Sample records for leho kiv simmo

  1. Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL.

    PubMed

    Caterer, Nigel R; Graversen, Jonas H; Jacobsen, Christian; Moestrup, Søren K; Sigurskjold, Bent W; Etzerodt, Michael; Thøgersen, Hans C

    2002-11-01

    Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1-110)]. Previous studies indicated that lipoprotein(a) non-covalently binds the N-terminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surface-exposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).

  2. Karolinska Interpersonal Violence Scale predicts suicide in suicide attempters.

    PubMed

    Jokinen, Jussi; Forslund, Kaj; Ahnemark, Ewa; Gustavsson, J Petter; Nordström, Peter; Asberg, Marie

    2010-08-01

    Both childhood trauma and violent behavior are important risk factors for suicidal behavior. The aim of the present study was to construct and validate a clinical rating scale that could measure both the exposure to and the expression of violence in childhood and during adult life and to study the ability of the Karolinska Interpersonal Violence Scale (KIVS) to predict ultimate suicide in suicide attempters. A total of 161 suicide attempters and 95 healthy volunteers were assessed with the KIVS measuring exposure to violence and expressed violent behavior in childhood (between 6-14 years of age) and during adult life (15 years or older). The Buss-Durkee Hostility Inventory (BDHI), "Urge to act out hostility" subscale from the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Early Experience Questionnaire (EEQ) were used for validation. All patients were followed up for cause of death and a minimum of 4 years from entering in the study. Five patients who committed suicide within 4 years had significantly higher scores in exposure to violence as a child, in expressed violent behavior as an adult, and in KIVS total score compared to survivors. Suicide attempters scored significantly higher compared to healthy volunteers in 3 of the 4 KIVS subscales. There were significant correlations between the subscales measuring exposure to and expression of violent behavior during the life cycle. BDHI, Urge to act out hostility, and EEQ validated the KIVS. Exposure to violence in childhood and violent behavior in adulthood are risk factors for completed suicide in suicide attempters. Behavioral dysregulation of aggression is important to assess in clinical work. The KIVS is a valuable new tool for case detection and long-term clinical suicide prevention. Copyright 2010 Physicians Postgraduate Press, Inc.

  3. The effect of enriched environment across ages: A study of anhedonia and BDNF gene induction.

    PubMed

    Dong, B E; Xue, Y; Sakata, K

    2018-05-02

    Enriched environment treatment (EET) is a potential intervention for depression by inducing brain-derived neurotrophic factor (BDNF). However, its age dependency remains unclear. We recently found that EET during early-life development (ED) was effective in increasing exploratory activity and anti-despair behavior, particularly in promoter IV-driven BDNF deficient mice (KIV), with the largest BDNF protein induction in the hippocampus and frontal cortex. Here, we further determined age dependency of EET effects on anhedonia and promoter-specific BDNF transcription, by using the sucrose preference test and qRT-PCR. Wild-type (WT) and KIV mice received 2 months of EET during ED, young-adulthood and old-adulthood (0-2, 2-4 and 12-14 months, respectively). All KIV groups showed reduced sucrose preference, which EET equally reversed regardless of age. EET increased hippocampal BDNF mRNA levels for all ages and genotypes, but increased frontal cortex BDNF mRNA levels only in ED KIV and old WT mice. Transcription by promoters I and IV was age-dependent in the hippocampus of WT mice: more effective induction of exon IV or I during ED or old-adulthood, respectively. Transcription by almost all 9 promoters was age-specific in the frontal cortex, mostly observed in ED KIV mice. After discontinuance of EET, the EET effects on anti-anhedonia and BDNF transcription in both regions persisted only in ED KIV mice. These results suggested that EET was equally effective in reversing anhedonia and inducing hippocampal BDNF transcription, but was more effective during ED in inducing frontal cortex BDNF transcription and for lasting anti-anhedonic and BDNF effects particularly in promoter IV-BDNF deficiency. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  4. Combining the Suicide Intent Scale and the Karolinska Interpersonal Violence Scale in suicide risk assessments.

    PubMed

    Stefansson, J; Nordström, P; Runeson, B; Åsberg, M; Jokinen, J

    2015-09-23

    High suicide intent, childhood trauma, and violent behavior are risk factors for suicide in suicide attempters. The aim of this study was to investigate whether the combined assessment of suicide intent and interpersonal violence would provide a better prediction of suicide risk than an assessment of only suicide intent or interpersonal violence. This is a cohort study involving 81 suicide attempters included in the study between 1993 and 1998. Patients were assessed with both the Suicide Intent Scale (SIS) and the Karolinska Interpersonal Violence Scale (KIVS). Through the unique personal identification number in Sweden, patients were linked to the Cause of Death Register maintained by the Swedish National Board of Health and Welfare. Suicides were ascertained from the death certificates. Seven of 14 patients who had died before April 2013 had committed suicide. The positive predictive value for the Suicide Intent Scale alone was 16.7 %, with a specificity of 52 % and an area under the curve of 0.74. A combined assessment with the KIVS gave higher specificity (63 %) and a positive predictive value of 18.8 % with an AUC of 0.83. Combined use of SIS and KIVS expressed interpersonal violence as an adult subscale gave a sensitivity of 83.3 %, a specificity of 80.3 %, and a positive predictive value of 26 % with an AUC of 0.85. The correlation between KIVS and SIS scores was not significant. Using both the the SIS and the KIVS combined may be better for predicting completed suicide than using them separately. The nonsignificant correlation between the scales indicates that they measure different components of suicide risk.

  5. Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians.

    PubMed

    Khalifa, Mahmoud; Noureen, Asma; Ertelthalner, Kathrin; Bandegi, Ahmad Reza; Delport, Rhena; Firdaus, Wance J J; Geethanjali, Finney S; Luthra, Kalpana; Makemaharn, Orawan; Pang, Richard W C; Salem, Abdel-Halim; Sasaki, Jun; Schiefenhoevel, Wulf; Lingenhel, Arno; Kronenberg, Florian; Utermann, Gerd; Schmidt, Konrad

    2015-10-01

    The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Electrostatic Ion-Cyclotron Waves in Magnetospheric Plasmas: Non-Local Aspects.

