Virulence characterization of Campylobacter jejuni isolated from resident wild birds in Tokachi area, Japan.

PubMed

Shyaka, Anselme; Kusumoto, Akiko; Chaisowwong, Warangkhana; Okouchi, Yoshiki; Fukumoto, Shinya; Yoshimura, Aya; Kawamoto, Keiko

2015-08-01

The prevalence of Campylobacter jejuni in wild birds is a potential hazard for human and animal health. The aim of this study was to establish the prevalence of C. jejuni in wild birds in Tokachi area, Hokkaido, Japan and investigate their virulence in vitro. In total, 173 cloacal swabs from individual wild birds were collected for the detection of Campylobacter spp. Thirty four samples (19.7%) were positive for Campylobacter of which 94.1% (32/34 samples) were C. jejuni. Additionally, one C. coli and one C. fetus were isolated. Seven C. jejuni isolates (one from crows and the other from pigeons) had important virulence genes including all three CDT genes (cdtA, cdtB and cdtC) and flaA, flaB, ciaB and cadF, and the other isolates were lacking cdtA gene. Further studies on in vitro virulence-associated phenotypes, such as motility assay on soft agar and invasion assay in Caco-2 cells, were performed. The wild bird C. jejuni isolates adhered and invaded human cells. Although the numbers of viable intracellular bacteria of wild bird isolates were lower than a type strain NCTC11168, they persisted at 48-hr and underwent replication in host cells.

Virulence characterization of Campylobacter jejuni isolated from resident wild birds in Tokachi area, Japan

PubMed Central

SHYAKA, Anselme; KUSUMOTO, Akiko; CHAISOWWONG, Warangkhana; OKOUCHI, Yoshiki; FUKUMOTO, Shinya; YOSHIMURA, Aya; KAWAMOTO, Keiko

2015-01-01

The prevalence of Campylobacter jejuni in wild birds is a potential hazard for human and animal health. The aim of this study was to establish the prevalence of C. jejuni in wild birds in Tokachi area, Hokkaido, Japan and investigate their virulence in vitro. In total, 173 cloacal swabs from individual wild birds were collected for the detection of Campylobacter spp. Thirty four samples (19.7%) were positive for Campylobacter of which 94.1% (32/34 samples) were C. jejuni. Additionally, one C. coli and one C. fetus were isolated. Seven C. jejuni isolates (one from crows and the other from pigeons) had important virulence genes including all three CDT genes (cdtA, cdtB and cdtC) and flaA, flaB, ciaB and cadF, and the other isolates were lacking cdtA gene. Further studies on in vitro virulence-associated phenotypes, such as motility assay on soft agar and invasion assay in Caco-2 cells, were performed. The wild bird C. jejuni isolates adhered and invaded human cells. Although the numbers of viable intracellular bacteria of wild bird isolates were lower than a type strain NCTC11168, they persisted at 48-hr and underwent replication in host cells. PMID:25843040

Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins

PubMed Central

Tamilselvam, Batcha; Spiegelman, Lindsey M.; Son, Sophia B.; Eshraghi, Aria; Blanke, Steven R.; Bradley, Kenneth A.

2015-01-01

Cytolethal distending toxins (CDTs) are heterotrimeric protein exotoxins produced by a diverse array of Gram-negative pathogens. The enzymatic subunit, CdtB, possesses DNase and phosphatidylinositol 3-4-5 trisphosphate phosphatase activities that induce host cell cycle arrest, cellular distension and apoptosis. To exert cyclomodulatory and cytotoxic effects CDTs must be taken up from the host cell surface and transported intracellularly in a manner that ultimately results in localization of CdtB to the nucleus. However, the molecular details and mechanism by which CDTs bind to host cells and exploit existing uptake and transport pathways to gain access to the nucleus are poorly understood. Here, we report that CdtA and CdtC subunits of CDTs derived from Haemophilus ducreyi (Hd-CDT) and enteropathogenic E. coli (Ec-CDT) are independently sufficient to support intoxication by their respective CdtB subunits. CdtA supported CdtB-mediated killing of T-cells and epithelial cells that was nearly as efficient as that observed with holotoxin. In contrast, the efficiency by which CdtC supported intoxication was dependent on the source of the toxin as well as the target cell type. Further, CdtC was found to alter the subcellular trafficking of Ec-CDT as determined by sensitivity to EGA, an inhibitor of endosomal trafficking, colocalization with markers of early and late endosomes, and the kinetics of DNA damage response. Finally, host cellular cholesterol was found to influence sensitivity to intoxication mediated by Ec-CdtA, revealing a role for cholesterol or cholesterol-rich membrane domains in intoxication mediated by this subunit. In summary, data presented here support a model in which CdtA and CdtC each bind distinct receptors on host cell surfaces that direct alternate intracellular uptake and/or trafficking pathways. PMID:26618479

Coenzyme Q10 as a potent compound that inhibits Cdt1-geminin interaction.

PubMed

Mizushina, Yoshiyuki; Takeuchi, Toshifumi; Takakusagi, Yoichi; Yonezawa, Yuko; Mizuno, Takeshi; Yanagi, Ken-Ichiro; Imamoto, Naoko; Sugawara, Fumio; Sakaguchi, Kengo; Yoshida, Hiromi; Fujita, Masatoshi

2008-02-01

A human replication initiation protein Cdt1 is a very central player in the cell cycle regulation of DNA replication, and geminin down-regulates Cdt1 function by directly binding to it. It has been demonstrated that Cdt1 hyperfunction resulting from Cdt1-geminin imbalance, for example by geminin silencing with siRNA, induces DNA re-replication and eventual cell death in some cancer-derived cell lines. In the present study, we first established a high throughput screening system based on modified ELISA (enzyme linked immunosorbent assay) to identify compounds that interfere with human Cdt1-geminin binding. Using this system, we found that coenzyme Q(10) (CoQ(10)) can inhibit Cdt1-geminin interaction in vitro. CoQ compound is an isoprenoid quinine that functions as an electron carrier in the mitochondrial respiratory chain in eukaryotes. CoQ(10), having a longer isoprenoid chain, was the strongest inhibitor of Cdt1-geminin binding in the tested CoQs, with 50% inhibition observed at concentrations of 16.2 muM. Surface plasmon resonance analysis demonstrated that CoQ(10) bound selectively to Cdt1, but did not interact with geminin. Moreover, CoQ(10) had no influence on the interaction between Cdt1 and mini-chromosome maintenance (MCM)4/6/7 complexes. These results suggested that CoQ(10) inhibits Cdt1-geminin complex formation by binding to Cdt1 and thereby could liberate Cdt1 from inhibition by geminin. Using three-dimensional computer modeling analysis, CoQ(10) was considered to interact with the geminin interaction interface on Cdt1, and was assumed to make hydrogen bonds with the residue of Arg243 of Cdt1. CoQ(10) could prevent the growth of human cancer cells, although only at high concentrations, and it remains unclear whether such an inhibitory effect is associated with the interference with Cdt1-geminin binding. The application of inhibitors for the formation of Cdt1-geminin complex is discussed.

Haemophilus parasuis encodes two functional cytolethal distending toxins: CdtC contains an atypical cholesterol recognition/interaction region.

PubMed

Zhou, Mingguang; Zhang, Qiang; Zhao, Jianping; Jin, Meilin

2012-01-01

Haemophilus parasuis is the causative agent of Glässer's disease of pigs, a disease associated with fibrinous polyserositis, polyarthritis and meningitis. We report here H. parasuis encodes two copies of cytolethal distending toxins (Cdts), which these two Cdts showed the uniform toxin activity in vitro. We demonstrate that three Cdt peptides can form an active tripartite holotoxin that exhibits maximum cellular toxicity, and CdtA and CdtB form a more active toxin than CdtB and CdtC. Moreover, the cellular toxicity is associated with the binding of Cdt subunits to cells. Further analysis indicates that CdtC subunit contains an atypical cholesterol recognition/interaction amino acid consensus (CRAC) region. The mutation of CRAC site resulted in decreased cell toxicity. Finally, western blot analysis show all the 15 H. parasuis reference strains and 109 clinical isolates expressed CdtB subunit, indicating that Cdt is a conservative putative virulence factor for H. parasuis. This is the first report of the molecular and cellular basis of Cdt host interactions in H. parasuis.

Mismatch repair proteins recruited to ultraviolet light-damaged sites lead to degradation of licensing factor Cdt1 in the G1 phase.

PubMed

Tanaka, Miyuki; Takahara, Michiyo; Nukina, Kohei; Hayashi, Akiyo; Sakai, Wataru; Sugasawa, Kaoru; Shiomi, Yasushi; Nishitani, Hideo

2017-04-03

Cdt1 is rapidly degraded by CRL4 Cdt2 E3 ubiquitin ligase after UV (UV) irradiation. Previous reports revealed that the nucleotide excision repair (NER) pathway is responsible for the rapid Cdt1-proteolysis. Here, we show that mismatch repair (MMR) proteins are also involved in the degradation of Cdt1 after UV irradiation in the G1 phase. First, compared with the rapid (within ∼15 min) degradation of Cdt1 in normal fibroblasts, Cdt1 remained stable for ∼30 min in NER-deficient XP-A cells, but was degraded within ∼60 min. The delayed degradation was also dependent on PCNA and CRL4 Cdt2 . The MMR proteins Msh2 and Msh6 were recruited to the UV-damaged sites of XP-A cells in the G1 phase. Depletion of these factors with small interfering RNAs prevented Cdt1 degradation in XP-A cells. Similar to the findings in XP-A cells, depletion of XPA delayed Cdt1 degradation in normal fibroblasts and U2OS cells, and co-depletion of Msh6 further prevented Cdt1 degradation. Furthermore, depletion of Msh6 alone delayed Cdt1 degradation in both cell types. When Cdt1 degradation was attenuated by high Cdt1 expression, repair synthesis at the damaged sites was inhibited. Our findings demonstrate that UV irradiation induces multiple repair pathways that activate CRL4 Cdt2 to degrade its target proteins in the G1 phase of the cell cycle, leading to efficient repair of DNA damage.

Evidence of a Critical Role for Cellodextrin Transporte 2 (CDT-2) in Both Cellulose and Hemicellulose Degradation and Utilization in Neurospora crassa

PubMed Central

Cai, Pengli; Gu, Ruimeng; Wang, Bang; Li, Jingen; Wan, Li; Tian, Chaoguang; Ma, Yanhe

2014-01-01

CDT-1 and CDT-2 are two cellodextrin transporters discovered in the filamentous fungus Neurospora crassa. Previous studies focused on characterizing the role of these transporters in only a few conditions, including cellulose degradation, and the function of these two transporters is not yet completely understood. In this study, we show that deletion of cdt-2, but not cdt-1, results in growth defects not only on Avicel but also on xylan. cdt-2 can be highly induced by xylan, and this mutant has a xylodextrin consumption defect. Transcriptomic analysis of the cdt-2 deletion strain on Avicel and xylan showed that major cellulase and hemicellulase genes were significantly down-regulated in the cdt-2 deletion strain and artificial over expression of cdt-2 in N. crassa increased cellulase and hemicellulase production. Together, these data clearly show that CDT-2 plays a critical role in hemicellulose sensing and utilization. This is the first time a sugar transporter has been assigned a function in the hemicellulose degradation pathway. Furthermore, we found that the transcription factor XLR-1 is the major regulator of cdt-2, while cdt-1 is primarily regulated by CLR-1. These results deepen our understanding of the functions of both cellodextrin transporters, particularly for CDT-2. Our study also provides novel insight into the mechanisms for hemicellulose sensing and utilization in N. crassa, and may be applicable to other cellulolytic filamentous fungi. PMID:24586693

The Alcohol Use Disorders Identification Test and carbohydrate-deficient transferrin in alcohol-related sickness absence.

PubMed

Hermansson, Ulric; Helander, Anders; Brandt, Lena; Huss, Anders; Rönnberg, Sten

2002-01-01

Previous studies have shown that elevated, risky levels of alcohol consumption may lead to higher rates of sickness absence. However, no studies have examined the Alcohol Use Disorders Identification Test (AUDIT) or serum carbohydrate-deficient transferrin (CDT) in relation to sickness absence in the workplace. The purpose of this study was to examine the relationship between sick-days, 12 months before screening, and the AUDIT and CDT (CDTect kit). Serum gamma-glutamyltransferase also was used for comparison. The study was carried out over 36 months in a large workplace and formed part of an ongoing controlled study. In conjunction with a routine health examination, employees were offered the opportunity to undergo an alcohol screening. Absence data were obtained from the company payroll system, and sickness absence was analyzed by using a three-ordinal level cumulative logistic model on the number of sick-days. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Of the 989 subjects who participated in the study, 193 (19.5%) screened positive in relation to either the AUDIT (>or=8 points) or CDT (<20 units/liter for men, and <27 units/liter for women), or both. Employees who screened positive with the AUDIT had a significantly higher proportion of sick-days (p = 0.047) compared with those who screened negative (OR = 1.4, CI 1.0-1.9). Neither long, continuous periods of sickness absence nor absence on Mondays or Fridays gave a clear indication of individuals who screened positive on the AUDIT or CDT test. Our data indicate that individuals with moderately elevated or risky levels of alcohol consumption show an increase in sick-days. Accordingly, workplaces have a good reason for using a more systematic approach to alcohol screening in routine workplace health examinations.

Automated measurement of carbohydrate-deficient transferrin using the Bio-Rad %CDT by the HPLC test on a Variant HPLC system: evaluation and comparison with other routine procedures.

PubMed

Schellenberg, François; Mennetrey, Louise; Girre, Catherine; Nalpas, Bertrand; Pagès, Jean Christophe

2008-01-01

In this study, we evaluated the new %CDT by the HPLC method (Bio-Rad, Germany) on a Varianttrade mark HPLC system (Bio-Rad), checked the correlation with well-known methods and calculated the diagnostic value of the test. Intra-run and day-to-day precision values were calculated for samples with extreme serum transferrin concentrations, high trisialotransferrin and interfering conditions (haemolysed, lactescent and icteric samples). The method was compared with two routine procedures, the %CDT TIA (Bio-Rad, Hercules, CA, USA) and the Capillarystrade mark CDT (Sebia, France). A total of 350 clinical sera samples were used for a case-control study. Precision values were better in high CDT and medium CDT pools than in low CDT pools. The serum transferrin concentration had no effect on CDT measurement, except in samples with serum transferrin <1 g/L. Haemolysis was the only interfering situation. The method showed high correlation (r(2) > 0.95) with the two other methods (%CDT TIA and CZE %CDT). The global predictive value of the test was >0.90 at 1.9% cut-off. These results demonstrate that the %CDT by the HPLC test is suitable for CDT routine measurement; the results from the high-throughput Varianttrade mark system are well correlated with other methods and are of high diagnostic value.

The caenorhabditis elegans CDT-2 ubiquitin ligase is required for attenuation of EGFR signalling in vulva precursor cells

PubMed Central

2010-01-01

Background Attenuation of the EGFR (Epidermal Growth Factor Receptor) signalling cascade is crucial to control cell fate during development. A candidate-based RNAi approach in C. elegans identified CDT-2 as an attenuator of LET-23 (EGFR) signalling. Human CDT2 is a component of the conserved CDT2/CUL4/DDB1 ubiquitin ligase complex that plays a critical role in DNA replication and G2/M checkpoint. Within this complex, CDT2 is responsible for substrate recognition. This ubiquitin ligase complex has been shown in various organisms, including C. elegans, to target the replication-licensing factor CDT1, and the CDK inhibitor p21. However, no previous link to EGFR signalling has been identified. Results We have characterised CDT-2's role during vulva development and found that it is a novel attenuator of LET-23 signalling. CDT-2 acts redundantly with negative modulators of LET-23 signalling and CDT-2 or CUL-4 downregulation causes persistent expression of the egl-17::cfp transgene, a marker of LET-23 signalling during vulva development. In addition, we show that CDT-2 physically interacts with SEM-5 (GRB2), a known negative modulator of LET-23 signalling that directly binds LET-23, and provide genetic evidence consistent with CDT-2 functioning at or downstream of LET-23. Interestingly, both SEM-5 and CDT-2 were identified independently in a screen for genes involved in receptor-mediated endocytosis in oocytes, suggesting that attenuation of LET-23 by CDT-2 might be through regulation of endocytosis. Conclusions In this study, we have shown that CDT-2 and CUL-4, members of the CUL-4/DDB-1/CDT-2 E3 ubiquitin ligase complex attenuate LET-23 signalling in vulval precursor cells. In future, it will be interesting to investigate the potential link to endocytosis and to determine whether other signalling pathways dependent on endocytosis, e.g. LIN-12 (Notch) could be regulated by this ubiquitin ligase complex. This work has uncovered a novel function for the CUL-4/DDB-1/CDT-2 E3 ligase that may be relevant for its mammalian oncogenic activity. PMID:20977703

Standardization of the capillary electrophoresis procedures Capillarys® CDT and Minicap® CDT in comparison to the IFCC reference measurement procedure.

PubMed

Schellenberg, François; Humeau, Camille

2017-06-01

CDT is at present the most relevant routinely available biological marker of alcohol use and is widely used for screening and monitoring of patients. The lack of standardization leads to specific reference intervals for each procedure. The IFCC working group devoted to CDT demonstrated that the standardization is possible using calibrators assigned to the reference measurement procedure. In this study, we compare the capillary electrophoresis (CE) techniques Capillarys® CDT and Minicap® CDT (Sebia, Lisses, France) to the reference procedure before and after standardization in 126 samples covering the range of CDT measurement. Both capillary electrophoresis procedures show a high correlation (r=0,997) with the reference procedure and the concordance correlation coefficient evaluated according to Mc Bride is "almost perfect" (>0.997 for both CE procedures). The number of results with a relative difference higher than the acceptable difference limit is only 1 for Capillarys® CDT and 5 for Minicap® CDT. These results demonstrate the efficiency of the standardization of CDT measurements for both CE techniques from Sebia, achieved using calibrators assigned to the reference measurement procedure.

IFCC approved HPLC reference measurement procedure for the alcohol consumption biomarker carbohydrate-deficient transferrin (CDT): Its validation and use.

PubMed

Schellenberg, François; Wielders, Jos; Anton, Raymond; Bianchi, Vincenza; Deenmamode, Jean; Weykamp, Cas; Whitfield, John; Jeppsson, Jan-Olof; Helander, Anders

2017-02-01

Carbohydrate-deficient transferrin (CDT) is used as a biomarker of sustained high alcohol consumption. The currently available measurement procedures for CDT are based on various analytical techniques (HPLC, capillary electrophoresis, nephelometry), some differing in the definition of the analyte and using different reference intervals and cut-off values. The Working Group on Standardization of CDT (WG-CDT), initiated by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), has validated an HPLC candidate reference measurement procedure (cRMP) for CDT (% disialotransferrin to total transferrin based on peak areas), demonstrating that it is suitable as a reference measurement procedure (RMP) for CDT. Presented is a detailed description of the cRMP and its calibration. Practical aspects on how to treat genetic variant and so-called di-tri bridge samples are described. Results of method performance characteristics, as demanded by ISO 15189 and ISO 15193, are given, as well as the reference interval and measurement uncertainty and how to deal with that in routine use. The correlation of the cRMP with commercial CDT procedures and the performance of the cRMP in a network of laboratories are also presented. The performance of the CDT cRMP in combination with previously developed commutable calibrators allows for standardization of the currently available commercial measurement procedures for CDT. The cRMP has recently been approved by the IFCC and will be from now on be known as the IFCC-RMP for CDT, while CDT results standardized according to this RMP should be indicated as CDT IFCC . Copyright © 2016 Elsevier B.V. All rights reserved.

Pregnancy and variations of carbohydrate-deficient transferrin levels measured by the candidate reference HPLC method.

PubMed

Bianchi, Vincenza; Ivaldi, Alessandra; Raspagni, Alessia; Arfini, Carlo; Vidali, Matteo

2011-01-01

Contrasting data are available on the diagnostic accuracy of carbohydrate-deficient transferrin (CDT) during pregnancy. These differences may depend in part on how CDT was evaluated and expressed. Here, we report on variations of CDT levels in pregnant women using the high performance liquid chromatography (HPLC) candidate reference method. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, mean corpuscular volume, serum transferrin, urine and serum ethyl glucuronide and CDT were measured in 64 women, self-reporting as non-alcohol abusers (age: median 34, IQR: 28-38), at different stages of normal pregnancy (gestational weeks: median 28, IQR: 8-33). CDT was expressed as percentage of disialotransferrin to total transferrin (%CDT). Transferrin was associated with both %CDT (r = 0.66; P < 0.001) and gestational week (r = 0.68; P < 0.001). Interestingly, %CDT was highly correlated with gestational week (r = 0.77; P < 0.001), even after controlling for the effect of transferrin. Moreover, statistically significant differences in %CDT were also evident between women grouped for pregnancy trimester (first trimester: mean 1.01% (SD 0.19); second trimester: 1.30% (SD 0.14); third trimester: 1.53% (SD 0.22); ANOVA P < 0.001). Trend analysis confirmed a proportional increase of %CDT along with pregnancy trimesters (P < 0.001). %CDT, measured with the HPLC candidate reference method, is independently associated with gestational week. Differently from what has been previously reported or expected, the relationship between pregnancy and CDT could be more complex. The diagnostic accuracy of CDT for detecting alcohol abuse in a legal context may be limited in pregnant women and the effect of gestational age should be considered.

Cytolethal distending toxin in isolates of Aggregatibacter actinomycetemcomitans from Ghanaian adolescents and association with serotype and disease progression.

PubMed

Höglund Åberg, Carola; Antonoglou, Georgios; Haubek, Dorte; Kwamin, Francis; Claesson, Rolf; Johansson, Anders

2013-01-01

The cytolethal distending toxin (Cdt) is a highly conserved exotoxin that are produced by a number of Gram negative bacteria, including Aggregatibacter actinomycetemcomitans, and affects mammalian cells by inhibiting cell division and causing apoptosis. A complete cdt-operon is present in the majority of A. actinomycetemcomitans, but the proportion of isolates that lack cdt-encoding genes (A, B and C) varies according to the population studied. The objectives of this study were to examine serotype, Cdt-genotype, and Cdt-activity in isolates of A. actinomycetemcomitans collected from an adolescent West African population and to examine the association between the carrier status of A. actinomycetemcomitans and the progression of attachment loss (AL). A total of 249 A. actinomycetemcomitans isolates from 200 Ghanaian adolescents were examined for serotype and cdt-genotype by PCR. The activity of the Cdt-toxin was examined by DNA-staining of exposed cultured cells and documented with flow cytometry. The periodontal status of the participants was examined at baseline and at a two-year follow-up. Presence of all three cdt-encoding genes was detected in 79% of the examined A. actinomycetemcomitans isolates. All these isolates showed a substantial Cdt-activity. The two different cdt-genotypes (with and without presence of all three cdt-encoding genes) showed a serotype-dependent distribution pattern. Presence of A. actinomycetemcomitans was significantly associated with progression of AL (OR = 5.126; 95% CI = [2.994-8.779], p<0.001). A. actinomycetemcomitans isolated from the Ghanaian adolescents showed a distribution of serotype and cdt-genotype in line with results based on other previously studied populations. Presence of A. actinomycetemcomitans was significantly associated with disease progression, in particular the b serotype, whereas the association with disease progression was not particularly related to cdt-genotype, and Cdt-activity.

Sequential replication-coupled destruction at G1/S ensures genome stability

PubMed Central

Coleman, Kate E.; Grant, Gavin D.; Haggerty, Rachel A.; Brantley, Kristen; Shibata, Etsuko; Workman, Benjamin D.; Dutta, Anindya; Varma, Dileep; Purvis, Jeremy E.; Cook, Jeanette Gowen

2015-01-01

Timely ubiquitin-mediated protein degradation is fundamental to cell cycle control, but the precise degradation order at each cell cycle phase transition is still unclear. We investigated the degradation order among substrates of a single human E3 ubiquitin ligase, CRL4Cdt2, which mediates the S-phase degradation of key cell cycle proteins, including Cdt1, PR-Set7, and p21. Our analysis of synchronized cells and asynchronously proliferating live single cells revealed a consistent order of replication-coupled destruction during both S-phase entry and DNA repair; Cdt1 is destroyed first, whereas p21 destruction is always substantially later than that of Cdt1. These differences are attributable to the CRL4Cdt2 targeting motif known as the PIP degron, which binds DNA-loaded proliferating cell nuclear antigen (PCNADNA) and recruits CRL4Cdt2. Fusing Cdt1's PIP degron to p21 causes p21 to be destroyed nearly concurrently with Cdt1 rather than consecutively. This accelerated degradation conferred by the Cdt1 PIP degron is accompanied by more effective Cdt2 recruitment by Cdt1 even though p21 has higher affinity for PCNADNA. Importantly, cells with artificially accelerated p21 degradation display evidence of stalled replication in mid-S phase and sensitivity to replication arrest. We therefore propose that sequential degradation ensures orderly S-phase progression to avoid replication stress and genome instability. PMID:26272819

The relevance of hippocampal subfield integrity and clock drawing test performance for the diagnosis of Alzheimer's disease and mild cognitive impairment.

PubMed

Hirjak, Dusan; Sambataro, Fabio; Remmele, Barbara; Kubera, Katharina M; Schröder, Johannes; Seidl, Ulrich; Thomann, Anne K; Maier-Hein, Klaus H; Wolf, Robert C; Thomann, Philipp A

2017-08-31

The clock drawing test (CDT) is one of the worldwide most used screening tests for Alzheimer's disease (AD). MRI studies have identified temporo-parietal regions being involved in CDT impairment. However, the contributions of specific hippocampal subfields and adjacent extrahippocampal structures to CDT performance in AD and mild cognitive impairment (MCI) have not been investigated so far. It is unclear whether morphological alterations or CDT score, or a combination of both, are able to predict AD. 38 AD patients, 38 MCI individuals and 31 healthy controls underwent neuropsychological assessment and MRI at 3 Tesla. FreeSurfer 5.3 was used to perform hippocampal parcellation. We used a collection of statistical methods to better understand the relationship between CDT and hippocampal formation. We also tested the clinical feasibility of this relationship when predicting AD. Impaired CDT performance in AD was associated with widespread atrophy of the cornu ammonis, presubiculum, and subiculum, whereas MCI subjects showed CDT-related alterations of the CA4-dentate gyrus and subiculum. CDT correlates in AD and MCI showed regional and quantitative overlap. Importantly, CDT score was the best predictor of AD. Our findings lend support for an involvement of different hippocampal subfields in impaired CDT performance in AD and MCI. CDT seems to be more efficient than subfield imaging for predicting AD.

Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability

PubMed Central

Pozo, Pedro N.; Cook, Jeanette Gowen

2016-01-01

Successful cell proliferation requires efficient and precise genome duplication followed by accurate chromosome segregation. The Cdc10-dependent transcript 1 protein (Cdt1) is required for the first step in DNA replication, and in human cells Cdt1 is also required during mitosis. Tight cell cycle controls over Cdt1 abundance and activity are critical to normal development and genome stability. We review here recent advances in elucidating Cdt1 molecular functions in both origin licensing and kinetochore–microtubule attachment, and we describe the current understanding of human Cdt1 regulation. PMID:28025526

Expression of the p12 subunit of human DNA polymerase δ (Pol δ), CDK inhibitor p21(WAF1), Cdt1, cyclin A, PCNA and Ki-67 in relation to DNA replication in individual cells.

PubMed

Zhao, Hong; Zhang, Sufang; Xu, Dazhong; Lee, Marietta Ywt; Zhang, Zhongtao; Lee, Ernest Yc; Darzynkiewicz, Zbigniew

2014-01-01

We recently reported that the p12 subunit of human DNA polymerase δ (Pol δ4) is degraded by CRL4(Cdt2) which regulates the licensing factor Cdt1 and p21(WAF1) during the G1 to S transition. Presently, we performed multiparameter laser scanning cytometric analyses of changes in levels of p12, Cdt1 and p21(WAF1), detected immunocytochemically in individual cells, vis-à-vis the initiation and completion of DNA replication. The latter was assessed by pulse-labeling A549 cells with the DNA precursor ethynyl-2'-deoxyribose (EdU). The loss of p12 preceded the initiation of DNA replication and essentially all cells incorporating EdU were p12 negative. Completion of DNA replication and transition to G2 phase coincided with the re-appearance and rapid rise of p12 levels. Similar to p12 a decline of p21(WAF1) and Cdt1 was seen at the end of G1 phase and all DNA replicating cells were p21(WAF1) and Cdt1 negative. The loss of p21(WAF1) preceded that of Cdt1 and p12 and the disappearance of the latter coincided with the onset of DNA replication. Loss of p12 leads to conversion of Pol δ4 to its trimeric form, Pol δ3, so that the results provide strong support to the notion that Pol δ3 is engaged in DNA replication during unperturbed progression through the S phase of cell cycle. Also assessed was a correlation between EdU incorporation, likely reflecting the rate of DNA replication in individual cells, and the level of expression of positive biomarkers of replication cyclin A, PCNA and Ki-67 in these cells. Of interest was the observation of stronger correlation between EdU incorporation and expression of PCNA (r = 0.73) than expression of cyclin A (r = 0.47) or Ki-67 (r = 0.47).

Specificity of antibodies directed against the cytolethal distending toxin of Haemophilus ducreyi in patients with chancroid.

PubMed

Mbwana, Judica; Ahmed, Hinda J; Ahlman, Karin; Sundaeus, Vivian; Dahlén, Gunnar; Lyamuya, Eligius; Lagergård, Teresa

2003-09-01

Antibodies specific for the cytolethal-distending toxin of Haemophilus ducreyi (HdCDT) complex and for the CdtA, CdtB, and CdtC components were measured by ELISA in the sera of 50 patients with culture and/or PCR proven chancroid, 42 patients with periodontitis, 50 blood donors from Tanzania, 50 blood donors from Sweden. In addition, the biological activity e.g. neutralization capacity of the sera were tested. Our results demonstrate that majority of chancroid patients and healthy individuals had detectable levels of serum antibodies to HdCDT complex and to separate toxin components. However, high levels (> or =100 units) of antibodies to HdCDT complex were significantly more prevalent in the sera of patients with both chancroid and periodontitis than in the sera of the corresponding controls (P=0.001 and P=0.04, respectively). In the sera of the 50 patients with chancroid, antibodies to CdtA, CdtB, and CdtC were detected in 50, 35, and 34 individuals, respectively. Antibodies to CdtC, being less frequently detected than the antibodies to other components, show a good correlation with the neutralizing capacity of sera. High levels of neutralizing antibodies (> or =160) were detected in only 22 and 2% of the patients with chancroid and periodontitis, respectively. The data suggest that the low levels of anti-HdCDT antibodies, which include neutralizing antibodies, may contribute to limited protection in chancroid and since anti-HdCDT antibodies, may be detected in healthy individuals and in patients with certain disease conditions (e.g. periodontitis), they may not be specific markers for chancroid infection.

Mitotic UV Irradiation Induces a DNA Replication-Licensing Defect that Potentiates G1 Arrest Response

PubMed Central

Morino, Masayuki; Nukina, Kohei; Sakaguchi, Hiroki; Maeda, Takeshi; Takahara, Michiyo; Shiomi, Yasushi; Nishitani, Hideo

2015-01-01

Cdt1 begins to accumulate in M phase and has a key role in establishing replication licensing at the end of mitosis or in early G1 phase. Treatments that damage the DNA of cells, such as UV irradiation, induce Cdt1 degradation through PCNA-dependent CRL4-Cdt2 ubiquitin ligase. How Cdt1 degradation is linked to cell cycle progression, however, remains unclear. In G1 phase, when licensing is established, UV irradiation leads to Cdt1 degradation, but has little effect on the licensing state. In M phase, however, UV irradiation does not induce Cdt1 degradation. When mitotic UV-irradiated cells were released into G1 phase, Cdt1 was degraded before licensing was established. Thus, these cells exhibited both defective licensing and G1 cell cycle arrest. The frequency of G1 arrest increased in cells expressing extra copies of Cdt2, and thus in cells in which Cdt1 degradation was enhanced, whereas the frequency of G1 arrest was reduced in cell expressing an extra copy of Cdt1. The G1 arrest response of cells irradiated in mitosis was important for cell survival by preventing the induction of apoptosis. Based on these observations, we propose that mammalian cells have a DNA replication-licensing checkpoint response to DNA damage induced during mitosis. PMID:25798850

Direct Role for Proliferating Cell Nuclear Antigen in Substrate Recognition by the E3 Ubiquitin Ligase CRL4Cdt2*

PubMed Central

Havens, Courtney G.; Shobnam, Nadia; Guarino, Estrella; Centore, Richard C.; Zou, Lee; Kearsey, Stephen E.; Walter, Johannes C.

2012-01-01

The E3 ubiquitin ligase Cullin-ring ligase 4-Cdt2 (CRL4Cdt2) is emerging as an important cell cycle regulator that targets numerous proteins for destruction in S phase and after DNA damage, including Cdt1, p21, and Set8. CRL4Cdt2 substrates contain a “PIP degron,” which consists of a canonical proliferating cell nuclear antigen (PCNA) interaction motif (PIP box) and an adjacent basic amino acid. Substrates use their PIP box to form a binary complex with PCNA on chromatin and the basic residue to recruit CRL4Cdt2 for substrate ubiquitylation. Using Xenopus egg extracts, we identify an acidic residue in PCNA that is essential to support destruction of all CRL4Cdt2 substrates. This PCNA residue, which adjoins the basic amino acid of the bound PIP degron, is dispensable for substrate binding to PCNA but essential for CRL4Cdt2 recruitment to chromatin. Our data show that the interaction of CRL4Cdt2 with substrates requires molecular determinants not only in the substrate degron but also on PCNA. The results illustrate a potentially general mechanism by which E3 ligases can couple ubiquitylation to the formation of protein-protein interactions. PMID:22303007

Stability and infectivity of cytolethal distending toxin type V gene-carrying bacteriophages in a water mesocosm and under different inactivation conditions.

PubMed

Allué-Guardia, Anna; Jofre, Juan; Muniesa, Maite

2012-08-01

Two cytolethal distending toxin (Cdt) type V-encoding bacteriophages (Φ62 and Φ125) were induced spontaneously from their wild-type Escherichia coli strains and from the lysogens generated in Shigella sonnei. The stability of Cdt phages was determined at various temperatures and pH values after 1 month of storage by means of infectivity tests using a plaque blot assay and analysis of phage genomes using real-time quantitative PCR (qPCR): both were highly stable. We assessed the inactivation of Cdt phages by thermal treatment, chlorination, UV radiation, and in a mesocosm in both summer and winter. The results for the two Cdt phages showed similar trends and were also similar to the phage SOM23 used for reference, but they showed a much higher persistence than Cdt-producing E. coli. Cdt phages showed maximal inactivation after 1 h at 70°C, 30 min of UV radiation, and 30 min of contact with a 10-ppm chlorine treatment. Inactivation in a mesocosm was higher in summer than in winter, probably because of solar radiation. The treatments reduced the number of infectious phages but did not have a significant effect on the Cdt phage particles detected by qPCR. Cdt phages were quantified by qPCR in 73% of river samples, and these results suggest that Cdt phages are a genetic vehicle and the natural reservoir for cdt in the environment.

USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

PubMed

Hernández-Pérez, Santiago; Cabrera, Elisa; Amoedo, Hugo; Rodríguez-Acebes, Sara; Koundrioukoff, Stephane; Debatisse, Michelle; Méndez, Juan; Freire, Raimundo

2016-10-01

DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Safety of catheter-directed thrombolysis for the treatment of acute lower extremity deep vein thrombosis: A systematic review and meta-analysis.

PubMed

Wang, Li; Zhang, Chuanlin; Mu, Shaoyu; Yeh, Chao Hsing; Chen, Liqun; Zhang, Zeju; Wang, Xueqin

2017-09-01

Despite established guidelines, catheter-directed thrombolysis (CDT) for the management of acute lower extremity deep vein thrombosis (DVT) should not be overstated because the risks of CDT are uncertain. We performed a meta-analysis to comprehensively and quantitatively evaluate the safety of CDT for patients with acute lower extremity DVT. Relevant databases, including PubMed, Embase, Cochrane, Ovid MEDLINE, and Scopus, were searched up to January 2017. The inclusion criteria were applied to select patients with acute lower extremity DVT treated by CDT or compared CDT with anticoagulation. In case series studies, the pooled estimates of safety outcomes for complications, pulmonary embolism (PE), and mortality were calculated across studies. In studies comparing CDT with anticoagulation, summary odds ratios (ORs) were calculated. Of the 1696 citations identified, 24 studies (6 comparing CDT with anticoagulation and 18 case series) including 9157 patients met the eligibility criteria. In the case series studies, the pooled risks of major, minor, and total complications were 0.03 (95% confidence interval [CI]: 0.02-0.04), 0.07 (95% CI: 0.05-0.08), and 0.09 (95% CI: 0.08-0.11), respectively; other pooled risk results were 0.00 for PE (95% CI: 0.00-0.01) and 0.07 for mortality (95% CI: 0.03-0.11). Our meta-analysis of 6 studies comparing the risk of complications and PE related to CDT with those related to anticoagulation showed that CDT was associated with an increased risk of complications (OR = 4.36; 95% CI: 2.94-6.47) and PE (OR = 1.57; 95% CI: 1.37-1.79). Acute lower extremity DVT patients receiving CDT are associated with a low risk of complications. However, compared with anticoagulation, CDT is associated with a higher risk of complications and PE. Rare mortality related to thrombolytic therapy was reported. More evidence should be accumulated to prove the safety of CDT.

Shedding of Clostridium difficile PCR ribotype 078 by zoo animals, and report of an unstable metronidazole-resistant isolate from a zebra foal (Equus quagga burchellii).

PubMed

Álvarez-Pérez, Sergio; Blanco, José L; Martínez-Nevado, Eva; Peláez, Teresa; Harmanus, Celine; Kuijper, Ed; García, Marta E

2014-03-14

Clostridium difficile is an emerging and potentially zoonotic pathogen, but its prevalence in most animal species, including exhibition animals, is currently unknown. In this study we assessed the prevalence of faecal shedding of C. difficile by zoo animals, and determined the ribotype, toxin profile and antimicrobial susceptibility of recovered isolates. A total of 200 samples from 40 animal species (36.5% of which came from plains zebra, Equus quagga burchellii) were analysed. C. difficile was isolated from 7 samples (3.5% of total), which came from the following animal species: chimpanzee (Pan troglodytes troglodytes), dwarf goat (Capra hircus), and Iberian ibex (Capra pyrenaica hispanica), with one positive sample each; and plains zebra, with 4 positive samples from 3 different individuals. Most recovered isolates (4/7, 57.1%) belonged to the epidemic PCR ribotype 078, produced toxins A and B, and had the genes encoding binary toxin (i.e. A(+)B(+)CDT(+) isolates). The remaining three isolates belonged to PCR ribotypes 039 (A(-)B(-)CDT(-)), 042 (A(+)B(+)CDT(-)) and 110 (A(-)B(+)CDT(-)). Regardless of their ribotype, all isolates displayed high-level resistance to the fluoroquinolones ciprofloxacin, enrofloxacin and levofloxacin. Some isolates were also resistant to meropenem and/or ertapenem. A ribotype 078 isolate recovered from a male zebra foal initially showed in vitro resistance to metronidazole (MIC ≥ 256 μg/ml), but lost that trait after subculturing on non-selective media. We conclude that zoo animals belonging to different species can carry ribotype 078 and other toxigenic strains of C. difficile showing resistance to antimicrobial compounds commonly used in veterinary and/or human medicine. Copyright © 2014 Elsevier B.V. All rights reserved.

Mutant analysis of Cdt1's function in suppressing nascent strand elongation during DNA replication in Xenopus egg extracts.

PubMed

Nakazaki, Yuta; Tsuyama, Takashi; Azuma, Yutaro; Takahashi, Mikiko; Tada, Shusuke

2017-09-02

The initiation of DNA replication is strictly regulated by multiple mechanisms to ensure precise duplication of chromosomes. In higher eukaryotes, activity of the Cdt1 protein is temporally regulated during the cell cycle, and deregulation of Cdt1 induces DNA re-replication. In previous studies, we showed that excess Cdt1 inhibits DNA replication by suppressing progression of replication forks in Xenopus egg extracts. Here, we investigated the functional regions of Cdt1 that are required for the inhibition of DNA replication. We constructed a series of N-terminally or C-terminally deleted mutants of Cdt1 and examined their inhibitory effects on DNA replication in Xenopus egg extracts. Our results showed that the region spanning amino acids (a. a.) 255-620 is required for efficient inhibition of DNA replication, and that, within this region, a. a. 255-289 have a critical role in inhibition. Moreover, one of the Cdt1 mutants, Cdt1 R285A, was compromised with respect to the licensing activity but still inhibited DNA replication. This result suggests that Cdt1 has an unforeseen function in the negative regulation of DNA replication, and that this function is located within a molecular region that is distinct from those required for the licensing activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Cdt1 stabilizes an open MCM ring for helicase loading.

PubMed

Frigola, Jordi; He, Jun; Kinkelin, Kerstin; Pye, Valerie E; Renault, Ludovic; Douglas, Max E; Remus, Dirk; Cherepanov, Peter; Costa, Alessandro; Diffley, John F X

2017-06-23

ORC, Cdc6 and Cdt1 act together to load hexameric MCM, the motor of the eukaryotic replicative helicase, into double hexamers at replication origins. Here we show that Cdt1 interacts with MCM subunits Mcm2, 4 and 6, which both destabilizes the Mcm2-5 interface and inhibits MCM ATPase activity. Using X-ray crystallography, we show that Cdt1 contains two winged-helix domains in the C-terminal half of the protein and a catalytically inactive dioxygenase-related N-terminal domain, which is important for MCM loading, but not for subsequent replication. We used these structures together with single-particle electron microscopy to generate three-dimensional models of MCM complexes. These show that Cdt1 stabilizes MCM in a left-handed spiral open at the Mcm2-5 gate. We propose that Cdt1 acts as a brace, holding MCM open for DNA entry and bound to ATP until ORC-Cdc6 triggers ATP hydrolysis by MCM, promoting both Cdt1 ejection and MCM ring closure.

Cdt1 stabilizes an open MCM ring for helicase loading

PubMed Central

Frigola, Jordi; He, Jun; Kinkelin, Kerstin; Pye, Valerie E.; Renault, Ludovic; Douglas, Max E.; Remus, Dirk; Cherepanov, Peter; Costa, Alessandro; Diffley, John F. X.

2017-01-01

ORC, Cdc6 and Cdt1 act together to load hexameric MCM, the motor of the eukaryotic replicative helicase, into double hexamers at replication origins. Here we show that Cdt1 interacts with MCM subunits Mcm2, 4 and 6, which both destabilizes the Mcm2–5 interface and inhibits MCM ATPase activity. Using X-ray crystallography, we show that Cdt1 contains two winged-helix domains in the C-terminal half of the protein and a catalytically inactive dioxygenase-related N-terminal domain, which is important for MCM loading, but not for subsequent replication. We used these structures together with single-particle electron microscopy to generate three-dimensional models of MCM complexes. These show that Cdt1 stabilizes MCM in a left-handed spiral open at the Mcm2–5 gate. We propose that Cdt1 acts as a brace, holding MCM open for DNA entry and bound to ATP until ORC–Cdc6 triggers ATP hydrolysis by MCM, promoting both Cdt1 ejection and MCM ring closure. PMID:28643783

Increased Diagnostic Accuracy of Digital vs. Conventional Clock Drawing Test for Discrimination of Patients in the Early Course of Alzheimer's Disease from Cognitively Healthy Individuals.

PubMed

Müller, Stephan; Preische, Oliver; Heymann, Petra; Elbing, Ulrich; Laske, Christoph

2017-01-01

The conventional Clock Drawing Test (cCDT) is a rapid and inexpensive screening tool for detection of moderate and severe dementia. However, its usage is limited due to poor diagnostic accuracy especially in patients with mild cognitive impairment (MCI). The diagnostic value of a newly developed digital Clock Drawing Test (dCDT) was evaluated and compared with the cCDT in 20 patients with early dementia due to AD (eDAT), 30 patients with amnestic MCI (aMCI) and 20 cognitively healthy controls (HCs). Parameters assessed by dCDT were time while transitioning the stylus from one stroke to the next above the surface (i.e., time-in-air), time the stylus produced a visible stroke (i.e., time-on-surface) and total-time during clock drawing. Receiver-operating characteristic (ROC) curves were calculated and logistic regression analyses have been conducted for statistical analysis. Using dCDT, time-in-air was significantly increased in eDAT (70965.8 ms) compared to aMCI (54073.7 ms; p = 0.027) and HC (32315.6 ms; p < 0.001). In addition, time-in-air was significantly longer in patients with aMCI compared to HC ( p = 0.003), even in the aMCI group with normal cCDT score (54141.8 ms; p < 0.001). Time-in-air using dCDT allowed discrimination of patients with aMCI from HCs with a sensitivity of 81.3% and a specificity of 72.2% while cCDT scoring revealed a sensitivity of 62.5% and a specificity of 83.3%. Most interestingly, time-in-air allowed even discrimination of aMCI patients with normal cCDT scores (80% from all aMCI patients) from HCs with a clinically relevant sensitivity of 80.8% and a specificity of 77.8%. A combination of dCDT variables and cCDT scores did not improve the discrimination of patients with aMCI from HC. In conclusion, assessment of time-in-air using dCDT yielded a higher diagnostic accuracy for discrimination of aMCI patients from HCs than the use of cCDT even in those aMCI patients with normal cCDT scores. Modern digitizing devices offer the opportunity to measure subtle changes of visuo-constructive demands and executive functions that may be used as a fast and easy to perform screening instrument for the early detection of cognitive impairment in primary care.

Increased Diagnostic Accuracy of Digital vs. Conventional Clock Drawing Test for Discrimination of Patients in the Early Course of Alzheimer’s Disease from Cognitively Healthy Individuals

PubMed Central

Müller, Stephan; Preische, Oliver; Heymann, Petra; Elbing, Ulrich; Laske, Christoph

2017-01-01

The conventional Clock Drawing Test (cCDT) is a rapid and inexpensive screening tool for detection of moderate and severe dementia. However, its usage is limited due to poor diagnostic accuracy especially in patients with mild cognitive impairment (MCI). The diagnostic value of a newly developed digital Clock Drawing Test (dCDT) was evaluated and compared with the cCDT in 20 patients with early dementia due to AD (eDAT), 30 patients with amnestic MCI (aMCI) and 20 cognitively healthy controls (HCs). Parameters assessed by dCDT were time while transitioning the stylus from one stroke to the next above the surface (i.e., time-in-air), time the stylus produced a visible stroke (i.e., time-on-surface) and total-time during clock drawing. Receiver-operating characteristic (ROC) curves were calculated and logistic regression analyses have been conducted for statistical analysis. Using dCDT, time-in-air was significantly increased in eDAT (70965.8 ms) compared to aMCI (54073.7 ms; p = 0.027) and HC (32315.6 ms; p < 0.001). In addition, time-in-air was significantly longer in patients with aMCI compared to HC (p = 0.003), even in the aMCI group with normal cCDT score (54141.8 ms; p < 0.001). Time-in-air using dCDT allowed discrimination of patients with aMCI from HCs with a sensitivity of 81.3% and a specificity of 72.2% while cCDT scoring revealed a sensitivity of 62.5% and a specificity of 83.3%. Most interestingly, time-in-air allowed even discrimination of aMCI patients with normal cCDT scores (80% from all aMCI patients) from HCs with a clinically relevant sensitivity of 80.8% and a specificity of 77.8%. A combination of dCDT variables and cCDT scores did not improve the discrimination of patients with aMCI from HC. In conclusion, assessment of time-in-air using dCDT yielded a higher diagnostic accuracy for discrimination of aMCI patients from HCs than the use of cCDT even in those aMCI patients with normal cCDT scores. Modern digitizing devices offer the opportunity to measure subtle changes of visuo-constructive demands and executive functions that may be used as a fast and easy to perform screening instrument for the early detection of cognitive impairment in primary care. PMID:28443019

Gene Amplification on Demand Accelerates Cellobiose Utilization in Engineered Saccharomyces cerevisiae

PubMed Central

Oh, Eun Joong; Skerker, Jeffrey M.; Kim, Soo Rin; Wei, Na; Turner, Timothy L.; Maurer, Matthew J.; Arkin, Adam P.

2016-01-01

ABSTRACT Efficient microbial utilization of cellulosic sugars is essential for the economic production of biofuels and chemicals. Although the yeast Saccharomyces cerevisiae is a robust microbial platform widely used in ethanol plants using sugar cane and corn starch in large-scale operations, glucose repression is one of the significant barriers to the efficient fermentation of cellulosic sugar mixtures. A recent study demonstrated that intracellular utilization of cellobiose by engineered yeast expressing a cellobiose transporter (encoded by cdt-1) and an intracellular β-glucosidase (encoded by gh1-1) can alleviate glucose repression, resulting in the simultaneous cofermentation of cellobiose and nonglucose sugars. Here we report enhanced cellobiose fermentation by engineered yeast expressing cdt-1 and gh1-1 through laboratory evolution. When cdt-1 and gh1-1 were integrated into the genome of yeast, the single copy integrant showed a low cellobiose consumption rate. However, cellobiose fermentation rates by engineered yeast increased gradually during serial subcultures on cellobiose. Finally, an evolved strain exhibited a 15-fold-higher cellobiose fermentation rate. To identify the responsible mutations in the evolved strain, genome sequencing was performed. Interestingly, no mutations affecting cellobiose fermentation were identified, but the evolved strain contained 9 copies of cdt-1 and 23 copies of gh1-1. We also traced the copy numbers of cdt-1 and gh1-1 of mixed populations during the serial subcultures. The copy numbers of cdt-1 and gh1-1 in the cultures increased gradually with similar ratios as cellobiose fermentation rates of the cultures increased. These results suggest that the cellobiose assimilation pathway (transport and hydrolysis) might be a rate-limiting step in engineered yeast and copies of genes coding for metabolic enzymes might be amplified in yeast if there is a growth advantage. This study indicates that on-demand gene amplification might be an efficient strategy for yeast metabolic engineering. IMPORTANCE In order to enable rapid and efficient fermentation of cellulosic hydrolysates by engineered yeast, we delve into the limiting factors of cellobiose fermentation by engineered yeast expressing a cellobiose transporter (encoded by cdt-1) and an intracellular β-glucosidase (encoded by gh1-1). Through laboratory evolution, we isolated mutant strains capable of fermenting cellobiose much faster than a parental strain. Genome sequencing of the fast cellobiose-fermenting mutant reveals that there are massive amplifications of cdt-1 and gh1-1 in the yeast genome. We also found positive and quantitative relationships between the rates of cellobiose consumption and the copy numbers of cdt-1 and gh1-1 in the evolved strains. Our results suggest that the cellobiose assimilation pathway (transport and hydrolysis) might be a rate-limiting step for efficient cellobiose fermentation. We demonstrate the feasibility of optimizing not only heterologous metabolic pathways in yeast through laboratory evolution but also on-demand gene amplification in yeast, which can be broadly applicable for metabolic engineering. PMID:27084006

Gene Amplification on Demand Accelerates Cellobiose Utilization in Engineered Saccharomyces cerevisiae.

PubMed

Oh, Eun Joong; Skerker, Jeffrey M; Kim, Soo Rin; Wei, Na; Turner, Timothy L; Maurer, Matthew J; Arkin, Adam P; Jin, Yong-Su

2016-06-15

Efficient microbial utilization of cellulosic sugars is essential for the economic production of biofuels and chemicals. Although the yeast Saccharomyces cerevisiae is a robust microbial platform widely used in ethanol plants using sugar cane and corn starch in large-scale operations, glucose repression is one of the significant barriers to the efficient fermentation of cellulosic sugar mixtures. A recent study demonstrated that intracellular utilization of cellobiose by engineered yeast expressing a cellobiose transporter (encoded by cdt-1) and an intracellular β-glucosidase (encoded by gh1-1) can alleviate glucose repression, resulting in the simultaneous cofermentation of cellobiose and nonglucose sugars. Here we report enhanced cellobiose fermentation by engineered yeast expressing cdt-1 and gh1-1 through laboratory evolution. When cdt-1 and gh1-1 were integrated into the genome of yeast, the single copy integrant showed a low cellobiose consumption rate. However, cellobiose fermentation rates by engineered yeast increased gradually during serial subcultures on cellobiose. Finally, an evolved strain exhibited a 15-fold-higher cellobiose fermentation rate. To identify the responsible mutations in the evolved strain, genome sequencing was performed. Interestingly, no mutations affecting cellobiose fermentation were identified, but the evolved strain contained 9 copies of cdt-1 and 23 copies of gh1-1 We also traced the copy numbers of cdt-1 and gh1-1 of mixed populations during the serial subcultures. The copy numbers of cdt-1 and gh1-1 in the cultures increased gradually with similar ratios as cellobiose fermentation rates of the cultures increased. These results suggest that the cellobiose assimilation pathway (transport and hydrolysis) might be a rate-limiting step in engineered yeast and copies of genes coding for metabolic enzymes might be amplified in yeast if there is a growth advantage. This study indicates that on-demand gene amplification might be an efficient strategy for yeast metabolic engineering. In order to enable rapid and efficient fermentation of cellulosic hydrolysates by engineered yeast, we delve into the limiting factors of cellobiose fermentation by engineered yeast expressing a cellobiose transporter (encoded by cdt-1) and an intracellular β-glucosidase (encoded by gh1-1). Through laboratory evolution, we isolated mutant strains capable of fermenting cellobiose much faster than a parental strain. Genome sequencing of the fast cellobiose-fermenting mutant reveals that there are massive amplifications of cdt-1 and gh1-1 in the yeast genome. We also found positive and quantitative relationships between the rates of cellobiose consumption and the copy numbers of cdt-1 and gh1-1 in the evolved strains. Our results suggest that the cellobiose assimilation pathway (transport and hydrolysis) might be a rate-limiting step for efficient cellobiose fermentation. We demonstrate the feasibility of optimizing not only heterologous metabolic pathways in yeast through laboratory evolution but also on-demand gene amplification in yeast, which can be broadly applicable for metabolic engineering. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Clock drawing test in elderly individuals with different education levels: correlation with clinical dementia rating.

PubMed

Cecato, Juliana Francisca; Fiorese, Bruna; Montiel, José Maria; Bartholomeu, Daniel; Martinelli, José Eduardo

2012-12-01

The aim of this study was to describe the performance in Clock Drawing Test (CDT) of the elderly individuals assessed in a geriatric clinic, with at least 1 year of schooling, comparing with other groups with higher education and with Clinical Dementia Rating (CDR) levels. The study also aims to correlate the results of CDT and other used diagnostic tests for dementia by CDR levels, providing additional validity evidence to the CDT. Cross-sectional study with 426 elderly individuals, >60 years old and at least 1 year of education. All participants searched for medical assistance at Geriatric and Gerontology Ambulatory of Jundiaí city, in Brazil. The community-dwelling outpatients previously undergone a detailed clinical examination and neuropsychological evaluation: Cambrigde Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), andCDT. To differentiate data from diagnostic groups based on CDR, it Kruskal-Wallis test was used. Pearson statistics were calculated to compare data from CDT and CDR. The statistical analyses were 2-tailed and were considered significant when P < .05. Regarding CDT, groups with more years of schooling showed similar means in CDR = 0 and CDR = 0.5 and in CDR = 1 and CDR = 2. Shulman and Sunderland scale were high score in groups with more years of education and above of cutoff points in all CDT score. On the contrary, in Mendez scale we did not observed similar means. Otherwise, in the group with less years of schooling greater means differences in the CDT were observed. The CDT did not show a strong correlation with MMSE and CAMCOG, both important instruments in Brazilian population to investigate dementia. For elderly individuals with high education levels, the CDT did not seem to be a good test to detect cognitive impairment.

Elevated carbohydrate-deficient transferrin (CDT) and its normalization on dietary treatment as a useful biochemical test for hereditary fructose intolerance and galactosemia.

PubMed

Pronicka, Ewa; Adamowicz, Maciej; Kowalik, Agnieszka; Płoski, Rafał; Radomyska, Barbara; Rogaszewska, Małgorzata; Rokicki, Dariusz; Sykut-Cegielska, Jolanta

2007-07-01

Abnormalities in protein glycosylation are reported in fructosemia (HFI) and galactosemia, although, particularly in HFI, the published data are limited to single cases. The purpose was to investigate the usefulness of the carbohydrate-deficient transferrin (CDT) profile for identification and monitoring of these disorders. First we analyzed CDT values before and shortly after the diagnosis in 10 cases of HFI and 17 cases of galactosemia. In all patients, elevated CDT levels were found that significantly (p < 0.0001) decreased with the therapeutic diet (27.3 +/- 11.5% versus 9.3 +/- 5.1% for HFI and 43.8 +/- 14.1% versus 11.2 +/- 4.0% for galactosemia). To evaluate the use of CDT test in monitoring compliance, the test was performed in 25 HFI patients on fructose-restricted diet. We found an elevated CDT level on 104 from 134 tests (mean 11.3 +/- 5.5%, control 1.5%-6.2%). The fructose intake was found to be 90 +/- 70 mg/kg/d, and the diet was unbalanced. A number of patients presented lower height, elevated urinary uric acid excretion, and hypercalciuria. In conclusion, abnormal percentage of CDT (%CDT) values may allow prompt detection of HFI (or galactosemia). Persistence of some abnormalities in HFI on treatment may be caused by trace amounts of fructose ingestion and/or a deficient diet. Regular %CDT measurements are suggested for HFI treatment monitoring.

Regulation of TGF-β signaling, exit from the cell cycle, and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2.

PubMed

Abbas, Tarek; Keaton, Mignon; Dutta, Anindya

2013-07-15

Deregulation of the cell cycle and genome instability are common features of cancer cells and various mechanisms exist to preserve the integrity of the genome and guard against cancer. The cullin 4-RING ubiquitin ligase (CRL4) with the substrate receptor Cdt2 (CRL4 (Cdt2)) promotes cell cycle progression and prevents genome instability through ubiquitylation and degradation of Cdt1, p21, and Set8 during S phase of the cell cycle and following DNA damage. Two recently published studies report the ubiquitin-dependent degradation of Cdt2 via the cullin 1-RING ubiquitin ligase (CRL1) in association with the substrate specificity factor and tumor suppressor FBXO11 (CRL1 (FBXO11)). The newly identified pathway restrains the activity of CRL4 (Cdt2) on p21 and Set8 and regulates cellular response to TGF-β, exit from the cell cycle and cellular migration. Here, we show that the CRL1 (FBXO11) also promotes the degradation of Cdt2 during an unperturbed cell cycle to promote efficient progression through S and G 2/M phases of the cell cycle. We discuss how this new method of regulating the abundance of Cdt2 participates in various cellular activities.

Characterization of conserved arginine residues on Cdt1 that affect licensing activity and interaction with Geminin or Mcm complex.

PubMed

You, Zhiying; Ode, Koji L; Shindo, Mayumi; Takisawa, Haruhiko; Masai, Hisao

2016-05-02

All organisms ensure once and only once replication during S phase through a process called replication licensing. Cdt1 is a key component and crucial loading factor of Mcm complex, which is a central component for the eukaryotic replicative helicase. In higher eukaryotes, timely inhibition of Cdt1 by Geminin is essential to prevent rereplication. Here, we address the mechanism of DNA licensing using purified Cdt1, Mcm and Geminin proteins in combination with replication in Xenopus egg extracts. We mutagenized the 223th arginine of mouse Cdt1 (mCdt1) to cysteine or serine (R-S or R-C, respectively) and 342nd and 346th arginines constituting an arginine finger-like structure to alanine (RR-AA). The RR-AA mutant of Cdt1 could not only rescue the DNA replication activity in Cdt1-depleted extracts but also its specific activity for DNA replication and licensing was significantly increased compared to the wild-type protein. In contrast, the R223 mutants were partially defective in rescue of DNA replication and licensing. Biochemical analyses of these mutant Cdt1 proteins indicated that the RR-AA mutation disabled its functional interaction with Geminin, while R223 mutations resulted in ablation in interaction with the Mcm2∼7 complex. Intriguingly, the R223 mutants are more susceptible to the phosphorylation-induced inactivation or chromatin dissociation. Our results show that conserved arginine residues play critical roles in interaction with Geminin and Mcm that are crucial for proper conformation of the complexes and its licensing activity.

Quality of life of older adults in Canada and Norway: examining the Iowa model.

PubMed

Low, Gail; Molzahn, Anita E; Kalfoss, Mary

2008-06-01

In this study, Glick and Tripp-Reimer's (1996) Iowa model for gerontological nursing serves as a guiding framework for a descriptive exploratory study of quality of life (QOL) of older adults. Using secondary data, the authors explored whether the effects of health appraisal, morbidities, social support transitions (SST), and the environment on QOL would be partly mediated by cognitive developmental transitions (CDT). Data sets were available from studies with random samples of community-dwelling older adults from Canada (n = 202) and Norway (n = 490). The partly and fully mediated effects found suggest positive CDT in older age might be significantly enhanced by the presence of intimate ties, positive perceptions of one's health limitations, and residence in a healthy, safe, and resource-rich physical environment. These findings represent a novel attempt at testing complex linkages between aspects of elder, environment, and nursing concepts within the Iowa model warranting further research.

Specific algorithm method of scoring the Clock Drawing Test applied in cognitively normal elderly

PubMed Central

Mendes-Santos, Liana Chaves; Mograbi, Daniel; Spenciere, Bárbara; Charchat-Fichman, Helenice

2015-01-01

The Clock Drawing Test (CDT) is an inexpensive, fast and easily administered measure of cognitive function, especially in the elderly. This instrument is a popular clinical tool widely used in screening for cognitive disorders and dementia. The CDT can be applied in different ways and scoring procedures also vary. Objective The aims of this study were to analyze the performance of elderly on the CDT and evaluate inter-rater reliability of the CDT scored by using a specific algorithm method adapted from Sunderland et al. (1989). Methods We analyzed the CDT of 100 cognitively normal elderly aged 60 years or older. The CDT ("free-drawn") and Mini-Mental State Examination (MMSE) were administered to all participants. Six independent examiners scored the CDT of 30 participants to evaluate inter-rater reliability. Results and Conclusion A score of 5 on the proposed algorithm ("Numbers in reverse order or concentrated"), equivalent to 5 points on the original Sunderland scale, was the most frequent (53.5%). The CDT specific algorithm method used had high inter-rater reliability (p<0.01), and mean score ranged from 5.06 to 5.96. The high frequency of an overall score of 5 points may suggest the need to create more nuanced evaluation criteria, which are sensitive to differences in levels of impairment in visuoconstructive and executive abilities during aging. PMID:29213954

"Combined Diagnostic Tool" APPlication to a Retrospective Series of Patients Undergoing Total Joint Revision Surgery.

PubMed

Gallazzi, Enrico; Drago, Lorenzo; Baldini, Andrea; Stockley, Ian; George, David A; Scarponi, Sara; Romanò, Carlo L

2017-01-01

Background : Differentiating between septic and aseptic joint prosthesis may be challenging, since no single test is able to confirm or rule out infection. The choice and interpretation of the panel of tests performed in any case often relies on empirical evaluation and poorly validated scores. The "Combined Diagnostic Tool (CDT)" App, a smartphone application for iOS, was developed to allow to automatically calculate the probability of having a of periprosthetic joint infection, on the basis of the relative sensitivity and specificity of the positive and negative diagnostic tests performed in any given patient. Objective : The aim of the present study was to apply the CDT software to investigate the ability of the tests routinely performed in three high-volume European centers to diagnose a periprosthetic infection. Methods : This three-center retrospective study included 120 consecutive patients undergoing total hip or knee revision, and included 65 infected patients (Group A) and 55 patients without infection (Group B). The following parameters were evaluated: number and type of positive and negative diagnostic tests performed pre-, intra- and post-operatively and resultant probability calculated by the CDT App of having a peri-prosthetic joint infection, based on pre-, intra- and post-operative combined tests. Results : Serological tests were the most common performed, with an average 2.7 tests per patient for Group A and 2.2 for Group B, followed by joint aspiration (0.9 and 0.8 tests per patient, respectively) and imaging techniques (0.5 and 0.2 test per patient). Mean CDT App calculated probability of having an infection based on pre-operative tests was 79.4% for patients in Group A and 35.7 in Group B. Twenty-nine patients in Group A had > 10% chance of not having an infection, and 29 of Group B had > 10% chance of having an infection. Conclusion : This is the first retrospective study focused on investigating the number and type of tests commonly performed prior to joint revision surgery and aimed at evaluating their combined ability to diagnose a peri-prosthetic infection. CDT App allowed us to demonstrate that, on average, the routine combination of commonly used tests is unable to diagnose pre-operatively a peri-prosthetic infection with a probability higher than 90%.

A feasibility study of automatic lung nodule detection in chest digital tomosynthesis with machine learning based on support vector machine

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Kim, Ye-seul; Choi, Sunghoon; Lee, Haenghwa; Jo, Byungdu; Choi, Seungyeon; Shin, Jungwook; Kim, Hee-Joung

2017-03-01

The chest digital tomosynthesis(CDT) is recently developed medical device that has several advantage for diagnosing lung disease. For example, CDT provides depth information with relatively low radiation dose compared to computed tomography (CT). However, a major problem with CDT is the image artifacts associated with data incompleteness resulting from limited angle data acquisition in CDT geometry. For this reason, the sensitivity of lung disease was not clear compared to CT. In this study, to improve sensitivity of lung disease detection in CDT, we developed computer aided diagnosis (CAD) systems based on machine learning. For design CAD systems, we used 100 cases of lung nodules cropped images and 100 cases of normal lesion cropped images acquired by lung man phantoms and proto type CDT. We used machine learning techniques based on support vector machine and Gabor filter. The Gabor filter was used for extracting characteristics of lung nodules and we compared performance of feature extraction of Gabor filter with various scale and orientation parameters. We used 3, 4, 5 scales and 4, 6, 8 orientations. After extracting features, support vector machine (SVM) was used for classifying feature of lesions. The linear, polynomial and Gaussian kernels of SVM were compared to decide the best SVM conditions for CDT reconstruction images. The results of CAD system with machine learning showed the capability of automatically lung lesion detection. Furthermore detection performance was the best when Gabor filter with 5 scale and 8 orientation and SVM with Gaussian kernel were used. In conclusion, our suggested CAD system showed improving sensitivity of lung lesion detection in CDT and decide Gabor filter and SVM conditions to achieve higher detection performance of our developed CAD system for CDT.

Poorer clock draw test scores are associated with greater functional impairment in peripheral artery disease: the Walking and Leg Circulation Study II.

PubMed

Zimmermann, Laura J; Ferrucci, Luigi; Kiang Liu; Lu Tian; Guralnik, Jack M; Criqui, Michael H; Yihua Liao; McDermott, Mary M

2011-06-01

We hypothesized that, in the absence of clinically recognized dementia, cognitive dysfunction measured by the clock draw test (CDT) is associated with greater functional impairment in men and women with peripheral artery disease (PAD). Participants were men and women aged 60 years and older with Mini-Mental Status Examination scores ≥ 24 with PAD (n = 335) and without PAD (n = 234). We evaluated the 6-minute walk test, 4-meter walking velocity at usual and fastest pace, the Short Physical Performance Battery (SPPB), and accelerometer-measured physical activity. CDTs were scored using the Shulman system as follows: Category 1 (worst): CDT score 0-2; Category 2: CDT score 3; Category 3 (best): CDT score 4-5. Results were adjusted for age, sex, race, education, ankle-brachial index (ABI), and comorbidities. In individuals with PAD, lower CDT scores were associated with slower 4-meter usual-paced walking velocity (Category 1: 0.78 meters/second; Category 2: 0.83 meters/second; Category 3: 0.86 meters/second; p-trend = 0.025) and lower physical activity (Category 1: 420 activity units; Category 2: 677 activity units; Category 3: 701 activity units; p-trend = 0.045). Poorer CDT scores were also associated with worse functional performance in individuals without PAD (usual and fast-paced walking velocity and SPPB, p-trend = 0.022, 0.043, and 0.031, respectively). In conclusion, cognitive impairment identified with CDT is independently associated with greater functional impairment in older, dementia-free individuals with and without PAD. Longitudinal studies are necessary to explore whether baseline CDT scores and changes in CDT scores over time can predict long-term decline in functional performance in individuals with and without PAD.

Cadmium and cadmium-tolerant soil bacteria in cacao crops from northeastern Colombia.

PubMed

Bravo, D; Pardo-Díaz, S; Benavides-Erazo, J; Rengifo-Estrada, G; Braissant, O; Leon-Moreno, C

2018-05-01

This research aims to assess total-cadmium soil content and microbiological aspects to understand the dynamics of culturable cadmium-tolerant bacteria (CdtB) in cacao soils from northeastern Colombia. An integration of inverted dish plating, Cd determination and a microcalorimetry assay (IMC) was carried out. A farm in Boyacá showed the highest level of total soil Cd (3·74 mg kg -1 ) followed by farms in Santander and Arauca (2·76 and 1·16 mg kg -1 , respectively). Coefficient of determination between total soil Cd and CFU of CdtB was high (R 2  = 0·83) for the farm in Boyacá. Moreover, a pool of 129 CdtB was isolated, and phylogeny of 21 CdtB was discussed. Among CdtB strains isolated, Enterobacter sp. CdDB41 showed major Cd immobilization capacity (Q max of 2·21 and 2·32 J at 6 and 24 mg l -1 of CdCl 2 ), with an immobilization rate of 0·220 mg kg -1  h -1 . Among CdtB strains isolated, Enterobacter sp. CdDB41 showed major Cd immobilization capacity (Q max of 2·21 and 2·32 J at 6 and 24 mg l -1 of CdCl 2 ), with an immobilization rate of 0·220 mg kg -1  h -1 . Nothing is known about soil CdtB in cacao. Our data showed that CdtB such as Enterobacter sp. has high immobilization capacity. Furthermore, the otavite found in situ might be mineralized due to the bacterial metabolic activity of CdtB. © 2018 The Society for Applied Microbiology.

Laboratory diagnosis of Clostridium difficile infection: Comparison of Techlab C. diff Quik Chek Complete, Xpert C. difficile, and multistep algorithmic approach.

PubMed

Seo, Ja Young; Jeong, Ji Hun; Kim, Kyung Hee; Ahn, Jeong-Yeal; Park, Pil-Whan; Seo, Yiel-Hea

2017-11-01

Clostridium difficile is a major pathogen responsible for nosocomial infectious diarrhea. We explored optimal laboratory strategies for diagnosis of C. difficile infection (CDI) in our clinical settings, a 1400-bed tertiary care hospital. Using 191 fresh stool samples from adult patients, we evaluated the performance of Xpert C. difficile (Xpert CD), C. diff Quik Chek Complete (which simultaneously detects glutamate dehydrogenase [GDH] and C. difficile toxins [CDT]), toxigenic culture, and a two-step algorithm composed of GDH/CDT as a screening test and Xpert CD as a confirmatory test. Clostridium difficile was detected in 35 samples (18.3%), and all isolates were toxigenic strains. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of each assay for detecting CDI were as follows: Quik Chek Complete CDT (45.7%, 100%, 100%, 89.1%), Quik Chek Complete GDH (97.1%, 99.4%, 97.1%, 99.4%), Xpert CD (94.3%, 100%, 100%, 98.7%), and toxigenic culture (91.4%, 100%, 100%, 98.1%). A two-step algorithm performed identically with Xpert CD assay. Our data showed that most C. difficile isolates from adult patients were toxigenic. We demonstrated that a two-step algorithm based on GDH/CDT assay followed by Xpert CD assay as a confirmatory test was rapid, reliable, and cost effective for diagnosis of CDI in an adult patient setting with high prevalence of toxigenic C. difficile. © 2017 Wiley Periodicals, Inc.

Partial cure achieved in a patient with near-complete cervical spinal cord injury (95% injury) after 3 years of coordination dynamics therapy.

PubMed

Schalow, G

2009-01-01

This report describes a case of a now 20-year-old young lady with a severe spinal cord injury (SCI) at cervical 5/6 levels (ASIA A), in whom a repair of some spinal cord functions could be achieved within 3 years of optimal coordination dynamics therapy (CDT). Magnetic Resonance Imaging (MRI) showed a destruction of almost 95% of the cross-sectional area at the injury levels. The 5% (if at all) spared cord tissue most likely consisted of only sensory tracts, since no motor functions were preserved below the level of injury. A near-complete recovery of the important vegetative functions urinary bladder control, respiration, and vasomotor tone could be achieved. Her motor and sensory functions also improved to some extent, and she is off all medications. However, her motor recovery was limited and she is still wheel-chair-dependent. There is functional and structural (MRI) evidence that the human spinal cord regenerates upon CDT. The movement-based learning therapy included the training of supported crawling, up-righting, walking, running, jumping, balance training, and exercising on special CDT devices. The regeneration of the spinal cord started after more than one year of CDT, it was very limited but continuous, and gave rise to substantial functional recovery. The recovery induced by regeneration upon CDT was quantified in terms of transient increases of coordination dynamics values, the improvement of motor programs as assessed by surface electromyography (sEMG), the improvement of movement performances, and the increase of the spinal cord matter at the injury site, quantified by MRI. The similarity between the improvement at cellular and integrative (network) level during this regeneration and development is analyzed with respect to 'walking'. Comparing the effort, required to achieve substantial improvement in this case of severe cervical SCI (with 95% cord destruction; 5% spared tissue) with the effort required in the case of partial cervical SCI (50% destruction; 50% spared tissue), IT is noted that the 95% injury is 10 times more intractable. It is inferred that in severe SCI, the repair crucially depends on the percentage of the spared tissue (tracts fibres and neuronal networks) at the injury site. Improper handling of the patient therefore, as false transport or too late relief of spinal cord compression, may give rise to further mechanical damage of the cord tissue for which a later administered intensive cCDT cannot compensate for.

