dutch-mutated asz40 dasz1-40: Topics by WorldWideScience.org

Sample records for dutch-mutated asz40 dasz1-40

A novel TECTA mutation in a Dutch DFNA8/12 family confirms genotype-phenotype correlation.

NARCIS (Netherlands)

Plantinga, R.F.; Brouwer, A.P.M. de; Huygen, P.L.M.; Kunst, H.P.M.; Kremer, H.; Cremers, C.W.R.J.

2006-01-01

A novel TECTA mutation, p.R1890C, was found in a Dutch family with nonsyndromic autosomal dominant sensorineural hearing impairment. In early life, presumably congenital, hearing impairment occurred in the midfrequency range, amounting to about 40 dB at 1 kHz. Speech recognition was good with all
Screening of 1331 Danish breast and/or ovarian cancer families identified 40 novel BRCA1 and BRCA2 mutations

DEFF Research Database (Denmark)

Hansen, Thomas V O; Jønson, Lars; Steffensen, Ane Y

2011-01-01

Germ-line mutations in the tumour suppressor genes BRCA1 and BRCA2 predispose to breast and ovarian cancer. Since 1999 we have performed mutational screening of breast and/or ovarian cancer patients in East Denmark. During this period we have identified 40 novel sequence variations in BRCA1...... and BRCA2 in high risk breast and/or ovarian cancer families. The mutations were detected via pre-screening using dHPLC or high-resolution melting and direct sequencing. We identified 16 variants in BRCA1, including 9 deleterious frame-shift mutations, 2 intronic variants, 4 missense mutations, and 1......, the presumed significance of the missense mutations was predicted in silico using the align GVGD algorithm. In conclusion, the mutation screening identified 40 novel variants in the BRCA1 and BRCA2 genes and thereby extends the knowledge of the BRCA1/BRCA2 mutation spectrum. Nineteen of the mutations were...
Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man.

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Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Alvarez-Sala-Walther, Luis-Antonio; Cuadrado-Grande, Nuria; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

2011-03-01

The most common form of hemochromatosis is caused by mutations in the HFE gene. Rare forms of the disease are caused by mutations in other genes. We present a patient with hyperferritinemia and iron overload, and facial flushing. Magnetic resonance imaging was performed to measure hepatic iron overload, and a molecular study of the genes involved in iron metabolism was undertaken. The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and facial flushing improved after phlebotomy. Two of the patient's children were also studied, and the daughter was heterozygous for the mutation in the SLC40A1 gene, although she did not have hyperferritinemia. The patient presented a mild iron overload phenotype probably because of the two novel mutations in the HFE and SLC40A1 genes. © 2011 John Wiley & Sons A/S.
NMR structure of the Arctic mutation of the Alzheimer's Aβ(1-40) peptide docked to SDS micelles

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Usachev, K. S.; Filippov, A. V.; Khairutdinov, B. I.; Antzutkin, O. N.; Klochkov, V. V.

2014-11-01

The “Arctic” point mutation of the Alzheimer's amyloid β-peptide is a rare mutation leading to an early onset of Alzheimer's disease. The peptide may interact with neuronal membranes, where it can provide its toxic effects. We used 2D NMR spectroscopy to investigate the conformation of the “Arctic” mutant of Aβ1-40 Alzheimer's amyloid peptide in sodium dodecyl sulfate micelle solutions, which are the type of amphiphilic structures mimicking some properties of biomembranes. The study showed that the Arctic mutant of Aβ1-40 interacts with the surface of SDS micelles mainly through the Leu17-Asn27 310-helical region, while the Ile31-Val40 region is buried in the hydrophobic interior of the micelle. In contrast, wild-type Aβ1-40 interacts with SDS micelles through the Lys16-Asp23 α-helical region and Gly29-Met35. Both the Arctic mutant and the wild-type Aβ1-40 peptides interactions with SDS micelles are hydrophobic in nature. Aβ peptides are thought to be capable of forming pores in biomembranes that can cause changes in neuronal and endothelial cell membrane permeability. It has also been shown that Aβ peptides containing the “Arctic” mutation are more neurotoxic and aggregate more readily than the wild-type Aβ peptides at physiological conditions. Here, we propose that the extension of the helical structure of Leu17-Asn27 and a high aliphaticity (neutrality) of the C-terminal region in the Arctic Aβ peptides are consistent with the idea that formation of ion-permeable pores by Aβ oligomers may be one of prevailing mechanisms of a larger neuronal toxicity of the Arctic Aβ compared to the wild-type Aβ peptides, independent of oxidative damage and lipid peroxidation.
Ultraviolet-irradiated simian virus 40 activates a mutator function in rat cells under conditions preventing viral DNA replication

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Cornelis, J.; Su, Z.Z.; Dinsart, C.; Rommelaere, J. (Universite libre de Bruxelles, Rhode St Genese (Belgium))

The UV-irradiated temperature-sensitive early SV40 mutant tsA209 is able to activate at the nonpermissive temperature the expression of mutator and recovery functions in rat cells. Unirradiated SV40 activates these functions only to a low extent. The expression of these mutator and recovery functions in SV40-infected cells was detected using the single-stranded DNA parvovirus H-1 as a probe. Because early SV40 mutants are defective in the initiation of viral DNA synthesis at the nonpermissive temperature, these results suggest that replication of UV-damaged DNA is not a prerequisite for the activation of mutator and recovery functions in mammalian cells. The expression of the mutator function is dose-dependent, i.e., the absolute number of UV-irradiated SV40 virions introduced per cell determines its level. Implications for the interpretation of mutation induction curves in the progeny of UV-irradiated SV40 in permissive host cells are discussed.
Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations

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Johanna Wanngren

2014-01-01

Full Text Available The enzyme complex γ-secretase generates amyloid β-peptide (Aβ, a 37–43-residue peptide associated with Alzheimer disease (AD. Mutations in presenilin 1 (PS1, the catalytical subunit of γ-secretase, result in familial AD (FAD. A unifying theme among FAD mutations is an alteration in the ratio Aβ species produced (the Aβ42/Aβ40 ratio, but the molecular mechanisms responsible remain elusive. In this report we have studied the impact of several different PS1 FAD mutations on the integration of selected PS1 transmembrane domains and on PS1 active site conformation, and whether any effects translate to a particular amyloid precursor protein (APP processing phenotype. Most mutations studied caused an increase in the Aβ42/Aβ40 ratio, but via different mechanisms. The mutations that caused a particular large increase in the Aβ42/Aβ40 ratio did also display an impaired APP intracellular domain (AICD formation and a lower total Aβ production. Interestingly, seven mutations close to the catalytic site caused a severely impaired integration of proximal transmembrane/hydrophobic sequences into the membrane. This structural defect did not correlate to a particular APP processing phenotype. Six selected FAD mutations, all of which exhibited different APP processing profiles and impact on PS1 transmembrane domain integration, were found to display an altered active site conformation. Combined, our data suggest that FAD mutations affect the PS1 structure and active site differently, resulting in several complex APP processing phenotypes, where the most aggressive mutations in terms of increased Aβ42/Aβ40 ratio are associated with a decrease in total γ-secretase activity.
Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis.

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Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Cuadrado-Grande, Nuria; Alvarez-Sala-Walther, Luis-Antonio; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

2012-10-15

Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis. We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis. We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene. Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype. Copyright © 2012. Published by Elsevier B.V.
40 CFR 40.115-1 - Construction.

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2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Construction. 40.115-1 Section 40.115-1... DEMONSTRATION GRANTS § 40.115-1 Construction. May include the preliminary planning to determine the economic and... action necessary to the construction of a facility, the erection, acquisition, alteration, remodeling...
Effect of endogenous carotenoids on “adaptive” mutation in Escherichia coli FC40

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Bridges, Bryn A.; Foster, Patricia L.; Timms, Andrew R.

2010-01-01

The appearance over many days of Lac+ frameshift mutations in Escherichia coli strain FC40 incubated on lactose selection plates is a classic example of apparent “adaptive” mutation in an episomal gene. We show that endogenously overproduced carotenoids reduce adaptive mutation under selective conditions by a factor of around two. Carotenoids are known to scavenge singlet oxygen suggesting that the accumulation of oxidative base damage may be an integral part of the adaptive mutation phenomenon. If so, the lesion cannot be 7,8-dihydro-8-oxoguanine since adaptive mutation in FC40 is unaffected by mutM and mutY mutations. If active oxygen species such as singlet oxygen are involved in adaptive mutation then they should also induce frameshift mutations in FC40 under non-selective conditions. We show that such mutations can be induced under non-selective conditions by protoporphyrin photosensitisation and that this photodynamic induction is reduced by a factor of just over two when endogenous carotenoids are present. We argue that the involvement of oxidative damage would in no way be inconsistent with current understanding of the mechanism of adaptive mutation and the role of DNA polymerases. PMID:11166030
40 CFR 40.135-1 - Preapplication coordination.

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2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Preapplication coordination. 40.135-1 Section 40.135-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.135-1 Preapplication coordination. (a) All applicants. (1...
40 CFR 40.125-1 - Limitations on duration.

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2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Limitations on duration. 40.125-1 Section 40.125-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.125-1 Limitations on duration. (a) [Reserved] (b) No...
Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis.

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Wang, Yongwei; Du, Yali; Liu, Gang; Guo, Shanshan; Hou, Bo; Jiang, Xianyong; Han, Bing; Chang, Yanzhong; Nie, Guangjun

2017-04-01

Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders associated with pathogenic defects in the genes encoding hemochromatosis (HFE), hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well described. However, there have been only a few detailed reports of HH in Chinese populations. Thus, there is insufficient patient information for population-based analyses in Chinese populations or comparative studies among different ethical groups. In the current work, we describe eight Chinese cases of hereditary hemochromatosis. Gene sequencing results revealed eight mutations (five novel mutations) in HFE, HFE2, TfR2, and SLC40A1 genes in these Chinese HH patients. In addition, we used Polymorphism Phenotyping v2 (Polyphen), Sorting Intolerant From Tolerant (SIFT), and a sequence alignment program to predict the molecular consequences of missense mutations.
Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly

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Solbak Sara MØ

2011-02-01

Full Text Available Abstract Background The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L- domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX, is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6. Results Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site. Conclusions Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively
A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites

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Yne de Vries

2012-01-01

Full Text Available Fanconi anemia (FA is a recessive DNA instability disorder associated with developmental abnormalities, bone marrow failure, and a predisposition to cancer. Based on their sensitivity to DNA cross-linking agents, FA cells have been assigned to 15 complementation groups, and the associated genes have been identified. Founder mutations have been found in different FA genes in several populations. The majority of Dutch FA patients belongs to complementation group FA-C. Here, we report 15 patients of Dutch ancestry and a large Canadian Manitoba Mennonite kindred carrying the FANCC c.67delG mutation. Genealogical investigation into the ancestors of the Dutch patients shows that these ancestors lived in four distinct areas in The Netherlands. We also show that the Dutch and Manitoba Mennonite FANCC c.67delG patients share the same haplotype surrounding this mutation, indicating a common founder.
CD40-mediated apoptosis in murine B-lymphoma lines containing mutated p53

DEFF Research Database (Denmark)

Hollmann, Annette C; Gong, Qiaoke; Owens, Trevor

2002-01-01

Crosslinking CD40 induces normal B-cells to proliferate and differentiate but causes many tumor cell lines to undergo apoptosis. As p53 is required for many apoptotic pathways, we analyzed the effects of CD40 ligation and their correlation with p53 function in four murine B-lymphoma lines. A20...... of detectable p21 mRNA in A20 and M12 cells. P21 mRNA was increased to detectable levels in M12 cells upon CD40 ligation; however, blocking this effect with the p53 inhibitor pifithrin had no effect on CD40-mediated apoptosis. Sequencing showed that p53 in A20 and M12 cells contained point mutations leading...... to amino acid substitutions in DNA binding regions, but was unmutated in WEHI231 and WEHI 279. These results suggest that CD40-mediated apoptosis can occur in the absence of functional p53....
26 CFR 40.0-1 - Introduction.

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2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 40.0-1 Section 40.0-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX PROCEDURAL REGULATIONS § 40.0-1 Introduction. (a) In general. The regulations in this part 40 are...
Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers.

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Kurian, Allison W; Sigal, Bronislava M; Plevritis, Sylvia K

2010-01-10

Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death. We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers. With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%). Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.
Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa.

