture into account when conveying messages in advertisements. Cross cultural understanding is very important in order to produce successful localized advertising that would reflect the cultural values and norms of intended audience. Challenge in cross cultural advertising is the problem of communicating to people of diverse cultural background. Cross cultural solutions are applied in areas such as language, communication style, images and cultural values. Cross cultural advertising is simply about using common sense and analyzing how the different elements of an advertising campaign are impacted by culture and modifying them to best speak to the target audience. Other challenges are determining between standardization and adaptation of cultural values content of advertising when facing different people from diverse cultures. In academic side, the challenge is preparing students to design advertisements that communicate effectively to diverse cultures.

  16. ECONOMIC CHALLENGES FOR EUROPEAN DEFENCE

    Directory of Open Access Journals (Sweden)

    Maria CONSTANTINESCU

    2016-12-01

    Full Text Available The issue of a common European Union (EU defence is on the frontline of political and media discussions, in light of the recent evolutions in the security and defence environment. The main challenge in this respect is related to the realism and feasibility of moving beyond political declarations towards a more concrete implementation of a common defence policy, considering the numerous political, military and economic factors involved. The aim of this paper is to analyse the challenges faced by the concept of a common European defence from an economic point of view, considering the evolution of the defence expenditures in the EU member states, compared to the wider European and the global trend. Also, the paper will focus on the impact the economic crisis and the ensuing austerity measures had on the member states and on their cooperation in developing a common approach on defence, with a view on the ways ahead and recommendations on overcoming the difficult challenges in this respect.

  17. PROFESSIONAL MASTER AND ITS CHALLENGES

    Directory of Open Access Journals (Sweden)

    Lydia Masako Ferreira

    2015-01-01

    Full Text Available Objective: To describe the history, origin, objectives, characteristics, implications, the questions of the evaluation form and some examples of the Professional Masters (MP, to differentiate the Academic Master, and identify the challenges for the next quadrennial assessment. Methods: The CAPES site on Professional Masters and documents and meeting area of reports from 2004 to 2013 of Medicine III were read as well as the reports and the sub-page of the area in Capes site. The data relating to the evaluation process and the Scoreboard of the other areas were computed and analyzed. From these data it was detected the challenges of Medicine III for the next four years (2013-2016. Results: The creation of the Professional Master is very recent in Medicine III and no Professional Master of Medicine III course was evaluated yet. Were described the objectives, assumptions, characteristics, motivations, the possibilities, the feasibility, the profile of the students, the faculty, the curriculum, funding, intellectual production, social inclusion, the general requirements of Ordinance No. 193/2011 CAPES and some examples of proposals, technological lines of scientific activities, partnerships and counterparties. The evaluation form of the MP was discussed, the need for social, economic and political intellectual production and the differences with the MA. It was also reported the global importance of the MP and its evolution in Brazil. From the understanding of the MP, Medicine III outlined some challenges and goals to be developed in the 2013-2016 quadrennium. Conclusion: Medicine III understood the MP as a new technological scientific horizon within the strict sensu post-graduate and full consistency with the area.

  18. International migration: a global challenge.

    Science.gov (United States)

    Martin, P; Widgren, J

    1996-04-01

    Trends in international migration are presented in this multiregional analysis. Seven of the world's wealthiest countries have about 33% of the world's migrant population, but under 16% of the total world population. Population growth in these countries is substantially affected by the migrant population. The migration challenge is external and internal. The external challenge is to balance the need for foreign labor and the commitment to human rights for those migrants seeking economic opportunity and political freedom. The internal challenge is to assure the social adjustment of immigrants and their children and to integrate them into society as citizens and future leaders. Why people cross national borders and how migration flows are likely to evolve over the next decades are explained. This report also presents some ways that countries can manage migration or reduce the pressures which force people to migrate. It is recommended that receiving nations control immigration by accelerating global economic growth and reducing wars and human rights violations. This report examines the impact of immigration on international trade, aid, and direct intervention policies. Although migration is one of the most important international economic issues, it is not coordinated by an international group. The European experience indicates that it is not easy to secure international cooperation on issues that affect national sovereignty. It is suggested that countries desiring control of their borders should remember that most people never cross national borders to live or work in another country, that 50% of the world's migrants move among developing countries, and that countries can shift from being emigration to immigration countries. The author suggests that sustained reductions in migration pressure are a better alternative than the "quick fixes" that may invite the very much feared mass and unpredictable movements.

  19. Silicon photonics: some remaining challenges

    Science.gov (United States)

    Reed, G. T.; Topley, R.; Khokhar, A. Z.; Thompson, D. J.; Stanković, S.; Reynolds, S.; Chen, X.; Soper, N.; Mitchell, C. J.; Hu, Y.; Shen, L.; Martinez-Jimenez, G.; Healy, N.; Mailis, S.; Peacock, A. C.; Nedeljkovic, M.; Gardes, F. Y.; Soler Penades, J.; Alonso-Ramos, C.; Ortega-Monux, A.; Wanguemert-Perez, G.; Molina-Fernandez, I.; Cheben, P.; Mashanovich, G. Z.

    2016-03-01

    This paper discusses some of the remaining challenges for silicon photonics, and how we at Southampton University have approached some of them. Despite phenomenal advances in the field of Silicon Photonics, there are a number of areas that still require development. For short to medium reach applications, there is a need to improve the power consumption of photonic circuits such that inter-chip, and perhaps intra-chip applications are viable. This means that yet smaller devices are required as well as thermally stable devices, and multiple wavelength channels. In turn this demands smaller, more efficient modulators, athermal circuits, and improved wavelength division multiplexers. The debate continues as to whether on-chip lasers are necessary for all applications, but an efficient low cost laser would benefit many applications. Multi-layer photonics offers the possibility of increasing the complexity and effectiveness of a given area of chip real estate, but it is a demanding challenge. Low cost packaging (in particular, passive alignment of fibre to waveguide), and effective wafer scale testing strategies, are also essential for mass market applications. Whilst solutions to these challenges would enhance most applications, a derivative technology is emerging, that of Mid Infra-Red (MIR) silicon photonics. This field will build on existing developments, but will require key enhancements to facilitate functionality at longer wavelengths. In common with mainstream silicon photonics, significant developments have been made, but there is still much left to do. Here we summarise some of our recent work towards wafer scale testing, passive alignment, multiplexing, and MIR silicon photonics technology.

  20. Nanometrology - challenges for health regulation

    Directory of Open Access Journals (Sweden)

    Jailton Carreteiro Damasceno

    2013-11-01

    Full Text Available The relationship between metrology, nanotechnology and nanoscience and sanitary regulation is discussed from the point of view of its importance and the interrelationship between the themes for the development of products and services involving nanotech-nology. The discussion involves the main techniques for measuring dimensional, chemical and biological properties of materials, and presents some of the challenges for the future. Issues such as processes of standardization and regulation in Europe, U.S. and Brazil are also addressed, providing an overview of how these processes are related to sanitary regulation.

  1. Challenges in wind farm optimization

    DEFF Research Database (Denmark)

    Larsen, Gunner Chr.

    for the wind turbine modeling, where aeroelastic models are required, and for the wind farm flow field description, where in-stationary flow field modeling is needed to capture the complicated mixture of atmospheric boundary layer (ABL) flows and upstream emitted meandering wind turbine wakes, which together...... dictates the fatigue loading of the individual wind turbines. Within an optimization context, the basic challenge in describing the in-stationary wind farm flow field is computational speed. The Dynamic Wake Meandering (DWM) model includes the basic features of a CFD Large Eddy Simulation approach...

  2. The Challenges of Community Engagement.

    Science.gov (United States)

    Cormick, Craig

    2010-12-01

    Lyons and Whelan provide a useful list of recommendations as to how community engagement on nanotechnology could be improved, which very few people working in community engagement could disagree with. However, as the conclusions of any study are dependent on the data obtained, if more data had been obtained and analysed then different conclusions might have been reached. Addressing the key issues in the paper and providing more data, also allows an opportunity to expand on current issues relating to community engagement on nanotechnology and the challenges it provides for practitioners.

  3. Addressing the workforce pipeline challenge

    Energy Technology Data Exchange (ETDEWEB)

    Leonard Bond; Kevin Kostelnik; Richard Holman

    2006-11-01

    A secure and affordable energy supply is essential for achieving U.S. national security, in continuing U.S. prosperity and in laying the foundations to enable future economic growth. To meet this goal the next generation energy workforce in the U.S., in particular those needed to support instrumentation, controls and advanced operations and maintenance, is a critical element. The workforce is aging and a new workforce pipeline, to support both current generation and new build has yet to be established. The paper reviews the challenges and some actions being taken to address this need.

  4. Airport Noise Tech Challenge Overview

    Science.gov (United States)

    Bridges, James

    2011-01-01

    The Supersonics Project, operating under NASA Aeronautics Mission Directorate#s Fundamental Aero Program, has been organized around the Technical Challenges that have historically precluded commercial supersonic flight. One of these Challenges is making aircraft that are capable of such high aerodynamic performance quiet enough around airports that they will not be objectionable. It is recognized that a successful civilian supersonic aircraft will be a system where many new technologies will come together, and for this to happen not only will new low noise propulsion concepts be required, but new engineering tools that predict the noise of the aircraft as these technologies are combined and compromised with the rest of the aircraft design. These are the two main objectives of the Airport Noise Tech Challenge. " ! As a Project in the Fundamental Aero Program, we work at a relatively low level of technology readiness. However, we have high level milestones which force us to integrate our efforts to impact systems-level activities. To keep the low-level work tied to delivering engineering tools and low-noise concepts, we have structured our milestones around development of the concepts and organized our activities around developing and applying our engineering tools to these concepts. The final deliverables in these milestones are noise prediction modules validated against the best embodiment of each concept. These will then be used in cross-disciplinary exercises to demonstrate the viability of aircraft designs to meet all the Technical Challenges. Some of the concepts being developed are shown: Fan Flow Diverters, Multi-jet Shielding, High-Aspect Ratio Embedded Nozzles, Plasma Actuated Instability Manipulation, Highly Variable Cycle Mixer- Ejectors, and Inverted Velocity Profiles. These concepts are being developed for reduced jet noise along with the design tools which describe how they perform when used in various aircraft configurations. Several key upcoming

  5. Plain language and organisational challenges

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    2014-01-01

    an effect. I work with the case of the Danish tax authorities’ language project aimed at producing more readable letters. The empirical data that I work with are two qualitative informant interviews. One recorded at the language project’s headquarters where they lay out the general lines for the project......Changing the language in an organization is a major organizational change. In this article, I discuss some of the organizational challenges for one specific language change implementation, taking the stance that language change must be treated as any other organizational change for it to have...

  6. University education: Demands and challenges

    Directory of Open Access Journals (Sweden)

    Eduardo Pinos Vélez

    2013-06-01

    Full Text Available This paper presents a study on the current situation prevailing in the Universities from the point of view of a teacher whose academic since its inception has been Salesian, which allows for a “best approach” to young students and where the passion for teaching is clearly influenced by the teachings of one of the greatest teachers, Don Bosco. Also, these teachings are still of great relevance in our time, seek to adopt these methodologies in our workspaces teaching is challenging, where you can suggest new strategies for communication and integration with students and in this way to service the needy, such as programs aid Persons with Disabilities.

  7. Cleaning insertions and collimation challenges

    CERN Document Server

    Redaelli, S; Bertarelli, A; Bruce, R; Jowett, J M; Lechner, A; Losito, R

    2015-01-01

    High-performance collimation systems are essential for operating efficiently modern hadron machine with large beam intensities. In particular, at the LHC the collimation system ensures a clean disposal of beam halos in the superconducting environment. The challenges of the HL-LHC study pose various demanding requests for beam collimation. In this paper we review the present collimation system and its performance during the LHC Run 1 in 2010–2013. Various collimation solutions under study to address the HL-LHC requirements are then reviewed, identifying the main upgrade baseline and pointing out advanced collimation concept for further enhancement of the performance.

  8. LHC Status and Upgrade Challenges

    Science.gov (United States)

    Smith, Jeffrey

    2009-11-01

    The Large Hadron Collider has had a trying start-up and a challenging operational future lays ahead. Critical to the machine's performance is controlling a beam of particles whose stored energy is equivalent to 80 kg of TNT. Unavoidable beam losses result in energy deposition throughout the machine and without adequate protection this power would result in quenching of the superconducting magnets. A brief overview of the machine layout and principles of operation will be reviewed including a summary of the September 2008 accident. The current status of the LHC, startup schedule and upgrade options to achieve the target luminosity will be presented.

  9. Challenging and Reducing Cultural Stereotypes

    Institute of Scientific and Technical Information of China (English)

    黄鸣

    2011-01-01

    Abstract:Anyplace where differences are found leaves room for stereotypes.Each of us hears or makes stereotypical comments every day,and although sometimes it is necessary to make stereotypes in foreign language teaching and learning,we should always be aware of the negative effects of stereotyping people from other cultures when we use them to interpret behavior.This paper defines stereotypes,discusses how they impede communication and then focuses on some ways to challenge and reduce stereotypes in cross-cultural communication.

  10. Nonlinear dynamics: Challenges and perspectives

    Indian Academy of Sciences (India)

    M Lakshmanan

    2005-04-01

    The study of nonlinear dynamics has been an active area of research since 1960s, after certain path-breaking discoveries, leading to the concepts of solitons, integrability, bifurcations, chaos and spatio-temporal patterns, to name a few. Several new techniques and methods have been developed to understand nonlinear systems at different levels. Along with these, a multitude of potential applications of nonlinear dynamics have also been enunciated. In spite of these developments, several challenges, some of them fundamental and others on the efficacy of these methods in developing cutting edge technologies, remain to be tackled. In this article, a brief personal perspective of these issues is presented.

