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  1. Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling.

    Directory of Open Access Journals (Sweden)

    Yunping Li

    2009-10-01

    Full Text Available An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

  2. Oral focal epithelial hyperplasia: report of 3 cases with human papillomavirus DNA sequencing analysis.

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    Gültekin, S E; Tokman Yildirim, Benay; Sarisoy, S

    2011-01-01

    Focal epithelial hyperplasia (FEH), or Heck's disease, is a benign proliferative viral infection of the oral mucosa that is related to Human Papil-lomavirus (HPV), mainly subtypes 13 and 32. Although this condition is known to exist in numerous populations and ethnic groups, the reported cases among Caucasians are relatively rare. It presents as asymptomatic papules or nodules on the oral mucosa, gingiva, tongue, and lips. Histopathologically, it is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, fusion, and horizontal outgrowth of epithelial ridges and the cells named mitozoids. The purpose of this case report was to present 3 cases of focal epithelial hyperplasia in a pediatric age group. Histopathological and clinical features of cases are discussed and DNA sequencing analysis is reported in which HPV 13, HPV 32, and HPV 11 genomes are detected.

  3. Human Systems Integration Requirements

    Science.gov (United States)

    2009-09-01

    52 Stratofortress, C/ KC -135 Stratotanker, E-3 Sentry and contractor logistics support aircraft; as well as a substantial jet engine inventory...www.hqda.army.mil/ teo /Sutability%20Terms%20MOA%20Oct%2005.pdf q. ISO 9241-11, Ergonomic requirements for office work with visual display terminals (VDTs

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

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    Roa-Espitia, Ana L.; Hernández-Rendón, Eva R.; Baltiérrez-Hoyos, Rafael; Muñoz-Gotera, Rafaela J.; Cote-Vélez, Antonieta; Jiménez, Irma; González-Márquez, Humberto

    2016-01-01

    ABSTRACT 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. PMID:27402964

  5. Human fibroblasts display a differential focal adhesion phenotype relative to chimpanzee.

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    Advani, Alexander S; Chen, Annie Y; Babbitt, Courtney C

    2016-01-01

    There are a number of documented differences between humans and our closest relatives in responses to wound healing and in disease susceptibilities, suggesting a differential cellular response to certain environmental factors. In this study, we sought to look at a specific cell type, fibroblasts, to examine differences in cellular adhesion between humans and chimpanzees in visualized cells and in gene expression. We have found significant differences in the number of focal adhesions between primary human and chimpanzee fibroblasts. Additionally, we see that adhesion related gene ontology categories are some of the most differentially expressed between human and chimpanzee in normal fibroblast cells. These results suggest that human and chimpanzee fibroblasts may have somewhat different adhesive properties, which could play a role in differential disease phenotypes and responses to external factors. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  6. Focal seizure associated with human parvovirus B19 infection in a non-encephalopathic child.

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    Samanta, Debopam; Willis, Erin

    2016-02-01

    The incidence of acute symptomatic (at the time of documented brain insult) seizures and single unprovoked seizures are 29-39 and 23-61 per 100 000 per year, respectively. After stabilization of the patient, finding the etiology of the seizure is of paramount importance. A careful history and physical examination may allow a diagnosis without need for further evaluation. In the literature, severe central nervous system involvement has been reported from human parvovirus B19 infection. We reported a previously healthy 7-year-old girl who presented after an episode of focal seizure. She was afebrile and didn't have any focal neurological abnormalities. She had erythematous malar rash along with reticulating pattern of rash over her both upper extremities. Parvovirus infection was suspected due to the characteristic erythematous malar rash. Serum human parvovirus B19 DNA polymerase chain reaction was positive which was consistent with acute parvovirus infection. Further confirmation of current infection was done with Sandwich enzyme immunoassays showing positive anti-B19 IgM Index (>1.1). IgG index was equivocal (0.9-1.1). We report an extremely rare presentation of non-febrile seizure from acute parvovirus infection in a child without encephalopathy who had an excellent recovery. Timely diagnosis can provide counselling regarding future seizure recurrence risk, curtail expenditure from expensive diagnostic work up and provide additional recommendations about potential risks to a pregnant caregiver.

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

    Science.gov (United States)

    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.

  8. Focal Electrically Administered Therapy (FEAT): Device parameter effects on stimulus perception in humans

    Science.gov (United States)

    Borckardt, Jeffrey J.; Linder, Katie; Ricci, Raffaella; Li, Xingbao; Anderson, Berry; Arana, Ashley; Nahas, Ziad; Amassian, Vahe; Long, James; George, Mark S.; Sackeim, Harold A.

    2010-01-01

    Background Focal Electrically-Administered Therapy (FEAT) is a new method of transcranial electrical stimulation capable of focal modulation of cerebral activity. Other than invasive studies in animals and examination of motor output in humans, there are limited possibilities for establishing basic principles about how variation in stimulus parameters impact on patterns of intracortical stimulation. This study used a simpler paradigm, and evaluated the effects of different stimulation parameters on subjective perception of the quality and location of scalp pain. Methods In two studies, 19 subjects were randomly stimulated over the left forehead, varying the anode-cathode arrangement, the intensity of stimulation, the electrode size and placement, and whether the current flow was unidirectional or bidirectional. Subjects rated the location of the sensation, and its quality. Results The perceived center of stimulation moved toward the cathode, regardless of placement. This shift in subjective sensation was more prominent when the electricity was unidirectional. Additionally, more intense stimulation, as well as stimulation with a smaller electrode, caused greater perceived pain. Unidirectional stimulation was rated more painful when traveling from a large anode to a small cathode and less painful when traveling from a small anode to a large cathode. Finally, participants were more likely to perceive the electrical stimulation as moving towards a specific direction when the intensity was high than when it was low. Conclusions The intensity and location of sensations can be manipulated by varying the intensity, current direction, or geometry of electrodes. PMID:19092677

  9. Focal epithelial hyperplasia in a human immuno-deficiency virus patient treated with laser surgery.

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    Galanakis, Alexandros; Palaia, Gaspare; Tenore, Gianluca; Vecchio, Alessandro Del; Romeo, Umberto

    2014-07-16

    Focal epithelial hyperplasia (FEH), or Heck's disease, is a rare disease of the oral mucosa; it is mostly found in children or young adults who are immunosuppressed and who live in regions with low socioeconomic status. It is characterized by asymptomatic papules on the oral mucosa, gingiva, tongue, and lips. Healing can be spontaneous, and treatment is indicated if there are aesthetic or functional complications. Human papillomavirus, especially genotypes 13 and 32, has been associated with FEH and is detected in the majority of lesions. Histopathologically, FEH is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, and fusion and horizontal outgrowth of epithelial ridges. A 37-year-old male patient was referred to the Department of Oral and Maxillofacial Sciences at the Sapienza University of Rome, complaining of numerous exophytic lesions in his mouth. He stated that the lesions were not painful but he had experienced occasional bleeding after incidental masticatory trauma. He had received no previous treatment for the oral lesions. His medical history revealed that he was human immuno-deficiency virus positive and was a smoker with numerous, asymptomatic oral papules clinically and histologically corresponding to FEH. The labial and buccal mucosa were especially affected by lesions. Surgical treatment was performed using a 532-nm potassium titanyl phosphate laser (SmartLite, Deka, Florence, Italy) in continuous mode with a 300 μm fiber and power of 1.4 W (power density 1980.22 W/cm(2)). After anesthesia without vasoconstrictors, the lesions were tractioned with sutures or an Allis clamp and then completely excised. The lesions were preserved in 10% formalin for histological examination, which confirmed the clinical diagnosis of FEH. In this case, the laser allowed excellent control of bleeding, without postoperative sutures, and optimal wound healing.

  10. The parietal epithelial cell is crucially involved in human idiopathic focal segmental glomerulosclerosis.

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    Dijkman, Henry; Smeets, Bart; van der Laak, Jeroen; Steenbergen, Eric; Wetzels, Jack

    2005-10-01

    Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury encountered in human renal biopsies. Epithelial hyperplasia, which can be prominent in FSGS, has been attributed to dedifferentiation and proliferation of podocytes. Based on observations in a mouse model of FSGS, we pointed to the role of parietal epithelial cells (PECs). In the present study we investigated the relative role of PECs and podocytes in human idiopathic FSGS. We performed a detailed study of lesions from a patient with recurrent idiopathic FSGS by serial sectioning, marker analysis and three-dimensional reconstruction of glomeruli. We have studied the expression of markers for podocytes, PECs, mesangial cells, endothelium, and myofibroblasts. We also looked at proliferation and composition of the deposited extracellular matrix (ECM). We found that proliferating epithelial cells in FSGS lesions are negative for podocyte and macrophage markers, but stain for PEC markers. The composition of the matrix deposited by these cells is identical to Bowman's capsule. Our study demonstrates that PECs are crucially involved in the pathogenesis of FSGS lesions.

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

    Science.gov (United States)

    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. Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study.

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    Rajasekeran, Harindra; Reich, Heather N; Hladunewich, Michelle A; Cattran, Daniel; Lovshin, Julie A; Lytvyn, Yuliya; Bjornstad, Petter; Lai, Vesta; Tse, Josephine; Cham, Leslie; Majumder, Syamantak; Bowskill, Bridgit B; Kabir, M Golam; Advani, Suzanne L; Gibson, Ian W; Sood, Manish M; Advani, Andrew; Cherney, David Z I

    2018-03-01

    Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP). GFR (inulin) and renal plasma flow (para-aminohippurate), proteinuria, and BP were measured in patients with FSGS ( n = 10), and similar parameters were measured in subtotally nephrectomized (SNx) rats. In response to dapagliflozin, changes in GFR, renal plasma flow, and 24-h urine protein excretion were not statistically significant in humans or rats. Systolic BP (SBP) decreased in SNx rats (196 ± 26 vs. 165 ± 33 mmHg; P < 0.001), whereas changes were not statistically significant in humans (SBP 112.7 ± 8.5 to 112.8 ± 11.2 mmHg, diastolic BP 71.8 ± 6.5 to 69.6 ± 8.4 mmHg; P = not significant), although hematocrit increased (0.40 ± 0.05 to 0.42 ± 0.05%; P = 0.03). In archival kidney tissue from a separate patient cohort, renal parenchymal SGLT2 mRNA expression was decreased in individuals with FSGS compared with controls. Short-term treatment with the SGLT2i dapagliflozin did not modify renal hemodynamic function or attenuate proteinuria in humans or in experimental FSGS. This may be related to downregulation of renal SGLT2 expression. Studies examining the impact of SGLT2i on markers of kidney disease in patients with other causes of nondiabetic CKD are needed.

  13. Focal epithelial hyperplasia associated with human papillomavirus 13 and common human leukocyte antigen alleles in a Turkish family.

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    Akoğlu, Gülşen; Metin, Ahmet; Ceylan, Gülay Güleç; Emre, Selma; Akpolat, Demet; Süngü, Nuran

    2015-02-01

    Focal epithelial hyperplasia (FEH) is a rare and benign papillomatous disease of the oral cavity, which is closely associated with human papillomavirus (HPV) type 13 and 32. Genetic susceptibility to HPV infections are supported by recent studies involving the human leukocyte antigen system (HLA). In this report, we aimed to determine the clinicopathological features of a Turkish family with FEH and to detect the shared HLA DR and DQ types. HPV DNA typing of tissue samples and HLA determination from blood samples of four family members were performed by polymerase chain reaction. Histopathological examination of all patients revealed acanthotic papillomatous epidermis, koilocytes, apoptotic keratinocytes, and mitosoid bodies. HPV13 was detected by polymerase chain reaction. HLA DQA1*0501, HLA DQB1*0302, and HLA DRB1*11 alleles were common in all family members. HLA DRB1*04 was detected in three of them. This report is the first step for the investigation of involvement of HLA types in the pathogenesis of Turkish patients with FEH. © 2014 The International Society of Dermatology.

  14. Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

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    Liu, Na; Wang, Jiayi; Lei, Lei; Li, Yanzhong; Zhou, Min; Dan, Hongxia; Zeng, Xin; Chen, Qianming

    2013-05-01

    Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

  15. Focal myositis

    International Nuclear Information System (INIS)

    Kransdorf, M.J.; Temple, H.T.; Sweet, D.E.

    1998-01-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.)

  16. Focal myositis

    International Nuclear Information System (INIS)

    Galloway, H.R.; Dahlstrom, J.E.; Bennett, G.M.

    2001-01-01

    Focal myositis is a rare, benign focal inflammation of muscle. The lesion often presents as a mass that may be mistaken for a soft tissue sarcoma. This report describes the MRI and histopathological features of a case and illustrates how the diagnosis may be suspected on the basis of the MR findings. Copyright (2001) Blackwell Science Pty Ltd

  17. 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

    . 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...

  18. Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation

    DEFF Research Database (Denmark)

    Steffen, Anika; Ladwein, Markus; Dimchev, Georgi A

    2013-01-01

    can be potently stimulated by Rho GTPases of the Rac subfamily, but also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were...... filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac...

  19. Focal myositis

    Energy Technology Data Exchange (ETDEWEB)

    Kransdorf, M.J. [Saint Mary`s Hospital, Richmond, VA (United States). Dept. of Radiol.]|[Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Temple, H.T. [Department of Orthopedic Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia (United States)]|[Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Sweet, D.E. [Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)

    1998-05-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.) With 3 figs., 25 refs.

  20. 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

  1. Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase Chain Reaction Detection of Human Papillomavirus 13.

    Science.gov (United States)

    Brehm, Mary A; Gordon, Katie; Firan, Miahil; Rady, Peter; Agim, Nnenna

    2016-05-01

    Focal epithelial hyperplasia (FEH), or Heck's disease, is an uncommon benign proliferation of oral mucosa caused by the human papillomavirus (HPV), particularly subtypes 13 and 32. The disease typically presents in young Native American patients and is characterized by multiple asymptomatic papules and nodules on the oral mucosa, lips, tongue, and gingiva. The factors that determine susceptibility to FEH are unknown, but the ethnic and geographic distribution of FEH suggests that genetic predisposition, particularly having the human lymphocytic antigen DR4 type, may be involved in pathogenesis. We report a case of FEH with polymerase chain reaction detection of HPV13 in a healthy 11-year-old Hispanic girl and discuss the current understanding of disease pathogenesis, susceptibility, and treatment. © 2016 Wiley Periodicals, Inc.

  2. Simulated Microgravity Alters Actin Cytoskeleton and Integrin-Mediated Focal Adhesions of Cultured Human Mesenchymal Stromal Cells

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    Gershovich, P. M.; Gershovic, J. G.; Buravkova, L. B.

    2008-06-01

    Cytoskeletal alterations occur in several cell types including lymphocytes, glial cells, and osteoblasts, during spaceflight and under simulated microgravity (SMG) (3, 4). One potential mechanism for cytoskeletal gravisensitivity is disruption of extracellular matrix (ECM) and integrin interactions. Focal adhesions are specialized sites of cell-matrix interaction composed of integrins and the diversity of focal adhesion-associated cytoplasmic proteins including vinculin, talin, α-actinin, and actin filaments (4, 5). Integrins produce signals essential for proper cellular function, survival and differentiation. Therefore, we investigated the effects of SMG on F-actin cytoskeleton structure, vinculin focal adhesions, expression of some integrin subtypes and cellular adhesion molecules (CAMs) in mesenchymal stem cells derived from human bone marrow (hMSCs). Simulated microgravity was produced by 3D-clinostat (Dutch Space, Netherlands). Staining of actin fibers with TRITC-phalloidin showed reorganization even after 30 minutes of simulated microgravity. The increasing of cells number with abnormal F-actin was observed after subsequent terms of 3D-clinorotation (6, 24, 48, 120 hours). Randomization of gravity vector altered dimensional structure of stress fibers and resulted in remodeling of actin fibers inside the cells. In addition, we observed vinculin redistribution inside the cells after 6 hours and prolonged terms of clinorotation. Tubulin fibers in a contrast with F-actin and vinculin didn't show any reorganization even after long 3Dclinorotation (120 hours). The expression of integrin α2 increased 1,5-6-fold in clinorotated hMSCs. Also we observed decrease in number of VCAM-1-positive cells and changes in expression of ICAM-1. Taken together, our findings indicate that SMG leads to microfilament and adhesion alterations of hMSCs most probably associated with involvement of some integrin subtypes.

  3. Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol.

    Science.gov (United States)

    Donejko, Magdalena; Rysiak, Edyta; Galicka, Elżbieta; Terlikowski, Robert; Głażewska, Edyta Katarzyna; Przylipiak, Andrzej

    2017-01-01

    The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol.

  4. HAb18G/CD147 regulates vinculin-mediated focal adhesion and cytoskeleton organization in cultured human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Qiang Liang

    Full Text Available Focal adhesions (FAs, integrin-mediated macromolecular complexes located at the cell membrane extracellular interface, have been shown to regulate cell adhesion and migration. Our previous studies have indicated that HAb18G/CD147 (CD147 is involved in cytoskeleton reorganization and FA formation in human hepatocellular carcinoma (HCC cells. However, the precise mechanisms underlying these processes remain unclear. In the current study, we determined that CD147 was involved in vinculin-mediated FA focal adhesion formation in HCC cells. We also found that deletion of CD147 led to reduced vinculin-mediated FA areas (P<0.0001, length/width ratios (P<0.0001, and mean intensities (P<0.0001. CD147 promoted lamellipodia formation by localizing Arp2/3 to the leading edge of the cell. Deletion of CD147 significantly reduced the fluorescence (t1/2 recovery times (22.7±3.3 s of vinculin-mediated focal adhesions (P<0.0001. In cell-spreading assays, CD147 was found to be essential for dynamic focal adhesion enlargement and disassembly. Furthermore, the current data showed that CD147 reduced tyrosine phosphorylation in vinculin-mediated focal adhesions, and enhanced the accumulation of the acidic phospholipid phosphatidylinositol-4, 5-bisphosphate (PIP2. Together, these results revealed that CD147 is involved in vinculin-mediated focal adhesion formation, which subsequently promotes cytoskeleton reorganization to facilitate invasion and migration of human HCC cells.

  5. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection

    International Nuclear Information System (INIS)

    LaMuraglia, G.M.; Fischman, A.J.; Strauss, H.W.; Keech, F.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Rubin, R.H.

    1989-01-01

    The ability to diagnose and localize vascular graft infections has been a major challenge. Recent studies in animal models and humans with focal bacterial infection have shown that radiolabeled, polyclonal, human immunoglobulin G accumulates at the site of inflammation and can serve as the basis for an imaging technique. This study investigated this new technique for the diagnosis and localization of vascular graft infections. Twenty-five patients with suspected vascular infections involving grafts (22), atherosclerotic aneurysms (2), and subclavian vein thrombophlebitis (1) were studied. Gamma camera images of the suspected area were obtained between 5 and 48 hours after intravenous administration of 1.5 to 2.0 mCi (56 to 74 mBq) of indium 111-labeled, human, polyclonal immunoglobulin G. Scan results were interpreted without clinical information about the patient and were subsequently correlated with surgical findings, other imaging modalities, and/or clinical follow-up. In 10 of 10 patients found to have positive scan results, localized infections were confirmed at the involved sites. In 14 of 15 patients whose scan results were interpreted as negative, no vascular infections were identified at follow-up. The patient with false-negative results and recurrent bacteremia from an aortoduodenal fistula was found to have a negative scan outcome at a time when his disease was quiescent. These data suggest that nonspecific, human, indium 111-labeled immunoglobulin G scanning can be a useful noninvasive means of localizing vascular infections

  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. Manipulation of the response of human endothelial colony-forming cells by focal adhesion assembly using gradient nanopattern plates.

    Science.gov (United States)

    Cui, Long-Hui; Joo, Hyung Joon; Kim, Dae Hwan; Seo, Ha-Rim; Kim, Jung Suk; Choi, Seung-Cheol; Huang, Li-Hua; Na, Ji Eun; Lim, I-Rang; Kim, Jong-Ho; Rhyu, Im Joo; Hong, Soon Jun; Lee, Kyu Back; Lim, Do-Sun

    2018-01-01

    Nanotopography plays a pivotal role in the regulation of cellular responses. Nonetheless, little is known about how the gradient size of nanostructural stimuli alters the responses of endothelial progenitor cells without chemical factors. Herein, the fabrication of gradient nanopattern plates intended to mimic microenvironment nanotopography is described. The gradient nanopattern plates consist of nanopillars of increasing diameter ranges [120-200 nm (GP 120/200), 200-280 nm (GP 200/280), and 280-360 nm (GP 280/360)] that were used to screen the responses of human endothelial colony-forming cells (hECFCs). Nanopillars with a smaller nanopillar diameter caused the cell area and perimeter of hECFCs to decrease and their filopodial outgrowth to increase. The structure of vinculin (a focal adhesion marker in hECFCs) was also modulated by nanostructural stimuli of the gradient nanopattern plates. Moreover, Rho-associated protein kinase (ROCK) gene expression was significantly higher in hECFCs cultured on GP 120/200 than in those on flat plates (no nanopillars), and ROCK suppression impaired the nanostructural-stimuli-induced vinculin assembly. These results suggest that the gradient nanopattern plates generate size-specific nanostructural stimuli suitable for manipulation of the response of hECFCs, in a process dependent on ROCK signaling. This is the first evidence of size-specific nanostructure-sensing behavior of hECFCs. Nano feature surfaces are of growing interest as materials for a controlled response of various cells. In this study, we successfully fabricated gradient nanopattern plates to manipulate the response of blood-derived hECFCs without any chemical stimulation. Interestingly, we find that the sensitive nanopillar size for manipulation of hECFCs is range between 120 nm and 200 nm, which decreased the area and increased the filopodial outgrowth of hECFCs. Furthermore, we only modulate the nanopillar size to increase ROCK expression can be an

  10. Companies' human capital required for collaboration

    DEFF Research Database (Denmark)

    Albats, Ekaterina; Bogers, Marcel; Podmetina, Daria

    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......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...... with universities. Analysing the results of the survey among over 500 company managers we define the universal employees’ skills required for company’ successful collaborations with external stakeholders. Then through analysing qualitative interviews data we distinguish between these skills and capabilities...

  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. Inhibition of Focal Adhesion Kinase Signaling by Integrin α6β1 Supports Human Pluripotent Stem Cell Self-Renewal.

    Science.gov (United States)

    Villa-Diaz, Luis G; Kim, Jin Koo; Laperle, Alex; Palecek, Sean P; Krebsbach, Paul H

    2016-07-01

    Self-renewal of human embryonic stem cells and human induced pluripotent stem cells (hiPSCs)-known as pluripotent stem cells (PSC)-is influenced by culture conditions, including the substrate on which they are grown. However, details of the molecular mechanisms interconnecting the substrate and self-renewal of these cells remain unclear. We describe a signaling pathway in hPSCs linking self-renewal and expression of pluripotency transcription factors to integrin α6β1 and inactivation of focal adhesion kinase (FAK). Disruption of this pathway results in hPSC differentiation. In hPSCs, α6β1 is the dominant integrin and FAK is not phosphorylated at Y397, and thus, it is inactive. During differentiation, integrin α6 levels diminish and Y397 FAK is phosphorylated and activated. During reprogramming of fibroblasts into iPSCs, integrin α6 is upregulated and FAK is inactivated. Knockdown of integrin α6 and activation of β1 integrin lead to FAK phosphorylation and reduction of Nanog, Oct4, and Sox2, suggesting that integrin α6 functions in inactivation of integrin β1 and FAK signaling and prevention of hPSC differentiation. The N-terminal domain of FAK, where Y397 is localized, is in the nuclei of hPSCs interacting with Oct4 and Sox2, and this immunolocalization is regulated by Oct4. hPSCs remodel the extracellular microenvironment and deposit laminin α5, the primary ligand of integrin α6β1. Knockdown of laminin α5 resulted in reduction of integrin α6 expression, phosphorylation of FAK and decreased Oct4. In conclusion, hPSCs promote the expression of integrin α6β1, and nuclear localization and inactivation of FAK to supports stem cell self-renewal. Stem Cells 2016;34:1753-1764. © 2016 AlphaMed Press.

  13. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

    Directory of Open Access Journals (Sweden)

    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  14. Air humidity requirements for human comfort

    DEFF Research Database (Denmark)

    Toftum, Jørn; Fanger, Povl Ole

    1999-01-01

    level near 100% rh. For respiratory comfort are the requirements much more stringent and results in lower permissible indoor air humidities. Compared with the upper humidity limit specified in existing thermal comfort standards, e.g. ASHRAE Addendum 55a, the humidity limit based on skin humidity......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...

  15. Systems considerations in mosaic focal planes

    Science.gov (United States)

    White, K. P., III

    1983-08-01

    Two key reasons for pursuing the development of mosaic focal planes are reviewed and it is shown that rapid frame repetition rate is the only requirement that can be solved no other way than through mosaic focal planes. With the view that spaceborne mosaic focal plane sensors are necessarily 'smart sensors' requiring a lot of onboard processing just to function, it is pointed out that various artificial intelligence techniques may be the most appropriate to incorporate in the data processing. Finally, a novel mosaic focal plane design is proposed, termed a virtual mosaic focal plane, in response to other system constraints.

  16. 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.

  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. 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...

  1. Human Systems Integration: Requirements and Functional Decomposition

    Science.gov (United States)

    Berson, Barry; Gershzohn, Gary; Boltz, Laura; Wolf, Russ; Schultz, Mike

    2005-01-01

    This deliverable was intended as an input to the Access 5 Policy and Simulation Integrated Product Teams. This document contains high-level pilot functionality for operations in the National Airspace System above FL430. Based on the derived pilot functions the associated pilot information and control requirements are given.

  2. Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.

    Science.gov (United States)

    Nomura, Sadahiro; Fujii, Masami; Inoue, Takao; He, Yeting; Maruta, Yuichi; Koizumi, Hiroyasu; Suehiro, Eiichi; Imoto, Hirochika; Ishihara, Hideyuki; Oka, Fumiaki; Matsumoto, Mishiya; Owada, Yuji; Yamakawa, Takeshi; Suzuki, Michiyasu

    2014-05-01

    Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy. Nine patients underwent FBC at 15°C for 30 min prior to cortical resection (n = 6) or hippocampectomy (n = 3). Measurement of metabolites and CBF, as well as electrocorticography (ECoG), was performed. Epileptic discharge (ED), as observed by ECoG, disappeared in the cooling period and reappeared in the rewarming period. Glu concentrations were high during the precooling period and were reduced to 51.2% during the cooling period (p = 0.025). Glycerol levels showed a similar decrease (p = 0.028). Lactate concentration was high during the precooling period and was reduced during the cooling period (21.3% decrease; p = 0.005). Glucose and pyruvate levels were maintained throughout the procedure. Changes in CBF were parallel to those observed by ECoG. FBC reduced EDs and concentrations of Glu and glycerol. This demonstrates the neuroprotective effect of FBC. Our findings confirm that FBC is a reasonable and optimal treatment option for patients with intractable epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  3. 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.

  4. 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...

  5. Safety Requirements and Modern Technical Requirements in Human Information Systems in Amman Hotels

    OpenAIRE

    Farouq Ahmad Alazzam; Sattam Rakan Allahawiah; Mohammad Nayef Alsarayreh; Kafa Hmoud Abdallah al Nawaiseh

    2015-01-01

    This study aimed to demonstrate the availability of Safety requirements and modern technical requirements in human information systems in Amman hotels. an the most important results of this study is the availability of security and safety requirements in human information systems In Amman hotels and The adequacy of the information that it provided .and show that all departments are not connected by appropriate and effective communication networks in adequate form . Also sophisticated operatin...

  6. Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: Comparison with gallium-67 citrate and technetium-99m-labeled albumin

    International Nuclear Information System (INIS)

    Rubin, R.H.; Fischman, A.J.; Needleman, M.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Hansen, W.P.; Kramer, P.B.; Strauss, H.W.

    1989-01-01

    The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125 I or 111 In was compared to that of [ 67 Ga]citrate and [ 99m Tc]albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, [ 111 In]IgG showed greater accumulation at the lesion than [ 99m Tc]HSA (p less than 0.01). Both [ 125 I]IgG and [ 111 In]IgG showed greater accumulation than [ 67 Ga]citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of [ 67 Ga]citrate or [ 99m Tc]HSA (p less than 0.01). At all imaging times, [ 67 Ga]citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, [ 111 In]IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG

  7. Focal dermal hypoplasia without focal dermal hypoplasia

    NARCIS (Netherlands)

    Contreras-Capetillo, Silvina N.; Lombardi, Maria Paola; Pinto-Escalante, Doris; Hennekam, Raoul C.

    2014-01-01

    Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome) is an X-linked dominant disorder affecting mainly tissues of ectodermal and mesodermal origin. The phenotype is characterized by hypoplastic linear skin lesions, eye malformations, hair and teeth anomalies, and multiple limbs malformations. The

  8. 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.

  9. 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.

  10. 3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226

    International Nuclear Information System (INIS)

    Hehlgans, Stephanie; Lange, Inga; Eke, Iris; Cordes, Nils

    2009-01-01

    Background and purpose: Focal adhesion kinase (FAK), a main player in integrin signaling and survival, is frequently overexpressed in human cancers and therefore postulated as potential target in cancer therapy. The aim of this study was to evaluate the radiosensitizing potential of the FAK inhibitor TAE226 in three-dimensional (3D) tumor cell cultures. Materials and methods: Head and neck squamous cell carcinoma (HNSCC) cells (FaDu, UT-SCC15, UT-SCC45), lung cancer cells (A549), colorectal carcinoma cells (DLD-1, HCT-116) and pancreatic tumor cells (MiaPaCa2, Panc1) were treated with different concentrations of TAE226 (0-1 μm; 1 or 24 h) without or in combination with irradiation (0-6 Gy, X-ray, single dose). Subsequently, 3D clonogenic survival assays (laminin-rich extracellular matrix) and Western blotting (expression/phosphorylation, e.g. FAK, Akt, ERK1/2) were performed. Results: All investigated 3D cell cultures showed a dose-dependent reduction in clonogenic survival by TAE226. Intriguingly, TAE226 only significantly radiosensitized 3D HNSCC cell cultures accompanied by a pronounced dephosphorylation of FAK, Akt and ERK1/2. Conclusions: Our data demonstrate TAE226 as potent FAK inhibitor that enhances the cellular radiosensitivity particularly of HNSCC cells grown in a 3D cell culture model. Future in vitro and in vivo investigations will clarify, to which extent this approach might be clinically relevant for radiotherapy of HNSCC.

  11. Focal lesions in the central nervous system

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

    1980-01-01

    This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

  12. Working group 4B - human intrusion: Design/performance requirements

    International Nuclear Information System (INIS)

    Channell, J.

    1993-01-01

    There is no summary of the progress made by working group 4B (Human Intrusion: Design/performance Requirements) during the Electric Power Research Institute's EPRI Workshop on the technical basis of EPA HLW Disposal Criteria, March 1993. This group was to discuss the waste disposal standard, 40 CFR Part 191, in terms of the design and performance requirements of human intrusion. Instead, because there were so few members, they combined with working group 4A and studied the three-tier approach to evaluating postclosure performance

  13. 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.

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

    International Nuclear Information System (INIS)

    Kwak, Sang Log; Park, Chan Woo; Shin, Seung Ryoung

    2008-08-01

    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

  15. CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase.

    Science.gov (United States)

    Nishibaba, Rie; Higashi, Yuko; Su, Juan; Furukawa, Tatsuhiko; Kawai, Kazuhiro; Kanekura, Takuro

    2012-01-01

    CD147/basigin, highly expressed on the surface of malignant tumor cells including malignant melanoma (MM) cells, plays a critical role in the invasiveness and metastasis of MM. Metastasis is an orchestrated process comprised of multiple steps including adhesion and invasion. Integrin, a major adhesion molecule, co-localizes with CD147/basigin on the cell surface. Using the human MM cell line A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin is involved in adhesion in association with integrin. CD147/basigin was knocked-down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell adhesion was evaluated by adhesion assay on matrix-coated plates. The localization of integrin was inspected under a confocal microscope and the expression and phosphorylation of focal adhesion kinase (FAK), a downstream kinase of integrin, were examined by western blot analysis. Silencing of CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397. Integrin identified on the surface of parental cells was distributed in a speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in morphological changes from a round to a polygonal shape with pseudopodial protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their adhesiveness to collagen I and IV. Our results suggest that CD147/basigin regulates the adhesion of MM cells to extracellular matrices and of integrin β1 signaling via the phosphorylation of FAK. © 2011 Japanese Dermatological Association.

  16. Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment.

    Science.gov (United States)

    Gornicka-Pawlak, El Bieta; Janowski, Miroslaw; Habich, Aleksandra; Jablonska, Anna; Drela, Katarzyna; Kozlowska, Hanna; Lukomska, Barbara; Sypecka, Joanna; Domanska-Janik, Krystyna

    2011-01-01

    The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.

  17. Matriptase is required for the active form of hepatocyte growth factor induced Met, focal adhesion kinase and protein kinase B activation on neural stem/progenitor cell motility.

    Science.gov (United States)

    Fang, Jung-Da; Lee, Sheau-Ling

    2014-07-01

    Hepatocyte growth factor (HGF) is a chemoattractant and inducer for neural stem/progenitor (NS/P) cell migration. Although the type II transmembrane serine protease, matriptase (MTP) is an activator of the latent HGF, MTP is indispensable on NS/P cell motility induced by the active form of HGF. This suggests that MTP's action on NS/P cell motility involves mechanisms other than proteolytic activation of HGF. In the present study, we investigate the role of MTP in HGF-stimulated signaling events. Using specific inhibitors of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) or focal adhesion kinase (FAK), we demonstrated that in NS/P cells HGF-activated c-Met induces PI3k-Akt signaling which then leads to FAK activation. This signaling pathway ultimately induces MMP2 expression and NS/P cell motility. Knocking down of MTP in NS/P cells with specific siRNA impaired HGF-stimulation of c-Met, Akt and FAK activation, blocked HGF-induced production of MMP2 and inhibited HGF-stimulated NS/P cell motility. MTP-knockdown NS/P cells cultured in the presence of recombinant protein of MTP protease domain or transfected with the full-length wild-type but not the protease-defected MTP restored HGF-responsive events in NS/P cells. In addition to functioning as HGF activator, our data revealed novel function of MTP on HGF-stimulated c-Met signaling activation. Copyright © 2014. Published by Elsevier B.V.

  18. Focal retinal phlebitis.

    Science.gov (United States)

    Hoang, Quan V; Freund, K Bailey; Klancnik, James M; Sorenson, John A; Cunningham, Emmett T; Yannuzzi, Lawrence A

    2012-01-01

    To report three cases of solitary, focal retinal phlebitis. An observational case series. Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion.

  19. Recurrent Bilateral Focal Myositis.

    Science.gov (United States)

    Nagafuchi, Hiroko; Nakano, Hiromasa; Ooka, Seido; Takakuwa, Yukiko; Yamada, Hidehiro; Tadokoro, Mamoru; Shimojo, Sadatomo; Ozaki, Shoichi

    This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years.

  20. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  1. 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

  2. SNAP Satellite Focal Plane Development

    International Nuclear Information System (INIS)

    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.

    2003-01-01

    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 and 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

  3. Focal cortical dysplasia – review

    International Nuclear Information System (INIS)

    Kabat, Joanna; Król, Przemysław

    2012-01-01

    Focal cortical dysplasia is a malformation of cortical development, which is the most common cause of medically refractory epilepsy in the pediatric population and the second/third most common etiology of medically intractable seizures in adults. Both genetic and acquired factors are involved in the pathogenesis of cortical dysplasia. Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed – from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized. Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe. Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children. In this type, more extensive changes occur outside the temporal lobe with predilection for the frontal lobes. New type III is one of the above dysplasias with associated another principal lesion as hippocampal sclerosis, tumor, vascular malformation or acquired pathology during early life. Brain MRI imaging shows abnormalities in the majority of type II dysplasias and in only some of type I cortical dysplasias. The most common findings on MRI imaging include: focal cortical thickening or thinning, areas of focal brain atrophy, blurring of the gray-white junction, increased signal on T2- and FLAIR-weighted images in the gray and subcortical white matter often tapering toward the ventricle. On the basis of the MRI findings, it is possible to differentiate between type I and type II cortical dysplasia. A complete resection of the epileptogenic zone is required for seizure-free life. MRI imaging is very helpful to identify those patients who are likely to benefit from surgical treatment in a group of patients with drug-resistant epilepsy. However, in type I cortical dysplasia, MR imaging is often normal, and also in both

  4. Human Resources Requirements for New Nuclear Power Programs

    International Nuclear Information System (INIS)

    Goodnight, Charles T.

    2014-01-01

    Summary: Planning to Meet HR Requirements for New Nuclear Power Programs Must Begin Early. Many years of preparation are required before the “Right Number of the Right People” … will be … “In the Right Place at the Right Time”. • Seven key steps which must be taken include: 1) Identify detailed Human Resources requirements, based on the selected site and reactor design; 2) Conduct an assessment of national capacity to develop and/or provide those resources; 3) Conduct a Gap Analysis to determine what additional steps will be needed to fill any capacity shortfalls; 4) Develop initial and recurring recruiting and training plans; 5) Begin recruiting and training; 6) Review and adjust as personnel move and/or leave; 7) Ensure adequate relationships are in place for sources of future recruiting

  5. 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.

  6. Models and data requirements for human reliability analysis

    International Nuclear Information System (INIS)

    1989-03-01

    It has been widely recognised for many years that the safety of the nuclear power generation depends heavily on the human factors related to plant operation. This has been confirmed by the accidents at Three Mile Island and Chernobyl. Both these cases revealed how human actions can defeat engineered safeguards and the need for special operator training to cover the possibility of unexpected plant conditions. The importance of the human factor also stands out in the analysis of abnormal events and insights from probabilistic safety assessments (PSA's), which reveal a large proportion of cases having their origin in faulty operator performance. A consultants' meeting, organized jointly by the International Atomic Energy Agency (IAEA) and the International Institute for Applied Systems Analysis (IIASA) was held at IIASA in Laxenburg, Austria, December 7-11, 1987, with the aim of reviewing existing models used in Probabilistic Safety Assessment (PSA) for Human Reliability Analysis (HRA) and of identifying the data required. The report collects both the contributions offered by the members of the Expert Task Force and the findings of the extensive discussions that took place during the meeting. Refs, figs and tabs

  7. 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.

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

    International Nuclear Information System (INIS)

    Roelofs, Ferry; Flore, Massimo; Estorff, Ulrik von

    2017-01-01

    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.

  9. Cognition and procedure representational requirements for predictive human performance models

    Science.gov (United States)

    Corker, K.

    1992-01-01

    Models and modeling environments for human performance are becoming significant contributors to early system design and analysis procedures. Issues of levels of automation, physical environment, informational environment, and manning requirements are being addressed by such man/machine analysis systems. The research reported here investigates the close interaction between models of human cognition and models that described procedural performance. We describe a methodology for the decomposition of aircrew procedures that supports interaction with models of cognition on the basis of procedures observed; that serves to identify cockpit/avionics information sources and crew information requirements; and that provides the structure to support methods for function allocation among crew and aiding systems. Our approach is to develop an object-oriented, modular, executable software representation of the aircrew, the aircraft, and the procedures necessary to satisfy flight-phase goals. We then encode in a time-based language, taxonomies of the conceptual, relational, and procedural constraints among the cockpit avionics and control system and the aircrew. We have designed and implemented a goals/procedures hierarchic representation sufficient to describe procedural flow in the cockpit. We then execute the procedural representation in simulation software and calculate the values of the flight instruments, aircraft state variables and crew resources using the constraints available from the relationship taxonomies. The system provides a flexible, extensible, manipulative and executable representation of aircrew and procedures that is generally applicable to crew/procedure task-analysis. The representation supports developed methods of intent inference, and is extensible to include issues of information requirements and functional allocation. We are attempting to link the procedural representation to models of cognitive functions to establish several intent inference methods

  10. Model-based human reliability analysis: prospects and requirements

    International Nuclear Information System (INIS)

    Mosleh, A.; Chang, Y.H.

