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Sample records for insulinoma hit cells

  1. Antitumorigenic effect of proteasome inhibitors on insulinoma cells

    DEFF Research Database (Denmark)

    Størling, Joachim; Allaman-Pillet, Nathalie; Karlsen, Allan E

    2004-01-01

    inhibition of the proteasome has an antitumorigenic potential in insulinoma cells. Exposure of mouse betaTC3 insulinoma cells to the proteasome inhibitor N-Acetyl-Leu-Leu-Nle-CHO (ALLN) reduced cell viability, activated caspase-3, induced apoptosis, and suppressed insulin release. Treatment with ALLN also...

  2. Kupffer cell blockade prevents rejection of human insulinoma cell xenograft in rats

    International Nuclear Information System (INIS)

    Lazar, G. Jr.; Farkas, G.; Lazar, G.

    1998-01-01

    Alloantigens are recognized by T-cells in the context of both class I and class II antigen, but class II antigens predominate in the recognition of xenoantigens. Since class II molecules bind peptides derived from exogenous proteins that have been phagocytized and digested into small fragments by antigen presenting cells, in the present studies the effect of gadolinium chloride (GdCl 3 )-induced Kupffer cell blockade on the survival of discordant insulinoma cell xenografts was investigated. Insulinoma cells isolated by means of collagenase from human insulinoma and cultured were transplanted through the v. portae into the liver of streptozotocin-induced diabetic, male, CFY inbred rats. In the control, streptozotocin-treated rats, the decrease in blood glucose level was only transitory, in contrast with the GdCl 3 -pretreated diabetic rats, which remained normoglycaemic during the 2-week observation period. Histologically, in the liver and lung of rats pre-treated with GdCl 3 , large areas of extensively proliferating insulinoma cells were seen, whereas no insulinoma cells were seen in either the liver or the lung of diabetic-control rats, not-treated with GdCl 3 . These studies suggest that the Kupffer cells play significant roles in the recognition of xenoantigens and the induction of xenograft rejection. (orig.)

  3. Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

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    Anoopa A. Koshy MD

    2013-01-01

    Full Text Available A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment.

  4. Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas

    DEFF Research Database (Denmark)

    Møller, C J; Christgau, S; Williamson, M R

    1992-01-01

    The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin...... primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N...

  5. Statistics of hits to bone cell nuclei

    International Nuclear Information System (INIS)

    Kruglikov, I.L.; Polig, E.; Jee, W.S.S.

    1993-01-01

    The statistics of hits to the nuclei of bone cells irradiated from alpha sources labeling bone tissue is described. It is shown that the law of remodeling of a bone structural unit (BSU), which describes the distribution of quiescence periodes of this unit, affects the statistics of hits. It the irradiation of bone cells occurs during the whole cell cycle, the mean number of hits is independent of the law of remodeling. In this case the variance of hits has the minimum value for constant quiescence periods of BSUs (deterministic remodeling) and the maximum value for exponentially distributed quiescence periods (random remodeling). For the first generation of bone cells, i.e. for the cells which existed at the moment of the uptake of the nuclide, the mean number of hits depends on the law of remodeling. For random remodeling the mean number is equal to the mean value for the complete remodeling cycle. For deterministic remodeling the mean is only half this value. For the first generation of bone cells, changing the law of remodeling from random to deterministic increases the probability of no hits to the nuclei of bone cells. For the same mean value of hits, the difference does not exceed 13.3% of the total number of cells. For the subsequent generations of bone cells, such a change of the law of remodeling decreases the probability of no hits up to 20.4% of the total number of cells. (orig.)

  6. Introduction of exogenous growth hormone receptors augments growth hormone-responsive insulin biosynthesis in rat insulinoma cells

    DEFF Research Database (Denmark)

    Billestrup, N; Møldrup, A; Serup, P

    1990-01-01

    The stimulation of insulin biosynthesis in the pancreatic insulinoma cell line RIN5-AH by growth hormone (GH) is initiated by GH binding to specific receptors. To determine whether the recently cloned rat hepatic GH receptor is able to mediate the insulinotropic effect of GH, we have transfected ...

  7. A novel dual-color reporter for identifying insulin-producing beta-cells and classifying heterogeneity of insulinoma cell lines.

    Directory of Open Access Journals (Sweden)

    Nan Sook Lee

    Full Text Available Many research studies use immortalized cell lines as surrogates for primary beta- cells. We describe the production and use of a novel "indirect" dual-fluorescent reporter system that leads to mutually exclusive expression of EGFP in insulin-producing (INS(+ beta-cells or mCherry in non-beta-cells. Our system uses the human insulin promoter to initiate a Cre-mediated shift in reporter color within a single transgene construct and is useful for FACS selection of cells from single cultures for further analysis. Application of our reporter to presumably clonal HIT-T15 insulinoma cells, as well as other presumably clonal lines, indicates that these cultures are in fact heterogeneous with respect to INS(+ phenotype. Our strategy could be easily applied to other cell- or tissue-specific promoters. We anticipate its utility for FACS purification of INS(+ and glucose-responsive beta-like-cells from primary human islet cell isolates or in vitro differentiated pluripotent stem cells.

  8. Modeling Pharmacological Inhibition of Mast Cell Degranulation as a Therapy for Insulinoma

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    Laura Soucek

    2011-11-01

    Full Text Available Myc, a pleiotropic transcription factor that is deregulated and/or overexpressed in most human cancers, instructs multiple extracellular programs that are required to sustain the complex microenvironment needed for tumor maintenance, including remodeling of tumor stroma, angiogenesis, and inflammation. We previously showed in a model of pancreatic β-cell tumorigenesis that acute Myc activation in vivo triggers rapid recruitment of mast cells to the tumor site and that this is absolutely required for angiogenesis and macroscopic tumor expansion. More-over, systemic inhibition of mast cell degranulation with sodium cromoglycate induced death of tumor and endothelial cells in established tumors. Hence, mast cells are required both to establish and to maintain the tumors. Whereas this intimates that selective inhibition of mast cell function could be therapeutically efficacious, cromoglycate is not a practical drug for systemic delivery in humans, and no other systemic inhibitor of mast cell degranulation has hitherto been available. PCI-32765 is a novel inhibitor of Bruton tyrosine kinase (Btk that blocks mast cell degranulation and is currently in clinical trial as a therapy for B-cell non–Hodgkin lymphoma. Here, we show that systemic treatment of insulinoma-bearing mice with PCI-32765 efficiently inhibits Btk, blocks mast cell degranulation, and triggers collapse of tumor vasculature and tumor regression. These data reinforce the notion that mast cell function is required for maintenance of certain tumor types and indicate that the Btk inhibitor PCI-32765 may be useful in treating such diseases.

  9. ActivinB Is Induced in Insulinoma To Promote Tumor Plasticity through a β-Cell-Induced Dedifferentiation.

    Science.gov (United States)

    Ripoche, Doriane; Charbord, Jérémie; Hennino, Ana; Teinturier, Romain; Bonnavion, Rémy; Jaafar, Rami; Goehrig, Delphine; Cordier-Bussat, Martine; Ritvos, Olli; Zhang, Chang X; Andersson, Olov; Bertolino, Philippe

    2015-12-28

    Loss of pancreatic β-cell maturity occurs in diabetes and insulinomas. Although both physiological and pathological stresses are known to promote β-cell dedifferentiation, little is known about the molecules involved in this process. Here we demonstrate that activinB, a transforming growth factor β (TGF-β)-related ligand, is upregulated during tumorigenesis and drives the loss of insulin expression and β-cell maturity in a mouse insulinoma model. Our data further identify Pax4 as a previously unknown activinB target and potent contributor to the observed β-cell dedifferentiation. More importantly, using compound mutant mice, we found that deleting activinB expression abolishes tumor β-cell dedifferentiation and, surprisingly, increases survival without significantly affecting tumor growth. Hence, this work reveals an unexpected role for activinB in the loss of β-cell maturity, islet plasticity, and progression of insulinoma through its participation in β-cell dedifferentiation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Double-hit B-cell lymphomas

    NARCIS (Netherlands)

    Aukema, Sietse M.; Siebert, Reiner; Schuuring, Ed; van Imhoff, Gustaaf W.; Kluin-Nelemans, Hanneke C.; Boerma, Evert-Jan; Kluin, Philip M.

    2011-01-01

    In many B-cell lymphomas, chromosomal translocations are biologic and diagnostic hallmarks of disease. An intriguing subset is formed by the so-called double-hit (DH) lymphomas that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint,

  11. Canine and Human Insulinoma : prognostic factors, druggable genes and cancer stem cells

    NARCIS (Netherlands)

    Buishand, F.O.|info:eu-repo/dai/nl/411880381

    2016-01-01

    Insulinoma (INS), which causes clinical signs associated with hypoglycaemia, is the most common pancreatic neuroendocrine tumour (pNET) of dogs and humans. Ten tot fifteen percent of human INS metastasise to regional lymph nodes and the liver, and these are referred to as ‘malignant INS’. Surgical

  12. Regulation of ATP-sensitive K+ channels in insulinoma cells: Activation by somatostatin and protein kinase C and the role of cAMP

    International Nuclear Information System (INIS)

    De Weille, J.R.; Schmid-Antomarchi, H.; Fosset, M.; Lazdunski, M.

    1989-01-01

    The actions of somatostatin and of the phorbol ester 4β-phorbol 12-myristate 13-acetate (PMA) were studied in rat insulinoma (RINm5F) cells by electrophysiological and 86 Rb + flux techniques. Both PMA and somatostatin hyperpolarize insulinoma cells by activating ATP-sensitive K + channels. The presence of intracellular GTP is required for the somatostatin effects. PMA- and somatostatin-induced hyperpolarization and channel activity are inhibited by the sulfonylurea glibenclamide. Glibenclamide-sensitive 86 Rb + efflux from insulinoma cells is stimulated by somatostatin in a dose-dependent manner (half maximal effect at 0.7 nM) and abolished by pertussis toxin pretreatment. Mutual roles of a GTP-binding protein, of protein kinase C, and of cAMP in the regulation of ATP-sensitive K + channels are discussed

  13. Antioxidant effect of mogrosides against oxidative stress induced by palmitic acid in mouse insulinoma NIT-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Q.; Chen, S.Y.; Deng, L.D.; Feng, L.P.; Huang, L.Z.; Yu, R.R. [Department of Pharmacy, Guilin Medical University, Guilin (China)

    2013-11-18

    Excessive oxidative stress in pancreatic β cells, caused by glucose and fatty acids, is associated with the pathogenesis of type 2 diabetes. Mogrosides have shown antioxidant and antidiabetic activities in animal models of diabetes, but the underlying mechanisms remain unclear. This study evaluated the antioxidant effect of mogrosides on insulinoma cells under oxidative stress caused by palmitic acid, and investigated the underlying molecular mechanisms. Mouse insulinoma NIT-1 cells were cultured in medium containing 0.75 mM palmitic acid, mimicking oxidative stress. The effects of 1 mM mogrosides were determined with the dichlorodihydrofluorescein diacetate assay for intracellular reactive oxygen species (ROS) and FITC-Annexin V/PI assay for cell apoptosis. Expression of glucose transporter-2 (GLUT2) and pyruvate kinase was determined by semi-quantitative reverse-transcription polymerase chain reaction. Palmitic acid significantly increased intracellular ROS concentration 2-fold (P<0.05), and decreased expression of GLUT2 (by 60%, P<0.05) and pyruvate kinase (by 80%, P<0.05) mRNAs in NIT-1 cells. Compared with palmitic acid, co-treatment with 1 mM mogrosides for 48 h significantly reduced intracellular ROS concentration and restored mRNA expression levels of GLUT2 and pyruvate kinase. However, mogrosides did not reverse palmitic acid-induced apoptosis in NIT-1 cells. Our results indicate that mogrosides might exert their antioxidant effect by reducing intracellular ROS and regulating expression of genes involved in glucose metabolism. Further research is needed to achieve a better understanding of the signaling pathway involved in the antioxidant effect of mogrosides.

  14. Role of aryl hydrocarbon receptor nuclear translocator in KATP channel-mediated insulin secretion in INS-1 insulinoma cells

    International Nuclear Information System (INIS)

    Kim, Ji-Seon; Zheng Haifeng; Kim, Sung Joon; Park, Jong-Wan; Park, Kyong Soo; Ho, Won-Kyung; Chun, Yang-Sook

    2009-01-01

    Aryl hydrocarbon receptor nuclear translocator (ARNT) has been known to participate in cellular responses to xenobiotic and hypoxic stresses, as a common partner of aryl hydrocarbon receptor and hypoxia inducible factor-1/2α. Recently, it was reported that ARNT is essential for adequate insulin secretion in response to glucose input and that its expression is downregulated in the pancreatic islets of diabetic patients. In the present study, the authors addressed the mechanism by which ARNT regulates insulin secretion in the INS-1 insulinoma cell line. In ARNT knock-down cells, basal insulin release was elevated, but insulin secretion was not further stimulated by a high-glucose challenge. Electrophysiological analyses revealed that glucose-dependent membrane depolarization was impaired in these cells. Furthermore, K ATP channel activity and expression were reduced. Of two K ATP channel subunits, Kir6.2 was found to be positively regulated by ARNT at the mRNA and protein levels. Based on these results, the authors suggest that ARNT expresses K ATP channel and by so doing regulates glucose-dependent insulin secretion.

  15. Suppression of the Nuclear Factor Eny2 Increases Insulin Secretion in Poorly Functioning INS-1E Insulinoma Cells

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    P. Dames

    2012-01-01

    Full Text Available Eny2, the mammalian ortholog of yeast Sus1 and drosophila E(y2, is a nuclear factor that participates in several steps of gene transcription and in mRNA export. We had previously found that Eny2 expression changes in mouse pancreatic islets during the metabolic adaptation to pregnancy. We therefore hypothesized that the protein contributes to the regulation of islet endocrine cell function and tested this hypothesis in rat INS-1E insulinoma cells. Overexpression of Eny2 had no effect but siRNA-mediated knockdown of Eny2 resulted in markedly increased glucose and exendin-4-induced insulin secretion from otherwise poorly glucose-responsive INS-1E cells. Insulin content, cellular viability, and the expression levels of several key components of glucose sensing remained unchanged; however glucose-dependent cellular metabolism was higher after Eny2 knockdown. Suppression of Eny2 enhanced the intracellular incretin signal downstream of cAMP. The use of specific cAMP analogues and pathway inhibitors primarily implicated the PKA and to a lesser extent the EPAC pathway. In summary, we identified a potential link between the nuclear protein Eny2 and insulin secretion. Suppression of Eny2 resulted in increased glucose and incretin-induced insulin release from a poorly glucose-responsive INS-1E subline. Whether these findings extend to other experimental conditions or to in vivo physiology needs to be determined in further studies.

  16. Single-hit mechanism of tumour cell killing by radiation.

    Science.gov (United States)

    Chapman, J D

    2003-02-01

    To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells

  17. Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells.

    Science.gov (United States)

    Song, Jia-Le; Zhao, Xin; Wang, Qiang; Zhang, Ting

    2013-05-01

    Reactive oxygen species (ROS)-induced pancreatic β cell death affects insulin secretion and is important in the pathogenesis of diabetes. Lagerstroemia speciosa, a traditional folk medicine, has been used for t he prevention and treatment of diabetes. However, whether Lagerstroemia speciosa has a cytoprotective effect on pancreatic β cells remains to be elucidated. The present study aimed to investigate the cytoprotective effects of hot water extracts from Lagerstroemia speciosa leaves (LWE) on 3-morpholinosydnonimine (SIN-1)-induced oxidative damage in Syrian hamster pancreatic insulinoma HIT-T15 cells. The HIT-T15 cells were first treated with SIN-1 (50 µM) for 24 h and then co-incubated with LWE for 48 h. SIN-1 significantly decreased HIT-T15 cell viability (PHIT-T15 cells in a dose‑dependent manner. To further investigate the protective effects of LWE on SIN-1‑induced oxidative stress in HIT-T15 cells, the cellular levels of ROS, lipid peroxidation and endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px), were determined. LWE decreased the intracellular levels of ROS and lipid peroxidation, and increased the activities of antioxidant enzymes. These results suggest that LWE has a cytoprotective effect against SIN-1‑induced oxidative stress in HIT-T15 cells through the inhibition of lipid peroxidation, a decrease in ROS levels and an increase in antioxidant enzyme activity. In addition, LWE increased insulin secretion in SIN-1-treated HIT-T15 cells. Our results suggested that LWE were effective in the treatment of diabetes. Further studies are required to study the anti-diabetic molecular mechanism in a cell model.

  18. Electrical Characterization of HIT type solar cells

    NARCIS (Netherlands)

    Rath, J.K.

    2012-01-01

    The silicon heterojunction solar cell (SHJ) has made rapid progress in reaching high efficiency and it is already developed as an industrially viable product. However, much of its progress has come through process development while there is scarce knowledge on the microscopic nature of the

  19. Characterization of HIT type solar cells

    NARCIS (Netherlands)

    Rath, J.K.

    2011-01-01

    The silicon heterojunction solar cell (SHJ) has made rapid progress in reaching high efficiency and it is already developed as an industrially viable product. However, much of its progress has come through process development while there is scarce knowledge on the microscopic nature of the

  20. MRI in insulinomas

    International Nuclear Information System (INIS)

    Liessi, Guido; Pasquali, Claudio; Alfano D'Andrea, Alfonso; Pedrazzoli, Sergio; Scandellari, Cesare

    1992-01-01

    After establishing the diagnosis of an insulinoma, most surgeons prefer preoperative localization. Selective arteriography is usually considered the gold standard for this purpose. Recently, computed tomography (CT) and preoperative US have contended the role to angiography. MRI has been used in few cases of endocrine pancreatic tumors, and its role in this particular field has to be defined. Between November 1988-September 1990 7 adult patients who had undergone surgery were evaluated. Eight tumors were resected in 6 patients who were cured; in an 18-year-old woman surgical treatment was unsuccessful. Arterio-graphy, CT, preoperative US, MRI and intraoperative US detected 2, 6, 6, 5 and 6 tumors respectively. Two insulinomas (0.2 and 0.7 cm) were found at histologic examination in resected specimen. The ability of intra-operative US and careful surgical exploration to resolve more than 90 percent of cases makes the preoperative use of arteriography and CT questionable value. If further experience confirms these findings, US and MRI may suffice. (author). 13 refs.; 3 figs.; 1 tab

  1. Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells

    Directory of Open Access Journals (Sweden)

    Han Sung Kim

    2016-01-01

    Full Text Available 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER stress. We investigated whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308, and p-mTOR (Ser2481 were also significantly reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with 2-DG treatment in the presence/absence of melatonin. Intracellular insulin production increased in melatonin plus 2-DG but reduced in treatment with 2-DG with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a dose-dependent manner and subsequently resulted in a decrease in intracellular production of insulin. These results suggest that melatonin-mediated insulin synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat insulinoma INS-1E cells and subsequently results in a decrease in intracellular production of insulin.

  2. Proteomic analysis of INS-1 rat insulinoma cells: ER stress effects and the protective role of exenatide, a GLP-1 receptor agonist.

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    Mi-Kyung Kim

    Full Text Available Beta cell death caused by endoplasmic reticulum (ER stress is a key factor aggravating type 2 diabetes. Exenatide, a glucagon-like peptide (GLP-1 receptor agonist, prevents beta cell death induced by thapsigargin, a selective inhibitor of ER calcium storage. Here, we report on our proteomic studies designed to elucidate the underlying mechanisms. We conducted comparative proteomic analyses of cellular protein profiles during thapsigargin-induced cell death in the absence and presence of exenatide in INS-1 rat insulinoma cells. Thapsigargin altered cellular proteins involved in metabolic processes and protein folding, whose alterations were variably modified by exenatide treatment. We categorized the proteins with thapsigargin initiated alterations into three groups: those whose alterations were 1 reversed by exenatide, 2 exaggerated by exenatide, and 3 unchanged by exenatide. The most significant effect of thapsigargin on INS-1 cells relevant to their apoptosis was the appearance of newly modified spots of heat shock proteins, thimet oligopeptidase and 14-3-3β, ε, and θ, and the prevention of their appearance by exenatide, suggesting that these proteins play major roles. We also found that various modifications in 14-3-3 isoforms, which precede their appearance and promote INS-1 cell death. This study provides insights into the mechanisms in ER stress-caused INS-1 cell death and its prevention by exenatide.

  3. Tratamiento del insulinoma con diazóxido Insulinoma treated with diazoxide

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    M. V. Mateu

    2003-01-01

    Full Text Available Los insulinomas son tumores pancreáticos de las células beta que segregan insulina en cantidad suficiente como para producir hipoglucemia. Habitualmente benignos se manifiestan como adenomas solitarios, y en menor medida como microadenomas múltiples o carcinomas. Con una incidencia anual de un caso por millón de habitantes, generalmente en adultos de más de 30 años, se localizan con mayor frecuencia en el cuerpo y cola del páncreas. El diagnóstico se realiza sobre la base de los síntomas, la glucemia por debajo de 50mg% y niveles elevados de insulina plasmática y péptido C en ayunas. El mejor método preoperatorio para localizar el tumor es la arteriografía subselectiva del tronco celíaco. La mayoría de los adenomas que no logran evidenciarse por estudios por imágenes se diagnostican durante la cirugía. El tratamiento de elección del insulinoma es la cirugía. Cuando ésta fracasa o se contraindica, se utiliza tratamiento médico con diazóxido. Presentamos un caso de un paciente con un insulinoma que fue tratado médicamente, con excelente respuesta, realizando una actualización de las manifestaciones clínicas, los métodos diagnósticos y las opciones terapéuticas de una enfermedad muy poco frecuente.Insulinomas are islet cell tumors of the pancreas that produce hypoglycemia due to inappropriate insulin secretion. They appear generally as solitary adenomas, and less commonly as multifocal microadenomas or malignant insulinomas. Their incidence is approximately one case per 1 million population per year, and they appear mostly in patients above thirty years old. They are mainly situated in the pancreas tail or body. The diagnosis is based on the symptoms related to hypoglycemia, a blood glucose level under 50mg% and high levels of fast insulin and C-peptide. Selective angiography is the best preoperative procedure to localize the tumor. Occult adenomas, which cannot be represented by preoperative imaging diagnosis, are

  4. The H+/K+ ATPase Inhibitor SCH-28080 Inhibits Insulin Secretion and Induces Cell Death in INS-1E Rat Insulinoma Cells

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    Martin Jakab

    2017-10-01

    Full Text Available Background/Aims: Glucose-stimulated insulin secretion (GSIS of pancreatic β-cells involves glucose uptake and metabolism, closure of KATP channels and depolarization of the cell membrane potential (Vmem, activation of voltage-activated Ca2+ currents (ICav and influx of Ca2+, which eventually triggers hormone exocytosis. Beside this classical pathway, KATP-independent mechanisms such as changes in intracellular pH (pHi or cell volume, which also affect β-cell viability, can elicit or modify insulin release. In β-cells the regulation of pHi is mainly accomplished by Na+/H+ exchangers (NHEs. To investigate if other proton extrusion mechanisms than NHEs are involved in pH regulation, we tested for the presence of the non-gastric H+/K+ ATPase in rat insulinoma cells and assessed effects of the H+/K+ ATPase inhibitor SCH-28080 on insulin secretion, cell viability and apoptosis. Methods: In INS-1E cell cultures, H+/K+ ATPase gene and protein expression was analyzed by reverse transcription PCR and Western blotting. Intracellular pH (pHi recovery after acute acidic load was measured by NH4Cl prepulsing using BCECF. Insulin secretion was determined by ELISA from the cell culture supernatant. Vmem, K+ and Ca2+ currents were recorded using patch clamp. Overall cell responses were determined using resazurin (viability and cytotoxicity assays. The mean cell volume (MCV, cell granularity (side-scatter; SSC, phosphatidylserine (PS exposure, cell membrane integrity, caspase activity and the mitochondrial membrane potential (ΔΨm were measured by flow cytometry. Results: We found that the α-subunit of the non-gastric H+/K+ ATPase (HKα2 is expressed on mRNA and protein level. However, compared to rat colon tissue, in INS-1E cells mRNA abundance was very low. In NH4Cl prepulsing experiments no K+-dependent pHi recovery was observed under Na+-free extracellular conditions. Nonetheless within 1 h, 20 µM SCH-28080 inhibited GSIS by ∼50%, while basal release

  5. Andrographolide Suppress Tumor Growth by Inhibiting TLR4/NF-κB Signaling Activation in Insulinoma

    Science.gov (United States)

    Zhang, Qian-Qian; Ding, Yi; Lei, Yan; Qi, Cui-Ling; He, Xiao-Dong; Lan, Tian; Li, Jiang-Chao; Gong, Ping; Yang, Xuesong; Geng, Jian-Guo; Wang, Li-Jing

    2014-01-01

    Insulinomas are rare tumors, and approximately 10% of insulinomas are malignant. Accumulating evidence has implicated that we still lack effective therapy to treat the patients who are diagnosed with rare malignant insulinoma. Previous studies have reported that Andrographolide (Andro) could inhibit cell cycle progression, reduce cell invasion and induce cell apoptosis in many common cancer cells. However, the effects of andro are cell type-dependent. So we emplored the β-TC-6 cells and the RIP1-Tag2 transgenic mouse model of endogenously growing insulinoma model to elucidate the possible anti-cancer effect of Andro on insulinoma, an uncommon type of malignant cancers in this study. Our experiments revealed that Andro significantly inhibited tumor growth at both the early-stage and the advanced-stage of insulinoma through targeting the TLR4/NF-κB signaling pathway. This work initially provides the evidence that the TLR4/NF-κB signaling pathway might be vital as a potential therapeutic target, and also indispensable in Andro-mediated anti-cancer effect in insulinoma. PMID:24719558

  6. HIT Solar Cells with N-Type Low-Cost Metallurgical Si

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    Xing Yang

    2018-01-01

    Full Text Available A conversion efficiency of 20.23% of heterojunction with intrinsic thin layer (HIT solar cell on 156 mm × 156 mm metallurgical Si wafer has been obtained. Applying AFORS-HET software simulation, HIT solar cell with metallurgical Si was investigated with regard to impurity concentration, compensation level, and their impacts on cell performance. It is known that a small amount of impurity in metallurgical Si materials is not harmful to solar cell properties.

  7. Malignant insulinoma: The problems of tumour localization and ...

    African Journals Online (AJOL)

    Malignant insulinomas of the pancreas are rare tumours, accounting for 10% of ... Histological examination showed a R-cell malignant tumour of the pancreas with ... Associated vaso-. SA MEDICAL JOURNAL VOLUME 63 23 APRIL 1983 ... 52 cases of pancreatic endocrine malignant tumours, which have similar behaviour.

  8. Efficiency Improvement of HIT Solar Cells on p-Type Si Wafers.

    Science.gov (United States)

    Wei, Chun-You; Lin, Chu-Hsuan; Hsiao, Hao-Tse; Yang, Po-Chuan; Wang, Chih-Ming; Pan, Yen-Chih

    2013-11-22

    Single crystal silicon solar cells are still predominant in the market due to the abundance of silicon on earth and their acceptable efficiency. Different solar-cell structures of single crystalline Si have been investigated to boost efficiency; the heterojunction with intrinsic thin layer (HIT) structure is currently the leading technology. The record efficiency values of state-of-the art HIT solar cells have always been based on n-type single-crystalline Si wafers. Improving the efficiency of cells based on p-type single-crystalline Si wafers could provide broader options for the development of HIT solar cells. In this study, we varied the thickness of intrinsic hydrogenated amorphous Si layer to improve the efficiency of HIT solar cells on p-type Si wafers.

  9. Simulation optimizing of n-type HIT solar cells with AFORS-HET

    Science.gov (United States)

    Yao, Yao; Xiao, Shaoqing; Zhang, Xiumei; Gu, Xiaofeng

    2017-07-01

    This paper presents a study of heterojunction with intrinsic thin layer (HIT) solar cells based on n-type silicon substrates by a simulation software AFORS-HET. We have studied the influence of thickness, band gap of intrinsic layer and defect densities of every interface. Details in mechanisms are elaborated as well. The results show that the optimized efficiency reaches more than 23% which may give proper suggestions to practical preparation for HIT solar cells industry.

  10. An Atypical Presentation on Insulinoma

    Science.gov (United States)

    2017-06-16

    PUBLICATIONS/ PRESENTATIONS 1. TO: CLINICAL RESEARCH 2. FROM: (Author’s Name, Rank, Grade, Office Symbol) 3. GME/GHSE STUDENT: 4. PROTOCOL NUMBER: Kluesner...PROCESSING OF PROFESSIONAL MEDICAL RESEARCH/TECHNICAL PUBLICATIONS/ PRESENTATIONS 1st ENDORSEMENT (59 MDW/SGVU Use Only) TO: Clinical Research Division 24...CAPT JOSEPH KLUESNER FROM: 59 MDW/SGYU SUBJECT: Professional Presentation Approval 1. Your paper, entitled An Atypical Presentation of Insulinoma

  11. Scaffold Architecture Controls Insulinoma Clustering, Viability, and Insulin Production

    Science.gov (United States)

    Blackstone, Britani N.; Palmer, Andre F.; Rilo, Horacio R.

    2014-01-01

    Recently, in vitro diagnostic tools have shifted focus toward personalized medicine by incorporating patient cells into traditional test beds. These cell-based platforms commonly utilize two-dimensional substrates that lack the ability to support three-dimensional cell structures seen in vivo. As monolayer cell cultures have previously been shown to function differently than cells in vivo, the results of such in vitro tests may not accurately reflect cell response in vivo. It is therefore of interest to determine the relationships between substrate architecture, cell structure, and cell function in 3D cell-based platforms. To investigate the effect of substrate architecture on insulinoma organization and function, insulinomas were seeded onto 2D gelatin substrates and 3D fibrous gelatin scaffolds with three distinct fiber diameters and fiber densities. Cell viability and clustering was assessed at culture days 3, 5, and 7 with baseline insulin secretion and glucose-stimulated insulin production measured at day 7. Small, closely spaced gelatin fibers promoted the formation of large, rounded insulinoma clusters, whereas monolayer organization and large fibers prevented cell clustering and reduced glucose-stimulated insulin production. Taken together, these data show that scaffold properties can be used to control the organization and function of insulin-producing cells and may be useful as a 3D test bed for diabetes drug development. PMID:24410263

  12. Aggressive B cell Lymphoma: Optimal Therapy for MYC-positive, Double-Hit, and Triple-Hit DLBCL.

    Science.gov (United States)

    Dunleavy, Kieron

    2015-12-01

    Approximately 10% of cases of diffuse large B cell lymphoma (DLBCL) harbor a MYC rearrangement and this has been associated with an inferior outcome following standard therapy across many different studies. Double-hit and triple-hit lymphomas harbor concurrent rearrangements of MYC and BCL2 and/or BCL6 and are also associated with a very aggressive course and poor clinical outcome. It is unclear and there is lack of consensus on how these diseases should be approached therapeutically. They are characterized typically by high tumor proliferation and likely require Burkitt lymphoma-type strategies and several retrospective studies suggest that more intensive approaches than rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) may be beneficial. One challenge in this respect is that most patients with these diseases are older than 60 years and generally have poor tolerability of regimens typically used in Burkitt lymphoma. Dose-adjusted EPOCH-R is an alternative effective immunochemotherapy platform for DLBCL and is effective in Burkitt lymphoma, and retrospective studies suggest that it is effective and feasible in patients with DLBCL that harbors a MYC rearrangement with or without a BCL-2 translocation (double-hit). A multicenter study of this approach in MYC-rearranged DLBCL is ongoing and preliminary results are very encouraging. There is a lack of consensus on the role of consolidation stem cell transplantation in patients who achieve a good response to initial therapy but at this point in time, no (retrospective) studies have demonstrated any benefit. These diseases are also associated with a high rate of CNS involvement and progression and checking for cerebrospinal fluid by cytology and flow cytometry at initial diagnosis should be considered. In summary, based on retrospective data and preliminary prospective data (as more mature data is awaited), while Burkitt-type regimens may be feasible in young patients, DA-EPOCH-R is a

  13. Hit-and-run, hit-and-stay, and commensal bacteria present different peptide content when viewed from the perspective of the T cell.

    Science.gov (United States)

    He, Lu; De Groot, Anne S; Bailey-Kellogg, Chris

    2015-11-27

    Different types of bacteria face different pressures from the immune system, with those that persist ("hit-and-stay") potentially having to adapt more in order to escape than those prone to short-lived infection ("hit-and-run"), and with commensal bacteria potentially different from both due to additional physical mechanisms for avoiding immune detection. The Janus Immunogenicity Score (JIS) was recently developed to assess the likelihood of T cell recognition of an antigen, using an analysis that considers both binding of a peptide within the antigen by major histocompatability complex (MHC) and recognition of the peptide:MHC complex by cognate T cell receptor (TCR). This score was shown to be predictive of T effector vs. T regulatory or null responses in experimental data, as well as to distinguish viruses representative of the hit-and-stay vs. hit-and-run phenotypes. Here, JIS-based analyses were conducted in order to characterize the extent to which the pressure to avoid T cell recognition is manifested in genomic differences among representative hit-and-run, hit-and-stay, and commensal bacteria. Overall, extracellular proteins were found to have different JIS profiles from cytoplasmic ones. Contrasting the bacterial groups, extracellular proteins were shown to be quite different across the groups, much more so than intracellular proteins. The differences were evident even at the level of corresponding peptides in homologous protein pairs from hit-and-run and hit-and-stay bacteria. The multi-level analysis of patterns of immunogenicity across different groups of bacteria provides a new way to approach questions of bacterial immune camouflage or escape, as well as to approach the selection and optimization of candidates for vaccine design. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Insulinoma: A rare cause of hypoglycemia in a young female

    Directory of Open Access Journals (Sweden)

    Fnu Kelash

    2014-09-01

    Full Text Available Insulinoma is an exceedingly uncommon pancreatic islet cell neuroendocrine tumor. The estimated incidence is approximately four cases per million individuals per year and accounts for 60% of islets cell tumors. It causes glycopenic symptoms which includes headache, feeling irritable, confused, seizure or coma and leads to catecholamine excess which includes rapid heartbeat, sweating, palpitations and feelings of hunger. Early detection of the tumor prevents recurrent episodes of lethal hypoglycemia.

  15. Measurements and Simulations on the Mechanisms of Efficiency Losses in HIT Solar Cells

    Directory of Open Access Journals (Sweden)

    Silvio Pierro

    2015-01-01

    Full Text Available We study the electrical and the optical behavior of HIT solar cell by means of measurements and optoelectrical simulations by TCAD simulations. We compare the HIT solar cell with a conventional crystalline silicon solar cell to identify the strengths and weaknesses of the HIT technology. Results highlight different mechanisms of electrical and optical efficiency losses caused by the presence of the amorphous silicon layer. The higher resistivity of the a-Si layers implies a smaller distance between the metal lines that causes a higher shadowing. The worst optical coupling between the amorphous silicon and the antireflective coating implies a slight increase of reflectivity around the 600 nm wavelength.

  16. Insulinoma canino: relato de caso

    Directory of Open Access Journals (Sweden)

    L. Padovani

    Full Text Available RESUMO O insulinoma é um tumor das células β do pâncreas, que têm a função de produzir e secretar insulina e, geralmente são malignos em cães. O presente trabalho descreve o diagnóstico e o manejo terapêutico de três casos de insulinoma. Os sinais clínicos dos animais relatados variaram de acordo com a severidade e a duração da hipoglicemia. O diagnóstico presuntivo se deu através dos sinais clínicos e da dosagem de insulina sérica no momento de mais intensa hipoglicemia e, o diagnóstico definitivo foi obtido por meio de exame histopatológico nos três casos relatados. O tratamento realizado variou de acordo com a intensidade dos sinais clínicos.

  17. Altered MENIN expression disrupts the MAFA differentiation pathway in insulinoma.

    Science.gov (United States)

    Hamze, Z; Vercherat, C; Bernigaud-Lacheretz, A; Bazzi, W; Bonnavion, R; Lu, J; Calender, A; Pouponnot, C; Bertolino, P; Roche, C; Stein, R; Scoazec, J Y; Zhang, C X; Cordier-Bussat, M

    2013-12-01

    The protein MENIN is the product of the multiple endocrine neoplasia type I (MEN1) gene. Altered MENIN expression is one of the few events that are clearly associated with foregut neuroendocrine tumours (NETs), classical oncogenes or tumour suppressors being not involved. One of the current challenges is to understand how alteration of MENIN expression contributes to the development of these tumours. We hypothesised that MENIN might regulate factors maintaining endocrine-differentiated functions. We chose the insulinoma model, a paradigmatic example of well-differentiated pancreatic NETs, to study whether MENIN interferes with the expression of v-MAF musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA), a master glucose-dependent transcription factor in differentiated β-cells. Immunohistochemical analysis of a series of human insulinomas revealed a correlated decrease in both MENIN and MAFA. Decreased MAFA expression resulting from targeted Men1 ablation was also consistently observed in mouse insulinomas. In vitro analyses using insulinoma cell lines showed that MENIN regulated MAFA protein and mRNA levels, and bound to Mafa promoter sequences. MENIN knockdown concomitantly decreased mRNA expression of both Mafa and β-cell differentiation markers (Ins1/2, Gck, Slc2a2 and Pdx1) and, in parallel, increased the proliferation rate of tumours as measured by bromodeoxyuridine incorporation. Interestingly, MAFA knockdown alone also increased proliferation rate but did not affect the expression of candidate proliferation genes regulated by MENIN. Finally, MENIN variants with missense mutations detected in patients with MEN1 lost the WT MENIN properties to regulate MAFA. Together, our findings unveil a previously unsuspected MENIN/MAFA connection regarding control of the β-cell differentiation/proliferation balance, which could contribute to tumorigenesis.

  18. Influence of ITO deposition and post annealing on HIT solar cell structures

    NARCIS (Netherlands)

    Zhang, D.; Tavakoliyaraki, A.; Wu, Y.; Van Swaaij, R.A.C.M.M.; Zeman, M.

    2011-01-01

    Heterojunction silicon with intrinsic thin layer (HIT) solar cells that combine advanced thin-film hydrogenated amorphous silicon (a-Si:H) and crystalline silicon (c-Si) technologies are promising because of the high performance at low cost. Due to the low conductivity of a-Si:H, indium tin oxide

  19. Insulinoma

    Science.gov (United States)

    After fasting, your blood may be tested for: Blood C-peptide level Blood glucose level Blood insulin level Drugs ... to lower insulin production and prevent hypoglycemia. A water pill (diuretic) is given with this medicine to ...

  20. The average number of alpha-particle hits to the cell nucleus required to eradicate a tumour cell population

    International Nuclear Information System (INIS)

    Roeske, John C; Stinchcomb, Thomas G

    2006-01-01

    Alpha-particle emitters are currently being considered for the treatment of micrometastatic disease. Based on in vitro studies, it has been speculated that only a few alpha-particle hits to the cell nucleus are considered lethal. However, such estimates do not consider the stochastic variations in the number of alpha-particle hits, energy deposited, or in the cell survival process itself. Using a tumour control probability (TCP) model for alpha-particle emitters, we derive an estimate of the average number of hits to the cell nucleus required to provide a high probability of eradicating a tumour cell population. In simulation studies, our results demonstrate that the average number of hits required to achieve a 90% TCP for 10 4 clonogenic cells ranges from 18 to 108. Those cells that have large cell nuclei, high radiosensitivities and alpha-particle emissions occurring primarily in the nuclei tended to require more hits. As the clinical implementation of alpha-particle emitters is considered, this type of analysis may be useful in interpreting clinical results and in designing treatment strategies to achieve a favourable therapeutic outcome. (note)

  1. Though active on RINm5F insulinoma cells and cultured pancreatic islets, recombinant IL-22 fails to modulate cytotoxicity and disease in a protocol of streptozotocin-induced experimental diabetes.

    Directory of Open Access Journals (Sweden)

    Anika eBerner

    2016-01-01

    Full Text Available Interleukin (IL-22 is a cytokine displaying tissue protective and pro-regenerative functions in various preclinical disease models. Anti-bacterial, pro-proliferative, and anti-apoptotic properties mediated by activation of the transcription factor signal transducer and activator of transcription (STAT-3 are key to biological functions of this IL-10 family member. Herein, we introduce RINm5F insulinoma cells as rat ß-cell line that, under the influence of IL-22, displays activation of STAT3 with induction of its downstream gene targets Socs3, Bcl3, and Reg3ß. In addition, IL-22 also activates STAT1 in this cell type. To refine those observations, IL-22 biological activity was evaluated using ex vivo cultivated murine pancreatic islets. In accord with data on RINm5F cells, islet exposure to IL-22 activated STAT3 and upregulation of STAT3-inducible Socs3, Bcl3, and STEAP4 was evident under those conditions. As these observations supported the hypothesis that IL-22 may exert protective functions in toxic ß-cell injury, application of IL-22 was investigated in murine multiple-low-dose streptozotocin (STZ-induced diabetes. For that purpose, recombinant IL-22 was administered thrice either immediately before and at disease onset (at d4, d6, d8 or closely thereafter (at d8, d10, d12. These two IL-22-treatment periods coincide with two early peaks of ß-cell injury detectable in this model. Notably, none of the two IL-22-treatment strategies affected diabetes incidence or blood glucose levels in STZ-treated mice. Moreover, pathological changes in islet morphology analyzed 28 days after disease induction were not ameliorated by IL-22 administration. Taken together, despite being active on rat RINm5F insulinoma cells and murine pancreatic islets, recombinant IL-22 fails to protect pancreatic ß-cells in the tested protocols from toxic effects of STZ and thus is unable to ameliorate disease in the widely used model of STZ-induced diabetes.

  2. Concurrent inhibition of MYC and BCL2 is a potentially effective treatment strategy for double hit and triple hit B-cell lymphomas.

    Science.gov (United States)

    Cinar, Munevver; Rosenfelt, Fred; Rokhsar, Sepehr; Lopategui, Jean; Pillai, Raju; Cervania, Melissa; Pao, Andy; Cinar, Bekir; Alkan, Serhan

    2015-07-01

    Double hit lymphoma or triple hit lymphoma (DHL/THL) is a rare form of aggressive B-Cell Lymphoma. Overexpression of MYC, BCL2 or/and BCL6 due to genomic rearrangements are the key molecular features of DHL/THL. Patients with DHL/THL show very aggressive disease course and poor survival due to the lack of effective treatment modalities. Here, we established new THL cell model and assessed its in vitro growth characteristics along with the DHL cell line in response to potent MYC inhibitors, 10058-F4 and JQ-1, and a BCL2 inhibitor, ABT-199, with or without chemotherapeutic agent vincristine or doxorubicin. We found that 10058-F4, JQ-1 or ABT-199 exposure as a single agent inhibited the growth of DHL/THL cells in a dose-dependent manner. Combined exposure of 10058-F4 or JQ-1 and ABT-199 as well as vincristine or doxorubicin markedly suppressed the growth of DHL/THL cells compared with the single treatment. As assessed by multiple approaches, apoptosis induced by ABT-199, 10058-F4 or JQ-1 was underlying cause of the observed growth suppression. These findings suggest that co-inhibition of MYC and BCL2 signaling is a promising therapeutic strategy for patients with DHL/THL lymphomas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A hit and run approach to inducible direct reprogramming of astrocytes to neural stem cells

    Directory of Open Access Journals (Sweden)

    Maria ePoulou

    2016-04-01

    Full Text Available Temporal and spatial control of gene expression can be achieved using an inducible system as a fundamental tool for regulated transcription in basic, applied and eventually in clinical research. We describe a novel hit and run inducible direct reprogramming approach. In a single step, two days post-transfection, transiently transfected Sox2FLAG under the Leu3p-αIPM inducible control (iSox2 triggers the activation of endogenous Sox2, redirecting primary astrocytes into abundant distinct nestin-positive radial glia cells. This technique introduces a unique novel tool for safe, rapid and efficient reprogramming amendable to regenerative medicine.

  4. Experiencia clínica sobre 37 casos de insulinoma Clinical experience in 37 cases of insulinoma

    Directory of Open Access Journals (Sweden)

    Adriana G. Diaz

    2006-12-01

    Full Text Available El insulinoma es el tumor neuroendocrino pancreático más frecuente. Se manifiesta por signos adrenérgicos y de neuroglucopenia. Su diagnóstico se confirma documentando la existencia de hipoglucemia junto a una inapropiada secreción de insulina. Desde 1988 fueron estudiados 23 mujeres (48 ± 18 años y 14 varones (45 ± 19 años con diagnóstico de insulinoma. La evolución de la enfermedad hasta el diagnóstico fue de 2.8 ± 2.1 años. Veintisiete pacientes (73% presentaron principalmente síntomas de neuroglucopenia, y el 27% refirió síntomas adrenérgicos. El laboratorio mostró glucemia en ayunas 32.4 ± 8.7 mg/dl, insulina (RIA 38.2 ± 39.7 µU/ml (n=11, insulina (quimioluminiscencia 23.8 ± 18.1 µU/ml (n=26, péptido C 1.15 ± 1.6 nmol/l (n=14. El test de ayuno prolongado fue diagnóstico a las 9.0 ± 5.2 horas (n=21. La localización preoperatoria fue posible en el 73% por imágenes, arteriografía con estimulación de calcio y/o ecografía intraoperatoria. Once casos fueron operados por laparoscopia, y el resto por vía convencional. El diagnóstico fue confirmado por histología e inmunohistoquímica. Veintidos pacientes (61.1% presentaron insulinomas únicos (16 en cuerpo y cola, 6 en la cabeza y proceso uncinado, 6 eran portadores de insulinomas múltiples, 5 de insulinomas malignos, 1 de nesidioblastosis del adulto y en 2 casos los hallazgos fueron incaracterísticos. En 3 pacientes se halló un glucagonoma asociado (1 de ellos con NEM1. Una paciente no fue operada recibiendo tratamiento con verapamilo, con buena respuesta clínica. El seguimiento postquirúrgico fue de 60.4 ± 59.9 meses.Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis is established through demonstration of inappropriately elevated insulin serum concentrations in the presence of hypoglycemia. The aim of this study is to show our experience in the management of

  5. Tumor thrombus formation in two dogs with insulinomas.

    Science.gov (United States)

    Hambrook, Lydia E; Kudnig, Simon T

    2012-10-15

    A 9-year-old sexually intact male Staffordshire Bull Terrier and a 9-year-old neutered male Boxer were evaluated for intermittent neurologic signs including muscle tremors, ataxia, episodic collapse, disorientation, and seizures. Both dogs had low blood glucose and high serum insulin concentrations. Results of abdominal ultrasonography were unremarkable for both dogs. Exploratory laparotomy revealed a mass that extended from the body of the pancreas into the pancreaticoduodenal vein in each dog. Marginal resection of pancreatic masses was performed, and tumor thrombi were removed via venotomy in both dogs. Histologic evaluation indicated the masses were pancreatic islet cell tumors with tumor thrombi. Clinical signs resolved following surgical resection of tumors and tumor thrombi, and the dogs were euglycemic during the follow-up period (17 and 45 months after surgery). Although gross tumor thrombus formation has been identified in humans with insulinomas, tumor thrombi have not been previously reported for dogs with insulinomas. Surgical removal of tumor thrombi via venotomy seemed to be well tolerated by the dogs. Tumor thrombus formation did not seem to adversely affect prognosis for the 2 dogs of this report.