Advanced Cu chemical displacement technique for SiO2-based electrochemical metallization ReRAM application.

PubMed

Chin, Fun-Tat; Lin, Yu-Hsien; You, Hsin-Chiang; Yang, Wen-Luh; Lin, Li-Min; Hsiao, Yu-Ping; Ko, Chum-Min; Chao, Tien-Sheng

2014-01-01

This study investigates an advanced copper (Cu) chemical displacement technique (CDT) with varying the chemical displacement time for fabricating Cu/SiO2-stacked resistive random-access memory (ReRAM). Compared with other Cu deposition methods, this CDT easily controls the interface of the Cu-insulator, the switching layer thickness, and the immunity of the Cu etching process, assisting the 1-transistor-1-ReRAM (1T-1R) structure and system-on-chip integration. The modulated shape of the Cu-SiO2 interface and the thickness of the SiO2 layer obtained by CDT-based Cu deposition on SiO2 were confirmed by scanning electron microscopy and atomic force microscopy. The CDT-fabricated Cu/SiO2-stacked ReRAM exhibited lower operation voltages and more stable data retention characteristics than the control Cu/SiO2-stacked sample. As the Cu CDT processing time increased, the forming and set voltages of the CDT-fabricated Cu/SiO2-stacked ReRAM decreased. Conversely, decreasing the processing time reduced the on-state current and reset voltage while increasing the endurance switching cycle time. Therefore, the switching characteristics were easily modulated by Cu CDT, yielding a high performance electrochemical metallization (ECM)-type ReRAM.

Detection of CDT toxin genes in Campylobacter spp. strains isolated from broiler carcasses and vegetables in São Paulo, Brazil

PubMed Central

de Carvalho, Aline Feola; da Silva, Daniela Martins; Azevedo, Sergio Santos; Piatti, Rosa Maria; Genovez, Margareth Elide; Scarcelli, Eliana

2013-01-01

Campylobacteriosis is a worldwide distributed zoonosis. One of the main virulence factors related to Campylobacter spp. in animals and humans is the cytolethal distending toxin (CDT), encoded by three adjacent genes (cdtA, cdtB, cdtC). The occurrence of Campylobacter spp. in samples of vegetables has not been reported in Brazil yet, and has seldom been described in the international literature. The detection of CDT in these strains has not been reported, either. The objectives of the present study were to determine the occurrence of Campylobacter spp. strains carrying virulence factors in samples of poultry and vegetables (lettuce and spinach) from different points of sale, thus verifying if vegetables are as an important vehicle for potentially virulent Campylobacter spp. strains as poultry. Twenty four strains were identified as Campylobacter jejuni by phenotypic and genotypic methods: 22 from broiler carcasses and two from lettuce samples. Three strains were identified as Campylobacter coli: two from broiler carcasses and one from lettuce. The presence of the cdt genes were detected in 20/24 (83.3%) C. jejuni strains, and 3/3 (100%) C. coli strains. The isolation of Campylobacter spp. strains with the cdt gene cluster in lettuce samples points to a new possible source of contamination, which could have an impact in the vegetable production chain and risk to public health. Results show that potentially virulent C. jejuni and C. coli strains remain viable in samples of broiler carcasses and vegetables at the points of sale. PMID:24516435

Quantitative evaluation of anatomical noise in chest digital tomosynthesis, digital radiography, and computed tomography

NASA Astrophysics Data System (ADS)

Lee, D.; Choi, S.; Lee, H.; Kim, D.; Choi, S.; Kim, H.-J.

2017-04-01

Lung cancer is currently the worldwide leading cause of death from cancer. Thus, detection of lung cancer at its early stages is critical for improving the survival rate of patients. Chest digital tomosynthesis (CDT) is a recently developed imaging modality, combining many advantages of digital radiography (DR) and computed tomography (CT). This method has the potential to be widely used in the clinical setting. In this study, we introduce a developed CDT R/F system and compare its image quality with those of DR and CT, especially with respect to anatomical noise and lung nodule conspicuity, for LUNGMAN phantoms. The developed CDT R/F system consists of a CsI scintillator flat panel detector, X-ray tube, and tomosynthesis data acquisition geometry. For CDT R/F imaging, 41 projections were acquired at different angles, over the ± 20° angular range, in a linear translation geometry. To evaluate the clinical effectiveness of the CDT R/F system, the acquired images were compared with CT (Philips brilliance CT 64, Philips healthcare, U.S.) and DR (ADR-M, LISTEM, Korea) phantom images in terms of the anatomical noise power spectrum (aNPS). DR images exhibited low conspicuity for a small-size lung nodule, while CDT R/F and CT exhibited relatively high sensitivity for all lung nodule sizes. The aNPS of the CDT R/F system was better than that of DR, by resolving anatomical overlapping problems. In conclusion, the developed CDT R/F system is likely to contribute to early diagnosis of lung cancer, while requiring a relatively low patient dose, compared with CT.

The Standardization of the Clock Drawing Test (CDT) for People with Stroke Using Rasch Analysis

PubMed Central

Yoo, Doo Han; Hong, Deok Gi; Lee, Jae Shin

2014-01-01

[Purpose] The aim of this study was to standardize the clock drawing test (CDT) for people with stroke using Rasch analysis. [Subjects and Methods] Seventeen items of the CDT identified through a literature review were performed by 159 stroke patients. The data was analyzed with Winstep version 3.57 using the Rasch model to examine the unidimensionality of the items’ fit, the distribution of the items’ difficulty, and the reliability and appropriateness of the rating scale. [Result] Ten out of the 159 participations (6.2%) were considered misfit subjects, and one item of the CDT was determined to be a misfit item based on Rasch analysis. The rating scales were judged as suitable because the observed average showed an array of vertical orders and MNSQ values < 2. The separate index and reliability of the subject (1.98, 0.80) and item (6.45, 0.97) showed relatively high values. [Conclusion] This study is the first to examine the CDT scale in stroke patients by Rasch analysis. The CDT is expected to be useful for screening stroke patients with cognitive problems. PMID:24409026

Coherent destruction of tunnelling in laser-graphene interactions

NASA Astrophysics Data System (ADS)

Gagnon, Denis; Fillion-Gourdeau, François; Dumont, Joey; Lefebvre, Catherine; Maclean, Steve

Coherent destruction of tunnelling (CDT) is defined as a critical slow-down of the dynamics of a quantum system that occurs when its adiabatic eigenstates exhibit a close avoided crossing. CDT has been observed in several quantum systems such as semiconductor superlattices, superconducting qubits and molecules in laser fields. In this work, CDT in low-dimensional Dirac materials is described using the viewpoint of Floquet theory. More specifically, the case of photo-excited graphene is considered. Conduction band populations are computed for various combinations of incident laser pulse shapes and polarizations. It is shown that these laser parameters provide control knobs over the phenomenon of CDT in graphene. Specifically, multiphoton peaks in momentum space can be selectively suppressed or enhanced. The potential of experimental techniques such as ARPES for the future observation of CDT in graphene is also discussed.

Cytolethal Distending Toxin From Campylobacter jejuni Requires the Cytoskeleton for Toxic Activity.

PubMed

Méndez-Olvera, Estela T; Bustos-Martínez, Jaime A; López-Vidal, Yolanda; Verdugo-Rodríguez, Antonio; Martínez-Gómez, Daniel

2016-10-01

Campylobacter jejuni is one of the major causes of infectious diarrhea worldwide. The distending cytolethal toxin (CDT) of Campylobacter spp. interferes with normal cell cycle progression. This toxic effect is considered a result of DNase activity that produces chromosomal DNA damage. To perform this event, the toxin must be endocytosed and translocated to the nucleus. The aim of this study was to evaluate the role of the cytoskeleton in the translocation of CDT to the nucleus. Campylobacter jejuni ATCC 33291 and seven isolates donated from Instituto de Biotecnologia were used in this study. The presence of CDT genes in C. jejuni strains was determined by PCR. To evaluate the effect of CDT, HeLa cells were treated with bacterial lysate, and the damage and morphological changes were analyzed by microscopy, immunofluorescence staining, and flow cytometry. To evaluate the role of the cytoskeleton, HeLa cells were treated with either latrunculin A or by nocodazole and analyzed by microscopy, flow cytometry, and immunoquantification (ELISA). The results obtained showed that the eight strains of C. jejuni , including the reference strain, had the ability to produce the toxin. Usage of latrunculin A and nocodazole, two cytoskeletal inhibitors, blocked the toxic effect in cells treated with the toxin. This phenomenon was evident in flow cytometry analysis and immunoquantification of Cdc2-phosphorylated. This work showed that the cytotoxic activity of the C. jejuni CDT is dependent on its endocytosis. The alteration in the microtubules and actin filaments caused a blockage transit of the toxin, preventing it from reaching the nucleus of the cell, as well as preventing DNA fragmentation and alteration of the cell cycle. The CDT toxin appears to be an important element for the pathogenesis of campylobacteriosis, since all clinical isolates showed the presence of cdtA , cdtB and cdtC genes.

Cytolethal Distending Toxin From Campylobacter jejuni Requires the Cytoskeleton for Toxic Activity

PubMed Central

Méndez-Olvera, Estela T.; Bustos-Martínez, Jaime A.; López-Vidal, Yolanda; Verdugo-Rodríguez, Antonio; Martínez-Gómez, Daniel

2016-01-01

Background Campylobacter jejuni is one of the major causes of infectious diarrhea worldwide. The distending cytolethal toxin (CDT) of Campylobacter spp. interferes with normal cell cycle progression. This toxic effect is considered a result of DNase activity that produces chromosomal DNA damage. To perform this event, the toxin must be endocytosed and translocated to the nucleus. Objectives The aim of this study was to evaluate the role of the cytoskeleton in the translocation of CDT to the nucleus. Methods Campylobacter jejuni ATCC 33291 and seven isolates donated from Instituto de Biotecnologia were used in this study. The presence of CDT genes in C. jejuni strains was determined by PCR. To evaluate the effect of CDT, HeLa cells were treated with bacterial lysate, and the damage and morphological changes were analyzed by microscopy, immunofluorescence staining, and flow cytometry. To evaluate the role of the cytoskeleton, HeLa cells were treated with either latrunculin A or by nocodazole and analyzed by microscopy, flow cytometry, and immunoquantification (ELISA). Results The results obtained showed that the eight strains of C. jejuni, including the reference strain, had the ability to produce the toxin. Usage of latrunculin A and nocodazole, two cytoskeletal inhibitors, blocked the toxic effect in cells treated with the toxin. This phenomenon was evident in flow cytometry analysis and immunoquantification of Cdc2-phosphorylated. Conclusions This work showed that the cytotoxic activity of the C. jejuni CDT is dependent on its endocytosis. The alteration in the microtubules and actin filaments caused a blockage transit of the toxin, preventing it from reaching the nucleus of the cell, as well as preventing DNA fragmentation and alteration of the cell cycle. The CDT toxin appears to be an important element for the pathogenesis of campylobacteriosis, since all clinical isolates showed the presence of cdtA, cdtB and cdtC genes. PMID:27942359

Comparison study of image quality and effective dose in dual energy chest digital tomosynthesis

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Choi, Sunghoon; Lee, Haenghwa; Kim, Dohyeon; Choi, Seungyeon; Kim, Hee-Joung

2018-07-01

The present study aimed to introduce a recently developed digital tomosynthesis system for the chest and describe the procedure for acquiring dual energy bone decomposed tomosynthesis images. Various beam quality and reconstruction algorithms were evaluated for acquiring dual energy chest digital tomosynthesis (CDT) images and the effective dose was calculated with ion chamber and Monte Carlo simulations. The results demonstrated that dual energy CDT improved visualization of the lung field by eliminating the bony structures. In addition, qualitative and quantitative image quality of dual energy CDT using iterative reconstruction was better than that with filtered backprojection (FBP) algorithm. The contrast-to-noise ratio and figure of merit values of dual energy CDT acquired with iterative reconstruction were three times better than those acquired with FBP reconstruction. The difference in the image quality according to the acquisition conditions was not noticeable, but the effective dose was significantly affected by the acquisition condition. The high energy acquisition condition using 130 kVp recorded a relatively high effective dose. We conclude that dual energy CDT has the potential to compensate for major problems in CDT due to decomposed bony structures, which induce significant artifacts. Although there are many variables in the clinical practice, our results regarding reconstruction algorithms and acquisition conditions may be used as the basis for clinical use of dual energy CDT imaging.

Cdt1p, through its interaction with Mcm6p, is required for the formation, nuclear accumulation and chromatin loading of the MCM complex.

PubMed

Wu, Rentian; Wang, Jiafeng; Liang, Chun

2012-01-01

Regulation of DNA replication initiation is essential for the faithful inheritance of genetic information. Replication initiation is a multi-step process involving many factors including ORC, Cdt1p, Mcm2-7p and other proteins that bind to replication origins to form a pre-replicative complex (pre-RC). As a prerequisite for pre-RC assembly, Cdt1p and the Mcm2-7p heterohexameric complex accumulate in the nucleus in G1 phase in an interdependent manner in budding yeast. However, the nature of this interdependence is not clear, nor is it known whether Cdt1p is required for the assembly of the MCM complex. In this study, we provide the first evidence that Cdt1p, through its interaction with Mcm6p with the C-terminal regions of the two proteins, is crucial for the formation of the MCM complex in both the cytoplasm and nucleoplasm. We demonstrate that disruption of the interaction between Cdt1p and Mcm6p prevents the formation of the MCM complex, excludes Mcm2-7p from the nucleus, and inhibits pre-RC assembly and DNA replication. Our findings suggest a function for Cdt1p in promoting the assembly of the MCM complex and maintaining its integrity by interacting with Mcm6p.

Production of a complete binary toxin (actin-specific ADP-ribosyltransferase) by Clostridium difficile CD196.

PubMed

Perelle, S; Gibert, M; Bourlioux, P; Corthier, G; Popoff, M R

1997-04-01

A Clostridium difficile isolate was found to produce an actin-specific ADP-ribosyltransferase (CDT) homologous to the enzymatic components of Clostridium perfringens iota toxin and Clostridium spiroforme toxin (M. R. Popoff, E. J. Rubin, D. M. Gill, and P. Boquet, Infect. Immun. 56:2299-2306, 1988). The CDT locus from C. difficile CD196 was cloned and sequenced. It contained two genes (cdtA and cdtB) which display organizations and sequences similar to those of the iota toxin gene. The deduced enzymatic (CDTa) and binding (CDTb) components have 81 and 84% identity, respectively, with the corresponding components of iota toxin. CDTa and CDTb induced actin cytoskeleton alterations similar to those caused by other clostridial binary toxins. The lower level of production of binary toxin by CD196 than of iota toxin by C. perfringens was related to a lower transcript level, possibly due to a promoter region different from that of iota toxin genes. The cdtA and cdtB genes have been detected in 3 of 24 clinical isolates examined, and cdtB alone was found in 2 additional strains. One strain (in addition to CD196) was shown by Western blotting to produce CDTa and CDTb. These results indicate that some C. difficile strains synthesize a binary toxin that could be an additional virulence factor.

Production of a complete binary toxin (actin-specific ADP-ribosyltransferase) by Clostridium difficile CD196.

PubMed Central

Perelle, S; Gibert, M; Bourlioux, P; Corthier, G; Popoff, M R

1997-01-01

A Clostridium difficile isolate was found to produce an actin-specific ADP-ribosyltransferase (CDT) homologous to the enzymatic components of Clostridium perfringens iota toxin and Clostridium spiroforme toxin (M. R. Popoff, E. J. Rubin, D. M. Gill, and P. Boquet, Infect. Immun. 56:2299-2306, 1988). The CDT locus from C. difficile CD196 was cloned and sequenced. It contained two genes (cdtA and cdtB) which display organizations and sequences similar to those of the iota toxin gene. The deduced enzymatic (CDTa) and binding (CDTb) components have 81 and 84% identity, respectively, with the corresponding components of iota toxin. CDTa and CDTb induced actin cytoskeleton alterations similar to those caused by other clostridial binary toxins. The lower level of production of binary toxin by CD196 than of iota toxin by C. perfringens was related to a lower transcript level, possibly due to a promoter region different from that of iota toxin genes. The cdtA and cdtB genes have been detected in 3 of 24 clinical isolates examined, and cdtB alone was found in 2 additional strains. One strain (in addition to CD196) was shown by Western blotting to produce CDTa and CDTb. These results indicate that some C. difficile strains synthesize a binary toxin that could be an additional virulence factor. PMID:9119480

Early Detection of Alzheimer's Disease Based on the Patient's Creative Drawing Process: First Results with a Novel Neuropsychological Testing Method.

PubMed

Heymann, Petra; Gienger, Regine; Hett, Andreas; Müller, Stephan; Laske, Christoph; Robens, Sibylle; Ostermann, Thomas; Elbing, Ulrich

2018-01-01

Based on the knowledge of art therapy, we developed a new neuropsychological drawing test in order to identify individuals with mild cognitive impairment (MCI) as well as dementia patients and healthy controls (HC). By observing a variety of drawing characteristics of 92 participants with a mean age of 67.7, art therapy and dementia experts discriminate HC from MCI, early dementia of the Alzheimer-type (eDAT), and moderate dementia of the Alzheimer-type (mDAT) by the process analysis of tree drawings on a digitizing tablet. The art therapist's average categorical rating of healthy and MCI or demented individuals matched the clinical diagnosis by 88%. In a first small study, we analyzed interrater reliability, sensitivity, specificity, negative and positive predicted values of our tree drawing test (TDT) in comparison with the clock drawing test (CDT). Similar values of moderate interrater reliability were found for the TDT (0.56) as well as for the CDT (0.54). A significant high sensitivity of 0.9 within this binary impairment scale (HC versus impaired or demented) can be demonstrated. Substantial values for the specificity (0.67) could be obtained that however remain under a perfect value of the CDT (1.0). Considering 31 individuals that received the clinical diagnosis "impaired or demented" the TDT shows a higher recognition rate for the MCI group than the CDT. Furthermore in 8 of 12 borderline cases of clinical diagnosis, the outcome of the TDT diagnosis was consistent with the final clinical result.

Value of ethyl glucuronide in plasma as a biomarker for recent alcohol consumption in the emergency room.

PubMed

Neumann, Tim; Helander, Anders; Dahl, Helen; Holzmann, Tilly; Neuner, Bruno; Weiss-Gerlach, Edith; Müller, Christian; Spies, Claudia

2008-01-01

This emergency department (ED) study compared the value of plasma ethyl glucuronide (EtG) testing with the information about alcohol consumption obtained using the standard alcohol biomarkers gamma-glutamyltransferase (GGT) and carbohydrate-deficient transferring (CDT) and the AUDIT questionnaire. Minimally injured and clinically non-intoxicated male patients (n = 81) admitted to an ED were screened regarding their alcohol consumption, using the computerized AUDIT questionnaire and a paper-and-pencil assessment including the type, amount and time of alcohol intake. Blood samples were collected for determination of ethanol, EtG (LC-MS) and GGT in plasma and %CDT in serum (Axis-Shield %CDT immunoassay). Out of the 81 patients, 23 (28%) were positive (>/=8 points) on the AUDIT questionnaire. Only 3 (4%) showed a detectable ethanol concentration (range 0.01-0.07 g/L) but 31 (38%) showed a detectable EtG (0.16-39.5 mg/L). In four patients, EtG was detectable in plasma for >48 h after estimated completed elimination of ethanol. EtG was not correlated with the long-term biomarkers %CDT or GGT, or the AUDIT results, but with the time since estimated completed ethanol elimination. EtG testing in blood was found useful in the ED as a way to detect recent drinking, even in cases of a negative ethanol test, and to confirm abstinence from alcohol. This sensitive and specific short-term biomarker provides valuable additional information about individual drinking habits and might also be helpful to identify an alcohol hangover.

Use of finger-prick dried blood spots (fpDBS) and capillary electrophoresis for carbohydrate deficient transferrin (CDT) screening in forensic toxicology.

PubMed

Bertaso, Anna; Sorio, Daniela; Vandoros, Anthula; De Palo, Elio F; Bortolotti, Federica; Tagliaro, Franco

2016-10-01

Continued progress in chronic alcohol abuse investigation requires the development of less invasive procedures for screening purposes. The application of finger-prick and related dried blood spots (fpDBS) for carbohydrate deficient transferrin (CDT) detection appears suitable for this aim. Therefore, the goal of this project was to develop a screening method for CDT using fpDBS with CZE analysis. Blood samples prepared by finger-prick were placed on DBS cards and left to air dry; each dried fpDBS disc was shredded into small pieces and suspended in acid solution (60 μL of HCl 120 mmol/L). After centrifugation (10 min at 1500 × g), the collected sample was adjusted to pH 3.5. After an overnight incubation, the pH was neutralised and an iron rich solution was added. After 1 h, CZE analysis was carried out. A group of 47 individuals was studied. Parallel serum samples were collected from each investigated subject and the %CDT for each sample was measured using HPLC and CZE techniques. The fpDBS transferrin sialo isoform electropherograms were similar to those obtained with serum. Moreover, fpDBS CZE CDT percentage levels demonstrated significant statistical correlation with those obtained from serum for both HPLC and CZE %CDT (p < 0.01; r 2 = 0.8913 and 0.8976, respectively), with %CDT from 0.8 to 13.7% for fpDBS and from 0.7 to 12.7% for serum. The newly developed fpDBS procedure for CDT analysis provides a simple and inexpensive tool for use in population screening. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clostridium difficile binary toxin CDT

PubMed Central

Gerding, Dale N; Johnson, Stuart; Rupnik, Maja; Aktories, Klaus

2014-01-01

Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed. PMID:24253566

Evaluation of the Cepheid® Xpert®C. difficile binary toxin (BT) diagnostic assay.

PubMed

McGovern, Alan M; Androga, Grace O; Moono, Peter; Collins, Deirdre A; Foster, Niki F; Chang, Barbara J; Riley, Thomas V

2018-06-01

Strains of Clostridium difficile producing only binary toxin (CDT) are found commonly in animals but not humans. However, human diagnostic tests rarely look for CDT. The Cepheid Xpert C. difficile BT assay detects CDT with equal sensitivity (≥92%) in human and animal faecal samples. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improvement of color and physiological properties of tuna-processing by-product by gamma irradiation

NASA Astrophysics Data System (ADS)

Choi, Jong-il; Kim, Hyun-Joo; Kim, Jae-Hun; Song, Beom-Seok; Chun, Byeong-Soo; Ahn, Dong-Hyun; Byun, Myung-Woo; Lee, Ju-Woon

2009-07-01

Although the by-products from fishery industry had many nutrients, it is being wasted or only used as bacteria media. In this study, the effect of a gamma irradiation on the cooking drips of Thunnus thynnus (CDT) was investigated to examine the possible use of the cooking drips as a functional material for food and cosmetic composition. Total aerobic bacteria, and yeasts/molds from CDT were detected at the level of 2.79 and 2.58 Log CFU/mL, respectively. But, CDT was efficiently sterilized by a gamma irradiation at a low dose of 1 kGy. The Hunter L* value of the gamma-irradiated ethanol extract of CDT was increased, and the a* and b* values were decreased compared to the non-irradiated extract, showing color improvement. Antioxidant activity of the ethanol extract of CDT was increased by a gamma irradiation depending on the irradiation dose. The increased contents of polyphenolic compounds and proteins in CDT extract by gamma irradiation may be the reason of the increased biological activity. These results suggested that the wasted cooking drips can be successfully used as functional components with gamma irradiation treatment.

CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication.

PubMed

Franz, André; Orth, Michael; Pirson, Paul A; Sonneville, Remi; Blow, J Julian; Gartner, Anton; Stemmann, Olaf; Hoppe, Thorsten

2011-10-07

Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4)-deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison study of noise reduction algorithms in dual energy chest digital tomosynthesis

NASA Astrophysics Data System (ADS)

Lee, D.; Kim, Y.-S.; Choi, S.; Lee, H.; Choi, S.; Kim, H.-J.

2018-04-01

Dual energy chest digital tomosynthesis (CDT) is a recently developed medical technique that takes advantage of both tomosynthesis and dual energy X-ray images. However, quantum noise, which occurs in dual energy X-ray images, strongly interferes with diagnosis in various clinical situations. Therefore, noise reduction is necessary in dual energy CDT. In this study, noise-compensating algorithms, including a simple smoothing of high-energy images (SSH) and anti-correlated noise reduction (ACNR), were evaluated in a CDT system. We used a newly developed prototype CDT system and anthropomorphic chest phantom for experimental studies. The resulting images demonstrated that dual energy CDT can selectively image anatomical structures, such as bone and soft tissue. Among the resulting images, those acquired with ACNR showed the best image quality. Both coefficient of variation and contrast to noise ratio (CNR) were the highest in ACNR among the three different dual energy techniques, and the CNR of bone was significantly improved compared to the reconstructed images acquired at a single energy. This study demonstrated the clinical value of dual energy CDT and quantitatively showed that ACNR is the most suitable among the three developed dual energy techniques, including standard log subtraction, SSH, and ACNR.

Catheter-directed Thrombolysis with Argatroban and tPA for Massive Iliac and Femoropopliteal Vein Thrombosis

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

Sharifi, Mohsen, E-mail: seyedmohsensharifi@yahoo.com; Bay, Curt; Nowroozi, Sasan

2013-12-15

Purpose: Catheter-directed thrombolysis (CDT) is a highly effective approach in the treatment of deep venous thrombosis (DVT). There are no data on the primary use of CDT with argatroban and tissue plasminogen activator (tPA) in patients without heparin-induced thrombocytopenia (HIT). The aim of this study was to evaluate the efficacy and safety of the combined administration of argatroban and tPA during CDT for massive DVT in patients without HIT. Methods: Thirty-three patients with massive symptomatic iliac and femoropopliteal DVT underwent CDT with tPA and argatroban within 28 {+-} 6 h of presentation. The dose of tPA was 0.75-1 mg/h throughmore » the infusion port and that of argatroban at 0.3-1 {mu}g/kg/min through the side port of the sheath. The patients were evaluated for the efficacy and safety of CDT and recurrent symptomatic venous thromboembolism (VTE) at a mean follow-up of 22 months. Results: There was no bleeding or iatrogenic pulmonary embolism with the CDT regimen we used. Grade III lysis (complete resolution of thrombus on venography) was achieved in 30 patients (91 %). In 3 patients with additional inferior vena cava filter thrombosis, further thrombectomy of the filter was required. No patient developed recurrent VTE. Conclusion: Concomitant administration of argatroban and tPA is a highly safe and effective regimen for CDT for massive DVT.« less

Catheter-Directed Thrombolysis via Small Saphenous Veins for Treating Acute Deep Venous Thrombosis.

PubMed

Yang, Bin; Xu, Xiao-Dong; Gao, Peng; Yu, Ji-Xiang; Li, Yu; Zhu, Ai-Dong; Meng, Ran-Ran

2016-08-23

BACKGROUND There is little data comparing catheter-directed thrombolysis (CDT) via small saphenous veins vs. systematic thrombolysis on complications and efficacy in acute deep venous thrombosis patients. The aim of our study was to compare the efficacy and safety of CDT via the small saphenous veins with systematic thrombolysis for patients with acute deep venous thrombosis (DVT). MATERIAL AND METHODS Sixty-six patients with acute DVT admitted from June 2012 to December 2013 were divided into 2 groups: 27 patients received systemic thrombolysis (ST group) and 39 patients received CDT via the small saphenous veins (CDT group). The thrombolysis efficiency, limb circumference differences, and complications such as post-thrombotic syndrome (PTS) in the 2 groups were recorded. RESULTS The angiograms demonstrated that all or part of the fresh thrombus was dissolved. There was a significant difference regarding thrombolysis efficiency between the CDT group and ST group (71.26% vs. 48.26%, P=0.001). In both groups the postoperative limb circumference changes were higher compared to the preoperative values. The differences between postoperative limb circumferences on postoperative days 7 and 14 were significantly higher in the CDT group than in the ST group (all P<0.05). The incidence of postoperative PTS in the CDT group (17.9%) was significantly lower in comparison to the ST group (51.85%) during the follow-up (P=0.007). CONCLUSIONS Catheter-directed thrombolysis via the small saphenous veins is an effective, safe, and feasible approach for treating acute deep venous thrombosis.

Cell and plastid division are coordinated through the prereplication factor AtCDT1

PubMed Central

Raynaud, Cécile; Perennes, Claudette; Reuzeau, Christophe; Catrice, Olivier; Brown, Spencer; Bergounioux, Catherine

2005-01-01

The cell division cycle involves nuclear and cytoplasmic events, namely organelle multiplication and distribution between the daughter cells. Until now, plastid and plant cell division have been considered as independent processes because they can be uncoupled. Here, down-regulation of AtCDT1a and AtCDT1b, members of the prereplication complex, is shown to alter both nuclear DNA replication and plastid division in Arabidopsis thaliana. These data constitute molecular evidence for relationships between the cell-cycle and plastid division. Moreover, the severe developmental defects observed in AtCDT1-RNA interference (RNAi) plants underline the importance of coordinated cell and organelle division for plant growth and morphogenesis. PMID:15928083

Identification of and Screening for Human Helicobacter cinaedi Infections and Carriers via Nested PCR

PubMed Central

Oyama, Kohta; Khan, Shahzada; Okamoto, Tatsuya; Fujii, Shigemoto; Ono, Katsuhiko; Matsunaga, Tetsuro; Yoshitake, Jun; Sawa, Tomohiro; Tomida, Junko; Kawamura, Yoshiaki

2012-01-01

Helicobacter cinaedi is the most frequently reported enterohepatic Helicobacter species isolated from humans. Earlier research suggested that certain patients with H. cinaedi infection may remain undiagnosed or incorrectly diagnosed because of difficulties in detecting the bacteria by conventional culture methods. Here, we report a nested PCR assay that rapidly detects the cytolethal distending toxin gene (cdt) of H. cinaedi with high specificity and sensitivity. Specificity of the assay was validated by using different species of Helicobacter and Campylobacter, as well as known H. cinaedi-positive and -negative samples. The sensitivity of detection for the cdt gene in the assay was 102 CFU/ml urine or 102 CFU/105 infected RAW 264.7 cells. In an H. cinaedi-infected mouse model, the cdt gene of H. cinaedi was effectively detected via the assay with urine (6/7), stool (2/3), and blood (2/6) samples. Importantly, it detected H. cinaedi in blood, urine, and stool samples from one patient with a suspected H. cinaedi infection and three patients with known infections. The assay was further used clinically to follow up two H. cinaedi-infected patients after antibiotic treatment. Stool samples from these two patients evaluated by nested PCR after antibiotic therapy showed clearance of bacterial DNA. Finally, analysis of stool specimens from healthy volunteers showed occasional positive reactions (4/30) to H. cinaedi DNA, which suggests intestinal colonization by H. cinaedi in healthy subjects. In conclusion, this nested PCR assay may be useful for the rapid diagnosis, antimicrobial treatment evaluation, and epidemiological study of H. cinaedi infection. PMID:23015666

Cyclopentadithiophene-Benzothiadiazole Donor-Acceptor Polymers as Prototypical Semiconductors for High-Performance Field-Effect Transistors.

PubMed

Li, Mengmeng; An, Cunbin; Pisula, Wojciech; Müllen, Klaus

2018-05-15

Donor-acceptor (D-A) conjugated polymers are of great interest as organic semiconductors, because they offer a rational tailoring of the electronic properties by modification of the donor and acceptor units. Nowadays, D-A polymers exhibit field-effect mobilities on the order of 10 -2 -10 0 cm 2 V -1 s -1 , while several examples showed a mobility over 10 cm 2 V -1 s -1 . The development of cyclopentadithiophene-benzothiadiazole (CDT-BTZ) copolymers one decade ago represents an important step toward high-performance organic semiconductors for field-effect transistors. The significant rise in field-effect mobility of CDT-BTZ in comparison to the existing D-A polymers at that time opened the door to a new research field with a large number of novel D-A systems. From this point, the device performance of CDT-BTZ was gradually improved by a systematic optimization of the synthesis and polymer structure as well as by an efficient solution processing into long-range ordered thin films. The key aspect was a comprehensive understanding of the relation between polymer structure and solid-state organization. Due to their fundamental role for the field of D-A polymers in general, this Account will for the first time explicitly focus on prototypical CDT-BTZ polymers, while other reviews provide an excellent general overview on D-A polymers. The first part of this Account discusses strategies for improving the charge carrier transport, focusing on chemical aspects. Improved synthesis as an essential stage toward high purity, and high molecular weight is a prerequisite for molecular order. The modification of substituents is a further crucial feature to tune the CDT-BTZ packing and self-assembly. Linear alkyl side chains facilitate intermolecular π-stacking interactions, while branched ones increase solubility and alter the polymer packing. Additional control over the supramolecular organization of CDT-BTZ polymers is introduced by alkenyl substituents via their cis-trans isomerization. The last discussed chemical concept is based on heteroatom variation within the CDT unit. The relationships found experimentally for CDT-BTZ between polymer chemical structure, solid-state organization, and charge carrier transport are explained by means of theoretical simulations. Besides the effects of molecular design, the second part of this Account discusses the processing conditions from solution. The film microstructure, defined as a mesoscopic domain organization, is critically affected by solution processing. Suitable processing techniques allow the formation of a long-range order and a uniaxial orientation of the CDT-BTZ chains, thus lowering the trapping density of grain boundaries for charge carriers. For instance, alignment of the CDT-BTZ polymer by dip-coating yields films with a pronounced structural and electrical anisotropy and favors a fast migration of charge carriers along the conjugated backbones in the deposition direction. By using film compression with the assistance of an ionic liquid, one even obtains CDT-BTZ films with a band-like transport and a transistor hole mobility of 10 cm 2 V -1 s -1 . This device performance is attributed to large domains in the compressed films being formed by CDT-BTZ with longer alkyl chains, which establish a fine balance between polymer interactions and growth kinetics during solvent evaporation. On the basis of the prototypical semiconductor CDT-BTZ, this Account provides general guidelines for achieving high-performance polymer transistors by taking into account the subtle balance of synthetic protocol, molecular design, and processing.

What and where information in the caudate tail guides saccades to visual objects

PubMed Central

Yamamoto, Shinya; Monosov, Ilya E.; Yasuda, Masaharu; Hikosaka, Okihide

2012-01-01

We understand the world by making saccadic eye movements to various objects. However, it is unclear how a saccade can be aimed at a particular object, because two kinds of visual information, what the object is and where it is, are processed separately in the dorsal and ventral visual cortical pathways. Here we provide evidence suggesting that a basal ganglia circuit through the tail of the monkey caudate nucleus (CDt) guides such object-directed saccades. First, many CDt neurons responded to visual objects depending on where and what the objects were. Second, electrical stimulation in the CDt induced saccades whose directions matched the preferred directions of neurons at the stimulation site. Third, many CDt neurons increased their activity before saccades directed to the neurons’ preferred objects and directions in a free-viewing condition. Our results suggest that CDt neurons receive both ‘what’ and ‘where’ information and guide saccades to visual objects. PMID:22875934

Internalization of Heterologous Sugar Transporters by Endogenous α-Arrestins in the Yeast Saccharomyces cerevisiae.

PubMed

Sen, Arpita; Acosta-Sampson, Ligia; Alvaro, Christopher G; Ahn, Jonathan S; Cate, Jamie H D; Thorner, Jeremy

2016-12-15

When expressed in Saccharomyces cerevisiae using either of two constitutive yeast promoters (PGK1 prom and CCW12 prom ), the transporters CDT-1 and CDT-2 from the filamentous fungus Neurospora crassa are able to catalyze, respectively, active transport and facilitated diffusion of cellobiose (and, for CDT-2, also xylan and its derivatives). In S. cerevisiae, endogenous permeases are removed from the plasma membrane by clathrin-mediated endocytosis and are marked for internalization through ubiquitinylation catalyzed by Rsp5, a HECT class ubiquitin:protein ligase (E3). Recruitment of Rsp5 to specific targets is mediated by a 14-member family of endocytic adaptor proteins, termed α-arrestins. Here we demonstrate that CDT-1 and CDT-2 are subject to α-arrestin-mediated endocytosis, that four α-arrestins (Rod1, Rog3, Aly1, and Aly2) are primarily responsible for this internalization, that the presence of the transport substrate promotes transporter endocytosis, and that, at least for CDT-2, residues located in its C-terminal cytosolic domain are necessary for its efficient endocytosis. Both α-arrestin-deficient cells expressing CDT-2 and otherwise wild-type cells expressing CDT-2 mutants unresponsive to α-arrestin-driven internalization exhibit an increased level of plasma membrane-localized transporter compared to that of wild-type cells, and they grow, utilize the transport substrate, and generate ethanol anaerobically better than control cells. Ethanolic fermentation of the breakdown products of plant biomass by budding yeast Saccharomyces cerevisiae remains an attractive biofuel source. To achieve this end, genes for heterologous sugar transporters and the requisite enzyme(s) for subsequent metabolism have been successfully expressed in this yeast. For one of the heterologous transporters examined in this study, we found that the amount of this protein residing in the plasma membrane was the rate-limiting factor for utilization of the cognate carbon source (cellobiose) and its conversion to ethanol. Copyright © 2016 Sen et al.

A feasibility study for anatomical noise reduction in dual-energy chest digital tomosynthesis

NASA Astrophysics Data System (ADS)

Lee, D.; Kim, Y.-s.; Choi, S.; Lee, H.; Choi, S.; Kim, H.-J.

2016-01-01

Lung cancer is the leading cause of cancer death worldwide. Thus, early diagnosis is of considerable importance. For early screening of lung cancer, computed tomography (CT) has been used as the gold standard. Chest digital tomosynthesis (CDT) is a recently introduced modality for lung cancer screening with a relatively low radiation dose compared to CT. The dual energy material decomposition method has been proposed for better detection of pulmonary nodules by means of reducing anatomical noise. In this study, the possibility of material decomposition in CDT was tested by both a simulation study and an experimental study using a CDT prototype. The Geant4 application for tomographic emission (GATE) v6 and tungsten anode spectral model using interpolating polynomials (TASMIP) codes were used for the simulation study to create simulated phantom shapes consisting of five inner cylinders filled with different densities of bone and airequivalent materials. Furthermore, the CDT prototype system and human phantom chest were used for the experimental study. CDT scan in both the simulation and experimental studies was performed with linear movement and 21 projection images were obtained over a 30 degree angular range with a 1.5 degree angular interval. To obtain materialselective images, a projectionbased energy subtraction technique was applied to high and low energy images. The resultant simulation images showed that dual-energy reconstruction could achieve an approximately 32% higher contrast to noise ratio (CNR) in images and the difference in CNR value according to bone density was significant compared to single energy CDT. Additionally, image artifacts were effectively corrected in dual energy CDT simulation studies. Likewise the experimental study with dual energy produced clear images of lung fields and bone structure by removing unnecessary anatomical structures. Dual energy tomosynthesis is a new technique; therefore, there is little guidance regarding its integration into clinical practice and this study can be used to improve the diagnostic efficiency of lung field and spinal bone screening using CDT.

Anatomical decomposition in dual energy chest digital tomosynthesis

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Kim, Ye-seul; Choi, Sunghoon; Lee, Haenghwa; Choi, Seungyeon; Kim, Hee-Joung

2016-03-01

Lung cancer is the leading cause of cancer death worldwide and the early diagnosis of lung cancer has recently become more important. For early screening lung cancer, computed tomography (CT) has been used as a gold standard for early diagnosis of lung cancer [1]. The major advantage of CT is that it is not susceptible to the problem of misdiagnosis caused by anatomical overlapping while CT has extremely high radiation dose and cost compared to chest radiography. Chest digital tomosynthesis (CDT) is a recently introduced new modality for lung cancer screening with relatively low radiation dose compared to CT [2] and also showing high sensitivity and specificity to prevent anatomical overlapping occurred in chest radiography. Dual energy material decomposition method has been proposed for better detection of pulmonary nodules as means of reducing the anatomical noise [3]. In this study, possibility of material decomposition in CDT was tested by simulation study and actual experiment using prototype CDT. Furthermore organ absorbed dose and effective dose were compared with single energy CDT. The Gate v6 (Geant4 application for tomographic emission), and TASMIP (Tungsten anode spectral model using the interpolating polynomial) code were used for simulation study and simulated cylinder shape phantom consisted of 4 inner beads which were filled with spine, rib, muscle and lung equivalent materials. The patient dose was estimated by PCXMC 1.5 Monte Carlo simulation tool [4]. The tomosynthesis scan was performed with a linear movement and 21 projection images were obtained over 30 degree of angular range with 1.5° degree of angular interval. The proto type CDT system has same geometry with simulation study and composed of E7869X (Toshiba, Japan) x-ray tube and FDX3543RPW (Toshiba, Japan) detector. The result images showed that reconstructed with dual energy clearly visualize lung filed by removing unnecessary bony structure. Furthermore, dual energy CDT could enhance spine bone hidden by heart effectively. The effective dose in dual energy CDT was slightly higher than single energy CDT, while only 10% of average thoracic CT [5]. Dual energy tomosynthesis is a new technique; therefore, there is little guidance for its integration into the clinical practice and this study can be used to improve diagnosis efficiency of lung field screening using CDT

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis.

PubMed

Enden, T; Resch, S; White, C; Wik, H S; Kløw, N E; Sandset, P M

2013-06-01

Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). To estimate the cost effectiveness of additional CDT compared with standard treatment alone. Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64,709 for additional CDT and $51,866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20,429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55,000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50,000/QALY gained. Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding. © 2013 International Society on Thrombosis and Haemostasis.

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis

PubMed Central

ENDEN, T.; RESCH, S.; WHITE, C.; WIK, H. S.; KLØW, N. E.; SANDSET, P. M.

2013-01-01

Summary Background Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). Objectives To estimate the cost effectiveness of additional CDT compared with standard treatment alone. Methods Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). Results In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64 709 for additional CDT and $51 866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20 429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55 000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50 000/QALY gained. Conclusions Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding. PMID:23452204

C/EBPα regulates CRL4Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint

PubMed Central

Hall, Jonathan R; Bereman, Michael S; Nepomuceno, Angelito I; Thompson, Elizabeth A; Muddiman, David C; Smart, Robert C

2014-01-01

The bZIP transcription factor, C/EBPα is highly inducible by UVB and other DNA damaging agents in keratinocytes. C/EBPα-deficient keratinocytes fail to undergo cell cycle arrest in G1 in response to UVB-induced DNA damage and mice lacking epidermal C/EBPα are highly susceptible to UVB-induced skin cancer. The mechanism through which C/EBPα regulates the cell cycle checkpoint in response to DNA damage is unknown. Here we report untreated C/EBPα-deficient keratinocytes have normal levels of the cyclin-dependent kinase inhibitor, p21, however, UVB-treated C/EBPα-deficient keratinocytes fail to up-regulate nuclear p21 protein levels despite normal up-regulation of Cdkn1a mRNA levels. UVB-treated C/EBPα-deficient keratinocytes displayed a 4-fold decrease in nuclear p21 protein half-life due to the increased proteasomal degradation of p21 via the E3 ubiquitin ligase CRL4Cdt2. Cdt2 is the substrate recognition subunit of CRL4Cdt2 and Cdt2 mRNA and protein levels were up-regulated in UVB-treated C/EBPα-deficient keratinocytes. Knockdown of Cdt2 restored p21 protein levels in UVB-treated C/EBPα-deficient keratinocytes. Lastly, the failure to accumulate p21 in response to UVB in C/EBPα-deficient keratinocytes resulted in decreased p21 interactions with critical cell cycle regulatory proteins, increased CDK2 activity, and inappropriate entry into S-phase. These findings reveal C/EBPα regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4Cdt2 mediated degradation of p21. PMID:25483090

PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase η and κ focus formation on UV damage.

PubMed

Tsanov, Nikolay; Kermi, Chames; Coulombe, Philippe; Van der Laan, Siem; Hodroj, Dana; Maiorano, Domenico

2014-04-01

Proliferating cell nuclear antigen (PCNA) is a well-known scaffold for many DNA replication and repair proteins, but how the switch between partners is regulated is currently unclear. Interaction with PCNA occurs via a domain known as a PCNA-Interacting Protein motif (PIP box). More recently, an additional specialized PIP box has been described, the « PIP degron », that targets PCNA-interacting proteins for proteasomal degradation via the E3 ubiquitin ligase CRL4(Cdt2). Here we provide evidence that CRL4(Cdt2)-dependent degradation of PIP degron proteins plays a role in the switch of PCNA partners during the DNA damage response by facilitating accumulation of translesion synthesis DNA polymerases into nuclear foci. We show that expression of a nondegradable PIP degron (Cdt1) impairs both Pol η and Pol κ focus formation on ultraviolet irradiation and reduces cell viability, while canonical PIP box-containing proteins have no effect. Furthermore, we identify PIP degron-containing peptides from several substrates of CRL4(Cdt2) as efficient inhibitors of Pol η foci formation. By site-directed mutagenesis we show that inhibition depends on a conserved threonine residue that confers high affinity for PCNA-binding. Altogether these findings reveal an important regulative role for the CRL4(Cdt2) pathway in the switch of PCNA partners on DNA damage.

ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication

PubMed Central

Iwahori, Satoko; Kohmon, Daisuke; Kobayashi, Junya; Tani, Yuhei; Yugawa, Takashi; Komatsu, Kenshi; Kiyono, Tohru; Sugimoto, Nozomi; Fujita, Masatoshi

2014-01-01

Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to DNA double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also by some changes in chromatin architecture, suggesting potential ATM function in cell cycle control. Here, we found that ATM is involved in timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least in certain cell types, degradation of p27Kip1 was also impaired by ATM inhibition. The novel ATM function for Cdt1 regulation was dependent on its kinase activity and NBS1. Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S phase. ATM silencing induced partial reduction in levels of Skp2, a component of SCFSkp2 ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2 silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as reported previously, ATM silencing partially prevented Akt phosphorylation at Ser473, indicative of its activation, and Akt inhibition led to modest stabilization of Cdt1. Therefore, the ATM-Akt-SCFSkp2 pathway may partly contribute to the novel ATM function. Finally, ATM inhibition rendered cells hypersensitive to induction of re-replication, indicating importance for maintenance of genome stability. PMID:24280901

Impact of CDT Toxin on Human Diseases.

PubMed

Faïs, Tiphanie; Delmas, Julien; Serres, Arnaud; Bonnet, Richard; Dalmasso, Guillaume

2016-07-15

Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects.

Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury

PubMed Central

Greune, Lilo; Jarosch, Kevin-André; Steil, Daniel; Zhang, Wenlan; He, Xiaohua; Lloubes, Roland; Fruth, Angelika; Kim, Kwang Sik; Schmidt, M. Alexander; Dobrindt, Ulrich; Mellmann, Alexander; Karch, Helge

2017-01-01

Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury. We demonstrate that O157 OMVs carry a cocktail of key virulence factors of EHEC O157 including Shiga toxin 2a (Stx2a), cytolethal distending toxin V (CdtV), EHEC hemolysin, and flagellin. The toxins are internalized by cells via dynamin-dependent endocytosis of OMVs and differentially separate from vesicles during intracellular trafficking. Stx2a and CdtV-B, the DNase-like CdtV subunit, separate from OMVs in early endosomes. Stx2a is trafficked, in association with its receptor globotriaosylceramide within detergent-resistant membranes, to the Golgi complex and the endoplasmic reticulum from where the catalytic Stx2a A1 fragment is translocated to the cytosol. CdtV-B is, after its retrograde transport to the endoplasmic reticulum, translocated to the nucleus to reach DNA. CdtV-A and CdtV-C subunits remain OMV-associated and are sorted with OMVs to lysosomes. EHEC hemolysin separates from OMVs in lysosomes and targets mitochondria. The OMV-delivered CdtV-B causes cellular DNA damage, which activates DNA damage responses leading to G2 cell cycle arrest. The arrested cells ultimately die of apoptosis induced by Stx2a and CdtV via caspase-9 activation. By demonstrating that naturally secreted EHEC O157 OMVs carry and deliver into cells a cocktail of biologically active virulence factors, thereby causing cell death, and by performing first comprehensive analysis of intracellular trafficking of OMVs and OMV-delivered virulence factors, we provide new insights into the pathogenesis of EHEC O157 infections. Our data have implications for considering O157 OMVs as vaccine candidates. PMID:28158302

Validation of a Spanish translation of the CLOX for use in Hispanic samples: the Hispanic EPESE study.

PubMed

Royall, Donald R; Espino, David V; Polk, Marsha J; Verdeja, Regina; Vale, Sandra; Gonzales, Hector; Palmer, Raymond R; Markides, Kyriakos P

2003-02-01

Clock drawing tests (CDT) appear to be less vulnerable to linguistic, cultural, or educational bias than traditional dementia screening instruments. We investigated a Spanish language translation of CLOX: an executive CDT, in a community sample of Hispanic elders. In-home CLOX evaluations of 1309 Mexican-American elders were reviewed. Both CLOX1 (an executive CDT) and CLOX2 (a constructional CDT) showed good internal consistency (Chronbach's alpha; both alpha = 0.82). Cultural-demographic variables had little effect on CLOX scores. Although language had a significant effect on CLOX1 failure rates, this was not mediated by age, education, acculturation or income. These results suggest that the Spanish CLOX can be validly administered to community-based Hispanic elder samples regardless of education or acculturation. Copyright 2003 John Wiley & Sons, Ltd.

PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase η and κ focus formation on UV damage

PubMed Central

Tsanov, Nikolay; Kermi, Chames; Coulombe, Philippe; Van der Laan, Siem; Hodroj, Dana; Maiorano, Domenico

2014-01-01

Proliferating cell nuclear antigen (PCNA) is a well-known scaffold for many DNA replication and repair proteins, but how the switch between partners is regulated is currently unclear. Interaction with PCNA occurs via a domain known as a PCNA-Interacting Protein motif (PIP box). More recently, an additional specialized PIP box has been described, the « PIP degron », that targets PCNA-interacting proteins for proteasomal degradation via the E3 ubiquitin ligase CRL4Cdt2. Here we provide evidence that CRL4Cdt2-dependent degradation of PIP degron proteins plays a role in the switch of PCNA partners during the DNA damage response by facilitating accumulation of translesion synthesis DNA polymerases into nuclear foci. We show that expression of a nondegradable PIP degron (Cdt1) impairs both Pol η and Pol κ focus formation on ultraviolet irradiation and reduces cell viability, while canonical PIP box-containing proteins have no effect. Furthermore, we identify PIP degron-containing peptides from several substrates of CRL4Cdt2 as efficient inhibitors of Pol η foci formation. By site-directed mutagenesis we show that inhibition depends on a conserved threonine residue that confers high affinity for PCNA-binding. Altogether these findings reveal an important regulative role for the CRL4Cdt2 pathway in the switch of PCNA partners on DNA damage. PMID:24423875

The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid.

PubMed

Wising, Catharina; Mölne, Lena; Jonsson, Ing-Marie; Ahlman, Karin; Lagergård, Teresa

2005-05-01

Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits cultured cell proliferation, leading to cell death. A rabbit model of dermal infection was used to investigate the roles of H. ducreyi bacteria and HdCDT in the development, clinical appearance, and persistence of infection. A non-toxin producing H. ducreyi strain, and for comparison purposes a non-capsulated Haemophilus influenzae strain, were inoculated intradermally, with and without co-administration of purified HdCDT. Co-administration of HdCDT resulted in significant aggravation of H. ducreyi-induced inflammatory lesions, and development of ulcers in rabbit skin. Less pronounced inflammatory lesions and lack of epithelial eruption were observed after inoculation with H. influenzae. Histopathological sections of the H. ducreyi-induced lesions, in both the presence and absence of HdCDT, showed dense infiltrates of the same type inflammatory cells, with the exception of a prominent endothelial cell proliferation noted in sections from lesions caused by H. ducreyi and toxin. Signs of chronic inflammation with involvement of T cells, macrophages, eosinophils, and granuloma formation were observed after H. ducreyi inoculation both with and without toxin. In conclusion, H. ducreyi causes a pronounced, chronic inflammation with involvement of T cells and macrophages, and in combination with HdCDT production of ulcers in the rabbit model. These pathogenic mechanisms may promote the development and persistence of chancroid ulcers.

A New Type of Toxin A-Negative, Toxin B-Positive Clostridium difficile Strain Lacking a Complete tcdA Gene

PubMed Central

Marín, Mercedes; Martín, Adoración; Rupnik, Maja

2014-01-01

Toxins A and B are the main virulence factors of Clostridium difficile and are the targets for molecular diagnostic tests. Here, we describe a new toxin A-negative, toxin B-positive, binary toxin CDT (Clostridium difficile transferase)-negative (A− B+ CDT−) toxinotype (XXXII) characterized by a variant type of pathogenicity locus (PaLoc) without tcdA and with atypical organization of the PaLoc integration site. PMID:25428159

The influence of education on performance of adults on the Clock Drawing Test.

PubMed

de Noronha, Ísis Franci Cavalcanti; Barreto, Simone Dos Santos; Ortiz, Karin Zazo

2018-01-01

The Clock Drawing Test (CDT) is an important instrument for screening individuals suspected of having cognitive impairment. To determine the influence of education on the performance of healthy adults on the CDT. A total of 121 drawings by healthy adults without neurological complaints or impairments were analysed. Participants were stratified by educational level into 4 subgroups: 27 illiterate adults, 34 individuals with 1-4 years of formal education, 30 with 5-11 years, and 30 adults with >11 years' formal education. Scores on the CDT were analyzed based on a scale of 1-10 points according to the criteria of Sunderland et al. (1989).¹ The Kruskal-Wallis test was applied to compare the different education groups. Tukey's multiple comparisons test was used when a significant factor was found. Although scores were higher with greater education, statistically significant differences on the CDT were found only between the illiterate and other educated groups. The CDT proved especially difficult for illiterate individuals, who had lower scores. These results suggest that this screening test is suitable for assessing mainly visuoconstructional praxis and providing an overall impression of cognitive function among individuals, independently of years of education.

The influence of education on performance of adults on the Clock Drawing Test

PubMed Central

de Noronha, Ísis Franci Cavalcanti; Barreto, Simone dos Santos; Ortiz, Karin Zazo

2018-01-01

ABSTRACT The Clock Drawing Test (CDT) is an important instrument for screening individuals suspected of having cognitive impairment. Objective: To determine the influence of education on the performance of healthy adults on the CDT. Methods: A total of 121 drawings by healthy adults without neurological complaints or impairments were analysed. Participants were stratified by educational level into 4 subgroups: 27 illiterate adults, 34 individuals with 1-4 years of formal education, 30 with 5-11 years, and 30 adults with >11 years' formal education. Scores on the CDT were analyzed based on a scale of 1-10 points according to the criteria of Sunderland et al. (1989).¹ The Kruskal-Wallis test was applied to compare the different education groups. Tukey's multiple comparisons test was used when a significant factor was found. Results: Although scores were higher with greater education, statistically significant differences on the CDT were found only between the illiterate and other educated groups. Conclusion: The CDT proved especially difficult for illiterate individuals, who had lower scores. These results suggest that this screening test is suitable for assessing mainly visuoconstructional praxis and providing an overall impression of cognitive function among individuals, independently of years of education. PMID:29682235

Antibiotic Susceptibility, Genetic Diversity, and the Presence of Toxin Producing Genes in Campylobacter Isolates from Poultry.

PubMed

Lee, Jeeyeon; Jeong, Jiyeon; Lee, Heeyoung; Ha, Jimyeong; Kim, Sejeong; Choi, Yukyung; Oh, Hyemin; Seo, Kunho; Yoon, Yohan; Lee, Soomin

2017-11-17

This study examined antibiotic susceptibility, genetic diversity, and characteristics of virulence genes in Campylobacter isolates from poultry. Chicken ( n = 152) and duck ( n = 154) samples were collected from 18 wet markets in Korea. Campylobacter spp. isolated from the carcasses were identified by PCR. The isolated colonies were analyzed for antibiotic susceptibility to chloramphenicol, amikacin, erythromycin, tetracycline, ciprofloxacin, nalidixic acid, and enrofloxacin. The isolates were also used to analyze genetic diversity using the DiversiLab TM system and were tested for the presence of cytolethal distending toxin ( cdt ) genes. Campylobacter spp. were isolated from 45 poultry samples out of 306 poultry samples (14.7%) and the average levels of Campylobacter contamination were 22.0 CFU/g and 366.1 CFU/g in chicken and duck samples, respectively. Moreover, more than 90% of the isolates showed resistance to nalidixic acid and ciprofloxacin. Genetic correlation analysis showed greater than 95% similarity between 84.4% of the isolates, and three cdt genes ( cdtA , cdtB , and cdtC ) were present in 71.1% of Campylobacter isolates. These results indicate that Campylobacter contamination should be decreased to prevent and treat Campylobacter foodborne illness.

The interaction between manganese exposure and alcohol on neurobehavioral outcomes in welders.

PubMed

Ellingsen, Dag G; Kusraeva, Zarina; Bast-Pettersen, Rita; Zibarev, Evgenij; Chashchin, Maxim; Thomassen, Yngvar; Chashchin, Valery

2014-01-01

Neurobehavioral functions were studied in 137 welders exposed to the geometric mean (GM) air concentration of 214 μg/m(3) (range 1-3230) of manganese (Mn) based on the individual mean from two days of air sampling. Only 22 μg/m(3) (GM) was soluble in the artificial lung fluid Hatch solution. The welders were compared to 137 referents (turner/fitters) recruited from the same plants. The GM concentrations of Mn in whole blood (B-Mn) and urine (U-Mn) were 12.8 μg/L and 0.36 μg/g creatinine versus 8.0 μg/L and 0.07 μg/g creatinine in the referents. Alcohol consumption was assessed by measuring carbohydrate deficient transferrin in serum (sCDT). The welders had poorer performance than the referents on the Grooved Pegboard, Finger Tapping, Simple Reaction Time (SRT) and possibly the Maximum Frequency tests. They also reported more subjective symptoms. Welders with sCDT above the upper reference limit had substantially poorer performances on the Grooved Pegboard test, Finger Tapping test and SRT than welders with sCDT below this level. No effect of high sCDT was observed in the referents, indicating an interaction between high sCDT and exposure to Mn for these tests. Self-reported alcohol consumption had no impact on these neurobehavioral test results. A statistically significant difference in the SRT and Grooved Pegboard test results remained after excluding all subjects with sCDT above the normal level, but the difference in test scores between the groups was smaller. These welders also reported more subjective symptoms than the referents. The results suggest that sCDT should be measured in neurobehavioral studies of occupationally Mn exposed populations for a more precise estimation of high alcohol consumption. Copyright © 2013 Elsevier Inc. All rights reserved.

[Multisite validation of CDT measurement by the %CDT TIA and the Tina Quant %CDT kits].

PubMed

Boehrer, J L; Cano, Y; Capolaghi, B; Desch, G; Dosbaa, I; Estepa, L; Hennache, B; Schellenberg, F

2007-01-01

The measurement of CDT (Carbohydrate Deficient Transferrin) is an essential biological tool in the diagnosis and follow-up of alcohol abuse. It is also employed as a marker of abstinence for the restitution of driving licences. However, the precision of measurement, and the between laboratory homogeneity of the results are still discussed. The ion exchange followed by immunodetermination of CDT is available in two products, the Tina Quant %CDT (Roche, Mannheim, Germany) and the %CDT TIA (Bio-Rad, Hercules, United States). This multicentre study was undertaken: 1) to evaluate the analytical characteristics of these kits and the homogeneity of the results from one laboratory to another, independently of the method used, 2) to validate the differences between the proposed normal values of both kits, 3) to study the possibility of using commercial control sera as external quality control. Four analytical systems were included in the study (Roche Modular/Hitachi 717, Beckman Coulter Immage and LX20, Dade Behring BNII). Determinations were carried out on pools of sera, commercial control sera, kit controls, and 30 serums of patients. These latter were also analyzed in capillary electrophoresis in order to establish correlations between the techniques. The calibrations were stable over one 2 weeks period. The repeatability of measurements spread out from 3,1% to 24,7%, for a mean value lower than 10%. The commercial control sera provided reliable results, with values adapted to a routine quality control use. The results of the Bio-Rad applications were lower by approximately 20% than those of the Roche application, which justifies the difference of the normal values (2,6% versus 3%), and an identical classification of the patients in at least 27 of the 30 samples. We conclude that the analytical quality of the compared techniques, even if it could be improved, is sufficient to guarantee a good reliability of the results. An external quality control could be proposed by using the control sera that we tested.

Fluorescent adduct formation with terbium: a novel strategy for transferrin glycoform identification in human body fluids and carbohydrate-deficient transferrin HPLC method validation.

PubMed

Sorio, Daniela; De Palo, Elio Franco; Bertaso, Anna; Bortolotti, Federica; Tagliaro, Franco

2017-02-01

This paper puts forward a new method for the transferrin (Tf) glycoform analysis in body fluids that involves the formation of a transferrin-terbium fluorescent adduct (TfFluo). The key idea is to validate the analytical procedure for carbohydrate-deficient transferrin (CDT), a traditional biochemical serum marker to identify chronic alcohol abuse. Terbium added to a human body-fluid sample produced TfFluo. Anion exchange HPLC technique, with fluorescence detection (λ exc 298 nm and λ em 550 nm), permitted clear separation and identification of Tf glycoform peaks without any interfering signals, allowing selective Tf sialoforms analysis in human serum and body fluids (cadaveric blood, cerebrospinal fluid, and dried blood spots) hampered for routine test. Serum samples (n = 78) were analyzed by both traditional absorbance (Abs) and fluorescence (Fl) HPLC methods and CDT% levels demonstrated a significant correlation (p < 0.001 Pearson). Intra- and inter-runs CV% was 3.1 and 4.6%, respectively. The cut-off of 1.9 CDT%, related to the HPLC Abs proposed as the reference method, by interpolation in the correlation curve with the present method demonstrated a 1.3 CDT% cut-off. Method comparison by Passing-Bablok and Bland-Altman tests demonstrated Fl versus Abs agreement. In conclusion, the novel method is a reliable test for CDT% analysis and provides a substantial analytical improvement offering important advantages in terms of types of body fluid analysis. Its sensitivity and absence of interferences extend clinical applications being reliable for CDT assay on body fluids usually not suitable for routine test. Graphical Abstract The formation of a transferrin-terbium fluorescent adduct can be used to analyze the transferrin glycoforms. The HPLC method for carbohydrate-deficient transferrin (CDT%) measurement was validated and employed to determine the levels in different body fluids.

Incidence and Outcomes of Inferior Vena Cava Filter Thrombus during Catheter-directed Thrombolysis for Proximal Deep Venous Thrombosis.

PubMed

Jiang, Jianguang; Tu, Jianfei; Jia, Zhongzhi; Chen, Jiezhong; Cao, Haitao; Meng, Qingli; Fuller, Tyler A; Tian, Feng

2017-01-01

The aim of the study was to retrospectively evaluate the incidence and outcomes of inferior vena cava (IVC) filter thrombus during catheter-directed thrombolysis (CDT) for acute proximal deep venous thrombosis (DVT). From October 2006 to June 2015, patients diagnosed with acute proximal DVT and received CDT after a retrievable IVC filter was placed were included. The incidence, treatment, and outcomes of IVC filter thrombus during CDT were recorded and analyzed. A total of 189 patients (91 women, 98 men; mean age, 57.6 ± 9.8 years; range, 24-85 years) were included in this study. Among the 189 cases, the DVTs involved popliteal iliofemoral veins in 54 patients, iliofemoral veins in 113 patients, and iliac veins in 22 patients, of which 18 patients had thrombus extended into the IVC. Of the 189 patients, a total of 8 (4.2%, 8 of 189) patients were identified with IVC filter thrombus during CDT. The IVC filter thrombus was detected on a median of 2 days (range, 2-4 days) of CDT therapy, including small-size (n = 6) and large-size (n = 2) filter thrombus. Of the 8 patients, CDTs were performed with a mean 7.6 ± 1.1 days (range, 6-11 days) after the presence of symptoms for the treatment of proximal DVT, and all the IVC filter thrombi were lysed during CDT for the proximal DVT. All the IVC filters were removed successfully with a mean of 12.8 ± 0.93 days from placement. There were no procedure- or thrombolysis-related major complications, and no symptomatic pulmonary embolism breakthrough was seen in any of the patients after the filter placement. IVC filter thrombus during CDT for the acute proximal DVT is uncommon, and all of them did not need any additional treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Charged Coupled Device Debris Telescope Observations of the Geosynchronous Orbital Debris Environment - Observing Year: 1998

NASA Technical Reports Server (NTRS)

Jarvis, K. S.; Thumm, T. L.; Matney, M. J.; Jorgensen, K.; Stansbery, E. G.; Africano, J. L.; Sydney, P. F.; Mulrooney, M. K.

2002-01-01

NASA has been using the charged coupled device (CCD) debris telescope (CDT)--a transportable 32-cm Schmidt telescope located near Cloudcroft, New Mexico-to help characterize the debris environment in geosynchronous Earth orbit (GEO). The CDT is equipped with a SITe 512 x 512 CCD camera whose 24 m2 (12.5 arc sec) pixels produce a 1.7 x 1.7-deg field of view. The CDT system can therefore detect l7th-magnitude objects in a 20-sec integration corresponding to an approx. 0.6-m diameter, 0.20 albedo object at 36,000 km. The telescope pointing and CCD operation are computer controlled to collect data automatically for an entire night. The CDT has collected more than 1500 hrs of data since November 1997. This report describes the collection and analysis of 58 nights (approx. 420 hrs) of data acquired in 1998.

Coherent destruction of tunneling in two-level system driven across avoided crossing via photon statistics

PubMed Central

Miao, Qiang; Zheng, Yujun

2016-01-01

In this paper, the nature of the multi-order resonance and coherent destruction of tunneling (CDT) for two-level system driven cross avoided crossing is investigated by employing the emitted photons 〈N〉 and the Mandel’s Q parameter based on the photon counting statistics. An asymmetric feature of CDT is shown in the spectrum of Mandel’s Q parameter. Also, the CDT can be employed to suppress the spontaneous decay and prolong waiting time noticeably. The photon emission pattern is of monotonicity in strong relaxation, and homogeneity in pure dephasing regime, respectively. PMID:27353375

Efficient Parvovirus Replication Requires CRL4Cdt2-Targeted Depletion of p21 to Prevent Its Inhibitory Interaction with PCNA

PubMed Central

Pintel, David J.

2014-01-01

Infection by the autonomous parvovirus minute virus of mice (MVM) induces a vigorous DNA damage response in host cells which it utilizes for its efficient replication. Although p53 remains activated, p21 protein levels remain low throughout the course of infection. We show here that efficient MVM replication required the targeting for degradation of p21 during this time by the CRL4Cdt2 E3-ubiquitin ligase which became re-localized to MVM replication centers. PCNA provides a molecular platform for substrate recognition by the CRL4Cdt2 E3-ubiquitin ligase and p21 targeting during MVM infection required its interaction both with Cdt2 and PCNA. PCNA is also an important co-factor for MVM replication which can be antagonized by p21 in vitro. Expression of a stable p21 mutant that retained interaction with PCNA inhibited MVM replication, while a stable p21 mutant which lacked this interaction did not. Thus, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, efficient viral replication required subsequent depletion of p21 to abrogate its inhibition of PCNA. PMID:24699724

Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA.

PubMed

Adeyemi, Richard O; Fuller, Matthew S; Pintel, David J

2014-04-01

Infection by the autonomous parvovirus minute virus of mice (MVM) induces a vigorous DNA damage response in host cells which it utilizes for its efficient replication. Although p53 remains activated, p21 protein levels remain low throughout the course of infection. We show here that efficient MVM replication required the targeting for degradation of p21 during this time by the CRL4Cdt2 E3-ubiquitin ligase which became re-localized to MVM replication centers. PCNA provides a molecular platform for substrate recognition by the CRL4Cdt2 E3-ubiquitin ligase and p21 targeting during MVM infection required its interaction both with Cdt2 and PCNA. PCNA is also an important co-factor for MVM replication which can be antagonized by p21 in vitro. Expression of a stable p21 mutant that retained interaction with PCNA inhibited MVM replication, while a stable p21 mutant which lacked this interaction did not. Thus, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, efficient viral replication required subsequent depletion of p21 to abrogate its inhibition of PCNA.

Dose-effect relation between daily ethanol intake in the range 0-70 grams and %CDT value: validation of a cut-off value.

PubMed

Schellenberg, François; Schwan, Raymund; Mennetrey, Louise; Loiseaux, Marie-Nadia; Pagès, Jean Christophe; Reynaud, Michel

2005-01-01

To evaluate the ability to infer alcohol consumption using the %CDT (carbohydrate deficient transferrin) immunoassay (Axis Shield). One hundred and eighty-three healthy subjects (143 men, 40 women) undergoing a routine medical check-up at their workplace declared frequency and quantity of alcohol consumption covering the last 4 weeks. Seven sub-groups were made up from this population, according to daily ethanol intake and by increments of 10 g from 0 to 70 g/day. A reference group that consisted of 133 healthy teetotallers (74 men, 59 women) was recruited by occupational medicine in the same conditions as the 183 subjects of the study. Percentage CDT and gamma glutamyl transferase (GGT) were assayed on a fasting blood sample. There was a proportional dose-response effect of daily ethanol intake on %CDT values in the range of 0-70 g per day. A threshold effect on %CDT values for patients having an alcohol intake of over 40 g per day was found, an effect which was not observed for GGT activity. The kit has clinical usefulness, and the value of 2.6% proposed by the manufacturer for the cut-off for hazardous drinking in both sexes has been validated.

The influence of asymmetric convections on typhoon cyclonic deflection tracks across Taiwan

NASA Astrophysics Data System (ADS)

Hsu, L. H.; Su, S. H.

2016-12-01

This study focus on the mechanisms of typhoon cyclonic deflection tracks (CDT) approaching the east coast of Taiwan. We analyzed for 84 landfall typhoons which has 49 CDT cases, 18 cases are with very large deflection angles (DA) ( > 20°) and another 7 cases are with cyclonic looping tracks (CLT). Most of the large DA and CLT cases are with relatively slow translation speeds of 4 m s-1 and occurred near the east coast, north of 23 °N in Taiwan. The Weather Research and Forecasting (WRF) Model was used to simulate the typhoon CDT cases. We use the potential vorticity (PV) tendency diagnosis to analyze the typhoon movements, and decompose the wave number one component of PV tendencies into horizontal advection (HA), vertical advection (VA) and diabatic heating (DH) terms. The northern landfall storms have significant vorticity stretching and subsidence warming to the south of the storm. The subsidence warming suppresses convections and produces heating asymmetries for the typhoon structure. The vorticity stretching (VA effect) and diabatic heating asymmetries (DH effect) which lead the southwestward deflection storm motion. The HA effect in general does not contribute to the CDT. Our results highlight the effects of vorticity stretching and asymmetric convective heating in producing the CDT to north of 23 °N near the east coast of Taiwan.

Anatomic and functional outcomes of pharmacomechanical and catheter-directed thrombolysis of iliofemoral deep venous thrombosis.

PubMed

Hager, Eric; Yuo, Theodore; Avgerinos, Efthymios; Naddaf, Abdullah; Jeyabalan, Geetha; Marone, Luke; Chaer, Rabih

2014-07-01

Pharmacomechanical thrombolysis (PMT) and catheter-directed thrombolysis (CDT) are commonly used for the treatment of iliofemoral deep venous thrombosis (DVT). The purpose of this study was to examine the short- and long-term venous patency and venous valvular function as well as clinical outcomes of patients treated for iliofemoral DVT by PMT and CDT. A retrospective review of all patients with symptomatic DVT treated between 2006 and 2011 with PMT or CDT was performed. All patients were treated by local tissue plasminogen activator delivered with PMT or CDT. Patients were divided into two groups on the basis of initial treatment modality: patients treated by PMT alone (group 1), and those who underwent PMT and CDT or CDT alone (group 2). Group comorbidities, initial presenting symptoms, and Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification scores were compared. Postprocedural duplex ultrasound was used to assess valve function and treated vein patency rates. At all visits, Villalta and CEAP scores were recorded and compared. Group demographic and procedural results were analyzed by Fisher exact test for dichotomous variables and Kruskal-Wallis equality-of-populations rank test for the ordinal and continuous data. Kaplan-Meier survival estimates were used to assess preserved valve function as well as primary and secondary patency rates. There were 79 patients with 102 limbs treated for extensive iliofemoral DVT (median age, 51.5 years; range, 16.6-83.8 years). There were 18 patients in group 1 and 61 patients in group 2 (PMT + CDT [n = 54] or CDT alone [n = 7]). There were no differences in demographics or comorbidities between groups aside from malignant disease, which was more common in group 1 (35.3% vs 11.5%; P = .03). A total of 102 limbs were analyzed, 24 in group 1 and 78 in group 2. Patients in group 1 had a shorter symptom duration compared with group 2 (7 days vs 16 days; P = .011). The median number of procedures in group 1 was lower than in group 2 (P < .001). At last clinical follow-up, there was no significant difference between the Villalta and CEAP scores or the rate of clinical improvement in symptoms between groups. By Kaplan-Meier analysis, there was no difference in primary patency, secondary patency, and treated valve function at 48 months. This study suggests that PMT as a stand-alone therapy is as effective as CDT with or without PMT in preserving valve function and preventing postthrombotic syndrome. Long-term physiologic and functional outcomes are comparable between the modalities, with preserved venous valve function in the majority of patients. Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

PCNA-coupled p21 degradation after DNA damage: The exception that confirms the rule?