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Nguyen, Thanh-Minh T; Hull, Sarah; Roepman, Ronald; van den Born, L Ingeborgh; Oud, Machteld M; de Vrieze, Erik; Hetterschijt, Lisette; Letteboer, Stef J F; van Beersum, Sylvia E C; Blokland, Ellen A; Yntema, Helger G; Cremers, Frans P M; van der Zwaag, Paul A; Arno, Gavin; van Wijk, Erwin; Webster, Andrew R; Haer-Wigman, Lonneke

2017-09-01

Recent findings suggesting that Abelson helper integration site 1 ( AHI1 ) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP). Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling. Ciliary parameters were evaluated in patient's fibroblasts, and recombinant mutant proteins were expressed in ciliated retinal pigmented epithelium cells. In the three patients with RP, three sets of compound heterozygous variants were detected in AHI1 (c.2174G>A; p.Trp725* and c.2258A>T; p.Asp753Val, c.660delC; p.Ser221Glnfs*10 and c.2090C>T; p.Pro697Leu, c.2087A>G; p.His696Arg and c.2429C>T; p.Pro810Leu). All four missense variants were present in the conserved WD40 domain of Jouberin, the ciliary protein encoded by AHI1 , with variable predicted implications for the domain structure. No significant changes in the percentage of ciliated cells, nor in cilium length or intraflagellar transport were detected. However, expression of mutant recombinant Jouberin in ciliated cells showed a significantly decreased enrichment at the ciliary base. This report confirms that mutations in AHI1 can underlie autosomal recessive RP. Moreover, it structurally and functionally validates the effect of the RP-associated AHI1 variants on protein function, thus proposing a new genotype-phenotype correlation for AHI1 mutation associated retinal ciliopathies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
33 CFR 1.07-40 - Counsel.

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2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Counsel. 1.07-40 Section 1.07-40 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL GENERAL PROVISIONS Enforcement; Civil and Criminal Penalty Proceedings § 1.07-40 Counsel. A party has the right to be represented...
Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

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Li, Junyan; Jing, Ruilin; Wei, Hongyi; Wang, Minghao; Qi, Xiaowei; Liu, Haoxi; Liu, Jian; Ou, Jianghua; Jiang, Weihua; Tian, Fuguo; Sheng, Yuan; Li, Hengyu; Xu, Hong; Zhang, Ruishan; Guan, Aihua; Liu, Ke; Jiang, Hongchuan; Ren, Yu; He, Jianjun; Huang, Weiwei; Liao, Ning; Cai, Xiangjun; Ming, Jia; Ling, Rui; Xu, Yan; Hu, Chunyan; Zhang, Jianguo; Guo, Baoliang; Ouyang, Lizhi; Shuai, Ping; Liu, Zhenzhen; Zhong, Ling; Zeng, Zhen; Zhang, Ting; Xuan, Zhaoling; Tan, Xuanni; Liang, Junbin; Pan, Qinwen; Chen, Li; Zhang, Fan; Fan, Linjun; Zhang, Yi; Yang, Xinhua; Li, Jingbo; Chen, Chongjian; Jiang, Jun

2018-05-12

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n=937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n=18), PALB2 (n=11), CHEK2 (n=6), ATM (n=6), and BARD1 (n=5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes. This article is protected by copyright. All rights reserved. © 2018 UICC.

Insulin inhibits amyloid beta-induced cell death in cultured human brain pericytes

NARCIS (Netherlands)

Rensink, Annemieke A M; Otte-Höller, Irene; de Boer, Roelie; Bosch, Remko R; ten Donkelaar, Hans J; de Waal, Robert M W; Verbeek, Marcel M; Kremer, Berry

Amyloid-beta (Abeta) deposition in the cerebral arterial and capillary walls is one of the characteristics of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type. In vitro, Abeta1-40, carrying the "Dutch" mutation (DAbeta1-40), induced reproducible degeneration of
Common mutations identified in the MLH1 gene in familial Lynch syndrome

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Jisha Elias

2017-12-01

In this study we identified three families with Lynch syndrome from a rural cancer center in western India (KCHRC, Goraj, Gujarat, where 70-75 CRC patients are seen annually. DNA isolated from the blood of consented family members of all three families (8-10 members/family was subjected to NGS sequencing methods on an Illumina HiSeq 4000 platform. We identified unique mutations in the MLH1 gene in all three HNPCC family members. Two of the three unrelated families shared a common mutation (154delA and 156delA. Total 8 members of a family were identified as carriers for 156delA mutation of which 5 members were unaffected while 3 were affected (age of onset: 1 member <30yrs & 2 were>40yr. The family with 154delA mutation showed 2 affected members (>40yr carrying the mutations.LYS618DEL mutation found in 8 members of the third family showed that both affected and unaffected carried the mutation. Thus the common mutations identified in the MLH1 gene in two unrelated families had a high risk for lynch syndrome especially above the age of 40.
mTORC1 Coordinates Protein Synthesis and Immunoproteasome Formation via PRAS40 to Prevent Accumulation of Protein Stress.

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Yun, Young Sung; Kim, Kwan Hyun; Tschida, Barbara; Sachs, Zohar; Noble-Orcutt, Klara E; Moriarity, Branden S; Ai, Teng; Ding, Rui; Williams, Jessica; Chen, Liqiang; Largaespada, David; Kim, Do-Hyung

2016-02-18

Reduction of translational fidelity often occurs in cells with high rates of protein synthesis, generating defective ribosomal products. If not removed, such aberrant proteins can be a major source of cellular stress causing human diseases. Here, we demonstrate that mTORC1 promotes the formation of immunoproteasomes for efficient turnover of defective proteins and cell survival. mTORC1 sequesters precursors of immunoproteasome β subunits via PRAS40. When activated, mTORC1 phosphorylates PRAS40 to enhance protein synthesis and simultaneously to facilitate the assembly of the β subunits for forming immunoproteasomes. Consequently, the PRAS40 phosphorylations play crucial roles in clearing aberrant proteins that accumulate due to mTORC1 activation. Mutations of RAS, PTEN, and TSC1, which cause mTORC1 hyperactivation, enhance immunoproteasome formation in cells and tissues. Those mutations increase cellular dependence on immunoproteasomes for stress response and survival. These results define a mechanism by which mTORC1 couples elevated protein synthesis with immunoproteasome biogenesis to protect cells against protein stress. Copyright © 2016 Elsevier Inc. All rights reserved.
Impaired CK1 delta activity attenuates SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo.

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Heidrun Hirner

Full Text Available Simian virus 40 (SV40 is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1δ mutants exhibited a reduced kinase activity compared to wtCK1δ in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1δ activity. When stably over-expressed in maximal transformed SV-52 cells, CK1δ mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1δ. To characterize the effects of CK1δ on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1δ under the control of the whey acidic protein (WAP gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T mice. Both WAP-T mice as well as WAP-mutCK1δ/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1δ/WAP-T bi-transgenic animals. The reduced CK1δ activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1δ activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1δ/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA
A Novel de Novo Mutation in the CD40 Ligand Gene in a Patient With a Mild X-Linked Hyper-IgM Phenotype Initially Diagnosed as CVID: New Aspects of Old Diseases

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Tábata T. França

2018-05-01

Full Text Available Mutations in the CD40 ligand (CD40L gene (CD40LG lead to X-linked hyper-IgM syndrome (X-HIGM, which is a primary immunodeficiency (PID characterized by decreased serum levels of IgG and IgA and normal or elevated IgM levels. Although most X-HIGM patients become symptomatic during the first or second year of life, during which they exhibit recurrent infections, some patients exhibit mild phenotypes, which are usually associated with hypomorphic mutations that do not abrogate protein expression or function. Here, we describe a 28-year-old man who initially presented with recurrent infections since the age of 7 years, when he exhibited meningitis caused by Cryptococcus neoformans. The patient had no family history of immunodeficiency, and based on clinical and laboratory presentation, he was initially diagnosed with common variable immunodeficiency (CVID. In subsequent years, he displayed several sporadic episodes of infection, including pneumonia, pharyngotonsillitis, acute otitis media, rhinosinusitis, fungal dermatosis, and intestinal helminthiasis. The evaluation of CD40L expression on the surface of activated CD3+CD4+ T cells from the patient showed decreased expression of CD40L. Genetic analysis revealed a novel de novo mutation consisting of a 6-nucleotide insertion in exon 1 of CD40LG, which confirmed the diagnosis of X-HIGM. In this report, we describe a novel mutation in the CD40L gene and highlight the complexities of PID diagnosis in light of atypical phenotypes and hypomorphic mutations as well as the importance of the differential diagnosis of PIDs.
Dural ectasia and FBN1 mutation screening of 40 patients with Marfan syndrome and related disorders: role of dural ectasia for the diagnosis.

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Attanasio, Monica; Pratelli, Elisa; Porciani, Maria Cristina; Evangelisti, Lucia; Torricelli, Elena; Pellicanò, Giannantonio; Abbate, Rosanna; Gensini, Gian Franco; Pepe, Guglielmina

2013-07-01

Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in the gene encoding fibrillin-1 (FBN1), a matrix component of microfibrils. Dural ectasia, i.e. enlargement of the neural canal mainly located in the lower lumbar and sacral region, frequently occurs in Marfan patients. The aim of our study was to investigate the role of dural ectasia in raising the diagnosis of Marfan syndrome and its association with FBN1 mutations. We studied 40 unrelated patients suspected for MFS, who underwent magnetic resonance imaging searching for dural ectasia. In all of them FBN1 gene analysis was also performed. Thirty-seven patients resulted affected by Marfan syndrome according to the '96 Ghent criteria; in 30 of them the diagnosis was confirmed when revaluated by the recently revised criteria (2010). Thirty-six patients resulted positive for dural ectasia. The degree of dural ectasia was grade 1 in 19 patients, grade 2 in 11 patients, and grade 3 in 6 patients. In 7 (24%) patients, the presence of dural ectasia allowed to reach a positive score for systemic feature criterion. Twenty-four patients carried an FBN1 mutation, that were represented by 13 missense (54%), and 11 (46%) mutations generating a premature termination codon (PTC, frameshifts and stop codons). No mutation was detected in the remaining 16 (6 patients with MFS and 10 with related disorders according to revised Ghent criteria). The prevalence of severe (grade 2 and grade 3) involvement of dura mater was higher in patients harbouring premature termination codon (PTC) mutations than those carrying missense-mutations (8/11 vs 2/13, P = 0.0111). Our data emphasizes the importance of dural ectasia screening to reach the diagnosis of Marfan syndrome especially when it is uncertain and indicates an association between PTC mutations and severe dural ectasia in Marfan patients. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Genetic and epigenetic regulation of YKL-40 in childhood.

Science.gov (United States)

Guerra, Stefano; Melén, Erik; Sunyer, Jordi; Xu, Cheng-Jian; Lavi, Iris; Benet, Marta; Bustamante, Mariona; Carsin, Anne-Elie; Dobaño, Carlota; Guxens, Mònica; Tischer, Christina; Vrijheid, Martine; Kull, Inger; Bergström, Anna; Kumar, Ashish; Söderhäll, Cilla; Gehring, Ulrike; Dijkstra, Dorieke J; van der Vlies, Pieter; Wickman, Magnus; Bousquet, Jean; Postma, Dirkje S; Anto, Josep M; Koppelman, Gerard H

2018-03-01

Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3-like 1 [CHI3L1]) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown. We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40 levels in the blood and (2) whether these biomarkers (CHI3L1 SNPs, methylation profiles, and YKL-40 levels) are associated with asthma in early childhood. We used data from up to 2405 participants from the Spanish Infancia y Medio Ambiente; the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey; and the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohorts. Associations between 68 CHI3L1 SNPs, methylation levels at 14 CHI3L1 CpG sites in whole-blood DNA, and circulating YKL-40 levels at 4 years of age were tested by using correlation analysis, multivariable regression, and mediation analysis. Each of these biomarkers was also tested for association with asthma at 4 years of age by using multivariable logistic regression. YKL-40 levels were significantly associated with 7 SNPs and with methylation at 5 CpG sites. Consistent associations between these 7 SNPs (particularly rs10399931 and rs4950928) and 5 CpG sites were observed. Alleles linked to lower YKL-40 levels were associated with higher methylation levels. Participants with high YKL-40 levels (defined as the highest YKL-40 tertile) had increased odds for asthma compared with subjects with low YKL-40 levels (meta-analyzed adjusted odds ratio, 1.90 [95% CI, 1.08-3.36]). In contrast, neither SNPs nor methylation levels at CpG sites in CHI3L1 were associated with asthma. The effects of CHI3L1 genetic variation on circulating YKL-40 levels are partly mediated by methylation profiles. In our study YKL-40 levels, but not CHI3L1 SNPs or
46 CFR 96.40-1 - Pilot boarding equipment.

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2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Pilot boarding equipment. 96.40-1 Section 96.40-1... CONTROL AND MISCELLANEOUS SYSTEMS AND EQUIPMENT Pilot Boarding Equipment § 96.40-1 Pilot boarding... boat or other vessel. (b) Each vessel must have suitable pilot boarding equipment available for use on...
46 CFR 195.40-1 - Pilot boarding equipment.

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2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Pilot boarding equipment. 195.40-1 Section 195.40-1... CONTROL AND MISCELLANEOUS SYSTEMS AND EQUIPMENT Pilot Boarding Equipment § 195.40-1 Pilot boarding... boat or other vessel. (b) Each vessel must have suitable pilot boarding equipment available for use on...
41 CFR 109-40.103-1 - Domestic transportation.