  6. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

    Science.gov (United States)

    Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

    2015-07-01

    A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

  7. Insulinoma-Induced Hypoglycemia in a Patient with Insulinoma after Gastrojejunostomy for Prepyloric Ulcer

    Directory of Open Access Journals (Sweden)

    Yavuz Savas Koca

    2015-01-01

    Full Text Available Hyperinsulinism due to dumping syndrome following gastric surgery is an uncommon condition. It is specified with hypoglycemic attacks. However, linking symptoms to dumping syndrome in each patient to whom gastric surgery was performed leads to inappropriate diagnosis and therapy. Insulinoma and other causes that give rise to hyperinsulinemia should not be ignored and these diagnoses should be excluded. In this paper, 71-year-old male patient who was followed up for 2 years with a false conclusion of dumping syndrome and operated on due to insulinoma diagnosed at endoscopic ultrasonography is presented in the light of the literature.

  8. Development of the IFJ single ion hit facility for cells irradiation

    International Nuclear Information System (INIS)

    Veselov, O.; Polak, W.; Ugenskiene, R.; Hajduk, R.; Lebed, K.; Lekki, J.; Horwacik, T.; Dutkiewicz, E.M.; Maranda, S.; Pieprzyca, T.; Sarnecki, C.; Stachura, Z.; Szklarz, Z.; Styczen, J.

    2005-12-01

    In recent years a single ion hit facility (SIHF) has been constructed at the IFJ ion microprobe. The setup is used for the precise irradiations of living cells by a controlled number of ions. The facility allows investigations in various aspects of biomedical research, such as adaptive response, bystander effect, inverse dose-rate effect, low-dose hypersensitivity, etc. Those investigations have two very important requirements: (i) cells must be examined in their natural state and environment, i.e. without previously being killed, and preferentially, neither fixed nor stained, and (ii) a possibility of automatic irradiation of large number of cells with a computer recognition of their positions must be provided. This work presents some of the crucial features of the off-line and on-line optical systems, including self-developed software responsible for the automatic cell recognition. We also show several tests carried out to determine the efficiency of the whole setup and some segments. In conclusion, the results of our first irradiation measurements performed with living cells are demonstrated. (author)

  9. Hit Parade

    DEFF Research Database (Denmark)

    Backe, Hans-Joachim

    2017-01-01

    Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2017, ITU, Copenhagen, DK, Oct 13, 2017.......Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2017, ITU, Copenhagen, DK, Oct 13, 2017....

  10. Hit Parade

    DEFF Research Database (Denmark)

    Cermak, Daniel; Wrighton, Max Alexander; Backe, Hans-Joachim

    2016-01-01

    Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Demo Night, ITU, Copenhagen, DK, Oct 5, 2016.......Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Demo Night, ITU, Copenhagen, DK, Oct 5, 2016....

  11. Hit Parade

    DEFF Research Database (Denmark)

    Cermak, Daniel; Wrighton, Max Alexander; Backe, Hans-Joachim

    2016-01-01

    Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2016, Danish Science Ministry, Copenhagen, DK, Oct 14, 2016.......Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2016, Danish Science Ministry, Copenhagen, DK, Oct 14, 2016....

  12. An unusual case of concurrent insulinoma and nesidioblastosis.

    Science.gov (United States)

    Bright, Elizabeth; Garcea, Giuseppe; Ong, Seok L; Madira, Webster; Berry, David P; Dennison, Ashley R

    2008-09-02

    Endogenous hyperinsulinaemic hypoglycaemia in adults is most commonly caused by an insulinoma. Adult nesidioblastosis is rarely reported. To the best of our knowledge the presence of both insulinoma and nesidioblastosis has not been reported before. We report a case of a 35-year-old female presenting with neuroglycaemic symptoms. A supervised 72-hour fast confirmed hypoglycaemia in the presence of hyperinsulinaemia. Thorough pre-operative biochemical and radiological investigations, including selective splenic, superior mesenteric and portal venous sampling inferred a tentative diagnosis of adult nesidioblastosis. However, a grossly elevated insulin level within the splenic vein on a second set of venous sampling produced a high index of suspicion for the presence of an insulinoma. At surgical exploration both an insulinoma and nesidioblastosis were identified and confirmed by histological examination. We report an even rarer entity of concurrent insulinoma and nesidioblastosis.

  13. Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo).

    Science.gov (United States)

    Chen, Sue

    2010-09-01

    Endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. Insulinoma is a tumor that produces and releases excessive amounts of insulin. Evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment options for insulinomas. Adrenocortical neoplasia in ferrets usually overproduces one or more sex hormones. Sex hormones which can result in progressive alopecia, vulvar swelling in females, and prostagomegaly in males. Abdominal ultrasonography and sex hormone assays can be used to diagnose adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate, and the hormone melatonin can be used to treat adrenocortical neoplasms in ferrets when surgery is not an option. Copyright 2010 Elsevier Inc. All rights reserved.

  14. Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

    Science.gov (United States)

    Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

    2012-11-01

    The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

  15. Road Accident due to a Pancreatic Insulinoma

    Science.gov (United States)

    Parisi, Amilcare; Desiderio, Jacopo; Cirocchi, Roberto; Grassi, Veronica; Trastulli, Stefano; Barberini, Francesco; Corsi, Alessia; Cacurri, Alban; Renzi, Claudio; Anastasio, Fabio; Battista, Francesca; Pucci, Giacomo; Noya, Giuseppe; Schillaci, Giuseppe

    2015-01-01

    Abstract Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays. PMID:25816027

  16. Dirty Hits

    OpenAIRE

    Clarke, Louise

    2010-01-01

    Issue 9 of the Saatchi Gallery Magazine: Art&Music is dedicated to Sex. The article Dirty Hits invited a cross-section of contemporary artists and musicians to answer: What makes a dirty hit? As one of the artists invited, I wrote an autobiographical piece to reveal how these fumbling, feral sexual experiences of my childhood landscape, along with irrational superstition and folk law inform my life and underpin my work. The article also included an artwork: Louise Clarke, Sip (2009)

  17. Intra-arterial digital subtraction angiography in the diagnosis of insulinomas

    International Nuclear Information System (INIS)

    Moulopoulou, A.; Vlahos, L.

    1988-01-01

    Two cases of surgically proved benign insulinoma of the pancreas were correctly localized with intra-arterial digital subtraction angiography (IA-DSA) of the coeliac and the superior mesenteric artery, while the respective dynamic computed tomography (CT) and ultrasound (US) examinations were negative. In a third case of organic hyperinsulinism, IA-DSA, CT and US suggested a pancreatic islet-cell tumor, but the histological examination of the resected suspicious area was that of focal hyperplasia. 17 refs.; 3 figs

  18. [Double localization of pancreatic insulinoma. Diagnostic and therapeutic difficulties].

    Science.gov (United States)

    Ungureanu, C D; David, L; Braşoveanu, V; Herlea, V; Coculescu, M; Popescu, I

    2005-01-01

    Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Because most of insulinomas are less than 2 cm in size and rarely they not may be visible by CT scan or transabdominal ultrasonography. Intraoperative ultrasonography may be a solution. Although as surgical method is preferred enucleation because operative time is shorter and easier and the low frequency postoperative complications, pancreaticoduodenectomy Whipple is indicated in selected cases. We report a case of double insulinoma located in the head of the pancreas in which the diagnosis and surgical treatment presented difficulties which determined a particular clinical evolution.

  19. Islet Cell Tumors of the Pancreas: A Variety of Multiphase Dynamic Imaging Findings with Pathologic Correlations Focusing on Nonfunctioning Tumors and Insulinomas

    International Nuclear Information System (INIS)

    Hong, Yoo Jin; Yu, Jeong Sik; Park, Chan Il; Kwon, Ji Eun; Chung, Jae Joon; Kim, Joo Hee; Kim, Ki Whang

    2010-01-01

    Islet cell tumors (ICTs) are rare pancreatic neoplasms of neuroendocrine origin, posing a diagnostic challenge to radiologists. We illustrated a spectrum of features of pancreatic ICTs that could be found on multiphase dynamic CT or MRI, and elucidated the histopathologic characteristics by determining the contrast enhancement pattern of the lesions. Various enhancement patterns were dependant on the internal composition of the tumor, that is, the proportion of vascular densities for early enhancement and non-hypervascular interstitial tissue for late enhancement regardless of the size or functional behavior. This knowledge of the imaging-pathologic spectrum of ICTs could be helpful for the proper differential diagnosis from other pancreatic tumors

  20. Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas.

    Science.gov (United States)

    Menguy, Sarah; Frison, Eric; Prochazkova-Carlotti, Martina; Dalle, Stephane; Dereure, Olivier; Boulinguez, Serge; Dalac, Sophie; Machet, Laurent; Ram-Wolff, Caroline; Verneuil, Laurence; Gros, Audrey; Vergier, Béatrice; Beylot-Barry, Marie; Merlio, Jean-Philippe; Pham-Ledard, Anne

    2018-03-26

    In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with

  1. Particular aspects of a pancreatic insulinoma case

    Directory of Open Access Journals (Sweden)

    Motoc R

    2016-06-01

    Full Text Available With a very low incidence (1-4 cases per 1 million per year, characterized by insulin hypersecretion, independent of the glycemia control system, insulinoma is a rare endocrine tumor, clinical with accentuated neuropsychological symptoms that hampers clinical diagnosis. We present a case of a 33 years old patient with no notable personal history, active lifestyle, non-smoker, a work environment that doesn’t involve professional toxicity; a remarkable family history of a brother with type 1 diabetes mellitus and grandmother with liver adenocarcinoma was noticed; in this particular case Whipple triad was strongly suggestive, gastrointestinal upper-ultrasonography endoscopy with tissue puncture as a tumor diagnostic tool was used and laparotomy was used successfully for removing the tumor, with favorable follow-up.

  2. The distribution of alpha hits per target cell: a parameter to improve risk assessment after inhalation exposure to actinide oxides

    International Nuclear Information System (INIS)

    Fritsch, P.

    2006-01-01

    After inhalation exposure to radionuclides, according to ICRP recommendations, the equivalent dose delivered to the different target regions of the respiratory tract corresponds to a mean value. Some actinide oxides have a very high specific activity, so that, the Annual Limit of Intake (A.L.I.) can be reached when only a few particles have been deposited. In this case, because of the short range of α radiation, only a small fraction of the tissues is irradiated, due to the presence of hot spots. Recently, animal studies have shown that, in the rat, for the same a dose delivered to the lungs, the risk for lung tumour induction varies over more than 1 order of magnitude, depending on the number of deposited particles. The aim of this work is to identify a parameter which could take into account heterogeneity of dose distribution for a realistic risk assessment from the result of a standard dose calculation. In vitro experiments have shown that, the risk for pre-neoplastic transformation per unit of dose gradually decreases when more than 1 α hit is received per target cell. This could be explained by a gradual increase of the ratio of cell death versus cell transformation. Thus, the distribution of the number of α hits per cell could be a useful parameter to improve dose calculation for a risk assessment purpose. The α hit distribution has been characterized in basal cells of the extra thoracic and bronchial epithelia irradiated from the sequestered regions (E.T. seq and B.B. seq ) after exposure inhalation to 1 A.L.I. of 238 U or 238-239 Pu oxide aerosols. Default parameters were used for calculation (aerosol size 5 μm, type S compounds, standard workers). In a first step, the number of particles deposited in the source regions and their activity was obtained after simulations which corresponded to a stochastic application of the ICRP 66 deposition model (the behaviour of each particle was taken into account, and for each particle size, the fraction deposited

  3. PDX-1 Is a Therapeutic Target for Pancreatic Cancer, Insulinoma and Islet Neoplasia Using a Novel RNA Interference Platform

    Science.gov (United States)

    Liu, Shi-He; Rao, Donald D.; Nemunaitis, John; Senzer, Neil; Zhou, Guisheng; Dawson, David; Gingras, Marie-Claude; Wang, Zhaohui; Gibbs, Richard; Norman, Michael; Templeton, Nancy S.; DeMayo, Francesco J.; O'Malley, Bert; Sanchez, Robbi; Fisher, William E.; Brunicardi, F. Charles

    2012-01-01

    Pancreatic and duodenal homeobox-1 (PDX-1) is a transcription factor that regulates insulin expression and islet maintenance in the adult pancreas. Our recent studies demonstrate that PDX-1 is an oncogene for pancreatic cancer and is overexpressed in pancreatic cancer. The purpose of this study was to demonstrate that PDX-1 is a therapeutic target for both hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Immunohistochemistry of human pancreatic and islet neoplasia specimens revealed marked PDX-1 overexpression, suggesting PDX-1 as a “drugable” target within these diseases. To do so, a novel RNA interference effector platform, bifunctional shRNAPDX-1, was developed and studied in mouse and human cell lines as well as in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Systemic delivery of bi-shRNAhumanPDX-1 lipoplexes resulted in marked reduction of tumor volume and improved survival in a human pancreatic cancer xenograft mouse model. bi-shRNAmousePDX-1 lipoplexes prevented death from hyperinsulinemia and hypoglycemia in an insulinoma mouse model. shRNAmousePDX-1 lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of islet neoplasia. PDX-1 was overexpressed in pancreatic neuroendocrine tumors and nesidioblastosis. These data demonstrate that PDX-1 RNAi therapy controls hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia, therefore, PDX-1 is a potential therapeutic target for these pancreatic diseases. PMID:22905092

  4. Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas.

    Science.gov (United States)

    He, Miaoxia; Chen, Keting; Li, Suhong; Zhang, Shimin; Zheng, Jianming; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin

    2016-01-01

    Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better

  5. Characterisation of a pre-cell hit detector to be used in single cell irradiation experiments at the Lund Nuclear Microprobe

    International Nuclear Information System (INIS)

    Nilsson, Charlotta; Pallon, Jan; Thungstroem, Goeran; Marrero, Natalia Arteaga; Elfman, Mikael; Kristiansson, Per; Nilsson, Christer; Wegden, Marie

    2008-01-01

    This paper describes the characterisation of an ultra-thin silicon semiconductor ΔE detector to be used as a pre-cell ion hit detector in single ion experiments on individual, living cells. The characteristics of interest for this specific application are the hit detection efficiency, which has to be close to 100% to enable bombardment with either a single ion or a counted number of ions, the beam spreading, which should be as small as possible to maintain the targeting accuracy, and the vacuum tightness, since the detector is intended, if possible, to be used simultaneously as vacuum window. The hit detection efficiency was shown to be above 99% when detecting alpha particles or 2 MeV protons, the increase in beam size was about 1 μm and the vacuum tightness was comparable to that of the Si 3 N 4 wafer which is normally used as vacuum window, thus the ΔE detector fulfils the main criteria to function properly as a single ion hit detector.

  6. Concurrent insulinoma with mosaic Turner syndrome: A case report.

    Science.gov (United States)

    Wang, Shaoyun; Yang, Lijuan; Li, Jie; Mu, Yiming

    2015-03-01

    Turner syndrome is a chromosomal abnormality in which the majority of patients have a 45XO karyotype, while a small number have a 45XO/47XXX karyotype. Congenital adrenal hyperplasia has been previously reported in patients with Turner syndrome. Although insulinomas are the most common type of functioning pancreatic neuroendocrine tumor and have been reported in patients with multiple endocrine neoplasias, the tumors have not been reported in patients with mosaic Turner syndrome. The present study reports the first case of an insulinoma in a patient with 45XO/47XXX mosaic Turner syndrome. The patient suffered from recurrent hypoglycemia, which was relieved following ingestion of glucose or food. A 5-h glucose tolerance test was performed and the levels of glucose, C-Peptide and insulin were detected. In addition, computed tomography (CT) and ultrasound scanning were performed to evaluate the possibility of an insulinoma. Pathological examination and karyotyping were performed on a surgical specimen and a whole blood sample, respectively. The patient was found to suffer from premature ovarian failure, and a physical examination was consistent with a diagnosis of Turner syndrome. An ultrasound scan demonstrated streak ovaries and the patient was found to have a 45XO/47XXX karyotype. Furthermore, a lesion was detected in the pancreas following CT scanning, which was identified as an insulinoma following surgical removal and histological examination. In conclusion, the present study reports the first case of an insulinoma in a patient with mosaic Turner syndrome. Since mosaic Turner syndrome and insulinoma are rare diseases, an association may exist that has not been previously identified.

  7. Laparoscopic surgery for solitary insulinoma in the absence of IOUS

    Directory of Open Access Journals (Sweden)

    Abhay Narendra Dalvi

    2018-01-01

    Full Text Available Background: Insulinomas are the most common pancreatic neuroendocrine neoplasms. In spite of adequate pre-operative localisation, conventional surgical methods rely on intraoperative palpation. Intraoperative ultrasonography (IOUS is said to aid in accurate localisation, decreases morbidity. Laparoscopic removal of pancreatic endocrine neoplasms is beneficial due to magnification and minimal invasion; however, in the absence of IOUS, error of judgement may lead to conversion to open surgery, thereby relying on 'palpation method' to localise the tumour. We combined laparoscopic surgical removal of insulinomas using an innovative method of 'laparoscopic finger palpation' with intraoperative blood glucose monitoring and frozen section for surgical cure. Materials and Methods: Patients were evaluated and investigated by the department of endocrinology and referred for surgical management of insulinoma. Pre-operative localisation of insulinoma was done by either contrast-enhanced computerised tomography angiogram – arterial and venous phase, or endoscopic ultrasound (EUS or DOTATATE scan. Intraoperative localisation was done by laparoscopic dissection and 'laparoscopic finger palpation'. After enucleation, the specimen was sent for frozen section, and in the interim period, serial monitoring of blood glucose was done by the anaesthetist. Maintenance of glucose levels for more than 45 min after enucleation and confirmation of neuroendocrine tumour on frozen section was the end point of surgical procedure. Results: A total of 19 patients were subjected to laparoscopic removal of solitary insulinomas. Enucleation was performed in 16 patients successfully. In three patients, laparoscopic distal pancreatectomy was performed. Three patients had pancreatic duct leak, of which two patients responded to conservative approach and the third patient required drainage by USG-guided pigtail catheter. All patients are cured of their disease and no patient has had

  8. Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel

    Directory of Open Access Journals (Sweden)

    Ralph A. Pietrofesa

    2016-06-01

    Full Text Available Spaceflight occasionally requires multiple extravehicular activities (EVA that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10 were exposed to >95% O2 for 8 h only (O2, 0.25 Gy ionizing γ-radiation (IR only, or a double-hit combination of both challenges (O2 + IR followed by 16 h of normoxia (ambient air containing 21% O2 and 5% CO2 (1 cycle = 24 h, 2 cycles = 48 h. Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05 decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP, apoptotic (cleaved caspase-3 and BAX, and antioxidant (HO-1 and Nqo1 proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O2 + IR exacerbated cell death and DNA damage compared to individual exposures O2 or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia

  9. Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

    Science.gov (United States)

    Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

    2014-04-01

    Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

  10. Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward streptozotocin-treated mice and HIT-T15 pancreatic β cells.

    Science.gov (United States)

    Joo, Hye-Eun; Lee, Hyo-Jung; Sohn, Eun Jung; Lee, Min-Ho; Ko, Hyun-Suk; Jeong, Soo-Jin; Lee, Hyo-Jeong; Kim, Sung-Hoon

    2013-01-01

    The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

  11. Double-hit BCL2/MYC translocations in a consecutive cohort of patients with large B-cell lymphoma - a single centre's experience

    DEFF Research Database (Denmark)

    Pedersen, Mette Ø; Gang, Anne O; Poulsen, Tim S

    2012-01-01

    Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence and correlat......Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence...

  12. Studies of insulin secretory responses and of arachidonic acid incorporation into phospholipids of stably transfected insulinoma cells that overexpress group VIA phospholipase A2 (iPLA2beta ) indicate a signaling rather than a housekeeping role for iPLA2beta.

    Science.gov (United States)

    Ma, Z; Ramanadham, S; Wohltmann, M; Bohrer, A; Hsu, F F; Turk, J

    2001-04-20

    A cytosolic 84-kDa group VIA phospholipase A(2) (iPLA(2)beta) that does not require Ca(2+) for catalysis has been cloned from several sources, including rat and human pancreatic islet beta-cells and murine P388D1 cells. Many potential iPLA(2)beta functions have been proposed, including a signaling role in beta-cell insulin secretion and a role in generating lysophosphatidylcholine acceptors for arachidonic acid incorporation into P388D1 cell phosphatidylcholine (PC). Proposals for iPLA(2)beta function rest in part on effects of inhibiting iPLA(2)beta activity with a bromoenol lactone (BEL) suicide substrate, but BEL also inhibits phosphatidate phosphohydrolase-1 and a group VIB phospholipase A(2). Manipulation of iPLA(2)beta expression by molecular biologic means is an alternative approach to study iPLA(2)beta functions, and we have used a retroviral construct containing iPLA(2)beta cDNA to prepare two INS-1 insulinoma cell clonal lines that stably overexpress iPLA(2)beta. Compared with parental INS-1 cells or cells transfected with empty vector, both iPLA(2)beta-overexpressing lines exhibit amplified insulin secretory responses to glucose and cAMP-elevating agents, and BEL substantially attenuates stimulated secretion. Electrospray ionization mass spectrometric analyses of arachidonic acid incorporation into INS-1 cell PC indicate that neither overexpression nor inhibition of iPLA(2)beta affects the rate or extent of this process in INS-1 cells. Immunocytofluorescence studies with antibodies directed against iPLA(2)beta indicate that cAMP-elevating agents increase perinuclear fluorescence in INS-1 cells, suggesting that iPLA(2)beta associates with nuclei. These studies are more consistent with a signaling than with a housekeeping role for iPLA(2)beta in insulin-secreting beta-cells.

  13. Rising Intracellular Zinc by Membrane Depolarization and Glucose in Insulin-Secreting Clonal HIT-T15 Beta Cells

    Directory of Open Access Journals (Sweden)

    Kira G. Slepchenko

    2012-01-01

    Full Text Available Zinc (Zn2+ appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30–60 mM was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

  14. Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.

    Science.gov (United States)

    Slepchenko, Kira G; Li, Yang V

    2012-01-01

    Zinc (Zn(2+)) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30-60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

  15. How to Hit Mesenchymal Stromal Cells and Make the Tumor Microenvironment Immunostimulant Rather Than Immunosuppressive

    Directory of Open Access Journals (Sweden)

    Alessandro Poggi

    2018-02-01

    Full Text Available Experimental evidence indicates that mesenchymal stromal cells (MSCs may regulate tumor microenvironment (TME. It is conceivable that the interaction with MSC can influence neoplastic cell functional behavior, remodeling TME and generating a tumor cell niche that supports tissue neovascularization, tumor invasion and metastasization. In addition, MSC can release transforming growth factor-beta that is involved in the epithelial–mesenchymal transition of carcinoma cells; this transition is essential to give rise to aggressive tumor cells and favor cancer progression. Also, MSC can both affect the anti-tumor immune response and limit drug availability surrounding tumor cells, thus creating a sort of barrier. This mechanism, in principle, should limit tumor expansion but, on the contrary, often leads to the impairment of the immune system-mediated recognition of tumor cells. Furthermore, the cross-talk between MSC and anti-tumor lymphocytes of the innate and adaptive arms of the immune system strongly drives TME to become immunosuppressive. Indeed, MSC can trigger the generation of several types of regulatory cells which block immune response and eventually impair the elimination of tumor cells. Based on these considerations, it should be possible to favor the anti-tumor immune response acting on TME. First, we will review the molecular mechanisms involved in MSC-mediated regulation of immune response. Second, we will focus on the experimental data supporting that it is possible to convert TME from immunosuppressive to immunostimulant, specifically targeting MSC.

  16. Road accident due to a pancreatic insulinoma: a case report.

    Science.gov (United States)

    Parisi, Amilcare; Desiderio, Jacopo; Cirocchi, Roberto; Grassi, Veronica; Trastulli, Stefano; Barberini, Francesco; Corsi, Alessia; Cacurri, Alban; Renzi, Claudio; Anastasio, Fabio; Battista, Francesca; Pucci, Giacomo; Noya, Giuseppe; Schillaci, Giuseppe

    2015-03-01

    Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays.

  17. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    Science.gov (United States)

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qHIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

  18. Exploration of 'over kill effect' of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death

    International Nuclear Information System (INIS)

    Mehnati, P.; Sasaki, Hiroshi; Morimoto, Shigeko; Yatagai, Fumio; Hanaoka, Fumio; Furusawa, Yoshiya; Kanai, Tatsuaki; Kobayashi, Yasuhiko; Wada, Seiichi

    2005-01-01

    The reason why relative biological effectiveness (RBE) for cell killing fell to less than unity (1.0) with very high-linear energy transfer (LET) heavy-ions ( 40 Ar: 1,640 keV/μm; 56 Fe: 780, 1,200, 2,000 keV/μm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). Chinese hamster ovary (CHO) cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/μm) or Fe-ions (2,000 keV/μm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/μm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/μm) was not particularly high (-15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/μm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by 'cellular over kill effect'. Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (σ[R]) began to increase when LET exceeded 100 keV/μm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/μm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and σ[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage

  19. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    International Nuclear Information System (INIS)

    Puddu, A.; Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L.

    2010-01-01

    Research highlights: → GLP-1 prevents AGEs-induced cell death. → GLP-1 prevents AGEs-induced oxidative stress. → GLP-1 ameliorated AGEs-induced cell dysfunction. → GLP-1 attenuates AGEs-induced RAGE increment. → GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  20. Embolization of an Insulinoma of the Pancreas with Trisacryl Gelatin Microspheres as Definitive Treatment

    International Nuclear Information System (INIS)

    Rott, Gernot; Biggemann, Martin; Pfohl, Martin

    2008-01-01

    Insulinomas are rare, mostly benign neuroendocrine tumors, originating in 99% of cases from the pancreas, that synthesize and secrete insulin, causing symptomatic hypoglycemia. Today the treatment of choice is surgical removal. We present the case of an 84-year-old woman with a symptomatic insulinoma who refused surgery and was treated with arterial embolization using trisacryl gelatin microspheres as definitive treatment

  1. 高效HIT太阳电池组件及其应用%High Efficiency HIT Solar Cell Assembly And Its Application

    Institute of Scientific and Technical Information of China (English)

    李正平; 沈文忠

    2015-01-01

    介绍带本征薄层的非晶硅/晶体硅异质结太阳电池(HIT)的结构特点。与常规晶体硅太阳电池组件相比,HIT太阳电池组件的单位面积发电量更高、高温时能发更多的电、制成双面组件能够利用反射光,发电量进一步提升。因此HIT太阳电池组件特别适合于分布式光伏电站。%This paper introduces intrinsic thin layer structural characteristics of amorphous silicon / crystal silicon heterojunction solar cell (HIT). Compared with the conventional components of crystalline silicon solar cells, HIT solar battery assembly has more high capacity per unit area, can generate more electricity at high temperature. When it is made of double component, it can use the reflected light to further improve power generation capacity. Therefore HIT solar cell components especially are suitable for distributed photovoltaic power station.

  2. Insulinoma in a black South African : a case report

    International Nuclear Information System (INIS)

    Huddle, K.R.L.; Mannell, A.; Hale, M.J.; Denath, F.M.

    1990-01-01

    A 69-year-old black woman with an insulinoma presented with recurrent episodes of sweating and confusion culminating in two episodes of hypoglycaemic coma. The diagnosis was confirmed by finding an inappropriately elevated serum insulin level in the presence of hypoglycaemia after a fast of 14 hours. Computed tomography revealed a large tumour in the head of the pancreas. Removal of the tumour necessitated partial resection of the head and body of the pancreas, which in turn necessitated certain repair and drainage procedures. Postoperative complications, while not insignificant, were acceptable. At 1-year follow-up the patient is well. 4 figs., 4 refs

  3. Severe deterioration of psoriasis due to an insulinoma.

    LENUS (Irish Health Repository)

    Field, S

    2008-03-01

    We report a case of a 56-year-old woman who presented with a severe exacerbation of psoriasis with concurrent hypoglycaemic episodes. Methotrexate 17.5 mg weekly was required to control her psoriasis. Investigation of her hypoglycaemia showed raised levels of insulin, C-peptide and proinsulin. Radiological investigation showed a tumour at the tail of the pancreas and the diagnosis was insulinoma. A spleen-preserving distal pancreatectomy was performed and the hypoglycaemic symptoms resolved. Immediately following the pancreatectomy, methotrexate was stopped and the patient\\'s psoriasis went into remission. During a 2-year follow-up, she has required only minimal topical treatment for her skin.

  4. Recurrent insulinoma in a 10-year-old boy with Down’s syndrome

    Directory of Open Access Journals (Sweden)

    Noman Ahmad

    2017-05-01

    Full Text Available An insulinoma is a rare tumour with an incidence of four cases per million per year in adults. The incidence in children is not established. There is limited literature available in children with insulinoma, and only one case is reported in association with Down’s syndrome in adults. Insulinoma diagnosis is frequently missed in adults as well as in children. The Whipple triad is the most striking feature although it has limited application in young children. Hypoglycaemia with elevated insulin, C-peptide and absent ketones is highly suggestive of hyperinsulinism. We present a case of 10-year-old boy with Down’s syndrome with recurrent insulinoma. He was initially misdiagnosed as having an adrenal insufficiency and developed cushingoid features and obesity secondary to hydrocortisone treatment and excessive sugar intake. The tumour was successfully localised in the head of the pancreas with an MRI and octreotide scan on first presentation. Medical treatment with diazoxide and octreotide could not achieve normal blood glucose levels. The insulinoma was laparoscopically enucleated and pathological examination confirmed a neuroendocrine tumour. Subsequently, he had complete resolution of symptoms. He had a recurrence after 2 years with frequent episodes of hypoglycaemia. The biochemical workup was suggestive of hyperinsulinism. MRI and PET scan confirmed the recurrence at the same site (head of the pancreas. He had an open laparotomy for insulinoma resection. The pathology was consistent with benign insulinoma, and subsequently, he had complete resolution of symptoms.

  5. A fast online hit verification method for the single ion hit system at GSI

    International Nuclear Information System (INIS)

    Du, G.; Fischer, B.; Barberet, P.; Heiss, M.

    2006-01-01

    For a single ion hit facility built to irradiate specific targets inside biological cells, it is necessary to prove that the ions hit the selected targets reliably because the ion hits usually cannot be seen. That ability is traditionally tested either indirectly by aiming at pre-etched tracks in a nuclear track detector or directly by making the ion tracks inside cells visible using a stain coupled to special proteins produced in response to ion hits. However, both methods are time consuming and hits can be verified only after the experiment. This means that targeting errors in the experiment cannot be corrected during the experiment. Therefore, we have developed a fast online hit verification method that measures the targeting accuracy electronically with a spatial resolution of ±1 μm before cell irradiation takes place. (authors)

  6. [Insulinoma of the pancreas: analysis of a clinical series of 30 cases].

    Science.gov (United States)

    Andronesi, D; Andronesi, A; Tonea, A; Andrei, S; Herlea, V; Lupescu, I; Ionescu-Târgovişte, C; Coculescu, M; Fica, S; Ionescu, M; Gheorghe, C; Popescu, I

    2009-01-01

    Insulinoma is the most frequent neuroendocrine pancreatic tumor and is the main cause for hypoglicemia due to endogenous hyperinsulinism. We performed an analysis of a clinical series in order to study the clinical and biological spectrum of presentation, the preoperatory imagistic diagnosis and results of the surgical approach. Between 1986-2009, 30 patients with symptoms suggesting an insulinoma were hospitalized in our department. Preoperatory localization of insulinomas was possible in 16 patients. The most sensitive imagistic methods were ecoendoscopy and magnetic resonance. Intraoperatory ultrasound was performed in 16 patients and its sensitivity in detection of insulinomas was 93%; the combination between intraoperative ultrasound and manual exploration of pancreas by the surgeon reached a 100% sensitivity. Before the intraoperatory ultrasound was used the tumor excision was predominantly done by extensive pancreatic resection, while after this was available in our centre more conservative (enucleo-resection) procedures were chosen. In 1 patient the resection was done by laparoscopy, and in 1 patient by robotic surgery. The dimensions of the tumor were less than 2 cm in most of the patients; 2 had nesidioblastosis and 2 had multiple insulinomas; all 28 patients proved to have benign insulinomas at histological specimens. Following surgery, the symptoms disappear in all patients. The most common complication following extensive pancreatic resections was acute pancreatitis, while after enucleation pancreatic fistula occurred more frequently. Due to small dimensions, the preoperative diagnosis of insulinomas is usually difficult, ecoendoscopy being the most sensitive method. Intraoperative ultrasound is essential for insulinoma localization and for chosing the optimal type of excision. Enucleation is the resection method to be chosen whenever this it is technical possible. In benign insulinomas the prognosis is excellent, surgical resection being curative in

  7. Tratamento cirúrgico dos insulinomas -- estudo de 59 casos Surgical treatment of insulinoma. Study of 59 cases

    Directory of Open Access Journals (Sweden)

    M.C.C. Machado

    1998-06-01

    Full Text Available Após a confirmação clínica e laboratorial de hiperinsulinismo, o principal problema consiste na localização precisa da lesão no parênquima pancreático, propiciando tratamento cirúrgico adequado. OBJETIVO: Analisar os métodos utilizados para o diagnóstico e localização pré e intra-operatório dos insulinomas, bem como as técnicas e os resultados do tratamento cirúrgico. MÉTODOS: Foram estudados 59 casos consecutivos de insulinoma submetidos a intervenção cirúrgica. Cada um dos métodos utilizados para a localização pré-operatória dessas lesões foi avaliado quanto à sua eficiência em confronto com os achados intra-operatórios. A palpação do pâncreas, isoladamente ou associada à ultra-sonografia intra-operatória, como métodos de localização dos insulinomas, foi também estudada. Os tipos de intervenção cirúrgica foram analisados quanto aos seus resultados imediatos e tardios. RESULTADOS: Dos 59 insulinomas, 55 eram benignos e quatro, malignos. Dos métodos utilizados para a localização pré-operatória, a ultra-sonografia foi eficiente em 28,1% dos casos, a tomografia computadorizada em 25%, a ultra-sonografia endoscópica em 27,2%, a arteriografia seletiva em 54,1% e a colheita de amostras de sangue portal para dosagem de insulina em 94,4% dos casos. A palpação bidigital, durante a intervenção cirúrgica, localizou as lesões em 54/55 casos (98,2%. A ultra-sonografia intra-operatória foi decisiva em apenas um caso. Cinco doentes apresentavam neoplasia endócrina múltipla tipo I e em todos as lesões pancreáticas eram múltiplas. Foram efetuadas 29 enucleações e 32 ressecções pancreáticas nos doentes com lesões benignas. Os doentes com lesões malignas foram submetidos a ressecções pancreáticas e quimioterapia. Não houve mortalidade, porém observaram-se complicações (fístulas em 29/59 casos. Os resultados foram bons em 98,1% dos doentes com lesões benignas. Apenas um dos doentes com

  8. Effects of transplantation and resection of a radiation-induced rat insulinoma on glucose homeostasis and the endocrine pancreas

    International Nuclear Information System (INIS)

    Flatt, P.R.; Tan, K.S.; Powell, C.J.; Swanston-Flatt, S.K.; Marks, V.; Bailey, C.J.

    1986-01-01

    Twenty-one days after s.c. subscapular transplantation of a radiation-induced insulinoma, male NEDH rats exhibited hyperinsulinaemia and hypoglycaemia. These features were associated with islet atrophy, degenerative changes in pancreatic A and B cells, and decreases in the pancreatic contents of insulin, glucagon and somatostatin. The immunoreactive glucagon and somatostatin contents of extrapancreatic tissues of insulinoma-bearing rats were unchanged. Surgical resection of the tumour resulted in an immediate fall of plasma insulin, attaining concentrations similar to those of anaesthetised control rats by 10 min. The estimated half-life of insulin was 3.5 min. Hypoglycaemia persisted until 60 min after resection, followed by hyperglycaemia of 1-2 days duration. Glucose tolerance was impaired 1 day after tumour resection despite the coexistence of raised insulin concentrations. Evidence for abnormal pancreatic B cell function was gained by injection of arginine which failed to evoke a plasma insulin response in the resected rats. Two days after resection, plasma glucose and insulin concentrations were similar to those of control rats. Plasma glucose and insulin responses to glucose and arginine were suggestive of tumour recurrence by 12 days. A single large encapsulated tumour was eventually observed in each rat, with resection giving a 17-56 day prolongation of life. (author)

  9. Giant insulinoma in a 15-year-old man: A case report

    Directory of Open Access Journals (Sweden)

    Vasin Vasikasin

    2016-01-01

    Conclusion: We report the youngest case of a giant insulinoma. Despite the size of the tumor, the pathological report confirmed the benign characteristics. However, long-term follow-up is still essential to detect recurrence in the future.

  10. Screening key candidate genes and pathways involved in insulinoma by microarray analysis.

    Science.gov (United States)

    Zhou, Wuhua; Gong, Li; Li, Xuefeng; Wan, Yunyan; Wang, Xiangfei; Li, Huili; Jiang, Bin

    2018-06-01

    Insulinoma is a rare type tumor and its genetic features remain largely unknown. This study aimed to search for potential key genes and relevant enriched pathways of insulinoma.The gene expression data from GSE73338 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between insulinoma tissues and normal pancreas tissues, followed by pathway enrichment analysis, protein-protein interaction (PPI) network construction, and module analysis. The expressions of candidate key genes were validated by quantitative real-time polymerase chain reaction (RT-PCR) in insulinoma tissues.A total of 1632 DEGs were obtained, including 1117 upregulated genes and 514 downregulated genes. Pathway enrichment results showed that upregulated DEGs were significantly implicated in insulin secretion, and downregulated DEGs were mainly enriched in pancreatic secretion. PPI network analysis revealed 7 hub genes with degrees more than 10, including GCG (glucagon), GCGR (glucagon receptor), PLCB1 (phospholipase C, beta 1), CASR (calcium sensing receptor), F2R (coagulation factor II thrombin receptor), GRM1 (glutamate metabotropic receptor 1), and GRM5 (glutamate metabotropic receptor 5). DEGs involved in the significant modules were enriched in calcium signaling pathway, protein ubiquitination, and platelet degranulation. Quantitative RT-PCR data confirmed that the expression trends of these hub genes were similar to the results of bioinformatic analysis.The present study demonstrated that candidate DEGs and enriched pathways were the potential critical molecule events involved in the development of insulinoma, and these findings were useful for better understanding of insulinoma genesis.

  11. A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas.

    Science.gov (United States)

    Grover, Amelia C; Skarulis, Monica; Alexander, H Richard; Pingpank, James F; Javor, Edward D; Chang, Richard; Shawker, Thomas; Gorden, Phil; Cochran, Craig; Libutti, Steven K

    2005-12-01

    Preoperative imaging studies localize insulinomas in less than 50% of patients. Arteriography with calcium stimulation and venous sampling (ASVS) regionalizes greater than 90% of insulinomas but requires specialized expertise and an invasive procedure. This prospective study evaluated laparoscopic exploration with IOUS compared with the other localization procedures in patients with a sporadic insulinoma. Between March 2001 and October 2004, 14 patients (7 women and 7 men; mean age, 53) with an insulinoma were enrolled in an IRB-approved protocol. Computed tomography, magnetic resonance imaging, ultrasound scan, and arteriography with calcium stimulation and venous sampling were performed preoperatively. A surgeon, blinded to the results of the localizing studies, performed a laparoscopic exploration with intraoperative ultrasound (IOUS). At the completion of the exploration, the success of laparoscopy for localization was scored, and the tumor was resected. Twelve of 14 tumors were localized successfully before laparoscopy (noninvasive, 7 of 14; invasive, 11 of 14). Laparoscopic IOUS localized successfully 12 of 14 tumors. All lesions were resected, and all patients were cured (median follow-up, 36 months). Laparoscopic IOUS identified 86% of tumors. The authors consider laparoscopic IOUS to be equivalent to ASVS in localizing insulinomas. Further study is therefore warranted to determine the role of laparoscopy with IOUS in the localization and treatment algorithm for patients with sporadic insulinoma.

  12. Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma

    Directory of Open Access Journals (Sweden)

    Chang Ho Ahn

    2014-12-01

    Full Text Available BackgroundAmong the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas.MethodsWe reviewed the medical records of patients who underwent evaluation for hypoglycemia from 2000 to 2013. Fourteen patients with histopathologically confirmed insulinoma and 18 patients without clinical evidence of insulinoma were included. The results of a prolonged fast test were analyzed according to the abovementioned criteria.ResultsFulfilling all three Endocrine Society criteria-plasma levels of glucose (24.0 (pmol/L/(mmol/L] gave the highest area under the receiver operating characteristic curve, with 93% sensitivity and 94% specificity.ConclusionFulfilling the glucose, insulin, and C-peptide criteria of the Endocrine Society guidelines exhibited the best diagnostic performance for insulinoma. Nonetheless, the insulin-glucose ratio may still have a role in the biochemical diagnosis of insulinoma.

  13. Nedley Depression Hit Hypothesis

    OpenAIRE

    Nedley, Neil; Ramirez, Francisco E.

    2014-01-01

    Depression is often diagnosed using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. We propose how certain lifestyle choices and non-modifiable factors can predict the development of depression. We identified 10 cause categories (hits or ?blows? to the brain) and theorize that four or more active hits could trigger a depression episode. Methods. A sample of 4271 participants from our community-based program (70% female; ages 17-94 years) was assessed ...

  14. Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience.

    Science.gov (United States)

    Guettier, Jean-Marc; Kam, Anthony; Chang, Richard; Skarulis, Monica C; Cochran, Craig; Alexander, H Richard; Libutti, Steven K; Pingpank, James F; Gorden, Phillip

    2009-04-01

    Selective intraarterial calcium injection of the major pancreatic arteries with hepatic venous sampling [calcium arterial stimulation (CaStim)] has been used as a localizing tool for insulinomas at the National Institutes of Health (NIH) since 1989. The accuracy of this technique for localizing insulinomas was reported for all cases until 1996. The aim of the study was to assess the accuracy and track record of the CaStim over time and in the context of evolving technology and to review issues related to result interpretation and procedure complications. CaStim was the only invasive preoperative localization modality used at our center. Endoscopic ultrasound (US) was not studied. We conducted a retrospective case review at a referral center. Twenty-nine women and 16 men (mean age, 47 yr; range, 13-78) were diagnosed with an insulinoma from 1996-2008. A supervised fast was conducted to confirm the diagnosis of insulinoma. US, computed tomography (CT), magnetic resonance imaging (MRI), and CaStim were used as preoperative localization studies. Localization predicted by each preoperative test was compared to surgical localization for accuracy. We measured the accuracy of US, CT, MRI, and CaStim for localization of insulinomas preoperatively. All 45 patients had surgically proven insulinomas. Thirty-eight of 45 (84%) localized to the correct anatomical region by CaStim. In five of 45 (11%) patients, the CaStim was falsely negative. Two of 45 (4%) had false-positive localizations. The CaStim has remained vastly superior to abdominal US, CT, or MRI over time as a preoperative localizing tool for insulinomas. The utility of the CaStim for this purpose and in this setting is thus validated.

  15. Value of fat suppression and dynamic contrast-enhanced MRI in the diagnosis of insulinoma

    International Nuclear Information System (INIS)

    Xu Zengbin; Ruan Lingxiang; Peng Zhiyi; Zhang Minming; Xu Shunliang; Zhang Xidao

    2003-01-01

    Objective: To evaluate the value of fat suppression and dynamic contrast-enhanced MRI in the preoperative localization of insulinoma. Methods: Twelve cases with pathologically proven insulinoma were evaluated with MRI. SE T 1 WI, FSE T 2 WI, T 1 WI and T 2 WI with fat suppression, dynamic contrast-enhanced FMPSPGR sequences were used in MR scanning. Results: On SE T 1 WI, the lesions displayed hypointense in 4, isointense in 8 cases. Lesions showed hyperintense in 4, isointense in 8 cases on FSE T 2 WI. In contrast, 7 cases appeared as hypointense on T 1 WI with fat suppression and 6 cases appeared as hyperintense on T 2 WI with fat suppression. With dynamic contrast-enhanced FMPSPGR sequence 11 of 12 insulinomas were detected. In the arterial phase, the lesions presented as hyperintense with different degrees in 11 cases and isointense in 1 case. 6 cases remained hyperintense and 6 cases were isointense in pancreatic parenchymal and portal phase. 4 lesions were identified only in dynamic enhancement images. The diagnostic accuracy of insulinoma by dynamic contrast-enhanced MRI was 91.7% (11/12) as compared with histological study. Conclusion: The results indicate that dynamic contrast-enhanced MRI is an sensitive and accurate method for the preoperative localization of insulinoma

  16. The SVT Hit Buffer

    International Nuclear Information System (INIS)

    Belforte, S.; Dell'Orso, M.; Donati, S.

