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Sample records for humans requires focal

  1. Integrin upregulation and localization to focal adhesion sites in pregnant human myometrium.

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    Burkin, Heather R; Rice, Monica; Sarathy, Apurva; Thompson, Sara; Singer, Cherie A; Buxton, Iain L O

    2013-07-01

    Focal adhesions are integrin-rich microdomains that structurally link the cytoskeleton to the extracellular matrix and transmit mechanical signals. In the pregnant uterus, increases in integrin expression and activation are thought to be critical for the formation of the mechanical syncytium required for labor. The aim of this study was to determine which integrins are upregulated and localized to focal adhesions in pregnant human myometrium. We used quantitative polymerase chain reaction, Western blotting, and confocal microscopy to determine the expression levels and colocalization with focal adhesion proteins. We observed increases in several integrin transcripts in pregnant myometrium. At the protein level, integrins such as α5-integrin (ITGA5), ITGA7, ITGAV, and ITGB3 were significantly increased during pregnancy. The integrins ITGA3, ITGA5, ITGA7, and ITGB1 colocalized with focal adhesion proteins in term human myometrium. These data suggest that integrins α3β1, α5β1, and α7β1 are the most likely candidates to transmit mechanical signals from the extracellular matrix through focal adhesions in pregnant human myometrium.

  2. Focal Areas for Measuring the Human Well-Being Impacts of a Conservation Initiative

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    M. Sanjayan

    2013-03-01

    Full Text Available Within conservation, the need to measure the impacts on people from conservation initiatives such as projects and programs is growing, but understanding and measuring the multidimensional impacts on human well-being from conservation initiatives is complex. To understand the constituent components of human well-being and identify which components of well-being are most common, we analyzed 31 known indices for measuring human well-being. We found 11 focal areas shared by two or more indices for measuring human well-being, and the focal areas of living standards, health, education, social cohesion, security, environment, and governance were in at least 14 of the 31 human well-being indices. We examined each of the common focal areas and assessed its relevance to measuring the human well-being impacts of a conservation initiative. We then looked for existing indices that include the relevant focal areas and recommend the use of Stiglitz et al. (2009—a framework designed to measure economic performance and social progress—as a starting place for understanding and selecting human well-being focal areas suitable for measuring the impacts on people from a conservation initiative.

  3. Zygotic Porcn paternal allele deletion in mice to model human focal dermal hypoplasia.

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    Steffen Biechele

    Full Text Available In mouse and humans, the X-chromosomal Porcupine homolog (Porcn gene is required for the acylation and secretion of all 19 Wnt ligands, thus representing a bottleneck in the secretion of Wnt ligands. In humans, mutations in PORCN cause the X-linked dominant syndrome Focal Dermal Hypoplasia (FDH, OMIM#305600. This disorder is characterized by ecto-mesodermal dysplasias and shows a highly variable phenotype, potentially due to individual X chromosome inactivation patterns. To improve the understanding of human FDH, we have established a mouse model by generation of Porcn heterozygous animals carrying a zygotic deletion of the paternal allele. We show that heterozygous female fetuses display variable defects that do not significantly affect survival in the uterus, but lead to perinatal lethality in more than 95% of females. Rare survivors develop to adulthood and display variable skeletal and skin defects, representing an adult zygotic mouse model for human FDH. Although not frequently reported in humans, we also observed bronchopneumonia, rhinitis, and otitis media in these animals, suggesting a potential link between Porcn function and the normal development of ciliated cells in these tissues.

  4. [Social-ecological focal prevalence of human diseases].

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    Aĭriian, A P

    1989-01-01

    The impact of environmental factors on community health status is analyzed. Methodological approaches to the assessment of causal and effective relationships of anthropotechnogenic changes in environment and community health are proposed. The necessity of the development of the integral concept of social and ecological causes of human diseases is underlined.

  5. Human Neuroma-in-Continuity Contains Focal Deficits in Myelination

    NARCIS (Netherlands)

    van Vliet, Arie C; Tannemaat, Martijn R; van Duinen, Sjoerd G; Verhaagen, J.; Malessy, Martijn J A; De Winter, Fred

    Functional recovery does not occur in 10% of patients with neonatal brachial plexus palsy. In these patients, resection of a neuroma-in-continuity (NIC) and surgical nerve reconstruction are required. The formation of a NIC seems to prohibit functional recovery, but the underlying biologic

  6. Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation

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    Ana L. Roa-Espitia

    2016-09-01

    Full Text Available Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK, paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca2+ dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton.

  7. Human Systems Integration Requirements

    Science.gov (United States)

    2009-09-01

    frequency signature? 14. Have any electro -optical or optical components on the system been hardened to reduce optical cross- sectional measurements...measures: • Electrocardiography ( EKG ) • Infrared (IR) facial flush • Galvanic Skin Response (GSR) • Eye tracking 45 HSI REQUIREMENTS GUIDE...E3 Electromagnetic Environmental Effects EA Evolutionary Acquisition EA Electronic Attack ECU Environmental Conditioning Unit EKG Electrocardiogram

  8. Detection of Human Papillomavirus in Human Focal Cortical Dysplasia Type IIB

    NARCIS (Netherlands)

    Chen, Julie; Tsai, Victoria; Parker, Whitney E.; Aronica, Eleonora; Baybis, Marianna; Crino, Peter B.

    2012-01-01

    Objective: Focal cortical dysplasia type IIB (FCDIIB) is a sporadic developmental malformation of the cerebral cortex highly associated with pediatric epilepsy. Balloon cells (BCs) in FCDIIB exhibit constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

  9. Stability of rotors and focal sources for human atrial fibrillation: focal impulse and rotor mapping (FIRM) of AF sources and fibrillatory conduction.

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    Swarup, Vijay; Baykaner, Tina; Rostamian, Armand; Daubert, James P; Hummel, John; Krummen, David E; Trikha, Rishi; Miller, John M; Tomassoni, Gery F; Narayan, Sanjiv M

    2014-12-01

    Several groups report electrical rotors or focal sources that sustain atrial fibrillation (AF) after it has been triggered. However, it is difficult to separate stable from unstable activity in prior studies that examined only seconds of AF. We applied phase-based focal impulse and rotor mapping (FIRM) to study the dynamics of rotors/sources in human AF over prolonged periods of time. We prospectively mapped AF in 260 patients (169 persistent, 61 ± 12 years) at 6 centers in the FIRM registry, using baskets with 64 contact electrodes per atrium. AF was phase mapped (RhythmView, Topera, Menlo Park, CA, USA). AF propagation movies were interpreted by each operator to assess the source stability/dynamics over tens of minutes before ablation. Sources were identified in 258 of 260 of patients (99%), for 2.8 ± 1.4 sources/patient (1.8 ± 1.1 in left, 1.1 ± 0.8 in right atria). While AF sources precessed in stable regions, emanating activity including spiral waves varied from collision/fusion (fibrillatory conduction). Each source lay in stable atrial regions for 4,196 ± 6,360 cycles, with no differences between paroxysmal versus persistent AF (4,290 ± 5,847 vs. 4,150 ± 6,604; P = 0.78), or right versus left atrial sources (P = 0.26). Rotors and focal sources for human AF mapped by FIRM over prolonged time periods precess ("wobble") but remain within stable regions for thousands of cycles. Conversely, emanating activity such as spiral waves disorganize and collide with the fibrillatory milieu, explaining difficulties in using activation mapping or signal processing analyses at fixed electrodes to detect AF rotors. These results provide a rationale for targeted ablation at AF sources rather than fibrillatory spiral waves. © 2014 Wiley Periodicals, Inc.

  10. Integrin-Associated Focal Adhesion Kinase Protects Human Embryonic Stem Cells from Apoptosis, Detachment, and Differentiation

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    Loriana Vitillo

    2016-08-01

    Full Text Available Human embryonic stem cells (hESCs can be maintained in a fully defined niche on extracellular matrix substrates, to which they attach through integrin receptors. However, the underlying integrin signaling mechanisms, and their contribution to hESC behavior, are largely unknown. Here, we show that focal adhesion kinase (FAK transduces integrin activation and supports hESC survival, substrate adhesion, and maintenance of the undifferentiated state. After inhibiting FAK kinase activity we show that hESCs undergo cell detachment-dependent apoptosis or differentiation. We also report deactivation of FAK downstream targets, AKT and MDM2, and upregulation of p53, all key players in hESC regulatory networks. Loss of integrin activity or FAK also induces cell aggregation, revealing a role in the cell-cell interactions of hESCs. This study provides insight into the integrin signaling cascade activated in hESCs and reveals in FAK a key player in the maintenance of hESC survival and undifferentiated state.

  11. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

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    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2012-01-01

    SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588

  12. Scintigraphic assessment of focal platelet accumulations following infrainguinal bypass surgery in humans

    DEFF Research Database (Denmark)

    Nielsen, Tina G; Hesse, B; Eiberg, J

    1997-01-01

    Enothelial injury is assumed to be of pathogenetic significance in the development of graft stenoses, which remain a major cause of failure of peripheral bypasses. The aim of this study was to assess endothelial injury related to infrainguinal bypass surgery by indium-111 platelet scintigraphy...... of flow in the graft. Platelet deposition was assessed by gamma-camera images of thigh and crus obtained 4 and/or 24 h after surgery. Areas of focally increased activity were recorded and graded as moderate or intense. In the 24 vein bypasses, a median of two (range 0-5) areas of focally increased...... radioactivity were seen at the proximal anastomosis (n = 21), in the body of the graft (n = 20) or at the distal anastomosis (n = 9). The activity was moderate in 27 cases and intense in 23 cases. Scintigraphic evidence of focal platelet aggregation in vein grafts was not correlated with preoperative...

  13. TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility.

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    Mónica Cáceres

    Full Text Available Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-NSCC that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca2+ influx, focal adhesion kinase (FAK and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility.

  14. TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility

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    Cáceres, Mónica; Ortiz, Liliana; Recabarren, Tatiana; Romero, Anibal; Colombo, Alicia; Leiva-Salcedo, Elías; Varela, Diego; Rivas, José; Silva, Ian; Morales, Diego; Campusano, Camilo; Almarza, Oscar; Simon, Felipe; Toledo, Hector; Park, Kang-Sik; Trimmer, James S.; Cerda, Oscar

    2015-01-01

    Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-NSCC) that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca2+ influx, focal adhesion kinase (FAK) and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility. PMID:26110647

  15. Febrile seizures - semiology in humans and animal models: evidence of focality and heterogeneity.

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    Neville, Brian G R; Gindner, Diane

    2010-01-01

    The relationship between febrile seizures and hippocampal sclerosis has been the subject of longstanding discussion. Animal models for prolonged seizures have shown a clear causal relationship with focal limbic features at low dose and hippocampal damage at high dose. Careful history taking of febrile seizure semiology has shown focal early features often with clear temporal lobe elements. This would suggest that many febrile seizures are secondarily generalised hippocampal seizures. There is evidence of varying levels of epileptogenicity in specific infective causes of febrile seizures. Seizure semiology also suggests that a proportion of such seizures may be non-epileptic reflex asystolic attacks. Seizure semiology in febrile seizures deserves closer scrutiny. Copyright 2009 Elsevier B.V. All rights reserved.

  16. Surgically Induced Focal Retinal Detachment Does Not Cause Detectable SD-OCT Retinal Changes in Normal Human Retina.

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    Kogachi, Kaitlin; Wolfe, Jeremy D; Kashani, Amir H

    2017-10-01

    Induction of focal retinal detachment (RD) for subretinal delivery of stem cells and gene therapy is increasingly common. In order to determine if this procedure has an adverse impact on the retina, we use spectral-domain optical coherence tomography (SD-OCT) to evaluate the pre- and postoperative retinal anatomy of the incidentally detached normal retina surrounding large submacular hemorrhages (SMH) during surgical displacement procedures. Retrospective, observational study of human subjects with monocular SMH evaluated before and after surgical displacement using clinical exam, fundus photography, and SD-OCT. Manual measurements of the inner retinal thickness (IRT), outer retinal thickness (ORT), and full retinal thickness (FRT) were made in regions involving the SMH and surrounding normal retina. Comparison of retinal thickness measurements was made using the Wilcoxon signed-rank test. Seven eyes were included in this study. All eyes successfully underwent surgical displacement of SMH. Visual acuity improved in 6/7 subjects and was unchanged in the remaining subject. Incidental RD of the normal retinal regions surrounding the SMH did not cause any significant change in IRT, ORT, or FRT that was detectable by SD-OCT. In contrast, mean FRT overlying regions with SMH was significantly greater before surgery compared to after displacement of SMH or normal adjacent retina. Surgically induced focal RD does not cause detectable retinal changes in the incidentally detached normal retina surrounding large SMH. Therefore, surgical induction of focal RD should not be considered to have the same adverse impact on the retina as pathologic RD.

  17. Spatial relationship of organized rotational and focal sources in human atrial fibrillation to autonomic ganglionated plexi.

    Science.gov (United States)

    Baykaner, Tina; Zografos, Theodoros A; Zaman, Junaid A B; Pantos, Ioannis; Alhusseini, Mahmood; Navara, Rachita; Krummen, David E; Narayan, Sanjiv M; Katritsis, Demosthenes G

    2017-08-01

    One approach to improve ablation for atrial fibrillation (AF) is to focus on physiological targets including focal or rotational sources or ganglionic plexi (GP). However, the spatial relationship between these potential mechanisms has never been studied. We tested the hypothesis that rotors and focal sources for AF may co-localize with ganglionated plexi (GP). We prospectively identified locations of AF rotors and focal sources, and correlated these to GP sites in 97 consecutive patients (age 59.9±11.4, 73% persistent AF). AF was recorded with 64-pole catheters with activation/phase mapping, and related to anatomic GP sites on electroanatomic maps. AF sources arose in 96/97 (99%) patients for 2.6±1.4 sources per patient (left atrium: 1.7±0.9 right atrium: 1.1±0.8), each with an area of 2-3cm2. On area analyses, the probability of an AF source randomly overlapping a GP area was 26%. Left atrial sources were seen in 94 (97%) patients, in whom ≥1 source co-localized with GP in 75 patients (80%; psources were more likely to colocalize with left vs right GPs (p65, diabetes; psources in the left atrium often colocalize with regions of autonomic innervation. Studies should define if the role of AF sources differs by their anatomical location. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling

    NARCIS (Netherlands)

    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2010-01-01

    The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration

  19. Scintigraphic assessment of focal platelet accumulations following infrainguinal bypass surgery in humans

    DEFF Research Database (Denmark)

    Nielsen, Tina G; Hesse, B; Eiberg, J

    1997-01-01

    Enothelial injury is assumed to be of pathogenetic significance in the development of graft stenoses, which remain a major cause of failure of peripheral bypasses. The aim of this study was to assess endothelial injury related to infrainguinal bypass surgery by indium-111 platelet scintigraphy....... In 28 patients undergoing in situ vein (n = 24), composite vein-polytetrafluoroethylene (PTFE) (n = 1) or PTFE (n = 3) bypass surgery, assumed vascular injuries were recorded intraoperatively. Autologous indium-111-labelled platelets were injected into the inflow artery immediately after restoration...... antiplatelet therapy or vein graft diameter. Only 2 of the 20 intragraft platelet depositions occurred in areas where intra-operative vascular injury was suspected. In the composite graft and the PTFE grafts, diffuse activity was observed throughout the entire bypass. In conclusion, focal activity...

  20. Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells

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    Huang Jianhua

    2008-12-01

    Full Text Available Abstract Background The use of abciximab (c7E3 Fab or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These β3 integrin inhibitors antagonize fibrinogen binding to αIIbβ3 integrins on platelets and ligand binding to αvβ3 integrins on vascular cells. αvβ3 integrins influence responses to insulin in various cell types but effects in human aortic smooth muscle cells (HASMC are unknown. Results and discussion Insulin elicited a dose-dependent proliferative response in HASMC. Pretreatment with m7E3 (an anti-β3 integrin monoclonal antibody from which abciximab is derived, c7E3 or LM609 inhibited proliferative responses to insulin by 81%, 59% and 28%, respectively. Eptifibatide or cyclic RGD peptides completely abolished insulin-induced proliferation whereas tirofiban, which binds αIIbβ3 but not αvβ3, had no effect. Insulin-induced increases in c-Jun NH2-terminal kinase-1 (JNK1 activity were partially inhibited by m7E3 and eptifibatide whereas antagonism of αvβ3 integrins had no effect on insulin-induced increases in extracellular signal-regulated kinase (ERK activity. Insulin stimulated a rapid increase in the number of vinculin-containing focal adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited insulin-induced increases in focal adhesions by 100%, 74% and 73%, respectively. Conclusion These results demonstrate that αvβ3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC.

  1. Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells

    Science.gov (United States)

    Pathak, Alokkumar; Zhao, Renyi; Huang, Jianhua; Stouffer, George A

    2008-01-01

    Background The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These β3 integrin inhibitors antagonize fibrinogen binding to αIIbβ3 integrins on platelets and ligand binding to αvβ3 integrins on vascular cells. αvβ3 integrins influence responses to insulin in various cell types but effects in human aortic smooth muscle cells (HASMC) are unknown. Results and discussion Insulin elicited a dose-dependent proliferative response in HASMC. Pretreatment with m7E3 (an anti-β3 integrin monoclonal antibody from which abciximab is derived), c7E3 or LM609 inhibited proliferative responses to insulin by 81%, 59% and 28%, respectively. Eptifibatide or cyclic RGD peptides completely abolished insulin-induced proliferation whereas tirofiban, which binds αIIbβ3 but not αvβ3, had no effect. Insulin-induced increases in c-Jun NH2-terminal kinase-1 (JNK1) activity were partially inhibited by m7E3 and eptifibatide whereas antagonism of αvβ3 integrins had no effect on insulin-induced increases in extracellular signal-regulated kinase (ERK) activity. Insulin stimulated a rapid increase in the number of vinculin-containing focal adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited insulin-induced increases in focal adhesions by 100%, 74% and 73%, respectively. Conclusion These results demonstrate that αvβ3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC. PMID:19108709

  2. Saccade abnormalities associated with focal cerebral lesions - How cortical and basal ganglia commands shape saccades in humans.

    Science.gov (United States)

    Terao, Yasuo; Fukuda, Hideki; Tokushuge, Shinnichi; Nomura, Yoshiko; Hanajima, Ritsuko; Ugawa, Yoshikazu

    2016-08-01

    To study saccade abnormalities associated with focal cerebral lesions, including the cerebral cortex and basal ganglia (BG). We studied the latency and amplitude of reflexive and voluntary saccades in 37 patients with focal lesions of the frontal and parietal cortices and BG (caudate and putamen), and 51 age-matched controls, along with the ability to inhibit unwanted reflexive saccades. Latencies of reflexive saccades were prolonged in patients with parietal lesions involving the parietal eye field (PEF), whereas their amplitude was decreased with parietal or putaminal lesions. In contrast, latency of voluntary saccades was prolonged and their success rate reduced with frontal lesions including the frontal eye field (FEF) or its outflow tract as well as the dorsolateral/medial prefrontal cortex, and caudate lesions, whereas their amplitude was decreased with parietal lesions. Inhibitory control of reflexive saccades was impaired with frontal, caudate and, less prominently, parietal lesions. PEF is important in triggering reflexive saccades, also determining their amplitude. Whereas FEF and the caudate emit commands for initiating voluntary saccades, their amplitude is mainly determined by PEF. Commands not only from FEF and dorsolateral/medial prefrontal cortex but also from the caudate and PEF serve to inhibit unnecessary reflexive saccades. The findings suggested how cortical and BG commands shape reflexive and voluntary saccades in humans. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. FAK/src-family dependent activation of the Ste20-like kinase SLK is required for microtubule-dependent focal adhesion turnover and cell migration.

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    Simona Wagner

    2008-04-01

    Full Text Available Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal.

  4. Triptolide-Mediated Apoptosis by Suppression of Focal Adhesion Kinase through Extrinsic and Intrinsic Pathways in Human Melanoma Cells

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    Haw-Young Kwon

    2013-01-01

    Full Text Available Triptolide (TPL has been shown to inhibit cell proliferation and induce apoptosis in various human cancer cells; however, the precise mechanism of apoptosis induced by TPL in human melanoma cells has not yet been elucidated. In this study, we investigated the precise mechanism underlying cytocidal effects of TPL on human melanoma cells. Treatment of human melanoma cells with TPL significantly inhibited cell growth and induced apoptosis, as evidenced by flow cytometry and annexin V-fluorescein isothiocyanate analyses. TPL increased the levels of Fas and Fas-associated death domain (FADD and induced cleavage of Bid by activation of caspase-8 and cytochrome c release from mitochondria to the cytosol, which resulted in activation of caspase-9 and caspase-3. Moreover, TPL-induced apoptosis in SK-MEL-2 cells was mediated through dephosphorylation of focal adhesion kinase (FAK and its cleavage by caspase-8-mediated caspase-3 activation via upregulation of Fas expression. We also found that TPL mediated the dissociation of receptor-interacting protein (RIP from FAK and enhanced the formation of RIP/Fas complex formation initiating cell death. In conclusion, our data firstly demonstrated that TPL induces apoptosis by both extrinsic and intrinsic apoptosis pathways in human melanoma cells and identified that RIP shuttles between Fas and FAK to mediate apoptosis.

  5. Prognostic Value of Focal Adhesion Kinase (FAK in Human Solid Carcinomas: A Meta-Analysis.

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    Xiao-Qing Zeng

    Full Text Available Recently, the number of reports on focal adhesion kinase (FAK as a vital therapeutic target in solid carcinomas has increased; however, the prognostic role of FAK status remains poorly understood. This study aims to evaluate the prognostic effect of FAK by means of a meta-analysis.We performed a systematic literature search in order to examine the correlation between expression of FAK and overall survival(OS. The hazard ratio (HR of OS was used to measure survival. A random-effects model was used to pool study statistics. Sensitivity and publication bias analyses were also conducted.Thirty eligible studies involving 4702 patients were included. The median expression rate of FAK was 54%. Meta-analysis of the HRs demonstrated that high FAK expression was associated with worse OS (average HR = 2.073, 95%confidence interval[CI]:1.712-2.510, p = 0.000. Regarding cancer type, FAK was associated with worse OS in gastric cancer (HR = 2.646,95% CI:1.743-4.017, p = 0.000, hepatocellular carcinoma (HR = 1.788,95% CI:1.228-2.602, p = 0.002, ovarian cancer (HR = 1.815, 95% CI: 1.193-2.762, p = 0.005, endometrial cancer (HR = 4.149, 95% CI:2.832-6.079, p = 0.000, gliomas (HR = 2.650, 95% CI: 1.205-5.829, p = 0.015, and squamous cell carcinoma (HR = 1,696, 95% CI: 1.030-2.793, p = 0.038. No association was found between HR and disease staging according to our meta-regression analysis.Our study shows that high expression of FAK is associated with a worse OS in patients with carcinomas, but the association between FAK and prognosis varies according to cancer type. The value of FAK status in clinical prognosis in cancer needs further research.

  6. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability

    Science.gov (United States)

    Akagi, Keiko; Li, Jingfeng; Broutian, Tatevik R.; Padilla-Nash, Hesed; Xiao, Weihong; Jiang, Bo; Rocco, James W.; Teknos, Theodoros N.; Kumar, Bhavna; Wangsa, Danny; He, Dandan; Ried, Thomas; Symer, David E.; Gillison, Maura L.

    2014-01-01

    Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole-genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions, and chromosomal translocations. We present a model of “looping” by which HPV integrant-mediated DNA replication and recombination may result in viral–host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability. PMID:24201445

  7. SNAP focal plane

    Energy Technology Data Exchange (ETDEWEB)

    Lampton, Michael L.; Kim, A.; Akerlof, C.W.; Aldering, G.; Amanullah, R.; Astier, P.; Barrelet, E.; Bebek, C.; Bergstrom, L.; Berkovitz, J.; Bernstein, G.; Bester, M.; Bonissent, A.; Bower, C.; Carithers Jr., W.C.; Commins, E.D.; Day, C.; Deustua, S.E.; DiGennaro,R.; Ealet, A.; Ellis, R.S.; Eriksson, M.; Fruchter, A.; Genat, J.-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Harris, S.E.; Harvey, P.R.; Heetderks, H.D.; Holland, S.E.; Huterer, D.; Karcher, A.; Kolbe, W.; Krieger, B.; Lafever, R.; Lamoureux, J.; Levi, M.E.; Levin, D.S.; Linder,E.V.; Loken, S.C.; Malina, R.; Massey, R.; McKay, T.; McKee, S.P.; Miquel, R.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Pratt, R.; Prieto, E.; Refregier, A.; Rhodes, J.; Robinson, K.; Roe, N.; Sholl, M.; Schubnell, M.; Smadja, G.; Smoot, G.; Spadafora, A.; Tarle, G.; Tomasch,A.; von der Lippe, H.; Vincent, R.; Walder, J.-P.; Wang, G.

    2002-07-29

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square-degree field sensitive in the visible and near-infrared wavelength regime. We describe the requirements for the instrument suite and the evolution of the focal plane design to the present concept in which all the instrumentation--visible and near-infrared imagers, spectrograph, and star guiders--share one common focal plane.

  8. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  9. In-vivo measurements of human brain tissue conductivity using focal electrical current injection through intracerebral multicontact electrodes.

    Science.gov (United States)

    Koessler, Laurent; Colnat-Coulbois, Sophie; Cecchin, Thierry; Hofmanis, Janis; Dmochowski, Jacek P; Norcia, Anthony M; Maillard, Louis G

    2017-02-01

    In-vivo measurements of human brain tissue conductivity at body temperature were conducted using focal electrical currents injected through intracerebral multicontact electrodes. A total of 1,421 measurements in 15 epileptic patients (age: 28 ± 10) using a radiofrequency generator (50 kHz current injection) were analyzed. Each contact pair was classified as being from healthy (gray matter, n = 696; white matter, n = 530) or pathological (epileptogenic zone, n = 195) tissue using neuroimaging analysis of the local tissue environment and intracerebral EEG recordings. Brain tissue conductivities were obtained using numerical simulations based on conductivity estimates that accounted for the current flow in the local brain volume around the contact pairs (a cube with a side length of 13 mm). Conductivity values were 0.26 S/m for gray matter and 0.17 S/m for white matter. Healthy gray and white matter had statistically different median impedances (P Brain Mapp 38:974-986, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Companies' human capital required for collaboration

    DEFF Research Database (Denmark)

    Albats, Ekaterina; Bogers, Marcel; Podmetina, Daria

    Universities are widely acknowledged as an important source of knowledge for corporate innovation, and collaboration with universities plays an important role in companies’ open innovation strategy. However, little is known about the human capital components required for collaboration...... building, relationship building, IPR management and negotiation for the context of collaboration with universities. Our research has revealed an importance of expectation management skills for university-industry collaboration (UIC) context. We found that human capital for UIC is to be continuously...... developed and contracted by engagement in various relationships with academia. Our research helps in filling the research gap on human capital components required from the company specifically for collaboration with academia. It also serves practitioners with a profile of a general (archetype) UIC manager....

  11. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  12. Canadian Ranger Rifle: Human Factors Requirements Validation

    Science.gov (United States)

    2010-08-01

    operations in remote, isolated, and coastal communities of Canada2 3. CR are comprised of approximately 4111 Inuit , First Nations, Métis, and non...was varied in gender, rank, age, years as a CR, patrol, and culture . Furthermore the operating environments of the CR varied from the arctic, to...while differences were observed in the culture between CRPGs. Page 32 CRR: Human Factors Requirements Validation Humansystems® 5.3 Technical

  13. Requirements for Human Exploration of Mars

    Science.gov (United States)

    Conley, Catharine

    In the exploration of other planets and the search for life outside of Earth, the unique capabilities provided by human astronauts will only be advantageous if the biological contamination associated with human presence is understood and controlled. Thus, Planetary Protection is a critical element in the human exploration of other solar system bodies, and should be incorporated from the earliest stages of mission planning and development. The issues covered by Planetary Protection involve both 'forward contamination,' or the contamination of other solar system bodies by Earth microbes and organic materials, and 'backward contamination,' which is the contamination of Earth systems by potential alien life. Forward contamination concerns include contamination that might invalidate current or future scientific exploration of a particular solar system body, and/or might disrupt the planetary environment or a potential endogenous (alien) ecosystem. Backward contamination concerns include both immediate and long-term effects on the health of the astronaut explorers from possible biologically-active materials encountered during exploration, as well as the possible contamination of the Earth. Although some degree of forward contamination associated with human astronaut explorers is inevitable, the principles and policies of Planetary Protection that have been imposed on robotic missions by the 1967 Outer Space Treaty should be followed to the greatest extent possible when humans are exploring space. A number of national and international workshops held over the last six years have generated a consensus framework on Planetary Protetction policies and requirements for human missions to Mars, and a 2007 workshop held by NASA has considered the issues and benefits to Planetary Protection that might be offered by a return to the Moon. Conclusions from these workshops are presented and synthesized in the context of future international missions of human exploration.

  14. Columbus payload requirements in human physiology

    Science.gov (United States)

    Stegemann, Juergen

    1993-03-01

    Most of the biological feedback loops in the human body are interrelated. This means that several different parameters have to be recorded simultaneously to understand the interrelationship of different subsystems within the body when fast and slow adaptation processes are to be studied. This determines the requirements for the payload in the Columbus module. In 1988 ESA asked some European scientists in different fields of physiology to provide a 'science study' for the Columbus payload requirements. Their report was the basis of a phase A study completed in December 1991, concerning the 'ANTHROLAB', a laboratory that covers all presently known research challenges in this area. Anthrolab is more or less an improvement of the Anthrorack to be flown on the German Spacelab mission D-2 and on the Columbus precursor flight E-1. Beside the present Anthrorack design, Anthrolab will also provide subelements for vestibular, neurophysiological, and biomechanical research.

  15. LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion Kinase Activity (FAK) and miRNA-200a.

    Science.gov (United States)

    Alowayed, Nour; Salker, Madhuri S; Zeng, Ni; Singh, Yogesh; Lang, Florian

    2016-01-01

    LEFTY2, a suppressor of cell proliferation, tumor growth, regulator of stemness and embryonic differentiation, is a negative regulator of cancer cell reprogramming. Malignant transformation may lead to migration requiring loss of adhesion and gain of migratory activity. Signaling involved in the orchestration of migration, proliferation and spreading of cells include focal adhesion kinase (FAK) and adhesion molecule E-cadherin. The present study explored whether LEFTY2 influences the proliferation marker MKi67, FAK activity, E-cadherin abundance and migration of Ishikawa human endometrial carcinoma cells. Moreover, the study explored the involvement of microRNA-200a (miR-200a), which is known to regulate cellular adhesion by targeting E-Cadherin. FAK activity was estimated from FAK phosphorylation quantified by Western blotting, migration utilizing a wound healing assay, miR-200a and MKi67 expression levels utilizing qRT-PCR, cell proliferation and apoptosis using BrdU and Annexin V staining, respectively, and E-Cadherin (E-Cad) abundance, using confocal microscopy. LEFTY2 (25 ng/ml, 48 hours) treatment was followed by decrease of MKi67 expression, FAK activity and migration. LEFTY2 upregulated miRNA-200a and E-Cad protein level in Ishikawa cells. The effect of LEFTY2 on migration was mimicked by FAK inhibitor PF 573228 (50 µM). Addition of LEFTY2 in the presence of PF-573228 did not result in a further significant decline of migration. In conclusion, LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration. © 2016 The Author(s) Published by S. Karger AG, Basel.

  16. Focal choroidal excavation associated with focal retinochoroiditis.

    Science.gov (United States)

    Ohki, Tetsutaro; Sakai, Tsutomu; Tsuneoka, Hiroshi

    2015-01-01

    To describe detailed spectral-domain optical coherence tomography (OCT) findings for two patients with focal choroidal excavation (FCE) associated with focal retinochoroiditis. Three eyes from two patients with FCE associated with focal retinochoroiditis were evaluated by funduscopy, fluorescence angiography, indocyanine green angiography, and spectral-domain OCT during follow-up. Both patients with focal retinochoroiditis developed new FCE after oral steroid treatment and two eyes showed regression of the FCE during the follow-up. Both eyes from one patient transformed from the conforming to the nonconforming type and neither of the eyes were stable during the follow-up. Ultimately, all eyes exhibited the conforming-type FCE. Focal choroidal excavation can be seen as a tomographic phenotype after the treatment of focal retinochoroiditis. Spectral-domain OCT was useful for detecting the development of FCE after the treatment and for observing FCE regression.

  17. Osthole Suppresses the Migratory Ability of Human Glioblastoma Multiforme Cells via Inhibition of Focal Adhesion Kinase-Mediated Matrix Metalloproteinase-13 Expression

    Directory of Open Access Journals (Sweden)

    Cheng-Fang Tsai

    2014-03-01

    Full Text Available Glioblastoma multiforme (GBM is the most common type of primary and malignant tumor occurring in the adult central nervous system. GBM often invades surrounding regions of the brain during its early stages, making successful treatment difficult. Osthole, an active constituent isolated from the dried C. monnieri fruit, has been shown to suppress tumor migration and invasion. However, the effects of osthole in human GBM are largely unknown. Focal adhesion kinase (FAK is important for the metastasis of cancer cells. Results from this study show that osthole can not only induce cell death but also inhibit phosphorylation of FAK in human GBM cells. Results from this study show that incubating GBM cells with osthole reduces matrix metalloproteinase (MMP-13 expression and cell motility, as assessed by cell transwell and wound healing assays. This study also provides evidence supporting the potential of osthole in reducing FAK activation, MMP-13 expression, and cell motility in human GBM cells.

  18. Mechanisms underlying the attachment and spreading of human osteoblasts: from transient interactions to focal adhesions on vitronectin-grafted bioactive surfaces.

    Science.gov (United States)

    Brun, Paola; Scorzeto, Michele; Vassanelli, Stefano; Castagliuolo, Ignazio; Palù, Giorgio; Ghezzo, Francesca; Messina, Grazia M L; Iucci, Giovanna; Battaglia, Valentina; Sivolella, Stefano; Bagno, Andrea; Polzonetti, Giovanni; Marletta, Giovanni; Dettin, Monica

    2013-04-01

    The features of implant devices and the reactions of bone-derived cells to foreign surfaces determine implant success during osseointegration. In an attempt to better understand the mechanisms underlying osteoblasts attachment and spreading, in this study adhesive peptides containing the fibronectin sequence motif for integrin binding (Arg-Gly-Asp, RGD) or mapping the human vitronectin protein (HVP) were grafted on glass and titanium surfaces with or without chemically induced controlled immobilization. As shown by total internal reflection fluorescence microscopy, human osteoblasts develop adhesion patches only on specifically immobilized peptides. Indeed, cells quickly develop focal adhesions on RGD-grafted surfaces, while HVP peptide promotes filopodia, structures involved in cellular spreading. As indicated by immunocytochemistry and quantitative polymerase chain reaction, focal adhesions kinase activation is delayed on HVP peptides with respect to RGD while an osteogenic phenotypic response appears within 24h on osteoblasts cultured on both peptides. Cellular pathways underlying osteoblasts attachment are, however, different. As demonstrated by adhesion blocking assays, integrins are mainly involved in osteoblast adhesion to RGD peptide, while HVP selects osteoblasts for attachment through proteoglycan-mediated interactions. Thus an interfacial layer of an endosseous device grafted with specifically immobilized HVP peptide not only selects the attachment and supports differentiation of osteoblasts but also promotes cellular migration. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. Detection is unaffected by the deployment of focal attention

    Directory of Open Access Journals (Sweden)

    Jeff eMoher

    2013-05-01

    Full Text Available There has been much debate regarding how much information humans can extract from their environment without the use of limited attentional resources. In a recent study, Theeuwes, Van der Burg, and Belopolsky (2008 argued that even detection of simple feature targets is not possible without selection by focal attention. Supporting this claim, they found response time benefits in a simple feature (color detection task when a target letter’s identity was repeated on consecutive trials, suggesting that the letter was selected by focal attention and identified prior to detection. This intertrial repetition benefit remained even when observers were required to simultaneously identify a central digit. However, we found that intertrial repetition benefits disappeared when a simple color target was presented among a heterogeneously (rather than homogeneously colored set of distractors, thus reducing its bottom-up salience. Still, detection performance remained high. Thus, detection performance was unaffected by whether a letter was focally attended and identified prior to detection or not. Intertrial identity repetition benefits also disappeared when observers were required to perform a simultaneous, attention-demanding central task (Experiment 2, or when unfamiliar Chinese characters were used (Experiment 3. Together, these results suggest that while shifts of focal attention can be affected by target salience, by the availability of excess cognitive resources, and by target familiarity, detection performance itself is unaffected by these manipulations and is thus unaffected by the deployment of focal attention.

  20. Analysis of the Maillard reaction in human hair using Fourier transform infrared spectroscopic imaging and a focal-plane array detector.

    Science.gov (United States)

    Jung, In-Keun; Park, Sang-Chul; Bin, Sung-Ah; Roh, Young Sup; Lee, John Hwan; Kim, Boo-Min

    2016-03-01

    The Maillard reaction has been well researched and used in the food industry and the fields of environmental science and organic chemistry. Here, we induced the Maillard reaction inside human hair and analyzed its effects by using Fourier transform infrared spectroscopy with a focal-plane array (FTIR-FPA) detector. We used arginine (A), glycine (G), and D-xylose (X) to generate the Maillard reaction by dissolving them in purified water and heating it to 150 °C. This label-free process generated a complex compound (named AGX after its ingredients) with a monomer structure, which was determined by using nuclear magnetic resonance (NMR) and FTIR-FPA. This compound was stable in hair and substantially increased its tensile strength. To our knowledge, we are the first to report the formation of this monomer in human hair, and our study provides insights into a new method that could be used to improve the condition of damaged or aging hair.

  1. Focal Choroidal Excavation.

    Science.gov (United States)

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-12-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation.

  2. CLASP2-dependent microtubule capture at the neuromuscular junction membrane requires LL5β and actin for focal delivery of acetylcholine receptor vesicles

    NARCIS (Netherlands)

    S. Basu (Saonli); S. Sladecek (Stefan); I.M. De La Peña Y Valenzuela (Isabel Martinez); M. Akaaboune (Mohammed); I. Smal (Ihor); K. Martin (Katrin); N.J. Galjart (Niels); H.R. Brenner (Hans Rudolf)

    2015-01-01

    textabstractA hallmark of the neuromuscular junction (NMJ) is the high density of acetylcholine receptors (AChRs) in the postsynaptic muscle membrane. The postsynaptic apparatus of the NMJ is organized by agrin secreted from motor neurons. The mechanisms that underlie the focal delivery of AChRs to

  3. Requirements engineering for human activity systems

    CSIR Research Space (South Africa)

    Erasmus, J

    2014-10-01

    Full Text Available requirements engineering and social systems may be unified, the example of an illustrative health care system is used. The paper concludes with the finding that it is a valid approach to use requirements to describe desired characteristics of social systems...

  4. Exploring the interaction between human focal adhesion kinase and inhibitors: a molecular dynamic simulation and free energy calculations.

    Science.gov (United States)

    Zhan, Jiu-Yu; Zhang, Ji-Long; Wang, Yan; Li, Ye; Zhang, Hong-Xing; Zheng, Qing-Chuan

    2016-11-01

    Focal adhesion kinase is an important target for the treatment of many kinds of cancers. Inhibitors of FAK are proposed to be the anticancer agents for multiple tumors. The interaction characteristic between FAK and its inhibitors is crucial to develop new inhibitors. In the present article, we used Molecular Dynamic (MD) simulation method to explore the characteristic of interaction between FAK and three inhibitors (PHM16, TAE226, and ligand3). The MD simulation results together with MM-GB/SA calculations show that the combinations are enthalpy-driven process. Cys502 and Asp564 are both essential residues due to the hydrogen bond interactions with inhibitors, which was in good agreement with experimental data. Glu500 can form a non-classical hydrogen bond with each inhibitor. Arg426 can form electrostatic interactions with PHM16 and ligand3, while weaker with TAE226. The electronic static potential was employed, and we found that the ortho-position methoxy of TAE226 has a weaker negative charge than the meta-position one in PHM16 or ligand3. Ile428, Val436, Ala452, Val484, Leu501, Glu505, Glu506, Leu553, Gly563 Leu567, Ser568 are all crucial residues in hydrophobic interactions. The key residues in this work will be available for further inhibitor design of FAK and also give assistance to further research of cancer.

  5. Focal femoral condyle resurfacing.

    LENUS (Irish Health Repository)

    Brennan, S A

    2013-03-01

    Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed. Cite this article: Bone Joint J 2013;95-B:301-4.

  6. Living aloft: Human requirements for extended spaceflight

    Science.gov (United States)

    Connors, M. M.; Harrison, A. A.; Akins, F. R.

    1985-01-01

    Human psychological and social adjustment to space is investigated. Studies and experiences bearing on human performance capability, psychological well being, and social organization, as they relate to space, were identified and assessed, and suggestions offered as to where further research could ease the Earth/space transition. Special emphasis was given to the variables of crew size, crew diversity, and mission duration, all of which can be expected to increase in future spaceflight. By providing a conceptual framework in which issues and related information can be integrated, the hope is to aid in discovering those conditions under which future space travelers can flourish.

  7. Chocolate Bars Based on Human Nutritional Requirements

    OpenAIRE

    Robson, Anthony,

    2013-01-01

    International audience; Key Points * The nutritional value of chocolate bars should be based on the nutritional value of the low energy dense late Paleolithic human diet to help reduce mental ill health, obesity, and other postprandial insults. * Current chocolate bars have a high energy density (>2 kcal/g). * Cocoa can be sweetened by the addition of calorie-free Purefruit™ (Tate & Lyle) monk fruit ( Siraitia grosvenorii ) extract. PUREFRUIT™ is approximately 200 times sweeter than sugar and...

  8. Focal neurological deficits

    Science.gov (United States)

    ... or head Electromyogram (EMG), nerve conduction velocities (NCV) MRI of the back, neck, or head Spinal tap Alternative Names Neurological deficits - focal Images Brain References Daroff RB, Jankovic ...

  9. Air humidity requirements for human comfort

    DEFF Research Database (Denmark)

    Toftum, Jørn; Fanger, Povl Ole

    1999-01-01

    Upper humidity limits for the comfort zone determined from two recently presented models for predicting discomfort due to skin humidity and insufficient respiratory cooling are proposed. The proposed limits are compared with the maximum permissible humidity level prescribed in existing standards...... for the thermal indoor environment. The skin humidity model predicts discomfort as a function of the relative humidity of the skin, which is determined by existing models for human heat and moisture transfer based on environmental parameters, clothing characteristics and activity level. The respiratory model...... predicts discomfort as a function of the driving forces for heat loss from the respiratory tract, namely the air temperature and humidity of the surrounding air. An upper humidity limit based on a relative skin humidity of 0.54, corresponding to 20% dissatisfied, results in a maximum permissible humidity...

  10. 45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b) of...

  11. Activation of focal adhesion kinase enhances the adhesion of Fusarium solani to human corneal epithelial cells via the tyrosine-specific protein kinase signaling pathway.

    Science.gov (United States)

    Pan, Xiaojing; Wang, Ye; Zhou, Qingjun; Chen, Peng; Xu, Yuanyuan; Chen, Hao; Xie, Lixin

    2011-03-05

    To determine the role of the integrin-FAK signaling pathway triggered by the adherence of F. solani to human corneal epithelial cells (HCECs). After pretreatment with/without genistein, HCECs were incubated with F. solani spores at different times (0-24 h). Cell adhesion assays were performed by optical microscopy. Changes of the ultrastructure were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The expression of F-actin and Paxillin (PAX) were detected by immunofluorescence and western blotting to detect the expression of these key proteins with/without genistein treatment. Cell adhesion assays showed that the number of adhered spores began to rise at 6 h after incubation and peaked at 8 h. SEM and TEM showed that the HCECs exhibited a marked morphological alteration induced by the attachment and entry of the spores. The expression of PAX increased, while the expression of F-actin decreased by stimulation with F. solani. The interaction of F. solani with HCECs causes actin rearrangement in HCECs. Genistein strongly inhibited FAK phosphorylation and the activation of the downstream protein (PAX). F. solani-induced enhancement of cell adhesion ability was inhibited along with the inhibition of FAK phosphorylation. Our results suggest that the integrin-FAK signaling pathway is involved in the control of F. solani adhesion to HCECs and that the activation of focal adhesion kinase enhances the adhesion of human corneal epithelial cells to F. solani via the tyrosine-specific protein kinase signaling pathway.

  12. Multispectral linear array (MLA) focal plane mechanical and thermal design

    Science.gov (United States)

    Mitchell, A. S.; Kaminski, E. F.

    1982-01-01

    The mechanical and thermal design of an integrated focal plane subsystem of a Multispectral Linear Array (MLA) instrument is discussed in terms of focal-plane alignment, thermoelastic performance, and thermal requirements. The modular construction and thermal control of the focal plane array are discussed.

  13. Selective binding and lateral clustering of α5β1 and αvβ3 integrins: Unraveling the spatial requirements for cell spreading and focal adhesion assembly.

    Science.gov (United States)

    Schaufler, Viktoria; Czichos-Medda, Helmi; Hirschfeld-Warnecken, Vera; Neubauer, Stefanie; Rechenmacher, Florian; Medda, Rebecca; Kessler, Horst; Geiger, Benjamin; Spatz, Joachim P; Cavalcanti-Adam, E Ada

    2016-09-02

    Coordination of the specific functions of α5β1 and αvβ3 integrins is crucial for the precise regulation of cell adhesion, spreading and migration, yet the contribution of differential integrin-specific crosstalk to these processes remains unclear. To determine the specific functions of αvβ3 and α5β1 integrins, we used nanoarrays of gold particles presenting immobilized, integrin-selective peptidomimetic ligands. Integrin binding to the peptidomimetics is highly selective, and cells can spread on both ligands. However, spreading is faster and the projected cell area is greater on α5β1 ligand; both depend on ligand spacing. Quantitative analysis of adhesion plaques shows that focal adhesion size is increased in cells adhering to αvβ3 ligand at 30 and 60 nm spacings. Analysis of αvβ3 and α5β1 integrin clusters indicates that fibrillar adhesions are more prominent in cells adhering to α5β1 ligand, while clusters are mostly localized at the cell margins in cells adhering to αvβ3 ligand. αvβ3 integrin clusters are more pronounced on αvβ3 ligand, though they can also be detected in cells adhering to α5β1 ligand. Furthermore, α5β1 integrin clusters are present in cells adhering to α5β1 ligand, and often colocalize with αvβ3 clusters. Taken together, these findings indicate that the activation of αvβ3 integrin by ligand binding is dispensable for initial adhesion and spreading, but essential to formation of stable focal adhesions.

  14. Focal epithelial hyperplasia by human papillomavirus (HPV)-32 misdiagnosed as HPV-16 and treated with combination of retinoids, imiquimod and quadrivalent HPV vaccine.

    Science.gov (United States)

    Gemigniani, Franco; Hernández-Losa, Javier; Ferrer, Berta; García-Patos, Vicente

    2015-12-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine. © 2015 Japanese Dermatological Association.

  15. Multichannel continuous electroencephalography-functional near-infrared spectroscopy recording of focal seizures and interictal epileptiform discharges in human epilepsy: a review.

    Science.gov (United States)

    Peng, Ke; Pouliot, Philippe; Lesage, Frédéric; Nguyen, Dang Khoa

    2016-07-01

    Functional near-infrared spectroscopy (fNIRS) has emerged as a promising neuroimaging technique as it allows noninvasive and long-term monitoring of cortical hemodynamics. Recent work by our group and others has revealed the potential of fNIRS, combined with electroencephalography (EEG), in the context of human epilepsy. Hemodynamic brain responses attributed to epileptic events, such as seizures and interictal epileptiform discharges (IEDs), are routinely observed with a good degree of statistical significance and in concordance with clinical presentation. Recording done with over 100 channels allows sufficiently large coverage of the epileptic focus and other areas. Three types of seizures have been documented: frontal lobe seizures, temporal lobe seizures, and posterior seizures. Increased oxygenation was observed in the epileptic focus in most cases, while rapid but similar hemodynamic variations were identified in the contralateral homologous region. While investigating IEDs, it was shown that their hemodynamic effect is observable with fNIRS, that their response is associated with significant (inhibitive) nonlinearities, and that the sensitivity and specificity of fNIRS to localize the epileptic focus can be estimated in a sample of 40 patients. This paper first reviews recent EEG-fNIRS developments in epilepsy research and then describes applications to the study of focal seizures and IEDs.

  16. Porcine focal symmetrical poliomyelomalacia.

    OpenAIRE

    Wilson, T.M.; Drake, T R

    1982-01-01

    An acute afebrile paretic condition was diagnosed in 16 of 100 feeder pigs between eight to ten weeks of age. Nine pigs died acutely and seven pigs were euthanized. Macroscopic lesions in the ventral horns of the cervical, thoracic, lumbar and sacral segments of the spinal cord consisted of focal, bilateral, grey depressed areas. There was a bilateral symmetrical focal poliomyelomalacia histopathologically characterized by microcavitation, endothelial and glial cell proliferation and infiltra...

  17. Identifying Requirements for Effective Human-Automation Teamwork

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey C. Joe; John O' Hara; Heather D. Medema; Johanna H. Oxstrand

    2014-06-01

    Previous studies have shown that poorly designed human-automation collaboration, such as poorly designed communication protocols, often leads to problems for the human operators, such as: lack of vigilance, complacency, and loss of skills. These problems often lead to suboptimal system performance. To address this situation, a considerable amount of research has been conducted to improve human-automation collaboration and to make automation function better as a “team player.” Much of this research is based on an understanding of what it means to be a good team player from the perspective of a human team. However, the research is often based on a simplified view of human teams and teamwork. In this study, we sought to better understand the capabilities and limitations of automation from the standpoint of human teams. We first examined human teams to identify the principles for effective teamwork. We next reviewed the research on integrating automation agents and human agents into mixed agent teams to identify the limitations of automation agents to conform to teamwork principles. This research resulted in insights that can lead to more effective human-automation collaboration by enabling a more realistic set of requirements to be developed based on the strengths and limitations of all agents.

  18. Focal brainstem gliomas

    Science.gov (United States)

    Sabbagh, Abdulrahman J.; Alaqeel, Ahmed M.

    2015-01-01

    Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals. PMID:25864061

  19. Porcine focal symmetrical poliomyelomalacia.

    Science.gov (United States)

    Wilson, T M; Drake, T R

    1982-04-01

    An acute afebrile paretic condition was diagnosed in 16 of 100 feeder pigs between eight to ten weeks of age. Nine pigs died acutely and seven pigs were euthanized. Macroscopic lesions in the ventral horns of the cervical, thoracic, lumbar and sacral segments of the spinal cord consisted of focal, bilateral, grey depressed areas. There was a bilateral symmetrical focal poliomyelomalacia histopathologically characterized by microcavitation, endothelial and glial cell proliferation and infiltration of eosinophils. Clinical and pathological findings resemble spontaneous and experimental lesions associated with acute nicotinamide deficiency and selenium toxicosis in swine.

  20. Vitelliform focal choroidal excavation.

    Science.gov (United States)

    Or, Chris; Forooghian, Farzin

    2014-05-30

    Focal choroidal excavations (FCE) are characterized by foveal or perifoveal choroid excavations seen on optical coherence tomography (OCT). The authors report a case of FCE associated with a vitelliform lesion within the excavation. A case of FCE associated with a small vitelliform lesion has been described previously, but the larger extent of the vitelliform lesion observed in the current case has not been previously reported. This may represent a novel category of FCE, vitelliform focal choroidal excavation, in which deposition of vitelliform material is associated with its development. Copyright 2014, SLACK Incorporated.

  1. Human Requirements of Flight. Aerospace Education III. Instructional Unit IV.

    Science.gov (United States)

    Hall, Arthur D.

    This curriculum guide is prepared for the Aerospace Education III series publication entitled "Human Requirements of Flight." It provides specific guidelines for teachers using the textbook. The guidelines for each chapter are organized according to objectives (traditional and behavioral), suggested outline, orientation, suggested key…

  2. Development of Human Factor Management Requirements and Human Error Classification for the Prevention of Railway Accident

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Sang Log; Park, Chan Woo; Shin, Seung Ryoung [Korea Railroad Research Institute, Uiwang (Korea, Republic of)

    2008-08-15

    Railway accident analysis results show that accidents cased by human factors are not decreasing, whereas H/W related accidents are steadily decreasing. For the efficient management of human factors, many expertise on design, conditions, safety culture and staffing are required. But current safety management activities on safety critical works are focused on training, due to the limited resource and information. In order to improve railway safety, human factors management requirements for safety critical worker and human error classification is proposed in this report. For this accident analysis, status of safety measure on human factor, safety management system on safety critical worker, current safety planning is analysis.

  3. SNAP Satellite Focal Plane Development

    Energy Technology Data Exchange (ETDEWEB)

    Bebek, C.; Akerlof, C.; Aldering, G.; Amanullah, R.; Astier, P.; Baltay, C.; Barrelet, E.; Basa, S.; Bercovitz, J.; Bergstrom, L.; Berstein, G.P.; Bester, M.; Bohlin, R.; Bonissent, A.; Bower, C.; Campbell, M.; Carithers, W.; Commins, E.; Day, C.; Deustua, S.; DiGennaro, R.; Ealet, A.; Ellis, R.; Emmett, W.; Eriksson, M.; Fouchez,D.; Fruchter, A.; Genat, J-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Heetderks, H.; Holland, S.; Huterer, D.; Johnson, W.; Kadel, R.; Karcher,A.; Kim, A.; Kolbe, W.; Lafever, R.; Lamoureaux, J.; Lampton, M.; Lefevre, O.; Levi, M.; Levin, D.; Linder, E.; Loken, S.; Malina, R.; Mazure, A.; McKay, T.; McKee, S.; Miquel, R.; Morgan, N.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Roe, N.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Prieto, E.; Rabinowitz,D.; Refregier, A.; Rhodes, J.; Schubnell, M.; Sholl, M.; Smadja, G.; Smith, R.; Smoot, G.; Snyder, J.; Spadafora, A.; Szymkowiak, A.; Tarle,G.; Taylor, K.; Tilquin, A.; Tomasch, A.; Vincent, D.; von der Lippe, H.; Walder, J-P.; Wang, G.

    2003-07-07

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square degree field in the visible and near-infrared wavelength regime. The requirements for the instrument suite and the present configuration of the focal plane concept are presented. A two year R&D phase, largely supported by the Department of Energy, is just beginning. We describe the development activities that are taking place to advance our preparedness for mission proposal in the areas of detectors and electronics.

  4. Cellular prion protein is required for neuritogenesis: fine-tuning of multiple signaling pathways involved in focal adhesions and actin cytoskeleton dynamics

    Directory of Open Access Journals (Sweden)

    Alleaume-Butaux A

    2013-07-01

    Full Text Available Aurélie Alleaume-Butaux,1,2 Caroline Dakowski,1,2 Mathéa Pietri,1,2 Sophie Mouillet-Richard,1,2 Jean-Marie Launay,3,4 Odile Kellermann,1,2 Benoit Schneider1,2 1INSERM, UMR-S 747, 2Paris Descartes University, Sorbonne Paris Cité, UMR-S 747, 3Public Hospital of Paris, Department of Biochemistry, INSERM UMR-S 942, Lariboisière Hospital, Paris, France; 4Pharma Research Department, Hoffmann La Roche Ltd, Basel, Switzerland Abstract: Neuritogenesis is a dynamic phenomenon associated with neuronal differentiation that allows a rather spherical neuronal stem cell to develop dendrites and axon, a prerequisite for the integration and transmission of signals. The acquisition of neuronal polarity occurs in three steps: (1 neurite sprouting, which consists of the formation of buds emerging from the postmitotic neuronal soma; (2 neurite outgrowth, which represents the conversion of buds into neurites, their elongation and evolution into axon or dendrites; and (3 the stability and plasticity of neuronal polarity. In neuronal stem cells, remodeling and activation of focal adhesions (FAs associated with deep modifications of the actin cytoskeleton is a prerequisite for neurite sprouting and subsequent neurite outgrowth. A multiple set of growth factors and interactors located in the extracellular matrix and the plasma membrane orchestrate neuritogenesis by acting on intracellular signaling effectors, notably small G proteins such as RhoA, Rac, and Cdc42, which are involved in actin turnover and the dynamics of FAs. The cellular prion protein (PrPC, a glycosylphosphatidylinositol (GPI-anchored membrane protein mainly known for its role in a group of fatal neurodegenerative diseases, has emerged as a central player in neuritogenesis. Here, we review the contribution of PrPC to neuronal polarization and detail the current knowledge on the signaling pathways fine-tuned by PrPC to promote neurite sprouting, outgrowth, and maintenance. We emphasize that Pr

  5. Recycling of trace elements required for humans in CELSS

    Science.gov (United States)

    Ashida, A.

    1994-11-01

    Recycle of complete nourishment necessary for human should be constructed in CELSS (Controlled Ecological Life Support Systems). Essential elements necessary for human support are categorized as major elements, semi-major elements and trace elements. Recently, trace elements have been identified from considerations of local diseases, food additive problems, pollution problems and adult diseases, consisting of Fe, Zn, Cu, Se, Co, F, Si, Mn, Cr, I, As, Mo, Ni, V, Sn, Li, Br, Cd, Pb, B. A review of the biogeochemical history of the earth's biosphere and the physiological nature of humans and plants explains some of the requirements. A possible route for intake of trace elements is considered that trace elements are dissolved in some chemical form in water, absorbed by plants through their roots and then transfered to human as foods. There may be a posibility that living things absorb some trace elements from atmosphere. Management and recycling of trace elements in CELSS is discussed.

  6. Modelling human resource requirements for the nuclear industry in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Roelofs, Ferry [Nuclear Research and Consultancy Group (NRG) (Netherlands); Flore, Massimo; Estorff, Ulrik von [Joint Research Center (JRC) (Netherlands)

    2017-11-15

    The European Human Resource Observatory for Nuclear (EHRO-N) provides the European Commission with essential data related to supply and demand for nuclear experts in the EU-28 and the enlargement and integration countries based on bottom-up information from the nuclear industry. The objective is to assess how the supply of experts for the nuclear industry responds to the needs for the same experts for present and future nuclear projects in the region. Complementary to the bottom-up approach taken by the EHRO-N team at JRC, a top-down modelling approach has been taken in a collaboration with NRG in the Netherlands. This top-down modelling approach focuses on the human resource requirements for operation, construction, decommissioning, and efforts for long term operation of nuclear power plants. This paper describes the top-down methodology, the model input, the main assumptions, and the results of the analyses.

  7. Meeting Human Reliability Requirements through Human Factors Design, Testing, and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    R. L. Boring

    2007-06-01

    In the design of novel systems, it is important for the human factors engineer to work in parallel with the human reliability analyst to arrive at the safest achievable design that meets design team safety goals and certification or regulatory requirements. This paper introduces the System Development Safety Triptych, a checklist of considerations for the interplay of human factors and human reliability through design, testing, and modeling in product development. This paper also explores three phases of safe system development, corresponding to the conception, design, and implementation of a system.

  8. Focal sampling of cow lying behaviour for automated welfare assessment

    NARCIS (Netherlands)

    Mattachini, G.; Riva, E.; Bisaglia, C.; Pompe, J.C.A.M.; Provolo, G.