PubMed

Soria, Gastón; Gottifredi, Vanesa

2010-04-04

While many are the examples of DNA damaging treatments that induce p21 accumulation, the conception of p21 upregulation as the universal response to genotoxic stress has come to an end. Compelling evidences have demonstrated the existence of converging signals that negatively regulate p21 bellow basal levels when replication forks are blocked. Moreover, conclusive reports identified the E3-ligase CRL4(CDT2) (CUL4-DDB1-CDT2) as the enzymatic complex that promotes p21 proteolysis when treatments such as UV irradiation trigger replication fork stress. A pre-requisite for CRL4(CDT2)-driven proteolysis is the interaction of p21 with PCNA. Interestingly as well, CRL4(CDT2)-dependent proteolysis is not limited to p21 and affects other PCNA partners, including the specialized DNA polymerase eta (pol eta). These recent discoveries are particularly intriguing since the UV-induced degradation of p21 has been shown to be required for efficient pol eta recruitment to DNA lesions. Herein we review the findings that lead to the identification of the molecular mechanism that triggers damage-induced PCNA-coupled protein proteolysis. We propose a novel model in which CRL4(CDT2)-dependent protein degradation facilitates a sequential and dynamic exchange between PIP box bearing proteins at stall forks during Translesion DNA synthesis (TLS). Moreover, given the tight spatiotemporal control that CRL4(CDT2)-driven proteolysis is able to confer to PCNA-regulated processes, we discuss the impact that this degradation mechanism might have in other molecular switches associated with the repair of damaged DNA. 2010 Elsevier B.V. All rights reserved.

Cdt2-mediated XPG degradation promotes gap-filling DNA synthesis in nucleotide excision repair

PubMed Central

Han, Chunhua; Wani, Gulzar; Zhao, Ran; Qian, Jiang; Sharma, Nidhi; He, Jinshan; Zhu, Qianzheng; Wang, Qi-En; Wani, Altaf A

2015-01-01

Xeroderma pigmentosum group G (XPG) protein is a structure-specific repair endonuclease, which cleaves DNA strands on the 3′ side of the DNA damage during nucleotide excision repair (NER). XPG also plays a crucial role in initiating DNA repair synthesis through recruitment of PCNA to the repair sites. However, the fate of XPG protein subsequent to the excision of DNA damage has remained unresolved. Here, we show that XPG, following its action on bulky lesions resulting from exposures to UV irradiation and cisplatin, is subjected to proteasome-mediated proteolytic degradation. Productive NER processing is required for XPG degradation as both UV and cisplatin treatment-induced XPG degradation is compromised in NER-deficient XP-A, XP-B, XP-C, and XP-F cells. In addition, the NER-related XPG degradation requires Cdt2, a component of an E3 ubiquitin ligase, CRL4Cdt2. Micropore local UV irradiation and in situ Proximity Ligation assays demonstrated that Cdt2 is recruited to the UV-damage sites and interacts with XPG in the presence of PCNA. Importantly, Cdt2-mediated XPG degradation is crucial to the subsequent recruitment of DNA polymerase δ and DNA repair synthesis. Collectively, our data support the idea of PCNA recruitment to damage sites which occurs in conjunction with XPG, recognition of the PCNA-bound XPG by CRL4Cdt2 for specific ubiquitylation and finally the protein degradation. In essence, XPG elimination from DNA damage sites clears the chromatin space needed for the subsequent recruitment of DNA polymerase δ to the damage site and completion of gap-filling DNA synthesis during the final stage of NER. PMID:25483071

Fatty acid ethyl ester concentrations in hair and self-reported alcohol consumption in 644 cases from different origin.

PubMed

Süsse, Silke; Selavka, Carl M; Mieczkowski, Tom; Pragst, Fritz

2010-03-20

For diagnosis of chronic alcohol abuse, fatty acid ethyl esters (FAEE) were determined in hair samples from 644 individuals, mainly parents from child protection cases. The analysis for ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate was performed according to a validated procedure consisting of external degreasing by two times washing with n-heptane, extraction with a mixture of dimethylsulfoxide and n-heptane, separation and evaporation of the n-heptane layer, headspace solid phase microextraction of the residue after addition of phosphate buffer pH 7.6 and gas chromatography-mass spectrometry using deuterated internal standards. For interpretation, the sum of the concentrations of the four esters C(FAEE) was used with the cut-off's 0.5 ng/mg for the proximal scalp hair segment 0-3 cm or less and 1.0 ng/mg for scalp hair samples with a length between 3 and 6 cm and for body hair. C(FAEE) ranged from 0.11 to 31 ng/mg (mean 1.77 ng/mg, median 0.82 ng/mg). The mean concentration ratio between the 4 esters was 8:45:38:9. 298 cases had C(FAEE) above the cut-off's. Self-reported drinking data were obtained in 553 of the cases in the categories abstinent (156 cases), moderate drinking (252 cases) and excessive drinking (145 cases). Median and box-plot data clearly demonstrate differentiation of these ingestor sub-populations by C(FAEE). However, in the abstinent and moderate groups the consumption was frequently underreported (37 and 110 cases positive) whereas in the group self-reported excessive drinking 32 cases were negative. Comparison of C(FAEE) with carbohydrate-deficient transferrin (CDT) in 139 cases and gamma-glutamyltransferase (GGT) in 136 cases showed a good agreement in CDT- and GGT positive cases (27/28 and 32/41) but a large portion of the negative CDT- and GGT-results with positive hair test (44/100 and 48/95) which is explained mainly by the much shorter time window of CDT and GGT. No significant correlation was found between persons weight and C(FAEE) showing that the test is not biased against physical fitness or obesity. Furthermore, there was no statistically significant difference between scalp hair (541 samples) and hair from other body sites (84 samples). In conclusion, FAEE in hair appeared to be suitable markers for the detection of excessive drinking. However, as there is no proportionality between drinking amount and C(FAEE), the additional use of other markers can increase the reliability of the interpretation. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Phenotypic Detection of Metallo-β-Lactamase in Imipenem-Resistant Pseudomonas aeruginosa

PubMed Central

Khosravi, Yalda; Loke, Mun Fai; Chua, Eng Guan; Tay, Sun Tee; Vadivelu, Jamuna

2012-01-01

Carbapenems are the primary choice of treatment for severe Pseudomonas aeruginosa infection. However, the emergence of carbapenem resistance due to the production of metallo-β-lactamases (MBLs) is of global concern. In this study, 90 imipenem- (IPM- or IP-) resistant P. aeruginosa (IRPA) isolates, including 32 previously tested positive and genotyped for MBL genes by PCR, were subjected to double-disk synergy test (DDST), combined disk test (CDT), and imipenem/imipenem-inhibitor (IP/IPI) E-test to evaluate their MBLs detection capability. All three methods were shown to have a sensitivity of 100%. However, DDST was the most specific of the three (96.6%), followed by IP/IPI E-test interpreted based on the single criteria of IP/IPI ≥8 as positive (62.1%), and CDT was the least specific (43.1%). Based on the data from this evaluation, we propose that only IRPA with IP MIC >16 μg/mL and IP/IPI ≥8 by IP/IPI E-test should be taken as positive for MBL activity. With the new dual interpretation criteria, the MBL IP/IPI E-test was shown to achieve 100% sensitivity as well as specificity for the IRPA in this study. Therefore, the IP/IPI E-test is a viable alternative phenotypic assay to detect MBL production in IRPA in our population in circumstances where PCR detection is not a feasible option. PMID:22792048

Dense proton injection into phosphate glasses using corona discharge treatment

NASA Astrophysics Data System (ADS)

Kinoshita, Takuya; Miyazaki, Atsushi; Kawaguchi, Keiga; Sakai, Daisuke; Yamaguchi, Takuya; Omata, Takahisa; Ishiyama, Tomohiro; Fujioka, Masaya; Kaiju, Hideo; Nishii, Junji

2018-01-01

Sodium ions in 25NaO1/2-6LaO3/2-6GeO2-63PO5/2 (mol%) glasses were substituted with protons using corona discharge treatment (CDT) under a H2 atmosphere. The substitution of sodium ion to proton proceeded from the anode side to the cathode side with constant current flow during the CDT. A crystalline free and transparent glass plate of 0.3 mm thickness was obtained after CDT for 96 h. The maximum decrease rate from sodium ion to proton was 78 ± 10%. The proton conductivity of 8.5 × 10-4 S/cm was attained at 400 °C.

PyCDT: A Python toolkit for modeling point defects in semiconductors and insulators

DOE PAGES

Broberg, Danny; Medasani, Bharat; Zimmermann, Nils E. R.; ...

2018-02-13

Point defects have a strong impact on the performance of semiconductor and insulator materials used in technological applications, spanning microelectronics to energy conversion and storage. The nature of the dominant defect types, how they vary with processing conditions, and their impact on materials properties are central aspects that determine the performance of a material in a certain application. This information is, however, difficult to access directly from experimental measurements. Consequently, computational methods, based on electronic density functional theory (DFT), have found widespread use in the calculation of point-defect properties. Here we have developed the Python Charged Defect Toolkit (PyCDT) tomore » expedite the setup and post-processing of defect calculations with widely used DFT software. PyCDT has a user-friendly command-line interface and provides a direct interface with the Materials Project database. This allows for setting up many charged defect calculations for any material of interest, as well as post-processing and applying state-of-the-art electrostatic correction terms. Our paper serves as a documentation for PyCDT, and demonstrates its use in an application to the well-studied GaAs compound semiconductor. As a result, we anticipate that the PyCDT code will be useful as a framework for undertaking readily reproducible calculations of charged point-defect properties, and that it will provide a foundation for automated, high-throughput calculations.« less

The Cytolethal Distending Toxin Induces Receptor Activator of NF-κB Ligand Expression in Human Gingival Fibroblasts and Periodontal Ligament Cells

PubMed Central

Belibasakis, G. N.; Johansson, A.; Wang, Y.; Chen, C.; Kalfas, S.; Lerner, U. H.

2005-01-01

Actinobacillus actinomycetemcomitans is associated with localized aggressive periodontitis, a disease characterized by rapid loss of the alveolar bone surrounding the teeth. Receptor activator of NF-κB Ligand (RANKL) and osteoprotegerin (OPG) are two molecules that regulate osteoclast formation and bone resorption. RANKL induces osteoclast differentiation and activation, whereas OPG blocks this process by acting as a decoy receptor for RANKL. The purpose of this study was to investigate the effect of A. actinomycetemcomitans on the expression of RANKL and OPG in human gingival fibroblasts and periodontal ligament cells. RANKL mRNA expression was induced in both cell types challenged by A. actinomycetemcomitans extract, whereas OPG mRNA expression remained unaffected. Cell surface RANKL protein was also induced by A. actinomycetemcomitans, whereas there was no change in OPG protein secretion. A cytolethal distending toxin (Cdt) gene-knockout strain of A. actinomycetemcomitans did not induce RANKL expression, in contrast to its wild-type strain. Purified Cdt from Haemophilus ducreyi alone, or in combination with extract from the A. actinomycetemcomitans cdt mutant strain, induced RANKL expression. Pretreatment of A. actinomycetemcomitans wild-type extract with Cdt antiserum abolished RANKL expression. In conclusion, A. actinomycetemcomitans induces RANKL expression in periodontal connective tissue cells. Cdt is crucial for this induction and may therefore be involved in the pathological bone resorption during the process of localized aggressive periodontitis. PMID:15618171

Evaluation of effective dose with chest digital tomosynthesis system using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Kim, Dohyeon; Jo, Byungdu; Lee, Youngjin; Park, Su-Jin; Lee, Dong-Hoon; Kim, Hee-Joung

2015-03-01

Chest digital tomosynthesis (CDT) system has recently been introduced and studied. This system offers the potential to be a substantial improvement over conventional chest radiography for the lung nodule detection and reduces the radiation dose with limited angles. PC-based Monte Carlo program (PCXMC) simulation toolkit (STUK, Helsinki, Finland) is widely used to evaluate radiation dose in CDT system. However, this toolkit has two significant limits. Although PCXMC is not possible to describe a model for every individual patient and does not describe the accurate X-ray beam spectrum, Geant4 Application for Tomographic Emission (GATE) simulation describes the various size of phantom for individual patient and proper X-ray spectrum. However, few studies have been conducted to evaluate effective dose in CDT system with the Monte Carlo simulation toolkit using GATE. The purpose of this study was to evaluate effective dose in virtual infant chest phantom of posterior-anterior (PA) view in CDT system using GATE simulation. We obtained the effective dose at different tube angles by applying dose actor function in GATE simulation which was commonly used to obtain the medical radiation dosimetry. The results indicated that GATE simulation was useful to estimate distribution of absorbed dose. Consequently, we obtained the acceptable distribution of effective dose at each projection. These results indicated that GATE simulation can be alternative method of calculating effective dose in CDT applications.

Quantity of residual thrombus after successful catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with recurrence.

PubMed

Aziz, F; Comerota, A J

2012-08-01

Iliofemoral deep venous thrombosis (IFDVT) is an independent risk factor for recurrent DVT. It has been observed that recurrent DVT correlates with residual thrombus. This study evaluates whether risk of recurrence is related to the amount of residual thrombus following catheter-directed thrombolysis (CDT) for IFDVT. Patients who underwent CDT for IFDVT had their degree of lysis quantified by a reader blind to the patients' long-term clinical outcome. Patients were classified into two groups, ≥50% and <50% residual thrombus. Recurrence was defined as a symptomatic presentation with image verification of new or additional thrombus. A total of 75 patients underwent CDT for IFDVT. Median follow-up was 35.9 months. Sixty-eight patients (91%) had no evidence of recurrence and seven (9%) developed recurrence. Of the patients who had ≥50% (mean 80%) residual thrombus, 50% (4/8) experienced recurrence, but in those with <50% (mean 35%) residual thrombus, only 5% (3/67) had recurrent DVT (P = 0.0014). The burden of residual thrombus at completion of CDT correlates with the risk of DVT recurrence. Patients having CDT for IFDVT had a lower risk of recurrence than expected. Successful clearing of acute clot in IFDVT patients significantly reduces the recurrence risk compared to patients with a large residual thrombus burden. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

PyCDT: A Python toolkit for modeling point defects in semiconductors and insulators

NASA Astrophysics Data System (ADS)

Broberg, Danny; Medasani, Bharat; Zimmermann, Nils E. R.; Yu, Guodong; Canning, Andrew; Haranczyk, Maciej; Asta, Mark; Hautier, Geoffroy

2018-05-01

Point defects have a strong impact on the performance of semiconductor and insulator materials used in technological applications, spanning microelectronics to energy conversion and storage. The nature of the dominant defect types, how they vary with processing conditions, and their impact on materials properties are central aspects that determine the performance of a material in a certain application. This information is, however, difficult to access directly from experimental measurements. Consequently, computational methods, based on electronic density functional theory (DFT), have found widespread use in the calculation of point-defect properties. Here we have developed the Python Charged Defect Toolkit (PyCDT) to expedite the setup and post-processing of defect calculations with widely used DFT software. PyCDT has a user-friendly command-line interface and provides a direct interface with the Materials Project database. This allows for setting up many charged defect calculations for any material of interest, as well as post-processing and applying state-of-the-art electrostatic correction terms. Our paper serves as a documentation for PyCDT, and demonstrates its use in an application to the well-studied GaAs compound semiconductor. We anticipate that the PyCDT code will be useful as a framework for undertaking readily reproducible calculations of charged point-defect properties, and that it will provide a foundation for automated, high-throughput calculations.

PyCDT: A Python toolkit for modeling point defects in semiconductors and insulators

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

Broberg, Danny; Medasani, Bharat; Zimmermann, Nils E. R.

Point defects have a strong impact on the performance of semiconductor and insulator materials used in technological applications, spanning microelectronics to energy conversion and storage. The nature of the dominant defect types, how they vary with processing conditions, and their impact on materials properties are central aspects that determine the performance of a material in a certain application. This information is, however, difficult to access directly from experimental measurements. Consequently, computational methods, based on electronic density functional theory DFT), have found widespread use in the calculation of point defect properties. Here we have developed the Python Charged Defect Toolkit (PyCDT)more » to expedite the setup and post-processing of defect calculations with widely used DFT software. PyCDT has a user-friendly command-line interface and provides a direct interface with the Materials Project database. This allows for setting up many charged defect calculations for any material of interest, as well as post-processing and applying state-of-the-art electrostatic correction terms. Our paper serves as a documentation for PyCDT, and demonstrates its use in an application to the well-studied GaAs compound semiconductor. We anticipate that the PyCDT code will be useful as a framework for undertaking readily reproducible calculations of charged point-defect properties, and that it will provide a foundation for automated, high-throughput calculations.« less

PyCDT: A Python toolkit for modeling point defects in semiconductors and insulators

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

Broberg, Danny; Medasani, Bharat; Zimmermann, Nils E. R.

Point defects have a strong impact on the performance of semiconductor and insulator materials used in technological applications, spanning microelectronics to energy conversion and storage. The nature of the dominant defect types, how they vary with processing conditions, and their impact on materials properties are central aspects that determine the performance of a material in a certain application. This information is, however, difficult to access directly from experimental measurements. Consequently, computational methods, based on electronic density functional theory (DFT), have found widespread use in the calculation of point-defect properties. Here we have developed the Python Charged Defect Toolkit (PyCDT) tomore » expedite the setup and post-processing of defect calculations with widely used DFT software. PyCDT has a user-friendly command-line interface and provides a direct interface with the Materials Project database. This allows for setting up many charged defect calculations for any material of interest, as well as post-processing and applying state-of-the-art electrostatic correction terms. Our paper serves as a documentation for PyCDT, and demonstrates its use in an application to the well-studied GaAs compound semiconductor. As a result, we anticipate that the PyCDT code will be useful as a framework for undertaking readily reproducible calculations of charged point-defect properties, and that it will provide a foundation for automated, high-throughput calculations.« less

Oral Candida colonization and its relation with predisposing factors in HIV-infected children and their uninfected siblings in Brazil: the era of highly active antiretroviral therapy.

PubMed

Cerqueira, Daniella Ferraz; Portela, Maristela Barbosa; Pomarico, Luciana; de Araújo Soares, Rosangela Maria; de Souza, Ivete Pomarico Ribeiro; Castro, Glória Fernanda

2010-02-01

To evaluate predisposing factors such as orofacial manifestations, immunosuppression status and antiretroviral therapy in relation to oral colonization by Candida spp. in Brazilian HIV-infected children and their uninfected siblings in the era of highly active antiretroviral therapy (HAART). Whole stimulated saliva was collected from 65 HIV-infected children (HIV+) and 40 uninfected siblings (HIV-), followed by assessment of orofacial manifestation, caries indexes and the number of cavitated dentinal carious teeth (CDT). The salivary samples were cultured and the colonies were counted. After which they were identified by sugar assimilation and fermentation (API 20C). Data was analyzed using chi-square, Mann-Whitney, Spearman tests and logistic regression. Regarding positive growth, HIV+ presented 80% (52/65) and HIV- 57.5% (23/40) (P = 0.013). Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05). Mean CD4%, immune-status and history of recurrent oral candidiasis (OC) had no influence on Candida isolation. Mixed Candida spp. cultures were observed in HIV+ (40%) and HIV- (52%): C. albicans was more frequently found in both groups, with a higher prevalence in HIV+ (P = 0.05); other non-albicans species were isolated in HIV+ and HIV-. Low prevalence of orofacial manifestations was observed in HIV+ (10.7% of OC). There was an association between means of CDT and Candida growth (P < 0.05) and a positive correlation between number of CDT and Candida cfu-counts in HIV+ and HIV-. Mean CD4% and immune-status had no influence on Candida isolation. Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05). The HIV infected children had a significantly higher prevalence of oral Candida spp. compared to their uninfected siblings. Absence of HAART and presence of dentinal carious teeth increased significantly Candida spp. colonization in these children.

75 FR 18240 - NASA Advisory Council; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (10-042)] NASA Advisory Council; Meeting... Space Administration announces a meeting of the NASA Advisory Council. DATES: Wednesday, April 28, 2010, 8 a.m.-5 p.m. CDT; Thursday, April 29, 2010, 8 a.m.-3 p.m. CDT ADDRESSES: NASA Johnson Space Center...

Investigating the Effectiveness of Classroom Diagnostic Tools

ERIC Educational Resources Information Center

Schultz, Robert K.

2012-01-01

The primary purposes of the study are to investigate what teachers experience while using the Classroom Diagnostic Tools (CDT) and to relate those experiences to the rate of growth in students' mathematics achievement. The CDT contains three components: an online computer adaptive diagnostic test, interactive web-based student reports, and…

Low prevalence of metallo-beta-lactamase in Pseudomonas aeruginosa isolated from a tertiary burn care center in Tehran.

PubMed

Lari, Abdolaziz Rastegar; Azimi, Leila; Soroush, Setareh; Taherikalani, Morovat

2015-09-01

Production of metallo-beta-lactamase (MBL) is one of the main mechanisms for resistance in carbapenem antibiotics. Detection of MBL-producer Pseudomonas aeruginosa is crucial in preventing its spread to other gram-negative bacteria. The aim of this study was to evaluate combination disc (CD) for identification of MBL-producer P. aeruginosa by polymerase chain reaction (PCR). A total of 255 imipenem resistant P. aeruginosa were collected from burn patients. Antibiotic susceptibility testing was conducted after purification and identification. Double-disc synergy test (DDST) with EDTA and combination disc test (CDT) with dipicolinic acid were performed for phenotypic detection of MBL and the PCR was carried out for blaVIM, blaIMP, blaNDM-1, blaSPM-1 genes. DDST with EDTA was negative in all cases, but 161 isolates were positive in CDT with dipicolinic acid. Further, blaVIM and blaIMP were detected in five and four strains, respectively. None of the isolates were positive for BlaNDM-1 and blaSPM-1 . The results of this study showed that the prevalence of MBL is low in imipenem resistance P. aeruginosa and that other mechanisms could be involved in resistance to imipenem in this bacterium. © The Author(s) 2015.

Clock Drawing Performance and Brain Morphology in Mild Cognitive Impairment and Alzheimer's Disease

ERIC Educational Resources Information Center

Thomann, Philipp A.; Toro, Pablo; Santos, Vasco Dos; Essig, Marco; Schroder, Johannes

2008-01-01

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer's disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive…

Hatch Opening OPS

NASA Image and Video Library

2009-08-31

S128-E-007009 (30 Aug. 2009) --- Astronaut Patrick Forrester, STS-128 mission specialist, prepares to open the hatch that will lead the entire Space Shuttle Discovery crew into the International Space Station. The two spacecraft docked at 7:54 p.m. (CDT), and the Discovery crew entered the orbital outpost at 9:59 p.m. (CDT) on Aug. 30.

Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer.

PubMed

Zhai, Yuanliang; Cheng, Erchao; Wu, Hao; Li, Ningning; Yung, Philip Yuk Kwong; Gao, Ning; Tye, Bik-Kwoon

2017-03-01

The minichromosome maintenance complex (MCM) hexameric complex (Mcm2-7) forms the core of the eukaryotic replicative helicase. During G1 phase, two Cdt1-Mcm2-7 heptamers are loaded onto each replication origin by the origin-recognition complex (ORC) and Cdc6 to form an inactive MCM double hexamer (DH), but the detailed loading mechanism remains unclear. Here we examine the structures of the yeast MCM hexamer and Cdt1-MCM heptamer from Saccharomyces cerevisiae. Both complexes form left-handed coil structures with a 10-15-Å gap between Mcm5 and Mcm2, and a central channel that is occluded by the C-terminal domain winged-helix motif of Mcm5. Cdt1 wraps around the N-terminal regions of Mcm2, Mcm6 and Mcm4 to stabilize the whole complex. The intrinsic coiled structures of the precursors provide insights into the DH formation, and suggest a spring-action model for the MCM during the initial origin melting and the subsequent DNA unwinding.

Detection of extended-spectrum β-lactamase in Enterobacter spp.--evaluation of six phenotypic tests.

PubMed

Nogueira-Miranda, Keite da Silva; Palmeiro, Jussara Kasuko; Conte, Danieli; Maia, Fernanda Valverde; Reason, Iara Taborda de Messias; Monteiro, Cristina Leise; Dalla-Costa, Libera Maria

2012-02-01

Extended-spectrum β-lactamases (ESBL) are plasmid-mediated enzymes that hydrolyze cephalosporins and monobactams. The lack of a standard method to detect ESBL in Enterobacter spp. has led to underestimating its frequency. The aim of this study was to evaluate ESBL detection in Enterobacter spp. By the double-disk synergy test (DDST) and combined disk test (CDT) assay using cefepime, cefotaxime, and ceftazime as substrates for ESBL, plus AmpC inhibitors in different associations. A total of 83 Enterobacter spp. ESBL and 31 non-ESBL Enterobacter spp. were tested, and a cutoff point ≥3 mm was defined using a receiver operating characteristic (ROC) curve for combined disc methods. All tests showed 100% specificity. The sensitivity was 89.2% for DDST and CDT without AmpC inibitor, 90.4% in the combined disc test in Mueller-Hinton agar containing phenylboronic acid (CDT-PBAA), and 94% in the combined disc test in Mueller-Hinton agar containing cloxacillin (CDT-CLXA). Cefepime was the best substrate, mainly when AmpC inhibitors were not used. However, superior results were achieved when all cephalosporins were evaluated together. In conclusion, to improve ESBL detection in Enterobacter spp., some modifications in phenotypic tests are needed, such as to reduce the distance between the discs to 20 mm in DDST, to use a cutoff point for ≥3 mm on the CDT, and to include a cefepime disk or an inhibitor of AmpC in all tests.

Outcomes of catheter-directed treatment of lower extremity deep vein thrombosis of patients presenting to a tertiary care hospital.

PubMed

Sundar, Gaurav; Keshava, Shyamkumar N; Moses, Vinu; Chiramel, George K; Ahmed, Munawwar; Mammen, Suraj; Aggarwal, Sunil; Stephen, Edwin

2016-01-01

Lower extremity deep vein thrombosis (DVT) is a common illness with an annual incidence of 1 per 1000 adults. The major long-term complication of DVT is post-thrombotic syndrome (PTS) which occurs in up to 60% of patients within 2 years of an episode of DVT. We aim to evaluate the outcomes of catheter-directed treatment (CDT) for symptomatic acute or subacute lower extremity DVT. A retrospective 12-year study was conducted on the outcomes of CDT on 54 consecutive patients who presented with acute or subacute lower extremity DVT to our hospital. Descriptive summary statistics and the Chi-square test were used to measure the outcomes of CDT. Grade 3 thrombolysis was achieved in 25 (46.3%) patients, grade 2 thrombolysis in 25 (46.3%) patients, and grade 1 thrombolysis in 4 (7.4%) patients. Significant recanalization (grade 2 or 3 thrombolysis) was possible in 50 (92.6%) patients. There was no statistically significant difference in the percentage of significant recanalization that could be achieved between patients who underwent CDT before and after 10 days. There was no significant difference between the thrombolysis achieved between urokinase and r-tPA. PTS was seen in 33% of the patients. Major complications were seen in 5.5% of the patients. CDT is a safe and effective therapeutic technique in patients with acute and subacute lower extremity DVT, if appropriate patient selection is made.

Evaluation of different phenotypic tests for detection of metallo-β-lactamases in imipenem-resistant Pseudomonas aeruginosa.

PubMed

Sachdeva, Rohit; Sharma, Babita; Sharma, Rajni

2017-01-01

Pseudomonas aeruginosa causes a wide spectrum of infections including bacteremia, pneumonia, urinary tract infection, etc., Metallo-beta-lactamase (MBL) producing P. aeruginosa is an emerging threat and cause of concern as they have emerged as one of the most feared resistance mechanisms. This study was designed to know the prevalence of MBL production in P. aeruginosa and to evaluate the four phenotypic tests for detection of MBL production in imipenem-resistant clinical isolates of P. aeruginosa . Totally, 800 isolates of P. aeruginosa isolated from various clinical samples were evaluated for carbapenem resistance and MBL production. All imipenem-resistant strains were tested for carabapenemase production by modified Hodge test. Screening for MBL production was done by double-disc synergy test and combined disc test (CDT). Confirmation of MBL production was done by the E-test (Ab BioDisk, Solna, Sweden). Out of the 800 isolates of P. aeruginosa , 250 isolates were found resistant to imipenem. Based on the results of E-test, 147 (18.37%) isolates of P. aeruginosa were positive for MBL production. The CDT has the highest sensitivity and specificity for the detection of MBL production as compared to other tests. The results of this study are indicative that MBL production is an important mechanism of carbapenem resistance among P. aeruginosa . Use of simple screening test like CDT will be crucial step toward large-scale monitoring of these emerging resistant determinants. Phenotypic test for MBL production has to be standardized, and all the isolates should be routinely screened for MBL production.

Evaluation of different phenotypic tests for detection of metallo-β-lactamases in imipenem-resistant Pseudomonas aeruginosa

PubMed Central

Sachdeva, Rohit; Sharma, Babita; Sharma, Rajni

2017-01-01

PURPOSE: Pseudomonas aeruginosa causes a wide spectrum of infections including bacteremia, pneumonia, urinary tract infection, etc., Metallo-beta-lactamase (MBL) producing P. aeruginosa is an emerging threat and cause of concern as they have emerged as one of the most feared resistance mechanisms. This study was designed to know the prevalence of MBL production in P. aeruginosa and to evaluate the four phenotypic tests for detection of MBL production in imipenem-resistant clinical isolates of P. aeruginosa. METHODS: Totally, 800 isolates of P. aeruginosa isolated from various clinical samples were evaluated for carbapenem resistance and MBL production. All imipenem-resistant strains were tested for carabapenemase production by modified Hodge test. Screening for MBL production was done by double-disc synergy test and combined disc test (CDT). Confirmation of MBL production was done by the E-test (Ab BioDisk, Solna, Sweden). RESULTS: Out of the 800 isolates of P. aeruginosa, 250 isolates were found resistant to imipenem. Based on the results of E-test, 147 (18.37%) isolates of P. aeruginosa were positive for MBL production. The CDT has the highest sensitivity and specificity for the detection of MBL production as compared to other tests. CONCLUSION: The results of this study are indicative that MBL production is an important mechanism of carbapenem resistance among P. aeruginosa. Use of simple screening test like CDT will be crucial step toward large-scale monitoring of these emerging resistant determinants. Phenotypic test for MBL production has to be standardized, and all the isolates should be routinely screened for MBL production. PMID:28966485

Is there a relationship between the presence of the binary toxin genes in Clostridium difficile strains and the severity of C. difficile infection (CDI)?

PubMed

Berry, C E; Davies, K A; Owens, D W; Wilcox, M H

2017-12-01

Some strains of Clostridium difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of C. difficile infection (CDI). Samples, isolates and clinical data were collected as part of a prospective multicentre diagnostic study. Clostridium difficile isolates (n = 1259) were tested by polymerase chain reaction (PCR) assay to detect binary toxin genes cdtA and cdtB. The PCR binary toxin gene results were compared with clinical severity and outcome data, including 30-day all-cause mortality. The 1259 isolates corresponded to 1083 different patients (October 2010 to September 2011). The prevalence of binary toxin positive strains was significantly higher in faecal samples with detectable toxin A/B than in those without toxin but that were positive by cytotoxigenic culture (26.3% vs. 10.3%, p < 0.001). The presence of binary toxin correlated moderately with markers of CDI severity (white cell count, serum albumin concentration and serum creatinine concentration). However, the risk ratio for all-cause mortality was 1.68 for binary toxin positive patients and patients were significantly less likely to survive if they had CDI caused by a binary toxin gene positive strain, even after adjusting for age (p < 0.001). The presence of binary toxin genes does not predict the clinical severity of CDI, but it is significantly associated with the risk of all-cause mortality.

Multiplex Real-Time PCR Method for Simultaneous Identification and Toxigenic Type Characterization of Clostridium difficile From Stool Samples

PubMed Central

Alam, Mohammad J.; Tisdel, Naradah L.; Shah, Dhara N.; Yapar, Mehmet; Lasco, Todd M.; Garey, Kevin W.

2015-01-01

Background The aim of this study was to develop and validate a multiplex real-time PCR assay for simultaneous identification and toxigenic type characterization of Clostridium difficile. Methods The multiplex real-time PCR assay targeted and simultaneously detected triose phosphate isomerase (tpi) and binary toxin (cdtA) genes, and toxin A (tcdA) and B (tcdB) genes in the first and sec tubes, respectively. The results of multiplex real-time PCR were compared to those of the BD GeneOhm Cdiff assay, targeting the tcdB gene alone. The toxigenic culture was used as the reference, where toxin genes were detected by multiplex real-time PCR. Results A total of 351 stool samples from consecutive patients were included in the study. Fifty-five stool samples (15.6%) were determined to be positive for the presence of C. difficile by using multiplex real-time PCR. Of these, 48 (87.2%) were toxigenic (46 tcdA and tcdB-positive, two positive for only tcdB) and 11 (22.9%) were cdtA-positive. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the multiplex real-time PCR compared with the toxigenic culture were 95.6%, 98.6%, 91.6%, and 99.3%, respectively. The analytical sensitivity of the multiplex real-time PCR assay was determined to be 103colonyforming unit (CFU)/g spiked stool sample and 0.0625 pg genomic DNA from culture. Analytical specificity determined by using 15 enteric and non-clostridial reference strains was 100%. Conclusions The multiplex real-time PCR assay accurately detected C. difficile isolates from diarrheal stool samples and characterized its toxin genes in a single PCR run. PMID:25932438

Surgery or EUS-guided choledochoduodenostomy for malignant distal biliary obstruction after ERCP failure

PubMed Central

Artifon, Everson L.A.; Loureiro, Jarbas F.; Baron, Todd H.; Fernandes, Kaie; Kahaleh, Michel; Marson, Fernando P.

2015-01-01

Background and Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) is the method of choice for drainage in patients with distal malignant biliary obstruction, but it fails in up to 10% of cases. Percutaneous transhepatic cholangiography (PTC) and surgical bypass are the traditional drainage alternatives. This study aimed to compare technical and clinical success, quality of life, and survival of surgical biliary bypass or hepaticojejunostomy (HJT) and endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDT) in patients with distal malignant bile duct obstruction and failed ERCP. Patients and Methods: A prospective, randomized trial was conducted. From March 2011 to September 2013, 32 patients with malignant distal biliary obstruction and failed ERCP were studied. The HJT group consisted of 15 patients and the CDT group consisted of 14 patients. Technical and clinical success, quality of life, and survival were assessed prospectively. Results: Technical success was 94% (15/16) in the HJT group and 88% (14/16) in the CDT group (P = 0.598). Clinical success occurred in 14 (93%) patients in the HJT group and in 10 (71%) patients in the CDT group (P = 0.169). During follow-up, a statistically significant difference was seen in mean functional capacity scores, physical health, pain, social functioning, and emotional and mental health aspects in both techniques (P < 0.05). The median survival time in both groups was the same (82 days). Conclusion: Data relating to technical and clinical success, quality of life, and survival were similar in patients who underwent HJT and CDT drainage after failed ERCP for malignant distal biliary obstruction. PMID:26374583

Cognitive and connectome properties detectable through individual differences in graphomotor organization.

PubMed

Lamar, Melissa; Ajilore, Olusola; Leow, Alex; Charlton, Rebecca; Cohen, Jamie; GadElkarim, Johnson; Yang, Shaolin; Zhang, Aifeng; Davis, Randall; Penney, Dana; Libon, David J; Kumar, Anand

2016-05-01

We investigated whether graphomotor organization during a digitized Clock Drawing Test (dCDT) would be associated with cognitive and/or brain structural differences detected with a tractography-derived structural connectome of the brain. 72 non-demented/non-depressed adults were categorized based on whether or not they used 'anchor' digits (i.e., 12, 3, 6, 9) before any other digits while completing dCDT instructions to "draw the face of a clock with all the numbers and set the hands to 10 after 11". 'Anchorers' were compared to 'non-anchorers' across dCDT, additional cognitive measures and connectome-based metrics. In the context of grossly intact clock drawings, anchorers required fewer strokes to complete the dCDT and outperformed non-anchorers on executive functioning and learning/memory/recognition tasks. Anchorers had higher local efficiency for the left medial orbitofrontal and transverse temporal cortices as well as the right rostral anterior cingulate and superior frontal gyrus versus non-anchorers suggesting better regional integration within local networks involving these regions; select aspects of which correlated with cognition. Results also revealed that anchorers' exhibited a higher degree of modular integration among heteromodal regions of the ventral visual processing stream versus non-anchorers. Thus, an easily observable graphomotor distinction was associated with 1) better performance in specific cognitive domains, 2) higher local efficiency suggesting better regional integration, and 3) more sophisticated modular integration involving the ventral ('what') visuospatial processing stream. Taken together, these results enhance our knowledge of the brain-behavior relationships underlying unprompted graphomotor organization during dCDT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Control System and Tests for the 13.2-m RAEGE Antenna at Yebes

NASA Astrophysics Data System (ADS)

de Vicente, P.; Bolaño, R.; Barbas, L.

2014-12-01

The RAEGE network is being deployed. The antenna at the Yebes Observatory is the first one in the network, and its construction finished in October 2013. During the construction phase, the remote control system for the antenna and the receivers was developed, and during the commisioning time the software was tested by MT-Mechatronics. As a result, both the control system from MT-Mechatronics and the remote control system by the IGN-CDT were debugged. We have tested the basic functionality of the antenna operated as a single dish telescope. First light at S, X, and Ka band was achieved on February 10^{th}. Afterwards a pointing model for the whole sky was determined, together with an optimum focus position as a function of elevation. Commisioning is not finished yet, and the antenna will be totally delivered to the IGN-CDT in the next weeks. VLBI equipment will be installed within three months, and VLBI observations are foreseen by the end of 2014. In this paper, we provide an overview of the control system and of the main results achieved.

Hatch Opening OPS

NASA Image and Video Library

2009-08-31

S128-E-007008 (30 Aug. 2009) --- Astronauts Rick Sturckow (right), STS-128 commander; and Patrick Forrester, mission specialist, are pictured near the hatch on the middeck of Space Shuttle Discovery after docking with the International Space Station. The two spacecraft docked at 7:54 p.m. (CDT), and the Discovery crew entered the orbital outpost at 9:59 p.m. (CDT) on Aug. 30.

Coherent destruction of tunneling in chaotic microcavities via three-state anti-crossings

PubMed Central

Song, Qinghai; Gu, Zhiyuan; Liu, Shuai; Xiao, Shumin

2014-01-01

Coherent destruction of tunneling (CDT) has been one seminal result of quantum dynamics control. Traditionally, CDT is understood as destructive interference between two intermediate transition paths near the level crossing. CDT near the level anti-crossings, especially the “locking”, has not been thoroughly explored so far. Taking chaotic microcavity as an example, here we study the inhibition of the tunneling via the strong couplings of three resonances. While the tunneling rate is only slightly affected by each strong coupling between two modes, the destructive interference between two strong couplings can dramatically improve the inhibition of the tunneling. A “locking” point, where dynamical tunneling is completely suppressed, has even been observed. We believe our finding will shed light on researches on micro- & nano-photonics. PMID:24781881

Efficacy of Acupuncture Therapy for Chemotherapy-Related Cognitive Impairment in Breast Cancer Patients.

PubMed

Tong, Taishan; Pei, Chunqin; Chen, Jun; Lv, Qing; Zhang, Fuquan; Cheng, Zaohuo

2018-05-08

BACKGROUND Chemotherapy can cause adverse effects such as chemotherapy-related cognitive impairment (CRCI). In this prospective study, the efficacy of traditional Chinese medicine acupuncture therapy in relieving CRCI and its impact on serum brain-derived neurotrophic factor (BDNF) are evaluated. MATERIAL AND METHODS Eighty patients were randomly divided into a treatment group and a control group with 40 patients in each group. The treatment group was treated at the following acupuncture points: Baihui (DU20), Sishencong (EX-HN1), Shenting (DU24), Zusanli (ST36), Taixi (K13), Dazhong (K14), and Juegu (GB39). Cognitive function was assessed using the functional assessment of cancer treatment cognition test (FACT-COG, version 3), the auditory-verbal learning test (AVLT), the verbal fluency test (VFT), the symbol digit modality test (SDMT), the clock-drawing test (CDT), and the trail-making test part B (TMT-B). In addition, blood serum levels of BDNF were measured before and after treatment. Correlations between change in BDNF levels and cognitive function were also analyzed. RESULTS CRCI was ameliorated in the acupuncture treatment group, with scores on FACT-COG, AVLT-recognition and CDT assessments all significantly increased (P<0.05 in all cases). In addition, serum BDNF levels after acupuncture treatment were significantly higher than before treatment ([i]t[/i]=3.242, [i]P[/i]<0.01). Moreover, the level of BDNF was positively correlated with the total score of FACT-COG, AVLT-recognition, and CDT ([i]r[/i]=0.694, 0.628, and 0.532, respectively; all P<0.05). The control group showed no statistically significant difference in any measures over the same period. CONCLUSIONS Acupuncture therapy is effective in the treatment of CRCI in breast cancer patients through a mechanism that may be related to an increase of BDNF.

Microbiological evaluation of different strategies for management of snakes in captivity.

PubMed

Campagner, M V; Bosco, S M G; Bagagli, E; Cunha, M L R S; Jeronimo, B C; Saad, E; Biscola, N P; Ferreira, R S; Barraviera, B

2012-01-01

Keeping snakes in captivity to produce venom for scientific research and production of inputs is now a worldwide practice. Maintaining snakes in captivity involves capture, infrastructure investments, management techniques, and appropriate qualified personnel. Further, the success of the project requires knowledge of habitat, nutrition, and reproduction, and control of opportunistic infections. This study evaluated the management of snakes in three types of captivity (quarantine, intensive, and semiextensive) and diagnosed bacterial and fungal contaminants. A bacteriological profile was obtained by swabbing the oral and cloacal cavities, scales, and venoms of healthy adult snakes from Bothrops jararaca (Bj) and Crotalus durissus terrificus (Cdt). There was predominance of Enterobacteriaceae, especially non-fermenting Gram-negative bacilli excluding Pseudomonas spp and Gram- positive bacteria. Statistically, intensive captivity resulted in the highest number of bacterial isolates, followed by recent capture (quarantine) and by semiextensive captivity. No statistical difference was found between Bj and Cdt bacterial frequency. In vitro bacterial susceptibility testing found the highest resistance against the semisynthetic penicillins (amoxicillin and ampicillin) and highest sensitivity to amicacin and tobramycin aminoglycosides. To evaluate mycological profile of snakes from intensive captivity, samples were obtained from two healthy Bj and one B. moojeni, one B. pauloensis, and one Cdt showing whitish lesions on the scales suggestive of ringworm. Using conventional methods and DNA-based molecular procedures, five samples of Trichosporon asahii were identified. Despite the traditional role of intense captivity in ophidian venom production, semiextensive captivity was more effective in the present study by virtue of presenting superior control of bacterial and fungal transmission, easier management, lowest cost, and decreased rate of mortality; therefore, it should be considered as a good alternative for tropical countries.

Stimulus-Food Pairings Produce Stimulus-Directed Touch-Screen Responding in Cynomolgus Monkeys (MACACA Fascicularis) With or Without a Positive Response Contingency

DTIC Science & Technology

2009-07-01

REPORT NUMBER US Army Medical Research Institute of Chemical Defense ATTN: MCMR-CDT-N 3100 Ricketts Point Road Aberdeen Proving Ground, MD...Medical Research Institute of Chemical Defense Aberdeen Proving Ground, MD 21010-5400 ATTN: MCMR-CDZ-I 11. SPONSOR/MONITOR’S REPORT 3100 Ricketts...CONTINGENCY CHRISTOPHER E. BULLOCK AND TODD M. MYERS UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE Acquisition and maintenance of

Hatch Opening OPS

NASA Image and Video Library

2009-08-31

S128-E-007010 (30 Aug. 2009) --- Astronauts Rick Sturckow (bottom), STS-128 commander; John “Danny” Olivas (right) and Patrick Forrester, both mission specialists, are pictured near the hatch on the middeck of Space Shuttle Discovery after docking with the International Space Station. The two spacecraft docked at 7:54 p.m. (CDT), and the Discovery crew entered the orbital outpost at 9:59 p.m. (CDT) on Aug. 30.

Establishment of a Hall Thruster Cluster

DTIC Science & Technology

2004-02-01

DURIP funds were used to develop a Hall thruster cluster test facility centered around the University of Michigan Large Vacuum Test Facility and a 2x2 cluster of BUSEK 600 W BHT-600 Hall thrusters. This capability will facilitate our three-year program to address the issue of high-power CDT operation and to provide insight on how chamber effects influence CDT engine/cluster characteristics.

The characteristics of transferrin variants by carbohydrate-deficient transferrin tests using capillary zone electrophoresis.

PubMed

Yoo, Gilsung; Kim, Juwon; Yoon, Kap Joon; Lee, Jong-Han

2018-04-17

Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%). We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice. © 2018 Wiley Periodicals, Inc.

A Retrospective Comparison of Ultrasound-Assisted Catheter-Directed Thrombolysis and Catheter-Directed Thrombolysis Alone for Treatment of Proximal Deep Vein Thrombosis

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

Tichelaar, Vladimir Y. I. G., E-mail: ynse.i.tichelaar@uit.no; Brodin, Ellen E.; Vik, Anders

BackgroundRecent studies have suggested that catheter-directed thrombolysis (CDT) reduces development of post-thrombotic syndrome (PTS). Ultrasound-assisted CDT (USCDT) might enhance the efficiency of thrombolysis. We aimed to compare USCDT with CDT on efficacy, safety, development of PTS, and quality of life after long-term follow-up.MethodsWe describe a retrospective case series of 94 consecutive patients admitted with iliofemoral or more proximal deep vein thrombosis (DVT) to the University Hospital from 2002 to 2011, treated either with CDT or USCDT. Scheduled follow-up visits took place between April 2013 and January 2014. Venography measured the degree of residual luminal obstruction of the affected veins. Eachmore » patient completed the Short Form 36-item health survey assessment and the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms questionnaires. PTS was assessed using the Villalta scale.ResultsRisk factors of DVT were equally distributed between groups. In the USCDT group, we observed a significant decline in the duration of thrombolytic treatment (<48 h: 27 vs. 10 %), shortened hospital stay (median 6.0 days (IQR 5.0–9.0) vs. 8.0 (IQR 5.8–12.0)), and less implantation of (intravenous) stents (30 vs. 55 %). There was no difference in patency (76 vs. 79 % fully patent), prevalence of PTS (52 vs. 55 %), or quality of life between groups after long-term follow-up (median 65 months, range: 15–141).ConclusionsIn this observational study, USCDT was associated with shortened treatment duration, shorter hospital stay, and less intravenous stenting, compared to CDT alone without affecting the long-term prevalence of PTS or quality of life.« less

Calibrated sulfur isotope abundance ratios of three IAEA sulfur isotope reference materials and V-CDT with a reassessment of the atomic weight of sulfur

NASA Astrophysics Data System (ADS)

Ding, T.; Valkiers, S.; Kipphardt, H.; De Bièvre, P.; Taylor, P. D. P.; Gonfiantini, R.; Krouse, R.

2001-08-01

Calibrated values have been obtained for sulfur isotope abundance ratios of sulfur isotope reference materials distributed by the IAEA (Vienna). For the calibration of the measurements, a set of synthetic isotope mixtures were prepared gravimetrically from high purity Ag2S materials enriched in32S, 33S, and 34S. All materials were converted into SF6 gas and subsequently, their sulfur isotope ratios were measured on the SF5+ species using a special gas source mass spectrometer equipped with a molecular flow inlet system (IRMM's Avogadro II amount comparator). Values for the 32S/34S abundance ratios are 22.650 4(20), 22.142 4(20), and 23.393 3(17) for IAEA-S-1, IAEA-S-2, and IAEA-S-3, respectively. The calculated 32S/34S abundance ratio for V-CDT is 22.643 6(20), which is very close to the calibrated ratio obtained by Ding et al. (1999). In this way, the zero point of the VCDT scale is anchored firmly to the international system of units SI. The 32S/33S abundance ratios are 126.942(47), 125.473(55), 129.072(32), and 126.948(47) for IAEA-S-1, IAEA-S-2, IAEA-S-3, and V-CDT, respectively. In this way, the linearity of the V-CDT scale is improved over this range. The values of the sulfur molar mass for IAEA-S-1 and V-CDT were calculated to be 32.063 877(56) and 32.063 911(56), respectively, the values with the smallest combined uncertainty ever reported for the sulfur molar masses (atomic weights).

Prevalence, antibiogram, and cdt genes of toxigenic Campylobacter jejuni in salad style vegetables (ulam) at farms and retail outlets in Terengganu.

PubMed

Khalid, Mohd Ikhsan; Tang, John Yew Huat; Baharuddin, Nabila Huda; Rahman, Nasiha Shakina; Rahimi, Nurul Faizzah; Radu, Son

2015-01-01

The present study was conducted to investigate the prevalence and antibiotic resistance among Campylobacter jejuni in ulam at farms and retail outlets located in Kuala Terengganu, Malaysia. A total of 526 samples (ulam, soil, and fertilizer) were investigated for the presence of C. jejuni and the gene for cytolethal distending toxin (cdt) by using a multiplex PCR method. Antibiotic susceptibility to 10 types of antibiotics was determined using the disk diffusion method for 33 C. jejuni isolates. The average prevalence of contaminated samples from farms, wet markets, and supermarkets was 35.29, 52.66, and 69.88%, respectively. The cdt gene was not detected in 24 of the 33 C. jejuni isolates, but 9 isolates harbored cdtC. Antibiotic resistance in C. jejuni isolates was highest to penicillin G (96.97% of isolates) followed by vancomycin (87.88%), ampicillin (75.76%), erythromycin (60.61%), tetracycline (9.09%), amikacin (6.06%), and norfloxacin (3.03%); none of the isolates were resistant to ciprofloxacin, enrofloxacin, and gentamicin. In this study, C. jejuni was present in ulam, and some isolates were highly resistant to some antibiotics but not to quinolones. Thus, appropriate attention and measures are required to prevent C. jejuni contamination on farms and at retail outlets.

Tropical Storm Bonnie as Observed by NASA Spaceborne Atmospheric Infrared Sounder AIRS

NASA Image and Video Library

2004-08-12

Tropical storm Bonnie, Gulf of Mexico, captured on August 11 at 1:30am CDT. Located in the Gulf of Mexico, the center of the storm is positioned about 280 miles south-southwest of the mouth of the Mississippi River. Bonnie is a small tropical storm with wind speeds sustained at 45 mph and extending 30 miles from the storm center. It is moving northward at 5 mph. http://photojournal.jpl.nasa.gov/catalog/PIA00441

Pathogenesis of Thromboembolism and Endovascular Management

PubMed Central

Behravesh, Sasan; Hoang, Peter; Nanda, Alisha; Wallace, Alex; Sheth, Rahul A.; Deipolyi, Amy R.; Memic, Adnan; Naidu, Sailendra

2017-01-01

Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted. PMID:28154761

Caracterisitiques des patients tuberculeux à l'ouest cameroun: 2000-2009

PubMed Central

Noubom, Michel; Nembot, Fabrice Djouma; Donfack, Hubert; Mfin, Patrick Stéphane Kouomboua; Tchasse, Floriane

2013-01-01

Introduction La tuberculose (TB) reste de nos jours un problème majeur de santé publique dans les pays en voie de développement. Elle devient de plus en plus importante à cause de l'infection au VIH. Cette étude avait pour but de caractériser les patients admis dans le plus grand Centre de Diagnostic et de Traitement de la Tuberculose (CDT) de l'Ouest Cameroun entre 2000 et 2009. Méthodes Les patients de 15 ans et plus admis au CDT de Baleng durant la période allant du 1er janvier 2000 au 31 décembre 2009 ont été inclus. Les données ont étés collectées grâce à une grille pré conçue. Le calcul des fréquences, moyennes et les comparaisons de groupes ont été faites pour ressortir les caractéristiques des participants. Résultats 2556 patients ont été inclus dans l’étude. 64,8% étaient de sexe masculin et l’âge médian étaient de 33ans. 2141 (83,7%) de patients présentaient une TPM+, 319 (12,5%) une TPM- et 96 (3,8%) une TEP. 64,7% des patients résidaient hors du district de santé d'implantation du CDT. 79,16% de patients tuberculeux ont fait le test de dépistage du VIH et la séroprévalence chez ceux testés était de 26,06%. Les différentes évolutions en fin de période de suivi de chaque patient ont été les suivantes: évolution favorable (guéri et traitement terminé) 1954(76,6%); perdus de vue 231(9,0%); décès 230(9,0%); transféré 92(3,6%); échec 49(1,9%). Conclusion Une proportion considérable de patients résident loin du CDT ce qui augmenterait le perdus de vue et les transferts pendant le traitement. En plus vulgariser les autres CDT de la région, il est nécessaire de renforcer le système de transfert pour éviter les perdus de vue entre deux CDT. PMID:24570799

Hormonal Involvement in Breast Cancer Gene Amplification

DTIC Science & Technology

2010-10-01

been shown to induce DN A amplification in yeast (Gopalakrishnan et al., 2001; Nguy en et al., 2001; Green et al., 2006) an d increased Cdt1 results in...re-replication in human cells (Dorn et al., 2008). The N- terminus of Cdt1 is important for re-replication, perhaps through interactions with PCNA...evolution of a cancer genome. Genome Res. (Epub. Dec. 3, 2008). Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Bras lavsky I, Causey M

Optimization of CDT-1 and XYL1 Expression for Balanced Co-Production of Ethanol and Xylitol from Cellobiose and Xylose by Engineered Saccharomyces cerevisiae

PubMed Central

Zha, Jian; Li, Bing-Zhi; Shen, Ming-Hua; Hu, Meng-Long; Song, Hao; Yuan, Ying-Jin

2013-01-01

Production of ethanol and xylitol from lignocellulosic hydrolysates is an alternative to the traditional production of ethanol in utilizing biomass. However, the conversion efficiency of xylose to xylitol is restricted by glucose repression, causing a low xylitol titer. To this end, we cloned genes CDT-1 (encoding a cellodextrin transporter) and gh1-1 (encoding an intracellular β-glucosidase) from Neurospora crassa and XYL1 (encoding a xylose reductase that converts xylose into xylitol) from Scheffersomyces stipitis into Saccharomyces cerevisiae, enabling simultaneous production of ethanol and xylitol from a mixture of cellobiose and xylose (main components of lignocellulosic hydrolysates). We further optimized the expression levels of CDT-1 and XYL1 by manipulating their promoters and copy-numbers, and constructed an engineered S. cerevisiae strain (carrying one copy of PGK1p-CDT1 and two copies of TDH3p-XYL1), which showed an 85.7% increase in xylitol production from the mixture of cellobiose and xylose than that from the mixture of glucose and xylose. Thus, we achieved a balanced co-fermentation of cellobiose (0.165 g/L/h) and xylose (0.162 g/L/h) at similar rates to co-produce ethanol (0.36 g/g) and xylitol (1.00 g/g). PMID:23844185

Effects of N-acetyl-L-cysteine on redox status and markers of renal function in mice inoculated with Bothrops jararaca and Crotalus durissus terrificus venoms.

PubMed

Barone, Juliana Marton; Frezzatti, Rodrigo; Silveira, Paulo Flavio

2014-03-01

Renal dysfunction is an important aggravating factor in accidents caused by Crotalus durissus terrificus (Cdt) and Bothrops jararaca (Bj) bites. N-acetyl-l-cysteine (NAC) is well known as a nephroprotective antioxidant with low toxicity. The present study investigated the effects of NAC on redox status and markers of renal function in mice that received vehicle (controls) or venoms (v) of Cdt and Bj. In controls NAC promoted hypercreatinemia, hypouremia, hyperosmolality with decreased urea in urine, hyperproteinuria, decreased protein and increased dipeptidyl peptidase IV (DPPIV) in membrane-bound fraction (MF) from renal cortex (RC) and medulla (RM). NAC ameliorated or normalized altered creatinuria, proteinemia and aminopeptidase (AP) acid in MF, AP basic (APB) in soluble fraction (SF), and neutral AP in SF and MF from RC and RM in vBj envenomation. NAC ameliorated or normalized altered neutral AP in SF from RC and RM, and DPPIV and protein in MF from RC in vCdt envenomation. NAC ameliorated or restored renal redox status respectively in vCdt and vBj, and normalized uricemia in both envenomations. These data are promising perspectives that recommend the clinical evaluation of NAC as potential coadjuvant in the anti venom serotherapy for accidents with these snake's genera. Copyright © 2014 Elsevier Ltd. All rights reserved.

Achievement of take-home dose privileges is associated with better-perceived sleep and with cognitive status among methadone maintenance treatment patients.

PubMed

Peles, Einat; Schreiber, Shaul; Domany, Yoav; Sason, Anat; Tene, Oren; Adelson, Miriam

2014-12-01

Methadone maintenance treatment (MMT) patients may achieve up to a 2-week privilege of methadone take-home doses (THD), which is associated with considerable responsibility. MMT patients are characterized as having poor sleep quality and low cognitive states. We studied sleep indices and cognitive status with respect to THD privileges. A sample of 123 MMT patients stratified by THD groups was studied. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the cognitive Clock Drawing Test (CDT) were performed. Thirty-one of 123 patients never had any THD and 92 did (25 had the maximum of 2 weeks). The never THD had history of longer duration of opiate usage and a shorter period in MMT. They had the highest rates of poor sleep (80.6%, PSQI > 5), daily sleepiness ("fall asleep while talking") (41.9%), and impaired cognitive status (58.1%, CDT < 3), while those who had 2-week privileges had the lowest (56, 8, and 28%, respectively). Logistic regression characterized THD patients as no-benzodiazepine and no-cocaine, short opiate usage duration, low ADHD scores, and no cognitive impairment (CDT = 3) and its interaction with treatment duration. Privileges that reflect patients' abstinence and rehabilitation were also expanded to be associated with better cognitive states. These finding confirm the THD dispensing performance. Including CDT as part of the decision for dispensing THD may be considered.

MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3.

PubMed

Mimura, Satoru; Kubota, Yumiko; Takisawa, Haruhiko

2018-01-01

The minichromosome maintenance (MCM) complex, consisting of six subunits, Mcm2-7, is loaded onto replication origins through loading factors (origin recognition complex [ORC], Cdc6, and Cdt1) and forms an MCM double hexamer that licenses the initiation of DNA replication. Previous studies with Xenopus egg extracts showed that loading factors, especially Cdc6, dissociate from chromatin on MCM loading, but the molecular mechanism and physiological significance remain largely unknown. Using a cell-free system for MCM loading onto plasmid DNA in Xenopus egg extracts, we found that MCM loaded onto DNA prevents DNA binding of the loading factors ORC, Cdc6, and Cdt1. We further report that a peptide of the C-terminal region of MCM3 (MCM3-C), previously implicated in the initial association with ORC/Cdc6 in budding yeast, prevents ORC/Cdc6/Cdt1 binding to DNA in the absence of MCM loading. ATP-γ-S suppresses inhibitory activities of both the MCM loaded onto DNA and the MCM3-C peptide. Other soluble factors in the extract, but neither MCM nor Cdt1, are required for the activity. Conservation of the amino acid sequences of MCM3-C and its activity in vertebrates implies a novel negative autoregulatory mechanism that interferes with MCM loading in the vicinity of licensed origins to ensure proper origin licensing.

An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol.

PubMed

Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Evers, Silvia; Duyverman, Lotte; Valkenburg-Vissers, Joyce; Cornelissen, Job; Bos, Michel; van Droffelaar, Maarten; Lemmens, Wim A; Donders, Rogier; van der Zande, Anneke; Visser, Leo H

2016-05-28

In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found that a 3-day intensive social cognitive program (Can Do Treatment [CDT]) with the participation of support partners was followed by substantial increases in self-efficacy control and health-related quality of life 6 months after treatment in those people with MS who had relapsing remitting disease and low disability. CDT is a sociologically oriented approach, its goal is to uncover and promote existing capabilities, and the notion "stressor" is the central concept. CDT's components are plenary group sessions, small group sessions, consultations, a theatre evening, and start of the day with a joint activity. The small group sessions form the actual training. Depending on their individual goals the participants join the training groups 'Body', 'Feeling' or 'Life', to work out their aims and to reduce their stressors. The multidisciplinary team includes a psychiatrist, psychiatric nurse, neurologist, specialized MS nurse, physiotherapist, dance therapist, and a person with MS. To evaluate the (cost)effectiveness of CDT in persons with relapsing remitting MS and low disability we perform a single-centre, randomized controlled trial in 140 patients, with or without support partners. The primary outcome is self-efficacy control. The secondary outcomes are self-efficacy function, health-related quality of life, autonomy and participation, anxiety, depression, cost effectiveness and cost utility. The tertiary outcome is care-related strain to support partners. Outcomes are assessed at baseline and at 1, 3 and 6 months after CDT. This randomized controlled trial will adequately evaluate the clinical and cost effectiveness of a 3-day intensive social cognitive program in people with relapsing remitting MS and low disability, with self-efficacy control as primary outcome. Application number: 22444.

Managing iliofemoral deep venous thrombosis of pregnancy with a strategy of thrombus removal is safe and avoids post-thrombotic morbidity.

PubMed

Herrera, Santiago; Comerota, Anthony J; Thakur, Subhash; Sunderji, Shiraz; DiSalle, Robert; Kazanjian, Sahira N; Assi, Zakaria

2014-02-01

Extensive deep venous thrombosis (DVT) during pregnancy is usually treated with anticoagulation alone, risking significant post-thrombotic syndrome (PTS) in young patients. Catheter-directed thrombolysis (CDT) and operative venous thrombectomy have been safely and effectively used in nonpregnant patients, demonstrating significant reduction in post-thrombotic morbidity. This report reviews short- and long-term outcomes of 13 patients with extensive DVT of pregnancy treated with a strategy of thrombus removal. From 1999 to 2013, 13 patients with iliofemoral DVT during pregnancy were offered CDT, pharmacomechanical thrombolysis (PMT), and/or venous thrombectomy. Gestational age ranged from 8 to 34 weeks. Fetal monitoring was performed throughout hospitalization. Radiation exposure was minimized with pelvic lead shields, focal fluoroscopy, and limited angiographic runs. Follow-up included objective vein evaluation using venous duplex and PTS assessment using the Villalta scale. CDT and/or PMT were used in 11 patients. Two patients underwent venous thrombectomy alone, and one patient had operative thrombectomy as an adjunct to CDT and PMT. Each patient had complete or near-complete thrombus resolution and rapid improvement in clinical symptoms. Eight of 11 having CDT or PMT underwent venoplasty and stenting of the involved iliac veins. Twelve of the 13 delivered healthy infants at term. One patient opted for termination of her pregnancy. Mean patient and gestational ages were 26 years and 26 weeks, respectively. Mean follow-up was 1.3 years, with only one recurrence. Duplex ultrasonography demonstrated patent veins in all but one patient and normal valve function in 10 patients. Eleven patients had Villalta scores <5 (considered normal), with a mean score of 0.7. Extensive DVT of pregnancy can be effectively and safely treated with a strategy of thrombus removal, resulting in a patent venous system, normal valve function in many, prevention of PTS, and reduction in recurrence. Copyright © 2014. Published by Mosby, Inc.

Percutaneous Pulmonary Embolism Thrombectomy and Thrombolysis: Technical Tips and Tricks.

PubMed

Devcic, Zlatko; Kuo, William T

2018-06-01

Catheter-directed therapy (CDT) is now acknowledged as a treatment option for select patients with acute massive or submassive pulmonary embolism (PE), and more patients are being considered for CDT if there is available expertise. Therefore, interventionalists should be aware of the variety of catheter-based treatment options, specific pitfalls to avoid during therapy, and the appropriate treatment endpoints. This article reviews currently available techniques and protocols for treating acute massive and submassive PE, with tips to safely and successfully perform percutaneous PE interventions.

Reward Value-Contingent Changes of Visual Responses in the Primate Caudate Tail Associated with a Visuomotor Skill

PubMed Central

Kim, Hyoung F.; Hikosaka, Okihide

2013-01-01

A goal-directed action aiming at an incentive outcome, if repeated, becomes a skill that may be initiated automatically. We now report that the tail of the caudate nucleus (CDt) may serve to control a visuomotor skill. Monkeys looked at many fractal objects, half of which were always associated with a large reward (high-valued objects) and the other half with a small reward (low-valued objects). After several daily sessions, they developed a gaze bias, looking at high-valued objects even when no reward was associated. CDt neurons developed a response bias, typically showing stronger responses to high-valued objects. In contrast, their responses showed no change when object values were reversed frequently, although monkeys showed a strong gaze bias, looking at high-valued objects in a goal-directed manner. The biased activity of CDt neurons may be transmitted to the oculomotor region so that animals can choose high-valued objects automatically based on stable reward experiences. PMID:23825426

The effect of relaxation techniques on edema, anxiety and depression in post-mastectomy lymphedema patients undergoing comprehensive decongestive therapy: A clinical trial.

PubMed

Abbasi, Bahareh; Mirzakhany, Navid; Angooti Oshnari, Leila; Irani, Ashkan; Hosseinzadeh, Samaneh; Tabatabaei, Seyed Mehdi; Haghighat, Shahpar

2018-01-01

Lymphedema is sometimes accompanied by high degrees of anxiety and depression. This study aimed to assess the effects of relaxation techniques on the level of edema, anxiety and depression in women undergoing Comprehensive Decongestive Therapy (CDT). This clinical trial compared two treatment methods in 31 women with post-mastectomy lymphedema, including 15 cases who received CDT and 16 who received RCDT (Relaxation plus CDT). The edema volume, anxiety and depression scores were compared at the first and last sessions of the first phase of the treatment and six weeks afterwards. The edema, anxiety and depression scores were 63.6%, 54.1% and 65.5% in the RCDT group and 60.7%, 31.4% and 35.2% in the CDT group. There were significant differences between the two groups in terms of the reduction in depression (p = 0.024) and anxiety (p = 0.011) scores throughout the study. This significant relationship was due to the differences in the depression score in the 3rd and 9th weeks of the study between the two groups. Similarly, anxiety levels differed significantly between the two groups at the 9th week of the study (P = 0.013). Relaxation techniques reduced the anxiety and depression scores and the volume of edema in the patients with lymphedema. The addition of this intervention to the therapeutic package for lymphedema patients requires further studies in terms of cost-effectiveness.

Performance evaluation of algebraic reconstruction technique (ART) for prototype chest digital tomosynthesis (CDT) system

NASA Astrophysics Data System (ADS)

Lee, Haenghwa; Choi, Sunghoon; Jo, Byungdu; Kim, Hyemi; Lee, Donghoon; Kim, Dohyeon; Choi, Seungyeon; Lee, Youngjin; Kim, Hee-Joung

2017-03-01

Chest digital tomosynthesis (CDT) is a new 3D imaging technique that can be expected to improve the detection of subtle lung disease over conventional chest radiography. Algorithm development for CDT system is challenging in that a limited number of low-dose projections are acquired over a limited angular range. To confirm the feasibility of algebraic reconstruction technique (ART) method under variations in key imaging parameters, quality metrics were conducted using LUNGMAN phantom included grand-glass opacity (GGO) tumor. Reconstructed images were acquired from the total 41 projection images over a total angular range of +/-20°. We evaluated contrast-to-noise ratio (CNR) and artifacts spread function (ASF) to investigate the effect of reconstruction parameters such as number of iterations, relaxation parameter and initial guess on image quality. We found that proper value of ART relaxation parameter could improve image quality from the same projection. In this study, proper value of relaxation parameters for zero-image (ZI) and back-projection (BP) initial guesses were 0.4 and 0.6, respectively. Also, the maximum CNR values and the minimum full width at half maximum (FWHM) of ASF were acquired in the reconstructed images after 20 iterations and 3 iterations, respectively. According to the results, BP initial guess for ART method could provide better image quality than ZI initial guess. In conclusion, ART method with proper reconstruction parameters could improve image quality due to the limited angular range in CDT system.

Digital Clock Drawing: differentiating "thinking" versus "doing" in younger and older adults with depression.

PubMed

Cohen, Jamie; Penney, Dana L; Davis, Randall; Libon, David J; Swenson, Rodney A; Ajilore, Olusola; Kumar, Anand; Lamar, Melissa

2014-10-01

Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: (i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and (ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite Z-scores of cognition, including attention/information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance. Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction: p=.03)-younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=-.46; p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=-.47; p=.03) and older euthymic groups (r=-.51; p=.01). The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics.

Checkpoint Kinase-Dependent Regulation of DNA Repair and Genome Instability in Breast Cancer

DTIC Science & Technology

2007-06-01

its misregulation (16). Exposure to exogenous DNA damaging agents induces the destruction of Cdt1 specifically by DDB1-Cul4A (7) (9). Our data...sodium citrate ) for 15 min at 37°C, fixed by multiple washes with Carnoy fixative (3:1 methanol-acetic acid), and dropped onto slides. Slides were...damaging agents induces the destruction of Cdt1 specifically by DDB1- Cul4A (24, 26). Our data indicate that DDB1 also has an important role in the

Catheter-Directed Thrombolysis of Inferior Vena Cava Thrombosis in a 13-Day-Old Neonate and Review of Literature

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

Khan, Jawad U.; Takemoto, Clifford M.; Casella, James F.

Complete inferior vena cava thrombosis (IVC) in neonates is uncommon, but may cause significant morbidity. A 13-day-old neonate suffered IVC thrombosis secondary to antithrombin III deficiency, possibly contributed to by a mutation in the methyl tetrahydrofolate reductase gene. Catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rt-PA, Alteplase) was used successfully to treat extensive venous thrombosis in this neonate without complications. We also review the literature on CDT for treatment of IVC thrombosis in critically ill neonates and infants.

Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review.

PubMed

Elbasty, Ahmed; Metcalf, James

2017-12-01

Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration's tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured.

Evidence for transceptor function of cellodextrin transporters in Neurospora crassa.

PubMed

Znameroski, Elizabeth A; Li, Xin; Tsai, Jordan C; Galazka, Jonathan M; Glass, N Louise; Cate, Jamie H D

2014-01-31

Neurospora crassa colonizes burnt grasslands and metabolizes both cellulose and hemicellulose from plant cell walls. When switched from a favored carbon source to cellulose, N. crassa dramatically up-regulates expression and secretion of genes encoding lignocellulolytic enzymes. However, the means by which N. crassa and other filamentous fungi sense the presence of cellulose in the environment remains unclear. Previously, we have shown that a N. crassa mutant carrying deletions of three β-glucosidase enzymes (Δ3βG) lacks β-glucosidase activity, but efficiently induces cellulase gene expression and cellulolytic activity in the presence of cellobiose as the sole carbon source. These observations indicate that cellobiose, or a modified version of cellobiose, functions as an inducer of lignocellulolytic gene expression and activity in N. crassa. Here, we show that in N. crassa, two cellodextrin transporters, CDT-1 and CDT-2, contribute to cellulose sensing. A N. crassa mutant carrying deletions for both transporters is unable to induce cellulase gene expression in response to crystalline cellulose. Furthermore, a mutant lacking genes encoding both the β-glucosidase enzymes and cellodextrin transporters (Δ3βGΔ2T) does not induce cellulase gene expression in response to cellobiose. Point mutations that severely reduce cellobiose transport by either CDT-1 or CDT-2 when expressed individually do not greatly impact cellobiose induction of cellulase gene expression. These data suggest that the N. crassa cellodextrin transporters act as "transceptors" with dual functions - cellodextrin transport and receptor signaling that results in downstream activation of cellulolytic gene expression. Similar mechanisms of transceptor activity likely occur in related ascomycetes used for industrial cellulase production.

Digital clock drawing: Differentiating ‘thinking’ versus ‘doing’ in younger and older adults with depression

PubMed Central

Cohen, Jamie; Penney, Dana L.; Davis, Randall; Libon, David J.; Swenson, Rodney A.; Ajilore, Olusola; Kumar, Anand; Lamar, Melissa

2015-01-01

Objective Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Method Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite z-scores of cognition, including attention/ information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance. Results Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction:p=.03)—younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=−.46;p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=−.47;p=.03) and older euthymic groups (r=−.51;p=.01). Conclusion The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics. PMID:25222513

Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry.

PubMed

Eshraghi, Aria; Dixon, Shandee D; Tamilselvam, Batcha; Kim, Emily Jin-Kyung; Gargi, Amandeep; Kulik, Julia C; Damoiseaux, Robert; Blanke, Steven R; Bradley, Kenneth A

2014-07-01

Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins.

Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry

PubMed Central

Eshraghi, Aria; Dixon, Shandee D.; Tamilselvam, Batcha; Kim, Emily Jin-Kyung; Gargi, Amandeep; Kulik, Julia C.; Damoiseaux, Robert; Blanke, Steven R.; Bradley, Kenneth A.

2014-01-01

Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins. PMID:25078082

Characteristics of successful and unsuccessful completers of 3 postacute brain injury rehabilitation pathways.