    1996-01-01

    The Hit Buffer is part of the Silicon Vertex Tracker, a trigger processor dedicated to the reconstruction of particle trajectories in the Silicon Vertex Detector and the Central Tracking Chamber of the Collider Detector at Fermilab. The Hit Buffer is a high speed data-traffic node, where thousands of words are received in arbitrary order and simultaneously organized in an internal structured data base, to be later promptly retrieved and delivered in response to specific requests. The Hit Buffer is capable of processing data at a rate of 25 MHz, thanks to the use of special fast devices like Cache-Tag RAMs and high performance Erasable Programmable Logic Devices from the XILINX XC7300 family

  17. How I treat double-hit lymphoma.

    Science.gov (United States)

    Friedberg, Jonathan W

    2017-08-03

    The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 . These lymphomas, which occur in hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

  18. Usefulness of intraoperative echography for resection of a insulinoma located in the head of pancreas

    International Nuclear Information System (INIS)

    Cepero Valdes, Manuel; Hernandez Rivero, Hanoi; Ugarte Moreno, Dayana; Chao Gonzalez, Lissette

    2011-01-01

    The insulinoma is the more frequent neoplasms among the neuroendocrine tumors of pancreas. The aim of present paper is to describe the clinical picture, laboratory and imaging examinations and the surgical features as well as the complications in a patient diagnosed with insulinoma without evidences by preoperative images. Surgery was prescribed on the base of clinical and analytic evidences of hypoglycemia and hyperinsulinism and the carrying out of an exploratory laparatomy without any lesion with direct palpation of pancreas. Intraoperative echography was used to locate a 0,8 cm nodule in the head of pancreas. After enucleation the only postoperative complication was a low-flow pancreatic fistula with a spontaneous remission. The histological diagnosis was a benign insulinoma. Patient had a clinical reversion of symptoms in addition to normalization of glycemia values, compared to those intraoperative. (author)

  19. Pancreatic insulinoma co-existing with gastric GIST in the absence of neurofibromatosis-1

    Directory of Open Access Journals (Sweden)

    O'Sullivan Brendan

    2009-02-01

    Full Text Available Abstract Background Gastrointestinal stromal tumours (GIST frequently occur in patients with neurofibromatosis type 1 (NF-1. It has been reported that GIST may co-exist with pancreatic endocrine tumors but this has only been in association with NF-1. Case presentation A 76 year old woman presented with a 12 month history of hypoglycaemia symptoms. Abdominal CT scan demonstrated a 13 mm insulinoma localized in the tail of her pancreas. She was commenced on diazoxide and later underwent surgery for enucleation of insulinoma when a small ( Conclusion This is the first case report of a pancreatic insulinoma co-existing with a GIST in a patient without NF-1. In addition, we make the first report of rapidly growing cystic GIST recurrence following resection of a primary GIST tumour.

  20. Pathway decision-making strategies for generating pancreatic beta-cells: systems biology or hit and miss?

    Science.gov (United States)

    Jensen, Jan

    2007-08-01

    Method selection strategies to achieve beta-cell differentiation from human embryonic stem cells are reviewed. Expectations are high for an embryonic stem cell derived cellular replacement method to cure diabetes, and recent observations indicate that mature beta-cells can be derived from human embryonic stem cells. In terms of the translational setting, however, we are not there yet; conversion of embryonic stem cells to fully mature beta-cells is not effective and does not provide an exclusive beta-cell population as the end-product. Studies emphasize that expecting development of a 'magic media bullet' that promotes endocrine fate is rather optimistic; consecutive administration of signaling inducers, carefully provided to mimic normal development, is more likely to succeed. To accomplish this task we need better understanding of the extracellular signaling pathways that drive progressive endodermal fate choices throughout development. Knowledge of cell-intrinsic control of fate assignments in pancreas is growing rapidly. Nevertheless, insufficient information regarding morphogen codes that operate in endoderm and pancreas is hindering development of better, directed differentiation schema of uncommitted embryonic stem cells toward endodermal, pancreatic, and subsequent endocrine specific fates. A systematic approach to defining morphogen codes in developing endoderm and pancreas appears timely and justified.

  1. Transcription Factors Synergistically Activated at the Crossing of the Restriction Point between G1 and S Cell Cycle Phases. Pathologic Gate Opening during Multi-Hit Malignant Transformation

    Directory of Open Access Journals (Sweden)

    Nicoletta Castagnino

    2016-12-01

    Full Text Available Transcription factors (TFs represent key regulators of gene-expression patterns controlling cell behavior. TFs are active at nuclear – chromatin levels. TFs do not act in isolation; small sets of TFs cooperate toward the transcription of sets of mRNAs and consequently the translation of new proteins (the molecular phenotypes of a cell. Most TFs are activated through a cascade of biochemical reactions mediated by receptors expressed on the target cell surface. Nuclear Receptors (NRs are transcription factors activated instead by small hydrophobic molecules capable of crossing the plasma membrane. The convergence of different pathways on TFs and their posttranslational modifications ensure that the external stimuli generate appropriate and integrated responses. The reconstruction of the molecular anatomy of these pathways through Molecular Interactions Maps (MIMs can depict these intricate interactions. A mathematical modeling approach simulates/mimics their mechanism of action in normal and pathological conditions. We can simulate the effect of virtual hits in neoplastic transformation as mutations/alterations in these pathways. We can also simulate the effect of targeted inhibitors on these deregulated pathways. This strategy can help to guide an appropriate combination of targeted drugs in the treatment of a cancer patient, a major innovative perspective of incoming years.

  2. Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas.

    Science.gov (United States)

    Islam, Shariful; Qi, Wenqing; Morales, Carla; Cooke, Laurence; Spier, Catherine; Weterings, Eric; Mahadevan, Daruka

    2017-10-01

    Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2 , which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan-Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083-93. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Localization of Hidden Insulinomas with ⁶⁸Ga-DOTA-Exendin-4 PET/CT: A Pilot Study.

    Science.gov (United States)

    Antwi, Kwadwo; Fani, Melpomeni; Nicolas, Guillaume; Rottenburger, Christof; Heye, Tobias; Reubi, Jean Claude; Gloor, Beat; Christ, Emanuel; Wild, Damian

    2015-07-01

    (111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. (68)Ga-DOTA-exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. These preliminary data suggest that the use of (68)Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  4. High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria.

    Science.gov (United States)

    Nakamura, Yoshio; Doi, Ryuichiro; Kohno, Yasuhiro; Shimono, Dai; Kuwamura, Naomitsu; Inoue, Koichi; Koshiyama, Hiroyuki; Imamura, Masayuki

    2002-11-01

    It is reported that some cases with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed as psychosis. Here we report a case of insulinoma masquerading as hysteria, whose final diagnosis could be made using high-dose calcium stimulation test. A 28-yr-old woman was referred presenting with substupor, mutism, mannerism, restlessness, and incoherence. Laboratory examinations revealed hypoglycemia (33 mg/dL) and detectable insulin levels (9.7 microU/mL), suggesting the diagnosis of insulinoma. However, neither imaging studies nor selective arterial calcium injection (SACI) test with a conventional dose of calcium (0.025 mEq/kg) indicated the tumor. High-dose calcium injection (0.05 mEq/kg) evoked insulin secretion when injected into superior mesenteric artery. A solitary tumor in the head of the pancreas was resected, and her plasma glucose returned to normal. Postoperatively, iv injection of secretin resulted in a normal response of insulin, which was not found preoperatively. This case suggests the usefulness of the SACI test with high-dose of calcium in the case of insulinoma when the standard dose fails to detect such a tumor.

  5. Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

    Science.gov (United States)

    Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

    2017-01-01

    Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

  6. Computational Physics' Greatest Hits

    Science.gov (United States)

    Bug, Amy

    2011-03-01

    The digital computer, has worked its way so effectively into our profession that now, roughly 65 years after its invention, it is virtually impossible to find a field of experimental or theoretical physics unaided by computational innovation. It is tough to think of another device about which one can make that claim. In the session ``What is computational physics?'' speakers will distinguish computation within the field of computational physics from this ubiquitous importance across all subfields of physics. This talk will recap the invited session ``Great Advances...Past, Present and Future'' in which five dramatic areas of discovery (five of our ``greatest hits'') are chronicled: The physics of many-boson systems via Path Integral Monte Carlo, the thermodynamic behavior of a huge number of diverse systems via Monte Carlo Methods, the discovery of new pharmaceutical agents via molecular dynamics, predictive simulations of global climate change via detailed, cross-disciplinary earth system models, and an understanding of the formation of the first structures in our universe via galaxy formation simulations. The talk will also identify ``greatest hits'' in our field from the teaching and research perspectives of other members of DCOMP, including its Executive Committee.

  7. 18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma

    International Nuclear Information System (INIS)

    Kiesewetter, Dale O.; Ma, Ying; Niu, Gang; Quan, Qimeng; Guo, Ning; Chen, Xiaoyuan; Gao, Haokao

    2012-01-01

    Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic β-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic β-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared 18 F radioligands for GLP-1R by the reaction of [ 18 F]FBEM, a maleimide prosthetic group, with [Cys 0 ] and [Cys 40 ] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [ 18 F]FBEM-[Cys x ]-exendin-4 analogs were obtained in good yield (34.3 ± 3.4%, n = 11), based on the starting compound [ 18 F]FBEM, and had a specific activity of 45.51 ± 16.28 GBq/μmol (1.23 ± 0.44 Ci/μmol, n = 7) at the end of synthesis. The C-terminal isomer, [ 18 F]FBEM-[Cys 40 ]-exendin-4, had higher affinity for INS-1 tumor cells (IC 50 1.11 ± 0.057 nM) and higher tumor uptake (25.25 ± 3.39 %ID/g at 1 h) than the N-terminal isomer, [ 18 F]FBEM-[Cys 0 ]-exendin-4 (IC 50 2.99 ± 0.06 nM, uptake 7.20 ± 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cys x ]-exendin-4 (p 18 F]FBEM-[Cys 40 ]-exendin-4 and [ 18 F]FBEM-[Cys 0 ]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors exhibited by [ 18 F]FBEM-[Cys 40 ]-exendin-4 suggests that this compound would be the better tracer for imaging

  8. Combined hit theory-microdosimetric explanation of cellular radiobiological action

    International Nuclear Information System (INIS)

    Bond, V.P.; Varma, M.N.

    1983-01-01

    Hit theory is combined with microdosimetry in a stochastic approach that explains the observed responses of cell populations exposed in radiation fields of different qualities. The central thesis is that to expose a population of cells in a low-level radiation field is to subject the cells to the potential for interaction with charged particles in the vicinity of the cells, quantifiable in terms of the charged particle fluence theta. When such an interaction occurs there is a resulting stochastic transfer of energy to a critical volume (CV) of cross section sigma, within the cell(s). The severity of cell injury is dependent on the amount of energy thus imparted, or the hit size. If the severity is above some minimal level, there is a non-zero probability that the injury will result in a quantal effect (e.g., a mutational or carcinogenic initial event, cell transformation). A microdosimetric proportional counter, viewed here as a phantom cell CV that permits measurements not possible in the living cell, is used to determine the incidence of hit cells and the spectrum of hit sizes. Each hit is then weighted on the basis of an empirically-determined function that provides the fraction of cells responding quantally, as a function of hit size. The sum of the hits so weighted provides the incidence of quantally-responding cells, for any amount of exposure theta in a radiation field of any quality or mixture qualities. The hit size weighting function for pink mutations in Tradescantia is discussed, as are its implications in terms of a replacement for RBE and dose equivalent. 14 references, 9 figures

  9. Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.

    Science.gov (United States)

    Miyaoka, Masashi; Kikuti, Yara Y; Carreras, Joaquim; Ikoma, Haruka; Hiraiwa, Shinichiro; Ichiki, Akifumi; Kojima, Minoru; Ando, Kiyoshi; Yokose, Tomoyuki; Sakai, Rika; Hoshikawa, Masahiro; Tomita, Naoto; Miura, Ikuo; Takata, Katsuyoshi; Yoshino, Tadashi; Takizawa, Jun; Bea, Silvia; Campo, Elias; Nakamura, Naoya

    2018-02-01

    Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (Phit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular

  10. Studies on a novel peptide isolated and purified from rat insulinoma tissue

    Energy Technology Data Exchange (ETDEWEB)

    Al-Akhras, G N

    1987-01-01

    Rat insulinoma peptide (RIP) which appears to be either a fragment of, or an altered rat C-peptide was isolated and purified by dialysis. The purity of this peptide was investigated using polyacrylamide gel electrophoresis with sodium dodecyl sulfate, isoelectric focusing, and high performance liquid chromatography. RIP may contain two peptides similar to each other but differing in their isoelectric points. The molecular weight of RIP was found to be 1982 daltons by fast atoms bombardment mass spectrometry giving a chain length of approximately 22 amino acid residues. From information obtained using radioimmunoassay employing antiserum R901, RIP appears to share a common C-terminus with rat C-peptide. A radioimmunoassay for RIP was developed using the purified RIP as immunogen and for standards and tracers. An indirect enzyme linked immunosorbent assay (ELISA) for rat insulinoma peptide was developed using purified RIP for immunogen and semi-purified RIP as a standard.

  11. Insulinoma: A retrospective study analyzing the differences between benign and malignant tumors.

    Science.gov (United States)

    Câmara-de-Souza, A B; Toyoshima, M T K; Giannella, M L; Freire, D S; Camacho, C P; Lourenço, D M; Rocha, M S; Bacchella, T; Jureidini, R; Machado, M C C; Almeida, M Q; Pereira, M A A

    2018-04-01

    Insulinoma is a rare pancreatic tumor and, usually, a benign disease but can be a malignant one and, sometimes, a highly aggressive disease. The aim of this study was to determine differences between benign and malignant tumors. Retrospective study of 103 patients with insulinoma treated in a tertiary center. It was analyzed demographic, clinical, laboratory, localization and histologic analysis of tumor and follow up data of subjects in order to identify differences between individuals benign and malignant disease. Almost all patients (87%) had a benign tumor and survival rates of 100% following pancreatic tumor surgery. Those with malignant tumors (13%) have a poor prognosis, 77% insulinoma-related deaths over a period of 1-300 months after the diagnosis with a survival rate of 24% in five years. The following factors are associated with an increased risk of malignant disease: duration of symptoms < 24 months, fasting time for the occurrence of hypoglycemia < 8 h, blood plasma insulin concentration ≥ 28 μU/mL and C-peptide ≥ 4.0 ng/mL at the glycemic nadir and tumor size ≥ 2.5 cm. Our data help to base the literature about these tumors, reinforcing that although insulinoma is usually a single benign and surgically treated neoplasia, the malignant one is difficult to treat. We highlight the data that help predict a malignancy behavior of tumor and suggest a long follow up after diagnosis in these cases. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  12. Dynamic computed tomography of the pancreas in normal dogs and in a dog with pancreatic insulinoma.

    Science.gov (United States)

    Iseri, Toshie; Yamada, Kazutaka; Chijiwa, Kousaku; Nishimura, Ryohei; Matsunaga, Satoru; Fujiwara, Reina; Sasaki, Nobuo

    2007-01-01

    To establish optimal imaging conditions for enhanced computed tomography (CT) for canine pancreatic tumors, 10 healthy beagles were subjected to dynamic CT. This technique was then applied to a dog with suspected insulinoma. The changes in mean peak enhancement and the delay time of the aorta and pancreas were determined. In normal beagles, maximal arterial and pancreatic CT enhancement was observed at 15 +/- 2 s (795 +/- 52 Housfield unit [HU]) and 28 +/- 9 s (118 +/- 16HU) after contrast medium injection, respectively. Multiphase enhanced CT was performed in a pug with suspected insulinoma using the CT protocol defined for the normal beagles with some parameters modified; the images were acquired at the arterial (14 s after contrast medium injection), pancreatic (after 28 s), and equilibrium (after 90 s) phases; scanning was followed by exploratory laparotomy. CT images were characterized by an enhanced mass in the left pancreatic lobe at the arterial phase, during which the difference between the CT values of the mass and normal pancreas was the highest. Histopathologic diagnosis of the pancreatic mass was insulinoma. Thus, it appears that enhanced CT imaging can be used to delineate the pancreas from a pancreatic mass, and it may be helpful in deciding the need for surgery.

  13. [Usefullness of scintigraphy with somatostatin analogues in the imaging of insulinoma of the pancreas].

    Science.gov (United States)

    Owecki, Maciej; Czepczyriński, Rafał; Biczysko, Maciej; Stawny, Bolesław; Drews, Michał; Sowiński, Jerzy

    2006-01-01

    We present a case of a 74-years-old female with insulinoma of the pancreas. Neuroglycopenic symptoms (Whipple's triad) and a positive fast test established the diagnosis. The fast was terminated after 5 hours and 40 minutes because of neuroglycopenic symptoms with the serum glucose and insulin levels of 40 mg/dl and 34,01 microU/ml respectively. The tumor was invisible in ultrasound, abdominal CT scan and MRL The only means that enabled preoperative visualization was 111-Indium labeled octreotide scintigraphy (OctreoScan). Laparotomy was performed, and a tumor was disclosed in intraoperative ultrasonography within the head of the pancreas. The tumor of 37 mm diameter was excised. Histopatological examination revealed benign insulinoma. After surgery the symptoms alleviated completely. The patient with proper glucose levels and insulin concentration of 3,04 microU/ml was discharged in good health. This case confirms high usefulness of preoperative OctreoScan and intraoperative ultrasonography in the approach to a patient with insulinoma.

  14. Somatostatin receptor scintigraphy and intraoperative gamma probe detection in the localisation and treatment of pancreatic insulinoma

    International Nuclear Information System (INIS)

    Loh, Nelson K.; Macdonald, William B.; Dunne, Marina L.; Rao, Sudhakar

    2009-01-01

    Full text: Aims: We report a case of insulinoma that was successfully enucleated under radio-guidance after an initial unsuccessful laparotomy. This case highlights the utility of Somatostatin Receptor Scintigraphy (SRS) and gamma probe in the localisation and treatment of neuroendocrine tumours. Methods: The patient presented with recurrent hypoglycaemia. An abdominal CT scan identified a lesion in the uncinate process of the pancreas, however, laparotomy with use of intraoperative ultrasound failed to localise the lesion. SRS with SPECTICT was then requested by the surgical team with a view to radio-guided surgery. Results: SRS demonstrated an octreotide-avid tumour in the posterior uncinate process of the pancreas, and confirmed suitability for radio-guided surgery. At re-exploration, the surgeon was again unable to palpate the lesion or localise it with intraoperative ultrasound, however, the lesion was successfully detected and removed with the use of a gamma probe. A postoperative SRS confirmed complete excision and histopathology was diagnostic of insulinoma. Conclusion: This case highlights the utility of SRS in the intraoperative localisation and surgical excision of neuroendocrine tumours. The lesion was unable to be localised clinically or with intraoperative ultrasound but was successfully detected with scintigraphic techniques. The surgical team acknowledge that the use of a gamma probe enabled enucleation of the insulinoma, which obviated the need for an invasive Whipple's procedure.

  15. Sporadic insulinomas on volume perfusion CT: dynamic enhancement patterns and timing of optimal tumour-parenchyma contrast

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Liang; Xue, Hua-dan; Liu, Wei; Wang, Xuan; Sun, Hao; Li, Ping; Jin, Zheng-yu [Peking Union Medical College Hospital, Department of Radiology, Beijing (China); Wu, Wen-ming; Zhao, Yu-pei [Peking Union Medical College Hospital, Department of General Surgery, Beijing (China)

    2017-08-15

    To assess enhancement patterns of sporadic insulinomas on volume perfusion CT (VPCT), and to identify timing of optimal tumour-parenchyma contrast. Consecutive patients who underwent VPCT for clinically suspected insulinomas were retrospectively identified. Patients with insulinomas confirmed by surgery were included, and patients with familial syndromes were excluded. Two radiologists evaluated VPCT images in consensus. Tumour-parenchyma contrast at each time point was measured, and timing of optimal contrast was determined. Time duration of hyperenhancement (tumour-parenchyma contrast >20 Hounsfield units, HU) was recorded. Perfusion parameters were evaluated. Three dynamic enhancement patterns were observed in 63 tumours: persistent hyperenhancement (hyperenhancement time window ≥10 s) in 39 (61.9%), transient hyperenhancement (hyperenhancement <10 s) in 19 (30.2%) and non-hyperenhancement in 5 (7.9%). Timing of optimal contrast was 9 s after abdominal aorta threshold (AAT) of 200 HU, with tumour-parenchyma contrast of 77.6 ± 57.2 HU. At 9 s after AAT, 14 (22.2%) tumours were non-hyperenhancing, nine of which had missed transient hyperenhancement. Insulinomas with transient and persistent hyperenhancement patterns had significantly increased perfusion. Insulinomas have variable enhancement patterns. Tumour-parenchyma contrast is time-dependent. Optimal timing of enhancement is 9 s after AAT. VPCT enables tumour detection even if the hyperenhancement is transient. (orig.)

  16. {sup 18}F-FDOPA PET/CT imaging of insulinoma revisited

    Energy Technology Data Exchange (ETDEWEB)

    Imperiale, Alessio; Namer, Izzie-Jacques [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); University of Strasbourg/CNRS and FMTS, Faculty of Medicine, ICube - UMR 7357, Strasbourg (France); Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, La Timone University Hospital, Marseille (France); Vix, Michel [University of Strasbourg, Department of General, Digestive, and Endocrine Surgery, IRCAD-IHU, Strasbourg (France); Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Diabetes and Metabolic Disorders, La Timone University Hospital, Marseille (France); Kessler, Laurence; Moreau, Francois [University of Strasbourg, Department of Diabetology, University Hospital of Strasbourg, Strasbourg (France); Bachellier, Philippe [University Hospitals of Strasbourg, Department of Visceral Surgery and Transplantation, Strasbourg (France); Guillet, Benjamin; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Aix-Marseille University, Biophysics and Nuclear Medecine, La Timone University Hospital, European Center for Research in Medical Imaging, Marseille (France)

    2014-11-01

    {sup 18}F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to {sup 18}F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with {sup 18}F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using {sup 18}F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after {sup 18}F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after {sup 18}F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, {sup 18}F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All {sup 18}F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted {sup 18}F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without

  17. 18F-FDOPA PET/CT imaging of insulinoma revisited

    International Nuclear Information System (INIS)

    Imperiale, Alessio; Namer, Izzie-Jacques; Sebag, Frederic; Vix, Michel; Castinetti, Frederic; Kessler, Laurence; Moreau, Francois; Bachellier, Philippe; Guillet, Benjamin; Mundler, Olivier; Taieb, David

    2015-01-01

    18 F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to 18 F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with 18 F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using 18 F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18 F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after 18 F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, 18 F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All 18 F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted 18 F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without CD premedication, eight patients), the final

  18. Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation.

    Science.gov (United States)

    Druce, Maralyn R; Muthuppalaniappan, Vasantha M; O'Leary, Benjamin; Chew, Shern L; Drake, William M; Monson, John P; Akker, Scott A; Besser, Michael; Sahdev, Anju; Rockall, Andrea; Vyas, Soumil; Bhattacharya, Satya; Matson, Matthew; Berney, Daniel; Reznek, R H; Grossman, Ashley B

    2010-05-01

    Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging. To review diagnostic features and localisation accuracy for insulinomas. Cross-sectional, retrospective analysis. A single tertiary referral centre. Patients with insulinoma in the years 1990-2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes. Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated. Insulinoma localisation was compared to histologically confirmed location following surgical excision. Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results. Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.

  19. Expression of an insulin/interleukin-1 receptor antagonist hybrid gene in insulin-producing cell lines (HIT-T15 and NIT-1) confers resistance against interleukin-1-induced nitric oxide production.

    Science.gov (United States)

    Welsh, N; Bendtzen, K; Welsh, M

    1995-01-01

    A hybrid gene consisting of the insulin gene enhancer/promoter region, the signal sequence, the insulin B- and C-chains, and the human interleukin-1 receptor antagonist (IL-1ra) gene was constructed. This hybrid gene was transfected together with the pSV2-neo construct into the insulin-producing cell lines HIT-T15 and NIT-1. One of the geneticin-selected clones, HITra2, expressed a 1.4-kb mRNA, which hybridized both to insulin and IL-1ra-cDNA in Northern blot analysis. Three proteins, with the mol wt 23, 17, and 14 kD, were immunoprecipitated with anti-IL-1ra antibodies from [35S]methionine-labeled HITra2 cells. Both at a low and at a high glucose concentration, 4-5 ng of IL-1ra/10(6) cells (ELISA) was released from these cells. On the other hand, a high glucose concentration evoked a three-fold increase in the release of insulin, suggesting that IL-1ra was released constitutively. Measured by nitrite production, transfected HIT, and NIT-1 cells exhibited a more than 10-fold decrease in IL-1 beta sensitivity. Since the conditioned culture media from the HITra2 cells exhibited an anti-IL-1 beta activity of only 0.5 U/ml, and mixed culture of HITra2 cells and isolated rat islets prevented IL-1 beta induced inhibition of insulin release, it is likely that IL-1ra acts locally at the cell surface. It is concluded that expression of a hybrid insulin/IL-1ra gene confers resistance to IL-1 and that this technique may be used to elucidate the role of IL-1 in autoimmune disorders such as insulin-dependent diabetes mellitus. Images PMID:7706480

  20. Mesenteric vein thrombosis after percitaneous transhepatic portal vein catheterisation for the localisation of an insulinoma

    International Nuclear Information System (INIS)

    Luska, G.; Langer, H.E.; Le Blanc, S.; Medizinische Hochschule Hannover

    1984-01-01

    The authors report on a fatal mesenteric vein thrombosis following an uncomplicated percutaneous transhepatic portal vein catheterisation for the localisation of an insulinoma. Several hours after the procedure the patient developed an acute abdomen. An emergency laparotomy revealed a haemorrhagic infarct of the ileum. The resected specimen showed an acute phlebitis with fresh thrombus. The cause of the phlebothrombosis was thought to be intimal damage from high osmolar contrast medium. There was no evidence of damage due to the catheder, either on the phlebogram or pathologically. (orig.) [de

  1. Unusual presentation of a pancreatic insulinoma in helical CT and dynamic contrast-enhanced MR imaging: case report

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, A.; Arias, M.; Brasa, J. [Unidad de Resonancia Magnetica (Medtec), Hospital Xeral-Cies, Vigo (Spain); Casal, M. [Unidad de Radiologia Intervencionista, Hospital Xeral-Cies, Vigo (Spain); Paramo, C. [Servicio de Endocrinologia, Hospital Xeral-Cies, Vigo (Spain); Fiano, C. [Servicio de Anatomia Patologica, Hospital Xeral-Cies, Vigo (Spain)

    2001-06-01

    Insulinomas are pancreatic neoplasms that can be radiologically characterized typically because of their tendency to present intense and early contrast enhancement with a wash-out phenomenon. In this sense, we report an unusual case of a hypovascular solid pancreatic insulinoma confirmed with surgery and pathologic analysis, in a patient with normal serum insulin levels. In the two-phase helical CT, the mass behaved as a hypodense lesion with respect to the surrounding pancreatic parenchyma during the arterial phase and as a hypointense lesion during the dynamic contrast-enhanced MR imaging. Pathologic examination demonstrated a hypercellular tumor with poor vascularization of intervening stroma which showed prominent amyloid deposits. (orig.)

  2. Unusual presentation of a pancreatic insulinoma in helical CT and dynamic contrast-enhanced MR imaging: case report

    International Nuclear Information System (INIS)

    Iglesias, A.; Arias, M.; Brasa, J.; Casal, M.; Paramo, C.; Fiano, C.

    2001-01-01

    Insulinomas are pancreatic neoplasms that can be radiologically characterized typically because of their tendency to present intense and early contrast enhancement with a wash-out phenomenon. In this sense, we report an unusual case of a hypovascular solid pancreatic insulinoma confirmed with surgery and pathologic analysis, in a patient with normal serum insulin levels. In the two-phase helical CT, the mass behaved as a hypodense lesion with respect to the surrounding pancreatic parenchyma during the arterial phase and as a hypointense lesion during the dynamic contrast-enhanced MR imaging. Pathologic examination demonstrated a hypercellular tumor with poor vascularization of intervening stroma which showed prominent amyloid deposits. (orig.)

  3. Rare transformation to double hit lymphoma in Waldenstrom's macroglobulinemia.

    Science.gov (United States)

    Okolo, Onyemaechi N; Johnson, Ariel C; Yun, Seongseok; Arnold, Stacy J; Anwer, Faiz

    2017-08-01

    Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL. The paper also broadens to include discussions on current topics in the classification, diagnosis, possible causes of transformation, and treatment of WM, including transformation to double hit lymphoma. The significance of this case lies in that the presence of double hit lymphoma-like genetic mutations in WM have not been previously described in the literature and potentially such changes are harbinger of extra-nodal presentation, aggressive growth, and possibly poor prognosis, if data from other double-hit lymphoma are extrapolated.

  4. Beyond "Hitting the Books"

    Science.gov (United States)

    Entress, Cole; Wagner, Aimee

    2014-01-01

    Scientists, science teachers, and serious students recognize that success in science classes requires consistent practice--including study at home. Whether balancing chemical equations, calculating angular momentum, or memorizing the steps of cell division, students must review material repeatedly to fully understand new ideas--and must practice…

  5. Isoattenuating insulinomas at biphasic contrast-enhanced CT: frequency, clinicopathologic features and perfusion characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Liang; Xue, Hua-dan; Sun, Hao; Wang, Xuan; He, Yong-lan; Jin, Zheng-yu [Peking Union Medical College Hospital, Department of Radiology, Beijing (China); Zhao, Yu-pei [Peking Union Medical College Hospital, Department of General Surgery, Beijing (China)

    2016-10-15

    We aimed to determine the frequency of isoattenuating insulinomas, to investigate their clinicopathological features and to assess their regional pancreatic perfusion characteristics. Institutional review board approval was obtained, and patient informed consent was waived. From July 2010 to June 2014, 170 patients (66 male, 104 female) with endogenous hyperinsulinemic hypoglycemia underwent biphasic contrast-enhanced CT before surgery, and 129 of those patients also received preoperative whole-pancreas CT perfusion. A total of 181 tumours were proved histopathologically after surgery. Enhancement pattern and regional pancreatic perfusion characteristics were analyzed. Clinical features, tumour size and pathological grading were investigated. The frequency of isoattenuating tumours was 24.9 %. Tumour size and WHO grading was not significantly different between isoattenuating and hyperattenuating tumours. Tumour-free regions had identical blood flow (BF) regardless of their location (p = 0.35). Isoattenuating tumour-harbouring regions had lower BF compared with hyperattenuating tumour-harbouring regions; both showed higher BF compared with tumour-free neighbourhood regions (all p < 0.01). For patients with isoattenuating tumours, the overall hospital stay was longer (p < 0.01). A substantial subset of insulinomas were isoattenuating on biphasic CT. CT perfusion showed higher BF in tumour-harbouring regions compared to tumour-free regions, providing a clue for tumour regionalization. (orig.)

  6. Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC- 99mTc/EDDA)NH2]-exendin-4 for the detection of insulinoma.

    Science.gov (United States)

    Sowa-Staszczak, Anna; Pach, Dorota; Mikołajczak, Renata; Mäcke, Helmut; Jabrocka-Hybel, Agata; Stefańska, Agnieszka; Tomaszuk, Monika; Janota, Barbara; Gilis-Januszewska, Aleksandra; Małecki, Maciej; Kamiński, Grzegorz; Kowalska, Aldona; Kulig, Jan; Matyja, Andrzej; Osuch, Czesław; Hubalewska-Dydejczyk, Alicja

    2013-04-01

    The objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4. Studies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed. Both sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis. [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.

  7. Mixed Hitting-Time Models

    NARCIS (Netherlands)

    Abbring, J.H.

    2009-01-01

    We study mixed hitting-time models, which specify durations as the first time a Levy process (a continuous-time process with stationary and independent increments) crosses a heterogeneous threshold. Such models of substantial interest because they can be reduced from optimal-stopping models with

  8. Preparation and evaluation of Exendin radio conjugates for detecting insulinomas and gastrinomas by molecular nuclear medicine techniques

    International Nuclear Information System (INIS)

    Medina G, V.

    2015-01-01

    The gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) are named based on the secreted hormones. Among them, the insulinomas and gastrinomas represent a diagnostic challenge because of their slow metabolic rate, small size and anatomical location that have limited their detection in some imaging procedures. About 90% of insulinomas are benign and 10% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over express SSTR or GLP-1R in low levels. A kit for the preparation of Lys 27 ( 99m Tc-EDDA/HYNIC)-Exendin(9-39)/ 99m Tc-EDDA/HYNIC-Tyr 3 -Octreotide was developed to detect 100% of gastrinomas and insulinomas. In order to reach this aim, the peptides were radiolabeled and characterized. Stability studies will be completed and the in vitro and in vivo behavior was evaluated. The Lys 27 ( 99m Tc-EDDA/HYNIC)-Exendin(9-39)/ 99m Tc-EDDA/HYNIC-Tyr 3 -Octreotide can be labeled with 99m Tc, obtaining high radiochemical purities (>94%), high stability in human serum and affinity to GLP-1 and SST-2 receptor. This new formulation showed properties suitable for use as a target-specific agent for molecular imaging of GLP-1R/SSTR positive tumors. In vivo micro-SPECT/CT images of Lys 27 ( 99m Tc-EDDA/HYNIC)-Exendin(9-39), 99m Tc-EDDA/HYNIC-Tyr 3 -Octreotide and of the pharmaceutical formulation Lys 27 ( 99m Tc-EDDA/HYNIC)-Exendin(9-39)/ 99m Tc-EDDA/HYNIC-Tyr 3 -Octreotide showed the main elimination pathways, and tumors higher uptake compared to the background tissues. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GLP-1R and SSTR. (Author)

  9. Distributed generation hits market

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    The pace at which vendors are developing and marketing gas turbines and reciprocating engines for small-scale applications may signal the widespread growth of distributed generation. Loosely defined to refer to applications in which power generation equipment is located close to end users who have near-term power capacity needs, distributed generation encompasses a broad range of technologies and load requirements. Disagreement is inevitable, but many industry observers associate distributed generation with applications anywhere from 25 kW to 25 MW. Ten years ago, distributed generation users only represented about 2% of the world market. Today, that figure has increased to about 4 or 5%, and probably could settle in the 20% range within a 3-to-5-year period, according to Michael Jones, San Diego, Calif.-based Solar Turbines Inc. power generation marketing manager. The US Energy Information Administration predicts about 175 GW of generation capacity will be added domestically by 2010. If 20% comes from smaller plants, distributed generation could account for about 35 GW. Even with more competition, it's highly unlikely distributed generation will totally replace current market structures and central stations. Distributed generation may be best suited for making market inroads when and where central systems need upgrading, and should prove its worth when the system can't handle peak demands. Typical applications include small reciprocating engine generators at remote customer sites or larger gas turbines to boost the grid. Additional market opportunities include standby capacity, peak shaving, power quality, cogeneration and capacity rental for immediate demand requirements. Integration of distributed generation systems--using gas-fueled engines, gas-fired combustion engines and fuel cells--can upgrade power quality for customers and reduce operating costs for electric utilities

  10. 42 CFR 495.344 - Approval of the State Medicaid HIT plan, the HIT PAPD and update, the HIT IAPD and update, and...

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Approval of the State Medicaid HIT plan, the HIT PAPD and update, the HIT IAPD and update, and the annual HIT IAPD. 495.344 Section 495.344 Public... Requirements Specific to the Medicaid Program § 495.344 Approval of the State Medicaid HIT plan, the HIT PAPD...

  11. Diagnosis of insulinoma in a patient with hypoglycemia without obvious hyperinsulinemia.

    Science.gov (United States)

    Coelho, Catarina; Druce, Maralyn R; Grossman, Ashley B

    2009-11-01

    A 41-year-old Maltese woman with a 12-month history of severe, morning episodes of confusion, blurred vision and sweating was referred to a specialist center for evaluation of fasting hypoglycemia. She was not taking medication and did not report any prior personal or familial history of endocrinopathy or other relevant pathology. Measurement of plasma glucose, insulin, C-peptide, and beta-hydroxybutyrate concentrations during a prolonged supervised fast; sulfonylurea screen; CT, MRI scan and endoscopic ultrasonography of the pancreas; calcium stimulation test; surgical exploration and intra-operative ultrasonography of the pancreas. Insulin-secreting lesion (insulinoma) in the tail of the pancreas. The tumor was resected with cure of symptoms.

  12. 77 FR 32639 - HIT Standards Committee and HIT Policy Committee; Call for Nominations

    Science.gov (United States)

    2012-06-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee and HIT Policy Committee; Call for... Health Information Technology Policy Committee (HITPC). Name of Committees: HIT Standards Committee and HIT Policy Committee. General Function of the Committees: The HITSC is charged to provide...

  13. {sup 18}F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kiesewetter, Dale O.; Ma, Ying; Niu, Gang; Quan, Qimeng; Guo, Ning; Chen, Xiaoyuan [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Gao, Haokao [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China)

    2012-03-15

    Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic {beta}-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic {beta}-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared {sup 18}F radioligands for GLP-1R by the reaction of [{sup 18}F]FBEM, a maleimide prosthetic group, with [Cys{sup 0}] and [Cys{sup 40}] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [{sup 18}F]FBEM-[Cys{sup x}]-exendin-4 analogs were obtained in good yield (34.3 {+-} 3.4%, n = 11), based on the starting compound [{sup 18}F]FBEM, and had a specific activity of 45.51 {+-} 16.28 GBq/{mu}mol (1.23 {+-} 0.44 Ci/{mu}mol, n = 7) at the end of synthesis. The C-terminal isomer, [{sup 18}F]FBEM-[Cys{sup 40}]-exendin-4, had higher affinity for INS-1 tumor cells (IC{sub 50} 1.11 {+-} 0.057 nM) and higher tumor uptake (25.25 {+-} 3.39 %ID/g at 1 h) than the N-terminal isomer, [{sup 18}F]FBEM-[Cys{sup 0}]-exendin-4 (IC{sub 50} 2.99 {+-} 0.06 nM, uptake 7.20 {+-} 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cys{sup x}]-exendin-4 (p < 0.05). [{sup 18}F]FBEM-[Cys{sup 40}]-exendin-4 and [{sup 18}F]FBEM-[Cys{sup 0}]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors

  14. In Vitro Effect of Fatty Acids Identified in the Plasma of Obese Adolescents on the Function of Pancreatic ?-Cells

    OpenAIRE

    Velasquez, Claudia; Vasquez, Juan Sebastian; Balcazar, Norman

    2017-01-01

    Background The increase in circulating free fatty acid (FFA) levels is a major factor that induces malfunction in pancreatic ?-cells. We evaluated the effect of FFAs reconstituted according to the profile of circulating fatty acids found in obese adolescents on the viability and function of the murine insulinoma cell line (mouse insulinoma [MIN6]). Methods From fatty acids obtained commercially, plasma-FFA profiles of three different youth populations were reconstituted: obese with metabolic ...

  15. Quantum walks with infinite hitting times

    International Nuclear Information System (INIS)

    Krovi, Hari; Brun, Todd A.

    2006-01-01

    Hitting times are the average time it takes a walk to reach a given final vertex from a given starting vertex. The hitting time for a classical random walk on a connected graph will always be finite. We show that, by contrast, quantum walks can have infinite hitting times for some initial states. We seek criteria to determine if a given walk on a graph will have infinite hitting times, and find a sufficient condition, which for discrete time quantum walks is that the degeneracy of the evolution operator be greater than the degree of the graph. The set of initial states which give an infinite hitting time form a subspace. The phenomenon of infinite hitting times is in general a consequence of the symmetry of the graph and its automorphism group. Using the irreducible representations of the automorphism group, we derive conditions such that quantum walks defined on this graph must have infinite hitting times for some initial states. In the case of the discrete walk, if this condition is satisfied the walk will have infinite hitting times for any choice of a coin operator, and we give a class of graphs with infinite hitting times for any choice of coin. Hitting times are not very well defined for continuous time quantum walks, but we show that the idea of infinite hitting-time walks naturally extends to the continuous time case as well

  16. Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome

    International Nuclear Information System (INIS)

    Peppa, Melpomeni; Brountzos, Elias; Economopoulos, Nicolaos; Boutati, Eleni; Pikounis, Vasilios; Patapis, Paul; Economopoulos, Theofanis; Raptis, Sotirios A.; Hadjidakis, Dimitrios

    2009-01-01

    Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

  17. MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

    Science.gov (United States)

    Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

    2018-05-21

    High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

  18. Enucleation and limited pancreatic resection provide long-term cure for insulinoma in multiple endocrine neoplasia type 1.

    Science.gov (United States)

    Bartsch, Detlef K; Albers, Max; Knoop, Richard; Kann, Peter H; Fendrich, Volker; Waldmann, Jens

    2013-01-01

    To assess the characteristics and long-term outcome after surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated insulinoma. Retrospective analysis of prospectively collected data of MEN1 patients with organic hyperinsulinism at a tertiary referral center. Thirteen (17%) of 74 patients with MEN1 had organic hyperinsulinism. The median age at diagnosis was 27 (range 9-48) years. In 7 patients insulinoma was the first manifestation of the syndrome. All patients had at least one pancreatic neuroendocrine neoplasm (pNEN) upon imaging, including CT, MRI or endoscopic ultrasonography. Seven patients had solitary lesions upon imaging, 4 patients had one dominant tumor with coexisting multiple small pNENs, and 2 patients had multiple lesions without dominance. Eight patients had limited resections (1 segmental resection, 7 enucleations), 4 subtotal distal pancreatectomies, and 1 patient a partial duodenopancreatectomy. There was no postoperative mortality. Six patients experienced complications, including pancreatic fistula in 5 patients. Pathological examination revealed median three (range 1-14) macro-pNENs sized between 6 and 40 mm, and a total of 14 potentially benign insulinomas were detected in the 13 patients. After median follow-up of 156 months, only 1 patient developed recurrent hyperinsulinism after initial enucleation. Twelve patients developed new pNENs in the pancreatic remnant and 4 patients underwent reoperations (3 for metastatic ZES, 1 for recurrent hyperinsulinism). One of 5 patients with an initial extended pancreatic resection developed insulin-dependent diabetes mellitus. Enucleation and limited resection provide long-term cure for MEN1 insulinoma in patients with solitary or dominant tumors. Subtotal distal pancreatectomy should thus be preserved for patients with multiple pNENs without dominance given the risk of exocrine and endocrine pancreas insufficiency in the mostly young patients. © 2013 S. Karger AG, Basel.

  19. Preparation and evaluation of Exendin radio conjugates for detecting insulinomas and gastrinomas by molecular nuclear medicine techniques; Preparacion y evaluacion de radioconjugados de Exendin para la deteccion de insulinomas y gastrinomas por tecnicas de medicina nuclear molecular

    Energy Technology Data Exchange (ETDEWEB)

    Medina G, V.

    2015-07-01

    The gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) are named based on the secreted hormones. Among them, the insulinomas and gastrinomas represent a diagnostic challenge because of their slow metabolic rate, small size and anatomical location that have limited their detection in some imaging procedures. About 90% of insulinomas are benign and 10% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over express SSTR or GLP-1R in low levels. A kit for the preparation of Lys{sup 27} ({sup 99m}Tc-EDDA/HYNIC)-Exendin(9-39)/{sup 99m}Tc-EDDA/HYNIC-Tyr{sup 3}-Octreotide was developed to detect 100% of gastrinomas and insulinomas. In order to reach this aim, the peptides were radiolabeled and characterized. Stability studies will be completed and the in vitro and in vivo behavior was evaluated. The Lys{sup 27}({sup 99m}Tc-EDDA/HYNIC)-Exendin(9-39)/{sup 99m}Tc-EDDA/HYNIC-Tyr{sup 3}-Octreotide can be labeled with {sup 99m}Tc, obtaining high radiochemical purities (>94%), high stability in human serum and affinity to GLP-1 and SST-2 receptor. This new formulation showed properties suitable for use as a target-specific agent for molecular imaging of GLP-1R/SSTR positive tumors. In vivo micro-SPECT/CT images of Lys{sup 27}({sup 99m}Tc-EDDA/HYNIC)-Exendin(9-39), {sup 99m}Tc-EDDA/HYNIC-Tyr{sup 3}-Octreotide and of the pharmaceutical formulation Lys{sup 27}({sup 99m}Tc-EDDA/HYNIC)-Exendin(9-39)/{sup 99m}Tc-EDDA/HYNIC-Tyr{sup 3}-Octreotide showed the main elimination pathways, and tumors higher uptake compared to the background tissues. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GLP-1R and SSTR. (Author)

  20. Carbohydrate metabolism and quality of life in patients after surgical treatment of insulinoma

    Directory of Open Access Journals (Sweden)

    2014-08-01

    Full Text Available Objectives. T study the quality of life and status of carbohydrate metabolism in patients after surgical treatment insulinoma. Methods: The study involved 20 patients divided in two groups: the first group with a catamnesis duration of up to five years; the second group with a catamnesis duration of more than five years. We studied anthropometric parameters and carbohydrate metabolism as well as psychological questioning of patients using SF-36 questionnaire, the data was considered statistically significant at p<0.05. Results. severe combined postoperative complications were more frequent in the first group (63.6% vs. 22.2%, p=0.07, due to extend of the performed surgery. Adrenergic symptoms prior to the surgery were detected in 90.9% of cases in the first group and in 77.7% of cases in the second group. After treatment these numbers decreased to 36.4% and 11.1% respectively (p=0.039 and 0.026. Neuroglycopeniс symptoms before treatment were detected in 90.9% of cases in the first group and for all patients in the second, while after treatment persisted only in 45.5% and 33.3% of cases respectively (p=0.045 and 0.036. Carbohydrate metabolism have normalized for the majority of patients. Two patients (18.2% of the first group showed impaired glucose tolerance. Improved carbohydrate metabolism was associated with a decrease in body weight in both groups. Results of psychological questionnaires were comparable with the survey data obtained in general population in the Russian Federation. Conclusion. Surgical treatment of insulinomas is highly effective. Physical and psychological status of patients in most cases corresponds with those typical for this age-sex group of the population of the Russian Federation. Long-term treatment results do not depend on duration of the catamnesis. Complications that developed from surgical treatment have the main influence on the health of patients.