    2013-01-01

    the objective of the current study was to determine the number of focal animals required to represent the daily lying behaviour of a herd of lactating dairy cows. the study was carried out at 3 commercial dairy farms. the lying time (h/d) and number of lying bouts (n/d) of 15 ± 3 focal dairy cows,

  9. A randomized controlled trial of Human Papillomavirus (HPV testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial

    Directory of Open Access Journals (Sweden)

    Smith Laurie W

    2010-03-01

    Full Text Available Abstract Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5% were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%. In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%. Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

  10. [The focal renal lesions].

    Science.gov (United States)

    Tuma, Jan

    2013-06-05

    The focal renal lesions are altogether common. Most frequently are found Columna Bertini hypertrophies (so called pseudotumors) and simple renal cysts. The role of sonography in the practice is to distinguish pseudotumors from real renal tumors, and simple renal cysts from complex cysts. The differentiation of complex renal cysts is possible with the help of the CEUS (= contrast enhanced ultrasound) and other imaging modalities such as CT or MRI. In these cases, the CEUS imaging agent has clear advantages over CT and MRI, because it is composed of gas bubbles, which are only slightly smaller than red blood cells and remains exclusively intravascularly while the CT and MRI contrast agents diffuse into the interstitial space without any real perfusion. The real tumors can be differentiated from certain focal non-tumorous changes based on the ultrasound and clinic. The further differentiation of individual kidney tumors and metastases using ultrasound, MRI, CT and CEUS is only partly possible. In all uncertain or unclear cases, therefore, an open or ultrasound-guided biopsy is useful.

  11. Expansive focal cemento-osseous dysplasia.

    Science.gov (United States)

    Bulut, Emel Uzun; Acikgoz, Aydan; Ozan, Bora; Zengin, Ayse Zeynep; Gunhan, Omer

    2012-01-01

    To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis

  12. Focal surfaces of hyperbolic cylinders

    Science.gov (United States)

    Georgiev, Georgi Hristov; Pavlov, Milen Dimov

    2017-12-01

    Cylindrical surfaces have many applications in geometric modeling, architecture and other branches of engineering. In this paper, we describe two cylindrical surfaces associated to a given hyperbolic cylinder. The first one is a focal surface which is determined by reciprocal principle curvature of the hyperbolic cylinder. The second one is a generalized focal surface obtained by reciprocal mean curvature of the same hyperbolic cylinder. In particular, we show that each of these surfaces admits three different parametric representations. As consequence, it is proved that the focal and generalized focal surfaces of the hyperbolic cylinder are rational surfaces. An illustrative example is included.

  13. Charging as a Focal Practice

    DEFF Research Database (Denmark)

    Bødker, Mads

    This position paper reflects on Borgmann’s notion of ‘focal things’ and its applicability in the discourse about interaction with technologies in nature. Using the example of a combined cooking burner and thermoelectric 5W smartphone charger (a BioLite cook stove), this position paper gives...... an example of how a mundance “device” turns focal once it is connected to a contextual infrastructure (the ‘wild’), and reflects on the applicability of the notion of focality. The guiding question is how the notion of ‘focal things and practices’ drawn from Borgmann might help us think about the (strained...

  14. Systemic focal epileptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Marcussen, W.H.

    1986-01-01

    Rats that receive radiation to 0.25 cc of one cerebral hemisphere are clinically and electroencephalographically normal until there is a breakdown of the blood-brain barrier (BBB) at 3 to 6 months postradiation. This BBB lesion can be detected by transient focal seizure activity produced by the BBB-excluded systemic convulsant bicuculline methiodide. In two rats the seizure activity induced by this one injection was self-sustaining. In seven of 15 other rats tested, the subsequent administration of repeated 2 mg/kg injections created a chronic focus that continued to spike with great frequency for 3 weeks or more without further administration of any convulsant. In three of eight other rats, implanted minipumps delivering 180 micrograms/h of bicuculline methiodide produced self-sustaining epileptic activity.

  15. Understanding the Information Requirements of Arts and Humanities Scholarship

    Directory of Open Access Journals (Sweden)

    Agiatis Benardou

    2010-07-01

    Full Text Available This paper reports on research of scholarly research practices and requirements conducted in the context of the Preparing DARIAH European e-Infrastructures project, with a view to ensuring current and future fitness for purpose of the planned digital infrastructure, services and tools. It summarises the findings of earlier research, primarily from the field of human information behaviour as applied in scholarly work, it presents a conceptual perspective informed by cultural-historical activity theory, it introduces briefly a formal conceptual model for scholarly research activity compliant with CIDOC CRM, it describes the plan of work and methodology of an empirical research project based on open-questionnaire interviews with arts and humanities researchers, and presents illustrative examples of segmentation, tagging and initial conceptual analysis of the empirical evidence. Finally, it presents plans for future work, consisting, firstly, of a comprehensive re-analysis of interview segments within the framework of the scholarly research activity model, and, secondly, of the integration of this analysis with the extended digital curation process model we presented in earlier work.

  16. Human rights and the requirement for international medical aid.

    Science.gov (United States)

    Tolchin, Benjamin

    2008-08-01

    Every year approximately 18 million people die prematurely from treatable medical conditions including infectious diseases and nutritional deficiencies. The deaths occur primarily amongst the poorest citizens of poor developing nations. Various groups and individuals have advanced plans for major international medical aid to avert many of these unnecessary deaths. For example, the World Health Organization's Commission on Macroeconomics and Health estimated that eight million premature deaths could be prevented annually by interventions costing roughly US$57 bn per year. This essay advances an argument that human rights require high-income nations to provide such aid. The essay briefly examines John Rawls' obligations of justice and the reasons that their applicability to cases of international medical aid remains controversial. Regardless, the essay argues that purely humanitarian obligations bind the governments and citizens of high-income liberal democracies at a minimum to provide major medical aid to avert premature deaths in poor nations. In refusing to undertake such medical relief efforts, developed nations fail to adequately protect a fundamental human right to life.

  17. Focal midbrain tumors in children

    NARCIS (Netherlands)

    Vandertop, W. P.; Hoffman, H. J.; Drake, J. M.; Humphreys, R. P.; Rutka, J. T.; Amstrong, D. C.; Becker, L. E.

    1992-01-01

    The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive

  18. 75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

    Science.gov (United States)

    2010-09-29

    ... 0910-AG13 Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products...) is amending its regulations governing safety reporting requirements for human drug and biological... implements internationally harmonized definitions and reporting standards. The revisions will improve the...

  19. Mosaic Focal Plane Development

    Science.gov (United States)

    Mason, D.; Horner, S.; Aamodt, E.

    Advances in manufacturing and applied sciences have enabled the development of large ground and spaced based astronomical instruments having a Field of View (FOV) large enough to capture a large portion of the universe in a single image. A large FOV can be accomplished using light weighted optics, improved structures, and the development of mosaic Focal Plane Assemblies (mFPAs). A mFPA comprises multiple Charged Coupled Devices (CCD) mounted onto a single baseplate integrated at the focus plane of the instrument. Examples of current, or proposed, missions utilizing mFPA technology include FAME, GEST, Kepler, GAIA, LSST, and SNAP. The development of a mFPA mandates tight control on the design trades of component development, CCD definition and characterization, component integration, and performance verification testing. This paper addresses the results of the Lockheed Martin Space Systems Company (LMSSC), Advanced Technology Center (ATC) developed mFPA. The design trades and performance characterization are services provided by the LMSSC ATC but not detailed in this paper.

  20. Imaging modalities in Focal Therapy: Multiparametric Ultrasound.

    Science.gov (United States)

    Wildeboer, R R; Panfilova, A P; Mischi, M; Wijkstra, H

    2016-07-01

    Prostate cancer (PCa) is the most common form of cancer among men in the US and the second most common cause of death. It has been observed that an increasing number of newly diagnosed patients exhibit low-risk features and that over-treatment with radical prostatectomy is a growing problem. The feasibility of focal therapy as an organsparing alternative, however, depends on the reliability of imaging techniques to identify, localize and monitor clinically relevant PCa lesions. The aim of this review is to investigate the potential of multiparametric ultrasound (mpUS) for focal therapy. We briefly introduce the most common focal therapies and thoroughly discuss the ability of available ultrasound modalities to localize PCa and reflect tissue properties. The imaging requirements of the focal therapies are studied to put the performance of the US techniques into perspective. We found that transrectal greyscale echography, Doppler sonography, elastography, contrast-enhanced ultrasonography and computerized ultrasound have been studied for the purpose of prostate imaging. Several of these modalities are already frequently used in current clinical practice; to add to the diagnostic process of PCa, to guide and monitor the application of focal therapy or to perform follow-up after treatment. Despite their capability to detect a large fraction of the PCa lesions, none of these modalities is currently considered sufficiently accurate for stand-alone tumour detection and localization. However, although there are only few studies reporting on a combined use of different ultrasound modalities, the results of an mpUS approach seem promising. Several US modalities have been successfully applied as a viable alternative to monitor tissue destruction during and after treatment. In view of the advantages of US and the promising results of a multiparametric approach in PCa detection and localization, researchers are urged to further investigate mpUS for therapeutic purposes.

  1. Focal encephalitis with enterovirus infections.

    Science.gov (United States)

    Modlin, J F; Dagan, R; Berlin, L E; Virshup, D M; Yolken, R H; Menegus, M

    1991-10-01

    We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.

  2. Membership Functions for Fuzzy Focal Elements

    Directory of Open Access Journals (Sweden)

    Porębski Sebastian

    2016-09-01

    Full Text Available The paper presents a study on data-driven diagnostic rules, which are easy to interpret by human experts. To this end, the Dempster-Shafer theory extended for fuzzy focal elements is used. Premises of the rules (fuzzy focal elements are provided by membership functions which shapes are changing according to input symptoms. The main aim of the present study is to evaluate common membership function shapes and to introduce a rule elimination algorithm. Proposed methods are first illustrated with the popular Iris data set. Next experiments with five medical benchmark databases are performed. Results of the experiments show that various membership function shapes provide different inference efficiency but the extracted rule sets are close to each other. Thus indications for determining rules with possible heuristic interpretation can be formulated.

  3. The computed cranial focal point

    NARCIS (Netherlands)

    Jong, G.A. de; Maal, T.J.J.; Delye, H.

    2015-01-01

    INTRODUCTION: Stereophotogrammetry is a radiation-free method for monitoring skull development after craniosynostosis repair. Lack of clear fixed reference points complicate longitudinal comparison of 3D photographs. Therefore we developed the 'computed cranial focal point' (CCFP). METHODS: The CCFP

  4. Teal Amber Visible Focal Plane Technology

    Science.gov (United States)

    Johnson, Charles R.; Burczewski, Ron

    1981-12-01

    Deep-space surveillance missions have imposed severe demands on existing technology and simulated the search for new, advanced technology developments to provide higher performance. Defense Advanced Research Projects Agency (DARPA) sponsored Teal Amber as a visible charge-coupled device (CCD) and associated focal plane signal processing technology development and demonstration program. This paper describes this large-scale, staring-array-sensor concept. The current state of art in the resulting visibled CCD imagers is specified, along with the focal plane signal processor implementation in low power-weight-volume large-scale integrated (LSI) circuitry. Performance requirements and analytic predictions are compared to demonstration system results from an electro-optical test site in White Sands, New Mexico.

  5. Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

    Energy Technology Data Exchange (ETDEWEB)

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R. (Dana-Farber Cancer Institute, Boston, MA (USA))

    1990-01-01

    Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV.

  6. 40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

    Science.gov (United States)

    2010-07-01

    ... pesticides human health assessment data requirements table. 158.2083 Section 158.2083 Protection of... Biochemical Pesticides § 158.2083 Experimental use permit biochemical pesticides human health assessment data... determine the human health assessment data requirements for a particular biochemical pesticide product. (2...

  7. 40 CFR 158.2050 - Biochemical pesticides human health assessment data requirements table.

    Science.gov (United States)

    2010-07-01

    ... § 158.2050 Biochemical pesticides human health assessment data requirements table. (a) General. (1... table shows the data requirements for biochemical pesticides human health assessment. The test notes are shown in paragraph (e) of this section. Table—Biochemical Pesticides Human Health Assessment Data...

  8. Exoskeleton Power and Torque Requirements Based on Human Biomechanics

    National Research Council Canada - National Science Library

    Crowell, Harrison

    2002-01-01

    .... In providing design guidance, the authors had two goals. The first goal was to provide estimates of the angles, torques, and powers for the ankles, knees, and hips of an exoskeleton based on data collected from humans...

  9. A practical approach to management of focal hand dystonia

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2015-01-01

    Full Text Available Dystonia can be focal, segmental, multifocal, generalized, or hemidystonia. Focal dystonia is localized to a specific part of the body. Overall upper limb is more commonly involved in focal dystonia than lower limb and since it starts from hand, focal hand dystonia (FHD is a more accepted terminology. Writer′s cramp and musician dystonia are commonest types of FHD. Typically this dystonia is task specific, but in some patients this specificity may be lost over a period of time. Segmental or generalized dystonia may also start as FHD, so a detailed clinical assessment is required, which should be supplemented by relevant investigations. Treatment includes oral medications, injection botulinum toxin, neurosurgery including neurostimulation, and rehabilitation. Role of injection botulinum toxin has been extensively studied in writer′s cramp patients and found to be effective; however, selection of muscles and techniques of injection are crucial in getting best results.

  10. Creation of identical multiple focal spots with prescribed axial distribution.

    Science.gov (United States)

    Yu, Yanzhong; Zhan, Qiwen

    2015-10-01

    We present a scheme for the construction of coaxially equidistant multiple focal spots with identical intensity profiles for each individual focus and a predetermined number and spacing. To achieve this, the radiation field from an antenna is reversed and then gathered by high numerical aperture objective lenses. Radiation patterns from three types of line sources, i.e., the electric current, magnetic current and electromagnetic current distributions, with cosine-squared taper are respectively employed to generate predominately longitudinally polarized bright spots, azimuthally polarized doughnuts, and focal spots with a perfect spherically symmetric intensity distribution. The required illuminations at the pupil plane of a 4Pi focusing configuration for the creation of these identical multiple focal spots can be easily derived by solving the inverse problem of the antenna radiation field. These unique focal field distributions may find potential applications in laser direct writing and optical microscopy, as well as multiple-particle trapping, alignment, and acceleration along the optical axis.

  11. Why a True Account of Human Development Requires Exemplar Research

    Science.gov (United States)

    Damon, William; Colby, Anne

    2013-01-01

    This chapter uses moral psychology to illustrate why exemplar methods are essential for building a valid, complete understanding of key domains of human development. Social psychological, economic, and biological-evolutionary paradigms for studying morality rely on samples drawn from the general population. This research reveals a bleak picture of…

  12. Human Requirements of Flight. Aviation and Spaceflight. Aerospace Education III.

    Science.gov (United States)

    Coard, E. A.

    This book, one in the series on Aerospace Education III, deals with the general nature of human physiology during space flights. Chapter 1 begins with a brief discussion of the nature of the atmosphere. Other topics examined in this chapter include respiration and circulation, principles and problems of vision, noise and vibration, and…

  13. Grupo Focal em Pesquisas Sociais

    OpenAIRE

    Maria Lúcia Silva Servo; Pricila Oliveira Araújo

    2012-01-01

    Este artigo tem como objetivo discutir a técnica de grupo focal em pesquisas sociais. Apresenta-se as concepções sobre grupo focal. Traz-se os postulados de Pichon-Rivière sobre grupo operativo, os instrumentos de planificação, os vetores do campo grupal para nortear a dinâmica e a observação do campo grupal, bem como a organização, a operacionalização e a análise dos dados das sessões de grupo focal. Através desta técnica de coleta de dados em pesquisas sociais, é possível a construção do EC...

  14. Continuously variable focal length lens

    Science.gov (United States)

    Adams, Bernhard W; Chollet, Matthieu C

    2013-12-17

    A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

  15. Human Computer Interface Design Criteria. Volume 1. User Interface Requirements

    Science.gov (United States)

    2010-03-19

    function may require modification when converted to certain European languages. For example, French and Italian replace the terminal vowel in an article...87 8.3.3 Types of Message Windows ........................................................................... 89 9.  User Support ...112 11.4.5 Support for Printing ...................................................................................... 113

  16. Constellation Program Human-System Integration Requirements. Revision E, Nov. 19, 2010

    Science.gov (United States)

    Dory, Jonathan

    2010-01-01

    The Human-Systems Integration Requirements (HSIR) in this document drive the design of space vehicles, their systems, and equipment with which humans interface in the Constellation Program (CxP). These requirements ensure that the design of Constellation (Cx) systems is centered on the needs, capabilities, and limitations of the human. The HSIR provides requirements to ensure proper integration of human-to-system interfaces. These requirements apply to all mission phases, including pre-launch, ascent, Earth orbit, trans-lunar flight, lunar orbit, lunar landing, lunar ascent, Earth return, Earth entry, Earth landing, post-landing, and recovery. The Constellation Program must meet NASA's Agency-level human rating requirements, which are intended to ensure crew survival without permanent disability. The HSIR provides a key mechanism for achieving human rating of Constellation systems.

  17. A Human Factors Analysis of EVA Time Requirements

    Science.gov (United States)

    Pate, Dennis W.

    1997-01-01

    Human Factors Engineering (HFE) is a discipline whose goal is to engineer a safer, more efficient interface between humans and machines. HFE makes use of a wide range of tools and techniques to fulfill this goal. One of these tools is known as motion and time study, a technique used to develop time standards for given tasks. During the summer of 1995, a human factors motion and time study was initiated with the goals of developing a database of EVA task times and developing a method of utilizing the database to predict how long an EVA should take. Initial development relied on the EVA activities performed during the STS-61 (Hubble) mission. The first step of the study was to become familiar with EVA's, the previous task-time studies, and documents produced on EVA's. After reviewing these documents, an initial set of task primitives and task-time modifiers was developed. Data was collected from videotaped footage of two entire STS-61 EVA missions and portions of several others, each with two EVA astronauts. Feedback from the analysis of the data was used to further refine the primitives and modifiers used. The project was continued during the summer of 1996, during which data on human errors was also collected and analyzed. Additional data from the STS-71 mission was also collected. Analysis of variance techniques for categorical data was used to determine which factors may affect the primitive times and how much of an effect they have. Probability distributions for the various task were also generated. Further analysis of the modifiers and interactions is planned.

  18. The human genome: Some assembly required. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    The Human Genome Project promises to be one of the most rewarding endeavors in modern biology. The cost and the ethical and social implications, however, have made this project the source of considerable debate both in the scientific community and in the public at large. The 1994 Graduate Student Symposium addresses the scientific merits of the project, the technical issues involved in accomplishing the task, as well as the medical and social issues which stem from the wealth of knowledge which the Human Genome Project will help create. To this end, speakers were brought together who represent the diverse areas of expertise characteristic of this multidisciplinary project. The keynote speaker addresses the project`s motivations and goals in the larger context of biological and medical sciences. The first two sessions address relevant technical issues, data collection with a focus on high-throughput sequencing methods and data analysis with an emphasis on identification of coding sequences. The third session explores recent advances in the understanding of genetic diseases and possible routes to treatment. Finally, the last session addresses some of the ethical, social and legal issues which will undoubtedly arise from having a detailed knowledge of the human genome.

  19. Characterization of DECam focal plane detectors

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, H.Thomas; Angstadt, Robert; Campa, Julia; Cease, Herman; Derylo, Greg; Emes, John H.; Estrada, Juan; Kibik, Donna; Flaugher, Brenna L.; Holland, Steve E.; Jonas, Michelle; /Fermilab /Madrid, CIEMAT /LBL, Berkeley /Argonne /Pennsylvania U.

    2008-06-01

    DECam is a 520 Mpix, 3 square-deg FOV imager being built for the Blanco 4m Telescope at CTIO. This facility instrument will be used for the 'Dark Energy Survey' of the southern galactic cap. DECam has chosen 250 ?m thick CCDs, developed at LBNL, with good QE in the near IR for the focal plane. In this work we present the characterization of these detectors done by the DES team, and compare it to the DECam technical requirements. The results demonstrate that the detectors satisfy the needs for instrument.

  20. Expression of BMP-receptor type 1A correlates with progress of osteoarthritis in human knee joints with focal cartilage lesions

    DEFF Research Database (Denmark)

    Schmal, Hagen; Pilz, Ingo H; Mehlhorn, Alexander T

    2012-01-01

    was significantly higher in cartilage biopsies taken in type 3 lesions with intact subchondral layer compared with type 4 defects (P ...BACKGROUND AIMS: Bone morphogenetic protein-2 (BMP-2) and its receptor type 1A (BMPR-1A) play significant roles in cartilage metabolism. The aim of this study was to evaluate a possible correlation between intra-articular expression of these proteins and the degree of osteoarthritis (OA) in human...... knees. METHODS: Biopsies of synovia and debrided cartilage were taken in 15 patients undergoing autologous chondrocyte implantation. Expression of BMP-2 and BMPR-1A was evaluated semi-quantitatively by immunohistologic staining. These data were complemented by grading of cartilage lesions according...

  1. Expression of BMP-receptor type 1A correlates with progress of osteoarthritis in human knee joints with focal cartilage lesions.

    Science.gov (United States)

    Schmal, Hagen; Pilz, Ingo H; Mehlhorn, Alexander T; Dovi-Akue, David; Kirchhoff, Christina; Südkamp, Norbert P; Gerlach, Ulrike; Niemeyer, Philipp

    2012-08-01

    Bone morphogenetic protein-2 (BMP-2) and its receptor type 1A (BMPR-1A) play significant roles in cartilage metabolism. The aim of this study was to evaluate a possible correlation between intra-articular expression of these proteins and the degree of osteoarthritis (OA) in human knees. Biopsies of synovia and debrided cartilage were taken in 15 patients undergoing autologous chondrocyte implantation. Expression of BMP-2 and BMPR-1A was evaluated semi-quantitatively by immunohistologic staining. These data were complemented by grading of cartilage lesions according to International Cartilage Repair Society (ICRS), defect size, duration of complaints, knee osteoarthritis scoring system (KOSS) and Henderson and Kellgren-Lawrence scores. General histologic stainings were used to determine Mankin, Pritzker and Krenn scores. The expression of BMPR-1A but not of BMP-2 was significantly higher in cartilage biopsies taken in type 3 lesions with intact subchondral layer compared with type 4 defects (P < 0.05). In cartilage areas of bordering sectors, the intensity of immunohistologic staining of BMPR-1A was statistically significantly higher in mature cartilage compared with repair zones (P < 0.05). Expression of BMP-2 and its receptor 1A correlated in the cartilage biopsies (P < 0.02) but not in the synovia. The degree of OA was scored in all biopsies according to Mankin and Pritzker, and these scores correlated statistically significantly with BMPR-1A expression in the synovia (P < 0.05). In patients with an osteochondritis dissecans, the degree of OA was higher compared with other causes of chondromalacia, as evaluated by defect size, ICRS score, duration of complaints, Pritzker score and expression of BMPR-1A in cartilage (P < 0.05). These data support the role of BMPR-1A as an indicator of OA progression in human knees with circumscribed cartilage lesions.

  2. Navy Manpower: Values, Practices, and Human Resources Requirements.

    Science.gov (United States)

    1975-06-01

    deciles describing a 105 random sample of 22.000 people from 32 business organizations Human Resources Primacy Communication Flow Motivational...Procesb Consultation BUBL !B!SaSITE CLASS: PHury »rirnill* »rof I If for Co*Mr*<J trmoi 10t 201 30t «01 SOt «nx 70X 801 «OX 1001 199. Dtdtlon...like It to to: © © © © © G 5 3a The U S. should togm a »radur whether oiher countries do oi r tea may to timr O

  3. Focal therapy in prostate cancer

    NARCIS (Netherlands)

    van den Bos, W.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

  4. Focal lesions of the patella

    Energy Technology Data Exchange (ETDEWEB)

    Hedayati, B. [Royal national Orthopaedic Hospital Stanmore, Brockley Hill Stanmore, Department of Radiology, Middlesex (United Kingdom); Lewisham Hospital NHS Trust, Department of Radiology, London (United Kingdom); Saifuddin, A. [Royal national Orthopaedic Hospital Stanmore, Brockley Hill Stanmore, Department of Radiology, Middlesex (United Kingdom)

    2009-08-15

    Focal lesions of the patella may be identified during the investigation of anterior knee pain or as an incidental finding on radiological images. This pictorial review describes the radiographic appearances of a wide range of conditions that have been seen in this sesamoid bone. Where appropriate, computed tomography and magnetic resonance features have been included. (orig.)

  5. Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain.

    Science.gov (United States)

    Spiegler, Andreas; Hansen, Enrique C A; Bernard, Christophe; McIntosh, Anthony R; Jirsa, Viktor K

    2016-01-01

    When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation.

  6. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection...

  7. Focal spot size reduction using asymmetric collimation to enable reduced anode angles with a conventional angiographic x-ray tube for use with high resolution detectors

    Science.gov (United States)

    Russ, M.; Shankar, A.; Setlur Nagesh, S. V.; Ionita, C. N.; Bednarek, D. R.; Rudin, S.

    2017-03-01

    The high-resolution requirements for neuro-endovascular image-guided interventions (EIGIs) necessitate the use of a small focal-spot size; however, the maximum tube output limits for such small focal-spot sizes may not enable sufficient x-ray fluence after attenuation through the human head to support the desired image quality. This may necessitate the use of a larger focal spot, thus contributing to the overall reduction in resolution. A method for creating a higher-output small effective focal spot based on the line-focus principle has been demonstrated and characterized. By tilting the C-arm gantry, the anode-side of the x-ray field-of-view is accessible using a detector placed off-axis. This tilted central axis diminishes the resultant focal spot size in the anode-cathode direction by the tangent of the effective anode angle, allowing a medium focal spot to be used in place of a small focal spot with minimal losses in resolution but with increased tube output. Images were acquired of two different objects at the central axis, and with the C-arm tilted away from the central axis at 1° increments from 0°-7°. With standard collimation settings, only 6° was accessible, but using asymmetric extended collimation a maximum of 7° was accessed for enhanced comparisons. All objects were positioned perpendicular to the anode-cathode direction and images were compared qualitatively. The increasing advantage of the off-axis focal spots was quantitatively evidenced at each subsequent angle using the Generalized Measured-Relative Object Detectability metric (GM-ROD). This anode-tilt method is a simple and robust way of increasing tube output for a small field-of-view detector without diminishing the overall apparent resolution for neuro-EIGIs.

  8. NASA Space Safety Standards and Procedures for Human Rating Requirements

    Science.gov (United States)

    Shivers, C. Herbert

    2009-01-01

    The National Aeronautics and Space Administration of the United States of America (NASA) has arguably led this planet in space exploration and certainly has been one of two major leaders in those endeavors. NASA governance is institutionalized and managed in a series documents arranged in a hierarchy and flowing down to the work levels. A document tree of NASA s documentation in its totality would likely overwhelm and not be very informative. Taken in segments related to the various business topics and focusing in those segments, however, provides a logical and understandable relationship and flow of requirements and processes. That is the nature of this chapter, a selection of NASA documentation pertaining to space exploration and a description of how those documents together form the plan by which NASA business for space exploration is conducted. Information presented herein is taken from NASA publications and is available publicly and no information herein is protected by copyright or security regulations. While NASA documents are the source of information presented herein, any and all views expressed herein and any misrepresentations of NASA data that may occur herein are those of the author and should not be considered NASA official positions or statements, nor should NASA endorsement of anything presented in this work be assumed.

  9. Postures and Motions Library Development for Verification of Ground Crew Human Systems Integration Requirements

    Science.gov (United States)

    Jackson, Mariea Dunn; Dischinger, Charles; Stambolian, Damon; Henderson, Gena

    2012-01-01

    Spacecraft and launch vehicle ground processing activities require a variety of unique human activities. These activities are being documented in a Primitive motion capture library. The Library will be used by the human factors engineering in the future to infuse real to life human activities into the CAD models to verify ground systems human factors requirements. As the Primitive models are being developed for the library the project has selected several current human factors issues to be addressed for the SLS and Orion launch systems. This paper explains how the Motion Capture of unique ground systems activities are being used to verify the human factors analysis requirements for ground system used to process the STS and Orion vehicles, and how the primitive models will be applied to future spacecraft and launch vehicle processing.

  10. Postures and Motions Library Development for Verification of Ground Crew Human Factors Requirements

    Science.gov (United States)

    Stambolian, Damon; Henderson, Gena; Jackson, Mariea Dunn; Dischinger, Charles

    2013-01-01

    Spacecraft and launch vehicle ground processing activities require a variety of unique human activities. These activities are being documented in a primitive motion capture library. The library will be used by human factors engineering analysts to infuse real to life human activities into the CAD models to verify ground systems human factors requirements. As the primitive models are being developed for the library, the project has selected several current human factors issues to be addressed for the Space Launch System (SLS) and Orion launch systems. This paper explains how the motion capture of unique ground systems activities is being used to verify the human factors engineering requirements for ground systems used to process the SLS and Orion vehicles, and how the primitive models will be applied to future spacecraft and launch vehicle processing.

  11. Extend focal depth of a tracking lens by phase apodizers

    Science.gov (United States)

    Cai, Xianyang; Chang, Shoude; Flueraru, Costel

    2005-09-01

    In a conventional particle tracking system, the depth of field is usually very small because of the use of high power imaging lens. The tracking accuracy may also be affected by the smearing of spot image, caused by focal shift. Increasing the focal depth and keeping uniform spot size in the focal region is highly desirable for a high accurate tracking system. In this report, we study the design of phase apdodizer that could be used to increase the focal depth of a tracking lens. The design is based on the requirements by highly accurate tracking that the point-spread function (PSF) of the lens keep an even and concentrated energy distribution when the lens is defocused. To achieve this purpose, a pure phase-shifting apodizer is introduced on the pupil plane of the lens. The function of the apodizer is to control the energy distribution of the 3D diffraction pattern near the focal region and make the effective spot size uniform or minimum variation along optical axis. The pattern of the 3D PSF of the lens with the apodizer shapes closed to a cylinder. New method used to search and optimize the design of the phase apodizer that meet the requirements of a particle tracking system will be studied. Theoretical analysis and numerical simulation are given in support of the method.

  12. Upgrading pretransplant human islet culture technology requires human serum combined with media renewal.

    Science.gov (United States)

    Kerr-Conte, Julie; Vandewalle, Brigitte; Moerman, Ericka; Lukowiak, Bruno; Gmyr, Valery; Arnalsteen, Laurent; Caiazzo, Robert; Sterkers, Adrien; Hubert, Thomas; Vantyghem, Marie Christine; Pattou, François

    2010-05-15

    BACKGROUND.: The original Edmonton protocol used fresh islets, but for obvious logistic advantages most transplant centers have implemented pretransplant culture in human albumin. The aim of this study was to improve current pretransplant human islet culture techniques. METHODS.: Clinical-grade purified human islets from a total of 24 donors were directly resuspended after isolation in CMRL 1066-based media at 37 degrees C, and media additions and renewal were tested. At days 1 and 5 of culture, in vitro quality controls included islet viability, insulin content and function, apoptosis, and in vivo islet potency assay in nude mice. RESULTS.: Replacing human albumin with human AB serum improved 1- and 5-day preservation of islet function and viability which was further enhanced with antioxidant Stem Ease, leading to the iCulture medium (enriched CMRL: pyruvate, zinc sulfate, insulin, transferrin, selenium, 2.5% human AB serum and Stem Ease). Major damage occurs in the first day of culture and frequent media renewal (25% vol/hr) in this period further improved viability, apoptosis, islet recovery, and function in vitro and in vivo, compared with only changing medium after overnight culture. CONCLUSIONS.: The described human islet culture technique (iCulture medium+renewal) seems to be the best choice for clinical human islet culture when short (1 day) or long (5 days) periods are used. Media choice and dilution play a major role in the function and survival of human islets in culture.

  13. 21 CFR 201.316 - Drugs with thyroid hormone activity for human use; required warning.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs with thyroid hormone activity for human use... Drug Products § 201.316 Drugs with thyroid hormone activity for human use; required warning. (a) Drugs with thyroid hormone activity have been promoted for, and continue to be dispensed and prescribed for...

  14. Human CD4+ T cells require exogenous cystine for glutathione and DNA synthesis

    DEFF Research Database (Denmark)

    Levring, Trine B; Kongsbak-Wismann, Martin; Rode, Anna Kathrine Obelitz

    2015-01-01

    . The aim of this study was to elucidate why activated human T cells require exogenous Cys2 in order to proliferate. We activated purified naïve human CD4+ T cells and found that glutathione (GSH) levels and DNA synthesis were dependent on Cys2 and increased in parallel with increasing concentrations of Cys...

  15. Cross-Cultural Competence: Leader Requirements for Intercultural Effectiveness in the Human Domain

    Science.gov (United States)

    2014-06-13

    CROSS-CULTURAL COMPETENCE: LEADER REQUIREMENTS FOR INTERCULTURAL EFFECTIVENESS IN THE HUMAN DOMAIN A thesis presented to... Intercultural Effectiveness in the Human Domain 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Shawn...

  16. Recurrent focal myositis in a patient on maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Manjusha Yadla

    2015-04-01

    Full Text Available Focal myositis is a benign inflammatory process involving a single group of muscles. It may resolve with conservative measures or may be a harbinger for polymyositis. Very few focal myosites are recurrent, and recurrence in patients with end-stage renal disease on hemodialysis is extremely rare. Clinical examination, electromyography, and magnetic resonance imaging help in identifying this entity. Muscle biopsy and histopathological evaluation are mandatory in diagnosis. It often responds to conservative treatment with anti-inflammatory drugs and physiotherapy, but occasionally it requires therapy with steroids.

  17. A Path to Planetary Protection Requirements for Human Exploration: A Literature Review and Systems Engineering Approach

    Science.gov (United States)

    Johnson, James E.; Conley, Cassie; Siegel, Bette

    2015-01-01

    As systems, technologies, and plans for the human exploration of Mars and other destinations beyond low Earth orbit begin to coalesce, it is imperative that frequent and early consideration is given to how planetary protection practices and policy will be upheld. While the development of formal planetary protection requirements for future human space systems and operations may still be a few years from fruition, guidance to appropriately influence mission and system design will be needed soon to avoid costly design and operational changes. The path to constructing such requirements is a journey that espouses key systems engineering practices of understanding shared goals, objectives and concerns, identifying key stakeholders, and iterating a draft requirement set to gain community consensus. This paper traces through each of these practices, beginning with a literature review of nearly three decades of publications addressing planetary protection concerns with respect to human exploration. Key goals, objectives and concerns, particularly with respect to notional requirements, required studies and research, and technology development needs have been compiled and categorized to provide a current 'state of knowledge'. This information, combined with the identification of key stakeholders in upholding planetary protection concerns for human missions, has yielded a draft requirement set that might feed future iteration among space system designers, exploration scientists, and the mission operations community. Combining the information collected with a proposed forward path will hopefully yield a mutually agreeable set of timely, verifiable, and practical requirements for human space exploration that will uphold international commitment to planetary protection.

  18. Interferon Induced Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Yusuf Kayar

    2016-01-01

    Full Text Available Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

  19. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    OpenAIRE

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-01

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repre...

  20. The myosin-II-responsive focal adhesion proteome: a tour de force?

    Science.gov (United States)

    Gallegos, Lisa; Ng, Mei Rosa; Brugge, Joan S

    2011-04-01

    The formation and maturation of focal adhesions involves significant changes in protein composition and requires acto-myosin contractility. A mass spectrometry approach reveals changes to the focal adhesion proteome on myosin inhibition, providing a valuable resource for the cell adhesion field. © 2011 Macmillan Publishers Limited. All rights reserved

  1. Identification of Staphylococcus aureus Factors Required for Pathogenicity and Growth in Human Blood.

    Science.gov (United States)

    Connolly, John; Boldock, Emma; Prince, Lynne R; Renshaw, Stephen A; Whyte, Moira K; Foster, Simon J

    2017-11-01

    Staphylococcus aureus is a human commensal but also has devastating potential as an opportunistic pathogen. S. aureus bacteremia is often associated with an adverse outcome. To identify potential targets for novel control approaches, we have identified S. aureus components that are required for growth in human blood. An ordered transposon mutant library was screened, and 9 genes involved specifically in hemolysis or growth on human blood agar were identified by comparing the mutants to the parental strain. Three genes ( purA , purB , and pabA ) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model. The pabA growth defect was specific to the red blood cell component of human blood, showing no difference from the parental strain in growth in human serum, human plasma, or sheep or horse blood. PabA is required in the tetrahydrofolate (THF) biosynthesis pathway. The pabA growth defect was found to be due to a combination of loss of THF-dependent dTMP production by the ThyA enzyme and increased demand for pyrimidines in human blood. Our work highlights pabA and the pyrimidine salvage pathway as potential targets for novel therapeutics and suggests a previously undefined role for a human blood factor in the activity of sulfonamide antibiotics. Copyright © 2017 Connolly et al.

  2. Idiopathic focal epilepsies: the "lost tribe".

    Science.gov (United States)

    Pal, Deb K; Ferrie, Colin; Addis, Laura; Akiyama, Tomoyuki; Capovilla, Giuseppe; Caraballo, Roberto; de Saint-Martin, Anne; Fejerman, Natalio; Guerrini, Renzo; Hamandi, Khalid; Helbig, Ingo; Ioannides, Andreas A; Kobayashi, Katsuhiro; Lal, Dennis; Lesca, Gaetan; Muhle, Hiltrud; Neubauer, Bernd A; Pisano, Tiziana; Rudolf, Gabrielle; Seegmuller, Caroline; Shibata, Takashi; Smith, Anna; Striano, Pasquale; Strug, Lisa J; Szepetowski, Pierre; Valeta, Thalia; Yoshinaga, Harumi; Koutroumanidis, Michalis

    2016-09-01

    epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state-of-the-art thinking on the topics explored. The symposium led to the formation of international working groups under the umbrella of "Luke's Idiopathic Focal Epilepsy Project" to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high-frequency oscillations, and parental resources (see www.childhood-epilepsy.org). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.

  3. A Cognitive Systems Engineering Approach to Developing Human Machine Interface Requirements for New Technologies

    Science.gov (United States)

    Fern, Lisa Carolynn

    This dissertation examines the challenges inherent in designing and regulating to support human-automation interaction for new technologies that will be deployed into complex systems. A key question for new technologies with increasingly capable automation, is how work will be accomplished by human and machine agents. This question has traditionally been framed as how functions should be allocated between humans and machines. Such framing misses the coordination and synchronization that is needed for the different human and machine roles in the system to accomplish their goals. Coordination and synchronization demands are driven by the underlying human-automation architecture of the new technology, which are typically not specified explicitly by designers. The human machine interface (HMI), which is intended to facilitate human-machine interaction and cooperation, typically is defined explicitly and therefore serves as a proxy for human-automation cooperation requirements with respect to technical standards for technologies. Unfortunately, mismatches between the HMI and the coordination and synchronization demands of the underlying human-automation architecture can lead to system breakdowns. A methodology is needed that both designers and regulators can utilize to evaluate the predicted performance of a new technology given potential human-automation architectures. Three experiments were conducted to inform the minimum HMI requirements for a detect and avoid (DAA) system for unmanned aircraft systems (UAS). The results of the experiments provided empirical input to specific minimum operational performance standards that UAS manufacturers will have to meet in order to operate UAS in the National Airspace System (NAS). These studies represent a success story for how to objectively and systematically evaluate prototype technologies as part of the process for developing regulatory requirements. They also provide an opportunity to reflect on the lessons learned in order

  4. The direct effect of Focal Adhesion Kinase (FAK, dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2009-08-01

    Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis. Methods To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD, and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors. Results Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p Conclusion Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal

  5. Human Factors Engineering Requirements for the International Space Station - Successes and Challenges

    Science.gov (United States)

    Whitmore, M.; Blume, J.

    2003-01-01

    Advanced technology coupled with the desire to explore space has resulted in increasingly longer human space missions. Indeed, any exploration mission outside of Earth's neighborhood, in other words, beyond the moon, will necessarily be several months or even years. The International Space Station (ISS) serves as an important advancement toward executing a successful human space mission that is longer than a standard trip around the world or to the moon. The ISS, which is a permanently occupied microgravity research facility orbiting the earth, will support missions four to six months in duration. In planning for the ISS, the NASA developed an agency-wide set of human factors standards for the first time in a space exploration program. The Man-Systems Integration Standard (MSIS), NASA-STD-3000, a multi-volume set of guidelines for human-centered design in microgravity, was developed with the cooperation of human factors experts from various NASA centers, industry, academia, and other government agencies. The ISS program formed a human factors team analogous to any major engineering subsystem. This team develops and maintains the human factors requirements regarding end-to-end architecture design and performance, hardware and software design requirements, and test and verification requirements. It is also responsible for providing program integration across all of the larger scale elements, smaller scale hardware, and international partners.

  6. Focal nodular hyperplasia in identical twins.

    Science.gov (United States)

    Mindikoglu, Ayse L; Regev, Arie; Levi, Joe U; Casillas, Javier; Schiff, Eugene R

    2005-07-01

    A unique case of a focal nodular hyperplasia (FNH) in identical twins is presented. The computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen demonstrated in both twins a mass of identical size in the same segment of their liver. Histopathologic examination of both masses confirmed the diagnosis of focal nodular hyperplasia. This case report strongly supports the theory of a congenital vascular anomaly playing a major role in the etiology of focal nodular hyperplasia.

  7. Periodontitis in patients with focal tuberculosis

    Directory of Open Access Journals (Sweden)

    Alexandrova Е.А.

    2010-12-01

    Full Text Available The research goal is to investigate the mechanisms of formation and peculiarities of periodontitis in patients with focal tuberculosis. Patients with periodontitis and focal tuberculosis are proved to develop local inflammatory reaction with increased infection and activation of proinflammatory cytokines in parodontal pockets fluid. The main risk factor of frequent and durable recurrence of parodontal pathology in case of focal tuberculosis was the development of pathologic process as a cause of disbalance of lipid peroxidation and antioxidant system, endotoxicosis syndrome

  8. RF/Optical Demonstration: Focal Plane Assembly

    Science.gov (United States)

    Hoppe, D. J.; Chung, S.; Kovalik, J.; Gama, E.; Fernandez, M. M.

    2016-11-01

    In this article, we describe the second-generation focal plane optical assembly employed in the RF/optical demonstration at DSS-13. This assembly receives reflected light from the two mirror segments mounted on the RF primary. The focal plane assembly contains a fast steering mirror (FSM) to stabilize the focal plane spot, a pupil camera to aid in aligning the two segments, and several additional cameras for receiving the optical signal prior to as well as after the FSM loop.

  9. Large Format Uncooled Focal Plane Array Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Black Forest Engineering has identified innovative modifications in uncooled focal plane array (UFPA) architecture and processing that allows development of large...

  10. Step 1: Human System Integration Pilot-Technology Interface Requirements for Weather Management

    Science.gov (United States)

    2005-01-01

    This document involves definition of technology interface requirements for Hazardous Weather Avoidance. Technology concepts in use by the Access 5 Weather Management Work Package were considered. Beginning with the Human System Integration (HIS) high-level functional requirement for Hazardous Weather Avoidance, and Hazardous Weather Avoidance technology elements, HSI requirements for the interface to the pilot were identified. Results of the analysis describe (1) the information required by the pilot to have knowledge of hazardous weather, and (2) the control capability needed by the pilot to obtain hazardous weather information. Fundamentally, these requirements provide the candidate Hazardous Weather Avoidance technology concepts with the necessary human-related elements to make them compatible with human capabilities and limitations. The results of the analysis describe how Hazardous Weather Avoidance operations and functions should interface with the pilot to provide the necessary Weather Management functionality to the UA-pilot system. Requirements and guidelines for Hazardous Weather Avoidance are partitioned into four categories: (1) Planning En Route (2) Encountering Hazardous Weather En Route, (3) Planning to Destination, and (4) Diversion Planning Alternate Airport. Each requirement is stated and is supported with a rationale and associated reference(s).

  11. Focal Choroidal Excavation in Retinal Dystrophies.

    Science.gov (United States)

    Braimah, Imoro Zeba; Rapole, Shruthi; Dumpala, Sunila; Chhablani, Jay

    2016-08-17

    To investigate the presence of focal choroidal excavation (FCE) in patients with retinitis pigmentosa (RP), Stargardt's disease (STGD), and Best disease in the Indian population. This retrospective consecutive case series included 309 eyes of 157 patients with RP (183 eyes), STGD (93 eyes), and Best disease (33 eyes) with good-quality, enhanced-depth spectral domain optical coherence tomography scans. Comprehensive ophthalmic examination data were collected. Characteristics of FCE, including location of FCE, type (conforming and non-conforming), maximal width, and depth, were noted. FCE was found in 2 out of 33 (6%) eyes with Best disease and no FCE was found in eyes with RP or STGD. The location of the FCE was extrafoveal in both cases. The first case had non-conforming FCE while the second case had the conforming type and the FCE occurred in association with choroidal neovascularization in the second case. The first case maintained good visual acuity of 20/20 over the entire period of follow-up (14 months), while the second case had a visual acuity of 20/200 at the last follow-up (three years) due to scarred choroidal neovascular membranes. The FCE showed no change in both eyes over the entire duration of follow-up. Focal choroidal excavation was found in 6% of eyes with Best disease, which remained stable throughout follow up. Eyes with RP and STGD did not have any FCE. Further studies are required to determine the role of vitelliform material in FCE development in Best disease.

  12. SIRTF Focal Plane Survey: A Pre-flight Error Analysis

    Science.gov (United States)

    Bayard, David S.; Brugarolas, Paul B.; Boussalis, Dhemetrios; Kang, Bryan H.

    2003-01-01

    This report contains a pre-flight error analysis of the calibration accuracies expected from implementing the currently planned SIRTF focal plane survey strategy. The main purpose of this study is to verify that the planned strategy will meet focal plane survey calibration requirements (as put forth in the SIRTF IOC-SV Mission Plan [4]), and to quantify the actual accuracies expected. The error analysis was performed by running the Instrument Pointing Frame (IPF) Kalman filter on a complete set of simulated IOC-SV survey data, and studying the resulting propagated covariances. The main conclusion of this study is that the all focal plane calibration requirements can be met with the currently planned survey strategy. The associated margins range from 3 to 95 percent, and tend to be smallest for frames having a 0.14" requirement, and largest for frames having a more generous 0.28" (or larger) requirement. The smallest margin of 3 percent is associated with the IRAC 3.6 and 5.8 micron array centers (frames 068 and 069), and the largest margin of 95 percent is associated with the MIPS 160 micron array center (frame 087). For pointing purposes, the most critical calibrations are for the IRS Peakup sweet spots and short wavelength slit centers (frames 019, 023, 052, 028, 034). Results show that these frames are meeting their 0.14" requirements with an expected accuracy of approximately 0.1", which corresponds to a 28 percent margin.

  13. Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration.

    Science.gov (United States)

    Grewal, Seema; Carver, Janet G; Ridley, Anne J; Mardon, Helen J

    2008-10-21

    Failure of the human embryo to implant into the uterine wall during the early stages of pregnancy is a major cause of infertility. Implantation involves embryo apposition and adhesion to the endometrial epithelium followed by penetration through the epithelium and invasion of the embryonic trophoblast through the endometrial stroma. Although gene-knockdown studies have highlighted several molecules that are important for implantation in the mouse, the molecular mechanisms controlling implantation in the human are unknown. Here, we demonstrate in an in vitro model for human implantation that the Rho GTPases Rac1 and RhoA in human endometrial stromal cells modulate invasion of the human embryo through the endometrial stroma. We show that knockdown of Rac1 expression in human endometrial stromal cells inhibits human embryonic trophoblast invasion into stromal cell monolayers, whereas inhibition of RhoA activity promotes embryo invasion. Furthermore, we demonstrate that Rac1 is required for human endometrial stromal cell migration and that the motility of the stromal cells increases at implantation sites. This increased motility correlates with a localized increase in Rac1 activation and a reciprocal decrease in RacGAP1 levels. These results reveal embryo-induced and localized endometrial responses that may govern implantation of the human embryo.

  14. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-09-15

    Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

  15. Focal-plane sensor-processor chips

    CERN Document Server

    Zarándy, Ákos

    2011-01-01

    Focal-Plane Sensor-Processor Chips explores both the implementation and application of state-of-the-art vision chips. Presenting an overview of focal plane chip technology, the text discusses smart imagers and cellular wave computers, along with numerous examples of current vision chips.

  16. Focal Cortical Thickness Correlates of Exceptional Memory Training in Vedic Priests

    Directory of Open Access Journals (Sweden)

    Giridhar Padmanabhan Kalamangalam

    2014-10-01

    Full Text Available The capacity for semantic memory – the ability to acquire and store knowledge of the world - is highly developed in the human brain. In particular, semantic memory assimilated through an auditory route may be a uniquely human capacity. One method of obtaining neurobiological insight into auditory semantic memory mechanisms is through the study of experts. In this work, we study a group of Hindu Vedic priests, whose religious training requires the memorization of vast tracts of scriptural texts through an oral tradition, recalled spontaneously during a lifetime of subsequent spiritual practice. We demonstrate focal increases of cortical thickness in the dominant prefrontal lobe and non-dominant temporal lobe in Vedic priests, in comparison to a group of matched controls. The findings are relevant to current hypotheses regarding cognitive processes underlying storage and recall of long-term declarative memory.

  17. Scaling Up Child and Adolescent Mental Health Services in South Africa: Human Resource Requirements and Costs

    Science.gov (United States)

    Lund, Crick; Boyce, Gerard; Flisher, Alan J.; Kafaar, Zuhayr; Dawes, Andrew

    2009-01-01

    Background: Children and adolescents with mental health problems have poor service cover in low- and middle-income countries. Little is known about the resources that would be required to provide child and adolescent mental health services (CAMHS) in these countries. The purpose of this study was to calculate the human resources and associated…

  18. Using a Functional Architecture to Identify Human-Automation Trust Needs and Design Requirements

    Science.gov (United States)

    2016-12-01

    example, Parasuraman cites a study performed by Muir (1988) on the use of an automated aid to control a simulated beverage manufacturing plant (1997, 236...Distribution is unlimited. USING A FUNCTIONAL ARCHITECTURE TO IDENTIFY HUMAN- AUTOMATION TRUST NEEDS AND DESIGN REQUIREMENTS Bradley A...1  B.  OVERVIEW OF AUTOMATION USE ..................................................2  C.  RESEARCH OBJECTIVE

  19. Functional Mobility Testing: A Novel Method to Establish Human System Interface Design Requirements

    Science.gov (United States)

    England, Scott A.; Benson, Elizabeth A.; Rajulu, Sudhakar

    2008-01-01

    Across all fields of human-system interface design it is vital to posses a sound methodology dictating the constraints on the system based on the capabilities of the human user. These limitations may be based on strength, mobility, dexterity, cognitive ability, etc. and combinations thereof. Data collected in an isolated environment to determine, for example, maximal strength or maximal range of motion would indeed be adequate for establishing not-to-exceed type design limitations, however these restraints on the system may be excessive over what is basally needed. Resources may potentially be saved by having a technique to determine the minimum measurements a system must accommodate. This paper specifically deals with the creation of a novel methodology for establishing mobility requirements for a new generation of space suit design concepts. Historically, the Space Shuttle and the International Space Station vehicle and space hardware design requirements documents such as the Man-Systems Integration Standards and International Space Station Flight Crew Integration Standard explicitly stated that the designers should strive to provide the maximum joint range of motion capabilities exhibited by a minimally clothed human subject. In the course of developing the Human-Systems Integration Requirements (HSIR) for the new space exploration initiative (Constellation), an effort was made to redefine the mobility requirements in the interest of safety and cost. Systems designed for manned space exploration can receive compounded gains from simplified designs that are both initially less expensive to produce and lighter, thereby, cheaper to launch.

  20. Focal therapy for prostate cancer. Alternative treatment.

    Science.gov (United States)

    Gómez-Veiga, F; Martínez-Breijo, S; Solsona-Narbón, E; Hernández, C; Ciudin, A; Ribal, M J; Dickinson, L; Moore, C; Ahmed, H; Rodríguez Antolín, A; Breda, A; Gaya, J; Portela-Pereira, P; Emberton, M

    2014-09-01

    The great controversy surrounding the treatment of localized prostate cancer is related with its possibilities of radical treatment or active surveillance. The objective of this paper is to analyze the rationale selection among current focal therapy modalities regarding tumor and patient selection. Current articles about advantages and disadvantages on the treatment of localized prostate cancer as well as information about focal therapy regarding tumour selection, characteristics and indications cited in MEDLINE search were reviewed. Focal therapy standardized criteria must be: low risk tumors, PSA15. Focal therapy is an alternative for localized prostate cancer treatment. However, some aspects of their diagnosis and selection criteria should be defined by prospective studies which should provide knowledge about the indication for focal therapy. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  1. Treatment of focal epithelial hyperplasia with trichloroacetic acid

    OpenAIRE

    Harris Ricardo, J.; M Carmona Lorduy; Díaz Caballero, A.

    2012-01-01

    Focal epithelial hyperplasia is a benign disease which has a chronic course that manifests as characteristic multiple small papules or nodules. They are predominantly found in the oral mucosa, gingiva and tongue. The surface of the lesions is smooth and it varies in size. It is an asymptomatic disease caused by human papillomavirus, affecting mainly children and adolescents. In this report, we describe four cases referred to the Stomatology and Oral Surgery Department of the Faculty of Dentis...

  2. Maintenance energy requirements of odor detection, explosive detection and human detection working dogs

    Directory of Open Access Journals (Sweden)

    Rebecca A. Mullis

    2015-02-01

    Full Text Available Despite their important role in security, little is known about the energy requirements of working dogs such as odor, explosive and human detection dogs. Previous researchers have evaluated the energy requirements of individual canine breeds as well as dogs in exercise roles such as sprint racing. This study is the first to evaluate the energy requirements of working dogs trained in odor, explosive and human detection. This retrospective study evaluated twenty adult dogs who maintained consistent body weights over a six month period. During this time, the average energy consumption was $136\\pm 38~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$136±38kcal⋅BWkg0.75 or two times the calculated resting energy requirement ($\\mathrm{RER}=70~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$RER=70kcal⋅BWkg0.75. No statistical differences were found between breeds, age or sex, but a statistically significant association (p = 0.0033, R-square = 0.0854 was seen between the number of searches a dog performs and their energy requirement. Based on this study’s population, it appears that working dogs have maintenance energy requirements similar to the 1974 National Research Council’s (NRC maintenance energy requirement of $132~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$132kcal⋅BWkg0.75 (National Research Council (NRC, 1974 and the $139\\pm 42~\\mathrm{kcal}\\cdot {\\mathrm{BW}}_{\\mathrm{kg}}^{0.75}$139±42kcal⋅BWkg0.75 reported for young laboratory beagles (Rainbird & Kienzle, 1990. Additional research is needed to determine if these data can be applied to all odor, explosive and human detection dogs and to determine if other types of working dogs (tracking, search and rescue etc. have similar energy requirements.

  3. The Nuremberg Code subverts human health and safety by requiring animal modeling

    Science.gov (United States)

    2012-01-01

    Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. Summary We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented. PMID:22769234

  4. The Nuremberg Code subverts human health and safety by requiring animal modeling.

    Science.gov (United States)

    Greek, Ray; Pippus, Annalea; Hansen, Lawrence A

    2012-07-08

    The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.

  5. Precise annealing of focal plane arrays for optical detection

    Energy Technology Data Exchange (ETDEWEB)

    Bender, Daniel A.

    2017-10-17

    Precise annealing of identified defective regions of a Focal Plane Array ("FPA") (e.g., exclusive of non-defective regions of the FPA) facilitates removal of defects from an FPA that has been hybridized and/or packaged with readout electronics. Radiation is optionally applied under operating conditions, such as under cryogenic temperatures, such that performance of an FPA can be evaluated before, during, and after annealing without requiring thermal cycling.

  6. Right focal boundary value problems for difference equations

    Directory of Open Access Journals (Sweden)

    Johnny Henderson

    2010-01-01

    Full Text Available An application is made of a new Avery et al. fixed point theorem of compression and expansion functional type in the spirit of the original fixed point work of Leggett and Williams, to obtain positive solutions of the second order right focal discrete boundary value problem. In the application of the fixed point theorem, neither the entire lower nor entire upper boundary is required to be mapped inward or outward. A nontrivial example is also provided.

  7. Vitamin D Signaling in the Bovine Immune System: A Model for Understanding Human Vitamin D Requirements

    Directory of Open Access Journals (Sweden)

    Corwin D. Nelson

    2012-03-01

    Full Text Available The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance.

  8. Landscape requirements of a primate population in a human-dominated environment

    Directory of Open Access Journals (Sweden)

    Hoffman Tali S

    2012-01-01

    Full Text Available Abstract Introduction As urban and rural land development become widespread features of the global landscape so an understanding of the landscape requirements of displaced and isolated wildlife species becomes increasingly important for conservation planning. In the Cape Peninsula, South Africa, rapid human population growth, and the associated urban and rural land transformation, threatens the sustainability of the local chacma baboon population. Here we analyse spatial data collected from nine of the 12 extant troops to determine their population-level landscape requirements. We use hurdle models to ascertain the key landscape features influencing baboon occurrence and abundance patterns on two hierarchical spatial scales. Results Both spatial scales produced similar results that were ecologically reliable and interpretable. The models indicated that baboons were more likely to occur, and be more abundant, at low altitudes, on steep slopes and in human-modified habitats. The combination of these landscape variables provides baboons with access to the best quality natural and anthropogenic food sources in close proximity to one another and suitable sleeping sites. Surface water did not emerge as an influential landscape feature presumably as the area is not water stressed. Conclusions The model results indicate that land development in the Cape Peninsula has pushed baboons into increasingly marginal natural habitat while simultaneously providing them with predictable and easily accessible food sources in human-modified habitats. The resultant spatial competition between humans and baboons explains the high levels of human-baboon conflict and further erosion of the remaining land fragments is predicted to exacerbate competition. This study demonstrates how the quantification of animal landscape requirements can provide a mechanism for identifying priority conservation areas at the human-wildlife interface.

  9. Technology and Research Requirements for Combating Human Trafficking: Enhancing Communication, Analysis, Reporting, and Information Sharing

    Energy Technology Data Exchange (ETDEWEB)

    Kreyling, Sean J.; West, Curtis L.; Olson, Jarrod

    2011-03-17

    DHS’ Science & Technology Directorate directed PNNL to conduct an exploratory study on the domain of human trafficking in the Pacific Northwest in order to examine and identify technology and research requirements for enhancing communication, analysis, reporting, and information sharing – activities that directly support efforts to track, identify, deter, and prosecute human trafficking – including identification of potential national threats from smuggling and trafficking networks. This effort was conducted under the Knowledge Management Technologies Portfolio as part of the Integrated Federal, State, and Local/Regional Information Sharing (RISC) and Collaboration Program.

  10. Focal Points on Constructing News Stories

    Directory of Open Access Journals (Sweden)

    Elena Yuryevna Ilyinova

    2015-11-01

    Full Text Available The issues stated in the article line with the current interest to pragmatic value of news releases in modern media. The news is thought to be a verbalized focal reflection of some event that was chosen by media professionals for setting the current information agenda. Having generated the opinions on the newsworthiness the authors present a set of values that may be used for measurement of relevance and clarity of an event reflection in the news content with frequency, clarity, predictability, unexpectedness, amplitude, cultural proximity, elite nations, elite people, personification, negativity among them. The novelty of the research is that the newsworthiness is checked with the focus to lexical (thematic representation of the news in a diachronic approach: the empirical base of the research was taken from the archives of UK national and local media sources (18–20th cent. and implied comparison of lexical means that reflected an event itself and some values of human interest potential in the news stories written in defined periods. The article states the trend for dynamics in the way the event is reflected in the news stories – the information core of the story is merged with detailed reporting parts, and their content is conditioned by social and moral values.