    DTIC Science & Technology

    1983-10-14

    moving observer will see a Doppler shifted frequency --- S where is the velocity vector of the observer (satellite) and k is the wave vector. Since k...direction) will not see any Doppler -shift, irrespective of the size of ky . Such a statement could not be made in the purely local theory, since there...a local theory, a wide range of Doppler shifts would be produced, from -kivs to +kivs, since the maximum value of kx is k1. Some of the observations

  7. Risk factors for adult interpersonal violence in suicide attempters

    PubMed Central

    2014-01-01

    Background Suicidal and violent behaviours are interlinked and share common biological underpinnings. In the present study we analysed the association between violent behaviour as a child, childhood trauma, adult psychiatric illness, and substance abuse in relation to interpersonal violence as an adult in suicide attempters with mood disorders. Methods A total of 161 suicide attempters were diagnosed with Structured Clinical Interviews and assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behaviour in childhood (between 6-14 years of age) and during adult life (15 years or older). Ninety five healthy volunteers were used as a comparison group. A logistic regression analysis was conducted with the two KIVS subscales, expressed violent behaviour as a child and exposure to violence in childhood together with substance abuse, personality disorder diagnoses and age as possible predictors of adult interpersonal violence in suicide attempters. Results Violent behaviour as a child, age and substance abuse were significant predictors of adult interpersonal violence. ROC analysis for the prediction model for adult violence with the KIVS subscale expressed violence as a child gave an AUC of 0.79. Using two predictors: violent behaviour as a child and substance abuse diagnosis gave an AUC of 0.84. The optimal cut-off for the KIVS subscale expressed violence as a child was higher for male suicide attempters. Conclusions Violent behaviour in childhood and substance abuse are important risk factors for adult interpersonal violent behaviour in suicide attempters. PMID:25001499

  8. Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV

    PubMed Central

    Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

    2016-01-01

    Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0–2 months), young adult (2–4 months), and old adult (12–14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults. PMID:27648918

  9. Lack of promoter IV-driven BDNF transcription results in depression-like behavior.

    PubMed

    Sakata, K; Jin, L; Jha, S

    2010-10-01

    Transcription of Bdnf is controlled by multiple promoters, in which promoter IV contributes significantly to activity-dependent Bdnf transcription. We have generated promoter IV mutant mice [brain-derived neurotrophic factor (BDNF)-KIV] in which promoter IV-driven expression of BDNF is selectively disrupted by inserting a green fluorescent protein (GFP)-STOP cassette within the Bdnf exon IV locus. BDNF-KIV animals exhibited depression-like behavior as shown by the tail suspension test (TST), sucrose preference test (SPT) and learned helplessness test (LHT). In addition, BDNF-KIV mice showed reduced activity in the open field test (OFT) and reduced food intake in the novelty-suppressed feeding test (NSFT). The mutant mice did not display anxiety-like behavior in the light and dark box test and elevated plus maze tests. Interestingly, the mutant mice showed defective response inhibition in the passive avoidance test (PAT) even though their learning ability was intact when measured with the active avoidance test (AAT). These results suggest that promoter IV-dependent BDNF expression plays a critical role in the control of mood-related behaviors. This is the first study that directly addressed the effects of endogenous promoter-driven expression of BDNF in depression-like behavior. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  10. 78 FR 41036 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ...-119 and KIV-119 Identify Friend or Foe (IFF) Systems Also provided are spare and repair parts...-119 Identify Friend or Foe (IFF) Systems Also provided are spare and repair parts, communication, test...

  11. Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men.

    PubMed

    Chatzittofis, Andreas; Savard, Josephine; Arver, Stefan; Öberg, Katarina Görts; Hallberg, Jonas; Nordström, Peter; Jokinen, Jussi

    2017-06-01

    Background and aims There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods This case-control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery-Åsberg Depression Rating Scale - Self-rating. Results Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.

  12. Lipoprotein (a): impact by ethnicity and environmental and medical conditions

    PubMed Central

    Enkhmaa, Byambaa; Anuurad, Erdembileg; Berglund, Lars

    2016-01-01

    Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan. Studies have demonstrated pronounced differences across ethnicities with regard to Lp(a) levels and some of this difference, but not all of it, can be explained by genetic variations across ethnic groups. Increasing evidence suggests that age, sex, and hormonal impact may have a modest modulatory influence on Lp(a) levels. Among clinical conditions, Lp(a) levels are reported to be affected by kidney and liver diseases. PMID:26637279

  13. Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men

    PubMed Central

    Chatzittofis, Andreas; Savard, Josephine; Arver, Stefan; Öberg, Katarina Görts; Hallberg, Jonas; Nordström, Peter; Jokinen, Jussi

    2017-01-01

    Background and aims There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods This case–control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire – Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery–Åsberg Depression Rating Scale – Self-rating. Results Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men. PMID:28467102

  14. Pharmacokinetics of ketoconazole administered intravenously to dogs and orally as tablet and solution to humans and dogs.

    PubMed

    Baxter, J G; Brass, C; Schentag, J J; Slaughter, R L

    1986-05-01

    The single-dose pharmacokinetics and bioavailability of three ketoconazole formulations were evaluated using HPLC in five healthy human volunteers and six male mongrel dogs. The human volunteers received 400 mg po of ketoconazole as tablet (Ktab) and solution (Ksol) formulations. The dogs received 400 mg po of Ktab and Ksol, and 376 mg iv of an intravenous dose (Kiv). In humans the AUC value for Ksol (62.21 +/- 21.2 microgram X h/ml; mean +/- SD) was significantly greater than for Ktab (50.0 +/- 15.2 micrograms X h/ml; p less than 0.05). Peak serum concentrations (Cmax), time to peak serum concentrations (tmax), t1/2, and the terminal elimination rate constant (kel) did not differ between Ktab and Ksol. This suggests that the administration of Ksol may be a useful alternative to dosage increases in situations where low bioavailability of ketoconazole in tablet form is suspected. The mean systemic clearance (CLs) of Kiv in dogs was 2.74 +/- 1.10 mL/min/kg, the volume of distribution at steady state (Vdss) was 0.72 +/- 0.28 L/kg, and the half-life was 2.7 +/- 1.6 h. Considerable variability was seen in the AUC of ketoconazole, particularly with the oral preparations. The absolute bioavailability of Ktab was 0.50 +/- 0.38, which did not differ statistically from that of Ksol, 0.56 +/- 0.23. The Ksol showed less variability in AUC, Cmax, and F values than did Ktab, and two dogs with low bioavailability with Ktab (0.04 and 0.07) had substantially greater bioavailability with Ksol (F = 0.96 and 0.57, respectively). Evaluation of Kiv in dogs confirms decreased bioavailability from orally administered tablet formulations of ketoconazole.

  15. Regulation of valine and. alpha. -ketoisocaproate metabolism in rat kidney mitochondria

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, R.H.; Harper, A.E.

    1988-10-01

    Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and {alpha}-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids {alpha}-ketoisocaproate (KIC) or {alpha}-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of {sup 14}C-labeled products formed. Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, {alpha}-ketoglutarate ({alpha}-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM {alpha}-KG as the aminomore » acceptor; these rates were 5- to 50-fold those without added {alpha}-KG. Rates of CO{sub 2} evolution from valine also increased when KIC was present; however, with KIC concentrations above 0.2 mM, rates of CO{sub 2} evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, {alpha}-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine. Thus the rate of oxidation of BCAA can be controlled by factors that influence the rate and direction of BCAA transamination and, thereby, the supply of substrate for BCKD.« less

  16. Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis.