    2004-01-01

    Major limitations of the conventional methods for human reliability analysis (HRA), particularly those developed for operator response analysis in probabilistic safety assessments (PSA) of nuclear power plants, are summarized as a motivation for the need and a basis for developing requirements for the next generation HRA methods. It is argued that a model-based approach that provides explicit cognitive causal links between operator behaviors and directly or indirectly measurable causal factors should be at the core of the advanced methods. An example of such causal model is briefly reviewed, where due to the model complexity and input requirements can only be currently implemented in a dynamic PSA environment. The computer simulation code developed for this purpose is also described briefly, together with current limitations in the models, data, and the computer implementation

  11. Models of Human Information Requirements: "When Reasonable Aiding Systems Disagree"

    Science.gov (United States)

    Corker, Kevin; Pisanich, Gregory; Shafto, Michael (Technical Monitor)

    1994-01-01

    Aircraft flight management and Air Traffic Control (ATC) automation are under development to maximize the economy of flight and to increase the capacity of the terminal area airspace while maintaining levels of flight safety equal to or better than current system performance. These goals are being realized by the introduction of flight management automation aiding and operations support systems on the flight deck and by new developments of ATC aiding systems that seek to optimize scheduling of aircraft while potentially reducing required separation and accounting for weather and wake vortex turbulence. Aiding systems on both the flight deck and the ground operate through algorithmic functions on models of the aircraft and of the airspace. These models may differ from each other as a result of variations in their models of the immediate environment. The resultant flight operations or ATC commands may differ in their response requirements (e.g. different preferred descent speeds or descent initiation points). The human operators in the system must then interact with the automation to reconcile differences and resolve conflicts. We have developed a model of human performance including cognitive functions (decision-making, rule-based reasoning, procedural interruption recovery and forgetting) that supports analysis of the information requirements for resolution of flight aiding and ATC conflicts. The model represents multiple individuals in the flight crew and in ATC. The model is supported in simulation on a Silicon Graphics' workstation using Allegro Lisp. Design guidelines for aviation automation aiding systems have been developed using the model's specification of information and team procedural requirements. Empirical data on flight deck operations from full-mission flight simulation are provided to support the model's predictions. The paper describes the model, its development and implementation, the simulation test of the model predictions, and the empirical

  12. Focal myositis: A review.

    Science.gov (United States)

    Devic, P; Gallay, L; Streichenberger, N; Petiot, P

    2016-11-01

    Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Human Resources Training Requirement on NPP Operation and Maintenance

    International Nuclear Information System (INIS)

    Nurlaila; Yuliastuti

    2009-01-01

    This paper discussed the human resources requirement on Nuclear Power Plant (NPP) operation and maintenance (O&M) phase related with the training required for O&M personnel. In addition, this paper also briefly discussed the availability of training facilities domestically include with some suggestion to develop the training facilities intended for the near future time in Indonesia. This paper was developed under the assumptions that Indonesia will build twin unit of NPP with capacity 1000 MWe for each using the turnkey contract method. The total of NPP O&M personnel were predicted about 692 peoples which consists of 42 personnel located in the head quarter and the rest 650 people work at NPP site. Up until now, Indonesia had the experience on operating and maintaining the nonnuclear power plant and several research reactors namely Kartini Reactor Yogyakarta, Triga Mark II Reactor Bandung, and GA Siwabessy Reactor Serpong. Beside that, experience on operating and maintaining the NPP in other countries would act as one of the reference to Indonesia in formulating an appropriate strategy to develop NPP human resources particularly in O&M phases. Education and training development program could be done trough the cooperation with vendor candidates. (author)

  14. Extensive Focal Epithelial Hyperplasia: A Case Report.

    Science.gov (United States)

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  15. Acute termination of human atrial fibrillation by identification and catheter ablation of localized rotors and sources: first multicenter experience of focal impulse and rotor modulation (FIRM) ablation.

    Science.gov (United States)

    Shivkumar, Kalyanam; Ellenbogen, Kenneth A; Hummel, John D; Miller, John M; Steinberg, Jonathan S

    2012-12-01

    Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. We prospectively enrolled the first (n = 14, 11 males) consecutive patients undergoing FIRM-guided ablation for persistent (n = 11) and paroxysmal AF at 5 centers. A 64-pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10% cycle length prolongation). Conventional ablation was performed only after FIRM-guided ablation. Twelve out of 14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9 ± 0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM-guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n = 8 (4.9 ± 3.9 minutes at the primary source), and organization in n = 4. Total FIRM time for all patients was 12.3 ± 8.6 minutes. FIRM-guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM-guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. © 2012 Wiley Periodicals, Inc.

  16. 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

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

    International Nuclear Information System (INIS)

    Ogilvie, Gina S; Cook, Darrel A; Mei, Wendy; Stuart, Gavin CE; Franco, Eduardo L; Coldman, Andrew J; Niekerk, Dirk J van; Krajden, Mel; Martin, Ruth E; Ehlen, Thomas G; Ceballos, Kathy; Peacock, Stuart J; Smith, Laurie W; Kan, Lisa

    2010-01-01

    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. 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 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. International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

  18. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Directory of Open Access Journals (Sweden)

    D.J. O'Rourke

    2014-01-01

    Full Text Available Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD and discuss the literature on this topic.

  19. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Science.gov (United States)

    O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  20. 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.

  1. 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.

  2. Establishment of human papillomavirus infection requires cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Dohun Pyeon

    2009-02-01

    Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

  3. Deriving human resource requirements for new nuclear plants

    International Nuclear Information System (INIS)

    Goodnight, Ch.T.

    2007-01-01

    For those contemplating the deployment of a new nuclear plant, critical issues include the development of the operational staff and its organization. This paper will discuss the key elements of deriving an appropriate staff plan for steady state operations. There are five areas that must be analyzed, and each area has unique requirements. These key areas are 1) Operations, 2) Engineering, 3) Maintenance, 4) Regulatory/Oversight, and 5) Site Support. After the analysis for each area is complete, and the human resource requirements are identified, an organizational structure must be developed to support the necessary management, potential centralization, and appropriate functional alignments for effective and safe plant operation. Four organizational design principals have been defined. The first design principal relates to the organizational structure: no more than 7 layers of management between an individual contributor and the senior nuclear manager in the NPP. The second design principal relates to the grouping of activities in order to ensure appropriate management of related or supporting activities. The third design principal relates to out-sourcing support activities when these activities comply with particular conditions for instance when they are not mission critical to day-to day plant operations. The fourth design principal relates to the centralization of some activities when there is more than one NPP operated by the same parent company

  4. The Department of Defense's Civilian Human Capital Strategic Plan Does Not Meet Most Statutory Requirements

    National Research Council Canada - National Science Library

    Farrell, Brenda S

    2008-01-01

    To examine the extent to which DOD's civilian human capital strategic plan addresses congressional reporting requirements, we obtained and analyzed the "Department of Defense Civilian Human Capital...

  5. 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.

  6. 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

  7. Early vision and focal attention

    Science.gov (United States)

    Julesz, Bela

    1991-07-01

    At the thirty-year anniversary of the introduction of the technique of computer-generated random-dot stereograms and random-dot cinematograms into psychology, the impact of the technique on brain research and on the study of artificial intelligence is reviewed. The main finding-that stereoscopic depth perception (stereopsis), motion perception, and preattentive texture discrimination are basically bottom-up processes, which occur without the help of the top-down processes of cognition and semantic memory-greatly simplifies the study of these processes of early vision and permits the linking of human perception with monkey neurophysiology. Particularly interesting are the unexpected findings that stereopsis (assumed to be local) is a global process, while texture discrimination (assumed to be a global process, governed by statistics) is local, based on some conspicuous local features (textons). It is shown that the top-down process of "shape (depth) from shading" does not affect stereopsis, and some of the models of machine vision are evaluated. The asymmetry effect of human texture discrimination is discussed, together with recent nonlinear spatial filter models and a novel extension of the texton theory that can cope with the asymmetry problem. This didactic review attempts to introduce the physicist to the field of psychobiology and its problems-including metascientific problems of brain research, problems of scientific creativity, the state of artificial intelligence research (including connectionist neural networks) aimed at modeling brain activity, and the fundamental role of focal attention in mental events.

  8. 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

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

    International Nuclear Information System (INIS)

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R.

    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

  10. The dispersion-focalization theory of sound systems

    Science.gov (United States)

    Schwartz, Jean-Luc; Abry, Christian; Boë, Louis-Jean; Vallée, Nathalie; Ménard, Lucie

    2005-04-01

    The Dispersion-Focalization Theory states that sound systems in human languages are shaped by two major perceptual constraints: dispersion driving auditory contrast towards maximal or sufficient values [B. Lindblom, J. Phonetics 18, 135-152 (1990)] and focalization driving auditory spectra towards patterns with close neighboring formants. Dispersion is computed from the sum of the inverse squared inter-spectra distances in the (F1, F2, F3, F4) space, using a non-linear process based on the 3.5 Bark critical distance to estimate F2'. Focalization is based on the idea that close neighboring formants produce vowel spectra with marked peaks, easier to process and memorize in the auditory system. Evidence for increased stability of focal vowels in short-term memory was provided in a discrimination experiment on adult French subjects [J. L. Schwartz and P. Escudier, Speech Comm. 8, 235-259 (1989)]. A reanalysis of infant discrimination data shows that focalization could well be the responsible for recurrent discrimination asymmetries [J. L. Schwartz et al., Speech Comm. (in press)]. Recent data about children vowel production indicate that focalization seems to be part of the perceptual templates driving speech development. The Dispersion-Focalization Theory produces valid predictions for both vowel and consonant systems, in relation with available databases of human languages inventories.

  11. 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...

  12. 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.

  13. Diagnostic imaging in focal epilepsy

    International Nuclear Information System (INIS)

    Zlatareva, D.

    2013-01-01

    Focal epilepsies account for 60% of all seizure disorders worldwide. In this review the classic and new classification system of epileptic seizures and syndromes as well as genetic forms are discussed. Magnetic resonance (MR) is the technique of choice for diagnostic imaging in focal epilepsy because of its sensitivity and high tissue contrast. The review is focused on the lack of consensus of imaging protocols and reported findings in refractory epilepsy. The most frequently encountered MRI findings in epilepsy are reported and their imaging characteristics are depicted. Diagnosis of hippocampal sclerosis and malformations of cortical development as two major causes of refractory focal epilepsy is described in details. Some promising new techniques as positron emission tomography computed tomography (PET/CT) and MR and PET/CT fusion are briefly discussed. Also the relevance of adequate imaging in focal epilepsy, some practical points in imaging interpretation and differential diagnosis are highlighted. (author)

  14. Medical and technology requirements for human solar system exploration missions

    Science.gov (United States)

    Nicogossian, Arnauld; Harris, Leonard; Couch, Lana; Sulzman, Frank; Gaiser, Karen

    1989-01-01

    Measures that need to be taken to cope with the health problems posed by zero gravity and radiation in manned solar system exploration missions are discussed. The particular systems that will be used aboard Space Station Freedom are addressed, and relevant human factors problems are examined. The development of a controlled ecological life support system is addressed.

  15. 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.

  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. DEPDC5 takes a second hit in familial focal epilepsy.

    Science.gov (United States)

    Anderson, Matthew P

    2018-04-30

    Loss-of-function mutations in a single allele of the gene encoding DEP domain-containing 5 protein (DEPDC5) are commonly linked to familial focal epilepsy with variable foci; however, a subset of patients presents with focal cortical dysplasia that is proposed to result from a second-hit somatic mutation. In this issue of the JCI, Ribierre and colleagues provide several lines of evidence to support second-hit DEPDC5 mutations in this disorder. Moreover, the authors use in vivo, in utero electroporation combined with CRISPR-Cas9 technology to generate a murine model of the disease that recapitulates human manifestations, including cortical dysplasia-like changes, focal seizures, and sudden unexpected death. This study provides important insights into familial focal epilepsy and provides a preclinical model for evaluating potential therapies.

  18. DNA repair synthesis in human fibroblasts requires DNA polymerase delta

    International Nuclear Information System (INIS)

    Nishida, C.; Reinhard, P.; Linn, S.

    1988-01-01

    When UV-irradiated cultured diploid human fibroblasts were permeabilized with Brij-58 then separated from soluble material by centrifugation, conservative DNA repair synthesis could be restored by a soluble factor obtained from the supernatant of similarly treated HeLa cells. Extensive purification of this factor yielded a 10.2 S, 220,000-dalton polypeptide with the DNA polymerase and 3'- to 5'-exonuclease activities reported for DNA polymerase delta II. Monoclonal antibody to KB cell DNA polymerase alpha, while binding to HeLa DNA polymerase alpha, did not bind to the HeLa DNA polymerase delta. Moreover, at micromolar concentrations N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate (BuPdGTP) and 2-(p-n-butylanilino)-2'-deoxyadenosine 5'-triphosphate (BuAdATP) were potent inhibitors of DNA polymerase alpha, but did not inhibit the DNA polymerase delta. Neither purified DNA polymerase alpha nor beta could promote repair DNA synthesis in the permeabilized cells. Furthermore, under conditions which inhibited purified DNA polymerase alpha by greater than 90%, neither monoclonal antibodies to DNA polymerase alpha, BuPdGTP, nor BuAdATP was able to inhibit significantly the DNA repair synthesis mediated by the DNA polymerase delta. Thus, it appears that a major portion of DNA repair synthesis induced by UV irradiation might be catalyzed by DNA polymerase delta. When xeroderma pigmentosum human diploid fibroblasts were utilized, DNA repair synthesis dependent upon ultraviolet light could be restored by addition of both T4 endonuclease V and DNA polymerase delta, but not by addition of either one alone

  19. Characterization of LIL laser UV focal spot

    International Nuclear Information System (INIS)

    Mangeant, M.; Dubois, J.L.; Behar, G.; Arroyo, P.; Durand, V.; Lahonde, C.

    2006-01-01

    One way to get the fusion of hydrogen in laboratory consists in heating and compressing a DT fuel capsule by using a laser. To reach this aim requires a new generation of high power laser facility. Cea (French board for atomic energy) is developing for this purpose a new 240 laser line facility, the LMJ facility. The LIL which is the prototype of four LMJ laser lines is operational now. In order to confirm the technical choices, a systematic characterization of LIL was carried out. A particular effort has been provided to measure the 3ω high energy focal spot (1.5 kJ/700 ps and 5 ns for one beam) and the synchronization of laser beams onto the target, which are key issues for the plasma production. An experimental device, SAT-3ω (a 3ω laser focal spot analysis) has been designed to perform these measures. That diagnostic which is located at the end of the laser lines delivered its first results during the 2004 quadruplet qualification campaigns. The near field imaging showed no diaphony and vignetting. Low power spots allowed us to control we had no ghost. The energy measurement quality showed the photometric transfer function was perfectly known. Our caustic image are given with an average dynamic range of 800, a spatial resolution of 10 μm and diameter accuracy about 1% for 50% and 3% for 90% of encircled energy. The high energy focal spot diameters are in agreement with low and very low energy diameters. The phase plate and 14 GHz effects are similar to what we had expected. For a laser shot completed with a continuous phase plate at 14 GHz, and for an energy level of 1.5 kJ per beam at 351 nm, the focal beam diameter at 3% of the peak level is (875 ± 45) μm

  20. 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.

  1. Cost of quality assurance in radiotherapy: human and material requirements

    International Nuclear Information System (INIS)

    Caudrelier, V.; Garcia, R.; Chauvet, B.; Bourhis, J.

    2005-01-01

    In 2004, three new important laws were passed concerning radiotherapy services. The first two concerns the internal and external quality control of linear accelerators and the last concerns the role of the medical physicist, whose presence was made mandatory during the whole length of the treatments. These laws, which aim to improve the quality and the security of treatments, represent an increase in price that we have calculated, and which prevents them being implemented, as a joint study realised by the SFRO and the SFPM has shown. The cost of quality in radiotherapy requires investment in material and manpower and improvement in availability of the accelerators which entails a complete reorganization of the services. Cost analysis is included. The difficulties in implementing these laws have also been evaluated and this evaluation already enables us to propose certain elements enabling us to go forward to globally improve the quality and security in radiotherapy. (author)

  2. Thermomechanical architecture of the VIS focal plane for Euclid

    International Nuclear Information System (INIS)

    Martignac, Jerome; Carty, Michael; Tourette, Thierry; Bachet, Damien; Berthe, Michel; Augueres, Jean-Louis; Amiaux, Jerome; Fontignie, Jean; Horeau, Benoit; Renaud, Diana

    2014-01-01

    One of the main challenges for current and near future space experiments is the increase of focal plane complexity in terms of amount of pixels. In the frame work of the ESA Euclid mission to be launched in 2020, the Euclid Consortium is developing an extremely large and stable focal plane for the VIS instrument. CEA has developed the thermomechanical architecture of that Focal Plane taking into account all the very stringent performance and mission related requirements. The VIS Focal Plane Assembly integrates 36 CCDs (operated at 150 K) connected to their front end electronics (operated at 280 K) as to obtain one of the largest focal plane (0.6 billion pixels) ever built for space application after the GAIA one. The CCDs are CCD273 type specially designed and provided by the e2v company under ESA contract, front end electronics is studied and provided by MSSL. In this paper we first recall the specific requirements that have driven the overall architecture of the VIS-FPA and especially the solutions proposed to cope with the scientific needs of an extremely stable focal plane, both mechanically and thermally. The mechanical structure based on SiC material used for the cold sub assembly supporting the CCDs is detailed. We describe also the modular architecture concept that we have selected taking into account AIT-AIV and programmatic constraints. (authors)

  3. Testing of focal plane arrays

    International Nuclear Information System (INIS)

    Merriam, J.D.

    1988-01-01

    Problems associated with the testing of focal plane arrays are briefly examined with reference to the instrumentation and measurement procedures. In particular, the approach and instrumentation used as the Naval Ocean Systems Center is presented. Most of the measurements are made with flooded illumination on the focal plane array. The array is treated as an ensemble of individual pixels, data being taken on each pixel and array averages and standard deviations computed for the entire array. Data maps are generated, showing the pixel data in the proper spatial position on the array and the array statistics

  4. Development of a human head FE model for the impact analysis using VOXEL approach and simulation for the assessment on the focal brain injury

    International Nuclear Information System (INIS)

    Watanabe, Dai; Yuge, Kohei; Nishimoto, Tetsuya; Murakami, Shigeyuki; Takao, Hiroyuki

    2008-01-01

    In this paper, a three-dimensional digital human-head model was developed and several dynamic analyses on the head trauma were conducted. This model was built up by the VOXEL approach using 433 slice CT images (512 x 512 pixels) and made of 1.22 million parallelepiped finite elements with 10 anatomical tissue properties such as scalp, cerebrospinal fluid (CSF), skull, brain, dura mater and so on. The numerical analyses were conducted using a finite element code the authors have developed. The main features of the code are it is based on the explicit time integration method and it uses the one point integration method to evaluate the equivalent nodal forces with the hourglass control proposed by Flanagan and Belythcko and it utilizes the parallel computation with the Massage Passing Interface (MPI). In order to verify the developed model, the head impact experiment for a cadaver by Nahum et al. was simulated. The calculated results showed good agreement with experimental ones. A front and rear impact analyses were also performed investigate the relation between the impact direction and the positions of the high measurement of pressure and stresses in brain. The obtained results represent that brain injury has a closer relation with the Mises equivalent stress rather than the pressure. At this time, the large deformation of a frontal cranial base was observed in both frontal and occipital impact analyses. We expect that it induces the brain injury in a frontal lobe regardless of the impact positions. (author)

  5. The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study.

    Directory of Open Access Journals (Sweden)

    Ching-Chung Liang

    Full Text Available Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO. Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment caused less infarction size than those infused after MCAO (post-treatment on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.

  6. The Simbol-X Focal Plane

    Science.gov (United States)

    Laurent, P.

    2009-05-01

    The Simbol-X focal plane is designed to detect photons focused by the mirror in the 0.5 to 100 keV energy band. Composed of two detectors, it will measure the position, energy, and arrival time of each incoming X-ray. On top of it will be a collimator to shield all photons not coming from the mirror field of view. The whole system is surrounded by an active and passive shielding in order to ensure the required very low background.

  7. 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.

  8. 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

  9. Gallbladder adenoma with focal adenocarcinoma.

    Science.gov (United States)

    Ciurea, S; Matei, E; Petrisor, P; Luca, L; Boros, Mirela; Herlea, V; Popescu, I

    2008-01-01

    The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

  10. 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...

  11. 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.

  12. Laparoscopic Partial Hepatectomy of Focal Nodular Hyperplasia

    Directory of Open Access Journals (Sweden)

    Mayu Sakata

    2012-11-01

    Full Text Available Focal nodular hyperplasia is a benign liver lesion incidentally discovered with increasing frequency because of the proliferation of imaging studies. Radiographic characterization can diagnose this pathologic lesion and nonoperative therapy is the standard of care. However, surgical resection may be required for diagnostic reasons or symptomatic patients. Depending on the anatomic location of the lesion, biopsy and/or resection can be performed laparoscopically. We herein report the case of a 26-year-old Japanese woman with a hepatic tumor who required a medical examination. Her medical history was negative for alcohol abuse, oral contraceptive administration and trauma. Clinical examination showed no significant symptoms. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass located in the left lateral segment of the liver with a diameter of about 40 mm. It was difficult to diagnose the tumor definitively from these imaging studies, so we performed laparoscopic partial hepatectomy with successive firing of endoscopic staplers. The histopathological diagnosis was focal nodular hyperplasia. Surgical procedures and postoperative course were uneventful and the patient was discharged from the hospital on postoperative day 5.

  13. Structural Design Requirements and Factors of Safety for Spaceflight Hardware: For Human Spaceflight. Revision A

    Science.gov (United States)

    Bernstein, Karen S.; Kujala, Rod; Fogt, Vince; Romine, Paul

    2011-01-01

    This document establishes the structural requirements for human-rated spaceflight hardware including launch vehicles, spacecraft and payloads. These requirements are applicable to Government Furnished Equipment activities as well as all related contractor, subcontractor and commercial efforts. These requirements are not imposed on systems other than human-rated spacecraft, such as ground test articles, but may be tailored for use in specific cases where it is prudent to do so such as for personnel safety or when assets are at risk. The requirements in this document are focused on design rather than verification. Implementation of the requirements is expected to be described in a Structural Verification Plan (SVP), which should describe the verification of each structural item for the applicable requirements. The SVP may also document unique verifications that meet or exceed these requirements with NASA Technical Authority approval.

  14. [Focal myositis: An unknown disease].

    Science.gov (United States)

    Gallay, L; Streichenberger, N; Benveniste, O; Allenbach, Y

    2017-10-01

    Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual. Copyright © 2017. Published by Elsevier SAS.

  15. 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.

  16. Synchrotron- and focal plane array-based Fourier-transform infrared spectroscopy differentiates the basalis and functionalis epithelial endometrial regions and identifies putative stem cell regions of human endometrial glands.

    Science.gov (United States)

    Theophilou, Georgios; Morais, Camilo L M; Halliwell, Diane E; Lima, Kássio M G; Drury, Josephine; Martin-Hirsch, Pierre L; Stringfellow, Helen F; Hapangama, Dharani K; Martin, Francis L

    2018-05-09

    The cyclical process of regeneration of the endometrium suggests that it may contain a cell population that can provide daughter cells with high proliferative potential. These cell lineages are clinically significant as they may represent clonogenic cells that may also be involved in tumourigenesis as well as endometriotic lesion development. To determine whether the putative stem cell location within human uterine tissue can be derived using vibrational spectroscopy techniques, normal endometrial tissue was interrogated by two spectroscopic techniques. Paraffin-embedded uterine tissues containing endometrial glands were sectioned to 10-μm-thick parallel tissue sections and were floated onto BaF 2 slides for synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy and globar focal plane array-based FTIR spectroscopy. Different spectral characteristics were identified depending on the location of the glands examined. The resulting infrared spectra were subjected to multivariate analysis to determine associated biophysical differences along the length of longitudinal and crosscut gland sections. Comparison of the epithelial cellular layer of transverse gland sections revealed alterations indicating the presence of putative transient-amplifying-like cells in the basalis and mitotic cells in the functionalis. SR-FTIR microspectroscopy of the base of the endometrial glands identified the location where putative stem cells may reside at the same time pointing towards ν s PO 2 - in DNA and RNA, nucleic acids and amide I and II vibrations as major discriminating factors. This study supports the view that vibration spectroscopy technologies are a powerful adjunct to our understanding of the stem cell biology of endometrial tissue. Graphical abstract ᅟ.

  17. The Effect of Focal Distance, Age, and Brightness on Near-Field Augmented Reality Depth Matching

    OpenAIRE

    Singh, Gujot; Ellis, Stephen R.; Swan II, J. Edward

    2017-01-01

    Many augmented reality (AR) applications operate within near-field reaching distances, and require matching the depth of a virtual object with a real object. The accuracy of this matching was measured in three experiments, which examined the effect of focal distance, age, and brightness, within distances of 33.3 to 50 cm, using a custom-built AR haploscope. Experiment I examined the effect of focal demand, at the levels of collimated (infinite focal distance), consistent with other depth cues...

  18. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    Science.gov (United States)

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  19. 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......Adaptive immune responses require activation and expansion of antigen-specific T cells. Whereas early T cell activation is independent of exogenous cystine (Cys2), T cell proliferation is dependent of Cys2. However, the exact roles of Cys2 in T cell proliferation still need to be determined...... for the activity of ribonucleotide reductase (RNR), the enzyme responsible for generation of the deoxyribonucleotide DNA building blocks. In conclusion, we show that activated human T cells require exogenous Cys2 to proliferate and that this is partly explained by the fact that Cys2 is required for production...

  20. TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly

    Science.gov (United States)

    Uchil, Pradeep D.; Pawliczek, Tobias; Reynolds, Tracy D.; Ding, Siyuan; Hinz, Angelika; Munro, James B.; Huang, Fang; Floyd, Robert W.; Yang, Haitao; Hamilton, William L.; Bewersdorf, Joerg; Xiong, Yong; Calderwood, David A.; Mothes, Walther

    2014-01-01

    ABSTRACT Focal adhesions are macromolecular complexes that connect the actin cytoskeleton to the extracellular matrix. Dynamic turnover of focal adhesions is crucial for cell migration. Paxillin is a multi-adaptor protein that plays an important role in regulating focal adhesion dynamics. Here, we identify TRIM15, a member of the tripartite motif protein family, as a paxillin-interacting factor and a component of focal adhesions. TRIM15 localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. Unlike other focal adhesion proteins, TRIM15 is a stable focal adhesion component with restricted mobility due to its ability to form oligomers. TRIM15-depleted cells display impaired cell migration and reduced focal adhesion disassembly rates, in addition to enlarged focal adhesions. Thus, our studies demonstrate a cellular function for TRIM15 as a regulatory component of focal adhesion turnover and cell migration. PMID:25015296

  1. The Sentinel-4 UVN focal plane assemblies

    Science.gov (United States)

    Hinger, Jürgen; Hohn, Rüdiger; Gebhardt, Eyk; Reichardt, Jörg

    2017-09-01

    The Sentinel-4 UVN Instrument is a dispersive imaging spectrometer covering the UV-VIS and the NIR wavelength. It is developed and built under an ESA contract by an industrial consortium led by Airbus Defence and Space. It will be accommodated on board of the MTG-S (Meteosat Third Generation - Sounder) satellite that will be placed in a geostationary orbit over Europe sampling data for generating two-dimensional maps of a number of atmospheric trace gases. The incoming light is dispersed by reflective gratings and detected by the two (UVVIS and NIR) CCDs mounted inside the focal plane assemblies. Both CCD detectors acquire spectral channels and spatial sampling in two orthogonal directions and will be operated at about 215 K mainly to minimize random telegraph signal effects and to reduce dark current. Stringent detector temperature as well as alignment stability requirements of less than +/-0.1 K per day respectively of less than 2 micrometers/2 arcseconds from ground to orbit are driving the FPA thermo-mechanical design. A specific FPA design feature is the redundant LED-calibration system for bad pixel detection as well as pixel gain and linearity monitoring. This paper reports on the design and qualification of the Focal Plane Assemblies with emphasis on thermo-mechanical as well as alignment stability verification.

  2. Structural and effective connectivity in focal epilepsy

    Directory of Open Access Journals (Sweden)

    Christopher S. Parker

    2018-01-01

    Full Text Available Patients with medically-refractory focal epilepsy may be candidates for neurosurgery and some may require placement of intracranial EEG electrodes to localise seizure onset. Assessing cerebral responses to single pulse electrical stimulation (SPES may give diagnostically useful data. SPES produces cortico-cortical evoked potentials (CCEPs, which infer effective brain connectivity. Diffusion-weighted images and tractography may be used to estimate structural brain connectivity. This combination provides the opportunity to observe seizure onset and its propagation throughout the brain, spreading contiguously along the cortex explored with electrodes, or non-contiguously. We analysed CCEPs and diffusion tractography in seven focal epilepsy patients and reconstructed the effective and structural brain networks. We aimed to assess the inter-modal similarity of the networks at a large scale across the cortex, the effective and structural connectivity of the ictal-onset zone, and investigate potential mechanisms of non-contiguous seizure spread. We found a significant overlap between structural and effective networks. Effective network CCEP amplitude, baseline variation, and outward connectivity was higher at ictal-onset zones, while structural connection strength within the ictal-onset zone tended to be higher. These findings support the concept of hyperexcitable cortex being associated with seizure generation. The high prevalence of structural and effective connections from the ictal-onset zone to sites of non-contiguous spread suggests that macroscopic structural and effective connections are plausible routes for non-contiguous seizure spread.

  3. Heterogeneity of Focal Adhesions and Focal Contacts in Motile Fibroblasts.

    Science.gov (United States)

    Gladkikh, Aleena; Kovaleva, Anastasia; Tvorogova, Anna; Vorobjev, Ivan A

    2018-01-01

    Cell-extracellular matrix (ECM) adhesion is an important property of virtually all cells in multicellular organisms. Cell-ECM adhesion studies, therefore, are very significant both for biology and medicine. Over the last three decades, biomedical studies resulted in a tremendous advance in our understanding of the molecular basis and functions of cell-ECM adhesion. Based on morphological and molecular criteria, several different types of model cell-ECM adhesion structures including focal adhesions, focal complexes, fibrillar adhesions, podosomes, and three-dimensional matrix adhesions have been described. All the subcellular structures that mediate cell-ECM adhesion are quite heterogeneous, often varying in size, shape, distribution, dynamics, and, to a certain extent, molecular constituents. The morphological "plasticity" of cell-ECM adhesion perhaps reflects the needs of cells to sense, adapt, and respond to a variety of extracellular environments. In addition, cell type (e.g., differentiation status, oncogenic transformation, etc.) often exerts marked influence on the structure of cell-ECM adhesions. Although molecular, genetic, biochemical, and structural studies provide important maps or "snapshots" of cell-ECM adhesions, the area of research that is equally valuable is to study the heterogeneity of FA subpopulations within cells. Recently time-lapse observations on the FA dynamics become feasible, and behavior of individual FA gives additional information on cell-ECM interactions. Here we describe a robust method of labeling of FA using plasmids with fluorescent markers for paxillin and vinculin and quantifying the morphological and dynamical parameters of FA.

  4. 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.

  5. Focal nodular hyperplasia: imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Kehagias, D.; Moulopoulos, L.; Antoniou, A.; Hatziioannou, A.; Smyrniotis, V.; Trakadas, S.; Lahanis, S.; Vlahos, L. [Dept. of Radiology, University of Athens (Greece)

    2001-02-01

    Focal nodular hyperplasia is an uncommon benign hepatic tumor that continues to pose diagnostic dilemmas. Imaging techniques are of great value in diagnosis of this tumor. In this article we present the US, CT, MR imaging, scintigraphy, and angiography findings. The demonstration of a central vascular scar is very helpful. Although the radiologic features may be diagnostic, many atypical cases must be differentiated from other benign or malignant hepatic tumors. In these cases excisional biopsy and histopathologic examination are necessary to determine a definite diagnosis. (orig.)

  6. Focal nodular hyperplasia: imaging findings

    International Nuclear Information System (INIS)

    Kehagias, D.; Moulopoulos, L.; Antoniou, A.; Hatziioannou, A.; Smyrniotis, V.; Trakadas, S.; Lahanis, S.; Vlahos, L.

    2001-01-01

    Focal nodular hyperplasia is an uncommon benign hepatic tumor that continues to pose diagnostic dilemmas. Imaging techniques are of great value in diagnosis of this tumor. In this article we present the US, CT, MR imaging, scintigraphy, and angiography findings. The demonstration of a central vascular scar is very helpful. Although the radiologic features may be diagnostic, many atypical cases must be differentiated from other benign or malignant hepatic tumors. In these cases excisional biopsy and histopathologic examination are necessary to determine a definite diagnosis. (orig.)

  7. MRI of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Lee, B.C.P.; Hatfield, G.A.; Bourgeois, B.; Park, T.S.

    1998-01-01

    We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain. (orig.) (orig.)

  8. Step 1: Human System Interface (HSI) Functional Requirements Document (FRD). Version 2

    Science.gov (United States)

    2006-01-01

    This Functional Requirements Document (FRD) establishes a minimum set of Human System Interface (HSI) functional requirements to achieve the Access 5 Vision of "operating High Altitude, Long Endurance (HALE) Unmanned Aircraft Systems (UAS) routinely, safely, and reliably in the National Airspace System (NAS)". Basically, it provides what functions are necessary to fly UAS in the NAS. The framework used to identify the appropriate functions was the "Aviate, Navigate, Communicate, and Avoid Hazards" structure identified in the Access 5 FRD. As a result, fifteen high-level functional requirements were developed. In addition, several of them have been decomposed into low-level functional requirements to provide more detail.

  9. 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).

  10. Requirements for growth and IL-10 expression of highly purified human T regulatory cells

    OpenAIRE

    Bonacci, Benedetta; Edwards, Brandon; Jia, Shuang; Williams, Calvin; Hessner, Martin J.; Gauld, Stephen; Verbsky, James

    2012-01-01

    Human regulatory T cells (TR) cells have potential for the treatment of a variety of immune mediated diseases but the anergic phenotype of these cells makes them difficult to expand in vitro. We have examined the requirements for growth and cytokine expression from highly purified human TR cells, and correlated these findings with the signal transduction events of these cells. We demonstrate that these cells do not proliferate or secrete IL-10 even in the presence of high doses of IL-2. Stimu...

  11. Lack of school requirements and clinician recommendations for human papillomavirus vaccination

    Directory of Open Access Journals (Sweden)

    Linda M. Niccolai

    2018-04-01

    Full Text Available Background: A strong recommendation from a clinician is one of the best predictors of human papillomavirus (HPV vaccination among adolescents, yet many clinicians do not provide effective recommendations. The objective of this study was to understand how the lack of school entry requirements for HPV vaccination influences clinicians’ recommendations. Design and Methods: Semi-structured interviews with a purposive sample of 32 clinicians were conducted in 2015 in Connecticut USA. Data were analysed using an iterative thematic approach in 2016-2017. Results: Many clinicians described presenting HPV vaccination as optional or non-urgent because it is not required for school entry. This was noted to be different from how other required vaccines were discussed. Even strong recommendations were often qualified by statements about the lack of requirements. Furthermore, lack of requirements was often raised initially by clinicians and not by parents. Many clinicians agreed that requirements would simplify the recommendation, but that parents may not agree with requirements. Personal opinions about school entry requirements were mixed. Conclusions: The current lack of school entry requirements for HPV vaccination is an important influence on clinicians’ recommendations that are often framed as optional or non-urgent. Efforts are needed to strengthen the quality of clinicians’ recommendations in a way that remains strong and focused on disease prevention yet uncoupled from the lack of requirements that may encourage delays. Additionally, greater support for requirements among clinicians may be needed to successfully enact requirements in the future.

  12. Pathogenesis of Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Beom Jin Lim

    2016-11-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

  13. 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

  14. 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.

  15. Step 1: Human System Integration (HSI) FY05 Pilot-Technology Interface Requirements for Contingency Management

    Science.gov (United States)

    2005-01-01

    This document involves definition of technology interface requirements for Contingency Management. This was performed through a review of Contingency Management-related, HSI requirements documents, standards, and recommended practices. Technology concepts in use by the Contingency Management Work Package were considered. Beginning with HSI high-level functional requirements for Contingency Management, and Contingency Management 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 system failures and associated contingency procedures, and (2) the control capability needed by the pilot to obtain system status and procedure information. Fundamentally, these requirements provide the candidate Contingency Management technology concepts with the necessary human-related elements to make them compatible with human capabilities and limitations. The results of the analysis describe how Contingency Management operations and functions should interface with the pilot to provide the necessary Contingency Management functionality to the UA-pilot system. Requirements and guidelines for Contingency Management are partitioned into four categories: (1) Health and Status and (2) Contingency Management. Each requirement is stated and is supported with a rationale and associated reference(s).

  16. RTG diagnostics of dental focal infection

    International Nuclear Information System (INIS)

    Petrasova, A.; Ondrasovicova, J.; Cecctkova, A.

    2008-01-01

    The theory of focal infection has always been and still is a controversial issue for many dentists and scientists. Even though the focal infection does not occupy the first place in modern medicine, its understanding is imperative. The authors summarized the knowledge about dental focal infection and its relationship to systemic the diseases of the whole body in their publication and they also focused on the radiodiagnostics of this disease. (authors)

  17. 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

  18. 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.

  19. Relating the Capabilities of the Handicapped to the Human Attribute Requirements of Jobs: Appendixes.

    Science.gov (United States)

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    Twenty-five appendixes from a study attempting to match capabilities of the handicapped to the human attribute requirements of three jobs (general secretary, automotive mechanic, and business data programmer) are presented. Appendixes include information on such topics as data analysis for identification of key tasks; job descriptions for the…

  20. ER-16 regulation. Requirements for granting the permit exceptional use of medical devices in humans

    International Nuclear Information System (INIS)

    2015-01-01

    The purpose of this regulation is to establish requirements for applying for a permit exceptional use of medical equipment in Human Beings, the procedures for the evaluation process and bestowal. This regulation is aimed at researchers and designers of medical equipment, related to or associated with National Health Service's priority programs of interest to health.

  1. Flux dynamics in ultrasensitive superconducting focal planes

    Data.gov (United States)

    National Aeronautics and Space Administration — The performance of superconducting focal planes will drive the achievable specifications of ultrasensitive instruments for NASA astrophysics missions, yet they have...