  11. Focal therapy for prostate cancer: pathologic basis.

    Science.gov (United States)

    Mouraviev, Vladimir; Madden, John F

    2009-03-01

    To summarize pathologic features of low-volume, low-risk prostate cancer relevant to the development of patient selection criteria and treatment strategies for focal therapy of prostate cancer, as an alternative to whole-gland radical treatments. Prostate cancer characteristically presents as a multifocal lesion within the prostate gland. Diagnosis of prostate cancer at an early stage has led to a recognition of subsets of patients whose disease may be either unifocal or multifocal, yet is unilateral or of small aggregate volume. Parenchyma-preserving partial-gland ablation may become a potentially feasible option in future treatment of early-stage, localized prostate cancer. Even for moderately selective protocols such as hemiablation, however, appropriate patient selection will be challenging because of the imperfect correlation among unifocality, unilaterality, low volume and low grade. Extended multicore biopsy protocols under imaging guidance may be required to map the tumor process with sufficient accuracy for treatment planning. Further research in molecular determinants and more precise imaging techniques should be pursued to optimize selection and treatment.

  12. Pathogenetic mechanisms of focal cortical dysplasia.

    Science.gov (United States)

    Marin-Valencia, Isaac; Guerrini, Renzo; Gleeson, Joseph G

    2014-07-01

    Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable epilepsy in children, and is one of the leading conditions requiring epilepsy surgery. Despite recent advances in the cellular and molecular biology of these conditions, the pathogenetic mechanisms of FCDs remain largely unknown. The purpose if this work is to review the molecular underpinnings of FCDs and to highlight potential therapeutic targets. A systematic review of the literature regarding the histologic, molecular, and electrophysiologic aspects of FCDs was conducted. Disruption of the mammalian target of rapamycin (mTOR) signaling comprises a common pathway underlying the structural and electrical disturbances of some FCDs. Other mechanisms such as viral infections, prematurity, head trauma, and brain tumors are also posited. mTOR inhibitors (i.e., rapamycin) have shown positive results on seizure management in animal models and in a small cohort of patients with FCD. Encouraging progress has been achieved on the molecular and electrophysiologic basis of constitutive cells in the dysplastic tissue. Despite the promising results of mTOR inhibitors, large-scale randomized trials are in need to evaluate their efficacy and side effects, along with additional mechanistic studies for the development of novel, molecular-based diagnostic and therapeutic approaches. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  13. Design of admission medication reconciliation technology: a human factors approach to requirements and prototyping.

    Science.gov (United States)

    Lesselroth, Blake J; Adams, Kathleen; Tallett, Stephanie; Wood, Scott D; Keeling, Amy; Cheng, Karen; Church, Victoria L; Felder, Robert; Tran, Hanna

    2013-01-01

    Our objectives were to (1) develop an in-depth understanding of the workflow and information flow in medication reconciliation, and (2) design medication reconciliation support technology using a combination of rapid-cycle prototyping and human-centered design. Although medication reconciliation is a national patient safety goal, limitations both of physical environment and in workflow can make it challenging to implement durable systems. We used several human factors techniques to gather requirements and develop a new process to collect a medication history at hospital admission. We completed an ethnography and time and motion analysis of pharmacists in order to illustrate the processes used to reconcile medications. We then used the requirements to design prototype multimedia software for collecting a bedside medication history. We observed how pharmacists incorporated the technology into their physical environment and documented usability issues. Admissions occurred in three phases: (1) list compilation, (2) order processing, and (3) team coordination. Current medication reconciliation processes at the hospital average 19 minutes to complete and do not include a bedside interview. Use of our technology during a bedside interview required an average of 29 minutes. The software represents a viable proof-of-concept to automate parts of history collection and enhance patient communication. However, we discovered several usability issues that require attention. We designed a patient-centered technology to enhance how clinicians collect a patient's medication history. By using multiple human factors methods, our research team identified system themes and design constraints that influence the quality of the medication reconciliation process and implementation effectiveness of new technology. Evidence-based design, human factors, patient-centered care, safety, technology.

  14. Treatment of focal epithelial hyperplasia with trichloroacetic acid

    Directory of Open Access Journals (Sweden)

    J Harris Ricardo

    2012-12-01

    Full Text Available Focal epithelial hyperplasia is a benign disease which has a chronic course that manifests as characteristic multiple small papules or nodules. They are predominantly found in the oral mucosa, gingiva and tongue. The surface of the lesions is smooth and it varies in size. It is an asymptomatic disease caused by human papillomavirus, affecting mainly children and adolescents. In this report, we describe four cases referred to the Stomatology and Oral Surgery Department of the Faculty of Dentistry, Cartagena University with a diagnosis of focal epithelial hyperplasia. Clinical features and histopathological characteristics of the patients were recorded. We also describe the properties and advantages of trichloroacetic acid as a therapeutic method.

  15. Focal Adhesion Kinases in Adhesion Structures and Disease

    Directory of Open Access Journals (Sweden)

    Pierre P. Eleniste

    2012-01-01

    Full Text Available Cell adhesion to the extracellular matrix (ECM is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases.

  16. Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits

    Science.gov (United States)

    Robinson, James E.; Hastie, Kathryn M.; Cross, Robert W.; Yenni, Rachael E.; Elliott, Deborah H.; Rouelle, Julie A.; Kannadka, Chandrika B.; Smira, Ashley A.; Garry, Courtney E.; Bradley, Benjamin T.; Yu, Haini; Shaffer, Jeffrey G.; Boisen, Matt L.; Hartnett, Jessica N.; Zandonatti, Michelle A.; Rowland, Megan M.; Heinrich, Megan L.; Martínez-Sobrido, Luis; Cheng, Benson; de la Torre, Juan C.; Andersen, Kristian G.; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Gbakie, Michael; Kanneh, Lansana; Koroma, Veronica J.; Fonnie, Richard; Jalloh, Simbirie C.; Kargbo, Brima; Vandi, Mohamed A.; Gbetuwa, Momoh; Ikponmwosa, Odia; Asogun, Danny A.; Okokhere, Peter O.; Follarin, Onikepe A.; Schieffelin, John S.; Pitts, Kelly R.; Geisbert, Joan B.; Kulakoski, Peter C.; Wilson, Russell B.; Happi, Christian T.; Sabeti, Pardis C.; Gevao, Sahr M.; Khan, S. Humarr; Grant, Donald S.; Geisbert, Thomas W.; Saphire, Erica Ollmann; Branco, Luis M.; Garry, Robert F.

    2016-01-01

    Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design. PMID:27161536

  17. Water and Energy Dietary Requirements and Endocrinology of Human Space Flight

    Science.gov (United States)

    Lane, Helen W.; Feeback, Daniel L.

    2002-01-01

    Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.

  18. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis

    DEFF Research Database (Denmark)

    Kain, R.; Exner, M.; Brandes, R.

    2008-01-01

    of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P41-49) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with Ill develop pauci-immune FNGN and also......Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present...

  19. Large Format Uncooled Focal Plane Array Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Uncooled focal plane arrays have improved dramatically and array sizes of 320x240 elements in a 50-?m pitch are commercially available at affordable cost. Black...

  20. Large Focal Plane Arrays for Future Missions

    OpenAIRE

    Scowen, Paul A.; Nikzad, Shouleh; Hoenk, Michael; Gontijo, Ivair; Shapiro, Andrew; Greer, Frank; Jones, Todd; Seshadri, Suresh; Jacquot, Blake; Monacos, Steve; Lisman, Doug; Dickie, Matthew; Blacksberg, Jordana

    2009-01-01

    We outline the challenges associated with the development and construction of large focal plane arrays for use both on the ground and in space. Using lessons learned from existing JPL-led and ASU/JPL partnership efforts to develop technology for, and design such arrays and imagers for large focal planes, we enumerate here the remaining problems that need to be solved to make such a venture viable. Technologies we consider vital for further development include: (1) architectures, processes, ci...

  1. Hyperinsulinism: molecular aetiology of focal disease.

    Science.gov (United States)

    Ryan, F; Devaney, D; Joyce, C; Nestorowicz, A; Permutt, M A; Glaser, B; Barton, D E; Thornton, P S

    1998-11-01

    Persistent hypoglycaemia in infancy is most commonly caused by hyperinsulinism. A case is reported of the somatic loss of the maternal 11p in an insulin secreting focal adenoma in association with a germline SUR-1 mutation on the paternal allele in a baby boy with hyperinsulinism diagnosed at 49 days old. A reduction to homozygosity of an SUR-1 mutation is proposed as a critical part of the cause of focal hyperinsulinism.

  2. Focal Adhesion Kinase: Insight into Molecular Roles and Functions in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Nadia Panera

    2017-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer-related death worldwide. Due to the high incidence of post-operative recurrence after current treatments, the identification of new and more effective drugs is required. In previous years, new targetable genes/pathways involved in HCC pathogenesis have been discovered through the help of high-throughput sequencing technologies. Mutations in TP53 and β-catenin genes are the most frequent aberrations in HCC. However, approaches able to reverse the effect of these mutations might be unpredictable. In fact, if the reactivation of proteins, such as p53 in tumours, holds great promise as anticancer therapy, there are studies arguing that chronic activation of these types of molecules may be deleterious. Thus, recently the efforts on potential targets have focused on actionable mutations, such as those occurring in the gene encoding for focal adhesion kinase (FAK. This tyrosine kinase, localized to cellular focal contacts, is over-expressed in a variety of human tumours, including HCC. Moreover, several lines of evidence demonstrated that FAK depletion or inhibition impair in vitro and in vivo HCC growth and metastasis. Here, we provide an overview of FAK expression and activity in the context of tumour biology, discussing the current evidence of its connection with HCC development and progression.

  3. Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Punsiri M Colonne

    2016-10-01

    Full Text Available Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections. Humans are typically infected by aerosol-mediated transmission, and C. burnetii initially targets alveolar macrophages wherein the pathogen replicates in a phagolysosome-like niche known as the parasitophorous vacuole (PV. C. burnetii manipulates host cAMP-dependent protein kinase (PKA signaling to promote PV formation, cell survival, and bacterial replication. In this study, we identified the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP as a PKA substrate that is increasingly phosphorylated at S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells and primary human alveolar macrophages, and this event required the Cα subunit of PKA. VASP phosphorylation also required bacterial protein synthesis and secretion of effector proteins via a type IV secretion system, indicating the pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation and intracellular bacterial replication required VASP activity, as siRNA-mediated depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic expression of a phospho-mimetic VASP (S239E mutant protein prevented optimal PV formation, whereas VASP (S157E mutant expression had no effect. VASP (S239E expression also prevented trafficking of bead-containing phagosomes to the PV, indicating proper VASP activity is critical for heterotypic fusion events that control PV expansion in macrophages. Finally, expression of dominant negative VASP (S157A in C. burnetii-infected cells impaired PV formation, confirming importance of the protein for proper infection. This study provides the first evidence of VASP manipulation by an intravacuolar bacterial pathogen via activation of PKA

  4. Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages

    Science.gov (United States)

    Colonne, Punsiri M.; Winchell, Caylin G.; Graham, Joseph G.; Onyilagha, Frances I.; MacDonald, Laura J.; Doeppler, Heike R.; Storz, Peter; Kurten, Richard C.; Beare, Paul A.; Voth, Daniel E.

    2016-01-01

    Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections. Humans are typically infected by aerosol-mediated transmission, and C. burnetii initially targets alveolar macrophages wherein the pathogen replicates in a phagolysosome-like niche known as the parasitophorous vacuole (PV). C. burnetii manipulates host cAMP-dependent protein kinase (PKA) signaling to promote PV formation, cell survival, and bacterial replication. In this study, we identified the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) as a PKA substrate that is increasingly phosphorylated at S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells and primary human alveolar macrophages, and this event required the Cα subunit of PKA. VASP phosphorylation also required bacterial protein synthesis and secretion of effector proteins via a type IV secretion system, indicating the pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation and intracellular bacterial replication required VASP activity, as siRNA-mediated depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic expression of a phospho-mimetic VASP (S239E) mutant protein prevented optimal PV formation, whereas VASP (S157E) mutant expression had no effect. VASP (S239E) expression also prevented trafficking of bead-containing phagosomes to the PV, indicating proper VASP activity is critical for heterotypic fusion events that control PV expansion in macrophages. Finally, expression of dominant negative VASP (S157A) in C. burnetii-infected cells impaired PV formation, confirming importance of the protein for proper infection. This study provides the first evidence of VASP manipulation by an intravacuolar bacterial pathogen via activation of PKA in human

  5. Sighting optics including an optical element having a first focal length and a second focal length

    Science.gov (United States)

    Crandall, David Lynn [Idaho Falls, ID

    2011-08-01

    One embodiment of sighting optics according to the teachings provided herein may include a front sight and a rear sight positioned in spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus, for a user, images of the front sight and the target.

  6. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Magaldi, Thomas G.; Almstead, Laura L. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Bellone, Stefania [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Prevatt, Edward G. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Santin, Alessandro D. [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States); DiMaio, Daniel, E-mail: daniel.dimaio@yale.edu [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Department of Therapeutic Radiology, Yale School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040 (United States); Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States)

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  7. Natural-focal diseases: mapping experience in Russia.

    Science.gov (United States)

    Malkhazova, Svetlana M; Mironova, Varvara A; Kotova, Tatiana V; Shartova, Natalia V; Orlov, Dmitry S

    2014-06-14

    Natural-focal diseases constitute a serious hazard for human health. Agents and vectors of such diseases belong to natural landscapes. The aim of this study is to identify the diversity and geography of natural-focal diseases in Russia and to develop cartographic approaches for their mapping, including mathematical-cartographical modeling. Russian medico-geographical mapping of natural-focal diseases is highly developed regionally and locally but extremely limited at the national level. To solve this problem, a scientific team of the Faculty of Geography at Lomonosov Moscow State University has developed and implemented a project of a medico-geographical Atlas of Russia "Natural-Focal Diseases". The mapping is based on medical statistics data. The Atlas contains a series of maps on disease incidence, long-term dynamics of disease morbidity, etc. In addition, other materials available to the authors were used: mapping of the natural environment, field data, archival materials, analyzed satellite images, etc. The maps are processed using ArcGIS (ESRI) software application. Different methods of rendering of mapped phenomena are used (geographical ranges, diagrams, choropleth maps etc.). A series of analytical, integrated, and synthetic maps shows disease incidence in the population at both the national and regional levels for the last 15 years. Maps of the mean annual morbidity of certain infections and maps of morbidity dynamics and nosological profiles allow for a detailed analysis of the situation for each of 83 administrative units of the Russian Federation. The degree of epidemic hazard in Russia by natural-focal diseases is reflected in a synthetic medico-geographical map that shows the degree of epidemic risks due to such diseases in Russia and allows one to estimate the risk of disease manifestation in a given region. This is the first attempt at aggregation and public presentation of diverse and multifaceted information about natural-focal diseases in Russia

  8. Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens.

    Science.gov (United States)

    Nakamura, Junko; Shigematsu, Satoshi; Yamauchi, Keishi; Takeda, Teiji; Yamazaki, Masanori; Kakizawa, Tomoko; Hashizume, Kiyoshi

    2008-10-03

    Migration and tube formation of endothelial cells are important in angiogenesis and require a coordinated response to the extra-cellular matrix (ECM) and growth factor. Since focal adhesion kinase (FAK) integrates signals from both ECM and growth factor, we investigated its role in angiogenesis. Type I and II collagens are fibril-forming collagens and stimulate human umbilical vein endothelial cells (HUVECs) to form tube structure. Although knockdown of FAK restrained cell motility and resulted in inhibition of tube formation, FAK degradation and tube formation occurred simultaneously after incubation with fibril-forming collagens. The compensation for the FAK degradation by a calpain inhibitor or transient over-expression of FAK resulted in disturbance of tube formation. These phenomena are specific to fibril-forming collagens and mediated via alpha2beta1 integrin. In conclusion, our data indicate that FAK is functioning in cell migration, but fibril-forming collagen-induced FAK degradation is necessary for endothelial tube formation.

  9. Neurotrophic requirements of human motor neurons defined using amplified and purified stem cell-derived cultures.

    Directory of Open Access Journals (Sweden)

    Nuno Jorge Lamas

    Full Text Available Human motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC(50 1-2 pM. The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening.

  10. The human rights context for ethical requirements for involving people with intellectual disability in medical research.

    Science.gov (United States)

    Iacono, T; Carling-Jenkins, R

    2012-11-01

    The history of ethical guidelines addresses protection of human rights in the face of violations. Examples of such violations in research involving people with intellectual disabilities (ID) abound. We explore this history in an effort to understand the apparently stringent criteria for the inclusion of people with ID in research, and differences between medical and other research within a single jurisdiction. The history of the Helsinki Declaration and informed consent within medical research, and high-profile examples of ethical misconduct involving people with ID and other groups are reviewed. The UN Convention on the Rights of Persons with Disabilities is then examined for its research implications. This background is used to examine a current anomaly within an Australian context for the inclusion of people with ID without decisional capacity in medical versus other types of research. Ethical guidelines have often failed to protect the human rights of people with ID and other vulnerable groups. Contrasting requirements within an Australian jurisdiction for medical and other research would seem to have originated in early deference to medical authority for making decisions on behalf of patients. Stringent ethical requirements are likely to continue to challenge researchers in ID. A human rights perspective provides a framework for engaging both researchers and vulnerable participant groups. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

  11. Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration.

    Science.gov (United States)

    Mendoza, Pablo A; Silva, Patricio; Díaz, Jorge; Arriagada, Cecilia; Canales, Jimena; Cerda, Oscar; Torres, Vicente A

    2017-11-03

    The early endosome protein Rab5 was recently shown to promote cell migration by enhancing focal adhesion disassembly through mechanisms that remain elusive. Focal adhesion disassembly is associated to proteolysis of talin, in a process that requires calpain2. Since calpain2 has been found at vesicles and endosomal compartments, we hypothesized that Rab5 stimulates calpain2 activity, leading to enhanced focal adhesion disassembly in migrating cells. We observed that calpain2 co-localizes with EEA1-positive early endosomes and co-immunoprecipitates with EEA1 and Rab5 in A549 lung carcinoma cells undergoing spreading, whereas Rab5 knock-down decreased the accumulation of calpain2 at early endosomal-enriched fractions. In addition, Rab5 silencing decreased calpain2 activity, as shown by cleavage of the fluorogenic substrate tBOC-LM-CMAC and the endogenous substrate talin. Accordingly, Rab5 promoted focal adhesion disassembly in a calpain2-dependent manner, as expression of GFP-Rab5 accelerated focal adhesion disassembly in nocodazole-synchronized cells, whereas pharmacological inhibition of calpain2 with N-acetyl-Leu-Leu-Met prevented both focal adhesion disassembly and cell migration induced by Rab5. In summary, these data uncover Rab5 as a novel regulator of calpain2 activity and focal adhesion proteolysis leading to cell migration.

  12. [MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy].

    Science.gov (United States)

    Franz, T; von Hardenberg, J; Blana, A; Cash, H; Baumunk, D; Salomon, G; Hadaschik, B; Henkel, T; Herrmann, J; Kahmann, F; Köhrmann, K-U; Köllermann, J; Kruck, S; Liehr, U-B; Machtens, S; Peters, I; Radtke, J P; Roosen, A; Schlemmer, H-P; Sentker, L; Wendler, J J; Witzsch, U; Stolzenburg, J-U; Schostak, M; Ganzer, R

    2017-02-01

    Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

  13. Human Cells Require Non-stop Ribosome Rescue Activity in Mitochondria.

    Science.gov (United States)

    Feaga, Heather A; Quickel, Michael D; Hankey-Giblin, Pamela A; Keiler, Kenneth C

    2016-03-01

    Bacteria use trans-translation and the alternative rescue factors ArfA (P36675) and ArfB (Q9A8Y3) to hydrolyze peptidyl-tRNA on ribosomes that stall near the 3' end of an mRNA during protein synthesis. The eukaryotic protein ICT1 (Q14197) is homologous to ArfB. In vitro ribosome rescue assays of human ICT1 and Caulobacter crescentus ArfB showed that these proteins have the same activity and substrate specificity. Both ArfB and ICT1 hydrolyze peptidyl-tRNA on nonstop ribosomes or ribosomes stalled with ≤6 nucleotides extending past the A site, but are unable to hydrolyze peptidyl-tRNA when the mRNA extends ≥14 nucleotides past the A site. ICT1 provided sufficient ribosome rescue activity to support viability in C. crescentus cells that lacked both trans-translation and ArfB. Likewise, expression of ArfB protected human cells from death when ICT1 was silenced with siRNA. These data indicate that ArfB and ICT1 are functionally interchangeable, and demonstrate that ICT1 is a ribosome rescue factor. Because ICT1 is essential in human cells, these results suggest that ribosome rescue activity in mitochondria is required in humans.

  14. Human-computer interaction requirements for abnormal situation management in industrial processes

    Energy Technology Data Exchange (ETDEWEB)

    Soken, N.; Bullemer, P.; Ramanathan, P.; Reinhart, W. [Honeywell Inc., Minneapolis, MN (United States). Honeywell Technology Center

    1995-10-01

    Honeywell is leading a multiyear effort to identify the causes of and propose solutions for abnormal situations in industrial processes. The authors define abnormal situations as those that necessitate human intervention because the automated distributed control system (DCS) cannot maintain the plant in an appropriate operating state. These situations are clearly of concern in the process industry because of their impact on revenues, human safety, and the environment. Interactions between the DCS and operating personnel are critical to mitigating abnormal situations in chemical plants. With the collaboration of major petrochemical and oil refining industries, Honeywell conducted on-site evaluations of the operating environments of various types of processes. Through this effort they identified process, equipment, people, and work context factors that contribute to abnormal situations. This paper describes human-computer interaction solution requirements based on the on-site plant evaluations. The results are discussed in terms of improvements to human-computer interactions and user interfaces and enhancements to conventional computer-based DCSs.

  15. Automated work packages architecture: An initial set of human factors and instrumentation and controls requirements

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Oxstrand, Johanna H. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Le Blanc, Katya L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-09-01

    The work management process in current fleets of national nuclear power plants is so highly dependent on large technical staffs and quality of work instruction, i.e., paper-based, that this puts nuclear energy at somewhat of a long-term economic disadvantage and increase the possibility of human errors. Technologies like mobile portable devices and computer-based procedures can play a key role in improving the plant work management process, thereby increasing productivity and decreasing cost. Automated work packages are a fundamentally an enabling technology for improving worker productivity and human performance in nuclear power plants work activities because virtually every plant work activity is accomplished using some form of a work package. As part of this year’s research effort, automated work packages architecture is identified and an initial set of requirements identified, that are essential and necessary for implementation of automated work packages in nuclear power plants.

  16. Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia.

    Science.gov (United States)

    Fuertinger, Stefan; Simonyan, Kristina

    2017-08-02

    Isolated focal dystonia is a debilitating movement disorder of unknown pathophysiology. Early studies in focal dystonias have pointed to segregated changes in brain activity and connectivity. Only recently has the notion that dystonia pathophysiology may lie in abnormalities of large-scale brain networks appeared in the literature. Here, we outline a novel concept of functional connectome-wide alterations that are linked to dystonia phenotype and genotype. Using a neural community detection strategy and graph theoretical analysis of functional MRI data in human patients with the laryngeal form of dystonia (LD) and healthy controls (both males and females), we identified an abnormally widespread hub formation in LD, which particularly affected the primary sensorimotor and parietal cortices and thalamus. Left thalamic regions formed a delineated functional community that highlighted differences in network topology between LD patients with and without family history of dystonia. Conversely, marked differences in the topological organization of parietal regions were found between phenotypically different forms of LD. The interface between sporadic genotype and adductor phenotype of LD yielded four functional communities that were primarily governed by intramodular hub regions. Conversely, the interface between familial genotype and abductor phenotype was associated with numerous long-range hub nodes and an abnormal integration of left thalamus and basal ganglia. Our findings provide the first comprehensive atlas of functional topology across different phenotypes and genotypes of focal dystonia. As such, this study constitutes an important step toward defining dystonia as a large-scale network disorder, understanding its causative pathophysiology, and identifying disorder-specific markers.SIGNIFICANCE STATEMENT The architecture of the functional connectome in focal dystonia was analyzed in a large population of patients with laryngeal dystonia. Breaking with the

  17. Human factors requirements for telerobotic command and control: The European Space Agency experimental programme

    Science.gov (United States)

    Stone, Robert J.

    1991-01-01

    Space Telerobotics research, performed under contract to the European Space Agency (ESA), concerning the execution of human factors experiments, and ultimately leading to the development of a telerobotics test bed, has been carried out since 1985 by a British Consortium consisting of British Aerospace, the United Kingdom Atomic Energy Authority and, more recently, the UK National Advanced Robotics Research Centre. The principal aim of the first study of the series was to derive preliminary requirements for a teleoperation servicing system, with reference to two mission model scenarios. The first scenario introduced the problem of communications time delays, and their likely effect on the ground-based operator in control of a manipulator system on board an unmanned servicing vehicle in Low Earth Orbit. In the second scenario, the operator was located on the NASA Orbiter aft flight deck, supervising the control of a prototype manipulator in the 'servicing' of an experimental payload in the cargo bay area. Human factors analyses centered on defining the requirements for the teleoperator workstation, such as identifying basic ergonomic requirements for workstation and panel layouts, defining teleoperation strategies, developing alphanumeric and graphic screen formats for the supervision or direct control of the manipulator, and the potential applications of expert system technology. The second study for ESA involved an experimental appraisal of some of the important issues highlighted in the first study, for which relevant human factors data did not exist. Of central importance during the second study was the issue of communications time delays and their effect on the manual control of a teleoperated manipulator from a ground-based command and control station.

  18. I Focalize, You Focalize, We All Focalize Together: Audience Participation in Persepolis

    Directory of Open Access Journals (Sweden)

    Lizzie Nixon

    2010-06-01

    Full Text Available

    Abstract (E: This article combines theories of cognition and empathy with focalization theory to examine how and why different forms of audience engagement in fictional worlds are cued. The article argues that critics should examine the differences between engagement that encourages audiences to apply their own frames to the world presented and type engagement cued by means of point-of-view shots and close-ups of facial expressions.

    Abstract (F: Cet article combine les théories de la cognition et de l’empathie avec la théorie de la focalisation afin d’analyser comment et pourquoi certaines œuvres construisent la manière dont le public est invité à s’investir dans des mondes fictionnels. Il défend l

  19. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2003-12-15

    Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review.

  20. Focal fatty infiltra- tion and focal fatty sparing of the liver

    African Journals Online (AJOL)

    Enrique

    gations and liver biopsies can be avoided. Introduction. Focal fatty infiltration of the liver is caused by focal ... invasive procedures such as biopsies, and further anxiety on the part of the patient. This diagnostic problem ... subsequently found to have type 2 diabetes, and her pain settled on oral hypoglycaemic agents. Case 2.

  1. Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis.

    Science.gov (United States)

    Miller, Matthew James; McGuire, Kerry M; Feigh, Karen M

    2017-06-01

    The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity. The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design.

  2. Human resources requirements for highly active antiretroviral therapy scale-up in Malawi

    Directory of Open Access Journals (Sweden)

    Rudatsikira Emmanuel

    2007-12-01

    Full Text Available Abstract Background Twelve percent of the adult population in Malawi is estimated to be HIV infected. About 15% to 20% of these are in need of life saving antiretroviral therapy. The country has a public sector-led antiretroviral treatment program both in the private and public health sectors. Estimation of the clinical human resources needs is required to inform the planning and distribution of health professionals. Methods We obtained data on the total number of patients on highly active antiretroviral treatment program from the Malawi National AIDS Commission and Ministry of Health, HIV Unit, and the number of registered health professionals from the relevant regulatory bodies. We also estimated number of health professionals required to deliver highly active antiretroviral therapy (HAART using estimates of human resources from the literature. We also obtained data from the Ministry of Health on the actual number of nurses, clinical officers and medical doctors providing services in HAART clinics. We then made comparisons between the human resources situation on the ground and the theoretical estimates based on explicit assumptions. Results There were 610 clinicians (396 clinical officers and 214 physicians, 44 pharmacists and 98 pharmacy technicians and 7264 nurses registered in Malawi. At the end of March 2007 there were 85 clinical officer and physician full-time equivalents (FTEs and 91 nurse FTEs providing HAART to 95,674 patients. The human resources used for the delivery of HAART comprised 13.9% of all clinical officers and physicians and 1.1% of all nurses. Using the estimated numbers of health professionals from the literature required 15.7–31.4% of all physicians and clinical officers, 66.5–199.3% of all pharmacists and pharmacy technicians and 2.6 to 9.2% of all the available nurses. To provide HAART to all the 170,000 HIV infected persons estimated as clinically eligible would require 4.7% to 16.4% of the total number of

  3. 3D Visualization of Earthquake Focal Mechanisms Using ArcScene

    Science.gov (United States)

    Labay, Keith A.; Haeussler, Peter J.

    2007-01-01

    We created a new tool, 3D Focal Mechanisms (3DFM), for viewing earthquake focal mechanism symbols three dimensionally. This tool operates within the Environmental Systems Research Institute (ESRI®) GIS software ArcScene® 9.x. The program requires as input a GIS point dataset of earthquake locations containing strike, dip, and rake values for a nodal plane of each earthquake. Other information, such as depth and magnitude of the earthquake, may also be included in the dataset. By default for each focal point, 3DFM will create a black and white sphere or “beach ball” that is oriented based on the strike, dip, and rake values. If depth values for each earthquake are included, the focal symbol will also be placed at its appropriate location beneath the Earth's surface.

  4. Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

    DEFF Research Database (Denmark)

    Bax, Daniel V; Mahalingam, Yashithra; Cain, Stuart

    2007-01-01

    We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated a......, and confirmed their role in focal adhesion formation. These integrin and syndecan adhesion motifs juxtaposed on fibrillin-1 are evolutionarily conserved and reminiscent of similar functional elements on fibronectin, highlighting their crucial functional importance....... a requirement for upstream domains for integrin-alpha(5)beta(1)-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding...

  5. Focal Cryoablation of Prostate: A Review

    Directory of Open Access Journals (Sweden)

    Duke K. Bahn

    2008-01-01

    Full Text Available Current treatment options for men with early localized prostate cancer are either some form of radical therapy or active surveillance. Radical therapy is usually associated with significant adverse effects that might jeopardize a man's quality of life. Some observers believe that PSA screening has resulted in the over diagnosis and over treatment of prostate cancer. Many men are being diagnosed with an early stage, small volume, unifocal or unilateral prostate cancer but are reluctant to accept watchful waiting or active surveillance. Focal cryoablation is the less than complete ablation of the gland with ice. Based on review of the limited amount of material available in the current literature, focal cryoablation can provide acceptable cancer control while preserving sexual potency and urinary continence. Focal cryoablation may fill a void in the therapeutic options available to patients with unifocal or unilateral prostate cancer who have a strong desire to maintain their quality of life.

  6. The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation.

    Science.gov (United States)

    Tang, Chieh-Ju C; Lin, Shin-Yi; Hsu, Wen-Bin; Lin, Yi-Nan; Wu, Chien-Ting; Lin, Yu-Chih; Chang, Ching-Wen; Wu, Kuo-Sheng; Tang, Tang K

    2011-10-21

    Centriole duplication involves the growth of a procentriole next to the parental centriole. Mutations in STIL and CPAP/CENPJ cause primary microcephaly (MCPH). Here, we show that human STIL has an asymmetric localization to the daughter centriole and is required for procentriole formation. STIL levels oscillate during the cell cycle. Interestingly, STIL interacts directly with CPAP and forms a complex with hSAS6. A natural mutation of CPAP (E1235V) that causes MCPH in humans leads to significantly lower binding to STIL. Overexpression of STIL induced the formation of multiple procentrioles around the parental centriole. STIL depletion inhibited normal centriole duplication, Plk4-induced centriole amplification, and CPAP-induced centriole elongation, and resulted in a failure to localize hSAS6 and CPAP to the base of the nascent procentriole. Furthermore, hSAS6 depletion hindered STIL targeting to the procentriole, implying that STIL and hSAS6 are mutually dependent for their centriolar localization. Together, our results indicate that the two MCPH-associated proteins STIL and CPAP interact with each other and are required for procentriole formation, implying a central role of centriole biogenesis in MCPH.

  7. Actinic Granuloma with Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ruedee Phasukthaworn

    2016-02-01

    Full Text Available Actinic granuloma is an uncommon granulomatous disease, characterized by annular erythematous plaque with central clearing predominately located on sun-damaged skin. The pathogenesis is not well understood, ultraviolet radiation is recognized as precipitating factor. We report a case of a 52-year-old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years. The clinical presentation and histopathologic findings support the diagnosis of actinic granuloma. During that period of time, she also developed focal segmental glomerulosclerosis. The association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies.

  8. Natural course of symptomatic focal choroidal excavation.

    Science.gov (United States)

    Pierro, Luisa; Casalino, Giuseppe; Introini, Ugo; Gagliardi, Marco; Sergenti, Jessica; Cascavilla, Maria Lucia; Bandello, Francesco

    2015-01-01

    A 32-year-old man was referred to the authors' department for nonspecified macular dystrophy with persistent metamorphopsia in the right eye diagnosed 10 years before and followed using optical coherence tomography. The patient underwent a comprehensive ocular examination, including multimodal imaging evaluation and electrofunctional testing. The diagnosis was consistent with nonconforming focal choroid excavation. Over 10 years, no complications occurred, visual acuity was stable, and optical coherence tomography showed no progression of the lesion during follow-up. In this case, nonconforming symptomatic focal choroid excavation was a nonprogressive condition with good long-term visual outcome. Copyright 2015, SLACK Incorporated.

  9. Ambroxol-induced focal epileptic seizure.

    Science.gov (United States)

    Lapenta, Leonardo; Morano, Alessandra; Fattouch, Jinane; Casciato, Sara; Fanella, Martina; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2014-01-01

    It is well known that in epileptic patients some compounds and different drugs used for the treatment of comorbidities can facilitate or provoke seizures, this evidence regarding a wide spectrum of pharmacological categories. The potential facilitating factors usually include direct toxic effects or pharmacological interactions of either active ingredients or excipients. We report the case of a patient with drug-resistant epilepsy who experienced focal epileptic seizures, easily and constantly reproducible, after each administration of a cough syrup. This is, to our knowledge, the first electroencephalogram-documented case of focal epileptic seizures induced by cough syrup containing ambroxol as active ingredient.

  10. DNA and Protein Requirements for Substrate Conformational Changes Necessary for Human Flap Endonuclease-1-catalyzed Reaction*

    Science.gov (United States)

    Algasaier, Sana I.; Exell, Jack C.; Bennet, Ian A.; Thompson, Mark J.; Gotham, Victoria J. B.; Shaw, Steven J.; Craggs, Timothy D.; Finger, L. David; Grasby, Jane A.

    2016-01-01

    Human flap endonuclease-1 (hFEN1) catalyzes the essential removal of single-stranded flaps arising at DNA junctions during replication and repair processes. hFEN1 biological function must be precisely controlled, and consequently, the protein relies on a combination of protein and substrate conformational changes as a prerequisite for reaction. These include substrate bending at the duplex-duplex junction and transfer of unpaired reacting duplex end into the active site. When present, 5′-flaps are thought to thread under the helical cap, limiting reaction to flaps with free 5′-termini in vivo. Here we monitored DNA bending by FRET and DNA unpairing using 2-aminopurine exciton pair CD to determine the DNA and protein requirements for these substrate conformational changes. Binding of DNA to hFEN1 in a bent conformation occurred independently of 5′-flap accommodation and did not require active site metal ions or the presence of conserved active site residues. More stringent requirements exist for transfer of the substrate to the active site. Placement of the scissile phosphate diester in the active site required the presence of divalent metal ions, a free 5′-flap (if present), a Watson-Crick base pair at the terminus of the reacting duplex, and the intact secondary structure of the enzyme helical cap. Optimal positioning of the scissile phosphate additionally required active site conserved residues Tyr40, Asp181, and Arg100 and a reacting duplex 5′-phosphate. These studies suggest a FEN1 reaction mechanism where junctions are bound and 5′-flaps are threaded (when present), and finally the substrate is transferred onto active site metals initiating cleavage. PMID:26884332

  11. [Regulatory requirements regarding cell-based medicinal products for human and veterinary use - a comparison].

    Science.gov (United States)

    Kuhlmann-Gottke, Johanna; Duchow, Karin

    2015-11-01

    At present, there is no separate regulatory framework for cell-based medicinal products (CBMP) for veterinary use at the European or German level. Current European and national regulations exclusively apply to the corresponding medicinal products for human use. An increasing number of requests for the regulatory classification of CBMP for veterinary use, such as allogeneic stem cell preparations and dendritic cell-based autologous tumour vaccines, and a rise in scientific advice for companies developing these products, illustrate the need for adequate legislation. Currently, advice is given and decisions are made on a case-by-case basis regarding the regulatory classification and authorisation requirements.Since some of the CBMP - in particular in the area of stem-cell products - are developed in parallel for human and veterinary use, there is an urgent need to create specific legal definitions, regulations, and guidelines for these complex innovative products in the veterinary sector as well. Otherwise, there is a risk that that the current legal grey area regarding veterinary medicinal products will impede therapeutic innovations in the long run. A harmonised EU-wide approach is desirable. Currently the European legislation on veterinary medicinal products is under revision. In this context, veterinary therapeutics based on allogeneic cells and tissues will be defined and regulated. Certainly, the legal framework does not have to be as comprehensive as for human CBMP; a leaner solution is conceivable, similar to the special provisions for advanced-therapy medicinal products laid down in the German Medicines Act.

  12. Capturing Safety Requirements to Enable Effective Task Allocation Between Humans and Automaton in Increasingly Autonomous Systems

    Science.gov (United States)

    Neogi, Natasha A.

    2016-01-01

    There is a current drive towards enabling the deployment of increasingly autonomous systems in the National Airspace System (NAS). However, shifting the traditional roles and responsibilities between humans and automation for safety critical tasks must be managed carefully, otherwise the current emergent safety properties of the NAS may be disrupted. In this paper, a verification activity to assess the emergent safety properties of a clearly defined, safety critical, operational scenario that possesses tasks that can be fluidly allocated between human and automated agents is conducted. Task allocation role sets were proposed for a human-automation team performing a contingency maneuver in a reduced crew context. A safety critical contingency procedure (engine out on takeoff) was modeled in the Soar cognitive architecture, then translated into the Hybrid Input Output formalism. Verification activities were then performed to determine whether or not the safety properties held over the increasingly autonomous system. The verification activities lead to the development of several key insights regarding the implicit assumptions on agent capability. It subsequently illustrated the usefulness of task annotations associated with specialized requirements (e.g., communication, timing etc.), and demonstrated the feasibility of this approach.

  13. Induction of cytotoxic granules in human memory CD8+ T cell subsets requires cell cycle progression.

    Science.gov (United States)

    Meng, Yuru; Harlin, Helena; O'Keefe, James P; Gajewski, Thomas F

    2006-08-01

    Memory CD8(+) T cell responses are thought to be more effective as a result of both a higher frequency of Ag-specific clones and more rapid execution of effector functions such as granule-mediated lysis. Murine models have indicated that memory CD8(+) T cells exhibit constitutive expression of perforin and can lyse targets directly ex vivo. However, the regulated expression of cytotoxic granules in human memory CD8(+) T cell subsets has been underexplored. Using intracellular flow cytometry, we observed that only a minor fraction of CD45RA(-)CD8(+) T cells, or of CD8(+) T cells reactive to EBV-HLA2 tetramer, expressed intracellular granzyme B (GrB). Induction of GrB-containing cytotoxic granules in both CD45RA(+) and CD45RA(-) cells was achieved by stimulation with anti-CD3/anti-CD28 mAb-coated beads, required at least 3 days, occurred after several rounds of cell division, and required cell cycle progression. The strongest GrB induction was seen in the CCR7(+) subpopulations, with poorest proliferation being observed in the CD45RA(-)CCR7(-) effector-memory pool. Our results indicate that, as with naive T cells, induction of cytotoxic granules in human Ag-experienced CD8(+) T cells requires time and cell division, arguing that the main numerical advantage of a memory T cell pool is a larger frequency of CTL precursors. The fact that granule induction can be achieved through TCR and CD28 ligation has implications for restoring lytic effector function in the context of antitumor immunity.

  14. Dot/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages

    Science.gov (United States)

    Beare, Paul A.; Gilk, Stacey D.; Larson, Charles L.; Hill, Joshua; Stead, Christopher M.; Omsland, Anders; Cockrell, Diane C.; Howe, Dale; Voth, Daniel E.; Heinzen, Robert A.

    2011-01-01

    ABSTRACT Central to Q fever pathogenesis is replication of the causative agent, Coxiella burnetii, within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear phagocytes. C. burnetii modulates PV biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a Dot/Icm type IVB secretion system (T4BSS). In this study, we utilized a C. burnetii strain carrying IcmD inactivated by the Himar1 transposon to investigate the requirements for Dot/Icm function in C. burnetii parasitism of human THP-1 macrophage-like cells. The icmD::Tn mutant failed to secrete characterized T4BSS substrates, a defect that correlated with deficient replication, PV development, and apoptosis protection. Restoration of type IVB secretion and intracellular growth of the icmD::Tn mutant required complementation with icmD, -J, and -B, indicating a polar effect of the transposon insertion on downstream dot/icm genes. Induction of icmDJB expression at 1 day postinfection resulted in C. burnetii replication and PV generation. Collectively, these data prove that T4BSS function is required for productive infection of human macrophages by C. burnetii. However, illustrating the metabolic flexibility of C. burnetti, the icmD::Tn mutant could replicate intracellularly when sequestered in a PV generated by wild-type bacteria, where Dot/Icm function is provided in trans, and within a phenotypically similar PV generated by the protozoan parasite Leishmania amazonensis, where host cells are devoid of Dot/Icm T4BSS effector proteins. PMID:21862628

  15. NEDD8-mediated neddylation is required for human endometrial stromal proliferation and decidualization.

    Science.gov (United States)

    Liao, Yixin; Jiang, Yaling; He, Hui; Ni, Hao; Tu, Zhaowei; Zhang, Shuang; Wang, Bingyan; Lou, Jiaoying; Quan, Song; Wang, Haibin

    2015-07-01

    knockdown p21 expression to test whether a clearance of p21 accumulation would correct the HESC defects from neddylation inhibition. We demonstrated that NEDD8 is ubiquitously expressed in human endometrium including luminal epithelium, glandular epithelium and the stromal cells during the menstrual cycle, as well as in the HESCs during proliferation and differentiation in culture. Employing multiple molecular, cellular and pharmacological approaches, we further observed that neddylation inhibition by MLN4924 significantly attenuates HESC proliferation (P-value endometrial epithelium, it is interesting to further study its potential role in stroma-epithelial interactions through isolating and culturing epithelial cells. p21 siRNA knockdown experiments revealed that there are differential molecular machineries, other than p21, that are subject to neddylation regulation during HESC proliferation compared with differentiation. This alternative mechanism warrants further investigation in future. Our findings add novel evidence showing, for what we believe the first time, that NEDD8-mediated neddylation is required for normal human endometrial functions, which raises the possibility of approaching the neddylation system for diagnosis and treatment of infertility in women. This work was supported in parts by the National Basic Research Program of China (2011CB944400 to H.W.) and the National Natural Science Foundation (81130009, 81330017 to H.W., 81170575 to S.Q. and 31471106 to S.Z.). The author declares that there is no conflict of interest. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. miRNA Signature and Dicer Requirement during Human Endometrial Stromal Decidualization In Vitro

    Science.gov (United States)

    Estella, Carlos; Herrer, Isabel; Moreno-Moya, Juan Manuel; Quiñonero, Alicia; Martínez, Sebastián; Pellicer, Antonio; Simón, Carlos

    2012-01-01

    Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs) decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human endometrial decidualization

  17. miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro.

    Directory of Open Access Journals (Sweden)

    Carlos Estella

    Full Text Available Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human

  18. Endogenous laminin is required for human airway smooth muscle cell maturation

    Directory of Open Access Journals (Sweden)

    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  19. Evidence that anandamide-signaling regulates human sperm functions required for fertilization.

    Science.gov (United States)

    Schuel, Herbert; Burkman, Lani J; Lippes, Jack; Crickard, Kent; Mahony, Mary C; Giuffrida, Andrea; Picone, Robert P; Makriyannis, Alexandros

    2002-11-01

    Ejaculated mammalian sperm require several hours exposure to secretions in female reproductive tracts, or incubation in appropriate culture medium in vitro, before acquiring the capacity to fertilize eggs. Arachidonylethanolamide (AEA), also known as anandamide, is a novel lipid-signal molecule that is an endogenous agonist (endocannabinoid) for cannabinoid receptors. We now report that AEA is present in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid analyzed by high-performance liquid chromatography/mass spectrometry. Sperm are sequentially exposed to these reproductive fluids as they move from the vagina to the site of fertilization in the oviduct. Specific binding of the potent cannabinoid agonist [(3)H]CP-55,940 to human sperm was saturable (K(D) 9.71 +/- 1.04 nM), suggesting that they express cannabinoid receptors. R-methanandamide [AM-356], a potent and metabolically stable AEA analog, and (-)delta(9) tetrahydrocannabinol (THC), the major psychoactive constituent of Cannabis, modulated capacitation and fertilizing potential of human sperm in vitro. AM-356 elicited biphasic effects on the incidence of hyperactivated sperm motility (HA) between 1 and 6 hr of incubation: at (2.5 nM) it inhibited HA, while at (0.25 nM) it stimulated HA. Both AM-356 and THC inhibited morphological alterations over acrosomal caps between 2 and 6 hr (IC(50) 5.9 +/- 0.6 pM and 3.5 +/- 1.5 nM, respectively). Sperm fertilizing capacity, measured in the Hemizona Assay, was reduced 50% by (1 nM) AM-356. These findings suggest that AEA-signaling may regulate sperm functions required for fertilization in human reproductive tracts, and imply that smoking of marijuana could impact these processes. This study has potential medical and public policy ramifications because of the incidence of marijuana abuse by adults in our society, previously documented reproductive effects of marijuana, and the ongoing debate about medicinal use of marijuana and cannabinoids. Copyright

  20. Human resource requirements for quality-assured electronic data capture of the tuberculosis case register

    Directory of Open Access Journals (Sweden)

    Hoa Nguyen B

    2012-01-01

    Full Text Available Abstract Background The tuberculosis case register is the data source for the reports submitted by basic management units to the national tuberculosis program. Our objective was to measure the data entry time required to complete and double-enter one record, and to estimate the time for the correction of errors in the captured information from tuberculosis case registers in Cambodia and Viet Nam. This should assist in quantifying the additional requirements in human resources for national programs moving towards electronic recording and reporting. Methods Data from a representative sample of tuberculosis case registers from Cambodia and Viet Nam were double-entered and discordances resolved by rechecking the original case register. Computer-generated data entry time recorded the time elapsed between opening of a new record and saving it to disk. Results The dataset comprised 22,732 double-entered records of 11,366 patients (37.1% from Cambodia and 62.9% from Viet Nam. The mean data entry times per record were 97.5 (95% CI: 96.2-98.8 and 66.2 (95% CI: 59.5-73.0 seconds with medians of 90 and 31 s respectively in Cambodia and in Viet Nam. The percentage of records with an error was 6.0% and 39.0% respectively in Cambodia and Viet Nam. Data entry time was inversely associated with error frequency. We estimate that approximately 118-person-hours were required to produce 1,000 validated records. Conclusions This study quantifies differences between two countries for data entry time for the tuberculosis case register and frequencies of data entry errors and suggests that higher data entry speed is partially offset by requiring revisiting more records for corrections.

  1. Optical interconnections to focal plane arrays

    Energy Technology Data Exchange (ETDEWEB)

    Rienstra, J.L.; Hinckley, M.K.

    2000-11-01

    The authors have successfully demonstrated an optical data interconnection from the output of a focal plane array to the downstream data acquisition electronics. The demonstrated approach included a continuous wave laser beam directed at a multiple quantum well reflectance modulator connected to the focal plane array analog output. The output waveform from the optical interconnect was observed on an oscilloscope to be a replica of the input signal. They fed the output of the optical data link to the same data acquisition system used to characterize focal plane array performance. Measurements of the signal to noise ratio at the input and output of the optical interconnection showed that the signal to noise ratio was reduced by a factor of 10 or more. Analysis of the noise and link gain showed that the primary contributors to the additional noise were laser intensity noise and photodetector receiver noise. Subsequent efforts should be able to reduce these noise sources considerably and should result in substantially improved signal to noise performance. They also observed significant photocurrent generation in the reflectance modulator that imposes a current load on the focal plane array output amplifier. This current loading is an issue with the demonstrated approach because it tends to negate the power saving feature of the reflectance modulator interconnection concept.

  2. Laser Dazzling of Focal Plane Array Cameras

    NARCIS (Netherlands)

    Schleijpen, H.M.A.; Dimmeler, A.; Eberle, B; Heuvel, J.C. van den; Mieremet, A.L.; Bekman, H.H.P.T.; Mellier, B.

    2007-01-01

    Laser countermeasures against infrared focal plane array cameras aim to saturate the full camera image. In this paper we will discuss the results of dazzling experiments performed with MWIR lasers. In the “low energy” pulse regime we observe an increasing saturated area with increasing power. The

  3. Focal dermal hypoplasia: A rare case report

    Directory of Open Access Journals (Sweden)

    Sahana M Srinivas

    2015-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem disorder primarily involving the skin, skeletal system, eyes, and face. We report the case of an eight-month-old female child who presented with multiple hypopigmented atrophic macules along the lines of blaschko, skeletal anomalies, umbilical hernia, developmental delay, hypoplastic nails, syndactyly, and lobster claw deformity characteristic of Goltz syndrome.

  4. Electric field depth–focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs

    Science.gov (United States)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2012-01-01

    Background Various transcranial magnetic stimulation (TMS) coil designs are available or have been proposed. However, key coil characteristics such as electric field focality and attenuation in depth have not been adequately compared. Knowledge of the coil focality and depth characteristics can help TMS researchers and clinicians with coil selection and interpretation of TMS studies. Objective To quantify the electric field focality and depth of penetration of various TMS coils. Methods The electric field distributions induced by 50 TMS coils were simulated in a spherical human head model using the finite element method. For each coil design, we quantified the electric field penetration by the half-value depth, d1/2, and focality by the tangential spread, S1/2, defined as the half-value volume (V1/2) divided by the half-value depth, S1/2 = V1/2/d1/2. Results The 50 TMS coils exhibit a wide range of electric field focality and depth, but all followed a depth–focality tradeoff: coils with larger half-value depth cannot be as focal as more superficial coils. The ranges of achievable d1/2 are similar between coils producing circular and figure-8 electric field patterns, ranging 1.0–3.5 cm and 0.9–3.4 cm, respectively. However, figure-8 field coils are more focal, having S1/2 as low as 5 cm2 compared to 34 cm2 for circular field coils. Conclusions For any coil design, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electrical field spread. Novel coil designs should be benchmarked against comparison coils with consistent metrics such as d1/2 and S1/2. PMID:22483681

  5. Polarimeter on a Chip: Antenna-Coupled Microbolometers and Polarimeters for Submillimeterwave and Millimeterwave Focal Planes Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Future missions to study astrophysical sources at millimeter and submillimeter wavelengths require focal planes of 1000's of detectors that must operate at the...

  6. Low-Noise, UV-to-SWIR Broadband Photodiodes for Large-Format Focal Plane Array Sensors Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Broadband focal plane arrays, operating in UV-to-SWIR wavelength range, are required for atmospheric monitoring of greenhouse gases. Currently, separate image...

  7. The Development of a Human Systems Simulation Laboratory at Idaho National Laoboratory: Progress, Requirements and Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    David I Gertman; Katya L. LeBlanc; William phoenix; Alan R Mecham

    2010-11-01

    Next generation nuclear power plants and digital upgrades to the existing nuclear fleet introduce potential human performance issues in the control room. Safe application of new technologies calls for a thorough understanding of how those technologies affect human performance and in turn, plant safety. In support of advancing human factors for small modular reactors and light water reactor sustainability, the Idaho National Laboratory (INL) has developed a reconfigurable simulation laboratory capable of testing human performance in multiple nuclear power plant (NPP) control room simulations. This paper discusses the laboratory infrastructure and capabilities, the laboratory’ s staffing requirements, lessons learned, and the researcher’s approach to measuring human performance in the simulation lab.

  8. Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

    Directory of Open Access Journals (Sweden)

    Negin N Blattman

    2014-04-01

    Full Text Available Human herpesvirus 8 (HHV8 infection leads to potent activation of nuclear factor kappa B (NFB in primary and transformed cells. We used recombinant HHV8 (rKSHV.219 expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF, noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.

  9. Body size and human energy requirements: reduced mass-specific resting energy expenditure in tall adults.

    Science.gov (United States)

    Heymsfield, Steven B; Childers, Douglas; Beetsch, Joel; Allison, David B; Pietrobelli, Angelo

    2007-11-01

    Two observations favor the presence of a lower mass-specific resting energy expenditure (REE/weight) in taller adult humans: an earlier report of height (H)-related differences in relative body composition; and a combined model based on Quetelet and Kleiber's classic equations suggesting that REE/weight proportional, variantH(-0.5). This study tested the hypothesis stating that mass-specific REE scales negatively to height with a secondary aim exploration of related associations between height, weight (W), surface area (SA), and REE. Two independent data sets (n = 344 and 884) were evaluated, both with REE measured by indirect calorimetry and the smaller of the two including fat estimates by dual-energy X-ray absorptiometry. Results support Quetelet's equation (W proportional, variantH(2)), but Kleiber's equation approached the interspecific mammal form (REE proportional, variantW(0.75)) only after adding adiposity measures to weight and age as REE predictors. REE/weight scaled as H( approximately (-0.5)) in support of the hypothesis with P values ranging from 0.17 to <0.001. REE and SA both scaled as H( approximately 1.5), and REE/SA was nonsignificantly correlated with height in all groups. These observations suggest that adiposity needs to be considered when evaluating the intraspecific scaling of REE to weight; that relative to their weight, taller subjects require a lower energy intake for replacing resting heat losses than shorter subjects; that fasting endurance, approximated as fat mass/REE, increases as H(0.5); and that thermal balance is maintained independent of stature by evident stable associations between resting heat production and capacity of external heat release. These observations have implications for the modeling of adult human energy requirements and associate with anthropological concepts founded on body size.

  10. Step 1: Human System Integration (HSI) FY05 Pilot-Technology Interface Requirements for Command, Control, and Communications (C3)

    Science.gov (United States)

    2005-01-01

    The document provides the Human System Integration(HSI) high-level functional C3 HSI requirements for the interface to the pilot. Description includes (1) the information required by the pilot to have knowledge C3 system status, and (2) the control capability needed by the pilot to obtain C3 information. Fundamentally, these requirements provide the candidate C3 technology concepts with the necessary human-related elements to make them compatible with human capabilities and limitations. The results of the analysis describe how C3 operations and functions should interface with the pilot to provide the necessary C3 functionality to the UA-pilot system. Requirements and guidelines for C3 are partitioned into three categories: (1) Pilot-Air Traffic Control (ATC) Voice Communications (2) Pilot-ATC Data Communications, and (3) command and control of the unmanned aircraft (UA). Each requirement is stated and is supported with a rationale and associated reference(s).

  11. The minimal active human SVA retrotransposon requires only the 5'-hexamer and Alu-like domains.

    Science.gov (United States)

    Hancks, Dustin C; Mandal, Prabhat K; Cheung, Ling E; Kazazian, Haig H

    2012-11-01

    RNA-based duplication mediated by reverse transcriptase (RT), a process termed retrotransposition, is ongoing in humans and is a source of significant inter- and perhaps intraindividual genomic variation. The long interspersed element 1 (LINE-1 or L1) ORF2 protein is the genomic source for RT activity required for mobilization of its own RNA in cis and other RNAs, such as SINE/variable-number tandem-repeat (VNTR)/Alu (SVA) elements, in trans. SVA elements are ~2-kb hominid-specific noncoding RNAs that have resulted in single-gene disease in humans through insertional mutagenesis or aberrant mRNA splicing. Here, using an SVA retrotransposition cell culture assay in U2OS cells, we investigated SVA domains important in L1-mediated SVA retrotransposition. Partial- and whole-domain deletions revealed that removal of either the Alu-like or SINE-R domain in the context of a full-length SVA has little to no effect, whereas removal of the CT hexamer or the VNTR domain can result in a 75% decrease in activity. Additional experiments demonstrate that the Alu-like fragment alone can retrotranspose at low levels while the addition of the CT hexamer can enhance activity as much as 2-fold compared to that of the full-length SVA. These results suggest that no SVA domain is essential for retrotransposition in U2OS cells and that the 5' end of SVA (hexamer and Alu-like domain) is sufficient for retrotransposition.

  12. Identification of cellular proteins required for replication of human immunodeficiency virus type 1.

    Science.gov (United States)

    Dziuba, Natallia; Ferguson, Monique R; O'Brien, William A; Sanchez, Anthony; Prussia, Andrew J; McDonald, Natalie J; Friedrich, Brian M; Li, Guangyu; Shaw, Michael W; Sheng, Jinsong; Hodge, Thomas W; Rubin, Donald H; Murray, James L

    2012-10-01

    Cellular proteins are essential for human immunodeficiency virus type 1 (HIV-1) replication and may serve as viable new targets for treating infection. Using gene trap insertional mutagenesis, a high-throughput approach based on random inactivation of cellular genes, candidate genes were found that limit virus replication when mutated. Disrupted genes (N=87) conferring resistance to lytic infection with several viruses were queried for an affect on HIV-1 replication by utilizing small interfering RNA (siRNA) screens in TZM-bl cells. Several genes regulating diverse pathways were found to be required for HIV-1 replication, including DHX8, DNAJA1, GTF2E1, GTF2E2, HAP1, KALRN, UBA3, UBE2E3, and VMP1. Candidate genes were independently tested in primary human macrophages, toxicity assays, and/or Tat-dependent β-galactosidase reporter assays. Bioinformatics analyses indicated that several host factors present in this study participate in canonical pathways and functional processes implicated in prior genome-wide studies. However, the genes presented in this study did not share identity with those found previously. Novel antiviral targets identified in this study should open new avenues for mechanistic investigation.