PubMed

Malec, James F; Degiorgio, Lisa

2002-12-01

To determine whether successful participants along different postacute brain injury rehabilitation pathways differ on demographic, injury-related, disability, and outcome variables. Secondary analysis of pre- and posttreatment, and 1-year follow-up data obtained in a previous study of specialized vocational services (SVS) for persons with brain injury. Outpatient brain injury rehabilitation clinic. One hundred fourteen persons with acquired brain injury. Participants in 3 distinct rehabilitation pathways were studied: SVS only; SVS and a 3-h/wk community reintegration outpatient group; and SVS and 6-h/d comprehensive day treatment (CDT). Mayo-Portland Adaptability Inventory (MPAI); Vocational Independence Scale; and "success," as defined by community-based employment (CBE) at 1-year follow-up. The percentage (77%-85%) of participants in CBE at 1-year follow-up did not differ among the 3 pathways. CDT participants had more limited educational backgrounds, were less recently injured, and showed greater disability and more impaired self-awareness than those receiving limited intervention (ie, SVS or community reintegration outpatient group). MPAI scores for limited-intervention participants who were unsuccessful were similar in level to successful participants in CDT. Logistic regression models were developed to predict the probability of success with limited intervention and CDT. Different rehabilitation pathways result in CBE for a large percentage of persons with brain injury if the intensity of service is appropriately matched to the severity of the disability, the time since injury, and other participant characteristics. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

From causal dynamical triangulations to astronomical observations

NASA Astrophysics Data System (ADS)

Mielczarek, Jakub

2017-09-01

This letter discusses phenomenological aspects of dimensional reduction predicted by the Causal Dynamical Triangulations (CDT) approach to quantum gravity. The deformed form of the dispersion relation for the fields defined on the CDT space-time is reconstructed. Using the Fermi satellite observations of the GRB 090510 source we find that the energy scale of the dimensional reduction is E* > 0.7 \\sqrt{4-d\\text{UV}} \\cdot 1010 \\text{GeV} at (95% CL), where d\\text{UV} is the value of the spectral dimension in the UV limit. By applying the deformed dispersion relation to the cosmological perturbations it is shown that, for a scenario when the primordial perturbations are formed in the UV region, the scalar power spectrum PS \\propto kn_S-1 , where n_S-1≈ \\frac{3 r (d\\text{UV}-2)}{(d\\text{UV}-1)r-48} . Here, r is the tensor-to-scalar ratio. We find that within the considered model, the predicted from CDT deviation from the scale invariance (n_S=1) is in contradiction with the up to date Planck and BICEP2.

Experimental Investigations with a 5-kW-Class Laboratory Model Closed-Drifted Hall Thruster

DTIC Science & Technology

2001-01-01

Hall thruster (CDT). The project was composed of the following segments: 1) a 5-kW-class CDT (P5) was built and characterized in terms of performance and plume divergence; 2) the molecular-beam mass spectrometer (MBMS) was used to measure the ion energy distribution finction and charge state throughout the PS plume; 3) laser-induced fluorescence was used to measure the ion velocity and temperature in the near-field plume; 4) a 35 GHz microwave interferometer was developed to measure plasma oscillations and electron density in the plume; and 5) the near-field and internal

Bowersox and Budarin wearing Russian Sokol suit in Soyuz Spacecraft during Expedition Six

NASA Image and Video Library

2003-04-14

ISS006-E-45796 (14 April 2003) --- Attired in their Russian Sokol suits, astronaut Kenneth D. Bowersox (left), Expedition 6 mission commander; cosmonaut Nikolai M. Budarin, flight engineer; along with astronaut Donald R. Pettit (out of frame), NASA ISS science officer, practice for their return flight home scheduled for May 3, 2003. The two astronauts and cosmonaut will leave the International Space Station (ISS) aboard the Soyuz TMA-1 spacecraft at 5:40 p.m. (CDT) Saturday. They are schedule to land in Kazakhstan at 9:03 p.m. (CDT) Saturday. Budarin represents Rosaviakosmos.

Progress 14P approaches the ISS during Expedition 9

NASA Image and Video Library

2004-05-27

ISS009-E-08847 (27 May 2004) --- Backdropped by the blackness of space and Earth’s horizon, an unpiloted Progress supply vehicle approaches the International Space Station (ISS). The Progress 14 resupply craft launched at 7:34 a.m. (CDT) on May 25, 2004 from the Baikonur Cosmodrome in Kazakhstan to deliver 2 ½ tons of food, water, fuel and supplies to the Expedition 9 crewmembers onboard the Station. Progress docked to the aft port of the Zvezda Service Module at 8:55 a.m. (CDT) on May 27 as the two craft flew 230 statute miles above Central Asia.

Progress 14P approaches the ISS during Expedition 9

NASA Image and Video Library

2004-05-27

ISS009-E-08842 (27 May 2004) --- Backdropped by a blue and white Earth, an unpiloted Progress supply vehicle approaches the International Space Station (ISS). The Progress 14 resupply craft launched at 7:34 a.m. (CDT) on May 25, 2004 from the Baikonur Cosmodrome in Kazakhstan to deliver 2 ½ tons of food, water, fuel and supplies to the Expedition 9 crewmembers onboard the Station. Progress docked to the aft port of the Zvezda Service Module at 8:55 a.m. (CDT) on May 27 as the two craft flew 230 statute miles above Central Asia.

Executive dysfunction assessed by Clock-Drawing Test in older non-demented subjects with metabolic syndrome is not mediated by white matter lesions.

PubMed

Viscogliosi, Giovanni; Chiriac, Iulia Maria; Andreozzi, Paola; Ettorre, Evaristo

2015-10-01

Metabolic syndrome (MetS) has been associated with greater occurrence of white matter hyperintensities (WMH). It remains uncertain whether MetS as a construct is associated with poorer cognitive performances. This study explores whether MetS is associated with poorer performances in global and domain-specific cognitive tests in older non-demented subjects independently of its individual components, WMH severity and other variables. MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III definition. Brain magnetic resonance studies (1.5T) were performed. Deep and periventricular WMH were graded using the Fazekas scale. Subjects underwent the Mini-Mental State Examination, the Babcock Short Story Recall test and the Clock-Drawing Test (CDT). Eighty community-dwellers aged 67-91 years were studied. Subjects with MetS (n = 35) had more severe WMH, and poorer performances on the CDT (P = 0.003) and the Babcock Short Story Recall test (P = 0.027). After multiple adjustment, MetS was inversely associated with CDT scores (B = -1.285; 95% confidence interval = -1.996--0.575; P = 0.001) but not with episodic memory. Results were not affected by WMH severity. Interestingly, none of the individual components of MetS predicted poorer cognitive performances. Impairment in executive functions assessed by CDT may represent an early and specific sign of cognitive decline in older individuals with MetS. Future longitudinal studies are needed to better establish the predictive role of MetS on dementia and to demonstrate the possibility of dementia prevention by targeting MetS. © 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.

Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review

PubMed Central

Elbasty, Ahmed; Metcalf, James

2017-01-01

Purpose Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. Materials and Methods MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration’s tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Results Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. Conclusion CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured. PMID:29354622

Variable implementation of good practice recommendations for the assessment and management of UK children with neurodisability.

PubMed

Gray, L; Gibbs, J; Jolleff, N; Williams, J; McConachie, H; Parr, J R

2015-11-01

The aims of this study were to determine whether UK child development teams (CDTs) have implemented good practice recommendations for the co-ordinated assessment and support of children with neurodisability and to explore some of the factors associated with variations in good practice implementation. Surveys were sent to every UK CDT in 2009/2010. Responses about CDT provision and ways of working were compared with good practice recommendations from national policy documents and professional organizations. The extent to which CDTs in England and Wales met 11 selected good practice recommendations was scored; teams in Scotland and Northern Ireland were given a score out of 9 to reflect the optional use of the common assessment framework and early support materials in these countries. Responses were received from 225/240 (94%) UK CDTs. Thirty-seven per cent of CDTs in England and Wales had implemented nine or more of the 11 recommendations. Fifty-nine per cent of teams in Scotland and 78% of teams in Northern Ireland met between six and nine recommendations of good working practice. Higher levels of implementation of recommendations were found when the CDT had a Child Development Centre base and for teams who had received increased funding in the 5 years preceding the survey. There was considerable variability in the degree to which CDTs implemented good practice recommendations for the diagnosis and management of children with neurodisability. Evidence about child and parent satisfaction, and the effectiveness of CDT practices and provision, is required, so policymakers, healthcare commissioners and clinicians can provide the most appropriate services to children with neurodisability and their families. © 2015 John Wiley & Sons Ltd.

Correlation between plasma homocysteine levels and craving in alcohol dependent stabilized patients.

PubMed

Coppola, Maurizio; Mondola, Raffaella

2018-06-01

Homocysteine is a sulfur amino acid strictly related with alcohol consumption. In alcoholics, hyperhomocysteinemia can increase the risk of various alcohol-related disorders such as: brain atrophy, epileptic seizures during withdrawal, and mood disorders. To evaluate the correlation among serum homocysteine concentrations, craving, hazardous and harmful patterns of alcohol consumption in patients stabilized for withdrawal symptoms. Participants were adult outpatients accessed at the Addiction Treatment Unit. Alcoholism was assessed using the following tools: Mini-International Neuropsychiatric Interview Plus (MINI Plus), Alcohol Use Disorder Identification test (AUDIT), Visual Analogic Scale for craving (VAS). Furthermore, during the first visit a blood sample was taken from all patients to measure the plasma concentration of both homocysteine and Carboxy Deficient Transferrin (CDT). Differences between groups in socio-demographic and clinical characteristics were analyzed using the t-test and the Mann-Whitney's U test for normally and non-normally distributed data, respectively. Correlation between clinical scale scores and plasma concentration of homocysteine and CDT was evaluated using the Pearson's correlation coefficient and the Kendall's Tau-b bivariate correlation coefficient for normally and non-normally distributed data, respectively. Our study included 92 patients. No difference was found in socio-demographic characteristics between groups. The group with high homocysteine had higher prevalence of mood disorders (p < 0.001), plasma CDT percentage (p < 0.001), VAS score (p < 0.001) and AUDIT score (p < 0.001) than group with normal homocysteine. Plasma homocysteine showed a positive correlation with both VAS score (p < 0.001), and AUDIT score (p < 0.05). In our study, plasma homocysteine concentration is associated with craving, hazardous and harmful patterns of alcohol consumption. In particular, homocysteine is correlated with alcoholism in a bidirectional manner because its level appears to be related with alcohol degree, but simultaneously, hyperhomocysteinemia could enhance the alcohol consumption increasing the severity of craving in a circular self reinforcing mechanism. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains.

PubMed

Beer, Lara-Antonia; Tatge, Helma; Schneider, Carmen; Ruschig, Maximilian; Hust, Michael; Barton, Jessica; Thiemann, Stefan; Fühner, Viola; Russo, Giulio; Gerhard, Ralf

2018-06-01

Binary toxins are produced by several pathogenic bacteria. Examples are the C2 toxin from Clostridium botulinum , the iota toxin from Clostridium perfringens, and the CDT from Clostridium difficile . All these binary toxins have ADP-ribosyltransferases (ADPRT) as their enzymatically active component that modify monomeric actin in their target cells. The binary C2 toxin was intensively described as a tool for intracellular delivery of allogenic ADPRTs. Here, we firstly describe the binary toxin CDT from C. difficile as an effective tool for heterologous intracellular delivery. Even 60 kDa glucosyltransferase domains of large clostridial glucosyltransferases can be delivered into cells. The glucosyltransferase domains of five tested large clostridial glucosyltransferases were successfully introduced into cells as chimeric fusions to the CDTa adapter domain (CDTaN). Cell uptake was demonstrated by the analysis of cell morphology, cytoskeleton staining, and intracellular substrate glucosylation. The fusion toxins were functional only when the adapter domain of CDTa was N -terminally located, according to its native orientation. Thus, like other binary toxins, the CDTaN/b system can be used for standardized delivery systems not only for bacterial ADPRTs but also for a variety of bacterial glucosyltransferase domains.

Cryo-EM structure of a helicase loading intermediate containing ORC–Cdc6–Cdt1–MCM2-7 bound to DNA

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

Sun, Jingchuan; Evrin, Cecile; Samel, Stefan A.

2013-07-14

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC–Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC–Cdc6 and Cdt1–MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC–Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC–Cdc6 undergoes a concertedmore » change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC–Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action.« less

Cystic dysplasia of the testis: a very rare paediatric tumor of the testis.

PubMed

Eberli, Daniel; Gretener, Heini; Dommann-Scherrer, Corina; Pestalozzi, Dietegen; Fehr, Jean-Luc

2002-01-01

To describe a case of cystic dysplasia of the testis (CDT), an uncommon cause of scrotal swelling in the pediatric patient. Clinic, therapy, fertility, and radiographic and pathologic findings are discussed and the 30 previously reported cases are reviewed. A 9-year-old boy presented with asymptomatic scrotal swelling. A scrotal ultrasound showed a multicystic scrotal mass in the rete testis and an ipsilateral renal agenesis. The growth in size of the mass forced the authors to perform an operative exploration. Intraoperative findings included a multicystic mass in the rete testis of the right testicle. Testicle-sparing total removal of the multicystic mass was performed and the pathologic examination revealed a benign, multilobulated configuration of the cysts in the region of the rete testis. These findings were similar to those found in previously reported cases of CDT. Ipsilateral renal agenesis is the most common associated anomaly. As a pathogenetic factor, mal-junction of the Wolffian duct in the 5th week of gestation is most creditable. CDT is a rare cause of pediatric scrotal mass. When feasible, a testicle-sparing approach should be considered and all patients should undergo evaluation for associated urologic anomalies.

Cost-Effectiveness Analysis of Initial Treatment Strategies for Nonembolic Acute Limb Ischemia Using Real-Word Data.

PubMed

Vaidya, Varun; Gangan, Nilesh; Comerota, Anthony; Lurie, Fedor

2017-02-01

Nonembolic acute limb ischemia (ALI) is a condition characterized by a sudden decrease in limb perfusion and requires immediate interventions. There are multiple treatment options available including surgery, catheter-directed thrombolysis (CDT), endovascular procedures, and hybrid treatment (a combination of open and endovascular techniques). Randomized trials provide information only on clinical efficacy, but not on economic outcomes. The objective of the study was to perform the cost-effective analysis comparing different treatment alternatives of ALI. The data were collected from 4r ProMedica community hospitals in the Northwest Ohio from January 2009 to December 2012. Patients were included if they were treated within 14 days of onset of symptoms for nonembolic ALI and were divided into groups of receiving CDT, surgery, endovascular, or hybrid treatments. Demographics, comorbidities, medications taken before admission, and smoking status were collected at baseline for all patients and were compared among the treatment groups. A cost-effectiveness decision tree was developed to calculate expected costs and life years gained associated with available treatment options. A probabilistic sensitivity analysis was also performed to check the robustness of the model. A population of 205 patients with the diagnosis of ALI was included and divided into different treatment groups. There was no major significant difference in baseline characteristics among the studied groups (P > 0.05). The total costs were $17,163.47 for surgery, $20,620.39 for endovascular, $21,277.61 for hybrid, and $30,675.42 for CDT. The life years gained were 17.25 for surgery, 18 for endovascular, 18 for hybrid, and 17 for CDT. CDT was dominated because of the high cost and the low effectiveness, while hybrid treatment was dominated when compared with endovascular treatment because these 2 treatments have similar outcomes. The incremental cost-effectiveness ratio of the endovascular group over the surgery group was found to be $4,609.23 per life year gained. The sensitivity analysis showed that the endovascular treatment was found to be cost-effective under willingness to pay $50,000. This study provides economic evaluation of ALI treatments for a defined clinical population in the real-world setting. Compared with other available alternatives, the endovascular treatment showed to be a cost-effective use of healthcare resources. Copyright © 2016 Elsevier Inc. All rights reserved.

Sunrise over the Philippine Sea

NASA Image and Video Library

1984-08-30

41D-32-14 (30 Aug 1984) --- A rainbow-like sunrise over the Philippine Sea greeted the six crew members aboard the Earth-orbiting Space Shuttle Discovery on its first day in space. A 70mm camera was used to record the scene at 3:08:14 p.m. (CDT), August 30, 1984, during Discovery's sixth orbit of a six-day mission. The spacecraft was above a position on Earth centered at 21.1 degrees north and 12.9 degrees east (about 250 miles north - northeast of the Philippine Islands). The scene was shown as one of the Post-Flight Press Conference (PFPC) visuals by the crew on September 12, 1984.

Hypothesis on the nature of time

NASA Astrophysics Data System (ADS)

Coumbe, D. N.

2015-06-01

We present numerical evidence that fictitious diffusing particles in the causal dynamical triangulation (CDT) approach to quantum gravity exceed the speed of light on small distance scales. We argue this superluminal behavior is responsible for the appearance of dimensional reduction in the spectral dimension. By axiomatically enforcing a scale invariant speed of light we show that time must dilate as a function of relative scale, just as it does as a function of relative velocity. By calculating the Hausdorff dimension of CDT diffusion paths we present a seemingly equivalent dual description in terms of a scale dependent Wick rotation of the metric. Such a modification to the nature of time may also have relevance for other approaches to quantum gravity.

Using the interactive systems framework to support a quality improvement approach to dissemination of evidence-based strategies to promote early detection of breast cancer: planning a comprehensive dynamic trial.

PubMed

Rapkin, Bruce D; Weiss, Elisa S; Lounsbury, David W; Thompson, Hayley S; Goodman, Robert M; Schechter, Clyde B; Merzel, Cheryl; Shelton, Rachel C; Blank, Arthur E; Erb-Downward, Jennifer; Williams, Abigail; Valera, Pamela; Padgett, Deborah K

2012-12-01

Dissemination efforts must optimize interventions for new settings and populations. As such, dissemination research should incorporate principles of quality improvement. Comprehensive Dynamic Trial (CDT) designs examine how information gained during dissemination may be used to modify interventions and improve performance. Although CDT may offer distinct advantages over static designs, organizing the many necessary roles and activities is a significant challenge. In this article, we discuss use of the Interactive Systems Framework for Dissemination and Implementation to systematically implement a CDT. Specifically, we describe "Bronx ACCESS", a program designed to disseminate evidence-based strategies to promote adherence to mammography guidelines. In Bronx ACCESS, the Intervention Delivery System will elicit information needed to adapt strategies to specific settings and circumstances. The Intervention Synthesis and Translation System will use this information to test changes to strategies through "embedded experiments". The Intervention Support System will build local capacities found to be necessary for intervention institutionalization. Simulation modeling will be used to integrate findings across systems. Results will inform on-going policy debate about interventions needed to promote population-level screening. More generally, this project is intended to advance understanding of research paradigms necessary to study dissemination.

Screening of transporters to improve xylodextrin utilization in the yeast Saccharomyces cerevisiae.

PubMed

Zhang, Chenlu; Acosta-Sampson, Ligia; Yu, Vivian Yaci; Cate, Jamie H D

2017-01-01

The economic production of cellulosic biofuel requires efficient and full utilization of all abundant carbohydrates naturally released from plant biomass by enzyme cocktails. Recently, we reconstituted the Neurospora crassa xylodextrin transport and consumption system in Saccharomyces cerevisiae, enabling growth of yeast on xylodextrins aerobically. However, the consumption rate of xylodextrin requires improvement for industrial applications, including consumption in anaerobic conditions. As a first step in this improvement, we report analysis of orthologues of the N. crassa transporters CDT-1 and CDT-2. Transporter ST16 from Trichoderma virens enables faster aerobic growth of S. cerevisiae on xylodextrins compared to CDT-2. ST16 is a xylodextrin-specific transporter, and the xylobiose transport activity of ST16 is not inhibited by cellobiose. Other transporters identified in the screen also enable growth on xylodextrins including xylotriose. Taken together, these results indicate that multiple transporters might prove useful to improve xylodextrin utilization in S. cerevisiae. Efforts to use directed evolution to improve ST16 from a chromosomally-integrated copy were not successful, due to background growth of yeast on other carbon sources present in the selection medium. Future experiments will require increasing the baseline growth rate of the yeast population on xylodextrins, to ensure that the selective pressure exerted on xylodextrin transport can lead to isolation of improved xylodextrin transporters.

Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression*

PubMed Central

Pefani, Dafni-Eleutheria; Dimaki, Maria; Spella, Magda; Karantzelis, Nickolas; Mitsiki, Eirini; Kyrousi, Christina; Symeonidou, Ioanna-Eleni; Perrakis, Anastassis; Taraviras, Stavros; Lygerou, Zoi

2011-01-01

Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development. PMID:21543332

Idas, a novel phylogenetically conserved geminin-related protein, binds to geminin and is required for cell cycle progression.

PubMed

Pefani, Dafni-Eleutheria; Dimaki, Maria; Spella, Magda; Karantzelis, Nickolas; Mitsiki, Eirini; Kyrousi, Christina; Symeonidou, Ioanna-Eleni; Perrakis, Anastassis; Taraviras, Stavros; Lygerou, Zoi

2011-07-01

Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development.

Ribonucleotide reductase activity is regulated by proliferating cell nuclear antigen (PCNA)

PubMed Central

Salguero, Israel; Guarino, Estrella; Shepherd, Marianne; Deegan, Tom; Havens, Courtney G.; MacNeill, Stuart A.; Walter, Johannes C.; Kearsey, Stephen E.

2014-01-01

Summary Synthesis of dNTPs is required for both DNA replication and DNA repair and is catalyzed by ribonucleotide reductases (RNR), which convert ribonucleotides to their deoxy forms [1, 2]. Maintaining the correct levels of dNTPs for DNA synthesis is important for minimising the mutation rate [3-7], and this is achieved by tight regulation of ribonucleotide reductase [2, 8, 9]. In fission yeast, ribonucleotide reductase is regulated in part by a small protein inhibitor, Spd1, which is degraded in S phase and after DNA damage to allow up-regulation of dNTP supply [10-12]. Spd1 degradation is mediated by the activity of the CRL4Cdt2 ubiquitin ligase complex [5, 13, 14]. This has been reported to be dependent on modulation of Cdt2 levels which are cell cycle regulated, peaking in S phase, and which also increase after DNA damage in a checkpoint-dependent manner [7, 13]. We show here that Cdt2 levels fluctuations are not sufficient to regulate Spd1 proteolysis and that the key step in this event is the interaction of Spd1 with the polymerase processivity factor PCNA, complexed onto DNA. This mechanism thus provides a direct link between DNA synthesis and ribonucleotide reductase regulation. PMID:22464192

Role of Catheter-directed Thrombolysis in Management of Iliofemoral Deep Venous Thrombosis.

PubMed

Chen, James X; Sudheendra, Deepak; Stavropoulos, S William; Nadolski, Gregory J

2016-01-01

The treatment for iliofemoral deep venous thrombosis (DVT) is challenging, as the use of anticoagulation alone can be insufficient for restoring venous patency and thus lead to prolongation of acute symptoms and an increased risk of chronic complications, including venous insufficiency and postthrombotic syndrome (PTS). In these cases, earlier and more complete thrombus removal can ameliorate acute symptoms and reduce long-term sequelae. Endovascular therapies involving the use of pharmacologic, mechanical, and combined pharmacomechanical modalities have been developed to achieve these goals. The most frequently used of these techniques, catheter-directed thrombolysis (CDT), involves the infusion of a thrombolytic agent through a multiple-side-hole catheter placed within the thrombosed vein to achieve high local doses and thereby break down the clot while minimizing systemic thrombolytic agent exposure. Randomized controlled trial results have indicated decreased PTS rates and improved venous patency rates in patients treated with CDT compared with these rates in patients treated with anticoagulation. The use of newer pharmacomechanical techniques, as compared with conventional CDT, reduces procedural times and thrombolytic agent doses and is the subject of ongoing investigations. Endovascular thrombus removal techniques offer a means to improve venous valvular function and decrease the risk of debilitating long-term complications such as PTS and are a promising option for treating patients with iliofemoral DVT. (©)RSNA, 2016.

Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response

PubMed Central

Guidi, Riccardo; Guerra, Lina; Levi, Laura; Stenerlöw, Bo; Fox, James G.; Josenhans, Christine; Masucci, Maria G.; Frisan, Teresa

2014-01-01

Summary Epidemiological evidence links chronic bacterial infections to the increased incidence of certain types of cancer but the molecular mechanisms by which bacteria contribute to tumour initiation and progression are still poorly characterized. Here we show that chronic exposure to the genotoxin cytolethal distending toxin (CDT) of Gram-negative bacteria promotes genomic instability and acquisition of phenotypic properties of malignancy in fibroblasts and colon epithelial cells. Cells grown for more than 30 weeks in the presence of sublethal doses of CDT showed increased mutation frequency, and accumulation of chromatin and chromosomal aberrations in the absence of significant alterations of cell cycle distribution, decreased viability or senescence. Cell survival was dependent on sustained activity of the p38 MAP kinase. The ongoing genomic instability was associated with impaired activation of the DNA damage response and failure to efficiently activate cell cycle checkpoints upon exposure to genotoxic stress. Independently selected sublines showed enhanced anchorage-independent growth as assessed by the formation of colonies in semisolid agarose. These findings support the notion that chronic infection by CDT-producing bacteria may promote malignant transformation, and point to the impairment of cellular control mechanisms associated with the detection and repair of DNA damage as critical events in the process. PMID:22998585

Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 subunit of DNA polymerase δ revealed in individual cells by cytometry

PubMed Central

Darzynkiewicz, Zbigniew; Zhao, Hong; Zhang, Sufang; Marietta, Y.W.T. Lee; Ernest, Y.C. Lee; Zhang, Zhongtao

2015-01-01

During our recent studies on mechanism of the regulation of human DNA polymerase δ in preparation for DNA replication or repair, multiparameter imaging cytometry as exemplified by laser scanning cytometry (LSC) has been used to assess changes in expression of the following nuclear proteins associated with initiation of DNA replication: cyclin A, PCNA, Ki-67, p21WAF1, DNA replication factor Cdt1 and the smallest subunit of DNA polymerase δ, p12. In the present review, rather than focusing on Pol δ, we emphasize the application of LSC in these studies and outline possibilities offered by the concurrent differential analysis of DNA replication in conjunction with expression of the nuclear proteins. A more extensive analysis of the data on a correlation between rates of EdU incorporation, likely reporting DNA replication, and expression of these proteins, is presently provided. New data, specifically on the expression of cyclin D1 and cyclin E with respect to EdU incorporation as well as on a relationship between expression of cyclin A vs. p21WAF1 and Ki-67 vs. Cdt1, are also reported. Of particular interest is the observation that this approach makes it possible to assess the temporal sequence of degradation of cyclin D1, p21WAF1, Cdt1 and p12, each with respect to initiation of DNA replication and with respect to each other. Also the sequence or reappearance of these proteins in G2 after termination of DNA replication is assessed. The reviewed data provide a more comprehensive presentation of potential markers, whose presence or absence marks the DNA replicating cells. Discussed is also usefulness of these markers as indicators of proliferative activity in cancer tissues that may bear information on tumor progression and have a prognostic value. PMID:26059433

Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 subunit of DNA polymerase δ revealed in individual cells by cytometry.

PubMed

Darzynkiewicz, Zbigniew; Zhao, Hong; Zhang, Sufang; Lee, Marietta Y W T; Lee, Ernest Y C; Zhang, Zhongtao

2015-05-20

During our recent studies on mechanism of the regulation of human DNA polymerase δ in preparation for DNA replication or repair, multiparameter imaging cytometry as exemplified by laser scanning cytometry (LSC) has been used to assess changes in expression of the following nuclear proteins associated with initiation of DNA replication: cyclin A, PCNA, Ki-67, p21(WAF1), DNA replication factor Cdt1 and the smallest subunit of DNA polymerase δ, p12. In the present review, rather than focusing on Pol δ, we emphasize the application of LSC in these studies and outline possibilities offered by the concurrent differential analysis of DNA replication in conjunction with expression of the nuclear proteins. A more extensive analysis of the data on a correlation between rates of EdU incorporation, likely reporting DNA replication, and expression of these proteins, is presently provided. New data, specifically on the expression of cyclin D1 and cyclin E with respect to EdU incorporation as well as on a relationship between expression of cyclin A vs. p21(WAF1) and Ki-67 vs. Cdt1, are also reported. Of particular interest is the observation that this approach makes it possible to assess the temporal sequence of degradation of cyclin D1, p21(WAF1), Cdt1 and p12, each with respect to initiation of DNA replication and with respect to each other. Also the sequence or reappearance of these proteins in G2 after termination of DNA replication is assessed. The reviewed data provide a more comprehensive presentation of potential markers, whose presence or absence marks the DNA replicating cells. Discussed is also usefulness of these markers as indicators of proliferative activity in cancer tissues that may bear information on tumor progression and have a prognostic value.

Consortia-mediated bioprocessing of cellulose to ethanol with a symbiotic Clostridium phytofermentans/yeast co-culture.

PubMed

Zuroff, Trevor R; Xiques, Salvador Barri; Curtis, Wayne R

2013-04-29

Lignocellulosic ethanol is a viable alternative to petroleum-based fuels with the added benefit of potentially lower greenhouse gas emissions. Consolidated bioprocessing (simultaneous enzyme production, hydrolysis and fermentation; CBP) is thought to be a low-cost processing scheme for lignocellulosic ethanol production. However, no single organism has been developed which is capable of high productivity, yield and titer ethanol production directly from lignocellulose. Consortia of cellulolytic and ethanologenic organisms could be an attractive alternate to the typical single organism approaches but implementation of consortia has a number of challenges (e.g., control, stability, productivity). Ethanol is produced from α-cellulose using a consortium of C. phytofermentans and yeast that is maintained by controlled oxygen transport. Both Saccharomyces cerevisiae cdt-1 and Candida molischiana "protect" C. phytofermentans from introduced oxygen in return for soluble sugars released by C. phytofermentans hydrolysis. Only co-cultures were able to degrade filter paper when mono- and co-cultures were incubated at 30°C under semi-aerobic conditions. Using controlled oxygen delivery by diffusion through neoprene tubing at a calculated rate of approximately 8 μmol/L hour, we demonstrate establishment of the symbiotic relationship between C. phytofermentans and S. cerevisiae cdt-1 and maintenance of populations of 105 to 106 CFU/mL for 50 days. Comparable symbiotic population dynamics were observed in scaled up 500 mL bioreactors as those in 50 mL shake cultures. The conversion of α-cellulose to ethanol was shown to improve with additional cellulase indicating a limitation in hydrolysis rate. A co-culture of C. phytofermentans and S. cerevisiae cdt-1 with added endoglucanase produced approximately 22 g/L ethanol from 100 g/L α-cellulose compared to C. phytofermentans and S. cerevisiae cdt-1 mono-cultures which produced approximately 6 and 9 g/L, respectively. This work represents a significant step toward developing consortia-based bioprocessing systems for lignocellulosic biofuels production which utilize scalable, environmentally-mediated symbiosis mechanisms to provide consortium stability.

How Langmuir-Blodgett trilayers act as templates for directed self-assembly of nanoparticles

NASA Astrophysics Data System (ADS)

Mukherjee, Smita; Datta, Alokmay; Biswas, Nupur; Giglia, Angelo; Nannarone, Stefano

2014-04-01

Atomic force microscopy (AFM) shows that Langmuir-Blodgett (LB) deposition of dissimilar metal stearates (MSt, M = Co, Zn, Cd) on templates of Co-stearate (Co-T) and Cd-stearate (Cd-T) results in self-assembly of MSts into nanocrystalline grains having clear and consistent morphological habits. The grains are better formed and well separated on Cd-T than on Co-T. Fourier transform infrared spectroscopy (FTIR) results show that the headgroup coordination of the overlayer is tuned by the coordination of the Cd-T template and remains unaffected by that of the Co-T template. They also indicate co-existence of a different kind of headgroup structure that is close to the undissociated fatty acid headgroup but differing more in the two types of carbon-oxygen bonds, suggesting an inter-headgroup bonding such as hydrogen bond that may exist on a nanocrystal surface. Results of synchrotron x-ray diffraction at C K-edge, of ZnSt on Cd-T (ZnSt/Cd-T) and Co-T (ZnSt/Co-T), point to a non-closed packed structure for ZnSt/Cd-T and a closed-packed structure for ZnSt/Co-T, with significant superlattice order in the former. The presence of crystalline phases of ZnSt in the nanometer scale, on LB templates, in contrast to the the presence of lamellar phase in bulk ZnSt, is attributed to the the presence of unidentate metal-carboxylate coordination in the former and absence of it in the latter, creating different gradients of dipolar forces at template overlayer interface. Relative strength of this long-range force over short-range intermolecular forces in the templates qualitatively explains better crystallinity and higher ordering in ZnSt/Cd-T compared to ZnSt/Co-T. We propose that the role of dipole moment gradient between template and overlayer in tuning of these metal-organic nanoparticles may be somewhat similar to structural and optical tunability of semiconductor nanocrystals by thermal and self-equilibrium strain.

Safety and efficacy of a novel disposable circumcision device: A pilot randomized controlled clinical trial at 2 centers

PubMed Central

Wang, Jingen; Zhou, Yongfei; Xia, Shuxia; Zhu, Zunwei; Jia, Linghua; Liu, Yong; Jiang, Min

2014-01-01

Background We evaluated the safety and efficacy of a novel disposable male circumcision (MC) device developed by Jiangxi-Yuansheng-Langhe Medical Instrument Co., Ltd. Material/Methods Adult male patients (n=120; mean age, 26.6 years) with redundant foreskin and/or phimosis were included in a randomized, multicenter pilot clinical trial from October 2011 to February 2012. Patients were divided into 2 groups and subjected to MC with a novel disposable device (Device Group) (n=60) or to conventional dissection technique (CDT) (Control Group) (n=60). Intraoperative bleeding, surgery duration, pain, healing, and satisfaction with penis appearance were assessed. Adverse events (AEs) were noted. Results Intraoperative bleeding volume [3.5±2.7 (15–35) ml vs. 13.1±6.1 (4–25) ml] and mean surgical time [7.6±4.5 (2–23) min vs. 23.6±4.4 (15–35) min] in the Device Group were significantly less than in the Control Group (P<0.01). No AEs were observed in either group. There were no significant differences in postoperative pain, healing, or satisfaction with penis appearance between groups (P>0.05). Conclusions This novel disposable circumcision device produced satisfactory preliminary adult MC results compared with CDT treatments. This device may be broadly used in men, such as those with phimosis, who are ineligible for CDT. PMID:24647226

Strain-dependent induction of epithelial cell oncosis by Campylobacter jejuni is correlated with invasion ability and is independent of cytolethal distending toxin.

PubMed

Kalischuk, Lisa D; Inglis, G Douglas; Buret, Andre G

2007-09-01

Induction of host cell death is thought to play an important role in bacterial pathogenesis. Campylobacter jejuni is a prevalent cause of bacterial enteritis; however, its effects on enterocytes remain unclear. The present study indicates for the first time that C. jejuni induces oncotic, rather than apoptotic death of T84 enterocytes. C. jejuni-treated enterocytes exhibited extensive cytoplasmic vacuolation, rapid (3-6 h) loss of plasma membrane integrity ('cytotoxicity'), loss of mitochondrial transmembrane potential, and ATP depletion. Enterocytes also exhibited increased oligonucleosomal DNA fragmentation, a feature characteristic of apoptosis. However, consistent with a non-apoptotic process, DNA fragmentation and cytotoxicity were not caspase dependent. During apoptosis, caspases mediate cleavage of poly(ADP-ribose) polymerase; however, cleavage was not observed in C. jejuni-treated monolayers. Cytotoxicity, ATP depletion and DNA fragmentation were not prevented by the deletion of the cytolethal distending toxin (CDT) gene, indicating that C. jejuni causes enterocyte oncosis via a mechanism that is CDT independent. The ability to cause oncosis was significantly decreased in a FlaAFlaB mutant (CDT(+)) that was defective in the ability to adhere and invade enterocytes. Analysis of clinical isolates revealed that oncosis was strain dependent and correlated with increased invasive ability. These observations offer new insights into the pathogenesis of C. jejuni infection.

A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT.

PubMed

Porpiglia, Nadia Maria; De Palo, Elio Franco; Savchuk, Sergey Alexandrovich; Appolonova, Svetlana Alexandrovna; Bortolotti, Federica; Tagliaro, Franco

2018-05-10

The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology. Copyright © 2018. Published by Elsevier B.V.

Visual Working Memory Capacity Can Be Increased by Training on Distractor Filtering Efficiency.

PubMed

Li, Cui-Hong; He, Xu; Wang, Yu-Juan; Hu, Zhe; Guo, Chun-Yan

2017-01-01

It is generally considered that working memory (WM) capacity is limited and that WM capacity affects cognitive processes. Distractor filtering efficiency has been suggested to be an important factor in determining the visual working memory (VWM) capacity of individuals. In the present study, we investigated whether training in visual filtering efficiency (FE) could improve VWM capacity, as measured by performance on the change detection task (CDT) and changes of contralateral delay activity (CDA) (contralateral delay activity) of different conditions, and evaluated the transfer effect of visual FE training on verbal WM and fluid intelligence, as indexed by performance on the verbal WM span task and Raven's Standard Progressive Matrices (RSPM) test, respectively. Participants were divided into high- and low-capacity groups based on their performance in a CDT designed to test VWM capacity, and then the low-capacity individuals received 20 days of FE training. The training significantly improved the group's performance in the CDT, and their CDA models of different conditions became more similar with high capacity group, and the effect generalized to improve verbal WM span. These gains were maintained at a 3-month follow-up test. Participants' RSPM scores were not changed by the training. These findings support the notion that WM capacity is determined, at least in part, by distractor FE and can be enhanced through training.

[Endovascular treatment of acute iliofemoral deep venous thrombosis - our results with catheter-directed thrombolysis and AngioJet].

PubMed

Berencsi, Anikó; Dósa, Edit; Nemes, Balázs; Hüttl, Kálmán; Legeza, Péter; Oláh, Zoltán; Kristóf, Vera; Acsády, György; Sótonyi, Péter

2017-03-01

Most of the patients with iliofemoral thrombosis treated with anticoagulants only are affected with postthrombotic syndrome (PTS) that worsens the patients' quality of life. In the acute phase of proximal deep venous thrombosis (DVT) catheter-directed (CDT) and pharmacomechanical thrombolysis may be a reasonable alternative therapeutic method. Our aim was to summarize our results using these methods. Since 2009 twenty-four patients with iliofemoral DVT were treated with these endovascular procedures and with stenting at our Institution. The median age of the patients was 35.83 ± 15.9 years, the female: male ratio was approximately 2:1. The mean time between the onset of the symptoms and the procedures was eleven days. CDT alone was performed in 8 patients, thrombus aspiration in addition to CDT using AngioJet device in 16 patients; in 19 cases the procedure was completed with venous stenting. During the follow-up we performed US examinations and estimated the severity of PTS by Villalta-scale. The total recanalization-rate was more than 50%, which even improved during the follow-up. The total lysis time and the amount of used recombinant tissue plasminogen activator decreased significantly by applying the AngioJet. We did not find any severe PTS among our patients during the follow-up visits. Our data suggests that these methods can be used efficiently and safely in the treatment of acute iliofemoral DVT.

Scientific basis for learning transfer from movements to urinary bladder functions for bladder repair in human patients with CNS injury.

PubMed

Schalow, G

2010-01-01

Coordination Dynamics Therapy (CDT) has been shown to be able to partly repair CNS injury. The repair is based on a movement-based re-learning theory which requires at least three levels of description: the movement or pattern (and anamnesis) level, the collective variable level, and the neuron level. Upon CDT not only the actually performed movement pattern itself is repaired, but the entire dynamics of CNS organization is improved, which is the theoretical basis for (re-) learning transfer. The transfer of learning for repair from jumping on springboard and exercising on a special CDT and recording device to urinary bladder functions is investigated at the neuron level. At the movement or pattern level, the improvement of central nervous system (CNS) functioning in human patients can be seen (or partly measured) by the improvement of the performance of the pattern. At the collective variable level, coordination tendencies can be measured by the so-called 'coordination dynamics' before, during and after treatment. At the neuron level, re-learning can additionally be assessed by surface electromyography (sEMG) as alterations of single motor unit firings and motor programs. But to express the ongoing interaction between the numerous neural, muscular, and metabolic elements involved in perception and action, it is relevant to inquire how the individual afferent and efferent neurons adjust their phase and frequency coordination to other neurons to satisfy learning task requirements. With the single-nerve fibre action potential recording method it was possible to measure that distributed single neurons communicate by phase and frequency coordination. It is shown that this timed firing of neurons is getting impaired upon injury and has to be improved by learning The stability of phase and frequency coordination among afferent and efferent neuron firings can be related to pattern stability. The stability of phase and frequency coordination at the neuron level can therefore be assessed integratively at the (non-invasive) collective variable level by the arrhythmicity of turning (coordination dynamics) when a patient is exercising on a special CDT device. Upon jumping on springboard and exercising on the special CDT device, the intertwined neuronal networks, subserving movements (somatic) and urinary bladder functions (autonomic and somatic) in the sacral spinal cord, are synchronously activated and entrained to give rise to learning transfer from movements to bladder functions. Jumping on springboard and other movements primarily repair the pattern dynamics, whereas the exactly coordinated performed movements, performed on the special CDT device for turning, primarily improve the preciseness of the timed firing of neurons. The synchronous learning of perceptuomotor and perceptuobladder functioning from a dynamical perspective (giving rise to learning transfer) can be understood at the neuron level. Especially the activated phase and frequency coordination upon natural stimulation under physiologic and pathophysiologic conditions among a and gamma-motoneurons, muscle spindle afferents, touch and pain afferents, and urinary bladder stretch and tension receptor afferents in the human sacral spinal cord make understandable that somatic and parasympathetic functions are integrated in their functioning and give rise to learning transfer from movements to bladder functions. The power of this human treatment research project lies in the unit of theory, diagnostic/measurement, and praxis, namely that CNS injury can partly be repaired, including urinary bladder functions, and the repair can partly be understood even at the neuron level of description in human.

Texas Fires

Atmospheric Science Data Center

2014-05-15

... one-year drought on record and the warmest month in Texas history. The Multi-angle Imaging SpectroRadiometer (MISR) instrument on NASA's Terra spacecraft passed over the wildfires at 12:05 p.m. CDT on ...

Utilization of a cognitive task analysis for laparoscopic appendectomy to identify differentiated intraoperative teaching objectives.

PubMed

Smink, Douglas S; Peyre, Sarah E; Soybel, David I; Tavakkolizadeh, Ali; Vernon, Ashley H; Anastakis, Dimitri J

2012-04-01

Experts become automated when performing surgery, making it difficult to teach complex procedures to trainees. Cognitive task analysis (CTA) enables experts to articulate operative steps and cognitive decisions in complex procedures such as laparoscopic appendectomy, which can then be used to identify central teaching points. Three local surgeon experts in laparoscopic appendectomy were interviewed using critical decision method-based CTA methodology. Interview transcripts were analyzed, and a cognitive demands table (CDT) was created for each expert. The individual CDTs were reviewed by each expert for completeness and then combined into a master CDT. Percentage agreement on operative steps and decision points was calculated for each expert. The experts then participated in a consensus meeting to review the master CDT. Each surgeon expert was asked to identify in the master CDT the most important teaching objectives for junior-level and senior-level residents. The experts' responses for junior-level and senior-level residents were compared using a χ(2) test. The surgeon experts identified 24 operative steps and 27 decision points. Eighteen of the 24 operative steps (75%) were identified by all 3 surgeon experts. The percentage of operative steps identified was high for each surgeon expert (96% for surgeon 1, 79% for surgeon 2, and 83% for surgeon 3). Of the 27 decision points, only 5 (19%) were identified by all 3 surgeon experts. The percentage of decision points identified varied by surgeon expert (78% for surgeon 1, 59% for surgeon 2, and 48% for surgeon 3). When asked to identify key teaching points, the surgeon experts were more likely to identify operative steps for junior residents (9 operative steps and 6 decision points) and decision points for senior residents (4 operative steps and 13 decision points) (P < .01). CTA can deconstruct the essential operative steps and decision points associated with performing a laparoscopic appendectomy. These results provide a framework to identify key teaching principles to guide intraoperative instruction. These learning objectives could be used to guide resident level-appropriate teaching of an essential general surgery procedure. Copyright © 2012 Elsevier Inc. All rights reserved.

Consortia-mediated bioprocessing of cellulose to ethanol with a symbiotic Clostridium phytofermentans/yeast co-culture

PubMed Central

2013-01-01

Background Lignocellulosic ethanol is a viable alternative to petroleum-based fuels with the added benefit of potentially lower greenhouse gas emissions. Consolidated bioprocessing (simultaneous enzyme production, hydrolysis and fermentation; CBP) is thought to be a low-cost processing scheme for lignocellulosic ethanol production. However, no single organism has been developed which is capable of high productivity, yield and titer ethanol production directly from lignocellulose. Consortia of cellulolytic and ethanologenic organisms could be an attractive alternate to the typical single organism approaches but implementation of consortia has a number of challenges (e.g., control, stability, productivity). Results Ethanol is produced from α-cellulose using a consortium of C. phytofermentans and yeast that is maintained by controlled oxygen transport. Both Saccharomyces cerevisiae cdt-1 and Candida molischiana “protect” C. phytofermentans from introduced oxygen in return for soluble sugars released by C. phytofermentans hydrolysis. Only co-cultures were able to degrade filter paper when mono- and co-cultures were incubated at 30°C under semi-aerobic conditions. Using controlled oxygen delivery by diffusion through neoprene tubing at a calculated rate of approximately 8 μmol/L hour, we demonstrate establishment of the symbiotic relationship between C. phytofermentans and S. cerevisiae cdt-1 and maintenance of populations of 105 to 106 CFU/mL for 50 days. Comparable symbiotic population dynamics were observed in scaled up 500 mL bioreactors as those in 50 mL shake cultures. The conversion of α-cellulose to ethanol was shown to improve with additional cellulase indicating a limitation in hydrolysis rate. A co-culture of C. phytofermentans and S. cerevisiae cdt-1 with added endoglucanase produced approximately 22 g/L ethanol from 100 g/L α-cellulose compared to C. phytofermentans and S. cerevisiae cdt-1 mono-cultures which produced approximately 6 and 9 g/L, respectively. Conclusion This work represents a significant step toward developing consortia-based bioprocessing systems for lignocellulosic biofuels production which utilize scalable, environmentally-mediated symbiosis mechanisms to provide consortium stability. PMID:23628342

Tocopherol in Elder Self-Neglect

NASA Technical Reports Server (NTRS)

Aung, K.; Burnett, J.; Dyer, C.; Smith, S. M.

2009-01-01

Although elder self-neglect is the most common form of elder mistreatment, its pathophysiology is not well understood. Alpha-tocopherol is a lipid soluble antioxidant required for the preservation of cell membranes. Since the association between tocopherol and cognitive impairment in older adults has been described, we explored the possibility of its role in elder self-neglect. OBJECTIVE: (1) To determine whether serum tocopherol levels are associated with elder self-neglect, and (2) to assess the association of serum tocopherol levels and cognitive function in elder self-neglect. METHODS: Serum tocopherol levels were measured in a cohort of 67 self-neglecting elders and 67 matched controls, recruited for the Consortium for Research in Elder Self-neglect of Texas. Pearson s correlation tests were performed to assess bivariate associations between serum tocopherol levels and cognitive function. RESULTS: Mean serum alpha-tocopherol levels were 10.8 +/- 4.7 ug/mL in self-neglect group and 13.0 +/- 4.9 ug/mL in control group (p = 0.006, unpaired student s t-test). None of the participants from either group had alpha-tocopherol level lower than the reference range. Mean serum gamma-tocopherol levels were 2.0 +/- 1.0 ug/mL in self-neglect group and 2.0 +/- 1.1 in control group (p=0.83). Proportion of the elders with gamma-tocopherol level lower than the reference range were 4.5% (3/66) in self-neglect group and 10.4% (7/67) in control group (p=0.32, Fisher s Exact Test). Among the self-neglecting elders, no association was found between serum alpha-tocopherol levels and the Mini-Mental State Examination (MMSE) or the Wolf-Klein Clock Drawing Test (CDT) scores (r =-0.42, p=0.75 for MMSE; r=0.08, p=0.54 for CDT). No association was found between serum gamma-tocopherol levels and the MMSE or the CDT (r=-0.12, p=0.35 for MMSE; r=0.05, p=0.68 for CDT). CONCLUSION: In our sample, neither alpha-tocopherol nor gamma-tocopherol appears to have a role in pathophysiology of elder self-neglect. Nevertheless, significantly lower serum alpha-tocopherol levels in the self neglect group merits further research.

The sensitivity and specificity of subjective memory complaints and the subjective memory rating scale, deterioration cognitive observee, mini-mental state examination, six-item screener and clock drawing test in dementia screening.

PubMed

Ramlall, S; Chipps, J; Bhigjee, A I; Pillay, B J

2013-01-01

The effectiveness of dementia screening depends on the availability of suitable screening tools with good sensitivity and specificity to confidently distinguish normal age-related cognitive decline from dementia. The aim of this study was to evaluate the discriminant validity of 7 screening measures for dementia. A sample of 140 participants aged ≥60 years living in a residential facility for the aged were assessed clinically and assigned caseness for dementia using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised diagnostic criteria. Sensitivity and specificity of a selection of the following screening measures were tested using receiver operating characteristic (ROC) analysis for individual and combined tests: the Mini-Mental State Examination (MMSE), Six-Item Screener (SIS), Subjective Memory Complaint, Subjective Memory Complaint Clinical (SMCC), Subjective Memory Rating Scale (SMRS), Deterioration Cognitive Observee (DECO) and the Clock Drawing Test (CDT). Using ROC analyses, the SMCC, MMSE and CDT were found to be 'moderately accurate' in screening for dementia with an area under the curve (AUC) >0.70. The AUCs for the SIS (0.526), SMRS (0.661) and DECO (0.687) classified these measures as being 'less accurate'. At recommended cutoff scores, the SMCC had a sensitivity of 90.9% and specificity of 45.7%; the MMSE had a sensitivity of 63.6% and a specificity of 76.0%, and the CDT had a sensitivity of 44.4% and a specificity of 88.9%. Combining the SMCC and MMSE did not improve their predictive power except for a modest increase when using the sequential rule. The SMCC is composed of valid screening questions that have high sensitivity, are simple to administer and ideal for administration at the community or primary health care level as a first level of 'rule-out' screening. The MMSE can be included at a second stage of screening at the general hospital level and the CDT in specialist clinical settings. Sequential use of the SMCC and MMSE will improve the specificity of the former and the sensitivity of the latter. Copyright © 2013 S. Karger AG, Basel.

Detection of Escherichia albertii from chicken meat and giblets.

PubMed

Maeda, Eriko; Murakami, Koichi; Sera, Nobuyuki; Ito, Kenitiro; Fujimoto, Shuji

2015-07-01

Escherichia albertii occasionally causes food-borne outbreaks of gastroenteritis in humans; however, little is known about the vehicle of transmission. To screen retail chicken products for the presence of E. albertii, 104 retail chicken products were investigated. Portions of enrichment cultures that were PCR-positive for E. albertii (n=3) were sub-cultured on agar medium. Only 2 strains obtained from 2 chicken giblet samples were identified as E. albertii by multi locus sequence typing. Antimicrobial susceptibility testing showed that 1 strain was resistant to streptomycin and sulfisoxazole. Both strains harbored the virulence genes cdt and eae. This study is the first description of E. albertii isolation from retail food, suggesting that chicken products are a potential vehicle of E. albertii transmission.

Medical Library Association

MedlinePlus

... CST, Fri Nov 10th, 2017 Harlingen, Texas Metadata Transformation Librarian Updated 9:27AM CDT, Wed Nov 1st, ... 05 PM Characteristics of multi-institutional health sciences education research: a systematic review Posted on: October 2, ...

Analysis of carbohydrate deficient transferrin by capillary zone electrophoresis.

PubMed

Prasad, R; Stout, R L; Coffin, D; Smith, J

1997-09-01

We report a capillary zone electrophoresis method to separate the various sialylated isoforms of transferrin. The separation is carried out under nondenaturing conditions and at basic pH. Under these conditions, transferrin exhibits two major and three minor peaks. Plasma samples from a population consuming varying amounts of alcohol at different intervals were studied. A cut-off value of 3% carbohydrate deficient transferrin (CDT: disialo, monosialo, and asialo transferrin), results in a clinical sensitivity of 88% in a population consuming at least 70 g/day alcohol for a minimum of two weeks. The sensitivity dropped significantly in a population consuming less than 70 g/day. This confirms previous reports of CDT as a specific marker for significant and chronic use of alcohol. Capillary electrophoresis offers an alternative method with respect to analysis time and throughput in the clinical laboratory.

Multidimensional fractional Schrödinger equation

NASA Astrophysics Data System (ADS)

Rodrigues, M. M.; Vieira, N.

2012-11-01

This work is intended to investigate the multi-dimensional space-time fractional Schrödinger equation of the form (CDt0+αu)(t,x) = iħ/2m(C∇βu)(t,x), with ħ the Planck's constant divided by 2π, m is the mass and u(t,x) is a wave function of the particle. Here (CDt0+α,C∇β are operators of the Caputo fractional derivatives, where α ∈]0,1] and β ∈]1,2]. The wave function is obtained using Laplace and Fourier transforms methods and a symbolic operational form of solutions in terms of the Mittag-Leffler functions is exhibited. It is presented an expression for the wave function and for the quantum mechanical probability density. Using Banach fixed point theorem, the existence and uniqueness of solutions is studied for this kind of fractional differential equations.

Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I).

PubMed

Huge, Volker; Lauchart, Meike; Förderreuther, Stefanie; Kaufhold, Wibke; Valet, Michael; Azad, Shahnaz Christina; Beyer, Antje; Magerl, Walter

2008-07-23

Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group. 61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT), the heat and cold pain thresholds (HPT; CPT) and the occurrence of paradoxical heat sensation (PHS) were observed. In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb. We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

Normative data for the Clock Drawing Test for French-Quebec mid- and older aged healthy adults.

PubMed

Turcotte, Valérie; Gagnon, Marie-Eve; Joubert, Sven; Rouleau, Isabelle; Gagnon, Jean-François; Escudier, Frédérique; Koski, Lisa; Potvin, Olivier; Macoir, Joël; Hudon, Carol

2018-05-09

The Clock Drawing Test (CDT) is frequently used to screen for cognitive impairment, however, normative data for Rouleau et al.'s scoring system are scarce. The present study aims to provide norms for Rouleau et al.'s scoring system that are tailored to Quebec French-speaking mid- and older aged healthy adults. Six researchers from various research centers across the Province of Quebec (Canada) sent anonymous data for 593 (391 women) healthy community-dwelling volunteers (age range: 43-93 years; education range: 5-23 years) who completed the CDT 'drawing on command' version. This command version (setting the clock hands to 11:10, without a pre-drawn circle) was administrated as part of a more extensive neuropsychological assessment, or along with cognitive screening instruments. Each drawn clock was scored according to the quantitative criteria set by Rouleau et al.'s scoring system. CDT scores were significantly correlated with age (r(592) = -.132, p = .001) and years of education (r(592) = .116, p = .005), but not with sex (r(592) = .065, p = .112). Since data were skewed towards higher test scores, the percentiles method was used for analysis. Percentile ranks stratified by age and education are presented. These normative data for Rouleau et al.'s scoring system will contribute towards adequately screening for cognitive decline in Quebec French-speaking healthy adults, by also taking into account individual characteristics such as age and education.

Metabolic parameters and cognitive function in a cohort of older diabetic patients.

PubMed

Herghelegiu, Anna Marie; Nacu, Raluca Mihaela; Prada, Gabriel Ioan

2016-12-01

Dementia is one of the most disabling conditions associated with old age. With increasing life expectancy, prevalence of both dementia and diabetes is rising. The complex pathological relationship between diabetes mellitus (DM) and dementia has been studied, but is not yet fully understood. The main objective of this study was to investigate the relationship between metabolic parameters and the cognitive function in older diabetics. A total number of 360 diabetic subjects, age 65 years and over, and 300 older people controls were included. Clinical and biological parameters, together with the cognitive function, were assessed every 6 months over a 18-month period, for each study participant. By employing a multivariate linear regression analysis, several significant relationships have been identified: between Clock Drawing Test (CDT) scores and HbA1c (R 2  = 0.68); between CDT scores (R 2  = 0.51) and overall MMSE scores (R 2  = 0.43) on one hand, and DM duration in years, on the other hand; also between CDT scores and BMI (R 2  = 0.59). There was no significant association between fasting serum glucose (FSG), total serum cholesterol, LDL cholesterol or triglycerides levels and cognitive function scores (p > 0.05). The close detailed monitoring of the cognitive function and a rigorous metabolic control are important, especially in the very early stages of DM. Addressing factors such as weight control in older diabetic patients could contribute to better cognitive outcomes.

EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin

PubMed Central

Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R.; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

2016-01-01

The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629

EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

PubMed

Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

2016-04-01

The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

Overreaching in coordination dynamics therapy in an athlete with a spinal cord injury.

PubMed

Schalow, G; Vaher, I; Jaigma, P

2008-03-01

A motocross athlete suffered a clinically complete spinal cord injury (SCI) during competition. Although MRIs (magnetic resonance imaging) showed a complete spinal cord injury at the Thoracic 11/12 levels, surface EMG recordings indicated the survival of few tract fibres across the injury site. Six weeks after the accident the subject began intensive Coordination Dynamics Therapy (CDT) at an up-to-date therapy centre. The subject trained at his physical limits to induce structural and functional repair. Exercising at variable loads between 20 and 200N (on a special CDT and recording device) generated periods of overreaching and super-compensation. By plotting coordination dynamics values (kinesiology), including high-load exertion (200N) and hysteresis curves, periods of overreaching and super-compensation were made graphically visible. It was found that symmetrical improvements of central nervous system (CNS) functioning occurred during overreaching. Improvements in spinal cord functioning were achieved throughout one year of CDT in this chronically injured subject with an almost anatomically complete SCI. It is discussed that the measuring of CNS functions by means of recording coordination dynamics is a powerful and non-invasive tool ideal for exact quantitative and qualitative measurements of improvement (or change) in CNS functioning. Such diagnostics may be of particular importance in sport during training and before competition. Also, coordination dynamics might be used to measure the effects of prolonged exposure to reduced gravitational conditions on CNS functions, such as faced by astronauts.

A Slow-moving Isaac Brings Flooding to Gulf States

NASA Image and Video Library

2012-08-30

Strong tropical storm Isaac continues to create havoc across the Gulf Coast, from eastern Texas to Florida. This infrared image from NASA Aqua spacecraft, was acquired at 2:41 p.m. CDT on Aug. 29, 2012.

77 FR 63845 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-17

... Scientific Review Special Emphasis Panel; Member Conflict: Multiple Sclerosis, Neuroimmunology and Brain... Treatments (CDT). Date: November 12-13, 2012. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and evaluate...

Biological construction of single-walled carbon nanotube electron transfer pathways in dye-sensitized solar cells.

PubMed

Inoue, Ippei; Watanabe, Kiyoshi; Yamauchi, Hirofumi; Ishikawa, Yasuaki; Yasueda, Hisashi; Uraoka, Yukiharu; Yamashita, Ichiro

2014-10-01

We designed and mass-produced a versatile protein supramolecule that can be used to manufacture a highly efficient dye-sensitized solar cell (DSSC). Twelve single-walled carbon-nanotube (SWNT)-binding and titanium-mineralizing peptides were genetically integrated on a cage-shaped dodecamer protein (CDT1). A process involving simple mixing of highly conductive SWNTs with CDT1 followed by TiO2 biomineralization produces a high surface-area/weight TiO2 -(anatase)-coated intact SWNT nanocomposite under environmentally friendly conditions. A DSSC with a TiO2 photoelectrode containing 0.2 wt % of the SWNT-TiO2 nanocomposite shows a current density improvement by 80% and a doubling of the photoelectric conversion efficiency. The SWNT-TiO2 nanocomposite transfers photon-generated electrons from dye molecules adsorbed on the TiO2 to the anode electrode swiftly. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characteristics of cytotoxic necrotizing factor and cytolethal distending toxin producing Escherichia coli strains isolated from meat samples in Northern Ireland.

PubMed

Kadhum, H J; Ball, H J; Oswald, E; Rowe, M T

2006-08-01

Swabs collected from pig, lamb and beef carcasses and samples of pork, lamb and beef mince were cultured for Escherichia coli strains. Strains harbouring cytotoxic necrotizing factors (CNF1 and 2) and cytolethal distending toxins (CDT-I,-II,-III and -IV) were identified in plate cultures of the isolates by colony hybridization with labelled probes and multiplex PCR assays. Simplex and multiplex PCR assays were used to further characterize the isolates to determine the presence of P, S and F17 fimbriae as well as afimbrial adhesins and haemolysin. The serotype was also determined where possible. Thirty strains with the capacity to code for CNF (4), CDT (24) or both (2) were isolated and characterized, and a wide range of associated factor patterns was observed. The methods utilized were successful in demonstrating the detection of viable strains with potentially significant pathogenic factors from human food sources.

Phlegmasia Caerulea Dolens in a Patient With an Inferior Vena Cava Filter: Treatment of Massive Iliocaval Thrombosis Using Local Intravenous Catheter-Directed Thrombolysis

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

Cookson, Daniel, E-mail: danielthomascookson@yahoo.co.uk; Caldwell, Stuart, E-mail: stuart.caldwell@middlemore.co.nz

Phlegmasia caerulea dolens (PCD) is a potentially disastrous complication of inferior vena cava filter insertion, and its optimum management has not been clearly established. We present a case report of a patient with pulmonary embolism and acute adrenal haemorrhage who developed PCD secondary to massive iliocaval thrombosis after insertion of a Cook Celect removable filter. Local intravenous catheter-directed thrombolysis (CDT), followed by systemic anticoagulation, achieved limb salvage and virtual resolution of symptoms at 3 months without complications. CDT can be a successful primary treatment of filter-associated PCD and can be safe in selected patients with acute nontraumatic haemorrhage. Systemic anticoagulationmore » may subsequently restore complete venous patency and may therefore be a useful approach to postthrombolysis management of residual iliocaval thrombus when filter removal is indicated.« less

Hurricane Harvey's Rapid Wind Intensification seen by NASA's SMAP

NASA Image and Video Library

2017-08-28

The rapid intensification of Hurricane Harvey is seen in this pair of images of ocean surface wind speeds as observed by the radiometer instrument aboard NASA's Soil Moisture Active Passive (SMAP) satellite at 7:29 a.m. CDT Aug. 24th, 2017 (left) and at 7 p.m. CDT Aug. 26th (right). Color indicates wind speed, with red being highest and blue lowest. The images show Harvey's maximum wind speeds increased from approximately 56 miles per hour (25 meters per second) to about 107 miles per hour (47.8 meters per second) in the 36 hours just before landfall. The higher wind speeds estimated near the mouth of the Mississippi River are erroneous and are due to errors in the ancillary sea-surface-salinity data product used by SMAP to estimate extreme wind speeds. https://photojournal.jpl.nasa.gov/catalog/PIA21884

Identification of the Cellular Receptor of Clostridium spiroforme Toxin

PubMed Central

Papatheodorou, Panagiotis; Wilczek, Claudia; Nölke, Thilo; Guttenberg, Gregor; Hornuss, Daniel; Schwan, Carsten

2012-01-01

Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) of C. spiroforme toxin in Bacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins Clostridium difficile transferase (CDT) and Clostridium perfringens iota toxin. Microscopic studies revealed that CST, but not the related Clostridium botulinum C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor. PMID:22252869

Identification of the cellular receptor of Clostridium spiroforme toxin.

PubMed

Papatheodorou, Panagiotis; Wilczek, Claudia; Nölke, Thilo; Guttenberg, Gregor; Hornuss, Daniel; Schwan, Carsten; Aktories, Klaus

2012-04-01

Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) of C. spiroforme toxin in Bacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins Clostridium difficile transferase (CDT) and Clostridium perfringens iota toxin. Microscopic studies revealed that CST, but not the related Clostridium botulinum C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor.

STS-49 Astronaut By Mission Peculiar Equipment Support Structure (MPESS)

NASA Technical Reports Server (NTRS)

1992-01-01

STS-49, the first flight of the Space Shuttle Orbiter Endeavour, lifted off from launch pad 39B on May 7, 1992 at 6:40 pm CDT. The STS-49 mission was the first U.S. orbital flight to feature 4 extravehicular activities (EVAs), and the first flight to involve 3 crew members working simultaneously outside of the spacecraft. The primary objective was the capture and redeployment of the INTELSAT VI (F-3), a communication satellite for the International Telecommunication Satellite organization, which was stranded in an unusable orbit since its launch aboard the Titan rocket in March 1990. In this onboard photo, astronaut Thomas Akers is positioned near the Mission Peculiar Equipment Support Structure (MPESS) in the cargo bay. The MPESS, developed by Marshall Space Flight Center, was used to support experiments.

Shortening the incubation time for the combination disk diffusion extended-spectrum β-lactamase (ESBL) confirmation test: how far can we go?

PubMed

van den Bijllaardt, Wouter; Voermans, Patricia C M; Buiting, Anton G; Mouton, Johan W; Muller, Anouk E

2017-09-01

The combination disk diffusion extended-spectrum β-lactamase (ESBL) confirmation test (CDT) is used for the confirmation of ESBL production in Enterobacteriaceae and usually takes 16-20 h to results. In this study, we searched for the shortest possible incubation time without a reduction in reliability. A total of 125 ESBL screening-positive isolates were subjected to CDT and were molecularly characterised by microarray. Inhibition zones were read every hour over 6-18 h of incubation. Concordance between earlier and 18-h readings was calculated for each hour. Results were validated on 224 isolates during routine clinical practice. For the initial 125 isolates, concordance (Cohen's κ) between the 6-h and 18-h readings was 0.88 [95% confidence interval (CI) 0.78-0.96; P <0.001]. The earliest time point for full concordance with the 18-h reading was 10 h. Validation of the 10-h reading for 224 clinical isolates resulted in a concordance of 0.99 (95% CI 0.98-1.0) between the 10-h and 18-h readings. Overall concordance on all 349 isolates was 0.99 (95% CI 0.97-1.0). Reading after 10 h of incubation has an excellent correlation with results after 18 h of incubation. This can significantly reduce the turnaround time for ESBL detection in laboratories with long opening hours or providing a 24/7 service. Consequently, there is a potential for implementing infection control measures up to 8 h earlier. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

A Combined Approach to Cartographic Displacement for Buildings Based on Skeleton and Improved Elastic Beam Algorithm

PubMed Central

Liu, Yuangang; Guo, Qingsheng; Sun, Yageng; Ma, Xiaoya

2014-01-01

Scale reduction from source to target maps inevitably leads to conflicts of map symbols in cartography and geographic information systems (GIS). Displacement is one of the most important map generalization operators and it can be used to resolve the problems that arise from conflict among two or more map objects. In this paper, we propose a combined approach based on constraint Delaunay triangulation (CDT) skeleton and improved elastic beam algorithm for automated building displacement. In this approach, map data sets are first partitioned. Then the displacement operation is conducted in each partition as a cyclic and iterative process of conflict detection and resolution. In the iteration, the skeleton of the gap spaces is extracted using CDT. It then serves as an enhanced data model to detect conflicts and construct the proximity graph. Then, the proximity graph is adjusted using local grouping information. Under the action of forces derived from the detected conflicts, the proximity graph is deformed using the improved elastic beam algorithm. In this way, buildings are displaced to find an optimal compromise between related cartographic constraints. To validate this approach, two topographic map data sets (i.e., urban and suburban areas) were tested. The results were reasonable with respect to each constraint when the density of the map was not extremely high. In summary, the improvements include (1) an automated parameter-setting method for elastic beams, (2) explicit enforcement regarding the positional accuracy constraint, added by introducing drag forces, (3) preservation of local building groups through displacement over an adjusted proximity graph, and (4) an iterative strategy that is more likely to resolve the proximity conflicts than the one used in the existing elastic beam algorithm. PMID:25470727

The Gesture Imitation in Alzheimer's Disease Dementia and Amnestic Mild Cognitive Impairment.

PubMed

Li, Xudong; Jia, Shuhong; Zhou, Zhi; Hou, Chunlei; Zheng, Wenjing; Rong, Pei; Jiao, Jinsong

2016-07-14

Alzheimer's disease dementia (ADD) has become an important health problem in the world. Visuospatial deficits are considered to be an early symptom besides memory disorder. The gesture imitation test was devised to detect ADD and amnestic mild cognitive impairment (aMCI). A total of 117 patients with ADD, 118 with aMCI, and 95 normal controls were included in this study. All participants were administered our gesture imitation test, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Clock Drawing Test (CDT), and the Clinical Dementia Rating Scale (CDR). Patients with ADD performed worse than normal controls on global scores and had a lower success rate on every item (p < 0.001). The area under the curve (AUC) for the global scores when comparing the ADD and control groups was 0.869 (p < 0.001). Item 4 was a better discriminator with a sensitivity of 84.62% and a specificity of 67.37%. The AUC for the global scores decreased to 0.621 when applied to the aMCI and control groups (p = 0.002). After controlling for age and education, the gesture imitation test scores were positively correlated with the MMSE (r = 0.637, p < 0.001), the MoCA (r = 0.572, p < 0.001), and the CDT (r = 0.514, p < 0.001) and were negatively correlated with the CDR scores (r = -0.558, p < 0.001). The gesture imitation test is an easy, rapid tool for detecting ADD, and is suitable for the patients suspected of mild ADD and aMCI in outpatient clinics.

Chronic sensory stroke with and without central pain is associated with bilaterally distributed sensory abnormalities as detected by quantitative sensory testing.

PubMed

Krause, Thomas; Asseyer, Susanna; Geisler, Frederik; Fiebach, Jochen B; Oeltjenbruns, Jochen; Kopf, Andreas; Villringer, Kersten; Villringer, Arno; Jungehulsing, Gerhard J

2016-01-01

Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. As compared with reference data from healthy controls, patients with CPSP showed alterations of thermal and mechanical thresholds on the body area contralateral to their stroke (P < 0.01). Patients with sensory stroke but without CPSP (non-pain sensory stroke [NPSS] patients) exhibited similar albeit less pronounced contralesional changes. Paradoxical heat sensation (PHS) and dynamic mechanical allodynia (DMA) showed higher values in CPSP, and an elevated cold detection threshold (CDT) was seen more often in CPSP than in patients with NPSS (P < 0.05). In patients with CPSP, changes in CDT, PHS, dynamic mechanical allodynia, and temporal pain summation (wind-up ratio) each correlated with the presence of pain (P < 0.05). On the homologous ipsilesional body area, both patient groups showed additional significant abnormalities as compared with the reference data, which strongly resembled the contralesional changes. In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.

Novel Helicobacter species H.japonicum isolated from laboratory mice from Japan induces typhlocolitis and lower bowel carcinoma in C57BL/129 IL10−/− mice

PubMed Central

Shen, Zeli; Feng, Yan; Muthupalani, Sureshkumar; Sheh, Alexander; Cheaney, Lenzie E.; Kaufman, Christian A.; Gong, Guanyu; Paster, Bruce J.; Fox, James G.

2016-01-01

A novel Helicobacter species Helicobacter japonicum was isolated from the stomach and intestines of clinically normal mice received from three institutes from Japan. The novel Helicobacter sp. was microaerobic, grew at 37°C and 42°C, was catalase and oxidase positive, but urease negative. It is most closely related to the 16S rRNA gene of H.muridarum (98.6%); to the 23S rRNA gene of H.hepaticus (97.9%); to the hsp60 gene of H.typhlonius (87%). The novel Helicobacter sp. has in vitro cytolethal distending toxin (CDT) activity; its cdtB gene sequence has 83.8% identity with that of H.hepaticus. The whole genome sequence of H.japonicum MIT 01-6451 has a 2.06-Mb genome length with a 37.5% G + C content. When the organism was inoculated into C57BL/129 IL10−/− mice, it was cultured from the stomach, colon and cecum of infected mice at 6 and 10 weeks post-infection. The cecum had the highest H.japonicum colonization levels by quantitative PCR. The histopathology of the lower bowel was characterized by moderate to severe inflammation, mild edema, epithelial defects, mild to severe hyperplasia, dysplasia and carcinoma. Inflammatory cytokines IFNγ, TNFα and IL17a, as well as iNOS were significantly upregulated in the cecal tissue of infected mice. These results demonstrate that the novel H.japonicum can induce inflammatory bowel disease and carcinoma in IL10−/− mice and highlights the importance of identifying novel Helicobacter spp. especially when they are introduced from outside mouse colonies from different geographic locations. PMID:27655833

Direct and indirect pathways for choosing objects and actions.

PubMed

Hikosaka, Okihide; Kim, Hyoung F; Amita, Hidetoshi; Yasuda, Masaharu; Isoda, Masaki; Tachibana, Yoshihisa; Yoshida, Atsushi

2018-02-23

A prominent target of the basal ganglia is the superior colliculus (SC) which controls gaze orientation (saccadic eye movement in primates) to an important object. This 'object choice' is crucial for choosing an action on the object. SC is innervated by the substantia nigra pars reticulata (SNr) which is controlled mainly by the caudate nucleus (CD). This CD-SNr-SC circuit is sensitive to the values of individual objects and facilitates saccades to good objects. The object values are processed differently in two parallel circuits: flexibly by the caudate head (CDh) and stably by the caudate tail (CDt). To choose good objects, we need to reject bad objects. In fact, these contrasting functions are accomplished by the circuit originating from CDt: The direct pathway focuses on good objects and facilitates saccades to them; the indirect pathway focuses on bad objects and suppresses saccades to them. Inactivation of CDt deteriorated the object choice, because saccades to bad objects were no longer suppressed. This suggests that the indirect pathway is important for object choice. However, the direct and indirect pathways for 'object choice', which aim at the same action (i.e., saccade), may not work for 'action choice'. One possibility is that circuits controlling different actions are connected through the indirect pathway. Additional connections of the indirect pathway with brain areas outside the basal ganglia may also provide a wider range of behavioral choice. In conclusion, basal ganglia circuits are composed of the basic direct/indirect pathways and additional connections and thus have acquired multiple functions. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors.