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2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Domestic transportation... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.103-1...
46 CFR 77.40-1 - Pilot boarding equipment.

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2010-10-01

... 46 Shipping 3 2010-10-01 2010-10-01 false Pilot boarding equipment. 77.40-1 Section 77.40-1... MISCELLANEOUS SYSTEMS AND EQUIPMENT Pilot Boarding Equipment § 77.40-1 Pilot boarding equipment. (a) This... vessel. (b) Each vessel must have suitable pilot boarding equipment available for use on each side of the...
40 CFR 40.115-6 - State.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false State. 40.115-6 Section 40.115-6... DEMONSTRATION GRANTS § 40.115-6 State. (a) Under the Federal Water Pollution Control Act, a State, the District... Territory of the Pacific Islands. (b) Under the Resource Conservation and Recovery Act, a State, the...
27 CFR 1.40 - Change of name.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Change of name. 1.40... Amendment and Duration of Basic Permits § 1.40 Change of name. In the event of any change in the name (trade or corporate name) of a permittee, or, in the event a permittee desires to engage in operations under...
The Genome of the Chicken DT40 Bursal Lymphoma Cell Line

DEFF Research Database (Denmark)

Molnar, Janos; Poti, Adam; Pipek, Orsolya

2014-01-01

The chicken DT40 cell line is a widely used model system in the study of multiple cellular processes due to the efficiency of homologous gene targeting. The cell line was derived from a bursal lymphoma induced by avian leukosis virus infection. In this study we characterized the genome of the cell...... chicken genomes and the Gallus gallus reference genome, we found no unique mutational processes shaping the DT40 genome except for a mild increase in insertion and deletion events, particularly deletions at tandem repeats. We mapped coding sequence mutations that are unique to the DT40 genome; mutations...
40 CFR 1.21 - General.

Science.gov (United States)

2010-07-01

... other national and international governmental organizations; (c) The Office of Inspector General; (d... 40 Protection of Environment 1 2010-07-01 2010-07-01 false General. 1.21 Section 1.21 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL STATEMENT OF ORGANIZATION AND GENERAL...
An FBXO40 knockout generated by CRISPR/Cas9 causes muscle hypertrophy in pigs without detectable pathological effects.

Science.gov (United States)

Zou, Yunlong; Li, Zhiyuan; Zou, Yunjing; Hao, Haiyang; Li, Ning; Li, Qiuyan

2018-04-15

The regulatory function of Fbxo40 has been well characterized in mice. As a key component of the SCF-E3 ubiquitin ligase complex, Fbxo40 induces IRS1 ubiquitination, thus inactivating the IGF1/Akt pathway. The expression of Fbxo40 is restricted to muscle, and mice with an Fbxo40 null mutation exhibit muscle hypertrophy. However, the function of FBXO40 has not been elucidated in pigs, and it is not known whether FBXO40 mutations affect their health. We therefore generated FBXO40 knockout pigs using somatic cell nuclear transfer (SCNT) technology. CRISPR/Cas9 technology was combined with G418 selection, making it possible to generate donor cells at an efficiency of 75.86%. In muscle from FBXO40 knockout pigs, IRS1 levels were higher, and the IGF1/Akt pathway was stimulated. Mutant animals also had approximately 4% more muscle mass compared to WT controls. The knockout pigs developed normally and no pathological changes were found in major organs. These results demonstrate that FBXO40 is a promising candidate gene for improving production traits in agricultural livestock and for developing therapeutic interventions for muscle diseases. Copyright © 2018. Published by Elsevier Inc.
40 CFR 97.1 - Purpose.

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2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Purpose. 97.1 Section 97.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX... transport of ozone and nitrogen oxides, an ozone precursor. ...
40 CFR 25.1 - Introduction.

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2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Introduction. 25.1 Section 25.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PUBLIC PARTICIPATION IN PROGRAMS UNDER THE... Introduction. This part sets forth minimum requirements and suggested program elements for public participation...
40 CFR 172.1 - Definitions.

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2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Definitions. 172.1 Section 172.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE... efficacious action on a pest. [73 FR 75599, Dec. 12, 2008] ...
40 CFR 76.1 - Applicability.

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2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Applicability. 76.1 Section 76.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.1 Applicability. (a) Except as provided in paragraphs (b...

BRCA1 and BRCA2 mutations in central and southern Italian patients

International Nuclear Information System (INIS)

Ottini, Laura; Carlini, Sandro; Guadagni, Fiorella; Bianco, Angelo Raffaele; Frati, Luigi; Contegiacomo, Alma; Mariani-Costantini, Renato; D'Amico, Cristina; Noviello, Cristiana; Lauro, Salvatore; Lalle, Maurizio; Fornarini, Giuseppe; Colantuoni, Orsola Anna; Pizzi, Claudia; Cortesi, Enrico

2000-01-01

Protein truncation test (PTT) and single-strand conformation polymorphism (SSCP) assay were used to scan the BRCA1 and BRCA2 genes in 136 unrelated Italian breast/ovarian cancer patients. In the sample tested, BRCA1 and BRCA2 equally contributed to site-specific breast cancer patients who reported one to two breast cancer-affected first-/ second-degree relative(s) or who were diagnosed before age 40 years in the absence of a family history of breast/ovarian cancer. BRCA1 and BRCA2 mutations were mostly found in patients with disease diagnosis before and after age 50 years, respectively. Moreover, in cases with familial clustering of site-specific breast cancer, BRCA1 mostly accounted for tumours diagnosed before age 40 years and BRCA2 for tumours diagnosed after age 50 years. The BRCA1 and BRCA2 mutation spectrum was consistent with a lack of significant founder effects in the sample of patients studied. Germline BRCA1 and BRCA2 mutations account for most hereditary breast/ovarian cancers and are associated with male breast cancer. Furthermore, constitutional mutations in these genes may occur in breast/ovarian cancer patients that do not meet stringent criteria of autosomal-dominant predisposition. The relevance of BRCA1 and BRCA2 mutations in such patients is still debated. We sought to determine the impact of BRCA1 and BRCA2 mutations in a population of patients from central and southern Italy. We analyzed the BRCA1 and BRCA2 coding regions in 136 unrelated probands: 117 females with breast/ovarian cancer and 19 males with breast cancer. This population of patients was mostly representative of cases who are at risk for hereditary susceptibility, but who do not meet stringent criteria of autosomal-dominant predisposition. Probands, subclassified as follows, were consecutively recruited depending on informed consent from patients attending breast cancer clinics in Rome and Naples. Selection criteria for females were as follows: breast cancer with breast cancer
Molecular dynamics simulations of site point mutations in the TPR domain of cyclophilin 40 identify conformational states with distinct dynamic and enzymatic properties

Science.gov (United States)

Gur, Mert; Blackburn, Elizabeth A.; Ning, Jia; Narayan, Vikram; Ball, Kathryn L.; Walkinshaw, Malcolm D.; Erman, Burak

2018-04-01

Cyclophilin 40 (Cyp40) is a member of the immunophilin family that acts as a peptidyl-prolyl-isomerase enzyme and binds to the heat shock protein 90 (Hsp90). Its structure comprises an N-terminal cyclophilin domain and a C-terminal tetratricopeptide (TPR) domain. Cyp40 is overexpressed in prostate cancer and certain T-cell lymphomas. The groove for Hsp90 binding on the TPR domain includes residues Lys227 and Lys308, referred to as the carboxylate clamp, and is essential for Cyp40-Hsp90 binding. In this study, the effect of two mutations, K227A and K308A, and their combinative mutant was investigated by performing a total of 5.76 μs of all-atom molecular dynamics (MD) simulations in explicit solvent. All simulations, except the K308A mutant, were found to adopt two distinct (extended or compact) conformers defined by different cyclophilin-TPR interdomain distances. The K308A mutant was only observed in the extended form which is observed in the Cyp40 X-ray structure. The wild-type, K227A, and combined mutant also showed bimodal distributions. The experimental melting temperature, Tm, values of the mutants correlate with the degree of compactness with the K308A extended mutant having a marginally lower melting temperature. Another novel measure of compactness determined from the MD data, the "coordination shell volume," also shows a direct correlation with Tm. In addition, the MD simulations show an allosteric effect with the mutations in the remote TPR domain having a pronounced effect on the molecular motions of the enzymatic cyclophilin domain which helps rationalise the experimentally observed increase in enzyme activity measured for all three mutations.
40 CFR 40.160-2 - Financial status report.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Financial status report. 40.160-2 Section 40.160-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.160-2 Financial status report. A financial status report...
40 CFR 87.1 - Definitions.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Definitions. 87.1 Section 87.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR... commercial aircraft engine. Emission measurement system means all of the equipment necessary to transport and...
Adhesion Regulating Molecule 1 Mediates HAP40 Overexpression-Induced Mitochondrial Defects

Science.gov (United States)

Huang, Zih-Ning; Chung, Her Min; Fang, Su-Chiung; Her, Lu-Shiun

2017-01-01

Striatal neuron death in Huntington's disease is associated with abnormal mitochondrial dynamics and functions. However, the mechanisms for this mitochondrial dysregulation remain elusive. Increased accumulation of Huntingtin-associated protein 40 (HAP40) has been shown to be associated with Huntington's disease. However, the link between increased HAP40 and Huntington's disease remains largely unknown. Here we show that HAP40 overexpression causes mitochondrial dysfunction and reduces cell viability in the immortalized mouse striatal neurons. HAP40-associated mitochondrial dysfunction is associated with reduction of adhesion regulating molecule 1 (ADRM1) protein. Consistently, depletion of ADRM1 by shRNAs impaired mitochondrial functions and increased mitochondrial fragmentation in mouse striatal cells. Moreover, reducing ADRM1 levels enhanced activity of fission factor dynamin-related GTPase protein 1 (Drp1) via increased phosphorylation at serine 616 of Drp1 (Drp1Ser616). Restoring ADRM1 protein levels was able to reduce HAP40-induced ROS levels and mitochondrial fragmentation and improved mitochondrial functions and cell viability. Moreover, reducing Drp1 activity by Drp1 inhibitor, Mdivi-1, ameliorates both HAP40 overexpression- and ADRM1 depletion-induced mitochondrial dysfunction. Taken together, our studies suggest that HAP40-mediated reduction of ADRM1 alters the mitochondrial fission activity and results in mitochondrial fragmentation and mitochondrial dysfunction. PMID:29209146
40 CFR 279.1 - Definitions.

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2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Definitions. 279.1 Section 279.1... THE MANAGEMENT OF USED OIL Definitions § 279.1 Definitions. Terms that are defined in §§ 260.10, 261.1... may also accept used oil from household do-it-yourselfers. Used oil fuel marketer means any person who...
40 CFR 95.1 - Definitions.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Definitions. 95.1 Section 95.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY... have the meaning given them by the Act. (b) Act means the Clean Air Act, as amended (42 U.S.C. §§ 7401...
Combined MRI and ³¹P-MRS investigations of the ACTA1(H40Y mouse model of nemaline myopathy show impaired muscle function and altered energy metabolism.

Directory of Open Access Journals (Sweden)

Charlotte Gineste

Full Text Available Nemaline myopathy (NM is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1 account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y. Skeletal muscle anatomy (hindlimb muscles and fat volumes and energy metabolism were studied using MRI and (31Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1-150 Hz and a fatigue protocol (80 stimuli at 40 Hz. H40Y mice showed a reduction of both absolute (-40% and specific (-25% maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40% and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.
Properties of the simian virus 40 (SV40) large T antigens encoded by SV40 mutants with deletions in gene A.

Science.gov (United States)

Cole, C N; Tornow, J; Clark, R; Tjian, R

1986-01-01

The biochemical properties of the large T antigens encoded by simian virus 40 (SV40) mutants with deletions at DdeI sites in the SV40 A gene were determined. Mutant large T antigens containing only the first 138 to 140 amino acids were unable to bind to the SV40 origin of DNA replication as were large T antigens containing at their COOH termini 96 or 97 amino acids encoded by the long open reading frame located between 0.22 and 0.165 map units (m.u.). All other mutant large T antigens were able to bind to the SV40 origin of replication. Mutants with in-phase deletions at 0.288 and 0.243 m.u. lacked ATPase activity, but ATPase activity was normal in mutants lacking origin-binding activity. The 627-amino acid large T antigen encoded by dlA2465, with a deletion at 0.219 m.u., was the smallest large T antigen displaying ATPase activity. Mutant large T antigens with the alternate 96- or 97-amino acid COOH terminus also lacked ATPase activity. All mutant large T antigens were found in the nuclei of infected cells; a small amount of large T with the alternate COOH terminus was also located in the cytoplasm. Mutant dlA2465 belonged to the same class of mutants as dlA2459. It was unable to form plaques on CV-1p cells at 37 or 32 degrees C but could form plaques on BSC-1 monolayers at 37 degrees C but not at 32 degrees C. It was positive for viral DNA replication and showed intracistronic complementation with any group A mutant whose large T antigen contained a normal carboxyl terminus. These findings and those of others suggest that both DNA binding and ATPase activity are required for the viral DNA replication function of large T antigen, that these two activities must be located on the same T antigen monomer, and that these two activities are performed by distinct domains of the polypeptide. These domains are distinct and separable from the domain affected by the mutation of dlA2465 and indicate that SV40 large T antigen is made up of at least three separate functional
49 CFR 40.1 - Who does this regulation cover?