  1. Mechanisms of pancreatic beta-cell growth and regeneration

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1989-01-01

    Information about the mechanism of beta-cell growth and regeneration may be obtained by studies of insulinoma cells. In the present study the growth and function of the rat insulinoma cell lines RINm5F and 5AH were evaluated by addition of serum, hormones, and growth factors. It was found...... of insulin mRNA content showed that the insulinoma cells only contained about 2% of that of normal rat beta-cells. These results are discussed in relation to the role of growth factors, oncogenes, and differentiation in the growth and regeneration of beta-cells....... that transferrin is the only obligatory factor whereas growth hormone, epidermal growth factor, fibroblast growth factor, and TRH had modulating effects. A heat-labile heparin binding serum factor which stimulated thymidine incorporation but not cell proliferation was demonstrated in human serum. Measurements...

  2. A combined hit theory-microdosimetric explanation of cellular radiobiological action

    International Nuclear Information System (INIS)

    Bond, V.P.; Varma, M.N.

    1983-01-01

    Hit theory is combined with microdosimetry in a stochastic approach that explains the observed responses of cell populations exposed in radiation fields of different qualities. The central thesis is that to expose a population of cells in a low-level radiation field is to subject the cells to the potential for interaction with charged particles, quantifiable in terms of the charged particle fluence PHI. When such an interaction occurs there is resulting stochastic transfer of energy to a critical volume (CV) of cross-section σ within the cell(s). The severity of cell injury is dependent on the amount of energy thus imparted, or the hit size. If the severity is above some minimal level, there is a non-zero probability that the injury will result in a quantal effect (e.g., a mutational or carcinogenic initial event, cell transformation). A microdosimetric proportional counter, viewed here as a phantom cell CV that permits measurements not possible in the living cell, is used to determine the incidence of hit cells and the spectrum of hit sizes. Each hit is then weighted on the basis of an empirically determined function that provides the fraction of cells responding quantally, as a function of hit size. The sum of the hits so weighted provides the incidence of quantally responding cells, for any amount of exposure PHI in a radiation field of any quality or mixture of qualities. The hit size weighting function for pink mutations in Tradescantia is discussed, as are its implications in terms of a replacement for relative biological effectiveness and dose equivalent. (author)

  3. Pattern recognition with vector hits

    International Nuclear Information System (INIS)

    Frühwirth, R

    2012-01-01

    Trackers at the future high-luminosity LHC, designed to have triggering capability, will feature layers of stacked modules with a small stack separation. This will allow the reconstruction of track stubs or vector hits with position and direction information, but lacking precise curvature information. This opens up new possibilities for track finding, online and offline. Two track finding methods, the Kalman filter and the convergent Hough transform are studied in this context. Results from a simplified fast simulation are presented. It is shown that the performance of the methods depends to a large extent on the size of the stack separation. We conclude that the detector design and the choice of the track finding algorithm(s) are strongly coupled and should proceed conjointly.

  4. 77 FR 23250 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Science.gov (United States)

    2012-04-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

  5. 76 FR 25355 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Science.gov (United States)

    2011-05-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

  6. 78 FR 29134 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Science.gov (United States)

    2013-05-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

  7. Developing Health Information Technology (HIT) Programs and HIT Curriculum: The Southern Polytechnic State University Experience

    Science.gov (United States)

    Zhang, Chi; Reichgelt, Han; Rutherfoord, Rebecca H.; Wang, Andy Ju An

    2014-01-01

    Health Information Technology (HIT) professionals are in increasing demand as healthcare providers need help in the adoption and meaningful use of Electronic Health Record (EHR) systems while the HIT industry needs workforce skilled in HIT and EHR development. To respond to this increasing demand, the School of Computing and Software Engineering…

  8. Insulinoma imaging with glucagon-like peptide-1 receptor targeting probe (18)F-FBEM-Cys (39)-exendin-4.

    Science.gov (United States)

    Xu, Yuping; Pan, Donghui; Xu, Qing; Zhu, Chen; Wang, Lizhen; Chen, Fei; Yang, Runlin; Luo, Shineng; Yang, Min

    2014-09-01

    Glucagon-like peptide-1 receptor (GLP-1R) is a specific target for insulinomas imaging since it is overexpressed in the tumor. Exendin-4 exhibits high affinity for the GLP-1R. In this study, a novel (18)F-labeled exendin-4 analog, (18)F-FBEM-Cys(39)-exendin-4, was synthesized and its potentials for GLP-1R imaging were also evaluated. (18)F-FBEM was synthesized by coupling (18)F-fluorobenzoic acid ((18)F-FBA) with N-(2-aminoethyl) maleimide, and the reaction conditions were optimized. Cys(39)-exendin-4 was then conjugated with (18)F-FBEM to obtain (18)F-FBEM-Cys(39)-exendin-4. The GLP-1R targeting potential and pharmacokinetic profile of the tracer were analyzed in INS-1 insulinoma and MDA-MB-435 breast tumor model, respectively. Under the optimal conditions, the yield of radiolabeled (18)F-FBEM was 49.1 ± 2.0 % (based on (18)F-FBA, non-decay corrected). The yield of (18)F-FBEM-Cys(39)-exendin-4 was 35.1 ± 2.6 % (based on the starting (18)F-FBEM, non-decay corrected). The radiochemical purity of (18)F-FBEM-Cys(39)-exendin-4 is >95 %, and the specific activity was at least 35 GBq/μmol. The GLP-1R-positive INS-1 insulinoma xenograft was clearly visible with good contrast to background, whereas GLP-1R-negative MDA-MB435 breast tumor was barely visible. Low levels of radioactivity were also detected at pancreas and lungs due to few GLP-1R expressions. GLP-1R binding specificity was demonstrated by reduced INS-1 tumor uptake of the tracer after coinjection with an excess of unlabeled Cys(39)-exendin-4 at 1 h postinjection. The thiol-reactive reagent, (18)F-FBEM, was prepared with high yield and successfully conjugated to Cys(39)-exendin-4. Favorable preclinical data showing specific and effective tumor targeting by (18)F-FBEM-Cys(39)-exendin-4 suggest that the tracer may be a potential probe for insulinomas imaging.

  9. Constructive Technology Assessment for HIT development

    DEFF Research Database (Denmark)

    Høstgaard, Anna Marie Balling; Bertelsen, Pernille; Petersen, Lone Stub

    2013-01-01

    Experience and time has shown a need for new evaluation methods for evaluating Health Information Technology (HIT), as summative evaluation methods fail to accommodate the rapid and constant changes in HIT over time and to involve end-users, which has been recognized as an important success facto...... during all the phases in the process. Thereby anumber of problems were prevented to occur later on.Thus, the CTA method and its framework are useful for evaluators and project-management in order to facilitate and support successful HIT development....

  10. The validation of Huffaz Intelligence Test (HIT)

    Science.gov (United States)

    Rahim, Mohd Azrin Mohammad; Ahmad, Tahir; Awang, Siti Rahmah; Safar, Ajmain

    2017-08-01

    In general, a hafiz who can memorize the Quran has many specialties especially in respect to their academic performances. In this study, the theory of multiple intelligences introduced by Howard Gardner is embedded in a developed psychometric instrument, namely Huffaz Intelligence Test (HIT). This paper presents the validation and the reliability of HIT of some tahfiz students in Malaysia Islamic schools. A pilot study was conducted involving 87 huffaz who were randomly selected to answer the items in HIT. The analysis method used includes Partial Least Square (PLS) on reliability, convergence and discriminant validation. The study has validated nine intelligences. The findings also indicated that the composite reliabilities for the nine types of intelligences are greater than 0.8. Thus, the HIT is a valid and reliable instrument to measure the multiple intelligences among huffaz.

  11. FO-SPR based dextrose sensor using Ag/ZnO nanorods/GOx for insulinoma detection.

    Science.gov (United States)

    Usha, Sruthi P; Shrivastav, Anand M; Gupta, Banshi D

    2016-11-15

    In this piece of work, a fiber optic sensor has been fabricated and characterized using surface plasmon resonance for dextrose sensing. The concentration range used in this study is for diagnosing the cases of hypoglycaemia especially in suppression tests of insulinoma. Insulinoma is a medical case in which the person is recognized being hypoglycaemic with the blood dextrose level falling down to 2.2mM or less. Thus, the sensor has been characterized for the dextrose concentration range of 0 mM-10mM including the cases of normal blood dextrose range. Coatings of silver layer and zinc oxide nanorods have been carried out on the bare core fiber with a dual role of zinc oxide followed by immobilization of glucose oxidase. A three stage optimization procedure has been adopted for the best performance of the sensor. Absorbance spectra have been plotted and peak absorbance wavelengths have been extracted for each concentration chosen along with the sensitivities. The results have been made conclusive with control experiments. The probe has also been tested on sample having blood serum to check the reliability of the sensor. The sensor shows better selectivity and response time along with its real time applications, online monitoring, remote sensing and reusability. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Development of pulsation technique for single ion hit system

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Takuro; Hamano, Tsuyoshi; Hirao, Toshio; Kamiya, Tomihiro [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1996-12-01

    When a high energy heavy ion enters into a substance, high density of ionization and excitement occurrs along its flying trace. Especially, when such an ion enters into a semiconductor cell, a bit inversion called single event is occurred or a phenomenon destroyed element itself on case of the worst is formed. The present semiconductor cell is made in a size of some micron square, as different from its accumulated degree. In order to analyze the single event phenomenon formed by entering ion into such fine region in detail, a technique possible enter heavy ion beam with space resolution under 1 micron to each sample is necessary. In order to develop this technique, a static type high speed beam switch for control of entering a beam into a sample and a single ion detector for detecting entrance of ion into the sample were installed to heavy ion microbeam forming apparatus. The single ion hit system in Takasaki Radiation Chemistry Research Establishment, JAERI succeeded in detection and control technique of the single ion and control of noise due to pulsization and finished development of basic technique of the single ion hit, since now. After today, it is planned to hit actually the single ion onto the sample and evaluate its accuracy. (G.K.)

  13. Tolosa-Hunt Syndrome in Double-Hit Lymphoma

    Directory of Open Access Journals (Sweden)

    Prakash Peddi

    2015-01-01

    Full Text Available Tolosa-Hunt syndrome (THS is a painful condition characterized by hemicranial pain, retroorbital pain, loss of vision, oculomotor nerve paralysis, and sensory loss in distribution of ophthalmic and maxillary division of trigeminal nerve. Lymphomas rarely involve cavernous sinus and simulate Tolosa-Hunt syndrome. Here we present a first case of double-hit B cell lymphoma (DHL relapsing and masquerading as Tolosa-Hunt syndrome. The neurological findings were explained by a lymphomatous infiltration of the right Gasserian ganglion which preceded systemic relapse. As part of this report, the diagnostic criteria for Tolosa-Hunt syndrome and double-hit lymphoma are reviewed and updated treatment recommendations are presented.

  14. Inflammatory Effects of Menthol vs. Non-menthol Cigarette Smoke Extract on Human Lung Epithelial Cells: A Double-Hit on TRPM8 by Reactive Oxygen Species and Menthol

    Directory of Open Access Journals (Sweden)

    Tzong-Shyuan Lee

    2017-04-01

    difference in these responses between the both CSE types using HBECs with TRPM8 knockdown and TRPM8 knockout, and using HEK293 cells transfected with hTRPM8. Thus, compared with exposure to Non-M-CSE, exposure to M-CSE induced greater TRPM8-mediated inflammatory responses in HBECs. These augmented effects may be due to a double-hit on lung epithelial TRPM8 by ROS generated from CSE and the menthol in M-CSE.

  15. Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

    NARCIS (Netherlands)

    Robben, J.H.; Brom, W.E. van den; Mol, J.A.; Haeften, T.W. van; Rijnberk, A.

    2006-01-01

    The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 lg

  16. A case of insulinoma with non-alcoholic fatty liver disease: Roles of hyperphagia and hyperinsulinemia in pathogenesis of the disease.

    Science.gov (United States)

    Rokutan, Mariyo; Yabe, Daisuke; Komoto, Izumi; Kurose, Takeshi; Kawai, Jun; Nakamura, Takefumi; Imamura, Masayuki; Seino, Yutaka

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a serious health-related condition all over the world; the number of patients is increasing in Asian countries including Japan. Better understanding of its pathophysiology is required to develop effective therapeutics, as patients may go on to develop non-alcoholic steatohepatitis and hepatocellular carcinomas. While NAFLD is believed to be associated with metabolic risk factors such as obesity, diabetes, and dyslipidemia, its etiology remains largely unknown and the development or co-existence of NAFLD in patients with insulinoma has not been investigated. A 33-year-old male with an insulinoma, who had been hypoglycemic during the previous four years, developed abnormally elevated levels of liver enzymes and histological fatty liver characteristic of NAFLD by the time of admission to our hospital for resection of an insulinoma. His medical records for the previous eight years revealed that his bodyweight had increased gradually from 60 kg to 71 kg for seven years and then acutely increased to 79 kg in the latest one-year period. This sudden increase was thought to be due to the patient's self-described overeating of fruits to forestall hypoglycemia. Fresh fruits are rich in fructose, and the patient's triglycerides, alanine and aspartate transaminases showed an acute increase in the previous one-year period. After resection of the insulinoma, the levels of these parameters all were mostly restored, which suggests that hyperinsulinemia and subsequent hyperphagia played a role in the development of NAFLD in this case. This is the first report of patient with NAFLD and an insulinoma.

  17. Loss of Serglycin Promotes Primary Tumor Growth and Vessel Functionality in the RIP1-Tag2 Mouse Model for Spontaneous Insulinoma Formation.

    Directory of Open Access Journals (Sweden)

    Andrew Hamilton

    Full Text Available The serglycin proteoglycan is mainly expressed by hematopoietic cells where the major function is to retain the content of storage granules and vesicles. In recent years, expression of serglycin has also been found in different forms of human malignancies and a high serglycin expression level has been correlated with a more migratory and invasive phenotype in the case of breast cancer and nasopharyngeal carcinoma. Serglycin has also been implicated in the development of the tumor vasculature in multiple myeloma and hepatocellular carcinoma where reduced expression of serglycin was correlated with a less extensive vasculature. To further investigate the contribution of serglycin to tumor development, we have used the immunocompetent RIP1-Tag2 mouse model of spontaneous insulinoma formation crossed into serglycin deficient mice. For the first time we show that serglycin-deficiency affects orthotopic primary tumor growth and tumor vascular functionality of late stage carcinomas. RIP1-Tag2 mice that lack serglycin develop larger tumors with a higher proliferative activity but unaltered apoptosis compared to normal RIP1-Tag2 mice. The absence of serglycin also enhances the tumor vessel functionality, which is better perfused than in tumors from serglycin wild type mice. The presence of the pro-angiogenic modulators vascular endothelial growth factor and hepatocyte growth factor were decreased in the serglycin deficient mice which suggests a less pro-angiogenic environment in the tumors of these animals. Taken together, we conclude that serglycin affects multiple aspects of spontaneous tumor formation, which strengthens the theory that serglycin acts as an important mediator in the formation and progression of tumors.

  18. NIMROD Simulations of the HIT-SI and HIT-SI3 Devices

    Science.gov (United States)

    Morgan, Kyle; Jarboe, Tom; Hossack, Aaron; Chandra, Rian; Everson, Chris

    2017-10-01

    The Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI) experiment uses a set of inductively driven helicity injectors to apply non-axisymmetric current drive on the edge of the plasma, driving an axisymmetric spheromak equilibrium in a central confinement volume. Significant improvements have been made to extended MHD modeling of HIT-SI, with both the resolution of disagreement at high injector frequencies in HIT-SI in addition to successes with the new upgraded HIT-SI3 device. Previous numerical studies of HIT-SI, using a zero-beta eMHD model, focused on operations with a drive frequency of 14.5 kHz, and found reduced agreement with both the magnetic profile and current amplification at higher frequencies (30-70 kHz). HIT-SI3 has three helicity injectors which are able to operate with different mode structures of perturbations through the different relative temporal phasing of the injectors. Simulations that allow for pressure gradients have been performed in the parameter regimes of both devices using the NIMROD code and show improved agreement with experimental results, most notably capturing the observed Shafranov-shift due to increased beta observed at higher finj in HIT-SI and the variety of toroidal perturbation spectra available in HIT-SI3. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Award Number DE-FG02- 96ER54361.

  19. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

    Science.gov (United States)

    Zhou, Xiao Yi; Lu, Xinyan; Raparia, Kirtee; Chen, Yi-Hua

    2018-06-01

    Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy.

  20. A freeze-dried kit formulation for the preparation of Lys27(99mTc-EDDA/HYNIC)-Exendin(9-39)/99mTc-EDDA/HYNIC-Tyr3-Octreotide to detect benign and malignant insulinomas

    International Nuclear Information System (INIS)

    Medina-García, Veronica; Ocampo-García, Blanca E.; Ferro-Flores, Guillermina; Santos-Cuevas, Clara L.; Aranda-Lara, Liliana; García-Becerra, Rocio; Ordaz-Rosado, David; Melendez-Alafort, Laura

    2015-01-01

    About 90% of insulinomas are benign and 5%–15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over-express SSTR or GLP-1R in low levels. A kit for the preparation of Lys 27 ( 99m Tc-EDDA/HYNIC)-Exendin(9-39)/ 99m Tc-EDDA/HYNIC-Tyr 3 Octreotide was formulated to detect 100% of insulinomas. The formulation showed radiochemical purity of 97 ± 1%, high stability in human serum, and GLP-1R and SSTR affinity. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GRP-1R- and/or SSTR-positive tumors.

  1. A freeze-dried kit formulation for the preparation of Lys(27)(99mTc-EDDA/HYNIC)-Exendin(9-39)/99mTc-EDDA/HYNIC-Tyr3-Octreotide to detect benign and malignant insulinomas.

    Science.gov (United States)

    Medina-García, Veronica; Ocampo-García, Blanca E; Ferro-Flores, Guillermina; Santos-Cuevas, Clara L; Aranda-Lara, Liliana; García-Becerra, Rocio; Ordaz-Rosado, David; Melendez-Alafort, Laura

    2015-12-01

    About 90% of insulinomas are benign and 5%-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over-express SSTR or GLP-1R in low levels. A kit for the preparation of Lys(27)((99m)Tc-EDDA/HYNIC)-Exendin(9-39)/(99m)Tc-EDDA/HYNIC-Tyr(3)Octreotide was formulated to detect 100% of insulinomas. The formulation showed radiochemical purity of 97±1%, high stability in human serum, and GLP-1R and SSTR affinity. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GRP-1R- and/or SSTR-positive tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Statistical properties and pre-hit dynamics of price limit hits in the Chinese stock markets.

    Science.gov (United States)

    Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

    2015-01-01

    Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders' short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners.

  3. Statistical Properties and Pre-Hit Dynamics of Price Limit Hits in the Chinese Stock Markets

    Science.gov (United States)

    Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

    2015-01-01

    Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders’ short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners. PMID:25874716

  4. Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

    DEFF Research Database (Denmark)

    Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

    2012-01-01

    Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

  5. Upgrade tracking with the UT Hits

    CERN Document Server

    Gandini, P; Wang, J

    2014-01-01

    The performance of the LHCb tracking system for the upgrade on long tracks is evaluated in terms of efficiency and ghost rate reduction for several different sets of requirements. We find that the efficiency is quite high and that the ghost rate reduction is substantial. We also describe the current algorithm for adding UT hits to the tracks.

  6. "Hit-and-Run" leaves its mark: catalyst transcription factors and chromatin modification.

    Science.gov (United States)

    Varala, Kranthi; Li, Ying; Marshall-Colón, Amy; Para, Alessia; Coruzzi, Gloria M

    2015-08-01

    Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome-wide evidence for a "Hit-and-Run" model of transcription. In this model, a master TF "hits" a target promoter to initiate a rapid response to a signal. As the "hit" is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the "run", the master TF "hits" other targets to propagate the response genome-wide. As such, a TF may act as a "catalyst" to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long-term adaptive behavior in the whole organism. This "Hit-and-Run" model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF-regulated and TF-bound genes, implicating transient TF-target binding. Here, we explore this "Hit-and-Run" model to suggest molecular mechanisms and its biological relevance. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

  7. LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes.

    Science.gov (United States)

    Carlson, Hanqian L; Quinn, Jeffrey J; Yang, Yul W; Thornburg, Chelsea K; Chang, Howard Y; Stadler, H Scott

    2015-12-01

    Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage.

  8. Stochastic, weighted hit size theory of cellular radiobiological action

    International Nuclear Information System (INIS)

    Bond, V.P.; Varma, M.N.

    1982-01-01

    A stochastic theory that appears to account well for the observed responses of cell populations exposed in radiation fields of different qualities and for different durations of exposure is described. The theory appears to explain well most cellular radiobiological phenomena observed in at least autonomous cell systems, argues for the use of fluence rate (phi) instead of absorbed dose for quantification of the amount of radiation involved in low level radiation exposure. With or without invoking the cell sensitivity function, the conceptual improvement would be substantial. The approach suggested also shows that the absorbed dose-cell response functions currently employed do not reflect the spectrum of cell sensitivities to increasing cell doses of a single agent, nor can RBE represent the potency ratio for different agents that can produce similar quantal responses. Thus, for accurate comparison of cell sensitivities among different cells in the same individual, or between the cells in different kinds of individuals, it is necessary to quantify cell sensitivity in terms of the hit size weighting or cell sensitivity function introduced here. Similarly, this function should be employed to evaluate the relative potency of radiation and other radiomimetic chemical or physical agents

  9. Health Information Technology (HIT) Adaptation: Refocusing on the Journey to Successful HIT Implementation.

    Science.gov (United States)

    Yen, Po-Yin; McAlearney, Ann Scheck; Sieck, Cynthia J; Hefner, Jennifer L; Huerta, Timothy R

    2017-09-07

    In past years, policies and regulations required hospitals to implement advanced capabilities of certified electronic health records (EHRs) in order to receive financial incentives. This has led to accelerated implementation of health information technologies (HIT) in health care settings. However, measures commonly used to evaluate the success of HIT implementation, such as HIT adoption, technology acceptance, and clinical quality, fail to account for complex sociotechnical variability across contexts and the different trajectories within organizations because of different implementation plans and timelines. We propose a new focus, HIT adaptation, to illuminate factors that facilitate or hinder the connection between use of the EHR and improved quality of care as well as to explore the trajectory of changes in the HIT implementation journey as it is impacted by frequent system upgrades and optimizations. Future research should develop instruments to evaluate the progress of HIT adaptation in both its longitudinal design and its focus on adaptation progress rather than on one cross-sectional outcome, allowing for more generalizability and knowledge transfer. ©Po-Yin Yen, Ann Scheck McAlearney, Cynthia J Sieck, Jennifer L Hefner, Timothy R Huerta. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 07.09.2017.

  10. Post-hit dynamics of price limit hits in the Chinese stock markets

    Science.gov (United States)

    Wu, Ting; Wang, Yue; Li, Ming-Xia

    2017-01-01

    Price limit trading rules are useful to cool off traders short-term trading mania on individual stocks. The price dynamics approaching the limit boards are known as the magnet effect. However, the price dynamics after opening price limit hits are not well investigated. Here, we provide a detailed analysis on the price dynamics after the hits of up-limit or down-limit is open based on all A-share stocks traded in the Chinese stock markets. A "W" shape is found in the expected return, which reveals high probability of a continuous price limit hit on the following day. We also find that price dynamics after opening limit hits are dependent on the market trends. The time span of continuously hitting the price limit is found to an influence factor of the expected profit after the limit hit is open. Our analysis provides a better understanding of the price dynamics around the limit boards and contributes potential practical values for investors.

  11. On the Hitting Probability of Max-Stable Processes

    OpenAIRE

    Hofmann, Martin

    2012-01-01

    The probability that a max-stable process {\\eta} in C[0, 1] with identical marginal distribution function F hits x \\in R with 0 < F (x) < 1 is the hitting probability of x. We show that the hitting probability is always positive, unless the components of {\\eta} are completely dependent. Moreover, we consider the event that the paths of standard MSP hit some x \\in R twice and we give a sufficient condition for a positive probability of this event.

  12. Simplified validation of borderline hits of database searches

    OpenAIRE

    Thomas, Henrik; Shevchenko, Andrej

    2008-01-01

    Along with unequivocal hits produced by matching multiple MS/MS spectra to database sequences, LC-MS/MS analysis often yields a large number of hits of borderline statistical confidence. To simplify their validation, we propose to use rapid de novo interpretation of all acquired MS/MS spectra and, with the help of a simple software tool, display the candidate sequences together with each database search hit. We demonstrate that comparing hit database sequences and independent de novo interpre...

  13. 78 FR 29135 - HIT Standards Committee Advisory Meeting

    Science.gov (United States)

    2013-05-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting AGENCY: Office of...: HIT Standards Committee. General Function of the Committee: To provide recommendations to the National... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy Committee...

  14. Cosmic Ray Hit Detection with Homogenous Structures

    Science.gov (United States)

    Smirnov, O. M.

    Cosmic ray (CR) hits can affect a significant number of pixels both on long-exposure ground-based CCD observations and on the Space Telescope frames. Thus, methods of identifying the damaged pixels are an important part of the data preprocessing for practically any application. The paper presents an implementation of a CR hit detection algorithm based on a homogenous structure (also called cellular automata ), a concept originating in artificial intelligence and dicrete mathematics. Each pixel of the image is represented by a small automaton, which interacts with its neighbors and assumes a distinct state if it ``decides'' that a CR hit is present. On test data, the algorithm has shown a high detection rate (~0.7 ) and a low false alarm rate (frame. A homogenous structure is extremely trainable, which can be very important for processing large batches of data obtained under similar conditions. Training and optimizing issues are discussed, as well as possible other applications of this concept to image processing.

  15. All hypertopologies are hit-and-miss

    Directory of Open Access Journals (Sweden)

    Somshekhar Naimpally

    2002-04-01

    Full Text Available We solve a long standing problem by showing that all known hypertopologies are hit-and-miss. Our solution is not merely of theoretical importance. This representation is useful in the study of comparison of the Hausdorff-Bourbaki or H-B uniform topologies and the Wijsman topologies among themselves and with others. Up to now some of these comparisons needed intricate manipulations. The H-B uniform topologies were the subject of intense activity in the 1960's in connection with the Isbell-Smith problem. We show that they are proximally locally finite topologies from which the solution to the above problem follows easily. It is known that the Wijsman topology on the hyperspace is the proximal ball (hit-and-miss topology in”nice” metric spaces including the normed linear spaces. With the introduction of a new far-miss topology we show that the Wijsman topology is hit-and-miss for all metric spaces. From this follows a natural generalization of the Wijsman topology to the hyperspace of any T1 space. Several existing results in the literature are easy consequences of our work.

  16. 99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma

    Science.gov (United States)

    Sowa-Staszczak, Anna; Trofimiuk-Müldner, Małgorzata; Stefańska, Agnieszka; Tomaszuk, Monika; Buziak-Bereza, Monika; Gilis-Januszewska, Aleksandra; Jabrocka-Hybel, Agata; Głowa, Bogusław; Małecki, Maciej; Bednarczuk, Tomasz; Kamiński, Grzegorz; Kowalska, Aldona; Mikołajczak, Renata; Janota, Barbara; Hubalewska-Dydejczyk, Alicja

    2016-01-01

    Introduction The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. Materials and Methods Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. Results Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). Conclusions 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective

  17. Evaluation of an [18F]AlF-NOTA Analog of Exendin-4 for Imaging of GLP-1 Receptor in Insulinoma

    Directory of Open Access Journals (Sweden)

    Dale O. Kiesewetter, Ning Guo, Jinxia Guo, Haokao Gao, Lei Zhu, Ying Ma, Gang Niu, Xiaoyuan Chen

    2012-01-01

    Full Text Available Introduction: The GLP-1 receptor plays an important role in glucose homeostasis and thus is a very important target for diabetes therapy. The receptor is also overexpressed in insulinoma, a tumor of pancreatic beta-cells. We previously evaluated two fluorine-18-labeled analogs of exendin-4 prepared by conjugation with [18F]FBEM (N-[2-(4-[18F]fluorobenzamideethyl]maleimide. Both compounds demonstrated good tumor uptake, but the synthesis of the radiotracers was time consuming. To overcome this challenge, we developed a NOTA analog and performed radiolabeling using aluminum [18F]fluoride complexation.Methods: Cys40-exendin-4 was conjugated with NOTA mono N-ethylmaleimide. [18F]AlF conjugation was conducted and the radiolabeled product purified by preparative HPLC. Dynamic and static PET imaging scans were conducted on nude mice with established INS-1 xenografts. Uptake of tumor and other major organs in static images was quantitated (%ID/g and comparison with blocking studies was made. PET quantification was also compared with ex vivo biodistribution results.Results: The radiosynthesis provided [18F]AlF-NOTA-MAL-cys40-exendin-4 in 23.6 ± 2.4 % radiochemical yield (uncorrected, n = 3 after HPLC; the process required about 55 min. The specific activity at time of injection ranged from 19.6 to 31.4 GBq (0.53-0.85 Ci/µmol. Tumor uptake had reached its maximum (16.09 ± 1.18% ID/g, n = 4 by 5 min and remained nearly constant for the duration of the study. Kidney uptake continued to increase throughout the entire one hour time course. Pre-injection of exendin-4 caused a marked reduction in tissue uptake with the major exception of liver and kidneys, in which uptake was not affected. HPLC analysis of the radioactive components in extracts of the tumor and plasma showed primarily parent compound at 60 min post-injection, whereas extracts of kidney and urine contained exclusively one polar radioactive component.Conclusion: The radiotracer is prepared in

  18. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis.

    Science.gov (United States)

    Padmanabhan, Anand; Jones, Curtis G; Bougie, Daniel W; Curtis, Brian R; McFarland, Janice G; Wang, Demin; Aster, Richard H

    2015-01-01

    Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain "delayed HIT" seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. © 2015 by The American Society of Hematology.

  19. Eyewitness Identification Reforms: Are Suggestiveness-Induced Hits and Guesses True Hits?

    Science.gov (United States)

    Wells, Gary L; Steblay, Nancy K; Dysart, Jennifer E

    2012-05-01

    Research-based reforms for collecting eyewitness identification evidence (e.g., unbiased pre-lineup instructions, double-blind administration) have been proposed by psychologists and adopted in increasing numbers of jurisdictions across the United States. It is well known that reducing rates of mistaken identifications can also reduce accurate identification rates (hits). But the reforms are largely designed to reduce the suggestiveness of the procedures they are meant to replace. Accordingly, we argue that it is misleading to label any hits obtained because of suggestive procedures as "hits" and then saddle reforms with the charge that they reduce the rate of these illegitimate hits. Eyewitness identification evidence should be based solely on the independent memory of the witness, not aided by biased instructions, cues from lineup administrators, or the use of lineup fillers who make the suspect stand out. Failure to call out these hits as being illegitimate can give solace to those who are motivated to preserve the status quo. © The Author(s) 2012.

  20. Expression of the growth hormone receptor gene in insulin producing cells

    DEFF Research Database (Denmark)

    Møldrup, Annette; Billestrup, N; Nielsen, Jens Høiriis

    1990-01-01

    Growth hormone (GH) plays a dual role in glucose homeostasis. On the one hand, it exerts an insulin antagonistic effect on the peripheral tissue, on the other hand, it stimulates insulin biosynthesis and beta-cell proliferation. The expression of GH-receptors on the rat insulinoma cell line RIN-5...

  1. Health information technology knowledge and skills needed by HIT employers.

    Science.gov (United States)

    Fenton, S H; Gongora-Ferraez, M J; Joost, E

    2012-01-01

    To evaluate the health information technology (HIT) workforce knowledge and skills needed by HIT employers. Statewide face-to-face and online focus groups of identified HIT employer groups in Austin, Brownsville, College Station, Dallas, El Paso, Houston, Lubbock, San Antonio, and webinars for rural health and nursing informatics. HIT employers reported needing an HIT workforce with diverse knowledge and skills ranging from basic to advanced, while covering information technology, privacy and security, clinical practice, needs assessment, contract negotiation, and many other areas. Consistent themes were that employees needed to be able to learn on the job and must possess the ability to think critically and problem solve. Many employers wanted persons with technical skills, yet also the knowledge and understanding of healthcare operations. The HIT employer focus groups provided valuable insight into employee skills needed in this fast-growing field. Additionally, this information will be utilized to develop a statewide HIT workforce needs assessment survey.

  2. PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

    Science.gov (United States)

    Haile, Lydia A; Rao, Roshni; Polumuri, Swamy K; Arepally, Gowthami M; Keire, David A; Verthelyi, Daniela; Sommers, Cynthia D

    2017-11-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies developed in response to multi-molecular complexes formed by platelet factor 4 (PF4) bound to heparin or cell surface glycosaminoglycans. These antibody complexes activate platelets and monocytes typically through FcγRIIA receptors increasing the production of PF4, inflammatory mediators, tissue factor and thrombin. The influence of underlying events in HIT including complex-induced pro-inflammatory cell activation and structural determinants leading to local inflammatory responses are not fully understood. The stoichiometry and complex component requirements were determined by incubating fresh peripheral blood mononuclear cells (PBMC) with different concentrations of unfractionated heparin (H), low molecular weight heparin (LMWH), PF4- and anti-PF4-H complex antibodies (KKO). Cytokine mRNA or protein were measured by qRT-PCR or Meso Scale Discovery technology, respectively. Gene expression profile analysis for 594 genes was performed using Nanostring technology and analyzed using Ingenuity Pathway Analysis software. The data show that antibodies magnify immune responses induced in PBMCs by PF4 alone or in complex with heparin or LMWH. We propose that following induction of HIT antibodies by heparin-PF4 complexes, binding of the antibodies to PF4 is sufficient to induce a local pro-inflammatory response which may play a role in the progression of HIT. In vitro assays using PBMCs may be useful in characterizing local inflammatory and innate immune responses induced by HIT antibodies in the presence of PF4 and different sources of heparins. The findings and conclusions in this article are solely the responsibility of the authors and are not being formally disseminated by the Food and Drug Administration. Thus, they should not be

  3. Gorlin syndrome with an ovarian leiomyoma associated with a PTCH1 second hit.

    Science.gov (United States)

    Akizawa, Yoshika; Miyashita, Toshiyuki; Sasaki, Ryo; Nagata, Reiko; Aoki, Ryoko; Ishitani, Ken; Nagashima, Yoji; Matsui, Hideo; Saito, Kayoko

    2016-04-01

    We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS. © 2016 Wiley Periodicals, Inc.

  4. Hype, Hope, and Hit in Movies

    DEFF Research Database (Denmark)

    Dholakia, Nikhilesh; Turcan, Romeo V.

    2012-01-01

    This paper is part of an ongoing project to develop an interdisciplinary metatheory of bubbles, relevant to the contemporary era of globalization and rapid, technology-aided communication flows. Just in the first few years of the 21st century, several bubbles have appeared – the so-called dotcom ...... cultural field where relatively small bubbles may form. Movies represent a good arena to examine cultural bubbles on a scale that is not daunting, and where the hype-hope-hit dynamics can be observed more frequently than in most other settings....

  5. The Rock that Hit New York

    Energy Technology Data Exchange (ETDEWEB)

    Meade, Roger Allen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Keksis, August Lawrence [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-03

    On January 12, 1975, a rock seemed to fall from the sky over New York State’s Schoharie County hitting the tractor of a local farmer, who was “preparing his fields for spring planting.” As the farmer later described the event to a reporter from the UFO INVESTIGATOR, the object glanced off the tractor, fell to the ground, and melted its way through a patch of ice that was two and one half inches thick. The farmer, Leonard Tillapaugh, called the county sheriff, Harvey Stoddard, who recovered the rock, noting that it “was still warm.” Why and how a sample of the rock came to Los Alamos is not known. However, it captivated a wide Laboratory audience, was subjected to rigorous testing and evaluation. Los Alamos used the scientific method in the manner promoted by Hynek. Did Los Alamos solve the mystery of the rock’s origin? Not definitively. Although the exact origin could not be determined, it was shown conclusively that the rock was not from outer space. With that said, the saga of Rock that hit New York came to an end. Nothing more was said or written about it. The principals involved have long since passed from the scene. The NICAP ceased operations in 1980. And, the rock, itself, has disappeared.

  6. Multiple-hit parameter estimation in monolithic detectors.

    Science.gov (United States)

    Hunter, William C J; Barrett, Harrison H; Lewellen, Tom K; Miyaoka, Robert S

    2013-02-01

    We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%-12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied.

  7. High energy ion hit technique to local area using microbeam

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Ryuichi; Kamiya, Tomihiro; Suda, Tamotsu; Sakai, Takuro; Hirao, Toshio; Kobayashi, Yasuhiko; Watanabe, Hiroshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1997-03-01

    Single energetic ion hit technique has been developed as an application of ion microbeam technique, in order to study the effect of local damage or injury to materials and living organisms. The overall performance is basically defined by those of separate techniques: microbeam formation, microbeam positioning, single ion detection, detection signal processing, hit timing control, and hit verification. Recent progress on the developments of these techniques at JAERI-TIARA facility are reviewed. (author)

  8. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma

    Directory of Open Access Journals (Sweden)

    Xiao Yi Zhou

    2018-06-01

    Full Text Available Purpose: Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. Observations: A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Conclusions and importance: Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy. Keywords: Lymphoma, Triple-hit lymphoma, Orbital mass

  9. Recent Improvements in the SHIELD-HIT Code

    DEFF Research Database (Denmark)

    Hansen, David Christoffer; Lühr, Armin Christian; Herrmann, Rochus

    2012-01-01

    Purpose: The SHIELD-HIT Monte Carlo particle transport code has previously been used to study a wide range of problems for heavy-ion treatment and has been benchmarked extensively against other Monte Carlo codes and experimental data. Here, an improved version of SHIELD-HIT is developed concentra......Purpose: The SHIELD-HIT Monte Carlo particle transport code has previously been used to study a wide range of problems for heavy-ion treatment and has been benchmarked extensively against other Monte Carlo codes and experimental data. Here, an improved version of SHIELD-HIT is developed...

  10. A Two-Hit Model of Autism: Adolescence as the Second Hit

    Science.gov (United States)

    Picci, Giorgia; Scherf, K. Suzanne

    2015-01-01

    Adolescence brings dramatic changes in behavior and neural organization. Unfortunately, for some 30% of individuals with autism, there is marked decline in adaptive functioning during adolescence. We propose a two-hit model of autism. First, early perturbations in neural development function as a “first hit” that sets up a neural system that is “built to fail” in the face of a second hit. Second, the confluence of pubertal hormones, neural reorganization, and increasing social demands during adolescence provides the “second hit” that interferes with the ability to transition into adult social roles and levels of adaptive functioning. In support of this model, we review evidence about adolescent-specific neural and behavioral development in autism. We conclude with predictions and recommendations for empirical investigation about several domains in which developmental trajectories for individuals with autism may be uniquely deterred in adolescence. PMID:26609500

  11. Current insights into the laboratory diagnosis of HIT.

    Science.gov (United States)

    Bakchoul, T; Zöllner, H; Greinacher, A

    2014-06-01

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune-mediated disorders, the currently available laboratory tests for anti-PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations. © 2014 John Wiley & Sons Ltd.

  12. Reduction of multiple hits in atom probe tomography

    International Nuclear Information System (INIS)

    Thuvander, Mattias; Kvist, Anders; Johnson, Lars J.S.; Weidow, Jonathan; Andrén, Hans-Olof

    2013-01-01

    The accuracy of compositional measurements using atom probe tomography is often reduced because some ions are not recorded when several ions hit the detector in close proximity to each other and within a very short time span. In some cases, for example in analysis of carbides, the multiple hits result in a preferential loss of certain elements, namely those elements that frequently field evaporate in bursts or as dissociating molecules. In this paper a method of reducing the effect of multiple hits is explored. A fine metal grid was mounted a few millimeters behind the local electrode, effectively functioning as a filter. This resulted in a decrease in the overall detection efficiency, from 37% to about 5%, but also in a decrease in the fraction of multiple hits. In an analysis of tungsten carbide the fraction of ions originating from multiple hits decreased from 46% to 10%. As a result, the measured carbon concentration increased from 48.2 at%to 49.8 at%, very close to the expected 50.0 at%. The characteristics of the multiple hits were compared for analyses with and without the grid filter. - Highlights: ► APT experiments have been performed with a reduced amount of multiple hits. ► The multiple hits were reduced by placing a grid behind the electrode. ► This resulted in improved carbon measurement of WC

  13. Sun exposure causes somatic second-hit mutations and angiofibroma development in tuberous sclerosis complex

    Science.gov (United States)

    Tyburczy, Magdalena E.; Wang, Ji-an; Li, Shaowei; Thangapazham, Rajesh; Chekaluk, Yvonne; Moss, Joel; Kwiatkowski, David J.; Darling, Thomas N.

    2014-01-01

    Tuberous sclerosis complex (TSC) is characterized by the formation of tumors in multiple organs and is caused by germline mutation in one of two tumor suppressor genes, TSC1 and TSC2. As for other tumor suppressor gene syndromes, the mechanism of somatic second-hit events in TSC tumors is unknown. We grew fibroblast-like cells from 29 TSC skin tumors from 22 TSC subjects and identified germline and second-hit mutations in TSC1/TSC2 using next-generation sequencing. Eighteen of 22 (82%) subjects had a mutation identified, and 8 of the 18 (44%) subjects were mosaic with mutant allele frequencies of 0 to 19% in normal tissue DNA. Multiple tumors were available from four patients, and in each case, second-hit mutations in TSC2 were distinct indicating they arose independently. Most remarkably, 7 (50%) of the 14 somatic point mutations were CC>TT ultraviolet ‘signature’ mutations, never seen as a TSC germline mutation. These occurred exclusively in facial angiofibroma tumors from sun-exposed sites. These results implicate UV-induced DNA damage as a cause of second-hit mutations and development of TSC facial angiofibromas and suggest that measures to limit UV exposure in TSC children and adults should reduce the frequency and severity of these lesions. PMID:24271014

  14. 42 CFR 495.340 - As-needed HIT PAPD update and as-needed HIT IAPD update requirements.

    Science.gov (United States)

    2010-10-01

    ... limited to any of the following: (a) A projected cost increase of $100,000 or more. (b) A schedule... implementation approach, or scope of activities beyond that approved in the HIT planning advance planning document or the HIT implementation advance planning document. (d) A change in implementation concept or a...

  15. Hitting your foothills target the first time

    Energy Technology Data Exchange (ETDEWEB)

    Ewanek, J. [MI Drilling Fluids Canada, Calgary, AB (Canada); Young, S. [M-I L.L.C., Calgary, AB (Canada)

    2001-07-01

    As the demand for gas increases, operators are exploring for more long-term gas reserves in the foothills and in more complex structural traps and reservoirs. The high tectonic activity in the foothills has rendered the structural geology complex, making it difficult to hit an exploration target the first time. Costly sidetracking operations are common. The use of oil based fluids is often necessary for drilling in such technically challenging environments. However, dips/structural evaluation tools such as the Formation Micro Imager (FMI) and the GeoVision 675 Logging While Drilling (LWD) tool cannot be used because of the non-conductive nature of oil based fluids. Therefore, a conductive oil based fluid was developed with the recent advances in oil based mud technology, and it is now available. This new conductive oil based fluid allows LWD tools to transmit structural information in real time and FMI logs to give detailed structural information while wireline logging the hole. The combination of LWD and FMI data plus a conductive oil based fluid makes it possible to gather better structural information while drilling. This minimizes sidetracks and leads to a better understanding of the structural geology in that field. It was concluded that the use of this technology well enable better pre-planning on future well sites and will make it possible to reduce costs associated with drilling and oilfield operations in the foothills. 9 refs., 2 tabs., 13 figs.

  16. The first neutron beam hits EAR2

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    On 25 July 2014, about a year after construction work began, the Experimental Area 2 (EAR2) of CERN’s neutron facility n_TOF recorded its first beam. Unique in many aspects, EAR2 will start its rich programme of experimental physics this autumn.   The last part of the EAR2 beamline: the neutrons come from the underground target and reach the top of the beamline, where they hit the samples. Built about 20 metres above the neutron production target, EAR2 is in fact a bunker connected to the n_TOF underground facilities via a duct 80 cm in diameter, where the beamline is installed. The feet of the bunker support pillars are located on the concrete structure of the n_TOF tunnel and part of the structure lies above the old ISR building. A beam dump located on the roof of the building completes the structure. Neutrons are used by physicists to study neutron-induced reactions with applications in a number of fields, including nuclear waste transmutation, nuclear technology, nuclear astrop...