PubMed

Dyck, P J; Zimmerman, I; Gillen, D A; Johnson, D; Karnes, J L; O'Brien, P C

1993-08-01

We recently found that vibratory detection threshold is greatly influenced by the algorithm of testing. Here, we study the influence of stimulus characteristics and algorithm of testing and estimating threshold on cool (CDT), warm (WDT), and heat-pain (HPDT) detection thresholds. We show that continuously decreasing (for CDT) or increasing (for WDT) thermode temperature to the point at which cooling or warming is perceived and signaled by depressing a response key ("appearance" threshold) overestimates threshold with rapid rates of thermal change. The mean of the appearance and disappearance thresholds also does not perform well for insensitive sites and patients. Pyramidal (or flat-topped pyramidal) stimuli ranging in magnitude, in 25 steps, from near skin temperature to 9 degrees C for 10 seconds (for CDT), from near skin temperature to 45 degrees C for 10 seconds (for WDT), and from near skin temperature to 49 degrees C for 10 seconds (for HPDT) provide ideal stimuli for use in several algorithms of testing and estimating threshold. Near threshold, only the initial direction of thermal change from skin temperature is perceived, and not its return to baseline. Use of steps of stimulus intensity allows the subject or patient to take the needed time to decide whether the stimulus was felt or not (in 4, 2, and 1 stepping algorithms), or whether it occurred in stimulus interval 1 or 2 (in two-alternative forced-choice testing). Thermal thresholds were generally significantly lower with a large (10 cm2) than with a small (2.7 cm2) thermode.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved ethanol production by engineered Saccharomyces cerevisiae expressing a mutated cellobiose transporter during simultaneous saccharification and fermentation.

PubMed

Lee, Won-Heong; Jin, Yong-Su

2017-03-10

Although simultaneous saccharification and fermentation (SSF) of cellulosic biomass can offer efficient hydrolysis of cellulose through alleviating feed-back inhibition of cellulases by glucose, supplementation of β-glucosidase is necessary because most fermenting microorganisms cannot utilize cellobiose. Previously, we observed that SSF of cellulose by an engineered Saccharomyces cerevisiae expressing a cellobiose transporter (CDT-1) and an intracellular β-glucosidase (GH1-1) without β-glucosidase could not be performed as efficiently as the traditional SSF with extracellular β-glucosidase. However, we improved the ethanol production from SSF of cellulose by employing a further engineered S. cerevisiae expressing a mutant cellobiose transporter [CDT-1 (F213L) exhibiting higher V MAX than CDT-1] and GH1-1 in this study. Furthermore, limitation of cellobiose formation by reducing the amounts of cellulases mixture in SSF could lead the further engineered strain to produce ethanol considerably better than the parental strain with β-glucosidase. Probably, better production of ethanol by the further engineered strain seemed to be due to a higher affinity to cellobiose, which might be attributed to not only 2-times lower Monod constant (K S ) for cellobiose than K S of the parental strain for glucose but also 5-times lower K S than Michaelis-Menten constant (K M ) of the extracellular β-glucosidase for glucose. Our results suggest that modification of the cellobiose transporter in the engineered yeast to transport lower level of cellobiose enables a more efficient SSF for producing ethanol from cellulose. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

PubMed

Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

2016-12-06

The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

Levels and Types of Alcohol Biomarkers in DUI and Clinic Samples for Estimating Workplace Alcohol Problemsa

PubMed Central

Marques, Paul R

2013-01-01

Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways – a workplace for many – provides an example for work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this report, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average 8 months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (DUI). Drivers in alcohol interlock programs log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher program entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This report summarizes selected biomarkers’ potential for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cutoff levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID:22311827

Kinematic assumptions and their consequences on the structure of field equations in continuum dislocation theory

NASA Astrophysics Data System (ADS)

Silbermann, C. B.; Ihlemann, J.

2016-03-01

Continuum Dislocation Theory (CDT) relates gradients of plastic deformation in crystals with the presence of geometrically necessary dislocations. Therefore, the dislocation tensor is introduced as an additional thermodynamic state variable which reflects tensorial properties of dislocation ensembles. Moreover, the CDT captures both the strain energy from the macroscopic deformation of the crystal and the elastic energy of the dislocation network, as well as the dissipation of energy due to dislocation motion. The present contribution deals with the geometrically linear CDT. More precise, the focus is on the role of dislocation kinematics for single and multi-slip and its consequences on the field equations. Thereby, the number of active slip systems plays a crucial role since it restricts the degrees of freedom of plastic deformation. Special attention is put on the definition of proper, well-defined invariants of the dislocation tensor in order to avoid any spurious dependence of the resulting field equations on the coordinate system. It is shown how a slip system based approach can be in accordance with the tensor nature of the involved quantities. At first, only dislocation glide in one active slip system of the crystal is allowed. Then, the special case of two orthogonal (interacting) slip systems is considered and the governing field equations are presented. In addition, the structure and symmetry of the backstress tensor is investigated from the viewpoint of thermodynamical consistency. The results will again be used in order to facilitate the set of field equations and to prepare for a robust numerical implementation.

Preliminary data on a mnemonic instrument with proverbs for tracking Alzheimer's disease.

PubMed

Santos, Mauricéa Tabósa Ferreira; Guerra, Gutemberg; de Menezes, Terce Liana; Carvalho, Tatiana Lins; Alchieri, João Carlos; Sougey, Everton Botelho

2008-01-01

In the differential diagnosis between Alzheimer's disease (AD) and normal aging, tests evaluating memory and executive functions are frequently used. The addition of abstraction tests may enhance the effectiveness of screening tests for AD. The aim of this study was to compare initial data of a new instrument - The Screening Test for Alzheimer's Disease with Proverbs (STADP) - against other screening tests used in AD diagnosis. Sixty elderly individuals (46 controls and 14 AD subjects with CDR=1), aged =60 years, with at least one year of schooling, were evaluated using the STADP at outpatient clinic. The STADP assesses short-term memory, episodic memory, executive functions and language, in addition to proverb recognition. The performance of the participants on the Mini-Mental State Examination (MMSE), semantic Verbal Fluency (VF) and Clock Drawing Test (CDT) were evaluated and the habit of reading, writing and sociodemographic data were also taken into account. There were significant correlations between STADP and the performance on the MMSE (r=0.64), CDT (r=0.50) and VF (r=0.56). Age influenced all sub-items of the STADP, specifically episodic memory (r= -0.54), whereas schooling mainly influenced executive functions and language (r=0.46). The total score, stages A and C and the "proverb recognition" of STADP (p<0.001), as well as the MMSE (p<0.001), CDT (p=0.016), VF (p<0.001) were significantly different in AD versus control groups. The findings point to the potential use of the STADP in AD, warranting the conducting of further studies.

76 FR 35228 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... Review Special Emphasis Panel, Small Business: Cancer Diagnostics and Treatments (CDT). Date: July 14-15... Musculoskeletal, Oral, and Skin Systems. Date: July 15, 2011. Time: 8 a.m. to 5 p.m. Agenda: To review and...

Measurement of longitudinal sulfur isotopic variations by laser ablation MC-ICP-MS in single human hair strands.

PubMed

Santamaria-Fernandez, Rebeca; Giner Martínez-Sierra, Justo; Marchante-Gayón, J M; García-Alonso, J Ignacio; Hearn, Ruth

2009-05-01

A new method for the measurement of longitudinal variations of sulfur isotope amount ratios in single hair strands using a laser ablation system coupled to a multicollector inductively coupled plasma mass spectrometer (LA-MC-ICP-MS) is reported here for the first time. Ablation parameters have been optimized for the measurement of sulfur isotope ratios in scalp human hair strands of 80-120-microm thickness and different washing procedures have been evaluated. The repeatability of the method has been tested and the ability to measure sulfur isotopic variations in 1,000-microm-long hair segments has been evaluated. A horse hair sample previously characterized for carbon and nitrogen isotope ratios in an interlaboratory study has been characterized by LA-MC-ICP-MS to be used as an in-house standard for the bracketing of human hair strands. (34)S/(32)S isotope amount ratios have been measured and corrected for instrumental mass bias adopting the external standardization approach using National Institute of Standards and Technology (NIST) RM8553 and full uncertainty budgets have been calculated using the Kragten approach. Results are reported as both (34)S/(32)S isotope amount ratios and deltaS(V-CDT) values (sulfur isotopic differences relative to a reference sample expressed in the Vienna Canyon Diablo Troilite (V-CDT) scale) calculated using NIST RM8553, NIST RM8554, and NIST RM8556 to anchor results to the V-CDT scale. The main advantage of the new method versus conventional gas source isotope ratio mass spectrometry measurements is that longitudinal variations in sulfur isotope amount ratios can be resolved. Proof of concept is shown with human scalp hair strands from three individuals, two UK residents and one traveler (long periods of time abroad). The method enables monitoring of longitudinal isotope ratio variations in single hair strands. Absolute ratios are reported and delta(34)S(V-CDT) values are plotted for comparison. Slight variations of <1.2 per thousand were detected in the hair strands from UK residents whereas the traveler presented a variation of >5 per thousand. Thus, the measurement of sulfur isotopic variations in hair samples has potential to be an indicator of geographical origin and recent movements and could be used in combination with isotope ratio measurements in water/foodstuffs from different geographical locations to provide important information in nutritional and geographical studies.

Development of a chest digital tomosynthesis R/F system and implementation of low-dose GPU-accelerated compressed sensing (CS) image reconstruction.

PubMed

Choi, Sunghoon; Lee, Haenghwa; Lee, Donghoon; Choi, Seungyeon; Lee, Chang-Lae; Kwon, Woocheol; Shin, Jungwook; Seo, Chang-Woo; Kim, Hee-Joung

2018-05-01

This work describes the hardware and software developments of a prototype chest digital tomosynthesis (CDT) R/F system. The purpose of this study was to validate the developed system for its possible clinical application on low-dose chest tomosynthesis imaging. The prototype CDT R/F system was operated by carefully controlling the electromechanical subsystems through a synchronized interface. Once a command signal was delivered by the user, a tomosynthesis sweep started to acquire 81 projection views (PVs) in a limited angular range of ±20°. Among the full projection dataset of 81 images, several sets of 21 (quarter view) and 41 (half view) images with equally spaced angle steps were selected to represent a sparse view condition. GPU-accelerated and total-variation (TV) regularization strategy-based compressed sensing (CS) image reconstruction was implemented. The imaged objects were a flat-field using a copper filter to measure the noise power spectrum (NPS), a Catphan ® CTP682 quality assurance (QA) phantom to measure a task-based modulation transfer function (MTF T ask ) of three different cylinders' edge, and an anthropomorphic chest phantom with inserted lung nodules. The authors also verified the accelerated computing power over CPU programming by checking the elapsed time required for the CS method. The resultant absorbed and effective doses that were delivered to the chest phantom from two-view digital radiographic projections, helical computed tomography (CT), and the prototype CDT system were compared. The prototype CDT system was successfully operated, showing little geometric error with fast rise and fall times of R/F x-ray pulse less than 2 and 10 ms, respectively. The in-plane NPS presented essential symmetric patterns as predicted by the central slice theorem. The NPS images from 21 PVs were provided quite different pattern against 41 and 81 PVs due to aliased noise. The voxel variance values which summed all NPS intensities were inversely proportional to the number of PVs, and the CS method gave much lower voxel variance by the factors of 3.97-6.43 and 2.28-3.36 compared to filtered backprojection (FBP) and 20 iterations of simultaneous algebraic reconstruction technique (SART). The spatial frequencies of the f 50 at which the MTF T ask reduced to 50% were 1.50, 1.55, and 1.67 cycles/mm for FBP, SART, and CS methods, respectively, in the case of Bone 20% cylinder using 41 views. A variety of ranges of TV reconstruction parameters were implemented during the CS method and we could observe that the NPS and MTF T ask preserved best when the regularization and TV smoothing parameters α and τ were in a range of 0.001-0.1. For the chest phantom data, the signal difference to noise ratios (SDNRs) were higher in the proposed CS scheme images than in the FBP and SART, showing the enhanced rate of 1.05-1.43 for half view imaging. The total averaged reconstruction time during 20 iterations of the CS scheme was 124.68 s, which could match-up a clinically feasible time (<3 min). This computing time represented an enhanced speed 386 times greater than CPU programming. The total amounts of estimated effective doses were 0.12, 0.53 (half view), and 2.56 mSv for two-view radiographs, the prototype CDT system, and helical CT, respectively, showing 4.49 times higher than conventional radiography and 4.83 times lower than a CT exam, respectively. The current work describes the development and performance assessment of both hardware and software for tomosynthesis applications. The authors observed reasonable outcomes by showing a potential for low-dose application in CDT imaging using GPU acceleration. © 2018 American Association of Physicists in Medicine.

Isolation and molecular characterization of Salmonella enterica serovar Javiana from food, environmental and clinical samples.

PubMed

Mezal, Ezat H; Stefanova, Rossina; Khan, Ashraf A

2013-06-03

A total of 50 Salmonella enterica serovar Javiana isolates, isolated from food, environmental and clinical samples, were analyzed for antibiotic resistance, presence of virulence genes, plasmids and plasmid replicon types. To assess the genetic diversity, pulsed-field gel electrophoresis (PFGE) fingerprinting and plasmid profiles were performed. All of the isolates were sensitive to chloramphenicol, nalidixic acid, and sulfisoxazole, and four isolates showed intermediate resistance to gentamicin or kanamycin. Eleven isolates, including representatives from each of the source types, were resistant to ampicillin. Four isolates from either clinical or environmental sources were resistant to tetracycline, while an additional 20 isolates showed intermediate resistance to this drug. Fourteen isolates, primarily from food sources, showed intermediate resistance to streptomycin. The S. Javiana isolates were screened by PCR for 17 virulence genes (spvB, spiA, pagC, msgA, invA, sipB, prgH, spaN, orgA, tolC, iroN, sitC, IpfC, sifA, sopB, cdtB, and pefA). All isolates were positive for nine to fourteen of these genes, but none were positive for pefA, spvB and lpfC, which are typically present on the Salmonella virulence plasmid. Seven of the virulence genes including cdtB were found in all 50 isolates, suggesting that S. Javiana from food and environmental sources had virulence similar to clinical isolates. Four clinical isolates and two food isolates carried one or more plasmids of approximately 30, 38, and 58 kb, with the 58 kb plasmids belonging to incompatibility group IncFIIA. Two clinical isolates carried IncI1 type mega plasmid (80 kb), and one clinical isolate carried plasmids of 4.5 and 7 kb. The PFGE profiles resulted 34 patterns in five clusters at a 90% similarity threshold. Our results indicate that S. Javiana isolates have a diverse clonal population among the clinical, food and environmental samples and this serotype possesses several virulent genes and plasmids that can contribute to the development of salmonellosis in human. This study provides data that support the potential transmission of S. Javiana virulence factors from food and environmental sources to cause infections in humans. Published by Elsevier B.V.

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

PubMed Central

de Munnik, Sonja A; Bicknell, Louise S; Aftimos, Salim; Al-Aama, Jumana Y; van Bever, Yolande; Bober, Michael B; Clayton-Smith, Jill; Edrees, Alaa Y; Feingold, Murray; Fryer, Alan; van Hagen, Johanna M; Hennekam, Raoul C; Jansweijer, Maaike C E; Johnson, Diana; Kant, Sarina G; Opitz, John M; Ramadevi, A Radha; Reardon, Willie; Ross, Alison; Sarda, Pierre; Schrander-Stumpel, Constance T R M; Schoots, Jeroen; Temple, I Karen; Terhal, Paulien A; Toutain, Annick; Wise, Carol A; Wright, Michael; Skidmore, David L; Samuels, Mark E; Hoefsloot, Lies H; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

2012-01-01

Meier–Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were identified in individuals with MGS. Here, we report on genotype–phenotype studies in 45 individuals with MGS (27 females, 18 males; age 3 months–47 years). Thirty-five individuals had biallelic mutations in one of the five causative pre-replication genes. No homozygous or compound heterozygous null mutations were detected. In 10 individuals, no definitive molecular diagnosis was made. The triad of microtia, absent/hypoplastic patellae, and short stature was observed in 82% of individuals with MGS. Additional frequent clinical features were mammary hypoplasia (100%) and abnormal genitalia (42% predominantly cryptorchidism and hypoplastic labia minora/majora). One individual with ORC1 mutations only had short stature, emphasizing the highly variable clinical spectrum of MGS. Individuals with ORC1 mutations had significantly shorter stature and smaller head circumferences than individuals from other gene categories. Furthermore, compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4 and more frequently pulmonary emphysema in CDT1. A lethal phenotype was seen in four individuals with compound heterozygous ORC1 and CDT1 mutations. No other clear genotype–phenotype association was observed. Growth hormone and estrogen treatment may be of some benefit, respectively, to growth retardation and breast hypoplasia, though further studies in this patient group are needed. PMID:22333897

Trans-Cinnamaldehyde, Carvacrol, and Eugenol Reduce Campylobacter jejuni Colonization Factors and Expression of Virulence Genes in Vitro

PubMed Central

Upadhyay, Abhinav; Arsi, Komala; Wagle, Basanta R.; Upadhyaya, Indu; Shrestha, Sandip; Donoghue, Ann M.; Donoghue, Dan J.

2017-01-01

Campylobacter jejuni is a major foodborne pathogen that causes severe gastroenteritis in humans characterized by fever, diarrhea, and abdominal cramps. In the human gut, Campylobacter adheres and invades the intestinal epithelium followed by cytolethal distending toxin mediated cell death, and enteritis. Reducing the attachment and invasion of Campylobacter to intestinal epithelium and expression of its virulence factors such as motility and cytolethal distending toxin (CDT) production could potentially reduce infection in humans. This study investigated the efficacy of sub-inhibitory concentrations (SICs, concentration not inhibiting bacterial growth) of three GRAS (generally recognized as safe) status phytochemicals namely trans-cinnamaldehyde (TC; 0.005, 0.01%), carvacrol (CR; 0.001, 0.002%), and eugenol (EG; 0.005, 0.01%) in reducing the attachment, invasion, and translocation of C. jejuni on human intestinal epithelial cells (Caco-2). Additionally, the effect of these phytochemicals on Campylobacter motility and CDT production was studied using standard bioassays and gene expression analysis. All experiments had duplicate samples and were replicated three times on three strains (wild type S-8, NCTC 11168, 81–176) of C. jejuni. Data were analyzed using ANOVA with GraphPad ver. 6. Differences between the means were considered significantly different at P < 0.05. The majority of phytochemical treatments reduced C. jejuni adhesion, invasion, and translocation of Caco-2 cells (P < 0.05). In addition, the phytochemicals reduced pathogen motility and production of CDT in S-8 and NCTC 11168 (P < 0.05). Real-time quantitative PCR revealed that phytochemicals reduced the transcription of select C. jejuni genes critical for infection in humans (P < 0.05). Results suggest that TC, CR, and EG could potentially be used to control C. jejuni infection in humans. PMID:28487683

Neuronal connections of direct and indirect pathways for stable value memory in caudal basal ganglia.

PubMed

Amita, Hidetoshi; Kim, Hyoung F; Smith, Mitchell; Gopal, Atul; Hikosaka, Okihide

2018-05-08

Direct and indirect pathways in the basal ganglia work together for controlling behavior. However, it is still a controversial topic whether these pathways are segregated or merged with each other. To address this issue, we studied the connections of these two pathways in the caudal parts of the basal ganglia of rhesus monkeys using anatomical tracers. Our previous studies showed that the caudal basal ganglia control saccades by conveying long-term values (stable values) of many visual objects toward the superior colliculus. In experiment 1, we injected a tracer in the caudate tail (CDt), and found local dense plexuses of axon terminals in the caudal-dorsal-lateral part of substantia nigra pars reticulata (cdlSNr) and the caudal-ventral part of globus pallidus externus (cvGPe). These anterograde projections may correspond to the direct and indirect pathways, respectively. To verify this in experiment 2, we injected different tracers into cdlSNr and cvGPe, and found many retrogradely labeled neurons in CDt and, in addition, the caudal-ventral part of the putamen (cvPut). These cdlSNr-projecting and cvGPe-projecting neurons were found intermingled in both CDt and cvPut (which we call 'striatum tail'). A small but significant proportion of neurons (< 15%) were double-labeled, indicating that they projected to both cdlSNr and cvGPe. These anatomical results suggest that stable value signals (good vs. bad) are sent from the striatum tail to cdlSNr and cvGPe in a biased (but not exclusive) manner. These connections may play an important role in biasing saccades toward higher-valued objects and away from lower-valued objects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells▿

PubMed Central

Banks, Keith E.; Humphreys, Tricia L.; Li, Wei; Katz, Barry P.; Wilkes, David S.; Spinola, Stanley M.

2007-01-01

Dendritic cells (DC) orchestrate innate and adaptive immune responses to bacteria. How Haemophilus ducreyi, which causes genital ulcers and regional lymphadenitis, interacts with DC is unknown. H. ducreyi evades uptake by polymorphonuclear leukocyte and macrophage-like cell lines by secreting LspA1 and LspA2. Many H. ducreyi strains express cytolethal distending toxin (CDT), and recombinant CDT causes apoptosis of DC in vitro. Here, we examined interactions between DC and H. ducreyi 35000HP, which produces LspA1, LspA2, and CDT. In human volunteers infected with 35000HP, the ratio of myeloid DC to plasmacytoid DC was 2.8:1 in lesions, compared to a ratio of 1:1 in peripheral blood. Using myeloid DC derived from monocytes as surrogates for lesional DC, we found that DC infected with 35000HP remained as viable as uninfected DC for up to 48 h. Gentamicin protection and confocal microscopy assays demonstrated that DC ingested and killed 35000HP, but killing was incomplete at 48 h. The expression of LspA1 and LspA2 did not inhibit the uptake of H. ducreyi, despite inactivating Src kinases. Infection of DC with live 35000HP caused less cell surface marker activation than infection with heat-killed 35000HP and lipopolysaccharide (LPS) and inhibited maturation by LPS. However, infection of DC with live bacteria caused the secretion of significantly higher levels of interleukin-6 and tumor necrosis factor alpha than infection with heat-killed bacteria and LPS. The survival of H. ducreyi in DC may provide a mechanism by which the organism traffics to lymph nodes. Partial activation of DC may abrogate the establishment of a full Th1 response and an environment that promotes phagocytosis. PMID:17923525

Preliminary data on a mnemonic instrument with proverbs for tracking Alzheimer’s disease

PubMed Central

Santos, Mauricéa Tabósa Ferreira; Guerra, Gutemberg; de Menezes, Terce Liana; Carvalho, Tatiana Lins; Alchieri, João Carlos; Sougey, Everton Botelho

2008-01-01

In the differential diagnosis between Alzheimer’s disease (AD) and normal aging, tests evaluating memory and executive functions are frequently used. The addition of abstraction tests may enhance the effectiveness of screening tests for AD. Objectives The aim of this study was to compare initial data of a new instrument – The Screening Test for Alzheimer’s Disease with Proverbs (STADP) – against other screening tests used in AD diagnosis. Methods Sixty elderly individuals (46 controls and 14 AD subjects with CDR=1), aged =60 years, with at least one year of schooling, were evaluated using the STADP at outpatient clinic. The STADP assesses short-term memory, episodic memory, executive functions and language, in addition to proverb recognition. The performance of the participants on the Mini-Mental State Examination (MMSE), semantic Verbal Fluency (VF) and Clock Drawing Test (CDT) were evaluated and the habit of reading, writing and sociodemographic data were also taken into account. Results There were significant correlations between STADP and the performance on the MMSE (r=0.64), CDT (r=0.50) and VF (r=0.56). Age influenced all sub-items of the STADP, specifically episodic memory (r= –0.54), whereas schooling mainly influenced executive functions and language (r=0.46). The total score, stages A and C and the “proverb recognition” of STADP (p<0.001), as well as the MMSE (p<0.001), CDT (p=0.016), VF (p<0.001) were significantly different in AD versus control groups. Conclusions The findings point to the potential use of the STADP in AD, warranting the conducting of further studies. PMID:29213595

Effect of Low-Frequency rTMS and NMES on Subacute Unilateral Hemispheric Stroke With Dysphagia

PubMed Central

Lim, Kil-Byung; Lee, Hong-Jae; Yoo, Jeehyun

2014-01-01

Objective To investigate the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) on post-stroke dysphagia. Methods Subacute (<3 months), unilateral hemispheric stroke patients with dysphagia were randomly assigned to the conventional dysphagia therapy (CDT), rTMS, or NMES groups. In rTMS group, rTMS was performed at 100% resting motor threshold with 1 Hz frequency for 20 minutes per session (5 days per week for 2 weeks). In NMES group, electrical stimulation was applied to the anterior neck for 30 minutes per session (5 days per week for 2 weeks). All three groups were given conventional dysphagia therapy for 4 weeks. We evaluated the functional dysphagia scale (FDS), pharyngeal transit time (PTT), the penetration-aspiration scale (PAS), and the American Speech-Language Hearing Association National Outcomes Measurement System (ASHA NOMS) swallowing scale at baseline, after 2 weeks, and after 4 weeks. Results Forty-seven patients completed the study; 15 in the CDT group, 14 in the rTMS group, and 18 in the NMES group. Mean changes in FDS and PAS for liquid during first 2 weeks in the rTMS and NMES groups were significantly higher than those in the CDT group, but no significant differences were found between the rTMS and NMES group. No significant difference in mean changes of FDS and PAS for semi-solid, PTT, and ASHA NOMS was observed among the three groups. Conclusion These results indicated that both low-frequency rTMS and NMES could induce early recovery from dysphagia; therefore, they both could be useful therapeutic options for dysphagic stroke patients. PMID:25379488

Impact of comprehensive day treatment on societal participation for persons with acquired brain injury.

PubMed

Malec, J F

2001-07-01

To evaluate comprehensive day treatment (CDT) for survivors of brain injury by time since injury and to identify outcome predictors. Before and after. Rehabilitation center. Ninety-six program graduates; 17 dropouts with acquired brain injury. Comprehensive Day Treatment Program: daily group sessions to build cognitive and behavioral skills through a transdisciplinary approach, supportive feedback, and a variety of therapeutic modalities. Obtained outcome measures before and after the program, and at 1-year follow-up. Independent living status, vocational independence scale at program end and 1-year follow-up; and Rasch-analyzed Mayo-Portland Adaptability Inventory (MPAI-22) and goal attainment scaling (GAS) at program end. age, education, severity of initial injury, time since injury, and preadmission MPAI-22. Significant goal achievement on GAS and improvement on MPAI-22; increased societal participation at 1-year follow-up for those treated postacutely and many years after injury: 72% of graduates living independently; 39% working independently, 10% in transitional placements, and 18% in supported or volunteer work. Long-term outcomes were modestly related linearly to preadmission MPAI-22 and nonlinearly to time since injury. CDT improves societal participation even among persons with a long history of limited participation after brain injury. This de facto extended baseline analysis indicates the effectiveness of CDT and paves the way for randomized control trials of active treatment components. Relationships of predictors to outcomes are not sufficiently strong for patient selection. More effective interventions for vocational reintegration are needed for those most severely disabled after brain injury. Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

75 FR 16197 - NASA Advisory Council; Space Operations Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (10-036)] NASA Advisory Council; Space..., the National Aeronautics and Space Administration announces a meeting of the NASA Advisory Council Space Operations Committee. DATES: Tuesday, April 13, 2010, 3-5 p.m. CDT. ADDRESSES: NASA Johnson Space...

[Proposal for early detection of ethanol consumption in students of the Universidad Autónoma del Estado de Morelos].

PubMed

García-Jiménez, Sara; Erazo-Mijares, Miguel; Toledano-Jaimes, Cairo D; Monroy-Noyola, Antonio; Bilbao-Marcos, Fernando; Sánchez-Alemán, Miguel A; Déciga-Campos, Myrna

2016-01-01

The present study determined through analytic techniques the quantification of some biomarkers that have been useful to detect early ethanol consumption in a college population. A group of 117 students of recent entry to the Universidad Autónoma del Estado de Morelos was analyzed. The enzyme determination of aspartate aminotransferase, alanine aminotransferase, and gamma glutamyltransferase as metabolic markers of ethanol, as well as the carbohydrate-deficient transferrin (CDT) detected by high chromatographic liquid (up to 1.8% of CDT), allowed us to identify that 6% of the college population presented a potential risk of alcohol consumption. The use of the biochemical-analytical method overall with the psychological drug and a risk factor instrument established by the Universidad Autónoma del Estado de Morelos permit us to identify students whose substance abuse consumption puts their terminal efficiency at risk as well as their academic level. The timely detection on admission to college can monitor and support a student consumer's substance abuse.

Effects of physical parameters on the cell-to-dendrite transition in directional solidification

NASA Astrophysics Data System (ADS)

Wei, Lei; Lin, Xin; Wang, Meng; Huang, Wei-Dong

2015-07-01

A quantitative cellular automaton model is used to study the cell-to-dendrite transition (CDT) in directional solidification. We give a detailed description of the CDT by carefully examining the influence of the physical parameters, including: the Gibbs-Thomson coefficient Γ, the solute diffusivity Dl, the solute partition coefficient k0, and the liquidus slope ml. It is found that most of the parameters agree with the Kurz and Fisher (KF) criterion, except for k0. The intrinsic relations among the critical velocity Vcd, the cellular primary spacing λc,max, and the critical spacing λcd are investigated. Project supported by the National Natural Science Foundation of China (Grant Nos. 51271213 and 51323008), the National Basic Research Program of China (Grant No. 2011CB610402), the National High Technology Research and Development Program of China (Grant No. 2013AA031103), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20116102110016), and the China Postdoctoral Science Foundation (Grant No. 2013M540771).

The Clock Drawing Test versus Mini-mental Status Examination as a Screening Tool for Dementia: A Clinical Comparison

PubMed Central

Palsetia, Delnaz; Rao, G. Prasad; Tiwari, Sarvada C.; Lodha, Pragya; De Sousa, Avinash

2018-01-01

There is a growing incidence of dementia patients in the community, and with this growth, there is need for rapid, valid, and easily administrable tests for the screening of dementia and mild cognitive impairment in the community. This review looks at the two most commonly used tests in dementia screening, namely, the clock drawing test (CDT) and the mini-mental status examination (MMSE). Both these tests have been used in dementia screening over the past three decades and have been the subject of scrutiny of various studies, reviews, and meta-analysis. Both these tests are analyzed on their ability to assess dementia and screen for it in the community, general practice and general hospital settings. The methods of administration and scoring of each test are discussed, and their advantages and disadvantages are explained. There is also a direct comparison made between the MMSE and CDT in dementia screening. Future research needs with these tests are also elucidated. PMID:29403122

Origin Licensing Requires ATP Binding and Hydrolysis by the MCM Replicative Helicase

PubMed Central

Coster, Gideon; Frigola, Jordi; Beuron, Fabienne; Morris, Edward P.; Diffley, John F.X.

2014-01-01

Summary Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. Assembly of these prereplicative complexes (pre-RCs) requires the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ORC, Cdc6, and MCM are members of the AAA+ family of ATPases, and pre-RC assembly requires ATP hydrolysis. Here we show that ORC and Cdc6 mutants defective in ATP hydrolysis are competent for origin licensing. However, ATP hydrolysis by Cdc6 is required to release nonproductive licensing intermediates. We show that ATP binding stabilizes the wild-type MCM hexamer. Moreover, by analyzing MCM containing mutant subunits, we show that ATP binding and hydrolysis by MCM are required for Cdt1 release and double hexamer formation. This work alters our view of how ATP is used by licensing factors to assemble pre-RCs. PMID:25087873

Scoring systems for the Clock Drawing Test: A historical review

PubMed Central

Spenciere, Bárbara; Alves, Heloisa; Charchat-Fichman, Helenice

2017-01-01

The Clock Drawing Test (CDT) is a simple neuropsychological screening instrument that is well accepted by patients and has solid psychometric properties. Several different CDT scoring methods have been developed, but no consensus has been reached regarding which scoring method is the most accurate. This article reviews the literature on these scoring systems and the changes they have undergone over the years. Historically, different types of scoring systems emerged. Initially, the focus was on screening for dementia, and the methods were both quantitative and semi-quantitative. Later, the need for an early diagnosis called for a scoring system that can detect subtle errors, especially those related to executive function. Therefore, qualitative analyses began to be used for both differential and early diagnoses of dementia. A widely used qualitative method was proposed by Rouleau et al. (1992). Tracing the historical path of these scoring methods is important for developing additional scoring systems and furthering dementia prevention research. PMID:29213488

Neuropathic pain in post-burn hypertrophic scars: a psychophysical and neurophysiological study.

PubMed

Isoardo, Gianluca; Stella, Maurizio; Cocito, Dario; Risso, Daniela; Migliaretti, Giuseppe; Cauda, Franco; Palmitessa, Angela; Faccani, Giuliano; Ciaramitaro, Palma

2012-06-01

Pain complicates hypertrophic post-burn pathologic scars (PPS) METHODS: To investigate the possible neuropathic origin of pain, 13 patients with painful PPS involving at least 1 hand underwent clinical examination, including the Douleur Neuropathique en 4 questions (DN4) questionnaire; median, ulnar, and radial nerve conduction studies (NCS); cold- (CDT) and heat-induced pain threshold evaluation by quantitative sensory testing; and cutaneous silent period (CSP) testing of the abductor pollicis brevis. Controls included 9 patients with non-painful PPS, 52 healthy subjects, and 28 patients with carpal tunnel syndrome (CTS). All patients with painful PPS had possible neuropathic pain (DN4 score ≥4). NCS signs of CTS were similarly present in PPS subjects with or without pain. Hands with painful PPS had lower CDT and CSP duration, more frequent cold- and heat-pain hypesthesia, and more thermal allodynia than controls. In PPS, possible neuropathic pain is associated with psychophysical and neurophysiological abnormalities suggestive of small-fiber damage. Copyright © 2011 Wiley Periodicals, Inc.

Earth Observations taken by the Expedition 13 crew

NASA Image and Video Library

2006-08-02

ISS013-E-62787 (2 August 2006) --- Tropical Storm Chris was located to the east of Puerto Rico and the Leeward Islands at at 9:29 a.m. (CDT), August 2, when one of the members of the Expedition 13 crew recorded this digital still image.

78 FR 64225 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

...: Cancer Diagnostics and Treatments (CDT). Date: November 4-5, 2013. Time: 8:00 a.m. to 5:00 p.m. Agenda... and Skin Systems. Date: November 4, 2013. Time: 8:00 a.m. to 7:00 p.m. Agenda: To review and evaluate...

Reliability and Validity of the Standing Heel-Rise Test

ERIC Educational Resources Information Center

Yocum, Allison; McCoy, Sarah Westcott; Bjornson, Kristie F.; Mullens, Pamela; Burton, Gay Naganuma

2010-01-01

A standardized protocol for a pediatric heel-rise test was developed and reliability and validity are reported. Fifty-seven children developing typically (CDT) and 34 children with plantar flexion weakness performed three tests: unilateral heel rise, vertical jump, and force measurement using handheld dynamometry. Intraclass correlation…

77 FR 47814 - Sunshine Act Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

... COMMISSION ON CIVIL RIGHTS Sunshine Act Notice AGENCY: United States Commission on Civil Rights. ACTION: Notice of briefing. DATE AND TIME: Friday, August 17, 2012; 9 a.m. CDT. PLACE: Sheraton... Agenda This briefing is open to the public. Topic: The Civil Rights Implications of Current State-Level...

Posing Cognitively Demanding Tasks to All Students

ERIC Educational Resources Information Center

Lambert, Rachel; Stylianou, Despina A.

2013-01-01

Cognitively demanding tasks (CDT) (Stein et al. 2000) are necessary for the development of students' mathematical reasoning skills. Research is unequivocal on the importance of giving students opportunities to engage in such tasks. Although current reform efforts call for mathematics learning for "all" students, learners who…

77 FR 30022 - U.S. Extractive Industries Transparency Initiative Stakeholder Assessment Public Listening...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... of Ocean Energy Management, 3801 Centerpoint Drive, Suite 100, Anchorage, AK 99503-5820, tel. 907... Surface Mining Reclamation and Enforcement, Building 3, Parkway Center, Conference Room, 2nd Floor...:00 pm CDT, June 12, 2012, Bureau of Ocean Energy Management, 1201 Elmwood Park Boulevard, Room 135...

75 FR 53349 - NASA Advisory Council; Commercial Space Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (10-098)] NASA Advisory Council; Commercial... Committee of the NASA Advisory Council. DATES: Tuesday September 14, 8 a.m. to 12 noon CDT. ADDRESSES: NASA..., Washington, DC 20546. Phone 202- 358-1686, fax: 202-358-3878, [email protected]nasa.gov . SUPPLEMENTARY...

75 FR 17437 - NASA Advisory Council; Commercial Space Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice: (10-039)] NASA Advisory Council; Commercial... Committee of the NASA Advisory Council. DATES: Monday, April 26, 2010, 1:30 p.m.-6 p.m. CDT. ADDRESSES: NASA Johnson Space Center, Gilruth Conference Center, 2101 NASA Parkway, Houston, TX 77058. FOR FURTHER...

Clostridium and bacillus binary enterotoxins: bad for the bowels, and eukaryotic being.

PubMed

Stiles, Bradley G; Pradhan, Kisha; Fleming, Jodie M; Samy, Ramar Perumal; Barth, Holger; Popoff, Michel R

2014-09-05

Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive bacteria and their toxins include Clostridium botulinum (C2 toxin), Clostridium difficile (C. difficile toxin or CDT), Clostridium perfringens (ι-toxin and binary enterotoxin, or BEC), Clostridium spiroforme (C. spiroforme toxin or CST), as well as Bacillus cereus (vegetative insecticidal protein or VIP). These gut-acting proteins form an AB complex composed of ADP-ribosyl transferase (A) and cell-binding (B) components that intoxicate cells via receptor-mediated endocytosis and endosomal trafficking. Once inside the cytosol, the A components inhibit normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. Important aspects of each bacterium and binary enterotoxin will be highlighted in this review, with particular focus upon the disease process involving the biochemistry and modes of action for each toxin.

Clostridium and Bacillus Binary Enterotoxins: Bad for the Bowels, and Eukaryotic Being

PubMed Central

Stiles, Bradley G.; Pradhan, Kisha; Fleming, Jodie M.; Samy, Ramar Perumal; Barth, Holger; Popoff, Michel R.

2014-01-01

Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive bacteria and their toxins include Clostridium botulinum (C2 toxin), Clostridium difficile (C. difficile toxin or CDT), Clostridium perfringens (ι-toxin and binary enterotoxin, or BEC), Clostridium spiroforme (C. spiroforme toxin or CST), as well as Bacillus cereus (vegetative insecticidal protein or VIP). These gut-acting proteins form an AB complex composed of ADP-ribosyl transferase (A) and cell-binding (B) components that intoxicate cells via receptor-mediated endocytosis and endosomal trafficking. Once inside the cytosol, the A components inhibit normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. Important aspects of each bacterium and binary enterotoxin will be highlighted in this review, with particular focus upon the disease process involving the biochemistry and modes of action for each toxin. PMID:25198129

Application of a High Throughput Method of Biomarker Discovery to Improvement of the EarlyCDT®-Lung Test

PubMed Central

Macdonald, Isabel K.; Murray, Andrea; Healey, Graham F.; Parsy-Kowalska, Celine B.; Allen, Jared; McElveen, Jane; Robertson, Chris; Sewell, Herbert F.; Chapman, Caroline J.; Robertson, John F. R.

2012-01-01

Background The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)). Methods and Findings Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7). Conclusion This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT­-Lung test, and so further aid the early detection of lung cancer. PMID:23272083

[The role of dosed walking in the combination with elements of cognitive training in the comprehensive treatment of the patients presenting with Alzheimer's disease].

PubMed

Zimushkina, N A; Kosareva, P V; Cherkasova, V G

The objective of the present study was to evaluate the effectiveness of dosed physical exercises for the combined treatment of the patients presenting with mild to moderate dementia associated with Alzheimer's disease (AD). The comprehensive examination involved 41 patients (32 women and 9 men) with the confirmed diagnosis of 'probable' AD with stages 1 and 2 of dementia and 17 healthy volunteers comprising the group of comparison. In all the patients, the neurological examination was supplemented by neuropsychological testing. Two treatment modalities were applied, one being conventional therapy with the use of memantine at the average effective dose, the other with the combination of memantine and dosed physical exercises including elements of cognitive training. In the group of patients treated with memantine alone, changes in cognitive performances among the men did not suggest any statistically significant positive trendency whereas the results of estimation in the women based on the clock drawing test (CDT) and the Mini-Mental State Examination (MMSE) scores revealed the significant improvement of cognitive performances. The most pronounced effects were documented in the women who had received combined therapy with the inclusion of dosed physical exercises in the form of walking. The comparison of the results of the treatment with observations of the patients included in the comparison group demonstrated the improvement of frontal cognitive functioning in the patients of both sexes under the influence of the combined treatment which manifested itself as the absence of the statistically significant differences between the results of the evaluation based on the Frontal Assessment Battery (FAB) scale. The prescription of dosed physical exercises with elements of cognitive training to be applied for the treatment of the patients presenting with dementia of different severity associated with Alzheimer's disease makes it possible to optimize the outcome of the conventional medical treatment and thereby to improve the results of scoring assessments of cognitive performances based on the MMSE, FAB, and CDT scales.

Student Attitudes Toward Instructional Variables in a Human Anatomy Class as Assessed by a Projective Technique.

ERIC Educational Resources Information Center

Allen, Ruth M.; And Others

1980-01-01

Explored the effectiveness of the self-initiated modular approach for learning a unit in a human gross anatomy course, and student preference of cadaver dissection versus cadaver prosection. A color scale, the Chromatic Differential Test (CDT), was used to assess general student attitude and preference. (CS)

75 FR 40816 - Marseilles Land and Water Company; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13351-000] Marseilles Land and Water Company; Notice of Meeting July 7, 2010. a. Date and Time of Meeting: Thursday, July 22, 2010 from 9 a.m. to 12 p.m. CDT. b. Place: Illinois Historic Preservation Agency, Old State Capitol...

Professional Doctoral Scholarship in Ghana: A Case Study of the CDT-BEPS Framework

ERIC Educational Resources Information Center

Owusu-Manu, D.; Edwards, D. J.; Afrane, S. K.; Dontwi, I. K.; Laycock, P.

2015-01-01

The constantly evolving paradigm of 21st century educational offerings and the growing demand for "professional practice" research degrees have raised concerns about the relevance of the traditional "theoretical" PhD award. To meet this growing demand, and address these concerns, alternative routes to achieving the doctoral…

78 FR 20166 - Meeting of the Regional Resource Stewardship Council

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

..., and partnership efforts to sustain trout hatcheries 3. Public Comments 4. Council Discussion and Advice The RRSC will hear opinions and views of citizens by providing a public comment session. The public comment session will be held at 9:30 a.m., CDT, on Thursday, April 25. Persons wishing to speak...

Alternative welding reconditioning solutions without post welding heat treatment of pressure vessel

NASA Astrophysics Data System (ADS)

Cicic, D. T.; Rontescu, C.; Bogatu, A. M.; Dijmărescu, M. C.

2017-08-01

In pressure vessels, working on high temperature and high pressure may appear some defects, cracks for example, which may lead to failure in operation. When these nonconformities are identified, after certain examination, testing and result interpretation, the decision taken is to repair or to replace the deteriorate component. In the current legislation it’s stipulated that any repair, alteration or modification to an item of pressurised equipment that was originally post-weld heat treated after welding (PWHT) should be post-weld heat treated again after repair, requirement that cannot always be respected. For that reason, worldwide, there were developed various welding repair techniques without PWHT, among we find the Half Bead Technique (HBT) and Controlled Deposition Technique (CDT). The paper presents the experimental results obtained by applying the welding reconditioning techniques HBT and CDT in order to restore as quickly as possible the pressure vessels made of 13CrMo4-5. The effects of these techniques upon the heat affected zone are analysed, the graphics of the hardness variation are drawn and the resulted structures are compared in the two cases.

Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression.

PubMed

Franz, André; Pirson, Paul A; Pilger, Domenic; Halder, Swagata; Achuthankutty, Divya; Kashkar, Hamid; Ramadan, Kristijan; Hoppe, Thorsten

2016-02-04

The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging.

The Putative Cellodextrin Transporter-like Protein CLP1 Is Involved in Cellulase Induction in Neurospora crassa*

PubMed Central

Cai, Pengli; Wang, Bang; Ji, Jingxiao; Jiang, Yongsheng; Wan, Li; Tian, Chaoguang; Ma, Yanhe

2015-01-01

Neurospora crassa recently has become a novel system to investigate cellulase induction. Here, we discovered a novel membrane protein, cellodextrin transporter-like protein 1 (CLP1; NCU05853), a putative cellodextrin transporter-like protein that is a critical component of the cellulase induction pathway in N. crassa. Although CLP1 protein cannot transport cellodextrin, the suppression of cellulase induction by this protein was discovered on both cellobiose and Avicel. The co-disruption of the cellodextrin transporters cdt2 and clp1 in strain Δ3βG formed strain CPL7. With induction by cellobiose, cellulase production was enhanced 6.9-fold in CPL7 compared with Δ3βG. We also showed that the suppression of cellulase expression by CLP1 occurred by repressing the expression of cellodextrin transporters, particularly cdt1 expression. Transcriptome analysis of the hypercellulase-producing strain CPL7 showed that the cellulase expression machinery was dramatically stimulated, as were the cellulase enzyme genes including the inducer transporters and the major transcriptional regulators. PMID:25398875

The putative cellodextrin transporter-like protein CLP1 is involved in cellulase induction in Neurospora crassa.

PubMed

Cai, Pengli; Wang, Bang; Ji, Jingxiao; Jiang, Yongsheng; Wan, Li; Tian, Chaoguang; Ma, Yanhe

2015-01-09

Neurospora crassa recently has become a novel system to investigate cellulase induction. Here, we discovered a novel membrane protein, cellodextrin transporter-like protein 1 (CLP1; NCU05853), a putative cellodextrin transporter-like protein that is a critical component of the cellulase induction pathway in N. crassa. Although CLP1 protein cannot transport cellodextrin, the suppression of cellulase induction by this protein was discovered on both cellobiose and Avicel. The co-disruption of the cellodextrin transporters cdt2 and clp1 in strain Δ3βG formed strain CPL7. With induction by cellobiose, cellulase production was enhanced 6.9-fold in CPL7 compared with Δ3βG. We also showed that the suppression of cellulase expression by CLP1 occurred by repressing the expression of cellodextrin transporters, particularly cdt1 expression. Transcriptome analysis of the hypercellulase-producing strain CPL7 showed that the cellulase expression machinery was dramatically stimulated, as were the cellulase enzyme genes including the inducer transporters and the major transcriptional regulators. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells.

PubMed

Ernst, Katharina; Schmid, Johannes; Beck, Matthias; Hägele, Marlen; Hohwieler, Meike; Hauff, Patricia; Ückert, Anna Katharina; Anastasia, Anna; Fauler, Michael; Jank, Thomas; Aktories, Klaus; Popoff, Michel R; Schiene-Fischer, Cordelia; Kleger, Alexander; Müller, Martin; Frick, Manfred; Barth, Holger

2017-06-02

Binary enterotoxins Clostridium (C.) botulinum C2 toxin, C. perfringens iota toxin and C. difficile toxin CDT are composed of a transport (B) and a separate non-linked enzyme (A) component. Their B-components mediate endocytic uptake into mammalian cells and subsequently transport of the A-components from acidic endosomes into the cytosol, where the latter ADP-ribosylate G-actin resulting in cell rounding and cell death causing clinical symptoms. Protein folding enzymes, including Hsp90 and peptidyl-prolyl cis/trans isomerases facilitate transport of the A-components across endosomal membranes. Here, we identified Hsp70 as a novel host cell factor specifically interacting with A-components of C2, iota and CDT toxins to facilitate their transport into the cell cytosol. Pharmacological Hsp70-inhibition specifically prevented pH-dependent trans-membrane transport of A-components into the cytosol thereby protecting living cells and stem cell-derived human miniguts from intoxication. Thus, Hsp70-inhibition might lead to development of novel therapeutic strategies to treat diseases associated with bacterial ADP-ribosylating toxins.

[Clinical analysis of patients with lower extremity deep venous thrombosis complicated with inferior vena cava thrombus].

PubMed

Dong, Dian-ning; Wu, Xue-jun; Zhang, Shi-yi; Zhong, Zhen-yue; Jin, Xing

2013-06-04

To explore the clinical profiles of patients with lower extremity deep venous thrombosis (DVT) complicated with inferior vena cava (IVC) thrombus and summarize their clinical diagnostic and therapeutic experiences. The clinical characteristics, diagnosis and treatment of 20 hospitalized patients with DVT complicated with inferior vena cava thrombus were analyzed retrospectively. All of them were of proximal DVT. There were phlegmasia cerulea dolens (n = 3), pulmonary embolism (n = 3) and completely occlusion of IVC (n = 5). Clinical manifestations were severe. Retrievable inferior vena cava filter (IVCF) was implanted for 17 cases. Catheter-directed thrombolysis (CDT) through ipsilateral popliteal vein was applied for 7 cases and systemic thrombolysis therapy for 8 cases. The effective rate of thrombolysis for fresh IVC thrombus was 100%. Among 5 cases with Cockett Syndrome, 3 cases underwent balloon dilatation angioplasty and endovascular stenting of iliac vein. And 17 IVCFs were retrieved successfully within 3 weeks. IVC thrombus disappeared completely in 15 cases. Systemic or local thrombolysis with protective IVCF is a safe and effective therapy for nonocclusive IVC thrombus in DVT. And CDT is recommended for symptomatic occlusive IVC thrombus.

Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression

PubMed Central

Franz, André; Pirson, Paul A.; Pilger, Domenic; Halder, Swagata; Achuthankutty, Divya; Kashkar, Hamid; Ramadan, Kristijan; Hoppe, Thorsten

2016-01-01

The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging. PMID:26842564

The complementarity-determining region sequences in IgY antivenom hypervariable regions.

PubMed

da Rocha, David Gitirana; Fernandez, Jorge Hernandez; de Almeida, Claudia Maria Costa; da Silva, Claudia Letícia; Magnoli, Fabio Carlos; da Silva, Osmair Élder; da Silva, Wilmar Dias

2017-08-01

The data presented in this article are related to the research article entitled "Development of IgY antibodies against anti-snake toxins endowed with highly lethal neutralizing activity" (da Rocha et al., 2017) [1]. Complementarity-determining region (CDR) sequences are variable antibody (Ab) sequences that respond with specificity, duration and strength to identify and bind to antigen (Ag) epitopes. B lymphocytes isolated from hens immunized with Bitis arietans (Ba) and anti- Crotalus durissus terrificus (Cdt) venoms and expressing high specificity, affinity and toxicity neutralizing antibody titers were used as DNA sources. The VLF1, CDR1, CDR2, VLR1 and CDR3 sequences were validated by BLASTp, and values corresponding to IgY V L and V H anti-Ba or anti-Cdt venoms were identified, registered [ Gallus gallus IgY Fv Light chain (GU815099)/ Gallus gallus IgY Fv Heavy chain (GU815098)] and used for molecular modeling of IgY scFv anti-Ba. The resulting CDR1, CDR2 and CDR3 sequences were combined to construct the three - dimensional structure of the Ab paratope.

Shiga toxin-producing Escherichia coli in drinking water supplies of north Paraná State, Brazil.

PubMed

Lascowski, K M S; Guth, B E C; Martins, F H; Rocha, S P D; Irino, K; Pelayo, J S

2013-04-01

To determine the occurrence and characteristics of Shiga toxin-producing Escherichia coli (STEC) in drinking water supplies treated and untreated. Drinking water samples (n = 1850) were collected from 41 municipalities in the north of Paraná State between February 2005 and January 2006. Escherichia coli isolates (n = 300) were recovered from water and investigated for the presence of virulence markers related to STEC by PCR. STEC isolates recovered were then characterized for both phenotypic and genotypic traits. A total of 12 isolates (11 from untreated water and one from treated water) were positive for stx, including five positive for both stx1 and stx2, two positive for stx1 and five positive for stx2. None of the STEC isolates contained eae, but other virulence genes were observed such as ehxA (100%), saa (100%), lpfAO113 (75%), iha (42%), subAB (25%) and cdtV (8%). Multidrug resistance was identified in 25% of the STEC isolates. The 12 STEC isolates belonged to seven distinct serotypes and pulsed-field gel electrophoresis typing revealed the presence of two clusters and two clones in this region. Drinking water, especially from untreated water supplies, can be source of STEC strains potentially pathogenic for humans. The investigation of the drinking water supplies for pathogenic E. coli, as STEC, may be useful to prevent waterborne outbreaks. © 2012 The Society for Applied Microbiology.

Incorporation of CAD/CAM Restoration Into Navy Dentistry

DTIC Science & Technology

2017-09-26

CAD/CAM Computer-aided design /Computer-assisted manufacturing CDT Common Dental Terminology DENCAS Dental Common Access System DTF Dental...to reduce avoidable dental emergencies for deployed sailors and marines. Dental Computer-aided design /Computer-assisted manufacturing (CAD/CAM...report will review and evaluate the placement rate by Navy dentists of digitally fabricated in-office ceramic restorations compared to traditional direct

Manufacturing Methods and Technology Program Plan, CY 1986

DTIC Science & Technology

1986-02-01

Sada Barik ) C: (201) 5 32- 4 035 Fort Monmouth, NJ 07T03 AV: 992-4995 DESCOM U.S. Army Depot Systems Command ATTN: AMSDS-RM-EM (-Mr. Mike Ahearn) C...A.MSETL-PC-SI-I (Mr. Sada Barik ) (-r, ATTN: AMSEL-POD-P-G (Messrs. Feddeler, Esposito, Resnic) Cdt ATTN: RD&E Technical Documents Center PM, 6ITTN: AMCPM

An Examination of Pennsylvania's Classroom Diagnostic Testing as a Predictive Model of Pennsylvania System of School Assessment Performance

ERIC Educational Resources Information Center

Matsanka, Christopher

2017-01-01

The purpose of this non-experimental quantitative study was to investigate the relationship between Pennsylvania's Classroom Diagnostic Tools (CDT) interim assessments and the state-mandated Pennsylvania System of School Assessment (PSSA) and to create linear regression equations that could be used as models to predict student performance on the…

78 FR 60366 - Meeting of the Regional Energy Resource Council

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

.... Public Comments. 4. Council Discussion. The RERC will hear opinions and views of citizens by providing a public comment session. The public comment session will be held at 1:30 p.m. C.D.T. on Wednesday, October 23, 2013. Persons wishing to speak are requested to register at the door by 12:30 p.m. on Wednesday...

DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression

PubMed Central

Barr, Alexis R.; Cooper, Samuel; Heldt, Frank S.; Butera, Francesca; Stoy, Henriette; Mansfeld, Jörg; Novák, Béla; Bakal, Chris

2017-01-01

Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability. PMID:28317845

Rectification of the chordal axis transform and a new criterion for shape decomposition.

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

Prasad, Lakshman

2004-01-01

In an earlier work we proposed the chordal axis transform (CAT) as a more useful alternative to the medial axis transform (MAT) for obtaining skeletons of discrete shapes. Since then, the CAT has benefited various applications in 2D and 3D shape analysis. In this paper, we revisit the CAT to address its deficiencies that are an artifact of the underlying constrained Delaunay triangulation (CDT). We introduce a valuation on the internal edges of a discrete shape's CDT based on a concept of approximate co-circularity. This valuation provides a basis for suppression of the role of certain edges in the constructionmore » of the CAT skeleton. The result is a rectified CAT skeleton that has smoother branches as well as branch points of varying degrees, unlike the original CAT skeleton whose branches exhibit oscillations in tapered sections of shapes and allows only degree 3 branch points. Additionally, the valuation leads to a new criterion for parsing shapes into visually salient parts that closely resemble the empirical decompositions of shapes by human subjects as recorded in experiments by M. Singh, G. Seyranian, and D. Hoffinan.« less

Effects of physiotherapy combined with sirolimus in a patient with vascular malformation: A case report.

PubMed

Akbayrak, Türkan; Orhan, Ceren; Baran, Emine; Kaya, Serap; Coskun, Gürsoy; Varan, Ali

2016-01-01

The aim of the present case report was to investigate the effects of a physiotherapy program combined with sirolimus in a child patient with upper extremity edema and joint limitation due to low-flow vascular malformation. This case report included an 11-year-old male patient (26 kg, 130 cm) diagnosed with congenital lymphovascular malformation on the left and right chest. The patient, who had edema on the upper left extremity and experienced joint limitations, was administered complete decongestive therapy (CDT) and manual therapy in combination with sirolimus. Physiotherapy included a total of 24 sessions, 3 sessions a week for 8 weeks. Following the physiotherapy, the patient was assigned to a home therapy program, and then the maintenance phase of the CDT was initiated. Evaluations were carried out at baseline, at the end of week 8, and after 12 months. Following the physiotherapy program combined with sirolimus, a decrease in extremity volume, an increase in joint movement range, and an improvement in disease-related complaints were observed. Physiotherapy methods combined with sirolimus may be an effective treatment method in patients with vascular malformations. However, further studies with larger sample size are warranted.

Lactobacillus salivarius and L. gasseri down-regulate Aggregatibacter actinomycetemcomitans exotoxins expression.

PubMed

Nissen, Lorenzo; Sgorbati, Barbara; Biavati, Bruno; Belibasakis, Georgios N

2014-01-01

Beneficial microbes, such as lactobacilli establish a symbiosis with the host and confer health-associated effects, by limiting the growth of indigenous pathogens and challenging microbes introduced by altered foods. Nevertheless, there is scarce information on the effects of beneficial microbes on the virulence properties of bacterial species associated with oral diseases, such as periodontitis. Aggregatibacter actinomycetemcomitans is a Gram-negative species highly implicated in the etiology of localized aggressive periodontitis. The objective of this study was to investigate the effect of lactobacilli on the expression of the two major virulence factors of A. actinomycetemcomitans . Lactobacillus salivarius and L. gasseri were selected as beneficial species. The gene expressions of leukotoxin ( LtxA ) and cytolethal distending toxin ( CdtB ) by A. actinomycetemcomitans were analyzed in response to challenge by lactobacilli cell-free supernatants. Neither lactobacilli affected the growth, but strongly attenuated the expressions of both CdtB and LtxA in the two A. actinomycetemcomitans strains tested. This reduction of the expression of these two exotoxins was time-dependent. These fundamental findings may indicate that lactobacilli can reduce the virulence of putative opportunistic oral pathogens, and may provide insights to future therapeutic approaches for the respective diseases.

STS-114 orbiter Discovery during docking of Raffaello

NASA Image and Video Library

2005-08-05

ISS011-E-11510 (5 August 2005) --- On the eve of the separation of Discovery and the International Space Station, an Expedition 11 crew member took this digital still picture. Crews onboard the orbital outpost and Discovery were wrapping up nine days of joint operations. The Space Shuttle is partially visible beneath other hardware. The Canadian-built robot arms for both spacecraft are dominant in the frame. A Russian Soyuz is docked to the Station in the foreground. After the Italian-built Multi-Purpose Logistics Module Raffaello was secured in Discovery's cargo bay, Astronauts Charles J. Camarda and Andrew S.W. Thomas, mission specialists operating from Discovery's aft flight deck, used the Shuttle arm to hand off the Orbiter Boom Sensor System to the Station arm. Then Astronauts Wendy B. Lawrence, mission specialist, and James M. Kelly, pilot, onboard Destiny, reberthed the OBSS in its position on the starboard sill of the cargo bay. Undocking is scheduled shortly before 2:30 a.m. (CDT) on August 6.

Prevalence and Characterization of a Binary Toxin (Actin-Specific ADP-Ribosyltransferase) from Clostridium difficile

PubMed Central

Gonçalves, Carina; Decré, Dominique; Barbut, Frédéric; Burghoffer, Béatrice; Petit, Jean-Claude

2004-01-01

In addition to the two large clostridial cytotoxins (TcdA and TcdB), some strains of Clostridium difficile also produce an actin-specific ADP-ribosyltransferase, called binary toxin CDT. We used a PCR method and Southern blotting for the detection of genes encoding the enzymatic (CDTa) and binding (CDTb) components of the binary toxin in 369 strains isolated from patients with suspected C. difficile-associated diarrhea or colitis. Twenty-two strains (a prevalence of 6%) harbored both genes. When binary toxin production was assessed by Western blotting, 19 of the 22 strains reacted with antisera against the iota toxin of C. perfringens (anti-Ia and anti-Ib). Additionally, binary toxin activity, detected by the ADP-ribosyltransferase assay, was present in only 17 of the 22 strains. Subsequently, all 22 binary toxin-positive strains were tested for the production of toxins TcdA and TcdB, toxinotyped, and characterized by serogrouping, PCR ribotyping, arbitrarily primed PCR, and pulsed-field gel electrophoresis. All binary toxin-positive strains also produced TcdB and/or TcdA. However, they had significant changes in the tcdA and tcdB genes and belonged to variant toxinotypes III, IV, V, VII, IX, and XIII. We could differentiate 16 profiles by using typing methods, indicating that most of the binary toxin-positive strains were unrelated. PMID:15131151

The Contribution of the Self-Efficacy of Curriculum Development Team and Curriculum Document Quality to the Implementation of Diversified Curriculum in Indonesia

ERIC Educational Resources Information Center

Susilana, Rudi; Asra; Herlina

2014-01-01

The aim of this study is to describe how the self-efficacy of curriculum development team (CDT) and curriculum document quality contributed to the implementation of diversified curriculum in elementary schools. This research is a survey study using descriptive method. Schools were the unit of analysis while respondents selected from the schools…

2001 Australian Defence Force Reserves Survey Report

DTIC Science & Technology

2001-11-01

56 71 Attitudes Towards Reserves Activities Being Part of Member’s Social Life..... 56v i 2...for Social and Economic Modelling NEOC New Entry Officer Course OFFICER CDT Officer Cadet OP GOLD Operation Gold ORs Other Ranks (LS/CPL and below) OSB...Reserve members. An evaluation of the data was undertaken by the National Centre of Social and Economic Modelling (NATSEM) to establish the

Skill Training Using Adaptive Technology: A Better Way to Hover

DTIC Science & Technology

2005-09-01

instructional presentation strategies as discussed below. Primary Presentations Merrill’s CDT suggests that instruction be organized around a series of...conducted a series of experiments designed to investigate the application of Shiffrin and Schneider’s (1977) theory of automatic and controlled...perceptual-motor in content. The results of a series of interlocking studies, using various cognitive and perceptual-motor tasks and observational

Expedition 15 Progress 26 Launch

NASA Image and Video Library

2007-08-02

JSC2007-E-41113(2 Aug. 2007) --- The ISS Progress 26 launched Aug. 2 from the Baikonur Cosmodrome in Kazakhstan on time at 12:33:46 pm (CDT) and 11:33:46 pm, Baikonur time. Ascent was nominal and by the book. Once in orbit, the Progress separated from the third stage of the booster and all appendages and antennas were deployed on time. Photo Credit: NASA/Mark Bowman

Genome-Based Comparison of Clostridioides difficile: Average Amino Acid Identity Analysis of Core Genomes.

PubMed

Cabal, Adriana; Jun, Se-Ran; Jenjaroenpun, Piroon; Wanchai, Visanu; Nookaew, Intawat; Wongsurawat, Thidathip; Burgess, Mary J; Kothari, Atul; Wassenaar, Trudy M; Ussery, David W

2018-02-14

Infections due to Clostridioides difficile (previously known as Clostridium difficile) are a major problem in hospitals, where cases can be caused by community-acquired strains as well as by nosocomial spread. Whole genome sequences from clinical samples contain a lot of information but that needs to be analyzed and compared in such a way that the outcome is useful for clinicians or epidemiologists. Here, we compare 663 public available complete genome sequences of C. difficile using average amino acid identity (AAI) scores. This analysis revealed that most of these genomes (640, 96.5%) clearly belong to the same species, while the remaining 23 genomes produce four distinct clusters within the Clostridioides genus. The main C. difficile cluster can be further divided into sub-clusters, depending on the chosen cutoff. We demonstrate that MLST, either based on partial or full gene-length, results in biased estimates of genetic differences and does not capture the true degree of similarity or differences of complete genomes. Presence of genes coding for C. difficile toxins A and B (ToxA/B), as well as the binary C. difficile toxin (CDT), was deduced from their unique PfamA domain architectures. Out of the 663 C. difficile genomes, 535 (80.7%) contained at least one copy of ToxA or ToxB, while these genes were missing from 128 genomes. Although some clusters were enriched for toxin presence, these genes are variably present in a given genetic background. The CDT genes were found in 191 genomes, which were restricted to a few clusters only, and only one cluster lacked the toxin A/B genes consistently. A total of 310 genomes contained ToxA/B without CDT (47%). Further, published metagenomic data from stools were used to assess the presence of C. difficile sequences in blinded cases of C. difficile infection (CDI) and controls, to test if metagenomic analysis is sensitive enough to detect the pathogen, and to establish strain relationships between cases from the same hospital. We conclude that metagenomics can contribute to the identification of CDI and can assist in characterization of the most probable causative strain in CDI patients.

Ten-year follow-up of a consecutive series of children with multichannel cochlear implants.

PubMed

Uziel, Alain S; Sillon, Martine; Vieu, Adrienne; Artieres, Françoise; Piron, Jean-Pierre; Daures, Jean-Pierre; Mondain, Michel

2007-08-01

To assess a group of children who consecutively received implants more than 10 years after implantation with regard to speech perception, speech intelligibility, receptive language level, and academic/occupational status. A prospective longitudinal study. Pediatric referral center for cochlear implantation. Eighty-two prelingually deafened children received the Nucleus multichannel cochlear implant. Cochlear implantation with Cochlear Nucleus CI22 implant. The main outcome measures were open-set Phonetically Balanced Kindergarten word test, discrimination of sentences in noise, connective discourse tracking (CDT) using voice and telephone, speech intelligibility rating (SIR), vocabulary knowledge measured using the Peabody Picture Vocabulary Test (Revised), academic performance on French language, foreign language, and mathematics, and academic/occupational status. After 10 years of implant experience, 79 children (96%) reported that they always wear the device; 79% (65 of 82 children) could use the telephone. The mean scores were 72% for the Phonetically Balanced Kindergarten word test, 44% for word recognition in noise, 55.3 words per minute for the CDT, and 33 words per minute for the CDT via telephone. Thirty-three children (40%) developed speech intelligible to the average listener (SIR 5), and 22 (27%) developed speech intelligible to a listener with little experience of deaf person's speech (SIR 4). The measures of vocabulary showed that most (76%) of children who received implants scored below the median value of their normally hearing peers. The age at implantation was the most important factor that may influence the postimplant outcomes. Regarding educational/vocational status, 6 subjects attend universities, 3 already have a professional activity, 14 are currently at high school level, 32 are at junior high school level, 6 additional children are enrolled in a special unit for children with disability, and 3 children are still attending elementary schools. Seventeen are in further noncompulsory education studying a range of subjects at vocational level. This long-term report shows that many profoundly hearing-impaired children using cochlear implants can develop functional levels of speech perception and production, attain age-appropriate oral language, develop competency level in a language other than their primary language, and achieve satisfactory academic performance.

Prevalence and characterization of Campylobacter jejuni isolated from pasture flock poultry.

PubMed

Hanning, Irene; Biswas, Debabrata; Herrera, Paul; Roesler, Mary; Ricke, Steven C

2010-09-01

The growing interest in organic and natural foods warrants a greater need for information on the food safety of these products. In this study, samples were taken from 2 pasture flock farms (N = 178; feed, water, drag swabs, and insect traps), pasture flock retail carcasses (N = 48) and 1 pasture flock processing facility (N = 16) over a period of 8 mo. A total of 105 Campylobacter isolates were obtained from 53 (30%), 36 (75%), and 16 (100%) samples from the farms, retail carcasses, and processing facility, respectively. Of the 105 isolates collected, 65 were C. jejuni, 31 were C. coli, and 9 were other Campylobacter spp. Using PCR, the C. jejuni isolates were further analyzed for virulence genes involved in colonization and survival (flaA, flaC, cadF, dnaJ, racR, cbrR), invasion (virB11, ciaB, pldA), protection against harsh conditions (sodB, htrA, clpA), toxin production (cdtA, cdtB, cdtC), siderophore transport (ceuE), and ganglioside mimicry (wlaN). In addition, the short variable region of the flaA locus (flaA SVR) was sequenced to determine the genetic diversity of the C. jejuni isolates. The flaA SVR diversity indices increased along the farm to carcass continuum. PCR-based analysis indicated a low prevalence of 5 genes involved in colonization (dnaJ, ciaB, pldA, racR, virB11). The results of this survey indicate that the prevalence of Campylobacter on organic retail carcasses is similar to prevalence reports of Campylobacter on conventional retail carcasses. However, the genetic diversity of the flaA SVR genotypes increased along the farm to carcass continuum that contrasted with conventional poultry studies. Campylobacter jejuni is a leading cause of foodborne illness with poultry and poultry products being leading sources of infection. Free-range and pasture flock chickens are becoming more popular; however, there is an inherent biosecurity risk that can increase the prevalence of foodborne pathogens in these flocks. This study aimed to determine sources and characterize C. jejuni isolated from pasture flocks.

Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high-risk cohort: A prospective study of allergy-prone children from birth to six years.

PubMed

Thomson, Jennifer A; Widjaja, Constance; Darmaputra, Abbi A P; Lowe, Adrian; Matheson, Melanie C; Bennett, Catherine M; Allen, Katrina; Abramson, Michael J; Hosking, Cliff; Hill, David; Dharmage, Shyamali C

2010-11-01

The role of early childhood infections and immunisation in the development of allergic diseases remains controversial. To examine these associations, six hundred and twenty infants with first-degree relatives with allergic diseases were recruited into the Melbourne Atopy Cohort Study. Information on risk factors and outcomes was collected by interviewer administered questionnaire and was based on parental report and/or a physician's diagnosis. Risk factors examined included early childhood infections (including gastroenteritis, otitis media and lower respiratory tract infections) and immunisations in the first 2 yr of life. Outcomes were current asthma, allergic rhinitis and eczema at 6 yr of age. Univariate and multivariate regression analysis were used to estimate relative risk (RR) and assess confounding. By 6 yr, 79% of the original cohort remained in the study. Those with at least three episodes of gastroenteritis showed an increased risk (crude RR 2.36, 95%CI 1.41 3.95; adjusted RR 2.03 95%CI 1.50 2.75) for the later development of asthma at age 6. Of the scheduled immunisations, Sabin immunisation in the second year had a reduced risk of asthma at 6 yr (crude RR 0.60, 95%CI 0.37 0.98; adjusted RR 0.63 95%CI 0.39 1.02). Combined diphtheria and tetanus (CDT) immunisation in the first year had an increased risk of asthma at 6 yr (RR 1.76, 95%CI 1.11 2.78; adjusted RR 1.88 95%CI 1.28 2.77). Recurrent gastroenteritis in early childhood is associated with a later risk of asthma. This may reflect a cause and effect relationship, or exposure to common risk factors. In contrast, Sabin immunisation in the second year is associated with a decreased risk of asthma in later childhood. CDT immunisation in the first year may be a risk factor for asthma, but the need for CDT immunisation may also be a marker of increased risk of asthma in later childhood. © 2010 John Wiley & Sons A/S.

[Alcohol intake, complex ability and responsibility towards others: experience on a cohort of personnel employed to public transport services].

PubMed

Bordini, L; Patrini, L; Ricci, Maria Grazia; Verga, A; Riboldi, L

2007-01-01

The excessive intake or the abuse of alcoholic substances represent an important hazard's source for the individual health and for the carrying out of any complex working activities, above all if characterized by elevated responsibility toward other people. In this context the recent Provision of 16 March 2006 of the Permanent Lecture for the Relationships among the State the Regions and the Autonomous Provinces of Trento and Bolzano, has individualized bus driver among the activities or tasks of which is forbidden the assumption of alcoholic drinks at work and can performed alcoholic controls by the competent physician (art. 15 of the Law March 30 th 2001, n. 125). Within the normative considering the DM 23 February 1999 n. 88s (Rule bringing norms dealing about the check and the control of the physical and psycho-aptitude ability of the personnel employed to public transport services), we introduced experience growing up in the period from January 2005 to August 2006, on about 1500 employees, for over 90% of men, employed in a public transport company of the Lombardy as bus driver or railwayman. In order to assess driver's alcoholic abuse the analytical determination of carbohydrate-deficient transferring (CDT) has been used as a marker of alcohol intake. Within the visits of hiring in service (equal to 10% of the total one of the effected visits) the determination of the CDT has always been performed, while in revision visits (equal to 90% of the total one) this analytical determination has been performed only if possible alcohol abuse has been hypothesized by elevated values of gamma-GT before the Provision March 16th 2006 (and eventually of MCV, AST and ALT) and of routine from April 2006. This experience on this large population has confirmed the importance of a careful behaviours of abuse monitoring in workers with high responsibility toward other people. The CDT values reflect high alcoholic consumption, while is poorly remarkable the contribution furnished by anamnestic questionnaire.

The Neoarchaean surficial sulphur cycle: An alternative hypothesis based on analogies with 20th-century atmospheric lead.

PubMed

Gallagher, M; Whitehouse, M J; Kamber, B S

2017-05-01

We revisit the S-isotope systematics of sedimentary pyrite in a shaly limestone from the ca. 2.52 Ga Gamohaan Formation, Upper Campbellrand Subgroup, Transvaal, South Africa. The analysed rock is interpreted to have been deposited in a water depth of ca. 50-100 m, in a restricted sub-basin on a drowning platform. A previous study discovered that the pyrites define a nonzero intercept δ 34 S V - CDT -Δ 33 S data array. The present study carried out further quadruple S-isotope analyses of pyrite, confirming and expanding the linear δ 34 S V - CDT -Δ 33 S array with an δ 34 S zero intercept at ∆ 33 S ca. +5. This was previously interpreted to indicate mixing of unrelated S-sources in the sediment environment, involving a combination of recycled sulphur from sulphides that had originally formed by sulphate-reducing bacteria, along with elemental sulphur. Here, we advance an alternative explanation based on the recognition that the Archaean seawater sulphate concentration was likely very low, implying that the Archaean ocean could have been poorly mixed with respect to sulphur. Thus, modern oceanic sulphur systematics provide limited insight into the Archaean sulphur cycle. Instead, we propose that the 20th-century atmospheric lead event may be a useful analogue. Similar to industrial lead, the main oceanic input of Archaean sulphur was through atmospheric raindown, with individual giant point sources capable of temporally dominating atmospheric input. Local atmospheric S-isotope signals, of no global significance, could thus have been transmitted into the localised sediment record. Thus, the nonzero intercept δ 34 S V - CDT -Δ 33 S data array may alternatively represent a very localised S-isotope signature in the Neoarchaean surface environment. Fallout from local volcanic eruptions could imprint recycled MIF-S signals into pyrite of restricted depositional environments, thereby avoiding attenuation of the signal in the subdued, averaged global open ocean sulphur pool. Thus, the superposition of extreme local S-isotope signals offers an alternative explanation for the large Neoarchaean MIF-S excursions and asymmetry of the Δ 33 S rock record. © 2017 John Wiley & Sons Ltd.