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2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Who does this regulation cover? 40.1 Section 40.1 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL... is intended to supersede or conflict with the implementation of the Federal Railroad Administration's...
46 CFR 25.40-1 - Tanks and engine spaces.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Tanks and engine spaces. 25.40-1 Section 25.40-1...-1 Tanks and engine spaces. (a) All motorboats or motor vessels, except open boats and as provided in... from the bilges of every engine and fuel tank compartment. There shall be at least one exhaust duct...
40 CFR 40.160-3 - Reporting of inventions.

Science.gov (United States)

2010-07-01

... application. (b) A final invention report is required within 90 days after completion of the project period... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Reporting of inventions. 40.160-3... ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.160-3 Reporting of inventions. As provided in appendix B of...
40 CFR 205.58-1 - Warranty.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Warranty. 205.58-1 Section 205.58-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.58-1 Warranty. (a) The vehicle manufacturer...
The role of women on Dutch farms

OpenAIRE

Meulen, van der, H.A.B.; Terluin, I.J.; Matser, I.A.

2015-01-01

In this paper an analysis is made of the contribution of women to labour input and management on Dutch farms. We used a written survey among the participants of the Dutch Farm Accountancy Data Network (FADN), in-depth interviews and a group discussion with farm women. Over half of the women on Dutch farms spend more than ten hours per week on agricultural activitieson the farm. More than 40% of women on Dutch farms have paid work off farm. The majority of the respondents’ farms is legally org...
[Construction and identification of Nogo extra cellular peptide residues 1-40 gene lentiviral vector].

Science.gov (United States)

Yuan, Haifeng; Song, Yueming; Liu, Hao; Zhou, Chunguang; Kong, Qingquan; Liu, Liming; Gong, Quan

2012-02-01

To construct a lentiviral expression vector carrying Nogo extra cellular peptide residues 1-40 (NEP1-40) and to obtain NEP1-40 efficient and stable expression in mammalian cells. The DNA fragment of NEP1-40 coding sequence was amplified by PCR with designed primer from the cDNA library including NEP1-40 gene, and then subcloned into pGC-FU vector with in-fusion technique to generate the lentiviral expression vector, pGC-FU-NEP1-40. The positive clones were screened by PCR and the correct NEP1-40 was confirmed by sequencing. Recombinant lentiviruses were produced in 293T cells after the cotransfection of pGC-FU-NEP1-40, and packaging plasmids of pHelper 1.0 and pHelper 2.0. Green fluorescent protein (GFP) expression of infected 293T cells was observed to evaluate gene delivery efficiency. NEP1-40 protein expression in 293T cells was detected by Western blot. The lentiviral expression vector carrying NEP1-40 was successfully constructed by GFP observation, and NEP1-40 protein expression was detected in 293T cells by Western blot. The recombinant lentivirus pGC-FU-NEP1-40 is successfully constructed and it lays a foundation for further molecular function study of NEP 1-40.
Early salpingectomy (TUbectomy) with delayed oophorectomy to improve quality of life as alternative for risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers (TUBA study): a prospective non-randomised multicentre study

International Nuclear Information System (INIS)

Harmsen, Marline G.; Arts-de Jong, Marieke; Hoogerbrugge, Nicoline; Maas, Angela H. E. M.; Prins, Judith B.; Bulten, Johan; Teerenstra, Steven; Adang, Eddy M. M.; Piek, Jurgen M. J.; Doorn, Helena C van; Beurden, Marc van; Mourits, Marian J. E.; Zweemer, Ronald P.; Gaarenstroom, Katja N.; Slangen, Brigitte F. M.; Vos, M. Caroline; Lonkhuijzen, Luc R. C. W. van; Massuger, Leon F. A. G.; Hermens, Rosella P. M. G.; Hullu, Joanne A. de

2015-01-01

Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80–96 % but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated. A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35–40 (BRCA1) or 40–45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40–45 (BRCA1) or 45–50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed. The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL. ClinicalTrials.gov: NCT02321228
Genetic variants in CHI3L1 influencing YKL-40 levels

DEFF Research Database (Denmark)

Kjaergaard, Alisa D; Johansen, Julia S; Nordestgaard, Børge G

2013-01-01

Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.......Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population....
40 CFR 721.6167 - Piperdinium, 1,1-dimethyl-, chloride.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Piperdinium, 1,1-dimethyl-, chloride... Substances § 721.6167 Piperdinium, 1,1-dimethyl-, chloride. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as piperdinium, 1,1-dimethyl-, chloride. (PMN...
NJP VOLUME 40 No 1B

African Journals Online (AJOL)

Prof Ezechukwu

2012-07-13

10.4314/njp.v40i1,9. Abstract Objective: Although the calibre of the airway is kept patent by multifactorial control system, there is evidence that ..... Lewinshohn HC, Capel LH, Smart. J. Changes in forced expiratory volumes throughout ...
40 CFR 27.40 - Stay ordered by the Department of Justice.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Stay ordered by the Department of Justice. 27.40 Section 27.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROGRAM FRAUD CIVIL REMEDIES § 27.40 Stay ordered by the Department of Justice. If at any time the Attorney...

Bloodstream Amyloid-beta (1-40) Peptide, Cognition, and Outcomes in Heart Failure.

Science.gov (United States)

Bayes-Genis, Antoni; Barallat, Jaume; de Antonio, Marta; Domingo, Mar; Zamora, Elisabet; Vila, Joan; Subirana, Isaac; Gastelurrutia, Paloma; Pastor, M Cruz; Januzzi, James L; Lupón, Josep

2017-11-01

In the brain, amyloid-beta generation participates in the pathophysiology of cognitive disorders; in the bloodstream, the role of amyloid-beta is uncertain but may be linked to sterile inflammation and senescence. We explored the relationship between blood levels of amyloid-beta 1-40 peptide (Aβ40), cognition, and mortality (all-cause, cardiovascular, and heart failure [HF]-related) in ambulatory patients with HF. Bloodstream Aβ40 was measured in 939 consecutive patients with HF. Cognition was evaluated with the Pfeiffer questionnaire (adjusted for educational level) at baseline and during follow-up. Multivariate Cox regression analyses and measurements of performance (discrimination, calibration, and reclassification) were used, with competing risk for specific causes of death. Over 5.1 ± 2.9 years, 471 patients died (all-cause): 250 from cardiovascular causes and 131 HF-related. The median Aβ40 concentration was 519.1 pg/mL [Q1-Q3: 361.8-749.9 pg/mL]. The Aβ40 concentration correlated with age, body mass index, renal dysfunction, and New York Heart Association functional class (all P < .001). There were no differences in Aβ40 in patients with and without cognitive impairment at baseline (P = .97) or during follow-up (P = .20). In multivariable analysis, including relevant clinical predictors and N-terminal pro-B-type natriuretic peptide, Aβ40 remained significantly associated with all-cause death (HR, 1.22; 95%CI, 1.10-1.35; P < .001) and cardiovascular death (HR, 1.18; 95%CI, 1.03-1.36; P = .02), but not with HF-related death (HR, 1.13; 95%CI, 0.93-1.37; P = .22). Circulating Aβ40 improved calibration and patient reclassification. Blood levels of Aβ40 are not associated with cognitive decline in HF. Circulating Aβ40 was predictive of mortality and may indicate systemic aging. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
46 CFR 91.40-1 - Definitions relating to hull examinations.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Definitions relating to hull examinations. 91.40-1... VESSELS INSPECTION AND CERTIFICATION Drydocking § 91.40-1 Definitions relating to hull examinations. As...-hull fittings. (b) Internal structural examination means an examination of the vessel while afloat or...
46 CFR 189.40-1 - Definitions relating to hull examinations.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Definitions relating to hull examinations. 189.40-1... VESSELS INSPECTION AND CERTIFICATION Drydocking § 189.40-1 Definitions relating to hull examinations. As...-hull fittings. (b) Internal structural examination means an examination of the vessel while afloat or...
40 CFR 131.40 - Puerto Rico

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Puerto Rico 131.40 Section 131.40... Federally Promulgated Water Quality Standards § 131.40 Puerto Rico (a) Use designations for marine waters. In addition to the Commonwealth's adopted use designations, the following waterbodies in Puerto Rico...
A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner

Science.gov (United States)

Koehler, Alexander; Kolesnikova, Larissa; Welzel, Ulla; Schudt, Gordian; Herwig, Astrid

2015-01-01

ABSTRACT Marburg virus (MARV) induces severe hemorrhagic fever in humans and nonhuman primates but only transient nonlethal disease in rodents. However, sequential passages of MARV in rodents boosts infection leading to lethal disease. Guinea pig-adapted MARV contains one mutation in the viral matrix protein VP40 at position 184 (VP40D184N). The contribution of the D184N mutation to the efficacy of replication in a new host is unknown. In the present study, we demonstrated that recombinant MARV containing the D184N mutation in VP40 [rMARVVP40(D184N)] grew to higher titers than wild-type recombinant MARV (rMARVWT) in guinea pig cells. Moreover, rMARVVP40(D184N) displayed higher infectivity in guinea pig cells. Comparative analysis of VP40 functions indicated that neither the interferon (IFN)-antagonistic function nor the membrane binding capabilities of VP40 were affected by the D184N mutation. However, the production of VP40-induced virus-like particles (VLPs) and the recruitment of other viral proteins to the budding site was improved by the D184N mutation in guinea pig cells, which resulted in the higher infectivity of VP40D184N-induced infectious VLPs (iVLPs) compared to that of VP40-induced iVLPs. In addition, the function of VP40 in suppressing viral RNA synthesis was influenced by the D184N mutation specifically in guinea pig cells, thus allowing greater rates of transcription and replication. Our results showed that the improved viral fitness of rMARVVP40(D184N) in guinea pig cells was due to the better viral assembly function of VP40D184N and its lower inhibitory effect on viral transcription and replication rather than modulation of the VP40-mediated suppression of IFN signaling. IMPORTANCE The increased virulence achieved by virus passaging in a new host was accompanied by mutations in the viral genome. Analyzing how these mutations affect the functions of viral proteins and the ability of the virus to grow within new host cells helps in the understanding
40 CFR 205.55-1 - General requirements.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false General requirements. 205.55-1 Section 205.55-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.55-1 General...
40 CFR 40.145-2 - Federal Water Pollution Control Act.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.145-2 Federal Water Pollution Control Act. (a... or control of acid or other mine water pollution; and (2) That the State shall provide legal and...
40 CFR 40.140-3 - Federal Water Pollution Control Act.

Science.gov (United States)

2010-07-01

... such safe water and such elimination or control of water pollution for all native villages in the State... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.140-3 Federal Water Pollution Control Act. (a...
40 CFR 721.10086 - Ethane, 2-(difluoromethoxy)-1,1,1-trifluoro-.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethane, 2-(difluoromethoxy)-1,1,1... Specific Chemical Substances § 721.10086 Ethane, 2-(difluoromethoxy)-1,1,1-trifluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as ethane, 2...
40 CFR 205.57-1 - Test request.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Test request. 205.57-1 Section 205.57-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-1 Test request. (a) The...
40 CFR 221.1 - Applications for permits.