  17. Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene

    DEFF Research Database (Denmark)

    Efrat, S; Linde, S; Kofod, Hans

    1988-01-01

    Three pancreatic beta-cell lines have been established from insulinomas derived from transgenic mice carrying a hybrid insulin-promoted simian virus 40 tumor antigen gene. The beta tumor cell (beta TC) lines maintain the features of differentiated beta cells for about 50 passages in culture. The ...... both to immortalize a rare cell type and to provide a selection for the maintenance of its differentiated phenotype....

  18. A Double Hit CD10-Negative B-Cell Lymphoma with t(3;8(q27;q24 Leading to Juxtaposition of the BCL6 and MYC Loci Associated with Good Clinical Outcome

    Directory of Open Access Journals (Sweden)

    Lucinda Sanders

    2014-01-01

    Full Text Available The WHO classification of lymphomas allows for a group of diseases that have features intermediate between those of Burkitt lymphoma and diffuse large B-cell lymphoma. These are a diverse group of diseases whose genetics and clinical course are yet to be fully described. We report an unusual case of high grade B-cell lymphoma, intermediate between DLBCL and BL, lacking CD10 expression in which the chromosomal translocation t(3;8(q27;q24 was found to be the sole chromosomal abnormality. FISH analysis demonstrated juxtaposition of the BCL6 and MYC loci without obvious involvement of the IGH locus, suggesting constitutive MYC expression due to promoter substitution. The patient responded to intensive chemotherapy and remains in remission two years after finishing therapy.

  19. Implementation of a rapid HIT immunoassay at a university hospital - Retrospective analysis of HIT laboratory orders in patients with thrombocytopenia.

    Science.gov (United States)

    Black, Anne; Heimerl, Susanne; Oertli, Linnéa; Wilczek, Wolf; Greinacher, Andreas; Spannagl, Michael; Herr, Wolfgang; Hart, Christina

    2017-10-01

    Heparin-induced thrombocytopenia (HIT) is a rare cause of thrombocytopenia and a potentially life-threatening adverse drug reaction. Clinical overdiagnosis of HIT results in costly laboratory tests and anticoagulation. Criteria and algorithms for diagnosis are established, but their translation into clinical practice is still challenging. In a retrospective approach we studied all HIT related laboratory test requests within four years and evaluated data before (1st period, 24month) and after (2nd period, 24month) replacing particle gel immunoassay (PaGIA) and enzyme-linked immunosorbent assay (ELISA) by a chemiluminescent immunoassay (CLIA). HIT was confirmed by heparin-induced platelet activation (HIPA) test. Clinical pretest probability for HIT using an implemented simplified 4Ts score and platelet count were evaluated. Costs for laboratory tests and alternative anticoagulation were calculated. In 1850 patients with suspected HIT, 2327 laboratory orders were performed. In 87.2% of these orders an intermediate/high simplified 4Ts score was found. Thrombocytopenia was present in 87.1%. After replacing PaGIA and ELISA by CLIA the number of immunological and functional laboratory tests was reduced by 38.2%. The number of positive HIT immunoassays declined from 22.6% to 6.0%, while the number of positive HIPA tests among positive immunological tests increased by 19%. Altogether, acute HIT was confirmed in 59 patients. A decline in the use of alternative anticoagulants was observed in the 2nd period. Our study shows that in a university hospital setting HIT is well-known, but diagnosis requires a precise laboratory confirmation. Replacing PaGIA and ELISA by CLIA did not influence laboratory order behavior but results in reduced overall costs for laboratory diagnostics and alternative anticoagulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Do pigeons prefer alternatives that include near-hit outcomes?

    Science.gov (United States)

    Stagner, Jessica P; Case, Jacob P; Sticklen, Mary F; Duncan, Amanda K; Zentall, Thomas R

    2015-07-01

    Pigeons show suboptimal choice on a gambling-like task similar to that shown by humans. Humans also show a preference for gambles in which there are near hits (losses that come close to winning). In the present research, we asked if pigeons would show a preference for alternatives with near-hit-like trials. In Experiment 1, we included an alternative that presented a near hit, in which a stimulus associated with reinforcement (a presumed conditioned reinforcer) changed to a stimulus associated with the absence of reinforcement (a presumed conditioned inhibitor). The pigeons tended to avoid this alternative. In Experiment 2, we varied the duration of the presumed conditioned reinforcer (2 vs. 8 s) that changed to a presumed conditioned inhibitor (8 vs. 2 s) and found that the longer the conditioned reinforcer was presented, the more the pigeons avoided it. In Experiment 3, the near-hit alternative involved an ambiguous stimulus for 8 s that changed to a presumed conditioned reinforcer (or a presumed conditioned inhibitor) for 2 s, but the pigeons still avoided it. In Experiment 4, we controlled for the duration of the conditioned reinforcer by presenting it first for 2 s followed by the ambiguous stimulus for 8 s. Once again, the pigeons avoided the alternative with the near-hit trials. In all 4 experiments, the pigeons tended to avoid alternatives that provided near-hit-like trials. We concluded that humans may be attracted to near-hit trials because near-hit trials give them the illusion of control, whereas this does not appear to be a factor for pigeons. (c) 2015 APA, all rights reserved).

  1. A fast DSP-based calorimeter hit scanning system

    International Nuclear Information System (INIS)

    Sekikawa, S.; Arai, I.; Suzuki, A.; Watanabe, A.; Marlow, D.R.; Mindas, C.R.; Wixted, R.L.

    1997-01-01

    A custom made digital signal processor (DSP) based system has been developed to scan calorimeter hits read by a 32-channel FASTBUS waveform recorder board. The scanner system identifies hit calorimeter elements by surveying their discriminated outputs. This information is used to generate a list of addresses, which guides the read-out process. The system is described and measurements of the scan times are given. (orig.)

  2. Overview of the HIT-SI3 spheromak experiment

    Science.gov (United States)

    Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Everson, C. J.; Penna, J. M.; Nelson, B. A.

    2017-10-01

    The HIT-SI and HIT-SI3 spheromak experiments (a = 23 cm) study efficient, steady-state current drive for magnetic confinement plasmas using a novel method which is ideal for low aspect ratio, toroidal geometries. Sustained spheromaks show coherent, imposed plasma motion and low plasma-generated mode activity, indicating stability. Analysis of surface magnetic fields in HIT-SI indicates large n = 0 and 1 mode amplitudes and little energy in higher modes. Within measurement uncertainties all the n = 1 energy is imposed by the injectors, rather than being plasma-generated. The fluctuating field imposed by the injectors is sufficient to sustain the toroidal current through dynamo action whereas the plasma-generated field is not (Hossack et al., Phys. Plasmas, 2017). Ion Doppler spectroscopy shows coherent, imposed plasma motion inside r 10 cm in HIT-SI and a smaller volume of coherent motion in HIT-SI3. Coherent motion indicates the spheromak is stable and a lack of plasma-generated n = 1 energy indicates the maximum q is maintained below 1 for stability during sustainment. In HIT-SI3, the imposed mode structure is varied to test the plasma response (Hossack et al., Nucl. Fusion, 2017). Imposing n = 2, n = 3, or large, rotating n = 1 perturbations is correlated with transient plasma-generated activity. Work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences, under Award Number DE-FG02-96ER54361.

  3. Verbs in the lexicon: Why is hitting easier than breaking?

    Science.gov (United States)

    McKoon, Gail; Love, Jessica

    2011-11-01

    Adult speakers use verbs in syntactically appropriate ways. For example, they know implicitly that the boy hit at the fence is acceptable but the boy broke at the fence is not. We suggest that this knowledge is lexically encoded in semantic decompositions. The decomposition for break verbs (e.g. crack, smash) is hypothesized to be more complex than that for hit verbs (e.g. kick, kiss). Specifically, the decomposition of a break verb denotes that "an entity changes state as the result of some external force" whereas the decomposition for a hit verb denotes only that "an entity potentially comes in contact with another entity." In this article, verbs of the two types were compared in a lexical decision experiment - Experiment 1 - and they were compared in sentence comprehension experiments with transitive sentences (e.g. the car hit the bicycle and the car broke the bicycle) - Experiments 2 and 3. In Experiment 1, processing times were shorter for the hit than the break verbs and in Experiments 2 and 3, processing times were shorter for the hit sentences than the break sentences, results that are in accord with the complexities of the postulated semantic decompositions.

  4. Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

    Science.gov (United States)

    Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens

    2016-01-01

    Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160596

  5. Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models.

    Science.gov (United States)

    Baeder, Desiree Y; Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens; Regoes, Roland R

    2016-05-26

    Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. © 2016 The Author(s).

  6. Hitting cancer where it hurts most

    NARCIS (Netherlands)

    Kuiken, H.J.

    2012-01-01

    The development of cancer is an evolutionary process with accumulating (epi)genetic alterations underlying the transformation of a normal cell into a potentially malignant population. Cancer cells may continue to depend on the presence of such (epi)genetic alterations for maintenance of their

  7. Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene

    DEFF Research Database (Denmark)

    Blume, N; Petersen, J S; Andersen, L C

    1992-01-01

    is induced in the transformed heterogeneous rat islet cell clone, NHI-6F, by transient in vivo passage. During this process a transfected human insulin gene is coactivated with the endogenous nonallelic rat insulin I and II genes. Newly established cultures from NHI-6F insulinomas having a high frequency...

  8. Hit discovery of 4-amino-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide: A novel EGFR inhibitor from a designed small library.

    Science.gov (United States)

    Elkamhawy, Ahmed; Paik, Sora; Hassan, Ahmed H E; Lee, Yong Sup; Roh, Eun Joo

    2017-12-01

    Searching for hit compounds within the huge chemical space resembles the attempt to find a needle in a haystack. Cheminformatics-guided selection of few representative molecules of a rationally designed virtual combinatorial library is a powerful tool to confront this challenge, speed up hit identification and cut off costs. Herein, this approach has been applied to identify hit compounds with novel scaffolds able to inhibit EGFR kinase. From a generated virtual library, six 4-aryloxy-5-aminopyrimidine scaffold-derived compounds were selected, synthesized and evaluated as hit EGFR inhibitors. 4-Aryloxy-5-benzamidopyrimidines inhibited EGFR with IC 50 1.05-5.37 μM. Cell-based assay of the most potent EGFR inhibitor hit (10ac) confirmed its cytotoxicity against different cancerous cells. In spite of no EGFR, HER2 or VEGFR1 inhibition was elicited by 4-aryloxy-5-(thio)ureidopyrimidine derivatives, cell-based evaluation suggested them as antiproliferative hits acting by other mechanism(s). Molecular docking study provided a plausible explanation of incapability of 4-aryloxy-5-(thio)ureidopyrimidines to inhibit EGFR and suggested a reasonable binding mode of 4-aryloxy-5-benzamidopyrimidines which provides a basis to develop more optimized ligands. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 75 FR 21629 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2010-04-26

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Standards Committee's Workgroups: Clinical Operations Vocabulary... developed by the HIT Policy Committee. Date and Time: The HIT Standards Committee Workgroups will hold the...

  10. 76 FR 46297 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... developed by the HIT Policy Committee. Date and Time: The HIT Standards Committee Workgroups will hold the...

  11. 75 FR 62399 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-10-08

    ... Technology; HIT Standards Committee Schedule for the Assessment of HIT Policy Committee Recommendations.... SUMMARY: Section 3003(b)(3) of the American Recovery and Reinvestment Act of 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy recommendations developed by the HIT...

  12. 77 FR 66617 - HIT Policy and Standards Committees; Workgroup Application Database

    Science.gov (United States)

    2012-11-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy and Standards Committees; Workgroup Application... of New ONC HIT FACA Workgroup Application Database. The Office of the National Coordinator (ONC) has.... Name of Committees: HIT Standards Committee and HIT Policy Committee. General Function of the...

  13. Enhancing hit identification in Mycobacterium tuberculosis drug discovery using validated dual-event Bayesian models.

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    Full Text Available High-throughput screening (HTS in whole cells is widely pursued to find compounds active against Mycobacterium tuberculosis (Mtb for further development towards new tuberculosis (TB drugs. Hit rates from these screens, usually conducted at 10 to 25 µM concentrations, typically range from less than 1% to the low single digits. New approaches to increase the efficiency of hit identification are urgently needed to learn from past screening data. The pharmaceutical industry has for many years taken advantage of computational approaches to optimize compound libraries for in vitro testing, a practice not fully embraced by academic laboratories in the search for new TB drugs. Adapting these proven approaches, we have recently built and validated Bayesian machine learning models for predicting compounds with activity against Mtb based on publicly available large-scale HTS data from the Tuberculosis Antimicrobial Acquisition Coordinating Facility. We now demonstrate the largest prospective validation to date in which we computationally screened 82,403 molecules with these Bayesian models, assayed a total of 550 molecules in vitro, and identified 124 actives against Mtb. Individual hit rates for the different datasets varied from 15-28%. We have identified several FDA approved and late stage clinical candidate kinase inhibitors with activity against Mtb which may represent starting points for further optimization. The computational models developed herein and the commercially available molecules derived from them are now available to any group pursuing Mtb drug discovery.

  14. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome.

    Science.gov (United States)

    Hagawane, T N; Gaikwad, R V; Kshirsagar, N A

    2016-05-01

    Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  15. Influence of Running on Pistol Shot Hit Patterns.

    Science.gov (United States)

    Kerkhoff, Wim; Bolck, Annabel; Mattijssen, Erwin J A T

    2016-01-01

    In shooting scene reconstructions, risk assessment of the situation can be important for the legal system. Shooting accuracy and precision, and thus risk assessment, might be correlated with the shooter's physical movement and experience. The hit patterns of inexperienced and experienced shooters, while shooting stationary (10 shots) and in running motion (10 shots) with a semi-automatic pistol, were compared visually (with confidence ellipses) and statistically. The results show a significant difference in precision (circumference of the hit patterns) between stationary shots and shots fired in motion for both inexperienced and experienced shooters. The decrease in precision for all shooters was significantly larger in the y-direction than in the x-direction. The precision of the experienced shooters is overall better than that of the inexperienced shooters. No significant change in accuracy (shift in the hit pattern center) between stationary shots and shots fired in motion can be seen for all shooters. © 2015 American Academy of Forensic Sciences.

  16. Recent results from the HIT-II and HIT-SI helicity injection current drive experiments

    International Nuclear Information System (INIS)

    Jarboe, T.R.; Hamp, W.T.; Izzo, V.A.; Nelson, B.A.; O'Neill, R.G.; Raman, R.; Redd, A.J.; Sieck, P.E.; Smith, R.J.

    2005-01-01

    Three important results are reported. 1) CHI startup has produced 100 kA of closed current without using poloidal field (PF) coils or any transformer action. The initial equilibrium is then driven to 240 kA with a 3 V transformer loop voltage, indicating high quality plasma. 2) For the first time CHI alone has produced toroidal currents (350 kA) that far exceed q a I inj , and with I p /I tf as high as 1.2. The key to these new results appears to be having the toroidal field small enough that relaxation will occur. 3) The steady inductive helicity injection spheromak experiment has operated at 5 kHz for 6 ms with current amplitudes up to 11 kA in each injector. The helicity injection rate is nearly constant with the ExB flow always into the plasma and not into the walls. NIMROD simulations of HIT-SI show a buildup of spheromak fields. (author)

  17. Multi-hit time-to-amplitude CAMAC module (MTAC)

    International Nuclear Information System (INIS)

    Kang, H.

    1980-10-01

    A Multi-Hit Time-to-Amplitude Module (MTAC) for the SLAC Mark III drift chamber system has been designed to measure drift time by converting time-proportional chamber signals into analog levels, and converting the analog data by slow readout via a semi-autonomous controller in a CAMAC crate. The single width CAMAC module has 16 wire channels, each with a 4-hit capacity. An externally generated common start initiates an internal precision ramp voltage which is then sampled using a novel shift register gating scheme and CMOS sampling switches. The detailed design and performance specifications are described

  18. Does ′heparin-induced thrombocytopenia′ hit our minds?

    Directory of Open Access Journals (Sweden)

    Arun R Thangavel

    2016-01-01

    Full Text Available Unfractionated heparin is a widely used drug to prevent deep vein thrombosis and pulmonary emboli in patients at risk. With the advent of newer anticoagulants having lesser side effects, its use has diminished but not out of service. Here, we report a case of deep venous thrombosis, in a patient on prophylactic dose of heparin, which was later found to be a manifestation of heparin-induced thrombocytopenia (HIT. Thrombosis in the presence of heparin prophylaxis should be considered as HIT rather than a failure of anticoagulation.

  19. Direct determination of the hit locations from experimental HPGe pulses

    Energy Technology Data Exchange (ETDEWEB)

    Désesquelles, P., E-mail: Pierre.Desesquelles@in2p3.fr [Univ. Paris-Sud, CSNSM CNRS/IN2P3, 15 rue G. Clémenceau, 91405 Orsay (France); Boston, A.J.; Boston, H.C.; Cresswell, J.R.; Dimmock, M.R. [Oliver Lodge Laboratory, The University of Liverpool, Oxford Street, Liverpool L69 7ZE (United Kingdom); Lazarus, I.H. [STFC Daresbury Laboratory, Daresbury, Warrington WA4 4AD (United Kingdom); Ljungvall, J. [Univ. Paris-Sud, CSNSM CNRS/IN2P3, 15 rue G. Clémenceau, 91405 Orsay (France); Nelson, L. [Oliver Lodge Laboratory, The University of Liverpool, Oxford Street, Liverpool L69 7ZE (United Kingdom); Nga, D.-T. [Univ. Paris-Sud, CSNSM CNRS/IN2P3, 15 rue G. Clémenceau, 91405 Orsay (France); Nolan, P.J.; Rigby, S.V. [Oliver Lodge Laboratory, The University of Liverpool, Oxford Street, Liverpool L69 7ZE (United Kingdom); Simpson, J. [STFC Daresbury Laboratory, Daresbury, Warrington WA4 4AD (United Kingdom); Van-Oanh, N.-T. [Univ. Paris-Sud, LCP UMR8000 CNRS, 15 rue G. Clémenceau, 91405 Orsay (France)

    2013-11-21

    The gamma-tracking technique optimises the determination of the energy and emission angle of gamma-rays detected by modern segmented HPGe detectors. This entails the determination, using the delivered pulse shapes, of the interaction points of the gamma-ray within the crystal. The direct method presented here allows the localisation of the hits using only a large sample of pulses detected in the actual operating conditions. No external crystal scanning system or pulse shape simulation code is needed. In order to validate this method, it is applied to sets of pulses obtained using the University of Liverpool scanning system. The hit locations are determined by the method with good precision.

  20. Possilibity of estimating payoff matrix from model for hit phenomena

    International Nuclear Information System (INIS)

    Ishii, Akira; Sakaidani, Shota; Iwanaga, Saori

    2016-01-01

    The conflicts of topics on social media is considered using an extended mathematical model based on the mathematical model for hit phenomena that has been used to analyze entertainment hits. The social media platform used in this study was blog. The calculation results shows examples of strong conflict, weak conflict, and no conflict cases. Since the conflict of two topics can be considered in the framework of game theory, the results can be used to determine each matrix element of the payoff matrix of game theory.

  1. Hit Identification and Optimization in Virtual Screening: Practical Recommendations Based Upon a Critical Literature Analysis

    Science.gov (United States)

    Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B.; Szukala, Richard; Johnson, Michael E.; Hevener, Kirk E.

    2013-01-01

    A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, drug-like, and ADMET filters were applied to the reported hits to assess the quality of compounds reported and a careful analysis of a subset of the studies which presented hit optimization was performed. This data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, defining hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria. PMID:23688234

  2. Hit identification and optimization in virtual screening: practical recommendations based on a critical literature analysis.

    Science.gov (United States)

    Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B; Szukala, Richard; Johnson, Michael E; Hevener, Kirk E

    2013-09-12

    A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses, and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, druglike, and ADMET filters were applied to the reported hits to assess the quality of compounds reported, and a careful analysis of a subset of the studies that presented hit optimization was performed. These data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, definition of hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria.

  3. Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1

    DEFF Research Database (Denmark)

    Rist, Oystein; Grimstrup, Marie; Receveur, Jean-Marie

    2009-01-01

    Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists....... Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7nM and functional...

  4. Do repeated rumble strip hits improve driver alertness?

    NARCIS (Netherlands)

    Watling, C.N.; Akerstedt, T.; Kecklund, L.G.; Anund, A.

    2016-01-01

    Driving while sleepy is associated with increased crash risk. Rumble strips are designed to alert a sleepy or inattentive driver when they deviate outside their driving lane. The current study sought to examine the effects of repeated rumble strip hits on levels of physiological and subjective

  5. Madoff Debacle Hits Colleges and Raises Questions about Trustee Conflicts

    Science.gov (United States)

    Fain, Paul

    2009-01-01

    Several colleges and universities lost millions in the alleged $50-billion Ponzi scheme run by the Wall Street trader Bernard L. Madoff. The losses include institutions' endowment holdings in hedge funds that were invested with Madoff as well as hits taken by supporting foundations and donors. Several foundations that have been active in higher…

  6. The probability of a tornado missile hitting a target

    International Nuclear Information System (INIS)

    Goodman, J.; Koch, J.E.

    1983-01-01

    It is shown that tornado missile transportation is a diffusion Markovian process. Therefore, the Green's function method is applied for the estimation of the probability of hitting a unit target area. This propability is expressed through a joint density of tornado intensity and path area, a probability of tornado missile injection and a tornado missile height distribution. (orig.)

  7. Concentrated Hitting Times of Randomized Search Heuristics with Variable Drift

    DEFF Research Database (Denmark)

    Lehre, Per Kristian; Witt, Carsten

    2014-01-01

    Drift analysis is one of the state-of-the-art techniques for the runtime analysis of randomized search heuristics (RSHs) such as evolutionary algorithms (EAs), simulated annealing etc. The vast majority of existing drift theorems yield bounds on the expected value of the hitting time for a target...

  8. COPD: A stepwise or a hit hard approach?

    Directory of Open Access Journals (Sweden)

    A.J. Ferreira

    2016-07-01

    Full Text Available Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or “hit hard” approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS are recommended, a step-up or “hit hard” approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications.This paper discusses and proposes stepwise, “hit hard”, step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach. Keywords: COPD, Stepwise, Hit hard, Step-up, ICS withdrawal, Bronchodilators, ICS

  9. Biophysics: for HTS hit validation, chemical lead optimization, and beyond.

    Science.gov (United States)

    Genick, Christine C; Wright, S Kirk

    2017-09-01

    There are many challenges to the drug discovery process, including the complexity of the target, its interactions, and how these factors play a role in causing the disease. Traditionally, biophysics has been used for hit validation and chemical lead optimization. With its increased throughput and sensitivity, biophysics is now being applied earlier in this process to empower target characterization and hit finding. Areas covered: In this article, the authors provide an overview of how biophysics can be utilized to assess the quality of the reagents used in screening assays, to validate potential tool compounds, to test the integrity of screening assays, and to create follow-up strategies for compound characterization. They also briefly discuss the utilization of different biophysical methods in hit validation to help avoid the resource consuming pitfalls caused by the lack of hit overlap between biophysical methods. Expert opinion: The use of biophysics early on in the drug discovery process has proven crucial to identifying and characterizing targets of complex nature. It also has enabled the identification and classification of small molecules which interact in an allosteric or covalent manner with the target. By applying biophysics in this manner and at the early stages of this process, the chances of finding chemical leads with novel mechanisms of action are increased. In the future, focused screens with biophysics as a primary readout will become increasingly common.

  10. Markov chains with quasitoeplitz transition matrix: first zero hitting

    Directory of Open Access Journals (Sweden)

    Alexander M. Dukhovny

    1989-01-01

    Full Text Available This paper continues the investigation of Markov Chains with a quasitoeplitz transition matrix. Generating functions of first zero hitting probabilities and mean times are found by the solution of special Riemann boundary value problems on the unit circle. Duality is discussed.

  11. First hitting probabilities for semi markov chains and estimation

    DEFF Research Database (Denmark)

    Georgiadis, Stylianos

    2017-01-01

    We first consider a stochastic system described by an absorbing semi-Markov chain with finite state space and we introduce the absorption probability to a class of recurrent states. Afterwards, we study the first hitting probability to a subset of states for an irreducible semi-Markov chain...

  12. Assessing the lipophilicity of fragments and early hits

    Science.gov (United States)

    Mortenson, Paul N.; Murray, Christopher W.

    2011-07-01

    A key challenge in many drug discovery programs is to accurately assess the potential value of screening hits. This is particularly true in fragment-based drug design (FBDD), where the hits often bind relatively weakly, but are correspondingly small. Ligand efficiency (LE) considers both the potency and the size of the molecule, and enables us to estimate whether or not an initial hit is likely to be optimisable to a potent, druglike lead. While size is a key property that needs to be controlled in a small molecule drug, there are a number of additional properties that should also be considered. Lipophilicity is amongst the most important of these additional properties, and here we present a new efficiency index (LLEAT) that combines lipophilicity, size and potency. The index is intuitively defined, and has been designed to have the same target value and dynamic range as LE, making it easily interpretable by medicinal chemists. Monitoring both LE and LLEAT should help both in the selection of more promising fragment hits, and controlling molecular weight and lipophilicity during optimisation.

  13. Third World PVs hit the roof.

    Science.gov (United States)

    Lenssen, N

    1992-01-01

    Rural areas in developing countries have no hope of benefiting from electricity generation programs because of a lack of resources. Currently the common practice is to use kerosene lamps for light, disposable batteries for radios, and auto batteries for television. The auto battery must be hauled by pack animal to a charging station. An alternative that is growing in popularity is the installation of photovoltaic (PV) systems in each house. The advantages include very low operating costs (sunshine is free), long life (PV cells last 20 years), they can be installed in any home without regard for power grids. The biggest disadvantage is very high initial cost. To solve this problem many programs have been developed to finance systems. Enersol Associates started with $10,000 seed money and developed a loan program that has helped bring electricity to 1500 homes in the Dominican Republic. The Solar Electric Light and Fund started with $150,000 and has brought electricity to 3500 homes in Sri Lanka. The United Nations Development Program gave $7 million to Zimbabwe to fund a project that is expected to bring electricity to 20,000 homes over the next 5 years.

  14. Single Hit Energy-resolved Laue Diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shamim; Suggit, Matthew J.; Stubley, Paul G.; Ciricosta, Orlando; Wark, Justin S.; Higginbotham, Andrew [Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom); Hawreliak, James A.; Collins, Gilbert W.; Eggert, Jon H. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Comley, Andrew J.; Foster, John M. [Atomic Weapons Establishment, Aldermaston, Reading RG7 4PR (United Kingdom)

    2015-05-15

    In situ white light Laue diffraction has been successfully used to interrogate the structure of single crystal materials undergoing rapid (nanosecond) dynamic compression up to megabar pressures. However, information on strain state accessible via this technique is limited, reducing its applicability for a range of applications. We present an extension to the existing Laue diffraction platform in which we record the photon energy of a subset of diffraction peaks. This allows for a measurement of the longitudinal and transverse strains in situ during compression. Consequently, we demonstrate measurement of volumetric compression of the unit cell, in addition to the limited aspect ratio information accessible in conventional white light Laue. We present preliminary results for silicon, where only an elastic strain is observed. VISAR measurements show the presence of a two wave structure and measurements show that material downstream of the second wave does not contribute to the observed diffraction peaks, supporting the idea that this material may be highly disordered, or has undergone large scale rotation.

  15. Single Hit Energy-resolved Laue Diffraction

    International Nuclear Information System (INIS)

    Patel, Shamim; Suggit, Matthew J.; Stubley, Paul G.; Ciricosta, Orlando; Wark, Justin S.; Higginbotham, Andrew; Hawreliak, James A.; Collins, Gilbert W.; Eggert, Jon H.; Comley, Andrew J.; Foster, John M.

    2015-01-01

    In situ white light Laue diffraction has been successfully used to interrogate the structure of single crystal materials undergoing rapid (nanosecond) dynamic compression up to megabar pressures. However, information on strain state accessible via this technique is limited, reducing its applicability for a range of applications. We present an extension to the existing Laue diffraction platform in which we record the photon energy of a subset of diffraction peaks. This allows for a measurement of the longitudinal and transverse strains in situ during compression. Consequently, we demonstrate measurement of volumetric compression of the unit cell, in addition to the limited aspect ratio information accessible in conventional white light Laue. We present preliminary results for silicon, where only an elastic strain is observed. VISAR measurements show the presence of a two wave structure and measurements show that material downstream of the second wave does not contribute to the observed diffraction peaks, supporting the idea that this material may be highly disordered, or has undergone large scale rotation

  16. Nedley Depression Hit Hypothesis: Identifying Depression and Its Causes.

    Science.gov (United States)

    Nedley, Neil; Ramirez, Francisco E

    2016-11-01

    Depression is often diagnosed using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. We propose how certain lifestyle choices and non-modifiable factors can predict the development of depression. We identified 10 cause categories (hits or "blows" to the brain) and theorize that four or more active hits could trigger a depression episode. Methods. A sample of 4271 participants from our community-based program (70% female; ages 17-94 years) was assessed at baseline and at the eighth week of the program using a custom test. Ten cause categories were examined as predictors of depression are (1) Genetic, (2)Developmental, (3)Lifestyle, (4)Circadian Rhythm, (5)Addiction, (6)Nutrition, (7)Toxic, (8)Social/Complicated Grief, (9)Medical Condition, and (10)Frontal Lobe. Results. The relationship between the DSM-5 score and a person having four hits categories in the first program week showed a sensitivity of 89.98 % (95% CI: 89.20 % - 90.73%), specificity 48.84% (CI 45.94-51.75) and Matthew Correlation Coefficient (MCC) .41 . For the eight-week test, the results showed a sensitivity 83.6% (CI 81.9-85.5), specificity 53.7% (CI 51.7-55.6) and MCC .38. Overall, the hits that improved the most from baseline after the eighth week were: Nutrition (47%), Frontal lobe (36%), Addiction (24%), Circadian rhythm (24%), Lifestyle (20%), Social (12%) and Medical (10%). Conclusions. The Nedley four-hit hypothesis seems to predict a depressive episode and correlates well with the DSM-5 criteria with good sensitivity and MCC but less specificity. Identifying these factors and applying lifestyle therapies could play an important role in the treatment of depressed individuals.

  17. Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

    Science.gov (United States)

    Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

    2017-01-01

    Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

  18. 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.

  19. Hit size effectiveness in relation to the microdosimetric site size

    International Nuclear Information System (INIS)

    Varma, M.N.; Wuu, C.S.; Zaider, M.

    1994-01-01

    This paper examines the effect of site size (that is, the diameter of the microdosimetric volume) on the hit size effectiveness function (HSEF), q(y), for several endpoints relevant in radiation protection. A Bayesian and maximum entropy approach is used to solve the integral equations that determine, given microdosimetric spectra and measured initial slopes, the function q(y). All microdosimetric spectra have been calculated de novo. The somewhat surprising conclusion of this analysis is that site size plays only a minor role in selecting the hit size effectiveness function q(y). It thus appears that practical means (e.g. conventional proportional counters) are already at hand to actually implement the HSEF as a radiation protection tool. (Author)

  20. Heparin- induced thrombocytopenia (HIT: a case report of CABG patient

    Directory of Open Access Journals (Sweden)

    Alireza Jahangirifard

    2016-08-01

    Full Text Available Heparin- induced thrombocytopenia (HIT is an antibody mediated adverse effect of heparin therapy which is classified into two subtypes, HITI which is non-immune, spontaneously reversible thrombocytopenia and; HITII which is an autoimmune-mediated adverse effect of heparin therapy. In this case report, we described a 65-year old male patient with HITII after coronary artery bypass grafting.Key words: Heparin- induced thrombocytopenia, Heparin- induced thrombosis, coronary artery bypass grafting.

  1. 76 FR 46298 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held virtually on August 17, 2011...

  2. 76 FR 55914 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-09-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  3. 77 FR 16035 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-03-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on March 27, 2012, from 9 a.m...

  4. 75 FR 65636 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-10-26

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  5. 76 FR 79684 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-12-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on January 25, 2012, from 9 a...

  6. 76 FR 50734 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on September 28, 2011, from 9...

  7. 77 FR 2727 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-01-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on February 29, 2012, from 9...

  8. 77 FR 15760 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-03-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on April 18, 2012, from 9 a.m...

  9. 76 FR 46297 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  10. 76 FR 14976 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on April 20, 2011, from 9 a.m...

  11. 76 FR 70455 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 14, 2011, from 9...

  12. 75 FR 5595 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2010-02-03

    ... Technology HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy Committee...

  13. 76 FR 4352 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2011-01-25

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Policy Committee's Workgroups: Meaningful Use, Privacy & Security Tiger..., implementation specifications, and certification criteria are needed. Date and Time: The HIT Policy Committee...

  14. 76 FR 39109 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-07-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on July 20, 2011, from 9 a.m...

  15. 77 FR 73661 - HIT Standards Committee Advisory Meetings; Notice of Meetings

    Science.gov (United States)

    2012-12-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meetings; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: These meetings will be held on the following dates and...

  16. 76 FR 70454 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... certification criteria are needed. Date and Time: The HIT Policy Committee Workgroups will hold the following...

  17. 75 FR 57027 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-09-17

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  18. 76 FR 28784 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... implementation of the Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT...

  19. 76 FR 28782 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on June 22, 2011, from 9 a.m...

  20. 77 FR 27459 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-05-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on June 20, 2012, from 9 a.m...

  1. 76 FR 22399 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  2. 76 FR 28784 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  3. 75 FR 29762 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2010-05-27

    ... Technology HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Policy Committee's Workgroups: Meaningful Use, Privacy & Security Policy... specifications, and certification criteria are needed. Date and Time: The HIT Policy Committee Workgroups will...

  4. 76 FR 50736 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... implementation of the Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT...

  5. 77 FR 37408 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-06-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... be open to the public. Name of Committee: HIT Standards Committee. General Function of the Committee... with policies developed by the HIT Policy Committee. Date and Time: The meeting will be held on July 19...

  6. 76 FR 14975 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... implementation of the Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT...

  7. 77 FR 22787 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-04-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on May 24, 2012, from 9 a.m...

  8. 77 FR 65691 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on November 13, 2012, from 9...

  9. 77 FR 50690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-08-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on September 19, 2012, from 9...

  10. 75 FR 21628 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2010-04-26

    ... Technology HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  11. 76 FR 14974 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  12. 76 FR 22396 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on May 18, 2011, from 9 a.m...

  13. 76 FR 55913 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-09-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held virtually on October 21, 2011...

  14. 76 FR 50735 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  15. 77 FR 60438 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-03

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on October 17, 2012, from 9 a...

  16. 75 FR 3906 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-01-25

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Policy Committee's Workgroups: Meaningful Use, Privacy & Security Policy... specifications, and certification criteria are needed. Date and Time: The HIT Policy Committee Workgroups will...

  17. 77 FR 65690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 19, 2012, from 9...

  18. 76 FR 9783 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-02-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on March 29, 2011, from 9 a.m...

  19. 77 FR 45353 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-07-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on August 15, 2012, from 9:00...

  20. 75 FR 42090 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-07-20

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  1. Effective progression of nuclear magnetic resonance-detected fragment hits.

    Science.gov (United States)

    Eaton, Hugh L; Wyss, Daniel F

    2011-01-01

    Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Reconstruction of hit time and hit position of annihilation quanta in the J-PET detector using the Mahalanobis distance

    Directory of Open Access Journals (Sweden)

    Sharma Neha Gupta

    2015-12-01

    Full Text Available The J-PET detector being developed at the Jagiellonian University is a positron emission tomograph composed of the long strips of polymer scintillators. At the same time, it is a detector system that will be used for studies of the decays of positronium atoms. The shape of photomultiplier signals depends on the hit time and hit position of the gamma quantum. In order to take advantage of this fact, a dedicated sampling front-end electronics that enables to sample signals in voltage domain with the time precision of about 20 ps and novel reconstruction method based on the comparison of examined signal with the model signals stored in the library has been developed. As a measure of the similarity, we use the Mahalanobis distance. The achievable position and time resolution depend on the number and values of the threshold levels at which the signal is sampled. A reconstruction method as well as preliminary results are presented and discussed.

  3. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F. (Hagedorn Research Laboratory, Gentofte (Denmark))

    1988-09-01

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

  4. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    International Nuclear Information System (INIS)

    Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F.

    1988-01-01

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression

  5. HIT and brain reward function: A case of mistaken identity (theory).

    Science.gov (United States)

    Wright, Cory; Colombo, Matteo; Beard, Alexander

    2017-08-01

    This paper employs a case study from the history of neuroscience-brain reward function-to scrutinize the inductive argument for the so-called 'Heuristic Identity Theory' (HIT). The case fails to support HIT, illustrating why other case studies previously thought to provide empirical support for HIT also fold under scrutiny. After distinguishing two different ways of understanding the types of identity claims presupposed by HIT and considering other conceptual problems, we conclude that HIT is not an alternative to the traditional identity theory so much as a relabeling of previously discussed strategies for mechanistic discovery. Copyright © 2017. Published by Elsevier Ltd.

  6. Novel HIT antibody detection method using Sonoclot® coagulation analyzer.

    Science.gov (United States)

    Wanaka, Keiko; Asada, Reiko; Miyashita, Kumiko; Kaneko, Makoto; Endo, Hirokazu; Yatomi, Yutaka

    2015-01-01

    Since heparin-induced thrombocytopenia (HIT), caused by the generation of antibodies against platelet factor 4 (PF4)/heparin complexes (HIT antibodies), may induce serious complications due to thrombosis, a prompt diagnosis is desirable. Functional tests with platelet activation to detect HIT antibodies are useful for diagnosis of HIT, in particular (14)C-selotonin release assay (SRA). However, they are complicated and so can be performed only in limited laboratories. We tested if a blood coagulation test using Sonoclot® analyzer can serve for the detection of HIT antibodies. A murine monoclonal antibody (HIT-MoAb) against PF4/heparin complexes was used as an alternative to human HIT antibodies. To the mixture of HIT-MoAb and heparin (0.5 U/mL, final), whole blood obtained from a healthy volunteer was added, and then the activated clotting time (ACT), clot rate (CR), and area under the curve (AUC) were measured with Sonoclot® analyzer for 30minutes. The HIT-MoAb (30 to 100μg/mL, final) concentration dependently suppressed the anticoagulation activity (prolongation of ACT and decrease of CR and AUC) of heparin. The suppression of anticoagulation effect of heparin by HIT-MoAb was demonstrated by measurements using Sonoclot® analyzer. This method may provide a new tool for screening of HIT antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

    Science.gov (United States)

    Klinkhammer, Brent; Gruchalla, Michael

    2018-03-01

    Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P HIT were significantly older than controls ( P HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

  8. Symptomatic Hypoglycemia Related to Inappropriately High IGF-II Serum Levels in a Patient with Desmoplastic Small Round Cell Tumor

    Directory of Open Access Journals (Sweden)

    Williams Fernandes Barra

    2010-01-01

    Full Text Available A 45-year old man was diagnosed with desmoplastic small round cell tumor (DSRCT with involvement of the peritoneum and pelvis. Disease progression was observed despite systemic chemotherapy. Six months after diagnosis, he developed severe hypoglycemia presented with seizures. He received intravenous glucose infusion and hydrocortisone with poor glycemic control, but with seizures resolution. The investigation excluded insulinoma, adrenal, liver and GH deficiencies. Laboratory showed slight rise of IGF-II and significant increase of the ratio IGF-II : IGF-I, which is pathognomonic of non-islet cell tumor hypoglycemia (NICTH. He received the diagnoses of NICTH related to IGF-II inappropriate production by DSRCT. Despite the attempt to control tumor mass and hypoglycemia, the patient died 9 months after diagnosis. NICTH related to inappropriate IGF-II secretion should be investigated in all cancer patients with refractory hypoglycemia whom insulinoma and other metabolic abnormalities were excluded from.

  9. Hit and target theories and the molecular theory of radiation action: Notes on the influence of radiation quality

    International Nuclear Information System (INIS)

    Dennis, J.A.

    1977-01-01

    The two target and two hit models are the simplest that can be invoked to explain the dependence of the response of eukaryotic cells on radiation quality. The formal mathematical developments of these two models are contrasted using the LET concept as a description of radiation quality. The two hit model is generalised in terms of event sizes in spherical volumes, as in the dual radiation action theory of Kellerer and Rossi. The effects of short tracks and oxygen enhancement are described. Biological damage is considered as originating in any one of a large number of sites within a cell as in the molecular theory of Chadwick and Leenhouts. Evidence from prokaryotic systems of the possible necessity for more complicated models of radiation action and, in particular, for the necessity to account for the dependence of repair and metabolic factors on radiation quality is cited. The 'track segment' and 'track structure' theories are briefly discussed as alternatives to LET for the description of radiation quality. It is suggested that it would be premature to apply the simple two target or two hit models as a basis for the specification of quality factor in radiological protection. The consequence of doing so would be that the current dose limits for gamma radiation would appear to be too high or that the limits for neutron radiation would appear to be too low. (author)

  10. Current drive experiments on the HIT-II spherical torus

    International Nuclear Information System (INIS)

    Jarboe, T.R.; Raman, R.; Nelson, B.A.; Holcomb, C.T.; McCollam, K.J.; Sieck, P.E.

    1999-01-01

    This paper describes the following new achievements from the Helicity Injected Torus (HIT) program: a) formation and sustainment of a toroidal magnetic equilibrium using coaxial helicity injection (CHI) in a conducting shell that has an L/R time much shorter than the pulse length; b) static formation of a spherical torus with plasma current over 180 kA using a transformer and feedback controlled equilibrium coils; and c) production of a current increase in a transformer produced spherical torus using CHI. (author)

  11. Current drive experiments on the HIT-II spherical torus

    International Nuclear Information System (INIS)

    Jarboe, T.; Raman, R.; Nelson, B.; Holcomb, C.T.; McCollam, K.J.; Sieck, P.E.

    2001-01-01

    This paper describes the following new achievements from the Helicity Injected Torus (HIT) program: a) formation and sustainment of a toroidal magnetic equilibrium using coaxial helicity injection (CHI) in a conducting shell that has an L/R time much shorter than the pulse length; b) static formation of a spherical torus with plasma current over 180 kA using a transformer and feedback controlled equilibrium coils; and c) production of a current increase in a transformer produced spherical torus using CHI. (author)

  12. Current drive experiments in the HIT-II spherical tokamak

    International Nuclear Information System (INIS)

    Jarboe, T.R.; Gu, P.; Isso, V.A.; Jewell, P.E.; McCollam, K.J.; Nelson, B.A.; Ramon, R.; Redd, A.J.; Sieck, P.E.; Smith, R.J.; Nagata, M.; Uyama, T.

    2001-01-01

    The Helicity Injected Torus (Hit) program has made progress in understanding relaxation and helicity injection current drive. Helicity-conserving MHD activity during the inductive (Ohmic) current ramp demonstrates the profile flattening needed for coaxial helicity injection (CHI). Results from cathode and anode central column (CC) CHI pulses are consistent with the electron locking model of current drive from a pure n=1 mode. Finally, low density CHI, compatible with Ohmic operation, has been achieved. Some enhancement of CHI discharges with the application of Ohmic is shown. (author)

  13. The Holistic Integrity Test (HIT - quantified resilience analysis

    Directory of Open Access Journals (Sweden)

    Dobson Mike

    2016-01-01

    Full Text Available The Holistic Integrity Test (HIT - Quantified Resilience Analysis. Rising sea levels and wider climate change mean we face an increasing risk from flooding and other natural hazards. Tough economic times make it difficult to economically justify or afford the desired level of engineered risk reduction. Add to this significant uncertainty from a range of future predictions, constantly updated with new science. We therefore need to understand not just how to reduce the risk, but what could happen should above design standard events occur. In flood terms this includes not only the direct impacts (damage and loss of life, but the wider cascade impacts to infrastructure systems and the longer term impacts on the economy and society. However, understanding the “what if” is only the first part of the equation; a range of improvement measures to mitigate such effects need to be identified and implemented. These measures should consider reducing the risk, lessening the consequences, aiding the response, and speeding up the recovery. However, they need to be objectively assessed through quantitative analysis, which underpins them technically and economically. Without such analysis, it cannot be predicted how measures will perform if the extreme events occur. It is also vital to consider all possible hazards as measures for one hazard may hinder the response to another. The Holistic Integrity Test (HIT, uses quantitative system analysis and “HITs” the site, its infrastructure, contained dangers and wider regional system to determine how it copes with a range of severe shock events, Before, During and After the event, whilst also accounting for uncertainty (as illustrated in figure 1. First explained at the TINCE 2014 Nuclear Conference in Paris, it was explained in terms of a Nuclear Facility needing to analyse the site in response to post Fukushima needs; the hit is however universally applicable. The HIT has three key risk reduction goals: The

  14. Liquid Argon TPC Signal Formation, Signal Processing and Hit Reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Baller, Bruce [Fermilab

    2017-03-11

    This document describes the early stage of the reconstruction chain that was developed for the ArgoNeuT and MicroBooNE experiments at Fermilab. These experiments study accelerator neutrino interactions that occur in a Liquid Argon Time Projection Chamber. Reconstructing the properties of particles produced in these interactions requires knowledge of the micro-physics processes that affect the creation and transport of ionization electrons to the readout system. A wire signal deconvolution technique was developed to convert wire signals to a standard form for hit reconstruction, to remove artifacts in the electronics chain and to remove coherent noise.