  11. CHALLENGES FOR DIGITAL LITERATURE TEACHING

    Directory of Open Access Journals (Sweden)

    Edgar Roberto Kirchof

    2013-12-01

    Full Text Available This paper addresses some challenges faced by researchers and teachers interested in teaching digital literature in formal educational institutions. Initially, a brief history of digital literature is presented, with emphasis on the first literary experiments with computational language that were carried out still in the 50s, under the mentorship of Max Bense in Germany. In addition, the paper brings forward two movements of digital literature arising after the 50s: thedigital poetry and its relation with avant-garde poetry movements; and the hypertext literature. Finally, the paper presents the results of some educational projects on teaching digital literature conducted in different European universities

  12. Facing Tomorrow's Challenges - An Overview

    Science.gov (United States)

    ,

    2008-01-01

    In 2007, the U.S. Geological Survey (USGS) developed a science strategy outlining the major natural-science issues facing the Nation in the next decade. The science strategy consists of six science directions of critical importance, focusing on areas where natural science can make a substantial contribution to the well-being of the Nation and the world. This fact sheet is an overview of the science strategy and describes how USGS research can strengthen the Nation with information needed to meet the challenges of the 21st century.

  13. Challenging the Service Cost Paradigm.

    Science.gov (United States)

    Seibert, Sandra

    2015-01-01

    Most healthcare organizations are looking to find more efficient and cost-effective ways of delivering service as they are challenged to assume more risk in order to provide timely and cost effective care. Alternative service with an independent service organization or third party may be an easy and rewarding solution. Serious consideration should be given purchase/service cycle and into a lower cost service paradigm designed to provide excellent service tailored to a facility's specific needs. In this article, an evaluation of all service model options is provided, as well as examples including a CT acquisition, pro formas, and program development.

  14. Challenging institutional logics in Gourmet

    DEFF Research Database (Denmark)

    Nickelsen, Niels Christian Mossfeldt; Scheuer, John Damm

    2015-01-01

    This paper focuses on the initial phase of an organizational transformation. More precisely the paper analyses the moment where an institutional entrepreneur produces ideas, which have the capacity to break with existing logics and thus produces the potential for change by challenging existing fi...... field logics. The empirical case is the gastronomic field in Denmark and in the Nordic countries - more specifically the paper discusses the cook and entrepreneur Claus Meyers ambitions to realize a food-political vision; The New Nordic Kitchen. The theoretical contribution of the paper...

  15. Electromobility - challenges for structural durability

    Energy Technology Data Exchange (ETDEWEB)

    Hiebl, A.; Krueger, L. [BMW Group, Muenchen (Germany); Martin, D.

    2011-10-15

    In this lecture the challenges of testing the structural durability of electric vehicles are highlighted. The requirements and in particular differences in those for electric vehicles and cars with internal-combustion engines are compared and illustrated. Current experiences with the MINI E and actual BMW hybrid cars are shown. Furthermore, testing concepts for specific electromobility components and their structural integration into the vehicle are explained. Finally an insight into possible future hybrid cars is presented. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. The coffee-time challenge

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The challenge to identify the LEP events displayed on coffee tables in Restaurant 1 (Bulletin 02-03/2010) sparked interest among readers who do not have the opportunity to see them . Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12 Table 13, Table 14, Table 15, Table 16       We have therefore decided to open the challenge to these readers by displaying the events on the web. We are also extending the deadline accordingly to 2 March. There are 16 events in total (in two areas), four from each of the four LEP experiments, and they include examples of different particle decays observed at LEP during its 11 years of operation. The list below indicates the decay channels represented. We are offering a prize of the ATLAS pop-up book, Voyage to the Heart of Matter, for the correct identification of all 16 events.  Entries should indicate the table number corresponding to each of the decays listed. There wi...

  17. Engineering ethics challenges and opportunities

    CERN Document Server

    Bowen, W Richard

    2014-01-01

    Engineering Ethics: Challenges and Opportunities aims to set a new agenda for the engineering profession by developing a key challenge: can the great technical innovation of engineering be matched by a corresponding innovation in the acceptance and expression of ethical responsibility?  Central features of this stimulating text include:   ·         An analysis of engineering as a technical and ethical practice providing great opportunities for promoting the wellbeing and agency of individuals and communities. ·         Elucidation of the ethical opportunities of engineering in three key areas:             - Engineering for Peace, emphasising practical amelioration of the root causes of    conflict rather than military solutions.             - Engineering for Health, focusing on close collaboration with healthcare professionals      for both the promotion and restoration of health.             - Engineering for Development, providing effective solution...

  18. Leadership Challenges in Academic Anesthesiology.

    Science.gov (United States)

    Mets, Berend

    2005-01-01

    The leadership challenge for academic anesthesiology lies in developing leadership at all levels in the department to create a meaningful, equitable, academic environment, with an attractive culture which challenges but supports and mentors individual growth and in so doing retains faculty. Education, research and clinical care, important as they are, are not ends in themselves, but a means to personal fulfillment lending meaning and identity to the individual which would be different from that which might be achieved in a private practice setting. The concepts of leadership from contemporary business literature are reviewed and a framework within which leadership can occur is described. This framework is based on an understanding of the role that the development of a departmental vision plays. This vision should be based on shared values as well as the mission of the department and should draw on the concepts of strategy, and commitment to realize the departmental goals. Based on these ideas, suggestions are made to illustrate how these business concepts might be applied in academic anesthesia departments.

  19. Multiphysics simulations: challenges and opportunities.

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, D.; McInnes, L. C.; Woodward, C.; Gropp, W.; Myra, E.; Pernice, M. (Mathematics and Computer Science); (KAUST and Columbia Univ.); (Lawrence Livermore National Laboratory); (Univ. of Illinois at Urbana-Champaign); (Univ. of Mich.); (Idaho National Lab.)

    2012-11-29

    This report is an outcome of the workshop Multiphysics Simulations: Challenges and Opportunities, sponsored by the Institute of Computing in Science (ICiS). Additional information about the workshop, including relevant reading and presentations on multiphysics issues in applications, algorithms, and software, is available via https://sites.google.com/site/icismultiphysics2011/. We consider multiphysics applications from algorithmic and architectural perspectives, where 'algorithmic' includes both mathematical analysis and computational complexity and 'architectural' includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. We also initiate a modest suite of test problems encompassing features present in many applications.

  20. The challenges of amblyopia treatment

    Directory of Open Access Journals (Sweden)

    Gail D.E. Maconachie

    2015-12-01

    Full Text Available The treatment of amblyopia, particularly anisometropic (difference in refractive correction and/or strabismic (turn of one eye amblyopia has long been a challenge for many clinicians. Achieving optimum outcomes, where the amblyopic eye reaches a visual acuity similar to the fellow eye, is often impossible in many patients. Part of this challenge has resulted from a previous lack of scientific evidence for amblyopia treatment that was highlight by a systematic review by Snowdon et al. in 1998. Since this review, a number of publications have revealed new findings in the treatment of amblyopia. This includes the finding that less intensive occlusion treatments can be successful in treating amblyopia. A relationship between adherence to treatment and visual acuity has also been established and has been shown to be influenced by the use of intervention material. In addition, there is growing evidence of that a period of glasses wearing only can significantly improve visual acuity alone without any other modes of treatment. This review article reports findings since the Snowdon's report.

  1. The challenges of amblyopia treatment.

    Science.gov (United States)

    Maconachie, Gail D E; Gottlob, Irene

    2015-12-01

    The treatment of amblyopia, particularly anisometropic (difference in refractive correction) and/or strabismic (turn of one eye) amblyopia has long been a challenge for many clinicians. Achieving optimum outcomes, where the amblyopic eye reaches a visual acuity similar to the fellow eye, is often impossible in many patients. Part of this challenge has resulted from a previous lack of scientific evidence for amblyopia treatment that was highlight by a systematic review by Snowdon et al. in 1998. Since this review, a number of publications have revealed new findings in the treatment of amblyopia. This includes the finding that less intensive occlusion treatments can be successful in treating amblyopia. A relationship between adherence to treatment and visual acuity has also been established and has been shown to be influenced by the use of intervention material. In addition, there is growing evidence of that a period of glasses wearing only can significantly improve visual acuity alone without any other modes of treatment. This review article reports findings since the Snowdon's report.

  2. Challenges in Double Beta Decay

    Directory of Open Access Journals (Sweden)

    Oliviero Cremonesi

    2014-01-01

    Full Text Available In the past ten years, neutrino oscillation experiments have provided the incontrovertible evidence that neutrinos mix and have finite masses. These results represent the strongest demonstration that the electroweak Standard Model is incomplete and that new Physics beyond it must exist. In this scenario, a unique role is played by the Neutrinoless Double Beta Decay searches which can probe lepton number conservation and investigate the Dirac/Majorana nature of the neutrinos and their absolute mass scale (hierarchy problem with unprecedented sensitivity. Today Neutrinoless Double Beta Decay faces a new era where large-scale experiments with a sensitivity approaching the so-called degenerate-hierarchy region are nearly ready to start and where the challenge for the next future is the construction of detectors characterized by a tonne-scale size and an incredibly low background. A number of new proposed projects took up this challenge. These are based either on large expansions of the present experiments or on new ideas to improve the technical performance and/or reduce the background contributions. In this paper, a review of the most relevant ongoing experiments is given. The most relevant parameters contributing to the experimental sensitivity are discussed and a critical comparison of the future projects is proposed.

  3. Meeting the Challenges for Agriculture

    Directory of Open Access Journals (Sweden)

    Les Copeland

    2011-06-01

    Full Text Available Ensuring food security is an ongoing global challenge. Many forecasts point to a need to increase food production by at least 70% if we are to feed the world’s projected population of nine billion in 2050. Recent volatility in commodity prices and the general upward trend in the cost of food are indicators that global food systems are now driven by demand rather than supply. There are various reasons for this: greater demand for animal protein with economic growth in developing countries; the continuing increase in world population; competition between food and bioenergy crops for land and water; low inventories of world grain stocks; reduced investment in agricultural R&D; and unfavorable weather resulting in a succession of poor harvests around the world. Increasing production of grains, which are the foundation of the human food supply, will have to be achieved through higher crop yields without boosting inputs of land, water and energy. Meeting community expectations for environmental stewardship and sustainability, and adapting food production to increasingly variable climate, add greatly to the challenge.

  4. Challenges in contemporary academic neurosurgery.

    Science.gov (United States)

    Black, Peter M

    2006-03-01

    Traditionally, the ideal academic neurosurgeon has been a "quadruple threat," with excellence in clinical work, teaching, research, and administration. This tradition was best exemplified in Harvey Cushing, who developed the field of neurosurgery 90 years ago. This paradigm will probably have to change as academic neurosurgeons face major challenges. In patient care, these include increasing regulatory control, increasing malpractice costs, consolidation of expensive care in academic centers, and decreasing reimbursement; in resident teaching, work hour limitations and a changing resident culture; in research, the increasing dominance of basic scientists in governmental funding decisions and decreased involvement of neurosurgeons in scientific review committees; and in administration, problems of relationships in the workplace, patient safety, and employment compliance in an increasingly bureaucratic system. To meet these challenges, the new academic neurosurgeon will probably not be a quadruple threat personally but will be part of a quadruple threat in a department and institution. Neurosurgeons in such a setting will have to work with hospital, medical school, and national and international groups to address malpractice, reimbursement, subspecialization, and training problems; find supplemental sources of income through grants, development funds, and hospital support; lead in the development of multidisciplinary centers for neuroscience, brain tumor, spine, and other initiatives; and focus on training leaders for hospital, regional, and national groups to reconfigure neurosurgery. Collaboration, flexibility, and leadership will be characteristic of the academic neurosurgeon in this new era.

  5. Responses to microbial challenges by SLAMF receptors

    Directory of Open Access Journals (Sweden)

    Boaz Job Van Driel

    2016-01-01

    Full Text Available The SLAMF Family (SLAMF of cell surface glycoproteins is comprised of nine glycoproteins and whilst SLAMF1, 3, 5, 6, 7, 8, 9 are self-ligand receptors, SLAMF2 and SLAMF4 interact with each other. Their interactions induce signal transduction networks in trans, thereby shaping immune cell-cell communications. Collectively, these receptors modulate a wide range of functions, such as myeloid cell and lymphocyte development and, T and B cell responses to microbes and parasites. In addition, several SLAMF receptors serve as microbial sensors, which either positively or negatively modulate the function of macrophages, dendritic cells, neutrophils and NK cells in response to microbial challenges. The SLAMF receptor-microbe interactions contribute both to intracellular microbicidal activity as well as to migration of phagocytes to the site of inflammation. In this review, we describe the current knowledge on how the SLAMF receptors and their specific adapters SAP and EAT-2 regulate innate and adaptive immune responses to microbes.

  6. Modern climate challenges and the geological record

    Science.gov (United States)

    Cronin, Thomas M.

    2010-01-01

    Today's changing climate poses challenges about the influence of human activity, such as greenhouse gas emissions and land use changes, the natural variability of Earth's climate, and complex feedback processes. Ice core and instrumental records show that over the last century, atmospheric carbon dioxide (CO2) concentrations have risen to 390 parts per million volume (ppmv), about 40% above pre-Industrial Age concentrations of 280 ppmv and nearly twice those of the last glacial maximum about 22,000 years ago. Similar historical increases are recorded in atmospheric methane (CH4) and nitrous oxide (N2O). There is general agreement that human activity is largely responsible for these trends. Substantial evidence also suggests that elevated greenhouse gas concentrations are responsible for much of the recent atmospheric and oceanic warming, rising sea level, declining Arctic sea-ice cover, retreating glaciers and small ice caps, decreased mass balance of the Greenland and parts of the Antarctic ice sheets, and decreasing ocean pH (ocean "acidification"). Elevated CO2 concentrations raise concern not only from observations of the climate system, but because feedbacks associated with reduced reflectivity from in land and sea ice, sea level, and land vegetation relatively slowly (centuries or longer) to elevated 2 levels. This means that additional human-induced climate change is expected even if the rate of CO2 emissions is reduced or concentrations immediately stabilized.