    PubMed

    Saleheen, Danish; Haycock, Philip C; Zhao, Wei; Rasheed, Asif; Taleb, Adam; Imran, Atif; Abbas, Shahid; Majeed, Faisal; Akhtar, Saba; Qamar, Nadeem; Zaman, Khan Shah; Yaqoob, Zia; Saghir, Tahir; Rizvi, Syed Nadeem Hasan; Memon, Anis; Mallick, Nadeem Hayyat; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, Fazal-Ur-Rehman; Mahmood, Khalid; Ahmed, Naveeduddin; Frossard, Philippe; Tsimikas, Sotirios; Witztum, Joseph L; Marcovina, Santica; Sandhu, Manjinder; Rader, Daniel J; Danesh, John

    2017-07-01

    The lipoprotein(a) pathway is a causal factor in coronary heart disease. We used a genetic approach to distinguish the relevance of two distinct components of this pathway, apolipoprotein(a) isoform size and circulating lipoprotein(a) concentration, to coronary heart disease. In this mendelian randomisation study, we measured lipoprotein(a) concentration and determined apolipoprotein(a) isoform size with a genetic method (kringle IV type 2 [KIV2] repeats in the LPA gene) and a serum-based electrophoretic assay in patients and controls (frequency matched for age and sex) from the Pakistan Risk of Myocardial Infarction Study (PROMIS). We calculated odds ratios (ORs) for myocardial infarction per 1-SD difference in either LPA KIV2 repeats or lipoprotein(a) concentration. In a genome-wide analysis of up to 17 503 participants in PROMIS, we identified genetic variants associated with either apolipoprotein(a) isoform size or lipoprotein(a) concentration. Using a mendelian randomisation study design and genetic data on 60 801 patients with coronary heart disease and 123 504 controls from the CARDIoGRAMplusC4D consortium, we calculated ORs for myocardial infarction with variants that produced similar differences in either apolipoprotein(a) isoform size in serum or lipoprotein(a) concentration. Finally, we compared phenotypic versus genotypic ORs to estimate whether apolipoprotein(a) isoform size, lipoprotein(a) concentration, or both were causally associated with coronary heart disease. The PROMIS cohort included 9015 patients with acute myocardial infarction and 8629 matched controls. In participants for whom KIV2 repeat and lipoprotein(a) data were available, the OR for myocardial infarction was 0·93 (95% CI 0·90-0·97; p<0·0001) per 1-SD increment in LPA KIV2 repeats after adjustment for lipoprotein(a) concentration and conventional lipid concentrations. The OR for myocardial infarction was 1·10 (1·05-1·14; p<0·0001) per 1-SD increment in lipoprotein

  17. Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

    PubMed Central

    Sakata, Kazuko; Martinowich, Keri; Woo, Newton H.; Schloesser, Robert J.; Jimenez, Dennisse V.; Ji, Yuanyuan; Shen, Liya; Lu, Bai

    2013-01-01

    Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal–PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders. PMID:23980178

  18. World Epidemiology Review, Number 105.

    DTIC Science & Technology

    1978-09-13

    human , animal, and plant diseases, insect pests and control, sanitation conditions, immunization and public health programs. 17. Key Words and...Document Analysis. 17a. Descriptors Worldwide Clinical Medicine Environmental Biology Hygiene and Sanitation Microbiology 17b. Identifiers /Open...KIV. ••71) THIS FORM MAY BE REPRODUCED USCOMM-OC UM1-*T1 JPRS 71863 13 September 19 78 WORLD EPIDEMIOLOGY REVIEW No. 105 CONTENTS PAGE HUMAN

  19. Annual Conference on Human Retrovirus Testing (9th) Held in Reno, Nevada on 2-4 March 1994

    DTIC Science & Technology

    1994-03-04

    Consider- Dodd. ations, C.FooM Neal, J. Wethers . 22 Detection of HIV-2 Antibodies in Saliva, 16 Blind Proficiency Studies for T-Lympho- Lindsay Hofman...Eluates of Dried Blood Spots, Neal, M., Timothy Granade, Barry Mitchell. Wethers , J. 29 KIV-l EUSA System Enhancements to 38 Evaluation of...5 Weiblein,B .............. 44 Schumacher, R.T ......... 40,44 Wethers , J ............ 15,35 Sehgal, B ................ 6 W illiams, L

  20. Significant differentiation in the apolipoprotein(a)/lipoprotein(a) trait between chimpanzees from Western and Central Africa.

    PubMed

    Noureen, Asma; Ronke, Claudius; Khalifa, Mahmoud; Halbwax, Michel; Fischer, Anne; André, Claudine; Atencia, Rebeca; Garriga, Rosa; Mugisha, Lawrence; Ceglarek, Uta; Thiery, Joachim; Utermann, Gerd; Schmidt, Konrad

    2017-09-01

    Elevated Lipoprotein(a) (Lp(a)) plasma concentrations are a risk factor for cardiovascular disease in humans, largely controlled by the LPA gene encoding apolipoprotein(a) (apo(a)). Lp(a) is composed of low-density lipoprotein (LDL) and apo(a) and restricted to Catarrhini. A variable number of kringle IV (KIV) domains in LPA lead to a size polymorphism of apo(a) that is inversely correlated with Lp(a) concentrations. Smaller apo(a) isoforms and higher Lp(a) levels in central chimpanzees (Pan troglodytes troglodytes [PTT]) compared to humans from Europe had been reported. We studied apo(a) isoforms and Lp(a) concentrations in 75 western (Pan troglodytes verus [PTV]) and 112 central chimpanzees, and 12 bonobos (Pan paniscus [PPA]), all wild born and living in sanctuaries in Sierra Leone, Republic of the Congo, and DR Congo, respectively, and 116 humans from Gabon. Lp(a) levels were severalfold higher in western than in central chimpanzees (181.0 ± 6.7 mg/dl vs. 56.5 ± 4.3 mg/dl), whereas bonobos showed intermediate levels (134.8 ± 33.4 mg/dl). Apo(a) isoform sizes differed significantly between subspecies (means 20.9 ± 2.2, 22.9 ± 4.4, and 23.8 ± 3.8 KIV repeats in PTV, PTT, and PPA, respectively). However, far higher isoform-associated Lp(a) concentrations for all isoform sizes in western chimpanzees offered the main explanation for the higher overall Lp(a) levels in this subspecies. Human Lp(a) concentrations (mean 47.9 ± 2.8 mg/dl) were similar to those in central chimpanzees despite larger isoforms (mean 27.1 ± 4.9 KIV). Lp(a) and LDL, apoB-100, and total cholesterol levels only correlated in PTV. This remarkable differentiation between chimpanzees from different African habitats and the trait's similarity in humans and chimpanzees from Central Africa poses the question of a possible impact of an environmental factor that has shaped the genetic architecture of LPA. Overall, studies on the cholesterol

  1. Supporting Command and Control (C2) of an Embarked Commander: Tunneling SIPRNet Data Across an UNCLAS Wireless LAN

    DTIC Science & Technology

    2011-09-01

    that you did to help me through this process. Your efforts and guidance truly made this a success. To SPAWAR SCTD expert Stephanie Koontz , your...ty%20and%20Safety%20Services/05– 500%20Security%20Services/5510.36A.pdf [accessed June 19, 2011]. [28] S. Koontz . “Secret client tunneling...devices - KOV-26 talon user procedures.” Unpublished survey, SPAWAR, Point Loma, CA. [29] S. Koontz . “Secret client tunneling devices - KIV-54 user