  2. METHOD FOR DETERMINATION OF FOCAL PLANE LOCATION OF FOCUSING COMPONENTS

    Directory of Open Access Journals (Sweden)

    A. I. Ivashko

    2017-01-01

    Full Text Available Mass-production of different laser systems often requires utilization of the focal spot size method for determination of output laser beam spatial characteristics. The main challenge of this method is high accuracy maintenance of a CCD camera beam profiler in the collecting lens focal plane. The aim of our work is development of new method for placing of photodetector array in the collecting lens focal plane with high accuracy.Proposed technique is based on focusing of several parallel laser beams. Determination of the focal plane position requires only longitudinal translation of the CCD-camera to find a point of laser beams intersection. Continuous-wave (CW diode-pumped laser emitting in the spectral region near 1μm was created to satisfy the requirements of the developed technique. Designed microchip laser generates two stigmatic Gaussian beams with automatically parallel beam axes due to independent pumping of different areas of the one microchip crystal having the same cavity mirrors.It was theoretically demonstrated that developed method provides possibility of the lenses focal plane determination with 1 % accuracy. The microchip laser generates two parallel Gaussian beams with divergence of about 10 mrad. Laser output power can be varied in the range of 0.1–1.5 W by changing the pumping laser diode electrical current. The distance between two beam axes can be changed in the range of 0.5–5.0 mm.We have proposed method for determination of positive lens focal plane location by using of CCDcamera and two laser beams with parallel axes without utilization of additional optical devices. We have developed CW longitudinally diode pumped microchip laser emitting in the 1-μm spectral region that can be used in the measuring instrument that doesn’t require precision mechanical components for determination of focal plane location with 1 % accuracy. The overall dimensions of laser head was 70 × 40 × 40 mm3 and maximum power consumption was

  3. Game Movement as Enactive Focalization

    Directory of Open Access Journals (Sweden)

    Yotam Shibolet

    2018-01-01

    Full Text Available This paper integrates thought on game narrative and embodied cognition, in order to consider the significance of movement to the embodied narrative experience of games. If games are a mode of ‘environmental storytelling’, determining the player’s mobile situatedness within the gamespace is of crucial importance. The metaphor of game design as narrative architecture should be expanded to include te the design of movement dynamics, alongside geographical gamespace. I suggest a theoretical infrastructure that aims to enable further analysis of movement design’s role in this scope. The theory of enactive perception asserts that all perception is inherently negotiated through embodied understanding of moving within environment. According to this model, by giving meaning to perception, movement is also directly related to the structure of consciousness and thought. Cognitive definitions of ‘narrative’ that integrate embodiment are applied to argue it can relevantly account for part of thought’s role in enactive perception. Mieke Bal’s concept of focalization (1997 broaches narrative perspective by underscoring the constant “movement of the look”. For enactive perception, such mobility should be understood as inseparable from the movement of the body even when perspective could appear detached from embodiment. Therefore, I offer the supplementary concept of “enactive focalization” – narrative perception as interpreted through the interconnected dynamics or perspectival and physical movement. To exemplify my ideas and the potential of future research in this scope, I discuss the uniquely effective and affective movement dynamic design of Journey. This paper concludes by reflecting on enactive focalization in light of the increased utilization of embodiment in the contemporary digital media landscape.

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

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2012-07-01

    Full Text Available Abstract 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    International Nuclear Information System (INIS)

    Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong

    2002-01-01

    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.

  10. Stable nuclide tracer studies and human amino acid requirements. A summary

    International Nuclear Information System (INIS)

    Young, V.R.

    1994-01-01

    The nutritional requirements for proteins have been estimated for various age groups. The current status of knowledge concerning the quantitative needs for specific indispensable amino acids was reviewed and it was concluded that, except for infants, current values for pre-school children, school age children and healthy adults are based on limited experimental data and/or on results from nitrogen balance determinations which are open to serious question regarding their nutritional significance. A review of 13 C-labelled tracer studies carried out in MIT laboratories was undertaken to demonstrate the applicability of stable nuclide tracer studies for purposes of determining the amino acid requirements of humans. 5 refs

  11. A 1.3 giga pixels focal plane for GAIA

    Science.gov (United States)

    Laborie, Anouk; Pouny, Pierre; Vetel, Cyril; Collados, Emmanuel; Rougier, Gilles; Davancens, Robert; Zayer, Igor; Perryman, Michael; Pace, Oscar

    2004-06-01

    The astrometric mission GAIA is a cornerstone mission of the European Space Agency, due for launch in the 2010 time frame. Requiring extremely demanding performance GAIA calls for the development of an unprecedented large focal plane featuring innovative technologies. For securing the very challenging GAIA development, a significant number of technology activities have been initiated by ESA through a competitive selection process. In this context, an industrial consortium led by EADS-Astrium (France) with e2v technologies (UK) as major subcontractor was selected for the GAIA CCD and Focal Plane Technology Demonstrators programme, which is by far the most significant and the most critical GAIA pre-development for all aspects: science performance, development schedule and cost. This programme has started since August 2002 and will end early 2005 prior to commencement of the GAIA Phase B. While the GAIA payload will host three instruments and related focal planes, the major mission objectives are assigned to the Astrometric (ASTRO) Focal Plane, which is the subject of this presentation.

  12. Position sensitive proportional counters as focal plane detectors

    International Nuclear Information System (INIS)

    Ford, J.L.C. Jr.

    1979-01-01

    The rise time and charge division techniques for position decoding with RC-line proportional counters are reviewed. The advantages that these detectors offer as focal plane counters for nuclear spectroscopy performed with magnetic spectrographs are discussed. The theory of operation of proportional counters as position sensing devices is summarized, as well as practical aspects affecting their application. Factors limiting the position and energy resolutions obtainable with a focal plane proportional counter are evaluated and measured position and energy loss values are presented for comparison. Detector systems capable of the multiparameter measurements required for particle identification, background suppression and ray-tracing are described in order to illustrate the wide applicability of proportional counters within complex focal plane systems. Examples of the use of these counters other than with magnetic spectrographs are given in order to demonstrate their usefulness in not only nuclear physics but also in fields such as solid state physics, biology, and medicine. The influence of the new focal plane detector systems on future magnetic spectrograph designs is discussed. (Auth.)

  13. Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

    Science.gov (United States)

    Fabri, Mario; Stenger, Steffen; Shin, Dong-Min; Yuk, Jae-Min; Liu, Philip T.; Realegeno, Susan; Lee, Hye-Mi; Krutzik, Stephan R.; Schenk, Mirjam; Sieling, Peter A.; Teles, Rosane; Montoya, Dennis; Iyer, Shankar S.; Bruns, Heiko; Lewinsohn, David M.; Hollis, Bruce W.; Hewison, Martin; Adams, John S.; Steinmeyer, Andreas; Zügel, Ulrich; Cheng, Genhong; Jo, Eun-Kyeong; Bloom, Barry R.; Modlin, Robert L.

    2012-01-01

    Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection. PMID:21998409

  14. 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

  15. Nonhuman primate models of focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2017-01-01

    Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  16. Do focal colors look particularly "colorful"?

    Science.gov (United States)

    Witzel, Christoph; Franklin, Anna

    2014-04-01

    If the most typical red, yellow, green, and blue were particularly colorful (i.e., saturated), they would "jump out to the eye." This would explain why even fundamentally different languages have distinct color terms for these focal colors, and why unique hues play a prominent role in subjective color appearance. In this study, the subjective saturation of 10 colors around each of these focal colors was measured through a pairwise matching task. Results show that subjective saturation changes systematically across hues in a way that is strongly correlated to the visual gamut, and exponentially related to sensitivity but not to focal colors.

  17. Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

    1995-01-01

    To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

  18. Oral focal epithelial hyperplasia: report of three cases.

    Science.gov (United States)

    Ghalayani, Parichehr; Tavakoli, Payam; Eftekhari, Mehdi; Haghighi, Mohammad Akhondzadeh

    2015-01-01

    Focal epithelial hyperplasia or Heck's disease is an infrequent asymptomatic condition caused by human papillomavirus types 13 or 32 affecting the mucous membrane of the mouth and is commonly seen in young individuals. Firstly, it was described in Indians and Eskimos, but it exists in various populations. We present three cases of Heck's disease in an Afghan immigrant family group living in Iran that seem to have familial predominance. The disease was identified as oral focal epithelial hyperplasia on the basis of histopathologic and clinical findings. The lesions were reduced significantly after 4 months of good oral hygiene. Dentists should be familiar with the clinical manifestations of these types of lesions that affect the oral cavity. In fact, histopathologic assessment and clinical observation are necessary to establish the diagnosis.

  19. Depression in focal, segmental and generalized dystonia.

    Science.gov (United States)

    Lewis, L; Butler, A; Jahanshahi, M

    2008-11-01

    Dystonia causes body disfigurement in the majority of those affected. Our aim was to test the hypothesis that low self-esteem resulting from the sense of disfigurement is an important component of self-reported depression in focal, segmental and generalized dystonia. Questionnaires to assess self-reported depression, self-esteem, body concept, disfigurement, disability and quality of life were completed by 329 community based dystonia patients. Moderate to severe depression was reported by 30 %. Self-reported depression had a strong somatic component, but patients also showed a specific concern with self-image. Extent of dystonia, body parts affected and marital status influenced self-reported depression in dystonia. Self esteem, body concept, disfigurement and quality of life emerged as factors which accounted for the variance of self-reported depression in dystonia. These results suggest that in dystonia, disfigurement, negative body concept, low self-esteem, and the impact of the disease on quality of life make important contributions to depression. However, longitudinal followup is required to firmly establish the direction of causality between depression and these psychosocial variables in dystonia.

  20. Focal skin defect, limb anomalies and microphthalmia.

    NARCIS (Netherlands)

    Jackson, K.E.; Andersson, H.C.

    2004-01-01

    We describe two unrelated female patients with congenital single focal skin defects, unilateral microphthalmia and limb anomalies. Growth and psychomotor development were normal and no brain malformation was detected. Although eye and limb anomalies are commonly associated, clinical anophthalmia and

  1. Focal adhesions and cell-matrix interactions

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1988-01-01

    Focal adhesions are areas of cell surfaces where specializations of cytoskeletal, membrane and extracellular components combine to produce stable cell-matrix interactions. The morphology of these adhesions and the components identified in them are discussed together with possible mechanisms...

  2. Genetics Home Reference: focal dermal hypoplasia

    Science.gov (United States)

    ... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

  3. 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.

  4. [Focal hyperhidrosis.Quality of life, socioeconomic importance and use of internal medicinal therapy].

    Science.gov (United States)

    Rzany, B; Müller, C; Hund, M

    2012-06-01

    Focal hyperhidrosis can have a substantial influence on the professional, physical, emotional and social life of those affected. This becomes clear when the results of quality of life studies and Health Service Research studies are reviewed, e.g. affected patients were prepared to contribute additional money for treatment of hyperhidrosis. The systemic therapy of focal hyperhidrosis with oral anticholinergic agents is a quite economical treatment strategy. These products can be administered continuously or sporadically. However, only good clinical date for the continous treatment exists. Focal hyperhidrosis is a disease which requires our full attention. It should be discussed whether e.g. QoL questionnaires should be used routinelly.

  5. Envisioning a Future Decision Support System for Requirements Engineering : A Holistic and Human-centred Perspective

    OpenAIRE

    Alenljung, Beatrice

    2008-01-01

    Complex decision-making is a prominent aspect of requirements engineering (RE) and the need for improved decision support for RE decision-makers has been identified by a number of authors in the research literature. The fundamental viewpoint that permeates this thesis is that RE decision-making can be substantially improved by RE decision support systems (REDSS) based on the actual needs of RE decision-makers as well as the actual generic human decision-making activities that take place in th...

  6. Neural network control of focal position during time-lapse microscopy of cells.

    Science.gov (United States)

    Wei, Ling; Roberts, Elijah

    2018-05-09

    Live-cell microscopy is quickly becoming an indispensable technique for studying the dynamics of cellular processes. Maintaining the specimen in focus during image acquisition is crucial for high-throughput applications, especially for long experiments or when a large sample is being continuously scanned. Automated focus control methods are often expensive, imperfect, or ill-adapted to a specific application and are a bottleneck for widespread adoption of high-throughput, live-cell imaging. Here, we demonstrate a neural network approach for automatically maintaining focus during bright-field microscopy. Z-stacks of yeast cells growing in a microfluidic device were collected and used to train a convolutional neural network to classify images according to their z-position. We studied the effect on prediction accuracy of the various hyperparameters of the neural network, including downsampling, batch size, and z-bin resolution. The network was able to predict the z-position of an image with ±1 μm accuracy, outperforming human annotators. Finally, we used our neural network to control microscope focus in real-time during a 24 hour growth experiment. The method robustly maintained the correct focal position compensating for 40 μm of focal drift and was insensitive to changes in the field of view. About ~100 annotated z-stacks were required to train the network making our method quite practical for custom autofocus applications.

  7. Automated diagnosis of focal liver lesions using bidirectional empirical mode decomposition features.

    Science.gov (United States)

    Acharya, U Rajendra; Koh, Joel En Wei; Hagiwara, Yuki; Tan, Jen Hong; Gertych, Arkadiusz; Vijayananthan, Anushya; Yaakup, Nur Adura; Abdullah, Basri Johan Jeet; Bin Mohd Fabell, Mohd Kamil; Yeong, Chai Hong

    2018-03-01

    Liver is the heaviest internal organ of the human body and performs many vital functions. Prolonged cirrhosis and fatty liver disease may lead to the formation of benign or malignant lesions in this organ, and an early and reliable evaluation of these conditions can improve treatment outcomes. Ultrasound imaging is a safe, non-invasive, and cost-effective way of diagnosing liver lesions. However, this technique has limited performance in determining the nature of the lesions. This study initiates a computer-aided diagnosis (CAD) system to aid radiologists in an objective and more reliable interpretation of ultrasound images of liver lesions. In this work, we have employed radon transform and bi-directional empirical mode decomposition (BEMD) to extract features from the focal liver lesions. After which, the extracted features were subjected to particle swarm optimization (PSO) technique for the selection of a set of optimized features for classification. Our automated CAD system can differentiate normal, malignant, and benign liver lesions using machine learning algorithms. It was trained using 78 normal, 26 benign and 36 malignant focal lesions of the liver. The accuracy, sensitivity, and specificity of lesion classification were 92.95%, 90.80%, and 97.44%, respectively. The proposed CAD system is fully automatic as no segmentation of region-of-interest (ROI) is required. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. 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

  11. Focal segmental glomerulosclerosis in a case of panhypopituitarism: a possible role of growth hormone treatment.

    Science.gov (United States)

    Fukasawa, H; Kato, A; Fujimoto, T; Suzuki, H; Fujigaki, Y; Yamamoto, T; Endoh, A; Yonemura, K; Hishida, A

    2002-10-01

    Panhypopituitarism manifests various symptoms including growth failure, hypothyroidism, adrenal insufficiency and hypogonadism. Dwarfism is an important problem in children with this condition, and long-term treatment with recombinant human growth hormone (GH) is usually required. We report a 24-year-old man with panhypopituitarism complicated by focal segmental glomerulosclerosis (FSGS). The patient had been treated with GH for hypopituitary dwarfism from 3 years of age. Proteinuria was initially noticed at 15 years of age and persisted despite cessation of GH supplementation at 18 years of age. A renal biopsy specimen showed glomerular hypertrophy and limited glomerulosclerosis, compatible with FSGS. To our knowledge, this is the first reported case of panhypopituitarism complicated by FSGS. Our case suggests that GH treatment for dwarfism may induce irreversible glomerular disease.

  12. Commercially-driven human interplanetary propulsion systems: Rationale, concept, technology, and performance requirements

    International Nuclear Information System (INIS)

    Williams, C.H.; Borowski, S.K.

    1996-01-01

    Previous studies of human interplanetary missions are largely characterized by long trip times, limited performance capabilities, and enormous costs. Until these missions become dramatically more open-quote open-quote commercial-friendly close-quote close-quote, their funding source and rationale will be restricted to national governments and their political/scientific interests respectively. A rationale is discussed for human interplanetary space exploration predicated on the private sector. Space propulsion system requirements are identified for interplanetary transfer times of no more than a few weeks/months to and between the major outer planets. Nuclear fusion is identified as the minimum requisite space propulsion technology. A conceptual design is described and evolutionary catalyzed-DD to DHe 3 fuel cycles are proposed. Magnetic nozzles for direct thrust generation and quantifying the operational aspects of the energy exchange mechanisms between high energy reaction products and neutral propellants are identified as two of the many key supporting technologies essential to satisfying system performance requirements. Government support of focused, breakthrough technologies is recommended at funding levels appropriate to other ongoing federal research. copyright 1996 American Institute of Physics

  13. Requirements for growth and IL-10 expression of highly purified human T regulatory cells

    Science.gov (United States)

    Bonacci, Benedetta; Edwards, Brandon; Jia, Shuang; Williams, Calvin; Hessner, Martin J.; Gauld, Stephen; Verbsky, James

    2013-01-01

    Human regulatory T cells (TR) cells have potential for the treatment of a variety of immune mediated diseases but the anergic phenotype of these cells makes them difficult to expand in vitro. We have examined the requirements for growth and cytokine expression from highly purified human TR cells, and correlated these findings with the signal transduction events of these cells. We demonstrate that these cells do not proliferate or secrete IL-10 even in the presence of high doses of IL-2. Stimulation with a superagonistic anti-CD28 antibody (clone 9D4) and IL-2 partially reversed the proliferative defect, and this correlated with reversal of the defective calcium mobilization in these cells. Dendritic cells were effective at promoting TR cell proliferation, and under these conditions the proliferative capacity of TR cells was comparable to conventional CD4 lymphocytes. Blocking TGF-β activity abrogated IL-10 expression from these cells, while addition of TGF-β resulted in IL-10 production. These data demonstrate that highly purified populations of TR cells are anergic even in the presence of high doses of IL-2. Furthermore, antigen presenting cells provide proper co-stimulation to overcome the anergic phenotype of TR cells, and under these conditions they are highly sensitive to IL-2. In addition, these data demonstrate for the first time that TGF-β is critical to enable human TR cells to express IL-10. PMID:22562448

  14. [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.

  15. 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

  16. Transparent meta-analysis: does aging spare prospective memory with focal vs. non-focal cues?

    Directory of Open Access Journals (Sweden)

    Bob Uttl

    Full Text Available BACKGROUND: Prospective memory (ProM is the ability to become aware of a previously-formed plan at the right time and place. For over twenty years, researchers have been debating whether prospective memory declines with aging or whether it is spared by aging and, most recently, whether aging spares prospective memory with focal vs. non-focal cues. Two recent meta-analyses examining these claims did not include all relevant studies and ignored prevalent ceiling effects, age confounds, and did not distinguish between prospective memory subdomains (e.g., ProM proper, vigilance, habitual ProM (see Uttl, 2008, PLoS ONE. The present meta-analysis focuses on the following questions: Does prospective memory decline with aging? Does prospective memory with focal vs. non-focal cues decline with aging? Does the size of age-related declines with focal vs. non-focal cues vary across ProM subdomains? And are age-related declines in ProM smaller than age-related declines in retrospective memory? METHODS AND FINDINGS: A meta-analysis of event-cued ProM using data visualization and modeling, robust count methods, and conventional meta-analysis techniques revealed that first, the size of age-related declines in ProM with both focal and non-focal cues are large. Second, age-related declines in ProM with focal cues are larger in ProM proper and smaller in vigilance. Third, age-related declines in ProM proper with focal cues are as large as age-related declines in recall measures of retrospective memory. CONCLUSIONS: The results are consistent with Craik's (1983 proposal that age-related declines on ProM tasks are generally large, support the distinction between ProM proper vs. vigilance, and directly contradict widespread claims that ProM, with or without focal cues, is spared by aging.

  17. Focal thyroid inferno” on color Doppler ultrasonography: A specific feature of focal Hashimoto's thyroiditis

    International Nuclear Information System (INIS)

    Fu, Xianshui; Guo, Limei; Zhang, Huabin; Ran, Weiqiang; Fu, Peng; Li, Zhiqiang; Chen, Wen; Jiang, Ling; Wang, Jinrui; Jia, Jianwen

    2012-01-01

    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 χ 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.

  18. Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis

    International Nuclear Information System (INIS)

    Casarin, Alberto; Jimenez-Ortega, Jose Carlos; Trevisson, Eva; Pertegato, Vanessa; Doimo, Mara; Ferrero-Gomez, Maria Lara; Abbadi, Sara; Artuch, Rafael; Quinzii, Catarina; Hirano, Michio; Basso, Giuseppe; Ocana, Carlos Santos; Navas, Placido; Salviati, Leonardo

    2008-01-01

    Defects in genes involved in coenzyme Q (CoQ) biosynthesis cause primary CoQ deficiency, a severe multisystem disorders presenting as progressive encephalomyopathy and nephropathy. The COQ4 gene encodes an essential factor for biosynthesis in Saccharomyces cerevisiae. We have identified and cloned its human ortholog, COQ4, which is located on chromosome 9q34.13, and is transcribed into a 795 base-pair open reading frame, encoding a 265 amino acid (aa) protein (Isoform 1) with a predicted N-terminal mitochondrial targeting sequence. It shares 39% identity and 55% similarity with the yeast protein. Coq4 protein has no known enzymatic function, but may be a core component of multisubunit complex required for CoQ biosynthesis. The human transcript is detected in Northern blots as a ∼1.4 kb single band and is expressed ubiquitously, but at high levels in liver, lung, and pancreas. Transcription initiates at multiple sites, located 333-23 nucleotides upstream of the ATG. A second group of transcripts originating inside intron 1 of the gene encodes a 241 aa protein, which lacks the mitochondrial targeting sequence (isoform 2). Expression of GFP-fusion proteins in HeLa cells confirmed that only isoform 1 is targeted to mitochondria. The functional significance of the second isoform is unknown. Human COQ4 isoform 1, expressed from a multicopy plasmid, efficiently restores both growth in glycerol, and CoQ content in COQ4 null yeast strains. Human COQ4 is an interesting candidate gene for patients with isolated CoQ 10 deficiency

  19. 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

  20. WE-E-BRE-04: Dual Focal Spot Dose Painting for Precision Preclinical Radiobiological Investigations

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, J; Lindsay, P [Princess Margaret Cancer Centre, Toronto (Canada); University of Toronto, Toronto (Canada); Jaffray, D [Princess Margaret Cancer Centre, Toronto (Canada); The Techna Institute for the Advancement of Technology for Health, Toronto (Canada)

    2014-06-15

    Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mm circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations

  1. WE-E-BRE-04: Dual Focal Spot Dose Painting for Precision Preclinical Radiobiological Investigations

    International Nuclear Information System (INIS)

    Stewart, J; Lindsay, P; Jaffray, D

    2014-01-01

    Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mm circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations

  2. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    International Nuclear Information System (INIS)

    Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun

    2003-01-01

    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

  3. 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.

  4. Focal lesions in the central nervous system: stereotaxic radioneurosurgery

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.f.; Hosobuchi, Y.; Born, J.L.; Tobias, C.A.

    1981-01-01

    The application of heavy-ion beams for fundamental and applied brain research has unusual potential. Methods are being developed in our laboratory for producing focal lesions in the central nervous system (e.g., the hypothalamus, thalamus, pituitary gland) to investigate nerve pathways and neuroendocrine responses, and for treating certain pathological disorders of the brain with stereotaxic Bragg peak heavy-ion radiosurgery. Studies in animals are demonstrating the value of this neuroscience tool for investigating mammalian brain response to induction of discrete focal lesions in the hypothalamus or in the cerebral cortex. These studies are also elucidating the neuroendocrinological response follwing ablation of various portions of the midbrain, without requiring complex neurosurgical preparations. Clinical studies are demonstrating the feasibility of stereotaxic neurological radiosurgery for treating certain inoperable vascular disorders of the brain [e.g., arteriovenous malformations (AVM), internal carotid artery-cavernous sinus fistulas and other cerebrovascular disorders] in patients who are already demonstrating progressive neurological deficit. Further applications of focal lesion production with the Bragg ionization peak can be extended to include localized radiation to centers of the brain and spinal cord for treatment of such disorders as Parkinson's disease, pituitary microadenomas, acoustic neuromas, and the control of pain. The eventual application of radioactive beams will provide accurate localization of the stopping points of the beam, thereby making it feasible to stop the beam accurately at a defined depth within the central nervous system

  5. 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

  6. Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy

    NARCIS (Netherlands)

    Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

    Objective: The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. Methods: In our center patients are referred for 7 T MRI if lesional focal epilepsy is

  7. Focal airtrapping at expiratory high-resolution CT: comparison with pulmonary function tests

    International Nuclear Information System (INIS)

    Kauczor, H.U.; Hast, J.; Heussel, C.P.; Mildenberger, P.; Thelen, M.; Schlegel, J.

    2000-01-01

    This study was undertaken to determine prevalence, extent, and severity of focal airtrapping at expiratory high-resolution CT, and to compare focal airtrapping with age, gender, pulmonary function tests, and blood gas analysis. Two-hundred seventeen patients with and without pulmonary disease underwent paired inspiratory/expiratory high-resolution CT. Six scan pairs with corresponding scan levels were visually assessed for focal - not diffuse - airtrapping using a four-point scale. Pulmonary function tests and blood gas analysis were available for correlation in all patients (mean interval 5 days). Focal airtrapping with lower lung predominance was observed in 80 % of patients. Twenty-six of 26 patients with restrictive lung function impairment exhibited focal airtrapping (mean score 2.4), whereas only 72 of 98 (74 %) patients with obstruction did (mean score 1.5; p < 0.05). Fifty-eight of 70 (83 %) patients with normal lung function (mean score 1.8) and 19 of 23 (83 %) patients with mixed impairment (mean score 1.8) had focal airtrapping. Focal airtrapping showed negative correlations with static lung volumes (-0.27 to -0.37; p < 0.001) in all patients and moderate positive correlations with dynamic parameters (0.3-0.4; p < 0.001) in patients with obstruction. No significant correlations were found with age, gender, and blood gas analysis. Visual assessment of focal - not diffuse - airtrapping at expiratory high-resolution CT does not correlate with physiological evidence of obstruction as derived from pulmonary function tests since the perception of focal airtrapping requires an adequate expiratory increase in lung density. (orig.)

  8. 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.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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.

  10. Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells

    Science.gov (United States)

    Wang, Jennifer T; Kong, Dong; Hoerner, Christian R; Loncarek, Jadranka

    2017-01-01

    Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next. PMID:28906251

  11. Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells.

    Science.gov (United States)

    Wang, Jennifer T; Kong, Dong; Hoerner, Christian R; Loncarek, Jadranka; Stearns, Tim

    2017-09-14

    Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next.

  12. TA-55 facility control system upgrade project - human-system interface functional requirements

    International Nuclear Information System (INIS)

    Atkins, W.H.; Pope, N.G.; Turner, W.J.; Brown, R.E.

    1995-11-01

    The functional requirements for that part of the Technical Area (TA)-55 Operations Center Upgrade Project that involves the human-system interface (HSI) are described in this document. The upgrade project seeks to replace completely the center's existing computerized data acquisition and display system, which consists of the field multiplexer units, Data General computer systems, and associated peripherals and software. The upgrade project has two parts-the Facility Data Acquisition Interface System (FDAIS) and the HSI. The HSI comprises software and hardware to provide a high-level graphical operator interface to the data acquisition system, as well as data archiving, alarm annunciation, and logging. The new system will be built with modern, commercially available components; it will improve reliability and maintainability, and it can be expanded for future needs

  13. 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.

  14. Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans.

    Science.gov (United States)

    Lermann, Ulrich; Morschhäuser, Joachim

    2008-11-01

    A well-known virulence attribute of the human-pathogenic yeast Candida albicans is the secretion of aspartic proteases (Saps), which may contribute to colonization and infection of different host niches by degrading tissue barriers, destroying host defence molecules, or digesting proteins for nutrient supply. The role of individual Sap isoenzymes, which are encoded by a large gene family, for the pathogenicity of C. albicans has been investigated by assessing the virulence of mutants lacking specific SAP genes and by studying the expression pattern of the SAP genes in various models of superficial and systemic infections. We used a recombination-based genetic reporter system to detect the induction of the SAP1-SAP6 genes during infection of reconstituted human vaginal epithelium. Only SAP5, but none of the other tested SAP genes, was detectably activated in this in vitro infection model. To directly address the importance of the SAP1-SAP6 genes for invasion of reconstituted human epithelia (RHE), we constructed a set of mutants of the wild-type C. albicans model strain SC5314 in which either single or multiple SAP genes were specifically deleted. Even mutants lacking all of the SAP1-SAP3 or the SAP4-SAP6 genes displayed the same capacity to invade and damage both oral and vaginal RHE as their wild-type parental strain, in contrast to a nonfilamentous efg1Delta mutant that was avirulent under these conditions. We therefore conclude from these results that the secreted aspartic proteases Sap1p-Sap6p are not required for invasion of RHE by C. albicans.

  15. 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).

  16. ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation

    Directory of Open Access Journals (Sweden)

    Timothy J. Mead

    2018-04-01

    Full Text Available Summary: Focal adhesions anchor cells to extracellular matrix (ECM and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM. : Mead et al. identify a proteolytic mechanism that actively maintains a pericellular microenvironment conducive to uterine smooth muscle activation prior to parturition. They show that pericellular matrix proteolysis by the secreted metalloprotease ADAMTS9 is crucial for maintenance of focal adhesions in uterine smooth muscle cells, and its absence impairs parturition. Keywords: metalloprotease, extracellular matrix, smooth muscle, proteoglycan, myometrium, parturition, uterus, focal adhesion, proteolysis, interference reflection microscopy

  17. 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.

  18. Focal splenic masses of the extramedullary hematopoiesis

    International Nuclear Information System (INIS)

    Incedayi, M.; Sivrioglu, A.

    2012-01-01

    Full text: Extramedullary hematopoiesis arises from pleuripotential stem cells distributed throughout the body. It is most common in patients with congenital hemolytic anemia, such as thalassemia, sickle cell anemia and hereditary spherocytosis as a response to ineffective red blood cell formation. Although microscopic foci of Extramedullary hematopoiesis are commonly seen in the spleen and liver parenchyma, focal mass-like lesion of extramedullary hematopoiesis in the liver and spleen are rare. We report a case of intrasplenic focal extramedullary hematopoiesis lesions and the imaging features of extramedullary hematopoiesis on computed tomography and magnetic resonance imaging. Extramedullary hematopoiesis should always be considered as a diagnosis in a patient with a known hematological disorder

  19. Protein S binding to human endothelial cells is required for expression of cofactor activity for activated protein C

    NARCIS (Netherlands)

    Hackeng, T. M.; Hessing, M.; van 't Veer, C.; Meijer-Huizinga, F.; Meijers, J. C.; de Groot, P. G.; van Mourik, J. A.; Bouma, B. N.

    1993-01-01

    An important feedback mechanism in blood coagulation is supplied by the protein C/protein S anticoagulant pathway. In this study we demonstrate that the binding of human protein S to cultured human umbilical vein endothelial cells (HUVECs) is required for the expression of cofactor activity of

  20. Human T cell colony formation in microculture: analysis of growth requirements and functional activities.

    Science.gov (United States)

    Gelfand, E W; Lee, J W; Dosch, H M; Price, G B

    1981-03-01

    A microculture method in methylcellulose has been developed for the study of human T cell colony formation. The technique is simple, reliable, does not require preincubation with lectin and requires small numbers of cells. Colony formation was dependent on the presence of phytohemagglutin-conditioned medium, a T colony precursor cell (TCPC), and a "helper" or accessory T cell. Plating efficiency was increased 10-fold in the presence of irradiated feeder cells. Progenitors of the T colony cells were identified in peripheral blood, tonsil, and spleen but not in thymus or thoracic duct. They were isolated in the E-rosetting, theophylline-resistant, Fc-IgG-negative cell populations. In peripheral blood the frequency of TCPC and accessory cells, the T colony forming unit, was estimated to be 8 X 10(-3). Colony cells proliferated in response to lectins and allogeneic cells. Forty to 80% of the cells were Ia-positive and stimulated both autologous and allogeneic mixed lymphocyte responses. They were incapable of mediating antibody-dependent cytotoxicity. In contrast, they were effective in assays of spontaneous cytotoxicity but only against certain target cells. This method for the analysis of T colony formation should prove valuable in the functional analysis of T cell subsets in immunodeficiency states or the transplant recipient.

  1. Subdural Empyema Presenting with Seizure, Confusion, and Focal Weakness

    Directory of Open Access Journals (Sweden)

    David I Bruner

    2012-12-01

    Full Text Available While sinusitis is a common ailment, intracranial suppurative complications of sinusitis are rare and difficult to diagnose and treat. The morbidity and mortality of intracranial complications of sinusitis have decreased significantly since the advent of antibiotics, but diseases such as subdural empyemas and intracranial abscesses still occur, and they require prompt diagnosis, treatment, and often surgical drainage to prevent death or long-term neurologic sequelae. We present a case of an immunocompetent adolescent male with a subdural empyema who presented with seizures,confusion, and focal arm weakness after a bout of sinusitis.

  2. Subdural Empyema Presenting with Seizure, Confusion, and Focal Weakness

    Science.gov (United States)

    Bruner, David I.; Littlejohn, Lanny; Pritchard, Amy

    2012-01-01

    While sinusitis is a common ailment, intracranial suppurative complications of sinusitis are rare and difficult to diagnose and treat. The morbidity and mortality of intracranial complications of sinusitis have decreased significantly since the advent of antibiotics, but diseases such as subdural empyemas and intracranial abscesses still occur, and they require prompt diagnosis, treatment, and often surgical drainage to prevent death or long-term neurologic sequelae. We present a case of an immunocompetent adolescent male with a subdural empyema who presented with seizures, confusion, and focal arm weakness after a bout of sinusitis. PMID:23358438

  3. Infrared MUSIC from Z technology focal planes

    International Nuclear Information System (INIS)

    Waters, C.R.; Sommese, A.; Johnston, D.; Landau, H.

    1989-01-01

    Presented is the Multiple Signal Classification (MUSIC) algorithm which uses the high frequency differences in sensed time signals to discriminate, count, and accurately locate closely spaced targets. Z technology focal planes allow the implementation of this algorithm and the trade-off between finer spatial resolution systems and systems with coarser resolution but higher sampling rates

  4. 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.

  5. 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

    2013-01-01

    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. To quantify the electric field focality and depth of penetration of various TMS coils. 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, d(1/2), and focality by the tangential spread, S(1/2), defined as the half-value volume (V(1/2)) divided by the half-value depth, S(1/2) = V(1/2)/d(1/2). 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 d(1/2) 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 S(1/2) as low as 5 cm(2) compared to 34 cm(2) for circular field coils. 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 d(1/2) and S(1/2). Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Comprehensive identification of Vibrio vulnificus genes required for growth in human serum.

    Science.gov (United States)

    Carda-Diéguez, M; Silva-Hernández, F X; Hubbard, T P; Chao, M C; Waldor, M K; Amaro, C

    2018-12-31

    Vibrio vulnificus can be a highly invasive pathogen capable of spreading from an infection site to the bloodstream, causing sepsis and death. To survive and proliferate in blood, the pathogen requires mechanisms to overcome the innate immune defenses and metabolic limitations of this host niche. We created a high-density transposon mutant library in YJ016, a strain representative of the most virulent V. vulnificus lineage (or phylogroup) and used transposon insertion sequencing (TIS) screens to identify loci that enable the pathogen to survive and proliferate in human serum. Initially, genes underrepresented for insertions were used to estimate the V. vulnificus essential gene set; comparisons of these genes with similar TIS-based classification of underrepresented genes in other vibrios enabled the compilation of a common Vibrio essential gene set. Analysis of the relative abundance of insertion mutants in the library after exposure to serum suggested that genes involved in capsule biogenesis are critical for YJ016 complement resistance. Notably, homologues of two genes required for YJ016 serum-resistance and capsule biogenesis were not previously linked to capsule biogenesis and are largely absent from other V. vulnificus strains. The relative abundance of mutants after exposure to heat inactivated serum was compared with the findings from the serum screen. These comparisons suggest that in both conditions the pathogen relies on its Na + transporting NADH-ubiquinone reductase (NQR) complex and type II secretion system to survive/proliferate within the metabolic constraints of serum. Collectively, our findings reveal the potency of comparative TIS screens to provide knowledge of how a pathogen overcomes the diverse limitations to growth imposed by serum.

  7. Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

    Science.gov (United States)

    Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

    2015-12-18

    Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

  8. Low-Noise, UV-to-SWIR Broadband Photodiodes for Large-Format Focal Plane Array Sensors, Phase I

    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...

  9. Polarimeter on a Chip: Antenna-Coupled Microbolometers and Polarimeters for Submillimeterwave and Millimeterwave Focal Planes, Phase I

    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...

  10. Performance of an Achromatic Focal Plane Mask for Exoplanet Imaging Coronagraphy

    Science.gov (United States)

    Newman, Kevin; Belikov, Ruslan; Pluzhnik, Eugene; Balasubramanian, Kunjithapatham; Wilson, Dan

    2014-01-01

    Coronagraph technology combined with wavefront control is close to achieving the contrast and inner working angle requirements in the lab necessary to observe the faint signal of an Earth-like exoplanet in monochromatic light. An important remaining technological challenge is to achieve high contrast in broadband light. Coronagraph bandwidth is largely limited by chromaticity of the focal plane mask, which is responsible for blocking the stellar PSF. The size of a stellar PSF scales linearly with wavelength; ideally, the size of the focal plane mask would also scale with wavelength. A conventional hard-edge focal plane mask has a fixed size, normally sized for the longest wavelength in the observational band to avoid starlight leakage. The conventional mask is oversized for shorter wavelengths and blocks useful discovery space. Recently we presented a solution to the size chromaticity challenge with a focal plane mask designed to scale its effective size with wavelength. In this paper, we analyze performance of the achromatic size-scaling focal plane mask within a Phase Induced Amplitude Apodization (PIAA) coronagraph. We present results from wavefront control around the achromatic focal plane mask, and demonstrate the size-scaling effect of the mask with wavelength. The edge of the dark zone, and therefore the inner working angle of the coronagraph, scale with wavelength. The achromatic mask enables operation in a wider band of wavelengths compared with a conventional hard-edge occulter.

  11. Isolated human islets require hyperoxia to maintain islet mass, metabolism, and function.

    Science.gov (United States)

    Komatsu, Hirotake; Kang, Dongyang; Medrano, Leonard; Barriga, Alyssa; Mendez, Daniel; Rawson, Jeffrey; Omori, Keiko; Ferreri, Kevin; Tai, Yu-Chong; Kandeel, Fouad; Mullen, Yoko

    2016-02-12

    Pancreatic islet transplantation has been recognized as an effective treatment for Type 1 diabetes; however, there is still plenty of room to improve transplantation efficiency. Because islets are metabolically active they require high oxygen to survive; thus hypoxia after transplant is one of the major causes of graft failure. Knowing the optimal oxygen tension for isolated islets would allow a transplant team to provide the best oxygen environment during pre- and post-transplant periods. To address this issue and begin to establish empirically determined guidelines for islet maintenance, we exposed in vitro cultured islets to different partial oxygen pressures (pO2) and assessed changes in islet volume, viability, metabolism, and function. Human islets were cultured for 7 days in different pO2 media corresponding to hypoxia (90 mmHg), normoxia (160 mmHg), and hyerpoxia (270 or 350 mmHg). Compared to normoxia and hypoxia, hyperoxia alleviated the loss of islet volume, maintaining higher islet viability and metabolism as measured by oxygen consumption and glucose-stimulated insulin secretion responses. We predict that maintaining pre- and post-transplanted islets in a hyperoxic environment will alleviate islet volume loss and maintain islet quality thereby improving transplant outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. PKCθ is required for the activation of human T lymphocytes induced by CD43 engagement

    International Nuclear Information System (INIS)

    Rio, Roxana del; Rincon, Mercedes; Layseca-Espinosa, Esther; Fierro, Nora A.; Rosenstein, Yvonne; Pedraza-Alva, Gustavo

    2004-01-01

    The turnover of phosphoinositides leading to PKC activation constitutes one of the principal axes of intracellular signaling. In T lymphocytes, the enhanced and prolonged PKC activation resulting from the engagement of the TcR and co-receptor molecules ensures a productive T cell response. The CD43 co-receptor promotes activation and proliferation, by inducing IL-2 secretion and CD69 expression. CD43 engagement has been shown to promote phosphoinositide turnover and DAG production. Moreover, PKC activation was found to be required for the activation of the MAP kinase pathway in response to CD43 ligation. Here we show that CD43 engagement led to the membrane translocation and enzymatic activity of specific PKC isoenzymes: cPKC (α/β), nPKC (ε and θ), aPKC (ζ) and PKCμ. We also show that activation of PKCθ resulting from CD43 ligation induced CD69 expression through an ERK-dependent pathway leading to AP-1, NF-κB activation and an ERK independent pathway promoting NFAT activation. Together, these data suggest that PKCθ plays a critical role in the co-stimulatory functions of CD43 in human T cells

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

    KAUST Repository

    Moon, Robert W.; Sharaf, Hazem; Hastings, Claire H.; Ho, Yung Shwen; Nair, Mridul; Rchiad, ‍ Zineb; Knuepfer, Ellen; Ramaprasad, Abhinay; Mohring, Franziska; Amir, Amirah; Yusuf, Noor A.; Hall, Joanna; Almond, Neil; Lau, Yee Ling; Pain, Arnab; Blackman, Michael J.; Holder, Anthony A.