  7. Gaucher disease: Progress and ongoing challenges.

    Science.gov (United States)

    Mistry, Pramod K; Lopez, Grisel; Schiffmann, Raphael; Barton, Norman W; Weinreb, Neal J; Sidransky, Ellen

    Over the past decades, tremendous progress has been made in the field of Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Many of the colossal achievements took place during the course of the sixty-year tenure of Dr. Roscoe Brady at the National Institutes of Health. These include the recognition of the enzymatic defect involved, the isolation and characterization of the protein, the localization and characterization of the gene and its nearby pseudogene, as well as the identification of the first mutant alleles in patients. The first treatment for Gaucher disease, enzyme replacement therapy, was conceived of, developed and tested at the Clinical Center of the National Institutes of Health. Advances including recombinant production of the enzyme, the development of mouse models, pioneering gene therapy experiments, high throughput screens of small molecules and the generation of induced pluripotent stem cell models have all helped to catapult research in Gaucher disease into the twenty-first century. The appreciation that mutations in the glucocerebrosidase gene are an important risk factor for parkinsonism further expands the impact of this work. However, major challenges still remain, some of which are described here, that will provide opportunities, excitement and discovery for the next generations of Gaucher investigators.

  8. Autoimmune hemolytic anemia: transfusion challenges and solutions

    Directory of Open Access Journals (Sweden)

    Barros MM

    2017-03-01

    Full Text Available Melca M O Barros, Dante M Langhi Jr, José O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA is defined as the increased destruction of red blood cells (RBCs in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct ­antiglobulin test

  9. Sustainable Materials Management (SMM) Electronics Challenge Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — On September 22, 2012, EPA launched the SMM Electronics Challenge. The Challenge encourages electronics manufacturers, brand owners and retailers to strive to send...

  10. 6 CFR 7.30 - Classification challenges.

    Science.gov (United States)

    2010-01-01

    ... 6 CFR 7.31. ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Classification challenges. 7.30 Section 7.30... INFORMATION Classified Information § 7.30 Classification challenges. (a) Authorized holders of...

  11. Challenges in diagnosing tuberculosis in children

    DEFF Research Database (Denmark)

    Rahman, Nadia; Pedersen, Karin Kæreby; Nielsen, Vibeke Rosenfeldt

    2012-01-01

    Clinical investigations of childhood tuberculosis (TB) are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. We investigated the challenges in diagnosing TB in children in a low-incidence country.......Clinical investigations of childhood tuberculosis (TB) are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. We investigated the challenges in diagnosing TB in children in a low-incidence country....

  12. Health Care Challenges in Iran

    Directory of Open Access Journals (Sweden)

    M Davari

    2005-10-01

    Full Text Available All health systems across the world have faced new challenges, which is primarily referable to increasing the cost of health care services as well as growing demands for new and expensive health technologies. The aim of this study is to analyse the main challenges facing the Iranian health system. A review of available governmental and relevant publications about Iranian health care system was undertaken to assess the direction of future healthcare policy. Electronic news agencies, newspapers, and parliament’s electronic news also reviewed to realise policy-makers points of view about the health system. Healthcare services in Iran have had a great success in primary healthcare services in last 25 years, which is mainly attributable to National Health Networks policy. Between 1979 and 2003, average life expectancy at birth increased from 57 to 70 and infant mortality rate fell from 104 to 26 per thousand live births. Active vaccination system, very good distribution and coverage, free end point services, family planning, maternal teaching, and primary referral system are of strong advantages of health networks in Iran. However, the healthcare system is now subject to a range of new pressures that must be addressed. Many of these pressures are common to all health services (rising consumer demands and expectations for expensive new technologies, changing disease patterns, and resources shortage, but some are largely specific to Iran. Financial fairness contribution of the population to health system, responsiveness of health system, overusing new technologies, inadequate integration of health services, and inequitable distribution of the resources are of the main challenges of health system in Iran. In addition, considering demographic changes of the Iranian population in recent decades, which made Iranian population young, potential pressures due to an aging population will reveal in coming years. Many of these pressures relate to policies and

  13. Emerging challenges in implementing universal health coverage in Asia.

    Science.gov (United States)

    Bredenkamp, Caryn; Evans, Timothy; Lagrada, Leizel; Langenbrunner, John; Nachuk, Stefan; Palu, Toomas

    2015-11-01

    As countries in Asia converge on the goal of universal health coverage (UHC), some common challenges are emerging. One is how to ensure coverage of the informal sector so as to make UHC truly universal; a second is how to design a benefit package that is responsive and appropriate to current health challenges, yet fiscally sustainable; and a third is how to ensure "supply-side readiness", i.e. the availability and quality of services, which is a necessary condition for translating coverage into improvements in health outcomes. Using examples from the Asia region, this paper discusses these three challenges and how they are being addressed. On the first challenge, two promising approaches emerge: using general revenues to fully cover the informal sector, or employing a combination of tax subsidies, non-financial incentives and contributory requirements. The former can produce fast results, but places pressure on government budgets and may induce informality, while the latter will require a strong administrative mandate and systems to track the ability-to-pay. With respect to benefit packages, we find considerable variation in the nature and rigor of processes underlying the selection and updating of the services included. Also, in general, packages do not yet focus sufficiently on non-communicable diseases (NCDs) and related preventive outpatient care. Finally, there are large variations and inequities in the supply-side readiness, in terms of availability of infrastructure, equipment, essential drugs and staffing, to deliver on the promises of UHC. Health worker competencies are also a constraint. While the UHC challenges are common, experience in overcoming these challenges is varied and many of the successes appear to be highly context-specific. This implies that researchers and policymakers need to rigorously, and regularly, assess different approaches, and share these findings across countries in Asia - and across the world.

  14. iSTEM: The Aerospace Engineering Challenge

    Science.gov (United States)

    English, Lyn D.; King, Donna T.; Hudson, Peter; Dawes, Les

    2014-01-01

    The authors developed The Paper Plane Challenge as one of a three-part response to The Aerospace Engineering Challenge. The Aerospace Engineering Challenge was the second of three multi-part activities that they had developed with the teachers during the year. Their aim was to introduce students to the exciting world of engineering, where they…

  15. Challenges and Opportunities for Libraries in Pakistan

    OpenAIRE

    Shafiq UR, Rehman; Pervaiz, Ahmad

    2007-01-01

    Abstract: This paper, based on review of literature, observation, and informal conversations, discusses various challenges regarding finance, collection development, ICTs, human resources, library education, library association and research & development faced by library profession in Pakistan. The opportunities to meet these challenges have also been explored. Keywords: Library challenges and opportunities (Pakistan); Librarianship (Pakistan); Library issues; Library profession in Pa...

  16. Builders Challenge Quality Criteria Support Document

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-06-01

    This document provides guidance to U.S. home builders participating in Builders Challenge. To qualify for the Builders Challenge, a home must score 70 or less on the EnergySmart Home Scale (E-Scale). Homes also must meet the Builders Challenge Quality Cri

  17. Reflections of a Faraday Challenge Day Leader

    Science.gov (United States)

    Sewell, Keira

    2014-01-01

    Keira Sewell has just finished her second year as a Challenge Leader for the Faraday Challenge, a STEM-based scheme run by the Institution of Engineering and Technology. Aimed at 12-13 year-old students, its purpose is to engage students in future careers in engineering. Each year, a new challenge is held in over sixty schools and universities…

  18. Challenges in uncomplicated acute appendicitis

    Institute of Scientific and Technical Information of China (English)

    Fernando Resende; Ana Beatriz Almeida; Jose Costa Maia; Renato Bessa Melo

    2016-01-01

    Acute appendicitis is one of the most common abdominal emergencies requiring surgery. It still represents, however, a challenging diagnosis. In order to facilitate this process, several scoring systems were developed, namely, the Alvarado score, acute inflammatory response and Raja Isteri Pengiran Anak Saleha Appendicitis scores, which are the most used in clinical practice. This clinical condition encompasses a wide spectrum of clinical presentations, from the uncomplicated form to the one with diffuse peritonitis. Treatment of uncomplicated acute appendicitis remains a matter of discussion. Although appen-dectomy has been regarded as the gold-standard, conservative management with antibi-otics is gaining more and more acceptance. The approach to appendectomy constitutes another controversial issue, namely, its performance through an open or a laparoscopic approach, which seems to be establishing itself, in some centers, as the standard of care. With this paper, we intend to give some insight on the aforementioned topics, through a review of the available literature on uncomplicated appendicitis.

  19. Nuclear energy safety - new challenges

    Energy Technology Data Exchange (ETDEWEB)

    Rausch, Julio Cezar; Fonseca, Renato Alves da, E-mail: jrausch@cnen.gov.b, E-mail: rfonseca@cnen.gov.b [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    Fukushima accident in March this year, the second most serious nuclear accident in the world, put in evidence a discussion that in recent years with the advent of the 'nuclear renaissance' has been relegated in the background: what factors influence the use safe nuclear energy? Organizational precursor, latent errors, reduction in specific areas of competence and maintenance of nuclear programs is a scenario where the guarantee of a sustainable development of nuclear energy becomes a major challenge for society. A deep discussion of factors that influenced the major accidents despite the nuclear industry use of the so-called 'lessons learned' is needed. Major accidents continue to happen if a radical change is not implemented in the focus of safety culture. (author)

  20. Challenges and opportunities in presbycusis.

    Science.gov (United States)

    Parham, Kourosh; McKinnon, Brian J; Eibling, David; Gates, George A

    2011-04-01

    The population aged 65 years and older is increasing at a faster rate than the total population, with predictions that by 2030, 20% of the population will be 65 years or older. In 2006, between 35% and 50% of those aged 65 years or older reportedly had presbycusis, a sensory impairment that contributes to social isolation and loss of autonomy and is associated with anxiety, depression, and cognitive decline. To address these concerns, the Geriatric Committee of the American Academy of Otolaryngology, in conjunction with the Hearing Committee, focused on 3 challenges and opportunities in the management of presbycusis: (1) the financial burden of caring for patients with presbycusis in the face of increasing costs and declining reimbursements; (2) future treatment options arising from improved understanding of the molecular mechanisms underlying presbycusis, and (3) recognition of central presbycusis as a condition commonly superimposed on peripheral age-related hearing loss whose diagnosis and management can improve outcomes.

  1. The sleepy teenager - diagnostic challenges

    Directory of Open Access Journals (Sweden)

    Anne-Marie eLandtblom

    2014-08-01

    Full Text Available The sleepy teenager is a diagnostic challenge because the problems may be physiological or pathological, with behavioural, social and pychological expressions. It is of great importance that health staff that encounter young people with sleep disturbance have good knowledge about the diseases that must be excluded. Narcolepsy, periodic hypersomnia like Kleine Levin syndrome, delayed sleep phase syndrome and obstructive sleep apnoea syndrome, depression and substance use as well as fatigue from chronic disease like multiple sclerosis should be investigated. Clinical assessment, neurophysiological and laboratory investigations constitute important support in these investigations. Functional methods, for example fMRI, are being developed. The role of computer gaming and use of social media in the night is discussed in relation to these diseases. Cognitive dysfunction may develop with several of the conditions. There is need for increased awareness of how to investigate sleep disturbance in children and young people.

  2. Crowdsourcing. A Citizen Participation Challenge

    Directory of Open Access Journals (Sweden)

    Junia Borges

    2014-05-01

    Full Text Available This paper is a work in progress on Crowdsourcing. First, its concepts and importance are discussed and then its value for citizenship and urban planning. The motivation for participation and the display of geo-tagged information, as well as its possible applications in dynamic spatial temporal issues are presented, as well as its different approaches and applications. Furthermore, Crowdsourcing is discussed when the “ONVCêVIU”, a VGI case study, is presented, revealing its origin, objective, free platform comparison - to select the proper tool to implement, the project’s main challenges, results so far and further steps to be taken. To conclude a short review of the author’s vision about what is to come in the future research.

  3. Multiphysics simulations: Challenges and opportunities

    KAUST Repository

    Keyes, David E.

    2013-02-01

    We consider multiphysics applications from algorithmic and architectural perspectives, where "algorithmic" includes both mathematical analysis and computational complexity, and "architectural" includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. © The Author(s) 2012.

  4. The Shigella human challenge model.

    Science.gov (United States)

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  5. HCI challenges in Dance Education

    Directory of Open Access Journals (Sweden)

    K.El Raheb

    2016-08-01

    Full Text Available Dance learning is by nature multimodal, while dance practice presents a wide diversity across genres and contexts. Choreography and artistic contemporary dance performances have been using interactive technologies to support their creative process for several decades. Nevertheless the use of interactive technologies to support dance learning and education is still relatively immature and raises many challenges and interesting questions when it comes to choosing the appropriate human computer interaction methods. In this paper, we present the characteristics of dance teaching and learning in relation to interactive technology and we highlight the points/feedback that dance, as a field of mastering expressive movement, can bring to the design of whole-body interaction experiences.

  6. The challenge of social media

    DEFF Research Database (Denmark)

    Tække, Jesper; Paulsen, Michael Eric

    must find new ways of doing things, because our media milieu has changed. Also in schools many things are changing; the classroom is no longer a closed room where interaction is isolated from the external world. Thousands of parallel interaction systems are intermingling within the social situations...... in the classrooms. On this basis, we present the action research project Socio Media Education, which tries to develop new ways of teaching that feed to the new media environment. The aim of the paper is, on an early stage, to report about the challenge of the new social media and how the project tries to find...... in classrooms, and many problems arise because of missing adequate norms. Students can now access knowledge in the Internet’s thousands of databases and wikis. The upshot is that the old teacher authority and traditional social norms for guiding teaching can no longer help outline efficient behavior...

  7. Nanotechnology for the energy challenge

    CERN Document Server

    2013-01-01

    With the daunting energy challenges faced by Mankind in the 21st century, revolutionary new technologies will be the key to a clean, secure and sustainable energy future. Nanostructures often have surprising and very useful capabilities and are thus paving the way for new methodologies in almost every kind of industry. This exceptional monograph provides an overview of the subject, and presents the current state of the art with regard to different aspects of sustainable production, efficient storage and low-impact use of energy. Comprised of eighteen chapters, the book is divided in three thematic parts: Part I Sustainable Energy Production covers the main developments of nanotechnology in clean energy production and conversion, including photovoltaics, hydrogen production, thermal-electrical energy conversion and fuel cells. Part II Efficient Energy Storage is concerned with the potential use of nanomaterials in more efficient energy storage systems such as advanced batteries, supercapacitors and hydrogen st...