  13. Rat model of focal cerebral ischemia in the dominant hemisphere.

    Science.gov (United States)

    Zhang, Hua; Shen, Yan; Wang, Wei; Gao, Huanmin

    2015-01-01

    In the human brain, the dominant hemisphere is more complex than the non-dominant hemisphere. Hence, cerebral ischemia of the dominant hemisphere often leads to serious consequences. This study aims to establish a rodent model of focal cerebral ischemia in the dominant hemisphere. The quadruped feeding test was used to screen 70 male Sprague Dawley rats. From this test, 48 rats with right paw preference were selected and randomly assigned numbers. Half were assigned to the dominant hemisphere ischemia (DHI) group, and the other half were assigned to the non-dominant hemisphere ischemia (NDHI) group. The middle cerebral artery was occluded 2 h before reperfusion. Neurological functions were tested. TTC and HE staining were performed. The volume of cerebral infarction was calculated. Rats in the DHI group had significantly worse neurological scores than rats in the NDHI group (P dominant hemisphere than in the non-dominant hemisphere. The dominant hippocampus indicated severe neuronal loss and disorderly cellular arrangement. The volume of cerebral infarction was also greater in the DHI group compared to the NDHI group (P dominant hemisphere, MCA occlusion in the dominant hemisphere caused greater impairment in neurological functions. The proposed rodent model is reliable and has high levels of reproducibility. Therefore, his model can be reliably for investigating the mechanism of focal cerebral ischemia in the dominant hemisphere of human brains.

  14. Distinct energy requirements for human memory CD4 T-cell homeostatic functions.

    Science.gov (United States)

    Taub, Dennis D; Hesdorffer, Charles S; Ferrucci, Luigi; Madara, Karen; Schwartz, Janice B; Goetzl, Edward J

    2013-01-01

    Differentiation and activation of CD4 memory T cells (T(mem) cells) require energy from different sources, but little is known about energy sources for maintenance and surveillance activities of unactivated T(mem) cells. Mitochondrial fatty acid oxidation (FAO) in human unactivated CD4 T(mem) cells was significantly enhanced by inhibition of glycolysis, with respective means of 1.7- and 4.5-fold for subjects 65 yr, and by stimulation of AMP-activated protein kinase, with respective means of 1.3- and 5.2-fold. However, CCL19 and sphingosine 1-phosphate (S1P), which control homeostatic lymphoid trafficking of unactivated T(mem) cells, altered FAO and glycolysis only minimally or not at all. Inhibition of CD4 T(mem)-cell basal FAO, but not basal glycolysis, significantly suppressed CCL19- and S1P-mediated adherence to collagen by >50 and 20%, respectively, and chemotaxis by >20 and 50%. Apoptosis of unactivated T(mem) cells induced by IL-2 deprivation or CCL19 was increased significantly by >150 and 70%, respectively, with inhibition of FAO and by >110 and 30% with inhibition of glycolysis. Anti-TCR antibody activation of T(mem) cells increased their chemotaxis to CCL5, which was dependent predominantly on glycolysis rather than FAO. The sources supplying energy for diverse functions of unactivated T(mem) cells differ from that required for function after immune activation.

  15. The First Development of Human Factors Engineering Requirements for Application to Ground Task Design for a NASA Flight Program

    Science.gov (United States)

    Dischinger, H. Charles, Jr.; Stambolian, Damon B.; Miller, Darcy H.

    2008-01-01

    The National Aeronautics and Space Administration has long applied standards-derived human engineering requirements to the development of hardware and software for use by astronauts while in flight. The most important source of these requirements has been NASA-STD-3000. While there have been several ground systems human engineering requirements documents, none has been applicable to the flight system as handled at NASA's launch facility at Kennedy Space Center. At the time of the development of previous human launch systems, there were other considerations that were deemed more important than developing worksites for ground crews; e.g., hardware development schedule and vehicle performance. However, experience with these systems has shown that failure to design for ground tasks has resulted in launch schedule delays, ground operations that are more costly than they might be, and threats to flight safety. As the Agency begins the development of new systems to return humans to the moon, the new Constellation Program is addressing this issue with a new set of human engineering requirements. Among these requirements is a subset that will apply to the design of the flight components and that is intended to assure ground crew success in vehicle assembly and maintenance tasks. These requirements address worksite design for usability and for ground crew safety.

  16. Starbugs: focal plane fiber positioning technology

    Science.gov (United States)

    Goodwin, Michael; Heijmans, Jeroen; Saunders, Ian; Brzeski, Jurek; Saunders, Will; Muller, Rolf; Haynes, Roger; Gilbert, James

    2010-07-01

    We report on the technological achievements of our latest Starbug prototypes and their implications for smart focal plane fiber positioning applications for wide-field astronomy. The Starbugs are innovative self-motile miniature robotic devices that can simultaneously and independently position fibers or payloads over a field plate located at the telescope's focal plane. The Starbugs concept overcomes many of the limitations associated with the traditional 'pick and place' positioners where a robot places fixed buttons onto the field plate. The new Starbug prototypes use piezoelectric actuators and have the following features: (i) new 'lift-and-step' method (discrete step) for accurate positioning over different surfaces; and (ii) operate in an inverted hanging position underneath a transparent field plate, removing the need for fibercable retractors. In this paper, we present aspects of the Starbug prototypes, including the theoretical model, mechanical design, experimental setup, algorithms, performance and applications for astronomical instrumentation.

  17. [Liver ultrasound: focal lesions and diffuse diseases].

    Science.gov (United States)

    Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

    2016-01-01

    Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Focal region fields of distorted reflectors

    Science.gov (United States)

    Buris, N. E.; Kauffman, J. F.

    1988-01-01

    The problem of the focal region fields scattered by an arbitrary surface reflector under uniform plane wave illumination is solved. The physical optics (PO) approximation is used to calculate the current induced on the reflector. The surface of the reflector is described by a number of triangular domain-wise 5th degree bivariate polynomials. A 2-dimensional Gaussian quadrature is employed to numerically evaluate the integral expressions of the scattered fields. No Freshnel or Fraunhofer zone approximations are made. The relation of the focal fields problem to surface compensation techniques and other applications are mentioned. Several examples of distorted parabolic reflectors are presented. The computer code developed is included, together with instructions on its usage.

  19. Sustainable oceans in a 'civilized' world requires a sustainable human civilization. (Invited)

    Science.gov (United States)

    Caldeira, K.; Ricke, K.; Maclaren, J. K.

    2013-12-01

    The sustainability of the ocean ecosystems is, in many areas, threatened by local and regional activities, including the discharge of pollutants, loss of wetlands, and overfishing. However, some threats to ocean ecosystems, notably ocean acidification and climate change, are a consequence decisions that cannot be substantively addressed only through action that is proximal to the affected ecosystem. The only practical way to reduce risks to the ocean posed by ocean acidification and climate change is to transform our energy system into one that does not use the atmosphere and the ocean as waste dumps for unwanted byproducts of modern civilization. The required revolution in our systems of energy production and consumption is a key component of the transition to a sustainable human civilization. It would be much easier to maintain a sustainable ocean if doing so did not require creating a sustainable human civilization; but unfortunately the ocean does not get to choose the problems it faces. Damage to the ocean is additive, or perhaps multiplicative. Thus, the response of an ecosystem exposed to coastal pollutants, loss of wetlands, overfishing, ocean acidification, and climate change will likely be more dramatic than the response of an ecosystem exposed to ocean acidification and climate change alone. Thus, there is merit in reducing coastal pollution, preserving and restoring wetlands, and reducing excess fishing, even if the ocean acidification and climate problems are not solved. Furthermore, damage from ocean acidification and climate change is not a yes or no question. Each CO2 emission causes a little more acidification and a little more climate change and thus a little more damage to existing ocean ecosystems. Hence, each CO2 emission that can be avoided helps avoid a little bit of damage to ocean ecosystems the world over. While the overall problem of sustainability of the ocean is very difficult to solve, there is no shortage of things to do that would be

  20. Focal Adhesion Induction at the Tip of a Functionalized Nanoelectrode

    OpenAIRE

    Fuentes, Daniela E.; Bae, Chilman; Butler, Peter J.

    2011-01-01

    Cells dynamically interact with their physical micro-environment through the assembly of nascent focal contacts and focal adhesions. The dynamics and mechanics of these contact points are controlled by transmembrane integrins and an array of intracellular adaptor proteins. In order to study the mechanics and dynamics of focal adhesion assembly, we have developed a technique for the timed induction of a nascent focal adhesion. Bovine aortic endothelial cells were approached at the apical surfa...

  1. Chest pain in focal musculoskeletal disorders

    DEFF Research Database (Denmark)

    Stochkendahl, Mette Jensen; Christensen, Henrik Wulff

    2010-01-01

    The musculoskeletal system is a recognized source of chest pain. However, despite the apparently benign origin, patients with musculoskeletal chest pain remain under-diagnosed, untreated, and potentially continuously disabled in terms of anxiety, depression, and activities of daily living. Several...... overlapping conditions and syndromes of focal disorders, including Tietze syndrome, costochondritis, chest wall syndrome, muscle tenderness, slipping rib, cervical angina, and segmental dysfunction of the cervical and thoracic spine, have been reported to cause pain. For most of these syndromes, evidence...

  2. The expanded spectrum of focal choroidal excavation.

    Science.gov (United States)

    Margolis, Ron; Mukkamala, Sri Krishna; Jampol, Lee M; Spaide, Richard F; Ober, Michael D; Sorenson, John A; Gentile, Ronald C; Miller, Joel A; Sherman, Jerome; Freund, K Bailey

    2011-10-01

    To describe the clinical and imaging findings in patients with focal choroidal excavation. Retrospective observational case series. The medical records of 12 patients (13 eyes) with focal choroidal excavation were reviewed. Clinical histories and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and enhanced depth imaging spectral-domain optical coherence tomography) were analyzed. The mean age of the patients was 45 years (range, 22-62 years). Four patients were Asian. Mean visual acuity was 20/31 (range, 20/20 to 20/100). Mean refractive error was -3.54 diopters (D) (range, 6.00 to -8.00 D). One patient had bilateral involvement. All patients manifested varying degrees of foveal pigmentary changes that were usually hypoautofluorescent on fundus autofluorescence images. Fluorescein angiographic findings varied with degree of retinal pigment epithelial alterations. Indocyanine green angiography revealed relative hypofluorescence. In 7 eyes, spectral-domain optical coherence tomography revealed outer retinal layers conforming to retinal pigment epithelial alterations within the excavation. In the other 6 eyes, spectral-domain optical coherence tomography revealed a separation between the outer retina and the retinal pigment epithelium within the excavation. In 7 eyes studied with enhanced depth imaging spectral-domain optical coherence tomography, there was no evidence of scleral ectasia. Mean choroidal thickness of the uninvolved choroid was thicker than normal at 319 μm (range, 244-439 μm). All lesions remained stable except for in 1 eye, which had findings of central serous chorioretinopathy and secondary type 2 (subretinal) neovascularization. Focal choroidal excavation is a newly described idiopathic entity in eyes having 1 or more focal areas of choroidal excavation. In some patients, there may be an association with central

  3. Epilepsy, Acquired Aphasia with Focal Cortical Dysplasia

    Directory of Open Access Journals (Sweden)

    Girija A.S

    1999-01-01

    Full Text Available A six year old boy having complex partial seizures with secondary generalization of four months duration developing isolated expressive dysphasia, later progressing to global aphasia is being reported. His awake EEG showed a left temporal spike wave discharge and sleep EEG showed continuous spike and ware discharges. MR imaging demonstrated focal cortical dysplasia in the left frontal and opercular region, a combination that has not been reported earlier.

  4. Focal dermal hypoplasia in a male

    Science.gov (United States)

    George, Leni; Agrawal, Nisha; Hogan, Peter

    2011-01-01

    Focal dermal hypoplasia (FDH) is a rare mesoectodermal dysplasia syndrome characterized by cutaneous, skeletal, dental, ocular and soft-tissue defects. An X-linked dominant mode of inheritance with lethality in male subjects has been proposed. Only around 30 cases of FDH have been reported in male subjects. Live born affected males are mosaic for mutations in PORCN gene . We present the mosaic pattern of FDH in a young boy. PMID:25386262

  5. Kalman Filter for Calibrating a Telescope Focal Plane

    Science.gov (United States)

    Kang, Bryan; Bayard, David

    2006-01-01

    The instrument-pointing frame (IPF) Kalman filter, and an algorithm that implements this filter, have been devised for calibrating the focal plane of a telescope. As used here, calibration signifies, more specifically, a combination of measurements and calculations directed toward ensuring accuracy in aiming the telescope and determining the locations of objects imaged in various arrays of photodetectors in instruments located on the focal plane. The IPF Kalman filter was originally intended for application to a spaceborne infrared astronomical telescope, but can also be applied to other spaceborne and ground-based telescopes. In the traditional approach to calibration of a telescope, (1) one team of experts concentrates on estimating parameters (e.g., pointing alignments and gyroscope drifts) that are classified as being of primarily an engineering nature, (2) another team of experts concentrates on estimating calibration parameters (e.g., plate scales and optical distortions) that are classified as being primarily of a scientific nature, and (3) the two teams repeatedly exchange data in an iterative process in which each team refines its estimates with the help of the data provided by the other team. This iterative process is inefficient and uneconomical because it is time-consuming and entails the maintenance of two survey teams and the development of computer programs specific to the requirements of each team. Moreover, theoretical analysis reveals that the engineering/ science iterative approach is not optimal in that it does not yield the best estimates of focal-plane parameters and, depending on the application, may not even enable convergence toward a set of estimates.

  6. Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ishii

    Full Text Available Human papillomavirus (HPV is a non-enveloped virus composed of a circular DNA genome and two capsid proteins, L1 and L2. Multiple interactions between its capsid proteins and host cellular proteins are required for infectious HPV entry, including cell attachment and internalization, intracellular trafficking and viral genome transfer into the nucleus. Using two variants of HPV type 51, the Ma and Nu strains, we have previously reported that MaL2 is required for efficient pseudovirus (PsV transduction. However, the cellular factors that confer this L2 dependency have not yet been identified. Here we report that the transport protein particle complex subunit 8 (TRAPPC8 specifically interacts with MaL2. TRAPPC8 knockdown in HeLa cells yielded reduced levels of reporter gene expression when inoculated with HPV51Ma, HPV16, and HPV31 PsVs. TRAPPC8 knockdown in HaCaT cells also showed reduced susceptibility to infection with authentic HPV31 virions, indicating that TRAPPC8 plays a crucial role in native HPV infection. Immunofluorescence microscopy revealed that the central region of TRAPPC8 was exposed on the cell surface and colocalized with inoculated PsVs. The entry of Ma, Nu, and L2-lacking PsVs into cells was equally impaired in TRAPPC8 knockdown HeLa cells, suggesting that TRAPPC8-dependent endocytosis plays an important role in HPV entry that is independent of L2 interaction. Finally, expression of GFP-fused L2 that can also interact with TRAPPC8 induced dispersal of the Golgi stack structure in HeLa cells, a phenotype also observed by TRAPPC8 knockdown. These results suggest that during viral intracellular trafficking, binding of L2 to TRAPPC8 inhibits its function resulting in Golgi destabilization, a process that may assist HPV genome escape from the trans-Golgi network.

  7. Group Development Phases as Working through Six Fundamental Human Problems.

    Science.gov (United States)

    Burnand, Gordon

    1990-01-01

    Following Bennis and Shepard's work, groups are thought to become preoccupied with problems of gaining reassurance about six basic human tasks in turn. One can show that these problems, called focal problems, have two forms, inclusive and narrowed, and that progressing through the problems requires three subphases. (Author/ABL)

  8. Focal Conic Flower Textures at Curved Interfaces

    Directory of Open Access Journals (Sweden)

    Daniel A. Beller

    2013-12-01

    Full Text Available Focal conic domains (FCDs in smectic-A liquid crystals have drawn much attention, both for their exquisitely structured internal form and for their ability to direct the assembly of micromaterials and nanomaterials in a variety of patterns. A key to directing FCD assembly is control over the eccentricity of the domain. Here, we demonstrate a new paradigm for creating spatially varying FCD eccentricity by confining a hybrid-aligned smectic with curved interfaces. In particular, we manipulate interface behavior with colloidal particles in order to experimentally produce two examples of what has recently been dubbed the flower texture [C. Meyer et al., Focal Conic Stacking in Smectic A Liquid Crystals: Smectic Flower and Apollonius Tiling, Materials 2, 499, 2009MATEG91996-194410.3390/ma2020499], where the focal hyperbolæ diverge radially outward from the center of the texture, rather than inward as in the canonical éventail or fan texture. We explain how this unconventional assembly can arise from appropriately curved interfaces. Finally, we present a model for this system that applies the law of corresponding cones, showing how FCDs may be embedded smoothly within a “background texture” of large FCDs and concentric spherical layers, in a manner consistent with the qualitative features of the smectic flower. Such understanding could potentially lead to disruptive liquid-crystal technologies beyond displays, including patterning, smart surfaces, microlens arrays, sensors, and nanomanufacturing.

  9. Focal adhesions, stress fibers and mechanical tension

    Energy Technology Data Exchange (ETDEWEB)

    Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu [Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, 12-016 Lineberger, CB#7295, University of North Carolina, Chapel Hill, NC (United States); Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr [Inserm UMR-S1087, CNRS UMR-C6291, L' institut du Thorax, and Université de Nantes, Nantes (France)

    2016-04-10

    Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.

  10. The Cult of Ancestors: A Focal Point for Prayers in African Traditional ...

    African Journals Online (AJOL)

    Religion Dept

    The Cult of Ancestors: A Focal Point for Prayers in African. Traditional Communities. Ezenweke, Elizabeth Onyedinma. Religion & Human Relations. Faculty of Arts,. Nnamdi Azikiwe University, Awka. Introduction. The spiritual world of Africa peoples is very densely populated with spiritual beings; spirits and the living- dead ...

  11. Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines.

    Science.gov (United States)

    Callow, Marinella G; Clairvoyant, Felix; Zhu, Shirley; Schryver, Brian; Whyte, David B; Bischoff, James R; Jallal, Bahija; Smeal, Tod

    2002-01-04

    p21-activated protein kinase (PAK) serine/threonine kinases are important effectors of Rho family GTPases and have been implicated in the regulation of cell morphology and motility, as well as in cell transformation. To further investigate the possible involvement of PAK kinases in tumorigenesis, we analyzed the expression of several family members in tumor cell lines. Here we demonstrate that PAK4 is frequently overexpressed in human tumor cell lines of various tissue origins. We also have identified serine (Ser-474) as the likely autophosphorylation site in the kinase domain of PAK4 in vivo. Mutation of this serine to glutamic acid (S474E) results in constitutive activation of the kinase. Phosphospecific antibodies directed against serine 474 detect activated PAK4 on the Golgi membrane when PAK4 is co-expressed with activated Cdc42. Furthermore, expression of the active PAK4 (S474E) mutant has transforming potential, leading to anchorage-independent growth of NIH3T3 cells. A kinase-inactive PAK4 (K350A,K351A), on the other hand, efficiently blocks transformation by activated Ras and inhibits anchorage-independent growth of HCT116 colon cancer cells. Taken together, our data strongly implicate PAK4 in oncogenic transformation and suggest that PAK4 activity is required for Ras-driven, anchorage-independent growth.

  12. Membrane repair of human skeletal muscle cells requires Annexin-A5.

    Science.gov (United States)

    Carmeille, Romain; Bouvet, Flora; Tan, Sisareuth; Croissant, Coralie; Gounou, Céline; Mamchaoui, Kamel; Mouly, Vincent; Brisson, Alain R; Bouter, Anthony

    2016-09-01

    Defect in membrane repair contributes to the development of limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. In healthy skeletal muscle, unraveling membrane repair mechanisms requires to establish an exhaustive list of the components of the resealing machinery. Here we show that human myotubes rendered deficient for Annexin-A5 (AnxA5) suffer from a severe defect in membrane resealing. This defect is rescued by the addition of recombinant AnxA5 while an AnxA5 mutant, which is unable to form 2D protein arrays, has no effect. Using correlative light and electron microscopy, we show that AnxA5 binds to the edges of the torn membrane, as early as a few seconds after sarcolemma injury, where it probably self-assembles into 2D arrays. In addition, we observed that membrane resealing is associated with the presence of a cluster of lipid vesicles at the wounded site. AnxA5 is present at the surface of these vesicles and may thus participate in plugging the cell membrane disruption. Finally, we show that AnxA5 behaves similarly in myotubes from a muscle cell line established from a patient suffering from LGMD2B, a myopathy due to dysferlin mutations, which indicates that trafficking of AnxA5 during sarcolemma damage is independent of the presence of dysferlin. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

    KAUST Repository

    Moon, Robert W.

    2016-06-15

    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

  14. Focal dystonia in musicians: From phenomenology to therapy

    Directory of Open Access Journals (Sweden)

    Hans-Christian Jabusch

    2006-01-01

    Full Text Available Background: Musician's dystonia is a task-specific movement disorder which manifests itself as a loss of voluntary motor control in extensively trained movements. In many cases, the disorder terminates the careers of affected musicians. Approximately 1% of all professional musicians are affected.Etiology and Pathophysiology: The pathophysiology of the disorder is still unclear. Findings include (a reduced inhibition in different levels of the central nervous system, (b maladaptive plasticity, e.g. in the somatosensory cortex and in the basal ganglia, and (c alterations in sensorimotor processing. Epidemiological data demon-strated a higher risk for those musicians who play instruments requiring maximal fine-motorskills. For instruments where workload differs across hands, focal dystonia appears more often in the more intensely used hand. In psychological studies, musicians with dystonia had more perfectionist tendencies than healthy musicians. These findings streng then the assumption that behavioral factors may be involved in the etiology of musician's dystonia. Hereditary factors may play a greater role than previously assumed. Preliminary findings suggest a genetic contributiont o focal task-specific dystonia with phenotypic variations including musician's dystonia.Treatment: Treatment options for musician's dystonia include pharmacological interventions such as administration of Trihexyphenidyl or Botulinum Toxin-A as well as retraining programs and ergonomic changes in the instrument. A long-term follow-up study was performed in 144 patients with musician's dystonia. The outcome was revealed on average 8.4 years after onset of symptoms. Outcome was assessed by patients' subjective rating of cumulative treatmentresponse and response to individual therapies. Seventy-seven patients (54% reported an alleviation of symptoms: 33% of the patients with Trihexyphenidyl, 49% with Botulinum Toxin, 50% with pedagogical retraining, 56% with unmonitored

  15. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    Directory of Open Access Journals (Sweden)

    Ohannessian Arthur

    2004-05-01

    Full Text Available Abstract Background Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK. Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK. Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC lines. Methods Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. Results In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. Conclusions We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway.

  16. Integrin activation and focal complex formation in cardiac hypertrophy

    Science.gov (United States)

    Laser, M.; Willey, C. D.; Jiang, W.; Cooper, G. 4th; Menick, D. R.; Zile, M. R.; Kuppuswamy, D.

    2000-01-01

    Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

  17. Requirement of retinoids for the expression of CD38 on human hematopoietic progenitors in vitro.

    Science.gov (United States)

    Muench, M O; Bárcena, A; Ohkubo, T; Harrison, M R

    1999-01-01

    Cells expressing high levels of CD34 and little or no CD38 comprise a primitive compartment of progenitors, thought to include hematopoietic stem cells. In this study we sought to determine the feasibility of using CD34 and CD38 as markers of hematopoietic differentiation in vitro, using retinoids to induce the expression of CD38. The effects over time of culture, sera and retinoids on the expression of CD34 and CD38 were determined using a base-medium lacking serum. Two early progenitor populations, isolated by FACS from human fetal liver, were studied: CD38(-)CD34(++) and CD38(+)CD34(++) cells. Additionally, HL-60 cells were adapted to grow in serum-deprived medium to study factors that control CD38 expression. Colony forming cell (CFC) assays and short-term expansion cultures were used to measure the effects of all-trans-retinoic acid (ATRA) oil the growth of fetal progenitors. Fetal progenitors and HL-60 cells grown under serum-deprived conditions exhibited almost no CD38 expression. However, CD34 expression was observed on fetal progenitors and declined slowly over time. Addition of FBS or human serum restored CD38 expression to cultured cells, but at levels below those found on progenitors in vivo. Addition of ATRA or 9-cis-retinoic acid (9CRA) to cultures of fetal progenitors or HL-60 cells, resulted in a time- and dose-dependent increase in CD38 expression, ATRA being the more potent of the two retinoids. However, ATRA inhibited colony formation, reduced the expansion of CFC and accelerated the loss of CD34 expression at doses required for the induction of CD38 expression. ATRA-induced CD38 expression on cells to levels comparable to those found on progenitors in vivo. ATRA also inhibited the growth of early progenitors, which was partly due to ATRA accelerating the differentiation of the progenitors. These findings indicate that CD34 and CD38 expression may be followed as markers of hematopoietic differentiation in vitro, but at the cost of culture

  18. FOCAL GROUPS ON-LINE: FROM THE CONCEPTUAL REFLECTIONS TO THE VIRTUAL ENVIRONMENT APPLICATION

    Directory of Open Access Journals (Sweden)

    Sônia M. Guedes Gondim

    2009-07-01

    Full Text Available Communication technologies have a renovating role in contemporaneity with regard to human interaction. One can however highlight their influence on other everyday aspects, like their influence in research. The objective of this paper is to describe and discuss the aspects that involve the application of focal groups in a virtual environment, denominated on-line focal groups, with the aim of highlighting factors that can guide their use in research, especially for research which is geared towards investigating opinions and perceptions of social players. The aspects broached in this paper are based in part on the application experience of the players, with a view to elaborating a doctorate thesis. The theoretical fundamentals of presential focal groups and their migration to the virtual environment are also broached. Finally some suggestions are presented to those who are interested in this research strategy, based on the results obtained through this experience.

  19. A focal plane detector design for a wide-band Laue-lens telescope

    DEFF Research Database (Denmark)

    Caroli, E.; Auricchio, N.; Amati, L.

    2005-01-01

    , and the detection of nuclear and annihilation lines. Recently the development of high energy Laue lenses with broad energy bandpasses from 60 to 600 keV have been proposed for a Hard X ray focusing Telescope (HAXTEL) in order to study the X-ray continuum of celestial sources. The required focal plane detector...

  20. Existence of a positive solution to a right focal boundary value problem

    Directory of Open Access Journals (Sweden)

    R. I. Avery

    2010-01-01

    Full Text Available In this paper we apply the recent extension of the Leggett-Williams Fixed Point Theorem which requires neither of the functional boundaries to be invariant to the second order right focal boundary value problem. We demonstrate a technique that can be used to deal with a singularity and provide a non-trivial example.

  1. Thick lens chromatic effective focal length variation versus bending

    Science.gov (United States)

    Sparrold, Scott

    2017-11-01

    Longitudinal chromatic aberration (LCA) can limit the optical performance in refractive optical systems. Understanding a singlet's chromatic change of effective focal leads to insights and methods to control LCA. Long established, first order theory, shows the chromatic change in focal length for a zero thickness lens is proportional to it's focal length divided by the lens V number or inverse dispersion. This work presents the derivation of an equation for a thick singlet's chromatic change in effective focal length as a function of center thickness, t, dispersion, V, index of refraction, n, and the Coddington shape factor, K. A plot of bending versus chromatic focal length variation is presented. Lens thickness does not influence chromatic variation of effective focal length for a convex plano or plano convex lens. A lens's center thickness'influence on chromatic focal length variation is more pronounced for lower indices of refraction.

  2. ESCRT (Endosomal Sorting Complex Required for Transport) Machinery Is Essential for Acrosomal Exocytosis in Human Sperm.

    Science.gov (United States)

    Pocognoni, Cristian A; Berberián, María Victoria; Mayorga, Luis S

    2015-11-01

    The sperm acrosome reaction is a unique, regulated exocytosis characterized by the secretion of the acrosomal content and the release of hybrid vesicles formed by patches of the outer acrosomal and plasma membranes. In previous reports, we have shown that inward invaginations of the acrosomal membrane delineate ring-shaped membrane microdomains that contact the plasma membrane. We have postulated that the opening and expansion of fusion pores along these rings trigger acrosomal exocytosis. The invaginations of the acrosomal membrane topologically resemble the deformations of the endosomal membrane leading to the assembly of luminal vesicles in multivesicular bodies. In fact, intra-acrosomal vesicles are also formed during acrosomal exocytosis. Endosomal sorting complex required for transport (ESCRT) participates in the organization of membrane microdomains that are invaginated and released as intraluminal vesicles in endosomes. We report here that members of ESCRT I (TSG101), ESCRT III (CHMP4), and the AAA ATPase VPS4 are present in the acrosomal region of the human sperm. Perturbing the function of these factors with antibodies or recombinant proteins inhibited acrosomal exocytosis in permeabilized cells. A similar effect was observed with a dominant-negative mutant of VPS4A cross-linked to a cell-penetrating peptide in nonpermeabilized sperm stimulated with a calcium ionophore. When the function of ESCRTs was inhibited, acrosomes showed abnormal deformation of the acrosomal membrane, and SNARE proteins that participate in acrosomal exocytosis failed to be stabilized in neurotoxin-resistant complexes. However, the growing of membrane invaginations was not blocked, and numerous intra-acrosomal vesicles were observed. These observations indicate that ESCRT-mediated processes are essential for acrosomal secretion, implicating these multifunctional complexes in an exocytic event crucial for sperm-egg fusion. © 2015 by the Society for the Study of Reproduction, Inc.

  3. Identifying Functional Requirements for Flexible Airspace Management Concept Using Human-In-The-Loop Simulations

    Science.gov (United States)

    Lee, Paul U.; Bender, Kim; Pagan, Danielle

    2011-01-01

    Flexible Airspace Management (FAM) is a mid- term Next Generation Air Transportation System (NextGen) concept that allows dynamic changes to airspace configurations to meet the changes in the traffic demand. A series of human-in-the-loop (HITL) studies have identified procedures and decision support requirements needed to implement FAM. This paper outlines a suggested FAM procedure and associated decision support functionality based on these HITL studies. A description of both the tools used to support the HITLs and the planned NextGen technologies available in the mid-term are presented and compared. The mid-term implementation of several NextGen capabilities, specifically, upgrades to the Traffic Management Unit (TMU), the initial release of an en route automation system, the deployment of a digital data communication system, a more flexible voice communications network, and the introduction of a tool envisioned to manage and coordinate networked ground systems can support the implementation of the FAM concept. Because of the variability in the overall deployment schedule of the mid-term NextGen capabilities, the dependency of the individual NextGen capabilities are examined to determine their impact on a mid-term implementation of FAM. A cursory review of the different technologies suggests that new functionality slated for the new en route automation system is a critical enabling technology for FAM, as well as the functionality to manage and coordinate networked ground systems. Upgrades to the TMU are less critical but important nonetheless for FAM to be fully realized. Flexible voice communications network and digital data communication system could allow more flexible FAM operations but they are not as essential.

  4. Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations.

    Science.gov (United States)

    Pengelly, Reuben J; Tapper, William; Gibson, Jane; Knut, Marcin; Tearle, Rick; Collins, Andrew; Ennis, Sarah

    2015-09-03

    An understanding of linkage disequilibrium (LD) structures in the human genome underpins much of medical genetics and provides a basis for disease gene mapping and investigating biological mechanisms such as recombination and selection. Whole genome sequencing (WGS) provides the opportunity to determine LD structures at maximal resolution. We compare LD maps constructed from WGS data with LD maps produced from the array-based HapMap dataset, for representative European and African populations. WGS provides up to 5.7-fold greater SNP density than array-based data and achieves much greater resolution of LD structure, allowing for identification of up to 2.8-fold more regions of intense recombination. The absence of ascertainment bias in variant genotyping improves the population representativeness of the WGS maps, and highlights the extent of uncaptured variation using array genotyping methodologies. The complete capture of LD patterns using WGS allows for higher genome-wide association study (GWAS) power compared to array-based GWAS, with WGS also allowing for the analysis of rare variation. The impact of marker ascertainment issues in arrays has been greatest for Sub-Saharan African populations where larger sample sizes and substantially higher marker densities are required to fully resolve the LD structure. WGS provides the best possible resource for LD mapping due to the maximal marker density and lack of ascertainment bias. WGS LD maps provide a rich resource for medical and population genetics studies. The increasing availability of WGS data for large populations will allow for improved research utilising LD, such as GWAS and recombination biology studies.

  5. Human resources requirements for diabetic patients healthcare in primary care clinics of the Mexican Institute of Social Security

    OpenAIRE

    Doubova, Svetlana V; Claudine Ramírez-Sánchez; Alejandro Figueroa-Lara; Ricardo Pérez-Cuevas

    2013-01-01

    Objective. To estimate the requirements of human resources (HR) of two models of care for diabetes patients: conventional and specific, also called DiabetIMSS, which are provided in primary care clinics of the Mexican Institute of Social Security (IMSS). Materials and methods. An evaluative research was conducted. An expert group identified the HR activities and time required to provide healthcare consistent with the best clinical practices for diabetic patients. HR were estimated by using th...

  6. Ultrasonographic features of focal xanthogranulomatous pyelonephritis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Chul [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2003-09-15

    To analyze ultrasonographic (US) features of focal xanthogranulomatous pyelonephritis (XGP). US features of 15 patients with pathologically proven focal XGP were retrospectively analyzed by two radiologists who reached a consensus, in terms of the location, margin, size, and echo texture of the mass-like lesion, and presence or absence of associated calculi, lymphadenopathy, or local extension. These US findings were compared with CT findings. The patients were checked for the clinical symptom and sign through the review of hospital records. Thirteen of 15 patients were adults and 2 were children, and 10 were males. Their age ranged from 6 to 57 (mean, 39) years at presentation. Eight of 15 cases (53%) were in right kidney, and on US scan 12 cases (80%) were well circumscribed. The size of the mass ranged from 2.5 to 5.8 (mean, 3.8) cm. Of 15 masses, 13 (87%) were solid and two were cystic. Thirteen solid masses were composed of 10 masses (77%) with inner hypo- or anechoic foci and the other three masses without inner hypo- or anechoic foci, and the preoperative diagnosis was either renal cell carcinoma (n=11) or Wilms' tumor (n=2). The preoperative diagnosis in two cystic lesions (13%) was renal abscess. Renal calculi were found in one case, but lymphadenopathy or local extension was not depicted. Clinical symptoms and signs of flank pain, fever, leukocytosis, or anemia were found in 11 of 15 patients. Focal XGP revealed US features of solid or cystic masses confined within the renal outline mimicking renal tumor or abscess. US features, however, in association with clinical findings and other imaging findings (such as CT or MR imaging) may help the differential diagnosis of this lesion.

  7. Selecting focal species as surrogates for imperiled species using relative sensitivities derived from occupancy analysis

    Science.gov (United States)

    Silvano, Amy; Guyer, Craig; Steury, Todd; Grand, James B.

    2017-01-01

    Most imperiled species are rare or elusive and difficult to detect, which makes gathering data to estimate their response to habitat restoration a challenge. We used a repeatable, systematic method for selecting focal species using relative sensitivities derived from occupancy analysis. Our objective was to select suites of focal species that would be useful as surrogates when predicting effects of restoration of habitat characteristics preferred by imperiled species. We developed 27 habitat profiles that represent general habitat relationships for 118 imperiled species. We identified 23 regularly encountered species that were sensitive to important aspects of those profiles. We validated our approach by examining the correlation between estimated probabilities of occupancy for species of concern and focal species selected using our method. Occupancy rates of focal species were more related to occupancy rates of imperiled species when they were sensitive to more of the parameters appearing in profiles of imperiled species. We suggest that this approach can be an effective means of predicting responses by imperiled species to proposed management actions. However, adequate monitoring will be required to determine the effectiveness of using focal species to guide management actions.

  8. Simplified model of an O-ring-driven liquid-filled lens for calculating focal length

    Science.gov (United States)

    Lin, Chih-Wei; Shaw, Dein

    2009-07-01

    The purpose of this study was to develop a mathematical model that could be used to obtain the approximate focal length of O-ring-driven liquid-filled lenses. An O-ring-driven liquid-filled lens is composed of a base plate, a glass-covered liquid reservoir, a pliable membrane, an O-ring, a spring, and three actuators. The movement of the ring changes the focal length or the focus position. In previous studies, the commercial software ANSYS was used to find the membrane deformation and ZEMAX was used to find the focal length. The procedures used in those previous studies are complicated and generally require considerable design work. The proposed mathematical method employs the principle of liquid volume conservation to simplify the calculations that approximate the focal length of the lens. The result is confirmed on ZEMAX to ensure that the method is practicable. Consequently, focal lengths of lenses with different ring thicknesses, radii, and squeezing depths to contact the membrane can be calculated immediately.

  9. Hippocampal sclerosis and associated focal cortical dysplasia-related epilepsy in neurofibromatosis type I.

    Science.gov (United States)

    Gales, Jordan; Prayson, Richard A

    2017-03-01

    Neurofibromatosis type I (NF1) is a relatively common disorder associated with a range of neurologic sequelae. Refractory epilepsy occurs in 4-13% of NF1 patients. Hippocampal sclerosis and focal cortical dysplasia, both well-defined epilepsy-related entities, have been described in a subset of cases. To our knowledge, there has been only one other series describing coexistent focal cortical dysplasia and hippocampal sclerosis in the setting of NF1. We report two such patients who presented with intractable seizures requiring epilepsy surgery. Histologically, the hippocampal sclerosis specimen met criteria for the International League Against Epilepsy (ILAE) hippocampal sclerosis subtypes Ia and II respectively. The associated focal cortical dysplasia observed within the resected temporal lobe were both consistent with ILAE focal cortical dysplasia type IIIa (e.g. associated with a secondary lesion). Post-operatively, both patients had recurrence of habitual seizures, with one case continuing to have intractable seizures following two subsequent temporal lobectomies. Although hippocampal sclerosis association with focal cortical dysplasia is well document in epilepsy, it has been rarely described in the setting of neurofibromatosis type I. Although prior surgical series have shown good epilepsy surgery outcomes within neurofibromatosis type I, these two cases did not. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Strong reducing of the laser focal volume

    CSIR Research Space (South Africa)

    Godin, T

    2011-08-01

    Full Text Available high power within the focal volume, is much more ?general? and could then be applied to different applications such as 3-D laser prototyping, linear and non-linear fluorescence microscopy, nano-structuration of materials, optical tweezers, optical... laser beams? allowing to improve significantly the spatial resolution of a certain number of laser applications such as non-linear microscopy, optical trapping and tweezing, 3-D prototyping? Let us consider a collimated symmetrical Laguerre-Gauss 0pTEM...

  11. Focal inflammatory diseases of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-10-01

    Inflammatory lesions constitute an important subgroup of focal liver lesions. They may mimic primary or metastatic neoplastic lesions and their differentiation from neoplasia is clinically very important since management of the patient significantly changes. Radiologists should have an important role in both the diagnosis and therapy of these lesions by performing percutaneous aspirations and drainages. In this review we discussed the radiological findings of pyogenic abscesses, amebic abscesses, candidiasis, tuberculosis, hydatic cysts, fascioliasis, ascariasis, schistosomiasis, and sarcoidosis with a special emphasis on US, CT and MR characteristics.

  12. FOCAL EPITHELIAL HYPERPLASIA: HECK’S DISEASE

    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr

    2010-10-01

    Full Text Available Heck's disease (focal epithelial hyperplasia (FEH is clinically characterized by multiple circumscribed, soft elevated nodules of the oral mucosa. Papules and plaques are usually the color of normal mucosa, but may be pale or, rarely, white. Disease may persist for years, producing a significant reduction in quality of life. Lessions may be located in the area of mucous membranes of the lips, cheeks and tongue. It is believed that the two virus types are responsible for the FEH, are: HPV 13 and HPV 32. Different therapeutic procedures have been reported: surgical excision, laser ablation, cryotherapy, electrocauterization, interferon, retinoic acid, 5% immiquimod.

  13. Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation.

    Science.gov (United States)

    Lang, Julie; Kelly, Margot; Freed, Brian M; McCarter, Martin D; Kedl, Ross M; Torres, Raul M; Pelanda, Roberta

    2013-03-01

    The hematopoietic humanized mouse (hu-mouse) model is a powerful resource to study and manipulate the human immune system. However, a major and recurrent issue with this model has been the poor maturation of B cells that fail to progress beyond the transitional B cell stage. Of interest, a similar problem has been reported in transplant patients who receive cord blood stem cells. In this study, we characterize the development of human B and T cells in the lymph nodes (LNs) and spleen of BALB/c-Rag2(null)Il2rγ(null) hu-mice. We find a dominant population of immature B cells in the blood and spleen early, followed by a population of human T cells, coincident with the detection of LNs. Notably, in older mice we observe a major population of mature B cells in LNs and in the spleens of mice with higher T cell frequencies. Moreover, we demonstrate that T cells are necessary for B cell maturation, as introduction of autologous human T cells expedites the appearance of mature B cells, whereas in vivo depletion of T cells retards B cell maturation. The presence of the mature B cell population correlates with enhanced IgG and Ag-specific responses to both T cell-dependent and T cell-independent challenges, indicating their functionality. These findings enhance our understanding of human B cell development, provide increased details of the reconstitution dynamics of hu-mice, and validate the use of this animal model to study mechanisms and treatments for the similar delay of functional B cells associated with cord blood transplantations.

  14. THE STRATEGIC DEVELOPMENT OF HUMAN RESOURCES-IMPERATIVE REQUIREMENT OF THE PUBLIC ADMINISTRATION REFORM

    OpenAIRE

    Cristina MANOLE

    2011-01-01

    Together with the global economic crisis, the impact of organizational crises on human capital and its performances has become increasingly obvious. From this perspective, the strategic role of human resources’ development is crucial. This development can help the organizational management to improve their operational abilities, that allow a better management of the existing crises and also preventing future one. Most researchers agree that the strategic development of human resources implies...

  15. High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI).

    Science.gov (United States)

    Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

    2015-08-07

    the planning phase. The focal spot localization method has also been applied on ex vivo human breast tissue ablation and can be fully integrated into any HMI system for planning purposes.

  16. High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI)

    Science.gov (United States)

    Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

    2015-08-01

    inducing thermal changes during the planning phase. The focal spot localization method has also been applied on ex vivo human breast tissue ablation and can be fully integrated into any HMI system for planning purposes.

  17. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis.

    Science.gov (United States)

    Kain, Renate; Exner, Markus; Brandes, Ricarda; Ziebermayr, Reinhard; Cunningham, Dawn; Alderson, Carol A; Davidovits, Agnes; Raab, Ingrid; Jahn, Renate; Ashour, Oliver; Spitzauer, Susanne; Sunder-Plassmann, Gere; Fukuda, Minoru; Klemm, Per; Rees, Andrew J; Kerjaschki, Dontscho

    2008-10-01

    Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present in almost all individuals with FNGN. Consequently, its prevalence is nearly twice that of the classical ANCAs that recognize myeloperoxidase or proteinase-3. Furthermore, antibodies to LAMP-2 cause pauci-immune FNGN when injected into rats, and a monoclonal antibody to human LAMP-2 (H4B4) induces apoptosis of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P(41-49)) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with FimH develop pauci-immune FNGN and also develop antibodies to rat and human LAMP-2. Finally, we show that infections with fimbriated pathogens are common before the onset of FNGN. Thus, FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN.

  18. Estimation of dose requirements for sustained in vivo activity of a therapeutic human anti-CD20 antibody

    NARCIS (Netherlands)

    Bleeker, Wim K.; Munk, Martin E.; Mackus, Wendy J. M.; van den Brakel, Jeroen H. N.; Pluyter, Marielle; Glennie, Martin J.; van de Winkel, Jan G. J.; Parren, Paul W. H. I.

    We evaluated the dose requirements for sustained in vivo activity of ofatumumab, a human anti-CD20 antibody under development for the treatment of B cell-mediated diseases. In a mouse xenograft model, a single dose, resulting in an initial plasma antibody concentration of 5 mu g/ml, which was

  19. 21 CFR 201.57 - Specific requirements on content and format of labeling for human prescription drug and...

    Science.gov (United States)

    2010-04-01

    ... available concerning the use of the drug in other specified subpopulations (e.g., renal or hepatic... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1). 201.57 Section...

  20. FoCaLiZe: Inside an F-IDE

    Directory of Open Access Journals (Sweden)

    François Pessaux

    2014-04-01

    Full Text Available For years, Integrated Development Environments have demonstrated their usefulness in order to ease the development of software. High-level security or safety systems require proofs of compliance to standards, based on analyses such as code review and, increasingly nowadays, formal proofs of conformance to specifications. This implies mixing computational and logical aspects all along the development, which naturally raises the need for a notion of Formal IDE. This paper examines the FoCaLiZe environment and explores the implementation issues raised by the decision to provide a single language to express specification properties, source code and machine-checked proofs while allowing incremental development and code reusability. Such features create strong dependencies between functions, properties and proofs, and impose an particular compilation scheme, which is described here. The compilation results are runnable OCaml code and a checkable Coq term. All these points are illustrated through a running example.

  1. Benign focal hepatic lesions; Benigne fokale Leberlaesionen

    Energy Technology Data Exchange (ETDEWEB)

    Baroud, S.; Bastati, N.; Prosch, H.; Ba-Ssalamah, A. [AKH, Medizinische Universitaet Wien, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria); Schima, W. [Krankenhaus Goettlicher Heiland, Wien, Abteilung fuer Radiologie und Bildgebende Diagnostik, Wien (Austria)

    2011-08-15

    A profound knowledge of the various benign focal hepatic lesions and selection of the most suitable radiological examination modality is essential for achieving an accurate characterization of a hepatic lesion and in turn will determine the further patient management. This will avoid unnecessary agitation to both patient and the referring clinician and limits time-consuming, costly and risky biopsies to an absolute minimum. The following article will discuss the typical and atypical appearances of the most frequent and clinically relevant benign focal hepatic lesions with ultrasound, computed tomography and magnetic resonance imaging. (orig.) [German] Eine genaue Kenntnis des breiten Spektrums benigner fokaler Leberlaesionen und der geeigneten radiologischen Untersuchungsmethode ist essenziell, um eine sichere Diagnose bzgl. der Dignitaet und damit das weitere Vorgehen bestimmen zu koennen. Damit wird eine unnoetige Verunsicherung des Patienten und des behandelnden Arztes vermieden, und invasive, eventuell mit Komplikationen assoziierte Biopsien sowie zeit- und kostenintensive Verlaufskontrollen koennen reduziert werden. Der folgende Artikel erlaeutert die haeufigsten und klinisch wichtigsten benignen fokalen Leberlaesionen und deren typisches und atypisches Erscheinen in den 3 haeufig verwendeten bildgebenden Verfahren Sonographie, Computertomographie und Magnetresonanztomographie. (orig.)

  2. Focal cortical dysplasia and epilepsy surgery.

    Science.gov (United States)

    Lee, Sang Kun; Kim, Dong-Wook

    2013-12-01

    Focal cortical dysplasia (FCD) is the most commonly encountered developmental malformation that causes refractory epilepsy. With advances in neuroimaging techniques, in particular MRI, recent studies have revealed a higher prevalence of FCD than previously estimated and have improved the preoperative identification and classification of these abnormalities. However, MRI frequently does not show any abnormalities in patients with pathologically proven FCD. In this situation, functional neuroimaing such as FDG-PET and ictal SPECT can be helpful. FCD is thought to be intrinsically epileptogenic, because the dysplastic tissues contain aberrant neural networks that are highly susceptible to abnormal excitation. The response to the medical treatment of epilepsy has been documented as consistently poor. Therefore, surgical resection has been an important alternative treatment for patients with intractable epilepsy related to FCD. Incomplete resection of FCD has been consistently known to be a poor prognostic factor. However, the complete removal of FCD is often difficult because the demarcation of the lesion is frequently poor, and dysplastic tissues tend to be more extensive than is apparent on MRI. Evidence indicates that even patients with MRI abnormalities who have resective epilepsy surgery for FCD have worse surgical outcomes than those of patients who have surgery for other focal lesional epilepsy syndromes. Careful planning of evelauation using intracranial electrodes is necessary for successful epilepsy surgery.

  3. Human resources requirements for diabetic patients healthcare in primary care clinics of the Mexican Institute of Social Security

    Directory of Open Access Journals (Sweden)

    Svetlana V Doubova

    2013-11-01

    Full Text Available Objective. To estimate the requirements of human resources (HR of two models of care for diabetes patients: conventional and specific, also called DiabetIMSS, which are provided in primary care clinics of the Mexican Institute of Social Security (IMSS. Materials and methods. An evaluative research was conducted. An expert group identified the HR activities and time required to provide healthcare consistent with the best clinical practices for diabetic patients. HR were estimated by using the evidence-based adjusted service target approach for health workforce planning; then, comparisons between existing and estimated HRs were made. Results. To provide healthcare in accordance with the patients’ metabolic control, the conventional model required increasing the number of family doctors (1.2 times nutritionists (4.2 times and social workers (4.1 times. The DiabetIMSS model requires greater increase than the conventional model. Conclusions. Increasing HR is required to provide evidence-based healthcare to diabetes patients.

  4. [Human resources requirements for diabetic patients healthcare in primary care clinics of the Mexican Institute of Social Security].

    Science.gov (United States)

    Doubova, Svetlana V; Ramírez-Sánchez, Claudine; Figueroa-Lara, Alejandro; Pérez-Cuevas, Ricardo

    2013-12-01

    To estimate the requirements of human resources (HR) of two models of care for diabetes patients: conventional and specific, also called DiabetIMSS, which are provided in primary care clinics of the Mexican Institute of Social Security (IMSS). An evaluative research was conducted. An expert group identified the HR activities and time required to provide healthcare consistent with the best clinical practices for diabetic patients. HR were estimated by using the evidence-based adjusted service target approach for health workforce planning; then, comparisons between existing and estimated HRs were made. To provide healthcare in accordance with the patients' metabolic control, the conventional model required increasing the number of family doctors (1.2 times) nutritionists (4.2 times) and social workers (4.1 times). The DiabetIMSS model requires greater increase than the conventional model. Increasing HR is required to provide evidence-based healthcare to diabetes patients.

  5. Focal fatty infiltra- tion and focal fatty sparing of the liver

    African Journals Online (AJOL)

    Enrique

    Hounsfield units (HU) while the nor- mal parenchyma had a mean density measurement of 40 HU (Fig. 1a). The contrast-enhanced study demonstrat- ed decreased perfusion in those regions of low density (Fig. 1b). A diagnosis of focal fatty infiltration of the liver was made. The patient was subsequently found to have type 2.

  6. Metabolic demands for amino acids and the human dietary requirement: Millward and rRvers (1988) revisited.

    Science.gov (United States)

    Millward, D J

    1998-12-01

    In 1988, Millward and Rivers reappraised existing metabolic models for amino acid requirements. The metabolic demand for amino acids was reviewed in relation to both obligatory metabolic consumption and adaptive pathways of amino acid oxidation. The obligatory demand pattern was deemed unknowable from first principles except that the level of one amino acid would be similar to its concentration in an amount of tissue protein equivalent to the obligatory nitrogen loss. The adaptive demand pattern was predicted to vary in relation to the amount and the periodicity of food protein intake that influenced the amplitude of the diurnal cycle of gains and losses. A regulatory influence of protein intake on anabolism, the anabolic drive, was identified in animal studies; benefit appeared to derive from intakes in excess of the minimum for balance, which could facilitate definition of an optimal requirement. The inherent and design-related limitations of both nitrogen and stable isotope balance studies of requirement were recognized as a major problem in identifying secure values for indispensable amino acid requirements. A decade of research of increasing methodological sophistication has generated much new information, confirming the adaptive diurnal model of balance regulation and allowing development of the anabolic drive into a general protein-stat theory for coordinated control of growth and maintenance of the lean body mass. However, notwithstanding several new estimates of amino acid requirement values, definition of a widely accepted human amino acid requirement pattern remains unresolved. Although a case can be made for an adjusted 1985 FAO adult requirement pattern being a reasonable estimate of the obligatory indispensable amino acid requirements for human maintenance, the problems posed by adaptation, methodological inadequacies and lack of independent measures of adequacy mean that assessment of the adequacy of the human diet to satisfy amino acid needs remains

  7. Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2.

    Directory of Open Access Journals (Sweden)

    Carlos F Pereira

    2008-09-01

    Full Text Available Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused with embryonic stem (ES cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent state is initiated much more rapidly than previously thought, occurring in transient heterokaryons before nuclear fusion and cell division. Interestingly, reprogramming of human lymphocytes by mouse ES cells elicits the expression of a human ES-specific gene profile, in which markers of human ES cells are expressed (hSSEA4, hFGF receptors and ligands, but markers that are specific to mouse ES cells are not (e.g., Bmp4 and LIF receptor. Using genetically engineered mouse ES cells, we demonstrate that successful reprogramming of human lymphocytes is independent of Sox2, a factor thought to be required for induced pluripotent stem (iPS cells. In contrast, there is a distinct requirement for Oct4 in the establishment but not the maintenance of the reprogrammed state. Experimental heterokaryons, therefore, offer a powerful approach to trace the contribution of individual factors to the reprogramming of human somatic cells towards a multipotent state.

  8. Evaluation of the focal spot and MTF of mammographic equipment without alignment with the central beam; Avaliacao do ponto focal e da funcao de transferencia de modulacao de equipamentos mamograficos sem necessidade de alinhamento com o feixe central

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Junior, Paulo D.; Vieira, Marcelo A.C.; Schiabel, Homero [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Escola de Engenharia. Dept. de Engenharia Eletrica], e-mail: poliveira@sc.usp.br

    2010-03-15

    The image quality of a mammographic system is directly affected by the size of the focal spot and its measurement is very important for quality assurance evaluations. Modulation Transfer Function (MTF) is widely recognized as the best descriptor for spatial resolution evaluation of radiological equipment. However, focal spot size and MTF measurements have several complex technical procedures, such as the requirement of precise alignment and direct-exposure film, which have been making such measurements more difficult and time-consuming and besides sometimes less accurate. The purpose of this work is to present a new methodology to perform MTF and focal spot measurements from two focal spot projections at any position over the field acquired by using a pinhole camera and a CCD intraoral X-ray imaging device. Thus, it can allow those measurements in quality control procedures to be easier and faster, with no need of previous alignment. (author)

  9. Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse model.

    Science.gov (United States)

    Liu, Zhi; Sui, Wen; Zhao, Minglang; Li, Zhuowei; Li, Ning; Thresher, Randy; Giudice, George J; Fairley, Janet A; Sitaru, Cassian; Zillikens, Detlef; Ning, Gang; Marinkovich, M Peter; Diaz, Luis A

    2008-12-01

    Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease associated with subepidermal blistering and autoantibodies against BP180, a transmembrane collagen and major component of the hemidesmosome. Numerous inflammatory cells infiltrate the upper dermis in BP. IgG autoantibodies in BP fix complement and target multiple BP180 epitopes that are highly clustered within a non-collagen linker domain, termed NC16A. Anti-BP180 antibodies induce BP in mice. In this study, we generated a humanized mouse strain, in which the murine BP180NC14A is replaced with the homologous human BP180NC16A epitope cluster region. We show that the humanized NC16A (NC16A+/+) mice injected with anti-BP180NC16A autoantibodies develop BP-like subepidermal blisters. The F(ab')(2) fragments of pathogenic IgG fail to activate the complement cascade and are no longer pathogenic. The NC16A+/+ mice pretreated with mast cell activation blocker or depleted of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players.

  10. Kalman filtering techniques for focal plane electric field estimation.

    Science.gov (United States)

    Groff, Tyler D; Jeremy Kasdin, N

    2013-01-01

    For a coronagraph to detect faint exoplanets, it will require focal plane wavefront control techniques to continue reaching smaller angular separations and higher contrast levels. These correction algorithms are iterative and the control methods need an estimate of the electric field at the science camera, which requires nearly all of the images taken for the correction. The best way to make such algorithms the least disruptive to science exposures is to reduce the number required to estimate the field. We demonstrate a Kalman filter estimator that uses prior knowledge to create the estimate of the electric field, dramatically reducing the number of exposures required to estimate the image plane electric field while stabilizing the suppression against poor signal-to-noise. In addition to a significant reduction in exposures, we discuss the relative merit of this algorithm to estimation schemes that do not incorporate prior state estimate history, particularly in regard to estimate error and covariance. Ultimately the filter will lead to an adaptive algorithm which can estimate physical parameters in the laboratory for robustness to variance in the optical train.

  11. Long Telomeres Bypass the Requirement for Telomere Maintenance in Human Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Michael A.S. Taboski

    2012-02-01

    Full Text Available Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT or alternative lengthening of telomeres (ALT, it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis. We engineered human tumor cells containing loxP-flanked hTERT to enable extensive telomere elongation prior to complete hTERT excision. Despite unabated telomere erosion, hTERT-excised cells formed tumors in mice and proliferated in vitro for up to 1 year. Telomerase reactivation or ALT was not observed, and the eventual loss of telomeric signal coincided with loss of tumorigenic potential and cell viability. Crisis was averted via the reintroduction of active but not inactive hTERT. Thus, telomere maintenance is dispensable for human tumorigenesis when telomere reserves are long. Yet, despite telomere instability and the presence of oncogenic RAS, human tumors remain susceptible to crisis induced by critically short telomeres.

  12. Multiple focal nodular hyperplasias induced by oxaliplatin-based chemotherapy

    OpenAIRE

    Donadon, M.; Di Tommaso, L; Roncalli, M; Torzilli, G.

    2013-01-01

    Focal nodular hyperplasia (FNH) is a benign condition that affects normal liver with low prevalence. Recently, the extensive use of oxaliplatin to treat patients with colorectal cancer has been reported to be associated with the development of different liver injuries, as well as focal liver lesions. The present work describes two patients with multiple bilateral focal liver lesions misdiagnosed as colorectal liver metastases, and treated with liver resection. The first patient had up to 15 s...

  13. Physical Activity Performance of Focal Middle School Students

    Science.gov (United States)

    Erfle, Stephen E.; Gelbaugh, Corey M.

    2013-01-01

    Histograms of push-ups and curl-ups from a sample of more than 9,000 students show periodic spikes at five and 10 unit intervals. This article argues that these spikes are related to focal points, a game theoretic concept popularized by Nobel Laureate Thomas Schelling. Being focal on one test makes one more likely to be focal on the other. Focal…

  14. Focal Targeting of the Bacterial Envelope by Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Rafi eRashid

    2016-06-01

    Full Text Available Antimicrobial peptides (AMPs are utilized by both eukaryotic and prokaryotic organisms. AMPs such as the human beta defensins, human neutrophil peptides, human cathelicidin, and many bacterial bacteriocins are cationic and capable of binding to anionic regions of the bacterial surface. Cationic AMPs (CAMPs target anionic lipids (e.g. phosphatidylglycerol (PG and cardiolipins (CL in the cell membrane and anionic components (e.g. lipopolysaccharide (LPS and lipoteichoic acid (LTA of the cell envelope. Bacteria have evolved mechanisms to modify these same targets in order to resist CAMP killing, e.g. lysinylation of PG to yield cationic lysyl-PG and alanylation of LTA. Since CAMPs offer a promising therapeutic alternative to conventional antibiotics, which are becoming less effective due to rapidly emerging antibiotic resistance, there is a strong need to improve our understanding about the AMP mechanism of action. Recent literature suggests that AMPs often interact with the bacterial cell envelope at discrete foci. Here we review recent AMP literature, with an emphasis on focal interactions with bacteria, including (1 CAMP disruption mechanisms, (2 delocalization of membrane proteins and lipids by CAMPs, and (3 CAMP sensing systems and resistance mechanisms. We conclude with new approaches for studying the bacterial membrane, e.g., lipidomics, high resolution imaging and non-detergent-based membrane domain extraction.