Science.gov (United States)

2010-07-01

... of the proposed dumping on the marine environment, navigation, living and non-living marine resource... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Applications for permits. 221.1 Section 221.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING...
40 CFR 35.1605-1 - The Act.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false The Act. 35.1605-1 Section 35.1605-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL... The Act. The Clean Water Act, as amended (33 U.S.C. 1251 et seq.). ...
40 CFR 1.49 - Office of Water.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Office of Water. 1.49 Section 1.49... INFORMATION Headquarters § 1.49 Office of Water. The Office of Water, under the supervision of the Assistant Administrator for Water who serves as the principal adviser to the Administrator in matters pertaining to water...
A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress

Directory of Open Access Journals (Sweden)

Emmanuel Adu-Gyamfi

2014-10-01

Full Text Available Ebola virus (EBOV causes viral hemorrhagic fever in humans and can have clinical fatality rates of ~60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40. VP40 is the major Ebola virus matrix protein and regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane of human cells to regulate viral budding where VP40 can produce virus like particles (VLPs without other Ebola virus proteins present. The mechanistic details, however, of VP40 lipid-interactions and protein-protein interactions that are important for viral release remain to be elucidated. Here, we mutated a loop region in the N-terminal domain of VP40 (Lys127, Thr129, and Asn130 and find that mutations (K127A, T129A, and N130A in this loop region reduce plasma membrane localization of VP40. Additionally, using total internal reflection fluorescence microscopy and number and brightness analysis we demonstrate these mutations greatly reduce VP40 oligomerization. Lastly, VLP assays demonstrate these mutations significantly reduce VLP release from cells. Taken together, these studies identify an important loop region in VP40 that may be essential to viral egress.
Enhancement of hypermutation frequency in the chicken B cell line DT40 for efficient diversification of the antibody repertoire

Energy Technology Data Exchange (ETDEWEB)

Magari, Masaki; Kanehiro, Yuichi; Todo, Kagefumi; Ikeda, Mika; Kanayama, Naoki, E-mail: nkanayama@cc.okayama-u.ac.jp; Ohmori, Hitoshi

2010-05-28

Chicken B cell line DT40 continuously accumulates mutations in the immunoglobulin variable region (IgV) gene by gene conversion and point mutation, both of which are mediated by activation-induced cytidine deaminase (AID), thereby producing an antibody (Ab) library that is useful for screening monoclonal Abs (mAbs) in vitro. We previously generated an engineered DT40 line named DT40-SW, whose AID expression can be reversibly switched on or off, and developed an in vitro Ab generation system using DT40-SW cells. To efficiently create an Ab library with sufficient diversity, higher hypermutation frequency is advantageous. To this end, we generated a novel cell line DT40-SW{Delta}C, which conditionally expresses a C-terminus-truncated AID mutant lacking the nuclear export signal. The transcription level of the mutant AID gene in DT40-SW{Delta}C cells was similar to that of the wild-type gene in DT40-SW cells. However, the protein level of the truncated AID mutant was less than that of the wild type. The mutant protein was enriched in the nuclei of DT40-SW{Delta}C cells, although the protein might be highly susceptible to degradation. In DT40-SW{Delta}C cells, both gene conversion and point mutation occurred in the IgV gene with over threefold higher frequency than in DT40-SW cells, suggesting that a lower level of the mutant AID protein was sufficient to increase mutation frequency. Thus, DT40-SW{Delta}C cells may be useful for constructing Ab libraries for efficient screening of mAbs in vitro.
40 CFR 35.925-1 - Facilities planning.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Facilities planning. 35.925-1 Section... Facilities planning. That, if the award is for step 2, step 3, or step 2=3 grant assistance, the facilities planning requirements in § 35.917 et seq. have been met. ...
First evidence for spin-flip M1 strength in 40Ar

International Nuclear Information System (INIS)

Li, T.C.; Rainovski, G.; Pietralla, N.; Ahn, T.; Costin, A.; Tonchev, A.P.; Ahmed, M.W.; Blackston, M.A.; Parpottas, Y.; Perdue, B.A.; Tornow, W.; Weller, H.R.; Angell, C.; Keeter, K.J.; Li, J.; Mikhailov, S.; Wu, Y.K.; Lisetskiy, A.

2006-01-01

The 40 Ar(γ→,γ ' ) photon scattering reaction was used to search for spin-flip M1 strength in 40 Ar. The nearly monochromatic, linearly polarized photon beam of HIγS, in an energy region from 7.7 to 11 MeV, was employed in this study. 28 dipole excitations were observed. The azimuthal intensity asymmetry indicated that all of these states were E1 except for the state at E x =9.757 MeV. Shell-model calculations were used to interpret this state as one fragment of the spin-flip M1 strength in 40 Ar
Variation in treatment of blunt splenic injury in Dutch academic trauma centers

NARCIS (Netherlands)

D.C. Olthof; J.S.K. Luitse; P.P. de Rooij (Philippe); L.P.H. Leenen (Luke); K.W. Wendt (Klaus); F.W. Bloemers (Frank)

2015-01-01

textabstractBackground The incidence of splenectomy after trauma is institutionally dependent and varies from 18% to as much as 40%. This is important because variation in management influences splenic salvage. The aim of this study was to investigate whether differences exist between Dutch level 1
Variation in treatment of blunt splenic injury in Dutch academic trauma centers

NARCIS (Netherlands)

Olthof, D.C.; Luitse, J.S.K.; de Rooij, P.P.; Leenen, L.P.H.; Wendt, K.W.; Bloemers, F.W.; Goslings, J.C.

2015-01-01

Background The incidence of splenectomy after trauma is institutionally dependent and varies from 18% to as much as 40%. This is important because variation in management influences splenic salvage. The aim of this study was to investigate whether differences exist between Dutch level 1 trauma
A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa

NARCIS (Netherlands)

Van Schil, Kristof; Klevering, B. Jeroen; Leroy, Bart P.; Pott, Jan Willem R.; Bandah-Rozenfeld, Dikla; Zonneveld-Vrieling, Marijke N.; Sharon, Dror; den Hollander, Anneke I.; Cremers, Frans P. M.; De Baere, Elfride; Collin, Rob W. J.; van den Born, L. Ingeborgh

PURPOSE. To identify mutations in FAM161A underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch and Belgian populations and to investigate whether common FAM161A-associated phenotypic features could be identified. METHODS. Homozygosity mapping, amplification-refractory mutation

Study of 40Ca-40Ca elastic scattering at intermediate energy

International Nuclear Information System (INIS)

Kumar, Ashok; Srivastava, B.B.

1980-01-01

The differential cross sections for 40 Ca- 40 Ca elastic scattering have been calculated at laboratory incident energy of 240 MeV using a sharp cut off of the partial waves below a critical angular momentum, 1sub(c)' to account for absorption. The effective 40 Ca- 40 Ca potential is taken to be the sum of a real nuclear potential and the Coulomb potential. The calculated differential cross sections which are in fair agreement with the experimental data are presented and discussed. (author)
40 CFR 750.40 - Cross-examination.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Cross-examination. 750.40 Section 750... Processing and Distribution in Commerce Exemptions § 750.40 Cross-examination. (a) After the close of the... cross-examination. The request must be received by EPA within one week after a full transcript of the...
40 CFR 164.1 - Number of words.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Number of words. 164.1 Section 164.1... OTHER HEARINGS CALLED PURSUANT TO SECTION 6 OF THE ACT General § 164.1 Number of words. As used in this part, a word in the singular form shall be deemed to import the plural, and vice versa, as the case may...
Variation in treatment of blunt splenic injury in Dutch academic trauma centers

NARCIS (Netherlands)

Olthof, Dominique C.; Luitse, Jan S. K.; de Rooij, Philippe P.; Leenen, Loek P. H.; Wendt, Klaus W.; Bloemers, Frank W.; Goslings, J. Carel

2015-01-01

The incidence of splenectomy after trauma is institutionally dependent and varies from 18% to as much as 40%. This is important because variation in management influences splenic salvage. The aim of this study was to investigate whether differences exist between Dutch level 1 trauma centers with
40 CFR 1.29 - Office of Inspector General.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Office of Inspector General. 1.29 Section 1.29 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL STATEMENT OF ORGANIZATION... operations. The Office provides leadership and coordination and recommends policies for other Agency...
The impact of SF3B1 mutations in CLL on the DNA-damage response

DEFF Research Database (Denmark)

Te Raa, G D; Derks, I A M; Navrkalova, V

2015-01-01

Mutations or deletions in TP53 or ATM are well-known determinants of poor prognosis in chronic lymphocytic leukemia (CLL), but only account for approximately 40% of chemo-resistant patients. Genome-wide sequencing has uncovered novel mutations in the splicing factor sf3b1, that were in part assoc...
Sustainable innovations in Dutch SMEs

International Nuclear Information System (INIS)

Bertens, C.; Snoei, J.

2011-11-01

The 'Dutch Monitor Determinanten Bedrijfsprestaties in het MKB' (Determinants Company Performance Monitoring SMEs) has consulted almost 3.500 persons in SMEs on a number of questions, including on innovations. 40% of these persons perceive market opportunities for sustainable products, whereas only 25% of these businesses actually tries to capitalize on these opportunities. [nl
Data of evolutionary structure change: 1C40A-2ZLWD [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1C40A-2ZLWD 1C40 2ZLW A D -VLSAADKTNVKGVFSKISGHAEEYGAETLERMFTAYPQ...R VQLSGEEKAAVLALWDKV--NEEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSEL...dex> 2ZLW D 2ZLWD LWD
Surface chemistry of lipid raft and amyloid Aβ (1-40) Langmuir monolayer.

Science.gov (United States)

Thakur, Garima; Pao, Christine; Micic, Miodrag; Johnson, Sheba; Leblanc, Roger M

2011-10-15

Lipid rafts being rich in cholesterol and sphingolipids are considered to provide ordered lipid environment in the neuronal membranes, where it is hypothesized that the cleavage of amyloid precursor protein (APP) to Aβ (1-40) and Aβ (1-42) takes place. It is highly likely that the interaction of lipid raft components like cholesterol, sphingomylein or GM1 leads to nucleation of Aβ and results in aggregation or accumulation of amyloid plaques. One has investigated surface pressure-area isotherms of the lipid raft and Aβ (1-40) Langmuir monolayer. The compression-decompression cycles and the stability of the lipid raft Langmuir monolayer are crucial parameters for the investigation of interaction of Aβ (1-40) with the lipid raft Langmuir monolayer. It was revealed that GM1 provides instability to the lipid raft Langmuir monolayer. Adsorption of Aβ (1-40) onto the lipid raft Langmuir monolayer containing neutral (POPC) or negatively charged phospholipid (DPPG) was examined. The adsorption isotherms revealed that the concentration of cholesterol was important for adsorption of Aβ (1-40) onto the lipid raft Langmuir monolayer containing POPC whereas for the lipid raft Langmuir monolayer containing DPPG:cholesterol or GM1 did not play any role. In situ UV-vis absorption spectroscopy supported the interpretation of results for the adsorption isotherms. Copyright © 2011 Elsevier B.V. All rights reserved.
40 CFR 35.927-1 - Infiltration/inflow analysis.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Infiltration/inflow analysis. 35.927-1... ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act § 35.927-1 Infiltration/inflow analysis. (a) The infiltration/inflow analysis shall demonstrate the nonexistence or...
Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists

DEFF Research Database (Denmark)

Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian

2012-01-01

FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metaboli...
Water SA - Vol 40, No 1 (2014)

African Journals Online (AJOL)

Satellite-based annual evaporation estimates of invasive alien plant species and native vegetation in South Africa · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. WML Meijninger, C Jarmain, 95-108. http://dx.doi.org/10.4314/wsa.v40i1.12 ...
40 CFR 35.917 - Facilities planning (step 1).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Facilities planning (step 1). 35.917... Facilities planning (step 1). (a) Sections 35.917 through 35.917-9 establish the requirements for facilities... the facilities planning provisions of this subpart before award of step 2 or step 3 grant assistance...
Thioflavin T templates amyloid β(1-40) conformation and aggregation pathway

DEFF Research Database (Denmark)

Di Carlo, Maria Giovanna; Minicozzi, Velia; Foderà, Vito

2015-01-01

Aβ(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies...... in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effect of Thioflavin T (ThT), a worldwide used fluorescent dye to monitor amyloid growth, on the Aβ(1-40) conformation, stability and aggregation. By combining experimental information and Molecular Dynamics...... simulation results, we show that the presence of ThT in solution affects peptide conformation inducing peculiar supramolecular association. In particular ThT interactions with specific Aβ(1-40) residues promote a rigid partially-folded conformation which shifts the balance between different species...
18 CFR 40.1 - Applicability.

Science.gov (United States)

2010-04-01

... ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT MANDATORY RELIABILITY STANDARDS FOR THE BULK-POWER SYSTEM... in section 201(f) of the Federal Power Act. (b) Each Reliability Standard made effective by § 40.2... Reliability Standard applies. ...
40 CFR 97.40 - Trading program budget.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Trading program budget. 97.40 Section...) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Allowance Allocations § 97.40 Trading program budget. In accordance with §§ 97.41 and 97.42, the Administrator will allocate to the NOX...
Dose due to 40K

International Nuclear Information System (INIS)

Escareno J, E.; Vega C, H. R.

2011-10-01

The dose due to 40 K has been estimated. Potassium is one of the most abundant elements in nature, being approximately 2% of the Earth's crust. Potassium has three isotopes 39 K, 40 K and 41 K, two are stable while 40 K is radioactive with a half life of 1.2x10 9 years; there is 0.0117% 40 K-to-K ratio. Potassium plays an important role in plants, animals and humans growth and reproduction. Due to the fact that K is an essential element for humans, 40 K is the most abundant radioisotope in human body. In order to keep good health conditions K must be intake at daily basis trough food and beverages, however when K in ingested above the requirements produce adverse health effects in persons with renal, cardiac and hypertension problems or suffering diabetes. In 89.3% 40 K decays to 40 C through β-decay, in 10.3% decays through electronic capture and emitting 1.46 MeV γ-ray. K is abundant in soil, construction materials, sand thus γ-rays produced during 40 K decay contribute to external dose. For K in the body practically all 40 K decaying energy is absorbed by the body; thus 40 K contributes to total dose in humans and it is important to evaluate its contribution. In this work a set of 40 K sources were prepared using different amounts of KCl salt, a γ-ray spectrometer with a NaI(Tl) was characterized to standardized the sources in order to evaluate the dose due to 40 K. Using thermoluminescent dosemeters the dose due to 40 K was measured and related to the amount of 40 K γ-ray activity. (Author)
BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk breast cancer.