  2. Interpersonal violence and the prediction of short-term risk of repeat suicide attempt

    PubMed Central

    Haglund, Axel; Lindh, Åsa U.; Lysell, Henrik; Renberg, Ellinor Salander; Jokinen, Jussi; Waern, Margda; Runeson, Bo

    2016-01-01

    In this multi-center cohort study, suicide attempters presenting to hospital (N = 355, 63% women) were interviewed using the Karolinska Interpersonal Violence Scale (KIVS) and followed-up by medical record review. Main outcome was non-fatal or fatal repeat suicide attempt within six months. Also, repeat attempt using a violent method was used as an additional outcome in separate analyses. Data were analyzed for the total group and for men and women separately. Repeat attempts were observed within six months in 78 persons (22%) and 21 (6%) of these used a violent method. KIVS total score of 6 or more was associated with repeat suicide attempt within six months (OR = 1.81, CI 1.08–3.02) and predicted new attempts with a sensitivity of 62% and a specificity of 53%. A three-fold increase in odds ratio was observed for repeat attempt using a violent method (OR = 3.40, CI 1.22–9.49). An association between exposure to violence in adulthood and violent reattempt was seen in women (OR = 1.38, CI 1.06–1.82). The overall conclusions are that information about interpersonal violence may help predict short-term risk for repeat suicide attempt, and that structured assessment of interpersonal violence may be of value in risk assessment after attempted suicide. PMID:27841333

  3. Modern pollen assemblages and vegetational history of the moraines of the Klutlan Glacier and its surroundings, Yukon Territory, Canada*1

    NASA Astrophysics Data System (ADS)

    Birks, H. J. B.

    1980-07-01

    Modern pollen assemblages have been studied from surficial lake muds and moss polsters collected from five vegetated ice-cored moraines of the Klutlan Glacier. The youngest vegetated moraine (K-II) is characterized by high pollen values for Salix and Hedysarum, K-III by high Salix and Shepherdia canadensis and low Hedysarum and Picea, K-IV by high Betula, Salix, and Shepherdia, and K-V and the Harris Creek moraine (HCM) by high Picea. Variations are summarized by canonical variates analysis. A percentage pollen diagram from Gull Lake on the upland east of the glacier records vegetational development since the deposition of the White River volcanic ash 1220 14C yr ago. An initial species-rich treeless vegetation was replaced by birch-alder-willow shrub-tundra, and this by open Picea glauca forest similar to present vegetation around the lake. Sites on HCM show two basic stratigraphies. Triangle Lake reflects vegetational succession from Salix-Shepherdia canadensis scrub similar to that on K-III today, through open Picea woodland of K-IV type, to closed Picea forests of K-V and HCM. Heart Lake and Cotton Pond reflect vegetational development following melting of ice underlying the spruce forests of HCM. These two types are summarized by positioning the fossil spectra on the first two canonical variate axes of the modern surface spectra.

  4. CSF 5-HIAA and exposure to and expression of interpersonal violence in suicide attempters.

    PubMed

    Moberg, T; Nordström, P; Forslund, K; Kristiansson, M; Asberg, M; Jokinen, J

    2011-07-01

    Serotonin is implicated in impaired impulse control, aggression and suicidal behaviour. Low cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been found in violent suicide attempters, suicide victims and in violent offenders. CSF 5-HIAA concentrations have both genetic and environmental determinants. Childhood trauma may have an effect on central monoamine function as an adult. The aim of this study was to assess the relationship of CSF 5-HIAA and the exposure to and the expression of violence in childhood and during adult life measured with the Karolinska Interpersonal Violence Scale (KIVS). 42 medication free suicide attempters underwent lumbar puncture and were assessed with the Karolinska Interpersonal Violence Scale (KIVS) to assess history of childhood exposure to violence and lifetime expressed violent behaviour. In women, but not in men, CSF 5-HIAA showed a significant negative correlation to exposure to violence during childhood. Furthermore, suicide attempters with low CSF 5-HIAA were more prone to commit violent acts as an adult if exposed to violence as a child compared to suicide attempters with high CSF 5-HIAA. In the non-traumatized group, CSF 5-HIAA showed a significant negative correlation to expressed violent behaviour in childhood. Although central serotonergic function has important genetic determinants, exposure to childhood trauma may also affect serotonergic function. Low serotonergic function may facilitate impaired aggression control in traumatized suicide attempters. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. U. S. Naval Forces, Vietnam Monthly Historical Summary for December 1967

    DTIC Science & Technology

    1968-01-04

    Copy tot a#fU:>«.U-V (Hiat. fcrai;chf JS) GMO .-■p-Oi, ^1K) Praetor of Kaval history n,a.; .^aflxwtary ’.:•> ’:.v Appwved lot public leid...rietnajaese Army forces were leered near the coast of Qoang Trl Pro /xace, anproxlnately 70 •niles north of Danang, hile closing the beaah to iivoetigate...1) T flu n n r M T i m ÜNCCÄSSIFJED^^ UNCLASSIFIED Kivü PAm-.L raic^ -UMMARY HArrasment of a*KK - RDiiN units incraascd «% t* es« units con

  6. Perioperative epidural or intravenous ketamine does not improve the effectiveness of thoracic epidural analgesia for acute and chronic pain after thoracotomy.

    PubMed

    Tena, Beatriz; Gomar, Carmen; Rios, Jose

    2014-06-01

    Persistent postsurgical pain (PPP) after thoracotomy effect 50% to 80%. Nerve damage and central sensitization involving NDMDAr activation may play an important role. This study evaluates the efficacy of adding intravenous (IV) or epidural ketamine to thoracic epidural analgesia (TEA) after thoracotomy. Double-blind randomized study on patients undergoing thoracotomy allocated to one of the following: group Kiv (IV racemic ketamine 0.5 mg/kg preincisional +0.25 mg/kg/h for 48 h), group Kep (epidural racemic ketamine 0.5 mg/kg preincisional +0.25 mg/kg/h for 48 h), or group S (saline). Postoperative analgesia was ensured by TEA with ropivacaine and fentanyl. Pain visual analog scales (VAS), Neuropathic Pain Symptom Inventory, Catastrophizing Scale, and Quantitative Sensory Testing, measuring both the peri-incisional and distant hyperalgesia area, were conducted preoperatively and postoperatively until 6 months. Plasma ketamine levels and stability of the analgesic solutions were analyzed. A total of 104 patients were included. PPP incidence was 20% at 6 months. Pain scores on coughing were significantly lower in Kiv and Kep than in S at 24 and 72 hours, but there were no differences afterwards. There were no significant differences in pain at rest, Neuropathic Pain Symptom Inventory, and Catastrophizing Scale, or in the area of mechanical allodynia at any time. Adverse effects were mild. Plasma ketamine levels did not differ significantly between groups. Analgesic solutions were stable. Adding epidural or IV racemic ketamine to TEA after thoracotomy did not lead to any reduction in PPP or allodynia. Epidural administration produced similar plasma ketamine levels to the IV route.