  8. ETHICAL CHALLENGES IN AESTHETIC DENTISTRY

    Directory of Open Access Journals (Sweden)

    Marius NEAGU

    2015-12-01

    Full Text Available Aesthetic dentistry is a branch of dentistry which aims primarily at improving patient’s physical appearance and, to a lesser extent, the functionality of teeth. This field raises particular ethical dilemmas and requires a careful evaluation of patient’s needs and wishes versus his/her clinical best interests. In this article, the authors discuss the main ethical challenges in the field of aesthetic dentistry in the light of the four “classical” principles of bioethics: autonomy, beneficence, non-maleficence and justice. The authors conclude that the principles of medical ethics should be at the very foundation of the field of aesthetic dentistry, for establishing a patient-physician relationship which could lead to optimum clinical outcomes, while respecting the wishes of the patient and promoting his/her best interests.

  9. Molecular Imaging Challenges With PET

    CERN Document Server

    Lecoq, P

    2010-01-01

    The future trends in molecular imaging and associated challenges for in-vivo functional imaging are illustrated on the basis of a few examples, such as atherosclerosis vulnerable plaques imaging or stem cells tracking. A set of parameters are derived to define the specifications of a new generation of in-vivo imaging devices in terms of sensitivity, spatial resolution and signal-to-noise ratio. The limitations of strategies used in present PET scanners are discussed and new approaches are proposed taking advantage of recent progress on materials, photodetectors and readout electronics. A special focus is put on metamaterials, as a new approach to bring more functionality to detection devices. It is shown that the route is now open towards a fully digital detector head with very high photon counting capability over a large energy range, excellent timing precision and possibility of imaging the energy deposition process.

  10. Coordinated Exploration for Grand Challenges

    DEFF Research Database (Denmark)

    Ørding Olsen, Anders; Sofka, Wolfgang; Grimpe, Christoph

    2016-01-01

    Grand challenges are among the most complex problems for modern societies. Many governments and foundations provide substantial resources to encourage the search for solutions. Due to the significance of these problems, organizations often form partnerships in what we call search consortia...... to engage in joint search and compete for funding. Prior research on joint search highlights the role of specialized organizations, mainly regarding technological domains, to identify a superior solution. However, stakeholder theory leads us to believe that the success of any solution depends...... on the acceptance and support of important stakeholders. In this study, we suggest that search consortia are more likely to receive funding when they include representatives of stakeholder concerns, so-called advocacy groups. We extend theory on coordinated exploration in joint search by integrating mechanisms from...

  11. Multiphysics Simulations: Challenges and Opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, David; McInnes, Lois C.; Woodward, Carol; Gropp, William; Myra, Eric; Pernice, Michael; Bell, John; Brown, Jed; Clo, Alain; Connors, Jeffrey; Constantinescu, Emil; Estep, Don; Evans, Kate; Farhat, Charbel; Hakim, Ammar; Hammond, Glenn E.; Hansen, Glen; Hill, Judith; Isaac, Tobin; Jiao, Xiangmin; Jordan, Kirk; Kaushik, Dinesh; Kaxiras, Efthimios; Koniges, Alice; Lee, Ki Hwan; Lott, Aaron; Lu, Qiming; Magerlein, John; Maxwell, Reed M.; McCourt, Michael; Mehl, Miriam; Pawlowski, Roger; Randles, Amanda; Reynolds, Daniel; Riviere, Beatrice; Rude, Ulrich; Scheibe, Timothy D.; Shadid, John; Sheehan, Brendan; Shephard, Mark; Siegel, Andrew; Smith, Barry; Tang, Xianzhu; Wilson, Cian; Wohlmuth, Barbara

    2013-02-12

    We consider multiphysics applications from algorithmic and architectural perspectives, where ‘‘algorithmic’’ includes both mathematical analysis and computational complexity, and ‘‘architectural’’ includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities.

  12. CHALLENGES OF PERMANENT TEACHER TRAINING

    Directory of Open Access Journals (Sweden)

    María Manuela Valles-Ornelas

    2015-07-01

    Full Text Available The new challenges for teachers and managers require to assume permanent formation as a tool for responding effectively and efficiently to them, different perspective to strengthen from the initial teacher education programs. The research was done in a primary school in the state of Chihuahua. The method used was research action, the question was: How can we encourage the lifelong learning and training of the staff of this school, with the purpose to assist them in these processes to improve the service that the school provides to students. The school group is the center of the process, the cooperative and collaborative work accompanied by educational leadership and persuasive provide better results, and all accompanied by the professional selfinvitation.

  13. Emerging infections: a perpetual challenge.

    Science.gov (United States)

    Morens, David M; Folkers, Gregory K; Fauci, Anthony S

    2008-11-01

    Emerging and re-emerging infectious diseases, and their determinants, have recently attracted substantial scientific and popular attention. HIV/AIDS, severe acute respiratory syndrome, H5N1 avian influenza, and many other emerging diseases have either proved fatal or caused international alarm. Common and interactive co-determinants of disease emergence, including population growth, travel, and environmental disruption, have been increasingly documented and studied. Are emerging infections a new phenomenon related to modern life, or do more basic determinants, transcending time, place, and human progress, govern disease generation? By examining a number of historically notable epidemics, we suggest that emerging diseases, similar in their novelty, impact, and elicitation of control responses, have occurred throughout recorded history. Fundamental determinants, typically acting in concert, seem to underlie their emergence, and infections such as these are likely to continue to remain challenges to human survival.

  14. Managing neurocysticercosis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Fogang YF

    2015-10-01

    Full Text Available Yannick Fogoum Fogang, Abdoul Aziz Savadogo, Massaman Camara, Dènahin Hinnoutondji Toffa, Anna Basse, Adjaratou Djeynabou Sow, Mouhamadou Mansour Ndiaye Neurology Department, Fann Teaching Hospital, Cheikh Anta Diop University, Dakar, Senegal Abstract: Taenia solium neurocysticercosis (NCC is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline. Accurate patients' categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide. Keywords: neurocysticercosis, Taenia solium, epilepsy, headache, albendazole, praziquantel

  15. Facing the challenge of multimorbidity

    Directory of Open Access Journals (Sweden)

    Boris Azaïs

    2016-02-01

    Full Text Available Abstract Multimorbidity is a major public health challenge that is rising up the political and health agenda at an accelerated rate. Although the prevalence of multimorbidity increases with age, more than half of the population with multimorbidity are under the age of 65 years [1], with social deprivation a key determinant of multimorbidity in young and middle-aged adults [2,3]. From an individual’s perspective, multimorbidity reduces life expectancy [4–6], decreases physical functioning and quality of life [7], and increases the risk of depression and other mental health disorders [3]. From a healthcare provider’s perspective, multimorbidity is associated with increased health service use, a high risk of emergency and other hospital admissions, high rates of polypharmacy, and spiralling costs [8]. Current health systems, which are typically built around a single-disease framework, are poorly adapted to cope with patients with multimorbidity, who typically experience fragmented healthcare services, leading to potentially inefficient and ineffective care. It is increasingly clear that we need to change our perspective on multimorbidity in order to address it as a specific condition that requires tailored solutions and approaches. The urgent need to tackle multimorbidity in a more strategic, holistic, and cost-effective manner was evident at the 18th European Health Forum Gastein, a leading annual health policy event in the European Union (EU, held in the autumn of 2015. This Forum attracted policymakers, clinicians, health service managers, patients, and a broad range of other stakeholders, all of whom were invited to attend a session entitled “Facing the Challenge of Multimorbidity”. Journal of Comorbidity 2016;6(1:1–3

  16. Technical solutions to nonproliferation challenges

    Science.gov (United States)

    Satkowiak, Lawrence

    2014-05-01

    The threat of nuclear terrorism is real and poses a significant challenge to both U.S. and global security. For terrorists, the challenge is not so much the actual design of an improvised nuclear device (IND) but more the acquisition of the special nuclear material (SNM), either highly enriched uranium (HEU) or plutonium, to make the fission weapon. This paper provides two examples of technical solutions that were developed in support of the nonproliferation objective of reducing the opportunity for acquisition of HEU. The first example reviews technologies used to monitor centrifuge enrichment plants to determine if there is any diversion of uranium materials or misuse of facilities to produce undeclared product. The discussion begins with a brief overview of the basics of uranium processing and enrichment. The role of the International Atomic Energy Agency (IAEA), its safeguard objectives and how the technology evolved to meet those objectives will be described. The second example focuses on technologies developed and deployed to monitor the blend down of 500 metric tons of HEU from Russia's dismantled nuclear weapons to reactor fuel or low enriched uranium (LEU) under the U.S.-Russia HEU Purchase Agreement. This reactor fuel was then purchased by U.S. fuel fabricators and provided about half the fuel for the domestic power reactors. The Department of Energy established the HEU Transparency Program to provide confidence that weapons usable HEU was being blended down and thus removed from any potential theft scenario. Two measurement technologies, an enrichment meter and a flow monitor, were combined into an automated blend down monitoring system (BDMS) and were deployed to four sites in Russia to provide 24/7 monitoring of the blend down. Data was downloaded and analyzed periodically by inspectors to provide the assurances required.

  17. Comparative evaluation of infection methods and environmental factors on challenge success: Aeromonas salmonicida infection in vaccinated rainbow trout

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar; Skov, Jakob; Jaafar, Rzgar M.;

    2015-01-01

    When testing vaccine-induced protection an effective and reliable challenge method is a basic requirement and we here present a comparative study on different challenge methods used for infection of rainbow trout Oncorhynchus mykiss with Aeromonas salmonicida, a bacterial pathogen eliciting...

  18. Long-Term Protective Effects of Methamphetamine Preconditioning Against Single-Day Methamphetamine Toxic Challenges

    OpenAIRE

    Hodges, A.B; Ladenheim, B.; McCoy, M T; Beauvais, G; Cai, N; Krasnova, I. N.; Cadet, J.L.

    2011-01-01

    Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dos...

  19. Challenges in the Heterologous Production of Antibiotics in Streptomyces.

    Science.gov (United States)

    Bekiesch, Paulina; Basitta, Patrick; Apel, Alexander K

    2016-08-01

    The fast growing genome databases provide us with a large number of so far unknown secondary metabolite biosynthetic gene clusters. A key method to study these gene clusters is their heterologous expression in an engineered host strain. Gene clusters derived from actinomycetes are usually expressed in a Streptomyces host strain to identify and investigate the corresponding compounds. However, heterologous expression is often accompanied with some challenges affecting the production rates of secondary metabolites. The first step is therefore the selection of a suitable expression vector and host strain. Once production has been established, there are several possibilities to improve compound yields either by media screens, by overexpression of regulatory or transport genes or by introduction of constitutive or inducible promoters. A surely important, but hitherto little studied factor is also the regulation of a heterologously expressed gene cluster by its host strain. This review gives a short overview on the chances and challenges provided by heterologous production of secondary metabolites in Streptomyces.

  20. OBESITY: CHALLENGES TO VENTILATORY CONTROL DURING EXERCISE A BRIEF REVIEW

    Science.gov (United States)

    Babb, Tony G.

    2013-01-01

    Obesity is a national health issue in the US. Among the many physiological changes induced by obesity, it also presents a unique challenge to ventilatory control during exercise due to increased metabolic demand of moving larger limbs, increased work of breathing due to extra weight on the chest wall, and changes in breathing mechanics. These challenges to ventilatory control in obesity can be inconspicuous or overt among obese adults but for the most part adaptation of ventilatory control during exercise in obesity appears remarkably unnoticed in the majority of obese people. In this brief review, the changes to ventilatory control required for maintaining normal ventilation during exercise will be examined, especially the interaction between respiratory neural drive and ventilation. Also, gaps in our current knowledge will be discussed. PMID:23707540

  1. Ionospheric Challenges for GNSS Based Augmentation Systems

    Science.gov (United States)

    Doherty, P.; Valladares, C. E.

    2007-12-01

    The ionosphere is a highly dynamic physical phenomenon that presents a variable source of error for Global Navigation Satellite System (GNSS) signals and GNSS based operational systems. The Federal Aviation Administration's (FAA) Wide-Area Augmentation System (WAAS) was designed to enhance the GNSS standard positioning service by providing additional accuracy, availability and integrity that is sufficient for use in commercial aviation. It is the first of a number of planned regional Satellite Based Augmentation Systems (SBAS). Other systems in development include the European EGNOS system, the MSAS system in Japan and the GAGAN system in India. In addition, the South American countries are investigating the feasibility of operating an SBAS system in this region. Much of the WAAS ionospheric research and development focused on defining and mitigating ionospheric challenges characteristic of the mid-latitude regions, where the ionosphere is well studied and relatively quiescent. The EGNOS and MSAS systems will primarily operate under a similarly quiescent mid-latitude ionosphere. SBAS system development in South America, India and other low-latitude regions, however, will have to contend with much more extreme conditions. These conditions include strong spatial and temporal gradients, plasma depletions and scintillation. All of these conditions have a potential to limit SBAS performance in the low latitude regions. This presentation will review the effects that the ionosphere has on the mid-latitude WAAS system. It will present the techniques that are used to mitigate ionospheric disturbances induced on the system during severe geomagnetic activity and it will quantify the effect that this activity has on system performance. The presentation will then present data from the South American Low-latitude Ionospheric Sensor Network (LISN) that can be used to infer the ionospheric effects on SBAS performance in the most challenging low-latitude ionospheric environment

  2. 75 FR 21044 - Notice of Centennial Challenges 2011 CAFE Green Flight Challenge

    Science.gov (United States)

    2010-04-22

    ... SPACE ADMINISTRATION Notice of Centennial Challenges 2011 CAFE Green Flight Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2011 CAFE Green Flight Challenge. SUMMARY: This notice is issued in accordance with 42 U.S.C. 2451(314)(d). The 2011 CAFE...

