ClpE from Lactococcus lactis promotes repression of CtsR-dependent gene expression

DEFF Research Database (Denmark)

Varmanen, P.; Vogensen, F.K.; Hammer, Karin

2003-01-01

ATPase (ClpE) in Lactococcus lactis is required for such a decrease in expression of a gene negatively regulated by the heat shock regulator (CtsR). Northern blot analysis showed that while a shift to a high temperature in wild-type cells resulted in a temporal increase followed by a decrease...

Analysis of Linear Hybrid Systems in CLP

DEFF Research Database (Denmark)

Banda, Gourinath; Gallagher, John Patrick

2009-01-01

In this paper we present a procedure for representing the semantics of linear hybrid automata (LHAs) as constraint logic programs (CLP); flexible and accurate analysis and verification of LHAs can then be performed using generic CLP analysis and transformation tools. LHAs provide an expressive...

Preparation of 99Tcm-CLP imaging probe of lung carcinoma

International Nuclear Information System (INIS)

Qiang Yonggang; Liao Yonghua

2004-01-01

The process of preparing an imaging micro-probe 99 Tc m -CLP from bovine nose cartilage is described in detail. Both labeled rate and radiochemical purity of 99 Tc m -CLP are greater than 90%, and KA is 1.12 x 10 9 L/mol in vitro. After the Balb/c nu/nu mice with lung cancer were intravenously injected by the 99 Tc m -CLP, the radioactivity was found to be well concentrated at the lung-cancer region, which suggests that the 99 Tc m -CLP micro-probe can be used in imaging study of lung carcinoma. (authors)

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

Science.gov (United States)

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.

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

Science.gov (United States)

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 Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis.

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Jae Ho Seo

2016-07-01

Full Text Available Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics, but the role of these mechanisms in disease is poorly understood. Using a proteomics screen, we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory chain Complex II subunit succinate dehydrogenase B (SDHB in mitochondria of tumor cells. Knockdown of ClpXP subunits ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and ATP production while activating "stress" signals of 5' adenosine monophosphate-activated protein kinase (AMPK phosphorylation and autophagy. Deregulated mitochondrial respiration induced by ClpXP targeting causes oxidative stress, which in turn reduces tumor cell proliferation, suppresses cell motility, and abolishes metastatic dissemination in vivo. ClpP is universally overexpressed in primary and metastatic human cancer, correlating with shortened patient survival. Therefore, tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. This pathway may provide a "drugable" therapeutic target in cancer.

Implementation of CLP4NET in Bulgaria

International Nuclear Information System (INIS)

Naydenova, I.; Pironkov, L.; Filipov, A.; Petrova, T.; Tsochev, G.; Ganev, I.

2016-01-01

Full text: Networking solutions (networks of excellence, communities of practice, knowledge portals, etc.) are recognized as effective tools for nuclear training and education services, transfer of good practices, knowledge and programmes, and knowledge management. In addition, the e-learning is recommended as a state of the art and cost effective approach for supplementing the traditional face to face training and education programmes. Thus, the Cyber Learning Platform for Nuclear Education and Training (CLP4NET) was implemented into the Kozloduy Nuclear Power Plant (KNPP) Training System. Based on the experience of KNPP, the CLP4NET was implemented also at the College of Energy and Electronics (CEE), Technical University of Sofia (TU-Sofia), providing an appropriate tool for further establishment of a National Nuclear Network of Competency. The current study is focused mainly on specific issues and lessons learned during the installation of CLP4NET at the CEE, TU-Sofia. (author

Role of the disaggregase ClpB in processing of proteins aggregated as inclusion bodies.

Science.gov (United States)

Zblewska, Kamila; Krajewska, Joanna; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

2014-08-01

Overproduction of heterologous proteins in bacterial systems often results in the formation of insoluble inclusion bodies (IBs), which is a major impediment in biochemical research and biotechnology. In principle, the activity of molecular chaperones could be employed to gain control over the IB formation and to improve the recombinant protein yields, but the potential of each of the major bacterial chaperones (DnaK/J, GroEL/ES, and ClpB) to process IBs has not been fully established yet. We investigated the formation of inclusion bodies (IBs) of two aggregation-prone proteins, VP1LAC and VP1GFP, overproduced in Escherichiacoli in the presence and absence of the chaperone ClpB. We found that both ClpB isoforms, ClpB95 and ClpB80 accumulated in E. coli cells during the production of IBs. The amount of IB proteins increased in the absence of ClpB. ClpB supported the resolubilization and reactivation of the aggregated VP1LAC and VP1GFP in E. coli cells. The IB disaggregation was optimal in the presence of both ClpB95 and ClpB80. Our results indicate an essential role of ClpB in controlling protein aggregation and inclusion body formation in bacteria. Copyright © 2014 Elsevier Inc. All rights reserved.

Cooperation between two ClpB isoforms enhances the recovery of the recombinant {beta}-galactosidase from inclusion bodies

Energy Technology Data Exchange (ETDEWEB)

Guenther, Izabela [Department of Biochemistry, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk (Poland); Zolkiewski, Michal [Department of Biochemistry, Kansas State University, Manhattan, KS 66506 (United States); Kedzierska-Mieszkowska, Sabina, E-mail: kedzie@biotech.ug.gda.pl [Department of Biochemistry, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk (Poland)

2012-10-05

Highlights: Black-Right-Pointing-Pointer An important role of synergistic cooperation between the two ClpB isoforms. Black-Right-Pointing-Pointer Both ClpB isoforms are associated with IBs of {beta}-galactosidase. Black-Right-Pointing-Pointer ClpB is a key chaperone in IB protein release. -- Abstract: Bacterial ClpB is a molecular chaperone that solubilizes and reactivates aggregated proteins in cooperation with the DnaK chaperone system. The mechanism of protein disaggregation mediated by ClpB is linked to translocation of substrates through the central channel within the ring-hexameric structure of ClpB. Two isoforms of ClpB are produced in vivo: the full-length ClpB95 and the truncated ClpB80 (ClpB{Delta}N), which does not contain the N-terminal domain. The functional specificity of the two ClpB isoforms and the biological role of the N-terminal domain are still not fully understood. Recently, it has been demonstrated that ClpB may achieve its full potential as an aggregate-reactivating chaperone through the functional interaction and synergistic cooperation of its two isoforms. It has been found that the most efficient resolubilization and reactivation of stress-aggregated proteins occurred in the presence of both ClpB95 and ClpB80. In this work, we asked if the two ClpB isoforms functionally cooperate in the solubilization and reactivation of proteins from insoluble inclusion bodies (IBs) in Escherichia coli cells. Using the model {beta}-galactosidase fusion protein (VP1LAC), we found that solubilization and reactivation of enzymes entrapped in IBs occurred more efficiently in the presence of ClpB95 with ClpB80 than with either ClpB95 or ClpB80 alone. The two isoforms of ClpB chaperone acting together enhanced the solubility and enzymatic activity of {beta}-galactosidase sequestered into IBs. Both ClpB isoforms were associated with IBs of {beta}-galactosidase, what demonstrates their affinity to this type of aggregates. These results demonstrate a synergistic

Immunoreactivity of the AAA+ chaperone ClpB from Leptospira interrogans with sera from Leptospira-infected animals.

Science.gov (United States)

Krajewska, Joanna; Arent, Zbigniew; Więckowski, Daniel; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

2016-07-16

Leptospira interrogans is a spirochaete responsible for leptospirosis in mammals. The molecular mechanisms of the Leptospira virulence remain mostly unknown. Recently, it has been demonstrated that L. interrogans ClpB (ClpBLi) is essential for bacterial survival under stressful conditions and also during infection. The aim of this study was to provide further insight into the role of ClpB in L. interrogans and answer the question whether ClpBLi as a potential virulence factor may be a target of the humoral immune response during leptospiral infections in mammals. ClpBLi consists of 860 amino acid residues with a predicted molecular mass of 96.3 kDa and shows multi-domain organization similar to that of the well-characterized ClpB from Escherichia coli. The amino acid sequence identity between ClpBLi and E. coli ClpB is 52 %. The coding sequence of the clpB Li gene was cloned and expressed in E. coli BL21(DE3) strain. Immunoreactivity of the recombinant ClpBLi protein was assessed with the sera collected from Leptospira-infected animals and uninfected healthy controls. Western blotting and ELISA analysis demonstrated that ClpBLi activates the host immune system, as evidenced by an increased level of antibodies against ClpBLi in the sera from infected animals, as compared to the control group. Additionally, ClpBLi was found in kidney tissues of Leptospira-infected hamsters. ClpBLi is both synthesized and immunogenic during the infectious process, further supporting its involvement in the pathogenicity of Leptospira. In addition, the immunological properties of ClpBLi point to its potential value as a diagnostic antigen for the detection of leptospirosis.

Substrate Discrimination by ClpB and Hsp104

Directory of Open Access Journals (Sweden)

Danielle M. Johnston

2017-05-01

Full Text Available ClpB of E. coli and yeast Hsp104 are homologous molecular chaperones and members of the AAA+ (ATPases Associated with various cellular Activities superfamily of ATPases. They are required for thermotolerance and function in disaggregation and reactivation of aggregated proteins that form during severe stress conditions. ClpB and Hsp104 collaborate with the DnaK or Hsp70 chaperone system, respectively, to dissolve protein aggregates both in vivo and in vitro. In yeast, the propagation of prions depends upon Hsp104. Since protein aggregation and amyloid formation are associated with many diseases, including neurodegenerative diseases and cancer, understanding how disaggregases function is important. In this study, we have explored the innate substrate preferences of ClpB and Hsp104 in the absence of the DnaK and Hsp70 chaperone system. The results suggest that substrate specificity is determined by nucleotide binding domain-1.

Chance, destiny, and the inner workings of ClpXP.

Science.gov (United States)

Russell, Rick; Matouschek, Andreas

2014-07-31

AAA+ proteases are responsible for protein degradation in all branches of life. Using single-molecule and ensemble assays, Cordova et al. investigate how the bacterial protease ClpXP steps through a substrate's polypeptide chain and construct a quantitative kinetic model that recapitulates the interplay between stochastic and deterministic behaviors of ClpXP. Copyright © 2014 Elsevier Inc. All rights reserved.

Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

Science.gov (United States)

Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

2013-06-14

The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

Um modelo híbrido (CLP-MILP para scheduling de operações em polidutos

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Leandro Magatão

2008-12-01

Full Text Available A eficácia na transferência de derivados de petróleo através de dutos motiva a execução deste trabalho. O objetivo principal é a modelagem do scheduling de um poliduto, isto é, um sistema de dutos que transporta diferentes derivados de petróleo. O poliduto em estudo com 93,5 km de extensão conecta uma refinaria a um terminal portuário. Foi desenvolvido um modelo de otimização baseado na união de Constraint Logic Programming (CLP e Mixed Integer Linear Programming (MILP. O modelo utiliza uma abordagem de decomposição do problema, com representação temporal contínua e calcula janelas de tempo (restrições temporais que devem ser respeitadas. A abordagem híbrida CLP-MILP proporcionou a solução de cenários reais em tempo computacional da ordem de segundos. A resolução computacional do modelo proposto evidenciou novos pontos de operação para o poliduto, proporcionando ganhos operacionais significativos. O modelo implementado configura uma ferramenta de auxílio para tomada de decisões operacionais no cenário estudado.This work is motivated by the need of optimization in the pipeline-oil distribution scenario. The considered problem involves the short-term scheduling of activities in a specific pipeline. The pipeline is 93.5 km in length, and it connects refinery and harbor tankfarms, conveying different types of commodities (gasoline, diesel, kerosene, etc. An optimization model was developed to determine the pipeline scheduling with improved efficiency. Such model combines Constraint Logic Programming (CLP and Mixed Integer Linear Programming (MILP in an integrated CLP-MILP framework. The proposed model uses decomposition strategies, continuous time representation, and intervals that represent time constraints (time windows. Real cases were solved in a reduced computational time (order of seconds. The computational results have demonstrated that the model is able to define new operational points to the pipeline

Theoretical insight into the heat shock response (HSR) regulation in Lactobacillus casei and L. rhamnosus.

Science.gov (United States)

Rossi, Franca; Zotta, Teresa; Iacumin, Lucilla; Reale, Anna

2016-08-07

The understanding of the heat shock response (HSR) in lactobacilli from a regulatory point of view is still limited, though an increased knowledge on the regulation of this central stress response can lead to improvements in the exploitation of these health promoting microorganisms. Therefore the aim of this in silico study, that is the first to be carried out for members of the Lactobacillus genus, was predicting how HSR influences cell functions in the food associated and probiotic species Lactobacillus casei and Lactobacillus rhamnosus. To this purpose, thirteen whole genomes of these bacteria were analyzed to identify which genes involved in HSR are present. It was found that all the genomes share 25 HSR related genes, including those encoding protein repair systems, HSR repressors, HrcA and CtsR, and the positive regulators of HSR, alternative σ factors σ(32) and σ(24). Two genes encoding a σ(70)/σ(24) factor and a Lon protease, respectively, were found only in some genomes. The localization of the HSR regulators binding sites in genomes was analyzed in order to identify regulatory relationships driving HSR in these lactobacilli. It was observed that the binding site for the HrcA repressor is found upstream of the hrcA-grpE-dnaK-dnaJ and groES-groEL gene clusters, of two hsp genes, clpE, clpL and clpP, while the CtsR repressor binding site precedes the ctsR-clpC operon, clpB, clpE and clpP. Therefore the ClpE-ClpP protease complex is dually regulated by HrcA and CtsR. Consensus sequences for the promoters recognized by the HSR alternative σ factors were defined for L. casei and L. rhamnosus and were used in whole genome searches to identify the genes that are possibly regulated by these transcription factors and whose expression level is expected to increases in HSR. The results were validated by applying the same procedure of promoter consensus generation and whole genome search to an additional 11 species representative of the main Lactobacillus

Increased expression of clp genes in Lactobacillus delbrueckii UFV H2b20 exposed to acid stress and bile salts.

Science.gov (United States)

Ferreira, A B; De Oliveira, M N V; Freitas, F S; Alfenas-Zerbini, P; Da Silva, D F; De Queiroz, M V; Borges, A C; De Moraes, C A

2013-12-01

The ability to survive in harsh environments is an important criterion to select potential probiotics strains. The objective of this study was to identify and carry out phylogenetic and expression analysis by quantitative real-time PCR of the clpP, clpE, clpL and clpX genes in the probiotic strain Lactobacillus delbrueckii UFV H2b20 exposed to the conditions prevailing in the gastrointestinal tract (GIT). Phylogenetic trees reconstructed by Bayesian inference showed that the L. delbrueckii UFV H2b20 clpP, clpL and clpE genes and the ones from L. delbrueckii ATCC 11842 were grouped. The exposure of cells to MRS broth of pH 3.5 for 30 and 60 min resulted in an increased expression of the four genes. Exposure of the L. delbrueckii UFV H2b20 cells for 30 and 60 min to MRS broth containing 0.1% bile salts increased the expression of the clpP and clpE genes, while the expression level of the clpL and clpX genes increased only after 30 min of exposure. The involvement of the studied genes in the responses to acid stress and bile salts suggests a possible central role of these genes in the survival of L. delbrueckii UFV H2b20 during the passage through the GIT, a characteristic necessary for probiotic strains.

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

Science.gov (United States)

Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F; Oliveira, Solange

2016-01-01

The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

Directory of Open Access Journals (Sweden)

Ana Paço

Full Text Available The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials. The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants

GFA Taq I polymorphism and cleft lip with or without cleft palate (CL/P) risk

Science.gov (United States)

Dong, Lijia; Ma, Lian

2015-01-01

The transforming growth factor alpha (TGFA) Taq I polymorphism has been indicated to be correlated with cleft lip with or without cleft palate (CL/P) susceptibility, but study results are still debatable. Thus, a meta-analysis was conducted. We conducted a comprehensive search of Embase, Ovid, Web of Science, the Cochrane database, PubMed, the Chinese Biomedical Literature Database (CBM-disc, 1979-2014), the database of National Knowledge Infrastructure (CNKI, 1979-2014) and the full paper database of Chinese Science and Technology of Chongqing (VIP, 1989-2014) to identify suitable studies. There were 18 studies suitable for this meta-analysis, involving a total of 3135 cases and 3575 controls. Significantly increased CL/P risk was observed (OR = 1.49; 95% CI 1.17-1.89; P = 0.001). In subgroup analyses stratified by ethnicity, there was evidence in the Caucasian population for an association between this polymorphism and CL/P risk (OR = 1.52; 95% CI 1.14-2.02; P = 0.004). However, no significant association was found between this his polymorphism and CL/P risk in African and Hispanic populations. According to a specific CL/P type, increased clip lip and palate risk and clip palate risk were found (OR = 1.38; 95% CI 1.10-1.73; P = 0.005; OR = 1.29; 95% CI 1.01-1.66; P = 0.042). In conclusion, the present meta-analysis found that the TGFA Taq I polymorphism may be associated with CL/P susceptibility. PMID:26064247

In Vitro Evaluation of Dentin Tubule Occlusion for Novel Calcium Lactate Phosphate (CLP Paste

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Jen-Chang Yang

2017-02-01

Full Text Available Introduction: The objective of this in vitro study is to evaluate the effective and long-term occlusion of dentinal tubules using a novel calcium lactate phosphate (CLP based desensitizing agent. Methods: Dentin disks (n = 9 were pre-etched using 1 M lactic acid for 30 s and individually treated with Colgate® Pro-Relief™ paste, CLP paste, and double distilled water (ddH2O by a rubber-cupped handpiece. Dentin disks were analyzed under optical micrographs for pre-treatment, directly after treatment, and 14 days post-treatment. One-way ANOVA and post-hoc Tukey’s test were used to determine whether there were any statistically significant differences in dentinal tubule diameter. Results: A significant decrease occurred in the mean tubule diameter for dentin disks treated with CLP paste. A decrease was observed from 3.52 ± 0.83 µm to 2.62 ± 0.42 µm right after treatment, further decreasing to 1.71 ± 0.45 µm after immersion in artificial saliva for 14 days (p < 0.05. Conclusions: The results suggest that the CLP based desensitizing paste has remineralization properties and provides instant and lasting effectiveness in dentinal tubule occlusion.

Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

Science.gov (United States)

Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

2011-07-01

ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in Staphylococcus aureus Cells Lacking the ClpX Chaperone

DEFF Research Database (Denmark)

Baek, Kristoffer T.; Bowman, Lisa; Millership, Charlotte

2016-01-01

Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise...... not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement...

A simple fragment of cyclic acyldepsipeptides is necessary and sufficient for ClpP activation and antibacterial activity.

Science.gov (United States)

Carney, Daniel W; Compton, Corey L; Schmitz, Karl R; Stevens, Julia P; Sauer, Robert T; Sello, Jason K

2014-10-13

The development of new antibacterial agents, particularly those with unique biological targets, is essential to keep pace with the inevitable emergence of drug resistance in pathogenic bacteria. We identified the minimal structural component of the cyclic acyldepsipeptide (ADEP) antibiotics that exhibits antibacterial activity. We found that N-acyldifluorophenylalanine fragments function via the same mechanism of action as ADEPs, as evidenced by the requirement of ClpP for the fragments' antibacterial activity, the ability of fragments to activate Bacillus subtilis ClpP in vitro, and the capacity of an N-acyldifluorophenylalanine affinity matrix to capture ClpP from B. subtilis cell lysates. N-acyldifluorophenylalanine fragments are much simpler in structure than the full ADEPs and are also highly amenable to structural diversification. Thus, the stage has been set for the development of non-peptide activators of ClpP that can be used as antibacterial agents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biosynthesis of the antimicrobial cyclic lipopeptides nunamycin and nunapeptin by Pseudomonas fluorescens strain In5 is regulated by the LuxR-type transcriptional regulator NunF

DEFF Research Database (Denmark)

Hennessy, Rosanna Catherine; Phippen, Christopher; Nielsen, Kristian Fog

2017-01-01

-producing pseudomonads except for the border regions where putative LuxR-type regulators are located. This study focuses on understanding the regulatory role of the LuxR-type-encoding gene nunF in CLP production of P. fluorescens In5. Functional analysis of nunF coupled with liquid chromatography-high-resolution mass...... spectrometry (LC-HRMS) showed that CLP biosynthesis is regulated by nunF. Quantitative real-time PCR analysis indicated that transcription of the NRPS genes catalyzing CLP production is strongly reduced when nunF is mutated indicating that nunF is part of the nun-nup regulon. Swarming and biofilm formation...... that environmental elicitors may also influence nunF expression which upon activation regulates nunamycin and nunapeptin production required for the growth inhibition of phytopathogens....

Biosynthesis of the antimicrobial cyclic lipopeptides nunamycin and nunapeptin by Pseudomonas fluorescens strain In5 is regulated by the LuxR-type transcriptional regulator NunF

DEFF Research Database (Denmark)

Hennessy, Rosanna Catherine; Phippen, Christopher; Nielsen, Kristian Fog

2017-01-01

-producing pseudomonads except for the border regions where putative LuxR-type regulators are located. This study focuses on understanding the regulatory role of the LuxR-type-encoding gene nunF in CLP production of P. fluorescens In5. Functional analysis of nunF coupled with liquid chromatography-high-resolution mass......Nunamycin and nunapeptin are two antimicrobial cyclic lipopeptides (CLPs) produced by Pseudomonas fluorescens In5 and synthesized by nonribosomal synthetases (NRPS) located on two gene clusters designated the nun-nup regulon. Organization of the regulon is similar to clusters found in other CLP...... spectrometry (LC-HRMS) showed that CLP biosynthesis is regulated by nunF. Quantitative real-time PCR analysis indicated that transcription of the NRPS genes catalyzing CLP production is strongly reduced when nunF is mutated indicating that nunF is part of the nun-nup regulon. Swarming and biofilm formation...

Activated ClpP kills persisters and eradicates a chronic biofilm infection.

Energy Technology Data Exchange (ETDEWEB)

Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.; LaFleur, Michael D.; Isabella, Vincent M.; Coleman, K.; Leonard, Steve N.; Smith, Richard D.; Adkins, Joshua N.; Lewis, Kim

2013-11-21

The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated with biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.

Stepwise decrease in daptomycin susceptibility in clinical Staphylococcus aureus isolates associated with an initial mutation in rpoB and a compensatory inactivation of the clpX gene

DEFF Research Database (Denmark)

Bæk, Kristoffer Torbjørn; Thøgersen, Louise; Mogensen, René G.

2015-01-01

, reduced expression of virulence traits, induced expression of the stress-associated transcriptional regulator, Spx, and slow growth. A subsequent acquired loss-of-function mutation in clpX partly alleviated the growth defect conferred by the rpoB mutation without changing antibiotic susceptibility...

Biosynthesis of the antimicrobial cyclic lipopeptides nunamycin and nunapeptin by Pseudomonas fluorescens strain In5 is regulated by the LuxR-type transcriptional regulator NunF.

Science.gov (United States)

Hennessy, Rosanna C; Phippen, Christopher B W; Nielsen, Kristian F; Olsson, Stefan; Stougaard, Peter

2017-12-01

Nunamycin and nunapeptin are two antimicrobial cyclic lipopeptides (CLPs) produced by Pseudomonas fluorescens In5 and synthesized by nonribosomal synthetases (NRPS) located on two gene clusters designated the nun-nup regulon. Organization of the regulon is similar to clusters found in other CLP-producing pseudomonads except for the border regions where putative LuxR-type regulators are located. This study focuses on understanding the regulatory role of the LuxR-type-encoding gene nunF in CLP production of P. fluorescens In5. Functional analysis of nunF coupled with liquid chromatography-high-resolution mass spectrometry (LC-HRMS) showed that CLP biosynthesis is regulated by nunF. Quantitative real-time PCR analysis indicated that transcription of the NRPS genes catalyzing CLP production is strongly reduced when nunF is mutated indicating that nunF is part of the nun-nup regulon. Swarming and biofilm formation was reduced in a nunF knockout mutant suggesting that these CLPs may also play a role in these phenomena as observed in other pseudomonads. Fusion of the nunF promoter region to mCherry showed that nunF is strongly upregulated in response to carbon sources indicating the presence of a fungus suggesting that environmental elicitors may also influence nunF expression which upon activation regulates nunamycin and nunapeptin production required for the growth inhibition of phytopathogens. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

13 CFR 120.441 - How does a Lender become a CLP Lender?

Science.gov (United States)

2010-01-01

... consider whether the Lender: (1) Has the ability to process, close, service and liquidate loans; (2) Has a... application packages; (3) Has an acceptable SBA purchase rate; and (4) Has shown the ability to work well with... Lender may appeal to the D/FA, whose decision will be final. If SBA grants CLP status, it applies only in...

Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

Science.gov (United States)

Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

2015-04-10

The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

GSK-3β Inhibition Attenuates CLP-Induced Liver Injury by Reducing Inflammation and Hepatic Cell Apoptosis

Directory of Open Access Journals (Sweden)

Hui Zhang

2014-01-01

Full Text Available Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK- 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP, and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB but enhanced the transcriptional activity of cAMP response element binding protein (CREB in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis.

Whole-gene positive selection, elevated synonymous substitution rates, duplication, and indel evolution of the chloroplast clpP1 gene.

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Per Erixon

Full Text Available BACKGROUND: Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. METHODOLOGY/PRINCIPLE FINDINGS: We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family. Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. CONCLUSIONS/SIGNIFICANCE: We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the

The ClpS-like N-domain is essential for the functioning of Ubr11, an N-recognin in Schizosaccharomyces pombe.

Science.gov (United States)

Kitamura, Kenji

2014-01-01

Several Ubr ubiquitin ligases recognize the N-terminal amino acid of substrate proteins and promote their degradation via the Arg/N-end rule pathway. The primary destabilizing N-terminal amino acids in yeast are classified into type 1 (Arg, Lys, and His) and type 2 (Phe, Trp, Tyr, Leu, Ile, and Met-Ф) residues. The type 1 and type 2 residues bind to the UBR box and the ClpS/N-domain, respectively, in canonical Ubr ubiquitin ligases that act as N-recognins. In this study, the requirement for type 1 and type 2 amino acid recognition by Schizosaccharomyces pombe Ubr11 was examined in vivo. Consistent with the results of previous studies, the ubr11∆ null mutant was found to be defective in oligopeptide uptake and resistant to ergosterol synthesis inhibitors. Furthermore, the ubr11∆ mutant was also less sensitive to some protein synthesis inhibitors. A ubr11 ClpS/N-domain mutant, which retained ubiquitin ligase activity but could not recognize type 2 amino acids, phenocopied all known defects of the ubr11∆ mutant. However, the recognition of type 1 residues by Ubr11 was not required for its functioning, and no severe physiological abnormalities were observed in a ubr11 mutant defective in the recognition of type 1 residues. These results reinforce the fundamental importance of the ClpS/N-domain for the functioning of the N-recognin, Ubr11.

Differential regulation of tissue thiol-disulfide redox status in a murine model of peritonitis

Directory of Open Access Journals (Sweden)

Benton Shana M

2012-10-01

Full Text Available Abstract Background Glutathione (GSH/glutathione disulfide (GSSG and cysteine (Cys/cystine (CySS are major redox pools with important roles in cytoprotection. We determined the impact of septic peritonitis on thiol-disulfide redox status in mice. Methods FVB/N mice (6–12 week old; 8/group underwent laparotomy with cecal ligation and puncture (CLP or laparotomy alone (control. Sections of ileum, colon, lung and liver were obtained and GSH, GSSG, Cys and CySS concentrations determined by HPLC 24 h after laparotomy. Redox potential [Eh in millivolts (mV] of the GSH/GSSG and Cys/CySS pools was calculated using the Nernst equation. Data were analyzed by ANOVA (mean ± SE. Results GSH/GSSG Eh in ileum, colon, and liver was significantly oxidized in septic mice versus control mice (ileum: septic −202±4 versus control −228±2 mV; colon: -195±8 versus −214±1 mV; and liver: -194±3 vs. -210±1 mV, all Ph was unchanged with CLP, while liver and lung Cys/CySS Eh became significantly more reducing (liver: septic = −103±3 versus control −90±2 mV; lung: -101±5 versus −81±1 mV, each P Conclusions Septic peritonitis induced by CLP oxidizes ileal and colonic GSH/GSSG redox but Cys/CySS Eh remains unchanged in these intestinal tissues. In liver, CLP oxidizes the GSH/GSSG redox pool and CyS/CySS Eh becomes more reducing; in lung, CLP does not alter GSH/GSSG Eh, and Cys/CySS Eh is less oxidized. CLP-induced infection/inflammation differentially regulates major thiol-disulfide redox pools in this murine model.

Labelling of electronic cigarettes: regulations and current practice.

Science.gov (United States)

Buonocore, Federico; Marques Gomes, Ana C N; Nabhani-Gebara, Shereen; Barton, Stephen J; Calabrese, Gianpiero

2017-01-01

Over the past decade e-cigarettes have established themselves in the global market. E-cigarettes triggered much interest in relation to their content and efficacy as smoking cessation tools, but less attention has been paid to users and environmental safety warnings and guidance. Several regulations have been introduced to promote their safe handling and disposal. From May 2016, liquids and cartridges will be regulated by European Community Directives (ECDs) 2001/83/EC and 93/42/EEC, or 2014/40/EU if marketed as tobacco-related products. Currently, manufacturers and distributors must abide by the Chemical (Hazard Information and Packaging for Supply) Regulations 2009 (CHIP) or Classification, Labelling and Packaging Regulations (CLP), the latter replacing CHIP in June 2015. In this work, the compliance of marketed e-liquids and e-cigarettes with current European Union and UK legislations is assessed. E-liquids and e-cigarettes (21 and 9 brands, respectively) were evaluated. Evidence of non-compliance was found in relation to the CHIP/CLP toxic (13%) and environmental (37%) pictograms, tactile warning (23%), nominal amount of solution (30%), supplier contact telephone number and address (40%). None of the evaluated e-cigarettes displayed information on the correct disposal/recycling of batteries in line with the ECD 2006/66/EC. More stringent enforcement of regulations is needed to ensure not only the user's safety and awareness, but also the safeguarding of the environment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Down-regulation of E protein activity augments an ILC2 differentiation program in the thymus

Science.gov (United States)

Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Une...

In the shadow of the Cosmetic Directive — Inconsistencies in EU environmental hazard classification requirements for UV-filters

International Nuclear Information System (INIS)

Sobek, A.; Bejgarn, S.; Rudén, C.; Molander, L.; Breitholtz, M.

2013-01-01

UV-filters are chemicals with potentially environmental hazardous properties. In the European Union (EU), UV-filters contained in sunscreen products are currently regulated by the Cosmetic Directive (from July 2013 by the Cosmetic Products Regulation). Environmental hazard classifications according to the regulation on classification, labelling and packaging of substances and mixtures (CLP) must be determined for UV-filters contained in industrial chemical products, whereas UV-filters contained in sunscreens are exempted from CLP. In this study we determined the potential environmental hazard classifications of UV-filters and sunscreen products if the CLP regulation was to be required for cosmetic products. Two sunscreen products were evaluated in accordance with the aquatic environmental hazard criteria for mixtures. The results highlight that the inconsistencies in the current EU regulation of UV filters hamper the risk management of environmental hazards of UV filters used in cosmetic products. Almost 50% of the investigated UV-filters approved for use in cosmetic products on the European market according to the current Cosmetic Directive were identified to meet the CLP classification as being hazardous to the aquatic environment. Assuming a worst-case scenario, the two examined sunscreens could both be classified as hazardous to the aquatic environment with long-lasting effects according to CLP classification criteria. Hence, if the CLP regulation was applicable to sunscreen products, both brands could potentially be labelled with the environmental hazard pictogram and associated hazard and precautionary statements. Including cosmetic products, and thereby sunscreens, in the CLP regulation would contribute to a more harmonized and transparent regulation of potentially hazardous substances on the EU market. - Highlights: • UV-filters are used in both cosmetic and industrial products/applications • UV-filters in cosmetic products are excluded from CLP • We

30 CFR 253.3 - How are the terms used in this regulation defined?

Science.gov (United States)

2010-07-01

... in this regulation defined? Terms used in this part have the following meaning: Advertise means... well drilled from a mobile offshore drilling unit (MODU) and the associated riser and well control...

Development of an operational manual for a consultation-liaison psychiatry service.

Science.gov (United States)

Wand, Anne Pf; Sharma, Swapnil; Carpenter, Lindsay J; Gatsi, Mike

2018-02-01

Consultation-liaison psychiatry (CLP) services sit between mental health and the general hospital, and risk being poorly understood by both systems. The aim of this study was to develop an operational manual for a CLP service, which defined functions and governance. The CLP literature was reviewed with a focus on descriptions of CLP roles, organisational processes, quality measures and service development. The CLP team held service planning meetings and met with members of the mental health and hospital executives. Site visits and collaboration with other CLP services occurred in defining the roles of the CLP service and organisational governance. A CLP operational document was developed, including a description of the service, its functions, staff roles and governance. Procedural information such as the CLP timetable, referral process, triage and assessment, documentation, activity recording, quality assurance and relevant policies were outlined. The development of a dedicated operational manual for CLP clarified the roles, functions and governance of CLP within the general hospital and mental health systems. The development process facilitated the engagement of key clinicians and administrators of these systems, the determination of quality improvement targets and greater transparency and accountability.

How do older adult drivers self-regulate? Characteristics of self-regulation classes defined by latent class analysis.

Science.gov (United States)

Bergen, Gwen; West, Bethany A; Luo, Feijun; Bird, Donna C; Freund, Katherine; Fortinsky, Richard H; Staplin, Loren

2017-06-01

Motor-vehicle crashes were the second leading cause of injury death for adults aged 65-84years in 2014. Some older drivers choose to self-regulate their driving to maintain mobility while reducing driving risk, yet the process remains poorly understood. Data from 729 older adults (aged ≥60years) who joined an older adult ride service program between April 1, 2010 and November 8, 2013 were analyzed to define and describe classes of driving self-regulation. Latent class analysis was employed to characterize older adult driving self-regulation classes using driving frequency and avoidance of seven driving situations. Logistic regression was used to explore associations between characteristics affecting mobility and self-regulation class. Three classes were identified (low, medium, and high self-regulation). High self-regulating participants reported the highest proportion of always avoiding seven risky driving situations and the lowest driving frequency followed by medium and low self-regulators. Those who were female, aged 80years or older, visually impaired, assistive device users, and those with special health needs were more likely to be high self-regulating compared with low self-regulating. Avoidance of certain driving situations and weekly driving frequency are valid indicators for describing driving self-regulation classes in older adults. Understanding the unique characteristics and mobility limitations of each class can guide optimal transportation strategies for older adults. Published by Elsevier Ltd.

The collectins CL-L1, CL-K1 and CL-P1, and their roles in complement and innate immunity

DEFF Research Database (Denmark)

Hansen, Soren W K; Ohtani, Katsuki; Roy, Nitai

2016-01-01

as CL-LK) and its activation of the lectin pathway via MASPs, drew new attention in the complement biology, which was further strengthened by the observed interactions between CL-P1 and CRP-C1q-factor H or properdin. Deficiency of either CL-K1 or MASP-3 has been demonstrated in 3MC syndrome patients...

Lassomycin, a ribosomally synthesized cyclic peptide, kills mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2.

Science.gov (United States)

Gavrish, Ekaterina; Sit, Clarissa S; Cao, Shugeng; Kandror, Olga; Spoering, Amy; Peoples, Aaron; Ling, Losee; Fetterman, Ashley; Hughes, Dallas; Bissell, Anthony; Torrey, Heather; Akopian, Tatos; Mueller, Andreas; Epstein, Slava; Goldberg, Alfred; Clardy, Jon; Lewis, Kim

2014-04-24

Languishing antibiotic discovery and flourishing antibiotic resistance have prompted the development of alternative untapped sources for antibiotic discovery, including previously uncultured bacteria. Here, we screen extracts from uncultured species against Mycobacterium tuberculosis and identify lassomycin, an antibiotic that exhibits potent bactericidal activity against both growing and dormant mycobacteria, including drug-resistant forms of M. tuberculosis, but little activity against other bacteria or mammalian cells. Lassomycin is a highly basic, ribosomally encoded cyclic peptide with an unusual structural fold that only partially resembles that of other lasso peptides. We show that lassomycin binds to a highly acidic region of the ClpC1 ATPase complex and markedly stimulates its ATPase activity without stimulating ClpP1P2-catalyzed protein breakdown, which is essential for viability of mycobacteria. This mechanism, uncoupling ATPase from proteolytic activity, accounts for the bactericidal activity of lassomycin. Copyright © 2014 Elsevier Ltd. All rights reserved.

36 CFR 261.73 - Regulations applicable to Region 3, Southwestern Region, as defined in § 200.2. [Reserved

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2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Regulations applicable to Region 3, Southwestern Region, as defined in § 200.2. [Reserved] 261.73 Section 261.73 Parks, Forests... § 261.73 Regulations applicable to Region 3, Southwestern Region, as defined in § 200.2. [Reserved] ...

Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor

Energy Technology Data Exchange (ETDEWEB)

Zeymer, Cathleen, E-mail: cathleen.zeymer@mpimf-heidelberg.mpg.de; Barends, Thomas R. M.; Werbeck, Nicolas D.; Schlichting, Ilme; Reinstein, Jochen, E-mail: cathleen.zeymer@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg (Germany)

2014-02-01

High-resolution crystal structures together with mutational analysis and transient kinetics experiments were utilized to understand nucleotide sensing and the regulation of the ATPase cycle in an AAA+ molecular motor. ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg{sup 2+} ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis.

Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor

International Nuclear Information System (INIS)

Zeymer, Cathleen; Barends, Thomas R. M.; Werbeck, Nicolas D.; Schlichting, Ilme; Reinstein, Jochen

2014-01-01

High-resolution crystal structures together with mutational analysis and transient kinetics experiments were utilized to understand nucleotide sensing and the regulation of the ATPase cycle in an AAA+ molecular motor. ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg 2+ ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis

Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.

Directory of Open Access Journals (Sweden)

Jingru Zhao

2016-04-01

Full Text Available Although quorum-sensing (QS systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS. Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR, and its C-terminal HTH (helix-turn-helix domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator. Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.

Science.gov (United States)

Deville, Célia; Carroni, Marta; Franke, Kamila B; Topf, Maya; Bukau, Bernd; Mogk, Axel; Saibil, Helen R

2017-08-01

Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'- O -(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.

In the shadow of the Cosmetic Directive--inconsistencies in EU environmental hazard classification requirements for UV-filters.

Science.gov (United States)

Sobek, A; Bejgarn, S; Rudén, C; Molander, L; Breitholtz, M

2013-09-01

UV-filters are chemicals with potentially environmental hazardous properties. In the European Union (EU), UV-filters contained in sunscreen products are currently regulated by the Cosmetic Directive (from July 2013 by the Cosmetic Products Regulation). Environmental hazard classifications according to the regulation on classification, labelling and packaging of substances and mixtures (CLP) must be determined for UV-filters contained in industrial chemical products, whereas UV-filters contained in sunscreens are exempted from CLP. In this study we determined the potential environmental hazard classifications of UV-filters and sunscreen products if the CLP regulation was to be required for cosmetic products. Two sunscreen products were evaluated in accordance with the aquatic environmental hazard criteria for mixtures. The results highlight that the inconsistencies in the current EU regulation of UV filters hamper the risk management of environmental hazards of UV filters used in cosmetic products. Almost 50% of the investigated UV-filters approved for use in cosmetic products on the European market according to the current Cosmetic Directive were identified to meet the CLP classification as being hazardous to the aquatic environment. Assuming a worst-case scenario, the two examined sunscreens could both be classified as hazardous to the aquatic environment with long-lasting effects according to CLP classification criteria. Hence, if the CLP regulation was applicable to sunscreen products, both brands could potentially be labelled with the environmental hazard pictogram and associated hazard and precautionary statements. Including cosmetic products, and thereby sunscreens, in the CLP regulation would contribute to a more harmonized and transparent regulation of potentially hazardous substances on the EU market. Copyright © 2013 Elsevier B.V. All rights reserved.

[Preliminary study on self-concept psychological feature of cleft lip and palate adolescents].

Science.gov (United States)

Liao, Rui; Zheng, Qian; Shi, Bing; Wang, Yan; Li, Ling; Dong, Rui; Shi, Jin; Yang, Chao

2006-06-01

To obtain the self-concept psychological feature of cleft lip and palate (CLP) adolescents further and accurately, and offer reasons for timely and pointed psychological intervention. Based on the procedure and criteria of development of psychological questionnaire, a psychological questionnaire for CLP adolescents was designed. 93 CLP and 88 healthy adolescents were studied by using it and their half-quantified score raging 0-9 were analyzed statistically. (1) There was no statistical difference between CLP and normal adolescents, scored 5.91 and 5.66 respectively, which demonstrated that the self-concept of CLP adolescents was at a normal level without obvious passive tendency. (2) There was no significant difference between genders, but boys were more extroversion while girls did better on being unyielding and releasing strain. (3) CLP adolescents had a higher ability of psychological regulation and could face failure more bravely. CLP patients were in a tendency of protective behavior inhibition, companied less, and maximized delight mood unconsciously to decrease harm from enviroment. (4) CLP adolescents had a good parentage. (5) A majority of patients had low expectation of life-quality. (6) Much of CLP patients considered that speech was more important than appearance. Self-concept of CLP adolescents have normal self-concept and do better in psychological regulation and dependence than normal ones.

The role of ClpP, RpoS and CsrA in growth and filament formation of Salmonella enterica serovar Typhimurium at low temperature

DEFF Research Database (Denmark)

Knudsen, Gitte Maegaard; Nielsen, Maj-Britt; Thomsen, Line Elnif

2014-01-01

that the phenotype of the csrA mutant was independent from RpoS. Conclusions: The cold sensitivity of clpP mutant was associated with increased levels of RpoS and probably caused by toxic levels of RpoS. Although a csrA mutant also accumulated high level of RpoS, growth impairment caused by lack of csr...

The early activation marker CD69 regulates the expression of chemokines and CD4 T cell accumulation in intestine.

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Katarina Radulovic

Full Text Available Migration of naïve and activated lymphocytes is regulated by the expression of various molecules such as chemokine receptors and ligands. CD69, the early activation marker of C-type lectin domain family, is also shown to regulate the lymphocyte migration by affecting their egress from the thymus and secondary lymphoid organs. Here, we aimed to investigate the role of CD69 in accumulation of CD4 T cells in intestine using murine models of inflammatory bowel disease. We found that genetic deletion of CD69 in mice increases the expression of the chemokines CCL-1, CXCL-10 and CCL-19 in CD4(+ T cells and/or CD4(- cells. Efficient in vitro migration of CD69-deficient CD4 T cells toward the chemokine stimuli was the result of increased expression and/or affinity of chemokine receptors. In vivo CD69(-/- CD4 T cells accumulate in the intestine in higher numbers than B6 CD4 T cells as observed in competitive homing assay, dextran sodium sulphate (DSS-induced colitis and antigen-specific transfer colitis. In DSS colitis CD69(-/- CD4 T cell accumulation in colonic lamina propria (cLP was associated with increased expression of CCL-1, CXCL-10 and CCL-19 genes. Furthermore, treatment of DSS-administrated CD69(-/- mice with the mixture of CCL-1, CXCL-10 and CCL-19 neutralizing Abs significantly decreased the histopathological signs of colitis. Transfer of OT-II×CD69(-/- CD45RB(high CD4 T cells into RAG(-/- hosts induced CD4 T cell accumulation in cLP. This study showed CD69 as negative regulator of inflammatory responses in intestine as it decreases the expression of chemotactic receptors and ligands and reduces the accumulation of CD4 T cells in cLP during colitis.

Boolean models of biosurfactants production in Pseudomonas fluorescens.

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Adrien Richard

Full Text Available Cyclolipopeptides (CLPs are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene (plcC and not restored by plcC complementation. Their production is also subject to phenotypic variation. We used a modelling approach with Boolean networks, which takes into account all these observations concerning CLP production without any assumption on the topology of the considered network. Intensive computation yielded numerous models that satisfy these properties. All models minimizing the number of components point to a bistability in CLP production, which requires the presence of a yet unknown key self-inducible regulator. Furthermore, all suggest that a set of yet unexplained phenotypic variants might also be due to this epigenetic switch. The simplest of these Boolean networks was used to propose a biological regulatory network for CLP production. This modelling approach has allowed a possible regulation to be unravelled and an unusual behaviour of CLP production in P. fluorescens to be explained.

Anti-sigma factor YlaD regulates transcriptional activity of sigma factor YlaC and sporulation via manganese-dependent redox-sensing molecular switch in Bacillus subtilis.

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Kwak, Min-Kyu; Ryu, Han-Bong; Song, Sung-Hyun; Lee, Jin-Won; Kang, Sa-Ouk

2018-05-14

YlaD, a membrane-anchored anti-sigma factor of Bacillus subtilis , contains a HX 3 CXXC motif that functions as a redox-sensing domain and belongs to one of the zinc-coordinated anti-sigma factor families. Despite previously showing that the YlaC transcription is controlled by YlaD, experimental evidence of how the YlaC-YlaD interaction is affected by active cysteines and/or metal ions is lacking. Here, we showed that the P yla promoter is autoregulated solely by YlaC. Moreover, reduced YlaD contained zinc and iron, while oxidized YlaD did not. Cysteine substitution in YlaD led to changes in its secondary structure; Cys3 had important structural functions in YlaD, and its mutation caused dissociation from YlaC, indicating the essential requirement of a HX 3 CXXC motif for regulating interactions of YlaC with YlaD. Analyses of the far-UV CD spectrum and metal content revealed that the addition of Mn ions to Zn-YlaD changed its secondary structure and that iron was substituted for manganese. The ylaC gene expression using βGlu activity from P yla : gusA was observed at the late-exponential and early-stationary phase and the ylaC -overexpressing mutant constitutively expressed gene transcripts of clpP and sigH , an important alternative sigma factor regulated by ClpXP. Collectively, our data demonstrated that YlaD senses redox changes and elicits increase in manganese ion concentrations and that, in turn, YlaD-mediated transcriptional activity of YlaC regulates sporulation initiation under oxidative stress and manganese-substituted conditions by regulating clpP gene transcripts. This is the first report of the involvement of oxidative stress-responsive B. subtilis extracytoplasmic function sigma factors during sporulation via a manganese-dependent redox-sensing molecular switch. ©2018 The Author(s).

Impact of Char Livelihood Program (CLP of Char land Dwellers around the Char Areas in Sirajgonj District of Bangladesh

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Mohammad Anamul Haque

2017-12-01

Full Text Available In an attempt to address the impact of Char Livelihood Program (CLP of Char land dwellers, this study is carried out to examine the livelihood and income generation activities of the people of Bangala Char in Sirajgonj District, due to intervention of Char Livelihood Program (CLP by the DFID of United Kingdom (UK. The research question of the study was whether and to what extent the Char Livelihood Program (CLP brings any changes in the livelihood and income generation activities of the people of Bangala Char. Two areas have been studied, one area is under the intervention of the project (Bangala Char as program intervention area another is not under the program intervention (Sonatoni Char as control area. Both areas have been chosen of the vicinity of similar characteristics and geographical location for the ease of addressing the problems and analytical comparison. The study uses semi-structured questionnaire for household interview both for the program intervention and the control area as random sampling basis. This study a total of 96 households’ interviews conducted of the study areas among them 48 households from Bangala Char and 48 households from the Sonatoni Char (control area. Primary data collected from house hold respondent and secondary data were used from published and unpublished sources. Four variables are access to land, income and assets , food security and vulnerability identified and the analysis shows that access to land resources among the char dwellers has established legal ownership and entitlement of land and resolve the crisis of permanent settlement which bring change in livelihood in terms of access to land resources to some extent. The islands of char dwellers are in general disadvantaged with respect to their mainland counterparts in terms of physical isolation and vulnerability to flooding and erosion have created seasonal migration and higher dependency on traditional money lenders for accessing credit supply

Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture

International Nuclear Information System (INIS)

Marinucci, Lorella; Balloni, Stefania; Bodo, Maria; Carinci, Francesco; Pezzetti, Furio; Stabellini, Giordano; Carmela, Conte; Lumare, Eleonora

2009-01-01

Prenatal exposure to diazepam, a prototype sedative drug that belongs to Benzodiazepines, can lead to orofacial clefting in human newborns. By using real-time PCR, in the present study we investigated whether diazepam elicits gene expression alterations in extracellular matrix (ECM) components, growth factors and gamma-aminobutyric acid receptor (GABRB3), implicated in the coordinate regulation of palate development. Palate fibroblasts were treated with diazepam (Dz-N fibroblasts) and compared to cleft lip-palate (CLP) fibroblasts obtained from patients with no known exposure to diazepam or other teratogens. Untreated fibroblasts from non-CLP patients were used as control. The results showed significant convergences in gene expression pattern of collagens, fibromodulin, vitronectin, tenascin C, integrins and metalloprotease MMP13 between Dz-N and CLP fibroblasts. Among the growth factors, constitutive Fibroblast Growth Factor 2 (FGF2) was greatly enhanced in Dz-N and CLP fibroblasts and associated with a higher reduction of FGF receptor. Transforming Growth Factor beta 3 (TGFβ 3 ) resulted up-regulated in CLP fibroblasts and decreased in Dz-N fibroblasts. We found phenotypic differences exhibited by Dz-N and CLP fibroblasts in GABRB3 gene regulation, so further studies are necessary to determine whether GABAergic system could be involved in the development of diazepam mediated CLP phenotype. Taken together the results elucidate the molecular mechanisms underlying possible toxicology effects induced by diazepam. Counselling of women on the safety of diazepam exposure is clinically important, also for the forensic consequences

C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis.

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Ning Ma

Full Text Available OBJECTIVE: It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs to stimulate adaptive immune cells such as Th1 and Th17 in sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP. CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+DC, IFNγ(+Th1, and IL-17(+Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA. RESULTS: Our studies here showed that C5a induced IL-12(+DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+DC cells induced the expansion of pathogenic IFNγ(+Th1 and IL-17(+Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis. CONCLUSION: Our data suggests that C5a regulates IL-12(+DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.

Salt stress-induced transcription of σB- and CtsR-regulated genes in persistent and non-persistent Listeria monocytogenes strains from food processing plants.

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Ringus, Daina L; Ivy, Reid A; Wiedmann, Martin; Boor, Kathryn J

2012-03-01

Listeria monocytogenes is a foodborne pathogen that can persist in food processing environments. Six persistent and six non-persistent strains from fish processing plants and one persistent strain from a meat plant were selected to determine if expression of genes in the regulons of two stress response regulators, σ(B) and CtsR, under salt stress conditions is associated with the ability of L. monocytogenes to persist in food processing environments. Subtype data were also used to categorize the strains into genetic lineages I or II. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure transcript levels for two σ(B)-regulated genes, inlA and gadD3, and two CtsR-regulated genes, lmo1138 and clpB, before and after (t=10 min) salt shock (i.e., exposure of exponential phase cells to BHI+6% NaCl for 10 min at 37°C). Exposure to salt stress induced higher transcript levels relative to levels under non-stress conditions for all four stress and virulence genes across all wildtype strains tested. Analysis of variance (ANOVA) of induction data revealed that transcript levels for one gene (clpB) were induced at significantly higher levels in non-persistent strains compared to persistent strains (p=0.020; two-way ANOVA). Significantly higher transcript levels of gadD3 (p=0.024; two-way ANOVA) and clpB (p=0.053; two-way ANOVA) were observed after salt shock in lineage I strains compared to lineage II strains. No clear association between stress gene transcript levels and persistence was detected. Our data are consistent with an emerging model that proposes that establishment of L. monocytogenes persistence in a specific environment occurs as a random, stochastic event, rather than as a consequence of specific bacterial strain characteristics.

A host-specific biological control of grape crown gall by Agrobacterium vitis strain F2/5: its regulation and population dynamics.