  7. Prior human polyomavirus and papillomavirus infection and incident lung cancer: a nested case-control study.

    PubMed

    Colombara, Danny V; Manhart, Lisa E; Carter, Joseph J; Hawes, Stephen E; Weiss, Noel S; Hughes, James P; Barnett, Matt J; Goodman, Gary E; Smith, Jennifer S; Qiao, You-Lin; Galloway, Denise A

    2015-12-01

    To test whether infection with select human polyomaviruses (HPyV) and human papillomaviruses (HPV) is associated with incident lung cancer. We performed a nested case-control study, testing serum from the carotene and retinol efficacy trial, conducted 1985-2005, for antibodies to Merkel cell (MCV), KI (KIV), and WU (WUV) HPyVs as well as to six high-risk and two low-risk HPV types. Incident lung cancer cases (n = 200) were frequency-matched with controls (n = 200) on age, enrollment and blood draw dates, intervention arm assignment, and the number of serum freeze/thaw cycles. Sera were tested using multiplex liquid bead microarray antibody assays. We used logistic regression to assess the association between HPyV and HPV antibodies and lung cancer. There was no evidence of a positive association between levels of MCV, KIV, or WUV antibodies and incident lung cancer (p corrected >0.10 for all trend tests; odds ratio (OR) range 0.72-1.09, p corrected >0.10 for all). There was also no evidence for a positive association between HPV 16 or 18 infection and incident lung cancer (p corrected ≥0.10 for all trend tests; OR range 0.25-2.54, p > 0.05 for all OR > 1), but the number of persons with serologic evidence of these infections was small. Prior infection with any of several types of HPyV or HPV was not associated with subsequent diagnosis of lung cancer. Infection with these viruses likely does not influence a person's risk of lung cancer in Western smoking populations.

  8. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder.

    PubMed

    Tripp, Adam; Oh, Hyunjung; Guilloux, Jean-Philippe; Martinowich, Keri; Lewis, David A; Sibille, Etienne

    2012-11-01

    The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis

  9. Combining Task Execution and Background Knowledge for the Verification of Medical Guidelines

    NASA Astrophysics Data System (ADS)

    Hommersom, Arjen; Groot, Perry; Lucas, Peter; Balser, Michael; Schmitt, Jonathan

    The use of a medical guideline can be seen as the execution of computational tasks, sequentially or in parallel, in the face of patient data. It has been shown that many of such guidelines can be represented as a 'network of tasks', i.e., as a number of steps that have a specific function or goal. To investigate the quality of such guidelines we propose a formalization of criteria for good practice medicine a guideline should comply to. We use this theory in conjunction with medical background knowledge to verify the quality of a guideline dealing with diabetes mellitus type 2 using the interactive theorem prover KIV. Verification using task execution and background knowledge is a novel approach to quality checking of medical guidelines.

  10. RADIO ASTROMETRY OF THE CLOSE ACTIVE BINARY HR 5110

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abbuhl, E.; Mutel, R. L.; Lynch, C.

    2015-09-20

    The close active binary HR 5110 was observed at six epochs over 26 days using a global very long baseline interferometry array at 15.4 GHz. We used phase referencing to determine the position of the radio centroid at each epoch with an uncertainty significantly smaller than the component separation. After correcting for proper motion and parallax, we find that the centroid locations of all six epochs have barycenter separations consistent with an emission source located on the KIV secondary, and not in an interaction region between the stars or on the F primary. We used a homogeneous power-law gyrosynchrotron emissionmore » model to reproduce the observed flux densities and fractional circular polarization. The resulting ranges of mean magnetic field strength and relativistic electron densities are of the order of 10 G and 10{sup 5} cm{sup −3}, respectively, in the source region.« less

  11. Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients.

    PubMed

    Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

    2016-01-19

    Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide.

  12. Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

    PubMed

    Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

    2016-05-23

    The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients

    PubMed Central

    Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

    2016-01-01

    Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730

  14. Structure-Guided Engineering of α-Keto Acid Decarboxylase for the Production of Higher Alcohols at Elevated Temperature.

    PubMed

    Sutiono, Samuel; Carsten, Jörg; Sieber, Volker

    2018-06-28

    Branched chain keto acid decarboxylases (KDCs) are a class of enzymes that catalyze the decarboxylation of α-keto acids. It is a key enzyme for production of higher alcohols in vivo and in vitro. However, the two most active KDCs (KivD and KdcA) have only moderate thermostability (<55 °C) hindering the production of the alcohols at high temperatures. In this study, structure-guided engineering toward improved thermostability of KdcA is outlined. Several strategies such as, stabilization of the catalytic center, surface engineering, and optimization of dimer interactions were applied. With 7 point mutations, our mutant (7M.D) showed an increase of T501h by 14.8 °C without compromising its substrate specificity. 7M.D exhibited >400-fold improvement of half-life at 70 °C and >600-fold increase in process stability in the presence of 4 % isobutanol at 50 °C. 7M.D is more promising for the production of higher alcohols in thermophiles (>65 °C) as well as in cell-free applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Automatic reconstruction of the muscle architecture from the superficial layer fibres data.

    PubMed

    Kohout, Josef; Cholt, David

    2017-10-01

    Physiological cross-sectional area (PCSA) of a muscle plays a significant role in determining the force contribution of muscle fascicles to skeletal movement. This parameter is typically calculated from the lengths of muscle fibres selectively sampled from the superficial layer of the muscle. However, recent studies have found that the length of fibres in the superficial layer often differs significantly (p < 0.5) from the length of fibres in the deep layer. As a result, PCSA estimation is inaccurate. In this paper, we propose a method to automatically reconstruct fibres in the whole volume of a muscle from those selectively sampled on the superficial layer. The method performs a centripetal Catmull-Rom interpolation of the input fibres within the volume of a muscle represented by its 3D surface model, automatically distributing the fibres among multiple heads of the muscle and shortening the deep fibres to support large attachment areas with extremely acute angles. Our C++ implementation runs in a couple of seconds on commodity hardware providing realistic results for both artificial and real data sets we tested. The fibres produced by the method can be used directly to determine the personalised mechanical muscle functioning. Our implementation is publicly available for the researchers at https://mi.kiv.zcu.cz/. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Family history of suicide and exposure to interpersonal violence in childhood predict suicide in male suicide attempters.