  15. ANALYSIS MUSIC CONCERTS ADOPTING THE MATHEMATICAL MODEL OF HIT PHENOMENA

    OpenAIRE

    Kawahata Yasuko; Genda Etsuo; Ishii Akira

    2013-01-01

    A mathematical model for the hit phenomenon in entertainment within a society is presented as a stochastic process of interactions of human dynamics. In this paper, we analyzed music to the concert.Knowing the cost of advertising the concert is difficult. But exposure to the media of the artist can be seen. We tried to analysis of music concert itself by performing a prediction of reputation of artists during the concert tour from this exposure.In this paper, The world most pop...

  16. Capture orbits around asteroids by hitting zero-velocity curves

    Science.gov (United States)

    Wang, Wei; Yang, Hongwei; Zhang, Wei; Ma, Guangfu

    2017-12-01

    The problem of capturing a spacecraft from a heliocentric orbit into a high parking orbit around binary asteroids is investigated in the current study. To reduce the braking Δ V, a new capture strategy takes advantage of the three-body gravity of the binary asteroid to lower the inertial energy before applying the Δ V. The framework of the circular restricted three-body problem (CR3BP) is employed for the binary asteroid system. The proposed capture strategy is based on the mechanism by which inertial energy can be decreased sharply near zero-velocity curves (ZVCs). The strategy has two steps, namely, hitting the target ZVC and raising the periapsis by a small Δ V at the apoapsis. By hitting the target ZVC, the positive inertial energy decreases and becomes negative. Using a small Δ V, the spacecraft inserts into a bounded orbit around the asteroid. In addition, a rotating mass dipole model is employed for elongated asteroids, which leads to dynamics similar to that of the CR3BP. With this approach, the proposed capture strategy can be applied to elongated asteroids. Numerical simulations validate that the proposed capture strategy is applicable for the binary asteroid 90 Antiope and the elongated asteroid 216 Kleopatra.

  17. Adiabatic condition and the quantum hitting time of Markov chains

    International Nuclear Information System (INIS)

    Krovi, Hari; Ozols, Maris; Roland, Jeremie

    2010-01-01

    We present an adiabatic quantum algorithm for the abstract problem of searching marked vertices in a graph, or spatial search. Given a random walk (or Markov chain) P on a graph with a set of unknown marked vertices, one can define a related absorbing walk P ' where outgoing transitions from marked vertices are replaced by self-loops. We build a Hamiltonian H(s) from the interpolated Markov chain P(s)=(1-s)P+sP ' and use it in an adiabatic quantum algorithm to drive an initial superposition over all vertices to a superposition over marked vertices. The adiabatic condition implies that, for any reversible Markov chain and any set of marked vertices, the running time of the adiabatic algorithm is given by the square root of the classical hitting time. This algorithm therefore demonstrates a novel connection between the adiabatic condition and the classical notion of hitting time of a random walk. It also significantly extends the scope of previous quantum algorithms for this problem, which could only obtain a full quadratic speedup for state-transitive reversible Markov chains with a unique marked vertex.

  18. Promiscuous 2-aminothiazoles (PrATs): a frequent hitting scaffold.

    Science.gov (United States)

    Devine, Shane M; Mulcair, Mark D; Debono, Cael O; Leung, Eleanor W W; Nissink, J Willem M; Lim, San Sui; Chandrashekaran, Indu R; Vazirani, Mansha; Mohanty, Biswaranjan; Simpson, Jamie S; Baell, Jonathan B; Scammells, Peter J; Norton, Raymond S; Scanlon, Martin J

    2015-02-12

    We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), as frequent-hitting fragments in biophysical binding assays. This was exemplified by 4-phenylthiazol-2-amine being identified as a hit in 14/14 screens against a diverse range of protein targets, suggesting that this scaffold is a poor starting point for fragment-based drug discovery. This prompted us to analyze this scaffold in the context of an academic fragment library used for fragment-based drug discovery (FBDD) and two larger compound libraries used for high-throughput screening (HTS). This analysis revealed that such "promiscuous 2-aminothiazoles" (PrATs) behaved as frequent hitters under both FBDD and HTS settings, although the problem was more pronounced in the fragment-based studies. As 2-ATs are present in known drugs, they cannot necessarily be deemed undesirable, but the combination of their promiscuity and difficulties associated with optimizing them into a lead compound makes them, in our opinion, poor scaffolds for fragment libraries.

  19. Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K.

    Science.gov (United States)

    Pecchi, Sabina; Ni, Zhi-Jie; Han, Wooseok; Smith, Aaron; Lan, Jiong; Burger, Matthew; Merritt, Hanne; Wiesmann, Marion; Chan, John; Kaufman, Susan; Knapp, Mark S; Janssen, Johanna; Huh, Kay; Voliva, Charles F

    2013-08-15

    PI3 kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. The PI3 Kinase pathway is often de-regulated in cancer through PI3Kα overexpression, gene amplification, mutations and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe how the potency of a benzothiazole fragment hit was quickly improved based on structural information and how this early chemotype was further optimized through scaffold hopping. This effort led to the identification of a series of 2-acetamido-5-heteroaryl imidazopyridines showing potent in vitro activity against all class I PI3Ks and attractive pharmacokinetic properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Analysis and hit filtering of a very large library of compounds screened against Mycobacterium tuberculosis.

    Science.gov (United States)

    Ekins, Sean; Kaneko, Takushi; Lipinski, Christopher A; Bradford, Justin; Dole, Krishna; Spektor, Anna; Gregory, Kellan; Blondeau, David; Ernst, Sylvia; Yang, Jeremy; Goncharoff, Nicko; Hohman, Moses M; Bunin, Barry A

    2010-11-01

    There is an urgent need for new drugs against tuberculosis which annually claims 1.7-1.8 million lives. One approach to identify potential leads is to screen in vitro small molecules against Mycobacterium tuberculosis (Mtb). Until recently there was no central repository to collect information on compounds screened. Consequently, it has been difficult to analyze molecular properties of compounds that inhibit the growth of Mtb in vitro. We have collected data from publically available sources on over 300 000 small molecules deposited in the Collaborative Drug Discovery TB Database. A cheminformatics analysis on these compounds indicates that inhibitors of the growth of Mtb have statistically higher mean logP, rule of 5 alerts, while also having lower HBD count, atom count and lower PSA (ChemAxon descriptors), compared to compounds that are classed as inactive. Additionally, Bayesian models for selecting Mtb active compounds were evaluated with over 100 000 compounds and, they demonstrated 10 fold enrichment over random for the top ranked 600 compounds. This represents a promising approach for finding compounds active against Mtb in whole cells screened under the same in vitro conditions. Various sets of Mtb hit molecules were also examined by various filtering rules used widely in the pharmaceutical industry to identify compounds with potentially reactive moieties. We found differences between the number of compounds flagged by these rules in Mtb datasets, malaria hits, FDA approved drugs and antibiotics. Combining these approaches may enable selection of compounds with increased probability of inhibition of whole cell Mtb activity.

  1. EASY-HIT: HIV full-replication technology for broad discovery of multiple classes of HIV inhibitors.

    Science.gov (United States)

    Kremb, Stephan; Helfer, Markus; Heller, Werner; Hoffmann, Dieter; Wolff, Horst; Kleinschmidt, Andrea; Cepok, Sabine; Hemmer, Bernhard; Durner, Jörg; Brack-Werner, Ruth

    2010-12-01

    HIV replication assays are important tools for HIV drug discovery efforts. Here, we present a full HIV replication system (EASY-HIT) for the identification and analysis of HIV inhibitors. This technology is based on adherently growing HIV-susceptible cells, with a stable fluorescent reporter gene activated by HIV Tat and Rev. A fluorescence-based assay was designed that measures HIV infection by two parameters relating to the early and the late phases of HIV replication, respectively. Validation of the assay with a panel of nine reference inhibitors yielded effective inhibitory concentrations consistent with published data and allowed discrimination between inhibitors of early and late phases of HIV replication. Finer resolution of the effects of reference drugs on different steps of HIV replication was achieved in secondary time-of-addition assays. The EASY-HIT assay yielded high Z' scores (>0.9) and signal stabilities, confirming its robustness. Screening of the LOPAC(1280) library identified 10 compounds (0.8%), of which eight were known to inhibit HIV, validating the suitability of this assay for screening applications. Studies evaluating anti-HIV activities of natural products with the EASY-HIT technology led to the identification of three novel inhibitory compounds that apparently act at different steps of HIV-1 replication. Furthermore, we demonstrate successful evaluation of plant extracts for HIV-inhibitory activities, suggesting application of this technology for the surveillance of biological extracts with anti-HIV activities. We conclude that the EASY-HIT technology is a versatile tool for the discovery and characterization of HIV inhibitors.

  2. SHIELD-HIT12A - a Monte Carlo particle transport program for ion therapy research

    DEFF Research Database (Denmark)

    Bassler, Niels; Hansen, David Christoffer; Lühr, Armin

    2014-01-01

    . We experienced that new users quickly learn to use SHIELD-HIT12A and setup new geometries. Contrary to previous versions of SHIELD-HIT, the 12A distribution comes along with easy-to-use example files and an English manual. A new implementation of Vavilov straggling resulted in a massive reduction......Abstract. Purpose: The Monte Carlo (MC) code SHIELD-HIT simulates the transport of ions through matter. Since SHIELD-HIT08 we added numerous features that improves speed, usability and underlying physics and thereby the user experience. The “-A” fork of SHIELD-HIT also aims to attach SHIELD....... It supports native formats compatible with the heavy ion treatment planning system TRiP. Stopping power files follow ICRU standard and are generated using the libdEdx library, which allows the user to choose from a multitude of stopping power tables. Results: SHIELD-HIT12A runs on Linux and Windows platforms...

  3. Plasma response to sustainment with imposed-dynamo current drive in HIT-SI and HIT-SI3

    Science.gov (United States)

    Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Penna, J. M.; Everson, C. J.; Nelson, B. A.

    2017-07-01

    The helicity injected torus—steady inductive (HIT-SI) program studies efficient, steady-state current drive for magnetic confinement plasmas using a novel experimental method. Stable, high-beta spheromaks have been sustained using steady, inductive current drive. Externally induced loop voltage and magnetic flux are oscillated together so that helicity and power injection are always positive, sustaining the edge plasma current indefinitely. Imposed-dynamo current drive (IDCD) theory further shows that the entire plasma current is sustained. The method is ideal for low aspect ratio, toroidal geometries with closed flux surfaces. Experimental studies of spheromak plasmas sustained with IDCD have shown stable magnetic profiles with evidence of pressure confinement. New measurements show coherent motion of a stable spheromak in response to the imposed perturbations. On the original device two helicity injectors were mounted on either side of the spheromak and the injected mode spectrum was predominantly n  =  1. Coherent, rigid motion indicates that the spheromak is stable and a lack of plasma-generated n  =  1 energy indicates that the maximum q is maintained below 1 during sustainment. Results from the HIT-SI3 device are also presented. Three inductive helicity injectors are mounted on one side of the spheromak flux conserver. Varying the relative injector phasing changes the injected mode spectrum which includes n  =  2, 3, and higher modes.

  4. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

    Science.gov (United States)

    Warkentin, Theodore E; Pai, Menaka; Linkins, Lori-Ann

    2017-08-31

    Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban. © 2017 by The American Society of Hematology.

  5. Prenatal cannabis exposure - The "first hit" to the endocannabinoid system.

    Science.gov (United States)

    Richardson, Kimberlei A; Hester, Allison K; McLemore, Gabrielle L

    As more states and countries legalize medical and/or adult recreational marijuana use, the incidences of prenatal cannabis exposure (PCE) will likely increase. While young people increasingly view marijuana as innocuous, marijuana preparations have been growing in potency in recent years, potentially creating global clinical, public health, and workforce concerns. Unlike fetal alcohol spectrum disorder, there is no phenotypic syndrome associated with PCE. There is also no preponderance of evidence that PCE causes lifelong cognitive, behavioral, or functional abnormalities, and/or susceptibility to subsequent addiction. However, there is compelling circumstantial evidence, based on the principles of teratology and fetal malprogramming, suggesting that pregnant women should refrain from smoking marijuana. The usage of marijuana during pregnancy perturbs the fetal endogenous cannabinoid signaling system (ECSS), which is present and active from the early embryonic stage, modulating neurodevelopment and continuing this role into adulthood. The ECSS is present in virtually every brain structure and organ system, and there is also evidence that this system is important in the regulation of cardiovascular processes. Endocannabinoids (eCBs) undergird a broad spectrum of processes, including the early stages of fetal neurodevelopment and uterine implantation. Delta-9-tetrahydrocannabinol (THC), the psychoactive chemical in cannabis, enters maternal circulation, and readily crosses the placental membrane. THC binds to CB receptors of the fetal ECSS, altering neurodevelopment and possibly rewiring ECSS circuitry. In this review, we discuss the Double-Hit Hypothesis as it relates to PCE. We contend that PCE, similar to a neurodevelopmental teratogen, delivers the first hit to the ECSS, which is compromised in such a way that a second hit (i.e., postnatal stressors) will precipitate the emergence of a specific phenotype. In summary, we conclude that perturbations of the

  6. Validation of the Impact of Health Information Technology (I-HIT) Scale: an international collaborative.

    Science.gov (United States)

    Dykes, Patricia C; Hurley, Ann C; Brown, Suzanne; Carr, Robyn; Cashen, Margaret; Collins, Rita; Cook, Robyn; Currie, Leanne; Docherty, Charles; Ensio, Anneli; Foster, Joanne; Hardiker, Nicholas R; Honey, Michelle L L; Killalea, Rosaleen; Murphy, Judy; Saranto, Kaija; Sensmeier, Joyce; Weaver, Charlotte

    2009-01-01

    In 2005, the Healthcare Information Management Systems Society (HIMSS) Nursing Informatics Community developed a survey to measure the impact of health information technology (HIT), the I-HIT Scale, on the role of nurses and interdisciplinary communication in hospital settings. In 2007, nursing informatics colleagues from Australia, England, Finland, Ireland, New Zealand, Scotland and the United States formed a research collaborative to validate the I-HIT across countries. All teams have completed construct and face validation in their countries. Five out of six teams have initiated reliability testing by practicing nurses. This paper reports the international collaborative's validation of the I-HIT Scale completed to date.

  7. Inflammation and the Two-Hit Hypothesis of Schizophrenia

    Science.gov (United States)

    Feigenson, Keith A.; Kusnecov, Alex W.; Silverstein, Steven M.

    2014-01-01

    The high societal and individual cost of schizophrenia necessitates finding better, more effective treatment, diagnosis, and prevention strategies. One of the obstacles in this endeavor is the diverse set of etiologies that comprises schizophrenia. A substantial body of evidence has grown over the last few decades to suggest that schizophrenia is a heterogeneous syndrome with overlapping symptoms and etiologies. At the same time, an increasing number of clinical, epidemiological, and experimental studies have shown links between schizophrenia and inflammatory conditions. In this review, we analyze the literature on inflammation and schizophrenia, with a particular focus on comorbidity, biomarkers, and environmental insults. We then identify several mechanisms by which inflammation could influence the development of schizophrenia via the two-hit hypothesis. Lastly, we note the relevance of these findings to clinical applications in the diagnosis, prevention, and treatment of schizophrenia. PMID:24247023

  8. Tracking, aiming, and hitting the UAV with ordinary assault rifle

    Science.gov (United States)

    Racek, František; Baláž, Teodor; Krejčí, Jaroslav; Procházka, Stanislav; Macko, Martin

    2017-10-01

    The usage small-unmanned aerial vehicles (UAVs) is significantly increasing nowadays. They are being used as a carrier of military spy and reconnaissance devices (taking photos, live video streaming and so on), or as a carrier of potentially dangerous cargo (intended for destruction and killing). Both ways of utilizing the UAV cause the necessity to disable it. From the military point of view, to disable the UAV means to bring it down by a weapon of an ordinary soldier that is the assault rifle. This task can be challenging for the soldier because he needs visually detect and identify the target, track the target visually and aim on the target. The final success of the soldier's mission depends not only on the said visual tasks, but also on the properties of the weapon and ammunition. The paper deals with possible methods of prediction of probability of hitting the UAV targets.

  9. HIT-6 and MIDAS as measures of headache disability in a headache referral population.

    Science.gov (United States)

    Sauro, Khara M; Rose, Marianne S; Becker, Werner J; Christie, Suzanne N; Giammarco, Rose; Mackie, Gordon F; Eloff, Arnoldas G; Gawel, Marek J

    2010-03-01

    The objective of this study was to compare the headache impact test (HIT-6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache-related disability. The degree of headache-related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. We compared HIT-6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT-6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI-II) scores. A positive correlation was found between HIT-6 and MIDAS scores (r = 0.52). The BDI-II scores correlated equally with the HIT-6 and the MIDAS (r = 0.42). There was a non-monotonic relationship between headache frequency and the MIDAS, and a non-linear monotonic relationship between headache frequency and the HIT-6 (r = 0.24). The correlation was higher between the intensity and the HIT-6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy-nine percent of patients fell into the most severe HIT-6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT-6 than with the MIDAS (McNemar chi-square = 191 on 6 d.f., P MIDAS appear to measure headache-related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT-6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT-6 and MIDAS together may give a more accurate assessment of a patient's headache-related disability.

  10. Lead generation and examples opinion regarding how to follow up hits.

    Science.gov (United States)

    Orita, Masaya; Ohno, Kazuki; Warizaya, Masaichi; Amano, Yasushi; Niimi, Tatsuya

    2011-01-01

    In fragment-based drug discovery (FBDD), not only identifying the starting fragment hit to be developed but also generating a drug lead from that starting fragment hit is important. Converting fragment hits to leads is generally similar to a high-throughput screening (HTS) hits-to-leads approach in that properties associated with activity for a target protein, such as selectivity against other targets and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox), and physicochemical properties should be taken into account. However, enhancing the potency of the fragment hit is a key requirement in FBDD, unlike HTS, because initial fragment hits are generally weak. This enhancement is presently achieved by adding additional chemical groups which bind to additional parts of the target protein or by joining or combining two or more hit fragments; however, strategies for effecting greater improvements in effective activity are needed. X-ray analysis is a key technology attractive for converting fragments to drug leads. This method makes it clear whether a fragment hit can act as an anchor and provides insight regarding introduction of functional groups to improve fragment activity. Data on follow-up chemical synthesis of fragment hits has allowed for the differentiation of four different strategies: fragment optimization, fragment linking, fragment self-assembly, and fragment evolution. Here, we discuss our opinion regarding how to follow up on fragment hits, with a focus on the importance of fragment hits as an anchor moiety to so-called hot spots in the target protein using crystallographic data. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. 77 FR 57567 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-09-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  12. 77 FR 50690 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-08-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  13. 77 FR 15760 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-03-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  14. 76 FR 39108 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-07-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS ACTION: Notice of... the public. Name of Committee: HIT Policy Committee. General Function of the Committee: to provide...

  15. 77 FR 37407 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-06-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  16. 76 FR 22397 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  17. 77 FR 22787 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-04-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  18. 77 FR 27459 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-05-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  19. A C++ object-oriented toolkit for track finding with k-dimensional hits

    International Nuclear Information System (INIS)

    Uiterwijk, J.W.E.; Panman, J.; Vyver, B. van de

    2006-01-01

    A library is described for the recognition of tracks in a set of hits. The hits are assumed to be k-dimensional points (k-d), with k>=1, of which a subset can be grouped into tracks by using short-range correlations. A connection graph between the hits is created by sorting the hits first in k-d space using one of the developed, fast, k-space containers. The track-finding algorithm considers any connection between two hits as a possible track seed and grows these seeds into longer track segments using a modified depth-first search of the connection graph. All hit-acceptance decisions are called via abstract methods of an acceptance criterion class which isolates the library from the application's hit and track model. An application is tuned for a particular tracking environment by creating a concrete implementation for the hit and track acceptance calculations. The implementer is free to trade tracking time for acceptance complexity (influencing efficiency) depending on the requirements of the particular application. Results for simulated data show that the track finding is both efficient and fast even for high noise environments

  20. 76 FR 28783 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  1. 76 FR 79684 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-12-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  2. 77 FR 73660 - HIT Policy Committee Advisory Meetings; Notice of Meetings

    Science.gov (United States)

    2012-12-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  3. 77 FR 28881 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-05-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  4. 76 FR 46298 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  5. 77 FR 65691 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  6. 76 FR 70455 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  7. 77 FR 2727 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-01-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  8. 75 FR 21629 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2010-04-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee...

  9. 76 FR 14975 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  10. 76 FR 50734 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  11. 76 FR 55912 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-09-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... the public. Name of Committee: HIT Policy Committee. General Function of the Committee: To provide...

  12. 75 FR 6398 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-02-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Adoption/Certification Workgroup Meeting; Notice of Meeting AGENCY: Office... of Committee: HIT Policy Committee's Adoption/Certification Workgroup. General Function of the...

  13. 77 FR 41788 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-07-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  14. 76 FR 1432 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2011-01-10

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of Meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  15. 75 FR 8954 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-02-26

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  16. 75 FR 70923 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-11-19

    ... Technology; HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee...

  17. 75 FR 70923 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-11-19

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  18. 75 FR 29761 - Office of the National Coordinator for Health Information Technology: HIT Standards Committee...

    Science.gov (United States)

    2010-05-27

    ... Technology: HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  19. Role of Health Information Technology (HIT) in disability determinations: when medical records become medical evidence.

    Science.gov (United States)

    Tulu, Bengisu; Daniels, Susan; Feldman, Sue; Horan, Thomas A

    2008-11-06

    This exploratory study investigated the impact of incomplete medical evidence on the SSA disability determination process and the role of HIT as a solution. We collected qualitative data from nineteen expert-interviews. Findings indicate that HIT can lead to innovative solutions that can significantly improve the determination process.

  20. Development and psychometric evaluation of the Impact of Health Information Technology (I-HIT) scale.

    Science.gov (United States)

    Dykes, Patricia C; Hurley, Ann; Cashen, Margaret; Bakken, Suzanne; Duffy, Mary E

    2007-01-01

    The use of health information technology (HIT) for the support of communication processes and data and information access in acute care settings is a relatively new phenomenon. A means of evaluating the impact of HIT in hospital settings is needed. The purpose of this research was to design and psychometrically evaluate the Impact of Health Information Technology scale (I-HIT). I-HIT was designed to measure the perception of nurses regarding the ways in which HIT influences interdisciplinary communication and workflow patterns and nurses' satisfaction with HIT applications and tools. Content for a 43-item tool was derived from the literature, and supported theoretically by the Coiera model and by nurse informaticists. Internal consistency reliability analysis using Cronbach's alpha was conducted on the 43-item scale to initiate the item reduction process. Items with an item total correlation of less than 0.35 were removed, leaving a total of 29 items. Item analysis, exploratory principal component analysis and internal consistency reliability using Cronbach's alpha were used to confirm the 29-item scale. Principal components analysis with Varimax rotation produced a four-factor solution that explained 58.5% of total variance (general advantages, information tools to support information needs, information tools to support communication needs, and workflow implications). Internal consistency of the total scale was 0.95 and ranged from 0.80-0.89 for four subscales. I-HIT demonstrated psychometric adequacy and is recommended to measure the impact of HIT on nursing practice in acute care settings.

  1. 76 FR 4354 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2011-01-25

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  2. Visual Illusions and the Control of Ball Placement in Goal-Directed Hitting

    Science.gov (United States)

    Caljouw, Simone R.; Van der Kamp, John; Savelsbergh, Geert J. P.

    2010-01-01

    When hitting, kicking, or throwing balls at targets, online control in the target area is impossible. We assumed this lack of late corrections in the target area would induce an effect of a single-winged Muller-Lyer illusion on ball placement. After extensive practice in hitting balls to different landing locations, participants (N = 9) had to hit…

  3. PageRank, HITS and a unified framework for link analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Chris; He, Xiaofeng; Husbands, Parry; Zha, Hongyuan; Simon, Horst

    2001-10-01

    Two popular webpage ranking algorithms are HITS and PageRank. HITS emphasizes mutual reinforcement between authority and hub webpages, while PageRank emphasizes hyperlink weight normalization and web surfing based on random walk models. We systematically generalize/combine these concepts into a unified framework. The ranking framework contains a large algorithm space; HITS and PageRank are two extreme ends in this space. We study several normalized ranking algorithms which are intermediate between HITS and PageRank, and obtain closed-form solutions. We show that, to first order approximation, all ranking algorithms in this framework, including PageRank and HITS, lead to same ranking which is highly correlated with ranking by indegree. These results support the notion that in web resource ranking indegree and outdegree are of fundamental importance. Rankings of webgraphs of different sizes and queries are presented to illustrate our analysis.

  4. A static-cidal assay for Trypanosoma brucei to aid hit prioritisation for progression into drug discovery programmes.

    Directory of Open Access Journals (Sweden)

    Manu De Rycker

    Full Text Available Human African Trypanosomiasis is a vector-borne disease of sub-Saharan Africa that causes significant morbidity and mortality. Current therapies have many drawbacks, and there is an urgent need for new, better medicines. Ideally such new treatments should be fast-acting cidal agents that cure the disease in as few doses as possible. Screening assays used for hit-discovery campaigns often do not distinguish cytocidal from cytostatic compounds and further detailed follow-up experiments are required. Such studies usually do not have the throughput required to test the large numbers of hits produced in a primary high-throughput screen. Here, we present a 384-well assay that is compatible with high-throughput screening and provides an initial indication of the cidal nature of a compound. The assay produces growth curves at ten compound concentrations by assessing trypanosome counts at 4, 24 and 48 hours after compound addition. A reduction in trypanosome counts over time is used as a marker for cidal activity. The lowest concentration at which cell killing is seen is a quantitative measure for the cidal activity of the compound. We show that the assay can identify compounds that have trypanostatic activity rather than cidal activity, and importantly, that results from primary high-throughput assays can overestimate the potency of compounds significantly. This is due to biphasic growth inhibition, which remains hidden at low starting cell densities and is revealed in our static-cidal assay. The assay presented here provides an important tool to follow-up hits from high-throughput screening campaigns and avoid progression of compounds that have poor prospects due to lack of cidal activity or overestimated potency.

  5. Creating a safe place for pediatric care: A no hit zone.

    Science.gov (United States)

    Frazier, Erin R; Liu, Gilbert C; Dauk, Kelly L

    2014-07-01

    Our goal was to create and implement a program, Kosair Children's Hospital's No Hit Zone, which trains health care workers in de-escalation techniques to address parental disruptive behaviors and physical discipline of children commonly encountered in the hospital environment. The Child Abuse Task Force, a multidisciplinary group, along with key hospital administrators developed specific content for the policy, as well as marketing and educational materials. The No Hit Zone policy designates Kosair Children's Hospital as "an environment in which no adult shall hit a child, no adult shall hit another adult, no child shall hit an adult, and no child shall hit another child. When hitting is observed, it is everyone's responsibility to interrupt the behavior as well as communicate system policy to those present." Via a multidisciplinary, collaborative approach, the No Hit Zone was successfully implemented at Kosair Children's Hospital in 2012. Cost was nominal, and the support of key hospital administrators was critical to the program's success. Education of health professionals on de-escalation techniques and intervention with families at the early signs of parental stress occurred via live sessions and online training via case-based scenarios. The No Hit Zone is an important program used to provide a safe and caring environment for all families and staff of Kosair Children's Hospital. Demand for the program continues, demonstrated by the establishment of No Hit Zones at other local hospitals and multiple outpatient clinics. This article offers information for other organizations planning to conduct similar initiatives. Copyright © 2014 by the American Academy of Pediatrics.

  6. Scientific impact: the story of your big hit

    Science.gov (United States)

    Sinatra, Roberta; Wang, Dashun; Deville, Pierre; Song, Chaoming; Barabasi, Albert-Laszlo

    2014-03-01

    A gradual increase in performance through learning and practice characterize most trades, from sport to music or engineering, and common sense suggests this to be true in science as well. This prompts us to ask: what are the precise patterns that lead to scientific excellence? Does performance indeed improve throughout a scientific career? Are there quantifiable signs of an impending scientific hit? Using citation-based measures as a proxy of impact, we show that (i) major discoveries are not preceded by works of increasing impact, nor are followed by work of higher impact, (ii) the precise time ranking of the highest impact work in a scientist's career is uniformly random, with the higher probability to have a major discovery in the middle of scientific careers being due only to changes in productivity, (iii) there is a strong correlation between the highest impact work and average impact of a scientist's work. These findings suggest that the impact of a paper is drawn randomly from an impact distribution that is unique for each scientist. We present a model which allows to reconstruct the individual impact distribution, making possible to create synthetic careers that exhibit the same properties of the real data and to define a ranking based on the overall impact of a scientist. RS acknowledges support from the James McDonnell Foundation.

  7. Glucose-stimulated insulin secretion of insulinoma INS-1E cells is associated with elevation of both respiration and mitochondrial membrane potential

    Czech Academy of Sciences Publication Activity Database

    Špaček, Tomáš; Šantorová, Jitka; Zacharovová, K.; Berková, Z.; Hlavatá, Lydie; Saudek, F.; Ježek, Petr

    2008-01-01

    Roč. 40, č. 8 (2008), s. 1522-1535 ISSN 1357-2725 R&D Projects: GA MZd(CZ) NR7917 Institutional research plan: CEZ:AV0Z50110509 Keywords : in situ mitochondrial membrane potential * in situ mitochondrial respiration * glucose-stimulated insulin secretion Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.178, year: 2008

  8. Database for High Throughput Screening Hits (dHITS): a simple tool to retrieve gene specific phenotypes from systematic screens done in yeast.

    Science.gov (United States)

    Chuartzman, Silvia G; Schuldiner, Maya

    2018-03-25

    In the last decade several collections of Saccharomyces cerevisiae yeast strains have been created. In these collections every gene is modified in a similar manner such as by a deletion or the addition of a protein tag. Such libraries have enabled a diversity of systematic screens, giving rise to large amounts of information regarding gene functions. However, often papers describing such screens focus on a single gene or a small set of genes and all other loci affecting the phenotype of choice ('hits') are only mentioned in tables that are provided as supplementary material and are often hard to retrieve or search. To help unify and make such data accessible, we have created a Database of High Throughput Screening Hits (dHITS). The dHITS database enables information to be obtained about screens in which genes of interest were found as well as the other genes that came up in that screen - all in a readily accessible and downloadable format. The ability to query large lists of genes at the same time provides a platform to easily analyse hits obtained from transcriptional analyses or other screens. We hope that this platform will serve as a tool to facilitate investigation of protein functions to the yeast community. © 2018 The Authors Yeast Published by John Wiley & Sons Ltd.

  9. Numerical modelling of local deposition patients, activity distributions and cellular hit probabilities of inhaled radon progenies in human airways

    International Nuclear Information System (INIS)

    Farkas, A.; Balashazy, I.; Szoeke, I.

    2003-01-01

    The general objective of our research is modelling the biophysical processes of the effects of inhaled radon progenies. This effort is related to the rejection or support of the linear no threshold (LNT) dose-effect hypothesis, which seems to be one of the most challenging tasks of current radiation protection. Our approximation and results may also serve as a useful tool for lung cancer models. In this study, deposition patterns, activity distributions and alpha-hit probabilities of inhaled radon progenies in the large airways of the human tracheobronchial tree are computed. The airflow fields and related particle deposition patterns strongly depend on the shape of airway geometry and breathing pattern. Computed deposition patterns of attached an unattached radon progenies are strongly inhomogeneous creating hot spots at the carinal regions and downstream of the inner sides of the daughter airways. The results suggest that in the vicinity of the carinal regions the multiple hit probabilities are quite high even at low average doses and increase exponentially in the low-dose range. Thus, even the so-called low doses may present high doses for large clusters of cells. The cell transformation probabilities are much higher in these regions and this phenomenon cannot be modeled with average burdens. (authors)

  10. Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities.

    Science.gov (United States)

    Warkentin, Theodore E; Sheppard, Jo-Ann I; Chu, F Victor; Kapoor, Anil; Crowther, Mark A; Gangji, Azim

    2015-01-01

    Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (eg, platelet serotonin-release assay [SRA]) has been recommended as the target serological end point to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive. © 2015 by The American Society of Hematology.

  11. Throat hit in users of the electronic cigarette: An exploratory study.

    Science.gov (United States)

    Etter, Jean-François

    2016-02-01

    A cross-sectional survey on the Internet in 2012-2014 was used to study the "throat hit," the specific sensation in the throat felt by users of e-cigarettes. Participants were 1672 current users of e-cigarettes, visitors of Websites dedicated to e-cigarettes and to smoking cessation. It was assessed whether the strength of the throat hit was associated with the characteristics of e-cigarettes and e-liquids, modifications of the devices, patterns of use, reasons for use, satisfaction with e-cigarettes, dependence on e-cigarettes, smoking behavior, and perceived effects on smoking. The strongest throat hit was obtained by using better-quality models and liquids with high nicotine content. Those who reported a "very strong" throat hit used liquids with 17.3 mg/mL nicotine, versus 7.1 mg/mL for those reporting a "very weak" hit (p e-cigarette models that provide high levels of nicotine, a strong throat hit, high satisfaction, and more effects on smoking, but may also be addictive, and models than contain less nicotine and are less addictive, but produce a weaker throat hit, are less satisfactory, and are possibly less efficient at helping people quit smoking. This trade-off must be kept in mind when regulating e-cigarettes. (c) 2016 APA, all rights reserved).

  12. Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

    Science.gov (United States)

    Cucinotta, Francis A.; Ponomarev, Artem

    2009-01-01

    A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

  13. Double-hit lymphoma demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-hit translocations, MYC/BCL-2 and IRF4/BCL-2.

    Science.gov (United States)

    Tabata, Rie; Yasumizu, Ryoji; Tabata, Chiharu; Kojima, Masaru

    2013-01-01

    Here, we report a rare case of double-hit lymphoma, demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2. The present case had a rare abnormal chromosome, t(6;14;18)(p25;q32;q21), independently, in addition to known dual-hit chromosomal abnormalities, t(14;18)(q32;q21) and t(8;22)(q24;q11.2). Lymph node was characterized by a follicular and diffuse growth pattern with variously sized neoplastic follicles. The intrafollicular area was composed of centrocytes with a few centroblasts and the interfollicular area was occupied by uniformly spread medium- to large-sized lymphocytes. CD23 immunostaining demonstrated a disrupted follicular dendritic cell meshwork. The intrafollicular tumor cells had a germinal center phenotype with the expression of surface IgM, CD10, Bcl-2, Bcl-6, and MUM1/IRF4. However, the interfollicular larger cells showed plasmacytic differentiation with diminished CD20, Bcl-2, Bcl-6, and positive intracytoplasmic IgM, and co-expression of MUM1/IRF4 and CD138 with increased Ki-67-positive cells (> 90%). MUM1/IRF4 has been found to induce c-MYC expression, and in turn, MYC transactivates MUM1/IRF4, creating a positive autoregulatory feedback loop. On the other hand, MUM1/IRF4 functions as a tumor suppressor in c-MYC-induced B-cell leukemia. The present rare case arouses interest in view of the possible "dual" activation of both c-MYC and MUM1/IRF4 through two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2.

  14. Lower bounds on the periodic Hamming correlations of frequency hopping sequences with low hit zone

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this paper, several periodic Hamming correlation lower bounds for frequency hopping sequences with low hit zone, with respect to the size p of the frequency slot set, the sequence length L, the family size M, low hit zone LH ( or no hit zone NH ), the maximum periodic Hamming autocorrelation sidelobe Ha and the maximum periodic Hamming crosscorrelation Hc, are established. It is shown that the new bounds include the known Lempel-Greenberger bounds, T.S. Seay bounds and Peng-Fan bounds for the conventional frequency hopping sequences as special cases.

  15. Irradiation of bone lining cells from bone-seeking alpha-emitters

    International Nuclear Information System (INIS)

    Kruglikov, I.; Polig, E.

    1993-01-01

    The influence of bone remodeling and the non-uniform distribution of alpha-emitters on the hit statistics is discussed. It is shown that for the first generation of bone lining cells, bone remodeling decreases the probability of no hits to the nuclei of these cells whereas the randomness of the spatial distribution of nuclide increases this probability. For the subsequent generations bone remodeling as well as spatial distribution of nuclide increase the probability of no hits. The most conservative estimations for the variance of hits and probability of no hits, which are defined by the minimums of these values, are obtained. (orig.)

  16. The T10 beam produces a few hits per event. In ALICE the SSD will have to cope with many hits per strip. In the three centimeters of aluminium the beam will produce many secondary particles. This increases the chance of multiple hits per strip, although not to the level in ALICE.

    CERN Multimedia

    Nooren, G.

    2004-01-01

    The T10 beam produces a few hits per event. In ALICE the SSD will have to cope with many hits per strip. In the three centimeters of aluminium the beam will produce many secondary particles. This increases the chance of multiple hits per strip, although not to the level in ALICE.

  17. High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors.

    Science.gov (United States)

    Myers, Stephanie M; Bawn, Ruth H; Bisset, Louise C; Blackburn, Timothy J; Cottyn, Betty; Molyneux, Lauren; Wong, Ai-Ching; Cano, Celine; Clegg, William; Harrington, Ross W; Leung, Hing; Rigoreau, Laurent; Vidot, Sandrine; Golding, Bernard T; Griffin, Roger J; Hammonds, Tim; Newell, David R; Hardcastle, Ian R

    2016-08-08

    The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase.

  18. Optimal Fixed-Interval Integrated Guidance-Control Laws for Hit-to-Kill Missiles

    National Research Council Canada - National Science Library

    Menon, P. K; Sweriduk, G. D; Ohlmeyer, E. J

    2003-01-01

    Due to their potential for reducing the weapon size and efficiency, design methods for realizing hit-to- kill capabilities in missile systems are of significant research interest in the missile flight control community...

  19. 75 FR 32472 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-06-08

    ... Coordinator for Health Information Technology AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of committee recommendations and invitation for public input... Coordinator for Health Information Technology (ONC). Name of Committee: HIT Standards Committee. General...

  20. Development of the PRE-HIT instrument: patient readiness to engage in health information technology.

    Science.gov (United States)

    Koopman, Richelle J; Petroski, Gregory F; Canfield, Shannon M; Stuppy, Julie A; Mehr, David R

    2014-01-28

    Technology-based aids for lifestyle change are becoming more prevalent for chronic conditions. Important "digital divides" remain, as well as concerns about privacy, data security, and lack of motivation. Researchers need a way to characterize participants' readiness to use health technologies. To address this need, we created an instrument to measure patient readiness to engage with health technologies among adult patients with chronic conditions. Initial focus groups to determine domains, followed by item development and refinement, and exploratory factor analysis to determine final items and factor structure. The development sample included 200 patients with chronic conditions from 6 family medicine clinics. From 98 potential items, 53 best candidate items were examined using exploratory factor analysis. Pearson's Correlation for Test/Retest reliability at 3 months. The final instrument had 28 items that sorted into 8 factors with associated Cronbach's alpha: 1) Health Information Need (0.84), 2) Computer/Internet Experience (0.87), 3) Computer Anxiety (0.82), 4) Preferred Mode of Interaction (0.73), 5) Relationship with Doctor (0.65), 6) Cell Phone Expertise (0.75), 7) Internet Privacy (0.71), and 8) No News is Good News (0.57). Test-retest reliability for the 8 subscales ranged from (0.60 to 0.85). The Patient Readiness to Engage in Health Internet Technology (PRE-HIT) instrument has good psychometric properties and will be an aid to researchers investigating technology-based health interventions. Future work will examine predictive validity.

  1. Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits.

    Science.gov (United States)

    Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

    2015-01-01

    Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization. © 2014 Society for Laboratory Automation and Screening.

  2. Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

    Science.gov (United States)

    Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

    2015-01-01

    Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.

  3. HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.

    Science.gov (United States)

    Favaloro, Emmanuel J; McCaughan, Georgia; Mohammed, Soma; Lau, Kun Kan Edwin; Gemmell, Rosalie; Cavanaugh, Lauren; Donikian, Dea; Kondo, Mayuko; Brighton, Timothy; Pasalic, Leonardo

    2018-04-17

    Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG (PF4-H) ), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]. We observed both false positive and false negative test findings with most assays. Overall, the whole blood aggregation method provided a reasonable alternative to SRA for identifying functional HIT. STiC, AcuStar and ELISA procedures were fairly comparable in terms of screening for HIT, although STiC and AcuStar both yielded false negatives, albeit also resulting in fewer false positives than ELISA. The 4T score had less utility in our patient cohort than we were expecting, although there was an association with the likelihood of HIT. Nevertheless, we accept that our observations are based on limited test numbers. In conclusion, no single approach (clinical or laboratory) was associated with optimal sensitivity or specificity of HIT exclusion or identification, and thus, a combination of clinical evaluation and laboratory testing will best ensure the accuracy of diagnosis. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  4. Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

    Science.gov (United States)

    Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

    2017-10-05

    One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

  5. USER FRUSTRATION IN HIT INTERFACES: EXPLORING PAST HCI RESEARCH FOR A BETTER UNDERSTANDING OF CLINICIANS' EXPERIENCES.

    Science.gov (United States)

    Opoku-Boateng, Gloria A

    2015-01-01

    User frustration research has been one way of looking into clinicians' experience with health information technology use and interaction. In order to understand how clinician frustration with Health Information Technology (HIT) use occurs, there is the need to explore Human-Computer Interaction (HCI) literature that addresses both frustration and HIT use. In the past three decades, HCI frustration research has increased and expanded. Researchers have done a lot of work to understand emotions, end-user frustration and affect. This paper uses a historical literature review approach to review the origins of emotion and frustration research and explore the research question; Does HCI research on frustration provide insights on clinicians' frustration with HIT interfaces? From the literature review HCI research on emotion and frustration provides additional insights that can indeed help explain user frustration in HIT. Different approaches and HCI perspectives also help frame HIT user frustration research as well as inform HIT system design. The paper concludes with a suggested directions on how future design and research may take.

  6. The impact of Health Information Technology (I-HIT) Scale: the Australian results.

    Science.gov (United States)

    Cook, Robyn; Foster, Joanne

    2009-01-01

    One of role of the nurse in the clinical setting is that of co-ordinating communication across the healthcare team. On a daily basis nurses interact with the person receiving care, their family members, and multiple care providers thus placing the nurse in the central position with access to a vast array of information on the person. Through this nurses have historically functioned as "information repositories". With the advent of Health Information Technology (HIT) tools there is a potential that HIT could impact interdisciplinary communication, practice efficiency and effectiveness, relationships and workflow in acute care settings [1][3]. In 2005, the HIMSS Nursing Informatics Community developed the I-HIT Scale to measure the impact of HIT on the nursing role and interdisciplinary communication in USA hospitals. In 2007, nursing informatics colleagues from Australia, Finland, Ireland, New Zealand, Scotland and the USA formed a research collaborative to validate the I-HIT in six additional countries. This paper will discuss the background, methodology, results and implications from the Australian I-HIT survey of over 1,100 nurses. The results are currently being analyzed and will be presented at the conference.

  7. Are stripes beneficial? Dazzle camouflage influences perceived speed and hit rates.

    Directory of Open Access Journals (Sweden)

    Bettina von Helversen

    Full Text Available In the animal kingdom, camouflage refers to patterns that help potential prey avoid detection. Mostly camouflage is thought of as helping prey blend in with their background. In contrast, disruptive or dazzle patterns protect moving targets and have been suggested as an evolutionary force in shaping the dorsal patterns of animals. Dazzle patterns, such as stripes and zigzags, are thought to reduce the probability with which moving prey will be captured by impairing predators' perception of speed. We investigated how different patterns of stripes (longitudinal-i.e., parallel to movement direction-and vertical-i.e., perpendicular to movement direction affect the probability with which humans can hit moving objects and if differences in hitting probability are caused by a misperception of speed. A first experiment showed that longitudinally striped objects were hit more often than unicolored objects. However, vertically striped objects did not differ from unicolored objects. A second study examining the link between perceived speed and hitting probability showed that longitudinally and vertically striped objects were both perceived as moving faster and were hit more often than unicolored objects. In sum, our results provide evidence that striped patterns disrupt the perception of speed, which in turn influences how often objects are hit. However, the magnitude and the direction of the effects depend on additional factors such as speed and the task setup.

  8. The application of SHIELD-HIT12A computer code to calculate of absorption dose for in vitro and in vivo test in BNCT

    International Nuclear Information System (INIS)

    Yohannes Sardjono; Hamidatul Faqqiyyah; Niels Bassler

    2014-01-01

    The projection of world population growth and increased longevity are leading to a rapid increase in the total number of middle-aged and older adults, with a corresponding increase in the number of deaths caused by non communicable diseases. It is projected that the annual number of deaths due to cardiovascular disease will increase from 17 million in 2008 to 25 million in 2030 with annual cancer deaths increasing from 7.6 million to 13 million. Boron Neutron Capture Therapy is a therapy that utilizes the absorption interaction of Boron-10 with thermal neutron and become He-4 particle and located in cell target and very short half life gamma emission. Studies were carried out to dose distribution in HER-2+ breast cancer therapy by Boron Neutron Capture Therapy (BNCT) using SHIELD Heavy Ion Therapy (HIT12A) T program. The Monte Carlo particle transport code SHIELD-HIT1 is designed to precisely simulate therapeutic beams of protons and ions in biological tissue relevant for ion beam cancer therapy. SHIELD-HIT (Heavy Ion Therapy) evolved from the common SHIELD code that models interactions of hadrons and atomic nuclei in complex extended targets in the energy range up to 1 TeV/nucleon. Through this computer code can be applied to calculate of absorption dose in cell target. (author)

  9. NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

    Science.gov (United States)

    Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

    2017-01-01

    The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Influence of The Difference of Perception and Kinesthetic Exercise Methods Against Precision Hit The Ball Softball

    Directory of Open Access Journals (Sweden)

    Fajar Rokhayah

    2017-06-01

    Full Text Available The purpose of this study was to determine: 1 The difference between the effects of training methods and the gradual striking distance striking distance remains as to the accuracy of hitting the ball Softball. 2 The difference in accuracy influence Softball hitting the ball between the athletes who have a good kinesthetic perception, kinesthetic perception was, and kinesthetic perception less. 3 The effect of interaction between training methods with kinesthetic perception as to the accuracy of hitting the ball Softball. This study used an experimental method with 2x3 factorial design. The results of this study were: 1 There is a significant difference between the gradual striking distance training methods and training methods remain striking distance of the ability to hit a softball with the result of the acquisition value p-value = 0.027 smaller than 0.05. 2 There is a significant difference between athletes who have a kinesthetic perception of good, moderate, lacking the ability to hit a softball with the result of the acquisition value p-value = 0.000, which is smaller than 0.05. 3 There is an interaction between striking distance training methods and kinesthetic perception of the ability to hit a softball with the result of the acquisition value p-value = 0.000, which is smaller than 0.05 The conclusion of this study were: 1 Gradually striking distance training methods have a better effect than the fixed striking distance training methods. 2 Athletes who have less kinesthetic perception has better results than the athletes who have good kinesthetic perception and being. 3 There is an interaction between striking distance training methods and kinesthetic perception of the ability to hit a softball.