Science.gov (United States)

Kaewnum, Supaporn; Zheng, Desen; Reid, Cheryl L; Johnson, Kameka L; Gee, Jodi C; Burr, Thomas J

2013-05-01

Nontumorigenic Agrobacterium vitis strain F2/5 is able to prevent crown gall caused by tumorigenic A. vitis on grape but not on other plant species such as tobacco. Mutations in a quorum-sensing transcription factor, aviR, and in caseinolytic protease (clp) component genes clpA and clpP1 resulted in reduced or loss of biological control. All mutants were complemented; however, restoration of biological control by complemented clpA and clpP1 mutants was dependent on the copy number of vector that was used as well as timing of application of the complemented mutants to grape wounds in relation to inoculation with pathogen. Mutations in other quorum-sensing and clp genes and in a gene associated with polyketide synthesis did not affect biological control. It was determined that, although F2/5 inhibits transformation by tumorigenic A. vitis strains on grape, it does not affect growth of the pathogen in wounded grape tissue over time.

[Role of immune-related GTPase M1 in cortical neurons autophagy of mice with sepsis-induced brain injury].

Science.gov (United States)

Huang, Qun; Chen, Bin; Li, Yafei; Li, Xihong

2017-12-28

To investigate the role of immune-related GTPase M1 (IRGM1) in cortical neurons autophagy in mice with sepsis induced brain injury (SIBI).
 Methods: Sixty wild-type C57BL/6 mice and sixty IRGM1 gene knockout C57BL/6 mice were randomly divided into 4 groups: a sham-operated wild-type (SWT) group, a cecal ligation and puncture (CLP) model wild-type (MWT) group, a sham-operated knockout (SKO) group, and a CLP model knockout (MKO) group. Models of mice with sepsis were established by CLP. Six hours of after CLP, the neurobehavioral scores for mice were recorded. The mice were diagnosed with SIBI and enrolled for the studies in next step if the neurobehavioral score was less than 6 in the MWT and MKO groups. The sham operation group only opened the abdominal cavity without CLP. Pathological changes in mouse cerebral cortex were observed by HE staining. Electron microscope was used to observe the ultrastructure of autophagy in cortical neurons. The expression of IRGM1 and INF-γ mRNA in the cerebral cortex of mice were detected by Real time quantitative PCR. The protein expression of microtubule-associated protein 1 light chain 3 (LC3)-II, LC3-I, sequestosome-1 (SQSTM1) and IRGM1 were measured by Western blot. Immunofluorescence staining was used to examine the expression of IRGM1 in mouse cortical neurons.
 Results: In the MWT group, the cortical neurons showed dilated endoplasmic reticulum, swelling mitochondria, and increased number of autophagosomes after 6 or 24 h of CLP in contrast to the SWT group. At 6 h after CLP, the expression of LC3-II in the cerebral cortex began to up-regulate, and the up-regulation was maintained till 96 h after CLP; on the contrary, SQSTM1 began to decline after 6 h of CLP. Compared with SWT group, IRGM1 was strongly up-regulated in the cerebral cortex of mice at both mRNA and protein levels in the MWT group after 12 h of CLP, and the mRNA expression of IFN-γ was also increased significantly (PSIBI was 90% (27/30) in the MWT group

48 CFR 311.7000 - Defining electronic information technology requirements.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Defining electronic information technology requirements. 311.7000 Section 311.7000 Federal Acquisition Regulations System HEALTH... Accessibility Standards 311.7000 Defining electronic information technology requirements. HHS staff that define...

The national helpdesk activity in Italy: report of the first year (2010

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Ludovica Malaguti Aliberti

2011-01-01

Full Text Available National CLP heldpesk is a service established in every Member State providing advice to companies and other stakeholders on the obligations they may have under CLP. In Italy the national helpdesk is located into the Center of Chemical Substances (CSC in the National Institute of Health. Helpdesks will provide with wide ranging information on the provisions of CLP. They will also advice on the responsibilities the suppliers of chemical substances have to fulfill under these Regulations. Too specific questions cannot be answered as the aim of the helpdesk is to give a general interpretation of CLP principles and requirements instead of solving tailor made problems.

Expression of the stress-response regulators CtsR and HrcA in the uropathogen Staphylococcus saprophyticus during heat shock.

Science.gov (United States)

Rossi, Ciro César; de Oliveira, Lorayne Lauria; de Carvalho Rodrigues, Deivid; Ürményi, Turán Peter; Laport, Marinella Silva; Giambiagi-deMarval, Marcia

2017-08-01

The uropathogen Staphylococcus saprophyticus is an ubiquitous bacterium but little is known about mechanisms that allow its persistence in diverse environments. Here we evaluated S. saprophyticus growth and survival during heat shock, the expression of stress response regulators ctsR and hrcA through qRT-PCR and heat shock protein synthesis through 35 S-Met metabolic labeling. S. saprophyticus does not tolerate temperatures much higher than the optimal 37 °C, as its growth is greatly affected at 42 °C, though viability is maintained up to 48 °C. At 42 °C, the expression of ctsR and hrcA repressor genes approximately triple when compared to 37 °C and continue to increase together with temperature till 48 °C. Expression of hrcA peaks after 20 min of heat shock and decreases significantly after 30 min, indicating that heat stress response regulated by this gene may last 20-30 min. An increase in temperature is accompanied by the synthesis of at least eight proteins, three of which are likely the chaperones DnaK, GroEL and ClpB. In silico analysis indicate that the groEL gene may be regulated by HrcA, clpB by CtsR and dnaK by both repressors. This is the first work to discuss heat stress response in S. saprophyticus and a step forward in the understanding of mechanisms that make this a widespread and emergent pathogen.

Classical technical analysis of Latin American market indices. Correlations in Latin American Currencies (ARS, CLP, MXP) exchange rates with respect to DEM, GBP, JPY and USD

Science.gov (United States)

Ausloos, M.; Ivanova, K.

2004-06-01

The classical technical analysis methods of financial time series based on the moving average and momentum is recalled. Illustrations use the IBM share price and Latin American (Argentinian MerVal, Brazilian Bovespa and Mexican IPC) market indices. We have also searched for scaling ranges and exponents in exchange rates between Latin American currencies ($ARS$, $CLP$, $MXP$) and other major currencies $DEM$, $GBP$, $JPY$, $USD$, and $SDR$s. We have sorted out correlations and anticorrelations of such exchange rates with respect to $DEM$, $GBP$, $JPY$ and $USD$. They indicate a very complex or speculative behavior.

Coculture of Bifidobacterium longum and Bifidobacterium breve alters their protein expression profiles and enzymatic activities.

Science.gov (United States)

Ruiz, Lorena; Sánchez, Borja; de Los Reyes-Gavilán, Clara G; Gueimonde, Miguel; Margolles, Abelardo

2009-07-31

Some strains of the genus Bifidobacterium are probiotic bacteria commonly added to functional dairy products. The influence of coculturing Bifidobacterium longum NCIMB8809 and Bifidobacterium breve NCIMB8807 on their physiology was studied. 2DE separation of protein extracts, coupled to MS protein analysis allowed the identification of 16 proteins whose expression drastically changed when cells were grown in compartmentalized coculture, compared to monoculture. These included ribosomal proteins and proteins involved in carbohydrate metabolism, gene regulation, cell envelope biogenesis and transport processes. Significant changes in some glycoside-hydrolysing activities (beta-d-xylopyranosidase, alpha-l-arabinofuranosidase and beta-d-glucopyranosidase) were also detected. Furthermore, qRT-PCR experiments using as targets the B. breve genes clgR (transcriptional regulator) clpP1, clpP2 and clpC (chaperone- and protease-encoding genes positively regulated by clgR) supported the proteomic results, the four genes displaying a higher expression level in coculture. This study provides new insights to understand the communication among Bifidobacterium species.

Prevalence of Cleft Lip/Palate in the Fangshan District of Beijing, 2006-2012.

Science.gov (United States)

Yang, Yanfen; Liu, Hui; Ma, Ruixin; Jin, Lei

2018-01-01

To estimate the cleft lip with or without cleft palate (CL/P) prevalence among births between 2006 and 2012 in Fangshan district of Beijing, China. Surveillance data analysis. All hospitals that provide obstetric services in the district. The CL/P cases presented for this report were from 13 weeks' gestation to 7 days postpartum. The CL/P prevalence was defined as the number of cases per 10 000 births, including live births and stillbirths at 28 weeks' gestation or beyond. The overall CL/P prevalence was 18.9 (95% confidence interval [CI]: 15.1-22.7) per 10 000 births. From 2006 to 2012, the CL/P prevalence was 19.3, 20.2, 10.9, 16.1, 17.5, 25.4, and 22.3 per 10 000 births; annually, no significant change was noted ( P for trend = .311). The prevalence of cleft palate, cleft lip, and cleft lip and palate were 3.4 (95% CI: 2.0-5.4), 6.2 (95% CI: 4.2-8.8), and 9.4 (95% CI: 6.9-12.4) per 10 000 births, respectively. The CL/P prevalence among the nonpermanent residents (31.4 per 10 000 births) was 2.31 times that of permanent residents (13.6 per 10 000 births). Among nonpermanent residents, the CL/P prevalence showed an upward trend over the study period ( P for trend = .036), that increased from 38.8 (95% CI: 16.5-76.6) per 10 000 births in 2006 to 54.6 (95% CI: 25.7-100.4) per 10 000 births in 2012. The overall CL/P prevalence was stable in the Fangshan district. However, the CL/P prevalence of the nonpermanent residents increased significantly.

47 CFR 2.801 - Radiofrequency device defined.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Radiofrequency device defined. 2.801 Section 2... MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.801 Radiofrequency device defined. As used in this part, a radiofrequency device is any device which in its operation is capable of...

Verification of Imperative Programs by Constraint Logic Program Transformation

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Emanuele De Angelis

2013-09-01

Full Text Available We present a method for verifying partial correctness properties of imperative programs that manipulate integers and arrays by using techniques based on the transformation of constraint logic programs (CLP. We use CLP as a metalanguage for representing imperative programs, their executions, and their properties. First, we encode the correctness of an imperative program, say prog, as the negation of a predicate 'incorrect' defined by a CLP program T. By construction, 'incorrect' holds in the least model of T if and only if the execution of prog from an initial configuration eventually halts in an error configuration. Then, we apply to program T a sequence of transformations that preserve its least model semantics. These transformations are based on well-known transformation rules, such as unfolding and folding, guided by suitable transformation strategies, such as specialization and generalization. The objective of the transformations is to derive a new CLP program TransfT where the predicate 'incorrect' is defined either by (i the fact 'incorrect.' (and in this case prog is not correct, or by (ii the empty set of clauses (and in this case prog is correct. In the case where we derive a CLP program such that neither (i nor (ii holds, we iterate the transformation. Since the problem is undecidable, this process may not terminate. We show through examples that our method can be applied in a rather systematic way, and is amenable to automation by transferring to the field of program verification many techniques developed in the field of program transformation.

Structural color changes in permanent enamel of patients with cleft lip and palate: a case-control study.

Science.gov (United States)

Kulas, Antje; Illge, Christina; Bekes, Katrin; Eckert, Alexander W; Fuhrmann, Robert A W; Hirsch, Christian

2016-01-01

White spots are more common in patients with cleft lip and palate (CLP) than in the normal population. Whether these are due to the cleft itself or concomitant circumstances (e.g., surgical procedures, orthodontic treatments, systemic fluoridation, increased caries risk) remains unclear. This case-control study evaluated both their prevalence in CLP patients versus control subjects and associated risk factors. A total of 73 CLP patients (average age 8.7 years, range 6-18 years, 42 % male) and a control group of 73 age- and gender-matched non-CLP patients were included. Enamel color changes, subsuming mineralization defects (DDE index), mild dental fluorosis (Dean's index), and initial caries (ICDAS score 2), were recorded. Caries index (dmf-t/DMF-T) scores were also recorded to distinguish between high or low caries risk as defined by the Deutsche Arbeitsgemeinschaft für Jugendzahnpflege criteria. Histories of systemic fluoridation, trauma to primary teeth, surgery, and orthodontic treatment were obtained using a questionnaire. Statistical analysis included t test, χ (2) test, and multivariable logistic regression. Enamel color changes were observed three times more often in the CLP group than in the control group (39.7 vs. 12.3 %; p enamel color changes was associated with CLP itself [OR (odds ratio) 3.6; 95 % confidence interval (CI) 1.3-9.9] and table salt plus tablets combined for systemic fluoridation (OR 2.7, 95 % CI 1.1-6.9). No increased risks were identified for increased caries risk, history of primary-tooth trauma, or history of orthodontic treatment. The higher prevalence of enamel color changes in the CLP group (more than threefold compared to the control group) was not related to previous orthodontic treatments; however, systemic fluoridation (table salt and tablets) constituted a risk factor for the enamel color changes seen in the CLP patients.

7 CFR 28.950 - Terms defined.

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2010-01-01

... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., TESTING, AND STANDARDS Cotton Fiber and Processing Tests Definitions § 28.950 Terms defined. As used... Agricultural Marketing Service of the U.S. Department of Agriculture. (c) Administrator. The Administrator of...

Defining Legal Moralism

DEFF Research Database (Denmark)

Thaysen, Jens Damgaard

2015-01-01

This paper discusses how legal moralism should be defined. It is argued that legal moralism should be defined as the position that “For any X, it is always a pro tanto reason for justifiably imposing legal regulation on X that X is morally wrong (where “morally wrong” is not conceptually equivalent...... to “harmful”)”. Furthermore, a distinction between six types of legal moralism is made. The six types are grouped according to whether they are concerned with the enforcement of positive or critical morality, and whether they are concerned with criminalising, legally restricting, or refraining from legally...... protecting morally wrong behaviour. This is interesting because not all types of legal moralism are equally vulnerable to the different critiques of legal moralism that have been put forth. Indeed, I show that some interesting types of legal moralism have not been criticised at all....

The down-regulation of the mitogenic fibrinogen receptor (MFR) in serum-containing medium does not occur in defined medium.

Science.gov (United States)

Levesque, J P; Hatzfeld, A; Domart, I; Hatzfeld, J

1990-02-01

Normal human hemopoietic cells such as early bone marrow progenitors, or lymphoma-derived cell lines such as Raji or JM cells, possess a low-affinity receptor specific for fibrinogen. This receptor triggers a mitogenic effect. It differs from the glycoprotein IIb-IIIa which is involved in fibrinogen-induced platelet aggregation. We demonstrate here that this mitogenic fibrinogen receptor (MFR) can be internalized or reexpressed, depending on culture conditions. Internalization was temperature-dependent. At 37 degrees C in the presence of cycloheximide or actinomycin D, the half-life of cell surface MFRs was 2 h, independent of receptor occupancy. Binding of fibrinogen to the MFR resulted in a down-regulation which was fibrinogen dose-dependent. This occurred in serum-supplemented medium but not in defined medium supplemented with fatty acids. Reexpression of MFRs could be induced in 28 to 42 h by serum removal. The down-regulation of mitogenic receptors in plasma or serum could explain why normal cells do not proliferate in the peripheral blood.

MicroRNAs define distinct human neuroblastoma cell phenotypes and regulate their differentiation and tumorigenicity

International Nuclear Information System (INIS)

Samaraweera, Leleesha; Grandinetti, Kathryn B; Huang, Ruojun; Spengler, Barbara A; Ross, Robert A

2014-01-01

Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell lines are classified by phenotype, each having distinct differentiation and tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal features and includes stem cells (I-cells) and neuronal cells (N-cells). The non-neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with features of glial/smooth muscle precursor cells. This study identified miRNAs associated with each distinct cell phenotypes and investigated their role in regulating associated differentiation and tumorigenic properties. A miRNA microarray was performed on the three cell phenotypes and expression verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated using miRNA inhibitors or stable transfection. Neuronal differentiation was induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity were assayed by soft agar colony forming ability. N-myc binding to miR-375 promoter was assayed by chromatin-immunoprecipitation. Unsupervised hierarchical clustering of miRNA microarray data segregated neuroblastic and non-neuronal cell lines and showed that specific miRNAs define each phenotype. qRT-PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are associated with the non-neuronal phenotype, whereas increased levels of miR-124 and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non-neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of neuronal differentiation. Overexpression of miR-124 in stem cells induces terminal neuronal differentiation with reduced malignancy. Expression of miR-375 is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc. Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding protein HuD. Thus, miRNAs define distinct NB cell phenotypes

Platelet-derived microparticles regulates thrombin generation via phophatidylserine in abdominal sepsis.

Science.gov (United States)

Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Norström, Eva; Braun, Oscar Ö; Mörgelin, Matthias; Thorlacius, Henrik

2018-02-01

Sepsis is associated with dysfunctional coagulation. Recent data suggest that platelets play a role in sepsis by promoting neutrophil accumulation. Herein, we show that cecal ligation and puncture (CLP) triggered systemic inflammation, which is characterized by formation of IL-6 and CXC chemokines as well as neutrophil accumulation in the lung. Platelet depletion decreased neutrophil accumulation, IL-6, and CXC chemokines formation in septic lungs. Depletion of platelets increased peak thrombin formation and total thrombin generation (TG) in plasma from septic animals. CLP elevated circulating levels of platelet-derived microparticles (PMPs). In vitro generated PMPs were a potent inducer of TG. Interestingly, in vitro wild-type recombinant annexin V abolished PMP-induced thrombin formation whereas a mutant annexin V protein, which does not bind to phosphatidylserine (PS), had no effect. Administration of wild-type, but not mutant annexin V, significantly inhibited thrombin formation in septic animals. Moreover, CLP-induced formation of thrombin-antithrombin complexes were reduced in platelet-depleted mice and in animals pretreated with annexin V. PMP-induced TG attenuated in FXII- and FVII-deficient plasma. These findings suggest that sepsis-induced TG is dependent on platelets. Moreover, PMPs formed in sepsis are a potent inducer of TG via PS exposure, and activation of both the intrinsic and extrinsic pathway of coagulation. In conclusion, these observations suggest that PMPs and PS play an important role in dysfunctional coagulation in abdominal sepsis. © 2017 Wiley Periodicals, Inc.

Chronically Low-Performing Schools and Turnaround: Evidence from Three States

Science.gov (United States)

Hansen, Michael; Choi, Kilchan

2012-01-01

The criteria for determining the student outcomes that define a school as having "turned around" are not well defined, and the definition of turnaround performance varies across studies. Although current policy initiatives offer guidelines for identifying CLP schools, there is no standard definition or methodology in common usage. This…

Archwise distraction appliance: A novel approach for developing facial and dental esthetics in cleft lip and palate patients

Directory of Open Access Journals (Sweden)

Nejat Erverdi

2015-01-01

Full Text Available Cleft lip and palate (CLP is defined as a congenital deformity caused by failed fusion of medial and lateral palatine processes during 4-12 th weeks of embryogenesis, resulting in an open communication between oral and nasal cavities. In CLP patients, maxillary hypoplasia, velopharyngeal insufficiency, and alveolar clefts are the major issues that have to be taken care of after labiopalatal reconstruction. Rather than several consecutive operations, such as bone-grafting and orthognathic surgery, alveolar distraction can be a better treatment option in many cases. Archwise Distraction Appliance (AWDA is a rigid, tooth-borne, custom-made appliance that is developed to control the distraction vector with double archwire system. Our experiences show that the AWDA is a successful appliance in cases of distraction osteogenesis. Moreover, alveolar distraction has significant advantages over conventional treatment modalities for CLP patients.

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation.

Science.gov (United States)

Sakai, Mari; Suzuki, Tokiko; Tomita, Kengo; Yamashita, Shigeyuki; Palikhe, Sailesh; Hattori, Kohshi; Yoshimura, Naoki; Matsuda, Naoyuki; Hattori, Yuichi

2017-06-01

Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β 1 -adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support. NEW & NOTEWORTHY Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis

Graphs for information security control in software defined networks

Science.gov (United States)

Grusho, Alexander A.; Abaev, Pavel O.; Shorgin, Sergey Ya.; Timonina, Elena E.

2017-07-01

Information security control in software defined networks (SDN) is connected with execution of the security policy rules regulating information accesses and protection against distribution of the malicious code and harmful influences. The paper offers a representation of a security policy in the form of hierarchical structure which in case of distribution of resources for the solution of tasks defines graphs of admissible interactions in a networks. These graphs define commutation tables of switches via the SDN controller.

Hong Kong's electricity market beyond 2008

International Nuclear Information System (INIS)

Lam, Pun Lee

2004-01-01

In Hong Kong, electricity is supplied by two private utilities: Hongkong Electric and CLP Power (CLP). Both are regulated under the Scheme of Control (SOC). The SOC is a formal, long-term regulatory contract of 15 years, signed between a private firm and the Hong Kong Government. Under the SOC, the two electric utilities are subject to both rate-of-return control and price control. The current scheme will expire by 2008. In this paper, we propose a gradual and cautious approach to the introduction of market reform into the electricity industry in Hong Kong. For regulated markets, the government should consider replacing the SOC with performance-based regulation for wire businesses and the non-contestable market. For competitive markets, the government should consider introducing competitive tendering for new sources in the generation market and liberalising the supply market in phases. (author)

Hong Kong's electricity market beyond 2008

International Nuclear Information System (INIS)

Lam, P.-L.

2004-01-01

In Hong Kong, electricity is supplied by two private utilities: Hongkong Electric and CLP Power (CLP). Both are regulated under the Scheme of Control (SOC). The SOC is a formal, long-term regulatory contract of 15 years, signed between a private firm and the Hong Kong Government. Under the SOC, the two electric utilities are subject to both rate-of-return control and price control. The current scheme will expire by 2008. In this paper, we propose a gradual and cautious approach to the introduction of market reform into the electricity industry in Hong Kong. For regulated markets, the government should consider replacing the SOC with performance-based regulation for wire businesses and the non-contestable market. For competitive markets, the government should consider introducing competitive tendering for new sources in the generation market and liberalising the supply market in phases

Photometric Evaluation of Soft Tissue Changes in CLP Patients: Le Fort I Advancement Osteotomy (ALO) Versus Anterior Maxillary Distraction (AMD).

Science.gov (United States)

Paulose, Joby; Markose, Eldho

2014-12-01

This paper is a comparative photometric evaluation of soft tissue changes in patients with CLP associated with maxillary deficiency treated with conventional Le Fort I advancement osteotomy (ALO) and anterior maxillary distraction (AMD). Twenty patients with maxillary hypoplasia associated with cleft lip and palate who had undergone either LeFort I osteotomy or distraction osteogenesis with maxillary advancement were included in this study. Frontal and profile photographs were used to ascertain the changes post-surgically. Photographs were obtained before treatment and 1 year after surgical correction in both groups. Vertical as well as horizontal changes in pronasale was well observed in both groups. A substantial increase in nasal parameters was noted in case of AMD group in comparison to ALO group. Though maxillary advancement was quite evident in AMD and ALO groups, a significant and consistent change was observed in AMD group. Significant vertical and horizontal changes were seen with respect to subnasale and labrale superius in AMD group. The hard and soft tissue changes produced by AMD by intra oral distractors were being evaluated so far. The results of the above studies have proved the excellence of AMD over conventional osteotomies. The present study goes hand in hand with the research outcomes till date.

Collagen like peptide bioconjugates for targeted drug delivery applications

Science.gov (United States)

Luo, Tianzhi

Collagen is the most abundant protein in mammals, and there has been long-standing interest in understanding and controlling collagen assembly in the design of new materials. Collagen-like peptides (CLP), also known as collagen-mimetic peptides (CMP), are short synthetic peptides which mimic the triple helical conformation of native collagens. In the past few decades, collagen like peptides and their conjugated hybrids have become a new class of biomaterials that possesses unique structures and properties. In addition to traditional applications of using CLPs to decipher the role of different amino acid residues and tripeptide motifs in stabilizing the collagen triple helix and mimicking collagen fibril formation, with the introduction of specific interactions including electrostatic interactions, pi-pi stacking interaction and metal-ligand coordination, a variety of artificial collagen-like peptides with well-defined sequences have been designed to create higher order assemblies with specific biological functions. The CLPs have also been widely used as bioactive domains or physical cross-linkers to fabricate hydrogels, which have shown potential to improve cell adhesion, proliferation and ECM macromolecule production. Despite this widespread use, the utilization of CLPs as domains in stimuli responsive bioconjugates represents a relatively new area for the development of functional polymeric materials. In this work, a new class of thermoresponsive diblock conjugates, containing collagen-like peptides and a thermoresponsive polymer, namely poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA), is introduced. The CLP domain maintains its triple helix conformation after conjugation with the polymer. The engineered LCST of these conjugates has enabled temperature-induced assembly under aqueous conditions, at physiologically relevant temperatures, into well-defined vesicles with diameters of approximately 50-200 nm. The formation of nanostructures was driven by

Intergenic sequence between Arabidopsis caseinolytic protease B-cytoplasmic/heat shock protein100 and choline kinase genes functions as a heat-inducible bidirectional promoter.

Science.gov (United States)

Mishra, Ratnesh Chandra; Grover, Anil

2014-11-01

In Arabidopsis (Arabidopsis thaliana), the At1g74310 locus encodes for caseinolytic protease B-cytoplasmic (ClpB-C)/heat shock protein100 protein (AtClpB-C), which is critical for the acquisition of thermotolerance, and At1g74320 encodes for choline kinase (AtCK2) that catalyzes the first reaction in the Kennedy pathway for phosphatidylcholine biosynthesis. Previous work has established that the knockout mutants of these genes display heat-sensitive phenotypes. While analyzing the AtClpB-C promoter and upstream genomic regions in this study, we noted that AtClpB-C and AtCK2 genes are head-to-head oriented on chromosome 1 of the Arabidopsis genome. Expression analysis showed that transcripts of these genes are rapidly induced in response to heat stress treatment. In stably transformed Arabidopsis plants harboring this intergenic sequence between head-to-head oriented green fluorescent protein and β-glucuronidase reporter genes, both transcripts and proteins of the two reporters were up-regulated upon heat stress. Four heat shock elements were noted in the intergenic region by in silico analysis. In the homozygous transfer DNA insertion mutant Salk_014505, 4,393-bp transfer DNA is inserted at position -517 upstream of ATG of the AtClpB-C gene. As a result, AtCk2 loses proximity to three of the four heat shock elements in the mutant line. Heat-inducible expression of the AtCK2 transcript was completely lost, whereas the expression of AtClpB-C was not affected in the mutant plants. Our results suggest that the 1,329-bp intergenic fragment functions as a heat-inducible bidirectional promoter and the region governing the heat inducibility is possibly shared between the two genes. We propose a model in which AtClpB-C shares its regulatory region with heat-induced choline kinase, which has a possible role in heat signaling. © 2014 American Society of Plant Biologists. All Rights Reserved.

HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration

Science.gov (United States)

Hong, Peng; Chen, Kang; Huang, Bihui; Liu, Min; Cui, Miao; Rozenberg, Inna; Chaqour, Brahim; Pan, Xiaoyue; Barton, Elisabeth R.; Jiang, Xian-Cheng; Siddiqui, M.A.Q.

2012-01-01

The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell–mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases. PMID:23023707

The development of regulations

International Nuclear Information System (INIS)

Slokan Dusic, D.; Levstek, M.F.; Stritar, A.

2003-01-01

In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

20 CFR 220.102 - Non-severe impairment(s), defined.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Non-severe impairment(s), defined. 220.102 Section 220.102 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... these include— (1) Physical functions such as walking, standing, sitting, lifting, pushing, pulling...

Mapping posttranscriptional regulation of the human glycome uncovers microRNA defining the glycocode

OpenAIRE

Agrawal, Praveen; Kurcon, Tomasz; Pilobello, Kanoelani T.; Rakus, John F.; Koppolu, Sujeethraj; Liu, Zhongyin; Batista, Bianca S.; Eng, William S.; Hsu, Ku-Lung; Liang, Yaxuan; Mahal, Lara K.

2014-01-01

Carbohydrates (glycans) are complex cell surface molecules that control multiple aspects of cell biology, including cell–cell communication, cancer metastasis, and inflammation. Glycan biosynthesis requires the coordination of many enzymes, but how this is regulated is not well understood. Herein we show that microRNA (miRNA), small noncoding RNA, are a major regulator of cell surface glycosylation. We map miRNA expression onto carbohydrate signatures obtained by using lectin microarrays, a g...

Toward Edge-Defined Holey Boron Nitride Nanosheets

Science.gov (United States)

Lin, Yi; Liao, Yunlong; Chen, Zhongfan; Connell, John W.

2015-01-01

"Holey" two-dimensional (2D) nanosheets with well-defined holy morphology and edge chemistry are highly desirable for applications such as energy storage, catalysis, sensing, transistors, and molecular transport/separation. For example, holey grapheme is currently under extensive investigation for energy storage applications because of the improvement in ion transport due to through the thickness pathways provided by the holes. Without the holes, the 2D materials have significant limitations for such applications in which efficient ion transport is important. As part of an effort to apply this approach to other 2D nanomaterials, a method to etch geometrically defined pits or holes on the basal plane surface of hexagonal boron nitride (h-BN) nanosheets has been developed. The etching, conducted via heating in ambient air using metal nanoparticles as catalysts, was facile, controllable, and scalable. Starting h-BN layered crystals were etched and subsequently exfoliated into boron nitride nanosheets (BNNSs). The as-etched and exfoliated h-BN nanosheets possessed defined pit and hole shapes that were comprised of regulated nanostructures at the edges. The current finding are the first step toward the bulk preparation of holey BNNSs with defined holes and edges.

Cleft lip with or without cleft palate and dermatoglyphic asymmetry: evaluation of a Chinese population.

Science.gov (United States)

Neiswanger, K; Cooper, M E; Weinberg, S M; Flodman, P; Keglovits, A Bundens; Liu, Y; Hu, D N; Melnick, M; Spence, M A; Marazita, M L

2002-08-01

To determine if Chinese individuals with non syndromic cleft lip with or without cleft palate (CL/P) display more dermatoglyphic asymmetry than unaffected relatives or controls. Case-control study with two control groups (genetically related and unrelated). A total of 500 CL/P probands from Shanghai, China, 421 unaffected relatives, and 66 controls of Chinese heritage. Finger and palm prints were collected, and pattern frequencies, total ridge counts (TRC), and atd angles were calculated. Asymmetry scores between right and left hands were defined for each of the three dermatoglyphic measures. Probands' asymmetry scores were compared statistically with the scores of unaffected relatives and controls. In general, the probands' asymmetry scores for TRC and atd angle did not differ significantly from the scores of either unaffected relatives or controls. However, probands with a positive family history of clefting showed significantly more asymmetry in their pattern types than either probands without a family history, unaffected relatives or controls. These results suggest that a unique genetic mechanism of developmental instability may obtain in CL/P individuals with a positive family history of clefting.

Definably compact groups definable in real closed fields. I

OpenAIRE

Barriga, Eliana

2017-01-01

We study definably compact definably connected groups definable in a sufficiently saturated real closed field $R$. We introduce the notion of group-generic point for $\\bigvee$-definable groups and show the existence of group-generic points for definably compact groups definable in a sufficiently saturated o-minimal expansion of a real closed field. We use this notion along with some properties of generic sets to prove that for every definably compact definably connected group $G$ definable in...

New HCFA regulations clarify PSO requirements.

Science.gov (United States)

Brock, T H

1998-06-01

In March and April of 1998, HCFA promulgated regulations regarding various requirements for provider-sponsored organizations (PSOs). These regulations define what constitutes an affiliated provider to a PSO, identify what percentage of services must be provided directly to beneficiaries by PSO affiliated providers, define what constitutes provider ownership in a PSO, and set minimum capitalization and liquidity standards for PSOs.

Environmentally acceptable thread compounds: Requirements defined

International Nuclear Information System (INIS)

Stringfellow, W.D.; Hendriks, R.V.; Jacobs, N.L.

1993-01-01

New environmental regulations on thread compounds are now being enforced in several areas with strong maritime tradition and a sensitive environment. These areas include Indonesia, Alaska and portions of Norway. The industry generally recognizes the environmental concerns but, with wider enforcement of regulations imminent, has not been able to define clearly the requirements for environmental compliance. This paper, written in collaboration with The Netherlands State Supervision of Mines, is based on the National Policy on Thread Compounds of The Netherlands. This national policy is representative of policies being followed by other North Sea governments. Similar policies might well be adopted by other governments worldwide. These policies will affect the operator, drilling contractor, and supplier. This paper provides a specific and detailed definition of thread compound requirements by addressing four relevant categories. The categories of interest are regulatory approval, environmental, health, and performance

Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

Directory of Open Access Journals (Sweden)

Bin Cai

2016-01-01

Full Text Available Citrulline (Cit supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1β were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

Defined contribution health benefits.

Science.gov (United States)

Fronstin, P

2001-03-01

This Issue Brief discusses the emerging issue of "defined contribution" (DC) health benefits. The term "defined contribution" is used to describe a wide variety of approaches to the provision of health benefits, all of which have in common a shift in the responsibility for payment and selection of health care services from employers to employees. DC health benefits often are mentioned in the context of enabling employers to control their outlay for health benefits by avoiding increases in health care costs. DC health benefits may also shift responsibility for choosing a health plan and the associated risks of choosing a plan from employers to employees. There are three primary reasons why some employers currently are considering some sort of DC approach. First, they are once again looking for ways to keep their health care cost increases in line with overall inflation. Second, some employers are concerned that the public "backlash" against managed care will result in new legislation, regulations, and litigation that will further increase their health care costs if they do not distance themselves from health care decisions. Third, employers have modified not only most employee benefit plans, but labor market practices in general, by giving workers more choice, control, and flexibility. DC-type health benefits have existed as cafeteria plans since the 1980s. A cafeteria plan gives each employee the opportunity to determine the allocation of his or her total compensation (within employer-defined limits) among various employee benefits (primarily retirement or health). Most types of DC health benefits currently being discussed could be provided within the existing employment-based health insurance system, with or without the use of cafeteria plans. They could also allow employees to purchase health insurance directly from insurers, or they could drive new technologies and new forms of risk pooling through which health care services are provided and financed. DC health

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

International Nuclear Information System (INIS)

Lambertucci, Flavia; Motiño, Omar; Villar, Silvina; Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A; Martín-Sanz, Paloma; Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar; Ronco, María Teresa

2017-01-01

Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

Energy Technology Data Exchange (ETDEWEB)

Lambertucci, Flavia [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Motiño, Omar [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Villar, Silvina [Instituto de Inmunología, Facultad de Ciencias Médicas, UNR, Suipacha 531, 2000 Rosario (Argentina); Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Martín-Sanz, Paloma [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid (Spain); Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Ronco, María Teresa, E-mail: ronco@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina)

2017-01-15

Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice.

Culture as Mediator: Co-Regulation, Self-Regulation, and Middle School Mathematics Achievement

Science.gov (United States)

Hinnant-Crawford, Brandi Nicole; Faison, Morgan Z.; Chang, Mei-Lin

2016-01-01

Purpose: Self-regulation is defined as strategic, metacognitive behavior, motivation and cognition aimed at a goal (Zimmmerman and Schunk, 2011). Co-regulation, arguably more aligned with norms in communal cultures, is the process of learners sharing "a common problem-solving plane" through which self-regulatory strategies are learned…

Using riboswitches to regulate gene expression and define gene function in mycobacteria.

Science.gov (United States)

Van Vlack, Erik R; Seeliger, Jessica C

2015-01-01

Mycobacteria include both environmental species and many pathogenic species such as Mycobacterium tuberculosis, an intracellular pathogen that is the causative agent of tuberculosis in humans. Inducible gene expression is a powerful tool for examining gene function and essentiality, both in in vitro culture and in host cell infections. The theophylline-inducible artificial riboswitch has recently emerged as an alternative to protein repressor-based systems. The riboswitch is translationally regulated and is combined with a mycobacterial promoter that provides transcriptional control. We here provide methods used by our laboratory to characterize the riboswitch response to theophylline in reporter strains, recombinant organisms containing riboswitch-regulated endogenous genes, and in host cell infections. These protocols should facilitate the application of both existing and novel artificial riboswitches to the exploration of gene function in mycobacteria. © 2015 Elsevier Inc. All rights reserved.

Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model.

Science.gov (United States)

Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada Abdel-Hamid; Kato, Takenori; Sugiura, Takahiro; Kakita, Hiroki; Nobata, Masanori; Kamei, Michi; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika

2012-12-01

Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model. A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP. CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group. ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.

A comparison of cervical vertebral maturation assessment of skeletal growth stages with chronological age in Thai between cleft lip and palate and non-cleft patients.

Science.gov (United States)

Pisek, Poonsak; Godfrey, Keith; Manosudprasit, Montian; Wangsrimongkol, Tasanee; Leelasinjaroen, Pornnapha

2013-09-01

(1) To search for any difference in chronological age related to stages of the cervical vertebral maturation index stages (CVMIs) comparing groups of cleft lip and palate (CLP) and non-cleft (non-CLP) subjects; (2) To investigate the relationship between chronological age and CVMIs in both groups of subjects. Cervical vertebrae C2, C3, C4 were assessed on 1,549 cephalometric films (503 CLP films, 1,046 non-CLP films of subjects aged 5 to 18 years) using Hassel and Farman's method. T-tests showed mean chronological ages of CVMIs 2, 3 and 6 were different at p = 0.001, 0.024 and 0.016, respectively. CVMIs 1, 4 and 5 showed no significant differences. The CLP group achieved each CVMI score one year ahead of the non-CLP group, except for CVMI 4. Spearman's rank order correlations were r = 0.80 (95% CI: 0.76-0.83) for CLP, and 0.77 (95% CI: 0.74-0.79) for non-CLP. CLP subjects tended to have a slightly advanced growth compared with non-CLP subjects. A high correlation coefficient was found between chronological age and cervical vertebral skeletal maturation.

45 CFR 90.4 - How are the terms in these regulations defined?

Science.gov (United States)

2010-10-01

... education; or (2) A local educational agency (as defined in 20 U.S.C. 7801), system of vocational education... the Secretary of the Department of Health and Human Services. United States means the fifty States... possessions of the United States. (42 U.S.C. 6107) [44 FR 33776, June 12, 1979, as amended at 70 FR 24321, May...

Crystal structures of two transcriptional regulators from Bacillus cereus define the conserved structural features of a PadR subfamily.

Directory of Open Access Journals (Sweden)

Guntur Fibriansah

Full Text Available PadR-like transcriptional regulators form a structurally-related family of proteins that control the expression of genes associated with detoxification, virulence and multi-drug resistance in bacteria. Only a few members of this family have been studied by genetic, biochemical and biophysical methods, and their structure/function relationships are still largely undefined. Here, we report the crystal structures of two PadR-like proteins from Bacillus cereus, which we named bcPadR1 and bcPadR2 (products of gene loci BC4206 and BCE3449 in strains ATCC 14579 and ATCC 10987, respectively. BC4206, together with its neighboring gene BC4207, was previously shown to become significantly upregulated in presence of the bacteriocin AS-48. DNA mobility shift assays reveal that bcPadR1 binds to a 250 bp intergenic region containing the putative BC4206-BC4207 promoter sequence, while in-situ expression of bcPadR1 decreases bacteriocin tolerance, together suggesting a role for bcPadR1 as repressor of BC4206-BC4207 transcription. The function of bcPadR2 (48% identical in sequence to bcPadR1 is unknown, but the location of its gene just upstream from genes encoding a putative antibiotic ABC efflux pump, suggests a role in regulating antibiotic resistance. The bcPadR proteins are structurally similar to LmrR, a PadR-like transcription regulator in Lactococcus lactis that controls expression of a multidrug ABC transporter via a mechanism of multidrug binding and induction. Together these proteins define a subfamily of conserved, relatively small PadR proteins characterized by a single C-terminal helix for dimerization. Unlike LmrR, bcPadR1 and bcPadR2 lack a central pore for ligand binding, making it unclear whether the transcriptional regulatory roles of bcPadR1 and bcPadR2 involve direct ligand recognition and induction.

Definably compact groups definable in real closed fields.II

OpenAIRE

Barriga, Eliana

2017-01-01

We continue the analysis of definably compact groups definable in a real closed field $\\mathcal{R}$. In [3], we proved that for every definably compact definably connected semialgebraic group $G$ over $\\mathcal{R}$ there are a connected $R$-algebraic group $H$, a definable injective map $\\phi$ from a generic definable neighborhood of the identity of $G$ into the group $H\\left(R\\right)$ of $R$-points of $H$ such that $\\phi$ acts as a group homomorphism inside its domain. The above result and o...

IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

Directory of Open Access Journals (Sweden)

Kenneth Lyn-Kew

2010-06-01

Full Text Available Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM recovered from the lungs of mice undergoing cecal ligation and puncture (CLP display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3 and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/- mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

Science.gov (United States)

Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

2017-11-22

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

NCBI nr-aa BLAST: CBRC-TBEL-01-2084 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-TBEL-01-2084 ref|YP_865674.1| ATP-dependent Clp protease, ATP-binding subunit clpA [Magnet...ococcus sp. MC-1] gb|ABK44268.1| ATP-dependent Clp protease ATP-binding subunit ClpA [Magnetococcus sp. MC-1] YP_865674.1 1.0 34% ...

A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.

Directory of Open Access Journals (Sweden)

Pierre Raeven

Full Text Available INTRODUCTION: Plasminogen activator inhibitor 1 (PAI-1 is a key factor in trauma- and sepsis-induced coagulopathy. We examined how trauma-hemorrhage (TH modulates PAI-1 responses in subsequent cecal ligation and puncture (CLP-induced sepsis, and the association of PAI-1 with septic outcomes. METHODS: Mice underwent TH and CLP 48 h later in three separate experiments. In experiment 1, mice were sacrificed pre- and post-CLP to characterize the trajectory of PAI-1 in plasma (protein and tissues (mRNA. Post-CLP dynamics in TH-CLP (this study and CLP-Only mice (prior study were then compared for modulatory effects of TH. In experiment 2, to relate PAI-1 changes to outcome, mice underwent TH-CLP and were sampled daily and followed for 14 days to compare non-survivors (DEAD and survivors (SUR. In experiment 3, plasma and tissue PAI-1 expression were compared between mice predicted to die (P-DIE and to live (P-LIVE. RESULTS: In experiment 1, an early post-TH rise of circulating PAI-1 was contrasted by a delayed (post-TH decrease of PAI-1 mRNA in organs. In the post-CLP phase, profiles of circulating PAI-1 were similar between TH-CLP and CLP-Only mice. Conversely, PAI-1 mRNA declined in the liver and heart of TH-CLP mice versus CLP-Only. In experiment 2, there were no DEAD/SUR differences in circulating PAI-1 prior to CLP. Post-CLP, circulating PAI-1 in DEAD was 2-4-fold higher than in SUR. PAI-1 increase heralded septic deaths up to 48 h prior but DEAD/SUR thrombomodulin (endothelial injury marker levels were identical. In experiment 3, levels of circulating PAI-1 and its hepatic gene expression were higher in P-DIE versus P-LIVE mice and those increases closely correlated with liver dysfunction. CONCLUSIONS: Trauma modulated septic PAI-1 responses in a compartment-specific fashion. Only post-CLP increases in circulating PAI-1 predicted septic outcomes. In posttraumatic sepsis, pre-lethal release of PAI-1 was mostly of hepatic origin and was independent

The early psychological adjustment of cleft patients after maxillary distraction osteogenesis and conventional orthognathic surgery: a preliminary study.

Science.gov (United States)

Cheung, Lim Kwong; Loh, John Ser Pheng; Ho, Samuel M Y

2006-12-01

To compare the early psychological changes of cleft lip and palate (CLP) and noncleft patients after maxillofacial corrective surgery, including maxillary distraction osteogenesis and conventional orthognathic surgery. Nine CLP patients were compared with a group of 9 non-CLP patients having similar dentofacial deformities in a prospective longitudinal cohort study. Five of the CLP patients underwent maxillary distraction osteogenesis and 4 underwent conventional orthognathic surgery. A control group of 9 noncleft patients received conventional orthognathic surgery. All patients completed a set of questionnaires to enable their psychological profile to be assessed. The data were collected immediately before surgery (T1), and at 3 weeks (T2) and 12 weeks (T3) after surgery. The CLP patients treated with distraction osteogenesis were happier, but had a higher level of social anxiety and distress than the CLP patients receiving conventional orthognathic surgery. On the other hand, the CLP patients overall were happier, with lower social anxiety and distress, than the noncleft control group. The CLP patients showed a higher level of parental self-esteem than the noncleft patients. This preliminary study shows that CLP patients were generally happier, and had a higher level of parental support, than normal patients suffering from dentofacial deformities. Maxillary distraction osteogenesis seemed to induce a higher level of anxiety and distress in CLP patients than conventional orthognathic surgery in both cleft and noncleft patients.

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

Science.gov (United States)

Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

2015-11-01

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

Risk of Breast Cancer in Families with Cleft Lip and Palate

DEFF Research Database (Denmark)

Dietz, Alexander; Pedersen, Dorthe Almind; Jacobsen, Rune

2012-01-01

PURPOSE: To test whether female subjects in families with cleft lip and/or palate (CL/P) have an increased risk of breast cancer. METHODS: By using the Danish Facial Cleft Registry, we identified female subjects with CL/P, mothers of children with CL/P, and sisters to CL/P cases for the Danish...

Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

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Chao He

2018-01-01

Full Text Available Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF- 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO- 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp. before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg, after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

29 CFR 1620.8 - “Employer,” “employee,” and “employ” defined.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false âEmployer,â âemployee,â and âemployâ defined. 1620.8 Section 1620.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.8 “Employer,” “employee,” and “employ” defined. The words “employer,” “employee...

[Effect of compound hypertonic saline solution on septic rats].

Science.gov (United States)

Dong, Fang; Xu, Liang; Xu, Gang; Wang, Huabing; Lu, Huizhi; Cai, Liping

2015-01-01

To study the effect of compound hypertonic saline solution ( HSD ) on sepsis. 133 male Wistar rats were divided into four groups, sham operation group ( n = 15 ), cecal ligation and puncture ( CLP ) group ( n = 45 ), CLP plus normal saline ( NS ) group ( n = 45 ), and CLP plus HSD group ( n = 28 ). A rat model of sepsis was reproduced by CLP, and the rats in sham operation group received celiotomy without ligation and puncture. All rats in four groups received subcutaneous injection of 30 mL/kg 0.9% sodium chloride after laparotomy. The rats in CLP plus NS group and CLP plus HSD group received infusion of 5 mL/kg 0.9% sodium chloride or 7.5% sodium chloride/6% dextran post CLP via jugular vein for 3 hours, with the infusion rate of 0.4 mL×kg(-1)×min(-1). The survival rate of each group was observed 9 hours and 18 hours after laparotomy. Mean arterial pressure ( MAP ) at 0, 9, 18 hours were monitored. Blood specimens were collected from all rats 0, 9 and 18 hours after laparotomy, respectively, for measurement of the plasma levels of tumor necrosis factor-α ( TNF-α), interleukin-1β ( IL-1β ), and procalcitonin ( PCT ). The rats were all sacrificed, and their lung tissues were harvested for the neutrophil count in bronchoalveolar lavage fluid ( BALF ), myeloperoxidase ( MPO ) activity in lung tissue, wet/dry weight ratio ( W/D ) of lung, and pathological changes in lung tissue. There was no death in the sham operation group. The survival rates at 9 hours and 18 hours were 62.2% and 31.1% in the CLP group, 57.8% and 35.6% in the CLP plus NS group, 85.7% and 64.3% in the CLP plus HSD group, and they were all significantly higher compared with those of the CLP group and the CLP plus NS group ( Pmicroscope, no pathobiological changes were found in sham operation group. The lung tissues in the CLP group and the CLP plus NS group showed congestion, edema, infiltrating inflammatory changes, while the inflammatory changes in the lung tissue in the CLP plus HSD group

77 FR 4714 - Self-Regulation of Class II Gaming

Science.gov (United States)

2012-01-31

...: Notice of proposed rulemaking. SUMMARY: This action proposes to amend the NIGC's self-regulation regulations to tailor the self-regulating qualifying criteria to a tribe's regulation of class II gaming activity and more clearly define and streamline the self-regulation certification process. By tailoring the...

Cecal ligation and puncture followed by MRSA pneumonia increases mortality in mice and blunts production of local and systemic cytokines

Science.gov (United States)

Jung, Enjae; Perrone, Erin E.; Liang, Zhe; Breed, Elise R.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Burd, Eileen M.; Farris, Alton B.; Hotchkiss, Richard S.; Coopersmith, Craig M.

2011-01-01

Mortality in the ICU frequently results from the synergistic effect of two temporally-distinct infections. This study examined the pathophysiology of a new model of intraabdominal sepsis followed by methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Mice underwent cecal ligation and puncture (CLP) or sham laparotomy followed three days later by an intratracheal injection of MRSA or saline. Both CLP/saline and sham/MRSA mice had 100% survival while animals with CLP followed by MRSA pneumonia had 67% seven-day survival. Animals subjected to CLP/MRSA had increased bronchoalveolar lavage (BAL) concentrations of MRSA compared to sham/MRSA animals. Animals subjected to sham/MRSA pneumonia had increased BAL levels of IL-6, TNF-α, and G-CSF compared to those given intratracheal saline while CLP/MRSA mice had a blunted local inflammatory response with markedly decreased cytokine levels. Similarly, animals subjected to CLP/saline had increased peritoneal lavage levels of IL-6 and IL-1β compared to those subjected to sham laparotomy while this response was blunted in CLP/MRSA mice. Systemic cytokines were upregulated in both CLP/saline and sham/MRSA mice, and this was blunted by the combination of CLP/MRSA. In contrast, no synergistic effect on pneumonia severity, white blood cell count or lymphocyte apoptosis was identified in CLP/MRSA mice compared to animals with either insult in isolation. These results indicate that a clinically relevant model of CLP followed by MRSA pneumonia causes higher mortality than could have been predicted from studying either infection in isolation, and this was associated with a blunted local (pulmonary and peritoneal) and systemic inflammatory response and decreased ability to clear infection. PMID:21937950

Antiseptic Effects of New 3'-N-Substituted Carbazole Derivatives In Vitro and In Vivo.

Science.gov (United States)

Lee, Wonhwa; Kwak, Soyoung; Yun, Eunju; Lee, Jee Hyun; Na, MinKyun; Song, Gyu-Yong; Bae, Jong-Sup

2015-08-01

Inhibition of high-mobility group box 1 (HMGB1) protein and restoration of endothelial integrity are emerging as attractive therapeutic strategies in the management of sepsis. Here, new five structurally related 3'-N-substituted carbazole derivatives were examined for their effects on lipopolysaccharide (LPS)-mediated or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. We accessed this question by monitoring the effects of posttreatment carbazole derivatives on LPS- and CLP-mediated release of HMGB1 and HMGB1-mediated regulation of proinflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. The new 3'-N-substituted carbazole derivatives 1-5 inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. New compounds also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with each compound reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that the new 3'-N-substituted carbazole derivatives could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway.

Emotion Regulation: A Theme in Search of Definition.

Science.gov (United States)

Thompson, Ross A.

1994-01-01

This essay considers how emotion regulation should be defined, the various components of the management of emotion, how emotion regulation strategies fit into the dynamics of social interaction, and how individual differences in emotion regulation should be conceptualized and measured. (MDM)

Antibodies against homologous microbial caseinolytic proteases P characterise primary biliary cirrhosis.

Science.gov (United States)

Bogdanos, Dimitrios-Petrou; Baum, Harold; Sharma, Umesh C; Grasso, Alessandro; Ma, Yun; Burroughs, Andrew K; Vergani, Diego

2002-01-01

Antibodies to caseinolytic protease P(177-194) (ClpP(177-194)) of the proteolytic subunit of the Clp complex of Escherichia coli (E. coli) are uniquely present in primary biliary cirrhosis (PBC). Molecular mimicry between the regulatory subunit ClpX and the principal T-cell epitope of pyruvate dehydrogenase complex (PDC-E2) in PBC, has been proposed to account for this. Since ClpP is highly conserved among bacteria we investigated whether the micro-organisms triggering these antibodies may be other than E. coli. E. coli ClpP(177-194) is homologous with ClpP peptides of Yersinia enterocolitica (YEREN) and Haemophilus influenzae (HAEIN). Enzyme linked immunosorbent assay (ELISA) reactivity to these peptides was tested in 45 patients with PBC, 44 pathological and 32 healthy controls. Reactivity to at least one of the ClpP peptides was observed in 21 (47%) PBC patients, 5.8% pathological and 3.1% healthy controls (PECOLI ClpP(177-194), alone or in association with YEREN and/or HAEIN peptides, compared to three (14.2%) reactive with YEREN, two (9.5%) with YEREN/HAEIN and one (4.7%) with HAEIN peptide. Simultaneous reactivity to homologous sequences was due to cross-reactivity as confirmed by competition ELISAs. The PBC-specificity of anti-microbial ClpP reactivity is confirmed: the questions as to primary trigger(s) and relevance to PBC pathogenesis remain open.