  3. Injection-induced earthquakes.

    Science.gov (United States)

    Ellsworth, William L

    2013-07-12

    Earthquakes in unusual locations have become an important topic of discussion in both North America and Europe, owing to the concern that industrial activity could cause damaging earthquakes. It has long been understood that earthquakes can be induced by impoundment of reservoirs, surface and underground mining, withdrawal of fluids and gas from the subsurface, and injection of fluids into underground formations. Injection-induced earthquakes have, in particular, become a focus of discussion as the application of hydraulic fracturing to tight shale formations is enabling the production of oil and gas from previously unproductive formations. Earthquakes can be induced as part of the process to stimulate the production from tight shale formations, or by disposal of wastewater associated with stimulation and production. Here, I review recent seismic activity that may be associated with industrial activity, with a focus on the disposal of wastewater by injection in deep wells; assess the scientific understanding of induced earthquakes; and discuss the key scientific challenges to be met for assessing this hazard.

  4. Injection-induced earthquakes

    Science.gov (United States)

    Ellsworth, William L.

    2013-01-01

    Earthquakes in unusual locations have become an important topic of discussion in both North America and Europe, owing to the concern that industrial activity could cause damaging earthquakes. It has long been understood that earthquakes can be induced by impoundment of reservoirs, surface and underground mining, withdrawal of fluids and gas from the subsurface, and injection of fluids into underground formations. Injection-induced earthquakes have, in particular, become a focus of discussion as the application of hydraulic fracturing to tight shale formations is enabling the production of oil and gas from previously unproductive formations. Earthquakes can be induced as part of the process to stimulate the production from tight shale formations, or by disposal of wastewater associated with stimulation and production. Here, I review recent seismic activity that may be associated with industrial activity, with a focus on the disposal of wastewater by injection in deep wells; assess the scientific understanding of induced earthquakes; and discuss the key scientific challenges to be met for assessing this hazard.

  5. Tuberculosis diagnostics: Challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Vijay Nema

    2012-01-01

    Full Text Available Tuberculosis (TB has been a disease affecting almost all parts of the world since ages. Lot many efforts came in the past for improving diagnosis and treatment. Also, an effective vaccine has been sought after for long. With the emergence of resistant strains of Mycobacterium tuberculosis, the causal organisms of tuberculosis, and complexities emerging due to other associated infections and disease conditions, there is a desperate need for further research input in the field. Be it the better medication and care or better resistance management, proper diagnostics holds the key to success. It has been observed that a high burden of the disease was accompanied by resource limitations and poor research set-up. The scenario remained like this for several decades. With the refreshed vision of resourceful countries and funding agencies, funding is being provided in many areas of research in tuberculosis diagnosis and treatment. This review has been written with an aim to bring forth the limitations of available methods in the field of diagnostics and making researchers aware about the changing scenario with better funding opportunities and support. The author visualizes an enthusiasm from all over the world for the development of better modalities and urges scientists to join the struggle at this very perfect time to take the challenge and come forward with innovations in this field.

  6. CMS prepares for new challenges

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    One of the world’s largest physics experiments has just had a change in leadership. This is a chance for the collaboration to take stock of the tremendous work done for LS1 and to prepare for the challenges that lie ahead.   From left to right: Kerstin Borras, Tiziano Camporesi and Paris Sphicas. “The keyword is teamwork. That’s the only way you can effectively manage a large number of extremely talented and motivated people,” says Tiziano Camporesi who took the reins of the CMS collaboration at the beginning of the year. The recipe might seem easier on paper than in practice. However, given his 28 years at CERN, two of which he spent as the head of the DELPHI collaboration, Camporesi has extensive experience in managing large scientific collaborations and success in this respect is well within his reach: “I have learned many lessons from the past and I believe that building consensus is instrumental to successful leadership.” The C...

  7. New challenges for data design

    CERN Document Server

    2015-01-01

    The present work provides a platform for leading data designers whose vision and creativity help us to anticipate major changes occurring in the data design field, and pre-empt the future. Each of them strives to provide new answers to the question, “What challenges await data design?” To avoid falling into too narrow a mind-set, each works hard to elucidate the breadth of data design today and to demonstrate its widespread application across a variety of business sectors. With end users in mind, designer-contributors bring to light the myriad of purposes for which the field was originally intended, forging the bond even further between data design and the aims and intentions of those who contribute to it. The first seven parts of the book outline the scope of data design, and presents a line-up of “viewpoints” that highlight this discipline’s main topics, and offers an in-depth look into practices boasting both foresight and imagination. The eighth and final part features a series of interviews wit...

  8. Antiphospholipid syndrome: A diagnostic challenge.

    Science.gov (United States)

    Mallhi, R S; Kushwaha, Neerja; Chatterjee, T; Philip, J

    2016-12-01

    The antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilic disorder that is characterized by thrombosis (venous, arterial and microvascular) and obstetric morbidity due to a diverse family of antibodies against phospholipid-binding proteins present in plasma. The term antiphospholipid antibody is actually a misnomer as the antibodies are not against the phospholipid per se, but target the plasma protein co-factors, which bind to anionic PLs. The exact etiology has not been elucidated and is multifactorial. The initial guidelines for the diagnosis of APS were laid down in Sapporo, 1999, which were subsequently revised as the Sydney Consensus Conference criteria in 2006. Major changes were the inclusion of β2GPI as independent laboratory criteria, addition of ischemic stroke and transient cerebral ischemia as established clinical criteria and the requirement of repeating the test after 12 weeks. The laboratory tests recommended are coagulation assays, which study the effect of lupus anticoagulant on the clotting time and immunological assays, mostly ELISAs to detect IgG and IgM antibodies against cardiolipin and/or β2 glycoprotein I. For the diagnosis of APS, at least one clinical criterion and one laboratory criterion should be present. Limitations pertaining to the standardization, reproducibility and robustness of the currently recommended diagnostic tests still remain. Despite elaborate guidelines and syndrome defining criteria, the diagnosis of APS still remains a challenge. A greater interaction between the clinicians and the laboratory professionals is necessary for arriving at the correct diagnosis as a misdiagnosis of APS can have grave consequences.

  9. ECOPHARMACOVIGILANCE: ITS IMPORTANCE AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    Dr. Bhavana Srivastava

    2014-07-01

    Full Text Available Active pharmaceutical ingredients represent a group of emerging environmental contamination. Even in trace amounts, they are of great concern due to then continuous introduction into the environment, their impact an ecosystem and human and vetenery health is of great importance. This has given birth to the science of Ecopharmacovigilance (EPV. It aims to ensure that significant environmental issues associated with pharmaceuticals in the environment are identified and managed appropriately. EPV has become a research hotspot in Europe and North America. Environmental Risk assessment (ERA is now a regulatory requirement prior to launch of any new drug. The biggest difference and greatest challenge concerns signal detection in the environment and the dilemma of identifying cause and effect. In the background of growing Indian pharmaceutical industry and drug consumption, India should shoulder responsibility for its own environment and people along with the world ecosystem. Compared to the west EPV in India is in infancy ERA is now a regulatory requirement prior to launch of any new drug. However there is no formal frame-work to monitor for potential adverse effects in the environment, once a product has been launched. There should be laws and regulations on EPV, rational medication, drug take back programs, strengthening policy guided and scientific researches on EPV by pharmaceutical firms and academia.

  10. ALICE Holds Up to Challenge

    CERN Multimedia

    2006-01-01

    ALICE's main austenitic stainless steel support structure (the Space Frame) has recently gone through many tests that proved quite challenging: insuring the structure is sound and lowering it horizontally into the ALICE cavern. This structure is constructed to hold the large volume detectors, such as the Time Projection Chamber, Transition Radiation Detector and Time of Flight inside the ALICE solenoid magnet. After the final assembly at CERN, two large mobile cranes were needed for the job of lifting and turning the 14 tonne frame onto its side. Once shifted, it was placed in Building SX2, one of the surface assembly areas designated for ALICE. The structure, which is 8 m in diameter and 7 m long, underwent many tests in its new position. Geometric control tests were performed by measuring each of the 18 cells and placing wooden or metal samples constructed to the same dimensions as the real thing inside the structure. The most important check was the movement of the real Time Projection Chamber from its s...

  11. Challenges in Commercializing Biomimetic Membranes

    Directory of Open Access Journals (Sweden)

    Mark Perry

    2015-11-01

    Full Text Available The discovery of selective water channel proteins—aquaporins—has prompted growing interest in using these proteins, as the building blocks for designing new types of membranes. However, as with any other new and potentially disruptive technology, barriers for successful market entry exist. One category includes customer-related barriers, which can be influenced to some extent. Another category includes market-technical-related barriers, which can be very difficult to overcome by an organization/company aiming at successfully introducing their innovation on the market—in particular if both the organization and the technology are at early stages. Often, one faces barriers from both these categories at the same time, which makes it necessary to gain insight of the particular market when introducing a new innovative product. In this review we present the basic concepts and discuss some of these barriers and challenges associated with introducing biomimetic aquaporin membranes. These include technical issues in membrane production and product testing. Then we discuss possible business models for introducing new technologies in general, followed by a presentation of beach-head market segments relevant for biomimetic aquaporin membranes.

  12. Gaia and its spectrometric challenge

    Energy Technology Data Exchange (ETDEWEB)

    Thevenin, F [Universite de Nice, Laboratoire Cassiopee, CNRS, OCA, BP 4229, 06304 Nice Cedex (France)], E-mail: frederic.thevenin@oca.eu

    2008-12-15

    The Gaia program was kicked off at the beginning of 2006 and is now reaching a phase of construction and integration for a launch at the end of 2011, to reach the L2 point several months later. Apart from that industrial activity, the European astronomical community is actively preparing the data treatment and in particular how to extract the astrophysical parameter outputs from the use of the spectrographs on board the satellite. This work consists of the realization of algorithms to extract fundamental parameters of the detected source points with the help of an extensive grid of synthetic spectral libraries. The number of these estimated fundamental parameters and their accuracy depend on the ability of the algorithms to treat the spectra and to compare them with the computed ones, and also on the quality of the synthetic spectra themselves. Then, on the one hand a huge effort is underway to produce these extensive grids of one-dimensional (1D) local thermodynamic equilibrium (LTE) spectra of stars, galaxies, quasi-stellar objects and asteroids, and on the other hand, new physics is tested in the atmosphere model of stars to improve the theoretical libraries. An example of the questions we need to answer is: do we need 3D non-local thermodynamic equilibrium (NLTE) modelling? If yes, the libraries will then be improved by adding corrections checked on dedicated standard stars. Shall we be able to implement this new physics in a reasonable time? This is another challenge.

  13. Mystery photos: challenge No. 2!

    CERN Multimedia

    Alex Brown, Jens Vigen

    2014-01-01

    In the last issue of the Bulletin, we launched a public appeal for information to identify some CERN pictures that have recently been digitised by the CERN Library. The response has been huge. The story was picked up on many websites and discussion forums all over the Web, and hundreds of people sent in their suggestions. Time for a new challenge.   Many thousands of CERN's archived pictures are currently being scanned and uploaded to the CERN Document Server. While most of these pictures can be matched to existing historical information, many are harder to identify. Following the recent article in the last issue of the Bulletin, we have received submissions in five different languages from a dozen countries. We would like to express our thanks to everyone who has contributed their answers. We have now identified all of the pictures highlighted in the last issue of the Bulletin and we are updating the records accordingly. You can see them all here. To see a complete lis...

  14. Northern pipelines : challenges and needs

    Energy Technology Data Exchange (ETDEWEB)

    Dean, D.; Brownie, D. [ProLog Canada Inc., Calgary, AB (Canada); Fafara, R. [TransCanada PipeLines Ltd., Calgary, AB (Canada)

    2007-07-01

    Working Group 10 presented experiences acquired from the operation of pipeline systems in a northern environment. There are currently 3 pipelines operating north of 60, notably the Shiha gas pipeline near Fort Liard, the Ikhil gas pipeline in Inuvik and the Norman Wells oil pipeline. Each has its unique commissioning, operating and maintenance challenges, as well as specific training and logistical support requirements for the use of in-line inspection tools and other forms of integrity assessment. The effectiveness of cathodic protection systems in a permafrost northern environment was also discussed. It was noted that the delay of the Mackenzie Gas Pipeline Project by two to three years due to joint regulatory review may lead to resource constraints for the project as well as competition for already scarce human resources. The issue of a potential timing conflict with the Alaskan Pipeline Project was also addressed as well as land use issues for routing of supply roads. Integrity monitoring and assessment issues were outlined with reference to pipe soil interaction monitoring in discontinuous permafrost; south facing denuded slope stability; base lining projects; and reclamation issues. It was noted that automatic welding and inspection will increase productivity, while reducing the need for manual labour. In response to anticipated training needs, companies are planning to involve and train Aboriginal labour and will provide camp living conditions that will attract labour. tabs., figs.

  15. Virtual physiological human: training challenges.

    Science.gov (United States)

    Lawford, Patricia V; Narracott, Andrew V; McCormack, Keith; Bisbal, Jesus; Martin, Carlos; Bijnens, Bart; Brook, Bindi; Zachariou, Margarita; Freixa, Jordi Villà I; Kohl, Peter; Fletcher, Katherine; Diaz-Zuccarini, Vanessa

    2010-06-28

    The virtual physiological human (VPH) initiative encompasses a wide range of activities, including structural and functional imaging, data mining, knowledge discovery tool and database development, biomedical modelling, simulation and visualization. The VPH community is developing from a multitude of relatively focused, but disparate, research endeavours into an integrated effort to bring together, develop and translate emerging technologies for application, from academia to industry and medicine. This process initially builds on the evolution of multi-disciplinary interactions and abilities, but addressing the challenges associated with the implementation of the VPH will require, in the very near future, a translation of quantitative changes into a new quality of highly trained multi-disciplinary personnel. Current strategies for undergraduate and on-the-job training may soon prove insufficient for this. The European Commission seventh framework VPH network of excellence is exploring this emerging need, and is developing a framework of novel training initiatives to address the predicted shortfall in suitably skilled VPH-aware professionals. This paper reports first steps in the implementation of a coherent VPH training portfolio.