    PubMed

    Rajalin, Mia; Hirvikoski, Tatja; Jokinen, Jussi

    2013-05-15

    Family studies, including twin and adoption designs, have shown familial transmission of suicidal behaviors. Early environmental risk factors have an important role in the etiology of suicidal behavior. The aim of the present study was to assess the impact of family history of suicide and childhood trauma on suicide risk and on severity of suicide attempt in suicide attempters. A total of 181 suicide attempters were included. Family history of suicide was assessed with the Karolinska Suicide History Interview or through patient records. Childhood trauma was assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behavior in childhood (between 6 and 14 years of age) and during adult life (15 years or older). Suicide intent was measured with the Freeman scale. Male suicide attempters with a positive family history of suicide made more serious and well planned suicide attempts and had a significantly higher suicide risk. In logistic regression, family history of suicide and exposure to interpersonal violence as a child were independent predictors of suicide in male suicide attempters. The information about family history of suicide and exposure to interpersonal violence as a child derives from the patients only. In the first part of the inclusion period the information was collected from patient records. The results of this study imply that suicides among those at biological risk might be prevented with the early recognition of environmental risks. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Formate and Nitrate Utilization in Enterobacter aerogenes for Semi-Anaerobic Production of Isobutanol.

    PubMed

    Jung, Hwi-Min; Kim, Yong Hwan; Oh, Min-Kyu

    2017-11-01

    Anaerobic bioprocessing is preferred because of its economic advantages. However, low productivity and decreased growth of the host strain have limited the use of the anaerobic process. Anaerobic respiration can be applied to anoxic processing using formate and nitrate metabolism to improve the productivity of value-added metabolites. A isobutanol-producing strains is constructed using Enterobacter aerogenes as a host strain by metabolic engineering approaches. The byproduct pathway (ldhA, budA, and pflB) is knocked out, and heterologous keto-acid decarboxylase (kivD) and alcohol dehydrogenase (adhA) are expressed along with the L-valine synthesis pathway (ilvCD and budB). The pyruvate formate-lyase mutant shows decreased growth rates when cultivated in semi-anaerobic conditions, which results in a decline in productivity. When formate and nitrate are supplied in the culture medium, the growth rates and amount of isobutanol production is restored (4.4 g L -1 , 0.23 g g -1 glucose, 0.18 g L -1  h -1 ). To determine the function of the formate and nitrate coupling reaction system, the mutant strains that could not utilize formate or nitrate is contructed. Decreased growth and productivity are observed in the nitrate reductase (narG) mutant strain. This is the first report of engineering isobutanol-producing E. aerogenes to increase strain fitness via augmentation of formate and nitrate metabolism during anaerobic cultivation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. The correlation between Salter's criteria for avascular necrosis of the femoral head and Kalamchi's prognostic classification following the treatment of developmental dysplasia of the hip.

    PubMed

    Tsukagoshi, Y; Kamegaya, M; Kamada, H; Saisu, T; Morita, M; Kakizaki, J; Tomaru, Y; Yamazaki, M

    2017-08-01

    The aim of this study was to evaluate the correlation between Salter's criteria and Kalamchi's classification of avascular necrosis in patients treated for developmental dysphasia of the hip (DDH). The study involved a retrospective analysis of 123 patients (123 hips) with DDH treated by operative and non-operative reduction before the age of two years, with a minimum follow-up of ten years. Salter's criteria (S1 to S4) were determined from radiographs obtained at one to two years post-reduction, whilst the Kalamchi grade was determined from radiographs obtained at ten or more years of age. Early post-reduction radiographs were also used to evaluate the centre-head distance discrepancy (CHDD) and the occurrence of a dome-shaped deformity of the proximal femoral metaphysis (D-shaped metaphysis). The prognosis was described as good (Kalamchi grade K0 or KI), fair (Kalamchi grade KII) or poor (Kalamchi grade KIII or KIV) for analysis and correlation with the early Salter criteria, CHDD and D-shaped metaphysis. S1 and S2 criteria were predictive of a poor prognosis. The outcome following S3, S4 and S3 + S4 varied; 18 (40%) had a good prognosis, 17 (38%) a fair prognosis and ten (22%) a poor prognosis. A CHDD ≥ 10% and a D-shaped metaphysis were also predictive of a poor prognosis. The Salter criteria were predictive of the Kalamchi grade of avascular necrosis in patients with DDH aged ten or more years after reduction of the hip. Cite this article: Bone Joint J 2017;99-B:1115-20. ©2017 The British Editorial Society of Bone & Joint Surgery.

  19. Optimal filter parameters for low SNR seismograms as a function of station and event location

    NASA Astrophysics Data System (ADS)

    Leach, Richard R.; Dowla, Farid U.; Schultz, Craig A.

    1999-06-01

    Global seismic monitoring requires deployment of seismic sensors worldwide, in many areas that have not been studied or have few useable recordings. Using events with lower signal-to-noise ratios (SNR) would increase the amount of data from these regions. Lower SNR events can add significant numbers to data sets, but recordings of these events must be carefully filtered. For a given region, conventional methods of filter selection can be quite subjective and may require intensive analysis of many events. To reduce this laborious process, we have developed an automated method to provide optimal filters for low SNR regional or teleseismic events. As seismic signals are often localized in frequency and time with distinct time-frequency characteristics, our method is based on the decomposition of a time series into a set of subsignals, each representing a band with f/Δ f constant (constant Q). The SNR is calculated on the pre-event noise and signal window. The band pass signals with high SNR are used to indicate the cutoff filter limits for the optimized filter. Results indicate a significant improvement in SNR, particularly for low SNR events. The method provides an optimum filter which can be immediately applied to unknown regions. The filtered signals are used to map the seismic frequency response of a region and may provide improvements in travel-time picking, azimuth estimation, regional characterization, and event detection. For example, when an event is detected and a preliminary location is determined, the computer could automatically select optimal filter bands for data from non-reporting stations. Results are shown for a set of low SNR events as well as 379 regional and teleseismic events recorded at stations ABKT, KIV, and ANTO in the Middle East.

  20. Geophysical imaging of karst features in Missouri

    NASA Astrophysics Data System (ADS)

    Obi, Jeremiah Chukwunonso

    Automated electrical resistivity tomography (ERT) supported with multichannel analysis of surface waves (MASW) and boring data were used to map karst related features in Missouri in order to understand karst processes better in Missouri. Previous works on karst in Missouri were mostly surficial mapping of bedrock outcrops and joints, which are not enough to define the internal structure of karst system, since most critical processes in karst occur underground. To understand these processes better, the density, placement and pattern of karst related features like solution-widened joints and voids, as well as top of bedrock were mapped. In the course of the study, six study sites were visited in Missouri. The sites were in Nixa, Gasconade River Bridge in Lebanon, Battlefield, Aurora, Protem and Richland. The case studies reflect to a large extent some of the problems inherent in karst terrain, ranging from environmental problems to structural problems especially sinkhole collapses. The result of the study showed that karst in Missouri is mostly formed as a result of piping of sediments through solution-widened joints, with a pattern showing that the joints/fractures are mostly filled with moist clay-sized materials of low resistivity values. The highest density of mapped solution-widened joints was one in every one hundred and fifty feet, and these areas are where intense dissolution is taking place, and bedrock pervasively fractured. The study also showed that interpreted solution-widened joints trend in different directions, and often times conform with known structural lineaments in the area. About 40% of sinkhole collapses in the study areas are anthropogenic. Karst in Missouri varies, and can be classified as a combination of kI (juvenile), kIII (mature) and kIV (complex) karsts.