    2016-01-01

    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. 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.

  15. Comparison of different methods for determining the size of a focal spot of microfocus X-ray tubes

    International Nuclear Information System (INIS)

    Salamon, M.; Hanke, R.; Krueger, P.; Sukowski, F.; Uhlmann, N.; Voland, V.

    2008-01-01

    The EN 12543-5 describes a method for determining the focal spot size of microfocus X-ray tubes up to a minimum spot size of 5 μm. The wide application of X-ray tubes with even smaller focal spot sizes in computed tomography and radioscopy applications requires the evaluation of existing methods for focal spot sizes below 5 μm. In addition, new methods and conditions for determining submicron focal spot sizes have to be developed. For the evaluation and extension of the present methods to smaller focal spot sizes, different procedures in comparison with the existing EN 12543-5 were analyzed and applied, and the results are presented

  16. DESI focal plate mechanical integration and cooling

    Science.gov (United States)

    Lambert, A. R.; Besuner, R. W.; Claybaugh, T. M.; Silber, J. H.

    2016-08-01

    The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the Universe using the Baryon Acoustic Oscillation technique[1]. The spectra of 40 million galaxies over 14000 sq. deg will be measured during the life of the experiment. A new prime focus corrector for the KPNO Mayall telescope will deliver light to 5000 fiber optic positioners. The fibers in turn feed ten broad-band spectrographs. This paper describes the mechanical integration of the DESI focal plate and the thermal system design. The DESI focal plate is comprised of ten identical petal assemblies. Each petal contains 500 robotic fiber positioners. Each petal is a complete, self-contained unit, independent from the others, with integrated power supply, controllers, fiber routing, and cooling services. The major advantages of this scheme are: (1) supports installation and removal of complete petal assemblies in-situ, without disturbing the others, (2) component production, assembly stations, and test procedures are repeated and parallelizable, (3) a complete, full-scale prototype can be built and tested at an early date, (4) each production petal can be surveyed and tested as a complete unit, prior to integration, from the fiber tip at the focal surface to the fiber slit at the spectrograph. The ten petal assemblies will be installed in a single integration ring, which is mounted to the DESI corrector. The aluminum integration ring attaches to the steel corrector barrel via a flexured steel adapter, isolating the focal plate from differential thermal expansions. The plate scale will be kept stable by conductive cooling of the petal assembly. The guider and wavefront sensors (one per petal) will be convectively cooled by forced flow of air. Heat will be removed from the system at ten liquid-cooled cold plates, one per petal, operating at ambient temperature. The entire focal plate structure is enclosed in an insulating shroud, which serves as a thermal barrier

  17. Next generation sub-millimeter wave focal plane array coupling concepts: an ESA TRP project to develop multichroic focal plane pixels for future CMB polarization experiments

    Science.gov (United States)

    Trappe, N.; Bucher, M.; De Bernardis, P.; Delabrouille, J.; Deo, P.; DePetris, M.; Doherty, S.; Ghribi, A.; Gradziel, M.; Kuzmin, L.; Maffei, B.; Mahashabde, S.; Masi, S.; Murphy, J. A.; Noviello, F.; O'Sullivan, C.; Pagano, L.; Piacentini, F.; Piat, M.; Pisano, G.; Robinson, M.; Stompor, R.; Tartari, A.; van der Vorst, M.; Verhoeve, P.

    2016-07-01

    The main objective of this activity is to develop new focal plane coupling array concepts and technologies that optimise the coupling from reflector optics to the large number of detectors for next generation sub millimetre wave telescopes particularly targeting measurement of the polarization of the cosmic microwave background (CMB). In this 18 month TRP programme the consortium are tasked with developing, manufacturing and experimentally verifying a prototype multichroic pixel which would be suitable for the large focal plane arrays which will be demanded to reach the required sensitivity of future CMB polarization missions. One major development was to have multichroic operation to potentially reduce the required focal plane size of a CMB mission. After research in the optimum telescope design and definition of requirements based on a stringent science case review, a number of compact focal plane architecture concepts were investigated before a pixel demonstrator consisting of a planar mesh lens feeding a backend Resonant Cold Electron Bolometer RCEB for filtering and detection of the dual frequency signal was planned for manufacture and test. In this demonstrator the frequencies of the channels was chosen to be 75 and 105 GHz in the w band close to the peak CMB signal. In the next year the prototype breadboards will be developed to test the beams produced by the manufactured flat lenses fed by a variety of antenna configurations and the spectral response of the RCEBs will also be verified.

  18. Virtual reality technology as a tool for human factors requirements evaluation in design of the nuclear reactors control desks

    International Nuclear Information System (INIS)

    Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Mol, Antonio C.A.; Carvalho, Paulo V.R.; Silva, Antonio C.F.; Ferreira, Francisco J.O.; Dutra, Marco A.M.

    2007-01-01

    The Virtual Reality (VR) is an advanced computer interface technology that allows the user to internet or to explore a three-dimensional environment through the computer, as was part of the virtual world. This technology presents great applicability in the most diverse areas of the human knowledge. This paper presents a study on the use of the VR as tool for human factors requirements evaluation in design of the nuclear reactors control desks. Moreover, this paper presents a case study: a virtual model of the control desk, developed using virtual reality technology to be used in the human factors requirements evaluation. This case study was developed in the Virtual Reality Laboratory at IEN, and understands the stereo visualization of the Argonauta research nuclear reactor control desk for a static ergonomic evaluation using check-lists, in accordance to the standards and human factors nuclear international guides (IEC 1771, NUREG-0700). (author)

  19. Virtual reality technology as a tool for human factors requirements evaluation in design of the nuclear reactors control desks

    Energy Technology Data Exchange (ETDEWEB)

    Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Mol, Antonio C.A.; Carvalho, Paulo V.R.; Silva, Antonio C.F.; Ferreira, Francisco J.O.; Dutra, Marco A.M. [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: grecco@ien.gov.br; luquetti@ien.gov.br; mol@ien.gov.br; paulov@ien.gov.br; tonico@ien.gov.br; fferreira@ien.gov.br; dutra@ien.gov.br

    2007-07-01

    The Virtual Reality (VR) is an advanced computer interface technology that allows the user to internet or to explore a three-dimensional environment through the computer, as was part of the virtual world. This technology presents great applicability in the most diverse areas of the human knowledge. This paper presents a study on the use of the VR as tool for human factors requirements evaluation in design of the nuclear reactors control desks. Moreover, this paper presents a case study: a virtual model of the control desk, developed using virtual reality technology to be used in the human factors requirements evaluation. This case study was developed in the Virtual Reality Laboratory at IEN, and understands the stereo visualization of the Argonauta research nuclear reactor control desk for a static ergonomic evaluation using check-lists, in accordance to the standards and human factors nuclear international guides (IEC 1771, NUREG-0700). (author)

  20. Evaluation of focused ultrasound algorithms: Issues for reducing pre-focal heating and treatment time.

    Science.gov (United States)

    Yiannakou, Marinos; Trimikliniotis, Michael; Yiallouras, Christos; Damianou, Christakis

    2016-02-01

    Due to the heating in the pre-focal field the delay between successive movements in high intensity focused ultrasound (HIFU) are sometimes as long as 60s, resulting to treatment time in the order of 2-3h. Because there is generally a requirement to reduce treatment time, we were motivated to explore alternative transducer motion algorithms in order to reduce pre-focal heating and treatment time. A 1 MHz single element transducer with 4 cm diameter and 10 cm focal length was used. A simulation model was developed that estimates the temperature, thermal dose and lesion development in the pre-focal field. The simulated temperature history that was combined with the motion algorithms produced thermal maps in the pre-focal region. Polyacrylimde gel phantom was used to evaluate the induced pre-focal heating for each motion algorithm used, and also was used to assess the accuracy of the simulation model. Three out of the six algorithms having successive steps close to each other, exhibited severe heating in the pre-focal field. Minimal heating was produced with the algorithms having successive steps apart from each other (square, square spiral and random). The last three algorithms were improved further (with small cost in time), thus eliminating completely the pre-focal heating and reducing substantially the treatment time as compared to traditional algorithms. Out of the six algorithms, 3 were successful in eliminating the pre-focal heating completely. Because these 3 algorithms required no delay between successive movements (except in the last part of the motion), the treatment time was reduced by 93%. Therefore, it will be possible in the future, to achieve treatment time of focused ultrasound therapies shorter than 30 min. The rate of ablated volume achieved with one of the proposed algorithms was 71 cm(3)/h. The intention of this pilot study was to demonstrate that the navigation algorithms play the most important role in reducing pre-focal heating. By evaluating in

  1. 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 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...

  2. Radiopneumographic characteristics of focal pneumonia in children

    International Nuclear Information System (INIS)

    Smirnova, A.A.

    1980-01-01

    Zonal ventilation and blood flow were studied by the radiopneumography method in 50 children of school age with lower-lobe-of-the lung focal pneumonia (26 with left-side and 24 with right-side). It is established that during right-side localization of pneumonic focus preserved was the predomination of ventilation of right lung relative to left. Complete normalization of common and regional indexes of ventilation and blood flow was established by the 21st day from the beginning of treatment during right-side focal pneumonias. In case of left-side localization of pneumonic focus only partial reduction of external respiration and perfusion comes. Therefore, compensatory and reducing capabilities of right lung are preferrable

  3. Focal epilepsy in the Belgian shepherd

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...... seizures. In seven dogs, seizures could not be classified. The mode of inheritance of epilepsy was simple Mendelian. CLINICAL SIGNIFICANCE: This study identified that the Belgian shepherd suffers from genetically transmitted focal epilepsy. The seizure phenomenology expressed by family members have...

  4. Chest pain in focal musculoskeletal disorders

    DEFF Research Database (Denmark)

    Stochkendahl, Mette Jensen; Christensen, Henrik Wulff

    2010-01-01

    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......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...... arises mainly from case stories and empiric knowledge. For segmental dysfunction, clinical features of musculoskeletal chest pain have been characterized in a few clinical trials. This article summarizes the most commonly encountered syndromes of focal musculoskeletal disorders in clinical practice....

  5. Proximal focal femoral deficiency: A case report

    Directory of Open Access Journals (Sweden)

    Shashank Sharma

    2015-01-01

    Full Text Available Proximal focal femoral deficiency (PFFD is a rare congenital anomaly resulting in limb shortening and disability in young. The exact cause of the disease is not known and it may present as varying grades of affection involving the proximal femur and the acetabulum. Recognition of this rare abnormality on radiographs can help manage these cases better since early institution of therapy may help in achieving adequate growth of the femur.

  6. Syndecan-4 and focal adhesion function

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    2001-01-01

    Two groups have now reported the viability of mice that lack syndecan-4. These mice have wound healing/angiogenesis problems, and fibroblasts from these animals differ in adhesion and migration from normal. This is consistent with recent in vitro data indicating a need for signaling via syndecan-4...... for focal adhesion formation, and reports that overexpression of proteins that bind syndecan-4 can modify cell adhesion and migration....

  7. 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.

  8. Fabrication of Transition Edge Sensor Microcalorimeters for X-Ray Focal Planes

    Science.gov (United States)

    Chervenak, James A.; Adams, Joseph S.; Audley, Heather; Bandler, Simon R.; Betancourt-Martinez, Gabriele; Eckart, Megan E.; Finkbeiner, Fred M.; Kelley, Richard L.; Kilbourne, Caroline; Lee, Sang Jun; hide

    2015-01-01

    Requirements for focal planes for x-ray astrophysics vary widely depending on the needs of the science application such as photon count rate, energy band, resolving power, and angular resolution. Transition edge sensor x-ray calorimeters can encounter limitations when optimized for these specific applications. Balancing specifications leads to choices in, for example, pixel size, thermal sinking arrangement, and absorber thickness and material. For the broadest specifications, instruments can benefit from multiple pixel types in the same array or focal plane. Here we describe a variety of focal plane architectures that anticipate science requirements of x-ray instruments for heliophysics and astrophysics. We describe the fabrication procedures that enable each array and explore limitations for the specifications of such arrays, including arrays with multiple pixel types on the same array.

  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. Focal plane scanner with reciprocating spatial window

    Science.gov (United States)

    Mao, Chengye (Inventor)

    2000-01-01

    A focal plane scanner having a front objective lens, a spatial window for selectively passing a portion of the image therethrough, and a CCD array for receiving the passed portion of the image. All embodiments have a common feature whereby the spatial window and CCD array are mounted for simultaneous relative reciprocating movement with respect to the front objective lens, and the spatial window is mounted within the focal plane of the front objective. In a first embodiment, the spatial window is a slit and the CCD array is one-dimensional, and successive rows of the image in the focal plane of the front objective lens are passed to the CCD array by an image relay lens interposed between the slit and the CCD array. In a second embodiment, the spatial window is a slit, the CCD array is two-dimensional, and a prism-grating-prism optical spectrometer is interposed between the slit and the CCD array so as to cause the scanned row to be split into a plurality of spectral separations onto the CCD array. In a third embodiment, the CCD array is two-dimensional and the spatial window is a rectangular linear variable filter (LVF) window, so as to cause the scanned rows impinging on the LVF to be bandpass filtered into spectral components onto the CCD array through an image relay lens interposed between the LVF and the CCD array.

  11. 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.

  12. Brivaracetam: a novel antiepileptic drug for focal-onset seizures.

    Science.gov (United States)

    Stephen, Linda J; Brodie, Martin J

    2018-01-01

    Brivaracetam (BRV), the n -propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein. In animal models, BRV provides protection against focal and secondary generalized seizures and has significant anticonvulsant effects in genetic models of epilepsy. The drug undergoes first-order pharmacokinetics with an elimination half-life of 7-8 h. Although BRV is metabolized extensively, the main circulating compound is unchanged BRV. Around 95% of metabolites undergo renal elimination. No dose reduction is required in renal impairment, but it is recommended that the daily dose is reduced by one-third in hepatic dysfunction that may prolong half-life. BRV has a low potential for drug interactions. The efficacy and tolerability of adjunctive BRV in adults with focal-onset seizures have been explored in six randomized, placebo-controlled studies. These showed significant efficacy outcomes for doses of 50-200 mg/day. The most common adverse events reported were headache, somnolence, dizziness, fatigue and nausea. Patients who develop psychiatric symptoms with LEV appear to be at risk of similar side effects with BRV, although preliminary data suggest that these issues are likely to be less frequent and perhaps less severe. As with all AEDs, a low starting dose and slow titration schedule help to minimize side effects and optimize seizure control and thereby quality of life.

  13. Classification of Focal and Non Focal Epileptic Seizures Using Multi-Features and SVM Classifier.

    Science.gov (United States)

    Sriraam, N; Raghu, S

    2017-09-02

    Identifying epileptogenic zones prior to surgery is an essential and crucial step in treating patients having pharmacoresistant focal epilepsy. Electroencephalogram (EEG) is a significant measurement benchmark to assess patients suffering from epilepsy. This paper investigates the application of multi-features derived from different domains to recognize the focal and non focal epileptic seizures obtained from pharmacoresistant focal epilepsy patients from Bern Barcelona database. From the dataset, five different classification tasks were formed. Total 26 features were extracted from focal and non focal EEG. Significant features were selected using Wilcoxon rank sum test by setting p-value (p z > 1.96) at 95% significance interval. Hypothesis was made that the effect of removing outliers improves the classification accuracy. Turkey's range test was adopted for pruning outliers from feature set. Finally, 21 features were classified using optimized support vector machine (SVM) classifier with 10-fold cross validation. Bayesian optimization technique was adopted to minimize the cross-validation loss. From the simulation results, it was inferred that the highest sensitivity, specificity, and classification accuracy of 94.56%, 89.74%, and 92.15% achieved respectively and found to be better than the state-of-the-art approaches. Further, it was observed that the classification accuracy improved from 80.2% with outliers to 92.15% without outliers. The classifier performance metrics ensures the suitability of the proposed multi-features with optimized SVM classifier. It can be concluded that the proposed approach can be applied for recognition of focal EEG signals to localize epileptogenic zones.

  14. Effects of Focal Basal Ganglia Lesions on Timing and Force Control

    Science.gov (United States)

    Aparicio, P.; Diedrichsen, J.; Ivry, R.B.

    2005-01-01

    Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of…

  15. Insisting on the Healer's Art: The Implications of Required Participation in a Medical School Course on Values and Humanism.

    Science.gov (United States)

    Rabow, Michael W; Lapedis, Marissa; Feingold, Anat; Thomas, Mark; Remen, Rachel N

    2016-01-01

    Elective courses, by definition, allow medical students to self-select for participation in the class. In a small-group learning setting, students uninterested or not ready for a particular learning topic might change the educational experience ("poison the well") for those students most interested in the topic. It is not known how medical students required to take a course in humanism (that they otherwise would not have elected to take) might be impacted by the course or how their presence might affect students originally interested in the course. Medical students in a required course on humanism and values in medicine will have different experiences based on whether a particular student might have or not have elected to enroll in the course. Students uninterested in taking a course in humanism and values, but required to enroll, will limit the benefit of the course for those students originally interested in participating. In 2012, all 1st-year students at a U.S. medical school were required to take the Healer's Art, an elective on professional values and humanism offered at more than 90 other schools in the United States and internationally. Students completed pre/postcourse surveys assessing emotional exhaustion, work engagement, positive emotions, and cynicism. We analyzed differences between those who would have elected to take the course (Elective students) and those who would not have elected to take it (Required students). Elective students did not differ from Required students in baseline demographic characteristics, emotional exhaustion, work engagement, or positive emotions. At baseline, Elective students did report feeling safer to talk openly, a greater sense of community, and higher levels of cynicism. Over time, there were no differences in course evaluations or outcomes between Elective and Required students. Required students do not differ greatly from those who would have elected to take Healer's Art, and all students appear to have similar

  16. 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...

  17. 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...human trust are developed from a literature review covering theory and empirical studies that have investigated the importance of human trust in...The factors that affect human trust are developed from a literature review covering theory and empirical studies that have investigated the

  18. Focal colors across languages are representative members of color categories.

    Science.gov (United States)

    Abbott, Joshua T; Griffiths, Thomas L; Regier, Terry

    2016-10-04

    Focal colors, or best examples of color terms, have traditionally been viewed as either the underlying source of cross-language color-naming universals or derived from category boundaries that vary widely across languages. Existing data partially support and partially challenge each of these views. Here, we advance a position that synthesizes aspects of these two traditionally opposed positions and accounts for existing data. We do so by linking this debate to more general principles. We show that best examples of named color categories across 112 languages are well-predicted from category extensions by a statistical model of how representative a sample is of a distribution, independently shown to account for patterns of human inference. This model accounts for both universal tendencies and variation in focal colors across languages. We conclude that categorization in the contested semantic domain of color may be governed by principles that apply more broadly in cognition and that these principles clarify the interplay of universal and language-specific forces in color naming.

  19. 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

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

    International Nuclear Information System (INIS)

    Crowe, David L; Ohannessian, Arthur

    2004-01-01

    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. 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. 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. We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway

  1. 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.

  2. X-ray focal spot reconstruction by circular penumbra analysis-Application to digital radiography systems.

    Science.gov (United States)

    Di Domenico, Giovanni; Cardarelli, Paolo; Contillo, Adriano; Taibi, Angelo; Gambaccini, Mauro

    2016-01-01

    The quality of a radiography system is affected by several factors, a major one being the focal spot size of the x-ray tube. In fact, the measurement of such size is recognized to be of primary importance during acceptance tests and image quality evaluations of clinical radiography systems. The most common device providing an image of the focal spot emission distribution is a pin-hole camera, which requires a high tube loading in order to produce a measurable signal. This work introduces an alternative technique to obtain an image of the focal spot, through the processing of a single radiograph of a simple test object, acquired with a suitable magnification. The radiograph of a magnified sharp edge is a well-established method to evaluate the extension of the focal spot profile along the direction perpendicular to the edge. From a single radiograph of a circular x-ray absorber, it is possible to extract simultaneously the radial profiles of several sharp edges with different orientations. The authors propose a technique that allows to obtain an image of the focal spot through the processing of these radial profiles by means of a pseudo-CT reconstruction technique. In order to validate this technique, the reconstruction has been applied to the simulated radiographs of an ideal disk-shaped absorber, generated by various simulated focal spot distributions. Furthermore, the method has been applied to the focal spot of a commercially available mammography unit. In the case of simulated radiographs, the results of the reconstructions have been compared to the original distributions, showing an excellent agreement for what regards both the overall distribution and the full width at half maximum measurements. In the case of the experimental test, the method allowed to obtain images of the focal spot that have been compared with the results obtained through standard techniques, namely, pin-hole camera and slit camera. The method was proven to be effective for simulated

  3. X-ray focal spot reconstruction by circular penumbra analysis—Application to digital radiography systems

    Energy Technology Data Exchange (ETDEWEB)

    Di Domenico, Giovanni, E-mail: didomenico@fe.infn.it; Cardarelli, Paolo; Taibi, Angelo; Gambaccini, Mauro [Dipartimento di Fisica e Scienze della Terra, Università degli Studi di Ferrara, via Saragat 1, FE I-44122, Italy and INFN - sezione di Ferrara, via Saragat 1, FE I-44122 (Italy); Contillo, Adriano [Dipartimento di Fisica e Scienze della Terra, Università degli Studi di Ferrara, via Saragat 1, FE I-44122 (Italy)

    2016-01-15

    Purpose: The quality of a radiography system is affected by several factors, a major one being the focal spot size of the x-ray tube. In fact, the measurement of such size is recognized to be of primary importance during acceptance tests and image quality evaluations of clinical radiography systems. The most common device providing an image of the focal spot emission distribution is a pin-hole camera, which requires a high tube loading in order to produce a measurable signal. This work introduces an alternative technique to obtain an image of the focal spot, through the processing of a single radiograph of a simple test object, acquired with a suitable magnification. Methods: The radiograph of a magnified sharp edge is a well-established method to evaluate the extension of the focal spot profile along the direction perpendicular to the edge. From a single radiograph of a circular x-ray absorber, it is possible to extract simultaneously the radial profiles of several sharp edges with different orientations. The authors propose a technique that allows to obtain an image of the focal spot through the processing of these radial profiles by means of a pseudo-CT reconstruction technique. In order to validate this technique, the reconstruction has been applied to the simulated radiographs of an ideal disk-shaped absorber, generated by various simulated focal spot distributions. Furthermore, the method has been applied to the focal spot of a commercially available mammography unit. Results: In the case of simulated radiographs, the results of the reconstructions have been compared to the original distributions, showing an excellent agreement for what regards both the overall distribution and the full width at half maximum measurements. In the case of the experimental test, the method allowed to obtain images of the focal spot that have been compared with the results obtained through standard techniques, namely, pin-hole camera and slit camera. Conclusions: The method was

  4. 21 CFR 201.26 - Exceptions or alternatives to labeling requirements for human drug products held by the Strategic...

    Science.gov (United States)

    2010-04-01

    ... requirements for human drug products held by the Strategic National Stockpile. 201.26 Section 201.26 Food and... drug products held by the Strategic National Stockpile. (a) The appropriate FDA Center Director may... safety, effectiveness, or availability of such product that is or will be included in the Strategic...

  5. 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.

  6. Treatment planning for prostate focal laser ablation in the face of needle placement uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Cepek, Jeremy, E-mail: jcepek@robarts.ca; Fenster, Aaron [Robarts Research Institute, London, Ontario N6A 5K8, Canada and Biomedical Engineering, The University of Western Ontario, London, Ontario N6A 5B9 (Canada); Lindner, Uri; Trachtenberg, John [Department of Surgical Oncology, Division of Urology, University Health Network, Toronto, Ontario M5G 2C4 (Canada); Davidson, Sean R. H. [Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada); Haider, Masoom A. [Department of Medical Imaging, Sunnybrook Health Sciences Center, Toronto, Ontario M4N 3M5, Canada and Department of Medical Imaging, University of Toronto, Toronto, Ontario M5S 2J7 (Canada); Ghai, Sangeet [Department of Medical Imaging, University Health Network, Toronto, Ontario M5G 2M9 (Canada)

    2014-01-15

    Purpose: To study the effect of needle placement uncertainty on the expected probability of achieving complete focal target destruction in focal laser ablation (FLA) of prostate cancer. Methods: Using a simplified model of prostate cancer focal target, and focal laser ablation region shapes, Monte Carlo simulations of needle placement error were performed to estimate the probability of completely ablating a region of target tissue. Results: Graphs of the probability of complete focal target ablation are presented over clinically relevant ranges of focal target sizes and shapes, ablation region sizes, and levels of needle placement uncertainty. In addition, a table is provided for estimating the maximum target size that is treatable. The results predict that targets whose length is at least 5 mm smaller than the diameter of each ablation region can be confidently ablated using, at most, four laser fibers if the standard deviation in each component of needle placement error is less than 3 mm. However, targets larger than this (i.e., near to or exceeding the diameter of each ablation region) require more careful planning. This process is facilitated by using the table provided. Conclusions: The probability of completely ablating a focal target using FLA is sensitive to the level of needle placement uncertainty, especially as the target length approaches and becomes greater than the diameter of ablated tissue that each individual laser fiber can achieve. The results of this work can be used to help determine individual patient eligibility for prostate FLA, to guide the planning of prostate FLA, and to quantify the clinical benefit of using advanced systems for accurate needle delivery for this treatment modality.

  7. NeuroSeek dual-color image processing infrared focal plane array

    Science.gov (United States)

    McCarley, Paul L.; Massie, Mark A.; Baxter, Christopher R.; Huynh, Buu L.

    1998-09-01

    Several technologies have been developed in recent years to advance the state of the art of IR sensor systems including dual color affordable focal planes, on-focal plane array biologically inspired image and signal processing techniques and spectral sensing techniques. Pacific Advanced Technology (PAT) and the Air Force Research Lab Munitions Directorate have developed a system which incorporates the best of these capabilities into a single device. The 'NeuroSeek' device integrates these technologies into an IR focal plane array (FPA) which combines multicolor Midwave IR/Longwave IR radiometric response with on-focal plane 'smart' neuromorphic analog image processing. The readout and processing integrated circuit very large scale integration chip which was developed under this effort will be hybridized to a dual color detector array to produce the NeuroSeek FPA, which will have the capability to fuse multiple pixel-based sensor inputs directly on the focal plane. Great advantages are afforded by application of massively parallel processing algorithms to image data in the analog domain; the high speed and low power consumption of this device mimic operations performed in the human retina.

  8. Is Mars Sample Return Required Prior to Sending Humans to Mars?

    Science.gov (United States)

    Carr, Michael; Abell, Paul; Allwood, Abigail; Baker, John; Barnes, Jeff; Bass, Deborah; Beaty, David; Boston, Penny; Brinkerhoff, Will; Budney, Charles; hide

    2012-01-01

    Prior to potentially sending humans to the surface of Mars, it is fundamentally important to return samples from Mars. Analysis in Earth's extensive scientific laboratories would significantly reduce the risk of human Mars exploration and would also support the science and engineering decisions relating to the Mars human flight architecture. The importance of measurements of any returned Mars samples range from critical to desirable, and in all cases these samples will would enhance our understanding of the Martian environment before potentially sending humans to that alien locale. For example, Mars sample return (MSR) could yield information that would enable human exploration related to 1) enabling forward and back planetary protection, 2) characterizing properties of Martian materials relevant for in situ resource utilization (ISRU), 3) assessing any toxicity of Martian materials with respect to human health and performance, and 4) identifying information related to engineering surface hazards such as the corrosive effect of the Martian environment. In addition, MSR would be engineering 'proof of concept' for a potential round trip human mission to the planet, and a potential model for international Mars exploration.

  9. 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.

  10. A new focalize of quality auditorship for documentation control. A practical case

    International Nuclear Information System (INIS)

    Young, R.B.; Malanij, D.

    1994-01-01

    Available as short communication only. A practical case of auditorship for Documentation Control System is described, showing the increase of efficiency when operated in the concept of Business Process Improvement, and this focalize is compatible with the nuclear area requirements. (C.G.C.). 2 refs

  11. Part 1: MRI features of focal nodular hyperplasia with an emphasis on hepatobiliary contrast agents

    International Nuclear Information System (INIS)

    Sutherland, Tom; Seale, Melanie; Yap, Yap

    2014-01-01

    Focal nodular hyperplasia (FNH) is the second most common benign liver tumour and typically do not require any treatment. An accurate non-invasive diagnosis is therefore vital to avoid unnecessary intervention and to reassure patients. This article discusses the demographics and pathology of FNH and reviews the appearance of FNH at MRI using liver-specific contrast agents.

  12. Focal spot size predictions for beam transport through a gas-filled reactor

    International Nuclear Information System (INIS)

    Yu, S.S.; Lee, E.P.; Buchanan, H.L.

    1980-01-01

    Results from calculations of focal spot size for beam transport through a gas-filled reactor are summarized. In the converging beam mode, we find an enlargement of the focal spot due to multiple scattering and zeroth order self-field effects. This enlargement can be minimized by maintaining small reactors together with a careful choice of the gaseous medium. The self-focused mode, on the other hand, is relatively insensitive to the reactor environment, but is critically dependent upon initial beam quality. This requirement on beam quality can be significantly eased by the injection of an electron beam of modest current from the opposite wall

  13. Third-generation intelligent IR focal plane arrays

    Science.gov (United States)

    Caulfield, H. John; Jack, Michael D.; Pettijohn, Kevin L.; Schlesselmann, John D.; Norworth, Joe

    1998-03-01

    SBRC is at the forefront of industry in developing IR focal plane arrays including multi-spectral technology and '3rd generation' functions that mimic the human eye. 3rd generation devices conduct advanced processing on or near the FPA that serve to reduce bandwidth while performing needed functions such as automatic target recognition, uniformity correction and dynamic range enhancement. These devices represent a solution for processing the exorbitantly high bandwidth coming off large area FPAs without sacrificing systems sensitivity. SBRC's two-color approach leverages the company's HgCdTe technology to provide simultaneous multiband coverage, from short through long wave IR, with near theoretical performance. IR systems that are sensitive to different spectral bands achieve enhanced capabilities for target identification and advanced discrimination. This paper will provide a summary of the issues, the technology and the benefits of SBRC's third generation smart and two-color FPAs.

  14. Focal inflammatory diseases of the liver

    International Nuclear Information System (INIS)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-01-01

    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

  15. 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.

  16. Focal plane AIT sequence: evolution from HRG-Spot 5 to Pleiades HR

    Science.gov (United States)

    Le Goff, Roland; Pranyies, Pascal; Toubhans, Isabelle

    2017-11-01

    Optical and geometrical image qualities of Focal Planes, for "push-broom" high resolution remote sensing satellites, require the implementation of specific means and methods for the AIT sequence. Indeed the geometric performances of the focal plane mainly axial focusing and transverse registration, are duly obtained on the basis of adjustment, setting and measurement of optical and CCD components with an accuracy of a few microns. Since the end of the 1970s, EADS-SODERN has developed a series of detection units for earth observation instruments like SPOT and Helios. And EADS-SODERN is now responsible for the development of the Pleiades High Resolution Focal Plane assembly. This paper presents the AIT sequences. We introduce all the efforts, innovative solutions and improvements made on the assembly facilities to match the technical evolutions and breakthrough of the Pleiades HR FP concept in comparison with the previous High Resolution Geometric SPOT 5 Focal Plane. The main evolution drivers are the implementation of strip filters and the realization of 400 mm continuous retinas. For Pleiades HR AIT sequence, three specific integration and measuring benches, corresponding with the different assembly stages, are used: a 3-D non-contact measurement machine for the assembly of detection module, a 3-D measurement machine for mirror integration on the main Focal Plane SiC structure, and a 3-D geometric coordinates control bench to focus detection module lines and to ensure they are well registered together.

  17. An Approach to Establish Design Requirements for Human-System Interface (HSI) of Automatic Systems in Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Nuraslinda, Anuar; Kim, Jonghyun [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

    2013-05-15

    This paper aims to demonstrate an approach to establish the design requirements for automatic systems in nuclear power plant (NPP) by using a powerful tool called Itemized Sequence Diagram (ISD). The process starts with function allocation by defining a set of levels of automation (LOAs). Then, task allocation is done using the ISD and finally the design requirements are established by examining the interaction points between human operator and automation, which are all located on the interface as modeled in the ISD. The strengths of this approach are discussed and a suggestion to integrate with that of the methodology employed to produce the existing guidelines or guidance is included in this paper. Some issues of automation have been addressed earlier in this paper and 12 design requirements that address human-system interaction were suggested by using the ISD as a tool to identify the interaction points between human operator and automation. The integration of the proposed approach in this paper with that of existing guidance could result in the new issue identification that would call for the establishment of new guidance. For example, Requirement 11 states that the HSI should provide the means for take-over from automatic to manual control was not mentioned in the existing guidance.

  18. CT scan findings in focal epilepsy

    International Nuclear Information System (INIS)

    Kobayashi, Eiki; Mihara, Tadahiro; Yamamoto, Kunimitsu; Yamashita, Kenji; Asakura, Tetsuhiko

    1980-01-01

    In 80 cases of focal epilepsy, excluding such cases as late onset after the age of 30 and traumatic or expansive lesions, the epileptogenic foci have been studied by comparing the CT findings with the seizure types and the EEG findings. The results were as follows: (1) Abnormal CT findings were observed in 36% of the patients. (2) These findings were classified into 4 large groups: localized cerebral atrophy, localized low density, localized high density with contrast enhancement and diffuse cerebral atrophy. (3) The incidence of CT abnormality was higher in the cases with continuous and localized EEG abnormality than in the cases with other types of EEG abnormality. In 48% of the cases, the location of the abnormal CT findings coincided with their EEG foci. (4) In the cases of temporal lobe epilepsy without abnormal CT images, the print-out data compared with the bilateral promised temporal regions, before and after contrast enhancement. The EMI-No. of the medial temporal focus increased more than that of the contralateral side in 3 cases out of 4 after contrast-media injection. (5) Moreover, for the purpose of comparing the CT findings on general seizures with those in focal seizures, we have studied 80 cases of general seizures. In the cases of the general seizures, abnormal CT findings were observed in only 16%. These abnormal findings were diffuse in 5 cases, localized in 6 cases, and combined in 3 cases. (author)

  19. The Sentinel 4 focal plane subsystem

    Science.gov (United States)

    Hohn, Rüdiger; Skegg, Michael P.; Hermsen, Markus; Hinger, Jürgen; Williges, Christian; Reulke, Ralf

    2017-09-01

    The Sentinel 4 instrument is an imaging spectrometer, developed by Airbus under ESA contract in the frame of the joint European Union (EU)/ESA COPERNICUS program with the objective of monitoring trace gas concentrations. Sentinel 4 will provide accurate measurements of key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, formaldehyde, as well as aerosol and cloud properties. Sentinel 4 is unique in being the first geostationary UVN mission. The SENTINEL 4 space segment will be integrated on EUMETSAT's Meteosat Third Generation Sounder satellite (MTG-S). Sentinel 4 will provide coverage of Europe and adjacent regions. The Sentinel 4 instrument comprises as a major element two Focal Plane Subsystems (FPS) covering the wavelength ranges 305 nm to 500 nm (UVVIS) and 750 nm to 775 nm (NIR) respectively. The paper describes the Focal Plane Subsystems, comprising the detectors, the optical bench and the control electronics. Further the design and development approach will be presented as well as first measurement results of FPS Qualification Model.

  20. Focal CT abnormality and epileptogenic focus

    International Nuclear Information System (INIS)

    Yagi, Kazuichi; Mihara, Tadahiro; Tottori, Takayasu; Matsuda, Kazumi; Watanabe, Yutaka; Seino, Masakazu

    1989-01-01

    In 31 patients with temporal lobe epilepsy, the precise site of epileptogenic focus was determined by means of a depth EEG recording as one of the presurgical evaluations. In 13 patients, a CT scan revealed focal lesions; 7 in the left temporal lobe and 6 in the right temporal lobe. In 5 of the 7 patients and in 5 of the 6 patients the epileptogenic foci were determined in the temporal lobe on the side of a CT lesion. However, in 2 of the patients with a CT lesion in the left temporal lobe, independent epileptogenic foci were found in both the temporal lobes, and in the other patient with a CT lesion in the right temporal lobe, they were found in the right frontal and left temporal lobes. Thus, the CT lesions agreed in lateralization and focality with the epileptogenic foci in 10 of the 13 patients (77%), but they disagreed in 3 (23%). A CT lesion disclosed in the temporal lobe does not necessarily indicate the side and/or site where the epileptogenic focus may be localized. Although exceptions may be made, spatial disagreement was exemplified between the CT lesion and epileptogenic focus. Therefore, extreme caution has to be taken on the side and/or site of the epileptogenic focus when functional surgical indication is to be made. (author)

  1. Serial neuroradiological studies in focal cerebritis

    International Nuclear Information System (INIS)

    Hatta, S.; Mochizuki, H.; Kuru, Y.; Miwa, H.; Kondo, T.; Mori, H.; Mizuno, Y.

    1994-01-01

    We report serial neuroradiological studies in a patient with focal cerebritis in the head of the left caudate nucleus. On the day after the onset of symptoms, CT showed an ill-defined low density lesion. The lack of contrast enhancement appeared to be the most important finding for differentiating focal cerebritis from an encapsulated brain abscess or a tumour. MRI two days later revealed the centre of the lesion to be of slightly low intensity on T1-weighted inversion recovery (IR) images and very low intensity on T2-weighted spin echo images, which appeared to correspond to the early cerebritis stage of experimentally induced cerebritis and brain abscess. Ten days after the onset of symptoms, CT revealed a thin ring of enhancement in the head of the caudate nucleus, and a similar small ring was seen in the hypothalamus 16 days after the onset, corresponding to the late cerebritis stage. MRI nine days later revealed ill-defined high signal lesions within the involved area on the T1-weighted IR images. To our knowledge, this is the first published MRI documentation of the early cerebritis stage developing into an encapsulated brain abscess. The mechanisms underlying of these radiographic changes are discussed. (orig.)

  2. Ultrasound elastographic techniques in focal liver lesions.

    Science.gov (United States)

    Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

    2016-03-07

    Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.

  3. 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'.

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

    International Nuclear Information System (INIS)

    Koo, In Soo; Suh, S. M.; Park, G. O.

    2006-07-01

    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'

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

    African Journals Online (AJOL)

    Enrique

    Department of Radiology. Nelson Mandela School of Health Sciences. Durban. Fig. 1a. Unenhanced CT of the liver in case 1 demonstrates multiple focal low density regions in both lobes of the liver. Region of interest 1 over the fatty left lobe measured 10 HU while region of interest 2 over the right lobe measure 40 HU in.

  6. 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.

  7. 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.

  8. 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.