Chino del tomate virus:Relationships to Other Begomoviruses and Identification of A-Component Variants that Affect Symptom Expression.

PubMed

Brown, J K; Ostrow, K M; Idris, A M; Stenger, D C

2000-05-01

Phylogenetic and distance analyses place Chino del tomate virus (CdTV) in the New World clade of begomoviruses and indicate that CdTV and Tomato leaf crumple virus (TLCrV) are closely related strains of the same virus. One cloned CdTV A component (pCdTV-H6), when inoculated to tomato with the B component (pCdTV-B52), produced mild symptoms and low DNA titers. Another cloned CdTV A component (pCdTV-H8), when coinoculated to tomato with the B component, produced moderate leaf curling and veinal chlorosis similar to that of TLCrV. Coinoculation of both CdTV A components and the B component to tomato produced wild-type chino del tomate (CdT) disease symptoms consisting of severe leaf curling, veinal and interveinal chlorosis, and stunting. The two CdTV A components were nearly identical, except at nucleotide positions 1,722 and 2,324. The polymorphism at nucleotide 1,722 resulted in a change at Rep amino acid 261. The second polymorphism at nucleotide 2,324 resulted in changes at Rep amino acid 60 and AC4 amino acid 10. Two chimeric A components constructed by reciprocal exchange of a fragment bearing the polymorphic site at nucleotide 1,722 were evaluated for symptom phenotype. One chimeric A component (pCdTV-H86) produced wild-type CdT symptoms when coinoculated to tomato with the B component. The reciprocal chimeric A component (pCdTV-H68), when coin-oculated to tomato with the B component, also produced severe leaf curling, veinal chlorosis, and stunting. However, pCdTV-H68 induced less obvious interveinal chlorosis than wild-type or pCdTV-H86. Examination of A component genotypes recovered from tomato coinoculated with pCdTV-H6 and pCdTV-H8 indicated that recombination occurred to produce a genotype identical to pCdTV-H86. These results indicate that subtle genotypic variation has significant effects on symptom expression and may explain phenotypic differences observed among isolates and cloned DNAs of CdTV and TLCrV.

ASTP Apollo Command Module nears touchdown in Central Pacific

NASA Image and Video Library

1975-07-24

S75-29719 (24 July 1975) --- The ASTP Apollo Command Module, with astronauts Thomas P. Stafford, Vance D. Brand and Donald K. Slayton aboard, nears a touchdown in the Central Pacific Ocean to conclude the historic joint U.S.-USSR Apollo-Soyuz Test Project docking mission in Earth orbit. The spacecraft splashed down in the Hawaiian Islands area at 4:18 p.m. (CDT), July 24, 1975.

Analysis of re-replication from deregulated origin licensing by DNA fiber spreading

PubMed Central

Dorn, Elizabeth S.; Chastain, Paul D.; Hall, Jonathan R.; Cook, Jeanette Gowen

2009-01-01

A major challenge each human cell-division cycle is to ensure that DNA replication origins do not initiate more than once, a phenomenon known as re-replication. Acute deregulation of replication control ultimately causes extensive DNA damage, cell-cycle checkpoint activation and cell death whereas moderate deregulation promotes genome instability and tumorigenesis. In the absence of detectable increases in cellular DNA content however, it has been difficult to directly demonstrate re-replication or to determine if the ability to re-replicate is restricted to a particular cell-cycle phase. Using an adaptation of DNA fiber spreading we report the direct detection of re-replication on single DNA molecules from human chromosomes. Using this method we demonstrate substantial re-replication within 1 h of S phase entry in cells overproducing the replication factor, Cdt1. Moreover, a comparison of the HeLa cancer cell line to untransformed fibroblasts suggests that HeLa cells produce replication signals consistent with low-level re-replication in otherwise unperturbed cell cycles. Re-replication after depletion of the Cdt1 inhibitor, geminin, in an untransformed fibroblast cell line is undetectable by standard assays but readily quantifiable by DNA fiber spreading analysis. Direct evaluation of re-replicated DNA molecules will promote increased understanding of events that promote or perturb genome stability. PMID:19010964

Evaluation of Ethanol Production Activity by Engineered Saccharomyces cerevisiae Fermenting Cellobiose through the Phosphorolytic Pathway in Simultaneous Saccharification and Fermentation of Cellulose.

PubMed

Lee, Won-Heong; Jin, Yong-Su

2017-09-28

In simultaneous saccharification and fermentation (SSF) for production of cellulosic biofuels, engineered Saccharomyces cerevisiae capable of fermenting cellobiose has provided several benefits, such as lower enzyme costs and faster fermentation rate compared with wild-type S. cerevisiae fermenting glucose. In this study, the effects of an alternative intracellular cellobiose utilization pathway-a phosphorolytic pathway based on a mutant cellodextrin transporter (CDT-1 (F213L)) and cellobiose phosphorylase (SdCBP)-was investigated by comparing with a hydrolytic pathway based on the same transporter and an intracellular β-glucosidase (GH1-1) for their SSF performances under various conditions. Whereas the phosphorolytic and hydrolytic cellobiose-fermenting S. cerevisiae strains performed similarly under the anoxic SSF conditions, the hydrolytic S. cerevisiae performed slightly better than the phosphorolytic S. cerevisiae under the microaerobic SSF conditions. Nonetheless, the phosphorolytic S. cerevisiae expressing the mutant CDT-1 showed better ethanol production than the glucose-fermenting S. cerevisiae with an extracellular β-glucosidase, regardless of SSF conditions. These results clearly prove that introduction of the intracellular cellobiose metabolic pathway into yeast can be effective on cellulosic ethanol production in SSF. They also demonstrate that enhancement of cellobiose transport activity in engineered yeast is the most important factor affecting the efficiency of SSF of cellulose.

Living experiences of Indian adult cancer survivors--a brief report.

PubMed

Mohanti, Bidhu Kalyan; Kaur, Jaspreet

2015-01-01

This pilot study looked into the physical, social, psychological and economic issues of Indian adult cancer survivors. Assumed cancer free patients, after cancer directed therapy (CDT), were assessed on the basis of a questionnaire developed by the investigators. The mental status of the survivors was elicited by modified MINI international neuro-psychiatric interview. This cross sectional assessment was conducted as a direct interaction with each patient for 30 to 45 minutes at a cancer hospital in 2012. Thirty one adult cancer survivors participated in this study. Median age was 53 years with a median follow up duration of 21.8 months (Range 2.3-194.1 months). The majority (68%) did not receive financial support for treatment. Median interval after CDT to start of activity of daily living was 1.5 months (range: 0-24 months). Fatigue and loss of appetite were reported by 52% and 29% respectively. The cancer diagnosis and its treatment adversely impacted the financial condition in 42% of patients. Nineteen percent each showed social anxiety and post-traumatic stress disorder and another 13% patients reported depression. This prospective assessment highlights survivorship issues and the need to address those issues particularly in the context of developing countries where resources and manpower are limited.

Diurnal variation in invertebrate catch rates by sticky traps: Potential for biased indices of piping plover forage

USGS Publications Warehouse

Anteau, M.J.; Sherfy, M.H.

2010-01-01

Measuring abundance of invertebrate forage for piping plovers (Charadrius melodus; hereafter plovers), a federally listed species in the USA, is an important component of research and monitoring targeted toward species recovery. Sticky traps are commonly used to passively sample invertebrates, but catch rates may vary diurnally or in response to weather. We examined diurnal variation in catch rates of invertebrates using an experiment on reservoir shoreline and riverine sandbar habitats of the Upper Missouri River in 2006 and 2008. Highest catch rates of large invertebrates (>3 mm) on dry sand habitats occurred during 08:00-11:00 Central Daylight Time (CDT) on the reservoir and 08:00-14:00 CDT on the river. On wet sand habitats, catch rates were lowest during 17:00-20:00 on both the reservoir and the river. Catch rates decreased 24% for every 10 kph increase in wind. Sticky traps deployed continuously for 12 h or more had lower catch rates than four consecutive-composited 3-hour deployments, suggesting that trap effectiveness declined for >3-hour deployments. Thus, if sticky traps are used to index plover forage abundance without controlling for time of day and wind speed, data may be highly variable or estimates could be biased. 

Investigation of VOCs associated with different characteristics of breast cancer cells

PubMed Central

Lavra, Luca; Catini, Alexandro; Ulivieri, Alessandra; Capuano, Rosamaria; Baghernajad Salehi, Leila; Sciacchitano, Salvatore; Bartolazzi, Armando; Nardis, Sara; Paolesse, Roberto; Martinelli, Eugenio; Di Natale, Corrado

2015-01-01

The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems. On the other hand, in-vitro studies suggest that VOCs detection could also give important indications regarding molecular and tumorigenic characteristics of tumor cells. Aim of this study was to analyze VOCs in the headspace of breast cancer cell lines in order to ascertain the potentiality of VOCs signatures in giving information about these cells and set-up a new sensor system able to detect breast tumor-associated VOCs. We identified by Gas Chromatography-Mass Spectrometry analysis a VOCs signature that discriminates breast cancer cells for: i) transformed condition; ii) cell doubling time (CDT); iii) Estrogen and Progesterone Receptors (ER, PgR) expression, and HER2 overexpression. Moreover, the signals obtained from a temperature modulated metal oxide semiconductor gas sensor can be classified in order to recognize VOCs signatures associated with breast cancer cells, CDT and ER expression. Our results demonstrate that VOCs analysis could give clinically relevant information about proliferative and molecular features of breast cancer cells and pose the basis for the optimization of a low-cost diagnostic device to be used for tumors characterization. PMID:26304457

Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis

PubMed Central

Hua, Hui; Namdar, Mandana; Ganier, Olivier; Gregan, Juraj; Méchali, Marcel; Kearsey, Stephen E.

2013-01-01

Meiosis involves two successive rounds of chromosome segregation without an intervening S phase. Exit from meiosis I is distinct from mitotic exit, in that replication origins are not licensed by Mcm2-7 chromatin binding, but spindle disassembly occurs during a transient interphase-like state before meiosis II. The absence of licensing is assumed to explain the block to DNA replication, but this has not been formally tested. Here we attempt to subvert this block by expressing the licensing control factors Cdc18 and Cdt1 during the interval between meiotic nuclear divisions. Surprisingly, this leads only to a partial round of DNA replication, even when these factors are overexpressed and effect clear Mcm2-7 chromatin binding. Combining Cdc18 and Cdt1 expression with modulation of cyclin-dependent kinase activity, activation of Dbf4-dependent kinase, or deletion of the Spd1 inhibitor of ribonucleotide reductase has little additional effect on the extent of DNA replication. Single-molecule analysis indicates this partial round of replication results from inefficient progression of replication forks, and thus both initiation and elongation replication steps may be inhibited in late meiosis. In addition, DNA replication or damage during the meiosis I–II interval fails to arrest meiotic progress, suggesting absence of checkpoint regulation of meiosis II entry. PMID:23303250

Sensory Alterations in Patients with Isolated Idiopathic Dystonia: An Exploratory Quantitative Sensory Testing Analysis.

PubMed

Paracka, Lejla; Wegner, Florian; Blahak, Christian; Abdallat, Mahmoud; Saryyeva, Assel; Dressler, Dirk; Karst, Matthias; Krauss, Joachim K

2017-01-01

Abnormalities in the somatosensory system are increasingly being recognized in patients with dystonia. The aim of this study was to investigate whether sensory abnormalities are confined to the dystonic body segments or whether there is a wider involvement in patients with idiopathic dystonia. For this purpose, we recruited 20 patients, 8 had generalized, 5 had segmental dystonia with upper extremity involvement, and 7 had cervical dystonia. In total, there were 13 patients with upper extremity involvement. We used Quantitative Sensory Testing (QST) at the back of the hand in all patients and at the shoulder in patients with cervical dystonia. The main finding on the hand QST was impaired cold detection threshold (CDT), dynamic mechanical allodynia (DMA), and thermal sensory limen (TSL). The alterations were present on both hands, but more pronounced on the side more affected with dystonia. Patients with cervical dystonia showed a reduced CDT and hot detection threshold (HDT), enhanced TSL and DMA at the back of the hand, whereas the shoulder QST only revealed increased cold pain threshold and DMA. In summary, QST clearly shows distinct sensory abnormalities in patients with idiopathic dystonia, which may also manifest in body regions without evident dystonia. Further studies with larger groups of dystonia patients are needed to prove the consistency of these findings.

Balance, executive functions and falls in elderly with Alzheimer's disease (AD): a longitudinal study.

PubMed

Pedroso, Renata Valle; Coelho, Flávia Gomes de Melo; Santos-Galduróz, Ruth Ferreira; Costa, José Luiz Riani; Gobbi, Sebastião; Stella, Florindo

2012-01-01

Elderly individuals with AD are more susceptible to falls, which might be associated with decrements in their executive functions and balance, among other things. We aimed to analyze the effects of a program of dual task physical activity on falls, executive functions and balance of elderly individuals with AD. We studied 21 elderly with probable AD, allocated to two groups: the training group (TG), with 10 elderly who participated in a program of dual task physical activity; and the control group (CG), with 11 elderly who were not engaged in regular practice of physical activity. The Clock Drawing Test (CDT) and the Frontal Assessment Battery (FAB) were used in the assessment of the executive functions, while the Berg Balance Scale (BBS) and the Timed Up-and-Go (TUG)-test evaluated balance. The number of falls was obtained by means of a questionnaire. We observed a better performance of the TG as regards balance and executive functions. Moreover, the lower the number of steps in the TUG scale, the higher the scores in the CDT, and in the FAB. The practice of regular physical activity with dual task seems to have contributed to the maintenance and improvement of the motor and cognitive functions of the elderly with AD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A Study of Fire Hazards from Combustible Ammunition: Effects of Scale and Confinement

DTIC Science & Technology

1984-12-01

2268 171 02 Solna, Sweden Major Vincente Garcia Estado Major del Ejercito Division de Logistica Calle Prim. Madrid, Spain ...distance standards and classification test procedures for munition items in storage and transport with particular emphasis on items that present mainly...Operations 3 National Defence Headquarters 191 Colonel By Drive Ottawa, Ontario, Canada K1A 0K2 Cdt. P. Denecker Centre Logistique de la Force Terrestre

Clostridium difficile chimeric toxin receptor binding domain vaccine induced protection against different strains in active and passive challenge models.

PubMed

Tian, Jing-Hui; Glenn, Gregory; Flyer, David; Zhou, Bin; Liu, Ye; Sullivan, Eddie; Wu, Hua; Cummings, James F; Elllingsworth, Larry; Smith, Gale

2017-07-24

Clostridium difficile is the number one cause of nosocomial antibiotic-associated diarrhea in developed countries. Historically, pathogenesis was attributed two homologous glucosylating toxins, toxin-A (TcdA) and toxin-B (TcdB). Over the past decade, however, highly virulent epidemic strains of C. difficile (B1/NAP1/027) have emerged and are linked to an increase in morbidity and mortality. Increased virulence is attributed to multiple factors including: increased production of A- and B-toxins; production of binary toxin (CDT); and the emergence of more toxic TcdB variants (TcdB (027) ). TcdB (027) is more cytotoxicity to cells; causes greater tissue damage and toxicity in animals; and is antigenically distinct from historical TcdB (TcdB (003) ). Broadly protective vaccines and therapeutic antibody strategies, therefore, may target TcdA, TcdB variants and CDT. To facilitate the generation of multivalent toxin-based C. difficile vaccines and therapeutic antibodies, we have generated fusion proteins constructed from the receptor binding domains (RBD) of TcdA, TcdB (003) , TcdB (027) and CDT. Herein, we describe the development of a trivalent toxin (T-toxin) vaccine (CDTb/TcdB (003) /TcdA) and quadravalent toxin (Q-toxin) vaccine (CDTb/TcB (003) /TcdA/TcdB (027) ) fusion proteins that retain the protective toxin neutralizing epitopes. Active immunization of mice or hamsters with T-toxin or Q-toxin fusion protein vaccines elicited the generation of toxin neutralizing antibodies to each of the toxins. Hamsters immunized with the Q-toxin vaccine were broadly protected against spore challenge with historical C. difficile 630 (toxinotype 0/ribotype 003) and epidemic NAP1 (toxinotype III/ribotype 027) strains. Fully human polyclonal antitoxin IgG was produced by immunization of transgenic bovine with these fusion proteins. In passive transfer studies, mice were protected against lethal toxin challenge. Hamsters treated with human antitoxin IgG were completely protected when challenged with historical or epidemic strains of C. difficile. The use of chimeric fusion proteins is an attractive approach to producing multivalent antitoxin vaccines and therapeutic polyclonal antibodies for prevention and treatment of C. difficile infections (CDI). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Outcomes and predictors of failure of thrombolysis for iliofemoral deep venous thrombosis.

PubMed

Avgerinos, Efthymios D; Hager, Eric S; Naddaf, Abdallah; Dillavou, Ellen; Singh, Michael; Chaer, Rabih A

2015-01-01

Catheter-directed thrombolysis (CDT) with adjunctive mechanical techniques, when successful, is reported to alleviate symptoms of acute iliofemoral deep venous thrombosis (IFDVT) and to lower the occurrence of the post-thrombotic syndrome (PTS). This study aimed to determine longer term outcomes of catheter-based interventions for IFDVT and to identify predictors of immediate and mid-long-term failures that would guide optimal patient selection. Consecutive patients who underwent CDT or pharmacomechanical thrombolysis for IFDVT between May 2007 and March 2013 were identified from a prospectively maintained database. Assessment of predictors of immediate periprocedural failure was based on the degree of clot lysis (≤ 50% vs >50%) and 30-day recurrence of DVT. Long-term anatomic and clinical failures and outcomes were assessed by ultrasound imaging of the lysed segments and Villalta score (≥ 5 vs <5). Survival analysis was used to assess primary patency and PTS morbidity. Multivariate binary logistic and Cox regression models were used to determine predictors of anatomic and clinical failures. During the study period, 93 patients (118 limbs; mean age, 49.4 ± 16.2 years; 47 women) with symptoms averaging 11.1 ± 9.6 days in duration were treated with various combinations of CDT or pharmacomechanical thrombolysis; in 52 (56%), at least one iliocaval stent was deployed. Immediate treatment failure was seen in 11 patients (12%) predicted by the preoperative indication "phlegmasia" (odds ratio, 3.12; P = .042) and recent surgery (odds ratio, 19.6; P = .018). At a mean ultrasonographic follow-up of 16 ± 14 months (range, 1-65 months), six more patients sustained a rethrombosis, accounting for an overall 3-year primary patency of 72.1%. In the long-term model, loss of primary patency was associated with recent surgery (hazard ratio [HR], 4.04; P = .023), malignant disease (HR, 6.75; P = .016), and incomplete thrombolysis (≤ 50%) (HR, 5.83; P < .001). By stratification of PTS on the basis of postprocedure failures, at 2 years PTS occurred in 50.6% of patients and in 16.3% of patients without failure (P < .001). Thrombolysis for symptomatic IFDVT can achieve high rates of thrombus resolution and reduce long-term PTS morbidity on careful patient selection. Improved anatomic and clinical outcomes are associated with the completeness of thrombolysis. Copyright © 2015. Published by Elsevier Inc.

Usefulness of indirect alcohol biomarkers for predicting recidivism of drunk-driving among previously convicted drunk-driving offenders: results from the recidivism of alcohol-impaired driving (ROAD) study.

PubMed

Maenhout, Thomas M; Poll, Anneleen; Vermassen, Tijl; De Buyzere, Marc L; Delanghe, Joris R

2014-01-01

In several European countries, drivers under the influence (DUI), suspected of chronic alcohol abuse are referred for medical and psychological examination. This study (the ROAD study, or Recidivism Of Alcohol-impaired Driving) investigated the usefulness of indirect alcohol biomarkers for predicting drunk-driving recidivism in previously convicted drunk-driving offenders. The ROAD study is a prospective study (2009-13) that was performed on 517 randomly selected drivers in Belgium. They were convicted for drunk-driving for which their licence was confiscated. The initial post-arrest blood samples were collected and analysed for percentage carbohydrate-deficient transferrin (%CDT), transaminsase activities [alanine amino transferase (ALT), aspartate amino transferase (AST)], gamma-glutamyltransferase (γGT) and red cell mean corpuscular volume (MCV). The observation time for each driver was 3 years and dynamic. A logistic regression analysis revealed that ln(%CDT) (P < 0.001), ln(γGT) (P < 0.01) and ln(ALT) (P < 0.05) were the best biochemical predictors of recidivism of drunk-driving. The ROAD index (which includes ln(%CDT), ln(γGT), -ln(ALT) and the sex of the driver) was calculated and had a significantly higher area under the receiver operator characteristic curve (0.71) than the individual biomarkers for drunk-driving recidivism. Drivers with a high risk of recidivating (ROAD index ≥ 25%; third tertile) could be distinguished from drivers with an intermediate risk (16% ≤ ROAD index < 25%; second tertile; P < 0.001) and a low recidivism risk (ROAD index < 16%; first tertile; P < 0.05). Of all routinely used indirect alcohol markers, percentage of carbohydrate-deficient transferrin is the major predictor of recidivism of drunk-driving. The association with gamma-glutamyltransferase, alanine amino transferase and the sex of the driver could have additional value for identifying drunk-drivers at intermediate risk of recidivism. Non-specific indirect alcohol markers, such as alanine amino transferase, gamma-glutamyltransferase, aspartate amino transferase and red cell mean corpuscular volume have minimal added value to % carbohydrate-deficient transferrin for distinguishing drunk drivers with a low or high risk of recidivism. © 2013 Society for the Study of Addiction.

A Prognostic Modeling Approach for Predicting Recurring Maintenance for Shipboard Propulsion Systems

DTIC Science & Technology

2001-06-01

CIT CDT 1 CIP CDP η γ 1γ T T adb (1) Compressor fouling has also been shown to increase vibration , (Ozgur et al (2000) and Tsalavoutas et al) but... vibration increases and secondly is the poor reliability with which performance degradation severity may be assessed. In lieu of these practical...Industrial Gas Turbines” International Gas Turbine and Aeroengine Congress and Exposition, Belgium, June 1990 4. Kurtz, Rainer, Brun, Klaus, and

The Use of Tailored Testing with Instructional Programs.

DTIC Science & Technology

1986-03-01

AVAILABILITY OF REPORT Approved for public release: distribution un- t~X DWNCADNGSCHiEDULE li-mited. Reproduction in whole or in part is...of Education ,-’ Washington, DC 20V 0 Chicago, IL r06𔄁 Air Force Human Resources Lab Cdt. Arnold Bohrer . AFHRL/MPD Sectie Psychologisch Cnderzoek...University of Texas-Austin Univ-ir-tat Puss-ldorf Measurement and Evalu-,tion Er zi, gswi ssensch;ftl iches Cpnter Un ivf rsit ’tsst r. 1 Austin, TX 787

Krikalev dismantles probe-and-cone docking mechanism (StM) in the Progress M-53 (18P)

NASA Image and Video Library

2005-06-19

ISS011-E-09204 (19 June 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, dismantles the probe-and-cone docking mechanism in the Progress 18 spacecraft. The Progress docked to the aft port of the Zvezda Service Module of the International Space Station (ISS) at 7:42 p.m. (CDT) as the Station flew approximately 225 statute miles, above a point near Beijing, China.

New Functional Device using Bio Nano Process

DTIC Science & Technology

2011-09-20

anticipated that acid treatment of CNTs would reduce the electronic properties.2 In contrast, Pender et al. created a bifunctional peptide aptamer that has...of amino acids . Here we report that a novel bifunctional cage-shaped protein able to fabricate a SWNT-titanium nanocompound containing nano-porous...nanostructures.6-7 Two peptide aptamers, NHBP-1 (DYFSSPYYEQLF)8 and minTBP-1 (RKLPDA)9 were genetically fused at the Fig. 1 (a) Amino acid sequence of CDT1. The

Lonchakov ingresses the Earth-facing port of the SM after arrival of the Soyuz TMA-13 Spacecraft

NASA Image and Video Library

2008-10-14

ISS017-E-019022 (14 Oct. 2008) --- Russian Federal Space Agency cosmonaut Yury Lonchakov, Expedition 18 flight engineer, ingresses the Earth-facing port of the International Space Station's Zarya module after arriving onboard the Soyuz TMA-13 spacecraft with NASA astronaut Michael Fincke, commander, and American spaceflight participant Richard Garriott (both out of frame). Hatches between the two spacecraft were opened at 4:55 a.m. (CDT).

FAA Response to User Concensus Views and Recommendations: New Engineering and Development Initiatives - Policy and Technology Choices.

DTIC Science & Technology

1979-12-01

Increased Automation 52 35. ATC Responsibility for Weather Avoidance 53 36. Additional Simulation Needed - ATARS , BCAS, CDTI 53 37. Safety Impacts of...Address Beacon System (DABS)/Data Link, Automated Traffic Advisory and Resolution Service ( ATARS ) and Cockpit Display of Terminal Information (CDT[), are...should not consider down- linking of air derived data either to enhance ATARS or to be the basis for more closely spaced IFR approaches to parallel

The Fast-spectrum Transmutation Experimental Facility FASTEF: Main design achievements (part 2: Reactor building design and plant layout) within the FP7-CDT collaborative project of the European Commission

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

De Bruyn, D.; Engelen, J.; Ortega, A.

MYRRHA (Multi-purpose hybrid Research Reactor for High-tech Applications) is the flexible experimental accelerator-driven system (ADS) in development at SCK-CEN in replacement of its material testing reactor BR2. SCK-CEN in association with 17 European partners from industry, research centres and academia, responded to the FP7 (Seventh Framework Programme) call from the European Commission to establish a Central Design Team (CDT) for the design of a Fast Spectrum Transmutation Experimental Facility (FASTEF) able to demonstrate efficient transmutation and associated technology through a system working in subcritical and/or critical mode. The project has started on April 01, 2009 for a period of threemore » years. In this paper, we present the latest concept of the reactor building and the plant layout. The FASTEF facility has evolved quite a lot since the intermediate reporting done at the ICAPP'10 and ICAPP'11 conferences 1,2. Many iterations have been performed to take into account the safety requirements. The present configuration enables an easy operation and maintenance of the facility, including the possibility to change large components of the reactor. In a companion paper 3, we present the latest configuration of the reactor core and primary system. (authors)« less

MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.

PubMed

Evans, Debra L; Zhang, Haoxing; Ham, Hyoungjun; Pei, Huadong; Lee, SeungBaek; Kim, JungJin; Billadeau, Daniel D; Lou, Zhenkun

2016-01-01

The timely and precise duplication of cellular DNA is essential for maintaining genome integrity and is thus tightly-regulated. During mitosis and G1, the Origin Recognition Complex (ORC) binds to future replication origins, coordinating with multiple factors to load the minichromosome maintenance (MCM) complex onto future replication origins as part of the pre-replication complex (pre-RC). The pre-RC machinery, in turn, remains inactive until the subsequent S phase when it is required for replication fork formation, thereby initiating DNA replication. Multiple myeloma SET domain-containing protein (MMSET, a.k.a. WHSC1, NSD2) is a histone methyltransferase that is frequently overexpressed in aggressive cancers and is essential for normal human development. Several studies have suggested a role for MMSET in cell-cycle regulation; however, whether MMSET is itself regulated during cell-cycle progression has not been examined. In this study, we report that MMSET is degraded during S phase in a cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) and proteasome-dependent manner. Notably, we also report defects in DNA replication and a decreased association of pre-RC factors with chromatin in MMSET-depleted cells. Taken together, our results suggest a dynamic regulation of MMSET levels throughout the cell cycle, and further characterize the role of MMSET in DNA replication and cell-cycle progression.

Two Geminin homologs regulate DNA replication in silkworm, Bombyx mori.

PubMed

Tang, Xiao-Fang; Chen, Xiang-Yun; Zhang, Chun-Dong; Li, Yao-Feng; Liu, Tai-Hang; Zhou, Xiao-Lin; Wang, La; Zhang, Qian; Chen, Peng; Lu, Cheng; Pan, Min-Hui

2017-05-03

DNA replication is rigorously controlled in cells to ensure that the genome duplicates exactly once per cell cycle. Geminin is a small nucleoprotein, which prevents DNA rereplication by directly binding to and inhibiting the DNA replication licensing factor, Cdt1. In this study, we have identified 2 Geminin genes, BmGeminin1 and BmGeminn2, in silkworm, Bombyx mori. These genes contain the Geminin conserved coiled-coil domain and are periodically localized in the nucleus during the S-G2 phase but are degraded at anaphase in mitosis. Both BmGeminin1 and BmGeminin2 are able to homodimerize and interact with BmCdt1 in cells. In addition, BmGeminin1 and BmGeminin2 can interact with each other. Overexpression of BmGeminin1 affects cell cycle progression: cell cycle is arrested in S phase, and RNA interference of BmGeminin1 leads to rereplication. In contrast, overexpression or knockdown of BmGeminin2 with RNAi did not significantly affect cell cycle, while more rereplication occurred when BmGeminin1 and BmGeminin2 together were knocked down in cells than when only BmGeminin1 was knocked down. These data suggest that both BmGeminin1 and BmGeminin2 are involved in the regulation of DNA replication. These findings provide insight into the function of Geminin and contribute to our understanding of the regulation mechanism of cell cycle in silkworm.

Remnants of an ancient pathway to L-phenylalanine and L-tyrosine in enteric bacteria: Evolutionary implications and biotechnological impact. [Escherichia coli; Salmonella typhimurium; Neurospora crassa

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

Bonner, C.A.; Fischer, R.S.; Ahmad, S.

The pathway construction for biosynthesis of aromatic amino acids in Escherichia coli is atypical of the phylogenetic subdivision of gram-negative bacteria to which it belongs. Related organisms possess second pathways to phenylalanine and tyrosine which depend upon the expression of a monofunctional chorismate mutase (CM-F) and cyclohexadienyl dehydratase (CDT). Some enteric bacteria, unlike E. coli, possess either CM-F or CDT. These essentially cryptic remnants of an ancestral pathway can be a latent source of biochemical potential under certain conditions. As one example of advantageous biochemical potential, the presence of CM-F in Salmonella typhimurium increases the capacity for prephenate accumulation inmore » a tyrA auxotroph. We report the finding that a significant fraction of the latter prephenate is transaminated to L-arogenate. The tyrA19 mutant is now the organism of choice for isolation of L-arogenate, uncomplicated by the presence of other cyclohexadienyl products coaccumulated by a Neurospora crassa mutant that had previously served as the prime biological source of L-arogenate. Prephenate aminotransferase activity was not conferred by a discrete enzyme, but rather was found to be synonymous with the combined activities of aspartate aminotransferase (aspC), aromatic aminotransferase (tyrB), and branched-chain aminotransferase (ilvE).« less

Evaluation of a new computerized psychometric test battery: Effects of zolpidem and caffeine.

PubMed

Pilli, Raveendranadh; Naidu, Mur; Pingali, Usharani; Shobha, Jc

2013-10-01

To evaluate the effects of centrally active drugs using a new indigenously developed automated psychometric test system and compare the results with that obtained using pencil- and paper-based techniques. The tests were standardized in 24 healthy participants. Reproducibility of the test procedure was evaluated by performing the tests by a single experimenter on two occasions (interday reproducibility). To evaluate the sensitivity of the tests, the effects of zolpidem (5 mg) and caffeine (500 mg) versus placebo were studied in 24 healthy participants in a randomized, double-blind three-way crossover design. Psychometric tests were performed at baseline and at 1, 2, and 3 h after administration of study medication. The effects of zolpidem and caffeine on the psychomotor performance were most pronounced 1 h after administration. At this time, a significant impairment of performance in the simple reaction test (SRT), choice discrimination test (CDT), digit symbol substitution test (DSST), digit vigilance test (DVT), and card sorting test (CST) was observed with zolpidem. In contrast, caffeine showed a significant improvement in performance in CDT and DVT only. The results suggest that the tests of the computerized system are more sensitive and reliable then the pencil and paper tests in detecting the effects of central acting agents and are suitable for use in clinical areas to conduct studies with patients.

Geology, S-Pb isotopes, and 40Ar/39Ar geochronology of the Zhaxikang Sb-Pb-Zn-Ag deposit in Southern Tibet: implications for multiple mineralization events at Zhaxikang

NASA Astrophysics Data System (ADS)

Sun, Xiang; Zheng, Youye; Pirajno, Franco; McCuaig, T. Campbell; Yu, Miao; Xia, Shenlan; Song, Qingjie; Chang, Huifang

2018-03-01

Several Au, Sb, Sb-Au, Pb-Zn, and Sb-Pb-Zn-Ag deposits are present throughout the North Himalaya in southern Tibet, China. The largest Sb-Pb-Zn-Ag deposit is Zhaxikang (18 Mt at 0.6 wt% Sb, 2.0 wt% Pb, 3.5 wt% Zn, and 78 g/t Ag). Zhaxikang veins are hosted within N-S trending faults, which crosscut the Early-Middle Jurassic Ridang Formation consisting of shale interbedded with sandstone and limestone deposited on a passive continental margin. Ore paragenesis indicates that Zhaxikang mineralization occurred in two main phases composed of six total stages. The initial phase was characterized by assemblages of fine-grained Mn-Fe carbonate + arsenopyrite + pyrite + sphalerite (stage 1), followed by relatively coarse-grained Mn-Fe carbonate + Fe-rich sphalerite + galena + pyrite (stage 2). The second phase was marked by assemblages of quartz + pyrite + Fe-poor sphalerite and Ag-rich galena + tetrahedrite + sericite (stage 3), quartz + Sb-Pb sulfosalt minerals mainly composed of boulangerite and jamesonite (stage 4), quartz + stibnite ± cinnabar (stage 5), and quartz ± calcite (stage 6). Sulfides of stage 2 have δ34SV-CDT of 8.4-12.0‰, 206Pb/204Pb ratios of 19.648 to 19.659, 207Pb/204Pb ratios of 15.788 to 15.812, and 208Pb/204Pb ratios of 40.035 to 40.153. Sulfides of stage 3 have similar δ34SV-CDT of 6.1-11.2‰ and relatively more radiogenic lead isotopes (206Pb/204Pb = 19.683-19.792). Stage 4 Sb-Pb sulfosalt minerals have δ34SV-CDT of 5.0-7.2‰ and even more radiogenic lead (206Pb/204Pb = 19.811-19.981). By contrast, stibnite of stage 5 has δ34SV-CDT of 4.5-7.8‰ and less radiogenic lead (206Pb/204Pb = 18.880-18.974). Taken together with the geological observations that the Pb-Zn-bearing Mn-Fe carbonate veins were crosscut by various types of quartz veins, sphalerite and galena of stage 2 underwent dissolution and remobilization, and that Sb-Pb(-Fe) sulfosalts formed at the expense of Pb from stage 2 galena and of Fe from stage 2 sphalerite, we argue that the early Pb-Zn veins were overprinted by later Sb-rich fluids. Stage 2 fluids were likely acidic and oxidized and leached lead from high-grade metamorphic rocks of the Greater Himalayan crystalline complex (GHC) and sulfur from reduced rocks, such as slate of the Ridang Formation, along N-S trending faults, leading to precipitation of Pb-Zn sulfides and Mn-Fe carbonate and formation of solution collapse breccias. Later Sb-rich fluids leached Pb from the GHC and the pre-existing sulfides and deposited Fe-poor sphalerite, Ag-rich galena, tetrahedrite, Sb-Pb sulfosalts, and stibnite in quartz veins that cut pre-existing Pb-Zn-bearing Mn-Fe carbonate veins. The Sb-rich fluids also likely leached Pb from Early Cretaceous gabbro and formed stibnite at shallow levels where early Pb-Zn-bearing Mn-Fe carbonate veins are absent. A sericite 40Ar-39Ar plateau age of 17.9 ± 0.5 Ma from stage 3 veins represents the timing of the onset of stage 3 mineralization.

False Position, Double False Position and Cramer's Rule

ERIC Educational Resources Information Center

Boman, Eugene

2009-01-01

We state and prove the methods of False Position (Regula Falsa) and Double False Position (Regula Duorum Falsorum). The history of both is traced from ancient Egypt and China through the work of Fibonacci, ending with a connection between Double False Position and Cramer's Rule.

Toward a Neuroscience of Adult Cognitive Developmental Theory.

PubMed

Girgis, Fady; Lee, Darrin J; Goodarzi, Amir; Ditterich, Jochen

2018-01-01

Piaget's genetic epistemology has provided the constructivist approach upon which child developmental theories were founded, in that infants are thought to progress through distinct cognitive stages until they reach maturity in their early 20's. However, it is now well established that cognition continues to develop after early adulthood, and several "neo-Piagetian" theories have emerged in an attempt to better characterize adult cognitive development. For example, Kegan's Constructive Developmental Theory (CDT) argues that the thought processes used by adults to construct their reality change over time, and reaching higher stages of cognitive development entails becoming objectively aware of emotions and beliefs that were previously in the realm of the subconscious. In recent years, neuroscience has shown a growing interest in the biological substrates and neural mechanisms encompassing adult cognitive development, because psychological and psychiatric disorders can arise from deficiencies therein. In this article, we will use Kegan's CDT as a framework to discuss adult cognitive development in relation to closely correlated existing constructs underlying social processing, such as the perception of self and others. We will review the functional imaging and electrophysiologic evidence behind two key concepts relating to these posited developmental changes. These include self-related processing, a field that distinguishes between having conscious experiences ("being a self") and being aware of oneself having conscious experiences ("being aware of being a self"); and theory of mind, which is the objective awareness of possessing mental states such as beliefs and desires (i.e., having a "mind") and the understanding that others possess mental states that can be different from one's own. We shall see that cortical midline structures, including the medial prefrontal cortex and cingulate gyrus, as well as the temporal lobe, are associated with psychological tasks that test these models. In addition, we will review computational modeling approaches to cognitive development, and show how mathematical modeling can provide insights into how sometimes continuous changes in the neural processing substrate can give rise to relatively discrete developmental stages. Because deficiencies in adult cognitive development can result in disorders such as autism and depression, bridging the gaps between developmental psychology, neuroscience, and modeling has potential implications for clinical practice. As neuromodulation techniques such as deep brain and transcranial stimulation continue to advance, interfacing with these systems may lead to the emergence of novel investigational methods and therapeutic strategies in adults suffering from developmental disorders.

Cost-effectiveness of an autoantibody test (EarlyCDT-Lung) as an aid to early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules.

PubMed

Edelsberg, John; Weycker, Derek; Atwood, Mark; Hamilton-Fairley, Geoffrey; Jett, James R

2018-01-01

Patients who have incidentally detected pulmonary nodules and an estimated intermediate risk (5-60%) of lung cancer frequently are followed via computed tomography (CT) surveillance to detect nodule growth, despite guidelines for a more aggressive diagnostic strategy. We examined the cost-effectiveness of an autoantibody test (AABT)-Early Cancer Detection Test-Lung (EarlyCDT-LungTM)-as an aid to early diagnosis of lung cancer among such patients. We developed a decision-analytic model to evaluate use of the AABT versus CT surveillance alone. In the model, patients with a positive AABT-because they are at substantially enhanced risk of lung cancer-are assumed to go directly to biopsy, resulting in diagnosis of lung cancer in earlier stages than under current guidelines (a beneficial stage shift). Patients with a negative AABT, and those scheduled for CT surveillance alone, are assumed to have periodic CT screenings to detect rapid growth and thus to have their lung cancers diagnosed-on average-at more advanced stages. Among 1,000 patients who have incidentally detected nodules 8-30 mm, have an intermediate-risk of lung cancer, and are evaluated by CT surveillance alone, 95 (9.5%) are assumed to have lung cancer (local, 73.6%; regional, 22.0%; distant, 4.4%). With use of the AABT set at a sensitivity/specificity of 41%/93% (stage shift = 10.8%), although expected costs would be higher by $949,442 ($949 per person), life years would be higher by 53 (0.05 per person), resulting in a cost per life-year gained of $18,029 and a cost per quality-adjusted life year (QALY) gained of $24,330. With use of the AABT set at a sensitivity/specificity of 28%/98% (stage shift = 7.4%), corresponding cost-effectiveness ratios would be $18,454 and $24,833. Under our base-case assumptions, and reasonable variations thereof, using AABT as an aid in the early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules who are estimated to be at intermediate risk of lung cancer and are scheduled for CT surveillance alone is likely to be a cost-effective use of healthcare resources.

Deployment of the Telstar communications satellite

NASA Image and Video Library

1984-08-30

41D-37-050 (1 Sept 1984) --- Telstar, the third of three satellites to be placed into space via the Earth-orbiting Discovery, departs from the cargo bay of the manned vehicle during 41-D's third day in space. The scene was photographed at 9:35 a.m. (CDT), Sept. 1, 1984, with a 70mm handheld hasselblad camera aimed through the windows on the flight deck. Heavy clouds cover much of the water and land mass of Earth in the background.

Text to Speech (TTS) Capabilities for the Common Driver Trainer (CDT)

DTIC Science & Technology

2010-10-01

harnessing in’leigle jalClpeno jocelyn linu ~ los angeles lottery margarine mathematlze mathematized mathematized meme memes memol...including Julie, Kate, and Paul . Based upon the names of the voices, it may be that the VoiceText capability is the technology being used currently on...DFTTSExportToFileEx(O, " Paul ", 1, 1033, "Testing the Digital Future Text-to-Speech SDK.", -1, -1, -1, -1, -1, DFTTS_ TEXT_ TYPE_ XML, "test.wav", 0, "", -1

Special Technology Area Review on Displays. Report of Department of Defense Advisory Group on Electron Devices Working Group C (Electro-Optics)

DTIC Science & Technology

2004-03-01

mirror device ( DMD ) for C4ISR applications, the IBM 9.2 megapixel 22-in. diagonal active matrix liquid crystal display (AMLCD) monitor for data...FED, VFD, OLED and a variety of microdisplays (uD, comprising uLCD, uOLED, DMD and other MEMs) (see glossary). 3 CDT = cathode display tubes (used in...than SVGA, greater battery life and brightness, decreased weight and thickness, electromagnetic interference (EMI), and development of video

Phillips with probe-and-cone docking mechanism (StM) in the Zvezda module

NASA Image and Video Library

2005-06-19

ISS011-E-09205 (19 June 2005) --- Astronaut John L. Phillips, Expedition 11 NASA ISS science officer and flight engineer, works on the dismantled probe-and-cone docking mechanism from the Progress 18 spacecraft in the Zvezda Service Module of the International Space Station (ISS). The Progress docked to the aft port of the Service Module at 7:42 p.m. (CDT) as the two spacecraft flew approximately 225 statute miles, above a point near Beijing, China.

Krikalev with probe-and-cone docking mechanism (StM) in the Zvezda module

NASA Image and Video Library

2005-06-19

ISS011-E-09210 (19 June 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, holds the dismantled probe-and-cone docking mechanism from the Progress 18 spacecraft in the Zvezda Service Module of the International Space Station (ISS). The Progress docked to the aft port of the Service Module at 7:42 p.m. (CDT) as the two spacecraft flew approximately 225 statute miles, above a point near Beijing, China.

How Alterations in the Cdt1 Expression Lead to Gene Amplification in Breast Cancer

DTIC Science & Technology

2011-07-01

absence of extrinsic DNA damage. We measured the TLS activity by measuring the mutation frequency in a supF gene (in a shuttle vector) subjected to UV...induced DNA damage before its introduction into the cells. Error-prone TLS activity will mutate the supF gene , which is scored by a blue-white colony...Figure 4A). Sequencing of the mutant supF genes , revealed a mutation spectrum consistent with error prone TLS (Supplemental Table 1). Significantly

Expedition 17 Automated Transfer Vehicle (ATV) Undocking

NASA Image and Video Library

2008-09-05

ISS017-E-015468 (5 Sept. 2008) --- Backdropped by the blackness of space, European Space Agency's (ESA) "Jules Verne" Automated Transfer Vehicle (ATV) begins its relative separation from the International Space Station. The ATV undocked from the aft port of the Zvezda Service Module at 4:29 p.m. (CDT) on Sept. 5, 2008 and was placed in a parking orbit for three weeks, scheduled to be deorbited on Sept. 29 when lighting conditions are correct for an ESA imagery experiment of reentry.

Expedition 17 Automated Transfer Vehicle (ATV) Undocking

NASA Image and Video Library

2008-09-05

ISS017-E-015496 (5 Sept. 2008) --- Backdropped by a blanket of clouds, European Space Agency's (ESA) "Jules Verne" Automated Transfer Vehicle (ATV) continues its relative separation from the International Space Station. The ATV undocked from the aft port of the Zvezda Service Module at 4:29 p.m. (CDT) on Sept. 5, 2008 and was placed in a parking orbit for three weeks, scheduled to be deorbited on Sept. 29 when lighting conditions are correct for an ESA imagery experiment of reentry.

Expedition 17 Automated Transfer Vehicle (ATV) Undocking

NASA Image and Video Library

2008-09-05

ISS017-E-015451 (5 Sept. 2008) --- Backdropped by Earth's horizon and the blackness of space, European Space Agency's (ESA) "Jules Verne" Automated Transfer Vehicle (ATV) begins its relative separation from the International Space Station. The ATV undocked from the aft port of the Zvezda Service Module at 4:29 p.m. (CDT) on Sept. 5, 2008 and was placed in a parking orbit for three weeks, scheduled to be deorbited on Sept. 29 when lighting conditions are correct for an ESA imagery experiment of reentry.

Expedition 17 Automated Transfer Vehicle (ATV) Undocking

NASA Image and Video Library

2008-09-05

ISS017-E-015446 (5 Sept. 2008) --- Backdropped by the blackness of space, European Space Agency's (ESA) "Jules Verne" Automated Transfer Vehicle (ATV) begins its relative separation from the International Space Station. The ATV undocked from the aft port of the Zvezda Service Module at 4:29 p.m. (CDT) on Sept. 5, 2008 and was placed in a parking orbit for three weeks, scheduled to be deorbited on Sept. 29 when lighting conditions are correct for an ESA imagery experiment of reentry.

Interfacing Computer-Assisted Drafting and Design with the Building Loads Analysis and System Thermodynamics (BLAST) Program

DTIC Science & Technology

1992-10-01

Manual CI APPENDIX D: Drawing Navigator Field Test D1 DISTRIBUTION Accesion For NTIS CRA&I OTIC TAB Unannouncea JustiteCdtOn By Distribution I "".i•I...methods replace manual methods, the automation will handle the data for the designer, thus reducing error and increasing throughput. However, the two...actively move data from one automation tool (CADD) to the other (the analysis program). This intervention involves a manual rekeying of data already in

Telemetry Standards, Part 1

DTIC Science & Technology

2015-07-01

IMAGE FRAME RATE (R-x\\ IFR -n) PRE-TRIGGER FRAMES (R-x\\PTG-n) TOTAL FRAMES (R-x\\TOTF-n) EXPOSURE TIME (R-x\\EXP-n) SENSOR ROTATION (R-x...0” (Single frame). “1” (Multi-frame). “2” (Continuous). Allowed when: When R\\CDT is “IMGIN” IMAGE FRAME RATE R-x\\ IFR -n R/R Ch 10 Status: RO...the settings that the user wishes to modify. Return Value The impact : A partial IHAL <configuration> element containing only the new settings for

UCSF Protocol for Caries Arrest Using Silver Diamine Fluoride: Rationale, Indications, and Consent

PubMed Central

Horst, Jeremy A; Ellenikiotis, Hellene; Milgrom, Peter M

2016-01-01

The Food and Drug Administration recently cleared silver diamine fluoride for reducing tooth sensitivity. Clinical trials document arrest and prevention of dental caries by silver diamine fluoride; this off-label use is now permissible and appropriate under U.S. law. A CDT code was approved for caries arresting medicaments for 2016 to facilitate documentation and billing. We present a systematic review, clinical indications, clinical protocol, and consent procedure to guide application for caries arrest treatment. PMID:26897901

Performance Evaluation of a Database System in a Multiple Backend Configurations,

DTIC Science & Technology

1984-10-01

leaving a systemn process , the * internal performance measuremnents of MMSD have been carried out. Mathodo lo.- gies for constructing test databases...access d i rectory data via the AT, EDIT, and CDT. In designing the test database, one of the key concepts is the choice of the directory attributes in...internal timing. These requests are selected since they retrieve the seIaI lest portion of the test database and the processing time for each request is

MCC Guest Viewing Program of Pope Benedict XVI's call to the ISS/STS-134 crew.

NASA Image and Video Library

2011-05-21

JSC2011-E-046602 (21 May 2011) --- A group of guests in the viewing room of the Mission Control Center at NASA?s Johnson Space Center are pictured during a special call from Pope Benedict XVI (visible on the monitors) to the STS-134 and Expedition 27 crews on the International Space Station. The event was conducted from The Vatican at 6:11 a.m. (CDT) on May 21, 2011, and aired live on NASA television. Photo credit: NASA

Soyuz TMA-06M/32S launch

NASA Image and Video Library

2012-10-23

ISS033-E-015399 (23 Oct. 2012) --- This view of Earth’s horizon, shows smoke trails from the launch of the Soyuz TMA-06M spacecraft, was photographed by an Expedition 33 crew member on the International Space Station. The Soyuz, with Expedition 33 crew members Soyuz Commander Oleg Novitskiy, Flight Engineer Kevin Ford of NASA, and Flight Engineer Evgeny Tarelkin of Roscosmos onboard, launched at 4:51 p.m. Kazakhstan time (5:51 a.m. CDT) on Oct. 23, 2012, from Baikonur, Kazakhstan.

Soyuz TMA-06M/32S launch

NASA Image and Video Library

2012-10-23

ISS033-E-015386 (23 Oct. 2012) --- This view of Earth’s horizon, shows smoke trails from the launch of the Soyuz TMA-06M spacecraft, was photographed by an Expedition 33 crew member on the International Space Station. The Soyuz, with Expedition 33 crew members Soyuz Commander Oleg Novitskiy, Flight Engineer Kevin Ford of NASA, and Flight Engineer Evgeny Tarelkin of Roscosmos onboard, launched at 4:51 p.m. Kazakhstan time (5:51 a.m. CDT) on Oct. 23, 2012, from Baikonur, Kazakhstan.

Soyuz TMA-06M/32S launch

NASA Image and Video Library

2012-10-23

ISS033-E-015394 (23 Oct. 2012) --- This view of Earth’s horizon, shows smoke trails from the launch of the Soyuz TMA-06M spacecraft, was photographed by an Expedition 33 crew member on the International Space Station. The Soyuz, with Expedition 33 crew members Soyuz Commander Oleg Novitskiy, Flight Engineer Kevin Ford of NASA, and Flight Engineer Evgeny Tarelkin of Roscosmos onboard, launched at 4:51 p.m. Kazakhstan time (5:51 a.m. CDT) on Oct. 23, 2012, from Baikonur, Kazakhstan.

Progress 23 supply vehicle approach

NASA Image and Video Library

2006-10-26

ISS014-E-06544 (26 Oct. 2006) --- Backdropped by a blue and white Earth, an unpiloted Progress supply vehicle approaches the International Space Station. Progress docked to the aft port of the Zvezda Service Module at 9:29 a.m. (CDT) on Oct. 26. The spacecraft used the automated Kurs system to dock at the aft port of the Zvezda service module. Expedition 14 flight engineer Mikhail Tyurin stood by at the manual Toru docking system controls, but the automated system functioned as designed and manual intervention was not needed.

Recovery - Apollo 10

NASA Image and Video Library

1969-05-26

S69-36593 (26 May 1969) --- The Apollo 10 astronauts Thomas P. Stafford (center), John W. Young (left) and Eugene A. Cernan (waving) are greeted by Donald E. Stullken (lower left) of the Manned Space Center's (MSC) recovery operations team. The Apollo 10 crew splashed down in the South Pacific recovery area to conclude a successful eight-day lunar orbit mission. Splashdown occurred at 11:53 a.m. (CDT), May 26, 1969, about 400 miles east of American Samoa and about four miles from the prime recovery ship, USS Princeton.

Occupancy models for data with false positive and false negative errors and heterogeneity across sites and surveys

Treesearch

Paige F.B. Ferguson; Michael J. Conroy; Jeffrey Hepinstall-Cymerman; Nigel Yoccoz

2015-01-01

False positive detections, such as species misidentifications, occur in ecological data, although many models do not account for them. Consequently, these models are expected to generate biased inference.The main challenge in an analysis of data with false positives is to distinguish false positive and false negative...

A complete solution of cartographic displacement based on elastic beams model and Delaunay triangulation

NASA Astrophysics Data System (ADS)

Liu, Y.; Guo, Q.; Sun, Y.

2014-04-01

In map production and generalization, it is inevitable to arise some spatial conflicts, but the detection and resolution of these spatial conflicts still requires manual operation. It is become a bottleneck hindering the development of automated cartographic generalization. Displacement is the most useful contextual operator that is often used for resolving the conflicts arising between two or more map objects. Automated generalization researches have reported many approaches of displacement including sequential approaches and optimization approaches. As an excellent optimization approach on the basis of energy minimization principles, elastic beams model has been used in resolving displacement problem of roads and buildings for several times. However, to realize a complete displacement solution, techniques of conflict detection and spatial context analysis should be also take into consideration. So we proposed a complete solution of displacement based on the combined use of elastic beams model and constrained Delaunay triangulation (CDT) in this paper. The solution designed as a cyclic and iterative process containing two phases: detection phase and displacement phase. In detection phase, CDT of map is use to detect proximity conflicts, identify spatial relationships and structures, and construct auxiliary structure, so as to support the displacement phase on the basis of elastic beams. In addition, for the improvements of displacement algorithm, a method for adaptive parameters setting and a new iterative strategy are put forward. Finally, we implemented our solution on a testing map generalization platform, and successfully tested it against 2 hand-generated test datasets of roads and buildings respectively.

Short communication: Conversion of lactose and whey into lactic acid by engineered yeast.

PubMed

Turner, Timothy L; Kim, Eunbee; Hwang, ChangHoon; Zhang, Guo-Chang; Liu, Jing-Jing; Jin, Yong-Su

2017-01-01

Lactose is often considered an unwanted and wasted byproduct, particularly lactose trapped in acid whey from yogurt production. But using specialized microbial fermentation, the surplus wasted acid whey could be converted into value-added chemicals. The baker's yeast Saccharomyces cerevisiae, which is commonly used for industrial fermentation, cannot natively ferment lactose. The present study describes how an engineered S. cerevisiae yeast was constructed to produce lactic acid from purified lactose, whey, or dairy milk. Lactic acid is an excellent proof-of-concept chemical to produce from lactose, because lactic acid has many food, pharmaceutical, and industrial uses, and over 250,000 t are produced for industrial use annually. To ferment the milk sugar lactose, a cellodextrin transporter (CDT-1, which also transports lactose) and a β-glucosidase (GH1-1, which also acts as a β-galactosidase) from Neurospora crassa were expressed in a S. cerevisiae strain. A heterologous lactate dehydrogenase (encoded by ldhA) from the fungus Rhizopus oryzae was integrated into the CDT-1/GH1-1-expressing strain of S. cerevisiae. As a result, the engineered strain was able to produce lactic acid from purified lactose, whey, and store-bought milk. A lactic acid yield of 0.358g/g of lactose was achieved from whey fermentation, providing an initial proof of concept for the production of value-added chemicals from excess industrial whey using engineered yeast. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Two Geminin homologs regulate DNA replication in silkworm, Bombyx mori

PubMed Central

Tang, Xiao-Fang; Chen, Xiang-Yun; Zhang, Chun-Dong; Li, Yao-Feng; Liu, Tai-Hang; Zhou, Xiao-Lin; Wang, La; Zhang, Qian; Chen, Peng; Lu, Cheng; Pan, Min-Hui

2017-01-01

ABSTRACT DNA replication is rigorously controlled in cells to ensure that the genome duplicates exactly once per cell cycle. Geminin is a small nucleoprotein, which prevents DNA rereplication by directly binding to and inhibiting the DNA replication licensing factor, Cdt1. In this study, we have identified 2 Geminin genes, BmGeminin1 and BmGeminn2, in silkworm, Bombyx mori. These genes contain the Geminin conserved coiled-coil domain and are periodically localized in the nucleus during the S-G2 phase but are degraded at anaphase in mitosis. Both BmGeminin1 and BmGeminin2 are able to homodimerize and interact with BmCdt1 in cells. In addition, BmGeminin1 and BmGeminin2 can interact with each other. Overexpression of BmGeminin1 affects cell cycle progression: cell cycle is arrested in S phase, and RNA interference of BmGeminin1 leads to rereplication. In contrast, overexpression or knockdown of BmGeminin2 with RNAi did not significantly affect cell cycle, while more rereplication occurred when BmGeminin1 and BmGeminin2 together were knocked down in cells than when only BmGeminin1 was knocked down. These data suggest that both BmGeminin1 and BmGeminin2 are involved in the regulation of DNA replication. These findings provide insight into the function of Geminin and contribute to our understanding of the regulation mechanism of cell cycle in silkworm. PMID:28379781

Regional Epidemiologic Assessment of Prevalent Periodontitis Using an Electronic Health Record System

PubMed Central

Acharya, Amit; VanWormer, Jeffrey J.; Waring, Stephen C.; Miller, Aaron W.; Fuehrer, Jay T.; Nycz, Gregory R.

2013-01-01

An oral health surveillance platform that queries a clinical/administrative data warehouse was applied to estimate regional prevalence of periodontitis. Cross-sectional analysis of electronic health record data collected between January 1, 2006, and December 31, 2010, was undertaken in a population sample residing in Ladysmith, Wisconsin. Eligibility criteria included: 1) residence in defined zip codes, 2) age 25–64 years, and 3) ≥1 Marshfield dental clinic comprehensive examination. Prevalence was established using 2 independent methods: 1) via an algorithm that considered clinical attachment loss and probe depth and 2) via standardized Current Dental Terminology (CDT) codes related to periodontal treatment. Prevalence estimates were age-standardized to 2000 US Census estimates. Inclusion criteria were met by 2,056 persons. On the basis of the American Academy of Periodontology/Centers for Disease Control and Prevention method, the age-standardized prevalence of moderate or severe periodontitis (combined) was 407 per 1,000 males and 308 per 1,000 females (348/1,000 males and 269/1,000 females using the CDT code method). Increased prevalence and severity of periodontitis was noted with increasing age. Local prevalence of periodontitis was consistent with national estimates. The need to address potential sample selection bias in future electronic health record–based periodontitis research was identified by this approach. Methods outlined herein may be applied to refine oral health surveillance systems, inform dental epidemiologic methods, and evaluate interventional outcomes. PMID:23462966

Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.

PubMed

Kechagias, Stergios; Dernroth, Dženeta Nezirević; Blomgren, Anders; Hansson, Therese; Isaksson, Anders; Walther, Lisa; Kronstrand, Robert; Kågedal, Bertil; Nystrom, Fredrik H

2015-07-01

It is generally agreed that traditional alcohol biomarkers lack in sensitivity to detect hazardous alcohol consumption. The present study was undertaken to evaluate the ability of phosphatidylethanol (PEth) and traditional alcohol markers to detect moderate alcohol consumption and to distinguish between moderate alcohol consumption and abstinence. Forty-four subjects, 32 females and 12 males, were included in the study. They were randomized to alcohol abstention or to alcohol consumption. Female participants consumed 150 ml of red wine (equivalent to 16 g of alcohol) per 24 h and the male participants double the amount. The study lasted for 3 months. Blood samples were drawn at the start and at the end of the study period. Blood samples were analysed for PEth, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), γ-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). ROC curves for the various biochemical markers were plotted in order to assess their ability to discriminate between abstention and moderate daily consumption of alcohol. PEth and CDT were the only markers with AUROCs significantly higher than 0.5, and PEth was detected in all participants randomized to alcohol consumption. PEth was the only marker that could detect moderate intake and the present results also indicate that PEth probably can distinguish moderate alcohol consumption from abstinence. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Global brain atrophy is associated with physical performance and the risk of falls in older adults with cognitive impairment.

PubMed

Yamada, Minoru; Takechi, Hajime; Mori, Shuhei; Aoyama, Tomoki; Arai, Hidenori

2013-04-01

Falls are common in patients with cognitive disorder. The purpose of this study was to determine whether global brain atrophy is associated with cognitive function, physical performance and fall incidents in older adults with mild cognitive disorder. A total of 31 older adults with mild cognitive disorders (mean age 78.9 ± 7.3 years) were studied, and 10 of them had experienced falls and the others had not in the past 1 year. Cognitive function and physical performance were measured in these patients. Global brain atrophy was determined by the Voxel-Based Specific Regional Analysis System for Alzheimer's Disease software. Fallers showed significantly worse scores than the non-fallers in the Global Brain Atrophy Index, Clock Drawing Test (CDT), Verbal Fluency Test (animal), maximum walking time and Timed Up & Go (TUG) Test. The Global Brain Atrophy Index was correlated with the Verbal Fluency Test (animal; r = -0.522), the Verbal Fluency Test with letter (ka; r = -0.337), CDT (r = -0.547), TUG (r = 0.276) and Five Chair Stands Test (r = 0.303) by age-adjusted correlation analyses. Stepwise regression analysis showed that the Global Brain Atrophy Index (β = 1.265, 95% CI 1.022-1.567) was a significant and independent determinant of falls (R(2) = 0.356, P = 0.003). Global brain atrophy might be indicated as one of the risk factors for falls in older adults with mild cognitive disorders. © 2012 Japan Geriatrics Society.

Effects of Exercise on Cognition: The Finnish Alzheimer Disease Exercise Trial: A Randomized, Controlled Trial.

PubMed

Öhman, Hannareeta; Savikko, Niina; Strandberg, Timo E; Kautiainen, Hannu; Raivio, Minna M; Laakkonen, Marja-Liisa; Tilvis, Reijo; Pitkälä, Kaisu H

2016-04-01

To examine whether a regular, long-term exercise program performed by individuals with Alzheimer's disease (AD) at home or as group-based exercise at an adult daycare center has beneficial effects on cognition; to examine secondary outcomes of a trial that has been published earlier. Randomized, controlled trial. Community. Community-dwelling dyads (N = 210) of individuals with AD and their spousal caregivers randomized into three groups. Two types of intervention comprising customized home-based exercise (HE) and group-based exercise (GE), each twice a week for 1 year, were compared with a control group (CG) receiving usual community care. Cognitive function was measured using the Clock Drawing Test (CDT), Verbal Fluency (VF), Clinical Dementia Rating (CDR), and Mini-Mental State Examination (MMSE) at baseline and 3, 6, and 12 months of follow-up. Executive function, measured using CDT, improved in the HE group, and changes in the score were significantly better than those of the CG at 12 months (adjusted for age, sex, and CDR, P = .03). All groups deteriorated in VF and MMSE score during the intervention, and no significant differences between the groups were detected at 12-month follow-up when analyses were adjusted for age, sex, and CDR. Regular, long-term, customized HE improved the executive function of community-dwelling older people with memory disorders, but the effects were mild and were not observed in other domains of cognition. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis

PubMed Central

Herbert, Bethany A.; Novince, Chad M.; Kirkwood, Keith L.

2015-01-01

Summary Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and pre-clinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast mediated bone remodeling, which subsequently leads to net alveolar bone loss. PMID:26197893

A SIMS Study of Sulfur Isotopes of Accessory Pyrites Associated with Barites from Methane Cold Seeps in the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Morelli, E. C.; Aharon, P.

2017-12-01

Bacteria and archaea associated with seeps can fix methane from sublimating gas hydrates through coupled bacterial sulfate reduction/ anaerobic methane oxidation (BSR/AMO) and prevent outgassing to the atmosphere. The occurrence of such microbial processes has been established on the basis of the sulfur isotope compositions of microbial byproducts (pyrites; FeS2) that reflect the degree of fractionation between SO4 and FeS2 via the production of the H2S intermediate phase. BSR/AMO coupling has been discerned in accessory sulfides associated with carbonates from gas hydrate sites. Whether BSR/AMO coupling is also active in barites, another ubiquitous product of gas hydrate sublimation, has so far been overlooked. Here we present results of a new sulfur isotope study of accessory sulfides in barites associated with gas hydrates at the threshold of stability occurring on the Gulf of Mexico slope. Using a fractionation factor of 1.009 and a seawater δ34SSO4 value of 20.3‰ and assuming a Rayleigh distillation closed system model for marine sulfide precipitation, pyrites from barite gas seeps are predicted to exhibit a range of δ34S values (about -1‰ to 20‰ CDT) as the pool of sulfate is continuously depleted. Actual δ34S values could fall outside of the predicted range because the system in question is likely only partially closed and kinetic fractionations are likely. δ34S of accessory pyrites from three Garden Banks Lease Block 382 (510 - 640m water depth) and one Mississippi Canyon Lease Block 929 (590m) barite samples have been determined using an ims-1290 Secondary Ion Mass Spectrometer (SIMS). Two Garden Banks samples and one Mississippi Canyon sample reveal a spread of values from 5.30 ± 0.04 to 25.90 ± 0.09 (‰ CDT), which follow the predicted trend for gas seeps and indicate the source of fractionation is likely from the coupled BSR/AMO process. One Garden Banks sample yields a wide spread of values from -26.2 ± 0.05 to 20.5 ± 0.4 (‰ CDT). The negative values are unexpected because such values typically suggest a sole contribution by BSR. This sample was the youngest (12.8 ± 0.6 yrs versus 21.5 ± 1.9 to 44.23 ± 2.92 yrs) at time of collection, and thus some of the negative values could reflect kinetic effects governed by the BSR pathway or anaerobic bacterial disproportionation (BDS) of elemental sulfur.

Pathogenicity of the highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans and its geographic dissemination and role in aggressive periodontitis

PubMed Central

Haubek, Dorte; Johansson, Anders

2014-01-01

For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA) and cytolethal distending toxin (Cdt). LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are colonized with the JP2 clone, are likely to share this clone with several family members because the clone is transmitted through close contacts. This is a challenge to the clinicians. The patients need intense monitoring of their periodontal status as the risk for developing severely progressing periodontal lesions are relatively high. Furthermore, timely periodontal treatment, in some cases including periodontal surgery supplemented by the use of antibiotics, is warranted. Preferably, periodontal attachment loss should be prevented by early detection of the JP2 clone of A. actinomycetemcomitans by microbial diagnostic testing and/or by preventive means. PMID:25206940

Improving computer-aided detection assistance in breast cancer screening by removal of obviously false-positive findings.

PubMed

Mordang, Jan-Jurre; Gubern-Mérida, Albert; Bria, Alessandro; Tortorella, Francesco; den Heeten, Gerard; Karssemeijer, Nico

2017-04-01

Computer-aided detection (CADe) systems for mammography screening still mark many false positives. This can cause radiologists to lose confidence in CADe, especially when many false positives are obviously not suspicious to them. In this study, we focus on obvious false positives generated by microcalcification detection algorithms. We aim at reducing the number of obvious false-positive findings by adding an additional step in the detection method. In this step, a multiclass machine learning method is implemented in which dedicated classifiers learn to recognize the patterns of obvious false-positive subtypes that occur most frequently. The method is compared to a conventional two-class approach, where all false-positive subtypes are grouped together in one class, and to the baseline CADe system without the new false-positive removal step. The methods are evaluated on an independent dataset containing 1,542 screening examinations of which 80 examinations contain malignant microcalcifications. Analysis showed that the multiclass approach yielded a significantly higher sensitivity compared to the other two methods (P < 0.0002). At one obvious false positive per 100 images, the baseline CADe system detected 61% of the malignant examinations, while the systems with the two-class and multiclass false-positive reduction step detected 73% and 83%, respectively. Our study showed that by adding the proposed method to a CADe system, the number of obvious false positives can decrease significantly (P < 0.0002). © 2017 American Association of Physicists in Medicine.

Clostridium difficile infection

PubMed Central

Smits, Wiep Klaas; Lyras, Dena; Lacy, D. Borden; Wilcox, Mark H.; Kuijper, Ed J.

2017-01-01

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis — the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota. PMID:27158839

STS-100 crew in docking compartment after docking with ISS

NASA Image and Video Library

2001-04-21

ISS002-311-032 (23 April 2001) --- The six astronauts and one cosmonaut comprising the STS-100 crew assemble in the Pressurized Mating Adapter (PMA-2) while waiting to visit the Expedition Two crew and the International Space Station (ISS). With his arm extended to left foreground is astronaut Kent V. Rominger, STS-100 mission commander. In the circular arrangement of crewmembers, clockwise from Rominger's position, are astronauts Umberto Guidoni, Scott E. Parazynski, Chris A. Hadfield, Jeffrey S. Ashby and John L. Phillips. Cosmonaut Yuri V. Lonchakov's head emerges at bottom center. On the other side of the glass were the Expedition Two crewmembers--cosmonaut Yury V. Usachev and astronauts James S. Voss and Susan J. Helms. Lonchakov and Usachev represent Rosaviakosmos; Hadfield is with the Canadian Space Agency (CSA) and Guidoni is associated with the European Space Agency (ESA). The ten were beginning a day that went on to see the first opening of hatches linking the two spacecraft, an impressive first step by the station's new Canadarm2 and the berthing to the station of Raffaello, the Italian-built logistics module. Hatch opening was set for 4 a.m. (CDT), April 23.

Statistical approaches to account for false-positive errors in environmental DNA samples.

PubMed

Lahoz-Monfort, José J; Guillera-Arroita, Gurutzeta; Tingley, Reid

2016-05-01

Environmental DNA (eDNA) sampling is prone to both false-positive and false-negative errors. We review statistical methods to account for such errors in the analysis of eDNA data and use simulations to compare the performance of different modelling approaches. Our simulations illustrate that even low false-positive rates can produce biased estimates of occupancy and detectability. We further show that removing or classifying single PCR detections in an ad hoc manner under the suspicion that such records represent false positives, as sometimes advocated in the eDNA literature, also results in biased estimation of occupancy, detectability and false-positive rates. We advocate alternative approaches to account for false-positive errors that rely on prior information, or the collection of ancillary detection data at a subset of sites using a sampling method that is not prone to false-positive errors. We illustrate the advantages of these approaches over ad hoc classifications of detections and provide practical advice and code for fitting these models in maximum likelihood and Bayesian frameworks. Given the severe bias induced by false-negative and false-positive errors, the methods presented here should be more routinely adopted in eDNA studies. © 2015 John Wiley & Sons Ltd.

Easy fix for clinical laboratories for the false-positive defect with the Abbott AxSym total beta-hCG test.

PubMed

Cole, Laurence A; Khanlian, Sarah A

2004-05-01

False-positive hCG results can lead to erroneous diagnoses and needless chemotherapy and surgery. In the last 2 years, eight publications described cases involving false-positive hCG tests; all eight involved the AxSym test. We investigated the source of this abundance of cases and a simple fix that may be used by clinical laboratories. False-positive hCG was primarily identified by absence of hCG in urine and varying or negative hCG results in alternative tests. Seventeen false-positive serum samples in the AxSym test were evaluated undiluted and at twofold dilution with diluent containing excess goat serum or immunoglobulin. We identified 58 patients with false-positive hCG, 47 of 58 due to the Abbott AxSym total hCGbeta test (81%). Sixteen of 17 of these "false-positive" results (mean 100 mIU/ml) became undetectable when tested again after twofold dilution. A simple twofold dilution with this diluent containing excess goat serum or immunoglobulin completely protected 16 of 17 samples from patients having false-positive results. It is recommended that laboratories using this test use twofold dilution as a minimum to prevent false-positive results.

STS-101 Crew Portrait

NASA Technical Reports Server (NTRS)

2000-01-01

Six astronauts and a Russian cosmonaut comprised the STS-101 mission that launched aboard the Space Shuttle Atlantis on May 19, 2000 at 5:11 am (CDT). Seated in front are astronauts James D. Halsell (right), mission commander; and Scott J. Horowitz, pilot. Others, from the left, are Mary Ellen Weber, Jeffrey N. Williams, Yury V. Usachev, James S. Voss and Susan J. Helms, all mission specialists. Usachev represents the Russian Space Agency (RSA). The crew of the STS- 101 mission refurbished and replaced components in both the Zarya and Unity modules, with top priority being the Zarya module.

Return to flight SSME test at A2 test stand

NASA Image and Video Library

2004-07-16

The Space Shuttle Main Engine (SSME) reached a historic milestone July 16, 2004, when a successful flight acceptance test was conducted at NASA Stennis Space Center (SSC). The engine tested today is the first complete engine to be tested and shipped in its entirety to Kennedy Space Center for installation on Space Shuttle Discovery for STS-114, NASA's Return to Flight mission. The engine test, which began about 3:59 p.m. CDT, ran for 520 seconds (8 minutes), the length of time it takes for the Space Shuttle to reach orbit.

MCC Guest Viewing Program of Pope Benedict XVI's call to the ISS/STS-134 crew.