  15. Earthquake focal parameters and lithospheric structure of the anatolian plateau from complete regional waveform modeling

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, A

    2000-12-28

    This is an informal report on preliminary efforts to investigate earthquake focal mechanisms and earth structure in the Anatolian (Turkish) Plateau. Seismic velocity structure of the crust and upper mantle and earthquake focal parameters for event in the Anatolian Plateau are estimated from complete regional waveforms. Focal mechanisms, depths and seismic moments of moderately large crustal events are inferred from long-period (40-100 seconds) waveforms and compared with focal parameters derived from global teleseismic data. Using shorter periods (10-100 seconds) we estimate the shear and compressional velocity structure of the crust and uppermost mantle. Results are broadly consistent with previous studies and imply relatively little crustal thickening beneath the central Anatolian Plateau. Crustal thickness is about 35 km in western Anatolia and greater than 40 km in eastern Anatolia, however the long regional paths require considerable averaging and limit resolution. Crustal velocities are lower than typical continental averages, and even lower than typical active orogens. The mantle P-wave velocity was fixed to 7.9 km/s, in accord with tomographic models. A high sub-Moho Poisson's Ratio of 0.29 was required to fit the Sn-Pn differential times. This is suggestive of high sub-Moho temperatures, high shear wave attenuation and possibly partial melt. The combination of relatively thin crust in a region of high topography and high mantle temperatures suggests that the mantle plays a substantial role in maintaining the elevation.

  16. Pharmacological response of systemically derived focal epileptic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

    1986-11-01

    Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

  17. Focal cemento-osseous dysplasia of mandible.

    Science.gov (United States)

    Cankaya, Abdülkadir Burak; Erdem, Mehmet Ali; Olgac, Vakur; Firat, Deniz Refia

    2012-09-03

    Fibro-osseous lesions are disturbances in bone metabolism in which normal bone is replaced by a connective tissue matrix that then gradually develops into cemento-osseous tissue. Typically, the lesion is asymptomatic and is detected on routine radiographic examination. Radiologically, this lesion has three stages of maturation: pure radiolucent, radiopaque/mixed radiolucent, and radiopaque appearance. During these stages the lesion can be misdiagnosed. In this case report a 69-year- old patient with a a complaint of painless swelling of the left mandibular molar and premolar area is presented along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

  18. Focal epilepsy in the Belgian shepherd

    DEFF Research Database (Denmark)

    Berendt, Mette; Gulløv, Christina Hedal; Fredholm, Merete

    2009-01-01

    OBJECTIVES: To establish the mode of inheritance and describe the clinical features of epilepsy in the Belgian shepherd, taking the outset in an extended Danish dog family (199 individuals) of Groenendael and Tervueren with accumulated epilepsy. METHODS: Epilepsy positive individuals (living...... and deceased) were ascertained through a telephone interview using a standardised questionnaire regarding seizure history and phenomenology. Living dogs were invited to a detailed clinical evaluation. Litters more than five years of age, or where epilepsy was present in all offspring before the age of five......, were included in the calculations of inheritance. results: Out of 199 family members, 66 dogs suffered from epilepsy. The prevalence of epilepsy in the family was 33%. Fifty-five dogs experienced focal seizures with or without secondary generalisation, while four dogs experienced primary generalised...

  19. Smart trigger logic for focal plane arrays

    Energy Technology Data Exchange (ETDEWEB)

    Levy, James E; Campbell, David V; Holmes, Michael L; Lovejoy, Robert; Wojciechowski, Kenneth; Kay, Randolph R; Cavanaugh, William S; Gurrieri, Thomas M

    2014-03-25

    An electronic device includes a memory configured to receive data representing light intensity values from pixels in a focal plane array and a processor that analyzes the received data to determine which light values correspond to triggered pixels, where the triggered pixels are those pixels that meet a predefined set of criteria, and determines, for each triggered pixel, a set of neighbor pixels for which light intensity values are to be stored. The electronic device also includes a buffer that temporarily stores light intensity values for at least one previously processed row of pixels, so that when a triggered pixel is identified in a current row, light intensity values for the neighbor pixels in the previously processed row and for the triggered pixel are persistently stored, as well as a data transmitter that transmits the persistently stored light intensity values for the triggered and neighbor pixels to a data receiver.

  20. Idiopathic focal segmental glomerulosclerosis and HLA antigens

    Directory of Open Access Journals (Sweden)

    M. Gerbase-DeLima

    1998-03-01

    Full Text Available The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS. HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P<0.05. In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease

  1. Focal adhesion kinase signaling in unexpected places.

    Science.gov (United States)

    Kleinschmidt, Elizabeth G; Schlaepfer, David D

    2017-04-01

    Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase first identified at extracellular matrix and integrin receptor cell adhesion sites and is a key regulator of cell movement. FAK is activated by a variety of stimuli. Herein, we discuss advances in conformational-associated FAK activation and dimerization mechanisms. Additionally, new roles have emerged for FAK signaling at cell adhesions, adherens junctions, endosomes, and the nucleus. In light of these new findings, we review how FAK activation at these sites is connected to the regulation of integrin recycling-activation, vascular permeability, cell survival, and transcriptional regulation, respectively. Studies uncovering FAK signaling connections in unexpected places within cells have yielded important new regulatory insights in cell biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Focal choroidal excavation complicated by choroidal neovascularization.

    Science.gov (United States)

    Xu, Haifeng; Zeng, Fanxing; Shi, Depeng; Sun, Xiaolei; Chen, Xiuli; Bai, Yao

    2014-01-01

    To evaluate the clinical findings of focal choroidal excavation (FCE) complicated by choroidal neovascularization (CNV). Retrospective, observational case series. Twelve patients (15 eyes) with FCE and CNV. The medical records of the patients were reviewed. Clinical findings including age, sex, refraction, color photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (OCT) were analyzed. Fundus fluorescein angiography, ICGA, and OCT findings. The 12 patients included 6 women and 6 men. The mean age was 46.8±13.4 years (range, 26-64 years). One half of the patients were emmetropic, and the others were myopic (-0.5 to -3.0 diopters). All subjects were Chinese. Before CNV development, normal appearance or nonspecific pigment disturbance could be seen around the choroidal excavation. Corresponding to the excavation, window defects were observed by FFA, whereas hypofluorescence was found on ICGA images. Choroidal neovascularization in all eyes was classic as revealed by FFA. The OCT images showed that all eyes had a single choroidal excavation. In 7 of the 15 eyes, the choroidal excavation was located subfoveally, and in the other 8 eyes, it was eccentric. All CNV lesions grew from the bottom or slope of the excavation. Three patients had bilateral involvement. Choroidal neovascularization occurred in both conforming and nonconforming type FCEs, regardless of whether the excavation was shallow or deep, subfoveal or eccentric. All CNV lesions responded well to intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. After a single injection, CNV regressed in 13 of 15 eyes. Two eyes received an additional injection. Nonconforming FCE changed to the conforming type after successful treatment of CNV. Focal choroidal excavation is not always stable. Choroidal neovascularization commonly can be seen in patients with FCE and responds well to intravitreal anti-VEGF agents

  3. Focal choroidal excavation: Clinical findings and complications.

    Science.gov (United States)

    Castro Navarro, V; Montero Hernández, J; Navarro Palop, C; Palomares Fort, P; Cervera Taulet, E

    2016-01-01

    To describe the clinical findings and its complications in 2 patients with focal choroidal excavation (FCE). A retrospective case-series including 4 eyes of 2 patients with FCE that underwent a comprehensive ophthalmological examination including slit-lamp examination, colour fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography. In the 2 patients, both the anterior and posterior segment evaluations were mostly normal despite the of presence yellowish spots in the macular area of the right eye of patient 1, and of a small yellowish elevated lesion with serous macular detachment in the macular area of the left eye in patient 2. At diagnosis, SD-OCT revealed a conforming FCE in patient 1, and in patient 2, an FCE with perilesional subretinal fluid and a neuroepithelium detachment, suspicious of FCE complicated with central serous retinopathy (CSCR). At one year of follow-up, patient 1 developed choroidal neovascularisation (CNV) over the focal choroidal excavation. FA and indocyanine green angiography examinations revealed areas with hypofluorescence in earlier frames, and a diffuse leakage in late frames. After ranibizumab injections, the SD-OCT of patient 1 revealed no active exudation, while patient 2 showed partial resolution of subretinal fluid. FCE is a newly described entity of unclear aetiology. It is characterised by a choroidal excavation in eyes, with absence of posterior staphyloma, scleral ectasia, trauma, or retinal disease. Although most lesions remain stable, there could be an association with CRSC or CNV. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  4. CT findings of focal organizing pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Gyun; Yoon, Sang Wook; Nam, Ji Eun; Choe, Kyu Ok; Kim, Hyoung Jung; Lee, Du Yon; Kim, Sang Jin [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of); Ryu, Young Hoon [Gil General Hospital, Seoul (Korea, Republic of); Ryu, Suk Jong [Inje Univ. College of Medicine, Pusan (Korea, Republic of)

    2000-12-01

    Focal organizing pneumonia (FOP) is a benign condition which is often difficult to differentiate from bronchogenic carcinoma, and many patients with FOP undergo invasive procedures. We tried to determine which CT features might help provide a confident diagnosis of FOP. We retrospectively reviewed the medical records, chest radiographs and CT scans of 13 patients with histopathologically proven FOP. Initial chest radiographs in all 13 suggested bronchogenic carcinoma. The CT scans were reviewed by three radiologists, and final decisions were reached by consensus. They were analyzed in terms of the size, shape, contour and localization of the lesion, interior characteristics of the nodule, changes in surrounding structures, and changes in any of these findings, as revealed by follow-up chest CT scanning. FOP lesions were oval or triangular in shape and between 1.8 and 6.5cm in their largest diameter. All had irregular margins and all but one were peripherally located. Eight (61.5%) were in contact with the pleura and five (38.5%) were located along the peripheral bronchovascular bundle, with pleural indentation; in eight (61.5%), post-contrast CT scanning revealed inhomogeneous enhancement, and four (30.8%) had pleural tags. In five (38.5%), there was coarse spiculation; for six (46.2%), air bronchograms were available, and in four (30.8%), satellite nodules were present. Spotty calcification and lymph node enlargement were each evident in one case only. Follow-up CT scanning, available in four cases, showed that the mass decreased in size in three and disappeared completely in one. Although there were no consistent CT features for differentiating focal organizing pneumonia from lung cancer, the possibility of the former should be considered when a peripherally-located oval or triangular-shaped mass is in broad contact with the pleura or is located along the bronchovascular bundle, and satellite nodules are also present.

  5. Focal cryotherapy: step by step technique description

    Directory of Open Access Journals (Sweden)

    Cristina Redondo

    Full Text Available ABSTRACT Introduction and objective: Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa. The purpose of this video is to describe the procedure step by step. Materials and methods: We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. Results: The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipment utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40°C to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1–5. Conclusions: Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment.

  6. Focal cryotherapy: step by step technique description.

    Science.gov (United States)

    Redondo, Cristina; Srougi, Victor; da Costa, José Batista; Baghdad, Mohammed; Velilla, Guillermo; Nunes-Silva, Igor; Bergerat, Sebastien; Garcia-Barreras, Silvia; Rozet, François; Ingels, Alexandre; Galiano, Marc; Sanchez-Salas, Rafael; Barret, Eric; Cathelineau, Xavier

    2017-01-01

    Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa). The purpose of this video is to describe the procedure step by step. We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipament utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40ºC) to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1-5). Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment. Copyright® by the International Brazilian Journal of Urology.

  7. Management and Evaluation System on Human Error, Licence Requirements, and Job-aptitude in Rail and the Other Industries

    Energy Technology Data Exchange (ETDEWEB)

    Koo, In Soo; Suh, S. M.; Park, G. O. (and others)

    2006-07-15

    Rail system is a system that is very closely related to the public life. When an accident happens, the public using this system should be injured or even be killed. The accident that recently took place in Taegu subway system, because of the inappropriate human-side task performance, showed demonstratively how its results could turn out to be tragic one. Many studies have shown that the most cases of the accidents have occurred because of performing his/her tasks in inappropriate way. It is generally recognised that the rail system without human element could never be happened quite long time. So human element in rail system is going to be the major factor to the next tragic accident. This state of the art report studied the cases of the managements and evaluation systems related to human errors, license requirements, and job aptitudes in the areas of rail and the other industries for the purpose of improvement of the task performance of personnel which consists of an element and finally enhancement of rail safety. The human errors, license requirements, and evaluation system of the job aptitude on people engaged in agencies with close relation to rail do much for development and preservation their abilities. But due to various inside and outside factors, to some extent it may have limitations to timely reflect overall trends of society, technology, and a sense of value. Removal and control of the factors of human errors will have epochal roles in safety of the rail system through the case studies of this report. Analytical results on case studies of this report will be used in the project 'Development of Management Criteria on Human Error and Evaluation Criteria on Job-aptitude of Rail Safe-operation Personnel' which has been carried out as a part of 'Integrated R and D Program for Railway Safety'.

  8. Dogs’ recognition of human selfish and generous attitudes requires little but critical experience with people

    OpenAIRE

    Carballo, Fabricio; Freidin, Esteban; Emma B Casanave; Bentosela, Mariana

    2017-01-01

    There is some dispute regarding the role of experience in the development of dogs´ socio-cognitive abilities in their interaction with people. We sought to provide new evidence to this debate by comparing dogs with contrasting levels of experience with humans, in a task involving the discrimination of human generous and selfish attitudes. To this end, we compared the performance of adult family dogs against that of adult shelter dogs and puppies living in people´s homes. In training trials, t...

  9. The neural basis for establishing a focal point in pure coordination games.

    Science.gov (United States)

    McMillan, Corey T; Rascovsky, Katya; Khella, M Catherine; Clark, Robin; Grossman, Murray

    2012-11-01

    When making a decision, humans often have to 'coordinate'-reach the same conclusion-as another individual without explicitly communicating. Relatively, little is known about the neural basis for coordination. Moreover, previous fMRI investigations have supported conflicting hypotheses. One account proposes that individuals coordinate using a 'gut feeling' and that this is supported by insula recruitment. Another account proposes that individuals recruit strategic decision-making mechanisms in prefrontal cortex in order to coordinate. We investigate the neural basis for coordination in individuals with behavioral-variant frontotemporal dementia (bvFTD) who have limitations in social decision-making associated with disease in prefrontal cortex. We demonstrate that bvFTD are impaired at establishing a focal point in a semantic task (e.g. 'Tell me any boy's name') that requires coordination relative to a similar, control semantic task that does not. Additionally, coordination limitations in bvFTD are related to cortical thinning in prefrontal cortex. These findings are consistent with behavioral economic models proposing that, beyond a 'gut feeling', strategic decision-making contributes to the coordination process, including a probabilistic mechanism that evaluates the salience of a response (e.g. is 'John' a frequent boy's name), a hierarchical mechanism that iteratively models an opponent's likely response and a mechanism involved in social perspective taking.

  10. Sighting optics including an optical element having a first focal length and a second focal length and methods for sighting

    Science.gov (United States)

    Crandall, David Lynn

    2011-08-16

    Sighting optics include a front sight and a rear sight positioned in a spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus for a user images of the front sight and the target.

  11. Efficient human immunodeficiency virus replication requires a fine-tuned level of transcription

    NARCIS (Netherlands)

    Marzio, Giuseppe; Vink, Monique; Verhoef, Koen; de Ronde, Anthony; Berkhout, Ben

    2002-01-01

    Transcription represents a crucial step in the life cycle of human immunodeficiency virus (HIV) and is highly regulated. Here we show that the strength of the viral long terminal repeat (LTR) promoter is optimized for efficient replication. Artificially increasing the rate of LTR-driven

  12. Legal requirements for human-health based appeals of wind energy projects in ontario.

    Science.gov (United States)

    Engel, Albert M

    2014-01-01

    In 2009, the government of the province of Ontario, Canada passed new legislation to promote the development of renewable energy facilities, including wind energy facilities in the province. Throughout the legislative process, concerns were raised with respect to the effect of wind energy facilities on human health. Ultimately, the government established setbacks and sound level limits for wind energy facilities and provided Ontario residents with the right to appeal the approval of a wind energy facility on the ground that engaging in the facility in accordance with its approval will cause serious harm to human health. The first approval of a wind facility under the new legislation was issued in 2010 and since then, Ontario's Environmental Review Tribunal as well as Ontario's courts has been considering evidence proffered by appellants seeking revocation of approvals on the basis of serious harm to human health. To date, the evidence has been insufficient to support the revocation of a wind facility approval. This article reviews the legal basis for the dismissal of human-health based appeals.

  13. Legal Requirements for Human-Health based appeals of Wind Energy Projects in Ontario

    Directory of Open Access Journals (Sweden)

    Albert Michael Engel

    2014-12-01

    Full Text Available In 2009 the government of the province of Ontario, Canada passed new legislation to promote the development of renewable energy facilities, including wind energy facilities in the province. Throughout the legislative process, concerns were raised with respect to the effect of wind energy facilities on human health. Ultimately, the government established setbacks and sound level limits for wind energy facilities and provided Ontario residents with the right to appeal the approval of a wind energy facility on the ground that engaging in the facility in accordance with its approval will cause serious harm to human health. The first approval of a wind facility under the new legislation was issued in 2010 and since then, Ontario’s Environmental Review Tribunal as well as Ontario’s courts have been considering evidence proffered by appellants seeking revocation of approvals on the basis of serious harm to human health. To date, the evidence has been insufficient to support the revocation of a wind facility approval. This article reviews the legal basis for the dismissal of human-health based appeals.

  14. Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers

    DEFF Research Database (Denmark)

    Loft, Anne; Forss, Isabel; Siersbæk, Majken Storm

    2015-01-01

    Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-in...

  15. Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Final rule.

    Science.gov (United States)

    2014-12-04

    The Food and Drug Administration (FDA) is amending its regulations governing the content and format of the "Pregnancy," "Labor and delivery," and "Nursing mothers" subsections of the "Use in Specific Populations" section of the labeling for human prescription drug and biological products. The final rule requires the removal of the pregnancy categories A, B, C, D, and X from all human prescription drug and biological product labeling. For human prescription drug and biological products subject to the Agency's 2006 Physician Labeling Rule, the final rule requires that the labeling include a summary of the risks of using a drug during pregnancy and lactation, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and lactation. The final rule eliminates the "Labor and delivery" subsection because information about labor and delivery is included in the "Pregnancy" subsection. The final rule requires that the labeling include relevant information about pregnancy testing, contraception, and infertility for health care providers prescribing for females and males of reproductive potential. The final rule creates a consistent format for providing information about the risks and benefits of prescription drug and/or biological product use during pregnancy and lactation and by females and males of reproductive potential. These revisions will facilitate prescriber counseling for these populations.

  16. Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcγR Engagement.

    Science.gov (United States)

    Dahan, Rony; Barnhart, Bryan C; Li, Fubin; Yamniuk, Aaron P; Korman, Alan J; Ravetch, Jeffrey V

    2016-06-13

    While engagement of the inhibitory Fcγ-receptor (FcγR) IIB is an absolute requirement for in vivo antitumor activity of agonistic mouse anti-CD40 monoclonal antibodies (mAbs), a similar requirement for human mAbs has been disputed. By using a mouse model humanized for its FcγRs and CD40, we revealed that FcγRIIB engagement is essential for the activity of human CD40 mAbs, while engagement of the activating FcγRIIA inhibits this activity. By engineering Fc variants with selective enhanced binding to FcγRIIB, but not to FcγRIIA, significantly improved antitumor immunity was observed. These findings highlight the necessity of optimizing the Fc domain for this class of therapeutic antibodies by using appropriate preclinical models that accurately reflect the unique affinities and cellular expression of human FcγR. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Telecommunications system architecture and technology requirements for future human exploration of Mars

    Science.gov (United States)

    Riley, A. L.; Sue, M. K.; Hall, J. R.

    1991-01-01

    The Mars telecommunications system as currently conceived at JPL calls for the use of multifrequency bands in combination with advanced space and ground technologies. This paper reviews the architecture and technology requirements for the telecommunications system. It also presents an overview of the technology development plan.

  18. Modeling and Simulation for Exploring Human-Robot Team Interaction Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Dudenhoeffer, Donald Dean; Bruemmer, David Jonathon; Davis, Midge Lee

    2001-12-01

    Small-sized and micro-robots will soon be available for deployment in large-scale forces. Consequently, the ability of a human operator to coordinate and interact with largescale robotic forces is of great interest. This paper describes the ways in which modeling and simulation have been used to explore new possibilities for human-robot interaction. The paper also discusses how these explorations have fed implementation of a unified set of command and control concepts for robotic force deployment. Modeling and simulation can play a major role in fielding robot teams in actual missions. While live testing is preferred, limitations in terms of technology, cost, and time often prohibit extensive experimentation with physical multi-robot systems. Simulation provides insight, focuses efforts, eliminates large areas of the possible solution space, and increases the quality of actual testing.

  19. Radiologic manifestations of focal cerebral hyperemia in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Skriver, E B; Herning, M

    1991-01-01

    In 16 acute stroke patients with focal cerebral hyperemia angiography and regional cerebral blood flow (rCBF) were studied 1 to 4 days post stroke. CT was performed twice with and without contrast enhancement 3 +/- 1 days and 16 +/- 4 days post stroke. Angiographic evidence of focal cerebral hype...

  20. ORAL FOCAL MUCINOSIS: A RARE CASE REPORT OF TWO CASES

    African Journals Online (AJOL)

    User

    inflammatory cells consisting of mainly lymphocytes and plasma cells. All these features were suggestive of oral focal mucinosis (10). It must be emphasized that in many focal gingival lesions, clinically preoperative diagnosis is impossible due to their rarity. However, OFM should be considered in the differential diagnosis.

  1. Focal epilepsies in adult patients attending two epilepsy centers

    DEFF Research Database (Denmark)

    Gilioli, Isabella; Vignoli, Aglaia; Visani, Elisa

    2012-01-01

    PURPOSE: To classify the grade of antiepileptic drug (AED) resistance in a cohort of patients with focal epilepsies, to recognize the risk factors for AED resistance, and to estimate the helpfulness of "new-generation" AEDs. METHODS: We included 1,155 adults with focal epilepsies who were observe...

  2. Concordance of MRI and EEG Focal Slowing in Nonsyndromic Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-04-01

    Full Text Available Investigators at the Kangwon National University, Korea, and The Epilepsy Center, Lurie Children’s Hospital of Chicago, USA studied the correlation and significance of EEG focal slowing and focal MRI abnormalities in 253 children with nonsyndromic epilepsy.

  3. Are Protected Areas Required to Maintain Functional Diversity in Human-Modified Landscapes?

    OpenAIRE

    Cottee-Jones, H. Eden W.; Matthews, Thomas J.; Bregman, Tom P.; Barua, Maan; Tamuly, Jatin; Whittaker, Robert J.

    2015-01-01

    The conversion of forest to agriculture across the world's tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropic...

  4. On the dependence of information display quality requirements upon human characteristics and pilot/automatics relations

    Science.gov (United States)

    Wilckens, V.

    1972-01-01

    Present information display concepts for pilot landing guidance are outlined considering manual control as well as substitution of man by fully competent automatics. Display improvements are achieved by compressing the distributed indicators into an accumulative display and thus reducing information scanning. Complete integration of quantitative indications, outer loop information, and real world display in a pictorial information channel geometry constitutes an interface with human ability to differentiate and integrate for optimal manual control of the aircraft.

  5. Are protected areas required to maintain functional diversity in human-modified landscapes?

    Directory of Open Access Journals (Sweden)

    H Eden W Cottee-Jones

    Full Text Available The conversion of forest to agriculture across the world's tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropical forest ecosystems, in conserving frugivore composition and function in a human-modified landscape in Assam, India. We surveyed the frugivorous birds feeding at 122 isolated Ficus trees, 33 fruit trees, and 31 other large trees across a range of 32 km from the nearest intact forest. We found that Ficus trees attracted richer and more abundant assemblages of frugivores than the other tree categories. However, incidence function estimates revealed that forest specialist species decreased dramatically within the first kilometre of the forest edge. Despite this, species richness and functional diversity remained consistent across the human-modified landscape, as habitat generalists replaced forest-dependent frugivores, and accounted for most of the ecological function found in Ficus trees near the forest edge. We recommend that isolated Ficus trees are awarded greater conservation status, and suggest that their conservation can support ecologically functional networks of frugivorous bird communities.

  6. Are protected areas required to maintain functional diversity in human-modified landscapes?

    Science.gov (United States)

    Cottee-Jones, H Eden W; Matthews, Thomas J; Bregman, Tom P; Barua, Maan; Tamuly, Jatin; Whittaker, Robert J

    2015-01-01

    The conversion of forest to agriculture across the world's tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropical forest ecosystems, in conserving frugivore composition and function in a human-modified landscape in Assam, India. We surveyed the frugivorous birds feeding at 122 isolated Ficus trees, 33 fruit trees, and 31 other large trees across a range of 32 km from the nearest intact forest. We found that Ficus trees attracted richer and more abundant assemblages of frugivores than the other tree categories. However, incidence function estimates revealed that forest specialist species decreased dramatically within the first kilometre of the forest edge. Despite this, species richness and functional diversity remained consistent across the human-modified landscape, as habitat generalists replaced forest-dependent frugivores, and accounted for most of the ecological function found in Ficus trees near the forest edge. We recommend that isolated Ficus trees are awarded greater conservation status, and suggest that their conservation can support ecologically functional networks of frugivorous bird communities.

  7. Dogs’ recognition of human selfish and generous attitudes requires little but critical experience with people

    Science.gov (United States)

    Freidin, Esteban; Casanave, Emma B.

    2017-01-01

    There is some dispute regarding the role of experience in the development of dogs´ socio-cognitive abilities in their interaction with people. We sought to provide new evidence to this debate by comparing dogs with contrasting levels of experience with humans, in a task involving the discrimination of human generous and selfish attitudes. To this end, we compared the performance of adult family dogs against that of adult shelter dogs and puppies living in people´s homes. In training trials, the generous experimenter (G) signaled the bowl with food and allowed the dog to eat, whereas the selfish experimenter (S) also signaled the baited bowl, but she/he ate the food before the dog could have access to it. Then, subjects were allowed to freely choose between G and S in the choice test. The main finding was that adult subjects (both family and shelter dogs) developed a preference for G over S, but puppies did not. We conclude that the quality and/or quantity of everyday-contact with people did not affect the discrimination of human attitudes in the present protocol, but the amount of experience with people (in years) did matter. Finally, we discuss the relative role of domestication and ontogeny in the development of dogs´ socio-cognitive abilities. PMID:29045426

  8. Dogs' recognition of human selfish and generous attitudes requires little but critical experience with people.

    Science.gov (United States)

    Carballo, Fabricio; Freidin, Esteban; Casanave, Emma B; Bentosela, Mariana

    2017-01-01

    There is some dispute regarding the role of experience in the development of dogs´ socio-cognitive abilities in their interaction with people. We sought to provide new evidence to this debate by comparing dogs with contrasting levels of experience with humans, in a task involving the discrimination of human generous and selfish attitudes. To this end, we compared the performance of adult family dogs against that of adult shelter dogs and puppies living in people´s homes. In training trials, the generous experimenter (G) signaled the bowl with food and allowed the dog to eat, whereas the selfish experimenter (S) also signaled the baited bowl, but she/he ate the food before the dog could have access to it. Then, subjects were allowed to freely choose between G and S in the choice test. The main finding was that adult subjects (both family and shelter dogs) developed a preference for G over S, but puppies did not. We conclude that the quality and/or quantity of everyday-contact with people did not affect the discrimination of human attitudes in the present protocol, but the amount of experience with people (in years) did matter. Finally, we discuss the relative role of domestication and ontogeny in the development of dogs´ socio-cognitive abilities.

  9. [Color Doppler sonography of focal abdominal lesions].

    Science.gov (United States)

    Licanin, Zoran; Lincender, Lidija; Djurović, V; Salihefendić, Nizama; Smajlović, Fahrudin

    2004-01-01

    Color Doppler sonography (CDS--spectral, color and power), harmonic imaging techniques (THI, PHI), possibility of 3D analysis of picture, usage of contrast agents, have raised the values of ultrasound as a diagnostic method to a very high level. THI--non-linear gray scale modality, is based on the processing of higher reflected frequencies, that has improved a picture resolution, which is presented with less artifacts and limiting effects of obesity and gases. Ultrasound contrast agents improve analysis of micro and macro circulation of the examined area, and with the assessment of velocity of supply in ROI (wash in), distribution and time of signal weakening (wash out), are significantly increasing diagnostic value of ultrasound. Besides the anatomical and topographic presentation of examined region (color, power), Color Doppler sonography gives us haemodynamic-functional information on vascularisation of that region, as well as on pathologic vascularisation if present. Avascular aspect of a focal pathologic lesion corresponds to a cyst or haematoma, while coloration and positive spectral curve discover that anechogenic lesions actually represents aneurysms, pseudoaneurysms or AVF. In local inflammatory lesion, abscess in an acute phase, CDS shows first increased, and then decreased central perfusion, while in a chronic phase, a pericapsular vascularisation is present. Contribution of CDS in differentiation of hepatic tumors (hemangioma, HCC and metastasis) is very significant. Central color dots along the peripheral blood vessels and the blush phenomenon are characteristics of capillary hemangioma, peritumoral vascular ring "basket" of HCC, and "detour" sign of metastasis. The central artery, RI from 0.45 to 0.60 and radial spreading characterize FNH. Hepatic adenoma is characterized by an intratumoral vein, and rarely by a vascular hallo. Further on, blood velocity in tumor defined by Color Doppler, distinguishes malignant from benign lesion, where 40 cm/s is a

  10. TDP1 is required for efficient non-homologous end joining in human cells.

    Science.gov (United States)

    Li, Jing; Summerlin, Matthew; Nitiss, Karin C; Nitiss, John L; Hanakahi, Leslyn A

    2017-12-01

    Tyrosyl-DNA phosphodiesterase 1 (TDP1) can remove a wide variety of 3' and 5' terminal DNA adducts. Genetic studies in yeast identified TDP1 as a regulator of non-homologous end joining (NHEJ) fidelity in the repair of double-strand breaks (DSBs) lacking terminal adducts. In this communication, we show that TDP1 plays an important role in joining cohesive DSBs in human cells. To investigate the role of TDP1 in NHEJ in live human cells we used CRISPR/cas9 to produce TDP1-knockout (TDP1-KO) HEK-293 cells. As expected, human TDP1-KO cells were highly sensitive to topoisomerase poisons and ionizing radiation. Using a chromosomally-integrated NHEJ reporter substrate to compare end joining between wild type and TDP1-KO cells, we found that TDP1-KO cells have a 5-fold reduced ability to repair I-SceI-generated DSBs. Extracts prepared from TDP1-KO cells had reduced NHEJ activity in vitro, as compared to extracts from wild type cells. Analysis of end-joining junctions showed that TDP1 deficiency reduced end-joining fidelity, with a significant increase in insertion events, similar to previous observations in yeast. It has been reported that phosphorylation of TDP1 serine 81 (TDP1-S81) by ATM and DNA-PK stabilizes TDP1 and recruits TDP1 to sites of DNA damage. We found that end joining in TDP1-KO cells was partially restored by the non-phosphorylatable mutant TDP1-S81A, but not by the phosphomimetic TDP1-S81E. We previously reported that TDP1 physically interacted with XLF. In this study, we found that XLF binding by TDP1 was reduced 2-fold by the S81A mutation, and 10-fold by the S81E phosphomimetic mutation. Our results demonstrate a novel role for TDP1 in NHEJ in human cells. We hypothesize that TDP1 participation in human NHEJ is mediated by interaction with XLF, and that TDP1-XLF interactions and subsequent NHEJ events are regulated by phosphorylation of TDP1-S81. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Focal therapy for prostate cancer. Rationale, indications and selection.

    Science.gov (United States)

    Gómez-Veiga, F; Portela-Pereira, P; Cozar-Olmo, J M; Ahmed, H; Moore, C; Dickinson, L; Algaba, F; Izquierdo, L; Alcaraz Asensio, A; Martinez-Breijo, S; Emberton, M

    2014-01-01

    The great controversy surrounding the treatment of localized prostate cancer is related with its possibilities of radical treatment or active surveillance. The objective of this paper is to analyze the rationale selection among current focal therapy modalities regarding tumor and patient selection. Current articles about advantages and disadvantages on the treatment of localized prostate cancer as well as information about focal therapy regarding tumour selection, characteristics and indications cited in MEDLINE search were reviewed. Focal therapy standardized criteria must be: low risk tumors, PSA15. Focal therapy is an alternative for localized prostate cancer treatment. However, some aspects of their diagnosis and selection criteria should be defined by prospective studies which should provide knowledge about the indication for focal therapy. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  12. Combining PALM and SOFI for quantitative imaging of focal adhesions in living cells

    Science.gov (United States)

    Deschout, Hendrik; Lukes, Tomas; Sharipov, Azat; Feletti, Lely; Lasser, Theo; Radenovic, Aleksandra

    2017-02-01

    Focal adhesions are complicated assemblies of hundreds of proteins that allow cells to sense their extracellular matrix and adhere to it. Although most focal adhesion proteins have been identified, their spatial organization in living cells remains challenging to observe. Photo-activated localization microscopy (PALM) is an interesting technique for this purpose, especially since it allows estimation of molecular parameters such as the number of fluorophores. However, focal adhesions are dynamic entities, requiring a temporal resolution below one minute, which is difficult to achieve with PALM. In order to address this problem, we merged PALM with super-resolution optical fluctuation imaging (SOFI) by applying both techniques to the same data. Since SOFI tolerates an overlap of single molecule images, it can improve the temporal resolution compared to PALM. Moreover, an adaptation called balanced SOFI (bSOFI) allows estimation of molecular parameters, such as the fluorophore density. We therefore performed simulations in order to assess PALM and SOFI for quantitative imaging of dynamic structures. We demonstrated the potential of our PALM-SOFI concept as a quantitative imaging framework by investigating moving focal adhesions in living cells.

  13. Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells.

    Science.gov (United States)

    Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Sang-Hee; Kwon, Daeho; Shin, Ho-Joon

    2012-08-01

    Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.

  14. Murine and human tissue-engineered esophagus form from sufficient stem/progenitor cells and do not require microdesigned biomaterials.

    Science.gov (United States)

    Spurrier, Ryan Gregory; Speer, Allison L; Hou, Xiaogang; El-Nachef, Wael N; Grikscheit, Tracy C

    2015-03-01

    Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immune-deficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies.

  15. An empirical assessment of the focal species hypothesis.

    Science.gov (United States)

    Lindenmayer, D B; Lane, P W; Westgate, M J; Crane, M; Michael, D; Okada, S; Barton, P S

    2014-12-01

    Biodiversity surrogates and indicators are commonly used in conservation management. The focal species approach (FSA) is one method for identifying biodiversity surrogates, and it is underpinned by the hypothesis that management aimed at a particular focal species will confer protection on co-occurring species. This concept has been the subject of much debate, in part because the validity of the FSA has not been subject to detailed empirical assessment of the extent to which a given focal species actually co-occurs with other species in an assemblage. To address this knowledge gap, we used large-scale, long-term data sets of temperate woodland birds to select focal species associated with threatening processes such as habitat isolation and loss of key vegetation attributes. We quantified co-occurrence patterns among focal species, species in the wider bird assemblage, and species of conservation concern. Some, but not all, focal species were associated with high levels of species richness. One of our selected focal species was negatively associated with the occurrence of other species (i.e., it was an antisurrogate)-a previously undescribed property of nominated focal species. Furthermore, combinations of focal species were not associated with substantially elevated levels of bird species richness, relative to levels associated with individual species. Our results suggest that although there is some merit to the underpinning concept of the FSA, there is also a need to ensure that actions are sufficiently flexible because management tightly focused on a given focal species may not benefit some other species, including species of conservation concern, such of which might not occur in species-rich assemblages. © 2014 Society for Conservation Biology.

  16. Síndromes epilépticos focales

    Directory of Open Access Journals (Sweden)

    Albia J. Pozo Alonso

    2004-06-01

    Full Text Available En el año 2001 el Grupo de Trabajo para la Clasificación y Terminología de la Liga Internacional contra la Epilepsia propuso un esquema diagnóstico para las personas con crisis epilépticas y epilepsia. El propósito del trabajo fue mostrar las características principales de algunos de los síndromes epilépticos focales propuestos para ser incluidos dentro de este esquema diagnóstico, el cual ha sido concebido de una forma flexible que permitirá en un futuro la inclusión de otros síndromes epilépticos. Según este nuevo esquema diagnóstico los síndromes epilépticos focales se dividen en síndromes epilépticos focales idiopáticos, síndromes epilépticos focales familiares, síndromes epilépticos focales sintomáticos o probablemente sintomáticos.In 2001, the Working Group for the Classification and Terminology of the International League Against Epilepsy proposed a diagnostic scheme for those persons with epileptic seizures or with epilepsy. The aim of this paper is to show the main characteristics of some of the focal epileptic syndromes proposed to be included in this diagnostic scheme, which has been designed in such a flexible way that will allow the inclusion of other epileptic syndromes in a future. According to this new diagnostic scheme, the focal epileptic syndromes are divided into family focal idiopathic syndromes, symptomatic focal epileptic syndromes and symptomatic or probably symptomatic focal epileptic syndromes.

  17. Standardized Procedure Content And Data Structure Based On Human Factors Requirements For Computer-Based Procedures

    Energy Technology Data Exchange (ETDEWEB)

    Bly, Aaron; Oxstrand, Johanna; Le Blanc, Katya L

    2015-02-01

    Most activities that involve human interaction with systems in a nuclear power plant are guided by procedures. Traditionally, the use of procedures has been a paper-based process that supports safe operation of the nuclear power industry. However, the nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. Advances in digital technology make computer-based procedures (CBPs) a valid option that provides further enhancement of safety by improving human performance related to procedure use. The transition from paper-based procedures (PBPs) to CBPs creates a need for a computer-based procedure system (CBPS). A CBPS needs to have the ability to perform logical operations in order to adjust to the inputs received from either users or real time data from plant status databases. Without the ability for logical operations the procedure is just an electronic copy of the paper-based procedure. In order to provide the CBPS with the information it needs to display the procedure steps to the user, special care is needed in the format used to deliver all data and instructions to create the steps. The procedure should be broken down into basic elements and formatted in a standard method for the CBPS. One way to build the underlying data architecture is to use an Extensible Markup Language (XML) schema, which utilizes basic elements to build each step in the smart procedure. The attributes of each step will determine the type of functionality that the system will generate for that step. The CBPS will provide the context for the step to deliver referential information, request a decision, or accept input from the user. The XML schema needs to provide all data necessary for the system to accurately perform each step without the need for the procedure writer to reprogram the CBPS. The research team at the Idaho National Laboratory has developed a prototype CBPS for field workers as well as the

  18. Radiometric packaging of uncooled bolometric infrared focal plane arrays

    Science.gov (United States)

    García-Blanco, Sonia; Pope, Timothy; Côté, Patrice; Leclerc, Mélanie; Ngo Phong, Linh; Châteauneuf, François

    2017-11-01

    INO has a wide experience in the design and fabrication of different kinds of microbolometer focal plane arrays (FPAs). In particular, a 512x3 pixel microbolometer FPA has been selected as the sensor for the New Infrared Sensor Technology (NIRST) instrument, one of the payloads of the SACD/Aquarius mission. In order to make the absolute temperature measurements necessary for many infrared Earth observation applications, the microbolometer FPA must be integrated into a package offering a very stable thermal environment. The radiometric packaging technology developed at INO presents an innovative approach since it was conceived to be modular and adaptable for the packaging of different microbolometer FPAs and for different sets of assembly requirements without need for requalification of the assembly process. The development of the radiometric packaging technology has broadened the position of INO as a supplier of radiometric detector modules integrating FPAs of microbolometers inside a radiometric package capable of achieving the requirements of different space missions. This paper gives an overview of the design of INO's radiometric package. Key performance parameters are also discussed and the test campaign conducted with the radiometric package is presented.

  19. Charge integration successive approximation analog-to-digital converter for focal plane applications using a single amplifier

    Science.gov (United States)

    Zhou, Zhimin (Inventor); Pain, Bedabrata (Inventor)

    1999-01-01

    An analog-to-digital converter for on-chip focal-plane image sensor applications. The analog-to-digital converter utilizes a single charge integrating amplifier in a charge balancing architecture to implement successive approximation analog-to-digital conversion. This design requires minimal chip area and has high speed and low power dissipation for operation in the 2-10 bit range. The invention is particularly well suited to CMOS on-chip applications requiring many analog-to-digital converters, such as column-parallel focal-plane architectures.

  20. Terahertz detectors and focal plane arrays

    Science.gov (United States)

    Rogalski, A.; Sizov, F.

    2011-09-01

    Terahertz (THz) technology is one of emerging technologies that will change our life. A lot of attractive applications in security, medicine, biology, astronomy, and non-destructive materials testing have been demonstrated already. However, the realization of THz emitters and receivers is a challenge because the frequencies are too high for conventional electronics and the photon energies are too small for classical optics. As a result, THz radiation is resistant to the techniques commonly employed in these well established neighbouring bands. In the paper, issues associated with the development and exploitation of THz radiation detectors and focal plane arrays are discussed. Historical impressive progress in THz detector sensitivity in a period of more than half century is analyzed. More attention is put on the basic physical phenomena and the recent progress in both direct and heterodyne detectors. After short description of general classification of THz detectors, more details concern Schottky barrier diodes, pair braking detectors, hot electron mixers and field-effect transistor detectors, where links between THz devices and modern technologies such as micromachining are underlined. Also, the operational conditions of THz detectors and their upper performance limits are reviewed. Finally, recent advances in novel nanoelectronic materials and technologies are described. It is expected that applications of nanoscale materials and devices will open the door for further performance improvement in THz detectors.

  1. Medical image of the week: focal myopericaditis

    Directory of Open Access Journals (Sweden)

    Meenakshisundaram C

    2015-07-01

    Full Text Available No abstract available. Article truncated at 150 words. A 44-year-old man with no significant past medical history was admitted with a history of two episodes of substernal chest pain unrelated to exertion which had resolved spontaneously. Admission vital signs were within normal limits and physical examination was unremarkable. Basic lab tests were normal and urine toxicology was negative. Electrocardiogram was unremarkable with no ST/T changes. Troponin I was elevated at 4.19 which trended up to 6.57. An urgent cardiac angiogram was done which revealed normal patent coronaries. His transthoracic echocardiogram was also reported to be normal. He continued to have intermittent episodes of chest pain that was partially relieved by morphine. Erythrocyte sedimentation rate and C-reactive protein were elevated. Work up for autoimmune diseases, vasculitis, myocarditis panel were insignificant. Later, magnetic resonance imaging (MRI with gadolinium enhanced contrast (Figure 1 was obtained which showed abnormal epicardial/subepicardial myocardial enhancement within the inferolateral wall and cardiac apex consistent with focal ...

  2. Visual agnosia and focal brain injury.

    Science.gov (United States)

    Martinaud, O

    Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Focal adhesion kinase - the reversible molecular mechanosensor

    CERN Document Server

    Bell, Samuel

    2016-01-01

    Sensors are the first element of the pathways that control the response of cells to their environment. After chemical, the next most important cue is mechanical, and protein complexes that produce or enable a chemical signal in response to a mechanical stimulus are called mechanosensors. There is a sharp distinction between sensing an external force or pressure/tension applied to the cell, and sensing the mechanical stiffness of the environment. We call the first mechanosensitivity of the 1st kind, and the latter mechanosensitivity of the 2nd kind. There are two variants of protein complexes that act as mechanosensors of the 2nd kind: producing the one-off or a reversible action. The latent complex of TGF-beta is an example of the one-off action: on the release of active TGF-beta signal, the complex is discarded and needs to be replaced. In contrast, the focal adhesion kinase (FAK) in a complex with integrin is a reversible mechanosensor, which initiates the chemical signal in its active phosphorylated confor...

  4. Evaluation of tranexamic acid and ε-aminocaproic acid concentrations required to inhibit fibrinolysis in plasma of dogs and humans.

    Science.gov (United States)

    Fletcher, Daniel J; Blackstock, Kelly J; Epstein, Kira; Brainard, Benjamin M

    2014-08-01

    To determine minimum plasma concentrations of the antifibrinolytic agents tranexamic acid (TEA) and ε-aminocaproic acid (EACA) needed to completely inhibit fibrinolysis in canine and human plasma after induction of hyperfibrinolysis. Pooled citrated plasma from 7 dogs and commercial pooled citrated human plasma. Concentrations of EACA from 0 μg/mL to 500 μg/mL and of TEA from 0 μg/mL to 160 μg/mL were added to pooled citrated canine and human plasma. Hyperfibrinolysis was induced with 1,000 units of tissue plasminogen activator/mL, and kaolin-activated thromboelastography was performed in duplicate. The minimum concentrations required to completely inhibit fibrinolysis 30 minutes after maximum amplitude of the thromboelastography tracing occurred were determined. Minimum plasma concentrations necessary for complete inhibition of fibrinolysis by EACA and TEA in pooled canine plasma were estimated as 511.7 μg/mL (95% confidence interval [CI], 433.2 to 590.3 μg/mL) and 144.7 μg/mL (95% CI, 125.2 to 164.2 μg/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 μg/mL (95% CI, 106.2 to 137.8 μg/mL) and 14.7 μg/mL (95% CI, 13.7 to 15.6 μg/mL), respectively. Results supported the concept that dogs are hyperfibrinolytic, compared with humans. Higher doses of EACA and TEA may be required to fully inhibit fibrinolysis in dogs.

  5. Develop an environmental assessment technique for human comfort requirements in buildings

    Directory of Open Access Journals (Sweden)

    Ahmed Ahmed Fekry

    2014-04-01

    Full Text Available Environmental assessment methods have emerged to assess the environmental performance of buildings across the world. Accurate results obtained using these methods are considered highly important, especially when taking into account the global trend of being obligatory and the use of their results to compare the environmental performance of buildings creating a fair competition amongst them. They are used for assessing green buildings regarding issues such as energy, water …, etc. The indoor quality is one of these issues and human comfort is evaluated in those methods using a set of items to assess achieving the identified comfortable ranges by evaluating a number of factors influencing them. These items are using quantitative measurements, so the current assessing way is considered complex besides the consumption of time and effort without reaching significantly accurate results. Therefore the research problem appears in the lack of an appropriate mean in the current assessment methods to evaluate items linked with sensation and emotions. The research paper aims to propose a more credible and an accurate assessment approach to assess those items, and also helps evaluating another set of items which are linked to the psychological comfort. The previous type of comfort rarely appears in current assessment methods despite being one of the green architecture principles. The ‘Kano Model’ is the proposed way used for the application of questionnaires that are put through the information network and linked to assessment methods to get more accurate and creditable results when assessing human comfort items.

  6. Human-Chromatin-Related Protein Interactions Identify a Demethylase Complex Required for Chromosome Segregation

    Directory of Open Access Journals (Sweden)

    Edyta Marcon

    2014-07-01

    Full Text Available Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

  7. Towards an understanding and application of environmental flow requirements for human welfare in East African Rivers

    Science.gov (United States)

    McClain, Michael

    2013-04-01

    In semi-arid regions of Africa, rivers are of vital importance to humans for the many direct ecosystem services they provide and, in some cases, for their potential to irrigate and power larger-scale development. More than in most regions of the world, Africans still rely individually on rivers for domestic water, nutrition, and other materials contributing to their daily welfare. This has led to a uniquely African adaptation of the environmental flow concept to incorporate the basic water needs of people as well as ecosystems. The combined flow is referred to as the 'Reserve'. East Africa has seen comparatively little development of its water resources to-date, but ambitious initiatives are underway to increase water use in new large-scale irrigation schemes and hydropower projects. Consequently, a number of comprehensive environmental flow assessments and ecohydrological research activities have recently been carried out in the region. This presentation briefly reviews the initiatives underway across the region but focuses mainly on combined research and flow-setting efforts in the transboundary Mara River Basin of Kenya and Tanzania, home to more than 800,000 people and the region's most popular conservation areas, Masai-Mara National Reserve and Serengeti National Park. Since 2006 a team of scientists, in cooperation with water authorities and the World Wide Fund for Nature (WWF), has investigated the hydrology, hydraulics, biology, and human uses of the Mara River in order to make initial environmental flow (reserve) recommendations. The flow regime of the still largely unregulated Mara River, based on analyses or 20+ years of data from three gauging stations, is highly variable and perennial flow in the middle reaches is dependent on inflows from two tributaries draining the heavily deforested Mau Escarpment, one of Kenya's five water towers. Downstream flows are also seasonally influenced by inflows from ephemeral tributaries that drain degraded grazing

  8. Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health

    Directory of Open Access Journals (Sweden)

    Gerry Kurt Schwalfenberg

    2017-01-01

    Full Text Available Objective. To review the evidence for the use of vitamin K supplementation in clinical conditions such as osteoporosis, vascular calcification, arthritis, cancer, renal calculi, diabetes, and warfarin therapy. Quality of Evidence. PubMed was searched for articles on vitamin K (K1 and K2 along with books and conference proceedings and health conditions listed above. Level I and II evidence supports the use of vitamins K1 and K2 in osteoporosis and Level II evidence supports vitamin K2 in prevention of coronary calcification and cardiovascular disease. Evidence is insufficient for use in diabetes, arthritis, renal calculi, and cancer. Main Message. Vitamin K2 may be a useful adjunct for the treatment of osteoporosis, along with vitamin D and calcium, rivaling bisphosphonate therapy without toxicity. It may also significantly reduce morbidity and mortality in cardiovascular health by reducing vascular calcification. Vitamin K2 appears promising in the areas of diabetes, cancer, and osteoarthritis. Vitamin K use in warfarin therapy is safe and may improve INR control, although a dosage adjustment is required. Conclusion. Vitamin K supplementation may be useful for a number of chronic conditions that are afflicting North Americans as the population ages. Supplementation may be required for bone and cardiovascular health.

  9. Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

    Science.gov (United States)

    Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

    2008-06-01

    We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

  10. Dietary requirements of "nutritionally non-essential amino acids" by animals and humans.

    Science.gov (United States)

    Wu, Guoyao; Wu, Zhenlong; Dai, Zhaolai; Yang, Ying; Wang, Weiwei; Liu, Chuang; Wang, Bin; Wang, Junjun; Yin, Yulong

    2013-04-01

    Amino acids are necessary for the survival, growth, development, reproduction and health of all organisms. They were traditionally classified as nutritionally essential or non-essential for mammals, birds and fish based on nitrogen balance or growth. It was assumed that all "non-essential amino acids (NEAA)" were synthesized sufficiently in the body to meet the needs for maximal growth and health. However, there has been no compelling experimental evidence to support this assumption over the past century. NEAA (e.g., glutamine, glutamate, proline, glycine and arginine) play important roles in regulating gene expression, cell signaling, antioxidative responses, neurotransmission, and immunity. Additionally, glutamate, glutamine and aspartate are major metabolic fuels for the small intestine to maintain its digestive function and protect its mucosal integrity. Therefore, based on new research findings, NEAA should be taken into consideration in revising the classical "ideal protein" concept and formulating balanced diets to improve protein accretion, food efficiency, and health in animals and humans.

  11. Protease activated receptor signaling is required for African trypanosome traversal of human brain microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Dennis J Grab

    2009-07-01

    Full Text Available Using human brain microvascular endothelial cells (HBMECs as an in vitro model for how African trypanosomes cross the human blood-brain barrier (BBB we recently reported that the parasites cross the BBB by generating calcium activation signals in HBMECs through the activity of parasite cysteine proteases, particularly cathepsin L (brucipain. In the current study, we examined the possible role of a class of protease stimulated HBMEC G protein coupled receptors (GPCRs known as protease activated receptors (PARs that might be implicated in calcium signaling by African trypanosomes.Using RNA interference (RNAi we found that in vitro PAR-2 gene (F2RL1 expression in HBMEC monolayers could be reduced by over 95%. We also found that the ability of Trypanosoma brucei rhodesiense to cross F2RL1-silenced HBMEC monolayers was reduced (39%-49% and that HBMECs silenced for F2RL1 maintained control levels of barrier function in the presence of the parasite. Consistent with the role of PAR-2, we found that HBMEC barrier function was also maintained after blockade of Galpha(q with Pasteurella multocida toxin (PMT. PAR-2 signaling has been shown in other systems to have neuroinflammatory and neuroprotective roles and our data implicate a role for proteases (i.e. brucipain and PAR-2 in African trypanosome/HBMEC interactions. Using gene-profiling methods to interrogate candidate HBMEC pathways specifically triggered by brucipain, several pathways that potentially link some pathophysiologic processes associated with CNS HAT were identified.Together, the data support a role, in part, for GPCRs as molecular targets for parasite proteases that lead to the activation of Galpha(q-mediated calcium signaling. The consequence of these events is predicted to be increased permeability of the BBB to parasite transmigration and the initiation of neuroinflammation, events precursory to CNS disease.

  12. Differential requirement for de novo lipogenesis in cholangiocarcinoma and hepatocellular carcinoma of mice and humans.

    Science.gov (United States)

    Li, Lei; Che, Li; Tharp, Kevin M; Park, Hyo-Min; Pilo, Maria G; Cao, Dan; Cigliano, Antonio; Latte, Gavinella; Xu, Zhong; Ribback, Silvia; Dombrowski, Frank; Evert, Matthias; Gores, Gregory J; Stahl, Andreas; Calvisi, Diego F; Chen, Xin

    2016-06-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. These malignancies have limited treatment options, resulting in poor patient outcomes. Metabolism reprogramming, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty acid synthase (FASN) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-coenzyme A and malonyl-coenzyme A. Increased FASN expression has been reported in multiple tumor types, and inhibition of FASN expression has been shown to have tumor-suppressing activity. Intriguingly, we found that while FASN is up-regulated in human HCC samples, its expression is frequently low in human ICC specimens. Similar results were observed in mouse ICC models induced by different oncogenes. Ablating FASN in the mouse liver did not affect activated AKT and Notch (AKT/Notch intracellular domain 1) induced ICC formation in vivo. Furthermore, while both HCC and ICC lesions develop in mice following hydrodynamic injection of AKT and neuroblastoma Ras viral oncogene homolog oncogenes (AKT/Ras), deletion of FASN in AKT/Ras mice triggered the development almost exclusively of ICCs. In the absence of FASN, ICC cells might receive lipids for membrane synthesis through exogenous fatty acid uptake. In accordance with the latter hypothesis, ICC cells displayed high expression of fatty acid uptake-related proteins and robust long-chain fatty acid uptake. Our data demonstrate that FASN dependence is not a universal feature of liver tumors: while HCC development is highly dependent of FASN and its mediated lipogenesis, ICC tumorigenesis can be insensitive to FASN deprivation; our study supports novel therapeutic approaches to treat this pernicious tumor type with the inhibition of exogenous fatty acid uptake. (Hepatology 2016;63:1900-1913). © 2016 by the American Association for the Study of Liver Diseases.

  13. Focal Atrichia: A Diagnostic Clue in Female Pattern Hair Loss.

    Science.gov (United States)

    Olsen, Elise A; Whiting, David A

    2017-10-07

    Focal atrichia is a common clinical finding in female pattern hair loss whose specificity and histologic findings need further clarification. To determine the frequency of focal atrichia in various types of hair loss and its histologic characteristics in female pattern hair loss. Part 1: Review of 250 consecutive female patients seen with hair loss for the presence of focal atrichia and Part 2: paired biopsies of haired areas vs focal atrichia in 18 subjects with female pattern hair loss RESULTS: Focal atrichia was seen in 46/104 (44%) of women with female pattern hair loss, including 67% of late onset vs 15% of early onset, compared to 3/146 (2%) of those with other hair disorders Biopsy findings of focal atrichia in female pattern hair loss showed primarily a more progressive miniaturization process than that of haired areas of the scalp. Some women with female pattern hair loss may have had concomitant chronic telogen effluvium CONCLUSIONS: When present, focal atrichia is a clinical clue to the diagnosis of female pattern hair loss, particularly late onset subtype. Copyright © 2017. Published by Elsevier Inc.

  14. The semiology of febrile seizures: Focal features are frequent.

    Science.gov (United States)

    Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

    2017-08-01

    To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Focal Adhesion Induction at the Tip of a Functionalized Nanoelectrode.

    Science.gov (United States)

    Fuentes, Daniela E; Bae, Chilman; Butler, Peter J

    2011-12-01

    Cells dynamically interact with their physical micro-environment through the assembly of nascent focal contacts and focal adhesions. The dynamics and mechanics of these contact points are controlled by transmembrane integrins and an array of intracellular adaptor proteins. In order to study the mechanics and dynamics of focal adhesion assembly, we have developed a technique for the timed induction of a nascent focal adhesion. Bovine aortic endothelial cells were approached at the apical surface by a nanoelectrode whose position was controlled with a resolution of 10s of nanometers using changes in electrode current to monitor distance from the cell surface. Since this probe was functionalized with fibronectin, a focal contact formed at the contact location. Nascent focal adhesion assembly was confirmed using time-lapse confocal fluorescent images of red fluorescent protein (RFP) - tagged talin, an adapter protein that binds to activated integrins. Binding to the cell was verified by noting a lack of change of electrode current upon retraction of the electrode. This study demonstrates that functionalized nanoelectrodes can enable precisely-timed induction and 3-D mechanical manipulation of focal adhesions and the assay of the detailed molecular kinetics of their assembly.

  16. Inhibitors of Src and Focal Adhesion Kinase Promote Endocrine Specification

    Science.gov (United States)

    Afrikanova, Ivka; Yebra, Mayra; Simpkinson, Megan; Xu, Yang; Hayek, Alberto; Montgomery, Anthony

    2011-01-01

    Stepwise approaches for the derivation of β-cells from human embryonic stem cells have been described. However, low levels of endocrine specification limit the final yield of insulin-producing β-cells. In this study, we show that the pyrrolo-pyrimidine Src family kinase (SFK) inhibitor PP2 effectively promotes the endocrine specification of human embryonic stem cell derivatives based on its capacity to induce the expression of proendocrine transcription factors (NGN3, NEUROD1, NKX2.2, and PAX4) and to significantly increase the final yield of insulin-positive cells. We further demonstrate that PP2 inhibits the activation of focal adhesion kinase (FAK), and selective inhibition of this kinase is also sufficient to induce early endocrine commitment based on increased expression of NGN3, NEUROD1, and NKX2.2. Additional studies using dominant negative constructs and isolated human fetal pancreata suggest that c-Src is at least partially responsible for inhibiting early endocrine specification. Mechanistically, we propose that inhibition of SFK/FAK signaling can promote endocrine specification by limiting activation of the TGFβR/Smad2/3 pathway. Moreover, we show that inhibition of SFK/FAK signaling suppresses cell growth, increases the expression of the β-cell-associated cyclin-dependent kinase inhibitor p57kip2, and simultaneously suppresses the expression of Id1 and Id2. This study has important implications for the derivation of β-cells for the cell-based therapy of diabetes and sheds new light on the signaling events that regulate early endocrine specification. PMID:21852242

  17. Sororin pre-mRNA splicing is required for proper sister chromatid cohesion in human cells.

    Science.gov (United States)

    Watrin, Erwan; Demidova, Maria; Watrin, Tanguy; Hu, Zheng; Prigent, Claude

    2014-09-01

    Sister chromatid cohesion, which depends on cohesin, is essential for the faithful segregation of replicated chromosomes. Here, we report that splicing complex Prp19 is essential for cohesion in both G2 and mitosis, and consequently for the proper progression of the cell through mitosis. Inactivation of splicing factors SF3a120 and U2AF65 induces similar cohesion defects to Prp19 complex inactivation. Our data indicate that these splicing factors are all required for the accumulation of cohesion factor Sororin, by facilitating the proper splicing of its pre-mRNA. Finally, we show that ectopic expression of Sororin corrects defective cohesion caused by Prp19 complex inactivation. We propose that the Prp19 complex and the splicing machinery contribute to the establishment of cohesion by promoting Sororin accumulation during S phase, and are, therefore, essential to the maintenance of genome stability. © 2014 The Authors.