    2012-01-01

    Background: 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…

  9. CONSUMER PREFERENCES FOR SCANNING MODALITY TO DIAGNOSE FOCAL LIVER LESIONS.

    Science.gov (United States)

    Whitty, Jennifer; Filby, Alexandra; Smith, Adam B; Carr, Louise M

    2015-01-01

    Differences in the process of using liver imaging technologies might be important to patients. This study aimed to investigate preferences for scanning modalities used in diagnosing focal liver lesions. A discrete choice experiment was administered to 504 adults aged 25 ≥years. Respondents made repeated choices between two hypothetical scans, described according to waiting time for scan and results, procedure type, the chance of minor side-effects, and whether further scanning procedures were likely to be required. Choice data were analyzed using mixed-logit models with respondent characteristics used to explain preference heterogeneity. Respondents preferred shorter waiting times, the procedure to be undertaken with a handheld scanner on a couch instead of within a body scanner, no side-effects, and no follow–up scans (p≤.01). The average respondent was willing to wait an additional 2 weeks for the scan if it resulted in avoiding side-effects, 1.5 weeks to avoid further procedures or to be told the results immediately, and 1 week to have the scan performed on a couch with a handheld scanner. However, substantial heterogeneity was observed in the strength of preference for desirable imaging characteristics. An average individual belonging to a general population sub–group most likely to require imaging to characterize focal liver lesions in the United Kingdom would prefer contrast–enhanced ultrasound over magnetic resonance imaging or computed tomography. Insights into the patient perspective around differential characteristics of imaging modalities have the potential to be used to guide recommendations around the use of these technologie

  10. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

    OpenAIRE

    Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

    2008-01-01

    The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

  11. Do people with intellectual disability require special human subjects research protections? The interplay of history, ethics, and policy.

    Science.gov (United States)

    Feudtner, Chris; Brosco, Jeffrey P

    2011-01-01

    People with intellectual disability (ID) have a long history of discrimination and stigmatization, and a more recent history of pride and self-advocacy. The early history suggests that people with ID are a vulnerable population and deserve special research protections as do some other groups; the disability rights movement of the late 20th century aligns people with ID more closely with the principle of autonomy that has guided clinical and research ethics for the last 40 years. In examining the history of people with ID and the prevailing framework of human subjects research protections in the United States, we conclude that people with ID do not require special protection in human subjects research. The protections that have already been put in place for all individuals, if conscientiously and effectively implemented, achieve the right balance between safeguarding the interest of human research subjects and empowering individuals who choose to do so to participate in research. Copyright © 2012 Wiley Periodicals, Inc.

  12. Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination.

    Science.gov (United States)

    Wiese, Claudia; Hinz, John M; Tebbs, Robert S; Nham, Peter B; Urbin, Salustra S; Collins, David W; Thompson, Larry H; Schild, David

    2006-01-01

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks (ICLs). Ectopic expression of wild-type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  13. CT appearance of focal fatty infiltration of the liver

    International Nuclear Information System (INIS)

    Halvorsen, R.A.; Korobkin, M.; Ram, P.C.; Thompson, W.M.

    1982-01-01

    Focal fatty infiltration of the liver is an entity that may be confused with liver metastasis on computed tomography (CT). The imaging results and medical records of 16 patients with CT appearance suggestive of focal fatty liver were reviewed, three of whom had the simultaneous presence of metastitic liver disease. Focal fatty liver often has a distinctive appearance with CT, usually with a nonspherical shape, absence of mass effect, and density close to water. Liver metastases are usually round or oval, and unless cystic or necrotic, they have CT attenuation values closer to normal liver parenchyma than water. A radionuclide liver scan almost always resolves any confusion about the differential diagnosis of focal fatty liver: a well defined focus of photon deficiency is due to neoplasm rather than focal fatty infiltration. Sonography sometimes helps to confirm the CT impression, but may be misleading if the diagnosis of focal or diffuse fatty infiltration is not suspected before the examination

  14. The study of the focal trough in panoramic radiograph

    International Nuclear Information System (INIS)

    Park, C. S.; Kim, H. P.

    1982-01-01

    In the study of the focal trough of panoramic radiograph, using the Moritta company Panex EC a series of 48 exposures were taken with the 6-18 brass pins placed in the holes of the plastic model plate, then evaluated by 4 observers. The author analyzed the focal trough defined by the sharpness criteria and calculated the vertical and horizontal magnification range in the corrected focal trough. The results were as follows; 1. Continuous focal trough was not defined in the anterior region using a very high degree of sharpness. 2. As degree of sharpness used in the analysis became less, focal trough was continuous in the anterior and posterior regions, symmetrized bilaterally, and the widths of the focal trough increased more in the posterior region. 3. As sharpness criteria were reduced, the percentage range of image magnification increased in both vertical and horizontal magnification, and especially the percentage range of horizontal magnification was greater than that of vertical magnification.

  15. Multi-focal Vision and Gaze Control Improve Navigation Performance

    Directory of Open Access Journals (Sweden)

    Kolja Kuehnlenz

    2008-11-01

    Full Text Available Multi-focal vision systems comprise cameras with various fields of view and measurement accuracies. This article presents a multi-focal approach to localization and mapping of mobile robots with active vision. An implementation of the novel concept is done considering a humanoid robot navigation scenario where the robot is visually guided through a structured environment with several landmarks. Various embodiments of multi-focal vision systems are investigated and the impact on navigation performance is evaluated in comparison to a conventional mono-focal stereo set-up. The comparative studies clearly show the benefits of multi-focal vision for mobile robot navigation: flexibility to assign the different available sensors optimally in each situation, enhancement of the visible field, higher localization accuracy, and, thus, better task performance, i.e. path following behavior of the mobile robot. It is shown that multi-focal vision may strongly improve navigation performance.

  16. 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.

  17. Preparation of the requirements for the safety regulation related to human and organizational factors

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    The outline of the project in the current fiscal year is to investigate and analyze issues associated with Human and Organizational Factors involved in incidents of nuclear facilities, and to study and develop evaluation methods of these countermeasures. The guideline to evaluate licensee's safety culture and root cause analysis (RCA) had been developed for further improving safety on nuclear power plants at 2007. These guidelines have been used at regulatory inspection since that time. Based on experience of using these existing guidelines, some activities for improving guidelines are now under investigation; these are selecting candidate quantitative indicators for safety culture evaluation and researching good practices for RCA issues. JNES implemented human factor analysis about 18 domestic events including the Fukushima Dai-ichi nuclear power plant accident. (author)

  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. Growth of human T lymphocyte colonies from whole blood: culture requirements and applications

    International Nuclear Information System (INIS)

    Knox, S.J.; Wilson, F.D.; Greenberg, B.R.; Shifrine, M.

    1982-01-01

    Growth of human lymphocyte colonies from whole blood following stimulation with PHA, Con A, or PPD is described. Individual colony cells were identified as T lymphocytes on the basis of surface marker and enzyme cytochemical characterizations. Colony formation increased as a power function over a wide range of cell concentrations above a critical minimal concentration. The whole blood culture system eliminates possible selective effects of lymphocyte colony techniques utilizing gradient-enriched lymphocyte fractions and more closely approximates the in vivo milieu. The whole blood colony method is more sensitive for the detection of low-level radiation effects on lymphocytes than widely used tests that measure 3 H-thymidine incorporation. In preliminary studies, researchers used the whole blood method to determine the relative radiosensitivity of lymphocytes from humans with various hematopoietic disorders, and observed abnormalities in mitogen responsiveness and colony formation in some of the patient groups. This method has wide application for studies in cellular and clinical immunology

  20. The V protein of canine distemper virus is required for virus replication in human epithelial cells.

    Directory of Open Access Journals (Sweden)

    Noriyuki Otsuki

    Full Text Available Canine distemper virus (CDV becomes able to use human receptors through a single amino acid substitution in the H protein. In addition, CDV strains possessing an intact C protein replicate well in human epithelial H358 cells. The present study showed that CDV strain 007Lm, which was isolated from lymph node tissue of a dog with distemper, failed to replicate in H358 cells, although it possessed an intact C protein. Sequence analyses suggested that a cysteine-to-tyrosine substitution at position 267 of the V protein caused this growth defect. Analyses using H358 cells constitutively expressing the CDV V protein showed that the V protein with a cysteine, but not that with a tyrosine, at this position effectively blocked the interferon-stimulated signal transduction pathway, and supported virus replication of 007Lm in H358 cells. Thus, the V protein as well as the C protein appears to be functional and essential for CDV replication in human epithelial cells.

  1. 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. PMID:25946032

  2. 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

  3. Measuring the Flatness of Focal Plane for Very Large Mosaic CCD Camera

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Jiangang; Estrada, Juan; Cease, Herman; Diehl, H.Thomas; Flaugher, Brenna L.; Kubik, Donna; Kuk, Keivin; Kuropatkine, Nickolai; Lin, Huan; Montes, Jorge; Scarpine, Vic; /Fermilab

    2010-06-08

    Large mosaic multiCCD camera is the key instrument for modern digital sky survey. DECam is an extremely red sensitive 520 Megapixel camera designed for the incoming Dark Energy Survey (DES). It is consist of sixty two 4k x 2k and twelve 2k x 2k 250-micron thick fully-depleted CCDs, with a focal plane of 44 cm in diameter and a field of view of 2.2 square degree. It will be attached to the Blanco 4-meter telescope at CTIO. The DES will cover 5000 square-degrees of the southern galactic cap in 5 color bands (g, r, i, z, Y) in 5 years starting from 2011. To achieve the science goal of constraining the Dark Energy evolution, stringent requirements are laid down for the design of DECam. Among them, the flatness of the focal plane needs to be controlled within a 60-micron envelope in order to achieve the specified PSF variation limit. It is very challenging to measure the flatness of the focal plane to such precision when it is placed in a high vacuum dewar at 173 K. We developed two image based techniques to measure the flatness of the focal plane. By imaging a regular grid of dots on the focal plane, the CCD offset along the optical axis is converted to the variation the grid spacings at different positions on the focal plane. After extracting the patterns and comparing the change in spacings, we can measure the flatness to high precision. In method 1, the regular dots are kept in high sub micron precision and cover the whole focal plane. In method 2, no high precision for the grid is required. Instead, we use a precise XY stage moves the pattern across the whole focal plane and comparing the variations of the spacing when it is imaged by different CCDs. Simulation and real measurements show that the two methods work very well for our purpose, and are in good agreement with the direct optical measurements.

  4. 40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

    Science.gov (United States)

    2010-07-01

    ... use; terrestrial feed crop use; aquatic food crop use; greenhouse food crop use. (2) Nonfood use...; aquatic nonfood residential use; aquatic nonfood outdoor use; aquatic nonfood industrial use; greenhouse... insect repellents directly to the skin). Tier II data is required on a different test species from Tier I...

  5. Pathogen reduction requirements for direct potable reuse in Antarctica: evaluating human health risks in small communities.

    Science.gov (United States)

    Barker, S Fiona; Packer, Michael; Scales, Peter J; Gray, Stephen; Snape, Ian; Hamilton, Andrew J

    2013-09-01

    Small, remote communities often have limited access to energy and water. Direct potable reuse of treated wastewater has recently gained attention as a potential solution for water-stressed regions, but requires further evaluation specific to small communities. The required pathogen reduction needed for safe implementation of direct potable reuse of treated sewage is an important consideration but these are typically quantified for larger communities and cities. A quantitative microbial risk assessment (QMRA) was conducted, using norovirus, giardia and Campylobacter as reference pathogens, to determine the level of treatment required to meet the tolerable annual disease burden of 10(-6) DALYs per person per year, using Davis Station in Antarctica as an example of a small remote community. Two scenarios were compared: published municipal sewage pathogen loads and estimated pathogen loads during a gastroenteritis outbreak. For the municipal sewage scenario, estimated required log10 reductions were 6.9, 8.0 and 7.4 for norovirus, giardia and Campylobacter respectively, while for the outbreak scenario the values were 12.1, 10.4 and 12.3 (95th percentiles). Pathogen concentrations are higher under outbreak conditions as a function of the relatively greater degree of contact between community members in a small population, compared with interactions in a large city, resulting in a higher proportion of the population being at risk of infection and illness. While the estimates of outbreak conditions may overestimate sewage concentration to some degree, the results suggest that additional treatment barriers would be required to achieve regulatory compliance for safe drinking water in small communities. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. 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.

  7. Strong reducing of the laser focal volume

    CSIR Research Space (South Africa)

    Godin, T

    2011-08-01

    Full Text Available equal to -1 or +1 modeled on the p light rings of the incident TEMp0 beam. The transformation quality of a 30TEM beam into a single-lobed pattern in the focal plane is shown in Fig. 3. It is clear that the intensity pattern of the rectified beam... DOE (blue solid line), rectified 30TEM (red solid line) -3 -2 -1 0 1 2 3 0 1 2 3 4 z=0 z=f DOE Fig. 2 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 0,0 0,2 0,4 0,6 0,8 1,0 TEM30 without DOE "rectified" TEM30 TEM00 In te ns...

  8. Smart trigger logic for focal plane arrays

    Science.gov (United States)

    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.

  9. 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.

  10. 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.

  11. Innovative compact focal plane array for wide field vis and ir orbiting telescopes

    Science.gov (United States)

    Hugot, Emmanuel; Vives, Sébastien; Ferrari, Marc; Gaeremynck, Yann; Jahn, Wilfried

    2017-11-01

    The future generation of high angular resolution space telescopes will require breakthrough technologies to combine large diameters and large focal plane arrays with compactness and lightweight mirrors and structures. Considering the allocated volume medium-size launchers, short focal lengths are mandatory, implying complex optical relays to obtain diffraction limited images on large focal planes. In this paper we present preliminary studies to obtain compact focal plane arrays (FPA) for earth observations on low earth orbits at high angular resolution. Based on the principle of image slicers, we present an optical concept to arrange a 1D FPA into a 2D FPA, allowing the use of 2D detector matrices. This solution is particularly attractive for IR imaging requiring a cryostat, which volume could be considerably reduced as well as the relay optics complexity. Enabling the use of 2D matrices for such an application offers new possibilities. Recent developments on curved FPA allows optimization without concerns on the field curvature. This innovative approach also reduces the complexity of the telescope optical combination, specifically for fast telescopes. This paper will describe the concept and optical design of an F/5 - 1.5m telescope equipped with such a FPA, the performances and the impact on the system with a comparison with an equivalent 1.5m wide field Korsch telescope.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  13. Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

    DEFF Research Database (Denmark)

    Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas

    2018-01-01

    - with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

  14. 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

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

    Science.gov (United States)

    2014-06-13

    patience with me along the way. I also need to thank the Combined Arms Research Library staff for their assistance in many different ways, and the staff...and low levels of ethnocentrism required in jobs with complex international and multicultural responsibilities, as found in the empirical study by... multicultural perspective taking skills. Technical Report, U.S. Army Research Institute for the Behavioral and Social Sciences, Fort Belvoir, VA

  16. Focal degeneration of basal cells and the resultant auto-immunoreactions: a novel mechanism for prostate tumor progression and invasion.

    Science.gov (United States)

    Man, Yan-Gao; Gardner, William A

    2008-01-01

    The development of human prostate cancer is believed to be a multistep process, progressing sequentially from normal, to hyperplasia, to prostatic intraepithelial neoplasia (PIN), and to invasive and metastatic lesions. High grade PIN has been generally considered as the direct precursor of invasive lesions, and the progression of PIN is believed to be triggered primarily, if not solely, by the overproduction of proteolytic enzymes predominately by cancer cells, which result in the degradation of the basement membrane. These theories, however, are hard to reconcile with two main facts: (1) only about 30% untreated PIN progress to invasive stage, while none of the current approaches could accurately identify the specific PIN or individuals at greater risk for progression, and (2) results from recent world-wide clinical trials with a wide variety of proteolytic enzyme inhibitors have been very disappointing, casting doubt on the validity of the proteolytic enzyme theory. Since over 90% of prostate cancer-related deaths result from invasion-related illness and the incidence of PIN could be up to 16.5-25% in routine or ultrasound guided prostate biopsy, there is an urgent need to uncover the intrinsic mechanism of prostate tumor invasion. Promoted by the facts that the basal cell population is the source of several tumor suppressors and the absence of the basal cell layer is the most distinct feature of invasive lesions, our recent studies have intended to identify the early alterations of basal cell layers and their impact on tumor invasion using multidisciplinary approaches. Our studies revealed that a subset of pre-invasive tumors contained focal disruptions (the absence of basal cells resulting in a gap greater than the combined size of at least three epithelial cells) in surrounding basal cell layers. Compared to their non-disrupted counterparts, focally disrupted basal cell layers had several unique features: (1) significantly lower proliferation; (2

  17. Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles.

    Science.gov (United States)

    Chen, Hsin-Yi; Wu, Chien-Ting; Tang, Chieh-Ju C; Lin, Yi-Nan; Wang, Won-Jing; Tang, Tang K

    2017-08-15

    Mutations in many centriolar protein-encoding genes cause primary microcephaly. Using super-resolution and electron microscopy, we find that the human microcephaly protein, RTTN, is recruited to the proximal end of the procentriole at early S phase, and is located at the inner luminal walls of centrioles. Further studies demonstrate that RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. CRISPR/Cas9-mediated RTTN gene knockout in p53-deficient cells induce amplification of primitive procentriole bodies that lack the distal-half centriolar proteins, POC5 and POC1B. Additional analyses show that RTTN serves as an upstream effector of CEP295, which mediates the loading of POC1B and POC5 to the distal-half centrioles. Interestingly, the naturally occurring microcephaly-associated mutant, RTTN (A578P), shows a low affinity for STIL binding and blocks centriole assembly. These findings reveal that RTTN contributes to building full-length centrioles and illuminate the molecular mechanism through which the RTTN (A578P) mutation causes primary microcephaly.Mutations in many centriolar protein-encoding genes cause primary microcephaly. Here the authors show that human microcephaly protein RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly, contributing to building full-length centrioles.

  18. 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.

  19. Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

    Science.gov (United States)

    Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

    2015-01-01

    ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

  20. ROCK inhibitor is not required for embryoid body formation from singularized human embryonic stem cells.

    Science.gov (United States)

    Pettinato, Giuseppe; Vanden Berg-Foels, Wendy S; Zhang, Ning; Wen, Xuejun

    2014-01-01

    We report a technology to form human embryoid bodies (hEBs) from singularized human embryonic stem cells (hESCs) without the use of the p160 rho-associated coiled-coil kinase inhibitor (ROCKi) or centrifugation (spin). hEB formation was tested under four conditions: +ROCKi/+spin, +ROCKi/-spin, -ROCKi/+spin, and -ROCKi/-spin. Cell suspensions of BG01V/hOG and H9 hESC lines were pipetted into non-adherent hydrogel substrates containing defined microwell arrays. hEBs of consistent size and spherical geometry can be formed in each of the four conditions, including the -ROCKi/-spin condition. The hEBs formed under the -ROCKi/-spin condition differentiated to develop the three embryonic germ layers and tissues derived from each of the germ layers. This simplified hEB production technique offers homogeneity in hEB size and shape to support synchronous differentiation, elimination of the ROCKi xeno-factor and rate-limiting centrifugation treatment, and low-cost scalability, which will directly support automated, large-scale production of hEBs and hESC-derived cells needed for clinical, research, or therapeutic applications.

  1. 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.

  2. Human Cognitive Limitations. Broad, Consistent, Clinical Application of Physiological Principles Will Require Decision Support.

    Science.gov (United States)

    Morris, Alan H

    2018-02-01

    Our education system seems to fail to enable clinicians to broadly understand core physiological principles. The emphasis on reductionist science, including "omics" branches of research, has likely contributed to this decrease in understanding. Consequently, clinicians cannot be expected to consistently make clinical decisions linked to best physiological evidence. This is a large-scale problem with multiple determinants, within an even larger clinical decision problem: the failure of clinicians to consistently link their decisions to best evidence. Clinicians, like all human decision-makers, suffer from significant cognitive limitations. Detailed context-sensitive computer protocols can generate personalized medicine instructions that are well matched to individual patient needs over time and can partially resolve this problem.

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

    Science.gov (United States)

    Schwalfenberg, Gerry Kurt

    2017-01-01

    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. 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. 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. 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.

  4. 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.

  5. Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy.

    Science.gov (United States)

    Ribierre, Théo; Deleuze, Charlotte; Bacq, Alexandre; Baldassari, Sara; Marsan, Elise; Chipaux, Mathilde; Muraca, Giuseppe; Roussel, Delphine; Navarro, Vincent; Leguern, Eric; Miles, Richard; Baulac, Stéphanie

    2018-04-30

    DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch of the mTORC1 pathway. So far, its function in the brain remains largely unknown. Germline loss-of-function mutations in DEPDC5 have emerged as a major cause of familial refractory focal epilepsies, with case reports of sudden unexpected death in epilepsy (SUDEP). Remarkably, a fraction of patients also develop focal cortical dysplasia (FCD), a neurodevelopmental cortical malformation. We therefore hypothesized that a somatic second-hit mutation arising during brain development may support the focal nature of the dysplasia. Here, using postoperative human tissue, we provide the proof of concept that a biallelic 2-hit - brain somatic and germline - mutational mechanism in DEPDC5 causes focal epilepsy with FCD. We discovered a mutation gradient with a higher rate of mosaicism in the seizure-onset zone than in the surrounding epileptogenic zone. Furthermore, we demonstrate the causality of a Depdc5 brain mosaic inactivation using CRISPR-Cas9 editing and in utero electroporation in a mouse model recapitulating focal epilepsy with FCD and SUDEP-like events. We further unveil a key role of Depdc5 in shaping dendrite and spine morphology of excitatory neurons. This study reveals promising therapeutic avenues for treating drug-resistant focal epilepsies with mTORC1-targeting molecules.

  6. 111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection

    International Nuclear Information System (INIS)

    Rubin, R.H.; Fischman, A.J.; Callahan, R.J.; Khaw, B.A.; Keech, F.; Ahmad, M.; Wilkinson, R.; Strauss, H.W.

    1989-01-01

    We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers

  7. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusion-mediated viral entry

    International Nuclear Information System (INIS)

    Janas, Alicia M.; Dong, Chunsheng; Wang Jianhua; Wu Li

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters dendritic cells (DCs) through endocytosis and viral receptor-mediated fusion. Although endocytosis-mediated HIV-1 entry can generate productive infection in certain cell types, including human monocyte-derived macrophages, productive HIV-1 infection in DCs appears to be dependent on fusion-mediated viral entry. It remains to be defined whether endocytosed HIV-1 in DCs can initiate productive infection. Using HIV-1 infection and cellular fractionation assays to measure productive viral infection and entry, here we show that HIV-1 enters monocyte-derived DCs predominately through endocytosis; however, endocytosed HIV-1 cannot initiate productive HIV-1 infection in DCs. In contrast, productive HIV-1 infection in DCs requires fusion-mediated viral entry. Together, these results provide functional evidence in understanding HIV-1 cis-infection of DCs, suggesting that different pathways of HIV-1 entry into DCs determine the outcome of viral infection

  8. 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

    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...... 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...... activities and protein partners of RecQ4 are conserved with those of the other RecQ helicases....

  9. 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...

  10. Focal decompositions for linear differential equations of the second order

    Directory of Open Access Journals (Sweden)

    L. Birbrair

    2003-01-01

    two-points problems to itself such that the image of the focal decomposition associated to the first equation is a focal decomposition associated to the second one. In this paper, we present a complete classification for linear second-order equations with respect to this equivalence relation.

  11. Focal necrotizing pneumonia is a distinct entity from lung abscess.

    Science.gov (United States)

    Seo, Hyewon; Cha, Seung-Ick; Shin, Kyung-Min; Lim, Jaekwang; Yoo, Seung-Soo; Lee, Jaehee; Lee, Shin-Yup; Kim, Chang-Ho; Park, Jae-Yong

    2013-10-01

    'Focal necrotizing pneumonia' was defined as a localized type of necrotizing pneumonia characterized by a single or few cavities of low density without rim enhancement on computed tomography (CT) scan. The purpose of this study was to investigate the clinical features and course of patients with focal necrotizing pneumonia, thereby elucidating its clinical relevance. The present study was conducted retrospectively in patients who had been interpreted as having lung abscess or necrotizing pneumonia on CT scan. Clinical and radiological characteristics were compared between the focal necrotizing pneumonia and lung abscess groups. Overall, 68 patients with focal necrotizing pneumonia (n = 35) or lung abscess (n = 33) were included in the present study. The frequency of risk factors for aspiration was significantly lower in the focal necrotizing group, compared with the lung abscess group (14.3% vs 45.5%, P = 0.005). Compared with lung abscess, focal necrotizing pneumonia was observed more commonly in non-gravity-dependent segments (66% vs 36%, P lung abscess group (31% vs 12%, P = 0.08). However, in terms of treatment outcomes, a similar high rate of success was observed in both groups: 97%, respectively. Compared to lung abscess, focal necrotizing pneumonia occurs more commonly in non-gravity-dependent segments with lower incidence of risk factors for aspiration. Similar to lung abscess, the rate of success for treatment of focal necrotizing pneumonia was high. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  12. Proximal Focal Femoral Deficiency in Ibadan a Developing ...

    African Journals Online (AJOL)

    The cultural aversion to amputation in our environment makes it difficult to employ that option of treatment. Proximal focal femoral deficiency in Ibadan a developing country's perspective and a review of the literature. Keywords: Proximal focal femoral deficiency , congenital malformations , limb malformations , lower limb ...

  13. 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.

  14. The requirement for freshly isolated human colorectal cancer (CRC) cells in isolating CRC stem cells.

    Science.gov (United States)

    Fan, F; Bellister, S; Lu, J; Ye, X; Boulbes, D R; Tozzi, F; Sceusi, E; Kopetz, S; Tian, F; Xia, L; Zhou, Y; Bhattacharya, R; Ellis, L M

    2015-02-03

    Isolation of colorectal cancer (CRC) cell populations enriched for cancer stem cells (CSCs) may facilitate target identification. There is no consensus regarding the best methods for isolating CRC stem cells (CRC-SCs). We determined the suitability of various cellular models and various stem cell markers for the isolation of CRC-SCs. Established human CRC cell lines, established CRC cell lines passaged through mice, patient-derived xenograft (PDX)-derived cells, early passage/newly established cell lines, and cells directly from clinical specimens were studied. Cells were FAC-sorted for the CRC-SC markers CD44, CD133, and aldehyde dehydrogenase (ALDH). Sphere formation and in vivo tumorigenicity studies were used to validate CRC-SC enrichment. None of the markers studied in established cell lines, grown either in vitro or in vivo, consistently enriched for CRC-SCs. In the three other cellular models, CD44 and CD133 did not reliably enrich for stemness. In contrast, freshly isolated PDX-derived cells or early passage/newly established CRC cell lines with high ALDH activity formed spheres in vitro and enhanced tumorigenicity in vivo, whereas cells with low ALDH activity did not. PDX-derived cells, early passages/newly established CRC cell lines and cells from clinical specimen with high ALDH activity can be used to identify CRC-SC-enriched populations. Established CRC cell lines should not be used to isolate CSCs.

  15. 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.

  16. Technical, organizational and human-centered requirements for the purpose of accident management

    International Nuclear Information System (INIS)

    Berning, A.; Fassmann, W.; Preischl, W.

    1998-01-01

    A catalog of ergonomic recommendations for organizational measures and design of paper documented work aids for accident management situations in nuclear power plants was developed. Attention was given to provide recommendations meeting practical needs and being sufficiently flexible to allow plant specific [aptation. A weight was assigned to each recommendation indicating its importance. The development of the recommendations was based on the state of the art concerning research and practical experience. Results from walk-/talk-through experiments, training and exercises, discussions with on-site experts, and investigations of emergency manuals from German and foreign nuclear power plants were taken into account. The catalog is founded on a bro[ knowledge base covering important aspects. The catalog is intended for qualitative evaluation and design of organizational measures and procedures. The catalog shall assure high quality. The project further provides an important contribution to the standardization of organizational and human centered demands concerning accident management procedures. Thus it can contribute to develop general regulations regarding ergonomic design of accident management measures. (orig.) [de

  17. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival

    Directory of Open Access Journals (Sweden)

    Day Wanda V

    2005-04-01

    Full Text Available Abstract Background Androgens and androgen receptors (AR regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH and prostate cancer (PCa. Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA. This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. Results The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. Conclusion We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.

  18. Focal species and landscape "naturalness" corridor models offer complementary approaches for connectivity conservation planning

    Science.gov (United States)

    Meade Krosby; Ian Breckheimer; D. John Pierce; Peter H. Singleton; Sonia A. Hall; Karl C. Halupka; William L. Gaines; Robert A. Long; Brad H. McRae; Brian L. Cosentino; Joanne P. Schuett-Hames

    2015-01-01

    Context   The dual threats of habitat fragmentation and climate change have led to a proliferation of approaches for connectivity conservation planning. Corridor analyses have traditionally taken a focal species approach, but the landscape ‘‘naturalness’’ approach of modeling connectivity among areas of low human modification has gained popularity...

  19. The case for focal brachytherapy for the management of low grade prostate cancer

    International Nuclear Information System (INIS)

    Allen, B.J.; Enari, E.

    2011-01-01

    Full text: Radical therapy of low to intermediate prostate cancer patients can cause substantial adverse events relating to genitourinary and rectal toxicity. Yet there is little evidence that such treatment results in increased life expectancy. On the other hand, watchful waiting is associated with active surveillance and the patient must accept that the cancer remains untreated and has a risk of progression. Focal therapy of low grade prostate cancer provides an intermediate approach to the management of this cancer. The approach is to treat only those positive segments on biopsy and so reduce the likelihood of adverse events. However, continued surveillance is required because of the increased risk of disease progression. Focal therapy needs to be evaluated using available ablative therapies. Recent studies of focal HIFU for 20 patients showed PSA reduced from 7.3 to 1.5 ng/mL at 12 months. 1/20 patients had inadequate erections and 2120 required pads. 17/19 had no histological evidence of cancer and none had evidence of high volume or Gleason = 7 cancer in the treated lobe. Seed brachytherapy is commonly used for radical prostate treatment of low volume disease. As the same template can be used for seed therapy as is used for biopsy, the technique is ideally suited for focal brachytherapy. As any treatment involving less than the entire gland involves the risk of leaving viable cancer cells outside the treatment zone, a phase 3 randomised clinical trial between radical and focal brachytherapy is advocated to demonstrate the efficacy and safety of the latter relative to radical therapy.

  20. Functional requirements for the man-vehicle systems research facility. [identifying and correcting human errors during flight simulation

    Science.gov (United States)

    Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.

    1980-01-01

    The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.

  1. Human-gyrovirus-Apoptin triggers mitochondrial death pathway--Nur77 is required for apoptosis triggering.

    Science.gov (United States)

    Chaabane, Wiem; Cieślar-Pobuda, Artur; El-Gazzah, Mohamed; Jain, Mayur V; Rzeszowska-Wolny, Joanna; Rafat, Mehrdad; Stetefeld, Joerg; Ghavami, Saeid; Los, Marek J

    2014-09-01

    The human gyrovirus derived protein Apoptin (HGV-Apoptin) a homologue of the chicken anemia virus Apoptin (CAV-Apoptin), a protein with high cancer cells selective toxicity, triggers apoptosis selectively in cancer cells. In this paper, we show that HGV-Apoptin acts independently from the death receptor pathway as it induces apoptosis in similar rates in Jurkat cells deficient in either FADD (fas-associated death domain) function or caspase-8 (key players of the extrinsic pathway) and their parental clones. HGV-Apoptin induces apoptosis via the activation of the mitochondrial intrinsic pathway. It induces both mitochondrial inner and outer membrane permebilization, characterized by the loss of the mitochondrial potential and the release into cytoplasm of the pro-apoptotic molecules including apoptosis inducing factor and cytochrome c. HGV-Apoptin acts via the apoptosome, as lack of expression of apoptotic protease-activating factor 1 in murine embryonic fibroblast strongly protected the cells from HGV-Apoptin-induced apoptosis. Moreover, QVD-oph a broad-spectrum caspase inhibitor delayed HGV-Apoptin-induced death. On the other hand, overexpression of the anti-apoptotic BCL-XL confers resistance to HGV-Apoptin-induced cell death. In contrast, cells that lack the expression of the pro-apoptotic BAX and BAK are protected from HGV-Apoptin induced apoptosis. Furthermore, HGV-Apoptin acts independently from p53 signal but triggers the cytoplasmic translocation of Nur77. Taking together these data indicate that HGV-Apoptin acts through the mitochondrial pathway, in a caspase-dependent manner but independently from the death receptor pathway. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  2. Adenosinergic Immunosuppression by Human Mesenchymal Stromal Cells Requires Co-Operation with T cells.

    Science.gov (United States)

    Kerkelä, Erja; Laitinen, Anita; Räbinä, Jarkko; Valkonen, Sami; Takatalo, Maarit; Larjo, Antti; Veijola, Johanna; Lampinen, Milla; Siljander, Pia; Lehenkari, Petri; Alfthan, Kaija; Laitinen, Saara

    2016-03-01

    Mesenchymal stem/stromal cells (MSCs) have the capacity to counteract excessive inflammatory responses. MSCs possess a range of immunomodulatory mechanisms, which can be deployed in response to signals in a particular environment and in concert with other immune cells. One immunosuppressive mechanism, not so well-known in MSCs, is mediated via adenosinergic pathway by ectonucleotidases CD73 and CD39. In this study, we demonstrate that adenosine is actively produced from adenosine 5'-monophosphate (AMP) by CD73 on MSCs and MSC-derived extracellular vesicles (EVs). Our results indicate that although MSCs express CD39 at low level and it colocalizes with CD73 in bulge areas of membranes, the most efficient adenosine production from adenosine 5'-triphosphate (ATP) requires co-operation of MSCs and activated T cells. Highly CD39 expressing activated T cells produce AMP from ATP and MSCs produce adenosine from AMP via CD73 activity. Furthermore, adenosinergic signaling plays a role in suppression of T cell proliferation in vitro. In conclusion, this study shows that adenosinergic signaling is an important immunoregulatory mechanism of MSCs, especially in situations where ATP is present in the extracellular environment, like in tissue injury. An efficient production of immunosuppressive adenosine is dependent on the concerted action of CD39-positive immune cells with CD73-positive cells such as MSCs or their EVs. © 2016 AlphaMed Press.

  3. 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.

  4. 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.

  5. [Sotos syndrome associated with focal dystonia].

    Science.gov (United States)

    Bravo, M; Chacón, J; Bautista, E; Pérez-Camacho, I; Trujillo, A; Grande, M A

    Sotos syndrome is a form of infantile gigantism characterized by excessive body size from the time of birth, particular facies, acromegalic changes and signs of non-progressive cerebral involvement. The etiology is unknown. Diagnosis is based on somatometric data and the particular phenotype traits. Biochemical and endocrine studies are normal. Torticollis is a focal dystonia and therefore more common in adults. A 20 year old woman with macrosomic features since birth presented with: weight 104 kg, height 182 cm; prognathism, hypertelorism, a broad over hanging forehead with a high hair line; large ears, hands and feet; torticollis towards the right with elevation and anteroversion of the right shoulder which caused symptomatic scoliosis. She was bradypsychic and rather slow in speech. The complementary tests done (cerebral and cervical CT and MR, bone gammography, evoked potentials, EMG-ENG, sural nerve biopsy, biopsy of skin and muscle, EEG and hormone and biochemistry studies) were normal. The torticollis was treated with botulinus toxin and improved considerably, as did the scoliosis. To date, dystonia has not been described in association with Sotos syndrome. This may be a causal association, or even perhaps hereditary, since the patient's mother had dystonia (in the form of blepharospasm).

  6. 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.

  7. Evaluation of Hemodynamics in Focal Steatosis and Focal Spared Lesion of the Liver Using Contrast-Enhanced Ultrasonography with Sonazoid

    International Nuclear Information System (INIS)

    Shiozawa, K.; Watanabe, M.; Ikehara, T.; Kogame, M.; Shinohara, M.; Shinohara, M.; Ishii, K.; Igarashi, Y.; Sumino, Y.; Shiozawa, K.; Makino, H.

    2014-01-01

    We aim to investigate the hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography (CEUS) with Sonazoid. The subjects were 47 patients with focal steatosis and focal spared lesion. We evaluated enhancement patterns (hyper enhancement, iso enhancement, and hypo enhancement) in the vascular phase and the presence or absence of a hypoechoic area in the post vascular phase for these lesions using CEUS. Of the 24 patients with focal steatosis, the enhancement pattern was iso enhancement in 19 and hypo enhancement in 5. Hypoechoic areas were noted in the post vascular phase in 3 patients. Of the 23 patients with focal spared lesions, the enhancement pattern was iso enhancement in 18 and hyper enhancement in 5. No hypoechoic areas were noted in the post vascular phase in any patient. The hemodynamics in focal steatosis and focal spared lesions in non diffuse fatty liver can be observed using low-invasive procedures in real-time by CEUS. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by the fat deposits in the target lesion, the surrounding liver parenchyma, and the third inflow.

  8. DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells

    Science.gov (United States)

    Spada, Fabio; Haemmer, Andrea; Kuch, David; Rothbauer, Ulrich; Schermelleh, Lothar; Kremmer, Elisabeth; Carell, Thomas; Längst, Gernot; Leonhardt, Heinrich

    2007-01-01

    DNA methylation plays a central role in the epigenetic regulation of gene expression in vertebrates. Genetic and biochemical data indicated that DNA methyltransferase 1 (Dnmt1) is indispensable for the maintenance of DNA methylation patterns in mice, but targeting of the DNMT1 locus in human HCT116 tumor cells had only minor effects on genomic methylation and cell viability. In this study, we identified an alternative splicing in these cells that bypasses the disrupting selective marker and results in a catalytically active DNMT1 protein lacking the proliferating cell nuclear antigen–binding domain required for association with the replication machinery. Using a mechanism-based trapping assay, we show that this truncated DNMT1 protein displays only twofold reduced postreplicative DNA methylation maintenance activity in vivo. RNA interference–mediated knockdown of this truncated DNMT1 results in global genomic hypomethylation and cell death. These results indicate that DNMT1 is essential in mouse and human cells, but direct coupling of the replication of genetic and epigenetic information is not strictly required. PMID:17312023

  9. Production of flat KrF laser focal profiles with echelon free-induced spatial incoherence

    International Nuclear Information System (INIS)

    Deniz, A.V.; Obenschain, S.P.; Pronko, M.; Lehmberg, R.H.

    1990-01-01

    High gain direct-drive laser fusion requires a uniform spherical pellet implosion. This in turn requires that the focal profile of each driving beam be sufficiently uniform and controlled. Several methods for producing uniform beams have been proposed. One promising technique, echelon free-induced spatial incoherence (ISI), consists of propagating a broadband spatially incoherent beam through an entire laser system. This technique will be used in the Nike laser, which is a twenty-four- to forty-eight-beam multikilojoule KrF system currently under construction at the Naval Research Laboratory (NRL). This paper presents measurements of focal profiles of laser light smoothed by echelon free ISI from a KrF oscillator and amplifier. The initial implementation is shown

  10. Focal Impulse And Rotor Mapping (FIRM): Conceptualizing And Treating Atrial Fibrillation.

    Science.gov (United States)

    A B Zaman Ma Bm BChir, Junaid; Schricker Md, Amir; G Lalani Md, Gautam; Trikha Bs, Rishi; E Krummen Md, David; M Narayan Md PhD, Sanjiv

    2014-01-01

    Current approaches for the ablation of atrial fibrillation are often effective, but only partially rooted in mechanistic understanding. Accordingly, they are unable to predict whether a given patient will or will not do well, or which lesions sets should or should not be performed - in any given patient. This goal would require clearer mechanistic definition of what sustains AF after it has been triggered (i.e. electrophysiological substrates). There are two schools of thought. The first proposes disorganized activity that self-sustains with no 'driver', and the second describes drivers that then cause disorganization. Interestingly, these mechanisms can be separated in human studies by mapping approach - proponents of the disorganized hypothesis studying small atrial areas at high resolution, and proponents of the driver model studying wide fields-of-view at varying resolutions. Focal impulse and rotor modulation (FIRM) mapping combines a wide field of view with physiologically based signal filtering and phase analysis, and has revealed that human AF is often sustained by rotors. In the CONFIRM Trial, targeting stable AF rotors/sources for ablation improved the single-procedure efficacy for paroxysmal and persistent AF over conventional ablation alone, as now confirmed by independent laboratories. FIRM mapping gives a mechanistic foundation to predict whether any selected lesions should intersect AF sources in any given patient and which mechanisms may cause recurrence. Rotors of varying characteristics have now been shown by many groups. These insights have reinvigorated interest in AF mapping, and rationalizing these findings will likely translate into improved therapy for our patients.