NASA Image and Video Library

2011-05-21

JSC2011-E-046605 (21 May 2011) --- His Eminence Daniel Cardinal DiNardo, Archbishop of Galveston-Houston, speaks to a group of guests in the viewing room of the Mission Control Center at NASA?s Johnson Space Center following a special call from Pope Benedict XVI to the STS-134 and Expedition 27 crews on the International Space Station. The event was conducted from The Vatican at 6:11 a.m. (CDT) on May 21, 2011, and aired live on NASA television. Photo credit: NASA

CT Colonography with Computer-aided Detection: Recognizing the Causes of False-Positive Reader Results

PubMed Central

Dachman, Abraham H.; Wroblewski, Kristen; Vannier, Michael W.; Horne, John M.

2014-01-01

Computed tomography (CT) colonography is a screening modality used to detect colonic polyps before they progress to colorectal cancer. Computer-aided detection (CAD) is designed to decrease errors of detection by finding and displaying polyp candidates for evaluation by the reader. CT colonography CAD false-positive results are common and have numerous causes. The relative frequency of CAD false-positive results and their effect on reader performance on the basis of a 19-reader, 100-case trial shows that the vast majority of CAD false-positive results were dismissed by readers. Many CAD false-positive results are easily disregarded, including those that result from coarse mucosa, reconstruction, peristalsis, motion, streak artifacts, diverticulum, rectal tubes, and lipomas. CAD false-positive results caused by haustral folds, extracolonic candidates, diminutive lesions (<6 mm), anal papillae, internal hemorrhoids, varices, extrinsic compression, and flexural pseudotumors are almost always recognized and disregarded. The ileocecal valve and tagged stool are common sources of CAD false-positive results associated with reader false-positive results. Nondismissable CAD soft-tissue polyp candidates larger than 6 mm are another common cause of reader false-positive results that may lead to further evaluation with follow-up CT colonography or optical colonoscopy. Strategies for correctly evaluating CAD polyp candidates are important to avoid pitfalls from common sources of CAD false-positive results. ©RSNA, 2014 PMID:25384290

A Closer Look at Self-Reported Suicide Attempts: False Positives and False Negatives

ERIC Educational Resources Information Center

Ploderl, Martin; Kralovec, Karl; Yazdi, Kurosch; Fartacek, Reinhold

2011-01-01

The validity of self-reported suicide attempt information is undermined by false positives (e.g., incidences without intent to die), or by unreported suicide attempts, referred to as false negatives. In a sample of 1,385 Austrian adults, we explored the occurrence of false positives and false negatives with detailed, probing questions. Removing…

"False Positive" Claims of Near-Death Experiences and "False Negative" Denials of Near-Death Experiences

ERIC Educational Resources Information Center

Greyson, Bruce

2005-01-01

Some persons who claim to have had near-death experiences (NDEs) fail research criteria for having had NDEs ("false positives"); others who deny having had NDEs do meet research criteria for having had NDEs ("false negatives"). The author evaluated false positive claims and false negative denials in an organization that promotes near-death…

Risk of breast cancer after false-positive results in mammographic screening.

PubMed

Román, Marta; Castells, Xavier; Hofvind, Solveig; von Euler-Chelpin, My

2016-06-01

Women with false-positive results are commonly referred back to routine screening. Questions remain regarding their long-term outcome of breast cancer. We assessed the risk of screen-detected breast cancer in women with false-positive results. We conducted a joint analysis using individual level data from the population-based screening programs in Copenhagen and Funen in Denmark, Norway, and Spain. Overall, 150,383 screened women from Denmark (1991-2008), 612,138 from Norway (1996-2010), and 1,172,572 from Spain (1990-2006) were included. Poisson regression was used to estimate the relative risk (RR) of screen-detected cancer for women with false-positive versus negative results. We analyzed information from 1,935,093 women 50-69 years who underwent 6,094,515 screening exams. During an average 5.8 years of follow-up, 230,609 (11.9%) women received a false-positive result and 27,849 (1.4%) were diagnosed with screen-detected cancer. The adjusted RR of screen-detected cancer after a false-positive result was 2.01 (95% CI: 1.93-2.09). Women who tested false-positive at first screen had a RR of 1.86 (95% CI: 1.77-1.96), whereas those who tested false-positive at third screening had a RR of 2.42 (95% CI: 2.21-2.64). The RR of breast cancer at the screening test after the false-positive result was 3.95 (95% CI: 3.71-4.21), whereas it decreased to 1.25 (95% CI: 1.17-1.34) three or more screens after the false-positive result. Women with false-positive results had a twofold risk of screen-detected breast cancer compared to women with negative tests. The risk remained significantly higher three or more screens after the false-positive result. The increased risk should be considered when discussing stratified screening strategies. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

US women's attitudes to false positive mammography results and detection of ductal carcinoma in situ: cross sectional survey

PubMed Central

Schwartz, Lisa M; Woloshin, Steven; Sox, Harold C; Fischhoff, Baruch; Welch, H Gilbert

2000-01-01

Objective To determine women's attitudes to and knowledge of both false positive mammography results and the detection of ductal carcinoma in situ after screening mammography. Design Cross sectional survey. Setting United States. Participants 479 women aged 18-97 years who did not report a history of breast cancer. Main outcome measures Attitudes to and knowledge of false positive results and the detection of ductal carcinoma in situ after screening mammography. Results Women were aware that false positive results do occur. Their median estimate of the false positive rate for 10 years of annual screening was 20% (25th percentile estimate, 10%; 75th percentile estimate, 45%). The women were highly tolerant of false positives: 63% thought that 500 or more false positives per life saved was reasonable and 37% would tolerate 10 000 or more. Women who had had a false positive result (n=76) expressed the same high tolerance: 39% would tolerate 10 000 or more false positives. 62% of women did not want to take false positive results into account when deciding about screening. Only 8% of women thought that mammography could harm a woman without breast cancer, and 94% doubted the possibility of non-progressive breast cancers. Few had heard about ductal carcinoma in situ, a cancer that may not progress, but when informed, 60% of women wanted to take into account the possibility of it being detected when deciding about screening. Conclusions Women are aware of false positives and seem to view them as an acceptable consequence of screening mammography. In contrast, most women are unaware that screening can detect cancers that may never progress but feel that such information would be relevant. Education should perhaps focus less on false positives and more on the less familiar outcome of detection of ductal carcinoma in situ. PMID:10856064

Homocysteine and Cognitive Performance in Elders with Self-Neglect

NASA Technical Reports Server (NTRS)

Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

2009-01-01

Elevated plasma homocysteine has been associated with altered cognitive performance in older adults. Elders referred to Adult Protective Services (APS) for self-neglect have been reported to have elevated plasma homocysteine levels and to suffer from cognitive impairment. This study assesses the association, if any, between plasma homocysteine and cognitive performance among elders with self-neglect. Methods: Sixty-five community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 matched controls (matched for age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS), the Wolf-Klein Clock Drawing Tests (CDT) and a comprehensive nutritional biochemistry panel, which included plasma homocysteine. Student s t tests and Pearson correlations were conducted to assess for bivariate associations. Results: Elders with self-neglect had significantly higher plasma homocysteine levels (M=12.68umol/L, sd=4.4) compared to the controls (M=10.40umol/L, sd=3.61;t=3.21, df=127, p=.002). There were no statistically significant associations between cognitive performance and plasma homocysteine in the self-neglect group, however there was a significant correlation between plasma homocysteine and the CDT among the controls (r=-.296, p=.022). Conclusion: Mean plasma homocysteine levels were significantly higher in elders with self-neglect, however, they do not appear to be related to cognitive performance, indicating that cognitive impairment in elder self-neglect involve mechanisms other than hyperhomocysteinemia. These findings warrant further investigation

Development and Validation of a High Throughput System for Discovery of Antigens for Autoantibody Detection

PubMed Central

Macdonald, Isabel K.; Allen, Jared; Murray, Andrea; Parsy-Kowalska, Celine B.; Healey, Graham F.; Chapman, Caroline J.; Sewell, Herbert F.; Robertson, John F. R.

2012-01-01

An assay employing a panel of tumor-associated antigens has been validated and is available commercially (EarlyCDT®-Lung) to aid the early detection of lung cancer by measurement of serum autoantibodies. The high throughput (HTP) strategy described herein was pursued to identify new antigens to add to the EarlyCDT-Lung panel and to assist in the development of new panels for other cancers. Two ligation-independent cloning vectors were designed and synthesized, producing fusion proteins suitable for the autoantibody ELISA. We developed an abridged HTP version of the validated autoantibody ELISA, determining that results reflected the performance of the EarlyCDT assay, by comparing results on both formats. Once validated this HTP ELISA was utilized to screen multiple fusion proteins prepared on small-scale, by a HTP expression screen. We determined whether the assay performance for these HTP protein batches was an accurate reflection of the performance of R&D or commercial batches. A HTP discovery platform for the identification and optimal production of tumor- associated antigens which detects autoantibodies has been developed and validated. The most favorable conditions for the exposure of immunogenic epitopes were assessed to produce discriminatory proteins for use in a commercial ELISA. This process is rapid and cost-effective compared to standard cloning and screening technologies and enables rapid advancement in the field of autoantibody assay discovery. This approach will significantly reduce timescale and costs for developing similar panels of autoantibody assays for the detection of other cancer types with the ultimate aim of improved overall survival due to early diagnosis and treatment. PMID:22815807

Clock face drawing test performance in children with ADHD.

PubMed

Ghanizadeh, Ahmad; Safavi, Salar; Berk, Michael

2013-01-01

The utility and discriminatory pattern of the clock face drawing test in ADHD is unclear. This study therefore compared Clock Face Drawing test performance in children with ADHD and controls. 95 school children with ADHD and 191 other children were matched for gender ratio and age. ADHD symptoms severities were assessed using DSM-IV ADHD checklist and their intellectual functioning was assessed. The participants completed three clock-drawing tasks, and the following four functions were assessed: Contour score, Numbers score, Hands setting score, and Center score. All the subscales scores of the three clock drawing tests of the ADHD group were lower than that of the control group. In ADHD children, inattention and hyperactivity/ impulsivity scores were not related to free drawn clock test scores. When pre-drawn contour test was performed, inattentiveness score was statistically associated with Number score while none of the other variables of age, gender, intellectual functioning, and hand use preference were associated with that kind of score. In pre-drawn clock, no association of ADHD symptoms with any CDT subscales found significant. In addition, more errors are observed with free drawn clock and Pre-drawn contour than pre-drawn clock. Putting Numbers and Hands setting are more sensitive measures to screen ADHD than Contour and Center drawing. Test performance, except Hands setting, may have already reached a developmental plateau. It is probable that Hand setting deficit in children with ADHD may not decrease from age 8 to 14 years. Performance of children with ADHD is associated with complexity of CDT.

Experimental investigation of false positive errors in auditory species occurrence surveys

USGS Publications Warehouse

Miller, David A.W.; Weir, Linda A.; McClintock, Brett T.; Grant, Evan H. Campbell; Bailey, Larissa L.; Simons, Theodore R.

2012-01-01

False positive errors are a significant component of many ecological data sets, which in combination with false negative errors, can lead to severe biases in conclusions about ecological systems. We present results of a field experiment where observers recorded observations for known combinations of electronically broadcast calling anurans under conditions mimicking field surveys to determine species occurrence. Our objectives were to characterize false positive error probabilities for auditory methods based on a large number of observers, to determine if targeted instruction could be used to reduce false positive error rates, and to establish useful predictors of among-observer and among-species differences in error rates. We recruited 31 observers, ranging in abilities from novice to expert, that recorded detections for 12 species during 180 calling trials (66,960 total observations). All observers made multiple false positive errors and on average 8.1% of recorded detections in the experiment were false positive errors. Additional instruction had only minor effects on error rates. After instruction, false positive error probabilities decreased by 16% for treatment individuals compared to controls with broad confidence interval overlap of 0 (95% CI: -46 to 30%). This coincided with an increase in false negative errors due to the treatment (26%; -3 to 61%). Differences among observers in false positive and in false negative error rates were best predicted by scores from an online test and a self-assessment of observer ability completed prior to the field experiment. In contrast, years of experience conducting call surveys was a weak predictor of error rates. False positive errors were also more common for species that were played more frequently, but were not related to the dominant spectral frequency of the call. Our results corroborate other work that demonstrates false positives are a significant component of species occurrence data collected by auditory methods. Instructing observers to only report detections they are completely certain are correct is not sufficient to eliminate errors. As a result, analytical methods that account for false positive errors will be needed, and independent testing of observer ability is a useful predictor for among-observer variation in observation error rates.

Characterisation of false-positive observations in botanical surveys

PubMed Central

2017-01-01

Errors in botanical surveying are a common problem. The presence of a species is easily overlooked, leading to false-absences; while misidentifications and other mistakes lead to false-positive observations. While it is common knowledge that these errors occur, there are few data that can be used to quantify and describe these errors. Here we characterise false-positive errors for a controlled set of surveys conducted as part of a field identification test of botanical skill. Surveys were conducted at sites with a verified list of vascular plant species. The candidates were asked to list all the species they could identify in a defined botanically rich area. They were told beforehand that their final score would be the sum of the correct species they listed, but false-positive errors counted against their overall grade. The number of errors varied considerably between people, some people create a high proportion of false-positive errors, but these are scattered across all skill levels. Therefore, a person’s ability to correctly identify a large number of species is not a safeguard against the generation of false-positive errors. There was no phylogenetic pattern to falsely observed species; however, rare species are more likely to be false-positive as are species from species rich genera. Raising the threshold for the acceptance of an observation reduced false-positive observations dramatically, but at the expense of more false negative errors. False-positive errors are higher in field surveying of plants than many people may appreciate. Greater stringency is required before accepting species as present at a site, particularly for rare species. Combining multiple surveys resolves the problem, but requires a considerable increase in effort to achieve the same sensitivity as a single survey. Therefore, other methods should be used to raise the threshold for the acceptance of a species. For example, digital data input systems that can verify, feedback and inform the user are likely to reduce false-positive errors significantly. PMID:28533972

Kepler Certified False Positive Table

NASA Technical Reports Server (NTRS)

Bryson, Stephen T.; Batalha, Natalie Marie; Colon, Knicole Dawn; Coughlin, Jeffrey Langer; Haas, Michael R.; Henze, Chris; Huber, Daniel; Morton, Tim; Rowe, Jason Frank; Mullally, Susan Elizabeth;

Cumulative risk of false positive test in relation to breast symptoms in mammography screening: a historical prospective cohort study.

PubMed

Singh, Deependra; Pitkäniemi, Janne; Malila, Nea; Anttila, Ahti

2016-09-01

Mammography has been found effective as the primary screening test for breast cancer. We estimated the cumulative probability of false positive screening test results with respect to symptom history reported at screen. A historical prospective cohort study was done using individual screening data from 413,611 women aged 50-69 years with 2,627,256 invitations for mammography screening between 1992 and 2012 in Finland. Symptoms (lump, retraction, and secretion) were reported at 56,805 visits, and 48,873 visits resulted in a false positive mammography result. Generalized linear models were used to estimate the probability of at least one false positive test and true positive at screening visits. The estimates were compared among women with and without symptoms history. The estimated cumulative probabilities were 18 and 6 % for false positive and true positive results, respectively. In women with a history of a lump, the cumulative probabilities of false positive test and true positive were 45 and 16 %, respectively, compared to 17 and 5 % with no reported lump. In women with a history of any given symptom, the cumulative probabilities of false positive test and true positive were 38 and 13 %, respectively. Likewise, women with a history of a 'lump and retraction' had the cumulative false positive probability of 56 %. The study showed higher cumulative risk of false positive tests and more cancers detected in women who reported symptoms compared to women who did not report symptoms at screen. The risk varies substantially, depending on symptom types and characteristics. Information on breast symptoms influences the balance of absolute benefits and harms of screening.

Detecting false positives in multielement designs: implications for brief assessments.

PubMed

Bartlett, Sara M; Rapp, John T; Henrickson, Marissa L

2011-11-01

The authors assessed the extent to which multielement designs produced false positives using continuous duration recording (CDR) and interval recording with 10-s and 1-min interval sizes. Specifically, they created 6,000 graphs with multielement designs that varied in the number of data paths, and the number of data points per data path, using a random number generator. In Experiment 1, the authors visually analyzed the graphs for the occurrence of false positives. Results indicated that graphs depicting only two sessions for each condition (e.g., a control condition plotted with multiple test conditions) produced the highest percentage of false positives for CDR and interval recording with 10-s and 1-min intervals. Conversely, graphs with four or five sessions for each condition produced the lowest percentage of false positives for each method. In Experiment 2, they applied two new rules, which were intended to decrease false positives, to each graph that depicted a false positive in Experiment 1. Results showed that application of new rules decreased false positives to less than 5% for all of the graphs except for those with two data paths and two data points per data path. Implications for brief assessments are discussed.

Response time as a discriminator between true- and false-positive responses in suprathreshold perimetry.

PubMed

Artes, Paul H; McLeod, David; Henson, David B

2002-01-01

To report on differences between the latency distributions of responses to stimuli and to false-positive catch trials in suprathreshold perimetry. To describe an algorithm for defining response time windows and to report on its performance in discriminating between true- and false-positive responses on the basis of response time (RT). A sample of 435 largely inexperienced patients underwent suprathreshold visual field examination on a perimeter that was modified to record RTs. Data were analyzed from 60,500 responses to suprathreshold stimuli and from 523 false-positive responses to catch trials. False-positive responses had much more variable latencies than responses to suprathreshold stimuli. An algorithm defining RT windows on the basis of z-transformed individual latency samples correctly identified more than 70% of false-positive responses to catch trials, whereas fewer than 3% of responses to suprathreshold stimuli were classified as false-positive responses. Latency analysis can be used to detect a substantial proportion of false-positive responses in suprathreshold perimetry. Rejection of such responses may increase the reliability of visual field screening by reducing variability and bias in a small but clinically important proportion of patients.

Toward a Neuroscience of Adult Cognitive Developmental Theory

PubMed Central

Girgis, Fady; Lee, Darrin J.; Goodarzi, Amir; Ditterich, Jochen

2018-01-01

Piaget's genetic epistemology has provided the constructivist approach upon which child developmental theories were founded, in that infants are thought to progress through distinct cognitive stages until they reach maturity in their early 20's. However, it is now well established that cognition continues to develop after early adulthood, and several “neo-Piagetian” theories have emerged in an attempt to better characterize adult cognitive development. For example, Kegan's Constructive Developmental Theory (CDT) argues that the thought processes used by adults to construct their reality change over time, and reaching higher stages of cognitive development entails becoming objectively aware of emotions and beliefs that were previously in the realm of the subconscious. In recent years, neuroscience has shown a growing interest in the biological substrates and neural mechanisms encompassing adult cognitive development, because psychological and psychiatric disorders can arise from deficiencies therein. In this article, we will use Kegan's CDT as a framework to discuss adult cognitive development in relation to closely correlated existing constructs underlying social processing, such as the perception of self and others. We will review the functional imaging and electrophysiologic evidence behind two key concepts relating to these posited developmental changes. These include self-related processing, a field that distinguishes between having conscious experiences (“being a self”) and being aware of oneself having conscious experiences (“being aware of being a self”); and theory of mind, which is the objective awareness of possessing mental states such as beliefs and desires (i.e., having a “mind”) and the understanding that others possess mental states that can be different from one's own. We shall see that cortical midline structures, including the medial prefrontal cortex and cingulate gyrus, as well as the temporal lobe, are associated with psychological tasks that test these models. In addition, we will review computational modeling approaches to cognitive development, and show how mathematical modeling can provide insights into how sometimes continuous changes in the neural processing substrate can give rise to relatively discrete developmental stages. Because deficiencies in adult cognitive development can result in disorders such as autism and depression, bridging the gaps between developmental psychology, neuroscience, and modeling has potential implications for clinical practice. As neuromodulation techniques such as deep brain and transcranial stimulation continue to advance, interfacing with these systems may lead to the emergence of novel investigational methods and therapeutic strategies in adults suffering from developmental disorders. PMID:29410608

Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening.

PubMed

Ibáñez-Sanz, Gemma; Garcia, Montse; Rodríguez-Moranta, Francisco; Binefa, Gemma; Gómez-Matas, Javier; Domènech, Xènia; Vidal, Carmen; Soriano, Antonio; Moreno, Víctor

2016-10-01

The most common side effect in population screening programmes is a false-positive result which leads to unnecessary risks and costs. To identify factors associated with false-positive results in a colorectal cancer screening programme with the faecal immunochemical test (FIT). Cross-sectional study of 472 participants with a positive FIT who underwent colonoscopy for confirmation of diagnosis between 2013 and 2014. A false-positive result was defined as having a positive FIT (≥20μg haemoglobin per gram of faeces) and follow-up colonoscopy without intermediate/high-risk lesions or cancer. Women showed a two-fold increased likelihood of a false-positive result compared with men (adjusted OR, 2.3; 95%CI, 1.5-3.4), but no female-specific factor was identified. The other variables associated with a false-positive result were successive screening (adjusted OR, 1.5; 95%CI, 1.0-2.2), anal disorders (adjusted OR, 3.1; 95%CI, 2.1-4.5) and the use of proton pump inhibitors (adjusted OR, 1.8; 95%CI, 1.1-2.9). Successive screening and proton pump inhibitor use were associated with FP in men. None of the other drugs were related to a false-positive FIT. Concurrent use of proton pump inhibitors at the time of FIT might increase the likelihood of a false-positive result. Further investigation is needed to determine whether discontinuing them could decrease the false-positive rate. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

An open-label, randomized positron emission tomography (PET)study in healthy male volunteers consisiting of Part A and Part B.Part A: Clinical validation of norepinephrine transporter (NET) PET ligand, (S,S)-[11C]O-methylreboxetine ([11C]MRB) using different doses of oral atomoxetine as NET reuptake inhibitor.Part B: Evaluation of NET occupancy, as measured by [11C]MRB, with multiple dosing regimens of orally administered GSK372475.

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

Fowler, Joanna; Furey, Michael

Results from human studies with the PET radiotracer (S,S)-[(11)C]O-methyl reboxetine ([(11)C](S,S)-MRB), a ligand targeting the norepinephrine transporter (NET), are reported. Quantification methods were determined from test/retest studies, and sensitivity to pharmacological blockade was tested with different doses of atomoxetine (ATX), a drug that binds to the NET with high affinity (K(i)=2-5 nM). METHODS: Twenty-four male subjects were divided into different groups for serial 90-min PET studies with [(11)C](S,S)-MRB to assess reproducibility and the effect of blocking with different doses of ATX (25, 50 and 100 mg, po). Region-of-interest uptake data and arterial plasma input were analyzed for the distribution volumemore » (DV). Images were normalized to a template, and average parametric images for each group were formed. RESULTS: [(11)C](S,S)-MRB uptake was highest in the thalamus (THL) and the midbrain (MBR) [containing the locus coeruleus (LC)] and lowest for the caudate nucleus (CDT). The CDT, a region with low NET, showed the smallest change on ATX treatment and was used as a reference region for the DV ratio (DVR). The baseline average DVR was 1.48 for both the THL and MBR with lower values for other regions [cerebellum (CB), 1.09; cingulate gyrus (CNG) 1.07]. However, more accurate information about relative densities came from the blocking studies. MBR exhibited greater blocking than THL, indicating a transporter density approximately 40% greater than THL. No relationship was found between DVR change and plasma ATX level. Although the higher dose tended to induce a greater decrease than the lower dose for MBR (average decrease for 25 mg=24+/-7%; 100 mg=31+/-11%), these differences were not significant. The different blocking between MBR (average decrease=28+/- 10%) and THL (average decrease=17+/-10%) given the same baseline DVR indicates that the CDT is not a good measure for non-NET binding in both regions. Threshold analysis of the difference between the average baseline DV image and the average blocked image showed the expected NET distribution with the MBR (LC) and hypothalamus>THL>CNG and CB, as well as a significant change in the supplementary motor area. DVR reproducibility for the different brain regions was approximately 10%, but intersubject variability was large. CONCLUSIONS: The highest density of NETs was found in the MBR where the LC is located, followed by THL, whereas the lowest density was found in basal ganglia (lowest in CDT), consistent with the regional localization of NETs in the nonhuman primate brain. While all three doses of ATX were found to block most regions, no significant differences between doses were found for any region, although the average percent change across subjects of the MBR did correlate with ATX dose. The lack of a dose effect could reflect a low signal-to-noise ratio coupled with the possibility that a sufficient number of transporters were blocked at the lowest dose and further differences could not be detected. However, since the lowest (25 mg) dose is less than the therapeutic doses used in children for the treatment of attention-deficit/hyperactivity disorder ( approximately 1.0 mg/kg/day), this would suggest that there may be additional targets for ATX's therapeutic actions.« less

False negative rates in Drosophila cell-based RNAi screens: a case study

PubMed Central

2011-01-01

Background High-throughput screening using RNAi is a powerful gene discovery method but is often complicated by false positive and false negative results. Whereas false positive results associated with RNAi reagents has been a matter of extensive study, the issue of false negatives has received less attention. Results We performed a meta-analysis of several genome-wide, cell-based Drosophila RNAi screens, together with a more focused RNAi screen, and conclude that the rate of false negative results is at least 8%. Further, we demonstrate how knowledge of the cell transcriptome can be used to resolve ambiguous results and how the number of false negative results can be reduced by using multiple, independently-tested RNAi reagents per gene. Conclusions RNAi reagents that target the same gene do not always yield consistent results due to false positives and weak or ineffective reagents. False positive results can be partially minimized by filtering with transcriptome data. RNAi libraries with multiple reagents per gene also reduce false positive and false negative outcomes when inconsistent results are disambiguated carefully. PMID:21251254

[Roaming through methodology. XXXII. False test results].

PubMed

van der Weijden, T; van den Akker, M

2001-05-12

The number of requests for diagnostic tests is rising. This leads to a higher chance of false test results. The false-negative proportion of a test is the proportion of negative test results among the diseased subjects. The false-positive proportion is the proportion of positive test results among the healthy subjects. The calculation of the false-positive proportion is often incorrect. For example, instead of 1 minus the specificity it is calculated as 1 minus the positive predictive value. This can lead to incorrect decision-making with respect to the application of the test. Physicians must apply diagnostic tests in such a way that the risk of false test results is minimal. The patient should be aware that a perfectly conclusive diagnostic test is rare in medical practice, and should more often be informed of the implications of false-positive and false-negative test results.

Accurate decisions in an uncertain world: collective cognition increases true positives while decreasing false positives.

PubMed

Wolf, Max; Kurvers, Ralf H J M; Ward, Ashley J W; Krause, Stefan; Krause, Jens

2013-04-07

In a wide range of contexts, including predator avoidance, medical decision-making and security screening, decision accuracy is fundamentally constrained by the trade-off between true and false positives. Increased true positives are possible only at the cost of increased false positives; conversely, decreased false positives are associated with decreased true positives. We use an integrated theoretical and experimental approach to show that a group of decision-makers can overcome this basic limitation. Using a mathematical model, we show that a simple quorum decision rule enables individuals in groups to simultaneously increase true positives and decrease false positives. The results from a predator-detection experiment that we performed with humans are in line with these predictions: (i) after observing the choices of the other group members, individuals both increase true positives and decrease false positives, (ii) this effect gets stronger as group size increases, (iii) individuals use a quorum threshold set between the average true- and false-positive rates of the other group members, and (iv) individuals adjust their quorum adaptively to the performance of the group. Our results have broad implications for our understanding of the ecology and evolution of group-living animals and lend themselves for applications in the human domain such as the design of improved screening methods in medical, forensic, security and business applications.

Accurate decisions in an uncertain world: collective cognition increases true positives while decreasing false positives

PubMed Central

Wolf, Max; Kurvers, Ralf H. J. M.; Ward, Ashley J. W.; Krause, Stefan; Krause, Jens

2013-01-01

In a wide range of contexts, including predator avoidance, medical decision-making and security screening, decision accuracy is fundamentally constrained by the trade-off between true and false positives. Increased true positives are possible only at the cost of increased false positives; conversely, decreased false positives are associated with decreased true positives. We use an integrated theoretical and experimental approach to show that a group of decision-makers can overcome this basic limitation. Using a mathematical model, we show that a simple quorum decision rule enables individuals in groups to simultaneously increase true positives and decrease false positives. The results from a predator-detection experiment that we performed with humans are in line with these predictions: (i) after observing the choices of the other group members, individuals both increase true positives and decrease false positives, (ii) this effect gets stronger as group size increases, (iii) individuals use a quorum threshold set between the average true- and false-positive rates of the other group members, and (iv) individuals adjust their quorum adaptively to the performance of the group. Our results have broad implications for our understanding of the ecology and evolution of group-living animals and lend themselves for applications in the human domain such as the design of improved screening methods in medical, forensic, security and business applications. PMID:23407830

Categorizing mistaken false positives in regulation of human and environmental health.

PubMed

Hansen, Steffen Foss; Krayer von Krauss, Martin P; Tickner, Joel A

2007-02-01

One of the concerns often voiced by critics of the precautionary principle is that a widespread regulatory application of the principle will lead to a large number of false positives (i.e., over-regulation of minor risks and regulation of nonexisting risks). The present article proposes a general definition of a regulatory false positive, and seeks to identify case studies that can be considered authentic regulatory false positives. Through a comprehensive review of the science policy literature for proclaimed false positives and interviews with authorities on regulation and the precautionary principle we identified 88 cases. Following a detailed analysis of these cases, we found that few of the cases mentioned in the literature can be considered to be authentic false positives. As a result, we have developed a number of different categories for these cases of "mistaken false positives," including: real risks, "The jury is still out," nonregulated proclaimed risks, "Too narrow a definition of risk," and risk-risk tradeoffs. These categories are defined and examples are presented in order to illustrate their key characteristics. On the basis of our analysis, we were able to identify only four cases that could be defined as regulatory false positives in the light of today's knowledge and recognized uncertainty: the Southern Corn Leaf Blight, the Swine Flu, Saccharin, and Food Irradiation in relation to consumer health. We conclude that concerns about false positives do not represent a reasonable argument against future application of the precautionary principle.

Best Technical Approach Analysis (BTA) for Force Provider Wastewater Management

DTIC Science & Technology

1994-07-07

Sanitation methods involving burnout latrines and seepage pits are no longer permitted in many areas. Further, those methods are generally only applicable...and profit. * 4-3 I 4-jcrz E CO 3 I* 0U 0 c0 QQ 0 1%CDt 0 sJ19100IUMSOO 6AAlo soll~v4 l ss oUOIS~a M*. I I COLLECT PACKAGED FIELD OXIDATION AND PLANT...DISTRIBUTION: BQDA, ATTN: DALO-TST/D O-FD/DAMO-FDD/DAMO-FDL/DALO-PLZ/ DAMA-PPM/DALO-SMS/DýMO- C/DAPE- MBI CINC, USAREUR and Seventh y, ATTN: AEAGX-SA/AEAGC

Deployment of the P4 Truss SAW during Expedition 13 / STS-115 Joint Operations

NASA Image and Video Library

2006-09-15

S115-E-06184 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Sept. 12 and the deployment of the arrays set the stage for future expansion of the station.

Second set of solar arrays on the ISS during Expedition 13 / STS-115 Joint Operations

NASA Image and Video Library

2006-09-14

S115-E-06052 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Tuesday, and the deployment of the arrays set the stage for future expansion of the station.

Deployment of the P4 Truss SAW during Expedition 13 / STS-115 Joint Operations

NASA Image and Video Library

2006-09-15

S115-E-06186 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Sept. 12 and the deployment of the arrays set the stage for future expansion of the station.

Deployment of the P4 Truss FWD SAW during Expedition 13 and STS-115 EVA Joint Operations

NASA Image and Video Library

2006-09-14

S115-E-05996 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Tuesday and the deployment of the arrays set the stage for future expansion of the station.

P4 Truss FWD SAW during Expedition 13 and STS-115 EVA Joint Operations

NASA Image and Video Library

2006-09-14

S115-E-05999 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m CDT. The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Tuesday, and the deployment of the arrays set the stage for future expansion of the station.

Volkov prepares for the undocking of the ESA Jules Verne ATV during Expedition 17

NASA Image and Video Library

2008-09-05

ISS017-E-015230 (5 Sept. 2008) --- Russian Federal Space Agency cosmonaut Sergei Volkov, Expedition 17 commander, makes preparations in the International Space Station's Zvezda Service Module for the undocking of the European Space Agency's (ESA) "Jules Verne" Automated Transfer Vehicle (ATV). The ATV departed from the aft port of Zvezda at 4:29 p.m. (CDT) on Sept. 5, 2008 and was placed in a parking orbit for three weeks, scheduled to be deorbited on Sept. 29 when lighting conditions are correct for an ESA imagery experiment of reentry.

STS-114 Discovery's approach for docking

NASA Image and Video Library

2005-07-28

ISS011-E-11258 (28 July 2005) --- View of the Space Shuttle Discovery as photographed during the survey operations performed by the Expedition 11 crew on the International Space Station during the STS-114 R-Bar Pitch Maneuver on Flight Day 3. Discovery docked to the station at 6:18 a.m. (CDT) on Thursday, July 28, 2005. Parts of Switzerland are in the background. Onboard the shuttle were astronauts Eileen M. Collins, STS-114 commander; James M. Kelly, pilot; Andrew S. W. Thomas, Stephen K. Robinson, Wendy B. Lawrence, Charles J. Camarda and Japan Aerospace Exploration Agency (JAXA) astronaut Soichi Noguchi, all mission specialists.

Space Shuttle Projects

NASA Image and Video Library

1992-05-14

STS-49, the first flight of the Space Shuttle Orbiter Endeavour, lifted off from launch pad 39B on May 7, 1992 at 6:40 pm CDT. The STS-49 mission was the first U.S. orbital flight to feature 4 extravehicular activities (EVAs), and the first flight to involve 3 crew members working simultaneously outside of the spacecraft. The primary objective was the capture and redeployment of the INTELSAT VI (F-3), a communication satellite for the International Telecommunication Satellite organization, which was stranded in an unusable orbit since its launch aboard the Titan rocket in March 1990. This onboard photo captures the free flying INTELSAT IV.

Increasing Access to Modern Multidisciplinary Breast Cancer Care

DTIC Science & Technology

1998-08-01

S CD2 CD OS 0 cn CDCD r-. I-f fCf C- 0 00 ZZ CD ~ ~I II ADU ! t -l o 0 0 C CAD CD CD . j , - CD CD C >~ CD i -~ ~ ;~ CDCD C CD ~CD CD~ CDt~ CD- - -. CD... t -value Decisional Balance Barriers 6.9(2.9) 5.2(2.5) 4.36*** Promoters 12.7(1.9) 13.4(2.0) -1.97* Health Beliefs Fear 13.4(3.9) 13.2(4.2) NS Self...medical history, reproductive history, social desirability, aberrant eating patterns and depression , current behaviors and knowledge related to breast

Tuberculose chez le personnel de santé du secteur public au Burundi: fréquence et facteurs de risque

PubMed Central

Mukuku, Olivier; Ruhindiza, Bienvenu Mukuku; Mupepe, Alexis Kumba; Sawadogo, Michel

2013-01-01

Introduction Le but de cette étude était de déterminer la fréquence de la tuberculose (TB) chez le personnel de santé du secteur public en charge des patients tuberculeux et d’évaluer les facteurs de risque de contracter la tuberculose chez ce personnel au Burundi. Méthodes Il s’agit d’une étude transversale à visée analytique réalisée auprès de 300 travailleurs prestant dans 30 centres de dépistage et de traitement de la TB (CDT) au Burundi du 16 octobre au 15 novembre 2012. Les paramètres sociodémographiques et professionnels ainsi que l’antécédent de vaccination BCG de travailleurs ayant été touché par la TB ont été analysé et comparé à ceux de travailleurs qui ne l’ont pas été. Le seuil de signification a été fixé à p < 0,05. Résultats La fréquence de la TB chez le personnel de santé est de 15%. Le risque de souffrir de la TB est de près de 4 fois chez les travailleurs âgés d’au moins 50 ans (OR=3,73; 1,53-9,08), chez ceux qui n’ont jamais reçu de vaccin de BCG (OR=3,73; 1,24-11,03), chez ceux qui n’ont pas de cicatrice vaccinale de BCG (OR=3,80; 1,67-8,62) et chez ceux qui travaillent depuis au moins 6 ans dans un CDT (OR=3,79; 1,44-9,96); ce risque est de 9 fois chez ceux qui sont mariés (OR=9,42; 1,26-70,23), de 8 fois chez ceux qui n’aèrent pas leurs salles de travail (OR=8,20; 1,48-48,23) et de 6 fois chez ceux qui ont comme profession nettoyeur ou aide-soignant (OR=6,12; 2,92-12,82). Par contre, aucune corrélation statistiquement significative n’a été observée entre le fait de souffrir de la TB et le sexe mais aussi le nombre d’heures de contact d’un travailleur avec un patient tuberculeux (p>0,05). Conclusion L’âge, l’antécédent de vaccination de BCG ainsi que la majorité de paramètres professionnels sont en association avec la maladie TB des travailleurs de CDT. D’où, la maîtrise de certains facteurs de risque s’avère important pour faire face au fardeau de la TB parmi le personnel hospitalier. PMID:24847402

An analysis of false positive reactions occurring with the Captia Syph G EIA.

PubMed Central

Ross, J; Moyes, A; Young, H; McMillan, A

1991-01-01

AIM--The Captia Syph G enzyme immuno assay (EAI) offers the potential for the rapid automated detection of syphilis antibodies. This study was designed to assess the role of other sexually transmitted diseases (STDs) in producing false positive reactions in the Captia Syph G EIA. The role of rheumatoid factor (RF) as a potential source of false positives was also analysed. METHODS--Patients who attended a genitourinary medicine (GUM) department and gave a false positive reaction with the EIA between 1988 and 1990 were compared with women undergoing antenatal testing and with the control clinic population (EIA negative) over the same time period. The incidence of sexually transmitted disease (STD) in the clinic population and the false positive reactors was measured in relation to gonorrhoea, chlamydia, genital warts, candidiasis, "other conditions not requiring treatment" and "other conditions requiring treatment." Male: female sex ratios were also compared. Ninety two RF positive sera were analysed with the EIA. RESULTS--The rate of false positive reactions did not differ with respect to the diagnosis within the GUM clinic population. The antenatal group of women, however, had a lower incidence of false positive reactions than the GUM clinic group. No RF positive sera were positive on Captia Syph G EIA testing. CONCLUSIONS--There is no cross reaction between Captia Syph G EIA and any specific STD or with RF positive sera. The lower incidence of false positive reactions in antenatal women is unexplained but may be related to physiological changes associated with pregnancy. PMID:1743715

Frequency of false positive rapid HIV serologic tests in African men and women receiving PrEP for HIV prevention: implications for programmatic roll-out of biomedical interventions.

PubMed

Ndase, Patrick; Celum, Connie; Kidoguchi, Lara; Ronald, Allan; Fife, Kenneth H; Bukusi, Elizabeth; Donnell, Deborah; Baeten, Jared M

2015-01-01

Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results. We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests. A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits. When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.

Experimental investigation of observation error in anuran call surveys

USGS Publications Warehouse

McClintock, B.T.; Bailey, L.L.; Pollock, K.H.; Simons, T.R.

2010-01-01

Occupancy models that account for imperfect detection are often used to monitor anuran and songbird species occurrence. However, presenceabsence data arising from auditory detections may be more prone to observation error (e.g., false-positive detections) than are sampling approaches utilizing physical captures or sightings of individuals. We conducted realistic, replicated field experiments using a remote broadcasting system to simulate simple anuran call surveys and to investigate potential factors affecting observation error in these studies. Distance, time, ambient noise, and observer abilities were the most important factors explaining false-negative detections. Distance and observer ability were the best overall predictors of false-positive errors, but ambient noise and competing species also affected error rates for some species. False-positive errors made up 5 of all positive detections, with individual observers exhibiting false-positive rates between 0.5 and 14. Previous research suggests false-positive errors of these magnitudes would induce substantial positive biases in standard estimators of species occurrence, and we recommend practices to mitigate for false positives when developing occupancy monitoring protocols that rely on auditory detections. These recommendations include additional observer training, limiting the number of target species, and establishing distance and ambient noise thresholds during surveys. ?? 2010 The Wildlife Society.

Memory for media: investigation of false memories for negatively and positively charged public events.

PubMed

Porter, Stephen; Taylor, Kristian; Ten Brinke, Leanne

2008-01-01

Despite a large body of false memory research, little has addressed the potential influence of an event's emotional content on susceptibility to false recollections. The Paradoxical Negative Emotion (PNE) hypothesis predicts that negative emotion generally facilitates memory but also heightens susceptibility to false memories. Participants were asked whether they could recall 20 "widely publicised" public events (half fictitious) ranging in emotional valence, with or without visual cues. Participants recalled a greater number of true negative events (M=3.31/5) than true positive (M=2.61/5) events. Nearly everyone (95%) came to recall at least one false event (M=2.15 false events recalled). Further, more than twice as many participants recalled any false negative (90%) compared to false positive (41.7%) events. Negative events, in general, were associated with more detailed memories and false negative event memories were more detailed than false positive event memories. Higher dissociation scores were associated with false recollections of negative events, specifically.

Generalized site occupancy models allowing for false positive and false negative errors

USGS Publications Warehouse

Royle, J. Andrew; Link, W.A.

2006-01-01

Site occupancy models have been developed that allow for imperfect species detection or ?false negative? observations. Such models have become widely adopted in surveys of many taxa. The most fundamental assumption underlying these models is that ?false positive? errors are not possible. That is, one cannot detect a species where it does not occur. However, such errors are possible in many sampling situations for a number of reasons, and even low false positive error rates can induce extreme bias in estimates of site occupancy when they are not accounted for. In this paper, we develop a model for site occupancy that allows for both false negative and false positive error rates. This model can be represented as a two-component finite mixture model and can be easily fitted using freely available software. We provide an analysis of avian survey data using the proposed model and present results of a brief simulation study evaluating the performance of the maximum-likelihood estimator and the naive estimator in the presence of false positive errors.

Comparison of 4th-Generation HIV Antigen/Antibody Combination Assay With 3rd-Generation HIV Antibody Assays for the Occurrence of False-Positive and False-Negative Results.

PubMed

Muthukumar, Alagarraju; Alatoom, Adnan; Burns, Susan; Ashmore, Jerry; Kim, Anne; Emerson, Brian; Bannister, Edward; Ansari, M Qasim

2015-01-01

To assess the false-positive and false-negative rates of a 4th-generation human immunodeficiency virus (HIV) assay, the Abbott ARCHITECT, vs 2 HIV 3rd-generation assays, the Siemens Centaur and the Ortho-Clinical Diagnostics Vitros. We examined 123 patient specimens. In the first phase of the study, we compared 99 specimens that had a positive screening result via the 3rd-generation Vitros assay (10 positive, 82 negative, and 7 indeterminate via confirmatory immunofluorescent assay [IFA]/Western blot [WB] testing). In the second phase, we assessed 24 HIV-1 RNA-positive (positive result via the nuclear acid amplification test [NAAT] and negative/indeterminate results via the WB test) specimens harboring acute HIV infection. The 4th-generation ARCHITECT assay yielded fewer false-positive results (n = 2) than the 3rd-generation Centaur (n = 9; P = .02) and Vitros (n = 82; P <.001) assays. One confirmed positive case had a false-negative result via the Centaur assay. When specimens from the 24 patients with acute HIV-1 infection were tested, the ARCHITECT assay yielded fewer false-negative results (n = 5) than the Centaur (n = 10) (P = .13) and the other 3rd-generation tests (n = 16) (P = .002). This study indicates that the 4th-generation ARCHITECT HIV assay yields fewer false-positive and false-negative results than the 3rd-generation HIV assays we tested. Copyright© by the American Society for Clinical Pathology (ASCP).

Clinical usefulness of the clock drawing test applying rasch analysis in predicting of cognitive impairment.

PubMed

Yoo, Doo Han; Lee, Jae Shin

2016-07-01

[Purpose] This study examined the clinical usefulness of the clock drawing test applying Rasch analysis for predicting the level of cognitive impairment. [Subjects and Methods] A total of 187 stroke patients with cognitive impairment were enrolled in this study. The 187 patients were evaluated by the clock drawing test developed through Rasch analysis along with the mini-mental state examination of cognitive evaluation tool. An analysis of the variance was performed to examine the significance of the mini-mental state examination and the clock drawing test according to the general characteristics of the subjects. Receiver operating characteristic analysis was performed to determine the cutoff point for cognitive impairment and to calculate the sensitivity and specificity values. [Results] The results of comparison of the clock drawing test with the mini-mental state showed significant differences in according to gender, age, education, and affected side. A total CDT of 10.5, which was selected as the cutoff point to identify cognitive impairement, showed a sensitivity, specificity, Youden index, positive predictive, and negative predicive values of 86.4%, 91.5%, 0.8, 95%, and 88.2%. [Conclusion] The clock drawing test is believed to be useful in assessments and interventions based on its excellent ability to identify cognitive disorders.

A multimodal physical therapy approach to the management of a patient with temporomandibular dysfunction and head and neck lymphedema: a case report

PubMed Central

Crane, Patricia; Feinberg, Lauren; Morris, John

2015-01-01

Objective and importance: There is a paucity of research that investigates therapeutic interventions of patients with concurrent head and neck lymphedema and temporomandibular dysfunction (TMD). The purpose of this case report is to describe the management and outcomes of a patient with head and neck lymphedema and TMD using a multimodal physical therapy approach. Clinical presentation: A 74-year-old male with a past medical history of head and neck lymphedema and TMD was referred to physical therapy with chief complaints of inability to open his mouth in order to eat solid food, increased neck lymphedema, temporomadibular joint pain, and inability to speak for prolonged periods of time. Interventions: The patient was treated for three visits over 4 weeks. Treatment included complete decongestive therapy (CDT), manual therapy, therapeutic exercise, and a home exercise program. Upon discharge, the patient had improved mandibular depression, decreased head and neck lymphedema, improved deep neck flexor endurance, decreased pain, and improved function on the Patient Specific Functional Scale (PSFS). Conclusion: Utilization of a multimodal physical therapy approach to treat a patient with a complex presentation yielded positive outcomes. Further research on outcomes and treatment approaches in patients with TMD and head and neck lymphedema is warranted. PMID:26309380

A multimodal physical therapy approach to the management of a patient with temporomandibular dysfunction and head and neck lymphedema: a case report.

PubMed

Crane, Patricia; Feinberg, Lauren; Morris, John

2015-02-01

There is a paucity of research that investigates therapeutic interventions of patients with concurrent head and neck lymphedema and temporomandibular dysfunction (TMD). The purpose of this case report is to describe the management and outcomes of a patient with head and neck lymphedema and TMD using a multimodal physical therapy approach. A 74-year-old male with a past medical history of head and neck lymphedema and TMD was referred to physical therapy with chief complaints of inability to open his mouth in order to eat solid food, increased neck lymphedema, temporomadibular joint pain, and inability to speak for prolonged periods of time. The patient was treated for three visits over 4 weeks. Treatment included complete decongestive therapy (CDT), manual therapy, therapeutic exercise, and a home exercise program. Upon discharge, the patient had improved mandibular depression, decreased head and neck lymphedema, improved deep neck flexor endurance, decreased pain, and improved function on the Patient Specific Functional Scale (PSFS). Utilization of a multimodal physical therapy approach to treat a patient with a complex presentation yielded positive outcomes. Further research on outcomes and treatment approaches in patients with TMD and head and neck lymphedema is warranted.

False-positive alarms for bacterial screening of platelet concentrates with BacT/ALERT new-generation plastic bottles: a multicenter pilot study.

PubMed

Hundhausen, T; Müller, T H

2005-08-01

The microbial detection system BacT/ALERT (bioMérieux) is widely used to monitor bacterial contamination of platelet concentrates (PCs). Recently, the manufacturer introduced polycarbonate culture bottles and a modified pH-sensitive liquid emulsion sensor as microbial growth indicator. This reconfigured assay was investigated in a routine setting. In each of eight transfusion centers, samples from 500 consecutive PCs were monitored for 1 week. For all PCs with a positive BacT/ALERT signal, retained samples and, if available, original PC containers and concomitant red blood cell concentrates were analyzed independently. Initially BacT/ALERT-positive PCs without bacterial identification in any sample were defined as false-positive. BacT/ALERT-positive PCs with bacteria in the first sample only were called potentially positive. PCs with bacteria in the first sample and the same strain in at least one additional sample were accepted as positive. Five PCs (0.13%) were positive, 9 PCs (0.23%) were potentially positive, and 35 PCs (0.9%) were false-positive. The rate of false-positive BacT/ALERT results varied substantially between centers (<0.2%-3.2%). Tracings from false-positive cultures lacked an exponential increase of the signal during incubation. Most of these false-positives were due to malfunctioning cells in various BacT/ALERT incubation units. Careful assessment of individual tracings of samples with positive signals helps to identify malfunctioning incubation units. Their early shutdown or replacement minimizes the high rate of unrectifiable product rejects attributed to false-positive alarms and avoids unnecessary concern of doctors and patients after conversion to a reconfigured BacT/ALERT assay.

Functional territories in primate substantia nigra pars reticulata separately signaling stable and flexible values

PubMed Central

Hikosaka, Okihide

2014-01-01

Gaze is strongly attracted to visual objects that have been associated with rewards. Key to this function is a basal ganglia circuit originating from the caudate nucleus (CD), mediated by the substantia nigra pars reticulata (SNr), and aiming at the superior colliculus (SC). Notably, subregions of CD encode values of visual objects differently: stably by CD tail [CD(T)] vs. flexibly by CD head [CD(H)]. Are the stable and flexible value signals processed separately throughout the CD-SNr-SC circuit? To answer this question, we identified SNr neurons by their inputs from CD and outputs to SC and examined their sensitivity to object values. The direct input from CD was identified by SNr neuron's inhibitory response to electrical stimulation of CD. We found that SNr neurons were separated into two groups: 1) neurons inhibited by CD(T) stimulation, located in the caudal-dorsal-lateral SNr (cdlSNr), and 2) neurons inhibited by CD(H) stimulation, located in the rostral-ventral-medial SNr (rvmSNr). Most of CD(T)-recipient SNr neurons encoded stable values, whereas CD(H)-recipient SNr neurons tended to encode flexible values. The output to SC was identified by SNr neuron's antidromic response to SC stimulation. Among the antidromically activated neurons, many encoded only stable values, while some encoded only flexible values. These results suggest that CD(T)-cdlSNr-SC circuit and CD(H)-rvmSNr-SC circuit transmit stable and flexible value signals, largely separately, to SC. The speed of signal transmission was faster through CD(T)-cdlSNr-SC circuit than through CD(H)-rvmSNr-SC circuit, which may reflect automatic and controlled gaze orienting guided by these circuits. PMID:25540224

A dual-color marker system for in vivo visualization of cell cycle progression in Arabidopsis.

PubMed

Yin, Ke; Ueda, Minako; Takagi, Hitomi; Kajihara, Takehiro; Sugamata Aki, Shiori; Nobusawa, Takashi; Umeda-Hara, Chikage; Umeda, Masaaki

2014-11-01

Visualization of the spatiotemporal pattern of cell division is crucial to understand how multicellular organisms develop and how they modify their growth in response to varying environmental conditions. The mitotic cell cycle consists of four phases: S (DNA replication), M (mitosis and cytokinesis), and the intervening G1 and G2 phases; however, only G2/M-specific markers are currently available in plants, making it difficult to measure cell cycle duration and to analyze changes in cell cycle progression in living tissues. Here, we developed another cell cycle marker that labels S-phase cells by manipulating Arabidopsis CDT1a, which functions in DNA replication origin licensing. Truncations of the CDT1a coding sequence revealed that its carboxy-terminal region is responsible for proteasome-mediated degradation at late G2 or in early mitosis. We therefore expressed this region as a red fluorescent protein fusion protein under the S-specific promoter of a histone 3.1-type gene, HISTONE THREE RELATED2 (HTR2), to generate an S/G2 marker. Combining this marker with the G2/M-specific CYCB1-GFP marker enabled us to visualize both S to G2 and G2 to M cell cycle stages, and thus yielded an essential tool for time-lapse imaging of cell cycle progression. The resultant dual-color marker system, Cell Cycle Tracking in Plant Cells (Cytrap), also allowed us to identify root cells in the last mitotic cell cycle before they entered the endocycle. Our results demonstrate that Cytrap is a powerful tool for in vivo monitoring of the plant cell cycle, and thus for deepening our understanding of cell cycle regulation in particular cell types during organ development. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Experimental Psychological Stress on Quantitative Sensory Testing Response in Patients with Temporomandibular Disorders.

PubMed

Araújo Oliveira Ferreira, Dyna Mara; Costa, Yuri Martins; de Quevedo, Henrique Müller; Bonjardim, Leonardo Rigoldi; Rodrigues Conti, Paulo César

2018-05-15

To assess the modulatory effects of experimental psychological stress on the somatosensory evaluation of myofascial temporomandibular disorder (TMD) patients. A total of 20 women with myofascial TMD and 20 age-matched healthy women were assessed by means of a standardized battery of quantitative sensory testing. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR), and pressure pain threshold (PPT) were performed on the facial skin overlying the masseter muscle. The variables were measured in three sessions: before (baseline) and immediately after the Paced Auditory Serial Addition Task (PASAT) (stress) and then after a washout period of 20 to 30 minutes (poststress). Mixed analysis of variance (ANOVA) was applied to the data, and the significance level was set at P = .050. A significant main effect of the experimental session on all thermal tests was found (ANOVA: F > 4.10, P < .017), where detection tests presented an increase in thresholds in the poststress session compared to baseline (CDT, P = .012; WDT, P = .040) and pain thresholds were reduced in the stress (CPT, P < .001; HPT, P = .001) and poststress sessions (CPT, P = .005; HPT, P = .006) compared to baseline. In addition, a significant main effect of the study group on all mechanical tests (MPT, WUR, and PPT) was found (ANOVA: F > 4.65, P < .037), where TMD patients were more sensitive than healthy volunteers. Acute mental stress conditioning can modulate thermal sensitivity of the skin overlying the masseter in myofascial TMD patients and healthy volunteers. Therefore, psychological stress should be considered in order to perform an unbiased somatosensory assessment of TMD patients.

Scenery Picture Memory Test: A new type of quick and effective screening test to detect early stage Alzheimer’s disease patients

PubMed Central

Takechi, Hajime; Dodge, Hiroko H

2010-01-01

Aim It is highly desirable to develop a neuropsychological screening test which is sensitive to the early stage of Alzheimer’s disease (AD), and is easy to administer at the primary care physician’s (PCP’s) office. Methods Participants were 128 AD patients and 54 healthy volunteers. Brief cognitive screening tests were administered to the participants including the Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Verbal Fluency Test (VFT), a Verbal Category Cued Memory test (CCMT) and the Scenery Picture Memory Test (SPMT). In the SPMT, a scenery picture of a living room containing 23 familiar objects was used. The administration of the SPMT comprised the first shallow memory session (Pict 1) and the second deep memory session (Pict 2). The area under the receiver–operator curve (AUC) was used to compare the efficacy of SPMT with other cognitive tests. Results Pict 1, which requires less than 2 min to complete, had the same AUC as Pict 2, and showed significantly larger AUC than MMSE, CDT and VFT for all (MMSE 19–23) and very mild (MMSE ≥ 24) AD patients. When we conducted the similar analysis separately for those younger than 75 years and those aged 75 years or older, we obtained the same results as above among the older age group. Pict 1 showed larger AUC than CCMT in overall sample and also in the older age group, although the difference was not statistically significant. Conclusion The SPMT could be useful for detection of mild and very mild AD in settings even where time is limited. PMID:20446933

Development of a prototype chest digital tomosynthesis (CDT) R/F system with fast image reconstruction using graphics processing unit (GPU) programming

NASA Astrophysics Data System (ADS)

Choi, Sunghoon; Lee, Seungwan; Lee, Haenghwa; Lee, Donghoon; Choi, Seungyeon; Shin, Jungwook; Seo, Chang-Woo; Kim, Hee-Joung

2017-03-01

Digital tomosynthesis offers the advantage of low radiation doses compared to conventional computed tomography (CT) by utilizing small numbers of projections ( 80) acquired over a limited angular range. It produces 3D volumetric data, although there are artifacts due to incomplete sampling. Based upon these characteristics, we developed a prototype digital tomosynthesis R/F system for applications in chest imaging. Our prototype chest digital tomosynthesis (CDT) R/F system contains an X-ray tube with high power R/F pulse generator, flat-panel detector, R/F table, electromechanical radiographic subsystems including a precise motor controller, and a reconstruction server. For image reconstruction, users select between analytic and iterative reconstruction methods. Our reconstructed images of Catphan700 and LUNGMAN phantoms clearly and rapidly described the internal structures of phantoms using graphics processing unit (GPU) programming. Contrast-to-noise ratio (CNR) values of the CTP682 module of Catphan700 were higher in images using a simultaneous algebraic reconstruction technique (SART) than in those using filtered back-projection (FBP) for all materials by factors of 2.60, 3.78, 5.50, 2.30, 3.70, and 2.52 for air, lung foam, low density polyethylene (LDPE), Delrin® (acetal homopolymer resin), bone 50% (hydroxyapatite), and Teflon, respectively. Total elapsed times for producing 3D volume were 2.92 s and 86.29 s on average for FBP and SART (20 iterations), respectively. The times required for reconstruction were clinically feasible. Moreover, the total radiation dose from our system (5.68 mGy) was lower than that of conventional chest CT scan. Consequently, our prototype tomosynthesis R/F system represents an important advance in digital tomosynthesis applications.

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.

PubMed

Ciezka, Magdalena; Acosta, Milena; Herranz, Cristina; Canals, Josep M; Pumarola, Martí; Candiota, Ana Paula; Arús, Carles

2016-08-01

The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

Short-term and long-term effect of diaphragm biofeedback training in gastroesophageal reflux disease: an open-label, pilot, randomized trial.

PubMed

Sun, X; Shang, W; Wang, Z; Liu, X; Fang, X; Ke, M

2016-10-01

This study investigated the effectiveness of diaphragm biofeedback training (DBT) for patients with gastroesophageal reflux disease (GERD). A total of 40 patients with GERD treated at the Peking Union Medical College Hospital between September 2004 and July 2006 were randomized to receive DBT and rabeprazole proton pump inhibitor (PPI) or rabeprazole alone. The DBT + rabeprazole group received DBT during the 8-week initial treatment; the rabeprazole group did not. During the 6-month follow up, all patients took acid suppression according to their reflux symptoms, and the patients in the DBT + rabeprazole group were required to continue DBT. The primary outcome (used for power analysis) was the amount of acid suppression used at 6 months. Secondary outcomes were reflux symptoms, health-related quality of life (HRQL), and esophageal motility differences after the 8-week treatment compared with baseline. Acid suppression usage significantly decreased in the DBT + rabeprazole group compared with the rabeprazole group at 6 months (P < 0.05). At 8 weeks, reflux symptoms and GERD-HRQL were significantly improved in both groups (P < 0.05), without difference between them. Crural diaphragm tension (CDT) and gastroesophageal junction pressure (GEJP) significantly increased in the DBT + rabeprazole group (P < 0.05), but without change in lower esophageal sphincter (LES) pressure. There was no significant change in CDT, GEJP, and LES pressure compared with baseline in the rabeprazole group. In conclusion, long-term DBT could reduce acid suppression usage by enhancing the anti-reflux barrier, providing a non-pharmacological maintenance therapy and reducing medical costs for patients with GERD. © 2015 International Society for Diseases of the Esophagus.

Chemometric differentiation of crude oil families in the San Joaquin Basin, California

USGS Publications Warehouse

Peters, Kenneth E.; Coutrot, Delphine; Nouvelle, Xavier; Ramos, L. Scott; Rohrback, Brian G.; Magoon, Leslie B.; Zumberge, John E.

2013-01-01

Chemometric analyses of geochemical data for 165 crude oil samples from the San Joaquin Basin identify genetically distinct oil families and their inferred source rocks and provide insight into migration pathways, reservoir compartments, and filling histories. In the first part of the study, 17 source-related biomarker and stable carbon-isotope ratios were evaluated using a chemometric decision tree (CDT) to identify families. In the second part, ascendant hierarchical clustering was applied to terpane mass chromatograms for the samples to compare with the CDT results. The results from the two methods are remarkably similar despite differing data input and assumptions. Recognized source rocks for the oil families include the (1) Eocene Kreyenhagen Formation, (2) Eocene Tumey Formation, (3–4) upper and lower parts of the Miocene Monterey Formation (Buttonwillow depocenter), and (5–6) upper and lower parts of the Miocene Monterey Formation (Tejon depocenter). Ascendant hierarchical clustering identifies 22 oil families in the basin as corroborated by independent data, such as carbon-isotope ratios, sample location, reservoir unit, and thermal maturity maps from a three-dimensional basin and petroleum system model. Five families originated from the Eocene Kreyenhagen Formation source rock, and three families came from the overlying Eocene Tumey Formation. Fourteen families migrated from the upper and lower parts of the Miocene Monterey Formation source rocks within the Buttonwillow and Tejon depocenters north and south of the Bakersfield arch. The Eocene and Miocene families show little cross-stratigraphic migration because of seals within and between the source rocks. The data do not exclude the possibility that some families described as originating from the Monterey Formation actually came from source rock in the Temblor Formation.

Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function

DOE PAGES

Sun, Jingchuan; Li, Huilin; Fernandez-Cid, Alejandra; ...

2014-10-15

Eukaryotic cells license each DNA replication origin during G1 phase by assembling a prereplication complex that contains a Mcm2–7 (minichromosome maintenance proteins 2–7) double hexamer. During S phase, each Mcm2–7 hexamer forms the core of a replicative DNA helicase. However, the mechanisms of origin licensing and helicase activation are poorly understood. The helicase loaders ORC–Cdc6 function to recruit a single Cdt1–Mcm2–7 heptamer to replication origins prior to Cdt1 release and ORC–Cdc6–Mcm2–7 complex formation, but how the second Mcm2–7 hexamer is recruited to promote double-hexamer formation is not well understood. Here, structural evidence for intermediates consisting of an ORC–Cdc6–Mcm2–7 complex andmore » an ORC–Cdc6–Mcm2–7–Mcm2–7 complex are reported, which together provide new insights into DNA licensing. Detailed structural analysis of the loaded Mcm2–7 double-hexamer complex demonstrates that the two hexamers are interlocked and misaligned along the DNA axis and lack ATP hydrolysis activity that is essential for DNA helicase activity. Moreover, we show that the head-to-head juxtaposition of the Mcm2–7 double hexamer generates a new protein interaction surface that creates a multisubunit-binding site for an S-phase protein kinase that is known to activate DNA replication. The data suggest how the double hexamer is assembled and how helicase activity is regulated during DNA licensing, with implications for cell cycle control of DNA replication and genome stability.« less

GPU-accelerated compressed-sensing (CS) image reconstruction in chest digital tomosynthesis (CDT) using CUDA programming

NASA Astrophysics Data System (ADS)

Choi, Sunghoon; Lee, Haenghwa; Lee, Donghoon; Choi, Seungyeon; Shin, Jungwook; Jang, Woojin; Seo, Chang-Woo; Kim, Hee-Joung

2017-03-01

A compressed-sensing (CS) technique has been rapidly applied in medical imaging field for retrieving volumetric data from highly under-sampled projections. Among many variant forms, CS technique based on a total-variation (TV) regularization strategy shows fairly reasonable results in cone-beam geometry. In this study, we implemented the TV-based CS image reconstruction strategy in our prototype chest digital tomosynthesis (CDT) R/F system. Due to the iterative nature of time consuming processes in solving a cost function, we took advantage of parallel computing using graphics processing units (GPU) by the compute unified device architecture (CUDA) programming to accelerate our algorithm. In order to compare the algorithmic performance of our proposed CS algorithm, conventional filtered back-projection (FBP) and simultaneous algebraic reconstruction technique (SART) reconstruction schemes were also studied. The results indicated that the CS produced better contrast-to-noise ratios (CNRs) in the physical phantom images (Teflon region-of-interest) by factors of 3.91 and 1.93 than FBP and SART images, respectively. The resulted human chest phantom images including lung nodules with different diameters also showed better visual appearance in the CS images. Our proposed GPU-accelerated CS reconstruction scheme could produce volumetric data up to 80 times than CPU programming. Total elapsed time for producing 50 coronal planes with 1024×1024 image matrix using 41 projection views were 216.74 seconds for proposed CS algorithms on our GPU programming, which could match the clinically feasible time ( 3 min). Consequently, our results demonstrated that the proposed CS method showed a potential of additional dose reduction in digital tomosynthesis with reasonable image quality in a fast time.

Rapid and high-precision measurement of sulfur isotope and sulfur concentration in sediment pore water by multi-collector inductively coupled plasma mass spectrometry.

PubMed

Bian, Xiao-Peng; Yang, Tao; Lin, An-Jun; Jiang, Shao-Yong

2015-01-01

We have developed a technique for the rapid, precise and accurate determination of sulfur isotopes (δ(34)S) by MC-ICP-MS applicable to a range of sulfur-bearing solutions of different sulfur content. The 10 ppm Alfa-S solution (ammonium sulfate solution, working standard of the lab of the authors) was used to bracket other Alfa-S solutions of different concentrations and the measured δ(34)SV-CDT values of Alfa-S solutions deviate from the reference value to varying degrees (concentration effect). The stability of concentration effect has been verified and a correction curve has been constructed based on Alfa-S solutions to correct measured δ(34)SV-CDT values. The curve has been applied to AS solutions (dissolved ammonium sulfate from the lab of the authors) and pore water samples successfully, validating the reliability of our analytical method. This method also enables us to measure the sulfur concentration simultaneously when analyzing the sulfur isotope composition. There is a strong linear correlation (R(2)>0.999) between the sulfur concentrations and the intensity ratios of samples and the standard. We have constructed a regression curve based on Alfa-S solutions and this curve has been successfully used to determine sulfur concentrations of AS solutions and pore water samples. The analytical technique presented here enable rapid, precise and accurate S isotope measurement for a wide range of sulfur-bearing solutions - in particular for pore water samples with complex matrix and varying sulfur concentrations. Also, simultaneous measurement of sulfur concentrations is available. Copyright © 2014 Elsevier B.V. All rights reserved.

Gait and risk of falls associated with frontal cognitive functions at different stages of Alzheimer's disease.

PubMed

Coelho, Flávia Gomes de Melo; Stella, Florindo; de Andrade, Larissa Pires; Barbieri, Fabio Augusto; Santos-Galduróz, Ruth Ferreira; Gobbi, Sebastião; Costa, José Luiz Riani; Gobbi, Lilian Teresa Bucken

2012-09-01

The decline in frontal cognitive functions contributes to alterations of gait and increases the risk of falls in patients with dementia, a category which included Alzheimer's disease (AD). The objective of the present study was to compare the gait parameters and the risk of falls among patients at different stages of AD, and to relate these variables with cognitive functions. This is a cross-sectional study with 23 patients with mild and moderate AD. The Clinical Dementia Rating was used to classify the dementia severity. The kinematic parameters of gait (cadence, stride length, and stride speed) were analyzed under two conditions: (a) single task (free gait) and (b) dual task (walking and counting down). The risk of falls was evaluated using the Timed Up-and-Go test. The frontal cognitive functions were evaluated using the Frontal Assessment Battery (FAB), the Clock Drawing Test (CDT) and the Symbol Search Subtest. The patients who were at the moderate stage suffered reduced performance in their stride length and stride speed in the single task and had made more counting errors in the dual task and still had a higher fall risk. Both the mild and the moderate patients exhibited significant decreases in stride length, stride speed and cadence in the dual task. Was detected a significant correlation between CDT, FAB, and stride speed in the dual task condition. We also found a significant correlation between subtest Similarities, FAB and cadence in the dual task condition. The dual task produced changes in the kinematic parameters of gait for the mild and moderate AD patients and the gait alterations are related to frontal cognitive functions, particularly executive functions.

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents.

PubMed

Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

2015-07-09

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents.

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents

PubMed Central

Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

2015-01-01

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents. PMID:26158513

Effects of Cu2+ and humic acids on degradation and fate of TBBPA in pure culture of Pseudomonas sp. strain CDT.

PubMed

Ma, Yini; Zhao, Yingying; Wang, Yongfeng; Li, Xiangzhen; Sun, Feifei; Corvini, Phillippe Francois-Xavier; Ji, Rong

2017-12-01

Soil contamination with tetrabromobisphenol A (TBBPA) has caused great concerns; however, the presence of heavy metals and soil organic matter on the biodegradation of TBBPA is still unclear. We isolated Pseudomonas sp. strain CDT, a TBBPA-degrading bacterium, from activated sludge and incubated it with 14 C-labeled TBBPA for 87 days in the absence and presence of Cu 2+ and humic acids (HA). TBBPA was degraded to organic-solvent extractable (59.4%±2.2%) and non-extractable (25.1%±1.3%) metabolites, mineralized to CO 2 (4.8%±0.8%), and assimilated into cells (10.6%±0.9%) at the end of incubation. When Cu 2+ was present, the transformation of extractable metabolites into non-extractable metabolites and mineralization were inhibited, possibly due to the toxicity of Cu 2+ to cells. HA significantly inhibited both dissipation and mineralization of TBBPA and altered the fate of TBBPA in the culture by formation of HA-bound residues that amounted to 22.1%±3.7% of the transformed TBBPA. The inhibition from HA was attributed to adsorption of TBBPA and formation of bound residues with HA via reaction of reactive metabolites with HA molecules, which decreased bioavailability of TBBPA and metabolites in the culture. When Cu 2+ and HA were both present, Cu 2+ significantly promoted the HA inhibition on TBBPA dissipation but not on metabolite degradation. The results provide insights into individual and interactive effects of Cu 2+ and soil organic matter on the biotransformation of TBBPA and indicate that soil organic matter plays an essential role in determining the fate of organic pollutants in soil and mitigating heavy metal toxicity. Copyright © 2017. Published by Elsevier B.V.

Transthyretin familial amyloid polyneuropathy (TTR-FAP): Parameters for early diagnosis.

PubMed

Escolano-Lozano, Fabiola; Barreiros, Ana Paula; Birklein, Frank; Geber, Christian

2018-01-01

Familial transthyretin amyloidosis is a life-threatening disease presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has a detrimental effect on treatment and prognosis. To facilitate diagnosis, we analyzed data patterns of patients with transthyretin familial amyloid polyneuropathy (TTR-FAP) and compared them to polyneuropathies of different etiology for clinical and electrophysiological discriminators. Twenty-four patients with TTR-FAP and 48 patients with diabetic polyneuropathy (dPNP) were investigated (neurological impairment score NIS; neurological disability score NDS) in a cross-sectional design. Both groups were matched for gender and presence of pain. Quantitative sensory testing (QST), sympathetic skin response (SSR), heart rate variability (HRV), and nerve conduction studies (NCV) were performed. Both groups were compared using univariate analysis. In a stepwise discriminant analysis, discriminators between both neuropathies were identified. These discriminators were validated comparing TTR-FAP patients with a cohort of patients with chemotherapy-induced polyneuropathy (CIN) and chronic inflammatory demyelinating neuropathy (CIDP). TTR-FAP patients scored higher in NDS and NIS and had impaired cold detection (CDT, p  = .024), cold-warm discrimination (TSL, p  = .019) and mechanical hyperalgesia (MPT, p  = .029) at the hands, SSR (upper limb, p  = .022) HRV and ulnar and sural NCS (all p  < .05) were more affected in TTR-FAP. Ulnar nerve sensory NCV, CDT, and the MPT but not the other parameters discriminated TTR-FAP from dPNP (82% of cases), from CIN (86.7%) and from CIDP (68%; only ulnar sNCV). Low ulnar SNCV, impaired cold perception, and mechanical hyperalgesia at the hands seem to characterize TTR-FAP and might help to differentiate from other polyneuropathies.

Is there a positive bias in false recognition? Evidence from confabulating amnesia patients.

PubMed

Alkathiri, Nura H; Morris, Robin G; Kopelman, Michael D

2015-10-01

Although there is some evidence for a positive emotional bias in the content of confabulations in brain damaged patients, findings have been inconsistent. The present study used the semantic-associates procedure to induce false recall and false recognition in order to examine whether a positive bias would be found in confabulating amnesic patients, relative to non-confabulating amnesic patients and healthy controls. Lists of positive, negative and neutral words were presented in order to induce false recall or false recognition of non-presented (but semantically associated) words. The latter were termed 'critical intrusions'. Thirteen confabulating amnesic patients, 13 non-confabulating amnesic patients and 13 healthy controls were investigated. Confabulating patients falsely recognised a higher proportion of positive (but unrelated) words, compared with non-confabulating patients and healthy controls. No differences were found for recall memory. Signal detection analysis, however, indicated that the positive bias for false recognition memory might reflect weaker memory in the confabulating amnesic group. This suggested that amnesia patients with weaker memory are more likely to confabulate and the content of these confabulations are more likely to be positive. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

NASA Astrophysics Data System (ADS)

Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

2009-02-01

Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study.

PubMed

Karaceper, Maria D; Chakraborty, Pranesh; Coyle, Doug; Wilson, Kumanan; Kronick, Jonathan B; Hawken, Steven; Davies, Christine; Brownell, Marni; Dodds, Linda; Feigenbaum, Annette; Fell, Deshayne B; Grosse, Scott D; Guttmann, Astrid; Laberge, Anne-Marie; Mhanni, Aizeddin; Miller, Fiona A; Mitchell, John J; Nakhla, Meranda; Prasad, Chitra; Rockman-Greenberg, Cheryl; Sparkes, Rebecca; Wilson, Brenda J; Potter, Beth K

2016-02-03

There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use. We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life. The higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.

Accounting for false-positive acoustic detections of bats using occupancy models

USGS Publications Warehouse

Clement, Matthew J.; Rodhouse, Thomas J.; Ormsbee, Patricia C.; Szewczak, Joseph M.; Nichols, James D.