  18. Focal plane actuation to achieve ultra-high resolution on suborbital balloon payloads

    Science.gov (United States)

    Scowen, Paul A.; Miller, Alex; Challa, Priya; Veach, Todd; Groppi, Chris; Mauskopf, Phil

    2014-07-01

    Over the past few years there has been remarkable success flying imaging telescope systems suspended from suborbital balloon payload systems. These imaging systems have covered optical, ultraviolet, sub-­-millimeter and infrared passbands (i.e. BLAST, STO, SBI, Fireball and others). In recognition of these advances NASA is now considering ambitious programs to promote planetary imaging from high altitude at a fraction of the cost of similar fully orbital systems. The challenge with imaging from a balloon payload is delivering the full diffraction-­-limited resolution of the system from a moving payload. Good progress has been made with damping mechanisms and oscillation control to remove most macroscopic movement in the departures of the imaging focal plane from a static configuration, however a jitter component remains that is difficult to remove using external corrections. This paper reports on work to demonstrate in the laboratory the utility and performance of actuating a detector focal plane (of whatever type) to remove the final jitter terms using an agile hexapod design. The input to this demonstration is the jitter signal generated by the pointing system of a previously flown balloon mission (the Stratospheric Terahertz Observatory, STO). Our group has a mature jitter compensation system that thermally isolates the control head from the focal plane itself. This allows the hexapod to remain at ambient temperature in a vacuum environment with the focal plane cooled to cryogenic temperatures. Our lab design mounts the focal plane on the hexapod in a custom cryostat and delivers an active optical stimulus together with the corresponding jitter signal, using the actuation of the hexapod to correct for the departures from a static, stable configuration. We believe this demonstration will make the case for inclusion of this technological solution in future balloon-­-borne imaging systems requiring ultra-­-high resolution.

  19. Drug-resistant focal sleep related epilepsy: results and predictors of surgical outcome.

    Science.gov (United States)

    Losurdo, Anna; Proserpio, Paola; Cardinale, Francesco; Gozzo, Francesca; Tassi, Laura; Mai, Roberto; Francione, Stefano; Castana, Laura; Lo Russo, Giorgio; Casaceli, Giuseppe; Sartori, Ivana; Della Marca, Giacomo; Cossu, Massimo; Nobili, Lino

    2014-07-01

    In this study we report the results of surgery in a large population of patients affected by drug-resistant focal sleep related epilepsy (SRE) and the identified prognostic factors. We conducted a retrospective analysis of a case series of 955 patients operated on for drug-resistant focal epilepsy from 1997 to 2009. Ninety-five patients with focal SRE and a follow-up of at least 2 years were identified. Presurgical, surgical and histopathological variables were analyzed. Risk of seizures recurrence was assessed by univariate and multivariate analysis. Mean age at epilepsy onset was 5.6 ± 4.9 years. MRI revealed a focal abnormality in 78.9% of cases. Sixty-two percent of patients required a Stereo-EEG investigation. The cortical resection involved the frontal lobe in 61.1% of cases, while in 38.9% an extrafrontal resection was performed. Focal cortical dysplasia (FCD) type II was the most frequent histopathological finding. Mean postoperative follow-up was 82.3 months. Seventy-three patients (76.8%) were in Engel's class I. At univariate analysis, variables associated with a favorable outcome were: absence of Stereo-EEG investigation; positive MRI; complete removal of the epileptogenic zone (EZ); presence of FCD type II and FCD type IIb. A diagnosis of FCD type I was associated with postoperative recurrence of seizures. Multivariate analysis identified the complete removal of the EZ and FCD type I as independent predictors of a favorable and unfavorable outcome respectively. SRE can frequently originate outside the frontal lobe and a favorable surgical outcome is achieved in three-fourths of cases independently from the location of the EZ. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Vesicular trafficking of incoming human papillomavirus 16 to the Golgi apparatus and endoplasmic reticulum requires γ-secretase activity.

    Science.gov (United States)

    Zhang, Wei; Kazakov, Teymur; Popa, Andreea; DiMaio, Daniel

    2014-09-16

    The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact capsid prior to cell binding. With this pseudovirus, we used the proximity ligation assay immune detection technique to demonstrate that during entry HPV16 L2 traffics into and out of the early endosome prior to Golgi localization, and we demonstrated that L2 enters the endoplasmic reticulum during entry. The cellular membrane-associated protease, γ-secretase, is required for infection by HPV16 pseudovirus and authentic HPV16. We also showed that inhibition of γ-secretase does not interfere substantively with virus internalization, initiation of capsid disassembly, entry into the early endosome, or exit from this compartment, but γ-secretase is required for localization of L2 and viral DNA to the Golgi apparatus and the endoplasmic reticulum. These results show that incoming HPV16 traffics sequentially from the cell surface to the endosome and then to the Golgi apparatus and the endoplasmic reticulum prior to nuclear entry. The human papillomaviruses are small nonenveloped DNA viruses responsible for approximately 5% of all human cancer deaths, but little is known about the process by which these viruses transit from the cell surface to the nucleus. Here we show that incoming HPV16, the most common high-risk HPV, traffics though a series of vesicular compartments during infectious entry, including the endosome, Golgi apparatus, and endoplasmic reticulum. Furthermore, we show that γ-secretase, a cellular membrane-associated protease, is required for entry of the L2 minor capsid protein and viral DNA into the Golgi apparatus and endoplasmic reticulum. These studies reveal a new pathway of cell entry by DNA viruses and suggest that components of this pathway are candidate

  1. Focal Length Affects Depicted Shape and Perception of Facial Images.

    Directory of Open Access Journals (Sweden)

    Vít Třebický

    Full Text Available Static photographs are currently the most often employed stimuli in research on social perception. The method of photograph acquisition might affect the depicted subject's facial appearance and thus also the impression of such stimuli. An important factor influencing the resulting photograph is focal length, as different focal lengths produce various levels of image distortion. Here we tested whether different focal lengths (50, 85, 105 mm affect depicted shape and perception of female and male faces. We collected three portrait photographs of 45 (22 females, 23 males participants under standardized conditions and camera setting varying only in the focal length. Subsequently, the three photographs from each individual were shown on screen in a randomized order using a 3-alternative forced-choice paradigm. The images were judged for attractiveness, dominance, and femininity/masculinity by 369 raters (193 females, 176 males. Facial width-to-height ratio (fWHR was measured from each photograph and overall facial shape was analysed employing geometric morphometric methods (GMM. Our results showed that photographs taken with 50 mm focal length were rated as significantly less feminine/masculine, attractive, and dominant compared to the images taken with longer focal lengths. Further, shorter focal lengths produced faces with smaller fWHR. Subsequent GMM revealed focal length significantly affected overall facial shape of the photographed subjects. Thus methodology of photograph acquisition, focal length in this case, can significantly affect results of studies using photographic stimuli perhaps due to different levels of perspective distortion that influence shapes and proportions of morphological traits.

  2. Focal choroidal excavation in eyes with central serous chorioretinopathy.

    Science.gov (United States)

    Ellabban, Abdallah A; Tsujikawa, Akitaka; Ooto, Sotaro; Yamashiro, Kenji; Oishi, Akio; Nakata, Isao; Miyake, Masahiro; Akagi-Kurashige, Yumiko; Ueda-Arakawa, Naoko; Arichika, Shigeta; Yoshitake, Shin; Takahashi, Ayako; Yoshimura, Nagahisa

    2013-10-01

    To study the prevalence and 3-dimensional (3-D) tomographic features of focal choroidal excavations in eyes with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (OCT). Prospective, cross-sectional study. We examined 116 consecutive eyes with CSC with a prototype 3-D swept-source OCT. 3-D images of the shape of the macular area, covering 6 × 6 mm(2), were reconstructed by segmentation of the outer surface of the retinal pigment epithelium (RPE). The 3-D swept-source OCT detected focal choroidal excavations in 9 eyes (7.8%). The 3-D scanning protocol, coupled with en face scans, allowed for clear visualization of the excavation morphology. In 5 eyes with focal excavations, unusual choroidal tissue was found beneath the excavation, bridging the bottom of the excavation and the outer choroidal boundary. Additionally, 3 of those 5 eyes showed a suprachoroidal space below the excavation, as if the outer choroidal boundary is pulled inward by this bridging tissue. The focal choroidal excavations were located within fluorescein leakage points and areas of choroidal hyperpermeability. Eyes with focal choroidal excavations were more myopic (-4.42 ± 2.92 diopters) than eyes without excavations (-0.27 ± 1.80 diopters, P = .001). Subfoveal choroidal thickness was significantly thinner (301.3 ± 60.1 μm) in eyes with focal excavations than in eyes without the excavations (376.6 ± 104.8 μm, P = .036). Focal choroidal excavations were present in 7.8% of eyes with CSC. In these eyes, focal choroidal excavations may have formed from RPE retraction caused by focal scarring of choroidal connective tissue. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Sequence requirements for micro RNA processing and function in human cells

    Science.gov (United States)

    ZENG, YAN; CULLEN, BRYAN R.

    2003-01-01

    Most eukaryotes encode a substantial number of small noncoding RNAs termed micro RNAs (miRNAs). Previously, we have demonstrated that miR-30, a 22-nucleotide human miRNA, can be processed from a longer transcript bearing the proposed miR-30 stem-loop precursor and can translationally inhibit an mRNA-bearing artificial target sites. We also demonstrated that the miR-30 precursor stem can be substituted with a heterologous stem, which can be processed to yield novel miRNAs and can block the expression of endogenous mRNAs. Here, we show that a second human miRNA, termed miR-21, can also be effectively expressed when its precursor forms part of a longer mRNA. For both miR-30 and miR-21, mature miRNA production was highly dependent on the integrity of the precursor RNA stem, although the underlying sequence had little effect. In contrast, the sequence of the terminal loop affected miRNA production only moderately. Processing of the initial, miR-30-containing transcript led to the production of not only mature miR-30 but also to the largely nuclear excision of an ∼65-nucleotide RNA that is likely to represent an important intermediate in miR-30 processing. Consistent with this hypothesis, mutations that affected mature miR-30 production inhibited expression of this miR-30 pre-miRNA to an equivalent degree. Although point mutations could block the ability of both miR-30 and miR-21 to inhibit the translation of mRNAs bearing multiple artificial miRNA target sites, single point mutations only attenuated the miRNA-mediated inhibition of genes bearing single, fully complementary targets. These results suggest that miRNAs, and the closely similar small interfering RNAs, cannot totally discriminate between RNA targets differing by a single nucleotide. PMID:12554881

  4. Widespread EEG changes precede focal seizures.

    Directory of Open Access Journals (Sweden)

    Piero Perucca

    Full Text Available The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal, and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline. Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma and high-frequency bands (ripples and fast ripples. At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development, but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.

  5. Choroidal neovascularization associated with focal choroidal excavation.

    Science.gov (United States)

    Lee, Jae Hyung; Lee, Won Ki

    2014-03-01

    To describe the clinical and imaging characteristics of choroidal neovascularization (CNV) accompanied by focal choroidal excavation. Retrospective, interventional case series. The medical records of 16 patients (16 eyes) were reviewed. Imaging findings including fluorescein angiography (FA), indocyanine green angiography, and spectral-domain optical coherence tomography (SD OCT) were analyzed. CNV complexes were primarily located beneath the retinal pigment epithelium (type 1 CNV) in 9 eyes and in the subneurosensory retinal space (type 2 CNV) in 7 eyes, as assessed by SD OCT. Seven of 8 patients over 50 years old had type 1 CNV, and 6 of 8 patients under 50 had type 2 lesions. All 7 eyes with type 2 CNV exhibited classic CNV on FA. Additionally, 7 of 9 eyes with type 1 CNV had the classic pattern, and in these eyes, the CNV complexes were confined to the concavity of choroidal excavation. In 15 patients treated by anti-vascular endothelial growth factor (anti-VEGF) injections, the mean best-corrected visual acuity improved from 20/44 to 20/26 with a mean of 3.7 injections during a mean follow-up period of 14.5 months. The CNV growth pattern and extent seem to be determined by the degree of damage to the retinal pigment epithelium/Bruch membrane complex resulting from choroidal excavation, as well as age. Neovascular complexes tend to be located within the boundary of choroidal excavation and are revealed as classic patterns on FA, even in type 1 CNV. Anti-VEGF was notably effective for treating these lesions, with a low rate of recurrence. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Widespread EEG Changes Precede Focal Seizures

    Science.gov (United States)

    Perucca, Piero; Dubeau, François; Gotman, Jean

    2013-01-01

    The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal), and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline). Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma) and high-frequency bands (ripples and fast ripples). At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development), but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures. PMID:24260523

  7. The role of focal therapy in the management of localised prostate cancer: a systematic review.

    Science.gov (United States)

    Valerio, Massimo; Ahmed, Hashim U; Emberton, Mark; Lawrentschuk, Nathan; Lazzeri, Massimo; Montironi, Rodolfo; Nguyen, Paul L; Trachtenberg, John; Polascik, Thomas J

    2014-10-01

    delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required. Copyright © 2013 European Association of Urology. All rights reserved.

  8. Saturated very long chain fatty acids are required for the production of infectious human cytomegalovirus progeny.

    Directory of Open Access Journals (Sweden)

    Emre Koyuncu

    Full Text Available Human cytomegalovirus hijacks host cell metabolism, increasing the flux of carbon from glucose to malonyl-CoA, the committed precursor to fatty acid synthesis and elongation. Inhibition of acetyl-CoA carboxylase blocks the production of progeny virus. To probe further the role of fatty acid metabolism during infection, we performed an siRNA screen to identify host cell metabolic enzymes needed for the production of infectious cytomegalovirus progeny. The screen predicted that multiple long chain acyl-CoA synthetases and fatty acid elongases are needed during infection, and the levels of RNAs encoding several of these enzymes were upregulated by the virus. Roles for acyl-CoA synthetases and elongases during infection were confirmed by using small molecule antagonists. Consistent with a role for these enzymes, mass spectrometry-based fatty acid analysis with ¹³C-labeling revealed that malonyl-CoA is consumed by elongases to produce very long chain fatty acids, generating an approximately 8-fold increase in C26-C34 fatty acid tails in infected cells. The virion envelope was yet further enriched in C26-C34 saturated fatty acids, and elongase inhibitors caused the production of virions with lower levels of these fatty acids and markedly reduced infectivity. These results reveal a dependence of cytomegalovirus on very long chain fatty acid metabolism.

  9. Endocytosis is required for exocytosis and priming of respiratory burst activity in human neutrophils.

    Science.gov (United States)

    Creed, T Michael; Tandon, Shweta; Ward, Richard A; McLeish, Kenneth R

    2017-10-01

    Neutrophil generation of reactive oxygen species (ROS) is enhanced by exposure to pro-inflammatory agents in a process termed priming. Priming is depending on exocytosis of neutrophil granules and p47 phox phosphorylation-dependent translocation of cytosolic NADPH oxidase components. Clathrin-mediated endocytosis was recently reported to be necessary for priming, but the mechanism linking endocytosis to priming was not identified. The present study examined the hypothesis that endocytosis regulates neutrophil priming by controlling granule exocytosis. Clathrin-mediated endocytosis by isolated human neutrophils was inhibited by chlorpromazine, monodansylcadaverine, and sucrose. Exocytosis of granule subsets was measured as release of granule components by ELISA or chemiluminescence. ROS generation was measured as extracellular release of superoxide as reduction of ferrocytochrome c. p38 MAPK activation and p47 phox phosphorylation were measured by immunoblot analysis. Statistical analysis was performed using a one-way ANOVA with the Tukey-Kramer multiple-comparison test. Inhibition of endocytosis prevented priming of superoxide release by TNFα and inhibited TNFα stimulation and priming of exocytosis of all four granule subsets. Inhibition of endocytosis did not reduce TNFα-stimulated p38 MAPK activation or p47 phox phosphorylation. Inhibition of NADPH oxidase activity blocked TNFα stimulation of secretory vesicle and gelatinase granule exocytosis. Endocytosis is linked to priming of respiratory burst activity through ROS-mediated control of granule exocytosis.

  10. Focal cemento-osseous dysplasia: review and a case report.

    Science.gov (United States)

    Salem, Y M Y; Osman, Y I; Norval, E J G

    2010-10-01

    Focal cemento-osseous dysplasia is a benign fibro-osseous condition that can be seen in dentate and edentulous patients. It is an asymptomatic lesion and needs no treatment; however follow-up is essential due to the possibility that focal cemento-osseous dysplasia can progress to a condition called florid osseous dysplasia that involves multiple sites. A case report is presented here, along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

  11. FOCAL CHOROIDAL EXCAVATION AND CHOROIDAL NEOVASCULARIZATION WITH ASSOCIATED PACHYCHOROID.

    Science.gov (United States)

    Ghadiali, Quraish; Dansingani, Kunal K; Freund, K Bailey

    2016-01-01

    To report a case of focal choroidal excavation and choroidal neovascularization in the setting of pachychoroid disease. Multimodal imaging, including fundus photography, fundus autofluorescence, enhanced depth imaging optical coherence tomography, indocyanine green angiography, and en face structural and angiographic optical coherence tomography. The authors describe a 39-year-old female with moderately high myopia presenting with focal choroidal excavation and associated choroidal neovascularization. Multimodal imaging demonstrated pachychoroid features with dilated choroidal vessels surrounding the lesion. Optical coherence tomography angiography showed Type 2 neovascularization. Some cases of focal choroidal excavation and associated neovascularization may be related to structural abnormalities of the associated choroidal vasculature.

  12. Conversion of a neonatal hepatic hemangioma to focal nodular hyperplasia.

    Science.gov (United States)

    Turowski, Carmen; Feist, Henning; Alzen, Gerhard; Glüer, Sylvia; Petersen, Claus

    2009-04-01

    Hepatic hemangioma and focal nodular hyperplasia are both frequently observed benign lesions of the liver. Whereas hepatic hemangioma is the most frequent benign liver tumor in children, focal nodular hyperplasia occurs predominantly in adult patients. Concomitance of both entities has been described in adults, suggesting a similar pathogenesis. We report on a 6-month-old child with a continuously shrinking hepatic hemangioma after interventional therapy and a growing hepatic mass 5 years later, which emerged as focal nodular hyperplasia at the site of the former hemangioma. Diagnostic and therapeutic strategies regarding this patient are discussed. The present case supports the theory that these two entities may share a similar pathomechanism.

  13. Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Aanei, Carmen Mariana, E-mail: caanei@yahoo.com [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Eloae, Florin Zugun [Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Flandrin-Gresta, Pascale [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Tavernier, Emmanuelle [Service Hematologie Clinique, Institut de Cancerologie de la Loire, 42270, Saint-Priest-en-Jarez (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Carasevici, Eugen [Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Guyotat, Denis [Service Hematologie Clinique, Institut de Cancerologie de la Loire, 42270, Saint-Priest-en-Jarez (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Campos, Lydia [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France)

    2011-11-01

    Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their cellular microenvironment is essential to maintain 'stemness'. In cancer biology, focal adhesion (FA) proteins are involved in survival signal transduction in a wide variety of human tumours. To define the role of FA proteins in the haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and p130CAS, and analysed for reactivity, intensity and cellular localisation. Immunofluorescence microscopy allowed us to identify qualitative and quantitative differences, and subcellular localisation analysis revealed that in pathological MSCs, paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and enhanced nuclear co-localisation of these proteins correlated with a consistent proliferative advantage in MSCs from patients with refractory anaemia with excess blasts (RAEB) and negatively impacted clonogenicity of HPCs. These results suggest that signalling via FA proteins could be implicated in HPC-MSC interactions. Further, because FAK is an HSP90{alpha}/{beta} client protein, these results suggest the utility of HSP90{alpha}/{beta} inhibition as a target for adjuvant therapy for myelodysplasia.

  14. Fibronectin Binding Is Required for Acquisition of Mesenchymal/Endothelial Differentiation Potential in Human Circulating Monocytes

    Directory of Open Access Journals (Sweden)

    Noriyuki Seta

    2012-01-01

    Full Text Available We previously reported monocyte-derived multipotential cells (MOMCs, which include progenitors capable of differentiating into a variety of mesenchymal cells and endothelial cells. In vitro generation of MOMCs from circulating CD14+ monocytes requires their binding to extracellular matrix (ECM protein and exposure to soluble factor(s derived from circulating CD14- cells. Here, we investigated the molecular factors involved in MOMC generation by examining the binding of monocytes to ECM proteins. We found that MOMCs were obtained on the fibronectin, but not on type I collagen, laminin, or poly-L-lysine. MOMC generation was followed by changes in the expression profiles of transcription factors and was completely inhibited by either anti-α5 integrin antibody or a synthetic peptide that competed with the RGD domain for the β1-integrin binding site. These results indicate that acquisition of the multidifferentiation potential by circulating monocytes depends on their binding to the RGD domain of fibronectin via cell-surface α5β1 integrin.

  15. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation.

    NARCIS (Netherlands)

    Miltenburg, van M.H.; Nimwegen, van M.J.; Tijdens, R.B.; Lalai, R.A.; Kuiper, R.; Klarenbeek, S.; Schouten, P.C.; Vries, de A.; Jonkers, J.M.M.; Water, van de B.

    2014-01-01

    BACKGROUND Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in

  16. Tumor cell budding from focally disrupted tumor capsules: a common pathway for all breast cancer subtype derived invasion?

    Directory of Open Access Journals (Sweden)

    Yan-gao Man

    2010-01-01

    Full Text Available Human breast cancer represents a group of highly heterogeneous lesions consisting of about 20 morphologically and immnohistochemically distinct subtypes with substantially different prognoses. Our recent studies have suggested that all breast cancer subtypes, however, may share a common pathway, tumor cell budding from focally disrupted tumor capsules, for their invasion. The potential mechanisms and clinical implications of our observations are discussed.

  17. Focal seizures versus epileptic spasms in children with focal cortical dysplasia and epilepsy onset in the first year.

    Science.gov (United States)

    Serino, Domenico; Freri, Elena; Ragona, Francesca; D'Incerti, Ludovico; Bernardi, Bruno; Di Ciommo, Vincenzo; Granata, Tiziana; Vigevano, Federico; Fusco, Lucia

    2015-01-01

    Focal cortical dysplasia (FCD) has been recognized as one of the most frequent causes of drug resistant epilepsy, especially in children. In infancy, onset of FCD-related epilepsy is substantially characterized by epileptic spasms (ES) or focal seizures. Which elements pertaining to the FCD are responsible for the onset of one type of seizure over the other is still unclear. Purpose of our study was to compare the characteristics of FCDs in terms of lateralization and site in patients with epileptic spasms versus patients with focal seizures. We retrospectively reviewed data from 41 patients with FCD related epilepsy with onset during the first 14 months of life. Seizure semeiology and drug resistance were analyzed, as were age at onset and FCD site and lateralization. Twenty-one children had focal seizures, 11 had ES and nine had focal seizures followed by ES. Mean age at onset was respectively 8.2, 5.1 and 1.8 months. Drug resistance was present in respectively 38.5%, 34.6% and 26.9% of children. Among patients with only ES, 90.9% had an exclusively frontal FCD localization, versus 42.9% of patients with focal seizures and 11.1% of patients with focal seizures followed by ES. FCD lateralization was right sided respectively in 47.6%, 81.8% and 66.7% of patients. Frontal lobe localization of FCDs was closely associated with ES (p=0.001). Moreover we also found that patients with focal seizures followed by ES had a significantly earlier age at onset compared to patients with focal seizures only (pseizure type and drug resistance (p=0.08). Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A study of human resource competencies required to implement community rehabilitation in less resourced settings.

    Science.gov (United States)

    Gilmore, Brynne; MacLachlan, Malcolm; McVeigh, Joanne; McClean, Chiedza; Carr, Stuart; Duttine, Antony; Mannan, Hasheem; McAuliffe, Eilish; Mji, Gubela; Eide, Arne H; Hem, Karl-Gerhard; Gupta, Neeru

    2017-09-22

    implementing the WHO guidelines on the interaction between the health sector and CBR, particularly in the context of the Framework for Action for Strengthening Health Systems, in which human resources is one of six components. Realist syntheses can provide policy makers with detailed and practical information regarding complex health interventions, which may be valuable when planning and implementing programmes.

  19. Praxial disorders in focal lesions of cerebral hemispheres

    Directory of Open Access Journals (Sweden)

    Jorge Murillo Duran

    2007-11-01

    Full Text Available The purpose of this work is to analyze paraxial difficulties i.e, functional disorders in movementresulting from cerebral tissue lesions. In accordance with the literature on the subject, the following definition, the following definition of apraxia has been accepted: “Apraxia is inability in properly executing kinetic tasks without impairment or loss of motor or sensory functions or ataxia with would condition such inability”. “Proper execution” used in this definition concerns not only the effect of the action but also means of its realization. “Kinetic tasks” signify all aspects of motor activity defined by instructions, irrespective of the type of instruction (verbal or gestures, and regardless of whether it required −in the final effect− imitating the movement of the investigator or whether they were performed independently. The methodology has been based in the principle on Luria’s works.Deliberations on praxial disorders were based on investigation results embracing 90 patients with focal cerebral lesions. In fifty cases, changes were localized in the left cerebral hemisphere, in forty cases−in the right hemisphere. The summing up the results concerning a global comparison between cerebral hemispheres, indicate the following regularities: Results achieved made it possible to form the opinion that not all of the generally accepted tests investigating praxia in persons with cerebral lesions are solved faultlessly by healthy individuals; thus, a faulty execution should not always be regarded as a sign of pathological functioning of the cerebral tissue as a result of lesion.

  20. Through-focal HAADF-STEM of buried nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero-Lebrero, M P; Pizarro, J; Guerrero, E; Galindo, P L; Yanez, A [Department Lenguajes y Sist. Informaticos, Universidad de Cadiz (Spain); Molina, S I, E-mail: maria.guerrero@uca.e [Department Ciencia de los Materiales e I.M. y Q.I. Universidad de Cadiz (Spain)

    2010-02-01

    High-Angle Annular Dark-Field Scanning Transmission Electron Microscopy (HAADF-STEM) in combination with strain mapping techniques provides a powerful tool for quantitative analysis of crystalline semiconductor materials. Due to the complex interaction of a focused probe and a sample in HAADF, the calculation of each pixel in a simulation process requires a complete multislice iteration, making the overall computing process a rather demanding task in time and memory. SICSTEM is a parallel software code recently developed for running on the University of Cadiz Supercomputer (3.75 Tflops) that allows the simulation of images from large nanostructures containing more than one million atoms. The software has been designed to be able to generate not only one dimensional line scans or two dimensional images, but also to perform optical sectioning in the STEM simulation process, providing an easy way to simulate 3D HAADF-STEM images. In this work we consider GaAs capped GaSb nanostructures epitaxially oriented on a GaAs substrate. A methodology has been developed by combining the through-focal series STEM imaging and image analysis to estimate shape and position of buried GaSb nanostructures.

  1. Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells.

    Science.gov (United States)

    Blackstone, B N; Li, R; Ackerman, W E; Ghadiali, S N; Powell, H M; Kniss, D A

    2015-04-15

    Breast cancer is the second leading cause of malignant death among women. A crucial feature of metastatic cancers is their propensity to lose adhesion to the underlying basement membrane as they transition to a motile phenotype and invade surrounding tissue. Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins. Focal adhesion kinase (FAK) is pivotal for the organization of focal contacts and maturation into focal adhesions, and disruption of this process is a hallmark of early cancer invasive potential. Our recent work has revealed that myoferlin (MYOF) mediates breast tumor cell motility and invasive phenotype. In this study we demonstrate that noninvasive breast cancer cell lines exhibit increased cell-substrate adhesion and that silencing of MYOF using RNAi in the highly invasive human breast cancer cell line MDA-MB-231 also enhances cell-substrate adhesion. In addition, we detected elevated tyrosine phosphorylation of FAK (FAK(Y397)) and paxillin (PAX(Y118)), markers of focal adhesion protein activation. Morphometric analysis of PAX expression revealed that RNAi-mediated depletion of MYOF resulted in larger, more elongated focal adhesions, in contrast to cells transduced with a control virus (MDA-231(LVC) cells), which exhibited smaller focal contacts. Finally, MYOF silencing in MDA-MB-231 cells exhibited a more elaborate ventral cytoskeletal structure near focal adhesions, typified by pronounced actin stress fibers. These data support the hypothesis that MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells. Copyright © 2015 the American Physiological Society.

  2. Fabrication of multi-focal microlens array on curved surface for wide-angle camera module

    Science.gov (United States)

    Pan, Jun-Gu; Su, Guo-Dung J.

    2017-08-01

    In this paper, we present a wide-angle and compact camera module that consists of microlens array with different focal lengths on curved surface. The design integrates the principle of an insect's compound eye and the human eye. It contains a curved hexagonal microlens array and a spherical lens. Compared with normal mobile phone cameras which usually need no less than four lenses, but our proposed system only uses one lens. Furthermore, the thickness of our proposed system is only 2.08 mm and diagonal full field of view is about 100 degrees. In order to make the critical microlens array, we used the inkjet printing to control the surface shape of each microlens for achieving different focal lengths and use replication method to form curved hexagonal microlens array.

  3. The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4.

    Science.gov (United States)

    Hudson, J B; Podos, S D; Keith, K; Simpson, S L; Ferguson, E L

    1998-04-01

    The Transforming Growth Factor-beta superfamily member decapentaplegic (dpp) acts as an extracellular morphogen to pattern the embryonic ectoderm of the Drosophila embryo. To identify components of the dpp signaling pathway, we screened for mutations that act as dominant maternal enhancers of a weak allele of the dpp target gene zerknŁllt. In this screen, we recovered new alleles of the Mothers against dpp (Mad) and Medea genes. Phenotypic analysis of the new Medea mutations indicates that Medea, like Mad, is required for both embryonic and imaginal disc patterning. Genetic analysis suggests that Medea may have two independently mutable functions in patterning the embryonic ectoderm. Complete elimination of maternal and zygotic Medea activity in the early embryo results in a ventralized phenotype identical to that of null dpp mutants, indicating that Medea is required for all dpp-dependent signaling in embryonic dorsal-ventral patterning. Injection of mRNAs encoding DPP or a constitutively activated form of the DPP receptor, Thick veins, into embryos lacking all Medea activity failed to induce formation of any dorsal cell fates, demonstrating that Medea acts downstream of the thick veins receptor. We cloned Medea and found that it encodes a protein with striking sequence similarity to human SMAD4. Moreover, injection of human SMAD4 mRNA into embryos lacking all Medea activity conferred phenotypic rescue of the dorsal-ventral pattern, demonstrating conservation of function between the two gene products.

  4. FOCAL CORTICAL DYSPLASIAS: CLINICAL AND ELECTRO-NEUROIMAGING CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2016-01-01

    Full Text Available In spite of a notable advance made in epileptology, resistant epilepsies account for approximately 30 % of all forms of epilepsy particularly in patients with focal seizures. One of the main causes of therapy-resistant focal epilepsies is focal cortical dysplasias (FCD. This term was first introduced by D. Taylor et al. in 1971. FCD belongs to abnormal cortical development. Among all abnormalities of cortical development, FCD in surgically treated children amounts to 75 %. FCD is the most common cause of resistant epilepsy in children and the most frequent reason for diagnosing cryptogenic focal epilepsy with intractable seizures. The author gives a detailed literature review dedicated to FCD as a cause of resistant epilepsy, including the classification and histologic characteristics of FCD, its clinical manifestations and prognosis, and approaches to medical and surgical treatments. 

  5. Conserved helicase domain of human RecQ4 is required for strand annealing-independent DNA unwinding

    DEFF Research Database (Denmark)

    Rossi, Marie L; Ghosh, Avik K; Kulikowicz, Tomasz

    2010-01-01

    provide the first evidence that human RecQ4's unwinding is independent of strand annealing, and that it does not require the presence of excess ssDNA. Moreover, we demonstrate that a point mutation of the conserved lysine in the Walker A motif abolished helicase activity, implying that not the N......Humans have five members of the well conserved RecQ helicase family: RecQ1, Bloom syndrome protein (BLM), Werner syndrome protein (WRN), RecQ4, and RecQ5, which are all known for their roles in maintaining genome stability. BLM, WRN, and RecQ4 are associated with premature aging and cancer...... predisposition. Of the three, RecQ4's biological and cellular roles have been least thoroughly characterized. Here we tested the helicase activity of purified human RecQ4 on various substrates. Consistent with recent results, we detected ATP-dependent RecQ4 unwinding of forked duplexes. However, our results...

  6. A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells.

    Directory of Open Access Journals (Sweden)

    Li Xie

    Full Text Available Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53- human cancer cells. We find that compared to p53-competent (p53+ human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53- but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells.

  7. Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit

    Directory of Open Access Journals (Sweden)

    O. G. Lyublinskaya

    2015-01-01

    Full Text Available The present study focuses on the involvement of reactive oxygen species (ROS in the process of mesenchymal stem cells “waking up” and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs, we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0 phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation. This increase was registered before the eMSC entry to the S-phase of the cell cycle, and elimination of this increase by antioxidants (N-acetyl-L-cysteine, Tempol, and Resveratrol blocked G1–S-phase transition. Similarly, a cell cycle arrest which resulted from the antioxidant treatment was observed in the experiments with synchronized human mesenchymal stem cells derived from the adipose tissue. Thus, we showed that physiologically relevant level of ROS is required for the initiation of human mesenchymal stem cell proliferation and that low levels of ROS due to the antioxidant treatment can block the stem cell self-renewal.

  8. Dissecting Neuronal Participation to Focal Epileptic Events in Vivo

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0631 TITLE: Dissecting Neuronal Participation to Focal Epileptic Events in Vivo PRINCIPAL INVESTIGATOR: Stelios M...SUBTITLE 5a. CONTRACT NUMBER Dissecting Neuronal Participation to Focal Epileptic Events in Vivo 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...rational approaches to therapy we need to understand the role that individual neurons of different types play in epileptic events. The two-photon

  9. The cooling control system for focal plane assembly of astronomical satellite camera based on TEC

    Science.gov (United States)

    He, Yuqing; Du, Yunfei; Gao, Wei; Li, Baopeng; Fan, Xuewu; Yang, Wengang

    2017-02-01

    The dark current noise existing in the CCD of the astronomical observation camera has a serious influence on its working performance, reducing the working temperature of CCD can suppress the influence of dark current effectively. By analyzing the relationship between the CCD chip and the dark current noise, the optimum working temperature of the red band CCD focal plane is identified as -75°. According to the refrigeration temperature, a cooling control system for focal plane based on a thermoelectric cooler (TEC) was designed. It is required that the system can achieve high precision temperature control for the target. In the cooling control system, the 80C32 microcontroller was used as its systematic core processor. The advanced PID control algorithm is adopted to control the temperature of the top end of TEC. The bottom end of the TEC setting a constant value according to the target temperature used to assist the upper TEC to control the temperature. The experimental results show that the cooling system satisfies the requirements of the focal plane for the astronomical observation camera, it can reach the working temperature of -75° and the accuracy of ±2°.

  10. FAK dimerization controls its kinase-dependent functions at focal adhesions

    KAUST Repository

    Brami-Cherrier, Karen

    2014-01-30

    Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK\\'s kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

  11. Common and uncommon features of focal splenic lesions on contrast-enhanced ultrasound: a pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Zavariz, Julia D., E-mail: julia.zavariz@hc.fm.usp.br [Universidade de São Paulo (HC/FMUSP), São Paulo, SP (Brazil). Faculdade de Medicina. Hospital das Clínicas; Konstantatou, Eleni; Deganello Annamaria; Bosanac, Diana; Huang, Dean Y.; Sellars, Maria E.; Sidhu, Paul S. [Department of Radiology, King’s College Hospital, Denmark Hill, London (United Kingdom)

    2017-11-15

    The characterization of focal splenic lesions by ultrasound can be quite challenging. The recent introduction of contrast-enhanced ultrasound (CEUS) has come to play a valuable role in the field of imaging splenic pathologies, offering the possibility of an ionizing radiation-free investigation. Because CEUS has been incorporated into everyday clinical practice, malignant diseases such as focal lymphomatous infiltration, metastatic deposits, benign cysts, traumatic fractures, and hemangiomas can now be accurately depicted and characterized without the need for further imaging. More specifically, splenic traumatic fractures do not require additional imaging by computed tomography (with ionizing radiation exposure) for follow-up, because splenic fractures and their complications are safely imaged with CEUS. In the new era of CEUS, more patients benefit from radiation-free investigation of splenic pathologies with high diagnostic accuracy. (author)

  12. Another Form of Focal Choroidal Excavation Based on Multimodality Imaging.

    Science.gov (United States)

    Wang, Shiyuan; Zhao, Peiquan

    2016-10-01

    To describe a peculiar choroidal entity using multimodality imaging and to further understand the relationship between focal choroidal excavation and central serous chorioretinopathy. A peculiar entity was detected in both eyes of a 20-year-old male patient who was followed for more than 4 years; one perifoveal focal choroidal excavation and two extrafoveal focal choroidal excavations were noted in each eye. The bilateral perifoveal focal choroidal excavations exhibited progressive development with repeated interconversion between the nonconforming and conforming types. Dilated choroid blood vessels were detected by en face spectral-domain optical coherence tomography (SD-OCT). Although the ellipsoid zone and retinal pigment epithelium layer defect also involved the fovea, a visual acuity of 20/20 was maintained in both eyes, with neither metamorphopsia by Amsler grid nor abnormalities noted by multifocal electroretinogram. However, pigment epithelium detachment finally appeared in the right eye. The microperimetry test revealed reduced threshold sensitivity corresponding to the lesions, and near-infrared autofluorescence revealed increased hyperfluorescence at the latest visit. Idiopathic focal choroidal excavation may convert to the structure of central serous chorioretinopathy alike, which likely indicates another rare condition of focal choroidal excavation or central serous chorioretinopathy. Wide- and deep-scanning modes should be routinely applied in OCT imaging to detect choroidal disorders.

  13. Morfology of Focal Lesious of the Thiroid Gland

    Directory of Open Access Journals (Sweden)

    E Troshina

    2007-03-01

    Full Text Available To evaluate focal changes morphology the authors carried out a retrospective analysis in 297 patients who had earlier underwent surgery for different forms (multinodular/nodular of goiter. In all cases preoperative US examination revealed thyroid nodules and focal lesions under 1 cm in the surrounding thyroid tissue. The results after US study taken part in the preoperative period were compared with histological examination data. Average patients age was 47.4 ± 11.9; median was 48 [17; 81]. For evaluation expression of a proliferation marker (Ki 67 and a development of a functional independence (TSH receptor in the focuses of goiterous transformation at an immunnohistochemical study was formed a group of 25 cases (14 — focal hyperplasia and 11 — focal hypertrophy. 78.8% of focal changes were morphologically represented with goiterous or dystrophic origin (focuses of sclerosis, lymphoid infiltration and atrophy. Amongst them 56.6% were focal goiterous hypertrophy and hyperplasia. Evidently and moderately marked Ki 67 expression and negative expression of TSH-receptor in the focuses of goiterous hyperplasia proved the tendency to their growth with further transformation into colloid nodules and functional independence development.

  14. Focal and multifocal diabetic neuropathies Neuropatia diabética focal e multifocal

    Directory of Open Access Journals (Sweden)

    Gérard Said

    2007-12-01

    Full Text Available Diabetic neuropathy is the most common neuropathy in industrialized countries, with a remarkable range of clinical manifestations. The vast majority of the patients with clinical diabetic neuropathy have a distal symmetrical form that progress following a fiber-length dependent pattern, with predominant sensory and autonomic manifestations. This pattern of neuropathy is associated with a progressive distal axonopathy. Patients are exposed to trophic changes in the feet, pains and autonomic disturbances. Less often, diabetic patients may develop focal and multifocal neuropathy that includes cranial nerve involvement, limb and truncal neuropathies. This neuropathic pattern tends to occur after 50 years of age, mostly in patients with longstanding diabetes mellitus. The LDDP does not show any trend to improvement and either relentlessly progresses or remain relatively stable over years. Conversely the focal diabetic neuropathies, which are often associated with inflammatory vasculopathy on nerve biopsies, remain self limited, sometimes after a relapsing course.A neuropatia diabética é a mais predominante das neuropatias nos países industrializados apresentando uma gama variável de manifestações clinicas. A maioria dos pacientes com neuropatia diabética apresenta uma forma simétrica distal que progride para um padrão fibra comprimento dependente com manifestações sensitivas e autonomicas. Este tipo de neuropatia é associado com uma axonopatia distal progressiva. Os pacientes apresentam modificações tróficas nos pés, dores e distúrbios autonômicos. Menos freqüentemente os pacientes diabéticos podem desenvolver neuropatia focal e multifocal que incluem envolvimento de nervos cranianos, tronco e membros inferiores. Este padrão de neuropatia é mais freqüente em pacientes com mais de 50 anos e com longa historia de diabetes. Este tipo de neuropatia fibra-comprimento dependente não apresenta melhora, progride lentamente ou

  15. Conformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells

    KAUST Repository

    Kadaré, Gress

    2015-01-02

    Focal adhesion (FA) kinase (FAK) regulates cell survival and motility by transducing signals from membrane receptors. The C-terminal FA targeting (FAT) domain of FAK fulfils multiple functions, including recruitment to FAs through paxillin binding. Phosphorylation of FAT on Tyr925 facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. We investigated the importance of H1 opening in cells by comparing the properties of FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1 openings. These mutations did not alter the activation of FAK, but selectively affected its cellular functions, including self-association, Tyr925 phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation of Tyr861, located between the kinase and FAT domains, was also enhanced by the mutation that opened the FAT bundle. Similarly phosphorylation of Ser910 by ERK in response to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening markedly impaired FAK function. Our data support the biological importance of conformational dynamics of the FAT domain and its functional interactions with other parts of the molecule.

  16. Rotavirus structural proteins and dsRNA are required for the human primary plasmacytoid dendritic cell IFNalpha response.

    Directory of Open Access Journals (Sweden)

    Emily M Deal

    2010-06-01

    Full Text Available Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNalpha and beta correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV, have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs with either live or inactivated RRV induces substantial IFNalpha production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNalpha production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNalpha by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNalpha induction in primary

  17. Rotavirus structural proteins and dsRNA are required for the human primary plasmacytoid dendritic cell IFNalpha response.

    Science.gov (United States)

    Deal, Emily M; Jaimes, Maria C; Crawford, Sue E; Estes, Mary K; Greenberg, Harry B

    2010-06-03

    Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNalpha and beta) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV), have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs) with either live or inactivated RRV induces substantial IFNalpha production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNalpha production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNalpha by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNalpha induction in primary human pDCs by a ds

  18. Blaschko Linear Enamel Defects - A Marker for Focal Dermal Hypoplasia: Case Report of Focal Dermal Hypoplasia

    Directory of Open Access Journals (Sweden)

    Stefan Gysin

    2015-05-01

    Full Text Available Focal dermal hypoplasia (FDH is a rare genetic skin disorder. The inheritance of FDH or Goltz-Gorlin syndrome is X-linked dominant and the disease is associated with a PORCN gene mutation. This gene plays a key role in the Wnt pathway, which has an impact on embryonic development. Every tissue derived from meso- and ectoderm can be affected. Patients suffer from cutaneous, ocular, osseous, oral and dental defects. The skin and dental alterations manifest along the Blaschko lines. We present a woman (born in 1962 suffering from FDH with congenital skin changes and Blaschko linear enamel defects. Typical symptoms (e.g. fat herniations, scoliosis, syndactyly, microphthalmia, caries and alopecia plus vertical grooving of all teeth gave a first indication. Molecular genetic testing confirmed the definitive diagnosis of FDH. We hypothesize that, in the context of typical skin changes, visible Blaschko lines on the teeth in the form of vertical grooves are almost pathognomonic for FDH.

  19. Generation of a spherical focal spot in a 4Pi focusing system through reversing the radiation of infinite biconical antenna

    Science.gov (United States)

    Yu, Yanzhong; Zhan, Qiwen

    2015-09-01

    A method of generating spherical focal spot is demonstrated through reversely propagating and tightly focusing the electric field at the pupil plane radiated from an infinite biconical antenna centered at the foci of two confocal high numerical aperture aplanatic objective lenses. The required incident field distribution at the pupil plane is found by solving the inverse problem of radiation from an infinite biconical antenna using the Richards-Wolf vectorial diffraction theory. Numerical simulations show that a focal spot of excellent spherical symmetry along with extremely low sidelobe (~4.72% of the peak) and diffraction limited spot size of 0.432λ can be obtained in a 4Pi focusing system. It is also shown that the generated focal spot can be shifted along the optical axis while still maintaining its spherical shape and diffraction limited size through introducing a phase difference between the pupil illumination fields of the two objective lenses used in the 4Pi focusing system.

  20. Transforming growth factor-beta1 effects on endothelial monolayer permeability involve focal adhesion kinase/Src.

    Science.gov (United States)

    Lee, Young H; Kayyali, Usamah S; Sousa, Anne Marie; Rajan, Thomas; Lechleider, Robert J; Day, Regina M

    2007-10-01

    Transforming growth factor (TGF)-beta1 activity has been shown to increase vascular endothelial barrier permeability, which is believed to precede several pathologic conditions, including pulmonary edema and vessel inflammation. In endothelial monolayers, TGF-beta1 increases permeability, and a number of studies have demonstrated the alteration of cell-cell contacts by TGF-beta1. We hypothesized that focal adhesion complexes also likely contribute to alterations in endothelial permeability. We examined early signal transduction events associated with rapid changes in monolayer permeability and the focal adhesion complex of bovine pulmonary artery endothelial cells. Western blotting revealed rapid tyrosine phosphorylation of focal adhesion kinase (FAK) and Src kinase in response to TGF-beta1; inhibition of both of these kinases using pp2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), ameliorates TGF-beta1-induced monolayer permeability. Activation of FAK/Src requires activation of the epidermal growth factor receptor downstream of the TGF-beta receptors, and is blocked by the epidermal growth factor receptor inhibitor AG1478. Immunohistochemistry showed that actin and the focal adhesion proteins paxillin, vinculin, and hydrogen peroxide-inducible clone-5 (Hic-5) are rearranged in response to TGF-beta1; these proteins are released from focal adhesion complexes. Rearrangement of paxillin and vinculin by TGF-beta1 is not blocked by the FAK/Src inhibitor, pp2, or by SB431542 inhibition of the TGF-beta type I receptor, anaplastic lymphoma kinase 5; however, pp1 (4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), which inhibits both type I and type II TGF-beta receptors, does block paxillin and vinculin rearrangement. Hic-5 protein rearrangement requires FAK/Src activity. Together, these results suggest that TGF-beta1-induced monolayer permeability involves focal adhesion and cytoskeletal rearrangement through both FAK/Src-dependent and

  1. An Extension of a Parallel-Distributed Processing Framework of Reading Aloud in Japanese: Human Nonword Reading Accuracy Does Not Require a Sequential Mechanism

    Science.gov (United States)

    Ikeda, Kenji; Ueno, Taiji; Ito, Yuichi; Kitagami, Shinji; Kawaguchi, Jun

    2017-01-01

    Humans can pronounce a nonword (e.g., rint). Some researchers have interpreted this behavior as requiring a sequential mechanism by which a grapheme-phoneme correspondence rule is applied to each grapheme in turn. However, several parallel-distributed processing (PDP) models in English have simulated human nonword reading accuracy without a…

  2. Focal and Ambient Processing of Built Environments: Intellectual and Atmospheric Experiences of Architecture.

    Science.gov (United States)

    Rooney, Kevin K; Condia, Robert J; Loschky, Lester C

    2017-01-01

    Neuroscience has well established that human vision divides into the central and peripheral fields of view. Central vision extends from the point of gaze (where we are looking) out to about 5° of visual angle (the width of one's fist at arm's length), while peripheral vision is the vast remainder of the visual field. These visual fields project to the parvo and magno ganglion cells, which process distinctly different types of information from the world around us and project that information to the ventral and dorsal visual streams, respectively. Building on the dorsal/ventral stream dichotomy, we can further distinguish between focal processing of central vision, and ambient processing of peripheral vision. Thus, our visual processing of and attention to objects and scenes depends on how and where these stimuli fall on the retina. The built environment is no exception to these dependencies, specifically in terms of how focal object perception and ambient spatial perception create different types of experiences we have with built environments. We argue that these foundational mechanisms of the eye and the visual stream are limiting parameters of architectural experience. We hypothesize that people experience architecture in two basic ways based on these visual limitations; by intellectually assessing architecture consciously through focal object processing and assessing architecture in terms of atmosphere through pre-conscious ambient spatial processing. Furthermore, these separate ways of processing architectural stimuli operate in parallel throughout the visual perceptual system. Thus, a more comprehensive understanding of architecture must take into account that built environments are stimuli that are treated differently by focal and ambient vision, which enable intellectual analysis of architectural experience versus the experience of architectural atmosphere, respectively. We offer this theoretical model to help advance a more precise understanding of the

  3. Mechanical changes in human dental pulp stem cells during early odontogenic differentiation.

    Science.gov (United States)

    Jones, Taneka D; Naimipour, Hamed; Sun, Shan; Cho, Michael; Alapati, Satish B

    2015-01-01

    Cell adhesion and migration in bioactive scaffolds require actin cytoskeleton remodeling and focal adhesion formation. Additionally, human dental pulp stem cells (hDPSCs) undergo several changes in their mechanical properties during odontogenic differentiation. The effect of factors essential for odontogenesis on actin stress fiber elasticity and focal adhesion formation is not known. Live hDPSCs cultured in odontogenic media were imaged for cytoskeleton changes using an atomic force microscope. The Young's modulus (kPa) of the cytoskeleton was recorded as a function of culture medium for 10 days. Focal adhesion formation was assessed using immunofluorescence. Cultured hDPSCs were incubated with a monoclonal vinculin antibody, and filamentous actins were visualized using 0.5 μmol/L phalloidin. Cytoskeletal elasticity significantly increased in response to odontogenic media. Both the number and physical size of focal adhesions in hDPSCs also increased. Up-regulation of vinculin expression was evident. The increase in the formation of focal adhesions was consistent with actin remodeling to stress fibers. Our findings suggest that hDPSCs firmly attach to the glass substrate in response to odontogenic media. Successful regeneration of pulp-dentin tissue using biomimetic scaffolds will likely require cell-extracellular matrix interactions influenced by biochemical induction factors. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Stray light and its reduction of focal plane arrays

    Science.gov (United States)

    Yu, Chen-hui; Zhou, Jian-kang; Shi, Rong-bao; Shen, Wei-ming

    2011-08-01

    Existing studies have paid much attention to stray light of lenses. However, the ghost reflection inside FPA (Focal Plane Array) detector is almost ignored which is, in fact, also an unnegligible source of stray light in digital imaging systems. Ghosting between window surfaces and CCD photosensitive area is often a major source of stray light in FPA detectors, it may lead to image blur, color distortion, and contrast reduction. Besides, diffraction pattern can be observed from front-illuminated CCD as the incident beam can be diffracted by its polysilicon electrode gates at the surface. In this paper, we study the generation mechanism and the reduction approaches to such stray light. Both front-illuminated and back-illuminated CCDs (Charge Coupled Device) are investigated in our study. We build models to identify stray light paths and predict window ghost image characteristics. Furthermore, three methods, i.e., anti-reflective coating method, fluid-filled method and deconvolution method are presented to decrease the stray light. The first anti-reflective coating method can be effectively used in back-thinned CCDs to reduce the reflection and to maximize quantum efficiency. The second fluid-filled method attempts to reduce the effects of unwanted light contamination by simulating some characteristics of the human eyes. The use of liquid can reduce the fresnel reflectance of interface. In addition, the acquired images contaminated by FPA's stray light are post-processed with the deconvolution method. Effectiveness of our proposed methods is verified with experiments. It is shown that stray light of FPA can be efficiently reduced.

  5. Reversed Procrastination by Focal Disruption of Medial Frontal Cortex.

    Science.gov (United States)

    Jha, Ashwani; Diehl, Beate; Scott, Catherine; McEvoy, Andrew W; Nachev, Parashkev

    2016-11-07

    An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [12-14], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. The QWIP Focal Plane Assembly for NASA's Landsat Data Continuity Mission

    Science.gov (United States)

    Jhabvala, M; Choi, K.; Reuter, D.; Sundaram, M.; Jhabvala, C; La, Anh; Waczynski, Augustyn; Bundas, Jason

    2010-01-01

    The Thermal Infrared Sensor (TIRS) is a QWIP based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a dual channel far infrared imager with the two bands centered at 10.8[mu]m and 12.0[mu]m. The focal plane assembly (FPA) consists of three 640x512 GaAs Quantum Well Infrared Photodetector (QWIP) arrays precisely mounted to a silicon carrier substrate that is mounted on an invar baseplate. The two spectral bands are defined by bandpass filters mounted in close proximity to the detector surfaces. The focal plane operating temperature is 43K. The QWIP arrays are hybridized to Indigo ISC9803 readout integrated circuits (ROICs). Two varieties of QWIP detector arrays are being developed for this project, a corrugated surface structure QWIP and a grating surface structure QWIP. This paper will describe the TIRS system noise equivalent temperature difference sensitivity as it affects the QWIP focal plane performance requirements: spectral response, dark current, conversion efficiency, read noise, temperature stability, pixel uniformity, optical crosstalk and pixel yield. Additional mechanical constraints as well as qualification through Technology Readiness Level 6 (TRL 6) will also be discussed.

  7. Curved focal plane extreme ultraviolet detector array for a EUV camera on CHANG E lander.

    Science.gov (United States)

    Ni, Q; Song, K; Liu, S; He, L; Chen, B; Yu, W

    2015-11-30

    A novel curved focal plane extreme ultraviolet (EUV) detector array designed for a moon-based EUV camera is demonstrated. The curved focal plane detector array operating in a pulse-counting mode consists of a curved microchannel plate (MCP) stack and an induced charge wedge-strip anode (WSA). The curved MCP is fabricated by firstly thermally slumping of the MCPs, and then followed by optical polishing and core glass etching. By using this technology, curved MCPs with a length-to-diameter (L/D) ratio of 80:1 and a radius of curvature of 150 mm have been successfully achieved. The performance of the curved MCP detector is fully characterized in terms of the background noise, pulse height distribution, gain, image linearity and spatial resolution. It is measured that a spatial resolution of 7.13 lp/mm can be achieved with a background noise of less than 0.3 counts/cm2⋅s. The characterization results indicate that the curved focal plane detector can fulfill the requirements of the moon-based EUV camera.

  8. MIXS on BepiColombo and its DEPFET based focal plane instrumentation

    Energy Technology Data Exchange (ETDEWEB)

    Treis, J., E-mail: jft@hll.mpg.d [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Solar System Research, Max-Planck-Strasse 2, 37191 Katlenburg-Lindau (Germany); Andricek, L. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Physics, Foehringer Ring 6, 80805 Munich (Germany); Aschauer, F. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Extraterrestrial Physics, Giessenbachstrasse, 85748 Garching (Germany); Heinzinger, K. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); PNSensor GmbH, Roemerstrasse 28, 80803 Munich (Germany); Herrmann, S. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Extraterrestrial Physics, Giessenbachstrasse, 85748 Garching (Germany); Hilchenbach, M. [MPI for Solar System Research, Max-Planck-Strasse 2, 37191 Katlenburg-Lindau (Germany); Lauf, T. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Extraterrestrial Physics, Giessenbachstrasse, 85748 Garching (Germany); Lechner, P.; Lutz, G.; Majewski, P. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); PNSensor GmbH, Roemerstrasse 28, 80803 Munich (Germany); Porro, M. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Extraterrestrial Physics, Giessenbachstrasse, 85748 Garching (Germany); Richter, R.H. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Physics, Foehringer Ring 6, 80805 Munich (Germany); Schaller, G. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Extraterrestrial Physics, Giessenbachstrasse, 85748 Garching (Germany); Schnecke, M. [MPI Semiconductor Laboratory, Otto-Hahn-Ring 6, 81739 Munich (Germany); MPI for Physics, Foehringer Ring 6, 80805 Munich (Germany)

    2010-12-11

    Focal plane instrumentation based on DEPFET Macropixel devices, being a combination of the Detector-Amplifier structure DEPFET with a silicon drift chamber (SDD), has been proposed for the MIXS (Mercury Imaging X-ray Spectrometer) instrument on ESA's Mercury exploration mission BepiColombo. MIXS images X-ray fluorescent radiation from the Mercury surface with a lightweight X-ray mirror system on the focal plane detector to measure the spatially resolved element abundance in Mercury's crust. The sensor needs to have an energy resolution better than 200 eV FWHM at 1 keV and is required to cover an energy range from 0.5 to 10 keV, for a pixel size of 300x300{mu}m{sup 2}. Main challenges for the instrument are radiation damage and the difficult thermal environment in the mercury orbit. The production of the first batch of flight devices has been finished at the MPI semiconductor laboratory. Prototype modules have been assembled to verify the electrical properties of the devices; selected results are presented here. The prototype devices, Macropixel prototypes for the SIMBOL-X focal plane, are electrically fully compatible, but have a pixel size of 0.5x0.5 mm{sup 2}. Excellent homogeneity and near Fano-limited energy resolution at high readout speeds have been observed on these devices.

  9. Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo

    Science.gov (United States)

    Khurana, Mamta; Moriyama, Eduardo H.; Mariampillai, Adrian; Samkoe, Kimberley; Cramb, David; Wilson, Brian C.

    2009-11-01

    As part of an ongoing program to develop two-photon (2-γ) photodynamic therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD) and other vascular pathologies, we have evaluated the reciprocity of drug-light doses in focal-PDT. We targeted individual arteries in a murine window chamber model, using primarily the clinical photosensitizer Visudyne/liposomal-verteporfin. Shortly after administration of the photosensitizer, a small region including an arteriole was selected and irradiated with varying light doses. Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point metric, there was reciprocity between the drug and light doses, i.e., the response correlated with the drug-light product (DLP). These results provide the first quantification of photosensitizer and light dose relationships for localized irradiation of a single blood vessel and are compared to the DLP required for vessel closure between 1-γ and 2-γ activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-γ cross section. Demonstration of reciprocity over a wide range of DLP is important for further development of focal PDT treatments, such as the targeting of feeder vessels in 2-γ PDT of AMD.

  10. Focal adhesion signaling and actin stress fibers are dispensable for progression through the ongoing cell cycle.

    Science.gov (United States)

    Margadant, Coert; van Opstal, Angelique; Boonstra, Johannes

    2007-01-01

    Prevention of cell spreading or disruption of actin filaments inhibits growth factor stimulated cell cycle re-entry from quiescence, mainly because of a failure to induce cyclin D expression. Ectopic cyclin D expression overrules anchorage-dependency, suggesting that cell spreading per se is not required as long as cyclin D is otherwise induced. We investigated whether cyclin D expression in cells exiting mitosis is sufficient to drive morphology-independent cell cycle progression in continuously cycling (i.e. not quiescent) cells. Disruption of post-mitotic actin reorganization did not affect substratum reattachment but abolished the formation of filopodia, lamellipodia and ruffles, as well as stress fiber organization, focal adhesion assembly and cell spreading. Furthermore, integrin-mediated focal adhesion kinase (FAK) autophosphorylation and growth factor stimulated p42/p44 mitogen activated protein kinase (MAPK) activation were inhibited. Despite a progressive loss of cyclin D expression in late G1, cyclin E and cyclin A were normally induced. In addition, cells committed to DNA synthesis and completed their entire cycle. Our results demonstrate that post-mitotic disruption of the actin cytoskeleton allows cell cycle progression independent of focal adhesion signaling, cytoskeletal organization and cell shape, presumably because pre-existing cyclin D levels are sufficient to drive cell cycle progression at the M-G1 border.