  11. 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.

  12. 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.

  13. Focal Dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE)

    OpenAIRE

    David ePerruchoud; Micah M Murray; Micah M Murray; Jeremie eLefebvre; Silvio eIonta

    2014-01-01

    Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, and the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characteriz...

  14. Focal dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE)

    OpenAIRE

    Perruchoud David; Murray Micah; Lefebvre Jeremie; Ionta Silvio

    2014-01-01

    Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characterized b...

  15. 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.

  16. 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.

  17. 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.

  18. Focal Segmental Glomerulosclerosis: A Single Center Experience

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    Yavuz Ayar

    2016-09-01

    Full Text Available Aim: Focal segmental glomerulosclerosis (FSGS is one of the most common glomerulonephritis (GNP worldwide. Despite treatment, it may progress to end-stage renal disease. In the present study, we compared clinical and histopathological data on FSGS with primary and secondary GNP retrospectively. Methods: We retrospectively analyzed data on clinical and laboratory findings, treatment response, and risk factors associated with mortality in patients, who had been diagnosed with FSGS and other GNP via renal biopsy between January 2009 and December 2014. The average follow-up time was 22 (8-76 months. Results: FSGS and primary GNP were more frequently seen in males than in females (55.9% vs. 65.3%, p=0.033. Nephrotic syndrome was more common in patients with FSGS (41.2% and primary GNP (57.7%, while chronic renal disease was more frequent in patients with secondary GNP (35%. In FSGS, the complete remission rate was 54.4%. 63.2% of patients had continued to receive treatment. According to the biopsy findings, interstitial inflammation and fibrosis were observed in 100% and 98.5% of patients with FSGS, respectively (p=0.010 and p<0.001, respectively. Serum albumin level was found to be increased and proteinuria, total cholesterol, triglyceride, and LDL levels to be decreased after treatment (p<0.001. Serum creatinine levels and type of GNP (secondary GNP were detected to be 1.48 and 8.14 fold increased in mortality analysis, respectively. Conclusion: Renal biopsy is the gold standard for the diagnosis of glomerular diseases. Renal function at the time of diagnosis, follow-up and appropriate immunosuppressive therapy have effects on mortality and clinical progress in FSGS as is the case in all GNPs.

  19. Energy intake from human milk covers the requirement of 6-month-old Senegalese exclusively breast-fed infants

    International Nuclear Information System (INIS)

    Agne-Djigo, Anta; Kwadjode, Komlan M.; Idohou-Dossou, Nicole; Diouf, Adama; Guiro, Amadou T.; Wade, Salimata

    2013-01-01

    Exclusive breast-feeding until 6 months is advised by the WHO as the best practice to feed infants. Yet, some studies have suggested a gap between energy requirements and the energy provided by human milk for many infants at 6 months. In order to assess the adequacy of WHO recommendations in 6-month-old Senegalese lactating infants, a comprehensive study was designed to measure human milk intake by the dose-to-the mother 2H2O turnover method. Infants energy intakes were calculated using daily breast milk intake and the energy content of milk was estimated on the basis of creamatocrit. Of the fifty-nine mother-infant pairs enrolled, fifteen infants were exclusively breast-fed (Ex) while forty-four were partially breast-fed Infants breast milk intake was significantly higher in the Ex group (993 (SD 135)g/d, n 15) compared with the Part group (828 (SD 222)g/d, n 44, P= 0.009). Breast milk energy content as well as infants growth was comparable in both groups. However, infants' energy intake from human milk was significantly higher (364 (SD 50)kJ/kg per d (2586 (SD 448)kJ/d)) in the Ex group than in the Part group (289 (SD 66)kJ/kg per d (2150 (SD 552)kJ/d), P<0.01). Compared with WHO recommendations, the results demonstrate that energy intake from breast milk was low in partially breast-fed infants while exclusively breast-fed 6-month-old Senegalese infants received adequate energy from human milk alone, the most complete food for infants. Therefore, advocacy of exclusive breast-feeding until 6 months should be strengthened.

  20. 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.

  1. Effects on patient exposure dose and image quality by increasing focal film distance in abdominal radiography

    International Nuclear Information System (INIS)

    Kim, You Hyun; Kwon, Soo Il

    1998-01-01

    We can and must improve the diagnostic images using available knowledge and technology. At the same time we must strive to reduce thr patient's integral and entrance radiation dose. Reducing the integral dose to the patient during the radiologic procedure is a primary concern of the patient, especially the pediatric patient, the radiologist and the technologist. A 100cm focal film distance generally is used for most over-table radiography. The early x-ray tubes and screen film combinations required long exposures, which often resulted in motion artifacts. But nowadays, we have the generators and x-ray tubes that can deliver the energy necessary in a very short time and the receptors that can record the information just as rapidly. And, we performed this studies to evaluate the patient exposure dose and the image quality by increasing focal film distance in diagnostic radiography. There are many factors which affected to exposure factor, but we studied to verify of FFD increase, only. Effect of increasing the focal film distance to a 140 cm distance was tested as follows ; 1. The focal film distances were set at 100, 120, and 140cm. 2. A 18cm acryl(tissue equivalent) phantom was placed on the table top. 3. An Capintec 192 electrometer with PM 05 ion chamber was placed at the entrance surface of the phantom, and exposure were made at each focal film distances. 4. The procedure was repeated in the same manner as above except the ion chamber was placed beneath the phantom at the film plane. 5. Exit exposure were normalize to 8mR for each portions of the experiment. Based on the success of the empirical measurements, a detailed mathematical analysis of the dose reduction was performed using the percent depth dose data

  2. Infection-Related Focal Segmental Glomerulosclerosis in Children

    Directory of Open Access Journals (Sweden)

    Anne Katrin Dettmar

    2016-01-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is the most common cause of steroid resistant nephrotic syndrome in children. It describes a unique histological picture of glomerular damage resulting from several causes. In the majority of patients the causing agent is still unknown, but in some cases viral association is evident. In adults, the most established FSGS causing virus is the human immune-deficiency virus, which is related to a collapsing variant of FSGS. Nevertheless, other viruses are also suspected for causing a collapsing or noncollapsing variant, for example, hepatitis B virus, parvovirus B19, and Cytomegalovirus. Although the systemic infection mechanism is different for these viruses, there are similarities in the pathomechanism for the induction of FSGS. As the podocyte is the key structure in the pathogenesis of FSGS, a direct infection of these cells or immediate damage through the virus or viral components has to be considered. Although viral infections are a very rare cause for FSGS in children, the treating pediatric nephrologist has to be aware of a possible underlying infection, as this has a relevant impact on therapy and prognosis.

  3. The design of LMJ focal spots for indirect drive experiments

    International Nuclear Information System (INIS)

    Le Garrec, B J; Sajer, J M

    2008-01-01

    LMJ is a 240 high power laser beam facility for achieving laser matter interaction experiments, high energy density science, including the demonstration of fusion ignition through Inertial Confinement. The Laser Integration Line (LIL) facility is currently a 4-beam prototype for LMJ. The intensity I 0 at the focal spot centre drives hydrodynamic and plasma instabilities and the intensity in the wings must be low to go through the laser entrance Hohlraum. A simple model has been developed to compute the LMJ focal spot. The model gives the intensity at the centre as a function of the focal spot area at 3% of the maximum

  4. 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.

  5. Benign focal liver lesions: discrimination from malignant mimickers.

    Science.gov (United States)

    Alobaidi, Mohammad; Shirkhoda, Ali

    2004-01-01

    Focal lesions of the liver often have various imaging characteristics which may be interpreted as either benign or malignant. Understanding the underlying pathophysiology of these liver lesions may lead to characteristic imaging manifestations, which direct the radiologist to the diagnosis. Benign lesions include congenital hepatic cyst, autosomal dominant polycystic disease, hemangioma, focal nodular hyperplasia (FNH), hepatic adenoma, inflammatory pseudotumor, peliosis hepatis, focal fatty infiltration, hamartoma, and infectious processes such as hepatic abscess, echinococcal cyst, and candidiasis. Characteristic imaging features, clinical symptoms, and treatment/prognosis will be discussed. Emphasis will be placed on key reliable features of each disease to develop a method of discriminating these lesions from other benign and malignant disorders.

  6. Dual-layer electrode-driven liquid crystal lens with electrically tunable focal length and focal plane

    Science.gov (United States)

    Zhang, Y. A.; Lin, C. F.; Lin, J. P.; Zeng, X. Y.; Yan, Q.; Zhou, X. T.; Guo, T. L.

    2018-04-01

    Electric-field-driven liquid crystal (ELC) lens with tunable focal length and their depth of field has been extensively applied in 3D display and imaging systems. In this work, a dual-layer electrode-driven liquid crystal (DELC) lens with electrically tunable focal length and controllable focal plane is demonstrated. ITO-SiO2-AZO electrodes with the dual-layer staggered structure on the top substrate are used as driven electrodes within a LC cell, which permits the establishment of an alternative controllability. The focal length of the DELC lens can be adjusted from 1.41 cm to 0.29 cm when the operating voltage changes from 15 V to 40 V. Furthermore, the focal plane of the DELC lens can selectively move by changing the driving method of the applied voltage to the next driven electrodes. This work demonstrates that the DELC lens has potential applications in imaging systems because of electrically tunable focal length and controllable focal plane.

  7. Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis

    Science.gov (United States)

    Smeets, Bart; Kuppe, Christoph; Sicking, Eva-Maria; Fuss, Astrid; Jirak, Peggy; van Kuppevelt, Toin H.; Endlich, Karlhans; Wetzels, Jack F.M.; Gröne, Hermann-Josef; Floege, Jürgen

    2011-01-01

    The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis. PMID:21719782

  8. 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.

  9. Metallic plates lens focalizing a high power microwave beam

    International Nuclear Information System (INIS)

    Rebuffi, L.

    1987-08-01

    A metallic grating composed of thin parallel plates opportunely spaced, permits to correct the phase of an incident high power microwave beam. In this work we show how it is possible to obtain a beam focalisation (lens), a beam deflection (prisma), or a variation in the polarization (polarizer) using parallel metallic plates. The main design parameters are here presented, in order to obtain the wanted phase modification keeping low the diffraction, the reflected power, the ohmic losses and avoiding breakdowns. Following the given criteria, a metallic plate lens has been realized to focalize the 200 KW, 100 msec 60 GHz beam used in the ECRH experiment on the TFR tokamak. The experimental beam concentration followed satisfactory the design requirements. In fact, the maximum intensity increased about twice the value without lens. In correspondence of this distance a reduction of the beam size of about 50% have been measured for the -3 dB radius. The lens supported high power tests without breakdowns or increase of the reflected power

  10. Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To Enhance Hepatitis C Virus Entry.

    Science.gov (United States)

    Kachko, Alla; Costafreda, Maria Isabel; Zubkova, Iryna; Jacques, Jerome; Takeda, Kazuyo; Wells, Frances; Kaplan, Gerardo; Major, Marian E

    2018-03-15

    Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. Several host molecules participate in HCV cell entry, but this process remains unclear. The complete unraveling of the HCV entry process is important to further understand viral pathogenesis and develop therapeutics. Human hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a phospholipid receptor involved in cell entry of several enveloped viruses. Here, we studied the role of HAVCR1 in HCV infection. HAVCR1 antibody inhibited entry in a dose-dependent manner. HAVCR1 soluble constructs neutralized HCV, which did not require the HAVCR1 mucinlike region and was abrogated by a mutation of N to A at position 94 (N94A) in the Ig variable (IgV) domain phospholipid-binding pocket, indicating a direct interaction of the HAVCR1 IgV domain with HCV virions. However, knockout of HAVCR1 in Huh7 cells reduced but did not prevent HCV growth. Interestingly, the mouse HAVCR1 ortholog, also a phospholipid receptor, did not enhance infection and a soluble form failed to neutralize HCV, although replacement of the mouse IgV domain with the human HAVCR1 IgV domain restored the enhancement of HCV infection. Mutations in the cytoplasmic tail revealed that direct HAVCR1 signaling is not required to enhance HCV infection. Our data show that the phospholipid-binding function and other determinant(s) in the IgV domain of human HAVCR1 enhance HCV infection. Although the exact mechanism is not known, it is possible that HAVCR1 facilitates entry by stabilizing or enhancing attachment, leading to direct interactions with specific receptors, such as CD81. IMPORTANCE Hepatitis C virus (HCV) enters cells through a multifaceted process. We identified the human hepatitis A virus cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, as a facilitator of HCV entry. Antibody blocking and silencing or knockout of HAVCR1 in hepatoma cells reduced HCV entry. Our findings that the

  11. De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly.

    Science.gov (United States)

    Wang, Won-Jing; Acehan, Devrim; Kao, Chien-Han; Jane, Wann-Neng; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

    2015-11-26

    Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm.

  12. Managing focal fields of vector beams with multiple polarization singularities.

    Science.gov (United States)

    Han, Lei; Liu, Sheng; Li, Peng; Zhang, Yi; Cheng, Huachao; Gan, Xuetao; Zhao, Jianlin

    2016-11-10

    We explore the tight focusing behavior of vector beams with multiple polarization singularities, and analyze the influences of the number, position, and topological charge of the singularities on the focal fields. It is found that the ellipticity of the local polarization states at the focal plane could be determined by the spatial distribution of the polarization singularities of the vector beam. When the spatial location and topological charge of singularities have even-fold rotation symmetry, the transverse fields at the focal plane are locally linearly polarized. Otherwise, the polarization state becomes a locally hybrid one. By appropriately arranging the distribution of the polarization singularities in the vector beam, the polarization distributions of the focal fields could be altered while the intensity maintains unchanged.

  13. Focal myositis of lower extremity responsive to botulinum A toxin.

    Science.gov (United States)

    Mitrovic, Josko; Prka, Zeljko; Zic, Rado; Marusic, Srecko; Morovic-Vergles, Jadranka

    2014-01-01

    Focal myositis is a rare, mostly benign disease (pseudotumor) of skeletal muscle, histopathologically characterized by interstitial myositis and tumorous enlargement of a single muscle. The etiology of focal myositis remains unknown; however, localized myopathy has been postulated to be caused by denervation lesions. This case report describes a patient that presented with clinical, laboratory, electromyoneurography, and magnetic resonance imaging features of focal myositis complicated with intervertebral disk protrusion in the lumbosacral spine affected with radicular distress. In most cases, focal myositic lesions show spontaneous regression, relapses are rare, and long-term prognosis is good. There is a wide spectrum of therapeutic options, from no therapy at all through nonsteroidal antirheumatics and glucocorticoids to radiotherapy, surgical excision, and immunosuppressants. In the patient presented, treatment with glucocorticoids, methotrexate, and surgical excision failed to produce satisfactory results. Clinical improvement, pain relief, and reduction in lower leg volume were only achieved by local infiltration of botulinum A toxin.

  14. Mechanical design and analysis of focal plate for gravity deformation

    Science.gov (United States)

    Wang, Jianping; Chu, Jiaru; Hu, Hongzhuan; Li, Kexuan; Zhou, Zengxiang

    2014-07-01

    The surface accuracy of astronomical telescope focal plate is a key indicator to precision stellar observation. To conduct accurate deformation measurement for focal plate in different status, a 6-DOF hexapod platform was used for attitude adjustment. For the small adjustment range of a classic 6-DOF hexapod platform, an improved structural arrangement method was proposed in the paper to achieve ultimate adjustment of the focal plate in horizontal and vertical direction. To validate the feasibility of this method, an angle change model which used ball hinge was set up for the movement and base plate. Simulation results in MATLAB suggested that the ball hinge angle change of movement and base plate is within the range of the limiting angle in the process of the platform plate adjusting to ultimate attitude. The proposed method has some guiding significance for accurate surface measurement of focal plate.

  15. 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. 

  16. Electrocorticographic discharge patterns in glioneuronal tumors and focal cortical dysplasia

    NARCIS (Netherlands)

    Ferrier, Cyrille H.; Aronica, Eleanora; Leijten, Frans S. S.; Spliet, Wim G. M.; van Huffelen, Alexander C.; van Rijen, Peter C.; Binnie, Colin D.

    2006-01-01

    PURPOSE: To determine whether highly epileptiform electrocorticographical discharge patterns occur in patients with glioneuronal tumors (GNTs) and focal cortical dysplasia (FCD) and whether specific histopathological features are related to such patterns. METHODS: The series consists of operated

  17. Compliance with National Ethics Requirements for Human-Subject Research in Non-biomedical Sciences in Brazil: A Changing Culture?

    Science.gov (United States)

    de Albuquerque Rocha, Karina; Vasconcelos, Sonia M R

    2018-02-06

    Ethics regulation for human-subject research (HSR) has been established for about 20 years in Brazil. However, compliance with this regulation is controversial for non-biomedical sciences, particularly for human and social sciences (HSS), the source of a recent debate at the National Commission for Research Ethics. We hypothesized that for these fields, formal requirements for compliance with HSR regulation in graduate programs, responsible for the greatest share of Brazilian science, would be small in number. We analyzed institutional documents (collected from June 2014 to May 2015) from 171 graduate programs at six prestigious Brazilian universities in São Paulo and Rio de Janeiro, the states that fund most of the science conducted in Brazil. Among these programs, 149 were in HSS. The results suggest that non-compliance with standard regulation seems to be the rule in most of these programs. The data may reflect not only a resistance from scientists in these fields to comply with standard regulations for ethics in HSR but also a disciplinary tradition that seems prevalent when it comes to research ethics in HSR. However, recent encounters between Brazilian biomedical and non-biomedical scientists for debates over ethics in HSR point to a changing culture in the approach to research ethics in the country.

  18. A conserved histidine in human DNLZ/HEP is required for stimulation of HSPA9 ATPase activity.

    Science.gov (United States)

    Zhai, Peng; Vu, Michael T; Hoff, Kevin G; Silberg, Jonathan J

    2011-05-20

    The DNL-type zinc-finger protein DNLZ regulates the activity and solubility of the human mitochondrial chaperone HSPA9. To identify DNLZ residues that are critical for chaperone regulation, we carried out an alanine mutagenesis scan of charged residues in a W115I mutant of human DNLZ and assessed the effect of each mutation on interactions with HSPA9. All mutants analyzed promote the solubility of HSPA9 upon expression in Escherichia coli. However, binding studies examining the effect of DNLZ mutants on chaperone tryptophan fluorescence identified three mutations (R81A, H107A, and D111A) that decrease DNLZ binding affinity for nucleotide-free chaperone. In addition, ATPase measurements revealed that DNLZ-R81A and DNLZ-D111A both stimulate the catalytic activity HSPA9, whereas DNLZ-H107A does not elicit an increase in activity even when present at a concentration that is 10-fold higher than the level required for half-maximal stimulation by DNLZ. These findings implicate a conserved histidine as critical for DNLZ regulation of mitochondrial HSPA9 catalytic activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells.

    Science.gov (United States)

    Bilal, Mahmood Y; Zhang, Elizabeth Y; Dinkel, Brittney; Hardy, Daimon; Yankee, Thomas M; Houtman, Jon C D

    2015-04-01

    GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine production. However, this model is largely based on studies of disruption of the GADS/SLP-76 interaction and murine T cell differentiation in GADS deficient mice. The role of GADS in mediating TCR-induced signals in human CD4+ T cells has not been thoroughly investigated. In this study, we have suppressed the expression of GADS in human CD4+ HuT78 T cells. GADS deficient HuT78 T cells displayed similar levels of TCR-induced SLP-76 and PLC-γ1 phosphorylation but exhibited substantial decrease in TCR-induced IL-2 and IFN-γ release. The defect in cytokine production occurred because of impaired calcium mobilization due to reduced recruitment of SLP-76 and PLC-γ1 to the LAT complex. Surprisingly, both GADS deficient HuT78 and GADS deficient primary murine CD8+ T cells had similar TCR-induced adhesion when compared to control T cells. Overall, our results show that GADS is required for calcium influx and cytokine production, but not cellular adhesion, in human CD4+ T cells, suggesting that the current model for T cell regulation by GADS is incomplete. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Adult-onset Rasmussen encephalitis associated with focal cortical dysplasia.

    Science.gov (United States)

    Hohenbichler, Katharina; Lelotte, Julie; Lhommel, Renaud; Tahry, Riëm El; Vrielynck, Pascal; Santos, Susana Ferrao

    2017-12-01

    Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult-onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult-onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear.

  1. Focal plane for the next generation of earth observation instruments

    Science.gov (United States)

    Pranyies, P.; Toubhans, I.; Badoil, B.; Tanguy, F.; Descours, Francis

    2017-09-01

    Sodern is the French focal plane provider for Earth Observation (EO) satellites. Since the 1980's, Sodern has played an active role first in the SPOT program. Within the two-spacecraft constellation Pleiades 1A/1B over the next years, Sodern introduced advanced technologies as Silicon Carbide (SiC) focal plane structure and multispectral strip filters dedicated to multiple-lines detectors.

  2. Implementation of a Shoe-Embedded Human Interface and Collaborative Supplementation of Service Requirements on Smartphone System

    Directory of Open Access Journals (Sweden)

    Kaname Takaochi

    2013-01-01

    Full Text Available Although a handsfree man-machine interface is useful when the user’s hands are not free, existing handsfree input devices are not the type of device that are normally worn by people. We have focused on a shoe as an input device because people normally wear it when they go out, and proposed a shoe-embedded interface. The input device is a sensor shoe. Weight sensors have been attached at three positions on a sole: the first metatarsal, the fifth metatarsal, and the calcaneal tuberosity. These positions have been selected based on the characteristics of the human foot skeleton. Two types of foot operation have been used: tap and push. By combining these operations, 10 commands have been defined. To make it possible to use web applications with a limited number of commands, we have proposed a method of supplementing the user’s service requirements using collaborative filtering. The sensor shoe houses an insole with hetero-core optical fiber sensor elements attached to it. These elements are sensitive to weight. We have built an experimental system that runs on a smartphone and provides the shoe-embedded interface, and conducted experiments with three test subjects to evaluate the system. The average rate of successful command identification was 89 %. We have also evaluated this service requirements supplementation method theoretically, and confirmed that the proposed service recommendation function can be applied to smartphone systems.

  3. Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans.

    Science.gov (United States)

    Cho, Minsu; Hu, Guanggan; Caza, Mélissa; Horianopoulos, Linda C; Kronstad, James W; Jung, Won Hee

    2018-01-01

    Zinc is an important transition metal in all living organisms and is required for numerous biological processes. However, excess zinc can also be toxic to cells and cause cellular stress. In the model fungus Saccharomyces cerevisiae, a vacuolar zinc transporter, Zrc1, plays important roles in the storage and detoxification of excess intracellular zinc to protect the cell. In this study, we identified an ortholog of the S. cerevisiae ZRC1 gene in the human fungal pathogen Cryptococcus neoformans. Zrc1 was localized in the vacuolar membrane in C. neoformans, and a mutant lacking ZRC1 showed significant growth defects under high-zinc conditions. These results suggested a role for Zrc1 in zinc detoxification. However, contrary to our expectation, the expression of Zrc1 was induced in cells grown in zinc-limited conditions and decreased upon the addition of zinc. These expression patterns were similar to those of Zip1, the high-affinity zinc transporter in the plasma membrane of C. neoformans. Furthermore, we used the zrc1 mutant in a murine model of cryptococcosis to examine whether a mammalian host could inhibit the survival of C. neoformans using zinc toxicity. We found that the mutant showed no difference in virulence compared with the wildtype strain. This result suggests that Zrc1-mediated zinc detoxification is not required for the virulence of C. neoformans, and imply that zinc toxicity may not be an important aspect of the host immune response to the fungus.

  4. Inverse-designed stretchable metalens with tunable focal distance

    Science.gov (United States)

    Callewaert, Francois; Velev, Vesselin; Jiang, Shizhou; Sahakian, Alan Varteres; Kumar, Prem; Aydin, Koray

    2018-02-01

    In this paper, we present an inverse-designed 3D-printed all-dielectric stretchable millimeter wave metalens with a tunable focal distance. A computational inverse-design method is used to design a flat metalens made of disconnected polymer building blocks with complex shapes, as opposed to conventional monolithic lenses. The proposed metalens provides better performance than a conventional Fresnel lens, using lesser amount of material and enabling larger focal distance tunability. The metalens is fabricated using a commercial 3D-printer and attached to a stretchable platform. Measurements and simulations show that the focal distance can be tuned by a factor of 4 with a stretching factor of only 75%, a nearly diffraction-limited focal spot, and with a 70% relative focusing efficiency, defined as the ratio between power focused in the focal spot and power going through the focal plane. The proposed platform can be extended for design and fabrication of multiple electromagnetic devices working from visible to microwave radiation depending on scaling of the devices.

  5. Neuromorphic infrared focal plane performs sensor fusion on-plane local-contrast-enhancement spatial and temporal filtering

    Science.gov (United States)

    Massie, Mark A.; Woolaway, James T., II; Curzan, Jon P.; McCarley, Paul L.

    1993-08-01

    An infrared focal plane has been simulated, designed and fabricated which mimics the form and function of the vertebrate retina. The `Neuromorphic' focal plane has the capability of performing pixel-based sensor fusion and real-time local contrast enhancement, much like the response of the human eye. The device makes use of an indium antimonide detector array with a 3 - 5 micrometers spectral response, and a switched capacitor resistive network to compute a real-time 2D spatial average. This device permits the summation of other sensor outputs to be combined on-chip with the infrared detections of the focal plane itself. The resulting real-time analog processed information thus represents the combined information of many sensors with the advantage that analog spatial and temporal signal processing is performed at the focal plane. A Gaussian subtraction method is used to produce the pixel output which when displayed produces an image with enhanced edges, representing spatial and temporal derivatives in the scene. The spatial and temporal responses of the device are tunable during operation, permitting the operator to `peak up' the response of the array to spatial and temporally varying signals. Such an array adapts to ambient illumination conditions without loss of detection performance. This paper reviews the Neuromorphic infrared focal plane from initial operational simulations to detailed design characteristics, and concludes with a presentation of preliminary operational data for the device as well as videotaped imagery.

  6. FAK dimerization controls its kinase-dependent functions at focal adhesions

    KAUST Repository

    Brami-Cherrier, Karen; Gervasi, Nicolas; Arsenieva, Diana A.; Walkiewicz, Katarzyna; Boutterin, Marie Claude; Ortega, Á lvaro Darí o; Leonard, Paul G.; Seantier, Bastien; Gasmi, Laï la; Bouceba, Tahar; Kadaré , Gress; Girault -, Jean Antoine; Arold, Stefan T.

    2014-01-01

    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.

  7. 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.

  8. 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.

  9. 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)

  10. Single-session endoscopic resection and focal radiofrequency ablation for short-segment Barrett's esophagus with early neoplasia

    NARCIS (Netherlands)

    Barret, Maximilien; Belghazi, Kamar; Weusten, Bas L. A. M.; Bergman, Jacques J. G. H. M.; Pouw, Roos E.

    2016-01-01

    The management of early neoplasia in Barrett's esophagus (BE) requires endoscopic resection of visible lesions, followed by radiofrequency ablation (RFA) of the remaining BE. We evaluated the safety and efficacy of combining endoscopic resection and focal RFA in a single endoscopic session in

  11. 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.

  12. [The imaging diagnosis of hepatic focal nodular hyperplasia].

    Science.gov (United States)

    Bazzocchi, M; Macorig, D; Cecconi, P; Gozzi, G

    1991-12-01

    Focal nodular hyperplasia (FNH) is a rare benign hepatocellular tumor occurring in noncirrhotic patients, mostly females, 20-50 years of age. It is usually asymptomatic. The authors took the lead from 5 cases of FNH studied over last year to analyze the different patterns exhibited by the condition on the various imaging techniques currently available. At scintigraphy with 99mTc DISIDA or with TcSC, FNH can be hyper, normal, or hypocaptating. On US scans, the lesion is often homogeneous and isoechoic, but it can also be hyper/hypoechoic. With Doppler US, high-flow signals can be observed. On unenhanced CT scans the lesion is solid, well-demarcated, isodense or slightly hyperdense; sometimes it shows a central hypodense area corresponding to fibrovascular scar. On postcontrast scans it appears hyper/isodense. At dynamic CT the lesion density, which is high during the arterial phase, decreases quickly in the parenchymal and the venous phases and reaches equal/inferior values to surrounding liver parenchyma. On liver angio-CT it is sometimes possible to visualize the bile ducts in the central scar. At angiography, FNH is hypervascular and homogeneous. On MR scans, in T1-weighted SE sequences, the condition is isointense or slightly hypointense, whereas on T2-weighted pulse sequences it is slightly hyperintense; the central scar is hypointense on T1, and hyperintense on T2, weighted scans. As we have no pathognomonic patterns but only orientative ones, a reliable differential diagnosis with hepatocellular adenoma (HA) and fibrolamellar hepatocellular carcinoma (FL-HCC) must be based on biopsy or cytology or, even better, histology. The differential diagnosis is nevertheless necessary because, while FNH does not usually require a surgical approach but only a radiological follow-up, both HA (due to possible bleeding and degeneration) and FL-HCC require surgery.

  13. Detectors and focal plane modules for weather satellites

    Science.gov (United States)

    D'Souza, A. I.; Robinson, E.; Masterjohn, S.; Ely, P.; Khalap, V.; Babu, S.; Smith, D. S.

    2016-05-01

    Weather satellite instruments require detectors with a variety of wavelengths ranging from the visible to VLWIR. One of the remote sensing applications is the geostationary GOES-ABI imager covering wavelengths from the 450 to 490 nm band through the 13.0 to 13.6 μm band. There are a total of 16 spectral bands covered. The Cross-track infrared Sounder (CrIS) is a Polar Orbiting interferometric sensor that measures earth radiances at high spectral resolution, using the data to provide pressure, temperature and moisture profiles of the atmosphere. The pressure, temperature and moisture sounding data are used in weather prediction models that track storms, predict levels of precipitation etc. The CrIS instrument contains SWIR (λc ~ 5 μm at 98K), MWIR (λc ~ 9 μm at 98K) and LWIRs (λc ~ 15.5 μm at 81K) bands in three Focal Plane Array Assemblies (FPAAs). GOES-ABI contains three focal plane modules (FPMs), (i) a visible-near infrared module consisting of three visible and three near infrared channels, (ii) a MWIR module comprised of five channels from 3.9 μm to 8.6 μm and (iii) a 9.6 μm to 13.3 μm, five-channel LWIR module. The VNIR FPM operates at 205 K, and the MWIR and LWIR FPMs operate at 60 K. Each spectral channel has a redundant array built into a single detector chip. Switching is thus permitted from the primary selected array in each channel to the redundant array, given any degradation in performance of the primary array during the course of the mission. Silicon p-i-n detectors are used for the 0.47 μm to 0.86 μm channels. The thirteen channels above 1 μm are fabricated in various compositions of Hg1-xCdxTe, and in this particular case using two different detector architectures. The 1.38 μm to 9.61 μm channels are all fabricated in Hg1-xCdxTe grown by Liquid Phase Epitaxy (LPE) using the HDVIP detector architecture. Molecular beam epitaxy (MBE)-grown Hg1-xCdxTe material are used for the LWIR 10.35 μm to 13.3 μm channels fabricated in Double

  14. Quantification of the impacts of climate change and human agricultural activities on oasis water requirements in an arid region: a case study of the Heihe River basin, China

    Science.gov (United States)

    Liu, Xingran; Shen, Yanjun

    2018-03-01

    Ecological deterioration in arid regions caused by agricultural development has become a global issue. Understanding water requirements of the oasis ecosystems and the influences of human agricultural activities and climate change is important for the sustainable development of oasis ecosystems and water resource management in arid regions. In this study, water requirements of the main oasis in Heihe River basin during 1986-2013 were analyzed and the amount showed a sharp increase from 10.8 × 108 m3 in 1986 to 19.0 × 108 m3 in 2013. Both human agricultural activities and climate change could lead to the increase in water requirement. To quantify the contributions of agricultural activities and climate change to the increase in water requirements, partial derivative and slope method were used. Results showed that climate change and human agricultural activities, such as oasis expansion and changes in land cropping structure, has contributed to the increase in water requirement at rates of 6.9, 58.1, and 25.3 %, respectively. Overall, human agricultural activities were the dominant forces driving the increase in water requirement. In addition, the contribution of oasis expanding to the increased water requirement was significantly greater than that of other concerned variables. This reveals that controlling the oasis scale is extremely important and effective for balancing water for agriculture and ecosystems and to achieving a sustainable oasis development in arid regions.

  15. 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.

  16. Identification of critical regions in human SAMHD1 required for nuclear localization and Vpx-mediated degradation.

    Science.gov (United States)

    Guo, Haoran; Wei, Wei; Wei, Zhenhong; Liu, Xianjun; Evans, Sean L; Yang, Weiming; Wang, Hong; Guo, Ying; Zhao, Ke; Zhou, Jian-Ying; Yu, Xiao-Fang

    2013-01-01

    The sterile alpha motif (SAM) and HD domain-containing protein-1 (SAMHD1) inhibits the infection of resting CD4+ T cells and myeloid cells by human and related simian immunodeficiency viruses (HIV and SIV). Vpx inactivates SAMHD1 by promoting its proteasome-dependent degradation through an interaction with CRL4 (DCAF1) E3 ubiquitin ligase and the C-terminal region of SAMHD1. However, the determinants in SAMHD1 that are required for Vpx-mediated degradation have not been well characterized. SAMHD1 contains a classical nuclear localization signal (NLS), and NLS point mutants are cytoplasmic and resistant to Vpx-mediated degradation. Here, we demonstrate that NLS-mutant SAMHD1 K11A can be rescued by wild-type SAMHD1, restoring its nuclear localization; consequently, SAMHD1 K11A became sensitive to Vpx-mediated degradation in the presence of wild-type SAMHD1. Surprisingly, deletion of N-terminal regions of SAMHD1, including the classical NLS, generated mutant SAMHD1 proteins that were again sensitive to Vpx-mediated degradation. Unlike SAMHD1 K11A, these deletion mutants could be detected in the nucleus. Interestingly, NLS-defective SAMHD1 could still bind to karyopherin-β1 and other nuclear proteins. We also determined that the linker region between the SAM and HD domain and the HD domain itself is important for Vpx-mediated degradation but not Vpx interaction. Thus, SAMHD1 contains an additional nuclear targeting mechanism in addition to the classical NLS. Our data indicate that multiple regions in SAMHD1 are critical for Vpx-mediated nuclear degradation and that association with Vpx is not sufficient for Vpx-mediated degradation of SAMHD1. Since the linker region and HD domain may be involved in SAMHD1 multimerization, our results suggest that SAMHD1 multimerization may be required for Vpx-mediation degradation.

  17. E6AP is Required for Human Papillomavirus type 16 E6 to Cause Cervical Cancer in Mice

    Science.gov (United States)

    Shai, Anny; Pitot, Henry C.; Lambert, Paul F.

    2010-01-01

    High-risk human papillomaviruses cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins including Bak, E6BP1, E6TP1, and proteins that contain PDZ domains such as hScrib and hDlg. Many of these activities are thought to contribute to E6’s role in carcinogenesis. E6’s interaction with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through E6’s ability to recruit the ubiquitin ligase, E6AP into complexes with these cellular proteins resulting in their ubiquitin–mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating E6's acute and oncogenic phenotypes, including induction of epithelial hyperplasia, abrogation of DNA damage response and induction of cervical cancer. Loss of E6AP had no discernable effect on E6's ability to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of E6’s oncogenic potential in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer. PMID:20530688

  18. CT findings of focal organizing pneumonia: correlation with pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yang Soo; Kim, Young Goo; Park, Un Sup [College of Medicine, Chungang University, Seoul (Korea, Republic of)

    1994-11-15

    To evaluate the CT findings of focal organizing pneumonia and to correlate them with pathologic findings to help differentiating from lung cancer. We evaluated radiologic and pathologic findings of five patients with solitary pulmonary nodule which were confirmed as focal organizing pneumonia pathologically. On CT scan, focal organizing pneumonia had irregular margin contacting the pleura in all five cases. The shape of the nodules were spherical to wedge or elliptical and the size from 3.5cm to 5.5cm(average 4.2 cm) in largest diameter. On postcontrast CT scan, all nodules showed enhancement and four cases showed central low density components. Two nodules contained air within the nodule. In four cases, pleural changes such as effusion and/or focal thickening were noted. No lymphadenopathy was found in all cases. Pathologically, the enhancing portion on CT showed findings of organizing pneumonia such as granulation tissue with fibroblast proliferation in alveolar space and interstitial thickening. The central low density areas on CT were due to ischemic necrosis, abscess and exudate, transudate and infiltration of foamy histiocyte. The possibility of focal organizing pneumonia should be considered when peripherally located solitary pulmonary nodule had enhancing component with no combined lymphadenopathy on CT scan.

  19. CT findings of focal organizing pneumonia: correlation with pathologic findings

    International Nuclear Information System (INIS)

    Kim, Yang Soo; Kim, Young Goo; Park, Un Sup

    1994-01-01

    To evaluate the CT findings of focal organizing pneumonia and to correlate them with pathologic findings to help differentiating from lung cancer. We evaluated radiologic and pathologic findings of five patients with solitary pulmonary nodule which were confirmed as focal organizing pneumonia pathologically. On CT scan, focal organizing pneumonia had irregular margin contacting the pleura in all five cases. The shape of the nodules were spherical to wedge or elliptical and the size from 3.5cm to 5.5cm(average 4.2 cm) in largest diameter. On postcontrast CT scan, all nodules showed enhancement and four cases showed central low density components. Two nodules contained air within the nodule. In four cases, pleural changes such as effusion and/or focal thickening were noted. No lymphadenopathy was found in all cases. Pathologically, the enhancing portion on CT showed findings of organizing pneumonia such as granulation tissue with fibroblast proliferation in alveolar space and interstitial thickening. The central low density areas on CT were due to ischemic necrosis, abscess and exudate, transudate and infiltration of foamy histiocyte. The possibility of focal organizing pneumonia should be considered when peripherally located solitary pulmonary nodule had enhancing component with no combined lymphadenopathy on CT scan

  20. EEG dynamical correlates of focal and diffuse causes of coma.

    Science.gov (United States)

    Kafashan, MohammadMehdi; Ryu, Shoko; Hargis, Mitchell J; Laurido-Soto, Osvaldo; Roberts, Debra E; Thontakudi, Akshay; Eisenman, Lawrence; Kummer, Terrance T; Ching, ShiNung

    2017-11-15

    Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant.

  1. A targeted resequencing gene panel for focal epilepsy.

    Science.gov (United States)

    Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

    2016-04-26

    We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

  2. Grid-texture mechanisms in human vision: Contrast detection of regular sparse micro-patterns requires specialist templates.

    Science.gov (United States)

    Baker, Daniel H; Meese, Tim S

    2016-07-27

    Previous work has shown that human vision performs spatial integration of luminance contrast energy, where signals are squared and summed (with internal noise) over area at detection threshold. We tested that model here in an experiment using arrays of micro-pattern textures that varied in overall stimulus area and sparseness of their target elements, where the contrast of each element was normalised for sensitivity across the visual field. We found a power-law improvement in performance with stimulus area, and a decrease in sensitivity with sparseness. While the contrast integrator model performed well when target elements constituted 50-100% of the target area (replicating previous results), observers outperformed the model when texture elements were sparser than this. This result required the inclusion of further templates in our model, selective for grids of various regular texture densities. By assuming a MAX operation across these noisy mechanisms the model also accounted for the increase in the slope of the psychometric function that occurred as texture density decreased. Thus, for the first time, mechanisms that are selective for texture density have been revealed at contrast detection threshold. We suggest that these mechanisms have a role to play in the perception of visual textures.