Cecal ligation and puncture followed by methicillin-resistant Staphylococcus aureus pneumonia increases mortality in mice and blunts production of local and systemic cytokines.

Science.gov (United States)

Jung, Enjae; Perrone, Erin E; Liang, Zhe; Breed, Elise R; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Hotchkiss, Richard S; Coopersmith, Craig M

2012-01-01

Mortality in the intensive care unit frequently results from the synergistic effect of two temporally distinct infections. This study examined the pathophysiology of a new model of intra-abdominal sepsis followed by methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Mice underwent cecal ligation and puncture (CLP) or sham laparotomy followed 3 days later by an intratracheal injection of MRSA or saline. Both CLP/saline and sham/MRSA mice had 100% survival, whereas animals with CLP followed by MRSA pneumonia had 67% 7-day survival. Animals subjected to CLP/MRSA had increased bronchoalveolar lavage concentrations of MRSA compared with sham/MRSA animals. Animals subjected to sham/MRSA pneumonia had increased bronchoalveolar lavage levels of interleukin 6 (IL-6), tumor necrosis factor α, and granulocyte colony-stimulating factor compared with those given intratracheal saline, whereas CLP/MRSA mice had a blunted local inflammatory response with markedly decreased cytokine levels. Similarly, animals subjected to CLP/saline had increased peritoneal lavage levels of IL-6 and IL-1β compared with those subjected to sham laparotomy, whereas this response was blunted in CLP/MRSA mice. Systemic cytokines were upregulated in both CLP/saline and sham/MRSA mice, and this was blunted by the combination of CLP/MRSA. In contrast, no synergistic effect on pneumonia severity, white blood cell count, or lymphocyte apoptosis was identified in CLP/MRSA mice compared with animals with either insult in isolation. These results indicate that a clinically relevant model of CLP followed by MRSA pneumonia causes higher mortality than could have been predicted from studying either infection in isolation, and this was associated with a blunted local (pulmonary and peritoneal) and systemic inflammatory response and decreased ability to clear infection.

Complications of ventilation tube insertion in children with and without cleft palate: a nested case-control comparison.

Science.gov (United States)

Smillie, Ian; Robertson, Sophie; Yule, Anna; Wynne, David M; Russell, Craig J H

2014-10-01

Optimizing hearing in patients with cleft lip and/or palate (CLP) by early recognition and management of otitis media with effusion is essential for speech development. Some evidence has suggested higher complication rates from ventilation tube (VT) insertion in patients with CLP and has led to a trend not to treat these patients surgically. However, studies have failed to match comparison groups for age and sex. To compare complication rates from VT insertion in pediatric patients with and without CLP. The study used a nested case-control design to evaluate 60 pediatric patients with CLP who underwent VT insertion at a children's hospital. The control group of age- and sex-matched patients was selected from a database of 2943 VT insertions. All patients were administered general anesthesia and underwent VT insertion by a pediatric otorhinolaryngology (ENT) team. The primary outcomes were numbers of otorrhea complications. Secondarily, rates of attendance at an ENT clinic specifically for complications were evaluated. Finally, numbers of complications other than otorrhea were assessed but not statistically analyzed owing to the varied types and low numbers in each group. The control cohort had 151 documented cases of otorrhea compared with 121 in the CLP group (ratio 1.25:1); the difference between groups was not statistically significant (P = .52). There was no significant difference in mean ENT clinic visits per patient for complications between groups (0.80 in the CLP group, 0.78 for controls) (P = .66). Regarding complications other than otorrhea, the control group reported more than the CLP group (43 vs 25; ratio, 1.7:1). Complication rates of VT placement among patients with CLP were not higher than those among patients without CLP. Therefore, treatment with VT insertion should be administered to patients with CLP under the same guidelines as for those without CLP. Indeed, there could be an argument for a shift in practice toward more aggressive

Evidence for an association between non-syndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4

Energy Technology Data Exchange (ETDEWEB)

Healey, S.C.; Chenevix-Trench, G. [Queensland Institute of Medical Research, Brisbane (Australia); Mitchell, L.E. [Saint Louis Univ., MO (United States)

1994-09-01

Evidence of linkage has been reported for non-syndromic cleft lip with or without cleft palate (CL{+-}P) and two markers (D4S175 and D4S192) in the region 4q25-4q31.3. The linkage evidence comes from a single Caucasian pedigree with multiple cases of CL{+-}P in five generations. High-density pedigrees are, however, atypical of CL{+-}P and linkage evidence obtained from such a family may not be relevant to the majority of CL{+-}P families. We have, therefore, examined the association of CL{+-}P with both D4S175 and D4S192 in 95 unrelated CL{+-}P patients and 161 unselected controls. There was no evidence for an association between D4S175 and CL{+-}P in these data. There was, however, a significant association between D4S192 and CL{+-}P ({chi}{sup 2}{sub 4}=15.5,P=0.006), and the genotypic distribution was significantly heterogeneous between CL{+-}P patients and controls (P=0.025). Comparison of each of the four most common alleles (i.e A87, A89, A91 and A95), to all other alleles combined, indicated that A87 was significantly less common (OR=0.56,95% C.I. 0.34-0.90), and A95 was significantly more common (OR=1.88,95% C.I. 1.03-3.43) among the CL{+-}P patients than the controls. Although of only borderline significance, A89 also appeared to be more common among patients than controls (OR=1.43,95% C.I. 0.99-2.60). Hence, it appears that genetic variation at a CL{+-}P susceptibility locus (CSL) linked to D4S192 may be associated with both increased and decreased risk of CL{+-}P. In combination, A89 and A95 are significantly more common in CL{+-}P patients than in controls (OR=1.80;95% C.I. 1.24-2.60) and account for a risk ratio of 1.08 in the first degree relatives of CL{+-}P patients. These results provide further evidence for the presence of a CSL in the region 4q25-4q31.1, and indicate that the putative CSL is located closer to D4S192 than to D4S175.

Peak regulation right

International Nuclear Information System (INIS)

Gao, Z. |; Ren, Z.; Li, Z.; Zhu, R.

2005-01-01

A peak regulation right concept and corresponding transaction mechanism for an electricity market was presented. The market was based on a power pool and independent system operator (ISO) model. Peak regulation right (PRR) was defined as a downward regulation capacity purchase option which allowed PRR owners to buy certain quantities of peak regulation capacity (PRC) at a specific price during a specified period from suppliers. The PRR owner also had the right to decide whether or not they would buy PRC from suppliers. It was the power pool's responsibility to provide competitive and fair peak regulation trading markets to participants. The introduction of PRR allowed for unit capacity regulation. The PRR and PRC were rated by the supplier, and transactions proceeded through a bidding process. PRR suppliers obtained profits by selling PRR and PRC, and obtained downward regulation fees regardless of whether purchases are made. It was concluded that the peak regulation mechanism reduced the total cost of the generating system and increased the social surplus. 6 refs., 1 tab., 3 figs

78 FR 18902 - Defining Larger Participants of the Student Loan Servicing Market

Science.gov (United States)

2013-03-28

... BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Part 1090 [Docket No. CFPB-2013-0005] RIN 3170-AA35... Protection. ACTION: Proposed rule; request for public comment. SUMMARY: The Bureau of Consumer Financial Protection (Bureau or CFPB) proposes to amend the regulation defining larger participants of certain consumer...

Regulations for RA reactor operation

International Nuclear Information System (INIS)

1980-09-01

Regulations for RA reactor operation are written in accordance with the legal regulations defined by the Law about radiation protection and related legal acts, as well as technical standards according to the IAEA recommendations. The contents of this book include: fundamental data about the reactor; legal regulations for reactor operation; organizational scheme for reactor operation; general and detailed instructions for operation, behaviour in the reactor building, performing experiments; operating rules for operation under steady state and accidental conditions [sr

29 CFR 541.1 - Terms used in regulations.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Terms used in regulations. 541.1 Section 541.1 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS DEFINING AND DELIMITING THE EXEMPTIONS FOR EXECUTIVE, ADMINISTRATIVE, PROFESSIONAL, COMPUTER AND OUTSIDE SALES EMPLOYEES...

Defining Peer-to-Peer Accountability From the Nurse's Perspective.

Science.gov (United States)

Lockett, Jacqueline Jansen; Barkley, Leslie; Stichler, Jaynelle; Palomo, Jeanne; Kik, Bozena; Walker, Christopher; Donnelly, Janet; Willon, Judy; Sanborn, Julie; O'Byrne, Noeleen

2015-11-01

The aim of this study was to define and create a conceptual model for peer-to-peer accountability (P to PA). Many organizations cite the importance of peer accountability (PA) as essential in ensuring patient safety. Professionalism in nursing requires self-regulation of practice and PA. Although discussed in the literature, P to PA is not conceptually defined. A grounded theory study design with constant comparative data collection and analysis was used to explore nurses' definitions of P to PA and their perceptions of motivators and barriers to engaging in P to PA. Transcripts of digital recordings of all interviews were analyzed using line-by-line coding until identified themes emerged. P to PA was defined as the act of speaking up when one observes a peer not practicing to acceptable standards. A conceptual model illustrates the antecedents, attributes, and consequences of P to PA. P to PA is the professional responsibility of every nurse and healthcare provider and is essential for safe patient care. The conceptual definition facilitates actualization of P to PA in practice.

Cervical vertebral maturation of children with orofacial clefts.

Science.gov (United States)

Sun, Ling; Li, Wei Ran

2012-11-01

To evaluate the skeletal maturation of male children with orofacial clefts using the cervical vertebral maturation (CVM) method. Case-control study. The School of Stomatology, Peking University. Subjects were 443 boys with cleft lip and/or cleft palate (CL/P) aged 8 to 16 years who were compared with 1772 boys without clefts in an age-matched control group. The 8- to 10-year-old boys of both groups were in CS1. Most of the 11- to 14-year-old boys without CL/P were in CS3 and CS4, though it was not so obvious in boys with CL/P. Most 15- to 16-year-old boys without CL/P were in CS5 and CS6, while there were a lot of boys with CL/P who were still in cervical stages before CS5. Clefts had a significant effect on growth, and boys without CL/P were 1.737 times more likely to have achieved higher cervical stages. From Mann-Whitney test of every age phase, the difference existed in each year of the age range of 11 to 16 years, except from 12 to 13 years (p  =  .100). In these age phases, the cervical stages of boys with CL/P were lower than those for boys without CL/P. By the age of 14, children with CL/P had a 4.679 times higher risk of delayed CS3, and the 95% confidence interval for the odds ratio was 2.129 to 10.286. Boys with CL/P are at a higher risk of delayed growth period and retarded pubertal growth peak.

Genetics and Management of the Patient with Orofacial Cleft

Directory of Open Access Journals (Sweden)

Luciano Abreu Brito

2012-01-01

Full Text Available Cleft lip or palate (CL/P is a common facial defect present in 1 : 700 live births and results in substantial burden to patients. There are more than 500 CL/P syndromes described, the causes of which may be single-gene mutations, chromosomopathies, and exposure to teratogens. Part of the most prevalent syndromic CL/P has known etiology. Nonsyndromic CL/P, on the other hand, is a complex disorder, whose etiology is still poorly understood. Recent genome-wide association studies have contributed to the elucidation of the genetic causes, by raising reproducible susceptibility genetic variants; their etiopathogenic roles, however, are difficult to predict, as in the case of the chromosomal region 8q24, the most corroborated locus predisposing to nonsyndromic CL/P. Knowing the genetic causes of CL/P will directly impact the genetic counseling, by estimating precise recurrence risks, and the patient management, since the patient, followup may be partially influenced by their genetic background. This paper focuses on the genetic causes of important syndromic CL/P forms (van der Woude syndrome, 22q11 deletion syndrome, and Robin sequence-associated syndromes and depicts the recent findings in nonsyndromic CL/P research, addressing issues in the conduct of the geneticist.

Morphometric analysis of craniofacial features in mono- and dizygotic twins discordant for unilateral cleft lip and palate.

Science.gov (United States)

Tessler, Alexis Y; Franchi, Lorenzo; McNamara, James A; Baccetti, Tiziano

2011-09-01

To compare craniofacial differences between twins discordant for surgically repaired unilateral cleft lip and palate (CLP) during the developmental ages and to test the effect of zygosity on the shape and size of the craniofacial skeleton of the same twins by means of thin plate spline (TPS) analysis. Lateral and posteroanterior (PA) cephalometric films from 19 sets of monozygotic (MZ) twins (15 male and 4 female) and 10 dizygotic (DZ) twins (7 male and 3 female) were analyzed. TPS analysis evaluated statistically significant differences in the craniofacial shape and size between affected and unaffected twins within MZ and DZ twin couples. No statistically significant differences in craniofacial shape or size between CLP and non-CLP MZ or DZ twins were observed. The level of morphological similarity in CLP vs non-CLP MZ twins was statistically greater than in DZ twins. Morphometric analysis showed that surgically repaired CLP does not produce significant shape or size differences in the craniofacial features of MZ or DZ twins discordant for unilateral CLP.

The prevalence of specific dental anomalies in a group of Saudi cleft lip and palate patients

Directory of Open Access Journals (Sweden)

Ghada H. Al-Kharboush

2015-04-01

Conclusions: Dental anomalies were common in Saudi subjects with CLP type. This will complicate the health care required for the CL/P subjects. This study was conducted to epidemiologically explore the prevalence of dental anomalies among Saudi Arabian subjects with CLP.

The Primary Care Pediatrician and the Care of Children With Cleft Lip and/or Cleft Palate.

Science.gov (United States)

Lewis, Charlotte W; Jacob, Lisa S; Lehmann, Christoph U

2017-05-01

Orofacial clefts, specifically cleft lip and/or cleft palate (CL/P), are among the most common congenital anomalies. CL/P vary in their location and severity and comprise 3 overarching groups: cleft lip (CL), cleft lip with cleft palate (CLP), and cleft palate alone (CP). CL/P may be associated with one of many syndromes that could further complicate a child's needs. Care of patients with CL/P spans prenatal diagnosis into adulthood. The appropriate timing and order of specific cleft-related care are important factors for optimizing outcomes; however, care should be individualized to meet the specific needs of each patient and family. Children with CL/P should receive their specialty cleft-related care from a multidisciplinary cleft or craniofacial team with sufficient patient and surgical volume to promote successful outcomes. The primary care pediatrician at the child's medical home has an essential role in making a timely diagnosis and referral; providing ongoing health care maintenance, anticipatory guidance, and acute care; and functioning as an advocate for the patient and a liaison between the family and the craniofacial/cleft team. This document provides background on CL/P and multidisciplinary team care, information about typical timing and order of cleft-related care, and recommendations for cleft/craniofacial teams and primary care pediatricians in the care of children with CL/P. Copyright © 2017 by the American Academy of Pediatrics.

A "footprint" of plant carbon fixation cycle functions during the development of a heterotrophic fungus.

Science.gov (United States)

Lyu, Xueliang; Shen, Cuicui; Xie, Jiatao; Fu, Yanping; Jiang, Daohong; Hu, Zijin; Tang, Lihua; Tang, Liguang; Ding, Feng; Li, Kunfei; Wu, Song; Hu, Yanping; Luo, Lilian; Li, Yuanhao; Wang, Qihua; Li, Guoqing; Cheng, Jiasen

2015-08-11

Carbon fixation pathway of plants (CFPP) in photosynthesis converts solar energy to biomass, bio-products and biofuel. Intriguingly, a large number of heterotrophic fungi also possess enzymes functionally associated with CFPP, raising the questions about their roles in fungal development and in evolution. Here, we report on the presence of 17 CFPP associated enzymes (ten in Calvin-Benson-Basham reductive pentose phosphate pathway and seven in C4-dicarboxylic acid cycle) in the genome of Sclerotinia sclerotiorum, a heterotrophic phytopathogenic fungus, and only two unique enzymes: ribulose-1, 5-bisphosphate carboxylase-oxygenase (Rubisco) and phosphoribulokinase (PRK) were absent. This data suggested an incomplete CFPP-like pathway (CLP) in fungi. Functional profile analysis demonstrated that the activity of the incomplete CLP was dramatically regulated during different developmental stages of S. sclerotiorum. Subsequent experiments confirmed that many of them were essential to the virulence and/or sclerotial formation. Most of the CLP associated genes are conserved in fungi. Phylogenetic analysis showed that many of them have undergone gene duplication, gene acquisition or loss and functional diversification in evolutionary history. These findings showed an evolutionary links in the carbon fixation processes of autotrophs and heterotrophs and implicated the functions of related genes were in course of continuous change in different organisms in evolution.

An approach to scoring cursorial limb proportions in carnivorous dinosaurs and an attempt to account for allometry

Science.gov (United States)

Persons, W. Scott, IV; Currie, Philip J.

2016-01-01

From an initial dataset of 53 theropod species, the general relationship between theropod lower-leg length and body mass is identified. After factoring out this allometric relationship, theropod hindlimb proportions are assessed irrespective of body mass. Cursorial-limb-proportion (CLP) scores derived for each of the considered theropod taxa offer a measure of the extent to which a particular species deviates in favour of higher or lower running speeds. Within the same theropod species, these CLP scores are found to be consistent across multiple adult specimens and across disparate ontogenetic stages. Early theropods are found to have low CLP scores, while the coelurosaurian tyrannosauroids and compsognathids are found to have high CLP scores. Among deinonychosaurs, troodontids have consistently high CLP scores, while many dromaeosaur taxa, including Velociraptor and Deinonychus, have low CLP scores. This indicates that dromaeosaurs were not, overall, a particularly cursorily adapted group. Comparisons between the CLP scores of Tyrannosaurus and specimens referred to the controversial genus Nanotyrannus indicate a strong discrepancy in cursorial adaptations, which supports the legitimacy of Nanotyrannus and the previous suggestions of ecological partitioning between Nanotyrannus and the contemporaneous Tyrannosaurus.

An approach to scoring cursorial limb proportions in carnivorous dinosaurs and an attempt to account for allometry.

Science.gov (United States)

Persons, W Scott; Currie, Philip J

2016-01-27

From an initial dataset of 53 theropod species, the general relationship between theropod lower-leg length and body mass is identified. After factoring out this allometric relationship, theropod hindlimb proportions are assessed irrespective of body mass. Cursorial-limb-proportion (CLP) scores derived for each of the considered theropod taxa offer a measure of the extent to which a particular species deviates in favour of higher or lower running speeds. Within the same theropod species, these CLP scores are found to be consistent across multiple adult specimens and across disparate ontogenetic stages. Early theropods are found to have low CLP scores, while the coelurosaurian tyrannosauroids and compsognathids are found to have high CLP scores. Among deinonychosaurs, troodontids have consistently high CLP scores, while many dromaeosaur taxa, including Velociraptor and Deinonychus, have low CLP scores. This indicates that dromaeosaurs were not, overall, a particularly cursorily adapted group. Comparisons between the CLP scores of Tyrannosaurus and specimens referred to the controversial genus Nanotyrannus indicate a strong discrepancy in cursorial adaptations, which supports the legitimacy of Nanotyrannus and the previous suggestions of ecological partitioning between Nanotyrannus and the contemporaneous Tyrannosaurus.

DAMP-Mediated Innate Immune Failure and Pneumonia after Trauma

Science.gov (United States)

2017-10-01

AMP , CD39, Reactive Oxygen Species (ROS), Trauma Patients, Acute Lung Injury, Pneumonia, Oligonucleotides, CyTOF, Computational Modeling, Signal...experimental and clinical/translational studies to define interactions between purinergic signaling mediators (ATP, AMP , Ado, inosine) with oxygen, oxidative...genetic deletion (Figure 1A) • Increase in ATP and ADP hydrolysis and decrease in AMP hydrolysis in peritoneal cells from CLP septic mice (Figure 1B

Facial tissue depths in children with cleft lip and palate.

Science.gov (United States)

Starbuck, John M; Ghoneima, Ahmed; Kula, Katherine

2015-03-01

Cleft lip and palate (CLP) is a craniofacial malformation affecting more than seven million people worldwide that results in defects of the hard palate, teeth, maxilla, nasal spine and floor, and maxillodental asymmetry. CLP facial soft-tissue depth (FSTD) values have never been published. The purpose of this research is to report CLP FSTD values and compare them to previously published FSTD values for normal children. Thirty-eight FSTDs were measured on cone beam computed tomography images of CLP children (n = 86; 7-17 years). MANOVA and ANOVA tests determined whether cleft type, age, sex, and bone graft surgical status affect tissue depths. Both cleft type (unilateral/bilateral) and age influence FSTDs. CLP FSTDs exhibit patterns of variation that differ from normal children, particularly around the oronasal regions of the face. These differences should be taken into account when facial reconstructions of children with CLP are created. © 2014 American Academy of Forensic Sciences.

MicroRNA regulation of Autophagy

DEFF Research Database (Denmark)

Frankel, Lisa B; Lund, Anders H

2012-01-01

recently contributed to our understanding of the molecular mechanisms of the autophagy machinery, yet several gaps remain in our knowledge of this process. The discovery of microRNAs (miRNAs) established a new paradigm of post-transcriptional gene regulation and during the past decade these small non......RNAs to regulation of the autophagy pathway. This regulation occurs both through specific core pathway components as well as through less well-defined mechanisms. Although this field is still in its infancy, we are beginning to understand the potential implications of these initial findings, both from a pathological...

Deficient motion-defined and texture-defined figure-ground segregation in amblyopic children.

Science.gov (United States)

Wang, Jane; Ho, Cindy S; Giaschi, Deborah E

2007-01-01

Motion-defined form deficits in the fellow eye and the amblyopic eye of children with amblyopia implicate possible direction-selective motion processing or static figure-ground segregation deficits. Deficient motion-defined form perception in the fellow eye of amblyopic children may not be fully accounted for by a general motion processing deficit. This study investigates the contribution of figure-ground segregation deficits to the motion-defined form perception deficits in amblyopia. Performances of 6 amblyopic children (5 anisometropic, 1 anisostrabismic) and 32 control children with normal vision were assessed on motion-defined form, texture-defined form, and global motion tasks. Performance on motion-defined and texture-defined form tasks was significantly worse in amblyopic children than in control children. Performance on global motion tasks was not significantly different between the 2 groups. Faulty figure-ground segregation mechanisms are likely responsible for the observed motion-defined form perception deficits in amblyopia.

76 FR 33065 - Adaptation of Regulations to Incorporate Swaps

Science.gov (United States)

2011-06-07

... regulation 1.3 as well. The Commission also proposes adding the term ``retail forex customer'' to regulation... appears in regulation 5.1(k).\\21\\ \\21\\ 17 CFR 5.1(k) currently defines ``retail forex customer'' as ``a...,'' ``retail forex exchange transactions,'' and ``commodity option transactions'' with the term ``commodity...

Sinomenine Hydrochloride Protects against Polymicrobial Sepsis via Autophagy

Directory of Open Access Journals (Sweden)

Yu Jiang

2015-01-01

Full Text Available Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs. The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl is widely used to treat rheumatoid arthritis (RA. However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3 puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM. 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.

Inhibition of histone deacetylases protects septic mice from lung and splenic apoptosis.

Science.gov (United States)

Takebe, Mariko; Oishi, Hirofumi; Taguchi, Kumiko; Aoki, Yuta; Takashina, Michinori; Tomita, Kengo; Yokoo, Hiroki; Takano, Yasuo; Yamazaki, Mitsuaki; Hattori, Yuichi

2014-04-01

Epigenetic programming, dynamically regulated by histone acetylation, may play a key role in the pathophysiology of sepsis. We examined whether histone deacetylase (HDAC) can contribute to sepsis-associated inflammation and apoptosis. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in BALB/c mice. An intraperitoneal injection of CG200745 (10 mg/kg), a novel broad-spectrum HDAC inhibitor, or valproic acid (500 mg/kg), a predominant inhibitor of class I HDACs, was given 3 h before surgery. HDAC1, HDAC2, and HDAC3 protein levels were decreased in lungs after CLP. Furthermore, CLP-induced sepsis increased both histone H3 and H4 acetylation levels in lungs. When CG200745 was given, apoptosis induction was strongly suppressed in lungs and spleens of septic mice. This antiapoptotic effect of CG200745 was not accompanied by upregulation of antiapoptotic and downregulation of proapoptotic Bcl-2 family member proteins. Treatment with CG200745 failed to inhibit elevated levels of serum cytokines and prevent lung inflammation in septic mice. Valproic acid also showed antiapoptotic but not anti-inflammatory effects in septic mice. These findings imply that HDAC inhibitors are a unique agent to prevent cell apoptosis in sepsis at their doses that do not improve inflammatory features, indicating that septic inflammation and apoptosis may not necessarily be essential for one another's existence. This study also represents the first report that CLP-induced sepsis downregulates HDACs. Nevertheless, the data with HDAC inhibitors suggest that imbalance in histone acetylation may play a contributory role in expression or repression of genes involved in septic cell apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Selective constraints in experimentally defined primate regulatory regions.

Directory of Open Access Journals (Sweden)

Daniel J Gaffney

2008-08-01

Full Text Available Changes in gene regulation may be important in evolution. However, the evolutionary properties of regulatory mutations are currently poorly understood. This is partly the result of an incomplete annotation of functional regulatory DNA in many species. For example, transcription factor binding sites (TFBSs, a major component of eukaryotic regulatory architecture, are typically short, degenerate, and therefore difficult to differentiate from randomly occurring, nonfunctional sequences. Furthermore, although sites such as TFBSs can be computationally predicted using evolutionary conservation as a criterion, estimates of the true level of selective constraint (defined as the fraction of strongly deleterious mutations occurring at a locus in regulatory regions will, by definition, be upwardly biased in datasets that are a priori evolutionarily conserved. Here we investigate the fitness effects of regulatory mutations using two complementary datasets of human TFBSs that are likely to be relatively free of ascertainment bias with respect to evolutionary conservation but, importantly, are supported by experimental data. The first is a collection of almost >2,100 human TFBSs drawn from the literature in the TRANSFAC database, and the second is derived from several recent high-throughput chromatin immunoprecipitation coupled with genomic microarray (ChIP-chip analyses. We also define a set of putative cis-regulatory modules (pCRMs by spatially clustering multiple TFBSs that regulate the same gene. We find that a relatively high proportion ( approximately 37% of mutations at TFBSs are strongly deleterious, similar to that at a 2-fold degenerate protein-coding site. However, constraint is significantly reduced in human and chimpanzee pCRMS and ChIP-chip sequences, relative to macaques. We estimate that the fraction of regulatory mutations that have been driven to fixation by positive selection in humans is not significantly different from zero. We also find

The impact and cost-effectiveness of the Amref Health Africa-Smile ...

African Journals Online (AJOL)

Introduction: Cleft lip with or without cleft palate (CLP) is a congenital malformation that causes significant morbidity in low and middle income countries. Amref Health Africa has partnered with Smile Train to provide CLP surgeries since 2006. Methods: We analyzed anonymized data of 37,274 CLP patients from the Smile ...

Nursing care system development for patients with cleft lip-palate and craniofacial deformities in operating room Srinagarind Hospital.

Science.gov (United States)

Riratanapong, Saowaluck; Sroihin, Waranya; Kotepat, Kingkan; Volrathongchai, Kanittha

2013-09-01

For a successful surgical outcome for patients with cleft lip/palate (CLP), the attending nurses must continuously develop their potential, knowledge, capacity and skills. The goal is to meet international standards of patient safety and efficiency. To assess and improve the nursing care system for patients with CLP and craniofacial deformities at the operating room (OR), Srinagarind Hospital, Khon Kaen University. Data were collected for two months (between March 1, 2011 and April 30, 2011). Part I was an enquiry regarding the attitude of OR staff on serving patients with CLP; and, Part 2.1) patient and caregiver satisfaction with service from the OR staff and 2.2) patient and caregiver satisfaction with the OR transfer service. The authors interviewed 28 staff in OR unit 2 of the OR nursing division and 30 patients with CLP and his/her caregiver. The respective validity according to the Cronbach's alpha coefficient was 0.87 and 0.93. The OR staff attitude visa-vis service provision for patients with CLP service was middling. Patient and caregiver satisfaction with both OR staff and the transfer service was very satisfactory. Active development of the nursing care system for patients with CLP and craniofacial deformities in the operating room, Srinagarind Hospital improved staff motivation with respect to serving patients with CLP. The operating theater staff was able to co-ordinate the multidisciplinary team through the provision of surgical service for patients with CLP.

The challenge of defining risk-based metrics to improve food safety: inputs from the BASELINE project.

Science.gov (United States)

Manfreda, Gerardo; De Cesare, Alessandra

2014-08-01

In 2002, the Regulation (EC) 178 of the European Parliament and of the Council states that, in order to achieve the general objective of a high level of protection of human health and life, food law shall be based on risk analysis. However, the Commission Regulation No 2073/2005 on microbiological criteria for foodstuffs requires that food business operators ensure that foodstuffs comply with the relevant microbiological criteria. Such criteria define the acceptability of a product, a batch of foodstuffs or a process, based on the absence, presence or number of micro-organisms, and/or on the quantity of their toxins/metabolites, per unit(s) of mass, volume, area or batch. The same Regulation describes a food safety criterion as a mean to define the acceptability of a product or a batch of foodstuff applicable to products placed on the market; moreover, it states a process hygiene criterion as a mean indicating the acceptable functioning of the production process. Both food safety criteria and process hygiene criteria are not based on risk analysis. On the contrary, the metrics formulated by the Codex Alimentarius Commission in 2004, named Food Safety Objective (FSO) and Performance Objective (PO), are risk-based and fit the indications of Regulation 178/2002. The main aims of this review are to illustrate the key differences between microbiological criteria and the risk-based metrics defined by the Codex Alimentarius Commission and to explore the opportunity and also the possibility to implement future European Regulations including PO and FSO as supporting parameters to microbiological criteria. This review clarifies also the implications of defining an appropriate level of human protection, how to establish FSO and PO and how to implement them in practice linked to each other through quantitative risk assessment models. The contents of this review should clarify the context for application of the results collected during the EU funded project named BASELINE (www

"Dermatitis" defined.

Science.gov (United States)

Smith, Suzanne M; Nedorost, Susan T

2010-01-01

The term "dermatitis" can be defined narrowly or broadly, clinically or histologically. A common and costly condition, dermatitis is underresourced compared to other chronic skin conditions. The lack of a collectively understood definition of dermatitis and its subcategories could be the primary barrier. To investigate how dermatologists define the term "dermatitis" and determine if a consensus on the definition of this term and other related terms exists. A seven-question survey of dermatologists nationwide was conducted. Of respondents (n  =  122), half consider dermatitis to be any inflammation of the skin. Nearly half (47.5%) use the term interchangeably with "eczema." Virtually all (> 96%) endorse the subcategory "atopic" under the terms "dermatitis" and "eczema," but the subcategories "contact," "drug hypersensitivity," and "occupational" are more highly endorsed under the term "dermatitis" than under the term "eczema." Over half (55.7%) personally consider "dermatitis" to have a broad meaning, and even more (62.3%) believe that dermatologists as a whole define the term broadly. There is a lack of consensus among experts in defining dermatitis, eczema, and their related subcategories.

Enamel Hypomineralization in Children With Clefts and the Relationship to Treatment: A Cross-sectional Retrospective Study.

Science.gov (United States)

Allam, Eman; Ghoneima, Ahmed; Tholpady, Sunil S; Kula, Katherine

2018-06-19

The aim of this study was to determine whether molar incisor hypomineralization (MIH) is greater in patients with cleft lip and palate (CLP) who underwent primary alveolar grafting (PAG) as compared with CLP waiting for secondary alveolar grafting (SAG) and with controls. A retrospective analysis of intraoral photographs of 13 CLP patients who underwent a PAG, 28 CLP prior to SAG, and 60 controls without CLP was performed. Mantel-Haenszel χ tests were used to compare the 3 groups for differences in MIH scores, and Wilcoxon rank sum tests were used to compare the groups for differences in average MIH scores. A 5% significance level was used for all tests. Molar incisor hypomineralization scores were significantly higher for the PAG and SAG groups compared with the control group (P MIH (P = 0.016) compared with the SAG group. Molar incisor hypomineralization average scores were significantly higher for the 2 graft groups compared with the controls (P MIH score and average MIH score for incisors compared with the SAG group (P = 0.03). Cleft lip and palate patients have significantly greater MIH compared with controls, and CLP patients with PAGs have significantly greater MIH in the incisor region compared with CLP patients with SAGs, indicating that subjects with PAGs have more severely affected dentition.

Bilingual Children with Nonsyndromic Cleft Lip and/or Palate: Language and Memory Skills

Science.gov (United States)

Young, Selena Ee-Li; Purcell, Alison Anne; Ballard, Kirrie Jane; Liow, Susan Jane Rickard; Ramos, Sara Da Silva; Heard, Robert

2012-01-01

Purpose: Research shows that monolingual children with cleft lip and/or palate (CLP) have a higher incidence of cognitive-linguistic deficits, but it is not clear whether bilingual preschool children with CLP are especially vulnerable because they need to acquire 2 languages. We tested the hypothesis that bilingual children with CLP score lower…

Comparison of some European regulations

Energy Technology Data Exchange (ETDEWEB)

Argyriadis, K [Germanisher Lloyd, Hamburg (Germany)

1996-09-01

Fatigue calculations are an essential part in certification of a wind turbine. Manufacturers have to fulfill recommendations of several different regulations throughout Europe with the result that the design has often to be altered to satisfy them. In general three national (D/GL, NL, DK), and two international (GL, IEC) regulations are in use, with the IEC standard getting more importance with wind energy deploying to more in regions with no yet clearly defined national standards (India, Spain). The Germanischer Lloyd made calculations for wind turbines they are certifying and in one case we compared the resulting damages for different regulations and classes on a 600 kW, three bladed, stall regulated wind turbine. (EG) 18 refs.

77 FR 66287 - Adaptation of Regulations To Incorporate Swaps

Science.gov (United States)

2012-11-02

... the term ``retail forex customer'' in regulation 1.3 because it appears in several regulations in part... receive any comments to the Proposal's addition of a definition of ``retail forex customer'' to regulation 1.3. \\26\\ 17 CFR 5.1(k) currently defines ``retail forex customer'' as ``a person, other than an...

Natural Gas Regulation

International Nuclear Information System (INIS)

1995-01-01

The regulation of Natural Gas. Natural gas Regulation clarifies and consolidates the legal and institutional framework for development of the industry through six principal elements: 1) Establishment of a vision of the industry. 2) Development of regulatory objectives. 3) Determination of relationships among industry participants. 4) Clear specification of the role of PEMEX in the industry. 5) Definition of the functions of the Regulatory authority. 6) Creation of a transition regime. In parallel with the development of the substantive legal framework, the law of the Comision Reguladora de Energia (CRE) was also enacted by Congress in October 1995 to strength the institutional framework and implement the legal changes. This law defines the CRE as an agency of the Energy Ministry with technical, operational, and budgetary autonomy, and responsibility for implementing natural gas industry regulation. (Author)

A Population-Based Study of Effects of Genetic Loci on Orofacial Clefts

DEFF Research Database (Denmark)

Moreno Uribe, L M; Fomina, T; Munger, R G

2017-01-01

, and MAFB and isolated cleft lip only (CLO) and cleft lip and palate (CLP). Significant associations were observed between isolated CLO and fetal SNPs near TPM1 and NOG1 and between CLP and fetal SNPs at ABCA4-ARHGAP29, THADA, FOXE1, and SPRY2. Overall, effects were similar for isolated CLO and CLP, except...

Increased activation of the hippocampus during a Chinese character subvocalization task in adults with cleft lip and palate palatoplasty and speech therapy.

Science.gov (United States)

Zhang, Wenjing; Li, Chunlin; Chen, Long; Xing, Xiyue; Li, Xiangyang; Yang, Zhi; Zhang, Haiyan; Chen, Renji

2017-08-16

This study aimed to explore brain activation in patients with cleft lip and palate (CLP) using a Chinese character subvocalization task, in which the stimuli were selected from a clinical articulation evaluation test. CLP is a congenital disability. Individuals with CLP usually have articulation disorder caused by abnormal lip and palate structure. Previous studies showed that primary somatosensory and motor areas had a significant difference in activation in patients with CLP. However, whether brain activation was restored to a normal level after palatoplasty and speech rehabilitation is not clear. Two groups, adults after palatoplasty with speech training and age-matched and sex-matched controls, participated in this study. Brain activation during Chinese character subvocalization task and behavioral data were recorded using functional MRI. Patients with CLP responded to the target significantly more slowly compared with the controls, whereas no significant difference in accuracy was found between the groups. Brain activation had similar patterns between groups. Broca's area, Wernicke's area, motor areas, somatosensory areas, and insula in both hemispheres, and the dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex in the right hemisphere were activated in both groups, with no statistically significant difference. Furthermore, the two-sample t-test showed that the hippocampus in the left hemisphere was activated significantly in patients with CLP compared with the controls. The results suggested that the hippocampus might be involved in the language-related neural circuit in patients with CLP and play a role of pronunciation retrieval to help patients with CLP to complete the pronunciation effectively.

Defining 'Better'

DEFF Research Database (Denmark)

Pedersen, Morten Jarlbæk

2017-01-01

Better regulation is a political and scholarly theme, which has gained in both relevance and salience throughout the last two decades or so. Regulatory quality is the epicentre of these discussions. Despite this quality is seldom conceptualised in its own right. Thus, beyond loose principles, we...... are rarely aware of what we mean by ‘better’ regulation, and academic discussions hereof usually centre themselves on other topics such as meta-regulation and processes. This leaves the notion of quality hard to asses especially from a comparative perspective. In this paper, a core concept of quality...

Facial soft-tissue asymmetry in three-dimensional cone-beam computed tomography images of children with surgically corrected unilateral clefts.

Science.gov (United States)

Starbuck, John Marlow; Ghoneima, Ahmed; Kula, Katherine

2014-03-01

Cleft lip with or without cleft palate (CL/P) is a relatively common craniofacial malformation involving bony and soft-tissue disruptions of the nasolabial and dentoalveolar regions. The combination of CL/P and subsequent craniofacial surgeries to close the cleft and improve appearance of the cutaneous upper lip and nose can cause scarring and muscle pull, possibly resulting in soft-tissue depth asymmetries across the face. We tested the hypothesis that tissue depths in children with unilateral CL/P exhibit differences in symmetry across the sides of the face. Twenty-eight tissue depths were measured on cone-beam computed tomography images of children with unilateral CL/P (n = 55), aged 7 to 17 years, using Dolphin software (version 11.5). Significant differences in tissue depth symmetry were found around the cutaneous upper lip and nose in patients with unilateral CL/P.

29 CFR 2520.101-4 - Annual funding notice for multiemployer defined benefit pension plans.

Science.gov (United States)

2010-07-01

... pension plans. 2520.101-4 Section 2520.101-4 Labor Regulations Relating to Labor (Continued) EMPLOYEE... pension plans. (a) In general. (1) Except as provided in paragraph (a)(2) of this section, pursuant to section 101(f) of the Act, the administrator of a defined benefit, multiemployer pension plan shall...

Longitudinal Comparison of Early Speech and Language Milestones in Children with Cleft Palate: A Comparison of US and Slovak Children

Science.gov (United States)

Scherer, Nancy J.; Oravkinova, Zuzana; McBee, Matthew T.

2013-01-01

The purpose of this study was to compare early speech and language development of children with and without cleft lip and/or palate (CLP) in the US and Slovakia from 6 to 24 months of age. Thirty-two children from the US (eight with CLP and eight noncleft) and Slovakia (eight with CLP and eight noncleft) participated in this study. The children…

An introduction to use of the USACE HTRW program's data validation guidelines engineering manual

International Nuclear Information System (INIS)

Becker, L.D.; Coats, K.H.

1994-01-01

Data validation has been defined by regulatory agencies as a systematic process (consisting of data editing, screening, checking, auditing, verification, certification, and review) for comparing data to established criteria in order to provide assurance that data are adequate for their intended use. A problem for the USACE HTRW Program was that clearly defined data validation guidelines were available only for analytical data quality level IV. These functional data validation guidelines were designed for validation of data produced using protocols from the US E.P.A.'s Contract Laboratory Program (CLP). Unfortunately, USACE experience demonstrates that these level IV functional data validation guidelines were being used to validate data not produced under the CLP. The resulting data validation product was less than satisfactory for USACE HTRW needs. Therefore, the HTRW-MCX initiated an Engineering Manual (EM) for validation of analytical data quality levels other than IV. This EM is entitle ''USACE HTRW Data Validation Guidelines.'' Use of the EM is required for validation of analytical data relating to projects under the jurisdiction of the Department of the Army, Corps of Engineers, Hazardous, Toxic, and Radioactive Waste Program. These data validation guidelines include procedures and checklists for technical review of analytical data at quality levels I, II, III, and V

Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

International Nuclear Information System (INIS)

Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia; Mazzanti, Benedetta; Quercioli, Franco; Zecchi-Orlandini, Sandra; Formigli, Lucia

2014-01-01

Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7 + satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration

Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

Energy Technology Data Exchange (ETDEWEB)

Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Mazzanti, Benedetta [Dept. of Experimental and Clinical Medicine—Section of Haematology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Quercioli, Franco [CNR-National Institute of Optics (INO), Largo Enrico Fermi 6, 50125 Arcetri-Florence (Italy); Zecchi-Orlandini, Sandra [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Formigli, Lucia, E-mail: formigli@unifi.it [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy)

2014-05-01

Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7{sup +} satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration.

Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

Energy Technology Data Exchange (ETDEWEB)

Sethi, Aisha [Department of Pathology, Henry Ford Hospital, Detroit, MI 48202 (United States); Sholl, Lynette M., E-mail: lmsholl@partners.org [Department of Pathology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

2011-10-24

Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells.

Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

International Nuclear Information System (INIS)

Sethi, Aisha; Sholl, Lynette M.

2011-01-01

Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells

Foreign experience of regulating international trade transactions

Directory of Open Access Journals (Sweden)

Klymenko L. V.

2015-05-01

Full Text Available The article deals with the international experience of state regulating international trade transactions; nature, directions and contradictions of contemporary processes of globalization are defined; components of regulatory and incentive means in system of state supporting foreign trade activity of commodity producers are considered; general provisions for the improvement of state regulation mechanisms of export-import activities in Ukraine are determined.

Nasal airway and septal variation in unilateral and bilateral cleft lip and palate.

Science.gov (United States)

Starbuck, John M; Friel, Michael T; Ghoneima, Ahmed; Flores, Roberto L; Tholpady, Sunil; Kula, Katherine

2014-10-01

Cleft lip and palate (CLP) affects the dentoalveolar and nasolabial facial regions. Internal and external nasal dysmorphology may persist in individuals born with CLP despite surgical interventions. 7-18 year old individuals born with unilateral and bilateral CLP (n = 50) were retrospectively assessed using cone beam computed tomography. Anterior, middle, and posterior nasal airway volumes were measured on each facial side. Septal deviation was measured at the anterior and posterior nasal spine, and the midpoint between these two locations. Data were evaluated using principal components analysis (PCA), multivariate analysis of variance (MANOVA), and post-hoc ANOVA tests. PCA results show partial separation in high dimensional space along PC1 (48.5% variance) based on age groups and partial separation along PC2 (29.8% variance) based on CLP type and septal deviation patterns. MANOVA results indicate that age (P = 0.007) and CLP type (P ≤ 0.001) significantly affect nasal airway volume and septal deviation. ANOVA results indicate that anterior nasal volume is significantly affected by age (P ≤ 0.001), whereas septal deviation patterns are significantly affected by CLP type (P ≤ 0.001). Age and CLP type affect nasal airway volume and septal deviation patterns. Nasal airway volumes tend to be reduced on the clefted sides of the face relative to non-clefted sides of the face. Nasal airway volumes tend to strongly increase with age, whereas septal deviation values tend to increase only slightly with age. These results suggest that functional nasal breathing may be impaired in individuals born with the unilateral and bilateral CLP deformity. © 2014 Wiley Periodicals, Inc.

75 FR 19241 - Financial Crimes Enforcement Network; Amendment to the Bank Secrecy Act Regulations; Defining...

Science.gov (United States)

2010-04-14

... definition of mutual fund in the rule requiring mutual funds to establish anti-money laundering (``AML...-money laundering programs and compliance procedures.\\1\\ Regulations implementing the BSA appear at 31... transactions.\\7\\ \\5\\ Anti-Money Laundering Programs for Mutual Funds, 67 FR 21117 (April 29, 2002); Customer...

Potential application of cyclic lipopeptide biosurfactants produced by Bacillus subtilis strains in laundry detergent formulations.

Science.gov (United States)

Mukherjee, A K

2007-09-01

Crude cyclic lipopeptide (CLP) biosurfactants from two Bacillus subtilis strains (DM-03 and DM-04) were studied for their compatibility and stability with some locally available commercial laundry detergents. CLP biosurfactants from both B. subtilis strains were stable over the pH range of 7.0-12.0, and heating them at 80 degrees C for 60 min did not result in any loss of their surface-active property. Crude CLP biosurfactants showed good emulsion formation capability with vegetable oils, and demonstrated excellent compatibility and stability with all the tested laundry detergents. CLP biosurfactants from B. subtilis strains act additively with other components of the detergents to further improve the wash quality of detergents. The thermal resistance and extreme alkaline pH stability of B. subtilis CLP biosurfactants favour their inclusion in laundry detergent formulations. This study has great significance because it is already known that microbial biosurfactants are considered safer alternative to chemical or synthetic surfactants owing to lower toxicity, ease of biodegradability and low ecological impact. The present study provides further evidence that CLP biosurfactants from B. subtilis strains can be employed in laundry detergents.

Nonsyndromic cleft lip and palate: No evidence of linkage to HLA or factor 13A

Energy Technology Data Exchange (ETDEWEB)

Hecht, J.T.; Yaping Wang; Connor, B.; Daiger, S.P. (Univ. of Texas, Houston (United States)); Blanton, S.H. (Univ. of Texas, Houston (United States) Univ. of Virginia, Charlottesville (United States))

1993-06-01

Nonsyndromic cleft lip with or without cleft palate (CLP) is a common craniofacial anomaly, the etiology of which is not known. Population studies have shown that a large proportion of cases occur sporadically. Recently, segregation analyses applied to CLP families have demonstrated that an autosomal dominant/codominant gene(s) may cause clefting in cases. Associations of autosomal dominant CLP and nonsyndromic cleft palate (CP) with HLA and F13A genes on chromosome 6p have been suggested previously. Linkage to these two areas on chromosome 6p were tested in 12 autosomal dominant families with CLP. With a LOD score of [minus]2 or less for exclusion, no evidence of linkage was found to four chromosome 6p markers. Multipoint analysis showed no evidence of a clefting locus in this region spanning 54 cM on chromosome 6p in these CLP families. 30 refs., 2 figs., 1 tab.

eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci

DEFF Research Database (Denmark)

Mousavi, Kambiz; Zare, Hossein; Dell'orso, Stefania

2013-01-01

)RNA acted to activate the downstream myogenic genes. The deployment of transcriptional machinery to appropriate loci is contingent on chromatin accessibility, a rate-limiting step preceding Pol II assembly. By nuclease sensitivity assay, we found that eRNAs regulate genomic access of the transcriptional...... complex to defined regulatory regions. In conclusion, our data suggest that eRNAs contribute to establishing a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events....

Methodology for qualification of wood-based ash according to REACH - prestudy

Energy Technology Data Exchange (ETDEWEB)

Sjoeblom, Rolf [Tekedo AB, Nykoeping (Sweden); Tivegaard, Anna-Maria [SSAB Merox AB, Oxeloesund (Sweden)

2010-02-15

The new European Union framework directive on waste is to be implemented during the year 2010. According to this directive, much of what today is regarded as waste will instead be assessed as by-products and in many cases fall under the new European union regulation REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals). REACH applies in conjunction with the new European Union regulation CLP (Classification, Labelling and Packaging of substances and mixtures). There are introductory periods for both of these regulations, and in the case of CLP this regards transition from the present and previous rules under the dangerous substances and dangerous preparations directives (DSD and DPD, respectively). Similarly, the new framework directive on waste supersedes the previous directive and some other statements. There is a connection between the directives of waste and the rules for classification and labelling in that the classification of waste (in the categories hazardous and non-hazardous) build on (but are not identical to) the rules for labelling. Similarly, the national Swedish rules for acceptance of recycled material (waste) for use in geotechnical constructions relate to the provisions in REACH on assessment of chemical safety in the both request that the risk be assessed to be small, and that the same or similar methodologies can be applied to verify this. There is a 'reference alternative' in REACH that implies substantial testing prior to registration. Registration is the key to use of a substance even though a substance may be used as such, in a mixture, or to be released from an article. However, REACH as well as CLP contain a number of provisions for using literature data, data on similar chemicals e t c in order to avoid unnecessary testing. This especially applies to testing on humans and vertebrate animals. Vaermeforsk, through its Programme on Environmentally Friendly Use of Non-Coal Ashes has developed methodologies and

Methodology for qualification of wood-based ash according to REACH - prestudy

Energy Technology Data Exchange (ETDEWEB)

Sjoeblom, Rolf (Tekedo AB, Nykoeping (Sweden)); Tivegaard, Anna-Maria (SSAB Merox AB, Oxeloesund (Sweden))

2010-02-15

The new European Union framework directive on waste is to be implemented during the year 2010. According to this directive, much of what today is regarded as waste will instead be assessed as by-products and in many cases fall under the new European union regulation REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals). REACH applies in conjunction with the new European Union regulation CLP (Classification, Labelling and Packaging of substances and mixtures). There are introductory periods for both of these regulations, and in the case of CLP this regards transition from the present and previous rules under the dangerous substances and dangerous preparations directives (DSD and DPD, respectively). Similarly, the new framework directive on waste supersedes the previous directive and some other statements. There is a connection between the directives of waste and the rules for classification and labelling in that the classification of waste (in the categories hazardous and non-hazardous) build on (but are not identical to) the rules for labelling. Similarly, the national Swedish rules for acceptance of recycled material (waste) for use in geotechnical constructions relate to the provisions in REACH on assessment of chemical safety in the both request that the risk be assessed to be small, and that the same or similar methodologies can be applied to verify this. There is a 'reference alternative' in REACH that implies substantial testing prior to registration. Registration is the key to use of a substance even though a substance may be used as such, in a mixture, or to be released from an article. However, REACH as well as CLP contain a number of provisions for using literature data, data on similar chemicals e t c in order to avoid unnecessary testing. This especially applies to testing on humans and vertebrate animals. Vaermeforsk, through its Programme on Environmentally Friendly Use of Non-Coal Ashes has developed methodologies and

Defining behavioral and molecular differences between summer and migratory monarch butterflies

Science.gov (United States)

Zhu, Haisun; Gegear, Robert J; Casselman, Amy; Kanginakudru, Sriramana; Reppert, Steven M

2009-01-01

Background In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. Results Here we show that increasing juvenile hormone activity to induce summer-like reproductive development in fall migrants does not alter directional flight behavior or its time-compensated orientation, as monitored in a flight simulator. Reproductive summer butterflies, in contrast, uniformly fail to exhibit directional, oriented flight. To define molecular correlates of behavioral state, we used microarray analysis of 9417 unique cDNA sequences. Gene expression profiles reveal a suite of 40 genes whose differential expression in brain correlates with oriented flight behavior in individual migrants, independent of juvenile hormone activity, thereby molecularly separating fall migrants from summer butterflies. Intriguing genes that are differentially regulated include the clock gene vrille and the locomotion-relevant tyramine beta hydroxylase gene. In addition, several differentially regulated genes (37.5% of total) are not annotated. We also identified 23 juvenile hormone-dependent genes in brain, which separate reproductive from non-reproductive monarchs; genes involved in longevity, fatty acid metabolism, and innate immunity are upregulated in non-reproductive (juvenile-hormone deficient) migrants. Conclusion The results link key behavioral traits with gene expression profiles in brain that differentiate migratory

The prevalence of specific dental anomalies in a group of Saudi cleft lip and palate patients.