  11. Optimization of confocal laser induced fluorescence for long focal length applications

    Science.gov (United States)

    Jemiolo, Andrew J.; Henriquez, Miguel F.; Thompson, Derek S.; Scime, Earl E.

    2017-10-01

    Laser induced fluorescence (LIF) is a non-perturbative diagnostic for measuring ion and neutral particle velocities and temperatures in a plasma. The conventional method for single-photon LIF requires intersecting optical paths for light injection and collection. The multiple vacuum windows needed for such measurements are unavailable in many plasma experiments. Confocal LIF eliminates the need for perpendicular intersecting optical paths by using concentric injection and collection paths through a single window. One of the main challenges with using confocal LIF is achieving high resolution measurements at the longer focal lengths needed for many plasma experiments. We present confocal LIF measurements in HELIX, a helicon plasma experiment at West Virginia University, demonstrating spatial resolution dependence on focal length and spatial filtering. By combining aberration mitigating optics with spatial filtering, our results show high resolution measurements at focal lengths of 0.5 m, long enough to access the interiors of many laboratory plasma experiments. This work was supported by U.S. National Science Foundation Grant No. PHY-1360278.

  12. Monitoring in real-time focal adhesion protein dynamics in response to a discrete mechanical stimulus

    Science.gov (United States)

    von Bilderling, Catalina; Caldarola, Martín; Masip, Martín E.; Bragas, Andrea V.; Pietrasanta, Lía I.

    2017-01-01

    The adhesion of cells to the extracellular matrix is a hierarchical, force-dependent, multistage process that evolves at several temporal scales. An understanding of this complex process requires a precise measurement of forces and its correlation with protein responses in living cells. We present a method to quantitatively assess live cell responses to a local and specific mechanical stimulus. Our approach combines atomic force microscopy with fluorescence imaging. Using this approach, we evaluated the recruitment of adhesion proteins such as vinculin, focal adhesion kinase, paxillin, and zyxin triggered by applying forces in the nN regime to live cells. We observed in real time the development of nascent adhesion sites, evident from the accumulation of early adhesion proteins at the position where the force was applied. We show that the method can be used to quantify the recruitment characteristic times for adhesion proteins in the formation of focal complexes. We also found a spatial remodeling of the mature focal adhesion protein zyxin as a function of the applied force. Our approach allows the study of a variety of complex biological processes involved in cellular mechanotransduction.

  13. Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet.

    Science.gov (United States)

    Caraballo, Roberto; Noli, Daniel; Cachia, Pedro

    2015-06-01

    We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Two of the three children responded well to the ketogenic diet. One of these patients became seizure-free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.

  14. Focal nonconvulsive seizures during detoxification for benzodiazepine abuse.

    Science.gov (United States)

    Albiero, Anna; Brigo, Francesco; Faccini, Marco; Casari, Rebecca; Quaglio, Gianluca; Storti, Monica; Fiaschi, Antonio; Bongiovanni, Luigi Giuseppe; Lugoboni, Fabio

    2012-02-01

    Chronic benzodiazepine (BDZ) abuse is currently treated with detoxification using a low-dose flumazenil infusion, a relatively recently developed and promising procedure. Given the possibility reported in the literature of the occurrence of generalized seizures during therapeutic BDZ detoxification, we usually administer preventive antiepileptic drug (AED) therapy. We describe two patients with no previous history of seizures or evidence of intracerebral lesions who, during detoxification for benzodiazepine abuse, developed repetitive focal nonconvulsive seizures instead of generalized seizures, even with appropriate doses of preventive AED therapy. There are no previous reported cases of focal nonconvulsive seizures occurring during this procedure or, more generally, during abrupt BDZ discontinuation. The cases we describe suggest that during detoxification for BDZ abuse, not only generalized, but also focal nonconvulsive seizures may occur. In this context, the focal seizures probably result from a diffuse decrease in the seizure threshold (caused by a generalized excitatory rebound), which may trigger focal seizures arising from cortical regions with higher intrinsic epileptogenicity. Detoxification for benzodiazepine abuse, even if performed with adequate-dosage AED treatment, may not be as safe a procedure as previously considered, because not only convulsive, but also nonconvulsive seizures may occur and go unnoticed. It is therefore strongly advisable to perform this detoxification under close medical supervision and to maintain a low threshold for EEG monitoring in the event of sudden onset of behavioral changes. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Hot spot liver scan in focal nodular hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Piers, D.A. (Univ. Hospital, Groningen, Netherlands); Houthoff, H.J.; Krom, R.A.F.; Schuur, K.H.; Sikkens, H.; Weits, J.

    1980-12-01

    In scintigraphy of the liver with radiocolloid, space-occupying lesions generally are visualized as regions of decreased accumulation of radioactivity. Rarely focal areas of increased activity are depicted; most are related to altered vascular dynamics in the liver secondary to obstruction of the superior or inferior vena cava or the hepatic veins. There are reports of single cases of focally increased activity due to a hepatic hemangioma, hepatic venoocclusive disease, herniation of a part of the liver, and a liver hot spot found after radiocolloid injection via a malpositioned central venous catheter in one of the hepatic vein branches. In patients with focal nodular hyperplasia, liver scans with solitary defects as well as normal patterns are found. In some cases, increased uptake of colloid in the lesion has been documented. Pasquier and Dorta reported a patient with a palpable mass in the left liver lobe with increased accumulation of radioactivity on the radiocolloid liver scan. The histologic diagnosis was hamartoma, but reviewing the description and considering the confusion in the past concerning the nomenclature, this case is suggestive of focal nodular hyperplasia. We report a patient with focal nodular hyperplasia who had increased radiocolloid uptake in the lesion. The radionuclide studies are compared with angiography, sonography, and computed tomography. An explanation for the localized increased colloid accumulation based on histologic findings is suggested.

  16. Value of repeat brain MRI in children with focal epilepsy and negative findings on initial MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Tae Yeon; Kim, Ji Hye; Lee, Jee Hun; Yoo, So Young; Hwang, Sook Min; Lee, Mun Hyang [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-08-01

    To evaluate the value of repeat brain magnetic resonance imaging (MRI) in identifying potential epileptogenic lesions in children with initial MRI-negative focal epilepsy. Our Institutional Review Board approved this retrospective study and waived the requirement for informed consent. During a 15-year period, 257 children (148 boys and 109 girls) with initial MRI-negative focal epilepsy were included. After re-evaluating both initial and repeat MRIs, positive results at repeat MRI were classified into potential epileptogenic lesions (malformation of cortical development and hippocampal sclerosis) and other abnormalities. Contributing factors for improved lesion conspicuity of the initially overlooked potential epileptogenic lesions were analyzed and classified into lesion factors and imaging factors. Repeat MRI was positive in 21% (55/257) and negative in 79% cases (202/257). Of the positive results, potential epileptogenic lesions comprised 49% (27/55) and other abnormalities comprised 11% of the cases (28/257). Potential epileptogenic lesions included focal cortical dysplasia (n = 11), hippocampal sclerosis (n = 10), polymicrogyria (n = 2), heterotopic gray matter (n = 2), microlissencephaly (n = 1), and cortical tumor (n = 1). Of these, seven patients underwent surgical resection. Contributing factors for new diagnoses were classified as imaging factors alone (n = 6), lesion factors alone (n = 2), both (n = 18), and neither (n = 1). Repeat MRI revealed positive results in 21% of the children with initial MRI-negative focal epilepsy, with 50% of the positive results considered as potential epileptogenic lesions. Enhanced MRI techniques or considering the chronological changes of lesions on MRI may improve the diagnostic yield for identification of potential epileptogenic lesions on repeat MRI.

  17. Terapia Interpessoal: um modelo breve e focal Interpersonal Therapy: a brief and focal model

    Directory of Open Access Journals (Sweden)

    Marcelo Feijó de Mello

    2004-06-01

    Full Text Available A psicoterapia é uma forma particular de tratamento em psiquiatria. Seu uso é amplamente difundido e conta com várias linhas de abordagem. OBJETIVO: Neste trabalho, o autor faz considerações a respeito da terapia interpessoal (TIP, uma forma breve e focal de psicoterapia. Inicialmente usada para o tratamento da depressão, teve seu espectro de ação ampliado para outros transtornos. A TIP pode ser dividida em 3 fases: inicial, quando é feito um diagnóstico do transtorno nomeando os sintomas ao paciente e diagnosticando o foco interpessoal a ser trabalhado; fase intermediária, onde se trabalha o foco; e fase final, quando o paciente é encorajado a reconhecer e consolidar seus ganhos para usá-los no futuro. MÉTODOS: O autor faz uma revisão das evidências científicas da eficácia da TIP no tratamento da depressão. CONCLUSÕES: Os resultados mostram que a TIP é uma forma terapêutica eficaz e bem tolerada de tratamento para a depressão.Psychotherapy is a particular form of treatment in Psychiatry. Its use is widespread and has many different approaches. OBJECTIVE: In this article, the author makes some considerations about Interpersonal Therapy (IPT, a brief and focal psychotherapy. Initially created to treat depression, other researchers had successfully increase its spectrum. It could be divided in three phases. Initial, when the therapist makes the diagnosis of the disorder and also the interpersonal problematic is pointed out; the patient received a sick role. Intermediary when the focus is treated, and the final phase when the therapist encourages the patient to recognize and consolidate gains and prepare the patient to use it in the future. METHODS: It is stressed that IPT is a testable form of psychotherapy and the scientific evidences of its efficacy are showed. CONCLUSIONS: The results assure that IPT is an efficient form of psychotherapy for depression with a great acceptability from the patients.

  18. Advances in Focal Plane Wavefront Estimation for Directly Imaging Exoplanets

    Science.gov (United States)

    Eldorado Riggs, A. J.; Kasdin, N. Jeremy; Groff, Tyler Dean

    2015-01-01

    To image cold exoplanets directly in visible light, an instrument on a telescope needs to suppress starlight by about 9 orders of magnitude at small separations from the star. A coronagraph changes the point spread function to create regions of high contrast where exoplanets or disks can be seen. Aberrations on the optics degrade the contrast by several orders of magnitude, so all high-contrast imaging systems incorporate one or more deformable mirrors (DMs) to recover regions of high contrast. With a coronagraphic instrument planned for the WFIRST-AFTA space telescope, there is a pressing need for faster, more robust estimation and control schemes for the DMs. Non-common path aberrations limit conventional phase conjugation schemes to medium star-to-planet contrast ratios of about 1e-6. High-contrast imaging requires estimation and control of both phase and amplitude in the same beam path as the science camera. Field estimation is a challenge since only intensity is measured; the most common approach, including that planned for WFIRST-AFTA, is to use DMs to create diversity, via pairs of small probe shapes, thereby allowing disambiguation of the electric field. Most implementations of DM Diversity require at least five images per electric field estimate and require narrowband measurements. This paper describes our new estimation algorithms that improve the speed (by using fewer images) and bandwidth of focal plane wavefront estimation. For narrowband estimation, we are testing nonlinear, recursive algorithms such as an iterative extended Kalman filter (IEKF) to use three images each iteration and build better, more robust estimates. We are also exploring the use of broadband estimation without the need for narrowband sub-filters and measurements. Here we present simulations of these algorithms with realistic noise and small signals to show how they might perform for WFIRST-AFTA. Once validated in simulations, we will test these algorithms experimentally in

  19. Slow Activity in Focal Epilepsy During Sleep and Wakefulness

    DEFF Research Database (Denmark)

    Pellegrino, Giovanni; Tombini, Mario; Curcio, Giuseppe

    2017-01-01

    Introduction We aimed to test differences between healthy subjects and patients with respect to slow wave activity during wakefulness and sleep. Methods Fifteen patients affected by nonlesional focal epilepsy originating within temporal areas and fourteen matched controls underwent a 24-hour EEG...... recording. We studied the EEG power spectral density during wakefulness and sleep in delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz), and beta (16-20 Hz) bands. Results During sleep, patients with focal epilepsy showed higher power from delta to beta frequency bands compared with controls...... was the delta band during the first 2 sleep cycles (sleep cycle 1, P = .014; sleep cycle 2, P = .002). During wakefulness, patients showed higher delta/theta activity over the affected regions compared with controls. Conclusions Patients with focal epilepsy showed a pattern of power increases characterized...

  20. The cheating liver: imaging of focal steatosis and fatty sparing.

    Science.gov (United States)

    Dioguardi Burgio, Marco; Bruno, Onorina; Agnello, Francesco; Torrisi, Chiara; Vernuccio, Federica; Cabibbo, Giuseppe; Soresi, Maurizio; Petta, Salvatore; Calamia, Mauro; Papia, Giovanni; Gambino, Angelo; Ricceri, Viola; Midiri, Massimo; Lagalla, Roberto; Brancatelli, Giuseppe

    2016-06-01

    Focal steatosis and fatty sparing are a frequent finding in liver imaging, and can mimic solid lesions. Liver regional variations in the degree of fat accumulation can be related to vascular anomalies, metabolic disorders, use of certain drugs or coexistence of hepatic masses. CT and MRI are the modalities of choice for the noninvasive diagnosis of hepatic steatosis. Knowledge of CT and MRI appearance of focal steatosis and fatty sparing is crucial for an accurate diagnosis, and to rule-out other pathologic processes. This paper will review the CT and MRI techniques for the diagnosis of hepatic steatosis and the CT and MRI features of common and uncommon causes of focal steatosis and fatty sparing.

  1. Focalism: a source of durability bias in affective forecasting.

    Science.gov (United States)

    Wilson, T D; Wheatley, T; Meyers, J M; Gilbert, D T; Axsom, D

    2000-05-01

    The durability bias, the tendency to overpredict the duration of affective reactions to future events, may be due in part to focalism, whereby people focus too much on the event in question and not enough on the consequences of other future events. If so, asking people to think about other future activities should reduce the durability bias. In Studies 1-3, college football fans were less likely to overpredict how long the outcome of a football game would influence their happiness if they first thought about how much time they would spend on other future activities. Studies 4 and 5 ruled out alternative explanations and found evidence for a distraction interpretation, that people who think about future events moderate their forecasts because they believe that these events will reduce thinking about the focal event. The authors discuss the implications of focalism for other literatures, such as the planning fallacy.

  2. Protein kinase C involvement in focal adhesion formation

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1992-01-01

    Matrix molecules such as fibronectin can promote cell attachment, spreading and focal adhesion formation. Although some interactions of fibronectin with cell surface receptors have now been identified, the consequent activation of intracellular messenger systems by cell/matrix interactions have...... still to be elucidated. We show here that the kinase inhibitors H7 and HA1004 reduce focal adhesion and stress fiber formation in response to fibronectin in a dose-dependent manner, and that activators of protein kinase C can promote their formation under conditions where they do not normally form....... Fibroblasts spread within 1h on substrata composed of fibronectin and formed focal adhesions by 3h, as monitored by interference reflection microscopy (IRM) and by labeling for talin, vinculin and integrin beta 1 subunits. In addition, stress fibers were visible. When cells were allowed to spread for 1h...

  3. MRI of a family with focal abnormalities of gyration

    Energy Technology Data Exchange (ETDEWEB)

    Muntaner, L. [Department of Radiology, Son Dureta University Hospital, Palma de Mallorca (Spain)]|[Avda Alejandro Rossello 27, E-07002 Palma de Mallorca (Spain); Perez-Ferron, J.J. [Department of Pediatrics, Son Dureta University Hospital, Palma de Mallorca (Spain); Herrera, M. [Department of Radiology, Son Dureta University Hospital, Palma de Mallorca (Spain); Rosell, J. [Department of Genetics, Son Dureta University Hospital, Palma de Mallorca (Spain); Taboada, D. [Clinica Femenia, Palma de Mallorca (Spain); Climent, S. [Department of Pediatrics, Son Dureta University Hospital, Palma de Mallorca (Spain)

    1997-08-01

    Focal abnormalities of gyration (FAG) are developmental disorders that may occur in isolated patients or, as in the case being reported, as part of a familial disorder. Analysis of individuals in a family spanning three generations was carried out using MRI. Abnormalities, present in all members of generations II and III, included focal cortical dysplasia (three patients), focal cortical infolding (two patients) and schizencephaly (one patient); associated minor anomalies, such as white matter abnormalities, were seen in the remaining three members of generations II and III. MRI recognition of FAG in the family being reported proved useful in defining their phenotypical expression and providing proper counselling for individual family members. (orig.). With 6 figs.

  4. Mutations in KCNT1 cause a spectrum of focal epilepsies

    DEFF Research Database (Denmark)

    Møller, Rikke Steensbjerre; Heron, Sarah E.; Larsen, Line H. G.

    2015-01-01

    Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated...... with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy...... (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even...

  5. Multiple Focal Nodular Hyperplasia and Steatohepatitis: Atypical Imaging Characteristics

    Directory of Open Access Journals (Sweden)

    Robert P Myers

    2001-01-01

    Full Text Available Focal nodular hyperplasia is a rare, benign condition of the liver. A 28-year-old woman with malignant melanoma, mild liver enzyme abnormalities, steatohepatitis and newly documented hepatic lesions is described. Ultrasound, computed tomography and magnetic resonance imaging suggested only areas of focal fatty sparing but could not eliminate the concern for metastases. A 99mtechnetium-labelled sulphur colloid scan, however, revealed areas of increased uptake consistent with multiple focal nodular hyperplasia. This diagnosis was ultimately confirmed with a liver biopsy. The investigation of a patient with a malignancy and expanding hepatic lesions is challenging. This case illustrates the usefulness of the 99mtechnetium-labelled sulphur colloid scan in the evaluation of patients with hepatic lesions.

  6. Abnormalities of spatial discrimination in focal and generalized dystonia.

    Science.gov (United States)

    Molloy, F M; Carr, T D; Zeuner, K E; Dambrosia, J M; Hallett, M

    2003-10-01

    Sensory processing is impaired in focal hand dystonia (FHD), with most previous studies having evaluated only the symptomatic limb. The purpose of this study was to establish whether the sensory system is affected in other types of dystonias and whether the contralateral hand is also involved in FHD. We used a spatial acuity measure (Johnson-Van Boven-Phillips domes) to evaluate sensory spatial discrimination in both hands of patients with different forms of dystonias including primary generalized DYT1 dystonia (associated with a unique deletion in the DYT1 gene) (n = 13), FHD (n = 15), benign essential blepharospasm (n = 9), cervical dystonia (n = 10) and in age-matched controls. Clinical evaluation included the Fahn dystonia scale for the focal dystonia groups and the Marsden-Burke-Fahn scale for the generalized dystonia group. Spatial discrimination was normal in patients with DYT1 dystonia, despite all of these patients having hand dystonia. However, spatial discrimination thresholds were significantly increased in both hands in the focal dystonia groups (thresholds were similar for each group) and did not correlate significantly with either severity or duration of dystonic symptoms. Thresholds were significantly increased in the dominant hand compared with the non-dominant hand only within the FHD group. Our observations demonstrate involvement of both the dominant and non-dominant somatosensory cortices, and suggest that abnormal sensory processing is a fundamental disturbance in patients with focal dystonia. These findings of altered sensory processing in idiopathic focal but not generalized DYT1 dystonia suggest both a primary pathophysiological role for the phenomenon in focal dystonia and divergent pathophysiological processes in the two conditions.

  7. Earthquake focal mechanism forecasting in Italy for PSHA purposes

    Science.gov (United States)

    Roselli, Pamela; Marzocchi, Warner; Mariucci, Maria Teresa; Montone, Paola

    2018-01-01

    In this paper, we put forward a procedure that aims to forecast focal mechanism of future earthquakes. One of the primary uses of such forecasts is in probabilistic seismic hazard analysis (PSHA); in fact, aiming at reducing the epistemic uncertainty, most of the newer ground motion prediction equations consider, besides the seismicity rates, the forecast of the focal mechanism of the next large earthquakes as input data. The data set used to this purpose is relative to focal mechanisms taken from the latest stress map release for Italy containing 392 well-constrained solutions of events, from 1908 to 2015, with Mw ≥ 4 and depths from 0 down to 40 km. The data set considers polarity focal mechanism solutions until to 1975 (23 events), whereas for 1976-2015, it takes into account only the Centroid Moment Tensor (CMT)-like earthquake focal solutions for data homogeneity. The forecasting model is rooted in the Total Weighted Moment Tensor concept that weighs information of past focal mechanisms evenly distributed in space, according to their distance from the spatial cells and magnitude. Specifically, for each cell of a regular 0.1° × 0.1° spatial grid, the model estimates the probability to observe a normal, reverse, or strike-slip fault plane solution for the next large earthquakes, the expected moment tensor and the related maximum horizontal stress orientation. These results will be available for the new PSHA model for Italy under development. Finally, to evaluate the reliability of the forecasts, we test them with an independent data set that consists of some of the strongest earthquakes with Mw ≥ 3.9 occurred during 2016 in different Italian tectonic provinces.

  8. Focal therapy in prostate cancer: the current situation.

    Science.gov (United States)

    Jácome-Pita, Fx; Sánchez-Salas, R; Barret, E; Amaruch, N; Gonzalez-Enguita, C; Cathelineau, X

    2014-01-01

    Prostate cancer is one of the most significant pathologies in the field of urology. The adoption of screening strategies and improvements in biopsies have resulted in an increase in early-stage tumour detection. Radical global therapies provide very good oncological results in localised prostate cancer. However, excess treatment in low- and, in some cases, intermediate-risk groups affects the quality of life of these patients. In the case of localised prostate cancer, focal therapies offer a minimally invasive option with good results with respect to established treatments. Although this is currently not a standard treatment, it represents the therapeutic approach with the greatest potential. THIS LITERATURE REVIEW HAS THE FOLLOWING OBJECTIVES: to define selection criteria for patients who are candidates for focal therapy, to assess the current situation and results of the different therapeutic options, and to define procedures in cases of recurrence and for follow-ups. We concluded that focal therapy is a viable therapeutic alternative for localised prostate cancer, specifically cryosurgery and high-intensity targeted ultrasound, which have acceptable oncologic results and a lower comorbidity compared with global treatments. Studies with a high level of scientific evidence are still needed to validate these results. A search was carried out on the Medline (PubMed), EMBASE, Web of Science and Cochrane databases of all papers published before 31 July 2013. We included clinical studies and literature reviews that evaluated primary focal therapy for prostate cancer confirmed by biopsy and excluded focal rescue therapy studies. The keywords used were focal therapy and prostate cancer. Initially, we found 42 articles; 15 studies were excluded because they did not meet the minimum criteria for inclusion. A total of 1350 cases were treated throughout 27 studies.

  9. Posthumanism: beyond humanism?

    Science.gov (United States)

    Valera, Luca

    2014-01-01

    The focal point of posthumanism consists not as such in an a-critical acceptance of the technological promises - like there is for transhumanism - but in a total contamination and hybridization of human beings with other living beings and machines (these are the two main forms of contamination). The change of perspective untaken by posthumanism would be, thus, a paradigmatic shift in anthropology. As with ecologism, posthumanism, in order to obtain total contamination and man's openness to otherness, proposes the elimination and the fluidification of boundaries, thus even denying man's identity, and, with it, the very possibility of openness. However, by denying the identity, one denies the condition of possibility of thought, just as it has been manifested in history until now: hence we understand how, primarily, posthumanism is not configured as an adequate philosophical reflection, but as a narrative that takes origin from certain requirements, which are eminently human, and that discloses its deeply anthropogenic roots.

  10. Inseguridad alimentaria en latinos de California: observaciones de grupos focales Food insecurity among Latinos in California: A focal groups study

    Directory of Open Access Journals (Sweden)

    Hugo Melgar-Quiñonez

    2003-06-01

    Full Text Available OBJETIVO: Estudiar la percepción y la experiencia sobre inseguridad alimentaria entre latinoamericanos de California, así como su interpretación de los insumos incluidos en la Escala de Seguridad Alimentaria. MATERIAL Y MÉTODOS: Entre noviembre y diciembre de 2000, en los condados californianos de Solano y San Joaquín, se efectuaron cuatro grupos focales, con 30 adultos de origen latinoamericano residentes allí. Los comentarios de los participantes fueron codificados por dos investigadores para determinar los temas principales, y fueron confrontados para verificar su convergencia. RESULTADOS: Las preguntas fueron bien comprendidas, no percibiéndose como ofensivas. El marco conceptual se confirmó como "proceso manejado" con diferentes niveles de severidad. Las causas de inseguridad alimentaria identificadas fueron: desempleo, alto costo de algunos alimentos y falta de información nutricional. La necesidad de educación nutricional fue una constante. CONCLUSIONES: Para interpretar datos nacionales de inseguridad alimentaria en latinoamericanos es esencial considerar su percepción particular de ese fenómeno.OBJECTIVE: To assess the perception and experience with food insecurity among Latinos living in California, as well as their interpretation of the items included in the Food Security Scale. MATERIAL AND METHODS: A series of four focus groups were carried out among 30 adults of Latin-American descent living in California. The participant's responses were coded by two researchers to identify the main issues, and to compare them for assessing their convergence. RESULTS: The items were well understood and were not perceived as offensive. The conceptual framework was confirmed as a "managed process" with different severity levels. The causes of food insecurity were: unemployment, high cost of some food items, and lack of nutritional information. The demand for nutritional education was constant. CONCLUSION: Interpreting data on food

  11. The Minimal Active Human SVA Retrotransposon Requires Only the 5′-Hexamer and Alu-Like Domains

    Science.gov (United States)

    Hancks, Dustin C.; Mandal, Prabhat K.; Cheung, Ling E.

    2012-01-01

    RNA-based duplication mediated by reverse transcriptase (RT), a process termed retrotransposition, is ongoing in humans and is a source of significant inter- and perhaps intraindividual genomic variation. The long interspersed element 1 (LINE-1 or L1) ORF2 protein is the genomic source for RT activity required for mobilization of its own RNA in cis and other RNAs, such as SINE/variable-number tandem-repeat (VNTR)/Alu (SVA) elements, in trans. SVA elements are ∼2-kb hominid-specific noncoding RNAs that have resulted in single-gene disease in humans through insertional mutagenesis or aberrant mRNA splicing. Here, using an SVA retrotransposition cell culture assay in U2OS cells, we investigated SVA domains important in L1-mediated SVA retrotransposition. Partial- and whole-domain deletions revealed that removal of either the Alu-like or SINE-R domain in the context of a full-length SVA has little to no effect, whereas removal of the CT hexamer or the VNTR domain can result in a 75% decrease in activity. Additional experiments demonstrate that the Alu-like fragment alone can retrotranspose at low levels while the addition of the CT hexamer can enhance activity as much as 2-fold compared to that of the full-length SVA. These results suggest that no SVA domain is essential for retrotransposition in U2OS cells and that the 5′ end of SVA (hexamer and Alu-like domain) is sufficient for retrotransposition. PMID:23007156

  12. Focal myositis of the thigh: unusual MR pattern

    Energy Technology Data Exchange (ETDEWEB)

    Llauger, Jaume; Palmer, Jaume; San Roman, Luis [Department of Radiology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Bague, Silvia; Matias-Guiu, Xavier [Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Doncel, Antonio [Department of Orthopedic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain)

    2002-05-01

    Focal myositis is a commonly referenced, infrequently reported and poorly documented benign inflammatory pseudotumor which may be misdiagnosed clinically as a malignant tumor. We report the clinicopathologic features and magnetic resonance imaging findings in a case of focal myositis in the thigh of a 55-year-old woman. A different radiologic presentation of this disorder is described. The gross appearance of the lesion, previously undescribed, appears to be rather specific for such a pseudoneoplastic disorder, and correlates very well with the magnetic resonance imaging features. (orig.)

  13. Magnetic-resonance-guided biopsy of focal liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Ethan A. [University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Grove, Jason J. [University of Michigan Health System, Division of Interventional Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Der Spek, Abraham F.L.V. [University of Michigan Health System, Department of Anesthesiology, C.S. Mott Children' s Hospital, Ann Arbor, MI (United States); Jarboe, Marcus D. [University of Michigan Health System, Division of Interventional Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); University of Michigan Health System, Section of Pediatric Surgery, C.S. Mott Children' s Hospital, Department of Surgery, Ann Arbor, MI (United States)

    2017-05-15

    Image-guided biopsy techniques are widely used in clinical practice. Commonly used methods employ either ultrasound (US) or computed tomography (CT) for image guidance. In certain patients, US or CT guidance may be suboptimal, or even impossible, because of artifacts, suboptimal lesion visualization, or both. We recently began performing magnetic resonance (MR)-guided biopsy of focal liver lesions in select pediatric patients with lesions that are not well visualized by US or CT. This report describes our experience performing MR-guided biopsy of focal liver lesions, with case examples to illustrate innovative techniques and novel aspects of these procedures. (orig.)

  14. [Focal dystonia in musicians: Phenomenology and musical triggering factors].

    Science.gov (United States)

    Aránguiz, R; Chana-Cuevas, P; Alburquerque, D; Curinao, X

    2015-06-01

    Dystonias are defined as a joint sustained and involuntary contraction of agonist and antagonist muscles, which can cause torsion, repetitive abnormal involuntary movements, and/or abnormal postures. One special group of dystonias are those known as occupational, which include dystonia disorders triggered by a repetitive motor activity associated with a specific professional activity or task. Musicians are a population particularly vulnerable to these types of dystonia, which are presented as a loss of coordination and voluntary motor control movements highly trained in musical interpretation. Our aim is to describe a clinical series of focal dystonias in musicians evaluated and treated in our centre. Data is presented on a clinical series of 12 musicians with occupational dystonia. Their history and phenomenology are described, as well as well as their outcome after therapy. Demographic details: Mean age 34.8 ± 11.8 years, 10 males (83.3%) and 2 females (16.7%). History of trauma in dystonic segment, 6 patients (50%); family history of neurological diseases in first-degree relatives, 6 patients (50%); occupational history according to music category, 8 patients (66.6%) were classical musicians and 4 patients (33.3%) were popular musicians. The dystonia syndrome was characterised by having a mean age of onset of 28.2 ± 11.3 years (range 18-57 years). The segment affected was the hand (91.7%) in 11 patients. Of all the musicians seen in the clinic, 9 of them (75%) received therapy. The majority of patients appeared to have triggering factors specific to musical execution and linked to the requirement of fine motor control. It should be mentioned that 50% of the musicians treated maintained their professional activity or position in the orchestra to which they belonged. The majority of our phenomenological findings are consistent with those reported in the current literature. However, it is worth mentioning the presence of triggering factors attributed to the

  15. Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause.

    Science.gov (United States)

    Van Oudenhove, Jennifer J; Grandy, Rodrigo A; Ghule, Prachi N; Del Rio, Roxana; Lian, Jane B; Stein, Janet L; Zaidi, Sayyed K; Stein, Gary S

    2016-07-01

    Human embryonic stem cells (hESCs) have an abbreviated G1 phase of the cell cycle that allows rapid proliferation and maintenance of pluripotency. Lengthening of G1 corresponds to loss of pluripotency during differentiation. However, precise mechanisms that link alterations in the cell cycle and early differentiation remain to be defined. We investigated initial stages of mesendodermal lineage commitment in hESCs, and observed a cell cycle pause. Transcriptome profiling identified several genes with known roles in regulation of the G2/M transition that were differentially expressed early during lineage commitment. WEE1 kinase, which blocks entry into mitosis by phosphorylating CDK1 at Y15, was the most highly expressed of these genes. Inhibition of CDK1 phosphorylation by a specific inhibitor of WEE1 restored cell cycle progression by preventing the G2 pause. Directed differentiation of hESCs revealed that cells paused during commitment to the endo- and mesodermal, but not ectodermal, lineages. Functionally, WEE1 inhibition during meso- and endodermal differentiation selectively decreased expression of definitive endodermal markers SOX17 and FOXA2. Our findings identify a novel G2 cell cycle pause that is required for endodermal differentiation and provide important new mechanistic insights into early events of lineage commitment. Stem Cells 2016;34:1765-1775. © 2016 AlphaMed Press.

  16. Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor.

    Science.gov (United States)

    Modiano, Nir; Lu, Yanping E; Cresswell, Peter

    2005-06-14

    Human guanylate-binding protein-1 (hGBP-1) is a large GTPase, similar in structure to the dynamins. Like many smaller GTPases of the Ras/Rab family, it is farnesylated, suggesting it may dock into membranes and perhaps play a role in intracellular trafficking. To date, however, hGBP-1 has never been associated with a specific intracellular compartment. Here we present evidence that hGBP-1 can associate with the Golgi apparatus. Redistribution from the cytosol to the Golgi was observed by immunofluorescence and subcellular fractionation after aluminum fluoride treatment, suggesting that it occurs when hGBP-1 is in its GTP-bound state. Relocalization was blocked by a farnesyl transferase inhibitor. The C589S mutant of hGBP-1, which cannot be farnesylated, and the previously uncharacterized R48P mutant, which cannot bind GTP, both failed to localize to the Golgi. These two mutants had a dominant-negative effect, preventing endogenous wild-type hGBP-1 from efficiently redistributing after aluminum fluoride treatment. Furthermore, hGBP-1 requires another IFN-gamma-induced factor to be targeted to the Golgi, because constitutively expressed hGBP-1 remained cytosolic in cells treated with aluminum fluoride unless the cells were preincubated with IFN-gamma. Finally, two nonhydrolyzing mutants of hGBP-1, corresponding to active mutants of Ras family proteins, failed to constitutively associate with the Golgi; we propose three possible explanations for this surprising result.

  17. Three-dimensional photoacoustic tomography through coherent-weighted focal-line-based image reconstruction

    Science.gov (United States)

    Wang, Depeng; Wang, Yuehang; Zhou, Yang; Lovell, Jonathan F.; Xia, Jun

    2017-03-01

    Here, we introduce a new image reconstruction algorithm that combines coherent weighting with focal-line-based three-dimensional image reconstruction. The new algorithm addresses the major limitation of a linear ultrasound transducer array, i.e., the poor elevation resolution, and does not require any modification to the imaging system or the scanning geometry. We first numerically validated our approach through simulation and then experimentally tested it in phantom and in vivo. Both simulation and experimental results proved that the method can significantly improve the elevation resolution (up to 3.4 times in our experiment) and enhance object contrast.

  18. Radiation-induced focal cortical necrosis of the femur presenting as a lytic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Schils, Jean [Cleveland Clinic, Musculoskeletal Radiology, Cleveland, OH (United States); Joyce, Michael [Cleveland Clinic, Orthopedic Oncology, Cleveland, OH (United States); Shah, Chirag [Cleveland Clinic, Radiation Oncology, Cleveland, OH (United States); Zhang, Yaxia [Cleveland Clinic, Pathology, Cleveland, OH (United States)

    2017-11-15

    Management of soft tissue sarcomas is often complicated, requiring radiation before and in some cases after limb-sparing surgery. Radiation necrosis is a severe complication after radiation treatment and is typically dose related and involves medullary bone. We report on two cases of hitherto unreported focal circumscribed intra-cortical lytic lesions within the radiation portal, which appeared 19 months and 31 months, respectively, after the conclusion of radiation treatment. Both patients had a history of soft tissue sarcoma treated with radiation (66 Gy) and surgical resection. Biopsy of these lesions showed necrotic bone attributed to radiation. (orig.)

  19. Review of Concepts and Applications for Multispectral/Hyperspectral Focal Plane Array (FPA) Technology

    Science.gov (United States)

    McAdoo, James A.

    2001-01-01

    Multispectral, and ultimately hyperspectral, focal plane arrays (FPAs) represent the logical extension of two-color FPA technology, which has already shown its utility in military applications. Incorporating the spectral discrimination function directly in the FPA would offer the potential for orders-of-magnitude increase in remote sensor system performance. It would allow reduction or even elimination of optical components currently required to provide spectral discrimination in atmospheric remote sensors. The result would be smaller, simpler instruments with higher performance than exist today.

  20. Focal symmetrical encephalomalacia in sheep Encefalomalacia focal simétrica em ovino

    Directory of Open Access Journals (Sweden)

    Luciano A. Pimentel

    2010-05-01

    Full Text Available Focal symmetrical encephalomalacia (FSE is the most prominent lesion seen in the chronic form of enterotoxemia by Clostridium perfringens type D. This paper reports FSE in sheep in Brazil. Six deaths occurred within a seven days period in a flock of 70, four to 30-month-old Santa Inês sheep in the state of Paraíba in the Brazilian semiarid. The flock was grazing a paddock of irrigated sprouting Cynodon dactylon (Tifton grass, and supplemented, ad libitum, with a concentrate of soybean, corn and wheat. Nervous signs included blindness and recumbence. A 19 month-old sheep was examined clinically and necropsied after a clinical course of three days. Gross lesions were herniation of the cerebellar vermis and multifocal, bilateral, symmetric brownish areas in the internal capsule, thalamus and cerebellar peduncles. Histologic lesions were multifocal, bilateral malacia with some neutrophils, swelling of blood vessels endothelium, perivascular edema, and hemorrhages. The flock was vaccinated, before the outbreak, with only one dose of Clostridium perfringens type D vaccine. Two factors are suggested to be important for the occurrence of the disease: insufficient immunity due to the incorrect vaccination; and high nutritional levels by the supplementation with highly fermentable carbohydrates.Encefalomalacia focal simétrica (EFS é a lesão mais proeminente vista nas formas subaguda ou crônica da enterotoxemia por Clostridium perfringens tipo D. Este trabalho relata EFS em ovinos no semiárido do estado da Paraíba. Seis ovinos morreram, em um período de sete dias, dentro de um rebanho de 70 animais, da raça Santa Inês, entre 4-30 meses de idade, que pastavam em piquete de Cynodon dactylon (capim Tifton, que estava rebrotando. Os ovinos eram suplementados com um concentrado de soja, trigo e milho. Os sinais nervosos incluíam cegueira e decúbito lateral. Um ovino de 19 meses de idade foi examinado clinicamente e necropsiado, depois de um curso

  1. Specialized podosome- or invadopodia-like structures (PILS) for focal trabecular meshwork extracellular matrix turnover.

    Science.gov (United States)

    Aga, Mini; Bradley, John M; Keller, Kate E; Kelley, Mary J; Acott, Ted S

    2008-12-01

    There are distinctive areas of colocalization of matrix metalloproteinase (MMP)-2 and -14 on trabecular meshwork (TM) cells that resemble podosomes or invadopodia. Studies were conducted to determine whether TM cells exhibit podosome- or invadopodia-like structures (PILS) and whether they produce focal extracellular matrix (ECM) turnover. Porcine and human TM cells and perfused anterior segment organ cultures were studied. Localization of PILS components on TM cells and in sections from anterior segments was determined by immunohistochemistry and confocal microscopy. Cells were grown on type I collagen labeled with fluorescein isothiocyanate (FITC) for degradation analysis. Confocal time lapse images were taken of labeled TM cells on FITC-collagen. Immunostaining for MMP-2, MMP-14, and the typical PILS components cortactin, caldesmon, alpha-actinin, N-WASP, Arp-3, and cdc42 colocalized on these distinctive structures. Integrin-alphaV and -beta1, fibronectin, and versican colocalized with PILS components. TM cells on FITC-conjugated collagen developed focal regions of degradation. Time-lapse imaging showed dramatic and controlled movement of TM cell processes during this ECM degradation and fragment internalization. MMP-2, MMP-14, and cortactin colocalized at regions that appear to be PILS on cells within the outflow pathway in sections of human anterior segments. TM cells exhibit areas where PILS components colocalize with MMP-2 and -14. Similar structures are found in sections, suggesting that PILS occur in situ in the outflow pathway. The collagen degradation suggests that PILS may serve as focal sites for targeted ECM turnover, an event linked to modifications of aqueous outflow resistance and intraocular pressure homeostasis.

  2. Laser Beam Caustic Measurement with Focal Spot Analyser

    DEFF Research Database (Denmark)

    Olsen, Flemming Ove; Gong, Hui; Bagger, Claus

    2005-01-01

    In industrial applications of high power CO2-lasers the caustic characteristics of the laser beam have great effects on the performance of the lasers. A welldefined high intense focused spot is essential for reliable production results. This paper presents a focal spot analyser that is developed...... for measuring the beam profiles of focused high power CO2-lasers....

  3. Is diffusion weighted imaging adding value in diagnosis of focal ...

    African Journals Online (AJOL)

    The examination was done on 1.5T superconducting magnet MRI machines; Philips Gyroscan Intera version 12.1.1.2 (Best, The Netherlands) and Siemens Magnetom Avanto (Erlangen, Germany) machine. Results: All studied patients had a focal hepatic lesion either on top of cirrhotic liver or non cirrhotic liver. DWI was ...

  4. Differential diagnosis of focal pancreatitis and pancreatic cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

    1999-01-01

    The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

  5. The challenge of diagnosing focal hand dystonia in musicians

    Science.gov (United States)

    Rosset-Llobet, J.; Candia, V.; Molas, S. Fàbregas i; Dolors Rosinés i Cubells, D.; Pascual-Leone, A.

    2012-01-01

    Background and purpose To most clinicians, medical problems in musicians, particularly those concerning focal hand dystonia, constitute an unfamiliar domain difficult to manage. The latter can importantly influence diagnostics and the course of treatment. The purpose of this study was to enlighten the issue and to identify possible problems in diagnosing musicians’ cramp within the Spanish medical community. Methods We used a brief questions’ catalog and clinical histories of 665 musicians seen at our clinic for performing artists. We analyzed patients’ diagnosis records in 87 cases of focal hand dystonia (13.1%). In so doing, we surveyed previous diagnoses and diverse treatments prescriptions prior to referral to our clinic. Results Referrals came primarily from orthopaedists and neurologists. The 52.9% arrived at our clinic without a diagnosis or a suspicion of suffering from focal dystonia. The most frequently attempted diagnoses other than musicians’ dystonia included nerve compression, tendonitis and trigger fingers. Commonly prescribed treatments included rest, various surgical procedures, physiotherapy and oral anti-inflammatory medication. Conclusions This data depicts the diagnostic challenges of medical professionals may encounter when confronted with musician’s focal dystonia. PMID:19473363

  6. Regional cerebral blood flow in focal cortical epilepsy

    DEFF Research Database (Denmark)

    Hougaard, Kristina Dupont; Oikawa, T; Sveinsdottir, E

    1976-01-01

    Regional cerebral blood flow (rCBF) was studied in ten patients with focal cortical epilepsy. The blood flow was measured by the intra-arterial injection of xenon 133 (133Xe), and the isotope clearance was recorded by a multidetector scintillation camera with 254 detectors. Three patients were st...

  7. Management of oral focal infection in patients with asthmatic symptoms

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2006-09-01

    Full Text Available Asthma is commonly related to allergic diseases, nevertheless only 40% of asthma patients are related to allergy or atopy. There are some unknown etiologies of asthma that are still in researches. One of the possible causes of asthma is the multiple chemical sensitivity syndrome (MCS which related to the “neurogenic switching hypothesis”. Since rhinitis, sinusitis and asthma are closely related, treatments which are successfully reduce or eliminate the rhinitis and sinusitis symptoms should also be advantageous to asthma management. There were a lot of sinusitis treatments which reduced asthma symptoms such as nasal corticosteroid, diathermy and surgery. It was also been reported that oral focal infection might cause sinusitis. However, the involvement of oral focal infection in the etiopathogenesis of asthma was seldom discussed. The objective of this study is to propose a mechanism of the relationship between oral focal infection and asthma which is explained by the “neurogenic switching hypothesis”. Two asthmatic patients who also had periodontal disease, pulpal and periapical infection were treated with conventional and/or surgical dental treatments. After the dental and periodontal treatments were completed, the usual triggers of severe asthma attacks such as cold and house dust did not elicit the asthma symptoms. It concluded that regarding to the disappearing of asthma symptoms, the elimination of oral focal infection had a beneficial effect in reducing asthma symptoms.

  8. Quantum-Well Infrared Photodetector (QWIP) Focal Plane Assembly

    Science.gov (United States)

    Jhabvala, Murzy; Jhabvala, Christine A.; Ewin, Audrey J.; Hess, Larry A.; Hartmann, Thomas M.; La, Anh T.

    2012-01-01

    A paper describes the Thermal Infrared Sensor (TIRS), a QWIP-based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a far-infrared imager operating in the pushbroom mode with two IR channels: 10.8 and 12 microns. The focal plane will contain three 640x512 QWIP arrays mounted on a silicon substrate. The silicon substrate is a custom-fabricated carrier board with a single layer of aluminum interconnects. The general fabrication process starts with a 4-in. (approx.10-cm) diameter silicon wafer. The wafer is oxidized, a single substrate contact is etched, and aluminum is deposited, patterned, and alloyed. This technology development is aimed at incorporating three large-format infrared detecting arrays based on GaAs QWIP technology onto a common focal plane with precision alignment of all three arrays. This focal plane must survive the rigors of flight qualification and operate at a temperature of 43 K (-230 C) for five years while orbiting the Earth. The challenges presented include ensuring thermal compatibility among all the components, designing and building a compact, somewhat modular system and ensuring alignment to very tight levels. The multi-array focal plane integrated onto a single silicon substrate is a new application of both QWIP array development and silicon wafer scale integration. The Invar-based assembly has been tested to ensure thermal reliability.

  9. The HIFI Focal Plane Beam Characterization and Alignment Status

    NARCIS (Netherlands)

    Jellema, Willem; Jochemsen, M.; Peacocke, T.; Meinsma, L.; Lowes, P.; Withington, S.; Wild, Wolfgang; Wild, W

    In this paper we present the results of the characterization program of the beams in the focal plane of the HIFI flight model. We discuss the beam properties, quality of alignment, instrument footprint, performance impact and compliance and compare the results to predictions based on lower-level

  10. White matter integrity and cerebral network topology in focal epilepsy

    NARCIS (Netherlands)

    Otte, W.M.

    2012-01-01

    Worldwide more than fifty million people suffer from recurrent spontaneous seizures. Seizures are considered to be harmful to the brain and may have adverse long-term behavioral and cognitive consequences in particular in people with focal epilepsies that do not respond to pharmacotherapy.

  11. The Localizing Value Of Focal Delta Slowing In Temporal Lobe ...

    African Journals Online (AJOL)

    Background Clinical and structural correlates of lateralized interictal delta activity in patients with temporal lobe epilepsy (TLE) have been well documented in the literature. Nevertheless, its occurrence has not been considered a significant clinical feature. Objective To evaluate the significance of focal delta- range slowing ...

  12. Unilateral proximal focal femoral deficiency, fibular aplasia, tibial ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-04-30

    Apr 30, 2014 ... Unilateral proximal focal femoral deficiency, fibular aplasia, tibial campomelia and oligosyndactyly in an Egyptian child – Probable. FFU syndrome. Rabah M. ... Our patient is an Egyptian male child, fifteen months old, the third in order of .... 4th and 5th metatarsal bones are absent), absent middle phalanx.

  13. Infrared lens thermal effect: equivalent focal shift and calculating model

    Science.gov (United States)

    Zhang, Cheng-shuo; Shi, Zelin; Feng, Bin; Xu, Bao-shu

    2014-11-01

    It's well-know that the focal shift of infrared lens is the major factor in degeneration of imaging quality when temperature change. In order to figure out the connection between temperature change and focal shift, partial differential equations of thermal effect on light path are obtained by raytrace method, to begin with. The approximately solution of the PDEs show that focal shift is proportional to temperature change. And a formula to compute the proportional factor is given. In order to understand infrared lens thermal effect deeply, we use defocus by image plane shift at constant temperature to equivalently represent thermal effect on infrared lens. So equivalent focal shift (EFS) is defined and its calculating model is proposed at last. In order to verify EFS and its calculating model, Physical experimental platform including a motorized linear stage with built-in controller, blackbody, target, collimator, IR detector, computer and other devices is developed. The experimental results indicate that EFS make the image plane shift at constant temperature have the same influence on infrared lens as thermal effect and its calculating model is correct.

  14. Unilateral proximal focal femoral deficiency, fibular aplasia, tibial ...

    African Journals Online (AJOL)

    ... dominant mutation with possible gonadal mosaicism and with variable expression in the family, as limb anomaly in one child and cyanotic congenital heart disease in another child. Keywords: Short femur; Limb anomaly; FFU syndrome; Proximal focal femoral deficiency; Fibular aplasia; Tibial campomelia; Oligosyndactyly ...

  15. Focal and optional ergative marking in Warrwa (Kimberley, Western Australia)

    DEFF Research Database (Denmark)

    McGregor, William

    2006-01-01

    accords prominence to an Agent (i.e. transitive subject), singling it out asboth unexpected and highly agentive; accordingly it can be considered to be a focal ergative marker.By contrast, -na is an ordinary ergative marker, with no pragmatic components to its meaning; the situation for -ma is uncertain...

  16. Focal adhesion signaling and therapy resistance in cancer.

    Science.gov (United States)

    Eke, Iris; Cordes, Nils

    2015-04-01

    Interlocking gene mutations, epigenetic alterations and microenvironmental features perpetuate tumor development, growth, infiltration and spread. Consequently, intrinsic and acquired therapy resistance arises and presents one of the major goals to solve in oncologic research today. Among the myriad of microenvironmental factors impacting on cancer cell resistance, cell adhesion to the extracellular matrix (ECM) has recently been identified as key determinant. Despite the differentiation between cell adhesion-mediated drug resistance (CAMDR) and cell adhesion-mediated radioresistance (CAMRR), the underlying mechanisms share great overlap in integrin and focal adhesion hub signaling and differ further downstream in the complexity of signaling networks between tumor entities. Intriguingly, cell adhesion to ECM is per se also essential for cancer cells similar to their normal counterparts. However, based on the overexpression of focal adhesion hub signaling receptors and proteins and a distinct addiction to particular integrin receptors, targeting of focal adhesion proteins has been shown to potently sensitize cancer cells to different treatment regimes including radiotherapy, chemotherapy and novel molecular therapeutics. In this review, we will give insight into the role of integrins in carcinogenesis, tumor progression and metastasis. Additionally, literature and data about the function of focal adhesion molecules including integrins, integrin-associated proteins and growth factor receptors in tumor cell resistance to radio- and chemotherapy will be elucidated and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. ORAL FOCAL MUCINOSIS: A RARE CASE REPORT OF TWO CASES

    African Journals Online (AJOL)

    User

    histological analysis and the treatment involves complete surgical excision. Its recurrence ... KEYWORDS: Oral focal mucinosis, Soft tissue lesions, Gingival lesions ... It has an unknown etiology, possibly from overproduction of hyaluronic acid by fibroblasts (2).Clinically, the lesion appears as asymptomatic round elevations,.

  18. Focal Intracranial Suppuration: Clinical Features and Outcome of 21 ...

    African Journals Online (AJOL)

    Alasia Datonye

    Focal intracranial suppurations are localised infections of the intracranial ... however, it is not possible to identify a primary source of infection. Even though there has been a gradual decline in their incidence worldwide, FIS continue to pose considerable .... subdural empyema, cavernous sinus thrombosis and thrombosis of ...

  19. Management of HIV-associated focal brain lesions in developing ...

    African Journals Online (AJOL)

    Background. HIV-associated focal brain lesions (FBLs) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries toxoplasma encephalitis (TE) is the most frequent cause followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes have been proposed ...

  20. Dense Focal Plane Arrays for Pushbroom Satellite Radiometers

    DEFF Research Database (Denmark)

    Iupikov, O. A.; Ivashina, M. V.; Pontoppidan, K.

    2014-01-01

    Performance of a dense focal plane array feeding an offset toroidal reflector antenna system is studied and discussed in the context of a potential application in multi-beam radiometers for ocean surveillance. We present a preliminary design of the array feed for the 5-m diameter antenna at X-ban...

  1. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Al-Qaisieh, Bashar [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Mason, Josh, E-mail: joshua.mason@nhs.net [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Bownes, Peter; Henry, Ann [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Dickinson, Louise [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Radiology, Northwick Park Hospital, London North West NHS Trust, London (United Kingdom); Ahmed, Hashim U. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); University College London Hospital, London (United Kingdom); Emberton, Mark [University College London Hospital, London (United Kingdom); Langley, Stephen [St Luke' s Cancer Centre, Guildford (United Kingdom)

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  2. Insulin-increased L-arginine transport requires A(2A adenosine receptors activation in human umbilical vein endothelium.

    Directory of Open Access Journals (Sweden)

    Enrique Guzmán-Gutiérrez

    Full Text Available Adenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1. This process involves the activation of A(2A adenosine receptors (A(2AAR in human umbilical vein endothelial cells (HUVECs. Insulin increases hCAT-1 activity and expression in HUVECs, and A(2AAR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A(2AAR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37°C in the absence or presence of nitrobenzylthioinosine (NBTI, 10 µmol/L, adenosine transport inhibitor and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR, and SLC7A1 (for hCAT-1 reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent K(m for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1(-1606 or pGL3-hCAT-1(-650 constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1(-1606, and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A(2AAR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes.

  3. Interferometric focal length measurement of positive and negative lenses using a lateral-shearing cyclic path optical configuration setup and polarization phase-shifting interferometry.

    Science.gov (United States)

    Kumar, Y Pavan; Negi, Sarvendra Singh; Kamath, M Pandurang; Chatterjee, Sanjib; Sharma, S D; Joshi, A S

    2017-10-20

    We present a simple interferometric focal length measurement technique for measuring the focal length of positive and negative lenses using a lateral-shearing cyclic path optical configuration (CPOC) setup and polarization phase-shifting interferometry (PPSI). The technique requires an auxiliary lens, whose focal length need not be known accurately, for generating a focused point source at its focal plane. The focal point of the test lens is adjusted to be in the vicinity of the focus of the auxiliary lens. The radii of the resulting spherical wave fronts emerging from the test lens, due to the defocus, for two different longitudinal shifted positions of the test lens are measured using the lateral-shearing CPOC setup and PPSI. Focal length of the test lens is determined from the known longitudinal shift and from the measured radii of the spherical wave fronts. Results obtained for 200.0 mm convex and 100.0 mm concave test lenses are presented.

  4. Model development and behavioral assessment of focal cerebral ischemia in rats.

    Science.gov (United States)

    Petullo, D; Masonic, K; Lincoln, C; Wibberley, L; Teliska, M; Yao, D L

    1999-01-01

    Stroke in humans is usually focal and occurs in the Middle Cerebral Artery (MCA) distribution. There are several rat models that mimic strokes clinically seen in human. Severity of ischemia can be determined by occlusion time, arteries occluded i.e. MCA alone or combined with one or both Common Carotid Arteries (CCA), and/or location of the occlusion. In this study three focal cerebral infarctions (stroke) were induced for 90 and 120 minutes due to the occlusion of: the MCA alone (MCAo); MCA plus unilateral CCA (MCAo+1CCAo); and MCA plus bilateral CCA (MCAo+2CCAo). Histological parameters included infarct lesion size and hemispheric swelling. Since functional recovery of clinical deficits in stroke often correlates with the efficacy of anti-ischemic therapy, we focused on the behavioral recovery. We combined many sources to obtain comprehensive guidelines for clinical behavior evaluation. Tests included limb flexion, torso twisting, circling, lateral push resistance, beam balancing and walking, hindlimb placing, and inverted angle-board gripping. Occlusion lasting 90 minutes was found to have consistent and repeatable deficits. Results from our study demonstrate 120 minutes of occlusion produced a 60% morality rate and was therefore dropped. Body weight changes between groups showed that increased occlusion time produced more weight loss. Behavior changes indicated that MCAo+2CCAo for 90 minutes demonstrated assessable and consistent clinical deficits for the screening of potential therapeutics.

  5. Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites.

    Science.gov (United States)

    Xiong, S; Chirala, S S; Wakil, S J

    2000-04-11

    To understand cholesterol-mediated regulation of human fatty acid synthase promoter I, we tested various 5'-deletion constructs of promoter I-luciferase reporter gene constructs in HepG2 cells. The reporter gene constructs that contained only the Sp-1-binding site (nucleotides -82 to -74) and the two tandem sterol regulatory elements (SREs; nucleotides -63 to -46) did not respond to cholesterol. Only the reporter gene constructs containing a nuclear factor-Y (NF-Y) sequence, the CCAAT sequence (nucleotides -90 to -86), an Sp-1 sequence, and the two tandem SREs responded to cholesterol. The NF-Y-binding site, therefore, is essential for cholesterol response. Mutating the SREs or the NF-Y site and inserting 4 bp between the Sp-1- and NF-Y-binding sites both resulted in a minimal cholesterol response of the reporter genes. Electrophoretic mobility-shift assays using anti-SRE-binding protein (SREBP) and anti-NF-Ya antibodies confirmed that these SREs and the NF-Y site bind the respective factors. We also identified a second Sp-1 site located between nucleotides -40 and -30 that can substitute for the mutated Sp-1 site located between nucleotides -82 and -74. The reporter gene expression of the wild-type promoter and the Sp-1 site (nucleotides -82 to -74) mutant promoter was similar when SREBP1a [the N-terminal domain of SREBP (amino acids 1-520)] was constitutively overexpressed, suggesting that Sp-1 recruits SREBP to the SREs. Under the same conditions, an NF-Y site mutation resulted in significant loss of reporter gene expression, suggesting that NF-Y is required to activate the cholesterol response.

  6. (abstract) 9 (micro)m Cutoff 640x480 Quantum Well Infrared Photodetector (QWIP) Focal Plane Array Camera

    Science.gov (United States)

    Gunapala, S. D.; Sundaram, M.; Liu, J. K.; Bandara, S. V.; Shott, C. A.; Hoelter, T.

    1997-01-01

    Long wavelength infrared (LWIR) detectors, 8 (micro)m to 12 (micro)m, are of great interest for a variety of ground-based and space-borne applications. These applications have placed stringent requirements on the performance of the infrared detectors and arrays including high detectivity, low dark current, uniformity, radiation hardness, and low power dissipation. I will discuss the development and progress of GaAs based long-wavelength quantum well infrared photodetectors (QWIPs) to meet those stringent requirements and the demonstration of a 9 (micro)m cutoff 640x480 QUIP focal plane array camera. The noise equivalent temperature difference of the focal plane array is 25 mK at 300 K background and the operating temperature is 70 K.

  7. Focal osteoporosis defects play a key role in hip fracture.

    Science.gov (United States)

    Poole, Kenneth E S; Skingle, Linda; Gee, Andrew H; Turmezei, Thomas D; Johannesdottir, Fjola; Blesic, Karen; Rose, Collette; Vindlacheruvu, Madhavi; Donell, Simon; Vaculik, Jan; Dungl, Pavel; Horak, Martin; Stepan, Jan J; Reeve, Jonathan; Treece, Graham M

    2017-01-01

    Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than a

  8. Focal segmental glomerulosclerosis is associated with a PDSS2 haplotype and, independently, with a decreased content of coenzyme Q10

    Science.gov (United States)

    Winkler, Cheryl A.; Peng, Min; An, Ping; McKenzie, Louise M.; Kirk, Gregory D.; Shi, Yuchen; Xie, Letian X.; Marbois, Beth N.; Clarke, Catherine F.; Kopp, Jeffrey B.