  11. Progress on FIR interferometry and Thomson Scattering measurements on HIT-SI3

    Science.gov (United States)

    Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

    2017-10-01

    Spatially resolved measurements of the electron temperature (Te) and density (ne) will be fundamental in assessing the degree to which HIT-SI3 demonstrates closed magnetic flux and energy confinement. Further, electron temperature measurements have not yet been made on an inductively-driven spheromak. Far infrared (FIR) interferometer and Thomson Scattering (TS) systems have been installed on the HIT-SI3 spheromak. The TS system currently implemented on HIT-SI3 was originally designed for other magnetic confinement experiments, and progress continues toward modifying and optimizing for HIT-SI3 plasmas. Initial results suggest that the electron temperature is of order 10 eV. Plans to modify the TS system to provide more sensitivity and accuracy at low temperatures are presented. The line-integrated ne is measured on one chord by the FIR interferometer, with densities near 5x1019 m-3. Four cylindrical volumes have been added to the HIT-SI3 apparatus to enhance passive pumping. It is hoped that this will allow for more control of the density during the 2 ms discharges. Density measurements from before and after the installation of the passive pumping volumes are presented for comparison.

  12. Laboratory tests for identification or exclusion of heparin induced thrombocytopenia: HIT or miss?

    Science.gov (United States)

    Favaloro, Emmanuel J

    2018-02-01

    Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin ("anti-PF4-heparin"). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay ("screening"), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed. The most common contemporary immunological assays comprise enzyme-linked immunosorbent assay [ELISA], chemiluminescence, lateral flow, and particle gel techniques. The most common functional assays measure platelet aggregation or platelet activation events (e.g., serotonin release assay; heparin-induced platelet activation (HIPA); flow cytometry). All assays have some sensitivity and specificity to HIT antibodies, but differ in terms of relative sensitivity and specificity for pathological HIT, as well as false negative and false positive error rate. This brief article overviews the different available laboratory methods, as well as providing a suggested approach to diagnosis or exclusion of HIT. © 2017 Wiley Periodicals, Inc.

  13. Anticipating mismatches of HIT investments: Developing a viability-fit model for e-health services.

    Science.gov (United States)

    Mettler, Tobias

    2016-01-01

    Albeit massive investments in the recent years, the impact of health information technology (HIT) has been controversial and strongly disputed by both research and practice. While many studies are concerned with the development of new or the refinement of existing measurement models for assessing the impact of HIT adoption (ex post), this study presents an initial attempt to better understand the factors affecting viability and fit of HIT and thereby underscores the importance of also having instruments for managing expectations (ex ante). We extend prior research by undertaking a more granular investigation into the theoretical assumptions of viability and fit constructs. In doing so, we use a mixed-methods approach, conducting qualitative focus group discussions and a quantitative field study to improve and validate a viability-fit measurement instrument. Our findings suggest two issues for research and practice. First, the results indicate that different stakeholders perceive HIT viability and fit of the same e-health services very unequally. Second, the analysis also demonstrates that there can be a great discrepancy between the organizational viability and individual fit of a particular e-health service. The findings of this study have a number of important implications such as for health policy making, HIT portfolios, and stakeholder communication. Copyright © 2015. Published by Elsevier Ireland Ltd.

  14. A microwell cell culture platform for the aggregation of pancreatic β-cells.

    Science.gov (United States)

    Bernard, Abigail B; Lin, Chien-Chi; Anseth, Kristi S

    2012-08-01

    Cell-cell contact between pancreatic β-cells is important for maintaining survival and normal insulin secretion. Various techniques have been developed to promote cell-cell contact between β-cells, but a simple yet robust method that affords precise control over three-dimensional (3D) β-cell cluster size has not been demonstrated. To address this need, we developed a poly(ethylene glycol) (PEG) hydrogel microwell platform using photolithography. This microwell cell-culture platform promotes the formation of 3D β-cell aggregates of defined sizes from 25 to 210 μm in diameter. Using this platform, mouse insulinoma 6 (MIN6) β-cells formed aggregates with cell-cell adherin junctions. These naturally formed cell aggregates with controllable sizes can be removed from the microwells for macroencapsulation, implantation, or other biological assays. When removed and subsequently encapsulated in PEG hydrogels, the aggregated cell clusters demonstrated improved cellular viability (>90%) over 7 days in culture, while the β-cells encapsulated as single cells maintained only 20% viability. Aggregated MIN6 cells also exhibited more than fourfold higher insulin secretion in response to a glucose challenge compared with encapsulated single β-cells. Further, the cell aggregates stained positively for E-cadherin, indicative of the formation of cell junctions. Using this hydrogel microwell cell-culture method, viable and functional β-cell aggregates of specific sizes were created, providing a platform from which other biologically relevant questions may be answered.

  15. Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

    Science.gov (United States)

    Sanders, John M; Beshore, Douglas C; Culberson, J Christopher; Fells, James I; Imbriglio, Jason E; Gunaydin, Hakan; Haidle, Andrew M; Labroli, Marc; Mattioni, Brian E; Sciammetta, Nunzio; Shipe, William D; Sheridan, Robert P; Suen, Linda M; Verras, Andreas; Walji, Abbas; Joshi, Elizabeth M; Bueters, Tjerk

    2017-08-24

    High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter. These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected liabilities that may require significant optimization. Accordingly, these in silico data can direct ADMET experimentation and profoundly impact the progression of hit series. Several prospective examples are presented to substantiate the value of this approach.

  16. Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase Omega-1 as an Example.

    Science.gov (United States)

    Xie, Yiyue; Dahlin, Jayme L; Oakley, Aaron J; Casarotto, Marco G; Board, Philip G; Baell, Jonathan B

    2018-05-10

    Early stage drug discovery reporting on relatively new or difficult targets is often associated with insufficient hit triage. Literature reviews of such targets seldom delve into the detail required to critically analyze the associated screening hits reported. Here we take the enzyme glutathione transferase omega-1 (GSTO1-1) as an example of a relatively difficult target and review the associated literature involving small-molecule inhibitors. As part of this process we deliberately pay closer-than-usual attention to assay interference and hit quality aspects. We believe this Perspective will be a useful guide for future development of GSTO1-1 inhibitors, as well serving as a template for future review formats of new or difficult targets.

  17. A New Track Reconstruction Algorithm suitable for Parallel Processing based on Hit Triplets and Broken Lines

    Directory of Open Access Journals (Sweden)

    Schöning André

    2016-01-01

    Full Text Available Track reconstruction in high track multiplicity environments at current and future high rate particle physics experiments is a big challenge and very time consuming. The search for track seeds and the fitting of track candidates are usually the most time consuming steps in the track reconstruction. Here, a new and fast track reconstruction method based on hit triplets is proposed which exploits a three-dimensional fit model including multiple scattering and hit uncertainties from the very start, including the search for track seeds. The hit triplet based reconstruction method assumes a homogeneous magnetic field which allows to give an analytical solutions for the triplet fit result. This method is highly parallelizable, needs fewer operations than other standard track reconstruction methods and is therefore ideal for the implementation on parallel computing architectures. The proposed track reconstruction algorithm has been studied in the context of the Mu3e-experiment and a typical LHC experiment.

  18. An automated single ion hit at JAERI heavy ion microbeam to observe individual radiation damage

    International Nuclear Information System (INIS)

    Kamiya, Tomihiro; Sakai, Takuro; Naitoh, Yutaka; Hamano, Tsuyoshi; Hirao, Toshio

    1999-01-01

    Microbeam scanning and a single ion hit technique have been combined to establish an automated beam positioning and single ion hit system at the JAERI Takasaki heavy ion microbeam system. Single ion irradiation on preset points of a sample in various patterns can be performed automatically in a short period. The reliability of the system was demonstrated using CR-39 nuclear track detectors. Single ion hit patterns were achieved with a positioning accuracy of 2 μm or less. In measurement of single event transient current using this system, the reduction of the pulse height by accumulation of radiation damages was observed by single ion injection to the same local areas. This technique showed a possibility to get some quantitative information about the lateral displacement of an individual radiation effect in silicon PIN photodiodes. This paper will give details of the irradiation system and present results from several experiments

  19. Transfusion as an Inflammation Hit: Knowns and Unknowns

    Science.gov (United States)

    Garraud, Olivier; Tariket, S.; Sut, C.; Haddad, A.; Aloui, C.; Chakroun, T.; Laradi, S.; Cognasse, F.

    2016-01-01

    Transfusion of blood cell components is frequent in the therapeutic arsenal; it is globally safe or even very safe. At present, residual clinical manifestations are principally inflammatory in nature. If some rare clinical hazards manifest as acute inflammation symptoms of various origin, most of them linked with conflicting and undesirable biological material accompanying the therapeutic component (infectious pathogen, pathogenic antibody, unwanted antigen, or allergen), the general feature is subtler and less visible, and essentially consists of alloimmunization or febrile non-hemolytic transfusion reaction. The present essay aims to present updates in hematology and immunology that help understand how, when, and why subclinical inflammation underlies alloimmunization and circumstances characteristic of red blood cells and – even more frequently – platelets that contribute inflammatory mediators. Modern transfusion medicine makes sustained efforts to limit such inflammatory hazards; efforts can be successful only if one has a clear view of each element’s role. PMID:27965664

  20. #MaybeHeDoesntHitYou: Social Media Underscore the Realities of Intimate Partner Violence.

    Science.gov (United States)

    McCauley, Heather L; Bonomi, Amy E; Maas, Megan K; Bogen, Katherine W; O'Malley, Teagen L

    2018-03-22

    Public intimate partner violence (IPV) discourse emphasizes physical violence. In May 2016, the Twitter hashtag #MaybeHeDoesntHitYou generated a public conversation about abuse beyond physical IPV. Because of the often-disconnect between IPV research and what survivors struggle to name as abuse in their daily lives, we sought to understand how IPV discourse was unfolding as a result of the #MaybeHeDoesntHitYou hashtag. NCapture was used to collect publically available Twitter data containing the hashtag "#MaybeHeDoesntHitYou" from May 10, 2016 to May 17, 2016. Using the Duluth Power and Control Wheel (a range of tactics used by abusers to control and harm their partners) and the Women's Experience with Battering (WEB) framework (emotional and behavioral responses to being abused), we analyzed 1,229 original content tweets using qualitative content analysis. All dimensions of the Power and Control Wheel and five of six dimensions of the WEB framework were expressed via #MaybeHeDoesntHitYou; users did not express yearning for intimacy with their abusive partners. Users described one form of IPV not currently represented within the Power and Control Wheel-reproductive coercion (e.g., "#MaybeHeDoesntHitYou but he refuses to use condoms and forces you not to use contraception so you try to do it behind his back"). Two additional themes emerged; users challenged the gender pronoun of the hashtag, highlighting that abuse may happen with partners of all genders, and users provided social support for others (e.g., "#MaybeHeDoesntHitYou is real. Bruises and scars aren't the only measure of abuse! If this is you, help is there…"). Results from our study underscore the potential for social media platforms to be powerful agents for engaging public dialogue about the realities of IPV, as well as a space for seeking and providing social support about this critical women's health issue.

  1. HIT or miss: the application of health care information technology to managing uncertainty in clinical decision making.

    Science.gov (United States)

    Kazandjian, Vahé A; Lipitz-Snyderman, Allison

    2011-12-01

    To discuss the usefulness of health care information technology (HIT) in assisting care providers minimize uncertainty while simultaneously increasing efficiency of the care provided. An ongoing study of HIT, performance measurement (clinical and production efficiency) and their implications to the payment for care represents the design of this study. Since 2006, all Maryland hospitals have embarked on a multi-faceted study of performance measures and HIT adoption surveys, which will shape the health care payment model in Maryland, the last of the all-payor states, in 2011. This paper focuses on the HIT component of the Maryland care payment initiative. While the payment model is still under review and discussion, 'appropriateness' of care has been discussed as an important dimension of measurement. Within this dimension, the 'uncertainty' concept has been identified as associated with variation in care practices. Hence, the methods of this paper define how HIT can assist care providers in addressing the concept of uncertainty, and then provides findings from the first HIT survey in Maryland to infer the readiness of Maryland hospital in addressing uncertainty of care in part through the use of HIT. Maryland hospitals show noteworthy variation in their adoption and use of HIT. While computerized, electronic patient records are not commonly used among and across Maryland hospitals, many of the uses of HIT internally in each hospital could significantly assist in better communication about better practices to minimize uncertainty of care and enhance the efficiency of its production. © 2010 Blackwell Publishing Ltd.

  2. Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology: description and application to clinical feedback systems.

    Science.gov (United States)

    Lyon, Aaron R; Lewis, Cara C; Melvin, Abigail; Boyd, Meredith; Nicodimos, Semret; Liu, Freda F; Jungbluth, Nathaniel

    2016-09-22

    Health information technologies (HIT) have become nearly ubiquitous in the contemporary healthcare landscape, but information about HIT development, functionality, and implementation readiness is frequently siloed. Theory-driven methods of compiling, evaluating, and integrating information from the academic and commercial sectors are necessary to guide stakeholder decision-making surrounding HIT adoption and to develop pragmatic HIT research agendas. This article presents the Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology, a structured, theory-driven method for compiling and evaluating information from multiple sectors. As an example demonstration of the methodology, we apply HIT-ACE to mental and behavioral health measurement feedback systems (MFS). MFS are a specific class of HIT that support the implementation of routine outcome monitoring, an evidence-based practice. HIT-ACE is guided by theories and frameworks related to user-centered design and implementation science. The methodology involves four phases: (1) coding academic and commercial materials, (2) developer/purveyor interviews, (3) linking putative implementation mechanisms to hit capabilities, and (4) experimental testing of capabilities and mechanisms. In the current demonstration, phase 1 included a systematic process to identify MFS in mental and behavioral health using academic literature and commercial websites. Using user-centered design, implementation science, and feedback frameworks, the HIT-ACE coding system was developed, piloted, and used to review each identified system for the presence of 38 capabilities and 18 additional characteristics via a consensus coding process. Bibliometic data were also collected to examine the representation of the systems in the scientific literature. As an example, results are presented for the application of HIT-ACE phase 1 to MFS wherein 49 separate MFS were identified, reflecting a diverse array of characteristics

  3. Chronic Porcine Two-Hit Model with Hemorrhagic Shock and textitPseudomonas aeruginosa Sepsis

    OpenAIRE

    Eissner, B.;Matz, K.;Smorodchenko, A.;Röschmann, A.;Specht, B. U. v.

    2016-01-01

    Background: Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as ‘first hit’ followed by a Pseudomonas aeruginosa infusion as ‘second hit’. Materials and Methods: Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic...

  4. On hitting children: a review of corporal punishment in the United States.

    Science.gov (United States)

    Knox, Michele

    2010-01-01

    Research has clearly demonstrated associations between corporal punishment of children and maladaptive behavior patterns such as aggression and delinquency. Hitting children is an act of violence and a clear violation of children's human rights. In this article, the position of the United States on corporal punishment of children is discussed. Professional and international progress on ending corporal punishment is explained, and the relationship between corporal punishment and child abuse is discussed. An appeal is made for prevention efforts such as parent education and removal of social sanctions for hitting children that may hold significant promise for preventing child maltreatment.

  5. Improvements to the ion Doppler spectrometer diagnostic on the HIT-SI experiments

    Science.gov (United States)

    Hossack, Aaron; Chandra, Rian; Everson, Chris; Jarboe, Tom

    2018-03-01

    An ion Doppler spectrometer diagnostic system measuring impurity ion temperature and velocity on the HIT-SI and HIT-SI3 spheromak devices has been improved with higher spatiotemporal resolution and lower error than previously described devices. Hardware and software improvements to the established technique have resulted in a record of 6.9 μs temporal and ≤2.8 cm spatial resolution in the midplane of each device. These allow Ciii and Oii flow, displacement, and temperature profiles to be observed simultaneously. With 72 fused-silica fiber channels in two independent bundles, and an f/8.5 Czerny-Turner spectrometer coupled to a video camera, frame rates of up to ten times the imposed magnetic perturbation frequency of 14.5 kHz were achieved in HIT-SI, viewing the upper half of the midplane. In HIT-SI3, frame rates of up to eight times the perturbation frequency were achieved viewing both halves of the midplane. Biorthogonal decomposition is used as a novel filtering tool, reducing uncertainty in ion temperature from ≲13 to ≲5 eV (with an instrument temperature of 8-16 eV) and uncertainty in velocity from ≲2 to ≲1 km/s. Doppler shift and broadening are calculated via the Levenberg-Marquardt algorithm, after which the errors in velocity and temperature are uniquely specified. Axisymmetric temperature profiles on HIT-SI3 for Ciii peaked near the inboard current separatrix at ≈40 eV are observed. Axisymmetric plasma displacement profiles have been measured on HIT-SI3, peaking at ≈6 cm at the outboard separatrix. Both profiles agree with the upper half of the midplane observable by HIT-SI. With its complete midplane view, HIT-SI3 has unambiguously extracted axisymmetric, toroidal current dependent rotation of up to 3 km/s. Analysis of the temporal phase of the displacement uncovers a coherent structure, locked to the applied perturbation. Previously described diagnostic systems could not achieve such results.

  6. Interactive football training based on rebounders with hit position sensing and audio/light feedback

    DEFF Research Database (Denmark)

    Jensen, Mads Møller; Grønbæk, Kaj; Rasmussen, Majken Kirkegård

    A Danish football club has established a (24/7/365) football training facility, where the authors developed an interactive training installation (http://vimeo.com/28446312). The training installation consist of a 12*12 m square with 4 M­Station Pro rebounders equipped with sensors that enable hit...... position sensing. The rebounders are equipped with loudspeakers and lights being used to call for the ball. Here we discuss one game “Pass ­and ­Turn”, which is meant to train speed in controlling a returned ball, reaction to a call for the ball and turning to hit rebounders to the left, right, behind...

  7. Distributions of hit-numbers in single targets

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J F [Postgraduate Medical School, Hammersmith Hospital, London (United Kingdom)

    1966-07-01

    Very general models can be proposed for relating the surviving proportion of an irradiated population of cells or bacteria to the absorbed dose, but if the number of free parameters is large the model can never be tested experimentally (Zimmer; Zirkie; Tobias). A relatively simple model is therefore proposed here, based on the physical facts of energy deposition in small volumes which are currently under active investigation (Rossi), and on cell-survival experiments over a wide range of LET (e.g. Barendsen et al.; Barendsen). It is not suggested that the model is correct or final, but only that its shortcomings should be demonstrated by comparison with experimental results before more complicated models are worth pursuing. It is basically a multihit model applied first to a single target volume, but also applicable to the situation where only one out of many potential target volumes has to be inactivated to kill the organism. It can be extended to two or more target volumes if necessary. Emphasis is placed upon the amount of energy locally deposited in certain sensitive volumes called 'target volumes'.

  8. Blueprint for antimicrobial hit discovery targeting metabolic networks.

    Science.gov (United States)

    Shen, Y; Liu, J; Estiu, G; Isin, B; Ahn, Y-Y; Lee, D-S; Barabási, A-L; Kapatral, V; Wiest, O; Oltvai, Z N

    2010-01-19

    Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy.

  9. Hitting the nail on the head: Force vectors in verb semantics

    NARCIS (Netherlands)

    Goldschmidt, A.; Zwarts, J.

    2016-01-01

    Hitting the nail on the head: Forces in verb meanings Anja Goldschmidt (UU) & Joost Zwarts (UU) There is a growing recognition of the role of forces in verb meanings, starting with the seminal work of Leonard Talmy (Talmy 1985). In one line of research these forces are analyzed in terms of vectors,

  10. The accelerator facility of the Heidelberg Ion-Beam Therapy Centre (HIT)

    Science.gov (United States)

    Peters, Andreas

    The following sections are included: * Introduction * Beam parameters * General layout of the HIT facility * The accelerator chain in detail * Operational aspects of a particle therapy facility * 24/7 accelerator operation at 335 days per year * Safety and regulatory aspects * Status and perspectives * References

  11. Assessment of HIT Antibody Complex in Hip Fracture Patients Receiving Enoxaparin or Unfractionated Heparin

    DEFF Research Database (Denmark)

    Griffin, Justin W; Hopkinson, William J; Rud-Lassen, Michael

    2011-01-01

    of antiheparin-PF4 antibodies and a greater prevalence of immunoglobulin G (IgG) subtype. Heparin and enoxaparin are capable of generating heparin-induced thrombocytopenia (HIT) antibodies in elderly patients undergoing orthopedic surgery but perhaps not to the same extent. When comparing low...

  12. Cost-effectiveness of the HIT programme in patients with schizophrenia and persistent auditory hallucinations

    NARCIS (Netherlands)

    Stant, AD; TenVergert, EM; Groen, H; Jenner, JA; Nienhuis, FJ; van de Willige, G; Wiersma, D

    Objective: To examine the cost-effectiveness of Hallucination focused Integrative Treatment (HIT) in patients with schizophrenia and a history of persistent auditory hallucinations. Method: Costs, in and outside the health care sector, and outcomes were registered prospectively during a period of 18

  13. 75 FR 8078 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-02-23

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  14. 76 FR 1432 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2011-01-10

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  15. 75 FR 33811 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-06-15

    ... Technology; HIT Policy Committee's Privacy & Security Tiger Team Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This... National Coordinator for Health Information Technology (ONC). The meeting will be open to the public. Name...

  16. 75 FR 369 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-01-05

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  17. 75 FR 51818 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-08-23

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  18. 75 FR 12752 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-03-17

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of Meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  19. 75 FR 65486 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-10-25

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  20. 75 FR 21630 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-04-26

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  1. 75 FR 57025 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-09-17

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  2. 75 FR 36658 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-06-28

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  3. 75 FR 8079 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-02-23

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  4. 76 FR 39107 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-07-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice... of the Office of the National Coordinator for Health Information Technology (ONC). The [[Page 39108...

  5. 76 FR 4353 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2011-01-25

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  6. 75 FR 12753 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-03-17

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  7. 75 FR 36657 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-06-28

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  8. 76 FR 1433 - Office of the National Coordinator for Health Information Technology HIT Standards Committee's...

    Science.gov (United States)

    2011-01-10

    ... Technology HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  9. 75 FR 70925 - Office of the National Coordinator for Health Information Technology; HIT; Standards Committee's...

    Science.gov (United States)

    2010-11-19

    ... Technology; HIT; Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  10. 75 FR 29761 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-05-27

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  11. 75 FR 368 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-01-05

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  12. 75 FR 3905 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee's...

    Science.gov (United States)

    2010-01-25

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  13. 75 FR 70924 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-11-19

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  14. 75 FR 34141 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-06-16

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces... for Health Information Technology (ONC). The meetings will be open to the public via dial-in access...

  15. 42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

    Science.gov (United States)

    2010-10-01

    ... and strategic plan for the next 5 years. (2) A description of how the State Medicaid HIT plan will be... processes that enable improved program administration for the Medicaid enterprise; (ii) Includes business... used certified EHR technology during the EHR reporting period, and that they have adopted, implemented...

  16. Visual strategies underpinning the development of visual-motor expertise when hitting a ball

    NARCIS (Netherlands)

    Sarpeshkar, Vishnu; Abernethy, B.; Mann, D.L.

    2017-01-01

    It is well known that skilled batters in fast-ball sports do not align their gaze with the ball throughout ball-flight, but instead adopt a unique sequence of eye and head movements that contribute toward their skill. However, much of what we know about visual-motor behavior in hitting is based on

  17. 75 FR 16126 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-03-31

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  18. 75 FR 16126 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-03-31

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... and Coordination, Office of the National Coordinator for Health Information Technology. [FR Doc. 2010...

  19. 75 FR 151 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-01-04

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  20. 75 FR 151 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-01-04

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Programs and Coordination Office of the National Coordinator for Health Information Technology. [FR Doc. E9...

  1. 76 FR 9784 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2011-02-22

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  2. Efficiency profile method to study the hit efficiency of drift chambers

    International Nuclear Information System (INIS)

    Abyzov, A.; Bel'kov, A.; Lanev, A.; Spiridonov, A.; Walter, M.; Hulsbergen, W.

    2002-01-01

    A method based on the usage of efficiency profile is proposed to estimate the hit efficiency of drift chambers with a large number of channels. The performance of the method under real conditions of the detector operation has been tested analysing the experimental data from the HERA-B drift chambers

  3. Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xuqing; Song, Fengbing; Kuo, Gee-Hong; Xiang, Amy; Gibbs, Alan C.; Abad, Marta C.; Sun, Weimei; Kuo, Lawrence C.; Sui, Zhihua (J); (J-PRD)

    2013-11-20

    A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties.

  4. Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors.

    Science.gov (United States)

    Zhang, Xuqing; Song, Fengbing; Kuo, Gee-Hong; Xiang, Amy; Gibbs, Alan C; Abad, Marta C; Sun, Weimei; Kuo, Lawrence C; Sui, Zhihua

    2011-08-15

    A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. As the Economic Crisis Hits Home, Colleges Seek Help from Congress

    Science.gov (United States)

    Field, Kelly

    2008-01-01

    Congress is crafting a second economic-stimulus bill, and the nation's colleges, hit by the deepening fiscal crisis, want a share of the money. Over the last few weeks, colleges and their lobbyists have bombarded members of Congress with letters and phone calls seeking money for research, student aid, and infrastructure. However, Congress is…

  6. FedWeb Greatest Hits: Presenting the New Test Collection for Federated Web Search

    NARCIS (Netherlands)

    Demeester, Thomas; Trieschnigg, Rudolf Berend; Zhou, Ke; Nguyen, Dong-Phuong; Hiemstra, Djoerd

    This paper presents 'FedWeb Greatest Hits', a large new test collection for research in web information retrieval. As a combination and extension of the datasets used in the TREC Federated Web Search Track, this collection opens up new research possibilities on federated web search challenges, as

  7. The effect of road and environmental characteristics on pedestrian hit-and-run accidents in Ghana.

    Science.gov (United States)

    Aidoo, Eric Nimako; Amoh-Gyimah, Richard; Ackaah, Williams

    2013-04-01

    The number of pedestrians who have died as a result of being hit by vehicles has increased in recent years, in addition to vehicle passenger deaths. Many pedestrians who were involved in road traffic accident died as a result of the driver leaving the pedestrian who was struck unattended at the scene of the accident. This paper seeks to determine the effect of road and environmental characteristics on pedestrian hit-and-run accidents in Ghana. Using pedestrian accident data extracted from the National Road Traffic Accident Database at the Building and Road Research Institute (BRRI) of the Council for Scientific and Industrial Research (CSIR), Ghana, a binary logit model was employed in the analysis. The results from the estimated model indicate that fatal accidents, unclear weather, nighttime conditions, and straight and flat road sections without medians and junctions significantly increase the likelihood that the vehicle driver will leave the scene after hitting a pedestrian. Thus, integrating median separation and speed humps into road design and construction and installing street lights will help to curb the problem of pedestrian hit-and-run accidents in Ghana. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Hitting the nail on the head: Force vectors in verb semantics

    NARCIS (Netherlands)

    Goldschmidt, A.; Zwarts, J.

    2016-01-01

    We present an analysis of force verbs, like hit, as involving paths with force-dynamic properties, modelled through force vectors. This allows us to explain a number of observations about the lexical meaning and composition of these verbs. For instance, force adverbs such as hard specify the

  9. An orthogonal-polynomial approach to first-hitting times of birth-death processes

    NARCIS (Netherlands)

    van Doorn, Erik A.

    In a recent paper in this journal, Gong, Mao and Zhang, using the theory of Dirichlet forms, extended Karlin and McGregor’s classical results on first-hitting times of a birth–death process on the nonnegative integers by establishing a representation for the Laplace transform E[exp(sTij)] of the

  10. An orthogonal-polynomial approach to first-hitting times of birth-death processes

    NARCIS (Netherlands)

    van Doorn, Erik A.

    In a recent paper [J. Theor. Probab. 25 (2012) 950-980] Gong, Mao and Zhang, using the theory of Dirichlet forms, extended Karlin and McGregor's classical results on first-hitting times of a birth-death process on the nonnegative integers by establishing a representation for the Laplace transform

  11. 75 FR 65486 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-10-25

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  12. 75 FR 29762 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-05-27

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  13. 75 FR 51820 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-08-23

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  14. 75 FR 8953 - Office of the National Coordinator for Health Information Technology HIT Policy Committee...

    Science.gov (United States)

    2010-02-26

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... a policy framework for the development and adoption of a nationwide health information technology...

  15. 76 FR 4352 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2011-01-25

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  16. 75 FR 5595 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-02-03

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  17. 75 FR 51819 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-08-23

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health [[Page 51820

  18. 75 FR 57026 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-09-17

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  19. 75 FR 42091 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-07-20

    ... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

  20. Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI

    Directory of Open Access Journals (Sweden)

    Madeleine L. Barnett

    2018-01-01

    Conclusion: This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury.

  1. Hit Dexter: A Machine-Learning Model for the Prediction of Frequent Hitters.

    Science.gov (United States)

    Stork, Conrad; Wagner, Johannes; Friedrich, Nils-Ole; de Bruyn Kops, Christina; Šícho, Martin; Kirchmair, Johannes

    2018-03-20

    False-positive assay readouts caused by badly behaving compounds-frequent hitters, pan-assay interference compounds (PAINS), aggregators, and others-continue to pose a major challenge to experimental screening. There are only a few in silico methods that allow the prediction of such problematic compounds. We report the development of Hit Dexter, two extremely randomized trees classifiers for the prediction of compounds likely to trigger positive assay readouts either by true promiscuity or by assay interference. The models were trained on a well-prepared dataset extracted from the PubChem Bioassay database, consisting of approximately 311 000 compounds tested for activity on at least 50 proteins. Hit Dexter reached MCC and AUC values of up to 0.67 and 0.96 on an independent test set, respectively. The models are expected to be of high value, in particular to medicinal chemists and biochemists who can use Hit Dexter to identify compounds for which extra caution should be exercised with positive assay readouts. Hit Dexter is available as a free web service at http://hitdexter.zbh. uni-hamburg.de. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. An explanation of closed-flux formation and sustainment using coaxial helicity injection on HIT-II

    International Nuclear Information System (INIS)

    Jarboe, T R

    2010-01-01

    An explanation of the closed-flux operation on HIT-II is given. This method of operation generated flux amplification and closed flux on HIT-II without the presence of n = 1 or any large amplitude mode as measured from the outside shell. The method of operating also prevents hard absorber arcs and maximizes the toroidal current.

  3. Antiproton annihilation physics annihilation physics in the Monte Carlo particle transport code particle transport code SHIELD-HIT12A

    DEFF Research Database (Denmark)

    Taasti, Vicki Trier; Knudsen, Helge; Holzscheiter, Michael

    2015-01-01

    The Monte Carlo particle transport code SHIELD-HIT12A is designed to simulate therapeutic beams for cancer radiotherapy with fast ions. SHIELD-HIT12A allows creation of antiproton beam kernels for the treatment planning system TRiP98, but first it must be benchmarked against experimental data. An...

  4. Computing Principal Eigenvectors of Large Web Graphs: Algorithms and Accelerations Related to PageRank and HITS

    Science.gov (United States)

    Nagasinghe, Iranga

    2010-01-01

    This thesis investigates and develops a few acceleration techniques for the search engine algorithms used in PageRank and HITS computations. PageRank and HITS methods are two highly successful applications of modern Linear Algebra in computer science and engineering. They constitute the essential technologies accounted for the immense growth and…

  5. Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skåne study.

    Science.gov (United States)

    Lundgren, Markus; Lynch, Kristian; Larsson, Christer; Elding Larsson, Helena

    2015-01-01

    The aim of this study was to examine the effect of cord blood autoantibodies on the risk for type 1 diabetes in children followed prospectively from birth. The Diabetes Prediction in Skåne (DiPiS) study consists of 35,853 children from the general population born during 2000-2004. Samples were collected at birth and analysed for HLA genotypes and autoantibodies to glutamate decarboxylase 65 (GAD65), insulin and insulinoma-associated protein 2 (IA-2). After adjusting for HLA, sex, maternal age and parental type 1 diabetes, independent associations with risk of diabetes were assessed using multivariate Cox proportional hazards models. In total, 151 children (0.4%) had developed type 1 diabetes by the end of 2013 at a median age of 5.8 years (0.8-12.2 years). In the multivariate analysis, the presence of IA-2 autoantibodies (IA-2A) in cord blood (HR 6.88, 95% CI 1.46,32.4; p = 0.003), but not maternal diabetes (HR 1.38, 95% CI 0.24,7.84; p = 0.71), was associated with risk of developing type 1 diabetes. No increased risk could be seen for the presence of autoantibodies to GAD65 or insulin. Our study indicates that the presence of cord blood IA-2A superimposes maternal diabetes and other cord blood islet autoantibodies as a predictor of type 1 diabetes development in the child. These findings may be of significance for future screening and study protocols on type 1 diabetes prediction.

  6. Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis.

    Science.gov (United States)

    Suzuki, Hitoshi

    2018-05-08

    IgA nephropathy (IgAN) is the most prevalent glomerular disease worldwide and is associated with a poor prognosis. Development of curative treatment strategies and approaches for early diagnosis is necessary. Renal biopsy is the gold standard for the diagnosis and assessment of disease activity. However, reliable biomarkers are needed for the noninvasive diagnosis of this disease and to more fully delineate the risk of progression. With regard to the pathogenesis of IgAN, the multi-hit hypothesis, including production of galactose-deficient IgA1 (Gd-IgA1; Hit 1), IgG or IgA autoantibodies that recognize Gd-IgA1 (Hit 2), and their subsequent immune complexes formation (Hit 3) and glomerular deposition (Hit 4), has been widely supported by many studies. Although the prognostic values of several biomarkers have been discussed, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of Gd-IgA1 and Gd-IgA1-containing immune complexes. In addition, urinary Gd-IgA1 may represent a disease-specific biomarker for IgAN. We also confirmed that there is a significant correlation between serum levels of these effector molecules and disease activity, suggesting that each can be considered a practical surrogate marker of therapeutic response. Thus, these disease-oriented specific serum and urine biomarkers may be useful for screening of potential IgAN with isolated hematuria, earlier diagnosis, disease activity, and eventually, response to treatment. In this review, we discuss these concepts, with a focus on potential clinical applications of these biomarkers.

  7. Effects of Experimental Volleyball Rules Quantified by Type and Number of Jumps, Hits and Contacts

    Directory of Open Access Journals (Sweden)

    Mladen Stankovic

    2017-10-01

    Full Text Available The purpose of this study was to determine the influence of the two new rules tested at the inaugural U23 Men’s Volleyball World Championship (21-point set excluding the fifth set, and 15 seconds between rallies–10 seconds from the finished point until the referee’s whistle for serve and five seconds for performing the serve on number and types of jumps and number of contacts and hits. The analysis comprised 25,930 jumps (an essential physical activity for volleyball, 15,706 contacts and 10,224 hits during 36 matches played by 144 males aged under 23 at the first Under 23 Men’s World Championships organized in Uberlandia, Brazil, in 2013. Two investigations were conducted: 1 Analysis of jumps by Jump type, In-game role and Level of set win; 2 Analysis of contacts (reception, setting, block, defense and hits (serve and attack by Type, In-game role and Set outcome. Significant differences (p=0.000 were found between in-game role and jump type, as Middle blocker performed the most (34.7%, followed by Outside hitter (24.9%, Setter (24.6% and Opposite (15.8%. Significant differences were found for number and types of Hits between set Winner and Loser teams only for serves by Setter (p<0.001 and Middle blocker (p<0.05. The results showed major differences in jumps, hits and contacts between in-game roles: Middle blocker was the most frequent jumping position, followed by Outside hitter and Setter. The Libero showed a new tendency of being Setter with a jump after the initial Setter defense.

  8. HYPERLEXIA AND DYSLEXIA IN AUTISM: HITTING A MOVING TARGET

    Directory of Open Access Journals (Sweden)

    Emily L. WILLIAMS

    2012-09-01

    Full Text Available The diagnostic histories of autism, dyslexia, and hyperlexia are complex. Because these conditions share both convergent and diver­gent properties, it is important to under­stand these relationships, especially in the case of research and how we interpret bodi­es of work which span decades of fluc­tuating criteria. It is also important to syn­the­size what we already know about the morpho­logy of these con­di­tions and pinpoint what we still don’t. Autism and dyslexia, for instance, share antipodal cerebral morpho­logies, such as minicolumnar den­sity, neuropil width, cell size, corpus callo­sal volume, gyral complexity, gyral window size, and cerebral volume, while hyperlexia has not been studied in this fashion, although it sha­res much in common with autism. Mean­while, the fluctuation in criteria of dyslexia over the years, means that older studies, such as some of the most highly cited in post­mortem research, have potentially used more heterogeneous groups of subjects than dys­lexia research typically uses today. Con­sider­ably, these older studies are often the basis of current animal model and genetics research. In conclusion, in consideration of the continued flux in criteria, particularly the proposed change from “Reading Disorder” to the broa­der “Specific Learning Disorder” within the DSM-5, we strongly recommend a separation of the various reading disorders under their own headings to promote specificity of diag­nosis and treatment, and to support better research.

  9. Evaluation of flow cytometric HIT assays in relation to an IgG-Specific immunoassay and clinical outcome.

    Science.gov (United States)

    Kerényi, Adrienne; Beke Debreceni, Ildikó; Oláh, Zsolt; Ilonczai, Péter; Bereczky, Zsuzsanna; Nagy, Béla; Muszbek, László; Kappelmayer, János

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment caused by platelet activating IgG antibodies generated against the platelet factor 4 (PF4)-heparin complex. Thrombocytopenia and thrombosis are the leading clinical symptoms of HIT. The clinical pretest probability of HIT was evaluated by the 4T score system. Laboratory testing of HIT was performed by immunological detection of antibodies against PF4-heparin complex (EIA) and two functional assays. Heparin-dependent activation of donor platelets by patient plasma was detected by flow cytometry. Increased binding of Annexin-V to platelets and elevated number of platelet-derived microparticles (PMP) were the indicators of platelet activation. EIA for IgG isotype HIT antibodies was performed in 405 suspected HIT patients. Based on negative EIA results, HIT was excluded in 365 (90%) of cases. In 40 patients with positive EIA test result functional tests were performed. Platelet activating antibodies were detected in 17 cases by Annexin V binding. PMP count analysis provided nearly identical results. The probability of a positive flow cytometric assay result was higher in patients with elevated antibody titer. 71% of patients with positive EIA and functional assay had thrombosis. EIA is an important first line laboratory test in the diagnosis of HIT; however, HIT must be confirmed by a functional test. Annexin V binding and PMP assays using flow cytometry are functional HIT tests convenient in a clinical diagnostic laboratory. The positive results of functional assays may predict the onset of thrombosis. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

  10. Preleukemic and second-hit mutational events in an acute myeloid leukemia patient with a novel germline RUNX1 mutation.

    Science.gov (United States)

    Ng, Isaac Ks; Lee, Joanne; Ng, Christopher; Kosmo, Bustamin; Chiu, Lily; Seah, Elaine; Mok, Michelle Meng Huang; Tan, Karen; Osato, Motomi; Chng, Wee-Joo; Yan, Benedict; Tan, Lip Kun

    2018-01-01

    Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear. We describe a patient of Malay descent with an unreported 7-bp germline RUNX1 frameshift deletion, who developed second-hit mutations that could have brought about the leukaemic transformation from a pre-leukaemic state. These mutations were charted through the course of the treatment and stem cell transplant, showing a clear correlation between her clinical presentation and the mutations present. The patient was a 27-year-old Malay woman who presented with AML on the background of hereditary thrombocytopenia affecting her father and 3 brothers. Initial molecular testing revealed the same novel RUNX1 mutation in all 5 individuals. The patient received standard induction, consolidation chemotherapy, and a haploidentical stem cell transplant from her mother with normal RUNX1 profile. Comprehensive genomic analyses were performed at diagnosis, post-chemotherapy and post-transplant. A total of 8 mutations ( RUNX1 , GATA2 , DNMT3A , BCORL1 , BCOR , 2 PHF6 and CDKN2A ) were identified in the pre-induction sample, of which 5 remained ( RUNX1 , DNMT3A , BCORL1 , BCOR and 1 out of 2 PHF6 ) in the post-treatment sample and none were present post-transplant. In brief, the 3 mutations which were lost along with the leukemic cells at complete morphological remission were most likely acquired leukemic driver mutations that were responsible for the AML transformation from a pre-leukemic germline RUNX1 -mutated state. On the contrary, the 5 mutations that persisted post

  11. In Vitro Effect of Fatty Acids Identified in the Plasma of Obese Adolescents on the Function of Pancreatic β-Cells

    Directory of Open Access Journals (Sweden)

    Claudia Velasquez

    2017-05-01

    Full Text Available BackgroundThe increase in circulating free fatty acid (FFA levels is a major factor that induces malfunction in pancreatic β-cells. We evaluated the effect of FFAs reconstituted according to the profile of circulating fatty acids found in obese adolescents on the viability and function of the murine insulinoma cell line (mouse insulinoma [MIN6].MethodsFrom fatty acids obtained commercially, plasma-FFA profiles of three different youth populations were reconstituted: obese with metabolic syndrome; obese without metabolic syndrome; and normal weight without metabolic syndrome. MIN6 cells were treated for 24 or 48 hours with the three FFA profiles, and glucose-stimulated insulin secretion, cell viability, mitochondrial function and antioxidant activity were evaluated.ResultsThe high FFA content and high polyunsaturated ω6/ω3 ratio, present in plasma of obese adolescents with metabolic syndrome had a toxic effect on MIN6 cell viability and function, increasing oxidative stress and decreasing glucose-dependent insulin secretion.ConclusionThese results could help to guide nutritional management of obese young individuals, encouraging the increase of ω-3-rich food consumption in order to reduce the likelihood of deterioration of β-cells and the possible development of type 2 diabetes mellitus.

  12. Transfer, loss and physical processing of water in hit-and-run collisions of planetary embryos

    Science.gov (United States)

    Burger, C.; Maindl, T. I.; Schäfer, C. M.

    2018-01-01

    Collisions between large, similar-sized bodies are believed to shape the final characteristics and composition of terrestrial planets. Their inventories of volatiles such as water are either delivered or at least significantly modified by such events. Besides the transition from accretion to erosion with increasing impact velocity, similar-sized collisions can also result in hit-and-run outcomes for sufficiently oblique impact angles and large enough projectile-to-target mass ratios. We study volatile transfer and loss focusing on hit-and-run encounters by means of smooth particle hydrodynamics simulations, including all main parameters: impact velocity, impact angle, mass ratio and also the total colliding mass. We find a broad range of overall water losses, up to 75% in the most energetic hit-and-run events, and confirm the much more severe consequences for the smaller body also for stripping of volatile layers. Transfer of water between projectile and target inventories is found to be mostly rather inefficient, and final water contents are dominated by pre-collision inventories reduced by impact losses, for similar pre-collision water mass fractions. Comparison with our numerical results shows that current collision outcome models are not accurate enough to reliably predict these composition changes in hit-and-run events. To also account for non-mechanical losses, we estimate the amount of collisionally vaporized water over a broad range of masses and find that these contributions are particularly important in collisions of ˜ Mars-sized bodies, with sufficiently high impact energies, but still relatively low gravity. Our results clearly indicate that the cumulative effect of several (hit-and-run) collisions can efficiently strip protoplanets of their volatile layers, especially the smaller body, as it might be common, e.g., for Earth-mass planets in systems with Super-Earths. An accurate model for stripping of volatiles that can be included in future planet

  13. Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum.