Science.gov (United States)

Al-Kharboush, Ghada H; Al-Balkhi, Khalid M; Al-Moammar, Khalid

2015-04-01

The aims of this study were to investigate the prevalence and distribution of dental anomalies in a group of Saudi subjects with cleft lip and palate (CLP), to examine potential sex-based associations of these anomalies, and to compare dental anomalies in Saudi subjects with CLP with published data from other population groups. This retrospective study involved the examination of pre-treatment records obtained from three CLP centers in Riyadh, Saudi Arabia, in February and March 2010. The pre-treatment records of 184 subjects with cleft lip and palate were identified and included in this study. Pre-treatment maxillary occlusal radiographs of the cleft region, panoramic radiographs, and orthodontic study models of subjects with CLP were analyzed for dental anomalies. Orthopantomographs and occlusal radiographs may not be reliable for the accurate evaluation of root malformation anomalies. A total of 265 dental anomalies were observed in the 184 study subjects. Hypodontia was observed most commonly (66.8%), followed by microdontia (45.6%), intra-oral ectopic eruption (12.5%), supernumerary teeth (12.5%), intra-nasal ectopic eruption (3.2), and macrodontia (3.2%). No gender difference in the prevalence of these anomalies was observed. Dental anomalies were common in Saudi subjects with CLP type. This will complicate the health care required for the CL/P subjects. This study was conducted to epidemiologically explore the prevalence of dental anomalies among Saudi Arabian subjects with CLP.

The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

Directory of Open Access Journals (Sweden)

Wehby George L

2011-12-01

Full Text Available Abstract Background Cleft lip and/or palate (CL/P increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P in South America. Methods The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7th and 28th day of life. The primary outcomes were mortality between the 7th and 28th day of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates. Results There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group. Conclusions Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention. Trial Registration ClinicalTrials.gov: NCT00097149

Protective effects of oridonin on the sepsis in mice

Directory of Open Access Journals (Sweden)

Yan-Jun Zhao

2016-09-01

Full Text Available This study aimed to investigate the protective effects of oridonin (ORI on cecal ligation and puncture (CLP-induced sepsis in mice. Male C57BL/6 mice weighing 22–30 g and aged 8–10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin–eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6, and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05. Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05. The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05. Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.

Defining functional DNA elements in the human genome

Science.gov (United States)

Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E.; Dekker, Job; Dunham, Ian; Elnitski, Laura L.; Farnham, Peggy J.; Feingold, Elise A.; Gerstein, Mark; Giddings, Morgan C.; Gilbert, David M.; Gingeras, Thomas R.; Green, Eric D.; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D.; Myers, Richard M.; Pazin, Michael J.; Ren, Bing; Stamatoyannopoulos, John A.; Weng, Zhiping; White, Kevin P.; Hardison, Ross C.

2014-01-01

With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease. PMID:24753594

Nuclear safety: economic analysis of American, French and Japanese regulations

International Nuclear Information System (INIS)

Leveque, Francois

2013-05-01

While discussing and comparing the American, Japanese and French approaches and practices, and identifying the strengths and weaknesses of each of them, the author discusses why self-regulation and civil responsibility cannot guarantee a sufficient nuclear safety level, why the safety regulation authority must be independent from industry and government, whether a figure must be put to the safety objective (for example with a risk threshold), whether it is better to define detailed standards to be applied by manufacturers and operators or to define general performance criteria to be reached

Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus-Ventral Tegmental Area Neurocircuitry Depends on Energy State.

Science.gov (United States)

Liu, Jing-Jing; Bello, Nicholas T; Pang, Zhiping P

2017-12-06

Synaptic transmission controls brain activity and behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamic area (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types, and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole-cell patch-clamp recordings and post hoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding. A presynaptic mechanism mediated by distinct intracellular signaling mechanisms may account for this regulation by leptin. The regulatory effects of leptin depend on intact leptin receptor signaling. Interestingly, the synaptic regulatory function of leptin in the LHA-to-VTA neuronal pathway is highly sensitive to energy states: both energy deficiency (acute fasting) and excessive energy storage (high-fat diet-induced obesity) blunt the effect of leptin. These data revealed that leptin may regulate synaptic transmission in the LHA-to-VTA neurocircuitry in an inverted "U-shape" fashion dependent on plasma glucose levels and related to metabolic states. SIGNIFICANCE STATEMENT The lateral hypothalamic area (LHA) to ventral tegmental area (VTA) projection is an important neural pathway involved in balancing whole-body energy states and reward. We found that the excitatory synaptic inputs to both orexin- and melanin-concentrating hormone expressing LHA neurons projecting to the VTA were suppressed by leptin, a peptide hormone derived from adipocytes that signals peripheral energy status to the brain. Interestingly, energy states seem to affect how leptin regulates synaptic transmission since both the depletion of energy induced by acute food

The four key characteristics of interpersonal emotion regulation.

Science.gov (United States)

Niven, Karen

2017-10-01

Emotion researchers are increasingly interested in processes by which people influence others' feelings. Although one such process, interpersonal emotion regulation, has received particular attention in recent years, there remains confusion about exactly how to define this process. The present article aims to distinguish interpersonal emotion regulation from other, related processes by outlining its four key characteristics. Specifically, interpersonal emotion regulation is presented as a process of (i) regulation, that (ii) has an affective target, (iii) is deliberate, and (iv) has a social target. Considering these characteristics raises questions for future research concerning factors that may influence the process of interpersonal emotion regulation, why interpersonal emotion regulation sometimes fails, and whether interventions can improve people's use of interpersonal emotion regulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The CLP(OIH) Language

DEFF Research Database (Denmark)

Hougaard, Ole Ildsgaard

1998-01-01

Type inference is generally thought of as being an exclusive property of the functional programming paradigm. We argue that such a feature may be of significant benefit for also standard imperative languages. We present a working tool (available by WWW) providing these benefits for a full version...... of Turbo Pascal. It has the form of a preprocessor that analyzes programs in which the type annotations are only partial or even absent. The resulting program has full type annotations, will be accepted by the standard Turbo Pascal compiler, and has polymorphic use of procedures resolved by means of code...

The regulations of the Nuclear Technology Committee

International Nuclear Information System (INIS)

Schwarzer, W.

1984-01-01

The work of the Nuclear Technology Committee (NTC) is characterised by the key words 'safety related regulations' and 'nuclear technology'. The rationalisation effect desired from regulations and the not unlimited number of experts qualified for working out regulations, make it necessary to establish priorities. The NTC has almost exclusively worked out regulations for nuclear powerstations and mainly for light water reactors. The program defined at present seems to cover the most important areas. Future developments can be foreseen in the execution of the part of the program not yet concluded, the maintenance of the regulations and, depending on the development of nuclear technology, the greater inclusion of the HTR and possibly the expansion of the regulations to fast breeder reactors and plant of the fuel circuit. (orig./HSCH) [de

ATTACHMENT IN INFANTS WITH CLEFT LIP AND/OR PALATE: MARGINAL SECURITY AND ITS CHANGES OVER TIME.

Science.gov (United States)

Borghini, Ayala; Despars, Josée; Habersaat, Stéphanie; Turpin, Hélène; Monnier, Maryline; Ansermet, François; Hohlfeld, Judith; Muller-Nix, Carole

2018-03-01

This study examines the attachment quality and how this changed over time among infants who had cleft lip and palate (CLP), by conducting a prospective longitudinal study addressing the effects of this type of perinatal event on the parent-infant relationship and the emotional development of the infants. At 12 months of age, the Strange Situation Paradigm (SSP; M. Ainsworth, M.C. Blehar, E. Waters, & T. Wall, 1978) was administered to a sample of 38 CLP infants (born between 2003 and 2010) and 17 healthy controls. At 4 years of age, the Attachment Story Completion Task (ASCT; I. Bretherton, D. Ridgeway, & J. Cassidy, 1990) was administered to 32 individuals from the CLP sample and 14 from the control group. As reported in the literature, CLP infants display secure attachment behaviors as frequently as do control infants (55%). However, a more detailed analysis of the attachment scales revealed that CLP infants show more avoidance and less proximity seeking. In addition, a closer examination of the subcategories of attachment styles revealed that most CLP infants (71%) displayed distal attachment strategies such as the B1/B2 or A1/A2 subcategories. At 4 years old, CLP infants clearly displayed more deactivation and less security than did the control sample. Moreover, when detailing the evolution of attachment individually, almost 60% of the CLP children showing distal strategies at 12 months became deactivated or disorganized when they reached 4 years. Indeed, subtle differences in attachment behaviors at 12 months old-which can be considered marginally secure at that age-may reveal attachment vulnerabilities, which seem to be more apparent over the course of development. © 2018 Michigan Association for Infant Mental Health.

Population-based study of birth prevalence and factors associated with cleft lip and/or palate in Taiwan 2002-2009.

Directory of Open Access Journals (Sweden)

Ruoh-Lih Lei

Full Text Available BACKGROUND: Facial cleft deformities, including cleft lip with or without cleft palate (CL/P and cleft palate (CP, are common congenital birth anomalies, especially in Asia. This study aimed to analyze the prevalence of CL/P and CP and to identify associated factors in Taiwan. METHODS: This population-based epidemiological study retrospectively analyzed birth data obtained from the Department of Health in Taiwan for years 2002-2009. Frequency distribution, percentages and related predictors were investigated, and findings were presented by types of cleft deformities. Logistic regression analysis was performed to identify factors associated with cleft deformities. RESULTS: Overall prevalence of cleft deformities among 1,705,192 births was 0.1% for CL/P and 0.04% for CP over the 8-year study period. Higher prevalence of CL/P or CP was observed with multiple pregnancies, being male for CL/P, being female for CP, gestational age ≤37 weeks and lower birth weight (<1.5 kg. Both CL/P and CP were significantly associated with gestational age <37 weeks and birth weight<1.5 kg (all P <0.0001. CL/P was significantly associated with multiple parities (P = 0.0004-0.002. Male newborns and female newborns were significantly associated with CL/P and CP, respectively (both P<0.0001. CONCLUSIONS: Overall prevalence for congenital cleft deformities in study subjects was 0.1%, in keeping with high rates in Asia. Results suggest the need for awareness and early identification of those at high risk for cleft deformities, including newborns with gestational age <37 weeks, weighing <1.5 kg at birth and women with multiple parities, as a potential strategy to counter long-term adverse effects on speech and language in this population.

Regulating Corporate Governance in the EU

DEFF Research Database (Denmark)

Horn, Laura

In the context of the financial and economic crisis, corporate governance and regulatory supervision failures are at the centre of public debates. Who controls the modern corporation, and why, has become one of the defining social power relations in contemporary capitalism. Regulation Corporate...... transformation of company law and corporate governance regulation. Her findings about the marketization of corporate control are at the core to a better understanding of the broader context of capitalist restructuring in the European Union....

INVESTIGATING SELF-REGULATED LEARNING HABITS OF DISTANCE EDUCATION STUDENTS

OpenAIRE

Ozkan Kirmizi

2013-01-01

This study aims at exploring self-regulated learning habits of distance education students. Self-regulation can be defined as a process where learners take the initiative, with or without the guidance of others, in identifying their own needs, formulating goals, exploring resources, focusing on appropriate learning strategies, and evaluating learning outcomes. This study investigates self-regulated learning in terms of goal setting, environment structuring, time management, help seeking, self...

Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

International Nuclear Information System (INIS)

Yi, TacGhee; Kim, Hye-Jin; Cho, Je-Yoel; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa

2006-01-01

Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity

Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model

Directory of Open Access Journals (Sweden)

Elmira Zolali

2015-12-01

Full Text Available Objective (s: There is corroborating evidence to substantiate redox imbalance and oxidative stress in sepsis that finally leads to organ damage or even death. Gamma oryzanol (GO is one of the major bioactive components in rice bran has been considered to function as an antioxidant. The present study was carried out to evaluate the antioxidant activity of gamma oryzanol in vitro and its efficacy in sepsis. Materials and Methods: To induce sepsis, cecal ligation and puncture (CLP method was performed on the rats. A study group of forty male Wistar rats were divided into the following groups: sham group; CLP group; 50 mg/kg GO- treated CLP group and 100 mg/kg GO- treated CLP group. GO was administered with an oral gavage 2 hr prior to inducing sepsis. Tissue and blood samples were collected 12 hr after CLP to prepare tissue sections for histopathological study and assay the oxidative stress biomarkers including: SOD (Superoxide Dismutase, TAC (total antioxidant capacity, MDA (Malondialdehyde, MPO (Myeloperoxidase and PAI-1 (Plasminogen Activator Inhibitor-1. Data are given as mean ± SD. The ANOVA with Tukey post hoc test was used to determine the differences between groups and P Results: TAC level increased in GO- treated CLP groups (P

Empowering Volunteers at Tawanchai Centre for Patients with Cleft Lip and Palate.

Science.gov (United States)

Pradubwong, Suteera; Augsornwan, Darawan; Pathumwiwathana, Pornpen; Prathanee, Benjamas; Chowchuen, Bowornsilp

2015-08-01

Cleft lip and palate (CLP) congenital anomalies have a high prevalence in the Northeast of Thailand. A care team's understand of treatment plan would help to guide the family of patients with CLP to achieve the treatment. To examine the impact of the empowering volunteer project, established in the northeast Thailand. The Empowering Volunteer project was conducted in 2008 under the Tawanchai Royal Granted project. The patients and family's general information, treatment, the group brainstorming, and satisfaction with the project were analysed. Participants were 12 children with CLP their families and five volunteers with CLP; the participating patients were predominantly females and the mean age was 12.2 years. The treatment comprised of speech training, dental hygiene care, bone graft and orthodontic treatment. Four issues were addressed including: problems in taking care of breast feeding, instructions' needs for care at birth, difficulty in access information and society impact, and needs in having a network of volunteers. Empowering volunteer is important for holistic care of patients with CLP which provides easy access and multiple channels for patients and their families. It should be developed as part of the self-help and family support group, the development of community based team and comprehensive CLP care program.

The effectiveness of consultation-liaison psychiatry in the general hospital setting: a systematic review.

Science.gov (United States)

Wood, Rebecca; Wand, Anne P F

2014-03-01

The aim of this study was to review how the effectiveness of consultation liaison psychiatry (CLP) services has been measured and to evaluate the strength of the evidence for effectiveness. Systematic review of medical databases using broad search terms as well as expert opinion was sought. The literature search was restricted to studies of general, whole-of-hospital inpatient CLP services. Forty articles were found and grouped into five measurements of effectiveness: cost effectiveness including length of stay, concordance, staff and patient feedback, and follow-up outcome studies. All measurements contributed to the evaluation of CLP services, but no one measure in isolation could adequately cover the multifaceted roles of CLP. Concordance was the only measurement with an established, consistent approach for evaluation. Cost effectiveness and follow-up outcome studies were the only measures with levels of evidence above four, however the three follow-up outcome studies reported conflicting results. Subjective evidence derived from patient and staff feedback is important but presently lacking due to methodological problems. The effectiveness of CLP services was demonstrated by cost-effectiveness, earlier referrals to CLP predicting shorter length of stay, and concordance with some management recommendations. There is evidence that some CLP services are cost-effective and reduce length of stay when involved early and that referrers follow certain recommendations. However, many studies had disparate results and were methodologically flawed. Future research should focus on standardising patient and staff feedback, and short-term patient outcomes. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Dental Anomalies in Different Types of Cleft Lip and Palate: Is There Any Relation?

Science.gov (United States)

Germec Cakan, Derya; Nur Yilmaz, Rahime Burcu; Bulut, Feyza Nur; Aksoy, Ayca

2018-02-26

The aims of this study were to evaluate the prevalence of dental anomalies in Turkish patients with different types of cleft lip and palate (CLP) and investigate the relationship between the type of cleft and the dental anomaly. Eighty-eight patients with cleft lip and/or palate (mean age: 14.1 ± 6.4 years) were enrolled in this retrospective study. Dental models, panoramic radiographs, and intraoral photographs of these patients were evaluated to detect any maxillary dental anomaly (number and size anomalies). Two hundred fifty unaffected subjects (mean age: 15.2 ± 7.2 years) composed the control group. Data were evaluated using the independent t test, χ, Fischer exact test, and the odds ratio. Dental anomaly frequency was significantly higher in the cleft group compared with the control group. Tooth agenesis was the most common dental anomaly, followed by microdontia and supernumerary tooth. Lateral incisor agenesis was seen in 69% of the unilateral CLP, in 78% of the bilateral CLP, and in 18% of the cleft palate patients. A significant association was revealed between the right unilateral CLP and the right lateral incisor agenesis (P = 0.0001), the left unilateral CLP and the left lateral incisor agenesis (P = 0.002), and the bilateral CLP and the bilateral lateral incisor agenesis (P = 0.0001). Dental anomalies are more frequently seen in patients with CLP compared with the general population. There is a relationship between the cleft type and the ipsilateral lateral incisor agenesis.

Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis

Directory of Open Access Journals (Sweden)

Pia Rademann

2017-01-01

Full Text Available Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice (n=90 underwent cecal ligation and puncture (CLP and received SkQ1 (5 nmol/kg, MitoTEMPO (50 nmol/kg, or vehicle 5 times post-CLP. Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints. Neither MitoTEMPO nor SkQ1 exerted any protracted survival benefit. Conversely, SkQ1 exacerbated 28-day mortality by 29%. CLP induced release of 10 circulating cytokines, increased urea, ALT, and LDH, and decreased glucose but irrespectively of treatment. Similar occurred for CLP-induced lymphopenia/neutrophilia and the NO blood release. At 48 h post-CLP, dying mice had approximately 100-fold more CFUs in the spleen than survivors, but this was not SkQ1 related. At 48 h, macrophage and granulocyte counts increased in the peritoneal lavage but irrespectively of SkQ1. Similarly, hepatic mitophagy was not altered by SkQ1 at 24 h. The absence of survival benefit of mtAOX may be due to the extended treatment and/or a relatively moderate-risk-of-death CLP cohort. Long-term effect of mtAOX in abdominal sepsis appears different to sepsis/inflammation models arising from other body compartments.

Urban Green Network Design: Defining green network from an urban planning perspective

OpenAIRE

Andrea Tulisi

2017-01-01

From the theoretical context of Smart City various studies have emerged that adopt an analytical approach and description of urban phenomena based on the principles of “network design”; this line of research uses the network systems theory to define the principles that regulate the relationships among the various elements of urban sub-systems in order to optimize their functionality. From the same theoretical basis, urban greenspaces have also been studied as networks, by means of the creatio...

The NAD/NARB System: Advertising Self-Regulation at Work.

Science.gov (United States)

Hays, Robert

Self-regulation, as defined by the National Advertising Division/National Advertising Review Board (NAD/NARB), is a process whereby the advertising industry regulates itself and turns to the federal government only if the system fails. The NAD/NARB system involves a two-step process: complaints are initially handled by the NAD and then are either…

Can play be defined?

DEFF Research Database (Denmark)

Eichberg, Henning

2015-01-01

Can play be defined? There is reason to raise critical questions about the established academic demand that at phenomenon – also in humanist studies – should first of all be defined, i.e. de-lineated and by neat lines limited to a “little box” that can be handled. The following chapter develops....... Human beings can very well understand play – or whatever phenomenon in human life – without defining it....

Software Defined Cyberinfrastructure

Energy Technology Data Exchange (ETDEWEB)

Foster, Ian; Blaiszik, Ben; Chard, Kyle; Chard, Ryan

2017-07-17

Within and across thousands of science labs, researchers and students struggle to manage data produced in experiments, simulations, and analyses. Largely manual research data lifecycle management processes mean that much time is wasted, research results are often irreproducible, and data sharing and reuse remain rare. In response, we propose a new approach to data lifecycle management in which researchers are empowered to define the actions to be performed at individual storage systems when data are created or modified: actions such as analysis, transformation, copying, and publication. We term this approach software-defined cyberinfrastructure because users can implement powerful data management policies by deploying rules to local storage systems, much as software-defined networking allows users to configure networks by deploying rules to switches.We argue that this approach can enable a new class of responsive distributed storage infrastructure that will accelerate research innovation by allowing any researcher to associate data workflows with data sources, whether local or remote, for such purposes as data ingest, characterization, indexing, and sharing. We report on early experiments with this approach in the context of experimental science, in which a simple if-trigger-then-action (IFTA) notation is used to define rules.

Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Kwak, Soyoung [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715 (Korea, Republic of); Han, Min-Su [Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Fatima Hospital, Daegu 701-600 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

2014-11-15

Inhibition of high mobility group box 1 (HMGB1) protein and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, three structurally related polyphenols found in the Chinese herb Huang Qui, baicalin (BCL), baicalein (BCN), and wogonin (WGN), were examined for their effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. According to our data, BCL, BCN, and WGN inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. BCL, BCN, and WGN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with BCL, BCN, and WGN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that BCL, BCN, and WGN could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway. - Highlights: • HMGB1 is an inflammatory mediator for vascular inflammation. • Baicalin, baicalein and wogonin inhibited HMGB1-induced hyperpermeability in vitro and in vivo. • Baicalin, baicalein and wogonin inhibited HMGB1-mediated inflammatory responses. • Baicalin, baicalein and wogonin suppressed the activation of NF-κB and ERK1/2 and production of TNF-α and IL-6. • Baicalin, baicalein and wogonin prevent CLP-induced septic mortality.

Osteopontin, osteocalcin, and osteoprotegerin expression in human tissue affected by cleft lip and palate

Directory of Open Access Journals (Sweden)

Smane L.

2016-01-01

Full Text Available Cleft lip and palate (CLP is a common congenital anomaly with a complex etiology which has not been elucidated yet. This study investigated whether expression of osteopontin (OPN, osteoprotegerin (OPG, and osteocalcin (OC, which are essential for the normal craniofacial bone remodelling, is not regulated in children with CLP. Alveolar bone tissue samples were obtained from patients with complete bilateral (CB CLP (n = 14 during corrective plastic surgery and unaffected control subjects (n = 9. OPN, OPG, and OC expression was assessed by immunohistochemistry, and data were analyzed with the Mann-Whitney test. OPN expression was observed only sporadically in the alveolar bone of 3 patients, in contrast to the control group (z = −2.962; P < 0.003. The number of OPG-positive bone cells varied from occasional to moderate, in contrast to the control group (z = −2.247; P = 0.025. OC-positive osteocytes were present in moderate to numerous numbers in both patients and controls, with no significant difference between them (z = −1.356; P < 0.175. The prominent expression of OC characteristic for CBCLP affected hard tissue indicates a high potential of bone mineralization. Few OPG-positive osteocytes in the bone tissue implicate the disregulation of osteoclast differentiation, maturation, and activity, but few OPN-containing cells may prove the common disregulation of bone remodelling during cleft morphopathogenesis.

Environmental transcriptome analysis reveals physiological differences between biofilm and planktonic modes of life of the iron oxidizing bacteria Leptospirillum spp. in their natural microbial community

Directory of Open Access Journals (Sweden)

Parro Víctor

2010-06-01

Full Text Available Abstract Background Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy. Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers. In the Río Tinto (Spain, brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery and environmental applications (acid mine drainage, bioremediation. The aim of this study was to investigate the physiological differences between the free living (planktonic and the sessile (biofilm associated lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community. Results Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB, synthesis of cell wall structures (lnt, murA, murB, specific proteases (clpX/clpP, stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL, etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively in the acidic (pH 1.8 water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions. Conclusions Our results indicate that the

Environmental transcriptome analysis reveals physiological differences between biofilm and planktonic modes of life of the iron oxidizing bacteria Leptospirillum spp. in their natural microbial community.

Science.gov (United States)

Moreno-Paz, Mercedes; Gómez, Manuel J; Arcas, Aida; Parro, Víctor

2010-06-24

Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy). Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers). In the Río Tinto (Spain), brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum) and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery) and environmental applications (acid mine drainage, bioremediation). The aim of this study was to investigate the physiological differences between the free living (planktonic) and the sessile (biofilm associated) lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community. Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB), synthesis of cell wall structures (lnt, murA, murB), specific proteases (clpX/clpP), stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL), etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA) were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively) in the acidic (pH 1.8) water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions. Our results indicate that the acidophilic filaments are dynamic structures

Tezosentan reduces the microvascular filtration coefficient in isolated lungs from rats subjected to cecum ligation and puncture.

Science.gov (United States)

Kuklin, Vladimir; Sovershaev, Mikhail; Andreasen, Thomas; Skogen, Vegard; Ytrehus, Kirsti; Bjertnaes, Lars

2005-01-01

We recently demonstrated that the non-selective endothelin-1 (ET-1) receptor blocker tezosentan antagonizes ovine acute lung injury (ALI) following infusion of endotoxin or ET-1 by reducing the enhanced lung microvascular pressure, although we could not exclude the possibility of a simultaneous decline in microvascular permeability. In the present study, our aim was to find out if tezosentan reverses the rise in microvascular filtration coefficient (Kfc) in rat lungs that have been isolated and perfused 12 h after cecum ligation and puncture (CLP) or infusion of ET-1. Wistar rats (n = 42) were subjected to CLP. Postoperatively, rats were randomized to a CLP group (n = 7) and a CLP + tezosentan group (n = 7); the latter received tezosentan 30 mg/kg. A sham-operated group (n = 5) underwent laparotomy without CLP. Twelve hours postoperatively, the lungs were isolated and perfused with blood from similarly treated rats that also were used to assess plasma concentration of ET-1 and protein kinase Calpha (PKCalpha) in lung tissue. Additionally, isolated blood perfused lungs from healthy rats were randomized to a control group (n = 8), an ET-1 group (n = 7) subjected to pulmonary arterial injection of ET-1 10 nM, and an ET-1 + tezosentan group (n = 7) that received tezosentan 30 mg/kg. All lung preparations received papaverine 0.1 microg/kg added to the perfusate for vasoplegia. Pulmonary hemodynamic variables, Kfc and lung compliance (CL) were assessed. After CLP, the plasma concentration of ET-1 increased. Papaverine abolished the vasoconstrictor response to ET-1 and the pulmonary vascular pressures remained close to baseline throughout the experiments. Both CLP and injection of ET-1 caused significant changes in Kfc and CL that were prevented in tezosentan-treated rats. Compared to sham-operated animals, CLP increased the content of PKCalpha by 50% and 70% in the cytosolic and the membrane fractions of lung tissue homogenates, respectively. Tezosentan prevented the

Defining Documentary Film

DEFF Research Database (Denmark)

Juel, Henrik

2006-01-01

A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film......A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film...

[Performance based regulation: a strategy to increase breastfeeding rates].

Science.gov (United States)

Cobo-Armijo, Fernanda; Charvel, Sofía; Hernández-Ávila, Mauricio

2017-01-01

The decreasing breastfeeding rate in México is of public health concern. In this paper we discus an innovative regulatory approach -Performance Based Regulation- and its application to improve breastfeeding rates. This approach, forces industry to take responsibility for the lack of breastfeeding and its consequences. Failure to comply with this targets results in financial penalties. Applying performance based regulation as a strategy to improve breastfeeding is feasible because: the breastmilk substitutes market is an oligopoly, hence it is easy to identify the contribution of each market participant; the regulation's target population is clearly defined; it has a clear regulatory standard which can be easily evaluated, and sanctions to infringement can be defined under objective parameters. modify public policy, celebrate concertation agreements with the industry, create persuasive sanctions, strengthen enforcement activities and coordinate every action with the International Code of Marketing of Breast-milk Substitutes.

Disclosure of congenital cleft lip and palate to Japanese patients: reported patient experiences and relationship to self-esteem

OpenAIRE

Omiya, Tomoko; Ito, Mikiko; Yamazaki, Yoshihiko

2014-01-01

Background The present study investigated when and how Japanese people with cleft lip and palate (CL/P) learn that their condition is congenital; the perceived effects of withholding the CL/P diagnosis on patients; and whether the resulting social experience and self-esteem are related. A questionnaire survey was conducted in 71 adults with CL/P recruited through a hospital, a patients? association, and by snowball sampling. Results The participants became aware of their physical difference i...

Defining Quantum Control Flow

OpenAIRE

Ying, Mingsheng; Yu, Nengkun; Feng, Yuan

2012-01-01

A remarkable difference between quantum and classical programs is that the control flow of the former can be either classical or quantum. One of the key issues in the theory of quantum programming languages is defining and understanding quantum control flow. A functional language with quantum control flow was defined by Altenkirch and Grattage [\\textit{Proc. LICS'05}, pp. 249-258]. This paper extends their work, and we introduce a general quantum control structure by defining three new quantu...

Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

Science.gov (United States)

Weiss, Yoram G; Maloyan, Alina; Tazelaar, John; Raj, Nichelle; Deutschman, Clifford S

2002-09-01

The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis.

Science.gov (United States)

Villa, P; Demitri, M T; Meazza, C; Sironi, M; Gnocchi, P; Ghezzi, P

1996-12-01

The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.

Guide to the economic regulation of the electricity industry

International Nuclear Information System (INIS)

1999-06-01

Guide to the Economic Regulation of the Electricity Industry, part of the series of OXERA Guides to Regulation, is designed as an essential work of reference for those who work in regulation and for practitioners who need to understand the needs and mechanics of regulation. The 154-page document provides: comprehensive coverage of the institutional and legal framework which defines the regulation of the electricity industry; an examination of current regulatory issues and developments in the industry; explanations of the roles of the key players; a condensed account of all the relevant legal documents; coverage of the industry in Scotland and Northern Ireland. (Author)

Integrating international students into a project organized problem based learning environment

DEFF Research Database (Denmark)

Hansen, Søren; Du, Xiangyun

2004-01-01

The paper describes a recent developed didactic model for CLP teaching at Aalborg University in Denmark.......The paper describes a recent developed didactic model for CLP teaching at Aalborg University in Denmark....

Identification of Salmonella typhimurium Genes Required for Colonization of the Chicken Alimentary Tract and for Virulence in Newly Hatched Chicks

Science.gov (United States)

Turner, Arthur K.; Lovell, Margaret A.; Hulme, Scott D.; Zhang-Barber, Li; Barrow, Paul A.

1998-01-01

From a collection of 2,800 Tn5-TC1 transposon mutants of Salmonella typhimurium F98, 18 that showed reduced intestinal colonization of 3-week-old chicks were identified. The sites of transposon insertion were determined for most of the mutants and included insertions in the lipopolysaccharide biosynthesis genes rfaK, rfaY, rfbK, and rfbB and the genes dksA, clpB, hupA, and sipC. In addition, identification was made of an insertion into a novel gene that encodes a protein showing similarity to the IIC component of the mannose class of phosphoenolpyruvate-carbohydrate phosphotransferase systems, which we putatively called ptsC. Transduction of most of the transposon mutations to a fresh S. typhimurium F98 genetic background and construction of defined mutations in the rfbK, dksA, hupA, sipC, and ptsC genes of S. typhimurium F98 supported the role in colonization of all but the pts locus. The virulence of the rfbK, dksA, hupA, sipC, and ptsC defined mutants and clpB and rfaY transductants in 1-day-old chicks was tested. All but the ptsC and rfaY mutants were attenuated for virulence. A number of other phenotypes associated with some of the mutations are described. PMID:9573095

International multiphase mixed methods study protocol to develop a cross-cultural patient-reported outcome instrument for children and young adults with cleft lip and/or palate (CLEFT-Q).

Science.gov (United States)

Wong Riff, Karen W Y; Tsangaris, Elena; Goodacre, Tim; Forrest, Christopher R; Pusic, Andrea L; Cano, Stefan J; Klassen, Anne F

2017-01-11

Patient-reported outcome (PRO) instruments should be developed according to rigorous guidelines in order to provide clinically meaningful, scientifically sound measurement. Understanding the methodology behind instrument development informs the selection of the most appropriate tool. This mixed methods protocol describes the development of an internationally applicable PRO instrument, the CLEFT-Q, for evaluating outcomes of treatment for cleft lip and/or palate (CL/P). The study includes three main phases that occur iteratively and interactively. In phase I, we determine what concepts are important to patients regarding their outcome. A conceptual framework for the CLEFT-Q is formed through a systematic review and an extensive international qualitative study. The systematic review ascertains what concepts have previously been measured in patients with CL/P. The qualitative study employs interpretive description and involves in-depth interviews with patients in high-income and lower-middle income countries. Preliminary items are generated from the qualitative data. Preliminary scales are then created for each theme in the framework. Cognitive debriefing interviews and expert clinician input are used to refine the scales in an iterative process. In phase II, the preliminary scales are administered to a large international group of patients with CL/P. The modern psychometric method of Rasch Measurement Theory analysis is employed to define the measurement characteristics. The preliminary scales are shortened based on these results. In phase III, further tests assess reliability, validity and responsiveness of the instrument. The study is approved by Research Ethics Boards for each participating site. Findings from this study will be published in open access peer-reviewed journals and presented at national and international conferences. Integrated knowledge translation is employed to engage stakeholders from the outset of the study. Successful execution of the CLEFT

The Importance of Multidisciplinary Management during Prenatal Care for Cleft Lip and Palate

Directory of Open Access Journals (Sweden)

Hyun Ho Han

2016-03-01

Full Text Available BackgroundThe prenatal ultrasound detection of cleft lip with or without cleft palate (CL/P and its continuous management in the prenatal, perinatal, and postnatal periods using a multidisciplinary team approach can be beneficial for parents and their infants. In this report, we share our experiences with the prenatal detection of CL/P and the multidisciplinary management of this malformation in our institution's Congenital Disease Center.MethodsThe multidisciplinary team of the Congenital Disease Center for mothers of children with CL/P is composed of obstetricians, plastic and reconstructive surgeons, pediatricians, and psychiatrists. A total of 11 fetuses were diagnosed with CL/P from March 2009 to December 2013, and their mothers were referred to the Congenital Disease Center of our hospital. When CL/P is suspected in the prenatal ultrasound screening examination, the pregnant woman is referred to our center for further evaluation.ResultsThe abortion rate was 28% (3/11. The concordance rate of the sonographic and final diagnoses was 100%. Ten women (91% reported that they were satisfied with the multidisciplinary management in our center.ConclusionsAlthough a child with a birth defect is unlikely to be received well, the women whose fetuses were diagnosed with CL/P on prenatal ultrasound screening and who underwent multidisciplinary team management were more likely to decide to continue their pregnancy.

Hydroclimatic variability in loess δDwax records from the central Chinese Loess Plateau over the past 250 ka

Science.gov (United States)

Wang, Zheng; An, Zhisheng; Liu, Zhonghui; Qiang, Xiaoke; Zhang, Fan; Liu, Weiguo

2018-04-01

This study reports hydrogen isotopic records from the central Chinese Loess Plateau (CLP) over the past 250 ka. After eliminating the influence of ice and local temperatures, the δDwax records extracted from two loess sites at Xifeng and Luochuan can be taken to represent arid/humid alternations in the hydrological environment in this marginal Asian Summer Monsoon (ASM) region; they also contain integrated information on summer precipitation patterns and the corresponding responses to these changes by predominant vegetation cover types. These arid/humid alternations show 100 ka, 40 ka and 20 ka cycles. An increase in precipitation in association with an enhanced summer monsoon has historically been taken to be the major factor driving a humid environment in the central CLP. However, hydroclimatic changes in δDwax records differ for the central CLP, central China and southern China. Over a 20 ka cycle, the influence of solar insolation on hydroclimatic changes can be shown to be consistent throughout the central CLP. However, changes in the relative location of the land and sea may have caused different hydroclimatic responses between southern China and the central CLP on a glacial-interglacial scale. The hydroclimatic variability in the central CLP would suggest that an enhanced summer monsoon due to climatic warming is the key to understanding decreased drought degree in this marginal monsoonal region.

Association between maternal smoking, gender, and cleft lip and palate

Directory of Open Access Journals (Sweden)

Daniella Reis Barbosa Martelli

2015-10-01

Full Text Available ABSTRACT INTRODUCTION: Cleft lip and/or palate (CL/P represent the most common congenital anomalies of the face. OBJECTIVE: To assess the relationship between maternal smoking, gender and CL/P. METHODS: This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: Cases: mothers of children with CL/P (n = 843 and Controls: mothers of children without CL/P (n = 676. All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. RESULTS: An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR = 3.51; 95% CI 2.83-4.37. By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. CONCLUSION: Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential.

Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms

Directory of Open Access Journals (Sweden)

Albino Villegas-Bastida

2014-01-01

Full Text Available Electrical vagus nerve (VN stimulation during sepsis attenuates tumor necrosis factor (TNF production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36 on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP. The septic rats were subsequently treated with EA-ST36 (CLP+ST36, and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P<0.05, and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms.

Transients: The regulator's view

International Nuclear Information System (INIS)

Sheron, B.W.; Speis, T.P.

1984-01-01

This chapter attempts to clarify the basis for the regulator's concerns for transient events. Transients are defined as both anticipated operational occurrences and postulated accidents. Recent operational experience, supplemented by improved probabilistic risk analysis methods, has demonstrated that non-LOCA transient events can be significant contributors to overall risk. Topics considered include lessons learned from events and issues, the regulations governing plant transients, multiple failures, different failure frequencies, operator errors, and public pressure. It is concluded that the formation of Owners Groups and Regulatory Response Groups within the owners groups are positive signs of the industry's concern for safety and responsible dealing with the issues affecting both the US NRC and the industry

Decisions to regulate genotoxic substances

Energy Technology Data Exchange (ETDEWEB)

Bengtsson, G

1988-07-01

Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

Decisions to regulate genotoxic substances

International Nuclear Information System (INIS)

Bengtsson, G.

1988-01-01

Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

Understanding purposes of regulation: a case example in mental health.

Science.gov (United States)

Ziegenfuss, J T; Hadley, T

1980-01-01

This paper reviews the purposes of governmental regulation and how an exploration of purpose can contribute to our understanding of specific regulations. The primary regulatory purpose is defined as the achievement of quality control of a subject system, its process or its product. Quality control via regulation is achieved through one or a combination of approaches: (1) accountability, (2) organizational development, (3) protectionism. Regulatory purpose and approach is illustrated by a case example of the development of regulations for partial hospitalization mental health services.

The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

Science.gov (United States)

Steckert, Amanda V; Dominguini, Diogo; Michels, Monique; Abelaira, Helena M; Tomaz, Débora B; Sonai, Beatriz; de Moura, Airam B; Matos, Danyela; da Silva, Júlia B I; Réus, Gislaine Z; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe

2017-11-01

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Legal regulation of online advertising in the Czech Republic

OpenAIRE

Sládek, Ondřej

2012-01-01

The thesis focuses on regulation of advertising on the Internet. The aim of the thesis is to evaluate the current state and position of public regulation of online advertising, both in general and on the example of Google advertising network. The approach to achieve defined goals is to first present a theoretical overview of the legal regulation of advertising with an emphasis on online advertising, followed by a case study showing the practical functioning of online advertising rules in Goog...

Time-Transgressive Nature of the Magnetic Susceptibility Record across the Chinese Loess Plateau at the Pleistocene/Holocene Transition

Science.gov (United States)

Dong, Yajie; Wu, Naiqin; Li, Fengjiang; Huang, Linpei; Wen, Wenwen

2015-01-01

The loess stratigraphic boundary at the Pleistocene/Holocene transition defined by the magnetic susceptibility (MS) has previously been assumed to be synchronous with the Marine Isotope Stage (MIS) 2/1 boundary, and approximately time-synchronous at different sections across the Chinese Loess Plateau (CLP). However, although this assumption has been used as a basis for proxy-age model of Chinese loess deposits, it has rarely been tested by using absolute dating methods. In this study, we applied a single-aliquot regenerative-dose (SAR) protocol to the 45–63 μm quartz grain-size fraction to derive luminescence ages for the last glacial and Holocene sections of three loess sections on a transect from southeast to northwest across the CLP. Based on the 33 closely spaced optically stimulated luminescence (OSL) samples from the three sections, OSL chronologies were established using a polynomial curve fit at each section. Based on the OSL chronology, the timing of the Pleistocene/Holocene boundary, as defined by rapid changes in MS values, is dated at ~10.5 ka, 8.5 ka and 7.5 ka in the Yaoxian section, Jingchuan and Huanxian sections respectively. These results are clearly inconsistent with the MIS 2/1 boundary age of 12.05 ka, and therefore we conclude that the automatic correlation of the Pleistocene/Holocene transition, as inferred from the MS record, with the MIS 2/1 boundary is incorrect. The results clearly demonstrate that the marked changes in MS along the southeast to northwest transect are time-transgressive among the different sites, with the timing of significant paleosol development as indicated by the MS record being delayed by 3–4 ka in the northwest compared to the southeast. Our results suggest that this asynchronous paleosol development during the last deglacial was caused by the delayed arrival of the summer monsoon in the northwest CLP compared to the southeast. PMID:26186443

Time-Transgressive Nature of the Magnetic Susceptibility Record across the Chinese Loess Plateau at the Pleistocene/Holocene Transition.

Directory of Open Access Journals (Sweden)

Yajie Dong

Full Text Available The loess stratigraphic boundary at the Pleistocene/Holocene transition defined by the magnetic susceptibility (MS has previously been assumed to be synchronous with the Marine Isotope Stage (MIS 2/1 boundary, and approximately time-synchronous at different sections across the Chinese Loess Plateau (CLP. However, although this assumption has been used as a basis for proxy-age model of Chinese loess deposits, it has rarely been tested by using absolute dating methods. In this study, we applied a single-aliquot regenerative-dose (SAR protocol to the 45-63 μm quartz grain-size fraction to derive luminescence ages for the last glacial and Holocene sections of three loess sections on a transect from southeast to northwest across the CLP. Based on the 33 closely spaced optically stimulated luminescence (OSL samples from the three sections, OSL chronologies were established using a polynomial curve fit at each section. Based on the OSL chronology, the timing of the Pleistocene/Holocene boundary, as defined by rapid changes in MS values, is dated at ~10.5 ka, 8.5 ka and 7.5 ka in the Yaoxian section, Jingchuan and Huanxian sections respectively. These results are clearly inconsistent with the MIS 2/1 boundary age of 12.05 ka, and therefore we conclude that the automatic correlation of the Pleistocene/Holocene transition, as inferred from the MS record, with the MIS 2/1 boundary is incorrect. The results clearly demonstrate that the marked changes in MS along the southeast to northwest transect are time-transgressive among the different sites, with the timing of significant paleosol development as indicated by the MS record being delayed by 3-4 ka in the northwest compared to the southeast. Our results suggest that this asynchronous paleosol development during the last deglacial was caused by the delayed arrival of the summer monsoon in the northwest CLP compared to the southeast.

Brucella BioR Regulator Defines a Complex Regulatory Mechanism for Bacterial Biotin Metabolism

Science.gov (United States)

Xu, Jie; Zhang, Huimin; Srinivas, Swaminath

2013-01-01

The enzyme cofactor biotin (vitamin H or B7) is an energetically expensive molecule whose de novo biosynthesis requires 20 ATP equivalents. It seems quite likely that diverse mechanisms have evolved to tightly regulate its biosynthesis. Unlike the model regulator BirA, a bifunctional biotin protein ligase with the capability of repressing the biotin biosynthetic pathway, BioR has been recently reported by us as an alternative machinery and a new type of GntR family transcriptional factor that can repress the expression of the bioBFDAZ operon in the plant pathogen Agrobacterium tumefaciens. However, quite unusually, a closely related human pathogen, Brucella melitensis, has four putative BioR-binding sites (both bioR and bioY possess one site in the promoter region, whereas the bioBFDAZ [bio] operon contains two tandem BioR boxes). This raised the question of whether BioR mediates the complex regulatory network of biotin metabolism. Here, we report that this is the case. The B. melitensis BioR ortholog was overexpressed and purified to homogeneity, and its solution structure was found to be dimeric. Functional complementation in a bioR isogenic mutant of A. tumefaciens elucidated that Brucella BioR is a functional repressor. Electrophoretic mobility shift assays demonstrated that the four predicted BioR sites of Brucella plus the BioR site of A. tumefaciens can all interact with the Brucella BioR protein. In a reporter strain that we developed on the basis of a double mutant of A. tumefaciens (the ΔbioR ΔbioBFDA mutant), the β-galactosidase (β-Gal) activity of three plasmid-borne transcriptional fusions (bioBbme-lacZ, bioYbme-lacZ, and bioRbme-lacZ) was dramatically decreased upon overexpression of Brucella bioR. Real-time quantitative PCR analyses showed that the expression of bioBFDA and bioY is significantly elevated upon removal of bioR from B. melitensis. Together, we conclude that Brucella BioR is not only a negative autoregulator but also a repressor of

Development of methods and means to improve the financial monitoring system

International Nuclear Information System (INIS)

Spiridonov, A.M.

2011-01-01

The paper discusses the ways of enhancing the effectiveness of National system of financial monitoring, or Russian national system of counteraction to legalization (laundering) of proceeds from crime and financing of terrorism (NS CLP/FT). The author suggests that to achieve this goal it is necessary to solve the following main objectives: to study the current state of the NS CLP/FT, and to build its structural and functional models, to determine the criteria of efficiency of the system, to develop a methodology to assess the effectiveness of the NS CLP/FT, to apply it and to identify promising trends of this system development. On the basis of the obtained data, it is proposed to develop a means of increasing the effectiveness of the NS CLP/FT [ru

The going concern principle of entities in accounting regulations

Directory of Open Access Journals (Sweden)

Andrzej Tokarski

2012-12-01

Going concern is defined in both national and international accounting regulations, with no difference between the principle of going concern in the Polish law on accounting and international solutions.

Regulation of higher-activity NARM wastes by EPA

International Nuclear Information System (INIS)

Bandrowski, M.S.

1988-01-01

The US Environmental Protection Agency (EPA) is currently developing standards for the disposal of low-level radioactive waste (LLW). As part of this Standard, EPA is including regulations for the disposal of naturally occurring and accelerator-produced radioactive material (NARM) wastes not covered under the Atomic Energy Act (AEA). The regulations will cover only higher-activity NARM wastes, defined as NARM waste with specific activity exceeding two nanocuries per gram. The proposed regulations will specify that NARM wastes exceeding the above limits, except for specific exempted items, must be disposed of in regulated radioactive waste disposal facilities. The proposed EPA regulations for NARM wastes will be discussed, as well as the costs and benefits of the regulation, how it will be implemented by EPA, and the rationale for covering only higher-activity NARM wastes exceeding two nanocuries per gram

Emotion regulation and the dynamic of feelings: A conceptual and methodological framework

OpenAIRE

Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.

2004-01-01

The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed, identifies its goal, and illustrates how regulation is achieved. The thesis developed here is that feelings - the private mental experience of emotion - play a crucial role in emotion regulation. Spec...

Proposed Ordinance for the Regulation of Cable Television. Working Draft.

Science.gov (United States)

Chicago City Council, IL.

A model ordinance is proposed for the regulation of cable television in the city of Chicago. It defines the language of the ordinance, sets forth the method of granting franchises, and describes the terms of the franchises. The duties of a commission to regulate cable television are listed and the method of selecting commission members is…

Relevance of variation in use of terminology to define generic pharmaceutical products

Directory of Open Access Journals (Sweden)

Elize Massard da Fonseca

2015-02-01

Full Text Available The World Health Organization (WHO promotes the use of generic drug policies to foster competition in the pharmaceutical sector, reduce drug prices, and increase access to therapeutic drugs. However, little is known about how countries implement these policies. This article describes different terminology adopted by national regulatory authorities to define generic versus proprietary drug products in developing countries, including those in Latin America, and challenges that arise in their application of WHO guidelines, such as labeling issues. The author concludes that variation in generics terminology in these countries is a result of institutional context (i.e., the public sector setting as well as the body of laws and regulations that exists in the country and policy legacies, such as intellectual property regimes, and highlights the need for further analysis of pharmaceutical regulations to improve understanding of the barriers and political implications of generic drug policies.

Relevance of variation in use of terminology to define generic pharmaceutical products.

Science.gov (United States)

Fonseca, Elize Massard da

2015-02-01

The World Health Organization (WHO) promotes the use of generic drug policies to foster competition in the pharmaceutical sector, reduce drug prices, and increase access to therapeutic drugs. However, little is known about how countries implement these policies. This article describes different terminology adopted by national regulatory authorities to define generic versus proprietary drug products in developing countries, including those in Latin America, and challenges that arise in their application of WHO guidelines, such as labeling issues. The author concludes that variation in generics terminology in these countries is a result of institutional context (i.e., the public sector setting as well as the body of laws and regulations that exists in the country) and policy legacies, such as intellectual property regimes, and highlights the need for further analysis of pharmaceutical regulations to improve understanding of the barriers and political implications of generic drug policies.

Emotion regulation and the dynamic of feelings: A conceptual and methodological framework

NARCIS (Netherlands)

Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.

2004-01-01

The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed,

An increase in CD3+CD4+CD25+ regulatory T cells after administration of umbilical cord-derived mesenchymal stem cells during sepsis.

Directory of Open Access Journals (Sweden)

Yu-Hua Chao

Full Text Available Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by determining the changes of circulating inflammation-associated cytokine profiles and peripheral blood mononuclear cells 18 hours after CLP-induced sepsis. In vitro, bone marrow-derived MSCs (BMMSCs and umbilical cord-derived MSCs (UCMSCs showed a similar morphology and surface marker expression. UCMSCs had stronger potential for osteogenesis but lower for adipogenesis than BMMSCs. Compared with rats receiving PBS only after CLP, the percentage of circulating CD3+CD4+CD25+ regulatory T (Treg cells and the ratio of Treg cells/T cells were elevated significantly in rats receiving MSCs. Further experiment regarding Treg cell function demonstrated that the immunosuppressive capacity of Treg cells from rats with CLP-induced sepsis was decreased, but could be restored by administration of MSCs. Compared with rats receiving PBS only after CLP, serum levels of interleukin-6 and tumor necrosis factor-α were significantly lower in rats receiving MSCs after CLP. There were no differences between BMMSCs and UCMSCs. In summary, this work provides the first in vivo evidence that administering BMMSCs or UCMSCs to rats with CLP-induced sepsis could increase circulating CD3+CD4+CD25+ Treg cells and Treg cells/T cells ratio, enhance Treg cell suppressive function, and decrease serum levels of interleukin-6 and tumor necrosis factor-α, suggesting the immunomodulatory association of Treg cells and MSCs during sepsis.

Opportunities and Challenges in Establishing a Cohort Study: An Example From Cleft Lip/Palate Research in the United Kingdom.

Science.gov (United States)

Stock, Nicola Marie; Humphries, Kerry; Pourcain, Beate St; Bailey, Maggie; Persson, Martin; Ho, Karen M; Ring, Susan; Marsh, Cathy; Albery, Liz; Rumsey, Nichola; Sandy, Jonathan

2016-05-01

Cleft lip and/or palate (CL/P) is one of the most common birth conditions in the world, but little is known about its causes. Professional opinion remains divided as to which treatments may be the most beneficial for patients with CL/P, and the factors that contribute to psychological adjustment are poorly understood. The use of different methodological approaches and tools plays a key role in hampering efforts to address discrepancies within the evidence base. A new UK-wide program of research, The Cleft Collective, was established to combat many of these methodological challenges and to address some of the key research questions important to all CL/P stakeholders. To describe the establishment of CL/P cohort studies in the United Kingdom and to consider the many opportunities this resource will generate. To date, protocols have been developed and implemented within most UK cleft teams. Biological samples, environmental information, and data pertaining to parental psychological well-being and child development are being collected successfully. Recruitment is currently on track to meet the ambitious target of approximately 9800 individuals from just more than 3000 families. The Cleft Collective cohort studies represent a significant step forward for research in the field of CL/P. The data collected will form a comprehensive resource of information about individuals with CL/P and their families. This resource will provide the basis for many future projects and collaborations, both in the United Kingdom and around the world.