    2013-01-01

    Focal segmental glomerulosclerosis (FSGS) and collapsing glomerulopathy are common causes of nephrotic syndrome. Variants in >20 genes, including genes critical for mitochondrial function, have been associated with these podocyte diseases. One such gene, PDSS2, is required for synthesis of the decaprenyl tail of coenzyme Q10 (Q10) in humans. The mouse gene Pdss2 is mutated in the kd/kd mouse model of collapsing glomerulopathy. We examined the hypothesis that human PDSS2 polymorphisms are associated with podocyte diseases. We genotyped 377 patients with primary FSGS or collapsing glomerulopathy, together with 900 controls, for 9 single-nucleotide polymorphisms in the PDSS2 gene in a case-control study. Subjects included 247 African American (AA) and 130 European American (EA) patients and 641 AA and 259 EA controls. Among EAs, a pair of proxy SNPs was significantly associated with podocyte disease, and patients homozygous for one PDSS2 haplotype had a strongly increased risk for podocyte disease. By contrast, the distribution of PDSS2 genotypes and haplotypes was similar in AA patients and controls. Thus a PDSS2 haplotype, which has a frequency of 13% in the EA control population and a homozygote frequency of 1.2%, is associated with a significantly increased risk for FSGS and collapsing glomerulopathy in EAs. Lymphoblastoid cell lines from FSGS patients had significantly less Q10 than cell lines from controls; contrary to expectation, this finding was independent of PDSS2 haplotype. These results suggest that FSGS patients have Q10 deficiency and that this deficiency is manifested in patient-derived lymphoblastoid cell lines. PMID:23926186

  9. A Case Report of Adrenocorticotropic Hormone to Treat Recurrent Focal Segmental Glomerular Sclerosis Post-transplantation and Biomarker Monitoring

    Directory of Open Access Journals (Sweden)

    Anwar eSiddiq

    2015-03-01

    Full Text Available Background: Recurrent focal segmental glomerular sclerosis (rFSGS in renal transplant recipients (RTR is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies. Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb, soluble urokinase-type plasminogen activator receptor (suPAR serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab titer. Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance, and high dose steroids, the Palb and suPAR- β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel, 80 units subcutaneously twice weekly. Four-weeks later he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with less than 1 gram of proteinuria. Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.

  10. Exploring the challenges of habitation design for extended human presence beyond low-earth orbit: Are new requirements and processes needed?

    NARCIS (Netherlands)

    Robinson, D.K.R.; Sterenborg, Glenn; Häuplik, Sandra; Aguzzi, Manuela

    2008-01-01

    With the renewed interest in a sustained human presence beyond low-earth orbit, habitation in space, on planets and on moons is an area that requires re-evaluation in terms of mission and habitat design—there is a need for a paradigmatic move from a design focus on short-term LEO missions to that of

  11. Modeling gastrointestinal drug absorption requires more in vivo biopharmaceutical data: experience from in vivo dissolution and permeability studies in humans.

    Science.gov (United States)

    Lennernäs, Hans

    2007-10-01

    The majority (84%) of the 50 most-sold pharmaceutical products in the US and European markets are given orally. The dominating role of this route in drug therapy is a consequence of it being safe, efficient and easily accessible with minimal discomfort to the patient in comparison with other routes of drug administration. A successful drug discovery and development of oral pharmaceutical products require an in-depth understanding of multiple biochemical and physiological processes that determine the dissolution rate, intestinal permeability, gastrointestinal transit, first-pass extraction and systemic exposure-time profiles of drugs. It is crucial to realize that these basic biopharmaceutic and pharmacokinetic properties are crucial to focus on to allow successful drug development. Identification of the rate-limiting step(s) in order to overcome these barriers and understanding of the sources of variability are important in the selection of suitable candidate molecules in drug development. Several reports based on in vitro investigations in various cell models have suggested that carrier-mediated intestinal efflux may be a major reason for incomplete absorption and variable bioavailability of drugs, as well being a site for drug-drug and specific food-drug interactions. However, many drugs which were initially suggested to undergo significant efflux in vitro were later shown to be completely absorbed in vivo. This apparent discrepancy between in vitro and in vivo results may be due to several factors that will be discussed in this review. Novel data on solubility and dissolution in human gastrointestinal derived fluids will be reviewed. The effect of food intake on solubility and dissolution rate of a range of drugs including felodipine, danazol, griseofulvin, cyclosporine, probucol and ubiquinone in simulated and real intestinal fluids is discussed. The biopharmaceutic and physicochemical data discussed here can potentially be used as a benchmark set for

  12. Mapping the Isotropic Component of Focal Mechanisms in Hydraulic Fractures

    Science.gov (United States)

    Baig, A. M.; Urbancic, T. I.

    2009-12-01

    We present the results of a hydraulic fracture monitoring study where the events induced by the treatment are recorded with a three-dimensional sensor distribution. The fact that the microseismicity is recorded over multiple azimuths allows not only for better convergence of the location algorithm, but also acheives sufficient coverage of the focal sphere to reliably invert for the full moment tensor. Unlike in tectonic settings, many of these focal mechanisms have very strong non-double-couple components, due to the intrusion of proppants into the surrounding rock, and are thus characterized by mechanisms consistant with tensile cracks opening or closing. Mapping these mechanisms in time and space offers insight into both the processes responsible for the fracturing, but also how effectively the treatment propped open the rock and identifying which areas may have opened and subsequently closed.

  13. Is focal therapy an alternative to active surveillance?

    Science.gov (United States)

    Gravas, Stavros; de Reijke, Theo

    2010-05-01

    Because of the widespread use of prostate-specific antigen, urologists face an increasing number of patients with small-volume, low-grade prostatic carcinoma seeking the optimal therapeutic approach. Concerns about "overdiagnosis" of prostate cancer (PCa) and consequent overtreatment of clinically insignificant tumors in combination with the significant morbidity that traditional therapies carry have resulted in questioning the need for radical treatments of PCa for selected groups of patients with low-risk PCa. Active surveillance has been introduced as a conservative management option for PCa that closely monitors patients and treats them when progression is identified. Recently, because of technological advances, focal therapy has been introduced to optimize control of low-risk cancers while minimizing the adverse events of whole-gland therapy and the anxiety associated with delayed treatment. The rationales, merits, and limitations of both active surveillance and focal therapy are highlighted in this article.

  14. Focal neuromyotonia as a presenting feature of lumbosacral radiculopathy

    Directory of Open Access Journals (Sweden)

    Tushar Premraj Raut

    2013-01-01

    Full Text Available Neuromyotonia is characterized by motor, sensory, and autonomic features along with characteristic electrophysiologic findings, resulting from hyperexcitability of the peripheral nerves. We describe the case of a 36-year-old man, who presented with the disabling symptoms suggestive of focal neuromyotonia involving both the lower limbs. His neurological examination revealed continuous rippling of both the calf muscles with normal power, reflexes, and sensory examination. Electrophysiology revealed spontaneous activity in the form of doublets, triplets, and neuromyotonic discharges along with the neurogenic motor unit potentials in bilateral L5, S1 innervated muscles. Magnetic resonance imaging lumbosacral spine revealed lumbar intervertebral disc protrusion with severe foraminal and spinal canal stenosis. Patient had good response to steroids and carbamazepine. The disabling focal neuromyotonia, occurring as a result of chronic active radiculopathy, brought the patient to medical attention. Patient responded to medical management.

  15. Uncooled infrared focal plane array imaging in China

    Science.gov (United States)

    Lei, Shuyu

    2015-06-01

    This article reviews the development of uncooled infrared focal plane array (UIFPA) imaging in China in the past decade. Sensors based on optical or electrical read-out mechanism were developed but the latter dominates the market. In resistive bolometers, VOx and amorphous silicon are still the two major thermal-sensing materials. The specifications of the IRFPA made by different manufactures were collected and compared. Currently more than five Chinese companies and institutions design and fabricate uncooled infrared focal plane array. Some devices have sensitivity as high as 30 mK; the largest array for commercial products is 640×512 and the smallest pixel size is 17 μm. Emphasis is given on the pixel MEMS design, ROIC design, fabrication, and packaging of the IRFPA manufactured by GWIC, especially on design for high sensitivities, low noise, better uniformity and linearity, better stabilization for whole working temperature range, full-digital design, etc.

  16. Automatic Detection of Tuberculosis in Chest Radiographs Using a Combination of Textural, Focal, and Shape Abnormality Analysis.

    Science.gov (United States)

    Hogeweg, Laurens; Sánchez, Clara I; Maduskar, Pragnya; Philipsen, Rick; Story, Alistair; Dawson, Rodney; Theron, Grant; Dheda, Keertan; Peters-Bax, Liesbeth; van Ginneken, Bram

    2015-12-01

    Tuberculosis (TB) is a common disease with high mortality and morbidity rates worldwide. Automatic systems to detect TB on chest radiographs (CXRs) can improve the efficiency of diagnostic algorithms for pulmonary TB. The diverse manifestation of TB on CXRs from different populations requires a system that can be adapted to deal with different types of abnormalities. A computer aided detection (CAD) system was developed which combines several subscores of supervised subsystems detecting textural, shape, and focal abnormalities into one TB score. A general framework was developed to combine an arbitrary number of subscores: subscores were normalized, collected in a feature vector and then combined using a supervised classifier into one combined score. The method was evaluated on two databases, both consisting of 200 digital CXRs, from: (A) Western high-risk group screening, (B) TB suspect screening in Africa. The subscores and combined score were compared to (1) an external, non-radiological, reference and (2) a radiological reference determined by a human expert. Performance was measured using Receiver Operator Characteristic (ROC) analysis. Different subscores performed best in the two databases. The combined TB score performed better than the individual subscores, except for the external reference in database B. The performances of the independent observer were slightly higher than the combined TB score. Compared to the external reference, differences in performance between the combined TB score and the independent observer were not significant in both databases. Supervised combination to compute an overall TB score allows for a necessary adaptation of the CAD system to different settings or different operational requirements.

  17. Using Life-Cycle Human Factors Engineering to Avoid $2.4 Million in Costs: Lessons Learned from NASA's Requirements Verification Process for Space Payloads

    Science.gov (United States)

    Carr, Daniel; Ellenberger, Rich

    2008-01-01

    The Human Factors Implementation Team (HFIT) process has been used to verify human factors requirements for NASA International Space Station (ISS) payloads since 2003, resulting in $2.4 million in avoided costs. This cost benefit has been realized by greatly reducing the need to process time-consuming formal waivers (exceptions) for individual requirements violations. The HFIT team, which includes astronauts and their technical staff, acts as the single source for human factors requirements integration of payloads. HFIT has the authority to provide inputs during early design phases, thus eliminating many potential requirements violations in a cost-effective manner. In those instances where it is not economically or technically feasible to meet the precise metric of a given requirement, HFIT can work with the payload engineers to develop common sense solutions and formally document that the resulting payload design does not materially affect the astronaut s ability to operate and interact with the payload. The HFIT process is fully ISO 9000 compliant and works concurrently with NASA s formal systems engineering work flow. Due to its success with payloads, the HFIT process is being adapted and extended to ISS systems hardware. Key aspects of this process are also being considered for NASA's Space Shuttle replacement, the Crew Exploration Vehicle.

  18. Seizure ending signs in patients with dyscognitive focal seizures.

    Science.gov (United States)

    Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

    2015-09-01

    Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

  19. A Tumefactive Multiple Sclerosis Case Mimicking a Focal Cerebral Mass

    OpenAIRE

    Olcay Unver; Zehra Isik Hasiloglu; Umut Durak; Serap Uysal

    2013-01-01

    Tumefactive multiple sclerosis is a rare demyelinating disease presenting with a focal cerebral mass. Clinically and radiographically, the disease is usually difficult to differentiate from a tumor and abscess. If there is a doubt in the differential diagnosis, visual evoked potentials and CSF analysis and a trial with high dose corticosteroids should contribute to the evaluation of the patient before invasive procedures are started. Here we present a 13 year old girl with left hemiparesis, a...

  20. [Transhepatic drainage in focal liver diseases complicated by mechanical jaundice].

    Science.gov (United States)

    Zhuravlev, V A; Bakhtin, V A

    1986-11-01

    Results of using transhepatic drains in 43 patients with focal alterations of the liver complicated by a mechanical jaundice are described (55 operations). Transhepatic drains allowed widening the degree of surgical interventions in this group of patients. Risk of the operative interventions and lethality among these critical patients which were earlier thought to be inoperable became lower due to stage operations using the transhepatic drains.

  1. Nonprogressive familial leukoencephalopathy with porencephalic cyst and focal seizures.

    Science.gov (United States)

    Blumkin, Lubov; Watemberg, Nathan; Lev, Dorit; Malinger, Gustavo; Luckman, Yehudit; Ben-Zeev, Bruria; Lerman-Sagie, Tally

    2006-02-01

    Two siblings with a similar white-matter disease but different clinical symptoms are described. The first sibling suffers from nonprogressive spastic hemiparesis secondary to a congenital periventricular porencephalic cyst. Her brother has focal epilepsy. On magnetic resonance imaging, both patients show diffuse white-matter involvement predominantly of the posterior periventricular area. We suggest that this is a familial white-matter disorder with minimal symptoms and no progression in early childhood.

  2. Focal dermal hypoplasia (Goltz-Gorlin) syndrome with taurodontism.

    Science.gov (United States)

    McNamara, T; Trotman, C A; Hahessy, A M; Kavanagh, P

    1996-01-01

    This paper is a case report of a 10-year-old girl with focal dermal hypoplasia (FDH) who presented for dental care. She displayed many of the well-documented oral features associated with this syndrome. Additionally, she had taurodontism of a permanent mandibular molar. Although taurodontism affected only one tooth in this patient, the presentation of taurodontism with FDH has not been reported previously.

  3. Quantitative MRI analysis of dynamic enhancement of focal liver lesions

    Directory of Open Access Journals (Sweden)

    S. S. Bagnenko

    2012-01-01

    Full Text Available In our study 45 patients with different focal liver lesions (110 nodules were examined using high field MR-system (1,5 T. During this investigation quantitative MRI analysis of dynamic enhancement of various hepatic lesions and parenchymatous organs of abdomen were performed. It was shown that quantitative evaluation of enhanced MRI improves understanding of vascular transformation processes in pathologic hepatic focuses and in liver itself that is important for differential diagnoses of these diseases.

  4. Focal therapy in prostate cancer: the current situation

    OpenAIRE

    Jácome-Pita, FX; Sánchez-Salas, R; Barret, E.; Amaruch, N; Gonzalez-Enguita, C.; Cathelineau, X

    2014-01-01

    Prostate cancer is one of the most significant pathologies in the field of urology. The adoption of screening strategies and improvements in biopsies have resulted in an increase in early-stage tumour detection. Radical global therapies provide very good oncological results in localised prostate cancer. However, excess treatment in low- and, in some cases, intermediate-risk groups affects the quality of life of these patients. In the case of localised prostate cancer, focal therapies offer a ...

  5. Postsynthetic functionalization of glycodendrons at the focal point

    Directory of Open Access Journals (Sweden)

    Thisbe K. Lindhorst

    2014-07-01

    Full Text Available Glycodendrons are multivalent glycoconjugates bearing an orthogonal functional group at the focal point of the molecule. This allows for their postsynthetic elaboration to achieve amphiphilic glycolipid mimetics, for example, which eventually can be applied in biology, biophysics, or material science. Here, postsynthetic modification of di- and tetravalent polyether glycodendrons has been explored using etherification, thiol-ene reaction and in particular olefin cross metathesis.

  6. Hypereosinophilia with Multiple Thromboembolic Cerebral Infarcts and Focal Intracerebral Hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju; Lee, Young Jun; Lee, Seung Ro; Park, Dong Woo; Kim, Hyun Young [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2009-10-15

    We report a case of hypereosinophilia causing multiple areas of cerebral infarcts. A 52-year-old Korean man presented with dysarthria and weakness in both arms. A brain MRI revealed multiple acute infarcts in the distal border zone with focal intracerebral hemorrhage, whereas a cerebral angiogram was not remarkable. The eosinophil count was 5,500/{mu}L and was accompanied by elevated cardiac enzyme levels. The pattern of cerebral infarcts and laboratory results suggest a thromboembolic infarction associated with hypereosinophilia.

  7. [Incidence and significance of small focal liver lesions in MRI].

    Science.gov (United States)

    Kreft, B; Pauleit, D; Bachmann, R; Conrad, R; Krämer, A; Schild, H H

    2001-05-01

    Analysis of the frequency and significance of small focal liver lesions (< or = 2 cm) detected on MRI in the presence or absence of a history of malignancy. 628 MRI examinations of the liver performed during 1994-1996 were evaluated. The inclusion criterion into the study was the detection of a focal liver lesion with a size < or = 2 cm. The frequency, the size, the diagnostic proof, and the differential diagnosis of the focal liver lesions were analysed with regard to the patients history of a known malignant tumor. Overall, 179 of the 628 patients (28.5%) had focal liver lesions < or = 2 cm (n = 338). 58.9% of the lesions could be classified based upon follow-up studies by ultrasound, CT or MRI, or by biopsy. The remaining 41.1% of the lesions could not be classified due to the absence of follow-up examinations. 57.3% of all proven lesions were benign and 42.7% were malignant. A history of a malignant tumor was present in 76.7% of all patients with small liver lesions; however, lesions were benign in these patients in 50.6% of the cases. In patients with no known history of a malignancy, 75% of the lesions were benign and 25% were malignant. However, these malignant lesions were in 10/11 cases hepatocellular carcinomas in patients with liver cirrhosis. Even in the presence of a history of a malignant tumor, about 50% of the detected small liver lesions on MRI are benign. In the absence of a tumor history the probability of a small malignant liver lesion is very low, if the patients does not have liver cirrhosis where small hepatocellular carcinomas can be present.

  8. Focal dermal hypoplasia: Unusual presentation in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Awadh Alamri

    2016-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem characterized by multiple abnormalities of ectodermal and mesodermal origin. It is found predominantly in females. We report a case of a two month-old baby girl who had dermal hypoplasia, atrophic skin lesions with telangiectasia in a linear pattern, fat herniations, papillomas and cleft of the upper lip, ectrodactyly, claw hands, microphthalmia and unusual association of gastrointestinal omphalocele.

  9. Focal congenital hyperinsulinism managed by medical treatment: a diagnostic algorithm based on molecular genetic screening.

    Science.gov (United States)

    Maiorana, Arianna; Barbetti, Fabrizio; Boiani, Arianna; Rufini, Vittoria; Pizzoferro, Milena; Francalanci, Paola; Faletra, Flavio; Nichols, Colin G; Grimaldi, Chiara; de Ville de Goyet, Jean; Rahier, Jacques; Henquin, Jean-Claude; Dionisi-Vici, Carlo

    2014-11-01

    Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions. Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and (18) F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia. Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to (18) F-DOPA PET-CT. © 2014 John Wiley & Sons Ltd.

  10. Exploiting Satellite Focal Plane Geometry for Automatic Extraction of Traffic Flow from Single Optical Satellite Imagery

    Science.gov (United States)

    Krauß, T.

    2014-11-01

    The focal plane assembly of most pushbroom scanner satellites is built up in a way that different multispectral or multispectral and panchromatic bands are not all acquired exactly at the same time. This effect is due to offsets of some millimeters of the CCD-lines in the focal plane. Exploiting this special configuration allows the detection of objects moving during this small time span. In this paper we present a method for automatic detection and extraction of moving objects - mainly traffic - from single very high resolution optical satellite imagery of different sensors. The sensors investigated are WorldView-2, RapidEye, Pléiades and also the new SkyBox satellites. Different sensors require different approaches for detecting moving objects. Since the objects are mapped on different positions only in different spectral bands also the change of spectral properties have to be taken into account. In case the main distance in the focal plane is between the multispectral and the panchromatic CCD-line like for Pléiades an approach for weighted integration to receive mostly identical images is investigated. Other approaches for RapidEye and WorldView-2 are also shown. From these intermediate bands difference images are calculated and a method for detecting the moving objects from these difference images is proposed. Based on these presented methods images from different sensors are processed and the results are assessed for detection quality - how many moving objects can be detected, how many are missed - and accuracy - how accurate is the derived speed and size of the objects. Finally the results are discussed and an outlook for possible improvements towards operational processing is presented.

  11. Multiscale multichroic focal planes for measurements of the cosmic microwave background

    Science.gov (United States)

    Cukierman, Ari; Lee, Adrian T.; Raum, Christopher; Suzuki, Aritoki; Westbrook, Benjamin

    2018-01-01

    We report on the development of multiscale multichroic focal planes for measurements of the cosmic microwave background (CMB). A multichroic focal plane, i.e., one that consists of pixels that are simultaneously sensitive in multiple frequency bands, is an efficient architecture for increasing the sensitivity of an experiment as well as for disentangling the contamination due to galactic foregrounds, which is increasingly becoming the limiting factor in extracting cosmological information from CMB measurements. To achieve these goals, it is necessary to observe across a broad frequency range spanning roughly 30-350 GHz. For this purpose, the Berkeley CMB group has been developing multichroic pixels consisting of planar superconducting sinuous antennas coupled to extended hemispherical lenslets, which operate at sub-Kelvin temperatures. The sinuous antennas, microwave circuitry and the transition-edge-sensor (TES) bolometers to which they are coupled are integrated in a single lithographed wafer.We describe the design, fabrication, testing and performance of multichroic pixels with bandwidths of 3:1 and 4:1 across the entire frequency range of interest. Additionally, we report on a demonstration of multiscale pixels, i.e., pixels whose effective size changes as a function of frequency. This property keeps the beam width approximately constant across all frequencies, which in turn allows the sensitivity of the experiment to be optimal in every frequency band. We achieve this by creating phased arrays from neighboring lenslet-coupled sinuous antennas, where the size of each phased array is chosen independently for each frequency band. We describe the microwave circuitry in detail as well as the benefits of a multiscale architecture, e.g., mitigation of beam non-idealities, reduced readout requirements, etc. Finally, we discuss the design and fabrication of the detector modules and focal-plane structures including cryogenic readout components, which enable the

  12. Automatic location of microscopic focal planes for computerized stereology

    Science.gov (United States)

    Elozory, Daniel T.; Bonam, Om Pavithra; Kramer, Kurt; Goldgof, Dmitry B.; Hall, Lawrence O.; Mangual, Osvaldo; Mouton, Peter R.

    2011-03-01

    When applying design-based stereology to biological tissue, there are two primary applications for an auto-focusing function in the software of computerized stereology system. The system must first locate the in-focus optical planes at the upper and lower surfaces of stained tissue sections, thus identifying the top and bottom as well as the thickness of the tissue. Second, the system must find the start and end along the Z-axis of stained objects within a Z-stack of images through tissue sections. In contrast to traditional autofocus algorithms that seek a global maximum or peak on the focus curve, the goal of this study was to find the two "knees" of the focus curve that represent the "just out-of-focus" focal planes. The upper surface of the tissue section is defined as the image just before focus is detected moving down the Z-stack. Continuing down, the lower surface is defined as the first image of the last set of adjacent images where focus is no longer detected. The performance of seven focus algorithms in locating the top and bottom focal planes of tissue sections was analyzed by comparing each algorithm on 34 Z-stacks including a total of 828 images. The Thresholded Absolute Gradient algorithm outperformed all others, correctly identifying the top or bottom focal plane within an average of 1 μm on the training data as well as the test data.

  13. NATURAL-FOCAL DISEASES IN THE VLADIMIR REGION (RUSSIA

    Directory of Open Access Journals (Sweden)

    Tatiana A. Trifonova

    2015-01-01

    Full Text Available The paper describes a study that monitored the epidemiological situation of a complex of natural-focal diseases in the Vladimir region (Russia, from 1958 to 2012. The morbidity rates of these natural-focal diseases have been differentiated by territory using ArcView 3.1 (GIS software. The activity of natural foci for each zooanthroponosis varied between administrative districts in the region. A schematic map has been compiled; the map reflectsthe danger of infection caused by natural-focal diseases in the Vladimir region. The paperdiscusses the role of the anthropogenic factor in natural-ecosystem development: it likelypromotes the transit and localization rates of carriers. Correlation and regression analysis ofthe data showed that climatic factors such as the average temperatures in July and September in the preceding year influence Lyme disease (Lyme borreliosis patterns. This is likely related to particular stages in the life cycle of Ixodidae ticks. Using multiple linear regression analysis, a mathematical model for the prediction of Lyme borreliosis patterns has been created.

  14. A Micro-Thermal Sensor for Focal Therapy Applications.

    Science.gov (United States)

    Natesan, Harishankar; Hodges, Wyatt; Choi, Jeunghwan; Lubner, Sean; Dames, Chris; Bischof, John

    2016-02-26

    There is an urgent need for sensors deployed during focal therapies to inform treatment planning and in vivo monitoring in thin tissues. Specifically, the measurement of thermal properties, cooling surface contact, tissue thickness, blood flow and phase change with mm to sub mm accuracy are needed. As a proof of principle, we demonstrate that a micro-thermal sensor based on the supported "3ω" technique can achieve this in vitro under idealized conditions in 0.5 to 2 mm thick tissues relevant to cryoablation of the pulmonary vein (PV). To begin with "3ω" sensors were microfabricated onto flat glass as an idealization of a focal probe surface. The sensor was then used to make new measurements of 'k' (W/m.K) of porcine PV, esophagus, and phrenic nerve, all needed for PV cryoabalation treatment planning. Further, by modifying the sensor use from traditional to dynamic mode new measurements related to tissue vs. fluid (i.e. water) contact, fluid flow conditions, tissue thickness, and phase change were made. In summary, the in vitro idealized system data presented is promising and warrants future work to integrate and test supported "3ω" sensors on in vivo deployed focal therapy probe surfaces (i.e. balloons or catheters).

  15. HgCdTe focal plane array cost modeling

    Science.gov (United States)

    Sanders, Thomas J.; Hess, Glenn T.

    2003-09-01

    Focal plane arrays (FPAs) are used in many applications for detecting infrared (IR) radiation where normal sight with light in the visible spectrum is not possible. To effectively detect this IR radiation, complex semiconductor diodes, cooled to low temperatures, are usually used. The most common of these semiconductor materials is the II-VI alloy semiconductor system using HgCdTe, which is often called MCT. Focal plane arrays with over 1000 pixels have been fabricated. The cost of these very complex systems is becoming a very important consideration in decisions of where to use these FPAs. The focal plane array actually consists of two semiconductor parts with a sophisticated cooling assembly. The semiconductor parts are the MCT detector device itself and a companion device called the read-out circuit. The cost model presented in this paper consists of various expressions as functions of physical parameters that can be measured, calculated from data or estimated. Although accurate absolute cost data may not be available (because it does not exist or is proprietary to a company), cost estimates can be effectively used to determine relative cost between two designs or processes. In addition, when these cost models are coupled with the STADIUM design of experiments simulation methodology, accurate predictions of the most dominant cost drivers can be obtained. This cost model and its algorithms are coupled with a commercial software program called IR-SIM.

  16. Focal muscle vibration: evaluation of physical properties and his applications

    Directory of Open Access Journals (Sweden)

    Filippo Camerota

    2014-03-01

    Full Text Available Vibration is the sensation produced by sinusoidal oscillation of objects placed against the skin. The vibratory frequency is signaled bythe frequency of action potentials fired by the sensory nerves and the total number of active sensory nerves is linearly related to theamplitude of vibration. In the last years many works were done evaluating the different clinical applications of the focal musclevibration; the aim of this work is to analyze the interaction between the vibratory application and the skin. For this study theapparatus of focal muscle vibration analyzed was firstly calibrated by measuring the actual peak to peak displacement of the tip as afunction of the power supplied to the shaker; then were measured the Direct Component (DC of the force by which the shaker ispushed against the patient’s skin and the Alternate Component (AC. We observed that from displacements imposed by the tipranging from 0 to about 200 micrometers, the applied load increases monotonically, but non linearly, with the displacement; abovethis value, any further increase of the peak to peak displacements actually does not lead to an effective increase of the amplitude of themechanical stimulation. We can conclude that with this focal muscle vibration applied to the muscle we are able to stimulate thespindles that respond to 200 micrometers amplitude that are probably ones able to generate a proprioceptive signal.

  17. Inflammation-responsive focal constrictors in the mouse ear microcirculation

    Science.gov (United States)

    Ravnic, Dino J; Konerding, Moritz; Pratt, Juan P; Wolloscheck, Tanja; Huss, Harold T; Mentzer, Steven J

    2006-01-01

    In many capillary exchange beds, blood flow is locally regulated by precapillary sphincter-like activity. In this study, we used intravascular tracers and scanning electron microscopy to investigate precapillary blood flow regulation in the mouse ear. Gelatin ink injections of the normal mouse ear demonstrated 6.8 ± 2.3 axial vessels with a cutoff of detectable tracer in the early branches: 19 ± 11 focal constrictions were observed along the 1st to 5th order branches of the axial vessels. A perfusion tracer consisting of biotinylated anti-endothelial lectins (Ricinus Communis Agglutin, Lycopersicon Esculentum and Griffonia Simplicifolia) was circulated for 30 min under physiological conditions. Subsequent enzyme histochemistry demonstrated no significant change in distal perfusion or in the number of focal constrictions (P > 0.05). Furthermore, the focal constrictions were unresponsive to vasodilators such as organic nitrates and prostaglandin E1. By contrast, the presence of oxazolone-induced inflammation resulted in significant and sustained vasodilatation for more than 96 h (P > 0.001). Scanning electron microscopy demonstrated discrete constricting bands morphologically distinct from known precapillary sphincters. These results suggest that these previously unappreciated inflammation-responsive precapillary constrictors regulate capillary recruitment in the mouse ear microcirculation. PMID:17118067

  18. How will focal therapy fit in with existing treatments?

    Science.gov (United States)

    Emberton, M; Gómez-Veiga, F; Ahmed, H; Dickinson, L

    2013-01-01

    The current management of localized prostate cancer is a therapeutic challenge with different options including active radicals or active follow-up. The aim of this paper is to analyze the feasibility and validity of the «Focal» active treatment versus the concept of active follow-up or Radical Treatment. We reviewed the literature on the various diagnostic methods, advantages, and difficulties of active follow-up and Radical Treatment, versus focal therapy with the possibilities of defining characteristics of aggressiveness and patient selection. The mesh biopsy techniques along with multiparametric magnetic resonance imaging and association of factors such as tumor size, length of affected cylinder and Gleason are parameters that allow us to define location and definition of clinically significant tumors and subsidiary of focal therapies. The definition, location and aggressiveness of prostate cancer in low-intermediate risk tumors can be defined avoiding radical therapies with their side effects or the risks of underestimating tumors as in active follow-up without the minimum side effects. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  19. Slow Activity in Focal Epilepsy During Sleep and Wakefulness.

    Science.gov (United States)

    Pellegrino, Giovanni; Tombini, Mario; Curcio, Giuseppe; Campana, Chiara; Di Pino, Giovanni; Assenza, Giovanni; Tomasevic, Leo; Di Lazzaro, Vincenzo

    2017-05-01

    We aimed to test differences between healthy subjects and patients with respect to slow wave activity during wakefulness and sleep. Fifteen patients affected by nonlesional focal epilepsy originating within temporal areas and fourteen matched controls underwent a 24-hour EEG recording. We studied the EEG power spectral density during wakefulness and sleep in delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz), and beta (16-20 Hz) bands. During sleep, patients with focal epilepsy showed higher power from delta to beta frequency bands compared with controls. The effect was widespread for alpha band and above, while localized over the affected hemisphere for delta (sleep cycle 1, P = .006; sleep cycle 2, P = .008; sleep cycle 3, P = .017). The analysis of interhemispheric differences showed that the only frequency band stronger over the affected regions was the delta band during the first 2 sleep cycles (sleep cycle 1, P = .014; sleep cycle 2, P = .002). During wakefulness, patients showed higher delta/theta activity over the affected regions compared with controls. Patients with focal epilepsy showed a pattern of power increases characterized by a selective slow wave activity enhancement over the epileptic regions during daytime and sleep. This phenomenon was stronger and asymmetric during the first sleep cycles.

  20. Application of Entropy Measures on Intrinsic Mode Functions for the Automated Identification of Focal Electroencephalogram Signals

    Directory of Open Access Journals (Sweden)

    Rajeev Sharma

    2015-02-01

    Full Text Available The brain is a complex structure made up of interconnected neurons, and its electrical activities can be evaluated using electroencephalogram (EEG signals. The characteristics of the brain area affected by partial epilepsy can be studied using focal and non-focal EEG signals. In this work, a method for the classification of focal and non-focal EEG signals is presented using entropy measures. These entropy measures can be useful in assessing the nonlinear interrelation and complexity of focal and non-focal EEG signals. These EEG signals are first decomposed using the empirical mode decomposition (EMD method to extract intrinsic mode functions (IMFs. The entropy features, namely, average Shannon entropy (ShEnAvg, average Renyi’s entropy (RenEnAvg , average approximate entropy (ApEnAvg, average sample entropy (SpEnAvg and average phase entropies (S1Avg and S2Avg, are computed from different IMFs of focal and non-focal EEG signals. These entropies are used as the input feature set for the least squares support vector machine (LS-SVM classifier to classify into focal and non-focal EEG signals. Experimental results show that our proposed method is able to differentiate the focal and non-focal EEG signals with an average classification accuracy of 87% correct.

  1. Fast multifrequency focal beam analysis for 3D seismic acquisition geometry

    NARCIS (Netherlands)

    Wei, W.; Fu, L.; Blacquiere, G.

    2012-01-01

    A method for the efficient computation of multifrequency focal beams for 3D seismic acquisition geometry analysis has been developed. By computing them for all the frequency components of seismic data, single-frequency focal beams can be extended to multifrequency focal beams. However, this

  2. Semantic fluency: cognitive basis and diagnostic performance in focal dementias and Alzheimer's disease.

    Science.gov (United States)

    Reverberi, Carlo; Cherubini, Paolo; Baldinelli, Sara; Luzzi, Simona

    2014-05-01

    Semantic fluency is widely used both as a clinical test and as a basic tool for understanding how humans extract information from the semantic store. Recently, major efforts have been made to devise fine-grained scoring procedures to measure the multiple cognitive processes underlying fluency performance. Nevertheless, it is still unclear how many and which independent components are necessary to thoroughly describe performance on the fluency task. Furthermore, whether a combination of multiple indices can improve the diagnostic performance of the test should be assessed. In this study, we extracted multiple indices of performance on the semantic fluency test from a large sample of healthy controls (n = 307) and patients (n = 145) suffering from three types of focal dementia or Alzheimer's Disease (AD). We found that five independent components underlie semantic fluency performance. We argue that these components functionally map onto the generation and application of a search strategy (component 2), to the monitoring of the overall sequence to avoid repetitions (component 3) and out-of-category items (component 4), and to the full integrity of the semantic store (component 5). The integrated and effective work of all these components would relate to a "general effectiveness" component (component 1). Importantly, while all the focal dementia groups were equally impaired on general effectiveness measures, they showed differential patterns of failure in the other components. This finding suggests that the cognitive deficit that impairs fluency differs among the three focal dementia groups: a semantic store deficit in the semantic variant of primary progressive aphasia (sv-PPA), a strategy deficit in the non-fluent variant of primary progressive aphasia (nfv-PPA), and an initiation deficit in the behavioural variant of fronto-temporal dementia (bv-FTD). Finally, we showed that the concurrent use of multiple fluency indices improves the diagnostic accuracy of

  3. Human immunodeficiency virus integrase protein requires a subterminal position of its viral DNA recognition sequence for efficient cleavage

    NARCIS (Netherlands)

    C. Vink (Cornelis); D.C. van Gent (Dik); Y. Elgersma (Ype); R.H. Plassterk

    1991-01-01

    textabstractRetroviral integration requires cis-acting sequences at the termini of linear double-stranded viral DNA and a product of the retroviral pol gene, the integrase protein (IN). IN is required and sufficient for generation of recessed 3' termini of the viral DNA (the first

  4. Multi-focal HIFU reduces cavitation in mild-hyperthermia.

    Science.gov (United States)

    Chaplin, Vandiver; Caskey, Charles F

    2017-01-01

    Mild-hyperthermia therapy (40-45 °C) with high-intensity focused ultrasound (HIFU) is a technique being considered in a number of different treatments such as thermally activated drug delivery, immune-stimulation, and as a chemotherapy adjuvant. Mechanical damage and loss of cell viability associated with HIFU-induced acoustic cavitation may pose a risk during these treatments or may hinder their success. Here we present a method that achieves mild heating and reduces cavitation by using a multi-focused HIFU beam. We quantify cavitation level and temperature rise in multi-focal sonications and compare it to single-focus sonications at the transducer geometric focus. Continuous wave sonications were performed with the Sonalleve V2 transducer in gel phantoms and pork at 5, 10, 20, 40, 60, 80 acoustic watts for 30 s. Cavitation activity was measured with two ultrasound (US) imaging probes, both by computing the raw channel variance and using passive acoustic mapping (PAM). Temperature rise was measured with MR thermometry at 3 T. Cavitation and heating were compared for single- and multi-focal sonication geometries. Multi-focal sonications used four points equally spaced on a ring of either 4 mm or 8 mm diameter. Single-focus sonications were not steered. Multi-focal sonication generated distinct foci that were visible in MRI thermal maps in both phantoms and pork, and visible in PAM images in phantoms only. Cavitation activity (measured by channel variance) and mean PAM image value were highly correlated (r > 0.9). In phantoms, cavitation exponentially decreased over the 30-second sonication, consistent with depletion of cavitation nuclei. In pork, sporadic spikes signaling cavitation were observed with single focusing only. In both materials, the widest beam reduced average and peak cavitation level by a factor of two or more at each power tested when compared to a single focus. The widest beam reduced peak temperature by at least 10 °C at powers above 5

  5. Intraplate stress field in South America from earthquake focal mechanisms

    Science.gov (United States)

    Assumpção, Marcelo; Dias, Fábio L.; Zevallos, Ivan; Naliboff, John B.

    2016-11-01

    We present an updated compilation of earthquake focal mechanisms in Brazil together with focal mechanisms from the sub-Andean region (mainly from global CMT catalogs). All earthquakes in the sub-Andean region show reverse (majority) or strike-slip faulting mechanisms. Focal mechanisms in Brazil show reverse, strike-slip and normal faulting. Focal mechanisms of nearby earthquakes in the same tectonic environment were grouped and inverted for the stress tensor. In the sub-Andean region, stresses are compressional, as expected, with the principal major compression (S1) roughly E-W, on average. A slight rotation of S1 can be observed and is controlled by the orientation of the Andean plateau. In the sub-Andean region, the intermediate principal stress (S2) is also compressional (i.e., larger than the lithostatic pressure, Sv), a feature that is not always reproduced in numerical models published in the literature. In mid-plate South America stresses seem to vary in nature and orientation. In SE Brazil and the Chaco-Pantanal basins, S1 tends to be oriented roughly E-W with S2 approximately equal to S3. This stress pattern changes to purely compressional (both SHmax and Shmin larger than Sv) in the São Francisco craton. A rotation of SHmax from E-W to SE-NW is suggested towards the Amazon region. Along the Atlantic margin, the regional stresses are very much affected by coastal effects (due to continent/ocean spreading stresses as well as flexural effects from sediment load at the continental margin). This coastal effect tends to make SHmax parallel to the coastline and Shmin (usually S3) perpendicular to the coastline. Few breakout data and in-situ measurements are available in Brazil and are generally consistent with the pattern derived from the earthquake focal mechanisms. Although numerical models of global lithospheric stresses tend to reproduce the main large-scale features in most mid-plate areas, the S1 rotation from ∼E-W in SE Brazil to SE-NW in the Amazon

  6. Focal adhesion kinase (FAK) perspectives in mechanobiology: implications for cell behaviour.

    Science.gov (United States)

    Tomakidi, Pascal; Schulz, Simon; Proksch, Susanne; Weber, Wilfried; Steinberg, Thorsten

    2014-09-01

    Mechanobiology is a scientific interface discipline emerging from engineering and biology. With regard to tissue-regenerative cell-based strategies, mechanobiological concepts, including biomechanics as a target for cell and human mesenchymal stem cell behaviour, are on the march. Based on the periodontium as a paradigm, this mini-review discusses the key role of focal-adhesion kinase (FAK) in mechanobiology, since it is involved in mediating the transformation of environmental biomechanical signals into cell behavioural responses via mechanotransducing signalling cascades. These processes enable cells to adjust quickly to environmental cues, whereas adjustment itself relies on the specific intramolecular phosphorylation of FAK tyrosine residues and the multiple interactions of FAK with distinct partners. Furthermore, interaction-triggered mechanotransducing pathways govern the dynamics of focal adhesion sites and cell behaviour. Facets of behaviour not only include cell spreading and motility, but also proliferation, differentiation and apoptosis. In translational terms, identified and characterized biomechanical parameters can be incorporated into innovative concepts of cell- and tissue-tailored clinically applied biomaterials controlling cell behaviour as desired.

  7. Development of safety and regulatory requirements for Korean next generation reactor - Development of human factors design review guidelines (II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Lee, Hyun Chul; Cheon, Se Woo [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-02-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25. Human Factors Engineering Program Review Model' and '26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and the characteristics of the KNGR design, and reviewing the reference documents of NURGE-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides at KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system design review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we updated the guidelines by reviewing the literature related to alarm design that published after 1994. 12 refs., 11 figs., 2 tabs. (Author)

  8. Epileptogenic networks of type II focal cortical dysplasia: a stereo-EEG study.

    Science.gov (United States)

    Varotto, Giulia; Tassi, Laura; Franceschetti, Silvana; Spreafico, Roberto; Panzica, Ferruccio

    2012-07-02

    In the context of focal and drug-resistant epilepsy, surgical resection of the epileptogenic zone may be the only therapeutic option for reducing or suppressing seizures. In many such patients, intracranial stereo-EEG recordings remain the gold standard for the epilepsy surgery work-up. Assessing the extent of the epileptogenic zone and its organisation is a crucial objective, and requires advanced methods of signal processing. Over the last ten years, considerable efforts have been made to develop signal analysis techniques for characterising the connectivity between spatially distributed regions. The aim of this study was to evaluate the changes in dynamic connectivity pattern under inter-ictal, pre-ictal and ictal conditions using signals derived from stereo-EEG recordings of 10 patients with Taylor-type focal cortical dysplasia. A causal linear multivariate method - partial directed coherence - and indices derived from graph theory were used to characterise the synchronisation property of the lesional zone (corresponding to the epileptogenic zone in our patients) and to distinguish it from other regions involved in ictal activity or not. The results show that a significantly different connectivity pattern (mainly in the gamma band) distinguishes the epileptogenic zone from other cortical regions not only during the ictal event, but also during the inter- and pre-ictal periods. This indicates that the lesional nodes play a leading role in generating and propagating ictal EEG activity by acting as the hubs of the epileptic network originating and sustaining seizures. Our findings also indicate that the cortical regions beyond the dysplasia involved in the ictal activity essentially act as "secondary" generators of synchronous activity. The leading role of the lesional zone may account for the good post-surgical outcome of patients with type II focal cortical dysplasia as resecting the dysplasia removes the epileptogenic zone responsible for seizure organisation

  9. Thermography Examination of Abdominal Area Skin Temperatures in Individuals With and Without Focal-Onset Epilepsy.

    Science.gov (United States)

    King, Hollis H; Cayce, Charles Thomas; Herrin, Jeph

    Early osteopathic theory and practice, and the work of the medical intuitive Edgar Cayce suggested that the abdominal areas of individuals with epilepsy would manifest "cold spots." The etiology for this phenomenon was thought to be abdominal adhesions caused by inflammation and viscero-somatic reflexes caused by adhesions or injury to visceral or musculoskeletal system structures. Indeed, until that advent of electroencephalography in the 1930s, medical practice regarding epilepsy focused on abdominal neural and visceral structures. Following two hypotheses were formulated to evaluate any abdominal temperature phenomena: (1) an abdominal quadrant division analysis would find one or more quadrants "colder" in the focal-onset epilepsy group (ICD9-CM 345.4 and 345.5) compared to controls. (2) Total abdominal areas of individuals with focal-onset epilepsy wound be colder than a control group. Overall, 50 patients with the diagnosis of focal-onset epilepsy were recruited from the office of the Epilepsy Foundation of Florida and 50 control subjects with no history of epilepsy were recruited through advertising to the public. Under controlled room conditions all subjects had infrared thermographic images made and recorded by Med-Hot Model MH-731 FLIR equipment. There were no significant demographic difference between experimental patients and control subjects, though the control group tended to be younger and more often male; however, these were controlled for in all analyses. In the quadrant analysis, there were significant differences in that more epileptic patients had colder left upper abdominal quadrant temperatures than the control group (66.8% versus 44.9%; P = .030). In the total abdominal analysis, however, there were no significant differences. The results support the hypothesis that individuals with focal-onset epilepsy have colder abdominal areas. If substantiated in further research, present study results will require further examination of the mechanisms of

  10. Human RECQ1 is a DNA damage responsive protein required for genotoxic stress resistance and suppression of sister chromatid exchanges.

    Directory of Open Access Journals (Sweden)

    Sudha Sharma

    2007-12-01

    Full Text Available DNA helicases are ubiquitous enzymes that unwind DNA in an ATP-dependent and directionally specific manner. Unwinding of double-stranded DNA is essential for the processes of DNA repair, recombination, transcription, and DNA replication. Five human DNA helicases sharing sequence similarity with the E. coli RecQ helicase have been identified. Three of the human RecQ helicases are implicated in hereditary diseases (Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome which display clinical symptoms of premature aging and cancer. RECQ1 helicase is the most highly expressed of the human RecQ helicases; however, a genetic disease has yet not been linked to mutations in the RECQ1 gene, and the biological functions of human RECQ1 in cellular DNA metabolism are not known.In this study, we report that RECQ1 becomes phosphorylated upon DNA damage and forms irradiation-induced nuclear foci that associate with chromatin in human cells. Depletion of RECQ1 renders human cells sensitive to DNA damage induced by ionizing radiation or the topoisomerase inhibitor camptothecin, and results in spontaneous gamma-H2AX foci and elevated sister chromatid exchanges, indicating aberrant repair of DNA breaks. Consistent with a role in homologous recombinational repair, endogenous RECQ1 is associated with the strand exchange protein Rad51 and the two proteins directly interact with high affinity.Collectively, these results provide the first evidence for a role of human RECQ1 in the response to DNA damage and chromosomal stability maintenance and point to the vital importance of RECQ1 in genome homeostasis.

  11. Summary of the operational land imager focal plane array for the Landsat Data Continuity Mission

    Science.gov (United States)

    Lindahl, Kirk A.; Burmester, William; Malone, Kevin; Schrein, Ronald J.; Irwin, Ronda; Donley, Eric; Collins, Sandra R.

    2011-10-01

    The Landsat missions are the longest continuous record of changes in the Earth's surface as seen from space. The next follow-on activity is the Landsat Data Continuity Mission (LDCM). The LDCM objective is to extend the ability to detect and quantitatively characterize changes on the global land surface at a scale where natural and man-made causes of change can be detected and differentiated. The Operational Land Imager (OLI) is one of two instruments on the LDCM spacecraft. OLI will produce science data for the reflective bands, which include 6 visible and near-infrared (VNIR) and 3 short-wave infrared (SWIR) bands. The OLI instrument utilizes a pushbroom design with 15.5 degree field of view. As a result, the OLI Focal Plane Array (FPA) cross track dimension is large, and the FPA is a critical technology for the success of the mission. The FPA contains 14 critically aligned Focal Plane Modules (FPM) and consists of 6916 imaging pixels in each of the 8 multi-spectral bands, and 13,832 imaging pixels in the panchromatic band. Prior to integration into the FPA, the FPMs were characterized for radiometric, spectral, and spatial performance. The Flight FPA has been built and its performance has also been characterized. In this paper, the critical attributes of the FPMs and FPA are highlighted. Detailed description of the FPM and FPA test sets are provided. The performance results that demonstrate compliance to the science mission requirements are presented.

  12. Focal Suppression of Distractor Sounds by Selective Attention in Auditory Cortex.

    Science.gov (United States)

    Schwartz, Zachary P; David, Stephen V

    2018-01-01

    Auditory selective attention is required for parsing crowded acoustic environments, but cortical systems mediating the influence of behavioral state on auditory perception are not well characterized. Previous neurophysiological studies suggest that attention produces a general enhancement of neural responses to important target sounds versus irrelevant distractors. However, behavioral studies suggest that in the presence of masking noise, attention provides a focal suppression of distractors that compete with targets. Here, we compared effects of attention on cortical responses to masking versus non-masking distractors, controlling for effects of listening effort and general task engagement. We recorded single-unit activity from primary auditory cortex (A1) of ferrets during behavior and found that selective attention decreased responses to distractors masking targets in the same spectral band, compared with spectrally distinct distractors. This suppression enhanced neural target detection thresholds, suggesting that limited attention resources serve to focally suppress responses to distractors that interfere with target detection. Changing effort by manipulating target salience consistently modulated spontaneous but not evoked activity. Task engagement and changing effort tended to affect the same neurons, while attention affected an independent population, suggesting that distinct feedback circuits mediate effects of attention and effort in A1. © The Author 2017. Published by Oxford University Press.

  13. [Focal therapies: An alternative option for low-risk prostate cancer management?

    Science.gov (United States)

    Lebdai, Souhil; Lunelli, Luca; Bigot, Pierre; Cussenot, Olivier; Azzouzi, Abdel-Rahmene

    2017-10-11

    Recommended options for low-risk prostate cancer treatment are active surveillance, radical treatments or watchful waiting. Focal therapies are currently assessed for low risk prostate cancer treatment. Focal therapies can be performed in research protocols. Oncologic results of these focal treatments are encouraging and show excellent tolerance with few complications. Radical treatments are still possible after focal therapies failure. Focal therapies are a possible solution to over-treatment issue of low risk prostate cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. 'Focal thyroid inferno' on color Doppler ultrasonography: A specific feature of focal Hashimoto's thyroiditis

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Xianshui, E-mail: fuxs1968@163.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Guo, Limei, E-mail: guolimei@bjmu.edu.cn [Department of Pathology, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Zhang, Huabin, E-mail: huabinzhang@bjmu.edu.cn [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Ran, Weiqiang, E-mail: ranwq-sina@vip.sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Fu, Peng, E-mail: fupeng01@gmail.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Li, Zhiqiang, E-mail: lizhq126@126.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Chen, Wen, E-mail: wendy7989@sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Jiang, Ling, E-mail: papayaling@yahoo.com.cn [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Wang, Jinrui, E-mail: jinrui_wang@sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Jia, Jianwen, E-mail: drjia88@sohu.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China)

    2012-11-15

    Purpose: To evaluate color-Doppler features predictive of focal Hashimoto's thyroiditis. Materials and methods: A total of 521 patients with 561 thyroid nodules that underwent surgeries or gun biopsies were included in this study. These nodules were divided into three groups: focal Hashimoto's thyroiditis (104 nodules in 101 patients), benignity other than focal Hashimoto's thyroiditis (73 nodules in 70 patients), and malignancy (358 nodules in 350 patients). On color Doppler sonography, four vascularity types were determined as: hypovascularity, marked internal flow, marked peripheral flow and focal thyroid inferno. The {chi}{sup 2} test was performed to seek the potential vascularity type with the predictive ability of certain thyroid pathology. Furthermore, the gray-scale features of each nodule were also studied. Results: The vascularity type I (hypovascularity) was more often seen in focal Hashimoto's thyroiditis than other benignity and malignancy (46% vs. 20.5% and 19%). While the type II (marked internal flow) showed the opposite tendency (26.9% [focal Hashimoto's thyroiditis] vs. 45.2% [other benignity] and 52.8% [malignancy]). However, type III (marked peripheral flow) was unable to predict any thyroid pathology. Importantly, type IV (focal thyroid inferno) was exclusive to focal Hashimoto's thyroiditis. All 8 type IV nodules appeared to be solid, hypoechoic, and well-defined. Using 'focal thyroid inferno' as an indicator of FHT, the diagnostic sensitivity and specificity were 7.7% and 100% respectively. Conclusions: The vascularity type of 'focal thyroid inferno' is specific for focal Hashimoto thyroiditis. Recognition of this particular feature may avoid unnecessary interventional procedures for some solid hypoechoic thyroid nodules suspicious of malignancy.

  15. Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines.

    Science.gov (United States)

    Müller, Marcel A; Raj, V Stalin; Muth, Doreen; Meyer, Benjamin; Kallies, Stephan; Smits, Saskia L; Wollny, Robert; Bestebroer, Theo M; Specht, Sabine; Suliman, Tasnim; Zimmermann, Katrin; Binger, Tabea; Eckerle, Isabella; Tschapka, Marco; Zaki, Ali M; Osterhaus, Albert D M E; Fouchier, Ron A M; Haagmans, Bart L; Drosten, Christian

    2012-12-11

    A new human coronavirus (hCoV-EMC) has emerged very recently in the Middle East. The clinical presentation resembled that of the severe acute respiratory syndrome (SARS) as encountered during the epidemic in 2002/2003. In both cases, acute renal failure was observed in humans. HCoV-EMC is a member of the same virus genus as SARS-CoV but constitutes a sister species. Here we investigated whether it might utilize angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Knowledge of the receptor is highly critical because the restriction of the SARS receptor to deep compartments of the human respiratory tract limited the spread of SARS. In baby hamster kidney (BHK) cells, lentiviral transduction of human ACE2 (hACE2) conferred permissiveness and replication for SARS-CoV but not for hCoV-EMC. Monkey and human kidney cells (LLC-MK2, Vero, and 769-P) and swine kidney cells were permissive for both viruses, but only SARS-CoV infection could be blocked by anti-hACE2 antibody and could be neutralized by preincubation of virus with soluble ACE2. Our data show that ACE2 is neither necessary nor sufficient for hCoV-EMC replication. Moreover, hCoV-EMC, but not SARS-CoV, replicated in cell lines from Rousettus, Rhinolophus, Pipistrellus, Myotis, and Carollia bats, representing four major chiropteran families from both suborders. As human CoV normally cannot replicate in bat cells from different families, this suggests that hCoV-EMC might use a receptor molecule that is conserved in bats, pigs, and humans, implicating a low barrier against cross-host transmission. IMPORTANCE A new human coronavirus (hCoV) emerged recently in the Middle East. The disease resembled SARS (severe acute respiratory syndrome), causing a fatal epidemic in 2002/2003. Coronaviruses have a reservoir in bats and because this novel virus is related to SARS-CoV, we investigated whether it might replicate in bat cells and use the same receptor (angiotensin-converting enzyme 2 [ACE2]). This knowledge is

  16. Paxillin Enables Attachment-independent Tyrosine Phosphorylation of Focal Adhesion Kinase and Transformation by RAS*

    Science.gov (United States)

    Wade, Ramon; Brimer, Nicole; Lyons, Charles; Pol, Scott Vande

    2011-01-01

    Paxillin and HIC5 are closely related adapter proteins that regulate cell migration and are tyrosine-phosphorylated by focal adhesion kinase (FAK). Paxillin, HIC5, and FAK tyrosine phosphorylation increase upon cell attachment and decrease upon detachment from extracellular matrix. Unexpectedly, we found that although FAK tyrosine phosphorylation in attached cells did not require paxillin, in detached fibroblasts there was remaining FAK tyrosine phosphorylation that required expression of paxillin and was not supported by HIC5. The support of attachment-independent FAK tyrosine phosphorylation required the paxillin LIM domains and suggested that paxillin might facilitate oncogenic transformation. Paxillin but not HIC5 augmented anchorage-independent cell proliferation induced by RAS. Both anchorage-independent FAK tyrosine phosphorylation and RAS-induced colony formation required multiple docking sites on paxillin, including LD4 (docking sites for FAK-Src and GIT1/2-PIX-NCK-PAK complex), LD5, and all four carboxyl-terminal LIM domains (that bind tubulin and PTP-PEST). Analysis using paxillin mutants dissociated domains of paxillin that are required for regulation of cell migration from domains that are required for anchorage-independent cell proliferation and demonstrated essential functions of the paxillin LIM domains that are not found in HIC5 LIM domains. These results highlight the role of paxillin in facilitating attachment-independent signal transduction implicated in cancer. PMID:21900245

  17. The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist

    Energy Technology Data Exchange (ETDEWEB)

    Madauss, Kevin P.; Burkhart, William A.; Consler, Thomas G.; Cowan, David J.; Gottschalk, William K.; Miller, Aaron B; Short, Steven A.; Tran, Thuy B.; Williams, Shawn P.; (GSKNC); (Duke); (UNC)

    2009-06-15

    Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target. Although the enzyme is highly conserved amongst animals, only the yeast enzyme structure is available for rational drug design. The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence. This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex. The human ACC2 CT-domain C-terminus is comprised of three intertwined -helices that extend outwards from the enzyme on the opposite side to the ligand-binding site. Differences in the observed inhibitor conformation between the yeast and human structures are caused by differing residues in the binding pocket.

  18. STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells

    NARCIS (Netherlands)

    Schepers, Hein; van Gosliga, Djoke; Wierenga, Albertus T. J.; Eggen, Bart J. L.; Schuringa, Jan Jacob; Vellenga, Edo

    2007-01-01

    The transcription factor STAT5 fulfills a distinct role in the hematopoietic system, but its precise role in primitive human hematopoietic cells remains to be elucidated. Therefore, we performed STAT5 RNAi in sorted cord blood (CB) and acute myeloid leukemia (AML) CD34(+) cells by lentiviral

  19. Mitochondrial dysfunction in primary human fibroblasts triggers an adaptive cell survival program that requires AMPK-alpha

    NARCIS (Netherlands)

    Distelmaier, F.; Valsecchi, F.; Liemburg-Apers, D.; Lebiedzinska, M.; Rodenburg, R.; Heil, S.; Keijer, J.; Fransen, J.; Imamura, H.; Danhauser, K.; Seibt, A.; Viollet, B.; Gellerich, F.; Smeitink, J.; Wieckowski, M.; Willems, P.; Koopman, W.J.H.

    2015-01-01

    Dysfunction of complex I (CI) of the mitochondrial electron transport chain (ETC) features prominently in human pathology. Cell models of ETC dysfunction display adaptive survival responses that still are poorly understood but of relevance for therapy development. Here we comprehensively examined

  20. Mitochondrial dysfunction in primary human fibroblasts triggers an adaptive cell survival program that requires AMPK-α

    NARCIS (Netherlands)

    F. Distelmaier (Felix); F. Valsecchi (Federica); D.C. Liemburg-Apers (Dania C.); M. Lebiedzinska (Magdalena); R.J.T. Rodenburg (Richard); S.G. Heil (Sandra); J. Keijer (Jaap); J.A.M. Fransen (Jack); H. Imamura (Hiromi); K. Danhauser (Katharina); A. Seibt (Annette); B. Viollet (Benoit); F.N. Gellerich (Frank); J.A.M. Smeitink (Jan); M.R. Wieckowski (Mariusz R.); P.H.G.M. Willems (Peter H.G.M.); W.J.H. Koopman (W. J H)

    2015-01-01

    textabstractDysfunction of complex I (CI) of the mitochondrial electron transport chain (ETC) features prominently in human pathology. Cell models of ETC dysfunction display adaptive survival responses that still are poorly understood but of relevance for therapy development. Here we comprehensively