Science.gov (United States)

El Saghir, Nagi S; Zgheib, Nathalie K; Assi, Hussein A; Khoury, Katia E; Bidet, Yannick; Jaber, Sara M; Charara, Raghid N; Farhat, Rania A; Kreidieh, Firas Y; Decousus, Stephanie; Romero, Pierre; Nemer, Georges M; Salem, Ziad; Shamseddine, Ali; Tfayli, Arafat; Abbas, Jaber; Jamali, Faek; Seoud, Muhieddine; Armstrong, Deborah K; Bignon, Yves-Jean; Uhrhammer, Nancy

2015-04-01

Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before the age of 50 years. Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases. Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patients (5.3%) aged 41-50 years with FH had a deleterious mutation. Only 1 of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed. Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended. ©AlphaMed Press.
Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

DEFF Research Database (Denmark)

Winkelmann, Juliane; Lin, Ling; Schormair, Barbara

2012-01-01

to HDAC2. It is also highly expressed in immune cells and required for the differentiation of CD4+ into T regulatory cells. Mutations in exon 20 of this gene were recently reported to cause hereditary sensory neuropathy with dementia and hearing loss (HSAN1). Our mutations are all located in exon 21......Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT...
Transfection with extracellularly UV-damaged DNA induces human and rat cells to express a mutator phenotype towards parvovirus H-1

International Nuclear Information System (INIS)

Dinsart, C.; Cornelis, J.J.; Klein, B.; van der Eb, A.J.; Rommelaere, J.

1984-01-01

Human and rat cells transfected with UV-irradiated linear double-stranded DNA from calf thymus displayed a mutator activity. This phenotype was identified by growing a lytic thermosensitive single-stranded DNA virus (parvovirus H-1) in those cells and determining viral reversion frequencies. Likewise, exogenous UV-irradiated closed circular DNAs, either double-stranded (simian virus 40) or single-stranded (phi X174), enhanced the ability of recipient cells to mutate parvovirus H-1. The magnitude of mutator activity expression increased along with the number of UV lesions present in the inoculated DNA up to a saturation level. Unirradiated DNA displayed little inducing capacity, irrespective of whether it was single or double stranded. Deprivation of a functional replication origin did not impede UV-irradiated simian virus 40 DNA from providing rat and human cells with a mutator function. Our data suggest that in mammalian cells a trans-acting mutagenic signal might be generated from UV-irradiated DNA without the necessity for damaged DNA to replicate

Reliability of self-reported diagnostic radiation history in BRCA1/2 mutation carriers

International Nuclear Information System (INIS)

Pijpe, Anouk; Manders, Peggy; Mulder, Renee L.; Leeuwen, Flora E. van; Rookus, Matti A.

2010-01-01

We assessed reliability of self-reported diagnostic radiation history in BRCA1/2 mutation carriers with and without breast cancer. Within the frame-work of the HEBON study, 401 BRCA1/2 mutation carriers completed a baseline (1999-2004) and a follow-up questionnaire (2006-2007). Test-retest reliability of self-reported exposure to chest X-rays, fluoroscopies and mammograms was assessed for the entire study population and by case status. Overall proportion agreement on reporting ever/never exposure was good (> 75%), while the corresponding kappa coefficients were between 0.40 and 0.75, indicating at least moderate reliability beyond chance. Reliability of number of exposures was also good (> 75%). Proportion agreement on reporting age at first mammogram was low (40%) for exact consistency and moderate (60%) for consistency ± 1 year. Reliability of age at first mammogram was higher for cases than for unaffected carriers (P < 0.001) but this difference disappeared when excluding diagnostic mammograms (P = 0.60). In unaffected carriers proportion agreement on age at last mammogram was 50%. In general, the direction of disagreement on all items was equally distributed. More consistent reporting was mainly determined by a younger age at questionnaire completion. In conclusion, inconsistent self-report of diagnostic radiation by BRCA1/2 mutation carriers was mainly non-differential by disease status.
The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer.

Science.gov (United States)

Pejerrey, Sasha M; Dustin, Derek; Kim, Jin-Ah; Gu, Guowei; Rechoum, Yassine; Fuqua, Suzanne A W

2018-05-07

After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several "hot spot mutations," a cluster of mutations found in the hormone-binding domain of the ESR1 gene. Throughout the course of treatment, tumor evolution can occur, and ESR1 mutations emerge and become enriched in the metastatic setting. Sensitive techniques to continually monitor mutant burden in vivo are needed to effectively treat patients with mutant ESR1. The full impact of these mutations on tumor response to different therapies remains to be determined. However, recent studies indicate that mutant-bearing tumors may be less responsive to specific hormonal therapies, and suggest that aromatase inhibitor (AI) therapy may select for the emergence of ESR1 mutations. Additionally, different mutations may respond discretely to targeted therapies. The need for more preclinical mechanistic studies on ESR1 mutations and the development of better agents to target these mutations are urgently needed. In the future, sequential monitoring of ESR1 mutational status will likely direct personalized therapeutic regimens appropriate to each tumor's unique mutational landscape.
40 CFR 80.55 - Measurement methods for benzene and 1,3-butadiene.

Science.gov (United States)

2010-07-01

... accomplished by bag sampling as used for total hydrocarbons determination. This procedure is detailed in 40 CFR 86.109. (b) Benzene and 1,3-butadiene must be analyzed by gas chromatography. Expected values for benzene and 1,3-butadiene in bag samples for the baseline fuel are 4.0 ppm and 0.30 ppm respectively. At...
46 CFR 1.03-40 - Appeals from decisions or actions of the National Maritime Center.

Science.gov (United States)

2010-10-01

... Maritime Center. 1.03-40 Section 1.03-40 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES... Appeal § 1.03-40 Appeals from decisions or actions of the National Maritime Center. Any person directly affected by a decision or action of an officer or employee of the National Maritime Center (NMC) involving...
Estimating the risk of dengue transmission from Dutch blood donors travelling to Suriname and the Dutch Caribbean.

Science.gov (United States)

Oei, W; Lieshout-Krikke, R W; Kretzschmar, M E; Zaaijer, H L; Coutinho, R A; Eersel, M; Jubithana, B; Halabi, Y; Gerstenbluth, I; Maduro, E; Tromp, M; Janssen, M P

2016-05-01

The risk of dengue transmitted by travellers is known. Methods to estimate the transmission by transfusion (TT) risk from blood donors travelling to risk areas are available, for instance, the European Up-Front Risk Assessment Tool (EUFRAT). This study aimed to validate the estimated risk from travelling donors obtained from EUFRAT. Surveillance data on notified dengue cases in Suriname and the Dutch Caribbean islands (Aruba, Curaçao, St. Maarten, Bonaire, St. Eustatius and Saba) in 2001-2011 was used to calculate local incidence rates. Information on travel and donation behaviour of Dutch donors was collected. With the EUFRAT model, the TT risks from Dutch travelling donors were calculated. Model estimates were compared with the number of infections in Dutch travellers found by laboratory tests in the Netherlands. The expected cumulative number of donors becoming infected during travels to Suriname and the Dutch Caribbean from 2001 to 2011 was estimated at 5 (95% CI, 2-11) and 86 (45-179), respectively. The infection risk inferred from the laboratory-based study was 19 (9-61) and 28 (14-92). Given the independence of the data sources, these estimates are remarkably close. The model estimated that 0·02 (0·001-0·06) and 0·40 (0·01-1·4) recipients would have been infected by these travelling donors. The EUFRAT model provided an estimate close to actual observed number of dengue infections. The dengue TT risk among Dutch travelling donors can be estimated using basic transmission, travel and donation information. The TT risk from Dutch donors travelling to Suriname and the Dutch Caribbean is small. © 2016 International Society of Blood Transfusion.
Glaucoma and Cytochrome P4501B1 Gene Mutations

Directory of Open Access Journals (Sweden)

Mukesh Tanwar

2010-01-01

Full Text Available Developmental anomalies of the ocular anterior chamber angle may lead to an incomplete development of the structures that form the conventional aqueous outflow pathway. Thus, disorders that present with such dysfunction tend to be associated with glaucoma. Among them, Axenfeld-Rieger (ARS malformation is a rare clinical entity with an estimated prevalence of one in every 200,000 individuals. The changes in eye morphogenesis in ARS are highly penetrant and are associated with 50% risk of development of glaucoma. Mutations in the cytochrome P4501B1 (CYP1B1 gene have been reported to be associated with primary congenital glaucoma and other forms of glaucoma and mutations in pituitary homeobox 2 (PITX2 gene have been identified in ARS in various studies. This case was negative for PITX2 mutations and compound heterozygote for CYP1B1 mutations. Clinical manifestations of this patient include bilateral elevated intraocular pressure (>40 mmHg with increased corneal diameter (>14 mm and corneal opacity. Patient also had iridocorneal adhesions, anteriorly displaced Schwalbe line, anterior insertion of iris, broad nasal bridge and protruding umbilicus. This is the first study from north India reporting CYP1B1 mutations in Axenfeld-Rieger syndrome with bilateral buphthalmos and early onset glaucoma. Result of this study supports the role of CYP1B1 as a causative gene in ASD disorders and its role in oculogenesis.
40 CFR 721.4880 - Methanol, trichloro-, carbonate (2:1).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Methanol, trichloro-, carbonate (2:1... Substances § 721.4880 Methanol, trichloro-, carbonate (2:1). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as methanol, trichloro-, carbonate (2:1) (CAS...
40 CFR 96.40 - State trading program budget.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false State trading program budget. 96.40... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.40 State trading program budget. The State trading program budget...
40 CFR 721.3248 - Ethane, 1,2,2- trichlorodifluoro-.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethane, 1,2,2- trichlorodifluoro-. 721... Substances § 721.3248 Ethane, 1,2,2- trichlorodifluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as ethane, 1,2,2-trichlorodifluoro- (CAS No...
Aggregation process of Aβ1-40 with non-Aβ amyloid component of α-synuclein

International Nuclear Information System (INIS)

Eugene, Cindie; Mousseau, Normand

2015-01-01

Many neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, are characterized by the presence of amyloid fibers. Recently, attention has turned from the fibers to the early stages of oligomerization where toxicity could be highest. Here, we focus on the interactions between non-Aβ amyloid component of a-synuclein (NAC) and Aβ 1-40 , two proteins found in amyloid fibrils associated with Alzheimer's disease. We combine the coarse-grained OPEP potential with a Hamiltonian and temperature replica exchange molecular dynamics simulation (HT-REMD) to identify mechanisms leading to the formation of secondary structures promoting fibrillation. We observe that the propensity to form beta-sheet remains the same for Aβ 1-40 whereas is decreases significantly for NAC. In particular, the 25-35 region of Aβ 1-40 is a significant area of secondary structure stabilization with NAC. The ionic interactions between salt-bridge D23 and K28 in Aβ 1-40 and K20 and E23 in NAC of the heterogeneous dimer are consistent with the salt-bridges found in NAC and Aβ 1-40 homogenous dimers and allow us to see that these interactions don't necessarily dominate the interchain stabilizations. Our numerical simulation also show the formation of interaction between the early oligomer of NAC and Aβ 1-40 . (paper)
Soluble CD40 ligand stimulates CD40-dependent activation of the β2 integrin Mac-1 and protein kinase C zeda (PKCζ in neutrophils: implications for neutrophil-platelet interactions and neutrophil oxidative burst.

Directory of Open Access Journals (Sweden)

Rong Jin

Full Text Available Recent work has revealed an essential involvement of soluble CD40L (sCD40L in inflammation and vascular disease. Activated platelets are the major source of sCD40L, which has been implicated in platelet and leukocyte activation, although its exact functional impact on leukocyte-platelet interactions and the underlying mechanisms remain undefined. We aimed to determine the impact and the mechanisms of sCD40L on neutrophils. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte recruitment to the sites of injury. Our data show that CD40L contributes to neutrophil firm adhesion to and transmigration across activated surface-adherent platelets, possibly through two potential mechanisms. One involves the direct interaction of ligand-receptor (CD40L-CD40, i.e., platelet surface CD40L interaction with neutrophil CD40; another involves an indirect mechanism, i.e. soluble CD40L stimulates activation of the leukocyte-specific β2 integrin Mac-1 in neutrophils and thereby further promotes neutrophil adhesion and migration. Activation of the integrin Mac-1 is known to be critical for mediating neutrophil adhesion and migration. sCD40L activated Mac-1 in neutrophils and enhanced neutrophil-platelet interactions in wild-type neutrophils, but failed to elicit such responses in CD40-deficient neutrophils. Furthermore, our data show that the protein kinase C zeta (PKCζ is critically required for sCD40L-induced Mac-1 activation and neutrophil adhesive function. sCD40L strongly stimulated the focal clustering of Mac-1 (CD11b and the colocalization of Mac-1 with PKCζ in wild-type neutrophils, but had minimal effect in CD40-deficient neutrophils. Blocking PKCζ completely inhibited sCD40L-induced neutrophil firm adhesion. Moreover, sCD40L strongly stimulates neutrophil oxidative burst via CD40-dependent activation of PI3K/NF-KB, but independent of Mac-1 and PKCζ. These findings may contribute to a better
Roles of the kinase TAK1 in TRAF6-dependent signaling by CD40 and its oncogenic viral mimic, LMP1.