  3. A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes.

    Science.gov (United States)

    Crossland, Hannah; Timmons, James A; Atherton, Philip J

    2017-12-01

    Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF-1-mediated myotube hypertrophy in vitro Primary skeletal myotubes were treated with IGF-1 (50 ng/ml) with or without 0.5 µM CX-5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre-rRNA expression (-64 ± 5% vs. IGF-1; P IGF-1; P IGF-1-treated myotubes. IGF-1-mediated increases in myotube diameter (1.27 ± 0.09-fold, P IGF-1 treatment did not prevent early increases in AKT (+203 ± 39% vs. CX; P IGF-1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF-1-induced myotube hypertrophy in vitro. -Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes. © The Author(s).

  4. Penalized maximum-likelihood sinogram restoration for dual focal spot computed tomography

    International Nuclear Information System (INIS)

    Forthmann, P; Koehler, T; Begemann, P G C; Defrise, M

    2007-01-01

    Due to various system non-idealities, the raw data generated by a computed tomography (CT) machine are not readily usable for reconstruction. Although the deterministic nature of corruption effects such as crosstalk and afterglow permits correction by deconvolution, there is a drawback because deconvolution usually amplifies noise. Methods that perform raw data correction combined with noise suppression are commonly termed sinogram restoration methods. The need for sinogram restoration arises, for example, when photon counts are low and non-statistical reconstruction algorithms such as filtered backprojection are used. Many modern CT machines offer a dual focal spot (DFS) mode, which serves the goal of increased radial sampling by alternating the focal spot between two positions on the anode plate during the scan. Although the focal spot mode does not play a role with respect to how the data are affected by the above-mentioned corruption effects, it needs to be taken into account if regularized sinogram restoration is to be applied to the data. This work points out the subtle difference in processing that sinogram restoration for DFS requires, how it is correctly employed within the penalized maximum-likelihood sinogram restoration algorithm and what impact it has on image quality

  5. Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

    Science.gov (United States)

    Merlini, Laura

    2016-01-01

    Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone–GPCR (G-protein-coupled receptor)–MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell–cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception. PMID:27798845

  6. 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.

  7. MIXS on BepiColombo and its DEPFET based focal plane instrumentation

    International Nuclear Information System (INIS)

    Treis, J.; Andricek, L.; Aschauer, F.; Heinzinger, K.; Herrmann, S.; Hilchenbach, M.; Lauf, T.; Lechner, P.; Lutz, G.; Majewski, P.; Porro, M.; Richter, R.H.; Schaller, G.; Schnecke, M.

    2010-01-01

    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 300x300μm 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 2 . Excellent homogeneity and near Fano-limited energy resolution at high readout speeds have been observed on these devices.

  8. MIXS on BepiColombo and its DEPFET based focal plane instrumentation

    Science.gov (United States)

    Treis, J.; Andricek, L.; Aschauer, F.; Heinzinger, K.; Herrmann, S.; Hilchenbach, M.; Lauf, T.; Lechner, P.; Lutz, G.; Majewski, P.; Porro, M.; Richter, R. H.; Schaller, G.; Schnecke, M.; Schopper, F.; Soltau, H.; Stefanescu, A.; Strüder, L.; de Vita, G.

    2010-12-01

    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 300×300μm2. 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 0.5×0.5 mm2. Excellent homogeneity and near Fano-limited energy resolution at high readout speeds have been observed on these devices.

  9. 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.

  10. 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.

  11. Perampanel for focal epilepsy: insights from early clinical experience.

    Science.gov (United States)

    Trinka, E; Steinhoff, B J; Nikanorova, M; Brodie, M J

    2016-03-01

    Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potential interactions or adverse events. Slower titration is generally recommended, and seizure control should be reassessed at a dose of 4 mg before further dose increases. Perampanel efficacy is similar in adolescents and adults; however, somnolence, nasopharyngitis, and aggression are more frequent in adolescents vs the overall population. Individualized and slow-dose titration can minimize adverse events. Low serum concentrations of perampanel may occur in patients also receiving some enzyme-inducing anti-epileptic drugs; a perampanel dose increase may be required. Adverse events of importance with perampanel include dizziness; anger, aggression, and hostile behavior (particularly in adolescents); and falls (particularly in patients >65 years). An individualized approach to dosing, including slower up-titration and bedtime dosing, reduces dizziness risk. Other drugs may cause or aggravate dizziness; reducing concomitant drugs may be necessary when up-titrating perampanel. It would seem clinically appropriate to give due consideration to avoiding use in patients with a history of anger or hostile/aggressive behavior. The possibility of such behaviors should be discussed with patients before starting perampanel, with monitoring during up-titration. Slower up-titration of perampanel in older patients helps reduce fall risk. © 2015 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

  12. Focal species candidates for pesticide risk assessment in European rice fields: A review.

    Science.gov (United States)

    Vallon, Martin; Dietzen, Christian; Laucht, Silke; Ludwigs, Jan-Dieter

    2018-04-25

    An assessment of potential risks of pesticides on wildlife is required during the process of product registration within Europe because of the importance of agricultural landscapes as wildlife habitats. Despite their peculiarity and their specific role as artificial wetlands, rice paddies are to date pooled with cereals in guidance documents on how to conduct risk assessments for birds and mammals in Europe. Hence, the focal species currently considered in risk assessments for rice paddies are those known from cereal fields and can therefore be expected to differ significantly from the species actually occurring in the wet environments of rice paddies. We present results of a comprehensive review on bird and mammal species regularly occurring in rice paddies during a time of potential pesticide exposure to identify appropriate focal species candidates for ecotoxicological pesticide risk assessment according to the European Food Safety Authority (EFSA). In addition, we present data on rice cultivation areas and agricultural practices in Europe to give background information supporting the species selection process. Our literature search identified a general scarcity of relevant data, particularly for mammals, which highlights the need for crop-specific focal species studies. However, our results clearly indicate that the relevant bird and mammal species in rice fields indeed differ strongly from the focal species used for the cereal risk assessment. They can thus be used as a baseline for more realistic wildlife risk assessments specific to rice and the development of a revised guidance document to bridge the gap for regulatory decision makers. Integr Environ Assess Manag 2018;00:000-000. © 2018 SETAC. © 2018 SETAC.

  13. 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.

  14. Initial independent outcomes from focal impulse and rotor modulation ablation for atrial fibrillation: multicenter FIRM registry.

    Science.gov (United States)

    Miller, John M; Kowal, Robert C; Swarup, Vijay; Daubert, James P; Daoud, Emile G; Day, John D; Ellenbogen, Kenneth A; Hummel, John D; Baykaner, Tina; Krummen, David E; Narayan, Sanjiv M; Reddy, Vivek Y; Shivkumar, Kalyanam; Steinberg, Jonathan S; Wheelan, Kevin R

    2014-09-01

    The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers. We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm View(TM) ; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI. Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had ≥1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145-354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89). Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of ≈80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each center's first cases. © 2014 Wiley Periodicals, Inc.

  15. Value of repeat brain MRI in children with focal epilepsy and negative findings on initial MRI

    International Nuclear Information System (INIS)

    Jeon, Tae Yeon; Kim, Ji Hye; Lee, Jee Hun; Yoo, So Young; Hwang, Sook Min; Lee, Mun Hyang

    2017-01-01

    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

  16. Focal Plane Alignment Utilizing Optical CMM

    Science.gov (United States)

    Liebe, Carl Christian; Meras, Patrick L.; Clark, Gerald J.; Sedaka, Jack J.; Kaluzny, Joel V.; Hirsch, Brian; Decker, Todd A.; Scholtz, Christopher R.

    2012-01-01

    In many applications, an optical detector has to be located relative to mechanical reference points. One solution is to specify stringent requirements on (1) mounting the optical detector relative to the chip carrier, (2) soldering the chip carrier onto the printed circuit board (PCB), and (3) installing the PCB to the mechanical structure of the subsystem. Figure 1 shows a sketch of an optical detector mounted relative to mechanical reference with high positional accuracy. The optical detector is typically a fragile wafer that cannot be physically touched by any measurement tool. An optical coordinate measuring machine (CMM) can be used to position optical detectors relative to mechanical reference points. This approach will eliminate all requirements on positional tolerances. The only requirement is that the PCB is manufactured with oversized holes. An exaggerated sketch of this situation is shown in Figure 2. The sketch shows very loose tolerances on mounting the optical detector in the chip carrier, loose tolerance on soldering the chip carrier to the PCB, and finally large tolerance on where the mounting screws are located. The PCB is held with large screws and oversized holes. The PCB is mounted loosely so it can move freely around. The optical CMM measures the mechanical reference points. Based on these measurements, the required positions of the optical detector corners can be calculated. The optical CMM is commanded to go to the position where one detector corner is supposed to be. This is indicated with the cross-hairs in Figure 2(a). This figure is representative of the image of the optical CMM monitor. Using a suitable tapping tool, the PCB is manually tapped around until the corner of the optical detector is at the crosshairs of the optical CMM. The CMM is commanded to another corner, and the process is repeated a number of times until all corners of the optical detector are within a distance of 10 to 30 microns of the required position. The situation

  17. Role of scintigraphy in focally abnormal sonograms of fatty livers

    International Nuclear Information System (INIS)

    Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

    1988-01-01

    Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with 133 Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, [/sup 99m/Tc]RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis

  18. Role of scintigraphy in focally abnormal sonograms of fatty livers

    Energy Technology Data Exchange (ETDEWEB)

    Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

    1988-06-01

    Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with /sup 133/Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, (/sup 99m/Tc)RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis.

  19. US and CT findings in splenic focal lesions in AIDS

    International Nuclear Information System (INIS)

    Schinina, V.; Rizzi, E.B.; Mazzuoli, G.; Bibbolilno, C.; David, V.

    2000-01-01

    To evaluate the role of US and CT in focal splenic lesions in AIDS patients in relation to etiology. Material and Methods: A total of 66 patients with AIDS and focal splenic lesions were examined with sonography. CT with administration of contrast medium was performed in 12 cases. Results: Of the focal splenic lesions, 67% were correlated with an infective pathology with prevalence of Mycobacteria tuberculosis (75%), 26% were neoplastic and 6% splenic infarcts. The lesions were hypoechoic in 60% of the cases, while 10% were hypoanechoic and 1% anechoic. At CT, all lesions appeared hypodense, even after i.v. administration of contrast medium. Conclusion: The combination of echographic reports and clinical and laboratory data allows for a diagnosis that can be confirmed, and making a decision for effective therapy of AIDS is possible. CT does not provide any additional information

  20. Simulation of the Focal Spot of the Accelerator Bremsstrahlung Radiation

    Science.gov (United States)

    Sorokin, V.; Bespalov, V.

    2016-06-01

    Testing of thick-walled objects by bremsstrahlung radiation (BR) is primarily performed via high-energy quanta. The testing parameters are specified by the focal spot size of the high-energy bremsstrahlung radiation. In determining the focal spot size, the high- energy BR portion cannot be experimentally separated from the low-energy BR to use high- energy quanta only. The patterns of BR focal spot formation have been investigated via statistical modeling of the radiation transfer in the target material. The distributions of BR quanta emitted by the target for different energies and emission angles under normal distribution of the accelerated electrons bombarding the target have been obtained, and the ratio of the distribution parameters has been determined.

  1. MRI of a family with focal abnormalities of gyration

    International Nuclear Information System (INIS)

    Muntaner, L.; Perez-Ferron, J.J.; Herrera, M.; Rosell, J.; Taboada, D.; Climent, S.

    1997-01-01

    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

  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. Focal depth measurement of scanning helium ion microscope

    International Nuclear Information System (INIS)

    Guo, Hongxuan; Itoh, Hiroshi; Wang, Chunmei; Zhang, Han; Fujita, Daisuke

    2014-01-01

    When facing the challenges of critical dimension measurement of complicated nanostructures, such as of the three dimension integrated circuit, characterization of the focal depth of microscopes is important. In this Letter, we developed a method for characterizing the focal depth of a scanning helium ion microscope (HIM) by using an atomic force microscope tip characterizer (ATC). The ATC was tilted in a sample chamber at an angle to the scanning plan. Secondary electron images (SEIs) were obtained at different positions of the ATC. The edge resolution of the SEIs shows the nominal diameters of the helium ion beam at different focal levels. With this method, the nominal shapes of the helium ion beams were obtained with different apertures. Our results show that a small aperture is necessary to get a high spatial resolution and high depth of field images with HIM. This work provides a method for characterizing and improving the performance of HIM.

  4. Focal increase of blood flow in the cerebral cortex of man during vestibular stimulation

    DEFF Research Database (Denmark)

    Friberg, L; Olsen, T S; Roland, P E

    1985-01-01

    This study is an attempt to reveal projection areas for vestibular afferents to the human brain. Changes in regional cerebral blood flow (rCBF) were measured over 254 cortical regions during caloric vestibular stimulation with warm water (44 degrees C). rCBF was measured when the external auditory...... meatus was irrigated with water at body temperature as a control to vestibular stimulation. During vestibular stimulation there was only a single cortical area, located in the superior temporal region, which showed a consistent focal activation in the hemisphere contralateral to the stimulated side...... stimulation that gives rise to the associated conscious vestibular sensation of vertigo....

  5. 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.

  6. 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.

  7. Nodular focal fatty infiltration of the liver: CT appearance

    International Nuclear Information System (INIS)

    Baker, M.E.; Silverman, P.M.

    1985-01-01

    Focal fatty infiltration of the liver is a well recognized entity generally characterized by a nonspherical, low-density area without significant mass effect. CT usually distinguishes this from focal liver processes such as abscess or metastasis by its sharply marginated, geographic pattern and lack of mass effect on hepatic and portal veins. Recently, the authors formed a CT scan of the liver in one patient in whom fatty infiltration appeared nodular or rounded. The clinical presentation and radiographic and pathologic features form the basis of this report

  8. The radiological features of Goltz syndrome: Focal dermal hypoplasia

    International Nuclear Information System (INIS)

    Boothyrod, A.E.; Hall, C.M.

    1988-01-01

    Two female infants with Goltz syndrome (focal dermal hypoplasia) were recently investigated for severe feeding problems and failure to thrive. Both demonstrated severe skeletal malformations and marked gastrooesophageal reflux with laxity of the hiatus. One child (case 1) exhibited nasal regurgitation during feeding. Interestingly, both children had undergone surgery; Case 1 or a right parasagittal abdominal hernia associated with focal dermal hypoplasia of the abdominal wall and Case 2 for an exomphalos also associated with dermal hypoplasia. This observation suggests more widespread mesodermal abnormality. (orig./GDG)

  9. Focal myositis of the thigh: unusual MR pattern

    International Nuclear Information System (INIS)

    Llauger, Jaume; Palmer, Jaume; San Roman, Luis; Bague, Silvia; Matias-Guiu, Xavier; Doncel, Antonio

    2002-01-01

    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.)

  10. 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.)

  11. 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.)

  12. Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

    Science.gov (United States)

    Marchlinski, F; Callans, D; Gottlieb, C; Rodriguez, E; Coyne, R; Kleinman, D

    1998-08-01

    Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the

  13. 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....... This finding accords with earlier studies. All nine patients studied in the interictal phase showed, either spontaneously or during activation by intermittent light, focal flow increases in areas presumed to comprise the epileptic focus. These interictal hyperemic foci probably reflect subictal neuronal...

  14. Incidental Detection of Temporary Focal FDG Retention in the Spleen

    Energy Technology Data Exchange (ETDEWEB)

    Park, Youn Joon; Lee, Jai Hyuen; Jee, Keum Nahn; Namgung, Hwan [Dankook Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    F 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a valuable tool in discriminating malignancy from benign lesion. But because various false positive results reduce the diagnostic specificity, nuclear medicine physicians should be familiar with possible false positive cases. Although many cases of high FDG uptake mimicking malignancy have been reported, temporary intense focal FDG uptake of normal spleen has not been reported previously. We report herein a phenomenon of temporary intense focal FDG uptake of normal spleen without evidence of metastasis in a 46 year old woman with a history of anal cancer.

  15. Expansion characteristics of coronary stents in focal stenoses

    Directory of Open Access Journals (Sweden)

    Schmidt Wolfram

    2017-09-01

    Full Text Available The presented experimental in vitro approach was designed to assess the expansion behavior of stent systems in a resistant focal stenosis model with respect to a potential dog-boning effect. Five different stent systems (nominal diameter 3.0 mm were investigated. The focal stenosis was simulated by a stainless steel tube (ID ≤ 1.20 mm. Stent expansion was performed using a proprietary test device consisting of a test chamber with 37 °C water, 2-axis laser scanner and a pressure controller.

  16. 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

  17. A broad but restricted requirement for TAF-5 (human TAFII100) for embryonic transcription in Caenorhabditis elegans.

    Science.gov (United States)

    Walker, Amy K; Blackwell, T Keith

    2003-02-21

    As conserved components of the transcription factor (TF) IID- and TFTC/SAGA-related complexes, TATA-binding protein-associated factors (TAF(II)s) are important for eukaryotic mRNA transcription. In yeast, genetic analyses suggest that, although some individual TAF(II)s are required for transcription of most genes, others have highly specialized functions. Much less is known about the functions of TAF(II)s in metazoans, which have more complex genomes that include many tissue-specific genes. TAF-5 (human (h) TAF(II)100) is of particular interest because it is predicted to have an important structural role. Here we describe the first genetics-based analysis of TAF-5 in a metazoan. By performing RNA interference in Caenorhabditis elegans embryos, which can survive for several cell generations without transcription, we found that taf-5 is important for a significant fraction of transcription. However, TAF-5 is apparently not essential for the expression of multiple developmental and other metazoan-specific genes. This phenotype remarkably resembles the previously described effects of similarly depleting two C. elegans histone fold TAF(II)s, TAF-9 (hTAF(II)31/32) and TAF-10 (hTAF(II)30), but is distinct from the widespread transcription block caused by TAF-4 (hTAF(II)130) depletion. Our findings suggest that TAF-5, TAF-9, and TAF-10 are part of a functional module of TFIID- and TFTC/SAGA-related complexes that can be bypassed in many metazoan-specific genes.

  18. Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-fluorouracil or ftorafur and x rays

    International Nuclear Information System (INIS)

    Byfield, J.E.; Calabro-Jones, P.; Klisak, I.; Kulhanian, F.

    1982-01-01

    The combined effects of X ray and 5-fluorouracil (5-FU) in tissue culture have been studied using two human adenocarcinoma lines (HeLa and HT-29 cells). Both showed similar sensitivities to 5-FU, HeLa cells appearing somewhat more resistant to higher concentrations. Combined treatment of both cell types with 5-FU and X rays led to a time-dependent enhancement of cell killing (''radiosensitization''). Only post-radiation incubation had any effect, prior exposure to 5-FU being strictly additive. Enhanced cell killing by combined 5-FU and X rays could not be explained by either the infliction of additional acute damage in the immediate post-radiation period or an inhibitory effect of 5-FU on the repair of sub-lethal X ray injury. Rather, the enhanced cytotoxicity proved to be dependent on a damage expressed in time periods exceeding the duration of a cell doubling time in vitro. Overall, the data equally suggest that X rays may sensitize the cells to 5-FU. The enhanced cell killing is maximized if the cells are continuously exposed to 5-FU for 48 hours following the X ray exposure. These results indicate that clinical treatment regimens might be useful in evaluating 5-FU infusional scheduling in accordance with these unique requirements, which are not met by conventional bolus 5-FU and X ray therapy fractionation regimens. Ftorafur, a drug proposed to act as a slow release form of 5-FU, was found to show limited cytotoxic potential in vitro and did not significantly enhance cell killing after X ray exposure

  19. Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-{beta}1-mediated gene activation

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Yan [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Nguyen, Hong T. [Graduate Program in Biomedical Sciences, Tulane School of Medicine, New Orleans, LA 70112 (United States); Lasky, Joseph A. [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Cao, Subing [Graduate Program in Biomedical Sciences, Tulane School of Medicine, New Orleans, LA 70112 (United States); Li, Cui [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Xiangya Hospital, Central South University, Hunan 41008 (China); Hu, Jiyao; Guo, Xinyue; Burow, Matthew E. [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States); Shan, Bin, E-mail: bshan@tulane.edu [Department of Medicine, Tulane School of Medicine, New Orleans, LA 70112 (United States)

    2010-02-19

    Histone deacetylase 6 (HDAC6) belongs to the family of class IIb HDACs and predominantly deacetylates non-histone proteins in the cytoplasm via the C-terminal deacetylase domain of its two tandem deacetylase domains. HDAC6 modulates fundamental cellular processes via deacetylation of {alpha}-tubulin, cortactin, molecular chaperones, and other peptides. Our previous study indicates that HDAC6 mediates TGF-{beta}1-induced epithelial-mesenchymal transition (EMT) in A549 cells. In the current study, we identify a novel splicing variant of human HDAC6, hHDAC6p114. The hHDAC6p114 mRNA arises from incomplete splicing and encodes a truncated isoform of the hHDAC6p114 protein of 114 kDa when compared to the major isoform hHDAC6p131. The hHDAC6p114 protein lacks the first 152 amino acids from N-terminus in the hHDAC6p131 protein, which harbors a nuclear export signal peptide and 76 amino acids of the N-terminal deacetylase domain. hHDAC6p114 is intact in its deacetylase activity against {alpha}-tubulin. The expression hHDAC6p114 is elevated in a MCF-7 derivative that exhibits an EMT-like phenotype. Moreover, hHDAC6p114 is required for TGF-{beta}1-activated gene expression associated with EMT in A549 cells. Taken together, our results implicate that expression and function of hHDAC6p114 is differentially regulated when compared to hHDAC6p131.

  20. Fabrication of X-ray Microcalorimeter Focal Planes Composed of Two Distinct Pixel Types

    Science.gov (United States)

    Wassell, Edward J.; Adams, Joseph S.; Bandler, Simon R.; Betancour-Martinez, Gabriele L; Chiao, Meng P.; Chang, Meng Ping; Chervenak, James A.; Datesman, Aaron M.; Eckart, Megan E.; Ewin, Audrey J.; hide

    2016-01-01

    We develop superconducting transition-edge sensor (TES) microcalorimeter focal planes for versatility in meeting the specifications of X-ray imaging spectrometers, including high count rate, high energy resolution, and large field of view. In particular, a focal plane composed of two subarrays: one of fine pitch, high count-rate devices and the other of slower, larger pixels with similar energy resolution, offers promise for the next generation of astrophysics instruments, such as the X-ray Integral Field Unit Instrument on the European Space Agencys ATHENA mission. We have based the subarrays of our current design on successful pixel designs that have been demonstrated separately. Pixels with an all-gold X-ray absorber on 50 and 75 micron pitch, where the Mo/Au TES sits atop a thick metal heatsinking layer, have shown high resolution and can accommodate high count rates. The demonstrated larger pixels use a silicon nitride membrane for thermal isolation, thinner Au, and an added bismuth layer in a 250-sq micron absorber. To tune the parameters of each subarray requires merging the fabrication processes of the two detector types. We present the fabrication process for dual production of different X-ray absorbers on the same substrate, thick Au on the small pixels and thinner Au with a Bi capping layer on the larger pixels to tune their heat capacities. The process requires multiple electroplating and etching steps, but the absorbers are defined in a single-ion milling step. We demonstrate methods for integrating the heatsinking of the two types of pixel into the same focal plane consistent with the requirements for each subarray, including the limiting of thermal crosstalk. We also discuss fabrication process modifications for tuning the intrinsic transition temperature (T(sub c)) of the bilayers for the different device types through variation of the bilayer thicknesses. The latest results on these 'hybrid' arrays will be presented.

  1. [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

  2. ¿Disposable Matter or Personal Entity? The Human Body, Biotechnology and the Juridical Requirements of Dignity

    Directory of Open Access Journals (Sweden)

    Jorge Nicolás Lafferriere

    2018-01-01

    Full Text Available Biotechnological interventions affect the human body in new and powerful ways in the process of procreation, through actions of enhancement or replacement of the body, or by the search of the immortality of the body. This implies new legal challenges to prevent biotechnoscience from considering the human body as "operable and disposable matter", and treating it as the human person himself. In this article, we will study these challenges, starting from human dignity as a fundamental principle for an assessment of this biotechnology, and focusing on four legal issues: improvement interventions and their legal enforceability; the commodification of human life; growing social inequalities and the emergence of new forms of discrimination; and the principle of integrity of the human species.

  3. 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

  4. 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.)

  5. Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients?

    NARCIS (Netherlands)

    Deegens, J.K.J.; Assmann, K.J.M.; Steenbergen, E.; Hilbrands, L.B.; Gerlag, P.G.G.; Jansen, J.L.; Wetzels, J.F.M.

    2005-01-01

    BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently

  6. 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...

  7. Mass Equivalent Pantographs for Synthesis of Balanced Focal Mechanisms

    NARCIS (Netherlands)

    van der Wijk, V.; Lenarcic, Jadran; Merlet, Jean-Pierre

    2016-01-01

    Force balance is an important property in the design of high-speed high precision machinery to reduce base vibrations and also for the design of inherently safe large movable structures. This paper presents the synthesis of inherently balanced overconstrained focal mechanisms with mass equivalent

  8. A case of pathological rib fractures: focal osteolysis or osteoporosis?

    Science.gov (United States)

    Vrbanić, T S L; Novak, S; Sestan, B; Tudor, A; Gulan, G

    2008-03-01

    This paper reports on a unique, previously unreported, successful outcome in the case of a patient with focal osteolytic lesions of the ribs as a first sign of osteoporosis. The lesions were detected by chance after acute cough-induced rib fractures were seen on plain chest radiographs. The diagnosis had to be approached as a diagnosis of exclusion since known causes of the osteolytic process had to be eliminated. The authors describe multiple focal osteolytic lesions with rib fractures appearing in a pattern that could be confused with metastases. Laboratory results were normal. Final diagnosis was based on plain radiography, bone scan and bone densitometry. Pharmacomedical treatments for osteoporosis were applied. The patient was observed between the year 2000 and 2005. Five years later radiological and bone scintigraphy revealed resolution of the lesion. We conclude that osteoporosis should be included in the differential diagnosis of asymptomatic focal osteolysis of the ribs with rib fractures as a complication of acute cough. The case suggests that focal osteolytic lesions of the ribs may regress over time and become scintigraphically inactive.

  9. Shared Focal Plane Investigation for Serial Frame Cameras.

    Science.gov (United States)

    1980-03-01

    capability will be restored. 41. -.. TrABLE 1-1 SYSTEM LEADING P) ARTICULARS Lens Focal Length (inches) Range (ft) Contrast 12 18 24 Coverage 22.1...can be expected that signature bands will be apparent in the imagery. Such bands are at best distracting and at worst hindrances to image interpretation

  10. Tratamento focal e perifocal contra Aëdes aegypti

    Directory of Open Access Journals (Sweden)

    Milton Moura Lima

    1987-06-01

    Full Text Available Em quatro bairros da cidade do Rio de Janeiro, foram feitos ensaios de tratamento focal com abate granulado a 1 ppm e perifocal com pó molhável de Sumition a 2,5%. Esses tratamentos foram feitos tanto isoladamente quanto em conjunto e, também, associados à aplicação de inseticida a ultrabaixo volume. Os índices prediais, levantados um mês depois de terminado o trabalho, mostraram que o tratamento focal dispensa qualquer medida auxiliar. O tratamento perifocal mostrou-se inócuo e incapaz de impedir o aparecimento de larvas de Aëdes aegypti e de outros insetos, em pneus pintados, na face externa, com Sumition e com Malation.In four districts of the city of Rio dc Janeiro focal treatment essays with granulated Abate at 1 ppm and perifocal treatment essays with wettable powder of Sumithion at 2,5% were performed. These were made either alone or in combination as well as associated to insecticides applied at ultra low volume. The premise indices obtained one month after the treatments indicates that the focal treatment alone is effective, no other addicional methods being necessary. The perifocal treatment is not effective and did not prevent the development of Aedes aegypti larvae and other insects in tires which had their external surface painted with Sumithion and Malathion.

  11. Axial and focal-plane diffraction catastrophe integrals

    International Nuclear Information System (INIS)

    Berry, M V; Howls, C J

    2010-01-01

    Exact expressions in terms of Bessel functions are found for some of the diffraction catastrophe integrals that decorate caustics in optics and mechanics. These are the axial and focal-plane sections of the elliptic and hyperbolic umbilic diffraction catastrophes, and symmetric elliptic and hyperbolic unfoldings of the X 9 diffraction catastrophes. These representations reveal unexpected relations between the integrals.

  12. Neurophysiological evidence for cerebellar dysfunction in primary focal dystonia.

    NARCIS (Netherlands)

    Teo, J.T.; Warrenburg, B.P.C. van de; Schneider, S.A.; Rothwell, J.C.; Bhatia, K.P.

    2009-01-01

    Recent studies have suggested that there may be functional and structural changes in the cerebellum of patients with adult onset primary focal dystonia. The aim of this study was to establish whether there is any neurophysiological indicator of abnormal cerebellar function, using the classic

  13. The Localizing Value Of Focal Delta Slowing In Temporal Lobe ...

    African Journals Online (AJOL)

    Slow wave EEG had a higher marginal probability than neuropsychological assessment of predicting the focus, and was equally effective as other investigative methods. Conclusion These results suggest that focal temporal delta slowing is useful in the localization of epileptogenic foci. There was no discordance with the ...

  14. 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 ...

  15. 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.

  16. [Primary focal dystonia: descriptive study of 205 patients].

    Science.gov (United States)

    Bartolomé, F M; Fanjul, S; Cantarero, S; Hernández, J; García Ruiz, P J

    2003-03-01

    To describe the clinical and epidemiologic aspects of different types of focal dystonia. A total of 205 patients with primary focal dystonia were studied retrospectively and the following variables were analyzed: gender, age of onset, age at examination, evolution time, history of trauma, association with other movement disorders, fluctuations of dystonic symptoms as well as a family history of dystonia, Parkinson's disease, tremor, and lefthandedness or stuttering. We compared these variables among the different clinical categories of focal dystonia. Those patients with cranial and laryngeal dystonia were significantly older at the onset of symptoms compared with patients with writer's cramp. Males were more prevalent than females in all categories of focal dystonia except for cranial dystonia. Prior history of trauma and association with tremor were more frequent in patients with cervical dystonia than in those with others dystonic categories. Most patients with cranial, cervical and laryngeal dystonia had fluctuations in the intensity of dystonic symptoms, unlike the patients with writer's cramp. There is a caudo-cranial gradient in age of onset and the age of onset increases as the cranial presentation becomes greater. Females are more prevalent in cranial dystonia and there is a preponderance of males in the dystonias with a lower location. The dystonias with cranial distribution frequently present fluctuations of symptoms during the day. Association with other movement disorders, such as tremor, and prior history of trauma, is common in patients with cervical dystonia.

  17. Focal fibrocartilaginous dysplasia and tibia vara: a case report

    International Nuclear Information System (INIS)

    Cockshott, W.P.; Martin, R.; Friedman, L.; Yuen, M.

    1994-01-01

    A 2-year-old black boy with focal fibrocartilaginous dysplasia is described with illustrations of the typical radiographic appearances supplemented by computed tomographic and magnetic resonance images. Since this rare condition is self-correcting, diagnosis is important so that surgical intervention and biopsy can be avoided and conservative management instituted. (orig.)

  18. Focal fibrocartilaginous dysplasia and tibia vara: a case report.

    Science.gov (United States)

    Cockshott, W P; Martin, R; Friedman, L; Yuen, M

    1994-07-01

    A 2-year-old black boy with focal fibrocartilaginous dysplasia is described with illustrations of the typical radiographic appearances supplemented by computed tomographic and magnetic resonance images. Since this rare condition is self-correcting, diagnosis is important so that surgical intervention and biopsy can be avoided and conservative management instituted.

  19. Focal fibrocartilaginous dysplasia and tibia vara: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Cockshott, W.P. (Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada)); Martin, R. (Dept. of Orthopedics, McMaster Univ. Medical Centre, Hamilton, ON (Canada)); Friedman, L. (Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada)); Yuen, M. (Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada))

    1994-07-01

    A 2-year-old black boy with focal fibrocartilaginous dysplasia is described with illustrations of the typical radiographic appearances supplemented by computed tomographic and magnetic resonance images. Since this rare condition is self-correcting, diagnosis is important so that surgical intervention and biopsy can be avoided and conservative management instituted. (orig.)

  20. Contrast enhanced ultrasound in CT-undetermined focal liver lesions

    DEFF Research Database (Denmark)

    Sandrose, Sebastian; Karstrup, S.; Gerke, Oke

    2016-01-01

    , surgical resection, PET/CT and clinical follow-up. Results: The 78 included patients had 163 undetermined focal liver lesions, mean size 1.1 cm, range 0.1–5.3 cm. There were 18 malignant and 145 benign liver lesions, as defined by the standard of reference. In differentiating between benign vs. malignant...

  1. Automatic test comes to focal plane array production

    Science.gov (United States)

    Skaggs, Frank L.; Barton, T. D.

    1992-08-01

    To meet the needs of military and commercial markets, the infrared focal plane array industry must develop new, effective and low cost methods of fabricating and testing imaging detectors. This paper describes Texas Instruments new concepts in automated testing and cold probe technology as they apply to volume production.

  2. Focal irreversible electroporation as primary treatment for localized prostate cancer

    NARCIS (Netherlands)

    van den Bos, Willemien; Scheltema, Matthijs J.; Siriwardana, Amila R.; Kalsbeek, Anton M. F.; Thompson, James E.; Ting, Francis; Böhm, Maret; Haynes, Anne-Maree; Shnier, Ron; Delprado, Warick; Stricker, Phillip D.

    2017-01-01

    To determine the safety, quality of life (QoL) and short-term oncological outcomes of primary focal IRE for the treatment of localized prostate cancer. To identify potential risk factors for oncological failure. Patients that met both the consensus guidelines on patient criteria and selection

  3. 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.

  4. Mutations in KCNT1 cause a spectrum of focal epilepsies

    Science.gov (United States)

    Møller, Rikke S.; Heron, Sarah E.; Larsen, Line H. G.; Lim, Chiao Xin; Ricos, Michael G.; Bayly, Marta A.; van Kempen, Marjan J. A.; Klinkenberg, Sylvia; Andrews, Ian; Kelley, Kent; Ronen, Gabriel M.; Callen, David; McMahon, Jacinta M.; Yendle, Simone C.; Carvill, Gemma L.; Mefford, Heather C.; Nabbout, Rima; Poduri, Annapurna; Striano, Pasquale; Baglietto, Maria G.; Zara, Federico; Smith, Nicholas J.; Pridmore, Clair; Gardella, Elena; Nikanorova, Marina; Dahl, Hans Atli; Gellert, Pia; Scheffer, Ingrid E.; Gunning, Boudewijn; Kragh-Olsen, Bente; Dibbens, Leanne M.

    2018-01-01

    Summary 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 within the same family. This indicates that genotype–phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances. PMID:26122718

  5. 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

  6. 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 w...

  7. Report of a consultants meeting on impact of ageing on human energy, macro- and micronutrient metabolism and requirements

    International Nuclear Information System (INIS)

    2003-01-01

    The International Atomic Energy Agency (IAEA) in Vienna convened a Consultants' Meeting from 9-13 December, 2002, to provide the Agency with current insights into the application of nuclear and isotopic techniques as a means to support research on the impact of ageing on human energy and macro-nutrient metabolism and requirements. The Consultants were: Dr. Anura Kurpad, Dr. Victoria Lambert, Dr. June Stevens, Dr. Benjamin Torun and Dr. Mauro Valencia-Juillerat. Dr. Pirjo Pietinen, from the World Health Organization, and Dr. Barry Popkin, from the University of North Carolina at Chapel Hill, were present as Observers during the initial part of the Meeting. Given the Consultants' areas of expertise and the topics covered in the discussions, the scope of the Meeting was modified as 'The Application of Nuclear and Isotopic Techniques to improve Research on Body Composition, Energy Expenditure, Non-communicable Chronic Diseases, and the Ageing Process, with particular emphasis on Developing Countries'. The objectives of the Meeting were to: i) Evaluate the overall scope of a new Co-ordinated Research Project (CRP) and suggest options for specific areas of research within that scope; ii) Suggest approaches to improve the use of nuclear and isotopic techniques for the evaluation of energy and macro-nutrient requirements of older adults in diverse populations of the developing world; iii) Discuss and make recommendations for the use of these techniques in the measurement of energy expenditure, physical activity, total body fat and body fat distribution; and, iv) Propose a harmonization of methods for direct use or for validation of field measurements aimed at obtaining a better understanding of the ageing process and its relation to the incidence of obesity and non-communicable chronic diseases in communities in transition. This meeting benefited from the broad areas of experience of scientists from both developed and developing countries. Their expertise in the use of

  8. 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

  9. Standards and pitfalls of focal ischemia models in spontaneously hypertensive rats: With a systematic review of recent articles

    Directory of Open Access Journals (Sweden)

    Yao Hiroshi

    2012-07-01

    Full Text Available Abstract We reviewed the early development of various focal ischemia models in spontaneously hypertensive rats (SHR, and summarized recent reports on this topic. Among 6 focal ischemia models established in divergent substrains of SHR, distal middle cerebral artery occlusion is the most frequently used and relevant method of focal ischemia in the light of penumbra concept. We performed an online PubMed search (2001–2010, and identified 118 original articles with focal ischemia in SHR. Physiological parameters such as age, body weight, and even blood pressure were often neglected in the literature: the information regarding the physiological parameters of SHR is critical, and should be provided within the methodology section of all articles related to stroke models in SHR. Although the quality of recent studies on neuroprotective strategy is improving, the mechanisms underlying the protection should be more clearly recognized so as to facilitate the translation from animal studies to human stroke. To overcome the genetic heterogeneity in substrains of SHR, new approaches, such as a huge repository of genetic markers in rat strains and the congenic strategy, are currently in progress.

  10. The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Jensen, Kristian K; Manfra, Denise J; Grisotto, Marcos G

    2005-01-01

    Kaposi's sarcoma (KS)-associated herpesvirus or human herpes virus 8 is considered the etiological agent of KS, a highly vascularized neoplasm that is the most common tumor affecting HIV/AIDS patients. The KS-associated herpesvirus/human herpes virus 8 open reading frame 74 encodes a constitutively...

  11. Education for Personal Life: John MacMurray on Why Learning to Be Human Requires Emotional Discipline

    Science.gov (United States)

    MacAllister, James

    2014-01-01

    In this article I discuss the philosophy of John MacMurray, and in particular, his little-examined writings on discipline and emotion education. It is argued that discipline is a vital element in the emotion education MacMurray thought central to learning to be human, because for him it takes concerted effort to overcome the human tendency toward…

  12. Context cue focality influences strategic prospective memory monitoring.

    Science.gov (United States)

    Hunter Ball, B; Bugg, Julie M

    2018-02-12

    Monitoring the environment for the occurrence of prospective memory (PM) targets is a resource-demanding process that produces cost (e.g., slower responding) to ongoing activities. However, research suggests that individuals are able to monitor strategically by using contextual cues to reduce monitoring in contexts in which PM targets are not expected to occur. In the current study, we investigated the processes supporting context identification (i.e., determining whether or not the context is appropriate for monitoring) by testing the context cue focality hypothesis. This hypothesis predicts that the ability to monitor strategically depends on whether the ongoing task orients attention to the contextual cues that are available to guide monitoring. In Experiment 1, participants performed an ongoing lexical decision task and were told that PM targets (TOR syllable) would only occur in word trials (focal context cue condition) or in items starting with consonants (nonfocal context cue condition). In Experiment 2, participants performed an ongoing first letter judgment (consonant/vowel) task and were told that PM targets would only occur in items starting with consonants (focal context cue condition) or in word trials (nonfocal context cue condition). Consistent with the context cue focality hypothesis, strategic monitoring was only observed during focal context cue conditions in which the type of ongoing task processing automatically oriented attention to the relevant features of the contextual cue. These findings suggest that strategic monitoring is dependent on limited-capacity processing resources and may be relatively limited when the attentional demands of context identification are sufficiently high.