2014-01-01

4. Synthesis and applications. Our results suggest that false positives sufficient to affect inferences may be common in acoustic surveys for bats. We demonstrate an approach that can estimate occupancy, regardless of the false-positive rate, when acoustic surveys are paired with capture surveys. Applications of this approach include monitoring the spread of White-Nose Syndrome, estimating the impact of climate change and informing conservation listing decisions. We calculate a site-specific probability of occupancy, conditional on survey results, which could inform local permitting decisions, such as for wind energy projects. More generally, the magnitude of false positives suggests that false-positive occupancy models can improve accuracy in research and monitoring of bats and provide wildlife managers with more reliable information.

Analysis of false results in a series of 835 fine needle aspirates of breast lesions.

PubMed

Willis, S L; Ramzy, I

1995-01-01

To analyze cases of false diagnoses from a large series to help increase the accuracy of fine needle aspiration of palpable breast lesions. The results of FNA of 835 palpable breast lesions were analyzed to determine the reasons for false positive, false negative and false suspicious diagnoses. Of the 835 aspirates, 174 were reported as positive, 549 as negative and 66 as suspicious or atypical but not diagnostic of malignancy. Forty-six cases were considered unsatisfactory. Tissue was available for comparison in 286 cases. The cytologic diagnoses in these cases were reported as follows: positive, 125 (43.7%); suspicious, 33 (11.5%); atypical, 18 (6.2%); negative, 92 (32%); and unsatisfactory, 18 (6.2%). There was one false positive diagnosis, yielding a false positive rate of 0.8%. This lesion was a case of fibrocystic change with hyperplasia, focal fat necrosis and reparative atypia. There were 14 false negative cases, resulting in a false negative rate of 13.2%. Nearly all these cases were sampling errors and included infiltrating ductal carcinomas (9), ductal carcinomas in situ (2), infiltrating lobular carcinomas (2) and tubular carcinoma (1). Most of the suspicious and atypical lesions proved to be carcinomas (35/50). The remainder were fibroadenomas (6), fibrocystic change (4), gynecomastia (2), adenosis (2) and granulomatous mastitis (1). A positive diagnosis of malignancy by FNA is reliable in establishing the diagnosis and planning the treatment of breast cancer. The false-positive rate is very low, with only a single case reported in 835 aspirates. Most false negatives are due to sampling and not to interpretive difficulties. The category "suspicious but not diagnostic of malignancy" serves a useful purpose in management of patients with breast lumps.

Uncertainty in biological monitoring: a framework for data collection and analysis to account for multiple sources of sampling bias

USGS Publications Warehouse

Ruiz-Gutierrez, Viviana; Hooten, Melvin B.; Campbell Grant, Evan H.

2016-01-01

Biological monitoring programmes are increasingly relying upon large volumes of citizen-science data to improve the scope and spatial coverage of information, challenging the scientific community to develop design and model-based approaches to improve inference.Recent statistical models in ecology have been developed to accommodate false-negative errors, although current work points to false-positive errors as equally important sources of bias. This is of particular concern for the success of any monitoring programme given that rates as small as 3% could lead to the overestimation of the occurrence of rare events by as much as 50%, and even small false-positive rates can severely bias estimates of occurrence dynamics.We present an integrated, computationally efficient Bayesian hierarchical model to correct for false-positive and false-negative errors in detection/non-detection data. Our model combines independent, auxiliary data sources with field observations to improve the estimation of false-positive rates, when a subset of field observations cannot be validated a posteriori or assumed as perfect. We evaluated the performance of the model across a range of occurrence rates, false-positive and false-negative errors, and quantity of auxiliary data.The model performed well under all simulated scenarios, and we were able to identify critical auxiliary data characteristics which resulted in improved inference. We applied our false-positive model to a large-scale, citizen-science monitoring programme for anurans in the north-eastern United States, using auxiliary data from an experiment designed to estimate false-positive error rates. Not correcting for false-positive rates resulted in biased estimates of occupancy in 4 of the 10 anuran species we analysed, leading to an overestimation of the average number of occupied survey routes by as much as 70%.The framework we present for data collection and analysis is able to efficiently provide reliable inference for occurrence patterns using data from a citizen-science monitoring programme. However, our approach is applicable to data generated by any type of research and monitoring programme, independent of skill level or scale, when effort is placed on obtaining auxiliary information on false-positive rates.

[Predictive factors of contamination in a blood culture with bacterial growth in an Emergency Department].

PubMed

Hernández-Bou, S; Trenchs Sainz de la Maza, V; Esquivel Ojeda, J N; Gené Giralt, A; Luaces Cubells, C

2015-06-01

The aim of this study is to identify predictive factors of bacterial contamination in positive blood cultures (BC) collected in an emergency department. A prospective, observational and analytical study was conducted on febrile children aged on to 36 months, who had no risk factors of bacterial infection, and had a BC collected in the Emergency Department between November 2011 and October 2013 in which bacterial growth was detected. The potential BC contamination predicting factors analysed were: maximum temperature, time to positivity, initial Gram stain result, white blood cell count, absolute neutrophil count, band count, and C-reactive protein (CRP). Bacteria grew in 169 BC. Thirty (17.8%) were finally considered true positives and 139 (82.2%) false positives. All potential BC contamination predicting factors analysed, except maximum temperature, showed significant differences between true positives and false positives. CRP value, time to positivity, and initial Gram stain result are the best predictors of false positives in BC. The positive predictive values of a CRP value≤30mg/L, BC time to positivity≥16h, and initial Gram stain suggestive of a contaminant in predicting a FP, are 95.1, 96.9 and 97.5%, respectively. When all 3 conditions are applied, their positive predictive value is 100%. Four (8.3%) patients with a false positive BC and discharged to home were revaluated in the Emergency Department. The majority of BC obtained in the Emergency Department that showed positive were finally considered false positives. Initial Gram stain, time to positivity, and CRP results are valuable diagnostic tests in distinguishing between true positives and false positives in BC. The early detection of false positives will allow minimising their negative consequences. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Interpreting the results of the Semmes-Weinstein monofilament test: accounting for false-positive answers in the international consensus on the diabetic foot protocol by a new model.

PubMed

Slater, Robert A; Koren, Shlomit; Ramot, Yoram; Buchs, Andreas; Rapoport, Micha J

2014-01-01

The Semmes-Weinstein monofilament is the most widely used test to diagnose the loss of protective sensation. The commonly used protocol of the International Consensus on the Diabetic Foot includes a 'sham' application that allows for false-positive answers. We sought to study the heretofore unexamined significance of false-positive answers. Forty-five patients with diabetes and a history of pedal ulceration (Group I) and 81 patients with diabetes but no history of ulceration (Group II) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, 1st metatarsal and 5th metatarsal areas were used. At each location, the test was performed three times: 2 actual and 1 "sham" applications. Scores were graded from 0 to 3 based upon correct responses. Determination of loss of protective sensation was performed with and without calculating a false-positive answer as a minus 1 score. False-positive responses were found in a significant percentage of patients with and without history of ulceration. Introducing false-positive results as minus 1 into the test outcome significantly increased the number of patients diagnosed with loss of protective sensation in both groups. False-positive answers can significantly affect Semmes-Weinstein monofilament test results and the diagnosis of LOPS. A model that accounts for false-positive answers is offered. Copyright © 2013 John Wiley & Sons, Ltd.

Reducing false-positive incidental findings with ensemble genotyping and logistic regression based variant filtering methods.

PubMed

Hwang, Kyu-Baek; Lee, In-Hee; Park, Jin-Ho; Hambuch, Tina; Choe, Yongjoon; Kim, MinHyeok; Lee, Kyungjoon; Song, Taemin; Neu, Matthew B; Gupta, Neha; Kohane, Isaac S; Green, Robert C; Kong, Sek Won

2014-08-01

As whole genome sequencing (WGS) uncovers variants associated with rare and common diseases, an immediate challenge is to minimize false-positive findings due to sequencing and variant calling errors. False positives can be reduced by combining results from orthogonal sequencing methods, but costly. Here, we present variant filtering approaches using logistic regression (LR) and ensemble genotyping to minimize false positives without sacrificing sensitivity. We evaluated the methods using paired WGS datasets of an extended family prepared using two sequencing platforms and a validated set of variants in NA12878. Using LR or ensemble genotyping based filtering, false-negative rates were significantly reduced by 1.1- to 17.8-fold at the same levels of false discovery rates (5.4% for heterozygous and 4.5% for homozygous single nucleotide variants (SNVs); 30.0% for heterozygous and 18.7% for homozygous insertions; 25.2% for heterozygous and 16.6% for homozygous deletions) compared to the filtering based on genotype quality scores. Moreover, ensemble genotyping excluded > 98% (105,080 of 107,167) of false positives while retaining > 95% (897 of 937) of true positives in de novo mutation (DNM) discovery in NA12878, and performed better than a consensus method using two sequencing platforms. Our proposed methods were effective in prioritizing phenotype-associated variants, and an ensemble genotyping would be essential to minimize false-positive DNM candidates. © 2014 WILEY PERIODICALS, INC.

Reducing false positive incidental findings with ensemble genotyping and logistic regression-based variant filtering methods

PubMed Central

Hwang, Kyu-Baek; Lee, In-Hee; Park, Jin-Ho; Hambuch, Tina; Choi, Yongjoon; Kim, MinHyeok; Lee, Kyungjoon; Song, Taemin; Neu, Matthew B.; Gupta, Neha; Kohane, Isaac S.; Green, Robert C.; Kong, Sek Won

2014-01-01

As whole genome sequencing (WGS) uncovers variants associated with rare and common diseases, an immediate challenge is to minimize false positive findings due to sequencing and variant calling errors. False positives can be reduced by combining results from orthogonal sequencing methods, but costly. Here we present variant filtering approaches using logistic regression (LR) and ensemble genotyping to minimize false positives without sacrificing sensitivity. We evaluated the methods using paired WGS datasets of an extended family prepared using two sequencing platforms and a validated set of variants in NA12878. Using LR or ensemble genotyping based filtering, false negative rates were significantly reduced by 1.1- to 17.8-fold at the same levels of false discovery rates (5.4% for heterozygous and 4.5% for homozygous SNVs; 30.0% for heterozygous and 18.7% for homozygous insertions; 25.2% for heterozygous and 16.6% for homozygous deletions) compared to the filtering based on genotype quality scores. Moreover, ensemble genotyping excluded > 98% (105,080 of 107,167) of false positives while retaining > 95% (897 of 937) of true positives in de novo mutation (DNM) discovery, and performed better than a consensus method using two sequencing platforms. Our proposed methods were effective in prioritizing phenotype-associated variants, and ensemble genotyping would be essential to minimize false positive DNM candidates. PMID:24829188

The problem of false positives and false negatives in violent video game experiments.

PubMed

Ferguson, Christopher J

The problem of false positives and negatives has received considerable attention in behavioral research in recent years. The current paper uses video game violence research as an example of how such issues may develop in a field. Despite decades of research, evidence on whether violent video games (VVGs) contribute to aggression in players has remained mixed. Concerns have been raised in recent years that experiments regarding VVGs may suffer from both "false positives" and "false negatives." The current paper examines this issue in three sets of video game experiments, two sets of video game experiments on aggression and prosocial behaviors identified in meta-analysis, and a third group of recent null studies. Results indicated that studies of VVGs and aggression appear to be particularly prone to false positive results. Studies of VVGs and prosocial behavior, by contrast are heterogeneous and did not demonstrate any indication of false positive results. However, their heterogeneous nature made it difficult to base solid conclusions on them. By contrast, evidence for false negatives in null studies was limited, and little evidence emerged that null studies lacked power in comparison those highlighted in past meta-analyses as evidence for effects. These results are considered in light of issues related to false positives and negatives in behavioral science more broadly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed Central

Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M. Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

2015-01-01

Background Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Methodology/Principal Findings Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). Conclusion The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study. PMID:26161864

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed

Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

2015-01-01

Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

Relevance of cutoff on a 4th generation ELISA performance in the false positive rate during HIV diagnostic in a low HIV prevalence setting.

PubMed

Chacón, Lucía; Mateos, María Luisa; Holguín, África

2017-07-01

Despite the high specificity of fourth-generation enzyme immunoassays (4th-gen-EIA) for screening during HIV diagnosis, their positive predictive value is low in populations with low HIV prevalence. Thus, screening should be optimized to reduce false positive results. The influence of sample cutoff (S/CO) values by a 4th-gen-EIA with the false positive rate during the routine HIV diagnosis in a low HIV prevalence population was evaluated. A total of 30,201 sera were tested for HIV diagnosis using Abbott Architect ® HIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months. Architect S/CO values were recorded, comparing the HIV-1 positive results following Architect interpretation (S/CO≥1) with the final HIV-1 diagnosis by confirmatory tests (line immunoassay, LIA and/or nucleic acid test, NAT). ROC curve was also performed. Among the 30,201 HIV performed tests, 256 (0.85%) were positive according to Architect interpretation (S/CO≥1) but only 229 (0.76%) were definitively HIV-1 positive after LIA and/or NAT. Thus, 27 (10.5%) of 256 samples with S/CO≥1 by Architect were false positive diagnose. The false positive rate decreased when the S/CO ratio increased. All 19 samples with S/CO ≤10 were false positives and all 220 with S/CO>50 true HIV-positives. The optimal S/CO cutoff value provided by ROC curves was 32.7. No false negative results were found. We show that very low S/CO values during HIV-1 screening using Architect can result HIV negative after confirmation by LIA and NAT. The false positive rate is reduced when S/CO increases. Copyright © 2017 Elsevier B.V. All rights reserved.

Which Factors Contribute to False-Positive, False-Negative, and Invalid Results in Fetal Fibronectin Testing in Women with Symptoms of Preterm Labor?

PubMed

Bruijn, Merel M C; Hermans, Frederik J R; Vis, Jolande Y; Wilms, Femke F; Oudijk, Martijn A; Kwee, Anneke; Porath, Martina M; Oei, Guid; Scheepers, Hubertina C J; Spaanderman, Marc E A; Bloemenkamp, Kitty W M; Haak, Monique C; Bolte, Antoinette C; Vandenbussche, Frank P H A; Woiski, Mallory D; Bax, Caroline J; Cornette, Jérôme M J; Duvekot, Johannes J; Bijvank, Bas W A N I J; van Eyck, Jim; Franssen, Maureen T M; Sollie, Krystyna M; van der Post, Joris A M; Bossuyt, Patrick M M; Kok, Marjolein; Mol, Ben W J; van Baaren, Gert-Jan

2017-02-01

Objective  We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods  We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results  Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion  The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Saturn Apollo Program

NASA Image and Video Library

1969-07-16

This photograph shows the Saturn V launch vehicle (SA-506) for the Apollo 11 mission liftoff at 8:32 am CDT, July 16, 1969, from launch complex 39A at the Kennedy Space Center. Apollo 11 was the first manned lunar landing mission with a crew of three astronauts: Mission commander Neil A. Armstrong, Command Module pilot Michael Collins, and Lunar Module pilot Edwin E. Aldrin, Jr. It placed the first humans on the surface of the moon and returned them back to Earth. Astronaut Armstrong became the first man on the lunar surface, and astronaut Aldrin became the second. Astronaut Collins piloted the Command Module in a parking orbit around the Moon.

iss009e17915

NASA Image and Video Library

2004-08-12

ISS009-E-17915 (12 August 2004) --- This is an early morning view (6:29 a.m., CDT) from the International Space Station, which shows Hurricane Charley centered south of western Cuba over the Cayman Islands in the northwest Caribbean Sea. At the time of this image the storm was reported to be near 19.2N 80.5W with winds of 85 miles per hour as it moved northwest at 16 miles per hour. The north coast of Cuba is barely visible near the bottom of the image, which was taken by astronaut Mike Fincke looking to the south as the spacecraft flew on a track north of Cuba and the storm.

APOLLO COMMAND MODULE (CM) - SAFE TOUCHDOWN - PACIFIC OCEAN

NASA Image and Video Library

1971-08-07

S71-41999 (7 Aug. 1971) --- The Apollo 15 Command Module (CM), with astronauts David R. Scott, commander; Alfred M. Worden, command module pilot; and James B. Irwin, lunar module pilot, aboard, nears a safe touchdown in the mid-Pacific Ocean to conclude a highly successful lunar landing mission. Although causing no harm to the crewmen, one of the three main parachutes failed to function properly. The splashdown occurred at 3:45:53 p.m. (CDT), Aug. 7, 1971, some 330 miles north of Honolulu, Hawaii. The three astronauts were picked up by helicopter and flown to the prime recovery ship USS Okinawa, which was only 6 1/2 miles away.

RECOVERY - APOLLO 15

NASA Image and Video Library

1971-08-07

S71-43542 (7 Aug. 1971) --- The Apollo 15 Command Module (CM), with astronauts David R. Scott, commander; Alfred M. Worden, command module pilot; and James B. Irwin, lunar module pilot, aboard safely touches down in the mid-Pacific Ocean to conclude a highly successful lunar landing mission. Although causing no harm to the crew men, one of the three main parachutes failed to function properly. The splashdown occurred at 3:45:53 p.m. (CDT), Aug. 7, 1971, some 330 miles north of Honolulu, Hawaii. The three astronauts were picked up by helicopter and flown to the prime recovery ship, USS Okinawa, which was only 6 1/2 miles away.

RECOVERY - APOLLO 15

NASA Image and Video Library

1971-08-07

S71-43543 (7 Aug. 1971) --- The Apollo 15 Command Module (CM), with astronauts David R. Scott, commander; Alfred M. Worden, command module pilot; and James B. Irwin, lunar module pilot, aboard safely touches down in the mid-Pacific Ocean to conclude a highly successful lunar landing mission. Although causing no harm to the crew men, one of the three main parachutes failed to function properly. The splashdown occurred at 3:45:53 p.m. (CDT), Aug. 7, 1971, some 330 miles north of Honolulu, Hawaii. The three astronauts were picked up by helicopter and flown to the prime recovery ship, USS Okinawa, which was only 6 1/2 miles away.

Volkov and Kononenko prepare for the undocking of the ESA Jules Verne ATV during Expedition 17

NASA Image and Video Library

2008-09-05

ISS017-E-015234 (5 Sept. 2008) --- Russian Federal Space Agency cosmonauts Sergei Volkov (left) and Oleg Kononenko, Expedition 17 commander and flight engineer, respectively, make preparations in the International Space Station's Zvezda Service Module for the undocking of the European Space Agency's (ESA) "Jules Verne" Automated Transfer Vehicle (ATV). The ATV departed from the aft port of Zvezda at 4:29 p.m. (CDT) on Sept. 5, 2008 and was placed in a parking orbit for three weeks, scheduled to be deorbited on Sept. 29 when lighting conditions are correct for an ESA imagery experiment of reentry.

Volkov and Kononenko prepare for the undocking of the ESA Jules Verne ATV during Expedition 17

NASA Image and Video Library

2008-09-05

ISS017-E-015229 (5 Sept. 2008) --- Russian Federal Space Agency cosmonauts Sergei Volkov (left) and Oleg Kononenko, Expedition 17 commander and flight engineer, respectively, make preparations in the International Space Station's Zvezda Service Module for the undocking of the European Space Agency's (ESA) "Jules Verne" Automated Transfer Vehicle (ATV). The ATV departed from the aft port of Zvezda at 4:29 p.m. (CDT) on Sept. 5, 2008 and was placed in a parking orbit for three weeks, scheduled to be deorbited on Sept. 29 when lighting conditions are correct for an ESA imagery experiment of reentry.

International Space Station (ISS)

NASA Image and Video Library

2006-09-17

This view of the International Space Station, back dropped against the blackness of space and Earth, was taken shortly after the Space Shuttle Atlantis undocked from the orbital outpost at 7:50 a.m. CDT during the STS-115 mission. The unlinking completed after six days, two hours and two minutes of joint operations of the installation of the P3/P4 truss. The new 17 ton truss included batteries, electronics, a giant rotating joint, and sported a second pair of 240-foot solar wings. The new solar arrays will eventually double the onboard power of the Station when their electrical systems are brought online during the next shuttle flight, STS-116.

International Space Station (ISS)

NASA Image and Video Library

2006-09-17

This view of the International Space Station, back dropped against the blackness of space, was taken shortly after the Space Shuttle Atlantis undocked from the orbital outpost at 7:50 a.m. CDT during the STS-115 mission. The unlinking completed after six days, two hours and two minutes of joint operations of the installation of the P3/P4 truss. The new 17 ton truss included batteries, electronics, a giant rotating joint, and sported a second pair of 240-foot solar wings. The new solar arrays will eventually double the onboard power of the Station when their electrical systems are brought online during the next shuttle flight, STS-116.

LUNAR SAMPLES - APOLLO XI

NASA Image and Video Library

1969-07-27

S69-45002 (26 July 1969) --- A close-up view of the lunar rocks contained in the first Apollo 11 sample return container. The rock box was opened for the first time in the Vacuum Laboratory of the Manned Spacecraft Center’s Lunar Receiving Laboratory, Building 37, at 3:55 p.m. (CDT), Saturday, July 26, 1969. The gloved hand gives an indication of size. This box also contained the Solar Wind Composition experiment (not shown) and two core tubes for subsurface samples (not shown). These lunar samples were collected by astronauts Neil A. Armstrong and Edwin E. Aldrin Jr. during their lunar surface extravehicular activity on July 20, 1969.

Space Shuttle Projects

NASA Image and Video Library

1992-05-13

STS-49, the first flight of the Space Shuttle Orbiter Endeavour, lifted off from launch pad 39B on May 7, 1992 at 6:40 pm CDT. The STS-49 mission was the first U.S. orbital flight to feature 4 extravehicular activities (EVAs), and the first flight to involve 3 crew members working simultaneously outside of the spacecraft. The primary objective was the capture and redeployment of the INTELSAT VI (F-3), a communication satellite for the International Telecommunication Satellite organization, which was stranded in an unusable orbit since its launch aboard the Titan rocket in March 1990. In this onboard photo, astronauts Hieb, Akers, and Thuot have handholds on the satellite.

Space Shuttle Projects

NASA Image and Video Library

1992-05-14

STS-49, the first flight of the Space Shuttle Orbiter Endeavour, lifted off from launch pad 39B on May 7, 1992 at 6:40 pm CDT. The STS-49 mission was the first U.S. orbital flight to feature 4 extravehicular activities (EVAs), and the first flight to involve 3 crew members working simultaneously outside of the spacecraft. The primary objective was the capture and redeployment of the INTELSAT VI (F-3), a communication satellite for the International Telecommunication Satellite organization, which was stranded in an unusable orbit since its launch aboard the Titan rocket in March 1990. A view through Endeavour’s busy airlock reveals astronauts Thomas Akers and Kathryn Thornton.

Space Shuttle Projects

NASA Image and Video Library

1992-05-14

STS-49, the first flight of the Space Shuttle Orbiter Endeavour, lifted off from launch pad 39B on May 7, 1992 at 6:40 pm CDT. The STS-49 mission was the first U.S. orbital flight to feature 4 extravehicular activities (EVAs), and the first flight to involve 3 crew members working simultaneously outside of the spacecraft. The primary objective was the capture and redeployment of the INTELSAT VI (F-3) which was stranded in an unusable orbit since its launch aboard the Titan rocket in March 1990. In this STS-49 onboard photo, Astronaut Kathryn Thornton joins three struts together during her Extra Vehicular Activity (EVA).

Consensus-based identification of factors related to false-positives in ultrasound scanning of synovitis and tenosynovitis.

PubMed

Ikeda, Kei; Narita, Akihiro; Ogasawara, Michihiro; Ohno, Shigeru; Kawahito, Yutaka; Kawakami, Atsushi; Ito, Hiromu; Matsushita, Isao; Suzuki, Takeshi; Misaki, Kenta; Ogura, Takehisa; Kamishima, Tamotsu; Seto, Yohei; Nakahara, Ryuichi; Kaneko, Atsushi; Nakamura, Takayuki; Henmi, Mihoko; Fukae, Jun; Nishida, Keiichiro; Sumida, Takayuki; Koike, Takao

2016-01-01

We aimed to identify causes of false-positives in ultrasound scanning of synovial/tenosynovial/bursal inflammation and provide corresponding imaging examples. We first performed systematic literature review to identify previously reported causes of false-positives. We next determined causes of false-positives and corresponding example images for educational material through Delphi exercises and discussion by 15 experts who were an instructor and/or a lecturer in the 2013 advanced course for musculoskeletal ultrasound organized by Japan College of Rheumatology Committee for the Standardization of Musculoskeletal Ultrasonography. Systematic literature review identified 11 articles relevant to sonographic false-positives of synovial/tenosynovial inflammation. Based on these studies, 21 candidate causes of false-positives were identified in the consensus meeting. Of these items, 11 achieved a predefined consensus (≥ 80%) in Delphi exercise and were classified as follows: (I) Gray-scale assessment [(A) non-specific synovial findings and (B) normal anatomical structures which can mimic synovial lesions due to either their low echogenicity or anisotropy]; (II) Doppler assessment [(A) Intra-articular normal vessels and (B) reverberation)]. Twenty-four corresponding examples with 49 still and 23 video images also achieved consensus. Our study provides a set of representative images that can help sonographers to understand false-positives in ultrasound scanning of synovitis and tenosynovitis.

Skin irritation, false positives and the local lymph node assay: a guideline issue?

PubMed

Basketter, David A; Kimber, Ian

2011-10-01

Since the formal validation and regulatory acceptance of the local lymph node assay (LLNA) there have been commentaries suggesting that the irritant properties of substances can give rise to false positives. As toxicology aspires to progress rapidly towards the age of in vitro alternatives, it is of increasing importance that issues relating to assay selectivity and performance are understood fully, and that true false positive responses are distinguished clearly from those that are simply unpalatable. In the present review, we have focused on whether skin irritation per se is actually a direct cause of true false positive results in the LLNA. The body of published work has been examined critically and considered in relation to our current understanding of the mechanisms of skin irritation and skin sensitisation. From these analyses it is very clear that, of itself, skin irritation is not a cause of false positive results. The corollary is, therefore, that limiting test concentrations in the LLNA for the purpose of avoiding skin irritation may lead, unintentionally, to false negatives. Where a substance is a true false positive in the LLNA, the classic example being sodium lauryl sulphate, explanations for that positivity will have to reach beyond the seductive, but incorrect, recourse to its skin irritation potential. Copyright © 2011 Elsevier Inc. All rights reserved.

Hypertension is strongly associated with false-positive bicycle exercise stress echocardiography testing results.

PubMed

Keller, Karsten; Stelzer, Kathrin; Munzel, Thomas; Ostad, Mir Abolfazl

2016-12-01

Exercise echocardiography is a reliable routine test in patients with known or suspected coronary artery disease. However, in ∼15% of all patients, stress echocardiography leads to false-positive stress echocardiography results. We aimed to investigate the impact of hypertension on stress echocardiographic results. We performed a retrospective study of patients with suspected or known stable coronary artery disease who underwent a bicycle exercise stress echocardiography. Patients with false-positive stress results were compared with those with appropriate results. 126 patients with suspected or known coronary artery disease were included in this retrospective study. 23 patients showed false-positive stress echocardiography results. Beside comparable age, gender distribution and coronary artery status, hypertension was more prevalent in patients with false-positive stress results (95.7% vs. 67.0%, p = 0.0410). Exercise peak load revealed a borderline-significance with lower loads in patients with false-positive results (100.0 (IQR 75.0/137.5) vs. 125.0 (100.0/150.0) W, p = 0.0601). Patients with false-positive stress results showed higher systolic (2.05 ± 0.69 vs. 1.67 ± 0.39 mmHg/W, p = 0.0193) and diastolic (1.03 ± 0.38 vs. 0.80 ± 0.28 mmHg/W, p = 0.0165) peak blood pressure (BP) per wattage. In a multivariate logistic regression test, hypertension (OR 17.6 [CI 95% 1.9-162.2], p = 0.0115), and systolic (OR 4.12 [1.56-10.89], p = 0.00430) and diastolic (OR 13.74 [2.46-76.83], p = 0.00285) peak BP per wattage, were associated with false-positive exercise results. ROC analysis for systolic and diastolic peak BP levels per wattage showed optimal cut-off values of 1.935mmHg/W and 0.823mmHg/W, indicating false-positive exercise echocardiographic results with AUCs of 0.660 and 0.664, respectively. Hypertension is a risk factor for false-positive stress exercise echocardiographic results in patients with known or suspected coronary artery disease. Presence of hypertension was associated with 17.6-fold elevated risk of false-positive results.

False Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease-Disinhibition or Amnesia?

PubMed

Flanagan, Emma C; Wong, Stephanie; Dutt, Aparna; Tu, Sicong; Bertoux, Maxime; Irish, Muireann; Piguet, Olivier; Rao, Sulakshana; Hodges, John R; Ghosh, Amitabha; Hornberger, Michael

2016-01-01

Episodic memory recall processes in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centers (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits-false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.

False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

PubMed

Tenore, Peter L

2012-01-01

In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

Diurnal rhythm and concordance between objective and subjective hot flashes: the Hilo Women's Health Study.

PubMed

Sievert, Lynnette L; Reza, Angela; Mills, Phoebe; Morrison, Lynn; Rahberg, Nichole; Goodloe, Amber; Sutherland, Michael; Brown, Daniel E

2010-01-01

The aims of this study were to test for a diurnal pattern in hot flashes in a multiethnic population living in a hot, humid environment and to examine the rates of concordance between objective and subjective measures of hot flashes using ambulatory and laboratory measures. Study participants aged 45 to 55 years were recruited from the general population of Hilo, HI. Women wore a Biolog hot flash monitor (UFI, Morro Bay, CA), kept a diary for 24 hours, and also participated in 3-hour laboratory measures (n = 199). Diurnal patterns were assessed using polynomial regression. For each woman, objectively recorded hot flashes that matched subjective experience were treated as true-positive readings. Subjective hot flashes were considered the standard for computing false-positive and false-negative readings. True-positive, false-positive, and false-negative readings were compared across ethnic groups by chi analyses. Frequencies of sternal, nuchal, and subjective hot flashes peaked at 1500 +/- 1 hours with no difference by ethnicity. Laboratory results supported the pattern seen in ambulatory monitoring. Sternal and nuchal monitoring showed the same frequency of true-positive measures, but nonsternal electrodes picked up more false-positive readings. Laboratory monitoring showed very low frequencies of false negatives. There were no ethnic differences in the frequency of true-positive or false-positive measures. Women of European descent were more likely to report hot flashes that were not objectively demonstrated (false-negative measures). The diurnal pattern and peak in hot flash occurrence in the hot humid environment of Hilo were similar to results from more temperate environments. Lack of variation in sternal versus nonsternal measures and in true-positive measures across ethnicities suggests no appreciable effect of population variation in sweating patterns.

Diurnal rhythm and concordance between objective and subjective hot flashes: The Hilo Women’s Health Study

PubMed Central

Sievert, Lynnette L.; Reza, Angela; Mills, Phoebe; Morrison, Lynn; Rahberg, Nichole; Goodloe, Amber; Sutherland, Michael; Brown, Daniel E.

2010-01-01

Objective To test for a diurnal pattern in hot flashes in a multi-ethnic population living in a hot, humid environment. To examine rates of concordance between objective and subjective measures of hot flashes using ambulatory and laboratory measures. Methods Study participants aged 45–55 were recruited from the general population of Hilo, Hawaii. Women wore a Biolog hot flash monitor, kept a diary for 24-hours, and also participated in 3-hour laboratory measures (n=199). Diurnal patterns were assessed using polynomial regression. For each woman, objectively recorded hot flashes that matched subjective experience were treated as true positive readings. Subjective hot flashes were considered the standard for computing false positive and false negative readings. True positive, false positive, and false negative readings were compared across ethnic groups by chi-square analyses. Results Frequencies of sternal, nuchal and subjective hot flashes peaked at 15:00 ± 1 hour with no difference by ethnicity. Laboratory results supported the pattern seen in ambulatory monitoring. Sternal and nuchal monitoring showed the same frequency of true positive measures, but non-sternal electrodes picked up more false positive readings. Laboratory monitoring showed very low frequencies of false negatives. There were no ethnic differences in the frequency of true positive or false positive measures. Women of European descent were more likely to report hot flashes that were not objectively demonstrated (false negative measures). Conclusions The diurnal pattern and peak in hot flash occurrence in the hot humid environment of Hilo was similar to results from more temperate environments. Lack of variation in sternal vs. non-sternal measures, and in true positive measures across ethnicities suggests no appreciable effect of population variation in sweating patterns. PMID:20220538

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

PubMed Central

Li, Bingshan; Leal, Suzanne M.

2008-01-01

Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1] that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents in the analysis. PMID:18073490

Biological false-positive venereal disease research laboratory test in cerebrospinal fluid in the diagnosis of neurosyphilis - a case-control study.

PubMed

Zheng, S; Lin, R J; Chan, Y H; Ngan, C C L

2018-03-01

There is no clear consensus on the diagnosis of neurosyphilis. The Venereal Disease Research Laboratory (VDRL) test from cerebrospinal fluid (CSF) has traditionally been considered the gold standard for diagnosing neurosyphilis but is widely known to be insensitive. In this study, we compared the clinical and laboratory characteristics of true-positive VDRL-CSF cases with biological false-positive VDRL-CSF cases. We retrospectively identified cases of true and false-positive VDRL-CSF across a 3-year period received by the Immunology and Serology Laboratory, Singapore General Hospital. A biological false-positive VDRL-CSF is defined as a reactive VDRL-CSF with a non-reactive Treponema pallidum particle agglutination (TPPA)-CSF and/or negative Line Immuno Assay (LIA)-CSF IgG. A true-positive VDRL-CSF is a reactive VDRL-CSF with a concordant reactive TPPA-CSF and/or positive LIA-CSF IgG. During the study period, a total of 1254 specimens underwent VDRL-CSF examination. Amongst these, 60 specimens from 53 patients tested positive for VDRL-CSF. Of the 53 patients, 42 (79.2%) were true-positive cases and 11 (20.8%) were false-positive cases. In our setting, a positive non-treponemal serology has 97.6% sensitivity, 100% specificity, 100% positive predictive value and 91.7% negative predictive value for a true-positive VDRL-CSF based on our laboratory definition. HIV seropositivity was an independent predictor of a true-positive VDRL-CSF. Biological false-positive VDRL-CSF is common in a setting where patients are tested without first establishing a serological diagnosis of syphilis. Serological testing should be performed prior to CSF evaluation for neurosyphilis. © 2017 European Academy of Dermatology and Venereology.

False positive circumsporozoite protein ELISA: a challenge for the estimation of the entomological inoculation rate of malaria and for vector incrimination

PubMed Central

2011-01-01

Background The entomological inoculation rate (EIR) is an important indicator in estimating malaria transmission and the impact of vector control. To assess the EIR, the enzyme-linked immunosorbent assay (ELISA) to detect the circumsporozoite protein (CSP) is increasingly used. However, several studies have reported false positive results in this ELISA. The false positive results could lead to an overestimation of the EIR. The aim of present study was to estimate the level of false positivity among different anopheline species in Cambodia and Vietnam and to check for the presence of other parasites that might interact with the anti-CSP monoclonal antibodies. Methods Mosquitoes collected in Cambodia and Vietnam were identified and tested for the presence of sporozoites in head and thorax by using CSP-ELISA. ELISA positive samples were confirmed by a Plasmodium specific PCR. False positive mosquitoes were checked by PCR for the presence of parasites belonging to the Haemosporidia, Trypanosomatidae, Piroplasmida, and Haemogregarines. The heat-stability and the presence of the cross-reacting antigen in the abdomen of the mosquitoes were also checked. Results Specimens (N = 16,160) of seven anopheline species were tested by CSP-ELISA for Plasmodium falciparum and Plasmodium vivax (Pv210 and Pv247). Two new vector species were identified for the region: Anopheles pampanai (P. vivax) and Anopheles barbirostris (Plasmodium malariae). In 88% (155/176) of the mosquitoes found positive with the P. falciparum CSP-ELISA, the presence of Plasmodium sporozoites could not be confirmed by PCR. This percentage was much lower (28% or 5/18) for P. vivax CSP-ELISAs. False positive CSP-ELISA results were associated with zoophilic mosquito species. None of the targeted parasites could be detected in these CSP-ELISA false positive mosquitoes. The ELISA reacting antigen of P. falciparum was heat-stable in CSP-ELISA true positive specimens, but not in the false positives. The heat-unstable cross-reacting antigen is mainly present in head and thorax and almost absent in the abdomens (4 out of 147) of the false positive specimens. Conclusion The CSP-ELISA can considerably overestimate the EIR, particularly for P. falciparum and for zoophilic species. The heat-unstable cross-reacting antigen in false positives remains unknown. Therefore it is highly recommended to confirm all positive CSP-ELISA results, either by re-analysing the heated ELISA lysate (100°C, 10 min), or by performing Plasmodium specific PCR followed if possible by sequencing of the amplicons for Plasmodium species determination. PMID:21767376

77 FR 48045 - Supplemental Nutrition Assistance Program: Disqualified Recipient Reporting and Computer Matching...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-13

... false positive match rate of 10 percent. Making the match mandatory for the States who did not perform... number of prisoners from 1995 to 2013 and assumed a 10 percent false positive match rate. Finally, we... matches are false positives. We estimate that mandatory matches at certification will identify an...

NASA Sees Tropical Storm Bill Making Landfall in Texas

NASA Image and Video Library

2015-06-16

On June 15 at 19:15 UTC (3:15 p.m. EDT) the MODIS instrument aboard NASA's Aqua satellite captured a visible image of Tropical Storm Bill approaching Texas and Louisiana. Powerful thunderstorms circled the center in fragmented bands. At 11 a.m. CDT on June 16, a Tropical Storm Warning was in effect from Baffin Bay to High Island Texas as Bill was making landfall. The National Hurricane Center noted that Bill is expected to produce total rain accumulations of 4 to 8 inches over eastern Texas and eastern Oklahoma and 2 to 4 inches over western Arkansas and southern Missouri, with possible isolated maximum amounts of 12 inches in eastern Texas. In eastern Texas and far western Louisiana today and tonight, isolated tornadoes are also possible, as with any landfalling tropical storm. Tropical storm conditions are expected to continue into the evening in the warning area. Along the coasts, the combination of a storm surge and the tide will cause normally dry areas near the coast to be flooded by rising waters. The water could reach the following heights above ground if the peak surge occurs at the time of high tide. The NHC noted that the Upper Texas coast could experience 2 to 4 feet, and the western Louisiana coast between 1 to 2 feet. At 10 a.m. CDT (1500 UTC), the center of Tropical Storm Bill was located near latitude 28.2 North, longitude 96.4 West. Bill was moving toward the northwest near 10 mph (17 kph) and that general motion is expected to continue today. The latest minimum central pressure reported by an Air Force Reserve Hurricane Hunter aircraft was 997 millibars. Reports from an Air Force Reserve reconnaissance aircraft indicate that maximum sustained winds remain near 60 mph (95 kph) with higher gusts. Unlike Carlos, Bill is not a compact storm. Tropical-storm-force winds extend outward up to 150 miles (240 km) from the center. Between 9 and 10 a.m. CDT, an automated observing station at Port O'Connor also reported a sustained wind of 44 mph (70 kph) and a gust to 53 mph (85 kph). For updated forecasts, watches and warnings, visit the National Hurricane Center webpage at www.nhc.noaa.gov. For local forecasts and advisories, visit: www.weather.gov. Bill is forecast to continue moving inland and is expected to be a tropical depression by Wednesday, June 17, west of Dallas. The remnants of Bill are forecast to move into the Midwest later in the week. Credit: NASA/GSFC/Jeff Schmaltz/MODIS Land Rapid Response Team NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Sulfur and Oxygen Isotopic Analysis of a Cosmic Symplectite from a Comet Wild 2 Stardust Terminal Particle

NASA Technical Reports Server (NTRS)

Nguyen, A. N.; Berger, E. L.; Nakamura-Messenger, K.; Messenger, S.

2015-01-01

Introduction: Analyses of comet 81P/Wild 2 samples re-turned from the Stardust mission have uncovered surprising simi-larities to meteoritic material, including the identification of inner solar system grains [1-3]. The TEM characterization of terminal particle (TP) 4 from Stardust track #147 revealed an assemblage consisting of symplectically intergrown pentlandite and nanocrys-talline maghemite coexisting with high-Ca pyroxene [4]. Mineral-ogically similar cosmic symplectites (COS) containing pentlandite and magnetite in the primitive Acfer 094 meteorite are highly de-pleted in 16O (?17O, ?18O 180 per mille) [5-7]. This isotopic signature is proposed to record alteration with primordial solar nebula water. Conversely, the normal O isotopic composition of the Stardust COS indicates alteration by a different aqueous reservoir, perhaps on the comet [8]. In this study, we analyzed the Wild 2 COS for S isotopes to further constrain its origin. Experimental: Thin sections of TP4 (12 ?m) were produced and their mineralogy was thoroughly characterized by TEM. Two of the sections were analyzed for O isotopes by isotopic imaging in the JSC NanoSIMS 50L. The sample in one of the slices was completely consumed. The remaining material in the adjacent slice was analyzed simultaneously for 16O, 32S, 33S, 34S, and 56Fe16O in electron multipliers using a Cs+ primary ion beam. Quasi-simulta-neous arrival (QSA) can have a significant effect on S isotopic ra-tios when using electron multipliers, resulting in undercounting of 32S [9]. Canyon Diablo troilite (CDT) was measured numerous times to deduce a correction factor for QSA and ensure measure-ment reproducibility. Isotopic ratios are reported relative to CDT. Results and Discussion: The Wild 2 COS is enriched in the heavy S isotopes relative to CDT (?33S = 6.5 +/- 1.6 per mille; ?34S = 5.1 +/- 0.7 per mille; 1?). The degree of 33S enrichment indicates mass-inde-pendent fractionation (MIF) with ?33S = 3.9 +/- 1.7 per mille. MIF of S has been observed in some chondrules (?33S up to 0.11per mille) [10], but this effect has not been identified in sulfides from carbonaceous chondrites [11] or IDPs [12]. S isotopic analysis of Stardust impact craters also did not reveal MIF or anomalies, save for one potential 32S-rich presolar sulfide [13]. Measurement errors on these impact craters were much larger than those in this study, however. MIF of S has been proposed to result from heterogeneities in the solar neb-ula from nucleosynthetic components [14] or photochemical irra-diation of solar nebula gas [10]. Presolar SiC grains are observed to have 32S enrichments [15, 16] contrary to the S isotopic compo-sition of the cometary COS. The S isotopic composition more likely reflects irradiation of nebular gas.

Bladder cancer diagnosis with CT urography: test characteristics and reasons for false-positive and false-negative results.

PubMed

Trinh, Tony W; Glazer, Daniel I; Sadow, Cheryl A; Sahni, V Anik; Geller, Nina L; Silverman, Stuart G

2018-03-01

To determine test characteristics of CT urography for detecting bladder cancer in patients with hematuria and those undergoing surveillance, and to analyze reasons for false-positive and false-negative results. A HIPAA-compliant, IRB-approved retrospective review of reports from 1623 CT urograms between 10/2010 and 12/31/2013 was performed. 710 examinations for hematuria or bladder cancer history were compared to cystoscopy performed within 6 months. Reference standard was surgical pathology or 1-year minimum clinical follow-up. False-positive and false-negative examinations were reviewed to determine reasons for errors. Ninety-five bladder cancers were detected. CT urography accuracy: was 91.5% (650/710), sensitivity 86.3% (82/95), specificity 92.4% (568/615), positive predictive value 63.6% (82/129), and negative predictive value was 97.8% (568/581). Of 43 false positives, the majority of interpretation errors were due to benign prostatic hyperplasia (n = 12), trabeculated bladder (n = 9), and treatment changes (n = 8). Other causes include blood clots, mistaken normal anatomy, infectious/inflammatory changes, or had no cystoscopic correlate. Of 13 false negatives, 11 were due to technique, one to a large urinary residual, one to artifact. There were no errors in perception. CT urography is an accurate test for diagnosing bladder cancer; however, in protocols relying predominantly on excretory phase images, overall sensitivity remains insufficient to obviate cystoscopy. Awareness of bladder cancer mimics may reduce false-positive results. Improvements in CTU technique may reduce false-negative results.

Methods for threshold determination in multiplexed assays

DOEpatents

Tammero, Lance F. Bentley; Dzenitis, John M; Hindson, Benjamin J

2014-06-24

Methods for determination of threshold values of signatures comprised in an assay are described. Each signature enables detection of a target. The methods determine a probability density function of negative samples and a corresponding false positive rate curve. A false positive criterion is established and a threshold for that signature is determined as a point at which the false positive rate curve intersects the false positive criterion. A method for quantitative analysis and interpretation of assay results together with a method for determination of a desired limit of detection of a signature in an assay are also described.

Shear-wave elastography in the diagnosis of solid breast masses: what leads to false-negative or false-positive results?

PubMed

Yoon, Jung Hyun; Jung, Hae Kyoung; Lee, Jong Tae; Ko, Kyung Hee

2013-09-01

To investigate the factors that have an effect on false-positive or false-negative shear-wave elastography (SWE) results in solid breast masses. From June to December 2012, 222 breast lesions of 199 consecutive women (mean age: 45.3 ± 10.1 years; range, 21 to 88 years) who had been scheduled for biopsy or surgical excision were included. Greyscale ultrasound and SWE were performed in all women before biopsy. Final ultrasound assessments and SWE parameters (pattern classification and maximum elasticity) were recorded and compared with histopathology results. Patient and lesion factors in the 'true' and 'false' groups were compared. Of the 222 masses, 175 (78.8 %) were benign, and 47 (21.2 %) were malignant. False-positive rates of benign masses were significantly higher than false-negative rates of malignancy in SWE patterns, 36.6 % to 6.4 % (P < 0.001). Among both benign and malignant masses, factors showing significance among false SWE features were lesion size, breast thickness and lesion depth (all P < 0.05). All 47 malignant breast masses had SWE images of good quality. False SWE features were more significantly seen in benign masses. Lesion size, breast thickness and lesion depth have significance in producing false results, and this needs consideration in SWE image acquisition. • Shear-wave elastography (SWE) is widely used during breast imaging • At SWE, false-positive rates were significantly higher than false-negative rates • Larger size, breast thickness, depth and fair quality influences false-positive SWE features • Smaller size, larger breast thickness and depth influences false-negative SWE features.

Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications.

PubMed

Mordang, Jan-Jurre; Gubern-Mérida, Albert; den Heeten, Gerard; Karssemeijer, Nico

2016-04-01

In the past decades, computer-aided detection (CADe) systems have been developed to aid screening radiologists in the detection of malignant microcalcifications. These systems are useful to avoid perceptual oversights and can increase the radiologists' detection rate. However, due to the high number of false positives marked by these CADe systems, they are not yet suitable as an independent reader. Breast arterial calcifications (BACs) are one of the most frequent false positives marked by CADe systems. In this study, a method is proposed for the elimination of BACs as positive findings. Removal of these false positives will increase the performance of the CADe system in finding malignant microcalcifications. A multistage method is proposed for the removal of BAC findings. The first stage consists of a microcalcification candidate selection, segmentation and grouping of the microcalcifications, and classification to remove obvious false positives. In the second stage, a case-based selection is applied where cases are selected which contain BACs. In the final stage, BACs are removed from the selected cases. The BACs removal stage consists of a GentleBoost classifier trained on microcalcification features describing their shape, topology, and texture. Additionally, novel features are introduced to discriminate BACs from other positive findings. The CADe system was evaluated with and without BACs removal. Here, both systems were applied on a validation set containing 1088 cases of which 95 cases contained malignant microcalcifications. After bootstrapping, free-response receiver operating characteristics and receiver operating characteristics analyses were carried out. Performance between the two systems was compared at 0.98 and 0.95 specificity. At a specificity of 0.98, the sensitivity increased from 37% to 52% and the sensitivity increased from 62% up to 76% at a specificity of 0.95. Partial areas under the curve in the specificity range of 0.8-1.0 were significantly different between the system without BACs removal and the system with BACs removal, 0.129 ± 0.009 versus 0.144 ± 0.008 (p<0.05), respectively. Additionally, the sensitivity at one false positive per 50 cases and one false positive per 25 cases increased as well, 37% versus 51% (p<0.05) and 58% versus 67% (p<0.05) sensitivity, respectively. Additionally, the CADe system with BACs removal reduces the number of false positives per case by 29% on average. The same sensitivity at one false positive per 50 cases in the CADe system without BACs removal can be achieved at one false positive per 80 cases in the CADe system with BACs removal. By using dedicated algorithms to detect and remove breast arterial calcifications, the performance of CADe systems can be improved, in particular, at false positive rates representative for operating points used in screening.

Effects of depressive disorder on false memory for emotional information.

PubMed

Yeh, Zai-Ting; Hua, Mau-Sun

2009-01-01

This study explored with a false memory paradigm whether (1) depressed patients revealed more false memories and (2) whether more negative false than positive false recognition existed in subjects with depressive disorders. Thirty-two patients suffering from a major depressive episode (DSM-IV criteria), and 30 age- and education-matched normal control subjects participated in this study. After the presentation of a list of positive, negative, and neutral association items in the learning phase, subjects were asked to give a yes/no response in the recognition phase. They were also asked to rate 81 recognition items with emotional valence scores. The results revealed more negative false memories in the clinical depression group than in the normal control group; however, we did not find more negative false memories than positive ones in patients. When compared with the normal group, a more conservative response criterion for positive items was evident in patient groups. It was also found that when compared with the normal group, the subjects in the depression group perceived the positive items as less positive. On the basis of present results, it is suggested that depressed subjects judged the emotional information with criteria different from normal individuals, and patients' emotional memory intensity is attenuated by their mood.

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

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

Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.

1982-01-01

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadalmore » function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.« less

Occurrence of the invasion associated marker (iam) in Campylobacter jejuni isolated from cattle

PubMed Central

2011-01-01

Background The invasion associated marker (iam) has been detected in the majority of invasive Campylobacter jejuni retrieved from humans. Furthermore, the detection of iam in C. jejuni isolated from two important hosts, humans and chickens, suggested a role for this marker in C. jejuni's colonization of multiple hosts. However, no data exist regarding the occurrence of this marker in C. jejuni isolated from non-poultry food-animals such as cattle, an increasingly important source for human infections. Since little is known about the genetics associated with C. jejuni's capability for colonizing physiologically disparate hosts, we investigated the occurrence of the iam in C. jejuni isolated from cattle and assessed the potential of iam-containing cattle and human isolates for chicken colonization and human cell invasion. Results Simultaneous RAPD typing and iam-specific PCR analysis of 129 C. jejuni isolated from 1171 cattle fecal samples showed that 8 (6.2%) of the isolates were iam-positive, while 7 (54%) of human-associated isolates were iam-positive. The iam sequences were mostly heterogeneous and occurred in diverse genetic backgrounds. All iam-positive isolates were motile and possessed important genes (cadF, ciaB, cdtB) associated with adhesion and virulence. Although certain iam-containing isolates invaded and survived in INT-407 cells in high numbers and successfully colonized live chickens, there was no clear association between the occurrence, allelic sequence, and expression levels of the iam and the aforementioned phenotypes. Conclusions We show that the prevalence of iam in cattle C. jejuni is relatively lower as compared to isolates occurring in humans and chickens. In addition, iam was polymorphic and certain alleles occur in cattle isolates that were capable of colonizing and invading chickens and human intestinal cells, respectively. However, the iam did not appear to contribute to the cattle-associated C. jejuni's potential for invasion and intracellular survival in human intestinal cells as well as chicken colonization. PMID:22208406

The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45-74 years of age.

PubMed

Johnson, Susan L; Tabaei, Bahman P; Herman, William H

2005-02-01

To simulate the outcomes of alternative strategies for screening the U.S. population 45-74 years of age for type 2 diabetes. We simulated screening with random plasma glucose (RPG) and cut points of 100, 130, and 160 mg/dl and a multivariate equation including RPG and other variables. Over 15 years, we simulated screening at intervals of 1, 3, and 5 years. All positive screening tests were followed by a diagnostic fasting plasma glucose or an oral glucose tolerance test. Outcomes include the numbers of false-negative, true-positive, and false-positive screening tests and the direct and indirect costs. At year 15, screening every 3 years with an RPG cut point of 100 mg/dl left 0.2 million false negatives, an RPG of 130 mg/dl or the equation left 1.3 million false negatives, and an RPG of 160 mg/dl left 2.8 million false negatives. Over 15 years, the absolute difference between the most sensitive and most specific screening strategy was 4.5 million true positives and 476 million false-positives. Strategies using RPG cut points of 130 mg/dl or the multivariate equation every 3 years identified 17.3 million true positives; however, the equation identified fewer false-positives. The total cost of the most sensitive screening strategy was $42.7 billion and that of the most specific strategy was $6.9 billion. Screening for type 2 diabetes every 3 years with an RPG cut point of 130 mg/dl or the multivariate equation provides good yield and minimizes false-positive screening tests and costs.

Breast cancer detection risk in screening mammography after a false-positive result.

PubMed

Castells, X; Román, M; Romero, A; Blanch, J; Zubizarreta, R; Ascunce, N; Salas, D; Burón, A; Sala, M

2013-02-01

False-positives are a major concern in breast cancer screening. However, false-positives have been little evaluated as a prognostic factor for cancer detection. Our aim was to evaluate the association of false-positive results with the cancer detection risk in subsequent screening participations over a 17-year period. This is a retrospective cohort study of 762,506 women aged 45-69 years, with at least two screening participations, who underwent 2,594,146 screening mammograms from 1990 to 2006. Multilevel discrete-time hazard models were used to estimate the adjusted odds ratios (OR) of breast cancer detection in subsequent screening participations in women with false-positive results. False-positives involving a fine-needle aspiration cytology or a biopsy had a higher cancer detection risk than those involving additional imaging procedures alone (OR = 2.69; 95%CI: 2.28-3.16 and OR = 1.81; 95%CI: 1.70-1.94, respectively). The risk of cancer detection increased substantially if women with cytology or biopsy had a familial history of breast cancer (OR = 4.64; 95%CI: 3.23-6.66). Other factors associated with an increased cancer detection risk were age 65-69 years (OR = 1.84; 95%CI: 1.67-2.03), non-attendance at the previous screening invitation (OR = 1.26; 95%CI: 1.11-1.43), and having undergone a previous benign biopsy outside the screening program (OR = 1.24; 95%CI: 1.13-1.35). Women with a false-positive test have an increased risk of cancer detection in subsequent screening participations, especially those with a false-positive result involving cytology or biopsy. Understanding the factors behind this association could provide valuable information to increase the effectiveness of breast cancer screening. Copyright © 2012 Elsevier Ltd. All rights reserved.

Psychological distress in U.S. women who have experienced false-positive mammograms.

PubMed

Jatoi, Ismail; Zhu, Kangmin; Shah, Mona; Lawrence, William

2006-11-01

In the United States, approximately 10.7% of all screening mammograms lead to a false-positive result, but the overall impact of false-positives on psychological well-being is poorly understood. Data were analyzed from the 2000 U.S. National Health Interview Survey (NHIS), the most recent national survey that included a cancer control module. Study subjects were 9,755 women who ever had a mammogram, of which 1,450 had experienced a false-positive result. Psychological distress was assessed using the validated K6 questionnaire and logistic regression was used to discern any association with previous false-positive mammograms. In a multivariate analysis, women who had indicated a previous false-positive mammogram were more likely to report feeling sad (OR = 1.18, 95% CI, 1.03-1.35), restless (OR = 1.23, 95% CI, 1.08-1.40), worthless (OR = 1.27, 95% CI, 1.04-1.54), and finding that everything was an effort (OR = 1.27, 95% CI, 1.10-1.47). These women were also more likely to have seen a mental health professional in the 12 months preceding the survey (OR = 1.28, 95% CI, 1.03-1.58) and had a higher composite score on all items of the K6 scale (P < 0.0001), a reflection of increased psychological distress. Analyses by age and race revealed that, among women who had experienced false-positives, younger women were more likely to feel that everything was an effort, and blacks were more likely to feel restless. In a random sampling of the U.S. population, women who had previously experienced false-positive mammograms were more likely to report symptoms of anxiety and depression.

False Positive Probabilities for all Kepler Objects of Interest: 1284 Newly Validated Planets and 428 Likely False Positives

NASA Astrophysics Data System (ADS)

Morton, Timothy D.; Bryson, Stephen T.; Coughlin, Jeffrey L.; Rowe, Jason F.; Ravichandran, Ganesh; Petigura, Erik A.; Haas, Michael R.; Batalha, Natalie M.

2016-05-01

We present astrophysical false positive probability calculations for every Kepler Object of Interest (KOI)—the first large-scale demonstration of a fully automated transiting planet validation procedure. Out of 7056 KOIs, we determine that 1935 have probabilities <1% of being astrophysical false positives, and thus may be considered validated planets. Of these, 1284 have not yet been validated or confirmed by other methods. In addition, we identify 428 KOIs that are likely to be false positives, but have not yet been identified as such, though some of these may be a result of unidentified transit timing variations. A side product of these calculations is full stellar property posterior samplings for every host star, modeled as single, binary, and triple systems. These calculations use vespa, a publicly available Python package that is able to be easily applied to any transiting exoplanet candidate.

Metamorphic ore remobilization in the Hällefors district, Bergslagen, Sweden: constraints from mineralogical and small-scale sulphur isotope studies

NASA Astrophysics Data System (ADS)

Wagner, Thomas; Jonsson, Erik; Boyce, Adrian J.

2005-07-01

The marble- and metavolcanic-hosted Pb Zn (Ag Sb As) deposits of the Hällefors district, located in the Palaeoproterozoic Bergslagen ore province, south central Sweden, comprise both stratabound sulphides and discordant, Ag-rich sulphide sulphosalt veins. The complex sulphide sulphosalt assemblages of the Alfrida-Jan Olof mines at Hällefors were investigated by a combination of ore microscopy, electron-microprobe analysis, and in situ laser sulphur isotope analysis. The massive ore is characterized by positive and homogeneous δ34S (+1.4‰ to +2.7‰ V-CDT), whereas vein-hosted sulphides and sulphosalts exhibit similar, but generally less positive to slightly negative δ34S (-0.6‰ to +2.0‰). Comparison of the observed ore mineral assemblages with calculated phase equilibria in the system Fe As S O H and isotopic fractionation as a function of temperature, oxygen fugacity and pH indicates that the vein-type mineralization was formed from relatively reduced and rather alkaline hydrothermal fluids. At these reduced conditions, fractionation of δ34S via changes of fO2 is insignificant, and thus the isotopic signatures of the vein minerals directly reflect the composition of the sulphur source. We therefore conclude that the vein-type ore essentially inherited the sulphur isotope signature from the pre-existing massive sulphides via metamorphic remobilization at approximately 300 400°C and 2 3 kbar. Scales of remobilization observable are on the order of about 5 mm to 30 cm. Overall, the sulphide sulphosalt assemblages from the Alfrida-Jan Olof mines exhibit δ34S values which are comparable to a majority of metasupracrustal-hosted deposits in the Bergslagen province, thereby suggesting a common origin from ca. 1.90 1.88 Ga volcanic-hydrothermal processes.

High prevalence of sequence type 131 isolates producing CTX-M-15 among ESBL-producing Escherichia coli strains in north-east Iran.

PubMed

Moghanni, Marzie; Ghazvini, Kiarash; Farsiani, Hadi; Namaei, Mohammad Hasan; Derakhshan, Mohammad; Yousefi, Masoud; Maragheh, Alimohammad; Jamehdar, Saeid Amel

2018-05-25

The recent expansion of extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli (E. coli) is a worldwide problem. The purpose of this study was to investigate the molecular characteristic of ESBL-producing E. coli strains in Mashhad, located in the northeast of Iran. A total of 455 clinical isolates of E. coli were collected at three hospitals in Mashhad between April and September 2015. Antibiotic susceptibility was determined with the Kirby Bauer disk diffusion test. The Combination Disc Test (CDT) was performed for the phenotypic detection of ESBLs. PCR was used for screening isolates for ESBLs typing. Phylogenetic groups and sequence type 131 were determined by multiplex-PCR. The prevalence of ESBL-producing E. coli in the collected E. coli strains was 52% (235/455). Among the 235 ESBL producer strains, 94.4% (222/235) tested positive for the CTX-M type, while 115 (48.9%), 92 (39%) and 21 (8.9%) strains were positive for TEM, OXA and SHV, respectively. Moreover, CTX-M-15 (94.1%, 209/222) was the most common ESBL-producing E. coli. Based on multiplex-PCR, the phylogenetic group B2 was the most predominant (169 isolates, 71.9%), followed by D (32, 13.6%), A (21, 8.9%), and B1 (13, 5.5%). Of the 169 groups of B2 isolates, ST131 (151, 89.3%) was the predominant clonal group. The obtained results revealed that an urgent investigation of the source and the transmission pathways of the CTX-M15-B2ST131 E. coli clone was needed to countervail this emergent public health problem. Copyright © 2018. Published by Elsevier Ltd.

Clostridium difficile and Clostridium perfringens from wild carnivore species in Brazil.

PubMed

Silva, Rodrigo Otávio Silveira; D'Elia, Mirella Lauria; Tostes Teixeira, Erika Procópio; Pereira, Pedro Lúcio Lithg; de Magalhães Soares, Danielle Ferreira; Cavalcanti, Álvaro Roberto; Kocuvan, Aleksander; Rupnik, Maja; Santos, André Luiz Quagliatto; Junior, Carlos Augusto Oliveira; Lobato, Francisco Carlos Faria

2014-08-01

Despite some case reports, the importance of Clostridium perfringens and Clostridium difficile for wild carnivores remains unclear. Thus, the objective of this study was to identify C. perfringens and C. difficile strains in stool samples from wild carnivore species in Brazil. A total of 34 stool samples were collected and subjected to C. perfringens and C. difficile isolation. Suggestive colonies of C. perfringens were then analyzed for genes encoding the major C. perfringens toxins (alpha, beta, epsilon and iota) and the beta-2 toxin (cpb2), enterotoxin (cpe) and NetB (netb) genes. C. difficile strains were analyzed by multiplex-PCR for toxins A (tcdA) and B (tcdB) and a binary toxin gene (cdtB) and also submitted to a PCR ribotyping. Unthawed aliquots of samples positive for C. difficile isolation were subjected to the detection of A/B toxins by a cytotoxicity assay (CTA). C. perfringens was isolated from 26 samples (76.5%), all of which were genotyped as type A. The netb gene was not detected, whereas the cpb2 and cpe genes were found in nine and three C. perfringens strains, respectively. C. difficile was isolated from two (5.9%) samples. A non-toxigenic strain was recovered from a non-diarrheic maned wolf (Chrysocyon brachyurus). Conversely, a toxigenic strain was found in the sample of a diarrheic ocelot (Leopardus pardallis); an unthawed stool sample was also positive for A/B toxins by CTA, indicating a diagnosis of C. difficile-associated diarrhea in this animal. The present work suggests that wild carnivore species could carry C. difficile strains and that they could be susceptible to C. difficile infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

How to limit false positives in environmental DNA and metabarcoding?

PubMed

Ficetola, Gentile Francesco; Taberlet, Pierre; Coissac, Eric

2016-05-01

Environmental DNA (eDNA) and metabarcoding are boosting our ability to acquire data on species distribution in a variety of ecosystems. Nevertheless, as most of sampling approaches, eDNA is not perfect. It can fail to detect species that are actually present, and even false positives are possible: a species may be apparently detected in areas where it is actually absent. Controlling false positives remains a main challenge for eDNA analyses: in this issue of Molecular Ecology Resources, Lahoz-Monfort et al. () test the performance of multiple statistical modelling approaches to estimate the rate of detection and false positives from eDNA data. Here, we discuss the importance of controlling for false detection from early steps of eDNA analyses (laboratory, bioinformatics), to improve the quality of results and allow an efficient use of the site occupancy-detection modelling (SODM) framework for limiting false presences in eDNA analysis. © 2016 John Wiley & Sons Ltd.

Evaluation of MTANNs for eliminating false-positive with different computer aided pulmonary nodules detection software.

PubMed

Shi, Zhenghao; Ma, Jiejue; Feng, Yaning; He, Lifeng; Suzuki, Kenji

2015-11-01

MTANN (Massive Training Artificial Neural Network) is a promising tool, which applied to eliminate false-positive for thoracic CT in recent years. In order to evaluate whether this method is feasible to eliminate false-positive of different CAD schemes, especially, when it is applied to commercial CAD software, this paper evaluate the performance of the method for eliminating false-positives produced by three different versions of commercial CAD software for lung nodules detection in chest radiographs. Experimental results demonstrate that the approach is useful in reducing FPs for different computer aided lung nodules detection software in chest radiographs.

Computerized mass detection in whole breast ultrasound images: reduction of false positives using bilateral subtraction technique

NASA Astrophysics Data System (ADS)

Ikedo, Yuji; Fukuoka, Daisuke; Hara, Takeshi; Fujita, Hiroshi; Takada, Etsuo; Endo, Tokiko; Morita, Takako

2007-03-01

The comparison of left and right mammograms is a common technique used by radiologists for the detection and diagnosis of masses. In mammography, computer-aided detection (CAD) schemes using bilateral subtraction technique have been reported. However, in breast ultrasonography, there are no reports on CAD schemes using comparison of left and right breasts. In this study, we propose a scheme of false positive reduction based on bilateral subtraction technique in whole breast ultrasound images. Mass candidate regions are detected by using the information of edge directions. Bilateral breast images are registered with reference to the nipple positions and skin lines. A false positive region is detected based on a comparison of the average gray values of a mass candidate region and a region with the same position and same size as the candidate region in the contralateral breast. In evaluating the effectiveness of the false positive reduction method, three normal and three abnormal bilateral pairs of whole breast images were employed. These abnormal breasts included six masses larger than 5 mm in diameter. The sensitivity was 83% (5/6) with 13.8 (165/12) false positives per breast before applying the proposed reduction method. By applying the method, false positives were reduced to 4.5 (54/12) per breast without removing a true positive region. This preliminary study indicates that the bilateral subtraction technique is effective for improving the performance of a CAD scheme in whole breast ultrasound images.

Evaluation of fecal elastase and serum cholecystokinin in dogs with a false positive fecal elastase test.

PubMed

Steiner, J M; Rehfeld, J F; Pantchev, N

2010-01-01

An assay for the measurement of pancreatic elastase in dog feces has been introduced. The goal of this study was to evaluate the rate of false-positive fecal-elastase test results in dogs with suspected exocrine pancreatic insufficiency (EPI) and to assess serum cholecystokinin (CCK) concentrations in dogs with a false positive fecal elastase test result. Twenty-six fecal and serum samples from dogs suspected of EPI, for which samples had been submitted to a commercial laboratory (Vet Med Labor) for analysis. Prospective study. Serum trypsin-like immunoreactivity (TLI) was measured in 26 dogs with a decreased fecal elastase concentration of <10 microg/g feces. Serum CCK concentrations were measured in 21 of these dogs. Of 26 dogs with a decreased fecal elastase concentration, 6 (23%) had serum TLI concentrations within or above the reference range. Serum CCK concentrations were significantly higher in dogs with a true positive fecal elastase test result (median: 1.1 pmol/L; range: 0.1-3.3 pmol/L) than in those with a false positive fecal elastase test result (median: 0.1 pmol/L; range: 0.1-0.9 pmol/L; P value = .0163). The rate of false positive fecal elastase test results was high in this group of dogs, suggesting that diagnosis of EPI must be confirmed by other means. The decreased CCK concentration in dogs with a false positive fecal elastase test result could suggest that false positive results are because of decreased stimulation of exocrine pancreatic function caused by other conditions.

Sherlock Holmes and child psychopathology assessment approaches: the case of the false-positive.

PubMed

Jensen, P S; Watanabe, H

1999-02-01

To explore the relative value of various methods of assessing childhood psychopathology, the authors compared 4 groups of children: those who met criteria for one or more DSM diagnoses and scored high on parent symptom checklists, those who met psychopathology criteria on either one of these two assessment approaches alone, and those who met no psychopathology assessment criterion. Parents of 201 children completed the Child Behavior Checklist (CBCL), after which children and parents were administered the Diagnostic Interview Schedule for Children (version 2.1). Children and parents also completed other survey measures and symptom report inventories. The 4 groups of children were compared against "external validators" to examine the merits of "false-positive" and "false-negative" cases. True-positive cases (those that met DSM criteria and scored high on the CBCL) differed significantly from the true-negative cases on most external validators. "False-positive" and "false-negative" cases had intermediate levels of most risk factors and external validators. "False-positive" cases were not normal per se because they scored significantly above the true-negative group on a number of risk factors and external validators. A similar but less marked pattern was noted for "false-negatives." Findings call into question whether cases with high symptom checklist scores despite no formal diagnoses should be considered "false-positive." Pending the availability of robust markers for mental illness, researchers and clinicians must resist the tendency to reify diagnostic categories or to engage in arcane debates about the superiority of one assessment approach over another.

Retrospective imaging study on the diagnosis of pathological false positive iodine-131 scans in patients with thyroid cancer.

PubMed

Jia, Qiang; Meng, Zhaowei; Tan, Jian; Zhang, Guizhi; He, Yajing; Sun, Haoran; Yu, Chunshui; Li, Dong; Zheng, Wei; Wang, Renfei; Wang, Shen; Li, Xue; Zhang, Jianping; Hu, Tianpeng; Liu, N A; Upadhyaya, Arun

2015-11-01

Iodine-131 (I-131) therapy and post-therapy I-131 scanning are essential in the management of differentiated thyroid cancer (DTC). However, pathological false positive I-131 scans can lead to misdiagnosis and inappropriate I-131 treatment. This retrospective study aimed to investigate the best imaging modality for the diagnosis of pathological false positive I-131 scans in a DTC patient cohort, and to determine its incidence. DTC patient data archived from January 2008 to January 2010 was retrieved. Post-therapeutic I-131 scans were conducted and interpreted. The imaging modalities of magnetic resonance imaging (MRI), computed tomography and ultrasonography were applied and compared to check all suspected lesions. Biopsy or needle aspiration was conducted for patients who consented to the acquisition of histopathological confirmation. Data for 156 DTC patients were retrieved. Only 6 cases of pathological false-positives were found among these (incidence, 3.85%), which included 3 cases of thymic hyperplasia in the mediastinum, 1 case of pleomorphic adenoma in the parapharyngeal space and 1 case of thyroglossal duct cyst in the neck. MRI was demonstrated as the best imaging modality for diagnosis due to its superior soft tissue resolution. However, no imaging modality was able to identify the abdominal false positive-lesions observed in 2 cases, one of whom also had thymic hyperplasia. In conclusion, pathological false positive I-131 scans occurred with an incidence of 3.85%. MRI was the best imaging modality for diagnosing these pathological false-positives.

Variation in false-positive rates of mammography reading among 1067 radiologists: a population-based assessment.

PubMed

Tan, Alai; Freeman, Daniel H; Goodwin, James S; Freeman, Jean L

2006-12-01

The accuracy of mammography reading varies among radiologists. We conducted a population-based assessment on radiologist variation in false- positive rates of screening mammography and its associated radiologist characteristics. About 27,394 screening mammograms interpreted by 1067 radiologists were identified from a 5% non-cancer sample of Medicare claims during 1998-1999. The data were linked to the American Medical Association Masterfile to obtain radiologist characteristics. Multilevel logistic regression models were used to examine the radiologist variation in false-positive rates of screening mammography and the associated radiologist characteristics. Radiologists varied substantially in the false-positive rates of screening mammography (ranging from 1.5 to 24.1%, adjusting for patient characteristics). A longer time period since graduation is associated with lower false-positive rates (odds ratio [OR] for every 10 years increase: 0.87, 95% Confidence Interval [CI], 0.81-0.94) and female radiologists had higher false-positive rates than male radiologists (OR = 1.25, 95% CI, 1.05-1.49), adjusting for patient and other radiologist characteristics. The unmeasured factors contributed to about 90% of the between-radiologist variance. Radiologists varied greatly in accuracy of mammography reading. Female and more recently trained radiologists had higher false-positive rates. The variation among radiologists was largely due to unmeasured factors, especially unmeasured radiologist factors. If our results are confirmed in further studies, they suggest that system-level interventions would be required to reduce variation in mammography interpretation.

Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy?

PubMed

Mennuti, Michael T; Cherry, Athena M; Morrissette, Jennifer J D; Dugoff, Lorraine

2013-11-01

Testing cell-free DNA (cfDNA) in maternal blood samples has been shown to have very high sensitivity for the detection of fetal aneuploidy with very low false-positive results in high-risk patients who undergo invasive prenatal diagnosis. Recent observation in clinical practice of several cases of positive cfDNA tests for trisomy 18 and trisomy 13, which were not confirmed by cytogenetic testing of the pregnancy, may reflect a limitation of the positive predictive value of this quantitative testing, particularly when it is used to detect rare aneuploidies. Analysis of a larger number of false-positive cases is needed to evaluate whether these observations reflect the positive predictive value that should be expected. Infrequently, mechanisms (such as low percentage mosaicism or confined placental mosaicism) might also lead to positive cfDNA testing that is not concordant with standard prenatal cytogenetic diagnosis. The need to explore these and other possible causes of false-positive cfDNA testing is exemplified by 2 of these cases. Additional evaluation of cfDNA testing in clinical practice and a mechanism for the systematic reporting of false-positive and false-negative cases will be important before this test is offered widely to the general population of low-risk obstetric patients. In the meantime, incorporating information about the positive predictive value in pretest counseling and in clinical laboratory reports is recommended. These experiences reinforce the importance of offering invasive testing to confirm cfDNA results before parental decision-making. Copyright © 2013 Mosby, Inc. All rights reserved.