Directory of Open Access Journals (Sweden)

Kelly M Arcipowski

Full Text Available The Epstein-Barr virus (EBV-encoded protein latent membrane protein 1 (LMP1 is essential for EBV-mediated B cell transformation and plays a critical role in the development of post-transplant B cell lymphomas. LMP1 also contributes to the exacerbation of autoimmune diseases such as systemic lupus erythematosus (SLE. LMP1 is a functional mimic of the tumor necrosis factor receptor (TNFR superfamily member CD40, and relies on TNFR-associated factor (TRAF adaptor proteins to mediate signaling. However, LMP1 activation signals to the B cell are amplified and sustained compared to CD40 signals. We previously demonstrated that LMP1 and CD40 use TRAF molecules differently. Although associating with CD40 and LMP1 via separate mechanisms, TRAF6 plays a significant role in signal transduction by both. It is unknown whether TRAF6 mediates CD40 versus LMP1 functions via distinct or shared pathways. In this study, we tested the hypothesis that TRAF6 uses the kinase TAK1 to trigger important signaling pathways following both CD40 and LMP1 stimulation. We determined that TAK1 was required for JNK activation and interleukin-6 (IL-6 production mediated by CD40 and LMP1, in both mouse and human B cells. Additionally, TRAF3 negatively regulated TRAF6-dependent, CD40-mediated TAK1 activation by limiting TRAF6 recruitment. This mode of regulation was not observed for LMP1 and may contribute to the dysregulation of LMP1 compared to CD40 signals.
10 CFR 40.64 - Reports.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Reports. 40.64 Section 40.64 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL Records, Reports, and Inspections § 40.64 Reports. (a... in the fabrication of mixed-oxide fuels, shall complete a Nuclear Material Transaction Report in...
YKL-40 and genetic status of CHI3L1 in a large group of asthmatics

DEFF Research Database (Denmark)

Hansen, Jakob W; Thomsen, Simon F; Porsbjerg, Celeste

2015-01-01

BACKGROUND: Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (-131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40...... to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1....
Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis.

Science.gov (United States)

Qi, Guoyan; Liu, Peng; Gu, Shanshan; Yang, Hongxia; Dong, Huimin; Xue, Yinping

2018-04-01

Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.
Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers

DEFF Research Database (Denmark)

Bancroft, Elizabeth K; Page, Elizabeth C; Castro, Elena

2014-01-01

AND PARTICIPANTS: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng......BACKGROUND: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening....../ml were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. RESULTS AND LIMITATIONS: We...
25 CFR 40.4 - Security.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Security. 40.4 Section 40.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION ADMINISTRATION OF EDUCATIONAL LOANS, GRANTS AND OTHER ASSISTANCE FOR HIGHER EDUCATION § 40.4 Security. If a borrower or cosigner has security to offer for an...
A New COL3A1 Mutation in Ehlers-Danlos Syndrome Vascular Type With Different Phenotypes in the Same Family.

Science.gov (United States)

Cortini, Francesca; Marinelli, Barbara; Romi, Silvia; Seresini, Agostino; Pesatori, Angela Cecilia; Seia, Manuela; Montano, Nicola; Bassotti, Alessandra

2017-04-01

Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe connective tissue disorder caused by mutations in the collagen type III alpha I chain ( COL3A1) gene. We describe a pathogenetic heterozygous COL3A1 mutation c.3140 G>A, p. Gly1047Asp, identified using next-generation sequencing, in a 40-year-old Italian female. The genetic test performed on her relatives, which present different clinical phenotypes, confirmed that they carry the same mutation in heterozygous state. This finding confirms that mutations causing vEDS have an incomplete penetrance.
28 CFR 12.40 - Public examination.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Public examination. 12.40 Section 12.40... ESPIONAGE, COUNTERESPIONAGE, OR SABOTAGE MATTERS UNDER THE ACT OF AUGUST 1, 1956 § 12.40 Public examination. Registration statements shall be available for public examination at the offices of the Registration Unit...
Food insecurity among Dutch food bank recipients: a cross-sectional study.

Science.gov (United States)

Neter, Judith E; Dijkstra, S Coosje; Visser, Marjolein; Brouwer, Ingeborg A

2014-05-16

To determine the prevalence of (very) low food security among Dutch food bank recipients, and to identify potential demographic, lifestyle and nutrition-related factors associated with (very) low food security. 11 of 135 Dutch food banks were selected throughout the Netherlands. 251 Dutch food bank recipients participated in the study (93 men and 158 women). Inclusion criteria for participation were: (1) at least 18 years of age, (2) sufficiently fluent in Dutch to participate in oral and written interviews, (3) recipient of a Dutch food bank for at least 1 month and (4) collect own food parcel at the food bank. A single member per household was included. Level of food security. The prevalence of food insecurity was 72.9% (N=183), of which 40.4% (N=74) reported very low food security. Of the very low food secure participants, 56.8% (N=42) reported they were ever hungry but did not eat because they could not afford enough food in the previous 3 months. Adjusted multinomial logistic regression analyses showed that households without children were less likely to experience low food security (OR 0.39 (95% CI 0.18 to 0.88)) and men (OR 0.24 (95% CI 0.11 to 0.51)) were less likely to experience very low food security, while low-educated recipients (OR 5.05 (95% CI 1.37 to 18.61)) were more likely to experience very low food security. Furthermore, recipients with high satisfaction with overall food intake (OR 0.46 (95% CI 0.27 to 0.78)), high perceived healthiness of overall food intake (OR 0.34 (95% CI 0.19 to 0.62)) or high self-efficacy of eating healthy (OR 0.62 (95% CI 0.40 to 0.96)) were less likely to experience very low food security. Our study showed high prevalence rates of food insecurity among Dutch food bank recipients, and identified subgroups at increased risk of food insecurity. More research is urgently needed on the underlying determinants of food insecurity and the effectiveness of food assistance by food banks. Published by the BMJ Publishing

Dose due to {sup 40}K

Energy Technology Data Exchange (ETDEWEB)

Escareno J, E.; Vega C, H. R., E-mail: edmundoej@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

2011-10-15

The dose due to {sup 40}K has been estimated. Potassium is one of the most abundant elements in nature, being approximately 2% of the Earth's crust. Potassium has three isotopes {sup 39}K, {sup 40}K and {sup 41}K, two are stable while {sup 40}K is radioactive with a half life of 1.2x10{sup 9} years; there is 0.0117% {sup 40}K-to-K ratio. Potassium plays an important role in plants, animals and humans growth and reproduction. Due to the fact that K is an essential element for humans, {sup 40}K is the most abundant radioisotope in human body. In order to keep good health conditions K must be intake at daily basis trough food and beverages, however when K in ingested above the requirements produce adverse health effects in persons with renal, cardiac and hypertension problems or suffering diabetes. In 89.3% {sup 40}K decays to {sup 40}C through {beta}-decay, in 10.3% decays through electronic capture and emitting 1.46 MeV {gamma}-ray. K is abundant in soil, construction materials, sand thus {gamma}-rays produced during {sup 40}K decay contribute to external dose. For K in the body practically all {sup 40}K decaying energy is absorbed by the body; thus {sup 40}K contributes to total dose in humans and it is important to evaluate its contribution. In this work a set of {sup 40}K sources were prepared using different amounts of KCl salt, a {gamma}-ray spectrometer with a NaI(Tl) was characterized to standardized the sources in order to evaluate the dose due to {sup 40}K. Using thermoluminescent dosemeters the dose due to {sup 40}K was measured and related to the amount of {sup 40}K {gamma}-ray activity. (Author)
Autosomal recessive retinitis pigmentosa with RP1 mutations is associated with myopia.

Science.gov (United States)

Chassine, Thomas; Bocquet, Béatrice; Daien, Vincent; Avila-Fernandez, Almudena; Ayuso, Carmen; Collin, Rob Wj; Corton, Marta; Hejtmancik, J Fielding; van den Born, L Ingeborgh; Klevering, B Jeroen; Riazuddin, S Amer; Sendon, Nathacha; Lacroux, Annie; Meunier, Isabelle; Hamel, Christian P

2015-10-01

To determine the refractive error in patients with autosomal recessive retinitis pigmentosa (arRP) caused by RP1 mutations and to compare it with that of other genetic subtypes of RP. Twenty-six individuals had arRP with RP1 mutations, 25 had autosomal dominant RP (adRP) with RP1 mutation, 8 and 33 had X-linked RP (xlRP) with RP2 and RPGR mutations, respectively, 198 and 93 had Usher syndrome and arRP without RP1 mutations, respectively. The median of the spherical equivalent (SE) and the IQR (Q25-Q75) was determined and multiple comparisons were performed. arRP patients with RP1 mutations had SE median at -4.0 dioptres (D) OD (Ocula Dextra); -3.88 D OS (Ocula Sinistra), whereas arRP patients without RP1 mutations (-0.50 D OD; -0.75 D OS) and Usher syndrome patients (-0.50 D OD; -0.38 D OS) were significantly less myopic (pUsher syndrome and adRP with RP1 mutation had a narrow IQR (-9.06 to -1.13 D), whereas arRP with RP1 mutations and xlRP with RP2 or RPGR mutations had a larger range (-9.06; -1.13 D). arRP patients with RP1 mutations have myopia not different from patients with xlRP with RP2 or RPGR mutations, while RP patients from other genetic subgroups were emmetropic or mildly myopic. We suggest that arRP patients with high myopic refractive error should be preferentially analysed for RP1 mutations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Distinct pattern of p53 mutations in bladder cancer

DEFF Research Database (Denmark)

Spruck, C H; Rideout, W M; Olumi, A F

1993-01-01

A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder...... tumors from smokers and 13 of 40 (33%) tumors from lifetime nonsmokers. Overall, 13 of the 50 (26%) total point mutations discovered in this and previous work were G:C-->C:G transversions, a relatively rare mutational type in human tumors. In six tumors, identical AGA (Arg)-->ACA (Thr) point mutations...... double mutations, four of which were tandem mutations on the same allele. No double mutations were found in tumors from nonsmoking patients. None of the mutations in smokers were G:C-->T:A transversions, which would be anticipated for exposure to the suspected cigarette smoke carcinogen 4-aminobiphenyl...
Affect of Presenilin Mutations on APP Cleavage; Insights into the Pathogenesis of FAD

Directory of Open Access Journals (Sweden)

Nuomin eLi

2016-03-01

Full Text Available Alzheimer disease (AD is characterized by progressive memory loss, reduction in cognitive functions, and damage to the brain. The β-amyloid precursor protein can be sequentially cleaved by β- secretase and γ-secretase. Mutations in the presenilin1（PS1） are the most common cause of Familial Alzheimer’s disease ( FAD. PS1 mutations can alter the activity of γ-secretase on the cleavage of the β-amyloid precursor protein, causing increased Aβ production. Previous studies show that the βAPP-C-terminal fragment is first cleaved by β-scretase, primarily generating long fragments of Aβ48 and Aβ49, followed by the stepwise cleavage of every three amino acid residues at the C terminus, resulting in Aβ48-, 45-, 42 line and Aβ49-, 46-, 43-, 40 line. Here, we used LC-MS/MS to analyze unique peptides IAT, VVIA, ITL，TVI，IVI through sequential cleavage, combined with ELISA to test the level of Aβ42 and Aβ40 for validation. The results show that most FAD mutant PS1 can alter the level of Aβ42 and Aβ40 monitored by the Aβ42/Aβ40 ratio. Among them, 6 mutants (I143T, H163P, S170F, Q223R, M233V and G384A affect the Aβ42/40 ratio through both Aβ49-40 and Aβ48-38 lines; L166P through decreasing the Aβ49-40 line, 6 mutants (I143V, M146V, G217A, E280A, L381V and L392V through increasing the Aβ48-42 line. More importantly, we found some mutations can affect the γ-secretase cleavage preference of α-CTF and β-CTF. In conclusion, we found that the FAD PS1 mutations mainly increase the generation of Aβ42 by decreasing the cleavage of Aβ42-Aβ38 and Aβ43-Aβ40.
Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis.