  13. Human IgG is produced in a pro-form that requires clipping of C-terminal lysines for maximal complement activation

    DEFF Research Database (Denmark)

    van den Bremer, E. T. J.; Beurskens, F. J.; Voorhorst, M.

    2015-01-01

    Human IgG is produced with C-terminal lysines that are cleaved off in circulation. The function of this modification was unknown and generally thought not to affect antibody function. We recently reported that efficient C1q binding and complement-dependent cytotoxicity (CDC) requires IgG hexameri...

  14. Flotillins Regulate Focal Adhesions by Interacting with α-Actinin and by Influencing the Activation of Focal Adhesion Kinase

    Directory of Open Access Journals (Sweden)

    Antje Banning

    2018-04-01

    Full Text Available Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.

  15. A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region.

    Science.gov (United States)

    Moroco, Jamie A; Baumgartner, Matthew P; Rust, Heather L; Choi, Hwan Geun; Hur, Wooyoung; Gray, Nathanael S; Camacho, Carlos J; Smithgall, Thomas E

    2015-08-01

    The c-Src tyrosine kinase co-operates with the focal adhesion kinase to regulate cell adhesion and motility. Focal adhesion kinase engages the regulatory SH3 and SH2 domains of c-Src, resulting in localized kinase activation that contributes to tumor cell metastasis. Using assay conditions where c-Src kinase activity required binding to a tyrosine phosphopeptide based on the focal adhesion kinase SH3-SH2 docking sequence, we screened a kinase-biased library for selective inhibitors of the Src/focal adhesion kinase peptide complex versus c-Src alone. This approach identified an aminopyrimidinyl carbamate compound, WH-4-124-2, with nanomolar inhibitory potency and fivefold selectivity for c-Src when bound to the phospho-focal adhesion kinase peptide. Molecular docking studies indicate that WH-4-124-2 may preferentially inhibit the 'DFG-out' conformation of the kinase active site. These findings suggest that interaction of c-Src with focal adhesion kinase induces a unique kinase domain conformation amenable to selective inhibition. © 2014 John Wiley & Sons A/S.

  16. The flexible engagement of monitoring processes in non-focal and focal prospective memory tasks with salient cues.

    Science.gov (United States)

    Hefer, Carmen; Cohen, Anna-Lisa; Jaudas, Alexander; Dreisbach, Gesine

    2017-09-01

    Prospective memory (PM) refers to the ability to remember to perform a delayed intention. Here, we aimed to investigate the ability to suspend such an intention and thus to confirm previous findings (Cohen, Gordon, Jaudas, Hefer, & Dreisbach, 2016) demonstrating the ability to flexibly engage in monitoring processes. In the current study, we presented a perceptually salient PM cue (bold and red) to rule out that previous findings were limited to non-salient and, thus, easy to ignore PM cues. Moreover, we used both a non-focal (Experiment 1) and a focal PM (Experiment 2) cue. In both Experiments, three groups of participants performed an Eriksen flanker task as an ongoing task with an embedded PM task (they had to remember to press the F1 key if a pre-specified cue appeared). Participants were assigned to either a control condition (performed solely the flanker task), a standard PM condition (performed the flanker task along with the PM task), or a PM delayed condition (performed the flanker task but were instructed to postpone their PM task intention). The results of Experiment 1 with the non-focal PM cue closely replicated those of Cohen et al. (2016) and confirmed that participants were able to successfully postpone the PM cue intention without additional costs even when the PM cue was a perceptually salient one. However, when the PM cue was focal (Experiment 2), it was much more difficult for participants to ignore it as evidenced by commission errors and slower latencies on PM cue trials. In sum, results showed that the focality of the PM cue plays a more crucial role in the flexibility of the monitoring process whereas the saliency of the PM cue does not. Copyright © 2017 Elsevier B.V. All rights reserved.

  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. [Department of Computational and Structural Chemistry, GlaxoSmithKline Inc., Five Moore Drive, Research Triangle Park, NC 27709 (United States); Burkhart, William A.; Consler, Thomas G. [Department of Biochemical Reagents and Assay Development, GlaxoSmithKline Inc., Five Moore Drive, Research Triangle Park, NC 27709 (United States); Cowan, David J. [Department of Chemistry in the Center for Excellence in Metabolic Pathways Drug Discovery, GlaxoSmithKline Inc., Five Moore Drive, Research Triangle Park, NC 27709 (United States); Gottschalk, William K. [Institute for Genome Sciences and Policy and Department of Medicine, Division of Neurology, Duke University, Durham, NC 27708 (United States); Miller, Aaron B. [Department of Computational and Structural Chemistry, GlaxoSmithKline Inc., Five Moore Drive, Research Triangle Park, NC 27709 (United States); Short, Steven A. [Department of Biochemical Reagents and Assay Development, GlaxoSmithKline Inc., Five Moore Drive, Research Triangle Park, NC 27709 (United States); Tran, Thuy B. [Department of Physiology, UNC School of Medicine, University of North Carolina, Chapel Hill, NC 27515 (United States); Williams, Shawn P., E-mail: shawn.p.williams@gsk.com [Department of Computational and Structural Chemistry, GlaxoSmithKline Inc., Five Moore Drive, Research Triangle Park, NC 27709 (United States)

    2009-05-01

    The use of biophysical assays permitted the identification of a specific human ACC2 carboxyl transferase (CT) domain mutant that binds inhibitors and crystallizes in their presence. This mutant led to determination of the human ACC2 CT domain–CP-640186 complex crystal structure, which revealed differences in the inhibitor conformation from the yeast protein complex that are caused by differing residues in the binding pocket. 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 α-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. 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)

  19. 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)

  20. CXCR4 Is Required by a Nonprimate Lentivirus: Heterologous Expression of Feline Immunodeficiency Virus in Human, Rodent, and Feline Cells

    Science.gov (United States)

    Poeschla, Eric M.; Looney, David J.

    1998-01-01

    A heterologous feline immunodeficiency virus (FIV) expression system permitted high-level expression of FIV proteins and efficient production of infectious FIV in human cells. These results identify the FIV U3 element as the sole restriction to the productive phase of replication in nonfeline cells. Heterologous FIV expression in a variety of human cell lines resulted in profuse syncytial lysis that was FIV env specific, CD4 independent, and restricted to cells that express CXCR4, the coreceptor for T-cell-line-adapted strains of human immunodeficiency virus. Stable expression of human CXCR4 in CXCR4-negative human and rodent cell lines resulted in extensive FIV Env-mediated, CXCR4-dependent cell fusion and infection. In feline cells, stable overexpression of human CXCR4 resulted in increased FIV infectivity and marked syncytium formation during FIV replication or after infection with FIV Env-expressing vectors. The use of CXCR4 is a fundamental feature of lentivirus biology independent of CD4 and a shared cellular link to infection and cytopathicity for distantly related lentiviruses that cause AIDS. Their conserved use implicates chemokine receptors as primordial lentivirus receptors. PMID:9658135

  1. CT and ERCP findings of chronic focal pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Soo; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Eun Kyeong [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-10-01

    To evaluate the major radiologic features of chronic focal pancreatitis in various imaging studies, with special emphasis on CT and ERCP findings. From 1991 to 1995, twelve patients were pathologically proved to be suffering from focal chronic pancreatitis after pancreatico-duodenectomy;for retrospective evaluation, imaging studies were available for eight(seven men, one woman;mean age 58.9{+-}6.6, range 47 to 67). Clinical, surgical, and radiological findings, including CT(n=8), ultrasound(n=7), ERCP(n=8) and UGI(n=3) were analysed. Seven male patients had suffered from chronic alcoholism for between 20 and 50 years. Serum bilirubin levels were normal in eight patients and alkaline phosphatase levels were normal in seven patients. Serum CA 19-9 levels were normal in all five patients who had undergone preoperative evaluation. Seven patients(87.5%) showed focal enlargement without definable margin on CT, and five of the six lesions detectable on ultrasound(83.3%) were ill defined hypoechoic nodules. Dilated side branches within lesions were seen in five of eight patients(83.3%) on CT and ERCP. Double duct signs were observed in siven(87.5%) patients, and dilated intrahepatic ducts in six(75%), with diameters ranging from 5 to 8mm(average:5.42{+-}1.96mm). The average ratio of pancreatic duct caliber to gland width was 0.33{+-}0.19. None of the patients had calcification within the lesion and one case showed intraductal calcification. None showed perivascular fat obliteration around the superior mesenteric artery or celiac axis. The average biductal distance between abnormal common bile duct and the immediately adjacent pancreatic duct was 4.0{+-}1.15mm. One of three cases who under went a UGI examination showed severe luminal narrowing and mucosal thickening in the second protion of the duodenum, another showed double contour, and the other merely showed widening of the C-loop of the duodenum. Chronic focal pancreatitis mostly demonstrated ill defined focal

  2. CT and ERCP findings of chronic focal pancreatitis

    International Nuclear Information System (INIS)

    Kim, Hee Soo; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Eun Kyeong

    1996-01-01

    To evaluate the major radiologic features of chronic focal pancreatitis in various imaging studies, with special emphasis on CT and ERCP findings. From 1991 to 1995, twelve patients were pathologically proved to be suffering from focal chronic pancreatitis after pancreatico-duodenectomy;for retrospective evaluation, imaging studies were available for eight(seven men, one woman;mean age 58.9±6.6, range 47 to 67). Clinical, surgical, and radiological findings, including CT(n=8), ultrasound(n=7), ERCP(n=8) and UGI(n=3) were analysed. Seven male patients had suffered from chronic alcoholism for between 20 and 50 years. Serum bilirubin levels were normal in eight patients and alkaline phosphatase levels were normal in seven patients. Serum CA 19-9 levels were normal in all five patients who had undergone preoperative evaluation. Seven patients(87.5%) showed focal enlargement without definable margin on CT, and five of the six lesions detectable on ultrasound(83.3%) were ill defined hypoechoic nodules. Dilated side branches within lesions were seen in five of eight patients(83.3%) on CT and ERCP. Double duct signs were observed in siven(87.5%) patients, and dilated intrahepatic ducts in six(75%), with diameters ranging from 5 to 8mm(average:5.42±1.96mm). The average ratio of pancreatic duct caliber to gland width was 0.33±0.19. None of the patients had calcification within the lesion and one case showed intraductal calcification. None showed perivascular fat obliteration around the superior mesenteric artery or celiac axis. The average biductal distance between abnormal common bile duct and the immediately adjacent pancreatic duct was 4.0±1.15mm. One of three cases who under went a UGI examination showed severe luminal narrowing and mucosal thickening in the second protion of the duodenum, another showed double contour, and the other merely showed widening of the C-loop of the duodenum. Chronic focal pancreatitis mostly demonstrated ill defined focal enlargement and

  3. Removing defocused objects from single focal plane scans of cytological slides

    Directory of Open Access Journals (Sweden)

    David Friedrich

    2016-01-01

    Full Text Available Background: Virtual microscopy and automated processing of cytological slides are more challenging compared to histological slides. Since cytological slides exhibit a three-dimensional surface and the required microscope objectives with high resolution have a low depth of field, these cannot capture all objects of a single field of view in focus. One solution would be to scan multiple focal planes; however, the increase in processing time and storage requirements are often prohibitive for clinical routine. Materials and Methods: In this paper, we show that it is a reasonable trade-off to scan a single focal plane and automatically reject defocused objects from the analysis. To this end, we have developed machine learning solutions for the automated identification of defocused objects. Our approach includes creating novel features, systematically optimizing their parameters, selecting adequate classifier algorithms, and identifying the correct decision boundary between focused and defocused objects. We validated our approach for computer-assisted DNA image cytometry. Results and Conclusions: We reach an overall sensitivity of 96.08% and a specificity of 99.63% for identifying defocused objects. Applied on ninety cytological slides, the developed classifiers automatically removed 2.50% of the objects acquired during scanning, which otherwise would have interfered the examination. Even if not all objects are acquired in focus, computer-assisted DNA image cytometry still identified more diagnostically or prognostically relevant objects compared to manual DNA image cytometry. At the same time, the workload for the expert is reduced dramatically.

  4. 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.

  5. Low-Noise CMOS Circuits for On-Chip Signal Processing in Focal-Plane Arrays

    Science.gov (United States)

    Pain, Bedabrata

    The performance of focal-plane arrays can be significantly enhanced through the use of on-chip signal processing. Novel, in-pixel, on-focal-plane, analog signal-processing circuits for high-performance imaging are presented in this thesis. The presence of a high background-radiation is a major impediment for infrared focal-plane array design. An in-pixel, background-suppression scheme, using dynamic analog current memory circuit, is described. The scheme also suppresses spatial noise that results from response non-uniformities of photo-detectors, leading to background limited infrared detector readout performance. Two new, low-power, compact, current memory circuits, optimized for operation at ultra-low current levels required in infrared-detection, are presented. The first one is a self-cascading current memory that increases the output impedance, and the second one is a novel, switch feed-through reducing current memory, implemented using error-current feedback. This circuit can operate with a residual absolute -error of less than 0.1%. The storage-time of the memory is long enough to also find applications in neural network circuits. In addition, a voltage-mode, accurate, low-offset, low-power, high-uniformity, random-access sample-and-hold cell, implemented using a CCD with feedback, is also presented for use in background-suppression and neural network applications. A new, low noise, ultra-low level signal readout technique, implemented by individually counting photo-electrons within the detection pixel, is presented. The output of each unit-cell is a digital word corresponding to the intensity of the photon flux, and the readout is noise free. This technique requires the use of unit-cell amplifiers that feature ultra-high-gain, low-power, self-biasing capability and noise in sub-electron levels. Both single-input and differential-input implementations of such amplifiers are investigated. A noise analysis technique is presented for analyzing sampled

  6. In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein.

    Science.gov (United States)

    Deeg, Christoph M; Hassan, Ebrahim; Mutz, Pascal; Rheinemann, Lara; Götz, Veronika; Magar, Linda; Schilling, Mirjam; Kallfass, Carsten; Nürnberger, Cindy; Soubies, Sébastien; Kochs, Georg; Haller, Otto; Schwemmle, Martin; Staeheli, Peter

    2017-05-01

    Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population. © 2017 Deeg et al.

  7. 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.

  8. Focal points and principal solutions of linear Hamiltonian systems revisited

    Science.gov (United States)

    Šepitka, Peter; Šimon Hilscher, Roman

    2018-05-01

    In this paper we present a novel view on the principal (and antiprincipal) solutions of linear Hamiltonian systems, as well as on the focal points of their conjoined bases. We present a new and unified theory of principal (and antiprincipal) solutions at a finite point and at infinity, and apply it to obtain new representation of the multiplicities of right and left proper focal points of conjoined bases. We show that these multiplicities can be characterized by the abnormality of the system in a neighborhood of the given point and by the rank of the associated T-matrix from the theory of principal (and antiprincipal) solutions. We also derive some additional important results concerning the representation of T-matrices and associated normalized conjoined bases. The results in this paper are new even for completely controllable linear Hamiltonian systems. We also discuss other potential applications of our main results, in particular in the singular Sturmian theory.

  9. Focal sparing around the gallbladder in fatty liver

    International Nuclear Information System (INIS)

    Chen, Kemin; Hiramatsu, Yoshihiro; Yunoki, Masanori; Hirano, Yoko

    1989-01-01

    In evaluating fatty liver with CT, the residual normal liver tissues without fat deposits are occasionally detected on CT as high attenuation regions, especially surrounding the gallbladder. This study examined the incidence of this phenomenon in terms of the diagnostic value of CT in fatty liver. Fifty-seven patients with fatty liver were examined with CT. The incidence of focal sparing area was the highest in the gallbladder bed (42/57, 74%), followed by the interlobar fissure or subcapsular area (13, 23%), quadrate lobe (8, 14%), caudate lobe (2, 4%), and right lobe (one, 1.8%). These CT appearances were of spot, band, ring, and the mixed type. In 38 patients, fatty liver was too moderate to be detected without CT attenuation numbers. Among them, 27 patients (71%) had focal sparing area surrounding the gallbladder. This CT appearance seemed to be of significance in preventing the missing of moderate fatty liver. (Namekawa, K)

  10. Segmented focal plane detector for light and heavy ions

    International Nuclear Information System (INIS)

    Wolfs, F.L.H.; Bryan, D.C.; Kurz, K.L.; Herrick, D.M.; Perera, P.A.A.; White, C.A.

    1992-01-01

    A segmented focal plane detector for an Enge split-pole spectrograph has been developed for the study of breakup reactions at very low relative energies. It consists of a 61 cm long segmented position-sensitive parallel plate avalanche counter backed by a large Bragg curve detector. A segmented plastic scintillator is mounted behind the anode of the Bragg curve detector and is used for particle identification of low-ionizing particles. The dead space between the two sections of the focal plane detector is 2.5 mm. The intrinsic position resolution of the detector is 1 mm. The intrinsic energy resolution depends on the energy of the incident ion and can be as good as 0.55%. The nuclear charge and mass resolutions are 0.3 e and 0.3 u, respectively. (orig.)

  11. Exploiting Human Resource Requirements to Infer Human Movement Patterns for Use in Modelling Disease Transmission Systems: An Example from Eastern Province, Zambia.

    Directory of Open Access Journals (Sweden)

    Simon Alderton

    Full Text Available In this research, an agent-based model (ABM was developed to generate human movement routes between homes and water resources in a rural setting, given commonly available geospatial datasets on population distribution, land cover and landscape resources. ABMs are an object-oriented computational approach to modelling a system, focusing on the interactions of autonomous agents, and aiming to assess the impact of these agents and their interactions on the system as a whole. An A* pathfinding algorithm was implemented to produce walking routes, given data on the terrain in the area. A* is an extension of Dijkstra's algorithm with an enhanced time performance through the use of heuristics. In this example, it was possible to impute daily activity movement patterns to the water resource for all villages in a 75 km long study transect across the Luangwa Valley, Zambia, and the simulated human movements were statistically similar to empirical observations on travel times to the water resource (Chi-squared, 95% confidence interval. This indicates that it is possible to produce realistic data regarding human movements without costly measurement as is commonly achieved, for example, through GPS, or retrospective or real-time diaries. The approach is transferable between different geographical locations, and the product can be useful in providing an insight into human movement patterns, and therefore has use in many human exposure-related applications, specifically epidemiological research in rural areas, where spatial heterogeneity in the disease landscape, and space-time proximity of individuals, can play a crucial role in disease spread.

  12. Exploiting Human Resource Requirements to Infer Human Movement Patterns for Use in Modelling Disease Transmission Systems: An Example from Eastern Province, Zambia.

    Science.gov (United States)

    Alderton, Simon; Noble, Jason; Schaten, Kathrin; Welburn, Susan C; Atkinson, Peter M

    2015-01-01

    In this research, an agent-based model (ABM) was developed to generate human movement routes between homes and water resources in a rural setting, given commonly available geospatial datasets on population distribution, land cover and landscape resources. ABMs are an object-oriented computational approach to modelling a system, focusing on the interactions of autonomous agents, and aiming to assess the impact of these agents and their interactions on the system as a whole. An A* pathfinding algorithm was implemented to produce walking routes, given data on the terrain in the area. A* is an extension of Dijkstra's algorithm with an enhanced time performance through the use of heuristics. In this example, it was possible to impute daily activity movement patterns to the water resource for all villages in a 75 km long study transect across the Luangwa Valley, Zambia, and the simulated human movements were statistically similar to empirical observations on travel times to the water resource (Chi-squared, 95% confidence interval). This indicates that it is possible to produce realistic data regarding human movements without costly measurement as is commonly achieved, for example, through GPS, or retrospective or real-time diaries. The approach is transferable between different geographical locations, and the product can be useful in providing an insight into human movement patterns, and therefore has use in many human exposure-related applications, specifically epidemiological research in rural areas, where spatial heterogeneity in the disease landscape, and space-time proximity of individuals, can play a crucial role in disease spread.

  13. A focal plane detector for both light and heavy ions

    International Nuclear Information System (INIS)

    Ophel, T.R.; Johnston, A.

    1978-05-01

    The characteristics of a multi-element, ionization-type focal plane detector with an effective length of 53 cm have been evaluated for various ions ranging between protons and 32 S. The position resolution obtained is typically 1 mm. Excellent energy (0.49% for 16 O) and angular resolution (0.2 degrees with respect to beam direction for 7 Li) have been obtained enabling clean separation of ion species at essentially full angular acceptance of a split-pole spectrograph

  14. Perampanel for focal epilepsy: insights from early clinical experience

    OpenAIRE

    Trinka, E.; Steinhoff, B. J.; Nikanorova, M.; Brodie, M. J.

    2015-01-01

    Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potenti...

  15. Primary Focal Dystonia: Evidence for Distinct Neuropsychiatric and Personality Profiles

    OpenAIRE

    2009-01-01

    Abstract Background: Primary focal dystonia (PFD) is characterized by motor symptoms. Frequent co-occurrence of abnormal mental conditions has been mentioned for decades but is less well defined. We evaluated prevalence rates of psychiatric disorders, personality disorders and traits in a large cohort of PFD patients. Methods: Prevalence rates of clinical psychiatric diagnoses in 86 PFD patients were compared to a population-based sample (N=3943) using a multiple regress...

  16. The extracellular matrix and altered diffusion in focal cortical dysplasia

    Czech Academy of Sciences Publication Activity Database

    Homola, Aleš; Vargová, Lýdia; Cicanič, Michal; Zámečník, J.; Marusič, P.; Kršek, P.; Syková, Eva

    2011-01-01

    Roč. 59, S1 (2011), S106-S106 ISSN 0894-1491. [European meeting on Glia l Cells in Health and Disease /10./. 13.09.2011-17.09.2011, Prague] R&D Projects: GA MŠk 1M0538; GA ČR GA309/09/1597 Institutional research plan: CEZ:AV0Z50390703 Keywords : focal cortical dysplasia * diffusion * extracellular matrix Subject RIV: FH - Neurology

  17. Atypical Focal Osteomyelitis as Initial Manifestation of AIDS

    OpenAIRE

    A. Akiki; Y. Bilde

    2011-01-01

    Persistent pain development after a skeletal contusion rarely poses the diagnosis of osteomyelitis. We report the case of a fibular head contusion as an initial manifestation of a focal abscess development in a healthy young patient. The traditional treatment of surgical drainage revealed the presence of an atypical Mycobacterium haemophilum isolates in the abscess. This lead to further investigations that concluded and established the diagnosis of AIDS. Conclusion. Isolation of an atypical M...

  18. Explaining focal points: Cognitive hierarchy theory versus team reasoning

    OpenAIRE

    Bardsley, Nicholas; Mehta, Judith; Starmer, Chris; Sugden, Robert

    2008-01-01

    This paper reports experimental tests of two alternative explanations of how players use focal points to select equilibria in one-shot coordination games. Cognitive hierarchy theory explains coordination as the result of common beliefs about players’ pre-reflective inclinations towards the relevant strategies; the theory of team reasoning explains it as the result of the players’ using a non-standard form of reasoning. We report two experiments. One finds strong support for team reasoning; th...

  19. Focal epilepsy with ictal abdominal pain: a case report

    OpenAIRE

    Cerminara, Caterina; El Malhany, Nadia; Roberto, Denis; Curatolo, Paolo

    2013-01-01

    Focal epilepsy with ictal abdominal pain is an unusual partial epilepsy characterized by paroxysmal episodes of abdominal or visceral pain, disturbance of awareness and electroencephalographic abnormalities. We describe a new case of ictal abdominal pain in which gastrointestinal complaints were the only manifestation of seizures and review the previously described pediatric patients. In our patient clinical findings, ictal EEG abnormalities, and a good response to antiepileptic drugs allowed...

  20. 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].

  1. Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

    Science.gov (United States)

    Doppalapudi, Harish; Jin, Qi; Dosdall, Derek J; Qin, Hao; Walcott, Gregory P; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E; Huang, Jian

    2008-09-01

    Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

  2. [A case of focal epilepsy manifesting multiple psychiatric auras].

    Science.gov (United States)

    Ezura, Michinori; Kakisaka, Yosuke; Jin, Kazutaka; Kato, Kazuhiro; Iwasaki, Masaki; Fujikawa, Mayu; Aoki, Masashi; Nakasato, Nobukazu

    2015-01-01

    We present a case of epilepsy with multiple types of focal seizures that were misdiagnosed as psychiatric disorders. A 20-year-old female patient presented with a variety of episodes, including loss of consciousness, deja vu, fear, delusion of possession, violent movements, and generalized convulsions. Each of these symptoms appeared in a stereotypic manner. She was initially diagnosed with a psychiatric disorder and treated with psychoactive medications, which had no effect. Long-term video electroencephalography revealed that her episodes of violent movement with impaired consciousness and secondarily generalized seizure were epileptic events originating in the right hemisphere. High-field brain magnetic resonance imaging for detecting subtle lesions revealed bilateral lesions from periventricular nodular heterotopia. Her final diagnosis was right hemispheric focal epilepsy. Carbamazepine administration was started, which successfully controlled all seizures. The present case demonstrates the pitfall of diagnosing focal epilepsy when it presents with multiple types of psychiatric aura. Epilepsy should thus be included in differential diagnoses, considering the stereotypic nature of symptoms, to avoid misdiagnosis.

  3. How to diagnose and treat focal therapy failure and recurrence?

    Science.gov (United States)

    Barret, Eric; Harvey-Bryan, Kadi-Ann; Sanchez-Salas, Rafael; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier

    2014-05-01

    Focal therapy presents an alternative option for disease-targeted therapy while preserving erectile and urinary function without compromising oncological outcome. Such treatment, which preserves normal prostate parenchyma, presents a clinical challenge to the urologist, as typical disease surveillance parameters are not as reliable in post-ablation follow-up. We propose an integrated approach to post-ablation surveillance to identify treatment failure as well as recurrence. Post-ablation prostate-specific antigen kinetics, imaging based on multiparametric MRI and control biopsies are the tools currently used to follow patients after focal therapy. Good treatment response is indicated by a negative control biopsy, absence of persistent lesion on post-treatment imaging and a reduction in prostate-specific antigen of at least 50%. When histological evidence of therapeutic failure or recurrence is present, different options of management may be proposed to the patient including active surveillance, focal salvage therapy or radical salvage treatment, depending on the characteristics of the lesion found. A recommended post-ablation surveillance protocol is presented as well as a discussion of management strategies based on the data currently available.

  4. Achromatic Focal Plane Mask for Exoplanet Imaging Coronagraphy

    Science.gov (United States)

    Newman, Kevin Edward; Belikov, Ruslan; Guyon, Olivier; Balasubramanian, Kunjithapatham; Wilson, Dan

    2013-01-01

    Recent advances in coronagraph technologies for exoplanet imaging have achieved contrasts close to 1e10 at 4 lambda/D and 1e-9 at 2 lambda/D in monochromatic light. A remaining technological challenge is to achieve high contrast in broadband light; a challenge that is largely limited by chromaticity of the focal plane mask. The size of a star image scales linearly with wavelength. Focal plane masks are typically the same size at all wavelengths, and must be sized for the longest wavelength in the observational band to avoid starlight leakage. However, this oversized mask blocks useful discovery space from the shorter wavelengths. We present here the design, development, and testing of an achromatic focal plane mask based on the concept of optical filtering by a diffractive optical element (DOE). The mask consists of an array of DOE cells, the combination of which functions as a wavelength filter with any desired amplitude and phase transmission. The effective size of the mask scales nearly linearly with wavelength, and allows significant improvement in the inner working angle of the coronagraph at shorter wavelengths. The design is applicable to almost any coronagraph configuration, and enables operation in a wider band of wavelengths than would otherwise be possible. We include initial results from a laboratory demonstration of the mask with the Phase Induced Amplitude Apodization coronagraph.

  5. A Micro-Thermal Sensor for Focal Therapy Applications

    Science.gov (United States)

    Natesan, Harishankar; Hodges, Wyatt; Choi, Jeunghwan; Lubner, Sean; Dames, Chris; Bischof, John

    2016-02-01

    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).

  6. Development and construction of a focal-plane detector for the Munich Q3D spectrograph

    International Nuclear Information System (INIS)

    Lindner, H.

    1989-01-01

    For the Munich Q3D magnet spectrograph a focal-plane detector was developed, constructed, and taken in operation. It is primary layed out for light ions like p, d, t 3 He, and 4 He, but can be also applied for heavy ions. The position resolution amounts to about 0.1 mm at counting rates of about 10 kHz. In the detector filled with counting gas on anode wires along the focal plane charge avalanches are formed, which influence in several neighbouring cathode stripes of the dimension (3x25) mm 2 signals. These signals are singularily read out and digitized, i.e. to each of the at the whole 114 cathode strips is assigned an own preamplifier, puls shaper, peak detector, and analog-to-digital converter (ADC). After the digitization in a hardware-like constructed calculator unit the center of mass of the charge distribution influenced by the charge avalanche is calculated, the position of the incident particle is obtained. The detector yields beyond the position signal yet also a signal ΔE form the anode wires, which gives the energy loss of the particle in the gas space, as well as a residual-energy signal E rest from a scintillator, in which the particles are stopped. By this the radiation background (γ's and n) can be separated very well from the required particles. With the focal-plane detector the 103 Rh(d, p) 104 Rh transfer reaction was measured at three different spectrograph angles. The measured level energies and angular momentum transfers are compared with (n, γ) data and discussed. (orig.) [de

  7. 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

  8. A proposed regulatory policy statement on human factors requirements in the design and operation of Canadian nuclear facilities

    International Nuclear Information System (INIS)

    1986-10-01

    With the increasing complexity of new nuclear facilities and the extent to which automation is being applied, it is essential that the staff who operate a facility be considered as integral components in the design and safety analyses. This policy statement is proposed to indicate those areas of facility design and operation where the role of the human operator must be especially examined

  9. 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

    Science.gov (United States)

    2010-04-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...; (ii) Is prominently placed on the package; and (iii) Is so placed that it will be unaffected if the... product or, if the petition seeks an exemption for a drug class, the name of the drug class, and a list of...

  10. Bidirectional GPR119 agonism requires peptide YY and glucose for activity in mouse and human colon mucosa

    DEFF Research Database (Denmark)

    Tough, Iain R; Forbes, Sarah; Herzog, Herbert

    2018-01-01

    motility in wild-type (WT), GPR119-/- and PYY-/- mice.The water-soluble GPR119 agonist, AR440006 (that cannot traverse epithelial tight-junctions) elicited responses when added apically or basolaterally in mouse and human colonic mucosas. In both species, GPR119 responses were PYY, Y1 receptor...

  11. Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R; Henriksen, Zanne; Sørensen, Ole

    2002-01-01

    that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling...

  12. 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

  13. Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases.

    Science.gov (United States)

    Schlaepfer, D D; Hunter, T

    1996-10-01

    Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase (PTK) that associates with integrin receptors and participates in extracellular matrix-mediated signal transduction events. We showed previously that the c-Src nonreceptor PTK and the Grb2 SH2/SH3 adaptor protein bound directly to FAK after fibronectin stimulation (D. D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer, Nature [London] 372:786-791, 1994). Here, we present evidence that c-Src association with FAK is required for Grb2 binding to FAK. Using a tryptic phosphopeptide mapping approach, the in vivo phosphorylation of the Grb2 binding site on FAK (Tyr-925) was detected after fibronectin stimulation of NIH 3T3 cells and was constitutively phosphorylated in v-Src-transformed NIH 3T3 cells. In vitro, c-Src phosphorylated FAK Tyr-925 in a glutathione S-transferase-FAK C-terminal domain fusion protein, whereas FAK did not. Using epitope-tagged FAK constructs, transiently expressed in human 293 cells, we determined the effect of site-directed mutations on c-Src and Grb2 binding to FAK. Mutation of FAK Tyr-925 disrupted Grb2 binding, whereas mutation of the c-Src binding site on FAK (Tyr-397) disrupted both c-Src and Grb2 binding to FAK in vivo. These results support a model whereby Src-family PTKs are recruited to FAK and focal adhesions following integrin-induced autophosphorylation and exposure of FAK Tyr-397. Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. In Src-transformed cells, this pathway may be constitutively activated as a result of FAK Tyr-925 phosphorylation in the absence of integrin stimulation.

  14. Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

    Science.gov (United States)

    Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

    2008-12-15

    A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

  15. Reduction of herbivorous fish pressure can facilitate focal algal species forestation on artificial structures.

    Science.gov (United States)

    Gianni, Fabrizio; Bartolini, Fabrizio; Airoldi, Laura; Mangialajo, Luisa

    2018-07-01

    Coastal areas have been transformed worldwide by urbanization, so that artificial structures are now widespread. Current coastal development locally depletes many native marine species, while offering limited possibilities for their expansion. Eco-engineering interventions intend to identify ways to facilitate the presence of focal species and their associated functions on artificial habitats. An important but overlooked factor controlling restoration operations is overgrazing by herbivores. The aim of this study was to quantify the effects of different potential feeders on Cystoseira amentacea, a native canopy-forming alga of the Mediterranean infralittoral fringe, and test whether manipulation of grazing pressure can facilitate the human-guided installation of this focal species on coastal structures. Results of laboratory tests and field experiments revealed that Sarpa salpa, the only strictly native herbivorous fish in the Western Mediterranean Sea, can be a very effective grazer of C. amentacea in artificial habitats, up to as far as the infralittoral fringe, which is generally considered less accessible to fishes. S. salpa can limit the success of forestation operations in artificial novel habitats, causing up to 90% of Cystoseira loss after a few days. Other grazers, such as limpets and crabs, had only a moderate impact. Future engineering operations,intended to perform forestation of canopy-forming algae on artificial structures, should consider relevant biotic factors, such as fish overgrazing, identifying cost-effective techniques to limit their impact, as is the usual practice in restoration programmes on land. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Focal adhesion kinase maintains, but not increases the adhesion of dental pulp cells.

    Science.gov (United States)

    Qian, Yuyan; Shao, Meiying; Zou, Wenlin; Wang, Linyan; Cheng, Ran; Hu, Tao

    2017-04-01

    Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects.

  17. HIGH PERFORMANCE PIAA CORONAGRAPHY WITH COMPLEX AMPLITUDE FOCAL PLANE MASKS

    International Nuclear Information System (INIS)

    Guyon, Olivier; Martinache, Frantz; Belikov, Ruslan; Soummer, Remi

    2010-01-01

    We describe a coronagraph approach where the performance of a Phase-Induced Amplitude Apodization (PIAA) coronagraph is improved by using a partially transmissive phase-shifting focal plane mask and a Lyot stop. This approach combines the low inner working angle offered by phase mask coronagraphy, the full throughput and uncompromized angular resolution of the PIAA approach, and the design flexibility of Apodized Pupil Lyot Coronagraph. A PIAA complex mask coronagraph (PIAACMC) is fully described by the focal plane mask size, or, equivalently, its complex transmission which ranges from 0 (opaque) to -1 (phase shifting). For all values of the transmission, the PIAACMC theoretically offers full on-axis extinction and 100% throughput at large angular separations. With a pure phase focal plane mask (complex transmission = -1), the PIAACMC offers 50% throughput at 0.64 λ/D while providing total extinction of an on-axis point source. This performance is very close to the 'fundamental performance limit' of coronagraphy derived from first principles. For very high contrast level, imaging performance with PIAACMC is in practice limited by the angular size of the on-axis target (usually a star). We show that this fundamental limitation must be taken into account when choosing the optimal value of the focal plane mask size in the PIAACMC design. We show that the PIAACMC enables visible imaging of Jupiter-like planets at ∼1.2 λ/D from the host star, and can therefore offer almost three times more targets than a PIAA coronagraph optimized for this type of observation. We find that for visible imaging of Earth-like planets, the PIAACMC gain over a PIAA is probably much smaller, as coronagraphic performance is then strongly constrained by stellar angular size. For observations at 'low' contrast (below ∼ 10 8 ), the PIAACMC offers significant performance enhancement over PIAA. This is especially relevant for ground-based high contrast imaging systems in the near-IR, where

  18. Electrophysiological and pathological study of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Hodozuka, Akira; Hashizume, Kiyotaka; Hayashi, Yoshimitsu; Tanaka, Tatsuya

    2008-01-01

    Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted. The behavior of the rats and electroencephalography (EEG) were recorded using a digital video-EEG monitoring system. After observation periods of 1, 2 and 6 months, the rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than one month after the injection. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in gamma aminobutyric acid (GABA)-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were included in the clinical study. Neuro-imaging studies including high-resolution MRI and single photon emission computed tomography (SPECT) were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed in order to localize epileptic foci under neuroleptanalgesia. Fourteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and characteristics of the FCD in relation to EEG findings were analyzed. Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. In the lesions, immunohistochemical studies showed decrease in GABA-A receptors and increase in GABA-B receptors in both the lesions and perilesional areas, but N

  19. The solar UV exposure time required for vitamin D3 synthesis in the human body estimated by numerical simulation and observation in Japan

    Science.gov (United States)

    Nakajima, Hideaki; Miyauchi, Masaatsu; Hirai, Chizuko

    2013-04-01

    After the discovery of Antarctic ozone hole, the negative effect of exposure of human body to harmful solar ultraviolet (UV) radiation is widely known. However, there is positive effect of exposure to UV radiation, i.e., vitamin D synthesis. Although the importance of solar UV radiation for vitamin D3 synthesis in the human body is well known, the solar exposure time required to prevent vitamin D deficiency has not been well determined. This study attempted to identify the time of solar exposure required for vitamin D3 synthesis in the body by season, time of day, and geographic location (Sapporo, Tsukuba, and Naha, in Japan) using both numerical simulations and observations. According to the numerical simulation for Tsukuba at noon in July under a cloudless sky, 2.3 min of solar exposure are required to produce 5.5 μg vitamin D3 per 600 cm2 skin. This quantity of vitamin D represents the recommended intake for an adult by the Ministry of Health, Labour and Welfare, and the 2010 Japanese Dietary Reference Intakes (DRIs). In contrast, it took 49.5 min to produce the same amount of vitamin D3 at Sapporo in the northern part of Japan in December, at noon under a cloudless sky. The necessary exposure time varied considerably with the time of the day. For Tsukuba at noon in December, 14.5 min were required, but at 09:00 68.7 min were required and at 15:00 175.8 min were required for the same meteorological conditions. Naha receives high levels of UV radiation allowing vitamin D3 synthesis almost throughout the year. According to our results, we are further developing an index to quantify the necessary time of UV radiation exposure to produce required amount of vitamin D3 from a UV radiation data.

  20. Epigenetic Reprogramming of Lineage-Committed Human Mammary Epithelial Cells Requires DNMT3A and Loss of DOT1L

    Directory of Open Access Journals (Sweden)

    Jerrica L. Breindel

    2017-09-01

    Full Text Available Organogenesis and tissue development occur through sequential stepwise processes leading to increased lineage restriction and loss of pluripotency. An exception to this appears in the adult human breast, where rare variant epithelial cells exhibit pluripotency and multilineage differentiation potential when removed from the signals of their native microenvironment. This phenomenon provides a unique opportunity to study mechanisms that lead to cellular reprogramming and lineage plasticity in real time. Here, we show that primary human mammary epithelial cells (HMECs lose expression of differentiated mammary epithelial markers in a manner dependent on paracrine factors and epigenetic regulation. Furthermore, we demonstrate that HMEC reprogramming is dependent on gene silencing by the DNA methyltransferase DNMT3A and loss of histone transcriptional marks following downregulation of the methyltransferase DOT1L. These results demonstrate that lineage commitment in adult tissues is context dependent and highlight the plasticity of somatic cells when removed from their native tissue microenvironment.