A Population-Based Exploration of the Social Implications Associated with Cleft Lip and/or Palate.

Science.gov (United States)

Glener, Adam D; Allori, Alexander C; Shammas, Ronnie L; Carlson, Anna R; Pien, Irene J; Aylsworth, Arthur S; Meyer, Robert; Pimenta, Luiz; Strauss, Ronald; Watkins, Stephanie; Marcus, Jeffrey R

2017-06-01

Clefts of the lip and/or palate (CL/P) carry a social stigma that often causes psychosocial stress. The purpose of this study was to consider the association of cleft phenotype and age with self-reported aspects of psychosocial stress. Children with nonsyndromic CL/P and unaffected children born between 1997 and 2003 were identified through the North Carolina Birth Defects Monitoring Program and North Carolina birth records, respectively. The psychosocial concerns of children with CL/P were assessed via a 29-question subset of a larger survey. Responses were analyzed according to school age and cleft phenotype (cleft lip with/without cleft alveolus, CL ± A; cleft palate only, CP; or cleft lip with cleft palate, CL + P). Surveys were returned for 176 children with CL/P and 333 unaffected children. When compared with unaffected children, responses differed for CL ± A in 4/29 questions, for CP in 7/29 questions, and for CL + P in 8/29 questions ( P aesthetic concerns, bullying, and difficulties with friendship, and social interaction. Children with CL + P reported more severe aesthetic-related concerns than children with CL ± A or CP but experienced similar speech-related distress as children with CP only. Social implications associated with CL/P are most pronounced during middle school, and less so during elementary and high school. This information identifies areas of social improvement aimed at reducing the stigma of CL/P.

Nonsyndromic cleft lip with or without cleft palate: Evidence of linkage to BCL3 in 17 multigenerational families

Energy Technology Data Exchange (ETDEWEB)

Stein, J.; Hecht, T. [Univ. of Texas, Houston, TX (United States); Stal, S. [Texas Children`s Hospital, Houston, TX (United States)] [and others

1995-08-01

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was tested under two models, autosomal dominant with reduced penetrance and affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities {ge}50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families. 39 refs., 8 figs., 4 tabs.

Association between maternal smoking, gender, and cleft lip and palate.

Science.gov (United States)

Martelli, Daniella Reis Barbosa; Coletta, Ricardo D; Oliveira, Eduardo A; Swerts, Mário Sérgio Oliveira; Rodrigues, Laíse A Mendes; Oliveira, Maria Christina; Martelli Júnior, Hercílio

2015-01-01

Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. To assess the relationship between maternal smoking, gender and CL/P. This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: mothers of children with CL/P (n=843) and mothers of children without CL/P (n=676). All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR=3.51; 95% CI 2.83-4.37). By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

THREE-DIMENSIONAL ASSESSMENT OF THE PHARYNGEAL AIRWAY AND MAXILLARY SINUS VOLUMES IN INDIVIDUALS WITH NON-SYNDROMIC CLEFT LIP AND PALATE

Directory of Open Access Journals (Sweden)

Ana NEMȚOI

2015-09-01

Full Text Available Introduction: Children with cleft lip and palate (CLP are known to have airway problems. Introduction of ConeBeam CT (CBCT and imaging software has facilitated generation of 3D images for assessing the volume of maxillary sinuses and pharyngeal airway. Consequently, the present study aimed at evaluating and comparing the maxillary sinus and pharyngeal airway volume of patients with cleft lip and palate in healthy patients, using cone beam computed tomography (CBCT images. Materials and method: The sample group included 27 individuals (15 with cleft lip and palate subjects and 12 healthy subjects. The pharyngeal airway and each maxillary sinus were three-dimensionally assessed, segmented and their volume was calculated. A comparison between the right and left sinus was performed by Student t-test, and the differences between the control and cleft groups were calculated using ANOVA. Results: No statistically significant differences were found when the maxillary sinuses volumes from each side were compared (p >0.05. The unilateral CLP patients presented the lowest sinus volume. Individuals with CLP did not exhibit a total airway volume smaller than the nonCLP controls. Conclusions: 3D imaging using CBCT and Romexis software is reliable for assessing maxillary sinus and pharyngeal airway volume. The present study showed that the pharyngeal airway is not compromised in CLP individuals. The unilateral CLP individuals present maxillary sinuses with smaller volumes, no differences being recorded between the cleft and non-cleft side.

Current status of presurgical infant orthopaedic treatment for cleft lip and palate patients: A critical review

Directory of Open Access Journals (Sweden)

P Priyanka Niranjane

2014-01-01

Full Text Available Rehabilitation of cleft lip and palate (CLP patients is a challenge for all the concerned members of the cleft team, and various treatment modalities have been attempted to obtain aesthetic results. Presurgical infant orthopaedics (PSIO was introduced to reshape alveolar and nasal segments prior to surgical repair of cleft lip. However, literature reports lot of controversy regarding the use of PSIO in patients with CLP. Evaluation of long-term results of PSIO can provide scientific evidence on the efficacy and usefulness of PSIO in CLP patients. The aim was to assess the scientific evidence on the efficiency of PSIO appliances in patients with CLP and to critically analyse the current status of PSIO. A PubMed search was performed using the terms PSIO, presurgical nasoalveolar moulding and its long-term results and related articles were selected for the review. The documented studies report no beneficial effect of PSIO on maxillary arch dimensions, facial aesthetics and in the subsequent development of dentition and occlusion in CLP patients. Nasal moulding seems to be more beneficial and effective in unilateral cleft lip and palate patients with better long-term results.

Maternal plasma pyridoxal-5'-phosphate concentrations and risk of isolated oral clefts in the Philippines.

Science.gov (United States)

Tamura, Tsunenobu; Munger, Ronald G; Nepomuceno, Buena; Corcoran, Christopher; Cembrano, Joselito; Solon, Florentino

2007-04-01

We report that inadequate vitamin B-6 status of Filipino mothers, assessed by erythrocyte aspartate aminotransferase activity coefficient (EAST-AC), is associated with an increased risk for isolated cleft lip with or without cleft palate (CL/P) in their children. Its association with the status assessed by plasma pyridoxal-5'-phosphate (PLP) concentrations is unknown. In a case-control study in the Philippines including 46 cases (mothers of a child with CL/P) and 392 controls (mothers of an unaffected child), we evaluated the association between the risk for CL/P and maternal vitamin B-6 status assessed by PLP and EAST-AC. The ORs of CL/P were estimated by classifying mothers by PLP (>30, 20-30, and values, compared to those with adequate status by both values. Inadequate vitamin B-6 status assessed by maternal PLP and EAST-AC values independently and both combined was associated with an increased risk for CL/P. The association was highest when both values were considered, suggesting that the measurement of both PLP and EAST-AC provides better assessment of vitamin B-6 status than either measurement alone.

Languages for Software-Defined Networks

Science.gov (United States)

2013-02-01

switches, firewalls, and middleboxes) with closed and proprietary configuration inter- faces. Software - Defined Networks ( SDN ) are poised to change...how- ever, have seen growing interest in software - defined networks ( SDNs ), in which a logically-centralized controller manages the packet-processing...switches, firewalls, and middleboxes) with closed and proprietary configuration interfaces. Software - Defined Networks ( SDN ) are poised to change this

Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development

DEFF Research Database (Denmark)

Jakobsen, L.P.; Borup, R.; Vestergaard, J.

2009-01-01

. Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP...... and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed...... and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend...

17 CFR 230.100 - Definitions of terms used in the rules and regulations.

Science.gov (United States)

2010-04-01

... express reference to the Act or to the rules and regulations or to a portion thereof defines such term for... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Definitions of terms used in... terms used in the rules and regulations. (a) As used in the rules and regulations prescribed in this...

SWeRF--A method for estimating the relevant fine particle fraction in bulk materials for classification and labelling purposes.

Science.gov (United States)

Pensis, Ingeborg; Luetzenkirchen, Frank; Friede, Bernd

2014-05-01

In accordance with the European regulation for classification, labelling and packaging of substances and mixtures (CLP) as well as the criteria as set out in the Globally Harmonized System (GHS), fine fraction of crystalline silica (CS) has been classified as a specific target organ toxicity, the specific organ in this case being the lung. Generic cut-off values for products containing a fine fraction of CS trigger the need for a method for the quantification of the fine fraction of CS in bulk materials. This article describes the so-called SWeRF method, the size-weighted relevant fine fraction. The SWeRF method combines the particle size distribution of a powder with probability factors from the EN 481 standard and allows the relevant fine fraction of a material to be calculated. The SWeRF method has been validated with a number of industrial minerals. This will enable manufacturers and blenders to apply the CLP and GHS criteria for the classification of mineral products containing RCS a fine fraction of CS.

[Croatian and international regulations on the protection and rights of workers exposed to asbestos at work].

Science.gov (United States)

Zavalić, Marija; Macan, Jelena

2009-11-01

New regulations on the protection and rights of workers occupationally exposed to asbestos were introduced in Croatia in 2007 and 2008. They have been harmonised with the European Union (EU) and International Labour Organization (ILO) regulations, and make a step forward in safety at work, health protection, social rights, and pension schemes for Croatian workers occupationally exposed to asbestos. The 2007 Croatian regulation on the protection of workers from the risks related to exposure to asbestos at work defines and describes activities in which workers can be occupationally exposed to asbestos, defines the threshold value of asbestos in the air at work, defines valid methods for measurement of asbestos concentrations in the air, and establishes measures to reduce asbestos exposure at work or protect the exposed workers. Croatian law regulating obligatory health surveillance of workers occupationally exposed to asbestos from year 2007 defines activities and competent authorities to implement health surveillance of workers occupationally exposed to asbestos and to diagnose occupational diseases related to asbestos. This law also defines "occupational exposure to asbestos", and "occupational asbestos-related diseases", including asbestosis (pulmonary asbestos-related fibrosis), pleural asbestos-related disorders (plaques, pleural thickening, and benign effusion), lung and bronchial cancer, and malignant mesothelioma of serous membranes. These regulations have been harmonised with ILO, Directive 2003/18/EC amending Council Directive 83/477/EEC on the protection of workers from the risks related to exposure to asbestos at work, and with the Commission Recommendation 2003/670/EC concerning the European schedule of occupational diseases. The 2008 Croatian regulation on conditions of health surveillance, diagnostic procedures and criteria for confirmation of occupational asbestos-related diseases "defines the terms and the content of medical examination of workers

Dermatoglyphics and Cheiloscopy in the Inheritance of Cleft Lip and Palate: Unraveling the Mystery

Directory of Open Access Journals (Sweden)

Naveen Reddy Admala

2014-01-01

Conclusion: A highly significant correlation was observed in finger prints and lip patterns in parents with CL(P affected children and hence can prove to be an extremely useful screening tool for CL(P and other associated genetic anomalies.

Impact of global warming on the energetics of lower tropospheric ...

Indian Academy of Sciences (India)

Two oceanic anticyclones, one over Pacific and the other over Atlantic are sources of energy ... Northward transport of sensible heat during CLP1 changes to southward during CLP2. Larger ... tion because of its impact on the regional climate.

Personality, Self-Regulated Learning, and Academic Entitlement

Science.gov (United States)

McLellan, Chelsea K.; Jackson, Dennis L.

2017-01-01

The current study explored the relation between the Big-Five personality domains, self-regulated learning, and academic entitlement. Academic entitlement is defined as the tendency to possess expectations of unearned academic success, unearned/undeserved academic services, and/or the expectation of unrealistic accommodation (Chowning and Campbell…

Difficulties in emotion regulation in patients with eating disorders

OpenAIRE

Ruscitti, Catherine; Rufino, Katrina; Goodwin, Natalie; Wagner, Rebecca

2016-01-01

Background A defining characteristic of eating disorders (EDs) is difficulty with emotion regulation (ER). Previous research indicates that ED subtypes demonstrate differing ER difficulties. Specifically, individuals with Anorexia Nervosa (AN) or Bulimia Nervosa (BN) show greater impairment in their ability to regulate emotions in areas such as achieving goals while upset, reacting impulsively to distress, and effectively using coping strategies, as compared to those with Binge Eating Disorde...

CXCR1 regulates pulmonary anti-Pseudomonas host defense

Science.gov (United States)

Carevic, M.; Öz, H.; Fuchs, K.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Haug, M.; Schmidt, A.; Autenrieth, S. E.; Bucher, K.; Beer-Hammer, S.; Gaggar, A.; Kneilling, M.; Benarafa, C.; Gao, J.; Murphy, P.; Schwarz, S.; Moepps, B.; Hartl, D.

2016-01-01

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-Pseudomonas aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway Pseudomonas aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against Pseudomonas aeruginosa. Mechanistically, CXCR1 regulated anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with toll-like receptor 5 expression. These studies define CXCR1 as a novel non-canonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. PMID:26950764

Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes.

Science.gov (United States)

Lindgren, David; Eriksson, Pontus; Krawczyk, Krzysztof; Nilsson, Helén; Hansson, Jennifer; Veerla, Srinivas; Sjölund, Jonas; Höglund, Mattias; Johansson, Martin E; Axelson, Håkan

2017-08-08

Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Assessment and remediation of odor emissions from a complex industrial facility (Ambient air odor regulations in Canada and the United States)

International Nuclear Information System (INIS)

Boose, T.; Reusing, G.

2002-01-01

This paper describes the findings of a review and presents examples of ambient air odor regulations in Canada and the United States. State and provincial odor regulations were reviewed and other metropolitan cities or counties (regions) that have separate odor regulations were also included. The key topics addressed in this paper include an assessment of the methods used for odor regulation and the methods used to evaluate the odor impact to determine compliance with the regulation. Three types of ambient air odor regulations were identified: 1. 28 States, Provinces and regions (jurisdictions) have specific odor regulations. These regulations generally define what constitutes an odor impact and typically provide requirements for remedial measures; 2. 25 jurisdictions regulate odors by a general prohibition regulation. These regulations define odor in ambient air as a condition of air pollution, nuisance or objectionable odor that would typically prevent persons from the enjoyment of life and property; and 3. 13 jurisdictions do not have specific or general prohibition regulations regarding odors. For the jurisdictions that have specific or general prohibition odor regulations, there are a number of different techniques used to define what constitutes an odor impact. Odor impacts are typically defined in a regulation by one (or more) of the following techniques: dilution to threshold, or odor unit limit; determination of odor emission rates; odor concentration limits for selected chemicals (ppm); comparison with the n-butanol intensity scale (1 to 8); and investigation by an agency investigator. Compliance with odor regulations is typically determined using one (or more) of the following field methods: odor stack testing and dispersion modelling; odor panel analysis of stack or ambient air samples; chemical monitoring (ppm); odor school certified / agency investigator; and scentometer. (author)

Regulation of metabolism by the Mediator complex.

Science.gov (United States)

Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

2016-01-01

The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

75 FR 82217 - Community Reinvestment Act Regulations

Science.gov (United States)

2010-12-30

... Thrift Supervision 12 CFR Part 563e [Docket ID OTS-2010-0032] RIN 1550-AC45 Community Reinvestment Act... Federal Reserve System (Board); Federal Deposit Insurance Corporation (FDIC); Office of Thrift Supervision...) regulations to adjust the asset-size thresholds used to define ``small bank'' or ``small savings association...

The regulator's perspective

International Nuclear Information System (INIS)

Norrby, S.

1997-01-01

Recommendations on general safety objectives and good practices related to radioactive waste management are given by international organisations such as the OECD/NEA and the IAEA. Moreover, international conventions and other supranational legal instruments, such as EU directives, lay down requirements on the safe management of radioactive waste. The implementer of the system for waste management and disposal and the regulator will have different roles. The responsibility for the management and disposal of radioactive waste is with the implementer, who has taken over that responsibility from the generator of the waste. The regulator's responsibility is to define safety and radiation protection requirements, to issue guidance on safety assessment methodology and documentation, to review the implementer's safety assessments as a basis for licensing of waste management and disposal activities and facilities and to inspect and review construction and operation of nuclear facilities to ensure compliance with licensing conditions. (R.P.)

Caracterização anestésica da nanoemulsão não lipídica de propofol Caracterización anestésica de la nanoemulsión no lipídica de propofol Anesthetic profile of a non-lipid propofol nanoemulsion

Directory of Open Access Journals (Sweden)

Roberto Takashi Sudo

2010-10-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Uso clínico de formulação lipídica de propofol causa dor durante injeção, reação alérgica e crescimento microbiano. Propofol tem sido reformulado em diferentes apresentações não lipídicas para reduzir os efeitos adversos, mas essas mudanças podem modificar sua farmacocinética e farmacodinâmica. Neste trabalho, investigamos a farmacologia e a toxicologia do propofol lipídico (CLP e da nanoemulsão não lipídica (NLP. MÉTODO: CLP and NLP foram infundidos na veia jugular de ratos sob medida da pressão arterial (PA, frequência cardíaca (FC e frequência respiratória (FR. Ambas as formulações (1% foram infundidas (40 µL.min-1 durante 1 hora. Doses hipnóticas e anestésicas, assim como recuperações, foram determinadas. A dor induzida pelo veículo do CLP e NLP foi comparada por meio da contagem do número de contorções abdominais ("writhing test" após injeção intraperitonial (i.p. em camundongos. Ácido acético (0,6% foi usado como controle positivo. RESULTADOS: As doses hipnóticas e anestésicas com 1% CLP (6,0 ± 1,3 e 17,8 ± 2,6 mg.kg-1, respectivamente e 1% NLP (5,4 ± 1,0 e 16,0 ± 1,4 mg.kg-1, respectivamente não foram significativamente diferentes. A recuperação da hipnose e da anestesia foi mais rápida com NLP do que com CLP. As alterações de FC, PA e FR causadas pelo NLP não foram significativamente diferentes das do CLP. Ácido acético e veículo do CLP provocaram 46,0 ± 2,0 e 12,5 ± 0,6 contorções em 20 min após injeção i.p., respectivamente. Observou-se ausência de contorções abdominais com veículo de NLP. Nenhuma resposta inflamatória abdominal foi notada com a injeção i.p. de ambos os veículos de propofol. CONCLUSÕES: O NLP pode representar melhor alternativa do que o CLP para anestesia venosa com menores efeitos adversosJUSTIFICATIVA Y OBJETIVOS: El uso clínico de la formulación lipídica del propofol, causa dolor durante la inyección, reacci

Defining Plagiarism: A Literature Review

Directory of Open Access Journals (Sweden)

Akbar Akbar

2018-02-01

Full Text Available Plagiarism has repeatedly occurred in Indonesia, resulting in focusing on such academic misbehavior as a “central issue” in Indonesian higher education. One of the issues of addressing plagiarism in higher education is that there is a confusion of defining plagiarism. It seems that Indonesian academics had different perception when defining plagiarism. This article aims at exploring the issue of plagiarism by helping define plagiarism to address confusion among Indonesian academics. This article applies literature review by firs finding relevant articles after identifying databases for literature searching. After the collection of required articles for review, the articles were synthesized before presenting the findings. This study has explored the definition of plagiarism in the context of higher education. This research found that plagiarism is defined in the relation of criminal acts. The huge numbers of discursive features used position plagiaristic acts as an illegal deed. This study also found that cultural backgrounds and exposure to plagiarism were influential in defining plagiarism.

Frequency and socio-psychological impact of taunting in school-age patients with cleft lip-palate surgical repair.

Science.gov (United States)

Lorot-Marchand, A; Guerreschi, P; Pellerin, P; Martinot, V; Gbaguidi, C C; Neiva, C; Devauchelle, B; Frochisse, C; Poli-Merol, M L; Francois-Fiquet, C

2015-07-01

Cleft lip-palate (CLP) is a "social" pathology because of its impact on the child's facial appearance and speech. School is the first place where children are confronted to others and when they start socializing. Taunting and bullying are common and their psychological impact remains hard to assess. The aim of this study was to evaluate the importance of taunting in school and its impact in CLP patients who had surgical repair. We conducted a multicenter prospective study where we consecutively included patients ≥ 12 years who had CLP repair. During a multidisciplinary consultation they were asked to complete a questionnaire (3 parts: surgical outcomes, taunting and its impact, socio-economic status) previously approved by our psychologists. 55 patients were included (37 B, 18 G) (mean age 15.5 years): 11 CL, 13 CP and 31 CLP. 69% of patients reported having suffered from taunting and peer victimization in school. In 84% of the cases, taunting was linked to the CLP defect itself. The teasing started in primary school to reach a peak of aggressiveness in middle school. 42% of patients reported that bullying occurred at least once a day (16/38). Regarding the psychological impact of taunting, 50% of patients reported sadness, 31% depression and 26.3% were marked for life. At one time or another 29% of patients did not want to attend school because of the teasing. The grade retention rate amounted to 37.7% (20/53), and 2 patients were in special education classes. As a matter of fact, 50% of these children repeated their 1st or 2nd year of primary school. Furthermore, 47% of patients wanted to change something to their face, but 63% of them never spoke to their surgeon about additional surgeries even though they were teased in school. Taunting is common in children with CLP. This study highlights the high frequency and impact of taunting on the daily lives and self-perception of patients with CLP or CLP repair. It is important for healthcare professionals to be

Future Scenarios for Software-Defined Metro and Access Networks and Software-Defined Photonics

Directory of Open Access Journals (Sweden)

Tommaso Muciaccia

2017-01-01

Full Text Available In recent years, architectures, devices, and components in telecommunication networks have been challenged by evolutionary and revolutionary factors which are drastically changing the traffic features. Most of these changes imply the need for major re-configurability and programmability not only in data-centers and core networks, but also in the metro-access segment. In a wide variety of contexts, this necessity has been addressed by the proposed introduction of the innovative paradigm of software-defined networks (SDNs. Several solutions inspired by the SDN model have been recently proposed also for metro and access networks, where the adoption of a new generation of software-defined reconfigurable integrated photonic devices is highly desirable. In this paper, we review the possible future application scenarios for software-defined metro and access networks and software-defined photonics (SDP, on the base of analytics, statistics, and surveys. This work describes the reasons underpinning the presented radical change of paradigm and summarizes the most significant solutions proposed in literature, with a specific emphasis to physical-layer reconfigurable networks and a focus on both architectures and devices.

UniProt search blastx result: AK318569 [KOME

Lifescience Database Archive (English)

Full Text Available AK318569 J080307D05 B0TZA5|CLPP_FRAP2 ATP-dependent Clp protease proteolytic subunit OS=Francisella philo...miragia subsp. philomiragia (strain ATCC 25017) GN=clpP PE=3 SV=1 6.00E-34 ...

Directory of Open Access Journals (Sweden)

Yousry M. Issa

2017-03-01

Full Text Available The solubility and solubility product of the two ion-associates clomipraminium tetraphenylborate (CLP-TPB and silicotungstate ((CLP4-ST were determined using conductimetric and potentiometric measurements applying the standard addition method. The obtained values from both conductimetric measurements and standard addition method are close to each other. Thermodynamic parameters ΔG, ΔH and ΔS have been determined. Sodium tetraphenylborate has been used for the determination of CLP.Cl in model solution and pharmaceutical preparation by conductimetric titrations. The proposed method allowed the determination of CLP.Cl within the range of 0.17–35.15 mg. The accuracy of the method is indicated by the excellent recovery 99.95–101.23%, and the precision is supported by the low relative standard deviation 0.50–1.21%. The ruggedness and robustness of the proposed method were also studied.

Pattern of clefts and dental anomalies in six-year-old children: a retrospective observational study in western Norway.

Science.gov (United States)

Sæle, Paul; Østhus, Eirik; Ådalen, Sondre; Nasir, Elwalid F; Mustafa, Manal

2017-03-01

Clefts of the lip and/or palate (CL/P) are the most common congenital disorders of the head and neck. In Norway, the incidence is 1.9/1000 live births. The aim of this study was to investigate the frequency and distribution of various types of clefts and dental anomalies in patients treated by the cleft lip and palate (CLP) team in Bergen, Norway. The material comprised the records of patients 6 years of age, examined by the CLP team in Bergen from spring 1993 to autumn 2012, incomplete records were excluded. The records of 989 patients were analysed, using frequencies and Chi-square test to compare differences in percentages between groups. The gender distribution was 58.8% male and 41.2% female. Isolated cleft palate (CP) was the most common condition (39.5%). Clefts of the lip, jaw and palate (CLP) constituted (30%) of cases and (30.5%) had isolated cleft lip (CL). The frequencies of agenesis, supernumerary and peg-shaped teeth were (36.5%), (17.8%) and (7.5%), respectively. Over 50% of the study population were diagnosed with one or more malocclusion. Of the CLP patients, 61.4% had Angle Class III occlusion. Statistical analysis disclosed a positive association of agenesis with Class III occlusion (OR =1.8, p≤ 0.001). The findings supported the hypothesis that the distribution of dental anomalies and occlusal disorders varied among patients with CL, CP and CLP. In patients with cleft, there is a twofold chance to get Class III malocclusion in the presence of agenesis.

Definition of an XML markup language for clinical laboratory procedures and comparison with generic XML markup.

Science.gov (United States)

Saadawi, Gilan M; Harrison, James H

2006-10-01

Clinical laboratory procedure manuals are typically maintained as word processor files and are inefficient to store and search, require substantial effort for review and updating, and integrate poorly with other laboratory information. Electronic document management systems could improve procedure management and utility. As a first step toward building such systems, we have developed a prototype electronic format for laboratory procedures using Extensible Markup Language (XML). Representative laboratory procedures were analyzed to identify document structure and data elements. This information was used to create a markup vocabulary, CLP-ML, expressed as an XML Document Type Definition (DTD). To determine whether this markup provided advantages over generic markup, we compared procedures structured with CLP-ML or with the vocabulary of the Health Level Seven, Inc. (HL7) Clinical Document Architecture (CDA) narrative block. CLP-ML includes 124 XML tags and supports a variety of procedure types across different laboratory sections. When compared with a general-purpose markup vocabulary (CDA narrative block), CLP-ML documents were easier to edit and read, less complex structurally, and simpler to traverse for searching and retrieval. In combination with appropriate software, CLP-ML is designed to support electronic authoring, reviewing, distributing, and searching of clinical laboratory procedures from a central repository, decreasing procedure maintenance effort and increasing the utility of procedure information. A standard electronic procedure format could also allow laboratories and vendors to share procedures and procedure layouts, minimizing duplicative word processor editing. Our results suggest that laboratory-specific markup such as CLP-ML will provide greater benefit for such systems than generic markup.

Comparative Assessment of the Cleft Profile by Patients with Cleft Lip and Palate, Cleft Surgeons, and Lay People.

Science.gov (United States)

Meng, Tian; Ma, Lian; Wang, Zhi

2015-10-01

This cross-sectional study aimed to compare subjective assessments among patients with cleft lip and palate (CLP), cleft surgeons, and lay people regarding the soft tissue lateral profile of CLP patients. We also investigated the correlations between subjective assessments and photogrammetric measurements. A total of 150 CLP patients who wished to have treatment for their unattractive appearance were randomly selected. A standard lateral profile color photograph was taken. Panels of three cleft surgeons, ten CLP patients, and ten lay people were selected to be assessors. They rated nasal tip projection, nasolabial esthetics, upper and lower lip esthetics, and the profile for each photograph. Three angular measurements (nasal prominence angle, nasolabial angle, and lip angle) were measured for each photograph. Kendall's coefficient of concordance and logistic regression were used for statistical analysis. Kendall's coefficient of concordance of nasal tip projection, nasolabial esthetics, upper and lower lip esthetics, and the profile were 0.734, 0.683, 0.828, and 0.747, respectively (p lay people (p lay people have similar attitudes to the appearance of CLP patients. Upper and lower lip esthetics is associated with the assessment of the cleft profile that is provided by CLP patients, cleft surgeons, and lay people. In addition, nasal tip projection is another determining factor for lay people. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The association of emotion regulation with lifestyle behaviors in inner-city adolescents.

Science.gov (United States)

Isasi, Carmen R; Ostrovsky, Natania W; Wills, Thomas A

2013-12-01

Recent research suggests a role of cognitive self-regulation skills on obesity and lifestyle behaviors. However, very little is known about the role of emotion regulation. This study examined the association of emotion regulation with lifestyle behaviors and examined a mediational model testing the effects of emotion regulation through self-efficacy and depressive symptoms. A cross-sectional study was conducted with 602 adolescents (mean age 12.7 years) from 4 public schools in the Bronx, NY. The sample was 58% female, predominantly Hispanic (74%) and US born (81%). Emotion regulation was assessed by 3 indicators and defined as a latent variable. Dependent variables included fruit/vegetable intake, snack/junk food intake, frequency of physical activity, and time spent in sedentary behaviors. Structural equation modeling examined the association of emotion regulation with lifestyle behaviors, with self-efficacy and depressive symptoms defined as potential mediators. The analyses showed that there was a positive association of emotion regulation with higher intake of fruits/vegetable and greater physical activity, which was mediated by self-efficacy. Emotion regulation was related to snack/junk food intake and sedentary behavior, and the structural equation model indicated pathways through an inverse relation to depressive symptoms, but these pathways were only observed in adolescent girls and not boys. These findings indicate that the ability to regulate emotions among adolescents has a role in weight-related behaviors. Future studies may need to explore the relation of other dimensions of emotion to positive health behaviors and study aspects of emotion regulation that may be more relevant for boys. © 2013.

A constitutional critique on the regulations relating to artificial ...

African Journals Online (AJOL)

2017-06-30

Jun 30, 2017 ... ARTICLE. It is a basic constitutional requirement that all legislation must be ... This article considers the regulations relating to artificial fertilisation .... Zola[6] defines 'medicalisation' as the 'process whereby more and more of ...

Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations-Protective Effects of the Oxygen Radical Scavenger Edaravone

DEFF Research Database (Denmark)

Hara, Naomi; Chijiiwa, Miyuki; Yara, Miki

2015-01-01

at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups-CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE......), and sham-operated (Sham). Mice in CLPV and CLPE were injected with saline or edaravone intraperitoneally at a dose of 10 mg/kg twice daily. The treatments were initiated 4 days prior to the surgical procedure. Mortality, histological changes, electron microscopy (EM), and expression of Bcl-2 family genes...

Emotion Regulation and the Dynamics of Feelings: A Conceptual and Methodological Framework

Science.gov (United States)

Hoeksma, Jan B.; Oosterlaan, Jaap; Schipper, Eline M.

2004-01-01

The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed, identifies its goal, and illustrates how regulation…

Regulation on radioactive waste management, Governmental Agreement No. 559-98

International Nuclear Information System (INIS)

1998-01-01

This regulation defines the responsibilities on the radioactive waste management in Guatemala including the requirements of users, handling of radioactive wastes, authorization of radioactive waste disposal, transport of radioactive wastes and penalties

Regulations for the Safe Transport of Radioactive Materials. Vietnam Standard (TCVN 4985-89)

International Nuclear Information System (INIS)

1989-01-01

The regulations were prepared in line with the Safety Regulation for Ionizing Radiations 1988 of Vietnam. Its purpose is to provide requirements in transport of radioactive materials. The exposure levels of transport personnel are determined. The package for different types of materials is regulated. The orders and procedures in transport are defined. In addition, specific requirements for each mean of transport are given. (N.H.A)

Evidence for an association between nonsyndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4

Energy Technology Data Exchange (ETDEWEB)

Mitchell, L.E.; Healey, S.C.; Chenevix-Trench, G. [St. Louis Univ. Health Sciences Center, MO (United States)]|[Queensland Institute of Medical Research, Brisbane (Australia)

1995-11-01

Recent studies suggest that the familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL{+-}P) is likely to be attributable to the effects of several susceptibility loci, acting in a multiplicative fashion. Two potential CL{+-}P susceptibility loci (CSL), transforming growth factor alpha (TGFA) and retinoic acid receptor (RARA), have been identified through association studies. In addition, recent evidence of linkage between CL{+-}P and two markers (D4S175 and D4S192) in the region 4q25-4q31.3 raised the possibility that a CSL, with a larger effect than either TGFA or RARA, may reside within this region of the human genome. The present analyses were undertaken to determine whether D4S175 or D4S192 is significantly associated with CL{+-}P in a sample of unrelated patients that have previously provided evidence of associations between CL{+-}P and both TGFA and RARA. The results of these analyses provide further, tentative, evidence for the presence of a CSL locus on the long arm of chromosome 4 and help to refine the location of this locus in the region of D4S175 and D4S192. 28 refs., 4 tabs.

Effects of intra-abdominal sepsis on atherosclerosis in mice.

Science.gov (United States)

Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

2014-09-03

Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2

A prospective longitudinal study of postnatal dentoalveolar and palatal growth: The anatomical basis for CAD/CAM-assisted production of cleft-lip-palate feeding plates.

Science.gov (United States)

Bauer, Franz X; Güll, Florian D; Roth, Maximilian; Ritschl, Lucas M; Rau, Andrea; Gau, Dominik; Gruber, Maximilian; Eblenkamp, Markus; Hilmer, Bettina; Wolff, Klaus-Dietrich; Loeffelbein, Denys J

2017-10-01

This study describes the dentoalveolar and palatal growth during the first months of life. Knowledge concerning this development is essential to avoid unwanted events such as mucosal ulcerations or restriction of growth when cleft-lip and palate (CLP) patients are treated. The results involve the generation of CAD/CAM CLP-feeding plates. Intraoral impressions from 32 healthy newborns were taken monthly for 5 months, supplemented by measurements of body weight, length, and occipital-frontal head circumference. The casts were digitalized, and two observers manually selected defined anatomical landmarks on virtual 3-D models. The distances between these landmarks were evaluted. Statistical analysis included an inter-rater agreement analysis and the determination of growth. In total, 213 casts were analyzed, with 65 models excluded because of inaccuracies in impression-taking or cast production. Overall longitudinal growth was 20.3%, whereas transversal growth reached a maximum of 21.1%. Vertical growth was 32.4% at the tuberal level. On the basis of these results, a semiautomated series of feeding plates allowing for monthly expansion could be generated. The acquired data serve as a useful reference for other pediatric and orthofacial investigations and treatments. One such application is the automated, fully virtual manufacture of CLP-feeding plates based on only one impression-taking. Our data reveal when caution is needed to prevent ulceration. The series of plates generated can minimize the time-consuming impression-taking and the production of further plaster models. The method of measurement is suitable for documentary purposes. Clin. Anat. 30:846-854, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Variability in larval gut pH regulation defines sensitivity to ocean acidification in six species of the Ambulacraria superphylum.

Science.gov (United States)

Hu, Marian; Tseng, Yung-Che; Su, Yi-Hsien; Lein, Etienne; Lee, Hae-Gyeong; Lee, Jay-Ron; Dupont, Sam; Stumpp, Meike

2017-10-11

The unusual rate and extent of environmental changes due to human activities may exceed the capacity of marine organisms to deal with this phenomenon. The identification of physiological systems that set the tolerance limits and their potential for phenotypic buffering in the most vulnerable ontogenetic stages become increasingly important to make large-scale projections. Here, we demonstrate that the differential sensitivity of non-calcifying Ambulacraria (echinoderms and hemichordates) larvae towards simulated ocean acidification is dictated by the physiology of their digestive systems. Gastric pH regulation upon experimental ocean acidification was compared in six species of the superphylum Ambulacraria. We observed a strong correlation between sensitivity to ocean acidification and the ability to regulate gut pH. Surprisingly, species with tightly regulated gastric pH were more sensitive to ocean acidification. This study provides evidence that strict maintenance of highly alkaline conditions in the larval gut of Ambulacraria early life stages may dictate their sensitivity to decreases in seawater pH. These findings highlight the importance of identifying and understanding pH regulatory systems in marine larval stages that may contribute to substantial energetic challenges under near-future ocean acidification scenarios. © 2017 The Author(s).

Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes

DEFF Research Database (Denmark)

Carlson, Jenna C; Standley, Jennifer; Petrin, Aline

2017-01-01

Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes-cleft lip alone (CL) and CL plus cleft palate (CLP)-are typically grouped into a single phenotype for genetic analysis (i.e., CL with or without cleft palate, CL/P)...

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13

DEFF Research Database (Denmark)

Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R

2016-01-01

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental fac...

Constraint Programming versus Mathematical Programming

DEFF Research Database (Denmark)

Hansen, Jesper

2003-01-01

Constraint Logic Programming (CLP) is a relatively new technique from the 80's with origins in Computer Science and Artificial Intelligence. Lately, much research have been focused on ways of using CLP within the paradigm of Operations Research (OR) and vice versa. The purpose of this paper...

Safety Regulations for Ionizing Radiations. Vietnam Standard (TCVN 4397-87)

International Nuclear Information System (INIS)

1987-01-01

The regulations were prepared for purpose of providing basic requirements of ionizing radiation protection and giving guide for design criteria of radiation installations in Vietnam. The allowable maximum levels for personnel categories are established. Regulated are methods for handling sealed and unsealed sources of radiation, transfer and transport of radioactive materials. Defined requirements and operating conditions that must be met. Determined are procedures and actions of decontamination. (N.H.A)

Dental Caries Experience in Texan Children with Cleft Lip and Palate.

Science.gov (United States)

Sunderji, Sabrina; Acharya, Bhavini; Flaitz, Catherine; Chiquet, Brett

2017-09-15

The purpose of this study was to assess the caries experience in the primary dentition of children born with cleft lip and palate (CLP). A retrospective chart review was conducted on subjects between two and six years old recruited from a university-based pediatric dentistry residency clinic. The number of dental visits and professional fluoride applications, the plaque index and treatment modality, and the presence/location of caries, white spot lesions, and enamel hypoplastic lesions were compared between CLP patients and healthy age- and gender-matched controls. Descriptive statistics, Student's t test, Mann-Whitney U test, and regression analysis were completed. A total of 183 charts were reviewed. Compared to healthy children, CLP children had increases in number of dental visits (P0.05). Children with cleft lip and palate are at a greater risk of enamel hypoplasia and dental caries. No significant caries experience difference was found between unilateral or bilateral CLP cases.

A novel natural compound from garlic (Allium sativum L.) with therapeutic effects against experimental polymicrobial sepsis.

Science.gov (United States)

Lee, Sung Kyun; Park, Yoo Jung; Ko, Min Jung; Wang, Ziyu; Lee, Ha Young; Choi, Young Whan; Bae, Yoe-Sik

2015-08-28

Sepsis is a serious, life-threatening, infectious disease. In this study, we demonstrate that sucrose methyl 3-formyl-4-methylpentanoate (SMFM), a novel natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rates by inhibiting lung inflammation in a cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. SMFM strongly reduced bacterial colony units from peritoneal fluid in CLP mice by stimulating the generation of reactive oxygen species. Lymphocyte apoptosis in spleens from CLP mice was also markedly decreased by SMFM administration. SMFM also significantly inhibited the production of proinflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β) and IL-6, in CLP mice. Lipopolysaccharide-stimulated production of TNF-α and IL-6 were also strongly inhibited by SMFM in mouse bone marrow-derived macrophages. Taken together, our results indicate that SMFM has therapeutic effects against polymicrobial sepsis that are mediated by enhanced microbial killing and blockage of cytokine storm. Copyright © 2015 Elsevier Inc. All rights reserved.

The comparison of psychological adjustment of patients with cleft lip and palate after maxillary distraction osteogenesis and conventional orthognathic surgery.

Science.gov (United States)

Chua, Hannah Daile P; Ho, Samuel M Y; Cheung, Lim Kwong

2012-11-01

The objective of this study was to compare the psychological changes of patients with cleft lip and palate (CLP) undergoing maxillary Le Fort I advancement by distraction osteogenesis (DO) and conventional orthognathic surgery (CO). Prospective randomized controlled study. Participants completed a set of questionnaires to measure their psychological states preoperatively and postoperatively. When compared with CO, CLP patients treated with DO had lower social self-esteem and higher social avoidance and distress levels during the first 3 postoperative months. Their self-esteem, social avoidance, and distress levels improved after the distractors were removed. Both CO and DO patients had similar levels of self-esteem, social avoidance, and distress levels 2 years postoperatively. The CLP patients treated with DO were more satisfied with their lives after 2 years. DO may induce short-term distress to patients up to 3 months but CLP patients who received DO were more satisfied with their lives in the long term. Copyright © 2012 Elsevier Inc. All rights reserved.

Common dental anomalies in cleft lip and palate patients.

Science.gov (United States)

Haque, Sanjida; Alam, Mohammad Khursheed

2015-01-01

Cleft lip and palate (CLP) is the most common orofacial congenital malformation in live births. CLP can occur individually or in combination with other congenital deformities. Affected patients experience a number of dental, aesthetic, speech, hearing, and psychological complications and have a higher incidence of severe dental conditions. The purpose of this study is to characterise the different types of dental anomalies that are frequently associated with CLP patients based on a literature survey. By literature survey, this study characterises the different types of dental anomalies that are frequently associated with cleft lip and palate patients. Common dental anomalies associated with CLP are supernumerary tooth, congenitally missing tooth, delayed tooth development, morphological anomalies in both deciduous and permanent dentition, delayed eruption of permanent maxillary incisors, microdontia, and abnormal tooth number. The incidence of certain dental anomalies is strongly correlated with Cleft lip and palate, a finding that is consistent with previous studies.

The Difference in Cervical Vertebral Skeletal Maturation between Cleft Lip/Palate and Non-Cleft Lip/Palate Orthodontic Patients.

Science.gov (United States)

Batwa, Waeil; Almoammar, Khalid; Aljohar, Aziza; Alhussein, Abdullah; Almujel, Saad; Zawawi, Khalid H

2018-01-01

The aim was to evaluate differences in the cervical vertebral skeletal maturity of unilateral cleft lip and palate (UCLP) and non-cleft lip/palate (non-CLP) Saudi male orthodontic patients. This cross-sectional multicenter study took place at the dental school, King Saud University and King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between October 2014 and September 2015. The records of Saudi male orthodontic patients with UCLP ( n = 69) were collected. Cervical vertebral maturation was assessed using their cephalometric radiographs. The records of 138 age-matched non-CLP Saudi male orthodontic patients served as controls. There was a significant difference in skeletal maturity between the UCLP and non-CLP groups, as evident in the delayed skeletal development among the UCLP participants. Moreover, pubertal growth spurt onset was significantly earlier in the non-cleft participants in comparison with the UCLP participants ( p = 0.009). There is delayed skeletal maturity among the UCLP Saudi male population in comparison with their non-CLP age-matched peers.

Targeted scan of fifteen regions for nonsyndromic cleft lip and palate in Filipino families.

Science.gov (United States)

Schultz, R E; Cooper, M E; Daack-Hirsch, S; Shi, M; Nepomucena, B; Graf, K A; O'Brien, E K; O'Brien, S E; Marazita, M L; Murray, J C

2004-02-15

Cleft lip with or without cleft palate (CL/P) is a congenital anomaly with variable birth prevalence based on geographic origins, with the highest rates commonly found in Asian populations. About 70% of cases are nonsyndromic (NS), in which the affected individual has no other abnormalities. NS CL/P is a complex disorder with genetic and environmental effects and no specific genetic loci yet confirmed. Fifteen candidate regions were examined for linkage to NS CL/P. Regions were chosen based on previous suggestive linkage and/or association in human families, or suggestive animal model data. Polymorphic markers in these regions were genotyped for analysis on 36 Filipino families comprised of 126 affected and 218 unaffected individuals. An additional 70 families with 149 affecteds were used for replication of suggestive results. Parametric (LOD score) and nonparametric (SIMIBD) linkage analyses were performed as well as transmission disequilibrium test (TDT) analysis. Five markers yielded suggestive results from the 36 families. The parametric LOD scores for the MSX1-CA and D4S1629 were >1.0 and the SIMIBD P values for D6S1029 and RFC1 are suggestive (value of 0.01 for TGFA was significant. Since the Msx1 mouse knockout has cleft palate and MSX1 mutations have been found in rare cases of syndromic CL/P, this locus is especially plausible for linkage. Previous studies have also found linkage of NS CL/P to 4q31 and 6p23. These regions contain several candidate genes, including AP2 at 6p23 and FGF2, BMPR1B, and MADH1 at 4q31. TGFA has both linkage and linkage disequilibrium data supporting it as a candidate gene for NS CL/P. While no region was definitively confirmed for linkage to NS CL/P, the data do support further investigation using larger sample sizes and candidate gene studies at 2p13.2, 4p16.2, 4q31, 6p23, and 16q22-24. Copyright 2003 Wiley-Liss, Inc.

Insulin Modulates Liver Function in a Type I Diabetes Rat Model

Directory of Open Access Journals (Sweden)

Eduardo L. Nolasco

2015-07-01

Full Text Available Background/Aims: Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP in rats. Methods: Diabetic (alloxan, 42 mg/kg i.v., 10 days and non-diabetic (control male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a total and differential cell counts in peritoneal lavage (PeL and bronchoalveolar lavage (BAL fluids; (b quantification of tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA; (c total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d biochemical parameters (urea, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP by colorimetric analyses; and (e lung, kidney, and liver morphological analyses (hematoxylin and eosin staining. Results: Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1β, IL-6, IL-10, CINC-1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c., 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels. Conclusion: These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal

Effects of aging on the immunopathologic response to sepsis.

Science.gov (United States)

Turnbull, Isaiah R; Clark, Andrew T; Stromberg, Paul E; Dixon, David J; Woolsey, Cheryl A; Davis, Christopher G; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2009-03-01

Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine whether this represents a fundamental age-based difference in the host response or is secondary to the increased mortality seen in aged hosts. Prospective, randomized controlled study. Animal laboratory in a university medical center. Young (6-12 weeks) and aged (20-24 months) FVB/N mice. Mice were subjected to 2 x 25 or 1 x 30 cecal ligation and puncture (CLP). Survival was similar in young mice subjected to 2 x 25 CLP and aged mice subjected to 1 x 30 CLP (p = 0.15). Young mice subjected to 1 x 30 CLP had improved survival compared with the other groups (p < 0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and monocyte chemotactic protein-1 were elevated 24 hours after CLP in aged animals compared with young animals (p < 0.05). When mortality was similar but injury severity was different, there were no significant differences in systemic cytokines between aged mice and young mice. In contrast, peritoneal levels of tumor necrosis factor-alpha, IL-6, and IL-10 were higher in aged mice subjected to 1 x 30 CLP than young mice subjected to 2 x 25 CLP despite their similar mortalities (p < 0.05). There were no significant differences in either bacteremia or peritoneal cultures when animals of different ages sustained similar injuries or had different injuries with similar mortalities. Aged mice are more likely to die of sepsis than young mice when subjected to an equivalent insult, and this is associated with increases in both systemic and local inflammation. There is an exaggerated local but not systemic inflammatory response in aged mice compared with young mice when mortality is similar. This suggests that systemic processes that culminate in death may be age independent, but the local inflammatory response may be greater with aging.

Effects of aging on the immunopathological response to sepsis

Science.gov (United States)

Turnbull, Isaiah R.; Clark, Andrew T.; Stromberg, Paul E.; Dixon, David J.; Woolsey, Cheryl A.; Davis, Christopher G.; Hotchkiss, Richard S.; Buchman, Timothy G.; Coopersmith, Craig M.

2009-01-01

Objective Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine if this represents a fundamental age-based difference in the host response or is secondary to the increased mortality seen in aged hosts. Design Prospective, randomized controlled study. Setting Animal laboratory in a university medical center. Subjects Young (6–12 week) and aged (20–24 month) FVB/N mice. Interventions Mice were subjected to 2×25 or 1×30 cecal ligation and puncture (CLP). Measurements and Main Results Survival was similar in young mice subjected to 2×25 CLP and aged mice subjected to 1×30 CLP (p=0.15). Young mice subjected to 1×30 CLP had improved survival compared to both other groups (p<0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of TNF-α, IL-6, IL-10 and MCP-1 were elevated 24 hours after CLP in aged animals compared to young animals (p<0.05). When mortality was similar but injury severity was different, there were no significant differences in systemic cytokines between aged mice and young mice. In contrast, peritoneal levels of TNF-α, IL-6, and IL-10 were higher in aged mice subjected to 1×30 CLP than young mice subjected to 2×25 CLP despite their similar mortalities (p<0.05). There were no significant differences in either bacteremia or peritoneal cultures when animals of different ages sustained similar injuries or had different injuries with similar mortalities. Conclusions Aged mice are more likely to die from sepsis than young mice when subjected to an equivalent insult, and this is associated with increases in both systemic and local inflammation. There is an exaggerated local but not systemic inflammatory response in aged mice compared to young mice when mortality is similar. This suggests that systemic processes that culminate in death may be age-independent, but the local inflammatory response may be greater with aging. PMID:19237912

Growth and sporulation of Bacillus cereus ATCC 14579 under defined conditions: temporal expression of genes for key sigma factors

NARCIS (Netherlands)

Vries, de Y.P.; Hornstra, L.M.; Vos, de W.M.; Abee, T.

2004-01-01

An airlift fermentor system allowing precise regulation of pH and aeration combined with a chemically defined medium was used to study growth and sporulation of Bacillus cereus ATCC 14579. Sporulation was complete and synchronous. Expression of sigA, sigB, sigF, and sigG was monitored with real-time

Radiation security regulation. 1st revision

International Nuclear Information System (INIS)

1984-01-01

Established are allowable maximum levels for personnel occupationally exposed to ionizing radiation in the ININ and for the public, in accordance with the international standards; defined are categories of radiation facilities, requirements and operating conditions that must be met. Demarcated are the kinds of placards to be posted in controlled and restricted areas and the signs, symbols and tags to be used, defined and established is environmental dosimetric and medical radiation monitoring. Regulated are methods for handling sealed and unsealed sources of radiation, work clothes, closing of radiation installations, storage, transfer and transport of radioactive material; classified are types of possible radiation accidents, action to be taken upon the occurrence and subsequent clean up. (corporate author)

Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.

Science.gov (United States)

Luna-Zurita, Luis; Stirnimann, Christian U; Glatt, Sebastian; Kaynak, Bogac L; Thomas, Sean; Baudin, Florence; Samee, Md Abul Hassan; He, Daniel; Small, Eric M; Mileikovsky, Maria; Nagy, Andras; Holloway, Alisha K; Pollard, Katherine S; Müller, Christoph W; Bruneau, Benoit G

2016-02-25

Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

Energy Technology Data Exchange (ETDEWEB)

Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands); Pronk, Tessa E. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Brandhof, Evert-Jan van den [Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Ven, Leo T.M. van der [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)

2013-10-01

The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

Modular Software-Defined Radio

Directory of Open Access Journals (Sweden)

Rhiemeier Arnd-Ragnar

2005-01-01

Full Text Available In view of the technical and commercial boundary conditions for software-defined radio (SDR, it is suggestive to reconsider the concept anew from an unconventional point of view. The organizational principles of signal processing (rather than the signal processing algorithms themselves are the main focus of this work on modular software-defined radio. Modularity and flexibility are just two key characteristics of the SDR environment which extend smoothly into the modeling of hardware and software. In particular, the proposed model of signal processing software includes irregular, connected, directed, acyclic graphs with random node weights and random edges. Several approaches for mapping such software to a given hardware are discussed. Taking into account previous findings as well as new results from system simulations presented here, the paper finally concludes with the utility of pipelining as a general design guideline for modular software-defined radio.

Awareness, knowledge and attitude on cleft lip and palate among ...

African Journals Online (AJOL)

Background: Adequate knowledge and awareness of cleft lip and palate (CLP) deformity may help to counter the negative beliefs and attitudes toward the condition. The objective of this study was to assess the level of awareness, knowledge and attitude of women attending antenatal clinics about CLP. Materials and ...