  16. Challenging the Long Tail Recommendation

    CERN Document Server

    Yin, Hongzhi; Li, Jing; Yao, Junjie; Chen, Chen

    2012-01-01

    The success of "infinite-inventory" retailers such as Amazon.com and Netflix has been largely attributed to a "long tail" phenomenon. Although the majority of their inventory is not in high demand, these niche products, unavailable at limited-inventory competitors, generate a significant fraction of total revenue in aggregate. In addition, tail product availability can boost head sales by offering consumers the convenience of "one-stop shopping" for both their mainstream and niche tastes. However, most of existing recommender systems, especially collaborative filter based methods, can not recommend tail products due to the data sparsity issue. It has been widely acknowledged that to recommend popular products is easier yet more trivial while to recommend long tail products adds more novelty yet it is also a more challenging task. In this paper, we propose a novel suite of graph-based algorithms for the long tail recommendation. We first represent user-item information with undirected edge-weighted graph and i...

  17. Electrolyte materials - Issues and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Balbuena, Perla B. [Department of Chemical Engineering, and Department of Materials Science and Engineering, Texas A and M University, College Station, Texas, 77843 (United States)

    2014-06-16

    Electrolytes are vital components of an electrochemical energy storage device. They are usually composed of a solvent or mixture of solvents and a salt or a mixture of salts which provide the appropriate environment for ionic conduction. One of the main issues associated with the selection of a proper electrolyte is that its electronic properties have to be such that allow a wide electrochemical window - defined as the voltage range in which the electrolyte is not oxidized or reduced - suitable to the battery operating voltage. In addition, electrolytes must have high ionic conductivity and negligible electronic conductivity, be chemically stable with respect to the other battery components, have low flammability, and low cost. Weak stability of the electrolyte against oxidation or reduction leads to the formation of a solid-electrolyte interphase (SEI) layer at the surface of the cathode and anode respectively. Depending on the materials of the electrolyte and those of the electrode, the SEI layer may be composed by combinations of organic and inorganic species, and it may exert a passivating role. In this paper we discuss the current status of knowledge about electrolyte materials, including non-aqueous liquids, ionic liquids, solid ceramic and polymer electrolytes. We also review the basic knowledge about the SEI layer formation, and challenges for a rational design of stable electrolytes.

  18. Plant Biotechnology: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    P.V. Lakshmana Rao

    1996-01-01

    Full Text Available Development of procedures in cell biology to regenerate plants from single cells in any desired quantity provides the prerequisite for the practical use of plant tissue culture and genetic engineering in crop improvement. Such regenerating cell cultures are used for selection of mutants and for DNA transformation experiments. DNA transfer by means of engineered Ti and Ri plasmids has become an established technique for the rapidly growing list of dicotyledonous plants. Considerable success has also been achieved in making gene transfer techniques independent of cell culture methods. These techniques have given the opportunity to create, characterise and select plant cultivars which cannot be obtained by traditional breeding methods. The exploitation of plant cell cultures for production of pharmaceuticals, natural products of commercial importance and mass propagation of high-value crops by automation, have developed into an important industry with considerable potential for future. This paper discusses the recent advances and applications of plant biotechnology in agriculture and industry and the challenges the still exist.

  19. Gaia and its spectrometric challenge

    Science.gov (United States)

    Thévenin, F.

    2008-12-01

    The Gaia program was kicked off at the beginning of 2006 and is now reaching a phase of construction and integration for a launch at the end of 2011, to reach the L2 point several months later. Apart from that industrial activity, the European astronomical community is actively preparing the data treatment and in particular how to extract the astrophysical parameter outputs from the use of the spectrographs on board the satellite. This work consists of the realization of algorithms to extract fundamental parameters of the detected source points with the help of an extensive grid of synthetic spectral libraries. The number of these estimated fundamental parameters and their accuracy depend on the ability of the algorithms to treat the spectra and to compare them with the computed ones, and also on the quality of the synthetic spectra themselves. Then, on the one hand a huge effort is underway to produce these extensive grids of one-dimensional (1D) local thermodynamic equilibrium (LTE) spectra of stars, galaxies, quasi-stellar objects and asteroids, and on the other hand, new physics is tested in the atmosphere model of stars to improve the theoretical libraries. An example of the questions we need to answer is: do we need 3D non-local thermodynamic equilibrium (NLTE) modelling? If yes, the libraries will then be improved by adding corrections checked on dedicated standard stars. Shall we be able to implement this new physics in a reasonable time? This is another challenge.

  20. [Challenges and trends in rehabilitation].

    Science.gov (United States)

    Bautz-Holter, Erik; Sveen, Unni; Søberg, Helene; Røe, Cecilie

    2007-02-01

    The definition of rehabilitation is debated, but the true sense of the word is "reinstatement in dignity." There is often a need for rehabilitation after diseases and injuries. Rehabilitation is founded on the individual's right to participate in society and to have equal opportunities in general, and can be considered both in a medical and a sociological perspective. WHO has developed "International Classification of Functioning, disability and health"-ICF. ICF reflects an understanding of function and disability in a bio-psychosocial model. The issues discussed in this article will be limited to rehabilitation within the Norwegian healthcare system. Rehabilitation is based on the individual's loss of function, irrespective of the injury or disease, and should focus on resources. Its main issue is the subject's own goals and wishes with respect to quality of life and total life situation. Many groups that have, or are in danger of acquiring reduced function are in need of rehabilitation, if this can prevent or reduce loss of function or participation. The measures taken can be directed over a wide spectrum, directed towards function and activity, and often with participation in a variety of life aspects as the main goal. Rehabilitation is presented with many challenges caused by the general development in society, including implementation of the medical and technological development and demand of scientific documentation.

  1. Astronomy Education Challenges in Egypt

    Science.gov (United States)

    El Fady Beshara Morcos, Abd

    2015-08-01

    One of the major challenges in Egypt is the quality of education. Egypt has made significant progress towards achieving the Education for All and the Millennium Development Goals (MDGs). Many associations and committees as education reform program and education support programs did high efforts in supporting scientific thinking through the scientific clubs. The current state of astronomical education in Egypt has been developed. Astronomy became a part in both science and geography courses of primary, preparatory and secondary stages. Nowadays the Egyptian National Committee for Astronomy, put on its shoulders the responsibility of revising of astronomy parts in the education courses, beside preparation of some training programs for teachers of different stages of educations, in collaboration with ministry of education. General lectures program has been prepared and started in public places , schools and universities. Many TV and Radio programs aiming to spread astronomical culture were presented. In the university stage new astronomy departments are established and astrophysics courses are imbedded in physics courses even in some private universities.

  2. Design challenges for space bioreactors

    Science.gov (United States)

    Seshan, P. K.; Petersen, G. R.

    1989-01-01

    The design of bioreactors for operation under conditions of microgravity presents problems and challenges. Absence of a significant body force such as gravity can have profound consequences for interfacial phenomena. Marangoni convection can no longer be overlooked. Many speculations on the advantages and benefits of microgravity can be found in the literature. Initial bioreactor research considerations for space applications had little regard for the suitability of the designs for conditions of microgravity. Bioreactors can be classified in terms of their function and type of operation. The complex interaction of parameters leading to optimal design and operation of a bioreactor is illustrated by the JSC mammalian cell culture system. The design of a bioreactor is strongly dependent upon its intended use as a production unit for cell mass and/or biologicals or as a research reactor for the study of cell growth and function. Therefore a variety of bioreactor configurations are presented in rapid summary. Following this, a rationale is presented for not attempting to derive key design parameters such as the oxygen transfer coefficient from ground-based data. A set of themes/objectives for flight experiments to develop the expertise for design of space bioreactors is then proposed for discussion. These experiments, carried out systematically, will provide a database from which engineering tools for space bioreactor design will be derived.

  3. Organ printing: promises and challenges.

    Science.gov (United States)

    Mironov, Vladimir; Kasyanov, Vladimir; Drake, Christopher; Markwald, Roger R

    2008-01-01

    Organ printing or biomedical application of rapid prototyping, also defined as additive layer-by-layer biomanufacturing, is an emerging transforming technology that has potential for surpassing traditional solid scaffold-based tissue engineering. Organ printing has certain advantages: it is an automated approach that offers a pathway for scalable reproducible mass production of tissue engineered products; it allows a precised simultaneous 3D positioning of several cell types; it enables creation tissue with a high level of cell density; it can solve the problem of vascularization in thick tissue constructs; finally, organ printing can be done in situ. The ultimate goal of organ-printing technology is to fabricate 3D vascularized functional living human organs suitable for clinical implantation. The main practical outcomes of organ-printing technology are industrial scalable robotic biofabrication of complex human tissues and organs, automated tissue-based in vitro assays for clinical diagnostics, drug discovery and drug toxicity, and complex in vitro models of human diseases. This article describes conceptual framework and recent developments in organ-printing technology, outlines main technological barriers and challenges, and presents potential future practical applications.

  4. Challenges in Microseismic Monitoring of Hydrualic Fracturing

    Science.gov (United States)

    Venkataraman, A.; Li, R.

    2011-12-01

    To enhance well productivity, hydraulic fractures are stimulated by injecting fluid and/or gas with proppant into the rock matrix. This results in stress perturbations that induce fractures in the formation releasing minor amounts of seismic energy as microseismic events. Microseismicity can be recorded by properly positioned geophones and is one of the indirect methods that allow us to determine the actual volume of rock that was impacted during and after hydraulic fracturing. Specifically, microseismic data is acquired during hydro-fracture treatments to validate and assist completions, assist in placing wells in the formation, identify frac barriers, and to illuminate faults and potential fault re-activation. In the industry, microseismic data is acquired using geophones deployed in borehole and/or surface arrays. Borehole arrays are more traditional and have been used for nearly 20 years. Event location using borehole data is fairly robust, but azimuth and aperture are limited. Moreover, having dedicated boreholes can be expensive. The newer method of acquiring data is the use of geophones deployed on the surface or in shallow boreholes. Since microseismic events are very small (-4 to -0.5), surface records have weak P and S arrivals that are buried in the noise and traditional event location methods which use arrival time picks cannot be used. Migration based approaches which rely on the power of stacking waveforms is the common approach. However, poor signal-to-noise data and polarity in seismic waves generated by micro-earthquakes can result in uncertainty in event location. In this paper, we will discuss the pros and cons of both arrays, the status of the technology, its limitations and challenges. Specifically, we will focus on applications where industry-academic collaborations could lead to step changes in our understanding of the controls on microseismicity.

  5. Machine Learning wins the Higgs Challenge

    CERN Multimedia

    Abha Eli Phoboo

    2014-01-01

    The winner of the four-month-long Higgs Machine Learning Challenge, launched on 12 May, is Gábor Melis from Hungary, followed closely by Tim Salimans from the Netherlands and Pierre Courtiol from France. The challenge explored the potential of advanced machine learning methods to improve the significance of the Higgs discovery.   Winners of the Higgs Machine Learning Challenge: Gábor Melis and Tim Salimans (top row), Tianqi Chen and Tong He (bottom row). Participants in the Higgs Machine Learning Challenge were tasked with developing an algorithm to improve the detection of Higgs boson signal events decaying into two tau particles in a sample of simulated ATLAS data* that contains few signal and a majority of non-Higgs boson “background” events. No knowledge of particle physics was required for the challenge but skills in machine learning - the training of computers to recognise patterns in data – were essential. The Challenge, hosted by Ka...

  6. Five challenges for public administrations in Europe

    Directory of Open Access Journals (Sweden)

    Ongaro Edoardo

    2015-12-01

    Full Text Available This article examines five ‘challenges’ facing most administrative systems across Europe. The first challenge stems from the increasingly asymmetric nature of European multilevel governance; the second challenge arises from the missed opportunity of reforming in the absence of a dominant administrative paradigm; the third challenge lies in rescuing and transforming the welfare state; the fourth challenge is concerned with making the most of the knowledge generated in the field of strategic management for strategically managing public services; the fifth challenge lies in staff (demotivation. These challenges are pitched at very different levels: some are related to issues of public governance, some to issues of scholarly and practitioners’ collective understandings of public administration in Europe, and some to trends in the global economy, and notably the financial, economic and fiscal ‘crises’.

  7. Brucellosis: Epizootiologic and diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Radojičić Sonja

    2005-01-01

    Full Text Available Although it has been known as a separate etiological entity for almost 150 years, brucellosis is, on a global scale, one of the most frequent diseases that is transferred from animals to humans. It is present as an endemic disease in almost all countries of the Mediterranean Sea, which indicates that a large number of aspects in connection with the control and epizootiology of this disease still remain unexplained. Three of the six types of brucella have been officially confirmed in our country as well. They are Brucella melitensis biotip 3, Brucella suis biotip 2 and Brucella canis. Brucellosis is endemically present in Kosovo and Metohija province and in southern Serbia proper; over the past few years, the spread of brucellosis in sheep and goats as primary hosts for B. melitensis to new territories, mostly in Vojvodina province, has shown that risk analysis is one of the main factors in selecting and implementing control programmes. A correctly selected set of diagnostic tests yields reliable data in most cases, but interpretations of results are prone to result in subjective assessments as well. A special problem in the serological diagnosis of brucellosis is the cross reactivity of brucellas and some other bacteria, often a weak immunological response of the animal, or that the type of brucella that causes the infection determines the sensitivity and specificity of the applied tests, most often screenings tests. Due to the big economic losses resulting from disease control and eradication, and the serious risk to human health, brucellosis still poses an epizootiological, and, in particular, a diagnostic challenge.

  8. TWIN GESTATION : A CHALLENGING TASK

    Directory of Open Access Journals (Sweden)

    Vrunda V.