  1. Determination of branched chain amino acids, methionine, phenylalanine, tyrosine and alpha-keto acids in plasma and dried blood samples using HPLC with fluorescence detection.

    PubMed

    Kand'ár, Roman; Záková, Pavla; Jirosová, Jana; Sladká, Michaela

    2009-01-01

    The determination of branched chain amino acids [BCAA; valine (Val), leucine (Leu), isoleucine (Ile)], alpha-keto acids derived from BCAA [BCKA; alpha-ketoisovaleric acid (KIV), alpha-ketoisocaproic acid (KIC), alpha-ketomethylvaleric acid (KMV)], methionine (Met), phenylalanine (Phe) and tyrosine (Tyr) is currently the most reliable approach for the diagnosis of maple syrup urine disease (MSUD), hypermethioninemia, phenylketonuria (PKU) and tyrosinemia. The aim of this study was to develop rapid and simple HPLC methods for measurement of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples. Samples of peripheral venous blood with EDTA as anticoagulant were obtained from a group of healthy blood donors (n=70, 35 females, 27-41 years of age and 35 males, 28-43 years of age). Blood-spot samples from a group of newborns (n=80, 40 girls and 40 boys 3-5 days of age) were collected onto #903 Specimen Collection Paper and allowed to dry for at least 24 h before analysis. Prior to separation, the amino acids (AA) were derivatized with o-phthaldialdehyde (OPA) and BCKA with o-phenylenediamine (OPD). Reverse phase column chromatography (LiChroCart 125-4 Purospher RP-18e, 5 microm) was used for separation and fluorescence detection used to monitoring of effluent. For AA analysis, 25 mmol/L sodium hydrogenphosphate-methanol (90:10, v/v), pH 6.5+/-0.1 was used as mobile phase A and 100% methanol was used as mobile phase B. Measurement of BCKA used a mixture of methanol and deionized water (55:45, v/v) as mobile phase A and mobile phase B consisted of 100% methanol. Analytical performance of these methods was satisfactory for the determination of all AA and BCKA. The intra-assay and inter-assay coefficients of variation were below 10% and recovery ranged from 90%-110%. We have developed simple, rapid and selective HPLC methods with fluorescence detection for the determination of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples.

  2. Characterization of recombinantly expressed dihydroxy-acid dehydratase from Sulfobus solfataricus-A key enzyme for the conversion of carbohydrates into chemicals.

    PubMed

    Carsten, Jörg M; Schmidt, Anja; Sieber, Volker

    2015-10-10

    Dihydroxyacid dehydratases (DHADs) are excellent biocatalysts for the defunctionalization of biomass. Here, we report on the recombinant production of DHAD from Sulfolobus solfataricus (SsDHAD) in E. coli and its characterization with special focus on activity toward non-natural substrates, thermo-stability, thermo-inactivation kinetics and activation capabilities and its application within multi-step cascades for chemicals production. Using a simple heat treatment of cell lysate as major purification step we achieved a specific activity of 4.4 units per gram cell mass toward the substrate d-gluconate. The optimal temperature and pH value for this reaction are 77°C and pH 6.2. The inhibitory concentration (IC50, 50% residual activity) of different alcohols was determined to be 15% (v/v) for ethanol, 4.5% (v/v) for butanol and 4% (v/v) for isobutanol. Besides d-gluconate and the natural substrate 2,3-dihydroxyisovalerate (DHIV) SsDHAD is able to convert the C3-sugar-acid d-glycerate to pyruvate, a reaction, which does not occur in natural metabolic pathways, with a specific activity of 10.7±0.4mU/mg. The specific activity of the enzyme can be increased 3-fold by incubation with 2-mercaptoethanol. The activation has no impact on temperature dependence, but modulates the thermo-inactivation tolerance at 50°C. The total turnover numbers for all of the three reactions was found to be 35.5×10(3)±1.0×10(3) for the conversion of d-gluconate to 2-keto-3-deoxygluconate (KDG), 28.2×10(3)±0.8×10(3) for DHIV to 2-ketovalerate (KIV) and 943±0.28×10(2) for d-glycerate to pyruvate. With activated SsDHAD these values could be further increased 5- and 4-fold for the d-gluconate and d-glycerate conversion, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Crustal and uppermost mantle structure in the Middle East: assessing constraints provided by jointly modelling Ps and Sp receiver functions and Rayleigh wave group velocity dispersion curves

    NASA Astrophysics Data System (ADS)

    Agrawal, Mohit; Pulliam, Jay; Sen, Mrinal K.; Dutta, Utpal; Pasyanos, Michael E.; Mellors, Robert

    2015-05-01

    Seismic velocity models are found, along with uncertainty estimates, for 11 sites in the Middle East by jointly modelling Ps and Sp receiver functions and surface (Rayleigh) wave group velocity dispersion. The approach performs a search for models that satisfy goodness-of-fit criteria guided by a variant of simulated annealing and uses statistical tools to assess these products of searches. These tools, a parameter correlation matrix and marginal posterior probability density (PPD) function, allow us to evaluate quantitatively the constraints that each data type imposes on model parameters and to identify portions of each model that are well-constrained relative to other portions. This joint modelling technique, which we call `multi-objective optimization for seismology', does not require a good starting solution, although such a model can be incorporated easily, if available, and can reduce the computation time significantly. Applying the process described above to broadband seismic data reveals that crustal thickness varies from 15 km beneath Djibouti (station ATD) to 45 km beneath Saudi Arabia (station RAYN). A pronounced low velocity zone for both Vp and Vs is present at a depth of ˜12 km beneath station KIV located in northern part of greater Caucasus, which may be due to the presence of a relatively young volcano. Similarly, we also noticed a 6-km-thick low velocity zone for Vp beginning at 20 km depth beneath seismic station AGIN, on the Anatolian plateau, while positive velocity gradients prevail elsewhere in eastern Turkey. Beneath station CSS, located in Cyprus, an anomalously slow layer is found in the uppermost mantle, which may indicate the presence of altered lithospheric material. Crustal P- and S-wave velocities beneath station D2, located in the northeastern portion of central Zagros, range between 5.2-6.2 and 3.2-3.8 km s-1, respectively. In Oman, we find a Moho depth of 34.0 ± 1.0 km and 25.0 ± 1.0 to 30.0 ± 1.0 km beneath stations S02 and S

  4. Strategies towards advanced ion track-based biosensors

    NASA Astrophysics Data System (ADS)

    Alfonta, L.; Bukelman, O.; Chandra, A.; Fahrner, W. R.; Fink, D.; Fuks, D.; Golovanov, V.; Hnatowicz, V.; Hoppe, K.; Kiv, A.; Klinkovich, I.; Landau, M.; Morante, J. R.; Tkachenko, N. V.; Vacík, J.; Valden, M.