Application-Defined Decentralized Access Control

Science.gov (United States)

Xu, Yuanzhong; Dunn, Alan M.; Hofmann, Owen S.; Lee, Michael Z.; Mehdi, Syed Akbar; Witchel, Emmett

2014-01-01

DCAC is a practical OS-level access control system that supports application-defined principals. It allows normal users to perform administrative operations within their privilege, enabling isolation and privilege separation for applications. It does not require centralized policy specification or management, giving applications freedom to manage their principals while the policies are still enforced by the OS. DCAC uses hierarchically-named attributes as a generic framework for user-defined policies such as groups defined by normal users. For both local and networked file systems, its execution time overhead is between 0%–9% on file system microbenchmarks, and under 1% on applications. This paper shows the design and implementation of DCAC, as well as several real-world use cases, including sandboxing applications, enforcing server applications’ security policies, supporting NFS, and authenticating user-defined sub-principals in SSH, all with minimal code changes. PMID:25426493

Commission de regulation de l'energie. activity report 2015 - Reference document, 15 years of regulation

International Nuclear Information System (INIS)

2016-06-01

CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the June 2015 activity report of CRE. The report comes in two volumes. The first provides comprehensive details of the CRE's activities in 2015, while the second highlights just how far the CRE has come since it was established in 2000. Content: A - Message from the Board; B - The Energy Regulatory Commission: The organisation and missions of CRE (organisation of CRE, missions of CRE, CRE and other institutional actors, CRE consultation and transparency, Human resources and budgetary means; CRE playing a role at the heart of Europe (CRE within ACER and CEER, Cooperation with other regulators; C - CRE and the markets: As part of its monitoring task, CRE assesses the wholesale market (The wholesale energy market has been affected by the significant fall in prices, The European regulation (REMIT) is a legal tool for monitoring the markets at European level, The capacity mechanism has been defined to promote the security of supply at national level); The retail market was growing fast in 2015 (The implementation of the NOME law provides a new legal framework for regulated tariffs

The importance of product definitions in US e-cigarette laws and regulations.

Science.gov (United States)

Lempert, Lauren K; Grana, Rachel; Glantz, Stanton A

2016-04-01

How electronic cigarettes and similar products (e-cigarettes) are defined affects how they are regulated, particularly whether existing laws for cigarettes apply, including sales and marketing, youth access, smoke-free and taxation laws. We examined the text of 46 bills that define e-cigarettes enacted in 40 states and characterised how e-cigarettes and similar products were defined. States enact laws creating new product categories for e-cigarettes separate from the 'tobacco product' category (eg, 'alternative nicotine product,' 'vapour product,' 'electronic nicotine device'), with four states explicitly excluding e-cigarettes from 'tobacco products.' Twenty-eight states do not include e-cigarettes in their definitions of 'tobacco products' or 'smoking,' eight include e-cigarettes as 'tobacco products,' three include e-cigarettes in 'smoking.' Sixteen states' definitions of e-cigarettes require nicotine, and five states pre-empt more stringent local laws. Tobacco and e-cigarette industry representatives tried to shape laws that benefit their interests. Definitions separating e-cigarettes from other tobacco products are common. Similar to past 'Trojan horse' policies, e-cigarette policies that initially appear to restrict sales (eg, limit youth access) may actually undermine regulation if they establish local pre-emption or create definitions that divide e-cigarettes from other tobacco products. Comparable issues are raised by the European Union Tobacco Products Directive and e-cigarette regulations in other countries. Policymakers should carefully draft legislation with definitions of e-cigarettes that broadly define the products, do not require nicotine or tobacco, do not pre-empt stronger regulations and explicitly include e-cigarettes in smoke-free and taxation laws. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Barriers to Cleft Lip and Palate Repair Around the World.

Science.gov (United States)

Massenburg, Benjamin B; Jenny, Hillary E; Saluja, Saurabh; Meara, John G; Shrime, Mark G; Alonso, Nivaldo

2016-10-01

Cleft lip and/or palate (CLP) is estimated to occur in 1 out of every 700 births, but for many people residing in low- and middle-income countries this deformity may be repaired late in life or not at all. This study aims to analyze worldwide provider-perceived barriers to the surgical repair of CLP in low- and middle-income countries. From 2011 to 2014, Smile Train distributed a multiple-choice, voluntary survey to healthcare providers to identify areas of need in CLP care worldwide. Data on provider-reported barriers to care were aggregated by year, country, and larger world regions. A total of 1997 surveys were completed by surgeons and healthcare providers (60.7% response rate). The most commonly reported barriers were "patient travel costs" (60.7%), "lack of patient awareness" (54.1%), and "lack of financial support" (52.8%). "Patient travel costs" was the most commonly reported barrier in sub-Saharan Africa, the Middle East and North Africa, and South and Southeast Asia. "Lack of financial support" was the most commonly reported barrier in the Americas, Eastern Europe, and East Asia. This is the largest intercontinental study on healthcare provider-identified barriers to care, representing the limitations experienced by healthcare professionals in providing corrective surgery for CLP around the world. Financial risk protection from hidden costs, such as patient travel costs, is essential. Community health workers and nurses are critical for communication and linking CLP care to the rest of the community. Recognition of these barriers can inform future policy decisions, targeted by region, for surgical systems delivering care for patients with CLP worldwide.

Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and sepsis.

Science.gov (United States)

Keller, Steve A; Paxian, Marcus; Lee, Sun M; Clemens, Mark G; Huynh, Toan

2005-03-01

Prostaglandins, synthesized by cyclooxygenase (COX), play an important role in the pathophysiology of inflammation. Severe injuries result in immunosuppression, mediated, in part, by maladaptive changes in macrophages. Herein, we assessed Kupffer cell-mediated cyclooxygenase-2 (COX-2) expression on liver function and damage after trauma and sepsis. To ablate Kupffer cells, Sprague Dawley rats were treated with gadolinium chloride (GdCl3) 48 and 24 h before experimentation. Animals then underwent femur fracture (FFx) followed 48 h later by cecal ligation and puncture (CLP). Controls received sham operations. After 24 h, liver samples were obtained, and mRNA and protein expression were determined by PCR, Western blot, and immunohistochemistry. Indocyanine-Green (ICG) clearance and plasma alanine aminotransferase (ALT) levels were determined to assess liver function and damage, respectively. One-way analysis of variance (ANOVA) with Student-Newman-Keuls test was used to assess statistical significance. After CLP alone, FFx+CLP, and GdCl3+FFx+CLP, clearance of ICG decreased. Plasma ALT levels increased in parallel with severity of injury. Kupffer cell depletion attenuated the increased ALT levels after FFx+CLP. Femur fracture alone did not alter COX-2 protein compared with sham. By contrast, COX-2 protein increased after CLP and was potentiated by sequential stress. Again, Kupffer cell depletion abrogated the increase in COX-2 after sequential stress. Immunohistochemical data confirmed COX-2 positive cells to be Kupffer cells. In this study, sequential stress increased hepatic COX-2 protein. Depletion of Kupffer cells reduced COX-2 and attenuated hepatocellular injuries. Our data suggest that Kupffer cell-dependent pathways may contribute to the inflammatory response leading to increased mortality after sequential stress.

Thioredoxin-1 attenuates sepsis-induced cardiomyopathy after cecal ligation and puncture in mice.

Science.gov (United States)

Wilson, Rickesha L; Selvaraju, Vaithinathan; Lakshmanan, Rajesh; Thirunavukkarasu, Mahesh; Campbell, Jacob; McFadden, David W; Maulik, Nilanjana

2017-12-01

Sepsis is a leading cause of mortality among patients in intensive care units across the USA. Thioredoxin-1 (Trx-1) is an essential 12 kDa cytosolic protein that, apart from maintaining the cellular redox state, possesses multifunctional properties. In this study, we explored the possibility of controlling adverse myocardial depression by overexpression of Trx-1 in a mouse model of severe sepsis. Adult C57BL/6J and Trx-1 Tg/+ mice were divided into wild-type sham (WTS), wild-type cecal ligation and puncture (WTCLP), Trx-1 Tg/+ sham (Trx-1 Tg/+ S), and Trx-1 Tg/+ CLP groups. Cardiac function was evaluated before surgery, 6 and 24 hours after CLP surgery. Immunohistochemical and Western blot analysis were performed after 24 hours in heart tissue sections. Echocardiography analysis showed preserved cardiac function in the Trx-1 Tg/+ CLP group compared with the WTCLP group. Similarly, Western blot analysis revealed increased expression of Trx-1, heme oxygenase-1 (HO-1), survivin (an inhibitor of apoptosis [IAP] protein family), and decreased expression of thioredoxin-interacting protein (TXNIP), caspase-3, and 3- nitrotyrosine in the Trx-1 Tg/+ CLP group compared with the WTCLP group. Immunohistochemical analysis showed reduced 4-hydroxynonenal, apoptosis, and vascular leakage in the cardiac tissue of Trx-1 Tg/+ CLP mice compared with mice in the WTCLP group. Our results indicate that overexpression of Trx-1 attenuates cardiac dysfunction during CLP. The mechanism of action may involve reduction of oxidative stress, apoptosis, and vascular permeability through activation of Trx-1/HO-1 and anti-apoptotic protein survivin. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence of cleft lip and palate among four provinces in the West and North-West of Iran

Directory of Open Access Journals (Sweden)

Nahid Jalilevand

2015-01-01

Full Text Available Background: One of the most common anomalies in newborn infants is cleft lip and/or cleft palate (CL/P. In spite of several studies about the prevalence of this, no investigation evaluated this prevalence in the West and North-West of Iran. With due attention to different ethnic groups in this area, the aim of this study is to investigate whether the distribution of CL/P live births varies regionally in this area of Iran. Materials and Methods: A cross-sectional study was conducted using hospital registry records to identify all children born with CL/P. The hospitals with a maternity unit were selected in the capital cities of four provinces in the West and North-West of Iran, East Azarbaijan, Kurdestan, Gilan, and Markazi. The population under study included all infants born alive from 2008 to 2012. Results: During the study period, 107,317 live births were registered in the hospitals with a maternity unit of four cities, and 52 infants (0.485/1000 live births were born with CL/P. The prevalence in Rasht, Arak, Sanandaj, and Tabriz cities was 0.557, 0.352, 0.503, and 0.559/1000 live births, respectively (P 0.05, whereas the prevalence of CL/P based on sex was statistically different among the four provinces (P < 0.05. Conclusion: This study shows regional variations in the birth prevalence of clefts and various cleft types. The different effects of gender on the birth prevalence of CL/P from city-to-city may be explained environmentally and/or by genetic factors affecting the development of oral clefts.

Prevalence of dental anomalies in patients with cleft lip and palate.

Science.gov (United States)

Eslami, Neda; Majidi, Mohammad Reza; Aliakbarian, Majid; Hasanzadeh, Nadia

2013-09-01

The aim of the present study was to investigate the prevalence of dental anomalies in a group of patients with cleft lip and palate (CL/P) in the northeast of Iran. Ninety-one patients referring to the Cleft Lip and Palate Clinic of Mashhad Dental School were enrolled and classified into right CL/P, left CL/P, and bilateral CL/P groups. Photographs, dental casts, and panoramic and periapical radiographs were retrieved, and dental anomalies were recorded. χ test was used to analyze the frequency of dental anomalies according to type of cleft and sex. Missing maxillary lateral incisors was the most frequent dental anomaly, which was slightly higher in the bilateral group (61.1%). There were significantly more cases of missing lateral incisors outside the cleft area in right CL/P (P = 0.015). Peg lateral incisors were observed in 33.3% of bilateral CL/P compared with 28% of right and 23.3% of left unilateral cases. The sample presented rotations of central incisors in the cleft area in 33.3% of bilateral clefts. In unilateral clefts, it occurred more frequently in the right side (48%). Sexual dimorphism appeared only for maxillary central incisor rotation in the cleft area, which showed significantly greater frequency in females (P = 0.025). Transposition of maxillary canine and first premolars was found in 5.5% of bilateral, 8% of right, and 3.3% of left unilateral clefts. The prevalence of dental anomalies in the studied sample seems to be higher than that reported in the normal population. More anomalies were observed at the cleft side. The frequency of most anomalies was not significantly different between the 2 sexes.

Weight, Length, and Body Mass Index Growth of Children Under 2 Years of Age With Cleft Lip and Palate.

Science.gov (United States)

Miranda, Gabriela Serrano; Marques, Ilza Lazarini; de Barros, Suely Prietto; Arena, Eliane Petean; de Souza, Luiz

2016-05-01

To study the growth of length-for-age (L/A), weight-for-age (W/A), and body mass index (BMI) of children with cleft lip and palate receiving a normal diet; to establish specific growth curves for children with cleft palate with or without cleft lip (CLP/ICP) who had not undergone palatoplasty and for children with isolated cleft lip (ICL); and to assess if CLP/ICP growth differed from ICL growth and if CLP/ICP and ICL growth differed from growth for typical children. Prospective and cross-sectional study. Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, São Paulo, Brazil. Weight and length of 381 children with cleft lip and palate and who were younger than 2 years were recorded and used to calculate W/A, L/A, and BMI growth curves. The 2006 World Health Organization growth charts were used as a reference for typical children. All children received a normal diet for age. Children with CLP/ICP had median W/A and BMI growth curves below growth curves for typical children but showed spontaneous recovery starting at approximately 5 months of age, even with nonoperated cleft palate. Children with ICL had growth similar to that of typical children. Children with CLP/ICP, who initially had W/A and BMI values less than those of the ICL group, had W/A and BMI equal to or higher than the ICL group after 9 months of age. Children with CLP/ICP had impaired W/A and BMI growth with spontaneous recovery starting early in childhood. This study established specific W/A, BMI, and L/A growth curves for children with cleft lip and palate.

Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate.

Science.gov (United States)

Wolf, Zena T; Brand, Harrison A; Shaffer, John R; Leslie, Elizabeth J; Arzi, Boaz; Willet, Cali E; Cox, Timothy C; McHenry, Toby; Narayan, Nicole; Feingold, Eleanor; Wang, Xioajing; Sliskovic, Saundra; Karmi, Nili; Safra, Noa; Sanchez, Carla; Deleyiannis, Frederic W B; Murray, Jeffrey C; Wade, Claire M; Marazita, Mary L; Bannasch, Danika L

2015-03-01

Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13); adjusted p= 2.2 x 10(-3)). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

Define Project

DEFF Research Database (Denmark)

Munk-Madsen, Andreas

2005-01-01

"Project" is a key concept in IS management. The word is frequently used in textbooks and standards. Yet we seldom find a precise definition of the concept. This paper discusses how to define the concept of a project. The proposed definition covers both heavily formalized projects and informally...... organized, agile projects. Based on the proposed definition popular existing definitions are discussed....

Iodine chemistry in a reactor regulation

Energy Technology Data Exchange (ETDEWEB)

Powers, D A [Nuclear Regulatory Commission, Washington, DC (United States). Advisory Committee on Reactor Safeguards

1996-12-01

Radioactive iodine has always been an important consideration in the regulation of nuclear power reactors to assure the health and safety of the public. Regulators adopted conservatively bounding predictions of iodine behavior in the earliest days of the development of nuclear power because there was so little known about either accidents or the chemistry of iodine. Today there is a flood of new information and understanding of the chemistry of iodine under reactor accident conditions. This paper offers some thoughts on how the community of scientists engaged in the study of iodine chemistry can present the results of their work so that it is more immediately adopted by the regulator. It is suggested that the scientific community consider the concept of consensus standards so effectively used within the engineering community to define the status of the study of radioactive iodine chemistry for reactor safety. (author) 9 refs.

Iodine chemistry in a reactor regulation

International Nuclear Information System (INIS)

Powers, D.A.

1996-01-01

Radioactive iodine has always been an important consideration in the regulation of nuclear power reactors to assure the health and safety of the public. Regulators adopted conservatively bounding predictions of iodine behavior in the earliest days of the development of nuclear power because there was so little known about either accidents or the chemistry of iodine. Today there is a flood of new information and understanding of the chemistry of iodine under reactor accident conditions. This paper offers some thoughts on how the community of scientists engaged in the study of iodine chemistry can present the results of their work so that it is more immediately adopted by the regulator. It is suggested that the scientific community consider the concept of consensus standards so effectively used within the engineering community to define the status of the study of radioactive iodine chemistry for reactor safety. (author) 9 refs

Development of Critical Thinking with Metacognitive Regulation

Science.gov (United States)

Gotoh, Yasushi

2016-01-01

In this research the author defines critical thinking as the set of skills and dispositions which enable one to solve problems logically and to attempt to reflect autonomously by means of Metacognitive regulation on one's own problem-solving processes. In order to develop their critical thinking, it is important for students to be able to use this…

Regulation of Romantic Love Feelings: Preconceptions, Strategies, and Feasibility

OpenAIRE

Langeslag, Sandra J. E.; van Strien, Jan W.

2016-01-01

textabstractLove feelings can be more intense than desired (e.g., after a break-up) or less intense than desired (e.g., in long-Term relationships). If only we could control our love feelings! We present the concept of explicit love regulation, which we define as the use of behavioral and cognitive strategies to change the intensity of current feelings of romantic love. We present the first two studies on preconceptions about, strategies for, and the feasibility of love regulation. Questionna...

A response regulator interfaces between the Frz chemosensory system and the MglA/MglB GTPase/GAP module to regulate polarity in Myxococcus xanthus.

Directory of Open Access Journals (Sweden)

Daniela Keilberg

2012-09-01

Full Text Available How cells establish and dynamically change polarity are general questions in cell biology. Cells of the rod-shaped bacterium Myxococcus xanthus move on surfaces with defined leading and lagging cell poles. Occasionally, cells undergo reversals, which correspond to an inversion of the leading-lagging pole polarity axis. Reversals are induced by the Frz chemosensory system and depend on relocalization of motility proteins between the poles. The Ras-like GTPase MglA localizes to and defines the leading cell pole in the GTP-bound form. MglB, the cognate MglA GTPase activating protein, localizes to and defines the lagging pole. During reversals, MglA-GTP and MglB switch poles and, therefore, dynamically localized motility proteins switch poles. We identified the RomR response regulator, which localizes in a bipolar asymmetric pattern with a large cluster at the lagging pole, as important for motility and reversals. We show that RomR interacts directly with MglA and MglB in vitro. Furthermore, RomR, MglA, and MglB affect the localization of each other in all pair-wise directions, suggesting that RomR stimulates motility by promoting correct localization of MglA and MglB in MglA/RomR and MglB/RomR complexes at opposite poles. Moreover, localization analyses suggest that the two RomR complexes mutually exclude each other from their respective poles. We further show that RomR interfaces with FrzZ, the output response regulator of the Frz chemosensory system, to regulate reversals. Thus, RomR serves at the functional interface to connect a classic bacterial signalling module (Frz to a classic eukaryotic polarity module (MglA/MglB. This modular design is paralleled by the phylogenetic distribution of the proteins, suggesting an evolutionary scheme in which RomR was incorporated into the MglA/MglB module to regulate cell polarity followed by the addition of the Frz system to dynamically regulate cell polarity.

Defining asthma in genetic studies

NARCIS (Netherlands)

Koppelman, GH; Postma, DS; Meijer, G.

1999-01-01

Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

Integrative proteomics and biochemical analyses define Ptc6p as the Saccharomyces cerevisiae pyruvate dehydrogenase phosphatase.

Science.gov (United States)

Guo, Xiao; Niemi, Natalie M; Coon, Joshua J; Pagliarini, David J

2017-07-14

The pyruvate dehydrogenase complex (PDC) is the primary metabolic checkpoint connecting glycolysis and mitochondrial oxidative phosphorylation and is important for maintaining cellular and organismal glucose homeostasis. Phosphorylation of the PDC E1 subunit was identified as a key inhibitory modification in bovine tissue ∼50 years ago, and this regulatory process is now known to be conserved throughout evolution. Although Saccharomyces cerevisiae is a pervasive model organism for investigating cellular metabolism and its regulation by signaling processes, the phosphatase(s) responsible for activating the PDC in S. cerevisiae has not been conclusively defined. Here, using comparative mitochondrial phosphoproteomics, analyses of protein-protein interactions by affinity enrichment-mass spectrometry, and in vitro biochemistry, we define Ptc6p as the primary PDC phosphatase in S. cerevisiae Our analyses further suggest additional substrates for related S. cerevisiae phosphatases and describe the overall phosphoproteomic changes that accompany mitochondrial respiratory dysfunction. In summary, our quantitative proteomics and biochemical analyses have identified Ptc6p as the primary-and likely sole- S. cerevisiae PDC phosphatase, closing a key knowledge gap about the regulation of yeast mitochondrial metabolism. Our findings highlight the power of integrative omics and biochemical analyses for annotating the functions of poorly characterized signaling proteins. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Educational Programming: A Seminar for Young Adults with Cleft Lip and/or Palate.

Science.gov (United States)

Imhoff, Michael; And Others

1981-01-01

The social service staff of the H. K. Cooper Clinic (Lancaster, Pennsylvania) conducted a seminar for young adults with cleft lip and palate (CL/P) and their families. The seminar was designed to respond to questions and concerns regarding the impact of CL/P on employment, social relations, and genetics. (SB)

Cross genome comparisons of serine proteases in Arabidopsis and rice

Directory of Open Access Journals (Sweden)

Sowdhamini R

2006-08-01

Full Text Available Abstract Background Serine proteases are one of the largest groups of proteolytic enzymes found across all kingdoms of life and are associated with several essential physiological pathways. The availability of Arabidopsis thaliana and rice (Oryza sativa genome sequences has permitted the identification and comparison of the repertoire of serine protease-like proteins in the two plant species. Results Despite the differences in genome sizes between Arabidopsis and rice, we identified a very similar number of serine protease-like proteins in the two plant species (206 and 222, respectively. Nearly 40% of the above sequences were identified as potential orthologues. Atypical members could be identified in the plant genomes for Deg, Clp, Lon, rhomboid proteases and species-specific members were observed for the highly populated subtilisin and serine carboxypeptidase families suggesting multiple lateral gene transfers. DegP proteases, prolyl oligopeptidases, Clp proteases and rhomboids share a significantly higher percentage orthology between the two genomes indicating substantial evolutionary divergence was set prior to speciation. Single domain architectures and paralogues for several putative subtilisins, serine carboxypeptidases and rhomboids suggest they may have been recruited for additional roles in secondary metabolism with spatial and temporal regulation. The analysis reveals some domain architectures unique to either or both of the plant species and some inactive proteases, like in rhomboids and Clp proteases, which could be involved in chaperone function. Conclusion The systematic analysis of the serine protease-like proteins in the two plant species has provided some insight into the possible functional associations of previously uncharacterised serine protease-like proteins. Further investigation of these aspects may prove beneficial in our understanding of similar processes in commercially significant crop plant species.

Immunomodulatory intervention with Gamma interferon in mice with sepsis.

Science.gov (United States)

Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong

2017-09-15

Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Emotion regulation and the dynamics of feelings: A conceptual and methodological framework [IF: 3.3

OpenAIRE

Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.M.

2004-01-01

The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed, identifies its goal, and illustrates how regulation is achieved. The thesis developed here is that feelings - the private mental experience of emotion - play a crucial role in emotion regulation. Spec...

Capsule Pipeline Research Center. 3-year Progress report, September 1, 1993--August 31, 1994

Energy Technology Data Exchange (ETDEWEB)

1994-04-01

The Capsule Pipeline Research Center is devoted to performing research in capsule pipelines so that this emerging technology can be developed for early use to transport solids including coal, grain, other agricultural products, solid wastes, etc. Important research findings and accomplishments during the first-three years include: success in making durable binderless coal logs by compaction, success in underwater extrusion of binderless coal logs, success in compacting and extruding coal logs with less than 3% hydrophobic binder at room temperature, improvement in the injection system and the pump-bypass scheme, advancement in the state-of-the-art of predicting the energy loss (pressure drop) along both stationary and moving capsules, demonstrated the effectiveness of using polymer for drag reduction in CLP, demonstrated the influence of zeta potential on coal log fabrication, improved understanding of the water absorption properties of coal logs, better understanding of the mechanism of coal log abrasion (wear), completed a detailed economic evaluation of the CLP technology and compared coal transportation cost by CLP to that by rail, truck and slurry pipelines, and completion of several areas of legal research. The Center also conducted important technology transfer activities including workshops, work sessions, company seminars, involvement of companies in CLP research, issuance of newsletters, completion of a video tape on CLP, and presentation of research findings at numerous national and international meetings.

Capsule Pipeline Research Center. 3-year Progress report, September 1, 1993--August 31, 1994

International Nuclear Information System (INIS)

1994-01-01

The Capsule Pipeline Research Center is devoted to performing research in capsule pipelines so that this emerging technology can be developed for early use to transport solids including coal, grain, other agricultural products, solid wastes, etc. Important research findings and accomplishments during the first-three years include: success in making durable binderless coal logs by compaction, success in underwater extrusion of binderless coal logs, success in compacting and extruding coal logs with less than 3% hydrophobic binder at room temperature, improvement in the injection system and the pump-bypass scheme, advancement in the state-of-the-art of predicting the energy loss (pressure drop) along both stationary and moving capsules, demonstrated the effectiveness of using polymer for drag reduction in CLP, demonstrated the influence of zeta potential on coal log fabrication, improved understanding of the water absorption properties of coal logs, better understanding of the mechanism of coal log abrasion (wear), completed a detailed economic evaluation of the CLP technology and compared coal transportation cost by CLP to that by rail, truck and slurry pipelines, and completion of several areas of legal research. The Center also conducted important technology transfer activities including workshops, work sessions, company seminars, involvement of companies in CLP research, issuance of newsletters, completion of a video tape on CLP, and presentation of research findings at numerous national and international meetings

A new record of late Pliocene-early Pleistocene aeolian loess-red clay deposits from the western Chinese Loess Plateau and its palaeoenvironmental implications

Science.gov (United States)

Zan, Jinbo; Fang, Xiaomin; Zhang, Weilin; Yan, Maodu; Zhang, Dawen

2018-04-01

The loess-red clay sequences in northern China provide high-resolution terrestrial records of Asian monsoon evolution and aridification of the Asian interior. To date, however, aeolian deposits of late Pliocene-early Pleistocene age (3.5-2.4 Ma) have only rarely been reported from the western Chinese Loess Plateau (CLP), which significantly hinders our understanding of the distribution of aeolian deposits and the palaeoenvironmental evolution of the region. Here, we present magnetostratigraphic, lithologic and magnetic susceptibility results for two recently-drilled boreholes from the north bank of Baxie River, central Linxia Basin, which are highly correlative with those of the loess-red clay deposits spanning the interval from 3.6 to 2.4 Ma in the eastern CLP. Our results provide the first direct evidence for the occurrence of late Pliocene-early Pleistocene aeolian deposits in the western CLP and provide new insights into the distribution of aeolian deposits in northern China. The spatial coherence of the magnetic susceptibility fluctuations further indicates that magnetic susceptibility is a powerful tool for stratigraphic correlation of late Pliocene aeolian deposits in the western CLP. In addition, our results demonstrate that erosional events may have occurred in the early or middle Pleistocene, and they may provide new insights into the reasons for the absence of loess-red clay deposits from 3.5 to 2.4 Ma in most parts of the western CLP.

Development and validation of the quality-of-life adolescent cleft questionnaire in patients with cleft lip and palate.

Science.gov (United States)

Piombino, Pasquale; Ruggiero, Federica; Dell'Aversana Orabona, Giovanni; Scopelliti, Domenico; Bianchi, Alberto; De Simone, Federica; Carnevale, Nina; Brancati, Federica; Iengo, Maurizio; Grassia, Maria Gabriella; Cataldo, Rosanna; Califano, Luigi

2014-09-01

Only a few reports in the literature have described the use of specific instruments for assessing the quality of life in adolescents and young adults with cleft lip and palate (CLP). This condition markedly affects their lifestyle, even after surgical treatment. In the present study, we aimed to develop a quality-of-life assessment tool specifically designed for such patients with CLP. Our multidisciplinary team created a questionnaire focused on the physical, psychological, and social satisfaction of adolescents and young adults with CLP, which was adapted from 3 dimensions of the 36-item Short-Form Health Survey. The questionnaire was administered to a randomized sample of 40 adolescents and young adults (aged 16-24 years) with CLP who had completed treatment protocols and 40 (aged 16-24 years) who were not affected by CLP. The statistical results stated that the questionnaire had good reliability and validity; the Cronbach α coefficient was found to be 0.944. Moreover, factorial analysis confirmed the presence of 3 subscales that were the fundamental components of this questionnaire, which is consistent with the areas theoretically proposed and from which the items were designed and selected. Thus, we validated our novel questionnaire that was administered in the present study and proved its consistency. However, further investigations on a larger population would be useful to confirm these findings.

A Comparative Study of Oral Microbiota in Infants with Complete Cleft Lip and Palate or Cleft Soft Palate.

Science.gov (United States)

Machorowska-Pieniążek, Agnieszka; Mertas, Anna; Skucha-Nowak, Małgorzata; Tanasiewicz, Marta; Morawiec, Tadeusz

2017-01-01

Few reports have been published on the early microbiota in infants with various types of cleft palate. We assessed the formation of the oral microbiota in infants with complete cleft lip and palate (CLP n = 30) or cleft soft palate (CSP n = 25) in the neonatal period (T1 time) and again in the gum pad stage (T2 time). Culture swabs from the tongue, palate, and/or cleft margin at T1 and T2 were taken. We analysed the prevalence of the given bacterial species (the percentage) and the proportions in which the palate and tongue were colonised by each microorganism. At T1, Streptococcus mitis (S. mitis) were the most frequently detected in subjects with CLP or CSP (63% and 60%, resp.). A significantly higher frequency of methicillin-sensitive Staphylococcus aureus ( S. aureus MSSA) was observed in CLP compared to the CSP group. At T2, significantly higher percentages of S. mitis , S. aureus MSSA, Staphylococcus epidermidis , and members of the Enterobacteriaceae family were noted in CLP infants compared to the CSP. S. mitis and Streptococcus sanguinis appeared with the greatest frequency on the tongue, whereas Streptococcus salivarius was predominant on the palate. The development of the microbiota in CLP subjects was characterised by a significant increase in the prevalence of pathogenic bacteria.

Regulated software meets DevOps

DEFF Research Database (Denmark)

Laukkarinen, Teemu; Kuusinen, Kati; Mikkonen, Tommi

2018-01-01

Context: Regulatory authorities require proofs from critical systems manufacturers that the software in their products is developed in accordance to prescribed development practices before accepting the product to the markets. This is challenging when using DevOps, where continuous integration...... and deployment are the default practices, which are not a good match with the regulatory software development standards. Objective: We aim to bring DevOps and regulated software development closer to each other. First, we want to make it easier for developers to develop regulated software with tools...... and practices they are familiar with. Second, we want to allow regulatory authorities to build confidence on solutions provided by manufacturers by defining a mapping between DevOps and regulatory software development. Method: We performed a literature survey and created research suggestions using exploratory...

Defining depth of anesthesia.

Science.gov (United States)

Shafer, S L; Stanski, D R

2008-01-01

In this chapter, drawn largely from the synthesis of material that we first presented in the sixth edition of Miller's Anesthesia, Chap 31 (Stanski and Shafer 2005; used by permission of the publisher), we have defined anesthetic depth as the probability of non-response to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of non-responsiveness at defined effect site concentrations. This definition requires measurement of multiple different stimuli and responses at well-defined drug concentrations. There is no one stimulus and response measurement that will capture depth of anesthesia in a clinically or scientifically meaningful manner. The "clinical art" of anesthesia requires calibration of these observations of stimuli and responses (verbal responses, movement, tachycardia) against the dose and concentration of anesthetic drugs used to reduce the probability of response, constantly adjusting the administered dose to achieve the desired anesthetic depth. In our definition of "depth of anesthesia" we define the need for two components to create the anesthetic state: hypnosis created with drugs such as propofol or the inhalational anesthetics and analgesia created with the opioids or nitrous oxide. We demonstrate the scientific evidence that profound degrees of hypnosis in the absence of analgesia will not prevent the hemodynamic responses to profoundly noxious stimuli. Also, profound degrees of analgesia do not guarantee unconsciousness. However, the combination of hypnosis and analgesia suppresses hemodynamic response to noxious stimuli and guarantees unconsciousness.

Emotion regulation and the dynamics of feelings: A conceptual and methodological framework [IF: 3.3

NARCIS (Netherlands)

Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.M.

2004-01-01

The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed,

Fetal genetic risk of isolated cleft lip only versus isolated cleft lip and palate: A subphenotype analysis using two population-based studies of orofacial clefts in scandinavia

DEFF Research Database (Denmark)

Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian

2010-01-01

BACKGROUND: Cleft lip only (CLO) and cleft lip and palate (CLP) are commonly regarded as variants of the same defect and are traditionally combined to form the single group of cleft lip with or without cleft palate (CL/P) prior to analysis. However, recent data have suggested that at least a subg...

Spectral Analysis of Word-Initial Alveolar and Velar Plosives Produced by Iranian Children with Cleft Lip and Palate

Science.gov (United States)

Eshghi, Marziye; Zajac, David J.; Bijankhan, Mahmood; Shirazi, Mohsen

2013-01-01

Spectral moment analysis (SMA) was used to describe voiceless alveolar and velar stop-plosive production in Persian-speaking children with repaired cleft lip and palate (CLP). Participants included 11 children with bilateral CLP who were undergoing maxillary expansion and 20 children without any type of orofacial clefts. Four of the children with…

Short-term effect of short, intensive speech therapy on articulation and resonance in Ugandan patients with cleft (lip and) palate

NARCIS (Netherlands)

Anke Luyten; H. Vermeersch; A. Hodges; K. Bettens; K. van Lierde; G. Galiwango

2016-01-01

Objectives: The purpose of the current study was to assess the short-term effectiveness of short and intensive speech therapy provided to patients with cleft (lip and) palate (C(L)P) in terms of articulation and resonance. Methods: Five Ugandan patients (age: 7.3-19.6 years) with non-syndromic C(L)P

Adolescent and adult cleft lip and palate, in Ile-Ife, Nigeria | Oladele ...

African Journals Online (AJOL)

Introduction: Congenital cleft lip and palate (CLP) defects usually present in childhood, especially in places with available and affordable care. In Nigeria, their incidence is low but late presentation in Adult life have been reported. This article aims at reviewing adolescent and adult CLP patients in our center, with the advent ...

Drinking Levels Defined

Science.gov (United States)

... of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special ... Definition of Drinking at Low Risk for Developing Alcohol Use Disorder (AUD): For women, low-risk drinking is defined ...

Western diet enhances hepatic inflammation in mice exposed to cecal ligation and puncture

Directory of Open Access Journals (Sweden)

Houghton Jeff

2010-10-01

Full Text Available Abstract Background Obese patients display an exaggerated morbidity during sepsis. Since consumption of a western-style diet (WD is a major factor for obesity in the United States, the purpose of the present study was to examine the influence of chronic WD consumption on hepatic inflammation in mice made septic via cecal ligation and puncture (CLP. Feeding mice diets high in fat has been shown to enhance evidence of TLR signaling and this pathway also mediates the hepatic response to invading bacteria. Therefore, we hypothesized that the combined effects of sepsis and feeding WD on TRL-4 signaling would exacerbate hepatic inflammation. Male C57BL/6 mice were fed purified control diet (CD or WD that was enriched in butter fat (34.4% of calories for 3 weeks prior to CLP. Intravital microscopy was used to evaluate leukocyte adhesion in the hepatic microcirculation. To demonstrate the direct effect of saturated fatty acid on hepatocytes, C3A human hepatocytes were cultured in medium containing 100 μM palmitic acid (PA. Quantitative real-time PCR was used to assess mRNA expression of tumor necrosis factor-alpha (TNF-α, monocyte chemotactic protein-1 (MCP-1, intercellular adhesion molecule-1 (ICAM-1, toll-like receptor-4 (TLR-4 and interleukin-8 (IL-8. Results Feeding WD increased firm adhesion of leukocytes in the sinusoids and terminal hepatic venules by 8-fold six hours after CLP; the increase in platelet adhesion was similar to the response observed with leukocytes. Adhesion was accompanied by enhanced expression of TNF-α, MCP-1 and ICAM-1. Messenger RNA expression of TLR-4 was also exacerbated in the WD+CLP group. Exposure of C3A cells to PA up-regulated IL-8 and TLR-4 expression. In addition, PA stimulated the static adhesion of U937 monocytes to C3A cells, a phenomenon blocked by inclusion of an anti-TLR-4/MD2 antibody in the culture medium. Conclusions These findings indicate a link between obesity-enhanced susceptibility to sepsis and

Chemical Growth Regulators for Guayule Plants

Science.gov (United States)

Dastoor, M. N.; Schubert, W. W.; Petersen, G. R.

1982-01-01

Test Tubes containing Guayule - tissue cultures were used in experiments to test effects of chemical-growth regulators. The shoots grew in response to addition of 2-(3,4-dichlorophenoxy)-triethylamine (triethylamine (TEA) derivative) to agar medium. Preliminary results indicate that a class of compounds that promotes growth in soil may also promote growth in a culture medium. Further experiments are needed to define the effect of the TEA derivative.

Developing social standards for wilderness encounters in Mount Rainier National Park: Manager-defined versus visitor-defined standards

Science.gov (United States)

Kristopher J. Lah

2000-01-01

This research compared the differences found between manager-defined and visitor-defined social standards for wilderness encounters in Mount Rainier National Park. Social standards in recreation areas of public land are defined by what is acceptable to the public, in addition to the area’s management. Social standards for the encounter indicator in Mount Rainier’s...

Dynamics of hepatic gene expression and serum cytokine profiles in single and double-hit burn and sepsis animal models

Directory of Open Access Journals (Sweden)

Rohit Rao

2015-06-01

Full Text Available We simulate the pathophysiology of severe burn trauma and burn-induced sepsis, using rat models of experimental burn injury and cecal ligation and puncture (CLP either individually (singe-hit model or in combination (double-hit model. The experimental burn injury simulates a systemic but sterile pro-inflammatory response, while the CLP simulates the effect of polymicrobial sepsis. Given the liver׳s central role in mediating the host immune response and onset of hypermetabolism after burn injury, elucidating the alterations in hepatic gene expression in response to injury can lead to a better understanding of the regulation of the inflammatory response, whereas circulating cytokine protein expression, reflects key systemic inflammatory mediators. In this article, we present both the hepatic gene expression and circulating cytokine/chemokine protein expression data for the above-mentioned experimental model to gain insights into the temporal dynamics of the inflammatory and hypermetabolic response following burn and septic injury. This data article supports results discussed in research articles (Yang et al., 2012 [1,4]; Mattick et al. 2012, 2013 [2,3]; Nguyen et al., 2014 [5]; Orman et al., 2011, 2012 [6–8].

Systematic development and optimization of chemically defined medium supporting high cell density growth of Bacillus coagulans.

Science.gov (United States)

Chen, Yu; Dong, Fengqing; Wang, Yonghong

2016-09-01

With determined components and experimental reducibility, the chemically defined medium (CDM) and the minimal chemically defined medium (MCDM) are used in many metabolism and regulation studies. This research aimed to develop the chemically defined medium supporting high cell density growth of Bacillus coagulans, which is a promising producer of lactic acid and other bio-chemicals. In this study, a systematic methodology combining the experimental technique with flux balance analysis (FBA) was proposed to design and simplify a CDM. The single omission technique and single addition technique were employed to determine the essential and stimulatory compounds, before the optimization of their concentrations by the statistical method. In addition, to improve the growth rationally, in silico omission and addition were performed by FBA based on the construction of a medium-size metabolic model of B. coagulans 36D1. Thus, CDMs were developed to obtain considerable biomass production of at least five B. coagulans strains, in which two model strains B. coagulans 36D1 and ATCC 7050 were involved.

A 3-Year Study of Self-Regulation in Montessori and Non-Montessori Classrooms

Science.gov (United States)

Ervin, Barbara; Wash, Pamela D.; Mecca, Marilyn E.

2010-01-01

Albert Bandura, the leading pioneer in the study of self-regulation, has defined the term as the child's ability to self-educate, self-direct, regulate motivation, and learn to think about what she is learning (1994). Lev Vygotsky's theory that children can be taught to think independently about how to solve problems expands upon Bandura's work…

Safe space. How you can define fair market value for medical-office building lease agreements with hospitals.

Science.gov (United States)

Murray, Chuck

2007-04-01

When entering into office-space lease agreements with hospitals, physician practice administrators need to pay close attention to the federal antikick-back statute and the Stark law. Compliance with these regulations calls for adherence to fair market value and commercial reasonableness--blurry terms open to interpretation. This article provides you with a framework for defining fair market value and commercial reasonableness in regard to real-estate transactions with hospitals.

Performance based regulation: a strategy to increase breastfeeding rates

Directory of Open Access Journals (Sweden)

Fernanda Cobo-Armijo

2017-05-01

Full Text Available The decreasing breastfeeding rate in México is of public health concern. In this paper we discus an innovative regulatory ap­proach -Performance Based Regulation- and its application to improve breastfeeding rates. This approach, forces industry to take responsibility for the lack of breastfeeding and its consequences. Failure to comply with this targets results in financial penalties. Applying performance based regulation as a strategy to improve breastfeeding is feasible because: the breastmilk substitutes market is an oligopoly, hence it is easy to identify the contribution of each market participant; the regulation’s target population is clearly defined; it has a clear regulatory standard which can be easily evaluated, and sanctions to infringement can be defined under objective parameters. Recommendations: modify public policy, celebrate concertation agreements with the industry, create persuasive sanctions, strengthen enforcement activities and coordinate every action with the International Code of Marketing of Breast-milk Substitutes.

The Role of TSC Proteins in Regulating Cell Adhesion and Motility

National Research Council Canada - National Science Library

Krymskaya, Vera P

2006-01-01

The goal of this project was to define the molecular signaling mechanisms by which TSCI and TSC2 proteins regulate cell adhesion and motility as it relates to the genetic disorder tuberous sclerosis complex (TSC...

HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies

DEFF Research Database (Denmark)

Monforte, Antonella d'Arminio; Abrams, Donald; Pradier, Christian

2008-01-01

OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively......-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality...

Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

Directory of Open Access Journals (Sweden)

Charles E Bane

Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

Potential of Zimbabwean commercial probiotic products and strains of Lactobacillus plantarum as prophylaxis and therapy against diarrhoea caused by Escherichia coli in children.

Science.gov (United States)

Chingwaru, Walter; Vidmar, Jerneja

2017-01-01

To evaluate the potential of commercial fermented products sold in the country, and strains of Lactobacillus plantarum (L. plantarum) as prophylaxis and therapy against diarrhoea in children. The antimicrobial potential of cultures of lactobacilli enriched from 4 Zimbabwean commercial food/beverage products: Dairibord Lacto sour milk (DLSM), Probrand sour milk (PSM), Kefalos Vuka cheese (KVC) and Chibuku opaque beer (COB); and four strains of L. plantarum obtained from Balkan traditional cheeses against clinical strains of Escherichia coli (E. coli) was assayed using the well diffusion method. Three commercial paediatric antidiarrhoeal drug products: Biogaia (BG), Prolife (PL) and Probio Junior (PJ) and a mutant strain of E. coli [strain 11105 (ATCC) - a vitamin B-12 auxotroph and penicillin G acylase-producing strain] were used as controls. An agar diffusion assay and a competitive exclusion assay were carried out on Mueller Hinton agar. Crude cultures of putative lactobacillus strains obtained from Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer) had significantly higher antimicrobial activities against clinical strains of E. coli than strains of L. plantarum isolated from Balkan cheeses (CLP1, CLP2 or CLP3) and crude microbial cultures from commercial paediatric probiotic products (BG, PJ and PL) of a culture of Lactobacillus rhamnosus LGG (P sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer), and three strains of L. plantarum from Balkan cheeses (CLP1, CLP2 or CLP3) exhibited high antibacterial activities that can be harnessed to control paediatric diarrhoea that is caused by pathogenic strains of E. coli. Studies to characterise the probiotic potential of the live cultures in the products and the new strains of L. plantarum are underway. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Oral clefts, consanguinity, parental tobacco and alcohol use: a case-control study in Rio de Janeiro, Brazil

Directory of Open Access Journals (Sweden)

Isabel Cristina Gonçalves Leite

2009-03-01

Full Text Available This hospital-based, case-control study investigated the possible associations between family history of malformations, parental consanguinity, smoking and alcohol drinking and nonsyndromic orofacial cleft (OC, subdivided in 2 main groups: CL/P - cleft lip with or without cleft palate and CP - cleft palate alone. 274 cases were matched (age, sex and place of residence to 548 controls. Odds ratios (OR and 95% confidence intervals (95% CI - adjusted for maternal age, schooling and smoking / alcohol use - were calculated by conditional logistic regression. The results demonstrated that the history of oral clefts either in the father's (CL/P: OR = 16.00, 5.64-69.23; CP: OR = 6.64, 1.48-33.75 or in the mother's family (CL/P: OR = 5.00, 2.31-10.99, CP: OR = 12.44, 1.33-294.87 was strongly associated with both types of clefts, but parental consanguinity was associated only with CL/P (OR = 3.8, 1.27-12.18. Prevalence of maternal smoking during the first trimester of pregnancy was higher among cases but the OR (1.13, 0.81-1.57 was not statistically significant. Maternal passive smoking (nonsmoking mothers during pregnancy was associated with CL/P (1.39, 1.01-1.98 but not with CP. Maternal alcohol use during the 1st trimester increased odds for CL/P (OR = 2.08, 1.27-3.41 and CP (OR = 2.89, 1.25-8.30, and odds for OC tended to increase with dose. Neither smoking nor alcohol use by fathers increased risks for OC. This study provides further evidence of a possible role of maternal exposure to tobacco smoke and alcohol in the etiology of nonsyndromic oral clefts.

Dependence of the cyclization of branched tetraethers (CBT) on soil moisture in the Chinese Loess Plateau and the adjacent areas: implications for palaeorainfall reconstructions

Science.gov (United States)

Wang, H.; Liu, W.; Zhang, C. L.

2014-06-01

Branched glycerol dialkyl glycerol tetraethers (bGDGTs) have been show promising for continental paleotemperature studies in loess-paleosol sequences (LPSs). Thus far, however, little is known about the effect of soil moisture on their distributions on the Chinese Loess Plateau (CLP). In this study, the relationships between environmental variables and the cyclization of bGDGTs (the so called CBT index) were investigated in a comprehensive set of surface soils in the CLP and its adjacent arid/semi-arid areas. We find that CBT correlates best with soil water content (SWC) or mean annual precipitation (MAP) for the total sample set. Particularly for the CLP soils, there is a significant positive relationship between CBT and MAP (CBT = -0.0021 · MAP + 1.7, n = 37, R2 = 0.87; MAP range: 210-680 mm). This indicates that CBT is mainly controlled by soil moisture in the alkalescent soils (pH > 7) in arid/semi-arid regions, where it is not sensitive to soil pH. Therefore, we suggest that CBT can potentially be used as a palaeorainfall proxy on the CLP. According to the preliminary CBT-MAP relationship for modern CLP soils, palaeorainfall history was reconstructed from three LPSs (Yuanbao, Lantian, and Mangshan) with published bGDGT data spanning the past 70 ka. The CBT-derived MAP records of the three sites consistently show precession-driven variations resembling the speleothem δ18O monsoon record, and are also in general accord with the fluctuations of the respective magnetic susceptibility (MS) record, supporting CBT as a reasonable proxy for palaeorainfall reconstruction in LPS studies. Moreover, the comparison of CBT-derived MAP and bGDGT-derived temperature may enable us to further assess the relative timing and magnitude of hydrological and thermal changes on the CLP, independent of chronology.

Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate.

Directory of Open Access Journals (Sweden)

Zena T Wolf

2015-03-01

Full Text Available Cleft lip with or without cleft palate (CL/P is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13; adjusted p= 2.2 x 10(-3. Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3, which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6 with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

Point-Counterpoint: The FDA Has a Role in Regulation of Laboratory-Developed Tests.

Science.gov (United States)

Caliendo, Angela M; Hanson, Kimberly E

2016-04-01

Since the Food and Drug Administration (FDA) released its draft guidance on the regulation of laboratory-developed tests (LDTs) in October 2014, there has been a flurry of responses from commercial and hospital-based laboratory directors, clinicians, professional organizations, and diagnostic companies. The FDA defines an LDT as an "in vitrodiagnostic device that is intended for clinical use and is designed, manufactured, and used within a single laboratory." The draft guidance outlines a risk-based approach, with oversight of high-risk and moderate-risk tests being phased in over 9 years. High-risk tests would be regulated first and require premarket approval. Subsequently, moderate-risk tests would require a 510(k) premarket submission to the FDA and low-risk tests would need only to be registered. Oversight discretion would be exercised for LDTs focused on rare diseases (defined as fewer than 4,000 tests, not cases, per year nationally) and unmet clinical needs (defined as those tests for which there is no alternative FDA-cleared or -approved test). There was an open comment period followed by a public hearing in early January of 2015, and we are currently awaiting the final decision regarding the regulation of LDTs. Given that LDTs have been developed by many laboratories and are essential for the diagnosis and monitoring of an array of infectious diseases, changes in their regulation will have far-reaching implications for clinical microbiology laboratories. In this Point-Counterpoint, Angela Caliendo discusses the potential benefits of the FDA guidance for LDTs whereas Kim Hanson discusses the concerns associated with implementing the guidance and why these regulations may not improve clinical care. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

78 FR 69509 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Science.gov (United States)

2013-11-19

... incentives for the CLP Program\\5\\ and thereafter amended certain of the financial incentives and criteria for... of daily financial rewards on the number of SET Credits awarded to CLPs; (3) change the allocation of the daily financial rewards to a set dollar value per CLP in each class of security; and (4) make...

Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention

DEFF Research Database (Denmark)

Henriksen, Ulrik Lütken; Hansen, Hanne B; Ring-Larsen, Helmer

2015-01-01

the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. Results. In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 m...

Blood-informative transcripts define nine common axes of peripheral blood gene expression.

Directory of Open Access Journals (Sweden)

Marcela Preininger

Full Text Available We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs, generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.

Blood-informative transcripts define nine common axes of peripheral blood gene expression.

Science.gov (United States)

Preininger, Marcela; Arafat, Dalia; Kim, Jinhee; Nath, Artika P; Idaghdour, Youssef; Brigham, Kenneth L; Gibson, Greg

2013-01-01

We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB) cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs), generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.

The Difference in Cervical Vertebral Skeletal Maturation between Cleft Lip/Palate and Non-Cleft Lip/Palate Orthodontic Patients

Directory of Open Access Journals (Sweden)

Waeil Batwa

2018-01-01

Full Text Available Objective. The aim was to evaluate differences in the cervical vertebral skeletal maturity of unilateral cleft lip and palate (UCLP and non-cleft lip/palate (non-CLP Saudi male orthodontic patients. Method. This cross-sectional multicenter study took place at the dental school, King Saud University and King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between October 2014 and September 2015. The records of Saudi male orthodontic patients with UCLP n=69 were collected. Cervical vertebral maturation was assessed using their cephalometric radiographs. The records of 138 age-matched non-CLP Saudi male orthodontic patients served as controls. Results. There was a significant difference in skeletal maturity between the UCLP and non-CLP groups, as evident in the delayed skeletal development among the UCLP participants. Moreover, pubertal growth spurt onset was significantly earlier in the non-cleft participants in comparison with the UCLP participants p=0.009. Conclusions. There is delayed skeletal maturity among the UCLP Saudi male population in comparison with their non-CLP age-matched peers.

Disclosure of congenital cleft lip and palate to Japanese patients: reported patient experiences and relationship to self-esteem.

Science.gov (United States)

Omiya, Tomoko; Ito, Mikiko; Yamazaki, Yoshihiko

2014-12-16

The present study investigated when and how Japanese people with cleft lip and palate (CL/P) learn that their condition is congenital; the perceived effects of withholding the CL/P diagnosis on patients; and whether the resulting social experience and self-esteem are related. A questionnaire survey was conducted in 71 adults with CL/P recruited through a hospital, a patients' association, and by snowball sampling. The participants became aware of their physical difference in childhood, but many reported difficulty in understanding their condition. Participants reported that their families avoided the topic of diagnosis. Participants who understood their condition during childhood rather than in adulthood were significantly more likely to consider this scenario as positive (p self-esteem were more likely to feel that they received adequate support. It is important to explain the congenital nature of CL/P sufficiently and early. In addition, openness by the family about the diagnosis, rather than avoidance, may improve patients' self-esteem. Sufficient support from family, health care providers, and significant others is needed for patients to develop adequate self-esteem.