    Science.gov (United States)

    Avery, Vicky M; Bashyam, Sridevi; Burrows, Jeremy N; Duffy, Sandra; Papadatos, George; Puthukkuti, Shyni; Sambandan, Yuvaraj; Singh, Shivendra; Spangenberg, Thomas; Waterson, David; Willis, Paul

    2014-05-27

    In view of the need to continuously feed the pipeline with new anti-malarial agents adapted to differentiated and more stringent target product profiles (e.g., new modes of action, transmission-blocking activity or long-duration chemo-protection), a chemical library consisting of more than 250,000 compounds has been evaluated in a blood-stage Plasmodium falciparum growth inhibition assay and further assessed for chemical diversity and novelty. The selection cascade used for the triaging of hits from the chemical library started with a robust three-step in vitro assay followed by an in silico analysis of the resulting confirmed hits. Upon reaching the predefined requirements for selectivity and potency, the set of hits was subjected to computational analysis to assess chemical properties and diversity. Furthermore, known marketed anti-malarial drugs were co-clustered acting as 'signposts' in the chemical space defined by the hits. Then, in cerebro evaluation of the chemical structures was performed to identify scaffolds that currently are or have been the focus of anti-malarial medicinal chemistry programmes. Next, prioritization according to relaxed physicochemical parameters took place, along with the search for structural analogues. Ultimately, synthesis of novel chemotypes with desired properties was performed and the resulting compounds were subsequently retested in a P. falciparum growth inhibition assay. This screening campaign led to a 1.25% primary hit rate, which decreased to 0.77% upon confirmatory repeat screening. With the predefined potency (EC₅₀  10) criteria, 178 compounds progressed to the next steps where chemical diversity, physicochemical properties and novelty assessment were taken into account. This resulted in the selection of 15 distinct chemical series. A selection cascade was applied to prioritize hits resulting from the screening of a medium-sized chemical library against blood-stage P. falciparum. Emphasis was placed on chemical

  14. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Katalin Susztak

    2005-02-01

    Full Text Available Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis.Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  15. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    T N Hagawane

    2016-01-01

    Results: It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6 levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. Interpretation & conclusions: The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  16. Comparison of validity and reliability of the Migraine disability assessment (MIDAS) versus headache impact test (HIT) in an Iranian population.

    Science.gov (United States)

    Ghorbani, Abbas; Chitsaz, Ahmad

    2011-01-01

    Migraine is one of the most common headaches that affect 11% or more adult population. Recently, researchers have designed two questionnaires, namely Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS), with the aim of improving migraine care. These two tests provide a standard measurement about migraine's effects on people's life style that divide patients into 4 groups (grades) based on headaches intensity. The aim of this study was to compare the validity and reliability of these two tests. This study was designed as a multicenter, descriptive study to compare validity and reliability of Persian version of MIDAS and HIT questionnaires in 240 males and females with a migraine diagnosis according to criteria for headache and facial pain of the International Headache Society (IHS). The patients were enrolled in the study from 3 neurology clinics in Isfahan, Iran, between July 2004 and January 2005 and were evaluated at baseline (visit 1) and 4 weeks later (visit 2). According to our study, there was a high correlation between two tests (r = 0.94). This decreased their MIDAS grade in comparison to their grade HIT questionnaire. These findings demonstrated that Persian version of HIT have the same validity and reliability as MIDAS. Replying to HIT questionnaire was easier than MIDAS for Iranian patients. Physicians can reliably use the Persian translation of both MIDAS and HIT questionnaires to define the severity of illness and its treatment strategy as a self-administered report by migraine patients. However, we recommend HIT for its simplicity in headache clinics.

  17. Hit-size effectiveness theory applied to high doses of low LET radiation for pink mutations in Tradescantia

    International Nuclear Information System (INIS)

    Varma, M.N.; Bond, V.P.; Matthews, G.

    1985-01-01

    A hit-size effectiveness function which represents the probability of inducing a pink mutation in Tradescantia as a function of lineal energy density has been obtained (1) using observed pink mutation data for seven different radiation qualities and their respective single event microdosimetric spectra. In obtaining this function only the linear portions of dose-response curves were used. A significant improvement of the concepts embodied in the proposed hit-size effectiveness theory would be the demonstration of its applicability at high doses (where multiple hits are produced) and high dose rates (at which no significant biological repair takes place). In this article details are given on preliminary calculations of the pink mutation frequency in Tradescantia at 1, 5, 10, 20, and 60 rads for 250 kVp x rays, using the multi-hit spectra and the hit-size effectiveness function obtained on the basis of single hit microdosimetric spectra as outline in (1). A comparison of the calculated and observed pink mutation frequencies indicate excellent agreement and suggests the possibility of obtaining the hit-size effectiveness function from high dose biological-effect data obtained using low-LET radiations. 6 refs., 3 figs., 3 tabs

  18. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

  19. Demand spillovers of smash-hit papers: evidence from the 'Male Organ Incident'.

    Science.gov (United States)

    Kässi, Otto; Westling, Tatu

    2013-12-01

    This study explores the short-run spillover effects of popular research papers. We consider the publicity of 'Male Organ and Economic Growth: Does Size Matter?' as an exogenous shock to economics discussion paper demand, a natural experiment of a sort. In particular, we analyze how the very substantial visibility influenced the downloads of Helsinki Center of Economic Research discussion papers. Difference in differences and regression discontinuity analysis are conducted to elicit the spillover patterns. This study finds that the spillover effect to average economics paper demand is positive and statistically significant. It seems that hit papers increase the exposure of previously less downloaded papers. We find that part of the spillover effect could be attributable to Internet search engines' influence on browsing behavior. Conforming to expected patterns, papers residing on the same web page as the hit paper evidence very significant increases in downloads which also supports the spillover thesis. A11, C21. 97K80.

  20. Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi.

    Science.gov (United States)

    Keenan, Martine; Alexander, Paul W; Chaplin, Jason H; Abbott, Michael J; Diao, Hugo; Wang, Zhisen; Best, Wayne M; Perez, Catherine J; Cornwall, Scott M J; Keatley, Sarah K; Thompson, R C Andrew; Charman, Susan A; White, Karen L; Ryan, Eileen; Chen, Gong; Ioset, Jean-Robert; von Geldern, Thomas W; Chatelain, Eric

    2013-10-01

    Inhibitors of Trypanosoma cruzi with novel mechanisms of action are urgently required to diversify the current clinical and preclinical pipelines. Increasing the number and diversity of hits available for assessment at the beginning of the discovery process will help to achieve this aim. We report the evaluation of multiple hits generated from a high-throughput screen to identify inhibitors of T. cruzi and from these studies the discovery of two novel series currently in lead optimization. Lead compounds from these series potently and selectively inhibit growth of T. cruzi in vitro and the most advanced compound is orally active in a subchronic mouse model of T. cruzi infection. High-throughput screening of novel compound collections has an important role to play in diversifying the trypanosomatid drug discovery portfolio. A new T. cruzi inhibitor series with good drug-like properties and promising in vivo efficacy has been identified through this process.

  1. Clinical Computer Systems Survey (CLICS): learning about health information technology (HIT) in its context of use.

    Science.gov (United States)

    Lichtner, Valentina; Cornford, Tony; Klecun, Ela

    2013-01-01

    Successful health information technology (HIT) implementations need to be informed on the context of use and on users' attitudes. To this end, we developed the CLinical Computer Systems Survey (CLICS) instrument. CLICS reflects a socio-technical view of HIT adoption, and is designed to encompass all members of the clinical team. We used the survey in a large English hospital as part of its internal evaluation of the implementation of an electronic patient record system (EPR). The survey revealed extent and type of use of the EPR; how it related to and integrated with other existing systems; and people's views on its use, usability and emergent safety issues. Significantly, participants really appreciated 'being asked'. They also reminded us of the wider range of administrative roles engaged with EPR. This observation reveals pertinent questions as to our understanding of the boundaries between administrative tasks and clinical medicine - what we propose as the field of 'administrative medicine'.

  2. Hit and lead criteria in drug discovery for infectious diseases of the developing world.

    Science.gov (United States)

    Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

    2015-11-01

    Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

  3. MIDAS and HIT-6 French translation: reliability and correlation between tests.

    Science.gov (United States)

    Magnoux, E; Freeman, M A; Zlotnik, G

    2008-01-01

    The aim was to evaluate the test-retest reliability of the French translation of the Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT)-6 questionnaires as applied to episodic and chronic headaches and to assess the correlation between these two questionnaires. The MIDAS and HIT-6 questionnaires, which assess the degree of migraine-related functional disability, are widely used in headache treatment clinics. The French translation has not been checked for test-retest reliability. MIDAS involves recall, over the previous 3 months, of the number of days with functional disability with regard to work and to home and social life. HIT-6 involves a more subjective and general assessment of headache-related disability over the previous 4 weeks. We expect that there may be greater impact recall bias for chronic headaches than for episodic headaches and considered it important to be able to determine if the reliability of these questionnaires is equally good for these two patient populations. Given that both questionnaires have the same objective, that of assessing headache impact, it was thought useful to determine if their results might show a correlation and if they could thus be used interchangeably. The study was approved by an external ethics committee. The subjects were patients who regularly visit the Clinique de la Migraine de Montréal, which specializes in the treatment of headaches. The MIDAS and HIT-6 questionnaires were completed by the patients during their regular visit. Twelve days later, the same questionnaires were mailed with a prepaid return envelope. Sixty-five patients were required in both the episodic and chronic headache groups, assuming an 80% questionnaire return rate. One hundred and eighty-five patients were enrolled, and 143 completed the study, 75 with episodic headaches and 68 with chronic headaches. The questionnaire return rate was 78.9%. On average, questionnaires were completed a second time 21 days after the first

  4. B-HIT - A Tool for Harvesting and Indexing Biodiversity Data.

    Directory of Open Access Journals (Sweden)

    Patricia Kelbert

    Full Text Available With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF implemented a Harvesting and Indexing Toolkit (HIT, which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups.

  5. Sleeping beauties in psychology: comparisons of "hits" and "missed signals" in psychological journals.

    Science.gov (United States)

    Lange, Lydia L

    2005-05-01

    Scientific publications tend to be forgotten quickly. A few works, however, are still cited 100 years and more after their publication. The author used bibliometric methods to compare "hits" (works noticed by the scientific community soon after their publication) with "missed signals" (works that went unnoticed until much later) by investigating 2 psychological journals founded in the 1890s: Zeitschrift für Psychologie and Psychological Review. All articles that were published in either of these journals up to 1920 and cited more than 25 times in the Web of Science up to the year 2000 were considered for inclusion in the analysis. It emerged that hits corresponded more closely to the focus of scientific attention at the time of the publications than missed signals.

  6. Variation in number of hits for complex searches in Google Scholar

    Directory of Open Access Journals (Sweden)

    Wichor Matthijs Bramer, BSc

    2016-11-01

    Full Text Available Objective: Google Scholar is often used to search for medical literature. Numbers of results reported by Google Scholar outperform the numbers reported by traditional databases. How reliable are these numbers? Why are often not all available 1,000 references shown? Methods: For several complex search strategies used in systematic review projects, the number of citations and the total number of versions were calculated. Several search strategies were followed over a two-year period, registering fluctuations in reported search results. Results: Changes in numbers of reported search results varied enormously between search strategies and dates. Theories for calculations of the reported and shown number of hits were not proved. Conclusions: The number of hits reported in Google Scholar is an unreliable measure. Therefore, its repeatability is problematic, at least when equal results are needed.

  7. "Hits" emerge through self-organized coordination in collective response of free agents

    Science.gov (United States)

    Chakrabarti, Anindya S.; Sinha, Sitabhra

    2016-10-01

    Individuals in free societies frequently exhibit striking coordination when making independent decisions en masse. Examples include the regular appearance of hit products or memes with substantially higher popularity compared to their otherwise equivalent competitors or extreme polarization in public opinion. Such segregation of events manifests as bimodality in the distribution of collective choices. Here we quantify how apparently independent choices made by individuals result in a significantly polarized but stable distribution of success in the context of the box-office performance of movies and show that it is an emergent feature of a system of noninteracting agents who respond to sequentially arriving signals. The aggregate response exhibits extreme variability amplifying much smaller differences in individual cost of adoption. Due to self-organization of the competitive landscape, most events elicit only a muted response but a few stimulate widespread adoption, emerging as "hits".

  8. Powered two-wheeler drivers' risk of hitting a pedestrian in towns.

    Science.gov (United States)

    Clabaux, Nicolas; Fournier, Jean-Yves; Michel, Jean-Emmanuel

    2014-12-01

    The risk of collision between pedestrians and powered two-wheelers is poorly understood today. The objective of this research is to determine the risk for powered two-wheeler drivers of hitting and injuring a pedestrian per kilometer driven in towns and to compare this risk with that run by four-wheeled vehicle drivers. Using the bodily injury accidents recorded by the police on nine roads in the city of Marseille in 2011 and a campaign of observations of powered two-wheeler traffic, we estimated the risk per kilometer driven by powered two-wheeler drivers of hitting a pedestrian and compared it with the risk run by four-wheeled vehicle drivers. The results show that the risk for powered two-wheeler drivers of hitting and injuring a pedestrian is significantly higher than the risk run by four-wheeled vehicle drivers. On the nine roads studied, it is on average 3.33 times higher (95% CI: 1.63; 6.78). Taking four more years into account made it possible to consolidate these results and to tighten the confidence interval. There does indeed seem to be problems in the interactions between pedestrians and powered two-wheeler users in urban traffic. These interaction problems lead to a higher risk of hitting and injuring a pedestrian for powered two-wheeler drivers than for four-wheeled vehicle drivers. The analysis of the police reports suggests that part of this increased risk comes from filtering maneuvers by powered two-wheelers. Possible countermeasures deal with the urban street layout. Measures consisting in reducing the width and the number of traffic lanes to a strict minimum and installing medians or pedestrian islands could be an effective way for the prevention of urban accidents between pedestrians and powered two-wheelers. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

  9. Development and formative evaluation of the e-Health Implementation Toolkit (e-HIT

    Directory of Open Access Journals (Sweden)

    Mair Frances

    2010-10-01

    Full Text Available Abstract Background The use of Information and Communication Technology (ICT or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice. This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format. Results The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience. Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls Conclusions The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations.

  10. The immune imbalance in the second hit of pancreatitis is independent of IL-17A.

    Science.gov (United States)

    Thomson, John-Edwin; Brand, Martin; Fonteh, Pascaline

    2018-04-01

    Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP. Thirty-six patients with mild (n = 16), moderate (n = 10) and severe (n = 10) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for analysis of routine clinical markers as well as cytokine analysis. Flow cytometry and a IL-17A ELISA was performed to determine cytokine concentrations. There were no significant differences between days 7, 9, 11 and 13 for either the mild/moderate or SAP groups for IL-17A (CBA assay or ELISA), IFN-γ, TNF-α, IL-2 or IL-4. For each of the study days, the mean IL-6 and IL-10 concentrations were significantly higher in the SAP group compared to the mild/moderate group. WCC, CRP and PCT were all significantly higher in severe acute pancreatitis over the study days. An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  11. Integral transforms of the quantum mechanical path integral: Hit function and path-averaged potential

    Science.gov (United States)

    Edwards, James P.; Gerber, Urs; Schubert, Christian; Trejo, Maria Anabel; Weber, Axel

    2018-04-01

    We introduce two integral transforms of the quantum mechanical transition kernel that represent physical information about the path integral. These transforms can be interpreted as probability distributions on particle trajectories measuring respectively the relative contribution to the path integral from paths crossing a given spatial point (the hit function) and the likelihood of values of the line integral of the potential along a path in the ensemble (the path-averaged potential).

  12. Analysis of impact noise induced by hitting of titanium head golf driver.

    Science.gov (United States)

    Kim, Young Ho; Kim, Young Chul; Lee, Jun Hee; An, Yong-Hwi; Park, Kyung Tae; Kang, Kyung Min; Kang, Yeon June

    2014-11-01

    The hitting of titanium head golf driver against golf ball creates a short duration, high frequency impact noise. We analyzed the spectra of these impact noises and evaluated the auditory hazards from exposure to the noises. Noises made by 10 titanium head golf drivers with five maximum hits were collected, and the spectra of the pure impact sounds were studied using a noise analysis program. The noise was measured at 1.7 m (position A) and 3.4 m (position B) from the hitting point in front of the hitter and at 3.4 m (position C) behind the hitting point. Average time duration was measured and auditory risk units (ARUs) at position A were calculated using the Auditory Hazard Assessment Algorithm for Humans. The average peak levels at position A were 119.9 dBA at the sound pressure level (SPL) peak and 100.0 dBA at the overall octave level. The average peak levels (SPL and overall octave level) at position B were 111.6 and 96.5 dBA, respectively, and at position C were 111.5 and 96.7 dBA, respectively. The average time duration and ARUs measured at position A were 120.6 ms and 194.9 units, respectively. Although impact noises made by titanium head golf drivers showed relatively low ARUs, individuals enjoying golf frequently may be susceptible to hearing loss due to the repeated exposure of this intense impact noise with short duration and high frequency. Unprotected exposure to impact noises should be limited to prevent cochleovestibular disorders.

  13. Synthetic Medicinal Chemistry in Chagas' Disease: Compounds at The Final Stage of "Hit-To-Lead" Phase.

    Science.gov (United States)

    Cerecetto, Hugo; González, Mercedes

    2010-03-25

    Chagas' disease, or American trypanosomosiasis, has been the most relevant illness produced by protozoa in Latin America. Synthetic medicinal chemistry efforts have provided an extensive number of chemodiverse hits at the "active-to-hit" stage. However, only a more limited number of these have been studied in vivo in models of Chagas' disease. Herein, we survey some of the cantidates able to surpass the "hit-to-lead" stage discussing their limitations or merit to enter in clinical trials in the short term.

  14. Modeling distortion of HIT by an Actuator Disk in a periodic domain

    Science.gov (United States)

    Ghate, Aditya; Ghaisas, Niranjan; Lele, Sanjiva

    2017-11-01

    We study the distortion of incompressible, homogeneous isotropic turbulence (HIT) by a dragging actuator disk with a fixed thrust coefficient (under the large Reynolds number limit), using Large Eddy Simulation (LES). The HIT inflow is tailored to ensure that the largest length scales in the flow are smaller than the actuator disk diameter in order to minimize the meandering of the turbulent wake and isolate the length scales that undergo distortion. The numerical scheme (Fourier collocation with dealiasing) and the SGS closure (anisotropic minimum dissipation model) are carefully selected to minimize numerical artifacts expected due to the inviscid assumption. The LES is used to characterize the following 3 properties of the flow a) distortion of HIT due to the expanding streamtube resulting in strong anisotropy, b) turbulent pressure modulation across the actuator disk, and the c) turbulent wake state. Finally, we attempt to model the initial distortion and the pressure modulation using a WKB variant of RDT solved numerically using a set of discrete Gabor modes. Funding provided by Precourt Institute for Energy at Stanford University.

  15. Prediction of Potential Hit Song and Musical Genre Using Artificial Neural Networks

    Science.gov (United States)

    Monterola, Christopher; Abundo, Cheryl; Tugaff, Jeric; Venturina, Lorcel Ericka

    Accurately quantifying the goodness of music based on the seemingly subjective taste of the public is a multi-million industry. Recording companies can make sound decisions on which songs or artists to prioritize if accurate forecasting is achieved. We extract 56 single-valued musical features (e.g. pitch and tempo) from 380 Original Pilipino Music (OPM) songs (190 are hit songs) released from 2004 to 2006. Based on an effect size criterion which measures a variable's discriminating power, the 20 highest ranked features are fed to a classifier tasked to predict hit songs. We show that regardless of musical genre, a trained feed-forward neural network (NN) can predict potential hit songs with an average accuracy of ΦNN = 81%. The accuracy is about +20% higher than those of standard classifiers such as linear discriminant analysis (LDA, ΦLDA = 61%) and classification and regression trees (CART, ΦCART = 57%). Both LDA and CART are above the proportional chance criterion (PCC, ΦPCC = 50%) but are slightly below the suggested acceptable classifier requirement of 1.25*ΦPCC = 63%. Utilizing a similar procedure, we demonstrate that different genres (ballad, alternative rock or rock) of OPM songs can be automatically classified with near perfect accuracy using LDA or NN but only around 77% using CART.

  16. Ionoluminescence analysis of glass scintillators and application to single-ion-hit real-time detection

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Akihito, E-mail: yokoyama.akihito@jaea.go.jp [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Takasaki Advanced Radiation Research Institute (TARRI), Japan Atomic Energy Agency (JAEA), 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Kada, Wataru [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Satoh, Takahiro; Koka, Masashi [Takasaki Advanced Radiation Research Institute (TARRI), Japan Atomic Energy Agency (JAEA), 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Shimada, Keisuke; Yokoata, Yuya; Miura, Kenta; Hanaizumi, Osamu [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan)

    2016-03-15

    In this paper, we propose and test a real-time detection system for single-ion hits using mega-electronvolt (MeV)-heavy ions. The system was constructed using G2000 and G9 glass scintillators, as well as an electron-multiplying charge-coupled device (EMCCD) camera combined with an inverted microscope with a 10× objective lens. Commercially available G2000 and G9 glass scintillators, which have been reported to exhibit strong photoluminescence at 489, 543, 585, and 622 nm as a result of the Tb{sup 3+} f–f transition, were employed for highly accurate ionized particle detection. The EMCCD camera had a resolution of 512 × 512 pixels, each with a size of 16 μm × 16 μm, and a maximum linear gain of 8 × 10{sup 5} electrons. For 260-MeV Ne, 3 ion hits/s were detected by our system. The intensity of the ionoluminescence (IL) peak induced by the heavy ions was 140 times the noise intensity. In contrast, the luminous diameter at the full width at half maximum (FWHM) in both the horizontal and vertical directions was calculated to be approximately 4.5 μm. These results suggest that our detection system can accurately detect single-ion hits with a diameter of the order of 1 μm.

  17. A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis.

    Science.gov (United States)

    Davis, Justin; Eyre, Harris; Jacka, Felice N; Dodd, Seetal; Dean, Olivia; McEwen, Sarah; Debnath, Monojit; McGrath, John; Maes, Michael; Amminger, Paul; McGorry, Patrick D; Pantelis, Christos; Berk, Michael

    2016-06-01

    Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype-the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. A business case for HIT adoption: effects of "meaningful use" EHR financial incentives on clinic revenue.

    Science.gov (United States)

    Behkami, Nima A; Dorr, David A; Morrice, Stuart

    2010-01-01

    The goal of this study is to describe a framework that allows decision makers to efficiently evaluate factors that affect Electronic Health Record (EHR) adoption and test suitable interventions; specifically financial incentives. The United States healthcare delivery system is experiencing a transformation to improve population health. There is strong agreement that "meaningful use" of Health Information Technology (HIT) is a major enabler in this effort. However it's also understood that the high cost of implementing an EHR is an obstacle for adoption. To help understand these complexities we developed a simulation model designed to capture the dynamic nature of policy interventions that affect the adoption of EHR. We found that "Effective" use of HIT approaches break-even-point and larger clinic revenue many times faster that "average" or "poor" use of HIT. This study uses a systems perspective to the evaluate EHR adoption process through the "meaningful use" redesign as proposed in the American Reinvestment and Recovery Act 2009 in the United States healthcare industry by utilizing the System Dynamics methodology and Scenario Analysis.

  19. A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

    Science.gov (United States)

    Davis, Justin; Eyre, Harris; Jacka, Felice N; Dodd, Seetal; Dean, Olivia; McEwen, Sarah; Debnath, Monojit; McGrath, John; Maes, Michael; Amminger, Paul; McGorry, Patrick D; Pantelis, Christos; Berk, Michael

    2016-01-01

    Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype—the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders. PMID:27073049

  20. Hit discovery of Mycobacterium tuberculosis inosine 5'-monophosphate dehydrogenase, GuaB2, inhibitors.

    Science.gov (United States)

    Sahu, Niteshkumar U; Singh, Vinayak; Ferraris, Davide M; Rizzi, Menico; Kharkar, Prashant S

    2018-04-18

    Tuberculosis remains a global concern. There is an urgent need of newer antitubercular drugs due to the development of resistant forms of Mycobacterium tuberculosis (Mtb). Inosine 5'-monophosphate dehydrogenase (IMPDH), guaB2, of Mtb, required for guanine nucleotide biosynthesis, is an attractive target for drug development. In this study, we screened a focused library of 73 drug-like molecules with desirable calculated/predicted physicochemical properties, for growth inhibitory activity against drug-sensitive MtbH37Rv. The eight hits and mycophenolic acid, a prototype IMPDH inhibitor, were further evaluated for activity on purified Mtb-GuaB2 enzyme, target selectivity using a conditional knockdown mutant of guaB2 in Mtb, followed by cross-resistance to IMPDH inhibitor-resistant SRMV2.6 strain of Mtb, and activity on human IMPDH2 isoform. One of the hits, 13, a 5-amidophthalide derivative, has shown growth inhibitory potential and target specificity against the Mtb-GuaB2 enzyme. The hit, 13, is a promising molecule with potential for further development as an antitubercular agent. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Patterns of Hits to the Nearshore from a Major Fairway in the Gulf of Finland

    Science.gov (United States)

    Viikmae, B.; Soomere, T.

    2012-04-01

    The Baltic Sea hosts one of the heaviest ship traffic in the world. Although relatively small in size, still up to 15% of the world's cargo is transported along its numerous fairways. The largest threat to the environment is oil transportation that has increased more than by a factor of two in 2000-2008 and a 40% increase is expected by the year 2015. One of the major marine highways in the European waters enters the Baltic Sea through the Danish Straits, crosses the Baltic Proper and stretches through the Gulf of Finland to Saint Petersburg. An area that is highly vulnerable to ship pollution is the nearshore that usually has the largest ecological value. While the probability of coastal pollution for open ocean coasts can be reduced by shifting ship routes farther offshore, the problem for narrow bays, like the Gulf of Finland, is how to minimize the probability of hitting any of the coasts. To a certain extent, light can be shed to this problem by means of quantification of the offshore areas in terms of their ability to serve a danger to coastal environment if pollution would happen in these areas. A convenient way to address this problem is to use statistical analysis of a large number of Lagrangian trajectories of test particles representing the potential pollution and passively carried by surface currents. In this paper, we make and attempt to quantify the link between potential sources of pollution along an existing fairway and the sections of the coast reached by current-driven pollution. The problem is analysed by means of considering hits to the nearshore from a major fairway in the Gulf of Finland and by making sure whether certain parts of the coast are hit by pollution particles most frequently and whether or not these pollution particles stem from certain specific parts of the fairway. Trajectories are simulated in the Gulf of Finland by placing tracers among a line that follows one of the major fairways from the Baltic Proper to Saint Petersburg

  2. Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials hit 88/89 and hit 91

    International Nuclear Information System (INIS)

    Timmermann, Beate; Kortmann, Rolf-Dieter; Kuehl, Joachim; Meisner, Christoph; Slavc, Irene; Pietsch, Thorsten; Bamberg, Michael

    2000-01-01

    Purpose: To evaluate the outcome in children with anaplastic ependymomas after surgery, irradiation, and chemotherapy; and to identify prognostic factors for survival. Methods and Materials: Fifty-five children (n = 27 girls, 28 boys; median age at diagnosis, 6.2 years) with newly diagnosed anaplastic ependymomas were treated in the multicenter, prospective trials HIT 88/89 and HIT 91. Macroscopic complete resection was achieved in 28 patients; 27 patients underwent incomplete resection. All patients received chemotherapy before (n = 40) or after irradiation (n = 15). The irradiation volume encompassed either the neuraxis followed by a boost to the primary tumor site (n = 40) or the tumor region only (n = 13). No radiotherapy was administered in two patients. Results: Median follow-up was 38 months. The overall survival rate at 3 years after surgery was 75.6%. Disease progression occurred in 25 children with local progression occurring in 20. The median time to disease progression was 45 months. The only significant prognostic factor was the extent of resection (estimated progression-free survival [EPFS] after 3 years was 83.3% after complete resection and 38.5% after incomplete resection) and the presence of metastases at the time of diagnosis (0% vs. 65.8% 3-year EPFS in localized tumors). Age, sex, tumor site, mode of chemotherapy, and irradiation volume did not influence survival. Conclusions: Treatment centers should be meticulous about surgery and diagnostic workup. Because the primary tumor region is the predominant site of failure it is important to intensify local treatment. Dose escalation by hyperfractionation or stereotactic radiotherapy might be a promising approach in macroscopically residual disease. The role of adjuvant chemotherapy requires further study

  3. X-hitting: A new algorithm for novelty detection and dereplication by UV spectra of complex mixtures of natural products

    DEFF Research Database (Denmark)

    Hansen, Michael Edberg; Smedsgaard, Jørn; Larsen, Thomas Ostenfeld

    2005-01-01

    A major challenge in lead discovery is to detect well-known and trivial compounds rapidly, a process known as dereplication, so that isolation, structure elucidation, and pharmacological investigations can be focused on novel compounds. In this paper, we present a new algorithm, X-hitting, based...... on cross sample comparison of full UV spectra from HPLC analysis of highly complex natural product extracts/samples. X-Hitting allows automatic identification of known compounds but more important also allows finding of potentially new or similar compounds. We demonstrate this new algorithm by automatic...... identification of known structures, a task we call cross-hitting, and tentative identification of potentially new bioactive compounds, a task we call new-hitting, in HPLC data from analysis of fungal extracts. Both tasks are illustrated using 18 important reference compounds and complex fungal extracts obtained...

  4. Hydrolyzed infant formula and early β-cell autoimmunity

    DEFF Research Database (Denmark)

    Knip, Mikael; Åkerblom, Hans K; Becker, Dorothy

    2014-01-01

    -associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years). RESULTS......IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain...... intact proteins. OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children. DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA...

  5. Lessons learnt from the Wenchuan earthquake: performance evaluation of treatment of critical injuries in hardest-hit areas.

    Science.gov (United States)

    Jiang, Jie; Li, Youping; Huang, Xiaolin; Li, Bing; Su, Lin; Zhong, Dake; Shi, Chenghu; Li, Mingxu; Shan, Juan; Chen, Yin

    2012-08-01

    Critical injury treatment in the hardest-hit areas after a great earthquake was retrospectively analyzed to determine how best to reduce mortality and disability and increase the rehabilitation rate through postquake medical relief. Retrospective analysis, primary sources, and secondary sources were comprehensively retrieved and analyzed. According to incomplete data, 30,620 injured were rescued by themselves among the hardest-hit areas in the 72 hours immediately following the earthquake. Critically injured patients accounted for 22% of total inpatients. Mortality rates declined with greater distance from the epicenter: rates were 12.21% for municipal healthcare centers in the hardest-hit areas, 4.50% for municipal medical units in peripheral quake-hit areas, 2.50% for provincial medical units in peripheral quake-hit areas, and 2.17% for Ministry of Health-affiliated hospitals in peripheral quake-hit areas. The number of injured with fractures on body, limbs or unknown-parts, severe conditions as well as other kinds of non-traumatic diseases received in second-line hospitals was much more than those treated in first-line hospitals with more severe injuries. Among 10,373 injured in stable condition transferred to third-line hospitals, 99.07% were discharged from hospitals within four months, while the mortality rate was 0.017%. The medical relief model of "supervising body helping subordinate unit, severely stricken areas assisting hardest-hit areas, least-hit areas supporting both hardest-hit and severely stricken areas, and self help and mutual assistance applied between hardest-hit areas" was roughly established for injured from severely stricken areas after the Wenchuan Earthquake. The "four-centralization" treatment principle, which referred to concentrating patients, experts, resources and treatment for those injured in critical condition effectively reduced the mortality from 15.06% to 2.9%. Timely, scientific, and standard on-site triage and postmedical

  6. THEORY OF ACTIVE HITTINGS IS IN PROCESSES OF ELECTRO-COAGULATION THE ADMIXTURES IN WATER TECHNOLOGICAL ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    В.В. Березуцький

    2012-10-01

    Full Text Available  In the article theoretical bases of electro-coagulation of admixtures are examined in a water technological environment with the use of theory of the active hittings, which are based on the results of the executed researches and analysis of scientific information. Application of theory of the active hittings is in coagulation, provides high efficiency of process of extraction of admixtures from water environments during minimization of energy consumption and expenses of materials.

  7. Contribution of Visual Information about Ball Trajectory to Baseball Hitting Accuracy.

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    Takatoshi Higuchi

    Full Text Available The contribution of visual information about a pitched ball to the accuracy of baseball-bat contact may vary depending on the part of trajectory seen. The purpose of the present study was to examine the relationship between hitting accuracy and the segment of the trajectory of the flying ball that can be seen by the batter. Ten college baseball field players participated in the study. The systematic error and standardized variability of ball-bat contact on the bat coordinate system and pitcher-to-catcher direction when hitting a ball launched from a pitching machine were measured with or without visual occlusion and analyzed using analysis of variance. The visual occlusion timing included occlusion from 150 milliseconds (ms after the ball release (R+150, occlusion from 150 ms before the expected arrival of the launched ball at the home plate (A-150, and a condition with no occlusion (NO. Twelve trials in each condition were performed using two ball speeds (31.9 m·s-1 and 40.3 m·s-1. Visual occlusion did not affect the mean location of ball-bat contact in the bat's long axis, short axis, and pitcher-to-catcher directions. Although the magnitude of standardized variability was significantly smaller in the bat's short axis direction than in the bat's long axis and pitcher-to-catcher directions (p < 0.001, additional visible time from the R+150 condition to the A-150 and NO conditions resulted in a further decrease in standardized variability only in the bat's short axis direction (p < 0.05. The results suggested that there is directional specificity in the magnitude of standardized variability with different visible time. The present study also confirmed the limitation to visual information is the later part of the ball trajectory for improving hitting accuracy, which is likely due to visuo-motor delay.

  8. Computational Breakthrough of Natural Lead Hits from the Genus of Arisaema against Human Respiratory Syncytial Virus.

    Science.gov (United States)

    Kant, Kamal; Lal, Uma Ranjan; Ghosh, Manik

    2018-01-01

    To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV. Selected 60 phytochemical entities were evaluated on the docking behavior of human RSV receptor (PDB: 4UCC) using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). Furthermore, kinetic properties and toxicity nature of top graded ligands were analyzed through QikProp and ProTox tools. Notably, rutin (glide score: -8.49), schaftoside (glide score: -8.18) and apigenin-6,8-di-C-β-D-galactoside (glide score - 7.29) have resulted in hopeful natural lead hits with an ideal range of kinetic descriptors values. ProTox tool (oral rodent toxicity) has resulted in likely toxicity targets of apex-graded tested ligands. Finally, the whole efforts can be explored further as a model to confirm its anti-human RSV potential with wet laboratory experiments. Rutin, schaftoside, and apigenin-6,8-di-C-β-D-galactoside showed promising top hits docking profile against human respiratory syncytial virusMoreover, absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptorsProTox tool highlighted toxicity class ranges, LD 50 values, and possible toxicity targets of apex-graded tested ligands. Abbreviations used: RSV: Respiratory syncytial virus, PRRSV: Porcine respiratory and reproductive syndrome virus, ADME-T: Absorption, distribution, metabolism, excretion, and toxicity.

  9. Transfer plate radioassay using adsorbed anti-insulin antibody to detect insulin secreted by islet cell cultures

    International Nuclear Information System (INIS)

    Scearce, R.M.; Oie, H.K.; Gazdar, A.F.; Chick, W.L.; Eisenbarth, G.S.

    1981-01-01

    A solid-phase radioimmunoassay for detection of insulin synthesized by islet cell clones is described. This assay employs anti-insulin antibody adsorbed onto fenestrated polyvinyl chloride 96-well plates ('transfer plates'). The calibrated aperture in the bottom of each transfer plate well permits fluid to enter the wells when transfer plates are lowered into microculture wells containing insulin. With this assay it is possible to rapidly screen hundreds of islet cell cultures for insulin production. The authors have used this assay to facilitate cloning of the RIN rat insulinoma cell line. The assay readily detects insulin synthesis by RIN cells and [ 125 I]insulin is not displaced by culture medium from cells which do not produce insulin. The transfer plate format should be applicable to semiautomate other radioimmunoassays. (Auth.)

  10. Selective histone deacetylase 6 inhibition prolongs survival in a lethal two-hit model.

    Science.gov (United States)

    Cheng, Xin; Liu, Zhengcai; Liu, Baoling; Zhao, Ting; Li, Yongqing; Alam, Hasan B

    2015-07-01

    Hemorrhagic shock (HS) followed by a subsequent insult ("second hit") often initiates an exaggerated systemic inflammatory response and multiple organ failure. We have previously demonstrated that valproic acid, a pan histone deacetylase inhibitor, could improve survival in a rodent "two-hit" model. In the present study, our goal was to determine whether selective inhibition of histone deacetylase 6 with Tubastatin A (Tub-A) could prolong survival in a two-hit model where HS was followed by sepsis from cecal ligation and puncture (CLP). C57Bl/6J mice were subjected to sublethal HS (30% blood loss) and then randomly divided into two groups (n = 13 per group) such as Tub-A group (treatment) and vehicle (VEH) group (control). The Tub-A group was given an intraperitoneal injection of Tub-A (70 mg/kg) dissolved in dimethyl sulfoxide (DMSO). The VEH group was injected with DMSO (1 μl/g body weight). After 24 h, all mice were subjected CLP followed immediately by another dose of Tub-A or DMSO. Survival was monitored for 10 d. In a parallel study, peritoneal irrigation fluid and liver tissue from Tub-A- or DMSO-treated mice were collected 3 h after CLP. Enzyme-linked immunosorbent assay was performed to quantify activity of the myeloperoxidase and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in the peritoneal irrigation fluid. RNA was isolated from the liver tissue, and real-time polymerase chain reaction was performed to measure relative messenger RNA levels of TNF-α and IL-6. Treatment with Tub-A significantly improved survival compared with that of the control (69.2% versus 15.4%). In addition, Tub-A significantly suppressed myeloperoxidase activity (169.9 ± 8.4 ng/mL versus 70.4 ± 17.4 ng/mL; P hit model. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Long-range effects of direct-hit ultraviolet and particle radiation in oncogene activation

    International Nuclear Information System (INIS)

    Ladik, J.J.

    1990-01-01

    A simple statistical analysis shows that the oncogene-activation effect of chemical carcinogens cannot be explained if one takes into account only short-range effects. As one of the most probable solid state physical long-range effects, the generation at the site of carcinogen binding of travelling solitary waves, which can interfere with DNA-blocking protein interactions, is discussed. It has been shown that the direct hit carcinogenic effects on DNA by ultraviolet--or particle radiation can also be explained by the generation of solitary waves (in the latter case the first step is a collective plasma oscillation which decays to individual local excitations and ionizations)

  12. Hitting times of local and global optima in genetic algorithms with very high selection pressure

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    Eremeev Anton V.

    2017-01-01

    Full Text Available The paper is devoted to upper bounds on the expected first hitting times of the sets of local or global optima for non-elitist genetic algorithms with very high selection pressure. The results of this paper extend the range of situations where the upper bounds on the expected runtime are known for genetic algorithms and apply, in particular, to the Canonical Genetic Algorithm. The obtained bounds do not require the probability of fitness-decreasing mutation to be bounded by a constant which is less than one.

  13. The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512

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    Hassan Mziaut

    2016-08-01

    Full Text Available Objective: Insulin release from pancreatic islet β cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell autoantigen 512 (Ica512 (also known as islet antigen 2/Ptprn. Here we investigated how Ica512 modulates SG trafficking and exocytosis. Methods: Transcriptomic changes in Ica512−/− mouse islets were analyzed. Imaging as well as biophysical and biochemical methods were used to validate if and how the Ica512-regulated gene villin modulates insulin secretion in mouse islets and insulinoma cells. Results: The F-actin modifier villin was consistently downregulated in Ica512−/− mouse islets and in Ica512-depleted insulinoma cells. Villin was enriched at the cell cortex of β cells and dispersed villin−/− islet cells were less round and less deformable. Basal mobility of SGs in villin-depleted cells was enhanced. Moreover, in cells depleted either of villin or Ica512 F-actin cages restraining cortical SGs were enlarged, basal secretion was increased while glucose-stimulated insulin release was blunted. The latter changes were reverted by overexpressing villin in Ica512-depleted cells, but not vice versa. Conclusion: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion. Keywords: F-actin, Granules, Ica512, Insulin, Secretion, Villin

  14. The head tracks and gaze predicts: how the world's best batters hit a ball.

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    David L Mann

    Full Text Available Hitters in fast ball-sports do not align their gaze with the ball throughout ball-flight; rather, they use predictive eye movement strategies that contribute towards their level of interceptive skill. Existing studies claim that (i baseball and cricket batters cannot track the ball because it moves too quickly to be tracked by the eyes, and that consequently (ii batters do not - and possibly cannot - watch the ball at the moment they hit it. However, to date no studies have examined the gaze of truly elite batters. We examined the eye and head movements of two of the world's best cricket batters and found both claims do not apply to these batters. Remarkably, the batters coupled the rotation of their head to the movement of the ball, ensuring the ball remained in a consistent direction relative to their head. To this end, the ball could be followed if the batters simply moved their head and kept their eyes still. Instead of doing so, we show the elite batters used distinctive eye movement strategies, usually relying on two predictive saccades to anticipate (i the location of ball-bounce, and (ii the location of bat-ball contact, ensuring they could direct their gaze towards the ball as they hit it. These specific head and eye movement strategies play important functional roles in contributing towards interceptive expertise.

  15. Effects on ontogenesis of Carausius morosus hit by cosmic heavy ions

    International Nuclear Information System (INIS)

    Reitz, G.; Buecker, H.; Ruether, W.

    1990-01-01

    Among the biological problems that arise in long duration spaceflights, the effects of weightlessness and ionizing radiation appear to be the two main risk factors. Eggs of the stick insect Carausius morosus were exposed to spaceflight conditions during the 12.56 day Biosatellite mission Cosmos 1887. Five different ages were used, representing different sensitivities to radiation and different capacities for regeneration. During spaceflight the eggs continued their development. Already, in the Spacelab D1 mission in 1985, it has been shown that microgravity leads to a reduced hatching rate of eggs exposed during the early steps of development. When the eggs were hit by a heavy ion, a further but not significant reduction of the hatching rate was observed. Hatching was normal for eggs which were exposed on a 1 g reference centrifuge in space. Heavy ion hits caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high rate of anomalies. In the experiment on Cosmos 1887 these results were confirmed. Studies on the embryonic development before hatching showed no major difference between flight and ground control specimen, neither in speed of development nor in morphological anomalies. Hatching therefore seems to be the critical point in insect ontogenesis. (author)

  16. Pelvic rotation torque during fast-pitch softball hitting under three ball height conditions.

    Science.gov (United States)

    Iino, Yoichi; Fukushima, Atsushi; Kojima, Takeji

    2014-08-01

    The purpose of this study was to investigate the relevance of hip joint angles to the production of the pelvic rotation torque in fast-pitch softball hitting and to examine the effect of ball height on this production. Thirteen advanced female softball players hit stationary balls at three different heights: high, middle, and low. The pelvic rotation torque, defined as the torque acting on the pelvis through the hip joints about the pelvic superior-inferior axis, was determined from the kinematic and force plate data using inverse dynamics. Irrespective of the ball heights, the rear hip extension, rear hip external rotation, front hip adduction, and front hip flexion torques contributed to the production of pelvic rotation torque. Although the contributions of the adduction and external rotation torques at each hip joint were significantly different among the ball heights, the contributions of the front and rear hip joint torques were similar among the three ball heights owing to cancelation of the two torque components. The timings of the peaks of the hip joint torque components were significantly different, suggesting that softball hitters may need to adjust the timings of the torque exertions fairly precisely to rotate the upper body effectively.

  17. An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

    Science.gov (United States)

    Bradley, Stuart

    2015-11-20

    Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

  18. A framework of induced hyperspace dynamical systems equipped with the hit-or-miss topology

    International Nuclear Information System (INIS)

    Wang Yangeng; Wei Guo; Campbell, William H.; Bourquin, Steven

    2009-01-01

    For any dynamical system (E,d,f), where E is Hausdorff locally compact second countable (HLCSC), let F (resp., 2 E ) denote the space of all closed subsets (resp., non-empty closed subsets) of E equipped with the hit-or-miss topology τ f . Both F and 2 E are again HLCSC (F actually compact), thus metrizable. Let ρ be such a metric (three metrics available). The main purpose is to determine the conditions on f that ensure the continuity of the induced hyperspace maps 2 f :F→F and 2 f :2 E →2 E defined by 2 f (F)=f(F). With this setting, the induced hyperspace systems (F,ρ,2 f ) and (2 E ,ρ,2 f ) are compact and locally compact dynamical systems, respectively. Consequently, dynamical properties, particularly metric related dynamical properties, of the given system (E,d,f) can be explored through these hyperspace systems. In contrast, when the Vietoris topology τ v is equipped on 2 E , the space of the induced hyperspace topological dynamical system (2 E ,τ v ,2 f ) is not metrizable if E is not compact metrizable, e.g., E=R n , implying that metric related dynamical concepts cannot be defined for (2 E ,τ v ,2 f ). Moreover, two examples are provided to illustrate the advantages of the hit-or-miss topology as compared to the Vietoris topology.

  19. Double-hit mouse model of cigarette smoke priming for acute lung injury.

    Science.gov (United States)

    Sakhatskyy, Pavlo; Wang, Zhengke; Borgas, Diana; Lomas-Neira, Joanne; Chen, Yaping; Ayala, Alfred; Rounds, Sharon; Lu, Qing

    2017-01-01

    Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals.

  20. Cell Cycle Deregulation in the Neurons of Alzheimer’s Disease

    Science.gov (United States)

    Moh, Calvin; Kubiak, Jacek Z.; Bajic, Vladan P.; Zhu, Xiongwei; Smith, Mark A.

    2018-01-01

    The cell cycle consists of four main phases: G1, S, G2, and M. Most cells undergo these cycles up to 40–60 times in their life. However, neurons remain in a nondividing, nonreplicating phase, G0. Neurons initiate but do not complete cell division, eventually entering apoptosis. Research has suggested that like cancer, Alzheimer’s disease (AD) involves dysfunction in neuronal cell cycle reentry, leading to the development of the two-hit hypothesis of AD. The first hit is abnormal cell cycle reentry, which typically results in neuronal apoptosis and prevention of AD. However, with the second hit of chronic oxidative damage preventing apoptosis, neurons gain “immortality” analogous to tumor cells. Once both of these hits are activated, AD can develop and produce senile plaques and neurofibrillary tangles throughout brain tissue. In this review, we propose a mechanism for neuronal cell cycle reentry and the development of AD. PMID:21630160