    Three approaches towards ion track-based biosensors appear to be feasible. The development of the first one began a decade ago [Siwy, Z.; Trofin, L.; Kohl, P.; Baker, L.A.; Martin, C.R.; Trautmann, C. J. Am. Chem. Soc. 2005, 127, 5000-5001; Siwy, Z.S.; Harrell, C.C.; Heins, E.; Martin, C.R.; Schiedt, B.; Trautmann, C.; Trofin, L.; Polman, A. Presented at the 6th International Conference on Swift Heavy Ions in Matter, Aschaffenburg, Germany, May 28-31, 2005] and makes use of the concept that the presence of certain biomolecules within liquids can block the passage through narrow pores if being captured there, thus switching off the pore's electrical conductivity. The second, having been successfully tested half a year ago [Fink, D.; Klinkovich, I.; Bukelman, O.; Marks, R.S.; Fahrner, W.; Kiv, A.; Fuks, D.; Alfonta, L. Biosens. Bioelectron. 2009, 24, 2702-2706], is based on the accumulation of enzymatic reaction products within the confined volume of narrow etched ion tracks which modifies the pore's electrical conductivity. The third and most elegant, at present under development, will exploit the charge transfer from enzymes to semiconductors embedded within etched tracks, enabling the enzymes undergoing specific reactions with the biomolecules to be detected. These strategies can be realized either within carrier-free nanoporous polymeric membranes embedded in the corresponding bioliquids, or within contacted nanoporous insulating layers on semiconducting substrates, the so-called TEMPOS structures [Fink, D.; Petrov, A.; Hoppe, H.; Fahrner, W.R.; Papaleo, R.M.; Berdinsky, A.; Chandra, A.; Biswas, A.; Chadderton, L.T. Nucl. Instrum. Methods B 2004, 218, 355-361]. The latter have the advantage of exhibiting a number of peculiar electronic properties, such as the ability for logic and/or combination of input signals, tunable polarity, negative differential resistances, tunability by external parameters such as light, magnetic fields, etc. and self-pulsations, which

  5. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population.

    PubMed

    Kamstrup, Pia R; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2014-02-11

    The purpose of this study was to determine whether elevated lipoprotein(a) levels and corresponding LPA risk genotypes (rs10455872, rs3798220, kringle IV type 2 repeat polymorphism) prospectively associate with increased risk of aortic valve stenosis (AVS). The etiologic basis of AVS is unclear. Recent data implicate an LPA genetic variant (rs10455872), associated with Lp(a) levels, in calcific AVS. We combined data from 2 prospective general population studies, the Copenhagen City Heart Study (1991 to 2011; n = 10,803) and the Copenhagen General Population Study (2003 to 2011; n = 66,877), following up 77,680 Danish participants for as long as 20 years, during which time 454 were diagnosed with AVS. We conducted observational and genetic instrumental variable analyses in a Mendelian randomization study design. Elevated Lp(a) levels were associated with multivariable adjusted hazard ratios for AVS of 1.2 (95% confidence interval [CI]: 0.8 to 1.7) for 22nd to 66th percentile levels (5 to 19 mg/dl), 1.6 (95% CI: 1.1 to 2.4) for 67th to 89th percentile levels (20 to 64 mg/dl), 2.0 (95% CI: 1.2 to 3.4) for 90th to 95th percentile levels (65 to 90 mg/dl), and 2.9 (95% CI: 1.8 to 4.9) for levels greater than 95th percentile (>90 mg/dl), versus levels less than the 22nd percentile (<5 mg/dl; trend, p < 0.001). Lp(a) levels were elevated among carriers of rs10455872 and rs3798220 minor alleles, and of low number of KIV-2 repeats (trend, all p < 0.001). Combining all genotypes, instrumental variable analysis yielded a genetic relative risk for AVS of 1.6 (95% CI: 1.2 to 2.1) for a 10-fold Lp(a) increase, comparable to the observational hazard ratio of 1.4 (95% CI: 1.2 to 1.7) for a 10-fold increase in Lp(a) plasma levels. Elevated Lp(a) levels and corresponding genotypes were associated with increased risk of AVS in the general population, with levels >90 mg/dl predicting a threefold increased risk. Copyright © 2014 American College of Cardiology Foundation. Published

  6. Mechanism of Ca2+-influx and Ca2+/calmodulin-dependent protein kinase IV activity during in utero hypoxia in cerebral cortical neuronal nuclei of the guinea pig fetus at term.

    PubMed

    Vibert, Yanick M; Ashraf, Qazi M; Mishra, Om P; Delivoria-Papadopoulos, Maria

    2008-08-08

    Previously we showed that following hypoxia there is an increase in nuclear Ca(2+)-influx and Ca(2+)/calmodulin-dependent protein kinase IV activity (CaMK IV) in the cerebral cortex of term guinea pig fetus. The present study tests the hypothesis that clonidine administration will prevent hypoxia-induced increased neuronal nuclear Ca(2+)-influx and increased CaMK IV activity, by blocking high-affinity Ca(2+)-ATPase. Studies were conducted in 18 pregnant guinea pigs at term, normoxia (Nx, n=6), hypoxia (Hx, n=6) and clonidine with Hx (Hx+Clo, n=6). The pregnant guinea pig was exposed to a decreased FiO(2) of 0.07 for 60 min. Clonidine, an imidazoline inhibitor of high-affinity Ca(2+)-ATPase, was administered 12.5 microg/kg IP 30 min prior to hypoxia. Hypoxia was determined biochemically by ATP and phosphocreatine (PCr) levels. Nuclei were isolated and ATP-dependent (45)Ca(2+)-influx was determined. CaMK IV activity was determined by (33)P-incorporation into syntide 2 for 2 min at 37 degrees C in a medium containing 50mM HEPES (pH 7.5), 2mM DTT, 40muM syntide 2, 0.2mM (33)P-ATP, 10mM magnesium acetate, 5 microM PKI 5-24, 2 microM PKC 19-36 inhibitor peptides, 1 microM microcystine LR, 200 microM sodium orthovanadate and either 1mM EGTA (for CaMK IV-independent activity) or 0.8mM CaCl(2) and 1mM calmodulin (for total activity). ATP (mumoles/gbrain) values were significantly different in the Nx (4.62+/-0.2), Hx (1.65+/-0.2, p<0.05 vs. Nx), and Hx+Clo (1.92+/-0.6, p<0.05 vs. Nx). PCr (mumoles/g brain) values in the Nx (3.9+/-0.1), Hx (1.10+/-0.3, p<0.05 vs. Nx), and Hx+Clo (1.14+/-0.3, p<0.05 vs. Nx). There was a significant difference between nuclear Ca(2+)-influx (pmoles/mg protein/min) in Nx (3.98+/-0.4), Hx (10.38+/-0.7, p<0.05 vs. Nx), and Hx+Clo (7.35+/-0.9, p<0.05 vs. Nx, p<0.05 vs. Hx), and CaM KIV (pmoles/mg protein/min) in Nx (1314.00+/-195.4), Hx (2315.14+/-148.5, p<0.05 vs. Nx), and Hx+Clo (1686.75+/-154.3, p<0.05 vs. Nx, p<0.05 vs. Hx). We conclude that the