[Risk factors for teeth aplasia and hypoplasia in cleft lip and palate children].

Science.gov (United States)

Korolenkova, M V; Starikova, N V; Ageeva, L V

2016-01-01

The aim of the study was to assess the significance of environmental risk factors for teeth aplasia and hypoplasia in cleft lip and palate children. Two hundred and forty-seven cleft lip and palate (CLP) children were enrolled in the study including 105 (42.5%) with bilateral CLP and 57.5% with unilateral CLP. The mean age was 11.2±4.9 years. Teeth condition was assessed clinically and radiologically. The impact of risk factors for teeth anomalies was analyzed by retrospective data obtained from computer database (absence of preoperative orthopedic treatment, palatal defects after primary palatoplasty and type of primary procedures). Surgical trauma by early periosteoplasty (at the age of 3-4 months), excessive scarring and tissue traction due to absence of early orthopedic treatment and palatal defect were associated with significantly higher incidence of incisors hypoplasia (both developmental enamel defects and microdentia) and aplasia of central incisors not seen in the other study subgroups. Incisors aplasia and hypoplasia in CLP patients do not always have disembryogenic origin but may depend on external environmental factors, including surgical trauma.

ON DEFINING S-SPACES

Directory of Open Access Journals (Sweden)

Francesco Strati

2013-05-01

Full Text Available The present work is intended to be an introduction to the Superposition Theory of David Carfì. In particular I shall depict the meaning of his brand new theory, on the one hand in an informal fashion and on the other hand by giving a formal approach of the algebraic structure of the theory: the S-linear algebra. This kind of structure underpins the notion of S-spaces (or Carfì-spaces by defining both its properties and its nature. Thus I shall define the S-triple as the fundamental principle upon which the S-linear algebra is built up.

Association between alleles of the transforming growth factor alpha locus and cleft lip and palate in the Chilean population

Energy Technology Data Exchange (ETDEWEB)

Jara, L.; Blanco, R.; Chiffelle, I. [Univ. of Chile, Santiago (Chile)] [and others

1995-07-17

Two RFLPs at the TGFA locus were studied in 39 unrelated Chilean (Caucasoid-Mongoloid) patients with non-syndromic cleft lip/palate [CL(P)] and 51 control individuals. A highly significant association between BamHI A2 allele and CL(P) was detected ({chi}{sub 2} = 6.00; P = 0.014), while no association was found between TaqI RFLPs and clefting. No significant differences were found when comparing genotypes by type of cleft and a positive or negative family history of clefting. Our results seem to support rather definitively the association between TGFA and clefting but not support the hypothesis that TGFA is a major causal gene of CL(P). 29 refs., 5 tabs.

Development of French technical safety regulations: safety fundamental rules

International Nuclear Information System (INIS)

Lebouleux, P.

1982-09-01

The technical regulation related to nuclear safety in France is made of a set of regulation texts, of a different nature, that define the requirements for the construction, commissioning and operations of nuclear facilities. Simultaneously, the safety authorities (Service Central de Surete des Installations Nucleaires: SCSIN) issue recommendations or guides which are not strictly speaking regulations in the juridical sense; they are called ''Regles Fondamentales de Surete'' (RFS). The RFS set up and detail the conditions, the respect of which is deemed to be complying with the French regulation pratice, for the subject to which they relate. Their purpose is to make known rules judged acceptable by safety authorities, thus making the safety review easier. The RFS program is described. A RFS -or a letter- can also give the result of the examination of the constructor and operator code (RCC) by safety authorities

Development of French technical safety regulations: safety fundamental rules

International Nuclear Information System (INIS)

Lebouleux, P.

1983-01-01

The technical regulation related to nuclear safety in France is made of a set of regulation texts, of a different nature, that define the requirements for the construction, commissioning and operating of nuclear facilities. Simultaneously, the safety authorities (Service Central de Surete des Installations Nucleaires: SCSIN) issue recommendations or guides which are not strictly speaking regulations in the juridicial sense; they are called Regles Fondamentales de Surete (RFS). The RFS set up and detail the conditions, the respect of which is deemed to be complying with the French regulation practice, for the subject to which they relate. Their purpose is to make known rules judged acceptable by safety authorities, thus making the safety review easier. The RFS program is described. A RFS - or a letter - can also give the result of the examination of the constructor and operator codes (RCC) by safety authorities

78 FR 34020 - Federal Acquisition Regulation; Uniform Procurement Identification

Science.gov (United States)

2013-06-06

...: Submit comments in response to FAR Case 2012-023 by any of the following methods: Regulations.gov : http... defined to mean a distinct six- position code consisting of a combination of alpha and/or numeric... 17 alpha and/or numeric characters configured to convey certain information. Positions one through...

Regulation of Stem Cell Differentiation by Histone Methyltransferases and Demethylases

DEFF Research Database (Denmark)

Pasini, D; Bracken, A P; Agger, K

2008-01-01

The generation of different cell types from stem cells containing identical genetic information and their organization into tissues and organs during development is a highly complex process that requires defined transcriptional programs. Maintenance of such programs is epigenetically regulated...... and the factors involved in these processes are often essential for development. The activities required for cell-fate decisions are frequently deregulated in human tumors, and the elucidation of the molecular mechanisms that regulate these processes is therefore important for understanding both developmental...

Automated detection of alveolar arches for nasoalveolar molding in cleft lip and palate treatment

Directory of Open Access Journals (Sweden)

Bauer Franz X.

2016-09-01

Full Text Available Nasoalveolar moulding (NAM has become a widely accepted and evidence-based treatment strategy for newborns with cleft lip and palate (CLP, attempting to reduce the cleft gap and to form an appropriately shaped alveolar arch by an intraoral patient-specific NAM plate and to erect the usually flattened nostrils towards a natural nose wing occurrence. The generation of such an appropriately shaped NAM plate requires, besides 3d information of the patient’s initially cleft lip and palate, an estimated target model of the maxilla. Previous studies showed the applicability of curve-based approaches to describe the maxilla during early infancy. We have developed an automated algorithm implemented with the programming language Python, describing the alveolar arch by an approximated ellipse. Therefore, the digitalized data sets of human maxillae were aligned to a global coordinate system with a total least square method and subsequently analyzed with the curvature-based algebraic point set surfaces (APSS algorithm. The gathered information of height ratio and curvature allows the detection of points on the alveolar segments and therewith the fit of an ellipse describing the human maxilla. In 84.5% of 193 maxilla impressions of healthy newborns the fitted ellipses described the course of the maxilla within defined margins. Applying the algorithm to 38 newborns suffering from unilateral cleft lip and palate in 76.3% the fitted ellipses bridge the CLP alveolar segments, so that a harmonic alveolar arch can be deduced. Describing the alveolar arch by one or multiple ellipses allows (i to automatically measure the dimensions of the maxilla, (ii to derive a growth model during early infancy, (iii to derive a healthy harmonic arch from CLP alveolar segments and (iv to automatically generate a basic NAM device on the basis of the virtually modified maxilla.

Getting a grip on your feelings: Effects of action orientation and external demands on intuitive affect regulation

NARCIS (Netherlands)

Koole, S.L.; Jostmann, N.B.

2004-01-01

The authors propose that volitional action is supported by intuitive affect regulation, defined as flexible, efficient, and nonrepressive control of own affective states. Intuitive affect regulation should be most apparent among action-oriented individuals under demanding conditions. Consistent with

76 FR 26853 - Commercial Driver's License Testing and Commercial Learner's Permit Standards

Science.gov (United States)

2011-05-09

... that the proposed rule would require costly and time-consuming travel as well as delays to starting... REAL ID c. Domicile d. State Compliance Issues IV. Changes to the Proposed Rule in This Final Rule... prescribed by the Secretary and may have only one CLP at a time; that the CLP document must have the same...

Comparing caries risk profiles between 5- and 10- year-old children with cleft lip and/or palate and non-cleft controls.

Science.gov (United States)

Sundell, Anna Lena; Ullbro, Christer; Marcusson, Agneta; Twetman, Svante

2015-07-25

Previous studies have suggested that children with oral clefts may have higher caries prevalence in comparison with non-cleft controls but the relative importance of the potential risk factors is not clear. The aim of this study was to compare the caries risk profiles in a group of cleft lip and/or palate (CL(P)) children with non-cleft controls in the same age using a computerized caries risk assessment model. The study group consisted of 133 children with CL(P) (77 subjects aged 5 years and 56 aged 10 years) and 297 non-cleft controls (133 aged 5 years and 164 aged 10 years). A questionnaire was used to collect data concerning the child's oral hygiene routines, dietary habits and fluoride exposure. Oral hygiene was assessed using Quigley-Hein plaque Index and the caries prevalence and frequency was scored according to the International Caries Detection and Assessment System. Whole saliva samples were analyzed for mutans streptococci, lactobacilli, buffering capacity and secretion rate. The risk factors and risk profiles were compared between the groups with aid of Cariogram and the estimated risk for future caries was categorized as "high" or "low". Children with CL(P) (the entire study group) had significantly higher counts of salivary lactobacilli (p < 0.05) and displayed less good oral hygiene (p < 0.05). More 10-year-old children in the CL(P) group had low secretion rate but this difference was not significant. The average chance to avoid caries ranged from 59 to 67% but there were no significant differences between the groups. The odds of being categorized with high caries risk in the CL(P) group was significantly elevated (OR = 1.89; 95% CI = 1.25-2.86). In both groups, children in the high risk category had a higher caries experience than those with low risk. Children with CL(P) displayed increased odds of being categorized at high caries risk with impaired oral hygiene and elevated salivary lactobacilli counts as most influential factors. The results

ER-E3 regulation. Minimal instrumentation that must operate nuclear medicine in Cuba

International Nuclear Information System (INIS)

2015-01-01

The purpose of this regulation is to define the instrumentation that must exist in any institution conducting the practice of nuclear medicine in Cuba. This regulation emphasizes two aspects: The minimum equipment necessary to operate a nuclear medicine laboratory for use 'in vitro' and the minimum equipment required to operate a Nuclear Medicine use 'in vivo'

Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

International Nuclear Information System (INIS)

DiCicco-Bloom, E.; Black, I.B.

1988-01-01

While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating [ 3 H]thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of [ 3 H]thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain

Defining and Classifying Interest Groups

DEFF Research Database (Denmark)

Baroni, Laura; Carroll, Brendan; Chalmers, Adam

2014-01-01

The interest group concept is defined in many different ways in the existing literature and a range of different classification schemes are employed. This complicates comparisons between different studies and their findings. One of the important tasks faced by interest group scholars engaged...... in large-N studies is therefore to define the concept of an interest group and to determine which classification scheme to use for different group types. After reviewing the existing literature, this article sets out to compare different approaches to defining and classifying interest groups with a sample...... in the organizational attributes of specific interest group types. As expected, our comparison of coding schemes reveals a closer link between group attributes and group type in narrower classification schemes based on group organizational characteristics than those based on a behavioral definition of lobbying....

Removal of carbofuran is not affected by co-application of chlorpyrifos in a coconut fiber/compost based biomixture after aging or pre-exposure.

Science.gov (United States)

Chin-Pampillo, Juan Salvador; Masís-Mora, Mario; Ruiz-Hidalgo, Karla; Carazo-Rojas, Elizabeth; Rodríguez-Rodríguez, Carlos E

2016-08-01

Biomixtures constitute the biologically active part of biopurification systems (BPS), which are used to treat pesticide-containing wastewater. The aim of this work was to determine whether co-application of chlorpyrifos (CLP) affects the removal of carbofuran (CFN) (both insecticide/nematicides) in a coconut fiber-compost-soil biomixture (FCS biomixture), after aging or previous exposure to CFN. Removal of CFN and two of its transformation products (3-hydroxycarbofuran and 3-ketocarbofuran) was enhanced in pre-exposed biomixtures in comparison to aged biomixtures. The co-application of CLP did not affect CFN removal, which suggests that CLP does not inhibit microbial populations in charge of CFN transformation. Contrary to the removal behavior, mineralization of radiolabeled (14)C-pesticides showed higher mineralization rates of CFN in aged biomixtures (with respect to freshly prepared or pre-exposed biomixtures). In the case of CLP, mineralization was favored in freshly prepared biomixtures, which could be ascribed to high sorption during aging and microbial inhibition by CFN in pre-exposure. Regardless of removal and mineralization results, toxicological assays revealed a steep decrease in the acute toxicity of the matrix on the microcrustacean Daphnia magna (over 97%) after 8days of treatment of individual pesticides or the mixture CFN/CLP. Results suggest that FCS biomixtures are suitable to be used in BPS for the treatment of wastewater in fields where both pesticides are employed. Copyright © 2016. Published by Elsevier B.V.

Cultural and religious components in Nigerian parents' perceptions of the aetiology of cleft lip and palate: implications for treatment and rehabilitation.

Science.gov (United States)

Olasoji, H O; Ugboko, V I; Arotiba, G T

2007-06-01

The present study was conducted to find out the perceptions of mothers from two Nigerian ethnic groups who had children with cleft lip and palate (CLP) about the aetiology of the defect. Mothers of 16 children with CLP from the Yoruba ethnic group who attended the maxillofacial clinic of the Obafemi Awolowo University teaching hospital in southern Nigeria and 20 children with CLP from the Hausa/Fulani ethnic group who attended the maxillofacial clinic of the University of Maiduguri teaching hospital in northeastern Nigeria were interviewed over an 8-month period. We used standardised interviews including questions with ethnographic components to allow us to collect information about traditional beliefs about clefts. Interviews were recorded on tape for later analysis. Thirteen of the 16 parents from the Yoruba group attributed the aetiology of CLP to supernatural forces (evil spirits and ancestral spirits), while 16 of the 20 Hausa/Fulani parents attributed it to the "will of God". Twelve of 16 Yoruba parents had consulted traditional healers for treatment before coming to the hospital. Various plants and animal products were used to treat clefts and 10 of the Yoruba parents were referred to the hospital for further treatment by the traditional healers. Cultural and religious factors seem to have an important role in the explanations, labels and treatment that followed the birth of a child with CLP in this environment. There is a need for greater collaboration and sharing of information between modern medical practitioners and traditional healers.

Airway Obstruction and the Unilateral Cleft Lip and Palate Deformity: Contributions by the Bony Septum.

Science.gov (United States)

Friel, Michael T; Starbuck, John M; Ghoneima, Ahmed M; Murage, Kariuki; Kula, Katherine S; Tholpady, Sunil; Havlik, Robert J; Flores, Roberto L

2015-07-01

Patients with unilateral cleft lip and palate (CLP) deformities commonly develop nasal airway obstruction, necessitating septoplasty at the time of definitive rhinoplasty. We assessed the contribution of the bony septum to airway obstruction using computed tomography (CT) and cone beam CT (CBCT). A 2-year retrospective review of all subjects with unilateral CLP who underwent CBCT imaging (n = 22) and age-matched controls (n = 9) who underwent CT imaging was conducted. Control CT scans were used to determine the segment of nasal septum comprised almost entirely of bone. The CBCT of the nasal airway was assessed using Dolphin software to determine the contribution of the bony septum to septal deviation and airway obstruction. The nasal septum posterior to the midpoint between anterior and posterior nasal spine is comprised of 96% bone. The nasal airway associated with this posterior bony segment was 43.1% (P < 0.001) larger by volume on the non-cleft side in patients with unilateral CLP. The average septal deviation within the posterior bony segment was 5.4 mm, accounting for 74.4% of the maximal deviation within the nasal airway. The average airway stenosis within the posterior bony nasal airway was 0.45 mm (0-2.2 mm). In patients with unilateral CLP, the bony nasal septum can demonstrate significant deviation and airway stenosis. Surgeons should consider a bony septoplasty in their treatment algorithm in unilateral CLP patients who have reached skeletal maturity.

A qualitative study of psychosocial factors affecting expecting mothers who choose to continue a cleft lip and/or palate pregnancy to term.

Science.gov (United States)

Hsieh, Yueh-Tzu; Chao, Yu-Mei Yu; Shiao, Judith Shu-Chu

2013-03-01

Prenatal detection of cleft lip and/or palate (CL/P) leads to high rates of induced termination of pregnancy. There has been little research in Taiwan done on the psychosocial factors affecting those who decide to continue their CL/P pregnancy. This study identified the principal psychosocial factors that affect expecting mothers who chose to continue their CL/P pregnancy to term. Purposive sampling recruited expecting mothers with CL/P-diagnosed fetuses. Recruiting took place between May 2000 and March 2002 at a tertiary referral hospital in Taipei, Taiwan. Those who had decided to continue their pregnancy to term were asked to participate. Researchers obtained oral informed consent to be interviewed during the week following CL/P diagnosis. Interviews for each participant were completed within a 2-week period. All information was given to the interviewees in written and verbal forms before providing their written informed consent to participate. The five major themes central to participant experiences included (1) loss of self-value as a mother, (2) blaming the mother, (3) indecision about whether to continue the pregnancy, (4) anxiety triggered by insufficient information, and (5) burden of care and concerns about potential disadvantaged status. Significant psychological distress was identified among participants following their fetus' CL/P diagnosis. It was encouraging to learn that all participants told researchers in postpartum interviews that they did not regret the decision to take their child to term.

Novel FGFR1 and KISS1R Mutations in Chinese Kallmann Syndrome Males with Cleft Lip/Palate

Directory of Open Access Journals (Sweden)

Hao Xu

2015-01-01

Full Text Available Kallmann syndrome (KS is characterized by isolated hypogonadotropic hypogonadism (IHH with anosmia and is sometimes associated with cleft lip/palate (CLP. In order to describe the clinical features, genetic etiology, and treatment outcome of KS males with CLP, we performed genetic screening for 15 known causal IHH genes (KAL1, FGFR1, NELF, FGF8, CHD7, WDR11, SEMA3A, KISS1R, KISS1, PROKR2, PROK2, TAC3, TACR3, GNRH1, and GNRHR in four KS with CLP patients and six IHH patients without CLP. Two novel heterozygous missense mutations in FGFR1, (NM_001174066: c.776G>A (p.G259E and (NM_001174066: c.358C>T (p.R120C, were identified in a 23-year-old KS male with cleft lip and an 18-year-old KS patient with cleft lip and palate, dental agenesis, and high arched palate, respectively. These two mutations were not presented in their healthy parents and 200 normal controls. One novel heterozygous missense mutation in KISS1R, (NM_032551: c.587C>A (p.P196H, was identified in an 18-year-old KS male with cleft lip and dental agenesis who developed sperm after being treated with gonadotropin. This mutation was also presented in his healthy father and grandfather. These results have implications for the diagnosis, genetic counseling, and treatment of KS and CLP males with mutations in FGFR1 gene.

Association study between Van der Woude Syndrome causative gene GRHL3 and nonsyndromic cleft lip with or without cleft palate in a Chinese cohort.

Science.gov (United States)

Wang, Yirui; Sun, Yimin; Huang, Yongqing; Pan, Yongchu; Jia, Zhonglin; Ma, Lijuan; Ma, Lan; Lan, Feifei; Zhou, Yuxi; Shi, Jiayu; Yang, Xiong; Zhang, Lei; Jiang, Hongbing; Jiang, Min; Yin, Aihua; Cheng, Jing; Wang, Lin; Yang, Yinxue; Shi, Bing

2016-08-15

Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects worldwide and is characterized by abnormalities of the orofacial structure. Syndromic CL/P is mainly caused by Mendelian disorders such as Van der Woude Syndrome (VWS). However, >70% of CL/P cases are nonsyndromic, characterized by isolated orofacial cleft without any known syndrome. The etiology of nonsyndromic CL/P (NSCL/P) remains elusive, but it has been suggested that causative genes of syndromic CL/P might also contribute to NSCL/P. As such, the VWS causative gene IRF6 has been extensively studied in NSCL/P. Recently, GRHL3 was identified as another VWS causative gene. Thus, it may be a novel candidate gene for NSCL/P. In the present study, we genotyped 10 tag SNPs covering GRHL3 and performed association analysis with NSCL/P in 504 cases and 455 healthy controls. Our preliminary results identified rs10903078, rs4638975, and a haplotype rs10903078-rs6659209 of GRHL3 that exceeded the significance threshold (p<0.05), though none survived Bonferroni correction for multiple comparisons. As the first study between GRHL3 and NSCL/P, the contribution of this gene to NSCL/P etiology should be interpreted with caution based on existing evidence. Further, the robustness of association between GRHL3 and NSCL/P should be further validated in expanded cohorts. Copyright © 2016. Published by Elsevier B.V.

Categorizing Mistaken False Positives in Regulation of Human and Environmental Health

DEFF Research Database (Denmark)

Hansen, Steffen Foss; Krayer von Krauss, Martin Paul; Tickner, J.A.

2007-01-01

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......," 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...

Regulation of metabolic networks by small molecule metabolites

Directory of Open Access Journals (Sweden)

Kanehisa Minoru

2007-03-01

Full Text Available Abstract Background The ability to regulate metabolism is a fundamental process in living systems. We present an analysis of one of the mechanisms by which metabolic regulation occurs: enzyme inhibition and activation by small molecules. We look at the network properties of this regulatory system and the relationship between the chemical properties of regulatory molecules. Results We find that many features of the regulatory network, such as the degree and clustering coefficient, closely match those of the underlying metabolic network. While these global features are conserved across several organisms, we do find local differences between regulation in E. coli and H. sapiens which reflect their different lifestyles. Chemical structure appears to play an important role in determining a compounds suitability for use in regulation. Chemical structure also often determines how groups of similar compounds can regulate sets of enzymes. These groups of compounds and the enzymes they regulate form modules that mirror the modules and pathways of the underlying metabolic network. We also show how knowledge of chemical structure and regulation could be used to predict regulatory interactions for drugs. Conclusion The metabolic regulatory network shares many of the global properties of the metabolic network, but often varies at the level of individual compounds. Chemical structure is a key determinant in deciding how a compound is used in regulation and for defining modules within the regulatory system.

Regulated functions and integrability

Directory of Open Access Journals (Sweden)

Ján Gunčaga

2009-04-01

Full Text Available Properties of functions defined on a bounded closed interval, weaker than continuity, have been considered by many mathematicians. Functions having both sides limits at each point are called regulated and were considered by J. Dieudonné [2], D. Fraňková [3] and others (see for example S. Banach [1], S. Saks [8]. The main class of functions we deal with consists of piece-wise constant ones. These functions play a fundamental role in the integration theory which had been developed by Igor Kluvanek (see Š. Tkacik [9]. We present an outline of this theory.

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer

DEFF Research Database (Denmark)

Mezheyeuski, Artur; Lindh, Maja Bradic; Guren, Tormod Kyrre

2016-01-01

of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC).Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-β or α-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated......Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown.Here we report a novel method for digital quantitative analyses...... to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-α and -β...

75 FR 51374 - Regulated Navigation Areas, Safety Zones, Security Zones; Deepwater Ports in Boston Captain of...

Science.gov (United States)

2010-08-20

... Ocean off the coast of Gloucester, Massachusetts. The purpose of these regulated areas is to protect... a water area within a defined boundary for which regulations for vessels navigating within the area..., Neptune Deepwater Port (Neptune), is located in the Atlantic Ocean, approximately eight nautical miles...

The Relation between Self-Regulated Learning and Academic Achievement across Childhood and Adolescence: A Meta-Analysis

Science.gov (United States)

Dent, Amy L.; Koenka, Alison C.

2016-01-01

This research synthesis explores how academic achievement relates to two main components of self-regulated learning for students in elementary and secondary school. Two meta-analyses integrated previous findings on (1) the defining metacognitive processes of self-regulated learning and (2) students' use of cognitive strategies. Overall…

Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements.

Science.gov (United States)

Durrieu-Gaillard, Stéphanie; Dumay-Odelot, Hélène; Boldina, Galina; Tourasse, Nicolas J; Allard, Delphine; André, Fabrice; Macari, Françoise; Choquet, Armelle; Lagarde, Pauline; Drutel, Guillaume; Leste-Lasserre, Thierry; Petitet, Marion; Lesluyes, Tom; Lartigue-Faustin, Lydia; Dupuy, Jean-William; Chibon, Frédéric; Roeder, Robert G; Joubert, Dominique; Vagner, Stéphan; Teichmann, Martin

2018-01-01

RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential for cellular homeostasis and growth. Its activity is regulated by inactivation of tumor suppressor proteins and overexpression of the oncogene c-MYC, but the concerted action of these tumor-promoting factors on Pol III transcription has not yet been assessed. In order to comprehensively analyse the regulation of Pol III transcription during tumorigenesis we employ a model system that relies on the expression of five genetic elements to achieve cellular transformation. Expression of these elements in six distinct transformation intermediate cell lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well as the activation of RAS and the protection of telomeres by TERT, thereby conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III subunits and transcription factors are upregulated, including increased protein levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits. Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during transformation in this cellular transformation model. Collectively, our data indicate that increased expression of several components of the Pol III transcription system accompanied by a 2-fold increase in steady state levels of a subset of Pol III RNAs is sufficient for sustaining tumor formation.

Environmental contaminants and microRNA regulation: Transcription factors as regulators of toxicant-altered microRNA expression

Energy Technology Data Exchange (ETDEWEB)

Sollome, James; Martin, Elizabeth [Department of Environmental Science & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States); Sethupathy, Praveen [Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC (United States); Fry, Rebecca C., E-mail: rfry@unc.edu [Department of Environmental Science & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States); Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC (United States)

2016-12-01

MicroRNAs (miRNAs) regulate gene expression by binding mRNA and inhibiting translation and/or inducing degradation of the associated transcripts. Expression levels of miRNAs have been shown to be altered in response to environmental toxicants, thus impacting cellular function and influencing disease risk. Transcription factors (TFs) are known to be altered in response to environmental toxicants and play a critical role in the regulation of miRNA expression. To date, environmentally-responsive TFs that are important for regulating miRNAs remain understudied. In a state-of-the-art analysis, we utilized an in silico bioinformatic approach to characterize potential transcriptional regulators of environmentally-responsive miRNAs. Using the miRStart database, genomic sequences of promoter regions for all available human miRNAs (n = 847) were identified and promoter regions were defined as − 1000/+500 base pairs from the transcription start site. Subsequently, the promoter region sequences of environmentally-responsive miRNAs (n = 128) were analyzed using enrichment analysis to determine overrepresented TF binding sites (TFBS). While most (56/73) TFs differed across environmental contaminants, a set of 17 TFs was enriched for promoter binding among miRNAs responsive to numerous environmental contaminants. Of these, one TF was common to miRNAs altered by the majority of environmental contaminants, namely SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 3 (SMARCA3). These identified TFs represent candidate common transcriptional regulators of miRNAs perturbed by environmental toxicants. - Highlights: • Transcription factors that regulate environmentally-modulated miRNA expression are understudied • Transcription factor binding sites (TFBS) located within DNA promoter regions of miRNAs were identified. • Specific transcription factors may serve as master regulators of environmentally-mediated microRNA expression.

Environmental contaminants and microRNA regulation: Transcription factors as regulators of toxicant-altered microRNA expression

International Nuclear Information System (INIS)

Sollome, James; Martin, Elizabeth; Sethupathy, Praveen; Fry, Rebecca C.

2016-01-01

MicroRNAs (miRNAs) regulate gene expression by binding mRNA and inhibiting translation and/or inducing degradation of the associated transcripts. Expression levels of miRNAs have been shown to be altered in response to environmental toxicants, thus impacting cellular function and influencing disease risk. Transcription factors (TFs) are known to be altered in response to environmental toxicants and play a critical role in the regulation of miRNA expression. To date, environmentally-responsive TFs that are important for regulating miRNAs remain understudied. In a state-of-the-art analysis, we utilized an in silico bioinformatic approach to characterize potential transcriptional regulators of environmentally-responsive miRNAs. Using the miRStart database, genomic sequences of promoter regions for all available human miRNAs (n = 847) were identified and promoter regions were defined as − 1000/+500 base pairs from the transcription start site. Subsequently, the promoter region sequences of environmentally-responsive miRNAs (n = 128) were analyzed using enrichment analysis to determine overrepresented TF binding sites (TFBS). While most (56/73) TFs differed across environmental contaminants, a set of 17 TFs was enriched for promoter binding among miRNAs responsive to numerous environmental contaminants. Of these, one TF was common to miRNAs altered by the majority of environmental contaminants, namely SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 3 (SMARCA3). These identified TFs represent candidate common transcriptional regulators of miRNAs perturbed by environmental toxicants. - Highlights: • Transcription factors that regulate environmentally-modulated miRNA expression are understudied • Transcription factor binding sites (TFBS) located within DNA promoter regions of miRNAs were identified. • Specific transcription factors may serve as master regulators of environmentally-mediated microRNA expression

On defining semantics of extended attribute grammars

DEFF Research Database (Denmark)

Madsen, Ole Lehrmann

1980-01-01

Knuth has introduced attribute grammars (AGs) as a tool to define the semanitcs of context-free languages. The use of AGs in connection with programming language definitions has mostly been to define the context-sensitive syntax of the language and to define a translation in code for a hypothetic...

Regulation of romantic love feelings: Preconceptions, strategies, and feasibility

NARCIS (Netherlands)

S.J.E. Langeslag (Sandra); J.W. van Strien (Jan)

2016-01-01

textabstractLove feelings can be more intense than desired (e.g., after a break-up) or less intense than desired (e.g., in long-Term relationships). If only we could control our love feelings! We present the concept of explicit love regulation, which we define as the use of behavioral and cognitive

Comprehensive Plan for Public Confidence in Nuclear Regulator

International Nuclear Information System (INIS)

Choi, Kwang Sik; Choi, Young Sung; Kim, Ho ki

2008-01-01

Public confidence in nuclear regulator has been discussed internationally. Public trust or confidence is needed for achieving regulatory goal of assuring nuclear safety to the level that is acceptable by the public or providing public ease for nuclear safety. In Korea, public ease or public confidence has been suggested as major policy goal in the 'Nuclear regulatory policy direction' annually announced. This paper reviews theory of trust, its definitions and defines nuclear safety regulation, elements of public trust or public confidence developed based on the study conducted so far. Public ease model developed and 10 measures for ensuring public confidence are also presented and future study directions are suggested

Defining Modules, Modularity and Modularization

DEFF Research Database (Denmark)

Miller, Thomas Dedenroth; Pedersen, Per Erik Elgård

The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization.......The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization....

Apoptosis regulates notochord development in Xenopus

OpenAIRE

Malikova, Marina; Van Stry, Melanie; Symes, Karen

2007-01-01

The notochord is the defining characteristic of the chordate embryo, and plays critical roles as a signaling center and as the primitive skeleton. In this study we show that early notochord development in Xenopus embryos is regulated by apoptosis. We find apoptotic cells in the notochord beginning at the neural groove stage and increasing in number as the embryo develops. These dying cells are distributed in an anterior to posterior pattern that is correlated with notochord extension through ...

Rehabilitation of executive functioning with training in attention regulation applied to individually defined goals: a pilot study bridging theory, assessment, and treatment.

Science.gov (United States)

Novakovic-Agopian, Tatjana; Chen, Anthony J-W; Rome, Scott; Abrams, Gary; Castelli, Holli; Rossi, Annemarie; McKim, Ryan; Hills, Nancy; D'Esposito, Mark

2011-01-01

To assess feasibility and effects of training in goal-oriented attentional self-regulation for patients with brain injury and chronic executive dysfunction. Sixteen individuals with chronic brain injury and mild to moderate executive dysfunction. Participants were divided into 2 groups: one group completed goal-oriented attentional self-regulation training during the first 5 weeks, followed by a brief (2-hour) educational instruction session as a control midway through the second 5 weeks; the other group participated in reverse order. Neuropsychological and functional performance assessed at baseline and at weeks 5 and 10. Participants found training in goal-oriented attentional self-regulation engaging, incorporated some trained strategies into daily life, and reported subjective improvements in personal functioning. At week 5, participants who completed goals training significantly improved on tests of attention and executive function and had fewer functional task failures, while performance did not change after educational instruction. At week 10, participants who crossed over from educational instruction to goals training also significantly improved on attention and executive function tests. Participants who crossed from goals training to educational instruction maintained their week 5 gains. Training in goal-oriented attentional self-regulation is theoretically driven and feasible in a research setting. Pilot results suggest improvements in cognitive and functional domains targeted by the intervention.

Heat-resistant, extended-spectrum β-lactamase-producing Klebsiella pneumoniae in endoscope-mediated outbreak

DEFF Research Database (Denmark)

Jørgensen, S.B.; Bojer, Martin Saxtorph; Boll, E.J.

2016-01-01

disinfection in a decontaminator designated for such use. The genetic marker clpK, which increases microbial heat resistance, has previously been described in K. pneumoniae outbreak strains. Aim To investigate the role of clpK in biofilm formation and heat-shock stability in the outbreak strain. Methods...... construction and heat-shock assays. Findings Five patients and one intubation endoscope contained K. pneumoniae with the same amplified fragment length polymorphism pattern. The outbreak strain contained the clpK genetic marker, which rendered the strain its increased heat resistance. The survival rate....... Heat resistance of certain K. pneumoniae strains may facilitate survival in biofilms on medical equipment and hence increase the potential of those strains to persist and disperse in the hospital environment....

Evidence of an Unidentified Extracellular Heat-Stable Factor Produced by Lysobacter enzymogenes (OH11) that Degrade Fusarium graminearum PH1 Hyphae.

Science.gov (United States)

Odhiambo, Benard Omondi; Xu, Gaoge; Qian, Guoliang; Liu, Fengquan

2017-04-01

Lysobacter enzymogenes OH11 produces heat-stable antifungal factor (HSAF) and lytic enzymes possessing antifungal activity. This study bio-prospected for other potential antifungal factors besides those above. The cells and extracellular metabolites of L. enzymogenes OH11 and the mutants ΔchiA, ΔchiB, ΔchiC, Δclp, Δpks, and ΔpilA were examined for antifungal activity against Fusarium graminearum PH1, the causal agent of Fusarium head blight (FHB). Results evidenced that OH11 produces an unidentified extracellular heat-stable degrading metabolite (HSDM) that exhibit degrading activity on F. graminearum PH1 chitinous hyphae. Interestingly, both heat-treated and non-heat-treated extracellular metabolites of OH11 mutants exhibited hyphae-degrading activity against F. graminearum PH1. Enzyme activity detection of heat-treated metabolites ruled out the possibility of enzyme degradation activity. Remarkably, the PKS-NRPS-deficient mutant Δpks cannot produce HSAF or analogues, yet its metabolites exhibited hyphae-degrading activity. HPLC analysis confirmed no HSAF production by Δpks. Δclp lacks hyphae-degrading ability. Therefore, clp regulates HSDM and extracellular lytic enzymes production in L. enzymogenes OH11. ΔpilA had impaired surface cell motility and significantly reduced antagonistic properties. ΔchiA, ΔchiB, and ΔchiC retained hyphae-degrading ability, despite having reduced abilities to produce chitinase enzymes. Ultimately, L. enzymogenes OH11 can produce other unidentified HSDM independent of the PKS-NRPS genes. This suggests HSAF and lytic enzymes production are a fraction of the antifungal mechanisms in OH11. Characterization of HSDM, determination of its biosynthetic gene cluster and understanding its mode of action will provide new leads in the search for effective drugs for FHB management.

Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.

Science.gov (United States)

Wang, Xin; Min, Su; Xie, Fei; Yang, Jun; Li, Liang; Chen, Jingyuan

2018-02-05

Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR. Copyright © 2018. Published by Elsevier Inc.

Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality.

Science.gov (United States)

Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

2015-04-01

Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditionings with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in opposite to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a novel mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

Directory of Open Access Journals (Sweden)

Keqiang Chen

2015-04-01

Full Text Available Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP. This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Proposed general amendments to the atomic energy control regulations

International Nuclear Information System (INIS)

1986-01-01

Canada's Atomic Energy Control Act defines the powers and responsibilities of the Atomic Energy Control Board (AECB). Among these is to make regulations to control the development, application and use of atomic energy. In these proposed general amendments to the Atomic Energy Control Regulations substantial changes are proposed in the designation of the authority of AECB staff, exemptions from licensing, international safeguards, duties of licensees and atomic radiation workers, security of information, and provision for hearings. The scope of the control of atomic energy has been redefined as relating to matters of health, safety, security, international safeguards, and the protection of the environment

An action plan for radioactive substances regulation

International Nuclear Information System (INIS)

1998-01-01

This document sets out an action plan for the Agency's Radioactive Substances Regulation function. Our vision is to secure continuous improvement in the protection of the public and the environment from the harmful effects of radioactive substances. Radioactive Substances Regulation will work with others to realise this vision and contribute to the Agency's role in achieving sustainable development. We will also work to ensure that the Agency achieves its objectives in an efficient, consistent and integrated way. The main elements of our Action Plan are as follows: establishing indicators of sustainability and the means and methods of monitoring them; establishing performance indicators and a programme of targets and objectives to be achieved; establishing a database of all premises subject to RSA93 and to use it for work planning, resource targeting, and improvement to radioactive waste management; provision of systems of procedures and technical guidance to ensure nationally consistent and cost- effective regulation; establishing systems to audit the implementation of the procedures and guidance; ensuring quality of regulation by defining technical competencies of inspectors and the training programmes to secure them; an R and D programme targeted on improving radioactive waste management and radioactive substances regulation; and full and effective participation in development of national policy

Note n. SD3-DEM-01 regulations procedures relative to the based nuclear installations dismantling

International Nuclear Information System (INIS)

2003-02-01

This note aims to define the regulations procedures relative to the safety of based nuclear installations dismantling defined by the decree of the 11 december 1963 modified. The first part describes the two main phases of a based nuclear installation life, the operating and the dismantling phase. The second part is devoted to the procedures. (A.L.B.)

VanT, a central regulator of quorum sensing signalling in Vibrio anguillarum

OpenAIRE

Croxatto, Antony

2006-01-01

Many bacteria produce signal molecules that serve in a cell-to-cell communication system termed quorum sensing. This signalling system allows a bacterial population to co-ordinately regulate functions according to their cell number in a defined environment. As bacterial growth progresses towards the stationary phase, signalling molecules accumulate in the growth medium and, above a certain threshold level, regulate the expression of genes involved in diverse functions. Most of the functions m...

Wind/PV Generation for Frequency Regulation and Oscillation Damping in the Eastern Interconnection

Energy Technology Data Exchange (ETDEWEB)

Liu, Yong [Univ. of Tennessee, Knoxville, TN (United States); Gracia, Jose R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hadley, Stanton W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Liu, Yilu [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2013-12-01

This report presents the control of renewable energy sources, including the variable-speed wind generators and solar photovoltaic (PV) generators, for frequency regulation and inter-area oscillation damping in the U.S. Eastern Interconnection (EI). In this report, based on the user-defined wind/PV generator electrical control model and the 16,000-bus Eastern Interconnection dynamic model, the additional controllers for frequency regulation and inter-area oscillation damping are developed and incorporated and the potential contributions of renewable energy sources to the EI system frequency regulation and inter-area oscillation damping are evaluated.

DEFINED CONTRIBUTION PLANS, DEFINED BENEFIT PLANS, AND THE ACCUMULATION OF RETIREMENT WEALTH

Science.gov (United States)

Poterba, James; Rauh, Joshua; Venti, Steven; Wise, David

2010-01-01

The private pension structure in the United States, once dominated by defined benefit (DB) plans, is currently divided between defined contribution (DC) and DB plans. Wealth accumulation in DC plans depends on the participant's contribution behavior and on financial market returns, while accumulation in DB plans is sensitive to a participant's labor market experience and to plan parameters. This paper simulates the distribution of retirement wealth under representative DB and DC plans. It uses data from the Health and Retirement Study (HRS) to explore how asset returns, earnings histories, and retirement plan characteristics contribute to the variation in retirement wealth outcomes. We simulate DC plan accumulation by randomly assigning individuals a share of wages that they and their employer contribute to the plan. We consider several possible asset allocation strategies, with asset returns drawn from the historical return distribution. Our DB plan simulations draw earnings histories from the HRS, and randomly assign each individual a pension plan drawn from a sample of large private and public defined benefit plans. The simulations yield distributions of both DC and DB wealth at retirement. Average retirement wealth accruals under current DC plans exceed average accruals under private sector DB plans, although DC plans are also more likely to generate very low retirement wealth outcomes. The comparison of current DC plans with more generous public sector DB plans is less definitive, because public sector DB plans are more generous on average than their private sector counterparts. PMID:21057597

Small Area Estimate Maps: Does the FDA Regulate Tobacco? - Small Area Estimates

Science.gov (United States)

This metric is defined as a person 18 years of age or older who must have reported that he/she believes that the United States Food and Drug Administration (FDA) regulates tobacco products in the U.S.

Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ.

Directory of Open Access Journals (Sweden)

Till Adhikary

Full Text Available Peroxisome proliferator-activated receptors (PPARs are nuclear receptors with essential functions in lipid, glucose and energy homeostasis, cell differentiation, inflammation and metabolic disorders, and represent important drug targets. PPARs heterodimerize with retinoid X receptors (RXRs and can form transcriptional activator or repressor complexes at specific DNA elements (PPREs. It is believed that the decision between repression and activation is generally governed by a ligand-mediated switch. We have performed genomewide analyses of agonist-treated and PPARβ/δ-depleted human myofibroblasts to test this hypothesis and to identify global principles of PPARβ/δ-mediated gene regulation. Chromatin immunoprecipitation sequencing (ChIP-Seq of PPARβ/δ, H3K4me3 and RNA polymerase II enrichment sites combined with transcriptional profiling enabled the definition of 112 bona fide PPARβ/δ target genes showing either of three distinct types of transcriptional response: (I ligand-independent repression by PPARβ/δ; (II ligand-induced activation and/or derepression by PPARβ/δ; and (III ligand-independent activation by PPARβ/δ. These data identify PPRE-mediated repression as a major mechanism of transcriptional regulation by PPARβ/δ, but, unexpectedly, also show that only a subset of repressed genes are activated by a ligand-mediated switch. Our results also suggest that the type of transcriptional response by a given target gene is connected to the structure of its associated PPRE(s and the biological function of its encoded protein. These observations have important implications for understanding the regulatory PPAR network and PPARβ/δ ligand-based drugs.

Epigenetic regulation in Autism spectrum disorder

Directory of Open Access Journals (Sweden)

Sraboni Chaudhury

2016-12-01

Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder characterized by an impaired social communication skill and often results in repetitive, stereotyped behavior which is observed in children during the first few years of life. Other characteristic of this disorder includes language disabilities, difficulties in sensory integration, lack of reciprocal interactions and in some cases, cognitive delays. One percentage of the general population is affected by ASD and is four times more common in boys than girls. There are hundreds of genes, which has been identified to be associated with ASD etiology. However it remains difficult to comprehend our understanding in defining the genetic architecture necessary for complete exposition of its pathophysiology. Seeing the complexity of the disease, it is important to adopt a multidisciplinary approach which should not only focus on the “genetics” of autism but also on epigenetics, transcriptomics, immune system disruption and environmental factors that could all impact the pathogenesis of the disease. As environmental factors also play a key role in regulating the trigger of ASD, the role of chromatin remodeling and DNA methylation has started to emerge. Such epigenetic modifications directly link molecular regulatory pathways and environmental factors, which might be able to explain some aspects of complex disorders like ASD. The present review will focus on the role of epigenetic regulation in defining the underlying cause for ASD

22 CFR 92.36 - Authentication defined.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication defined. 92.36 Section 92.36... Notarial Acts § 92.36 Authentication defined. An authentication is a certification of the genuineness of... recognized in another jurisdiction. Documents which may require authentication include legal instruments...

How to Tackle the Challenge of siRNA Delivery with Sequence-Defined Oligoamino Amides.

Science.gov (United States)

Reinhard, Sören; Wagner, Ernst

2017-01-01

RNA interference (RNAi) as a mechanism of gene regulation provides exciting opportunities for medical applications. Synthetic small interfering RNA (siRNA) triggers the knockdown of complementary mRNA sequences in a catalytic fashion and has to be delivered into the cytosol of the targeted cells. The design of adequate carrier systems to overcome multiple extracellular and intracellular roadblocks within the delivery process has utmost importance. Cationic polymers form polyplexes through electrostatic interaction with negatively charged nucleic acids and present a promising class of carriers. Issues of polycations regarding toxicity, heterogeneity, and polydispersity can be overcome by solid-phase-assisted synthesis of sequence-defined cationic oligomers. These medium-sized highly versatile nucleic acid carriers display low cytotoxicity and can be modified and tailored in multiple ways to meet specific requirements of nucleic acid binding, polyplex size, shielding, targeting, and intracellular release of the cargo. In this way, sequence-defined cationic oligomers can mimic the dynamic and bioresponsive behavior of viruses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Canadian Government perspective on cost-effective regulation

International Nuclear Information System (INIS)

Martin, J.K.; Iwankow, C.

1996-01-01

Fiscal constraint, globalization of markets, and accelerated technological change have resulted in a new focus on the cost-effectiveness of government activities and, in turn, on methods of policy evaluation. An exploration of regulatory problems, and the use of regulation as a public policy instrument, reveals a commonalty of experience in all industrialized countries. This paper provides a brief synopsis of the Government of Canada's perspective on cost-effective regulation. To understand cost-effective regulation, this paper examines the principles of regulatory reform which underlie the current strategy of the federal government (collaborative decision-making mechanisms., methods of clear policy evaluation, and well defined lines of accountability). It discusses the nature of, and rationale for, government regulation, the reasons for regulatory reform in the economy, and the principal aims of Canadian regulatory reform and regulatory policy assessment. It does so by specifically addressing the role of cost-benefit analysis in the process of regulatory assessment - a method which involves systematically identifying, and quantifying where possible, the social benefits and costs associated with alternative public policy actions - with a particular focus on regulation which affects the Canadian nuclear industry. (author). 51 refs

The Canadian Government perspective on cost-effective regulation

Energy Technology Data Exchange (ETDEWEB)

Martin, J K; Iwankow, C [Treasury Board of Canada Secretariat, Ottawa, ON (Canada)

1997-12-31

Fiscal constraint, globalization of markets, and accelerated technological change have resulted in a new focus on the cost-effectiveness of government activities and, in turn, on methods of policy evaluation. An exploration of regulatory problems, and the use of regulation as a public policy instrument, reveals a commonalty of experience in all industrialized countries. This paper provides a brief synopsis of the Government of Canada`s perspective on cost-effective regulation. To understand cost-effective regulation, this paper examines the principles of regulatory reform which underlie the current strategy of the federal government (collaborative decision-making mechanisms., methods of clear policy evaluation, and well defined lines of accountability). It discusses the nature of, and rationale for, government regulation, the reasons for regulatory reform in the economy, and the principal aims of Canadian regulatory reform and regulatory policy assessment. It does so by specifically addressing the role of cost-benefit analysis in the process of regulatory assessment - a method which involves systematically identifying, and quantifying where possible, the social benefits and costs associated with alternative public policy actions - with a particular focus on regulation which affects the Canadian nuclear industry. (author). 51 refs.

Defining Game Mechanics

DEFF Research Database (Denmark)

Sicart (Vila), Miguel Angel

2008-01-01

This article defins game mechanics in relation to rules and challenges. Game mechanics are methods invoked by agents for interacting with the game world. I apply this definition to a comparative analysis of the games Rez, Every Extend Extra and Shadow of the Colossus that will show the relevance...... of a formal definition of game mechanics. Udgivelsesdato: Dec 2008...

State-federal interactions in nuclear regulation

Energy Technology Data Exchange (ETDEWEB)

Pasternak, A.D.; Budnitz, R.J.

1987-12-01

The Atomic Energy Act of 1954 established, and later Congressional amendments have confirmed, that except in areas which have been explicitly granted to the states, the federal government possesses preemptive authority to regulate radiation hazards associated with the development and use of atomic energy. Since the passage of the original Act, numerous decisions by the courts have reaffirmed the legitimacy of federal preemption, and have defined and redefined its scope. In this study, the aim is to explore the underlying issues involved in federal preemption of radiation-hazard regulation, and to recommend actions that the Department of Energy and other agencies and groups should consider undertaking in the near term to protect the preemption principle. Appropriate roles of the states are discussed, as well as recent state-level activities and their rationale, and several current arenas in which state-federal conflicts about regulation of hazards are being played out. The emphasis here is on four particular arenas that are now important arenas of conflict, but the issues discussed are far broader in scope. These four arenas are: state-level moratorium activity; emergency planning for reactors; conflicts arising from state financial regulation; and inroads in federal preemption through litigation under state law.

State-federal interactions in nuclear regulation

International Nuclear Information System (INIS)

Pasternak, A.D.; Budnitz, R.J.

1987-12-01

The Atomic Energy Act of 1954 established, and later Congressional amendments have confirmed, that except in areas which have been explicitly granted to the states, the federal government possesses preemptive authority to regulate radiation hazards associated with the development and use of atomic energy. Since the passage of the original Act, numerous decisions by the courts have reaffirmed the legitimacy of federal preemption, and have defined and redefined its scope. In this study, the aim is to explore the underlying issues involved in federal preemption of radiation-hazard regulation, and to recommend actions that the Department of Energy and other agencies and groups should consider undertaking in the near term to protect the preemption principle. Appropriate roles of the states are discussed, as well as recent state-level activities and their rationale, and several current arenas in which state-federal conflicts about regulation of hazards are being played out. The emphasis here is on four particular arenas that are now important arenas of conflict, but the issues discussed are far broader in scope. These four arenas are: state-level moratorium activity; emergency planning for reactors; conflicts arising from state financial regulation; and inroads in federal preemption through litigation under state law

Indico CONFERENCE: Define the Call for Abstracts

CERN Multimedia

CERN. Geneva; Ferreira, Pedro

2017-01-01

In this tutorial, you will learn how to define and open a call for abstracts. When defining a call for abstracts, you will be able to define settings related to the type of questions asked during a review of an abstract, select the users who will review the abstracts, decide when to open the call for abstracts, and more.

The effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on mice models of endotoxic and septic shock.

Science.gov (United States)

Ulu, Nadir; Iskit, Alper Bektaş; Sökmensüer, Cenk; Güç, Mustafa Oğuz

2015-01-01

Nitric oxide-donating nonsteroidal antiinflammatory drugs (NO-NSAIDs) are a promising new class of antiinflammatory agents, which are obtained by adding NO-donating moieties to the existing conventional NSAID molecules. The aim of this study was to investigate the effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on cecal ligation and puncture (CLP) and endotoxin-induced septic shock (LPS) models in mice. Overall survival and spleen and liver weights were monitored in LPS and CLP models. Histopathological examinations of liver and spleen were performed at the end of the experimental protocols. NCX 4016 was able to reverse the increased spleen weight in CLP-operated animals, whereas aspirin or flurbiprofen did not. Similar to the results of the CLP model, none of the drugs modified the survival rates in the LPS model. Flurbiprofen in particular produced significant histopathological damage in spleens and livers, which was less significant with aspirin. NCX 4016 did not cause any liver damage. NCX 4016 has the potential to be used in septic states, while special attention has to be paid to the effects of aspirin and flurbiprofen on the liver and spleen.

78 FR 13298 - Notice of Retrospective Review of the Americans With Disabilities Act Regulations for Over-the...

Science.gov (United States)

2013-02-27

... accessible OTRB service. An OTRB is defined as ``a bus characterized by an elevated passenger deck located...] Notice of Retrospective Review of the Americans With Disabilities Act Regulations for Over-the-Road Bus... bus (OTRB) operators. The DOT will review regulations specified in the SUPPLEMENTARY INFORMATION...

Defining Tobacco Regulatory Science Competencies.

Science.gov (United States)

Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

2017-02-01

In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps☆

OpenAIRE

Beatty, Gregory L.; O’Hara, Mark

2016-01-01

Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers t...

Defining and Selecting Independent Directors

Directory of Open Access Journals (Sweden)

Eric Pichet

2017-10-01

Full Text Available Drawing from the Enlightened Shareholder Theory that the author first developed in 2011, this theoretical paper with practical and normative ambitions achieves a better definition of independent director, while improving the understanding of the roles he fulfils on boards of directors. The first part defines constructs like firms, Governance system and Corporate governance, offering a clear distinction between the latter two concepts before explaining the four main missions of a board. The second part defines the ideal independent director by outlining the objective qualities that are necessary and adding those subjective aspects that have turned this into a veritable profession. The third part defines the ideal process for selecting independent directors, based on nominating committees that should themselves be independent. It also includes ways of assessing directors who are currently in function, as well as modalities for renewing their mandates. The paper’s conclusion presents the Paradox of the Independent Director.