    2015-03-01

    Full Text Available INTRODUCTION In the era of modern obstetrics when multiple pregnancies are on increase it is very important to know the incidence and obstetric outcomes of twin deliveries. Twin pregnancy is still associated with increased maternal and perinatal morbidity and mortality as well as healthcare costs . ( 1 , 2 , 3 MATERIALS AND METHODS : This is a r etrospective study of twin deliveries done in the rural medical college teaching hospital over a period of 3 years. RESULTS : During the study period , incidence of twin delivery was 19.37 per 1000 deliveries. Majority cases of twins were young primies in ag e group (20 - 30 years . Preterm delivery occurred in 68% cases and was therefore , the most common morbidity followed by anaemia (38% and PIH (28%. Most common presentation was vertex (66% and malpresentation were present in 44% of cases. 54% were deliver ed by caesarean section. In 88% second baby delivered within 15 minutes. Uterine inertia , PROM , fetal distress , PPH , cord prolapse and abruption were complications during labour. There was no maternal mortality in present study. Average weight of first baby was 1679.63 gms and 2 nd baby was 1586.94 gms. Perinatal mortality of 1 st baby was 27.55 for 1 st baby and 37.25% for 2 nd baby . Average gestational age for patients in whom cervical encirclage was done was 34 weeks. CONCLUSION: P reterm delivery and low birth weight babies are main challenges to the obstetrician. Incidence of LSCS is quite high with malpresentation of leading (twin A baby is a major indication for LSCS . The use of antenatal care services and good intrapartum mana gement will help improve outcome in twin pregnancies.

  9. Challenge of Biotechnology (Review Paper

    Directory of Open Access Journals (Sweden)

    Malcolm R. Dando

    2001-10-01

    Full Text Available The unravelling of the human genetic code whose first draft was announced in June 2000 has rightly blood been hailed as a momentous achievement, opening thc book of life, certain to be the dominant technology of the 21st century, which will inform all about medicine and biology. and lead us to a total understanding of life. Simultaneously, concerns have been expressed about thc implications of this work. In the past, major new technologies have been used intensively for hostile purposes. What is thc challenge that biotechnology poses in this regard'? This review paper looks at the enormous changes in civil society that thc genomics revolution could bring. Against this background, thc growing concerns about its potential misuses have been reviewed. Thc strengths and weaknesses or the Biological and Toxin Weapons Convention (BTWC are then touched upon. The BTWC presently lacks an adequate verification mechanism. Although biotechnology has been used by human beings since prehistoric times (eg. making of bread. cheese. wines its scientific understanding came only in the latter part of the 19th century. Thc decisive turning point in the field came in the 1970s with the advent of genetic engineering. In the military context classical agents like anthrax and toxin remain the threat today. Although thc current level or sophistication for many biological agents is low, there is enormous potential for making more sophisticated weapons. It might be possible to specifically target the genetic makeup of different ethnic groups. The limited varieties of staple crops and the limited strains of modern animals make agriculture particularly open to attack. Another serious possibility is the impact of genomics in neuroscience. With a better understanding of cellular receptor systems and bioregulators, it is not inconceivable that new means would be evolved for disturbing the functions of the nervous system. Thc genomics revolution can be used for peaceful purposes

  10. ESR dosimetry: achievements and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Baffa, O., E-mail: baffa@usp.br [Universidade de Sao Paulo, Departamento de Fisica, Av. Bandeirantes 3900, 14040-901 Ribeirao Preto, Sao Paulo (Brazil)

    2015-10-15

    Full text: Electron Spin Resonance (ESR), also known as Electron Paramagnetic Resonance (EPR) and more recently as Electron Magnetic Resonance (Emr), is a spectroscopy technique able to detect unpaired electrons such as those created by the interaction ionizing radiation with matter. When the unpaired electrons created by ionizing radiation are stable over some reasonable time, ESR can be used to measure the radiation dose deposited in the material under study. In principle, any insulating material that satisfies this requisite can be used as a dosimeter. ESR has been used in retrospective dosimetry in case of radiological accidents using natural constituents of human body such as teeth, bones and nails as well as fortuitous materials as sugar, sweeteners and plastics. When using teeth the typical detected dose is 0.5 Gy for, for X-Band spectrometers (9 GHz) and even lower doses if higher frequency spectrometers are used. Clinical dosimetry is another area of potential use of this dosimetric modality. In this application the amino acid alanine has been proposed and being used. Alanine dosimeters are very easy to prepare and require no complicated treatments for use. Alanine/ESR dosimetry satisfies many of the required properties for clinical applications such as water equivalent composition, independence of response for the energy range used in therapy and high precision. Other organic materials such as ammonium tartrate are being investigated to increase the sensitivity of ESR for clinical applications. Finally, industrial applications can also benefit from this dosimetry. The challenges to expand applications, the number of users and research groups of ESR dosimetry will be discussed. (Author)

  11. Intercultural challenge to language learning

    Directory of Open Access Journals (Sweden)

    Luz María Muñoz de Cote

    2012-10-01

    Full Text Available This paper presents the findings of a qualitative research project set to investigate the piloting process of an innovative language program for university students. It challenges traditional English language teaching courses celebrating a view centered on learning; classes become spaces for students to understand the language they are learning through the development of small projects. The approach moves from a teaching transmission paradigm to one where the most important agent is each student who has to engage with a topic of his or her interest. Students are seen as individuals whose knowledge and understanding of the world is valued and not as people whose lack of language skills prevents themfrom engaging in discussions of complex topics. The objective of this innovation is to enhance students’ understanding and use of academic English in their field of interest. In this project, we argue that knowledge and understanding of the mother tongue and culture play key roles in the development of a second language. A number of studies suggest that students who had strong first language literacy skills achieved higher proficiency levels in their second language. Based on this argument and Vygotsky’s sociocultural learning theory, we designed disciplinary content language learning workshops for first-degree students. The main tenet is that students can develop academic English given that they know about their discipline. Findings so far reveal the difficulty of students to take distance from their previous learning experiences. They also show that students’ ideas expressed in English are far more complex than what would be expected of them given their second language skills. The complexity is not only related to thecontent, but to the way they construct their paragraphs and the understanding of how the register of their field  may be used.

  12. The Dialog State Tracking Challenge Series

    OpenAIRE

    Williams, Jason D.; Microsoft Corporation; Henderson, Matthew; Cambridge University; Raux, Antoine; Lenovo Labs; Thomson, Blaise; VocalIQ, Ltd; Black, Alan; Carnegie Mellon University; Ramachandran, Deepak; Nuance Communications

    2014-01-01

    In spoken dialog systems, dialog state tracking refers to the task of correctly inferring the user's goal at a given turn, given all of the dialog history up to that turn. The Dialog State Tracking Challenge is a research community challenge task that has run for three rounds. The challenge has given rise to a host of new methods for dialog state tracking, and also deeper understandings about the problem itself, including methods for evaluation.

  13. Debugging Concurrent Software:Advances and Challenges

    Institute of Scientific and Technical Information of China (English)

    Jeff Huang; Charles Zhang

    2016-01-01

    Concurrency debugging is an extremely important yet challenging problem that has been hampering developer productivity and software reliability in the multicore era. We have worked on this problem in the past eight years and have developed several effective methods and automated tools for helping developers debugging shared memory concurrent programs. This article discusses challenges in concurrency debugging and summarizes our research contributions in four important directions: concurrency bug reproduction, detection, understanding, and fixing. It also discusses other recent advances in tackling these challenges.

  14. Disaster Risk Management - The Kenyan Challenges

    Science.gov (United States)

    Nabutola, W.

    2009-04-01

    Keywords: natural disasters; man-made disasters; terrorist attacks; land slides; disaster policies and legislations; fire; earthquakes; hurricanes; soil erosion; disaster research policy; Preamble: "Risk does not begin and end on the floor of the New York Stock Exchange. The vastness of the subject matter is daunting. Risk touches on the most profound aspects of psychology, mathematics, statistics and history. The literature is monumental; each day's headlines bring many new items of interest. But I know we are not unique, everywhere in the world risks abound." "AGAINST THE GODS the remarkable story of risk" by Peter L. Bernstein, 1998 The real challenge is what can we, as a nation do to avert, prevent them, or in the unfortunate event that they occur, how can we mitigate their impact on the economy? Introductory remarks: Disaster in Kenya, as indeed anywhere else, is not one of those happenings we can wish away. It can strike anywhere any time. Some of it is man-made but most of it is natural. The natural are sometimes induced by man in one way or another. For example, when we harvest trees without replacing them, this diminishes the forest cover and can lead to soil erosion, whose advanced form is land slides. Either way disasters in their different forms and sizes present challenges to the way we live our lives or not, perhaps, even how we die. Disasters in our country have reached crisis stage. ‘In Chinese language, crisis means danger, but it also means opportunity' Les Brown, motivational speaker in "the power of a larger vision" Why I am interested Whereas Kenya experiences man made and natural disasters, there are more sinister challenges of the man-made variety. These loom on the horizon and, from time to time raise their ugly heads, taking many Kenyan lives in their wake, and property destroyed. These are post election violence and terrorist attacks, both related to politics, internal and external. In January 2008, soon after presidential and national

  15. Disaster Risk Management - The Kenyan Challenge

    Science.gov (United States)

    Nabutola, W.; Scheer, S.

    2009-04-01

    Keywords: natural disasters; man-made disasters; terrorist attacks; land slides; disaster policies and legislations; fire; earthquakes; hurricanes; soil erosion; disaster research policy; Preamble: "Risk does not begin and end on the floor of the New York Stock Exchange. The vastness of the subject matter is daunting. Risk touches on the most profound aspects of psychology, mathematics, statistics and history. The literature is monumental; each day's headlines bring many new items of interest. But I know we are not unique, everywhere in the world risks abound." "AGAINST THE GODS the remarkable story of risk" by Peter L. Bernstein, 1998 The real challenge is what can we, as a nation do to avert, prevent them, or in the unfortunate event that they occur, how can we mitigate their impact on the economy? Introductory remarks: Disaster in Kenya, as indeed anywhere else, is not one of those happenings we can wish away. It can strike anywhere any time. Some of it is man-made but most of it is natural. The natural are sometimes induced by man in one way or another. For example, when we harvest trees without replacing them, this diminishes the forest cover and can lead to soil erosion, whose advanced form is land slides. Either way disasters in their different forms and sizes present challenges to the way we live our lives or not, perhaps, even how we die. Disasters in our country have reached crisis stage. ‘In Chinese language, crisis means danger, but it also means opportunity' Les Brown, motivational speaker in "the power of a larger vision" Why I am interested Whereas Kenya experiences man made and natural disasters, there are more sinister challenges of the man-made variety. These loom on the horizon and, from time to time raise their ugly heads, taking many Kenyan lives in their wake, and property destroyed. These are post election violence and terrorist attacks, both related to politics, internal and external. In January 2008, soon after presidential and national

  16. Climate challenges, vulnerabilities, and food security.

    Science.gov (United States)

    Nelson, Margaret C; Ingram, Scott E; Dugmore, Andrew J; Streeter, Richard; Peeples, Matthew A; McGovern, Thomas H; Hegmon, Michelle; Arneborg, Jette; Kintigh, Keith W; Brewington, Seth; Spielmann, Katherine A; Simpson, Ian A; Strawhacker, Colleen; Comeau, Laura E L; Torvinen, Andrea; Madsen, Christian K; Hambrecht, George; Smiarowski, Konrad

    2016-01-12

    This paper identifies rare climate challenges in the long-term history of seven areas, three in the subpolar North Atlantic Islands and four in the arid-to-semiarid deserts of the US Southwest. For each case, the vulnerability to food shortage before the climate challenge is quantified based on eight variables encompassing both environmental and social domains. These data are used to evaluate the relationship between the "weight" of vulnerability before a climate challenge and the nature of social change and food security following a challenge. The outcome of this work is directly applicable to debates about disaster management policy.

  17. Women and Smoking: Global Challenge

    Directory of Open Access Journals (Sweden)

    Taru Kinnunen

    2016-03-01

    Full Text Available Global tobacco control has led to a reduction in smoking prevalence and mortality in men, while the rates among women have not followed the same declining rates or patterns. Tobacco-induced diseases, including those unique to women (reproductive complications, cervical and breast cancer are becoming increasingly prevalent among women. Unfortunately, many tobacco control policies and cessation programs have been found to be less effective for women than men. This is alarming as disease risk for lung cancer, CVD, osteoporosis, and COPD, associated with smoking, is higher among women. Women are also more likely to be exposed to secondhand tobacco smoke and subsequent morbidity. Finally, quitting smoking appears to be harder for women than men. Current tobacco control and surveillance data come primarily from high resource countries. WHO estimates that in 2030, in low and medium resource countries, 7 out of 10 deaths will be smoking-related. While the prevalence of smoking in women is relatively low in these countries, more information is needed regarding their patterns of tobacco use uptake, and subsequent health outcomes, as theirs differ from men. Tobacco use in women is greatly influenced by social, cultural and political determinants, and needs to be conceptualized within an intersectional framework.

  18. Power-Efficient Design Challenges

    Science.gov (United States)

    Pangrle, Barry

    significant gains can be realized and why power-efficiency requirements will continue to challenge designers into the future. Despite new process technologies, the future will continue to rely on innovative design approaches.

  19. Exploring the challenges faced by polytechnic students

    Science.gov (United States)

    Matore, Mohd Effendi @ Ewan Mohd; Khairani, Ahmad Zamri

    2015-02-01

    This study aims to identify other challenges besides those already faced by students, in seven polytechnics in Malaysia as a continuation to the previous research that had identified 52 main challenges faced by students using the Rasch Model. The explorative study focuses on the challenges that are not included in the Mooney Problem Checklist (MPCL). A total of 121 polytechnic students submitted 183 written responses through the open questions provided. Two hundred fifty two students had responded from a students' perspective on the dichotomous questions regarding their view on the challenges faced. The data was analysed qualitatively using the NVivo 8.0. The findings showed that students from Politeknik Seberang Perai (PSP) gave the highest response, which was 56 (30.6%) and Politeknik Metro Kuala Lumpur (PMKL) had the lowest response of 2 (1.09%). Five dominant challenges were identified, which were the English language (32, 17.5%), learning (14, 7.7%), vehicles (13, 7.1%), information technology and communication (ICT) (13, 7.1%), and peers (11, 6.0%). This article, however, focus on three apparent challenges, namely, English language, vehicles, as well as computer and ICT, as the challenges of learning and peers had been analysed in the previous MPCL. The challenge of English language that had been raised was regarding the weakness in commanding the aspects of speech and fluency. The computer and ICT challenge covered the weakness in mastering ICT and computers, as well as computer breakdowns and low-performance computers. The challenge of vehicles emphasized the unavailability of vehicles to attend lectures and go elsewhere, lack of transportation service in the polytechnic and not having a valid driving license. These challenges are very relevant and need to be discussed in an effort to prepare polytechnics in facing the transformational process of polytechnics.