Plasma Cell Ontogeny Defined by Quantitative Changes in Blimp-1 Expression

Science.gov (United States)

Kallies, Axel; Hasbold, Jhagvaral; Tarlinton, David M.; Dietrich, Wendy; Corcoran, Lynn M.; Hodgkin, Philip D.; Nutt, Stephen L.

2004-01-01

Plasma cells comprise a population of terminally differentiated B cells that are dependent on the transcriptional regulator B lymphocyte–induced maturation protein 1 (Blimp-1) for their development. We have introduced a gfp reporter into the Blimp-1 locus and shown that heterozygous mice express the green fluorescent protein in all antibody-secreting cells (ASCs) in vivo and in vitro. In vitro, these cells display considerable heterogeneity in surface phenotype, immunoglobulin secretion rate, and Blimp-1 expression levels. Importantly, analysis of in vivo ASCs induced by immunization reveals a developmental pathway in which increasing levels of Blimp-1 expression define developmental stages of plasma cell differentiation that have many phenotypic and molecular correlates. Thus, maturation from transient plasmablast to long-lived ASCs in bone marrow is predicated on quantitative increases in Blimp-1 expression. PMID:15492122

Fungal Competitors Affect Production of Antimicrobial Lipopeptides in Bacillus subtilis Strain B9-5.

Science.gov (United States)

DeFilippi, Stefanie; Groulx, Emma; Megalla, Merna; Mohamed, Rowida; Avis, Tyler J

2018-04-01

Bacillus subtilis has shown success in antagonizing plant pathogens where strains of the bacterium produce antimicrobial cyclic lipopeptides (CLPs) in response to microbial competitors in their ecological niche. To gain insight into the inhibitory role of these CLPs, B. subtilis strain B9-5 was co-cultured with three pathogenic fungi. Inhibition of mycelial growth and spore germination was assessed and CLPs produced by B. subtilis B9-5 were quantified over the entire period of microbial interaction. B. subtilis B9-5 significantly inhibited mycelial growth and spore germination of Fusarium sambucinum and Verticillium dahliae, but not Rhizopus stolonifer. LC-MS analysis revealed that B. subtilis differentially produced fengycin and surfactin homologs depending on the competitor. CLP quantification suggested that the presence of Verticillium dahliae, a fungus highly sensitive to the compounds, caused an increase followed by a decrease in CLP production by the bacterium. In co-cultures with Fusarium sambucinum, a moderately sensitive fungus, CLP production increased more gradually, possibly because of its slower rate of spore germination. With co-cultures of the tolerant fungus Rhizopus stolonifer, B. subtilis produced high amounts of CLPs (per bacterial cell) for the duration of the interaction. Variations in CLP production could be explained, in part, by the pathogens' overall sensitivities to the bacterial lipopeptides and/or the relative growth rates between the plant pathogen and B. subtilis. CLP production varied substantially temporally depending on the targeted fungus, which provides valuable insight concerning the effectiveness of B. subtilis B9-5 protecting its ecological niche against the ingress of these pathogens.

Tawanchai Cleft Center quality of life outcomes: one of studies of patients with cleft lip and palate in Thailand and the Asia Pacific Region.

Science.gov (United States)

Patjanasoontorn, Niramol; Pradaubwong, Suteera; Rongbutsri, Somchit; Mongkholthawornchai, Siriporn; Chowchuen, Bowornsilp

2012-11-01

The needs and quality of life (QOL) of children with cleft lip and palate (CLP) after being processed through the healthcare system are important in order to understand how to improve the standards of care. The Tawanchai Cleft Center of Thailand in collaboration with Cleft Lip and Palate Care Center of the Asia Pacific Region, conducted a number of studies on various aspects of treatment outcomes as an indication of its performance. This paper presents the outcome effects on QOL. To determine (a) the QOL of children with CLP in Northeast Thailand registered and followed-up at the Tawanchai Centre, (b) their ongoing care needs and (c) the mental health of their parents when the children reach 5 years of age. Using the Need, Satisfaction, QOL and GHQ-12 questionnaires, the authors evaluated 36 five-year-old children with CLP, living in Northeast Thailand, registered at birth for treatment at the Tawanchai Cleft Center. The aspects most needing attention were: dental, speech therapy and local healthcare service. The QOL was low in the economic, child relationships and psychological domains. The parents need more training on how to raise children with CLP most appropriately. According to the GHQ-12, none of the families identified any mental problems. Children with CLP at five years of age under the care of the Tawanchai Cleft Center by their own self-assessment have satisfactory outcomes in most domains. Notwithstanding, there is need to improve parent training and access to dental care, speech therapy and local healthcare services.

Nasal Obstruction in Children With Cleft Lip and Palate: Results of a Cross-Sectional Study Utilizing the NOSE Scale.

Science.gov (United States)

Zhang, Rosaline S; Lin, Lawrence O; Hoppe, Ian C; Jackson, Oksana A; Low, David W; Bartlett, Scott P; Swanson, Jordan W; Taylor, Jesse A

2018-01-01

To characterize the epidemiology and risk factors for nasal obstruction among subjects with cleft lip and/or cleft palate (CL/P) utilizing the well-validated Nasal Obstruction Symptom Evaluation (NOSE) survey. Retrospective cross-sectional study. Cleft Lip and Palate Program, Children's Hospital of Philadelphia. Patients, Subjects: One thousand twenty-eight surveys obtained from 456 subjects (mean age: 10.10 (4.48) years) with CL/P evaluated between January 2015 and August 2017 with at least 1 completed NOSE survey. Nasal Obstruction Symptom Evaluation surveys completed at each annual visit. Composite NOSE and individual symptom scores. Sixty-seven percent of subjects had nasal obstruction at some point during the study period, with 49% reporting nasal obstruction at latest follow-up. subjects aged 14 years and older reported the most severe symptoms ( P = .002). Subjects with cleft lip and alveolus (CL+A) and unilateral cleft lip and palate (CLP) reported more severe nasal blockage than other phenotypes ( P = .021). subjects with a history of either posterior pharyngeal flap (PPF) or sphincter pharyngoplasty (SP) had significantly higher NOSE scores than subjects with no history of speech surgery ( P = .006). There was no significant difference ( P > .050) in NOSE scores with regard to history of primary tip rhinoplasty, nasal stent use, or nasoalveolar molding. There are more severe nasal obstructive symptoms among subjects older than 14 years of age, with CL+A or unilateral CLP, and with a history of PPF or SP. Future studies utilizing the NOSE are needed to evaluate and address this prevalent morbidity in the CLP population.

Adopting a child with cleft lip and palate: a study of parents' experiences.

Science.gov (United States)

Hansson, Emma; Ostman, Jenny; Becker, Magnus

2013-02-01

Adoption of Chinese children with cleft lip and palate (CLP) has become increasingly more common in Sweden. The aim of this study was to examine parents' experience when adopting a child with CLP. Since 2008, 34 adopted children with CLP have been treated in our department. A questionnaire was sent to 33 of the families and 30 of them answered (91%). The parents had queued from 1 month to 8 years before they were offered a child. Eighteen families reported that they received information on CLP from the adoption agency and 87% contacted the department of plastic surgery for additional information. In 15 cases (45%) previously unknown medical conditions or birth defects other than CLP were discovered in Sweden. Most parents (67%) had been informed before the adoption that their child could be a carrier of resistant bacteria, but not all had received enough information to grasp what it implies to be a carrier. The great majority of the families did not feel that the early hospitalisation for the first operation had a negative impact on the attachment between them and their adopted child. They thought that the aesthetic and functional results of the operations were "better than expected". Seventeen families stated that people react to the cleft and four of them think that the reactions are a problem. Presumptive adoptive parents should be informed that the child might have unsuspected medical conditions, resistant bacteria, what carriage implies, and that needed treatment and long-term results are not predictable.

Soil structural quality assessment for soil protection regulation

Science.gov (United States)

Johannes, Alice; Boivin, Pascal

2017-04-01

Soil quality assessment is rapidly developing worldwide, though mostly focused on the monitoring of arable land and soil fertility. Soil protection regulations assess soil quality differently, focusing on priority pollutants and threshold values. The soil physical properties are weakly considered, due to lack of consensus and experimental difficulties faced with characterization. Non-disputable, easy to perform and inexpensive methods should be available for environmental regulation to be applied, which is unfortunately not the case. As a consequence, quantitative soil physical protection regulation is not applied, and inexpensive soil physical quality indicators for arable soil management are not available. Overcoming these limitations was the objective of a research project funded by the Swiss federal office for environment (FOEN). The main results and the perspectives of application are given in this presentation. A first step of the research was to characterize soils in a good structural state (reference soils) under different land use. The structural quality was assessed with field expertise and Visual Evaluation of the Soil Structure (VESS), and the physical properties were assessed with Shrinkage analysis. The relationships between the physical properties and the soil constituents were linear and highly determined. They represent the reference properties of the corresponding soils. In a second step, the properties of physically degraded soils were analysed and compared to the reference properties. This allowed defining the most discriminant parameters departing the different structure qualities and their threshold limits. Equivalent properties corresponding to these parameters but inexpensive and easy to determine were defined and tested. More than 90% of the samples were correctly classed with this method, which meets, therefore, the requirements for practical application in regulation. Moreover, result-oriented agri-environmental schemes for soil quality

Differences in the regulation of chemicals and radionuclides

International Nuclear Information System (INIS)

Travis, C.C.

1993-12-01

Government regulations limiting public exposure to radionuclides and chemicals have historically been developed by regulatory agencies using different approaches with the result that levels of protection vary for the two classes of contaminants. These differences create difficulties in determining equitable regulatory measures when both radionuclides and chemical pollutants are involved. Generally, radiation exposure is not regulated as stringently as chemical exposure (Travis et al, 1989). The International commission on Radiological Protection (ICRP) recommends limiting excess environmental radiation exposure to the general public to 100 millirem per year (mrem/yr) (ICRP, 1991), a lifetime cancer risk of about 3.5E-3. An acceptable level of risk for chemical exposures is generally considered to be below 1E-6. Differences in regulatory approach for radionuclides and chemicals evoke debate over why they are different and which regulation strategy is better. Because these pollutants often coexist (mixed waste sites, contaminated metals and facilities, etc.), it is important to analyze inconsistencies in the regulation of chemicals and radionuclides and establish a more consistent approach to defining an acceptable level of exposure for these contaminants

RYBP and Cbx7 Define Specific Biological Functions of Polycomb Complexes in Mouse Embryonic Stem Cells

Directory of Open Access Journals (Sweden)

Lluis Morey

2013-01-01

Full Text Available The Polycomb repressive complex 1 (PRC1 is required for decisions of stem cell fate. In mouse embryonic stem cells (ESCs, two major variations of PRC1 complex, defined by the mutually exclusive presence of Cbx7 or RYBP, have been identified. Here, we show that although the genomic localization of the Cbx7- and RYBP-containing PRC1 complexes overlaps in certain genes, it can also be mutually exclusive. At the molecular level, Cbx7 is necessary for recruitment of Ring1B to chromatin, whereas RYBP enhances the PRC1 enzymatic activity. Genes occupied by RYBP show lower levels of Ring1B and H2AK119ub and are consequently more highly transcribed than those bound by Cbx7. At the functional level, we show that genes occupied by RYBP are primarily involved in the regulation of metabolism and cell-cycle progression, whereas those bound by Cbx7 predominantly control early-lineage commitment of ESCs. Altogether, our results indicate that different PRC1 subtypes establish a complex pattern of gene regulation that regulates common and nonoverlapping aspects of ESC pluripotency and differentiation.

Defining Cyberbullying.

Science.gov (United States)

Englander, Elizabeth; Donnerstein, Edward; Kowalski, Robin; Lin, Carolyn A; Parti, Katalin

2017-11-01

Is cyberbullying essentially the same as bullying, or is it a qualitatively different activity? The lack of a consensual, nuanced definition has limited the field's ability to examine these issues. Evidence suggests that being a perpetrator of one is related to being a perpetrator of the other; furthermore, strong relationships can also be noted between being a victim of either type of attack. It also seems that both types of social cruelty have a psychological impact, although the effects of being cyberbullied may be worse than those of being bullied in a traditional sense (evidence here is by no means definitive). A complicating factor is that the 3 characteristics that define bullying (intent, repetition, and power imbalance) do not always translate well into digital behaviors. Qualities specific to digital environments often render cyberbullying and bullying different in circumstances, motivations, and outcomes. To make significant progress in addressing cyberbullying, certain key research questions need to be addressed. These are as follows: How can we define, distinguish between, and understand the nature of cyberbullying and other forms of digital conflict and cruelty, including online harassment and sexual harassment? Once we have a functional taxonomy of the different types of digital cruelty, what are the short- and long-term effects of exposure to or participation in these social behaviors? What are the idiosyncratic characteristics of digital communication that users can be taught? Finally, how can we apply this information to develop and evaluate effective prevention programs? Copyright © 2017 by the American Academy of Pediatrics.

Defining Hardwood Veneer Log Quality Attributes

Science.gov (United States)

Jan Wiedenbeck; Michael Wiemann; Delton Alderman; John Baumgras; William Luppold

2004-01-01

This publication provides a broad spectrum of information on the hardwood veneer industry in North America. Veneer manufacturers and their customers impose guidelines in specifying wood quality attributes that are very discriminating but poorly defined (e.g., exceptional color, texture, and/or figure characteristics). To better understand and begin to define the most...

Defining Overweight and Obesity

Science.gov (United States)

... Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and Obesity Recommend on Facebook Tweet Share Compartir ... weight for a given height is described as overweight or obese. Body Mass Index, or BMI, is ...

The long and winding road--the journey of a cleft lip and palate patient part 1.

Science.gov (United States)

Madahar, Arun; Murray, Alison; Orr, Robert; Sandler, Paul Jonathan

2013-12-01

Patients with a cleft lip and palate (CLP) deformity require the highest standard of care that can be provided and this requires multidisciplinary care from teams located in regional cleft centres. Care of these cases is from birth to adulthood and requires several phases of intervention, corresponding to the stages of facial and dental development. Management ideally starts pre-natally, following the initial diagnosis, and occasionally pre-surgical appliances are prescribed. The lip is ideally repaired within three months, followed by palate closure between 12 and 18 months. Careful monitoring is required in the first few years and ENT referral, where necessary, will diagnose middle ear infection, which commonly affects CLP patients. Speech therapy is an integral part of the ongoing care. Excellent oral hygiene is essential and preventive dietary advice must be given and regularly reinforced. Orthodontic expansion is often needed at 9 years of age in preparation for a bone graft and, once the permanent dentition erupts, definitive orthodontic treatment will be required. Maxillary forward growth may have been constrained by scarring from previous surgery, so orthognathic correction may be required on growth completion. Final orthodontic alignment and high quality restorative care will allow the patients to have a pleasing aesthetic result. CLP patients and their families will need continuing support from medical and dental consultants, specialist nurses, health visitors, speech and language specialists and, perhaps, psychologists. These two articles outline the principles of care for the CLP patient and, secondly, illustrate this with a case report, documenting one patient's journey from birth to 21 years of age. A successful outcome for CLP patients requires a sound dentition.The general dental practitioner role is vital to establish and maintain excellent oral hygiene, a healthy diet and good routine preventive and restorative care. Understanding the total needs

Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene

Science.gov (United States)

Ludwig, Kerstin U.; Ahmed, Syeda Tasnim; Böhmer, Anne C.; Sangani, Nasim Bahram; Varghese, Sheryil; Klamt, Johanna; Schuenke, Hannah; Gültepe, Pinar; Hofmann, Andrea; Rubini, Michele; Aldhorae, Khalid Ahmed; Steegers-Theunissen, Regine P.; Rojas-Martinez, Augusto; Reiter, Rudolf; Borck, Guntram; Knapp, Michael; Nakatomi, Mitsushiro; Graf, Daniel; Mangold, Elisabeth; Peters, Heiko

2016-01-01

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdifflip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. PMID:26968009

Gene deletion of P-Selectin and ICAM-1 does not inhibit neutrophil infiltration into peritoneal cavity following cecal ligation-puncture

Directory of Open Access Journals (Sweden)

Hess Karen

2004-07-01

Full Text Available Abstract Background Neutrophil infiltration is one of the critical cellular components of an inflammatory response during peritonitis. The adhesion molecules, P-selectin and intercellular adhesion molecule (ICAM-1, mediate neutrophil-endothelial cell interactions and the subsequent neutrophil transendothelial migration during the inflammatory response. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy, suggesting that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the objective of this study was to determine the role of P-selectin and ICAM-1 in neutrophil infiltration into the peritoneal cavity during early and late phases of peritonitis. Methods Peritonitis was induced in both male wild-type and P-selectin/ICAM-1 double deficient (P/I null mice by cecal ligation-puncture (CLP. Peripheral blood and peritoneal lavage were collected at 6 and 24 hours after CLP. The total leukocyte and neutrophil contents were determined, and neutrophils were identified with the aid of in situ immunohistochemical staining. Comparisons between groups were made by applying ANOVA and student t-test analysis. Results CLP induced a severe inflammatory response associated with a significant leukopenia in both wild-type and P/I null mice. Additionally, CLP caused a significant neutrophil infiltration into the peritoneal cavity that was detected in both groups of mice. However, neutrophil infiltration in the P/I null mice at 6 hours of CLP was significantly lower than the corresponding wild-type mice, which reached a similar magnitude at 24 hours of CLP. In contrast, in peritonitis induced by intraperitoneal inoculation of 2% glycogen, no significant difference in neutrophil infiltration was observed between the P/I null and wild-type mice at 6 hours of peritonitis. Conclusions The data suggest that alternative adhesion pathway(s independent of P-selectin and ICAM

Distinct interferon-gamma and interleukin-9 expression in cutaneous and oral lichen planus.

Science.gov (United States)

Weber, B; Schlapbach, C; Stuck, M; Simon, H-U; Borradori, L; Beltraminelli, H; Simon, D

2017-05-01

Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP. Using immunofluorescence staining and laser scanning microscopy, we evaluated the cellular infiltrate (CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression (interleukin (IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis factor-α, transforming growth factor-β, interferon (IFN)-γ), and apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized biopsy specimens of LP (11 CLP, 10 OLP). Among infiltrating cells mainly T cells and natural killer (NK) cells as well as plasmacytoid dendritic cells (DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The expression of IL-9, IFN-γ and IL-22 was higher in CLP compared to that of OLP (P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas ligand as well as cleaved caspase-3-positive cells was observed in the epithelium of all LP samples. The cell and cytokine patterns of CLP and OLP were partially distinct and generally resembled those reported for autoimmune diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression suggested that various pathways involved in keratinocyte apoptosis are relevant for LP. These results might help to establish targeted therapies for LP. © 2016 European Academy of Dermatology and Venereology.

Tropomyosin 4 defines novel filaments in skeletal muscle associated with muscle remodelling/regeneration in normal and diseased muscle.

Science.gov (United States)

Vlahovich, Nicole; Schevzov, Galina; Nair-Shaliker, Visalini; Ilkovski, Biljana; Artap, Stanley T; Joya, Josephine E; Kee, Anthony J; North, Kathryn N; Gunning, Peter W; Hardeman, Edna C

2008-01-01

The organisation of structural proteins in muscle into highly ordered sarcomeres occurs during development, regeneration and focal repair of skeletal muscle fibers. The involvement of cytoskeletal proteins in this process has been documented, with nonmuscle gamma-actin found to play a role in sarcomere assembly during muscle differentiation and also shown to be up-regulated in dystrophic muscles which undergo regeneration and repair [Lloyd et al.,2004; Hanft et al.,2006]. Here, we show that a cytoskeletal tropomyosin (Tm), Tm4, defines actin filaments in two novel compartments in muscle fibers: a Z-line associated cytoskeleton (Z-LAC), similar to a structure we have reported previously [Kee et al.,2004], and longitudinal filaments that are orientated parallel to the sarcomeric apparatus, present during myofiber growth and repair/regeneration. Tm4 is upregulated in paradigms of muscle repair including induced regeneration and focal repair and in muscle diseases with repair/regeneration features, muscular dystrophy and nemaline myopathy. Longitudinal Tm4-defined filaments also are present in diseased muscle. Transition of the Tm4-defined filaments from a longitudinal to a Z-LAC orientation is observed during the course of muscle regeneration. This Tm4-defined cytoskeleton is a marker of growth and repair/regeneration in response to injury, disease state and stress in skeletal muscle.

A self-defining hierarchical data system

Science.gov (United States)

Bailey, J.

1992-01-01

The Self-Defining Data System (SDS) is a system which allows the creation of self-defining hierarchical data structures in a form which allows the data to be moved between different machine architectures. Because the structures are self-defining they can be used for communication between independent modules in a distributed system. Unlike disk-based hierarchical data systems such as Starlink's HDS, SDS works entirely in memory and is very fast. Data structures are created and manipulated as internal dynamic structures in memory managed by SDS itself. A structure may then be exported into a caller supplied memory buffer in a defined external format. This structure can be written as a file or sent as a message to another machine. It remains static in structure until it is reimported into SDS. SDS is written in portable C and has been run on a number of different machine architectures. Structures are portable between machines with SDS looking after conversion of byte order, floating point format, and alignment. A Fortran callable version is also available for some machines.

Clinical and histological responses to laparoscopically-induced peritonitis in rats Resposta clínica e histológica à indução de peritonite via laparoscopia em ratos

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Paulo Roberto Rodrigues Bicalho

2008-10-01

Full Text Available PURPOSE: To evaluate the efficacy of inducing peritonitis in rats through laparoscopic cecal ligation (CL, by means of an elastic band. METHODS: Twelve Wistar rats were subjected to cecal ligated with an elastic band applied using a specially constructed applicator. In six of the animals (the CL group the cecal sac was preserved intact whilst in the remaining animals (the CLP group the sac was perforated with scissors. Clinical parameters, characteristics of the peritoneal cavity and cecum, and histological features of the cecal tissue were observed in all experimental animals 8 and 24 h after surgery. RESULTS: CLP animals exhibited at least one clinical sign of sepsis within the first 8 h of observation. The peritoneal liquid was observed to be clear in almost all members of the CLP. Polymorphonucleated cells were detected in the tunica serosa of the cecum of CLP animals. In contrast, all members of the CL group were alive after 24h, and of polymorphonucleated cells in the muscle layer of the cecal wall were observed. The presence of peritoneal liquid was not detected in CL animals. CONCLUSION: Although elastic ligation of the cecum was reproducible, puncture of the cecal sac was essential for induction of sepsis.OBJETIVO: Avaliar a eficácia de induzir peritonite em ratos através da ligadura cecal laparoscópica (CL, por meio de banda elástica. MÉTODOS: Doze ratos Wistar foram submetidos a ligadura cecal com banda elástica aplicada com dispositivo especialmente construído para este fim. Em seis animais (grupo CL, a bolsa cecal foi mantida intacta, enquanto nos outros animais (grupo CLP, a bolsa foi perfurada com tesoura. Parâmetros clínicos, características da cavidade peritonial e ceco, e histologia do tecido cecal foram examinados em todos os animais 8 e 24 horas após a cirurgia. RESULTADOS: Os animais do grupo CLP apresentaram pelo menos um sinal clínico de sepses nas primeiras 8 h de observação. Líquido peritonial claro foi

16 CFR 304.1 - Terms defined.

Science.gov (United States)

2010-01-01

... political item means any political button, poster, literature, sticker, or any advertisement produced for... other business entity. (i) Regulations means any or all regulations prescribed by the Federal Trade...

Msx2 Plays a central Role in Regulating Branching Morphogenesis During Mammary Development

National Research Council Canada - National Science Library

Liu, Yi-Hsin

2002-01-01

The purpose of this study is to determine the role of a transcriptional factor, Msx2, in regulating branching events in the development of the mouse mammary gland To define the function of Msx2 gene...

Development of Critical Thinking with Metacognitive Regulation and Toulmin Model

Science.gov (United States)

Gotoh, Yasushi

2017-01-01

Developing critical thinking is an important factor in education. In this study, the author defines critical thinking as the set of skills and dispositions which enable one to solve problems logically and to attempt to reflect autonomously by means of metacognitive regulation of one's own problem-solving processes. To identify the validity and…

Private ordering and the rise of terms of service as cyber-regulation

Directory of Open Access Journals (Sweden)

Luca Belli

2016-12-01

Full Text Available Online communications and activities require the intermediation of numerous private entities that unilaterally define and implement their terms of service (ToS. The substantive provisions set in the ToS regulate the relationships between intermediaries and users with a binding force that may be even stronger than the one exercised by the law. Notably, we stress that internet intermediaries privately enforce their contractual regulation by shaping the architecture of the networks and platforms under their control. Such regulation and implementation do not need to rely on “traditional” public law-enforcement mechanisms and may apply in a transnational fashion. This paper argues that internet governance is witnessing the increasing centralisation of power in the hands of internet intermediaries defining private orderings. While acknowledging that ToS are an efficient and well-suited instrument to regulate the online world, we claim that ToS unilaterally impose rules, despite being presented as voluntarily accepted by the involved parties through the expression of free and informed consent. Based on empirical research, we highlight that ToS and their private implementation affect internet users’ capability to enjoy their human rights, with particular regard to freedom of expression (and innovation, the right to privacy and to due process. Lastly, we put forward some recommendations on internet intermediaries’ compliance with human rights standards.

How do people define moderation?

Science.gov (United States)

vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

2016-06-01

Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. Copyright © 2016 Elsevier Ltd. All rights reserved.

Poster: A Software-Defined Multi-Camera Network

OpenAIRE

Chen, Po-Yen; Chen, Chien; Selvaraj, Parthiban; Claesen, Luc

2016-01-01

The widespread popularity of OpenFlow leads to a significant increase in the number of applications developed in SoftwareDefined Networking (SDN). In this work, we propose the architecture of a Software-Defined Multi-Camera Network consisting of small, flexible, economic, and programmable cameras which combine the functions of the processor, switch, and camera. A Software-Defined Multi-Camera Network can effectively reduce the overall network bandwidth and reduce a large amount of the Capex a...

The effects of different regulation strategies on Jiangsu's wind integration

DEFF Research Database (Denmark)

Hong, Lixuan; Lund, Henrik; Möller, Bernd

This paper presents the influence of different regulation strategies on wind energy integration into existing Jiangsu’s energy system. The ability of wind integration is defined in terms of the ability to avoid excess electricity production, to conserve primary energy consumptions and to reduce CO2...... emissions in the system. Firstly, a reference model of Jiangsu’s energy system is built by using EnergyPLAN based on the year 2009. The model results then are compared to actual values from 2009 to validate its accuracy. Based on the reference model, different regulations of Jiangsu’s energy system...

Roquin Paralogs Differentially Regulate Functional NKT Cell Subsets.

Science.gov (United States)

Drees, Christoph; Vahl, J Christoph; Bortoluzzi, Sabrina; Heger, Klaus D; Fischer, Julius C; Wunderlich, F Thomas; Peschel, Christian; Schmidt-Supprian, Marc

2017-04-01

NKT cells represent a small subset of glycolipid-recognizing T cells that are heavily implicated in human allergic, autoimmune, and malignant diseases. In the thymus, precursor cells recognize self-glycolipids by virtue of their semi-invariant TCR, which triggers NKT cell lineage commitment and maturation. During their development, NKT cells are polarized into the NKT1, NKT2, and NKT17 subsets, defined through their cytokine-secretion patterns and the expression of key transcription factors. However, we have largely ignored how the differentiation into the NKT cell subsets is regulated. In this article, we describe the mRNA-binding Roquin-1 and -2 proteins as central regulators of murine NKT cell fate decisions. In the thymus, T cell-specific ablation of the Roquin paralogs leads to a dramatic expansion of NKT17 cells, whereas peripheral mature NKT cells are essentially absent. Roquin-1/2-deficient NKT17 cells show exaggerated lineage-specific expression of nearly all NKT17-defining proteins tested. We show through mixed bone marrow chimera experiments that NKT17 polarization is mediated through cell-intrinsic mechanisms early during NKT cell development. In contrast, the loss of peripheral NKT cells is due to cell-extrinsic factors. Surprisingly, Roquin paralog-deficient NKT cells are, in striking contrast to conventional T cells, compromised in their ability to secrete cytokines. Altogether, we show that Roquin paralogs regulate the development and function of NKT cell subsets in the thymus and periphery. Copyright © 2017 by The American Association of Immunologists, Inc.

Defining chaos.

Science.gov (United States)

Hunt, Brian R; Ott, Edward

2015-09-01

In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call "expansion entropy," and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

Thermoresponsive Self-Assembly of Nanostructures from a Collagen-Like Peptide-Containing Diblock Copolymera

OpenAIRE

Luo, Tianzhi; He, Lirong; Theato, Patrick; Kiick, Kristi L.

2014-01-01

Temperature-triggered formation of nanostructures with distinct biological activity offers opportunities in selective modification of matrices and in drug delivery. Toward these ends, diblock polymers comprising poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) conjugated to a triple helix-forming collagen-like peptide (CLP) is produced. The ability of the CLP domain to maintain its triple helix conformation after conjugation with the polymer is confirmed via circular dichroism (CD...

Bilayer graphene quantum dot defined by topgates

Energy Technology Data Exchange (ETDEWEB)

Müller, André; Kaestner, Bernd; Hohls, Frank; Weimann, Thomas; Pierz, Klaus; Schumacher, Hans W., E-mail: hans.w.schumacher@ptb.de [Physikalisch-Technische Bundesanstalt, Bundesallee 100, 38116 Braunschweig (Germany)

2014-06-21

We investigate the application of nanoscale topgates on exfoliated bilayer graphene to define quantum dot devices. At temperatures below 500 mK, the conductance underneath the grounded gates is suppressed, which we attribute to nearest neighbour hopping and strain-induced piezoelectric fields. The gate-layout can thus be used to define resistive regions by tuning into the corresponding temperature range. We use this method to define a quantum dot structure in bilayer graphene showing Coulomb blockade oscillations consistent with the gate layout.

On calculating double logarithmical asymptotics of vertex functions defined on the mass shell

International Nuclear Information System (INIS)

Belokurov, V.V.; Usyukina, N.I.

1981-01-01

The essence of the calculation method of double logarithmical asymptotics of vertex functions defined on the mass shell is presented. Using the method the asymptotics of the form-factor of electron is calculated. The ladder and cross-ladder diagrams are asymptotically considerable in every order of the perturbation theory. The way in which the asymptotics of the 4-order diagrams is calculated has been shown. The diagrams of this order and reduction procedures for them are given in a graphic form. The photon mass μ 2 not equal to 0 plays the role of a regulator, removing infrared divergencies. The double logarithmical asymptotics of the form-factor of electron on the mass shell is calculated rigorously in an arbitrary order of the perturbation theory [ru

Efficiency analysis of energy networks: An international survey of regulators

International Nuclear Information System (INIS)

Haney, Aoife Brophy; Pollitt, Michael G.

2009-01-01

Incentive regulation for networks has been an important part of the reform agenda in a number of countries. As part of this regulatory process, incentives are put in place to improve the cost efficiency of network companies by rewarding good performance relative to a pre-defined benchmark. The techniques used to establish benchmarks are central to the efficiency improvements that are ultimately achieved. Much experience has been gained internationally in the application of benchmarking techniques and we now have a solid understanding of the main indicators of best practice. What we are lacking is a more complete understanding of the factors that influence choice of methods by regulators. In this paper, we present the results of an international survey of energy regulators in 40 countries conducted electronically between June and October 2008. Regulators from European, Australasian and Latin American countries are represented in the survey. Our results show that benchmarking techniques are now widespread in the regulation of gas and electricity networks. Best practice, however, is limited to a small number of regulators. We conclude by summarising existing trends and offering some recommendations on overcoming barriers to best practice efficiency analysis.

Medical device software: defining key terms.

Science.gov (United States)

Pashkov, Vitalii; Gutorova, Nataliya; Harkusha, Andrii

one of the areas of significant growth in medical devices has been the role of software - as an integral component of a medical device, as a standalone device and more recently as applications on mobile devices. The risk related to a malfunction of the standalone software used within healthcare is in itself not a criterion for its qualification or not as a medical device. It is therefore, necessary to clarify some criteria for the qualification of stand-alone software as medical devices Materials and methods: Ukrainian, European Union, United States of America legislation, Guidelines developed by European Commission and Food and Drug Administration's, recommendations represented by international voluntary group and scientific works. This article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. the legal regulation of software which is used for medical purpose in Ukraine limited to one definition. In European Union and United States of America were developed and applying special guidelines that help developers, manufactures and end users to difference software on types standing on medical purpose criteria. Software becomes more and more incorporated into medical devices. Developers and manufacturers may not have initially appreciated potential risks to patients and users such situation could have dangerous results for patients or users. It is necessary to develop and adopt the legislation that will intend to define the criteria for the qualification of medical device software and the application of the classification criteria to such software, provide some illustrative examples and step by step recommendations to qualify software as medical device.

Numeric Computation of the Radar Cross Section of In-flight Projectiles

Science.gov (United States)

2016-11-01

projectile axis after SPY is aligned with the vertical axis. The difference between these 2 frames is illustrated in Fig. 4. Approved for public release...the antenna effective length,11 h, defined as t rjksci e r IjZ hE 0 2 0 −= λ , (38) for the transmitter antenna, and sHroV Eh= , (39) for the...0.119 (at Mach = 0.7) CLα 2.41 2.00 CNpα 0.51 N/A Clp –0.024 N/A CMα 4.65 – 2 CMq –26 –22 V0 (m/s) 564 243 p0 (rad/s) 1143 0 φB0 (°) 40 50

Regulation of the Hsp104 middle domain activity is critical for yeast prion propagation.

Directory of Open Access Journals (Sweden)

Jennifer E Dulle

Full Text Available Molecular chaperones play a significant role in preventing protein misfolding and aggregation. Indeed, some protein conformational disorders have been linked to changes in the chaperone network. Curiously, in yeast, chaperones also play a role in promoting prion maintenance and propagation. While many amyloidogenic proteins are associated with disease in mammals, yeast prion proteins, and their ability to undergo conformational conversion into a prion state, are proposed to play a functional role in yeast biology. The chaperone Hsp104, a AAA+ ATPase, is essential for yeast prion propagation. Hsp104 fragments large prion aggregates to generate a population of smaller oligomers that can more readily convert soluble monomer and be transmitted to daughter cells. Here, we show that the middle (M domain of Hsp104, and its mobility, plays an integral part in prion propagation. We generated and characterized mutations in the M-domain of Hsp104 that are predicted to stabilize either a repressed or de-repressed conformation of the M-domain (by analogy to ClpB in bacteria. We show that the predicted stabilization of the repressed conformation inhibits general chaperone activity. Mutation to the de-repressed conformation, however, has differential effects on ATP hydrolysis and disaggregation, suggesting that the M-domain is involved in coupling these two activities. Interestingly, we show that changes in the M-domain differentially affect the propagation of different variants of the [PSI+] and [RNQ+] prions, which indicates that some prion variants are more sensitive to changes in the M-domain mobility than others. Thus, we provide evidence that regulation of the M-domain of Hsp104 is critical for efficient prion propagation. This shows the importance of elucidating the function of the M-domain in order to understand the role of Hsp104 in the propagation of different prions and prion variants.

The pursuit of self-esteem: contingencies of self-worth and self-regulation.

Science.gov (United States)

Crocker, Jennifer; Brook, Amara T; Niiya, Yu; Villacorta, Mark

2006-12-01

Successful self-regulation is defined as the willingness to exert effort toward one's most important goals, while taking setbacks and failures as opportunities to learn, identify weaknesses and address them, and develop new strategies toward achieving those goals. Contingencies of self-worth can facilitate self-regulation because people are highly motivated to succeed and avoid failure in domains of contingency. However, because boosts in self-esteem are pleasurable and drops in self-esteem are painful, protection, maintenance, and enhancement of self-esteem can become the overriding goal. Several pitfalls for self-regulation can result, especially when tasks are difficult and failure is likely. In this article, we describe a program of research examining these self-regulation pitfalls associated with contingent self-worth and suggest that learning orientations, particularly the willingness to embrace failure for the learning it affords, foster successful self-regulation even in people with highly contingent self-esteem.

Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

Science.gov (United States)

Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

2009-11-30

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

The Financial Regulation of the Country’s Economic Development

Directory of Open Access Journals (Sweden)

Davydova Irina I.

2017-12-01

Full Text Available The article is aimed at disclosing the essence of the system of financial regulation of economic development of the country, defining institutional foundations in the process of development of financial mechanism. Approaches to strengthening the efficiency of financial policy as an important economic institution, which should significantly influence economic growth, have been developed. The directions of increase of efficiency of budget policy in conditions of institutional changes have been defined. Currently, financial regulation of the country is being formed in the context of socio-economic policy, which is resulting from the need for the State participation in the world economic and financial relations, for improving the quality of public services on the part of the State, which requires the implementation of a strategy of economic growth at a qualitatively new institutional level. The State financial policy should ultimately focus on the appropriate endogenous factors of economic growth. In modern conditions it is expedient to strengthen the role of financial policy as a significant macro-economic instrument, which provides an effective influence on achievement of financial and economic balance, efficiency of economic transformations.

Diverse Genetic Regulon of the Virulence-Associated Transcriptional Regulator MucR in Brucella abortus 2308

Science.gov (United States)

Caswell, Clayton C.; Elhassanny, Ahmed E. M.; Planchin, Emilie E.; Roux, Christelle M.; Weeks-Gorospe, Jenni N.; Ficht, Thomas A.; Dunman, Paul M.

2013-01-01

The Ros-type regulator MucR is one of the few transcriptional regulators that have been linked to virulence in Brucella. Here, we show that a Brucella abortus in-frame mucR deletion strain exhibits a pronounced growth defect during in vitro cultivation and, more importantly, that the mucR mutant is attenuated in cultured macrophages and in mice. The genetic basis for the attenuation of Brucella mucR mutants has not been defined previously, but in the present study the genes regulated by MucR in B. abortus have been elucidated using microarray analysis and real-time reverse transcription-PCR (RT-PCR). In B. abortus 2308, MucR regulates a wide variety of genes whose products may function in establishing and maintaining cell envelope integrity, polysaccharide biosynthesis, iron homeostasis, genome plasticity, and transcriptional regulation. Particularly notable among the MucR-regulated genes identified is arsR6 (nolR), which encodes a transcriptional regulator previously linked to virulence in Brucella melitensis 16 M. Importantly, electrophoretic mobility shift assays (EMSAs) determined that a recombinant MucR protein binds directly to the promoter regions of several genes repressed by MucR (including arsR6 [nolR]), and in Brucella, as in other alphaproteobacteria, MucR binds to its own promoter to repress expression of the gene that encodes it. Overall, these studies have uncovered the diverse genetic regulon of MucR in Brucella, and in doing so this work has begun to define the MucR-controlled genetic circuitry whose misregulation contributes to the virulence defect of Brucella mucR mutants. PMID:23319565

7 CFR 54.1002 - Terms defined.

Science.gov (United States)

2010-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) MEATS, PREPARED MEATS, AND...

Defining local food

DEFF Research Database (Denmark)

Eriksen, Safania Normann

2013-01-01

Despite evolving local food research, there is no consistent definition of “local food.” Various understandings are utilized, which have resulted in a diverse landscape of meaning. The main purpose of this paper is to examine how researchers within the local food systems literature define local...... food, and how these definitions can be used as a starting point to identify a new taxonomy of local food based on three domains of proximity....

Crown lengthening procedure following intentional endodontic therapy for correction of supra-erupted posterior teeth: Case series with long-term follow-up

Science.gov (United States)

Patil, Shruti Arun; Kulkarni, Sudhindra; Thakur, Srinath; Naik, Balaram

2016-01-01

Context: The crown lengthening procedure (CLP) is routinely carried out to correct gingival levels and achieve esthetic contours and adequate crown lengths for restorative purposes. Though the short-term outcomes have been found to be stable, long-term results are not much reported. Aims: To evaluate the long-term stability of the marginal bone levels, gingival levels, and the status of the teeth, which underwent endodontic therapy, followed by CLP and final restorations. Settings and Design: Institutional setting, long-term case series. Materials and Methods: Case records of the patients who underwent CLP and endodontic therapy for corrections of the supra-erupted teeth to regain the lost interocclusal spaces were retrieved, and the cases with complete set of the clinical and radiographs were taken. All the cases were recalled and bone levels on the radiographs, bleeding on probing, probing pocket depths, and changes in the soft tissue margins were evaluated. Statistical Analysis Used: Descriptive analysis. Results: A total of 25 teeth had undergone CLP and endodontic therapy and final restorations for a minimum of 24 months. The mean post-restorative duration was 50.8 ± 22.48 months (range 24–96 months). All the teeth were functional and asymptomatic with 100% survival. Interdental bone loss of 1 mm, probing pockets of 5 mm, and 1 mm buccal recession were observed in 16% of the sites. The amount of interocclusal space regained was adequate to restore the missing teeth in the opposing arch. Conclusions: The CLP is a predictive procedure for correction of supra-erupted teeth. The survival of the teeth that underwent the procedure in the present study was 100% over 24–96 months. PMID:27041850

Chronic Widespread Back Pain is Distinct From Chronic Local Back Pain: Evidence From Quantitative Sensory Testing, Pain Drawings, and Psychometrics.

Science.gov (United States)

Gerhardt, Andreas; Eich, Wolfgang; Janke, Susanne; Leisner, Sabine; Treede, Rolf-Detlef; Tesarz, Jonas

2016-07-01

Whether chronic localized pain (CLP) and chronic widespread pain (CWP) have different mechanisms or to what extent they overlap in their pathophysiology is controversial. The study compared quantitative sensory testing profiles of nonspecific chronic back pain patients with CLP (n=48) and CWP (n=29) with and fibromyalgia syndrome (FMS) patients (n=90) and pain-free controls (n = 40). The quantitative sensory testing protocol of the "German-Research-Network-on-Neuropathic-Pain" was used to measure evoked pain on the painful area in the lower back and the pain-free hand (thermal and mechanical detection and pain thresholds, vibration threshold, pain sensitivity to sharp and blunt mechanical stimuli). Ongoing pain and psychometrics were captured with pain drawings and questionnaires. CLP patients did not differ from pain-free controls, except for lower pressure pain threshold (PPT) on the back. CWP and FMS patients showed lower heat pain threshold and higher wind-up ratio on the back and lower heat pain threshold and cold pain threshold on the hand. FMS showed lower PPT on back and hand, and higher comorbidity of anxiety and depression and more functional impairment than all other groups. Even after long duration CLP presents with a local hypersensitivity for PPT, suggesting a somatotopically specific sensitization of nociceptive processing. However, CWP patients show widespread ongoing pain and hyperalgesia for different stimuli that is generalized in space, suggesting the involvement of descending control systems, as also suggested for FMS patients. Because mechanisms in nonspecific chronic back pain with CLP and CWP differ, these patients should be distinguished in future research and allocated to different treatments.

Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.

Science.gov (United States)

Gowans, Lord Jephthah Joojo; Oseni, Ganiyu; Mossey, Peter A; Adeyemo, Wasiu Lanre; Eshete, Mekonen A; Busch, Tamara D; Donkor, Peter; Obiri-Yeboah, Solomon; Plange-Rhule, Gyikua; Oti, Alexander A; Owais, Arwa; Olaitan, Peter B; Aregbesola, Babatunde S; Oginni, Fadekemi O; Bello, Seidu A; Audu, Rosemary; Onwuamah, Chika; Agbenorku, Pius; Ogunlewe, Mobolanle O; Abdur-Rahman, Lukman O; Marazita, Mary L; Adeyemo, A A; Murray, Jeffrey C; Butali, Azeez

2018-05-01

Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

Cleft characteristics and treatment outcomes in hemifacial microsomia compared to non-syndromic cleft lip/palate.

Science.gov (United States)

Dentino, K M; Valstar, A; Padwa, B L

2016-06-01

The goal of this study was to describe the clinical characteristics and treatment outcomes of patients with hemifacial microsomia (HFM) and cleft lip/palate (CL/P), and to compare them to a historic cohort of patients with non-syndromic CL/P treated at the same centre. A retrospective review of patients with HFM and CL/P was performed; the main outcome measures assessed were cleft type/side, surgical outcome, midfacial retrusion, and speech. Twenty-six patients (13 male, 13 female; mean age 22.7±14.9, range 1-52 years) with cleft lip with/without cleft palate (CL±P) were identified: three with cleft lip (12%), two with cleft lip and alveolus and an intact secondary palate (8%), and 21 with cleft lip and palate (CLP) (81%; 15 unilateral and six bilateral). Four patients (19%) had a palatal fistula after palatoplasty. Twelve of 22 patients aged >5 years (55%) had midfacial retrusion and two (9%) required a pharyngeal flap for velopharyngeal insufficiency (VPI). Fisher's exact test demonstrated a higher frequency of complete labial clefting (P=0.004), CLP (P=0.009), midfacial retrusion (P=0.0009), and postoperative palatal fistula (P=0.03) in HFM compared to non-syndromic CL±P. There was no difference in VPI prevalence. This study revealed that patients with HFM and CL±P have more severe forms of orofacial clefting than patients with non-syndromic CL±P. Patients with HFM and CL±P have more severe midfacial retrusion and a higher palatal fistula rate compared to patients with non-syndromic CL±P. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Initial Nutritional Assessment of Infants With Cleft Lip and/or Palate: Interventions and Return to Birth Weight.

Science.gov (United States)

Kaye, Alison; Thaete, Kristi; Snell, Audrey; Chesser, Connie; Goldak, Claudia; Huff, Helen

2017-03-01

  To assess and quantify cleft team practices with regard to nutritional support in the neonatal period Design :  Retrospective review.   Tertiary pediatric hospital.   One hundred consecutive newborn patients with a diagnosis of cleft lip and/or cleft palate between 2009 and 2012.   Birth weight, cleft type, initial cleft team weight measurements, initial feeding practices, recommended nutritional interventions, and follow-up nutritional assessments.   All patients in the study were evaluated by a registered dietitian and an occupational feeding therapist. Average birth weight and average age at the first cleft team visit were similar for each cleft type: cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP). The calculated age (in days) for return to birth weight was significantly different between cleft types: CL = 13.58 days, CLP = 15.88 days, and CP = 21.93 days. Exclusive use of breast milk was 50% for patients with CL, 30.3% for patients with CLP, and 21.4% for patients with CP. Detailed nutritional interventions were made for 31 patients at the first visit: two with CL, 14 with CLP, and 15 with CP.   Distinct differences were seen in neonatal weight gain between cleft types. There was significantly greater total weight gain for patients with CL at their first visit and significantly slower return to birth weight for patients with isolated CP. Patients with CL required far fewer interventions at the initial assessment and were more likely to be provided breast milk exclusively or in combination with formula. Infants with CP were far less likely to receive any breast milk. Patients with CLP and CP required frequent nutritional interventions.

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

International Nuclear Information System (INIS)

Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

1987-01-01

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14 C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis

Defining and classifying syncope

NARCIS (Netherlands)

Thijs, Roland D.; Wieling, Wouter; Kaufmann, Horacio; van Dijk, Gert

2004-01-01

There is no widely adopted definition or classification of syncope and related disorders. This lack of uniformity harms patient care, research, and medical education. In this article, syncope is defined as a form of transient loss of consciousness (TLOC) due to cerebral hypoperfusion. Differences

7 CFR 51.2 - Terms defined.

Science.gov (United States)

2010-01-01

... other factor which may occur, develop, or progress in the marketing channels. (g) Agricultural Marketing... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946...

ANATOMICAL VARIATIONS FINDINGS ON CONE BEAM-COMPUTED TOMOGRAPHY IN CLEFT LIP AND PALATE PATIENTS

Directory of Open Access Journals (Sweden)

Yllka DECOLLI

2015-09-01

Full Text Available Introduction: Cone beam computed tomography (CBCT is frequently used in surgery treatment planning in patients with cleft lip and palate (CLP. The aim of this study was to investigate the presence of different anatomical variations of patients with cleft lip and palate using CBCT images. Materials and method: CBCTs taken from consecutive patients (n =25; mean age 10.7±4 years, range 6.5–23 years with a non-syndromic cleft lip and palate (CLP, between June 2014-2015, were systematically evaluated. Sinuses, nasopharynx, oropharynx, hypopharynx, temporo-mandibular joint (TMJ, maxilla and mandible were checked for incidental findings. Results: On 90.1 % of the CBCTs, incidental findings were found. The most prevalent ones were airway/sinus findings (78.1%, followed by dental problems, e.g. missing teeth (54%, nasal septum deviation (93%, middle ear and mastoid opacification, suggestive for otitis media (8% and (chronic mastoiditis (7%, abnormal TMJ anatomy (4.3%. Conclusions: Incidental findings are common on CBCTs in cleft lip and palate patients. Compared with the literature, CLP patients have more dental, nasal and ear problems. The CBCT scan should be reviewed by all specialists in the CLP team, stress being laid on their specific background knowledge concerning symptoms and treatment of these patients.

Profile Changes and Stability following Distraction Osteogenesis with Rigid External Distraction in Adult Cleft Lip and Palate Deformities

Science.gov (United States)

Painatt, Jaeson M.; Veeraraghavan, Ravi; Puthalath, Ushass; Peter, Sherry; Rao, Latha P.; Kuriakose, Maria

2017-01-01

Objectives: The objective of this study is to analyze the hard and soft-tissue profile changes as well as the upper airway changes after distraction osteogenesis (DO) using rigid external distraction device in adult cleft lip and palate (CLP) patients. The study also evaluates the stability of the surgical result. Materials and Methods: Three lateral cephalometric radiographs were taken: Predistraction (T1), postdistraction (T2), and 1 year after distractor removal (T3). The treatment changes (T1 vs. T2) and the stability (T2 vs. T3) were analyzed. The overall treatment changes after 1 year were also evaluated (T1 vs. T3). The lateral cephalograms were digitally analyzed with the help of software named Dolphin. Statistical Analysis Used: Wilcoxon Signed-Ranks test was used, and the probability value (P value) of 0.05 was considered as statistically significant level. Results: Eleven adult patients with CLP were retrospectively analyzed. After distraction, there was a significant mean maxillary advancement of 14 mm (P maxillary relapse of 3.20 mm (P maxillary advancement for CLP patients with DO. There were significant improvements immediately after distraction, but during the 1-year follow-up, some relapse was seen. This stressed on the need for overcorrection of about 35%–40% for adult CLP patients. PMID:28839409

Long-term results of maxillary distraction osteogenesis in nongrowing cleft: 5-years experience using internal device.

Science.gov (United States)

Hirjak, D; Reyneke, J P; Janec, J; Beno, M; Kupcova, I

2016-01-01

Patients with cleft lip and palate (CLP) related deformities frequently have maxillary hypoplasia in all dimensions. These patients usually present with class III malocclusions, retruded midfaces and narrow hard palates. The skeletal problems can be treated by means of Le Fort I maxillary procedures. Surgical and orthodontic correction of severe maxillary hypoplasia, as often seen in CLP patients, has however proved to be challenging. The magnitude of the advancement is often hampered and the post operative stability significantly affected by palatal soft tissue scarring. The slow distraction of bone and the histogenic abilities of distraction osteogenesis (DO) have made it an atractive alternative treatment option for the management of maxillary hypoplasia in these patients. This paper presents the treatment results of 15 nongrowing CLP patients with severe maxillary hypoplasia treated by means of intra oral distraction. The mean anterior distraction of the maxillas was 12.7 mm (9-15.0 mm). The long-term cephalometric and clinical evaluation after a minimum of 60 months (mean follow-up 71 months) proved to be stable. The treatment results revealed, that distraction osteogenesis in nongrowing CLP patients with severe maxillary hypoplasia proved to be a predictable and stable option (Tab. 2, Fig. 3, Ref. 26).