  20. Challenges of Integrated Water Resources Management in Indonesia

    Directory of Open Access Journals (Sweden)

    Mohamad Ali Fulazzaky

    2014-07-01

    Full Text Available The increased demands for water and land in Indonesia as a consequence of the population growth and economic development has reportedly have been accelerated from the year to year. The spatial and temporal variability of human induced hydrological changes in a river basin could affect quality and quantity of water. The challenge is that integrated water resources management (IWRM should cope with complex issues of water in order to maximize the resultant economic and social welfare in an equitable manner, without compromising the sustainability of vital ecosystems. Even though the government of Indonesia has adopted new paradigm for water resources management by the enactment of Law No. 7/2004 on water resources, the implementation of IWRM may face the technical and managerial challenges. This paper briefly reviews the implementation of IWRM and related principles and provides an overview of potential water-related issues and progress towards implementation of IWRM in Indonesia. The availability of water and a broader range of water-related issues are identified. The recommended actions for improving the future IWRM are suggested. Challenges to improve the capacity buildings of IWRM related to enabling environment, institutional frameworks and management instruments are verified to contribute to the future directions for efficient problem-solving ability.

  1. Early life peripheral lipopolysaccharide challenge reprograms catecholaminergic neurons

    Science.gov (United States)

    Ong, Lin Kooi; Fuller, Erin A.; Sominsky, Luba; Hodgson, Deborah M.; Dunkley, Peter R.; Dickson, Phillip W.

    2017-01-01

    Neonatal immune challenge with the bacterial mimetic lipopolysaccharide has the capacity to generate long-term changes in the brain. Neonatal rats were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg) on postnatal day (PND) 3 and again on PND 5. The activation state of tyrosine hydroxylase (TH) was measured in the locus coeruleus, ventral tegmental area and substantia nigra on PND 85. In the locus coeruleus there was an approximately four-fold increase in TH activity. This was accompanied by a significant increase in TH protein together with increased phosphorylation of all three serine residues in the N-terminal region of TH. In the ventral tegmental area, a significant increase in TH activity and increased phosphorylation of the serine 40 residue was seen. Neonatal lipopolysaccharide had no effect on TH activation in the substantia nigra. These results indicate the capacity of a neonatal immune challenge to generate long-term changes in the activation state of TH, in particular in the locus coeruleus. Overall, the current results demonstrate the enduring outcomes of a neonatal immune challenge on specific brain catecholaminergic regions associated with catecholamine synthesis. This highlights a novel mechanism for long-term physiological and behavioural alterations induced by this model. PMID:28071709

  2. Challenges for the therapeutic use of pluripotent stem derived cells

    Directory of Open Access Journals (Sweden)

    Magda eForsberg

    2012-02-01

    Full Text Available Human embryonic stem cells (hESC and induced pluripotent stem cells (hiPSC are an attractive cell source for regenerative medicine. These cells can be expanded to vast numbers and can be differentiated to many cell types to generate pluripotent stem cells (PSC derived therapeutic cells. These cells are desired for cell transplantations. Cell replacement is promising, but it has many challenges. The challenge of introduction of exogenous cells in a recipient requires addressing several different topics; the immunological response and possible rejection, cleanliness, exclusion of tumor formation and functionality of the PSC derived therapeutic cells. Immunological rejection can be addressed with immunomodulation of the cells and the recipient. Cleanliness can be optimized using good manufacturing practice (GMP quality systems. Tumor formation requires the removal of any PSC remaining after differentiation. At last, the functionality of the cells must be tested in in-vitro and in animal models. After addressing these challenges, precise strategies are developed to monitor the status of the cells at different times and in case of undesired results, corresponding counteracting strategies must exist before any clinical attempt.

  3. Immune challenges and visual signalling in tree frogs

    Science.gov (United States)

    Desprat, Julia L.; Lengagne, Thierry; Mondy, Nathalie

    2017-04-01

    In animals, mate-choice is often based on sexual signals that carry information and help the receiver make the best choice to improve the receiver's fitness. Orange visual sexual signals have been hypothesised to carry immune information because they are often due to carotenoid pigments which are also involved in immunity response. Although many studies have focused on the direct relationships between coloration and immunocompetence, few studies have simultaneously studied immunocompetent response and coloration variation after an immune challenge. We tested this hypothesis on starved and ad libitum-fed males of the European tree frog Hyla arborea. Our results show that male coloration is not a reliable indicator of its immune response capacity in this species. However, after an immune challenge induced by a PHA ( Phaseolus vulgaris phytohaemagglutinin) injection, starved males presented a significant coloration loss and this alteration was related to the immune response intensity. Taken together, these results suggest that the brighter (lighter) coloration may be used as a cue by female to exclude males with a recent immune challenge, due to diseases or parasites for example.

  4. Controversies and challenges in the management of chronic urticaria.

    Science.gov (United States)

    Staubach, P; Zuberbier, T; Vestergaard, C; Siebenhaar, F; Toubi, E; Sussman, G

    2016-07-01

    This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. Despite the clear international guideline, there remain a number of controversies and challenges in the management of patients with chronic urticaria (CU). As a result of major advancements in urticaria over the past 4 years, the current EAACI/GA(2) LEN/EDF/WAO urticaria guideline treatment algorithm requires updating. Case studies from patients with chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], chronic inducible urticaria (CIndU) or diseases and syndromes related to CU are useful in describing and exploring challenges in disease management. Case studies of specific CSU patient populations such as children with CU or patients with angio-edema but no hives also require consideration as potentially challenging groups with unmet needs. The current EAACI/GA(2) LEN/EDF/WAO urticaria guideline provides a general framework for the management of patients with CU but, as these cases highlight, a personalized approach based on the expert knowledge of the physician may be required.

  5. EDITORIAL: Big challenges and nanosolutions Big challenges and nanosolutions

    Science.gov (United States)

    Demming, Anna

    2011-07-01

    population dynamics will evolve throughout future generations attracts considerable debate and a range of strong opinions. But in the meantime, as this issue's review highlights, there is a great deal of scope in exploiting nanotechnology to find potential technological solutions to the challenges increasing populations pose at present. And that's not to mention the intriguing insights into nanoscale physics that may be discovered along the way. References [1] Penza M, Rossi R, Alvisi M and Serra E 2010 Nanotechnology 21 105501 [2] Gu B, Zhu Y, Chang J, Peng C, Liu D, Min Y, Luo W, Howarth R W and Ge Y 2011 Environ. Res. Lett. 6 014011 [3] Galloway J N, Townsend A R, Erisman J W, Bekunda M, Cai Z, Freney J R, Martinelli L A, Seitzinger S P and Sutton M A 2008 Science 320 889-92 [4] Humplik T et al 2011 Nanotechnology 22 292001 [5] Guo Z, Meng F, Luo T, Li M and Liu J 2009 Nanotechnology 20 125501 [6] Chen Y, Chen Z, He Y, Lin H, Sheng P, Liu C, Luo S and Cai Q 2010 Nanotechnology 20 105102 [7] Ren L, Ma L, Jin L, Wang J-B, Qiu M and Yu Y 2009 Nanotechnology 20 405602 [8] Wang Y, Wang G, Wang H, Cai W, Liang C and Zhang L 2009 Nanotechnology 20 156604 [9] Hardin G 1968 Science 162 1243-8

  6. 50 top IT project management challenges

    CERN Document Server

    Doraiswamy, Premanand

    2012-01-01

    This book offers a focused and concise summary of 50 challenges facing today's IT project manager. The authors draw on years of practical experience (rather than classroom theory) to outline these challenges and offer useful tips and advice on how to deal with them.

  7. Challenges and reflections on exascale computing

    Institute of Scientific and Technical Information of China (English)

    Yang Xuejun

    2014-01-01

    This paper introduces the development of the exascale (1018) computing. Though exascale computing is a hot research direction worldwide,we are facing many challenges in the areas of memory wall,communica-tion wall,reliability wall,power wall and scalability of parallel computing. According to these challenges, some thoughts and strategies are proposed.

  8. Pedagogical Challenges for the World Wide Web.

    Science.gov (United States)

    Fetherston, Tony

    2001-01-01

    Presents some of the perceived pedagogical challenges posed by use of the World Wide Web. Proposes that the debate surrounding use of the Web in university teaching should center on learning and not technical issues. Learning issues and challenges discussed in this article include learning approaches, using the technical features of the Web to…

  9. Cultural Challenges of Social-Economic Innovation

    DEFF Research Database (Denmark)

    Bajde, Domen; Ottlewski, Lydia

    2016-01-01

    Purpose We introduce the concept of social-economic innovation (SEI) and point to cultural challenges involved in instituting SEI. In the second part of the paper, we delve into the alternative exchange system of “Housing for help” (HFH) to explore the challenging negotiation of roles and relatio...

  10. Taxonomy of Challenges for Digital Forensics.

    Science.gov (United States)

    Karie, Nickson M; Venter, Hein S

    2015-07-01

    Since its inception, over a decade ago, the field of digital forensics has faced numerous challenges. Despite different researchers and digital forensic practitioners having studied and analysed various known digital forensic challenges, as of 2013, there still exists a need for a formal classification of these challenges. This article therefore reviews existing research literature and highlights the various challenges that digital forensics has faced for the last 10 years. In conducting this research study, however, it was difficult for the authors to review all the existing research literature in the digital forensic domain; hence, sampling and randomization techniques were employed to facilitate the review of the gathered literature. Taxonomy of the various challenges is subsequently proposed in this paper based on our review of the literature. The taxonomy classifies the large number of digital forensic challenges into four well-defined and easily understood categories. The proposed taxonomy can be useful, for example, in future developments of automated digital forensic tools by explicitly describing processes and procedures that focus on addressing specific challenges identified in this paper. However, it should also be noted that the purpose of this paper was not to propose any solutions to the individual challenges that digital forensics face, but to serve as a survey of the state of the art of the research area.

  11. Observational Challenges for the Standard FLRW Model

    CERN Document Server

    Buchert, Thomas; Kleinert, Hagen; Roukema, Boudewijn F; Wiltshire, David L

    2015-01-01

    In the context of the "Fourteenth Marcel Grossman Meeting on General Relativity" parallel session DE3, "Large--scale Structure and Statistics", concerning observational issues in cosmology, we summarise some of the main observational challenges for the standard FLRW model and describe how the results presented in the session are related to these challenges.

  12. Censoring the Imagination: Challenges to Children's Books.

    Science.gov (United States)

    Saltman, Judith

    1998-01-01

    Presents a brief history of the censorship of children's books, and then focuses on recent challenges. The view of literature as a socializing force is discussed, and examples of challenged books in the United States and Canada are provided, illustrating different reasons for censorship on both sides of the political and social spectrum. (AEF)

  13. Methodological Challenges in Researching Inclusive School Cultures

    Science.gov (United States)

    Nind, Melanie; Benjamin, Shereen; Sheehy, Kieron; Collins, Janet; Hall, Kathy

    2004-01-01

    This article addresses the methodological challenges faced in a pilot study of the processes and cultures of inclusion and exclusion in two primary school classrooms. The authors, who were the research team, engaged with a range of practical and ethical challenges, some of which face any researcher entering classroom contexts and some of which…

  14. 22 CFR 9.8 - Classification challenges.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Classification challenges. 9.8 Section 9.8 Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.8 Classification... classification status is improper are expected and encouraged to challenge the classification status of...

  15. 49 CFR 8.17 - Classification challenges.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Classification challenges. 8.17 Section 8.17 Transportation Office of the Secretary of Transportation CLASSIFIED INFORMATION: CLASSIFICATION/DECLASSIFICATION/ACCESS Classification/Declassification of Information § 8.17 Classification challenges. (a)...

  16. The Challenges of Assessing Media Literacy Education

    Science.gov (United States)

    Schilder, Evelien; Lockee, Barbara; Saxon, D. Patrick

    2016-01-01

    In the media literacy literature, the challenges associated with assessment have, to a great extent, been ignored. The purpose of this mixed methods study was therefore to explore the views of media literacy scholars and professionals on assessment challenges through qualitative interviews (n = 10) with the intent of using this information to…

  17. "Egg Races" and Other Practical Challenges

    Science.gov (United States)

    Auty, Geoff

    2013-01-01

    This article presents ideas behind science and technology challenges and shares experiences of "egg races." Different challenges were set, but there was always the need to transport an egg across some obstacle course without breaking it. It was so popular in the 1980s that the term "egg race" came to mean any kind of simple…

  18. Challenges and reflections on exascale computing

    Institute of Scientific and Technical Information of China (English)

    Yang Xuejun

    2014-01-01

    This paper introduces the development of the exascale (1018) computing. Though exascalc computing is a hot research direction worldwide, we are facing many challenges in the areas of memory wall, communica- tion wall, reliability wall, power wall and scalability of parallel computing. According to these challenges, some thoughts and strategies are proposed.

  19. The 24-Hour Mathematical Modeling Challenge

    Science.gov (United States)

    Galluzzo, Benjamin J.; Wendt, Theodore J.

    2015-01-01

    Across the mathematics curriculum there is a renewed emphasis on applications of mathematics and on mathematical modeling. Providing students with modeling experiences beyond the ordinary classroom setting remains a challenge, however. In this article, we describe the 24-hour Mathematical Modeling Challenge, an extracurricular event that exposes…

  20. 28 CFR 17.30 - Classification challenges.

    Science.gov (United States)

    2010-07-01

    ... submit classification challenges in writing to the DRC, through the Office of Information and Privacy... DRC shall redact the identity of an individual challenging a classification under paragraph (a) of... 30 days, provide a written response to the DRC. The original classification authority may classify...