Science.gov (United States)

Bittencourt, Paulo Lisboa; Marin, Maria Lúcia Carnevale; Couto, Cláudia Alves; Cançado, Eduardo Luiz Rachid; Carrilho, Flair José; Goldberg, Anna Carla

2009-01-01

Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. In our cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%) were heterozygous for the H63D mutation, and one each (5%) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.
Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis

Directory of Open Access Journals (Sweden)

Paulo Lisboa Bittencourt

2009-01-01

Full Text Available BACKGROUND: Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2 and ferroportin 1 (SCL40A1. AIMS: To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. PATIENTS AND METHODS: Nineteen male subjects (median age 42 [range: 20-72] years with HH were evaluated using the Haemochromatosis StripAssay A®. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. RESULTS: In our cohort, nine (47% patients were homozygous for the C282Y mutation, two (11% were heterozygous for the H63D mutation, and one each (5% was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. CONCLUSIONS: One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.
Production of a Novel OX40 Ligand for Clinical Use

Science.gov (United States)

2012-10-01

that mutating the OX40L:Ig sequence would lead to a “safer” profile for FDA screening purposes, it was not clear whether mutating this sequence... green monkey kidney cell line, Vero, fits this description and was used. The indicator cells are maintained by WuXi AppTec’s Cell Production Laboratory...extra-nuclear and typically appears as small round bodies approximately 0.3 fim in diameter. 10.2 Direct Assay Change in color or turbidity of broth
BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

Science.gov (United States)

Zavitsanos, Peter J; Wazer, David E; Hepel, Jaroslaw T; Wang, Yihong; Singh, Kamaljeet; Leonard, Kara L

2018-05-18

Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5/6 or EGFR) was performed for BRCA patients who developed BM and their matched controls. We analyzed 60 patients: 20 BRCA and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA patients and 97% for BRCA controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA patients. All 3 BRCA1 patients who developed BM were of a basal-type triple negative phenotype. Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors.
Characterization of a sensitive mouse Aβ40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice.

Science.gov (United States)

Lu, Yanmei; Hoyte, Kwame; Montgomery, William H; Luk, Wilman; He, Dongping; Meilandt, William J; Zuchero, Y Joy Yu; Atwal, Jasvinder K; Scearce-Levie, Kimberly; Watts, Ryan J; DeForge, Laura E

2016-05-01

Transgenic mice that overexpress human amyloid precursor protein with Swedish or London (APPswe or APPlon) mutations have been widely used for preclinical Alzheimer's disease (AD) drug development. AD patients, however, rarely possess these mutations or overexpress APP. We developed a sensitive ELISA that specifically and accurately measures low levels of endogenous Aβ40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant Aβ reductions were observed in the periphery and the brain. APPlon transgenic mice showed a slightly less reduction, whereas APPswe mice did not have any decrease. This sensitive and well-characterized mouse Aβ40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.
40 CFR 230.40 - Sanctuaries and refuges.

Science.gov (United States)

2010-07-01

... Section 230.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION... Impacts on Special Aquatic Sites § 230.40 Sanctuaries and refuges. (a) Sanctuaries and refuges consist of...; (2) Create unplanned, easy and incompatible human access to remote aquatic areas; (3) Create the need...
40 CFR 467.40 - Applicability; description of the forging subcategory.

Science.gov (United States)

2010-07-01

... forging subcategory. 467.40 Section 467.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ALUMINUM FORMING POINT SOURCE CATEGORY Forging Subcategory § 467.40 Applicability; description of the forging subcategory. This subpart applies to discharges of...
The Japanese Mutant Aβ (ΔE22-Aβ1–39) Forms Fibrils Instantaneously, with Low-Thioflavin T Fluorescence: Seeding of Wild-Type Aβ1-40 into Atypical Fibrils by ΔE22-Aβ1-39

Science.gov (United States)

Cloe, Adam L.; Orgel, Joseph P.R.O.; Sachleben, Joseph R.; Tycko, Robert; Meredith, Stephen C.

2012-01-01

The ΔE693 (Japanese) mutation of the β-amyloid precursor protein leads to production of ΔE22-Aβ peptides such as ΔE22-Aβ1–39. Despite reports that these peptides do not form fibrils, here we show that, on the contrary, the peptide forms fibrils essentially instantaneously. The fibrils are typical amyloid fibrils in all respects except that they cause only low levels of thioflavin T (ThT) fluorescence, which, however, develops with no lag phase. The fibrils bind ThT, but with a lower affinity and a smaller number of binding sites than wild-type (WT) Aβ1–40. Fluorescence depolarization confirms extremely rapid aggregation of ΔE22-Aβ1–39. Size exclusion chromatography (SEC) indicates very low concentrations of soluble monomer and oligomer, but only in the presence of some organic solvent, e.g., 2% (v/v) DMSO. The critical concentration is approximately 1 order of magnitude lower for ΔE22-Aβ1–39 than for WTAβ1–40. Several lines of evidence point to an altered structure for ΔE22-Aβ1–39 compared to that of WT Aβ1–40 fibrils. In addition to differences in ThT binding and fluorescence, PITHIRDS-CT solid-state nuclear magnetic resonance (NMR) measurements of ΔE22-Aβ1–39 are not compatible with the parallel in-register β-sheet generally observed for WT Aβ1–40 fibrils. X-ray fibril diffraction showed different D spacings: 4.7 and 10.4 Å for WT Aβ1–40 and 4.7 and 9.6 Å for ΔE22-Aβ1–39. Equimolar mixtures of ΔE22-Aβ1–39 and WT Aβ1–40 also produced fibrils extremely rapidly, and by the criteria of ThT fluorescence and electron microscopic appearance, they were the same as fibrils made from pure ΔE22-Aβ1–39. X-ray diffraction of fibrils formed from 1:1 molar mixtures of ΔE22-Aβ1–39 and WT Aβ1–40 showed the same D spacings as fibrils of the pure mutant peptide, not the wild-type peptide. These findings are consistent with extremely rapid nucleation by ΔE22-Aβ1–39, followed by fibril extension by WT Aβ1–40, and
Two Finnish USH1B patients with three novel mutations in myosin VIIA.

Science.gov (United States)

Vastinsalo, Hanna; Isosomppi, Juha; Aittakorpi, Anne; Sankila, Eeva-Marja

2006-09-21

Usher syndrome (USH) is an autosomal recessive disorder resulting in retinal degeneration and sensorineural deafness caused by mutations in at least 10 gene loci. USH is divided into three main clinical types: USH1 (33-44%), USH2 (56-67%), and USH3. Worldwide, USH1 and USH2 account for most of the Usher syndrome cases with rare occurrence of USH3. In Finland, however, USH3 is the most common type (40%), explained by genetic and geographical isolation accompanied with a founder mutation, while USH1 is estimated to comprise 34% and USH2 12% of all USH cases. We examined two unrelated Finnish USH1 patients by sequencing. We found three new myosin VIIA (MYO7A) mutations: p.K923AfsX8, p.Q1896X, and p.E1349K. The p.K923AfsX8 mutation was present in both patients as well as in one of 200 Finnish control chromosomes. This is the first molecular genetic study of USH1 in Finland. We have found three new pathological mutations causing either premature termination of translation or replacement of an evolutionary conserved MYO7A amino acid.
40 CFR Table 1 to Subpart Nnnnnn... - HAP Emissions Sources

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 14 2010-07-01 2010-07-01 false HAP Emissions Sources 1 Table 1 to Subpart NNNNNN of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...: Chromium Compounds Pt. 63, Subpt. NNNNNN, Table 1 Table 1 to Subpart NNNNNN of Part 63—HAP Emissions...
Dimer formation enhances structural differences between amyloid β-protein (1-40 and (1-42: an explicit-solvent molecular dynamics study.

Directory of Open Access Journals (Sweden)

Bogdan Barz

Full Text Available Amyloid β-protein (Aβ is central to the pathology of Alzheimer's disease. A 5% difference in the primary structure of the two predominant alloforms, Aβ(1-40 and Aβ(1-42, results in distinct assembly pathways and toxicity properties. Discrete molecular dynamics (DMD studies of Aβ(1-40 and Aβ(1-42 assembly resulted in alloform-specific oligomer size distributions consistent with experimental findings. Here, a large ensemble of DMD-derived Aβ(1-40 and Aβ(1-42 monomers and dimers was subjected to fully atomistic molecular dynamics (MD simulations using the OPLS-AA force field combined with two water models, SPCE and TIP3P. The resulting all-atom conformations were slightly larger, less compact, had similar turn and lower β-strand propensities than those predicted by DMD. Fully atomistic Aβ(1-40 and Aβ(1-42 monomers populated qualitatively similar free energy landscapes. In contrast, the free energy landscape of Aβ(1-42 dimers indicated a larger conformational variability in comparison to that of Aβ(1-40 dimers. Aβ(1-42 dimers were characterized by an increased flexibility in the N-terminal region D1-R5 and a larger solvent exposure of charged amino acids relative to Aβ(1-40 dimers. Of the three positively charged amino acids, R5 was the most and K16 the least involved in salt bridge formation. This result was independent of the water model, alloform, and assembly state. Overall, salt bridge propensities increased upon dimer formation. An exception was the salt bridge propensity of K28, which decreased upon formation of Aβ(1-42 dimers and was significantly lower than in Aβ(1-40 dimers. The potential relevance of the three positively charged amino acids in mediating the Aβ oligomer toxicity is discussed in the light of available experimental data.
7 CFR 634.40 - Financial management.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Financial management. 634.40 Section 634.40..., DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Financial Management § 634.40 Financial management. (a)(1) Finance and accounting will be in conformance with Office of Management...
Royal Dutch Petroleum Company annual report 1992

International Nuclear Information System (INIS)

Anon.

1993-01-01

The Royal Dutch Petroleum Company has no operations of its own and virtually the whole of its income derives from its 60% interest in the companies known collectively as the Royal Dutch/Shell Group of Companies; the other 40% is owned by the Shell Transport and Trading Company, p.l.c. The company is engaged in the oil, natural gas, chemicals, coal and metals businesses throughout the world. The annual report summarises the year's results and analyses earnings in each industry segment. Financial statements for the year ended 31 December 1992 are presented. The Group companies' estimated net quantities of crude oil, natural gas and coal are given
40 CFR 258.40 - Design criteria.

Science.gov (United States)

2010-07-01

...) The State petitions EPA to review its determination; and (3) EPA approves the State determination or does not disapprove the determination within 30 days. Note to subpart D: 40 CFR part 239 is reserved to... Chemical MCL (mg/l) Arsenic 0.05 Barium 1.0 Benzene 0.005 Cadmium 0.01 Carbon tetrachloride 0.005 Chromium...
10 CFR 40.7 - Employee protection.

Science.gov (United States)

2010-01-01

... protected activities. An employee's engagement in protected activities does not automatically render him or... 10 Energy 1 2010-01-01 2010-01-01 false Employee protection. 40.7 Section 40.7 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL General Provisions § 40.7 Employee protection. (a...
18 CFR 35.40 - Ancillary services.

Science.gov (United States)

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Ancillary services. 35.40 Section 35.40 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Sales of Electric Energy, Capacity and Ancillary Services at Market-Based Rates § 35.40 Ancillary...

40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN P...
CSF studies facilitate DNA diagnosis in familial Alzheimer's disease due to a presenilin-1 mutation

NARCIS (Netherlands)

de Bot, Susanne T; Kremer, H P H; Dooijes, Dennis; Verbeek, Marcel M

2009-01-01

In sporadic Alzheimer's disease (AD), cerebrospinal fluid (CSF) analysis is becoming increasingly relevant to establish an early diagnosis. We present a case of familial AD due to a presenilin-1 mutation in which CSF studies suggested appropriate DNA diagnostics. A 38 year old Dutch man presented
Novel PSEN1 G209A mutation in early-onset Alzheimer dementia supported by structural prediction.

Science.gov (United States)

An, Seong Soo A; Bagyinszky, Eva; Kim, Hye Ryoun; Seok, Ju-Won; Shin, Hae-Won; Bae, SeunOh; Kim, SangYun; Youn, Young Chul

2016-05-20

Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.
40 CFR 112.1 - General applicability.

Science.gov (United States)

2010-07-01

... storage tanks deferred under 40 CFR part 280 that supply emergency diesel generators at a nuclear power generation facility licensed by the Nuclear Regulatory Commission and subject to any Nuclear Regulatory... single-family residence; (E) The capacity of pesticide application equipment and related mix containers...
Involvement of mitogen-activated protein kinases and NFκB in LPS-induced CD40 expression on human monocytic cells

International Nuclear Information System (INIS)

Wu Weidong; Alexis, Neil E.; Chen Xian; Bromberg, Philip A.; Peden, David B.

2008-01-01

CD40 is a costimulatory molecule linking innate and adaptive immune responses to bacterial stimuli, as well as a critical regulator of functions of other costimulatory molecules. The mechanisms regulating lipopolysaccharide (LPS)-induced CD40 expression have not been adequately characterized in human monocytic cells. In this study we used a human monocytic cell line, THP-1, to investigate the possible mechanisms of CD40 expression following LPS exposure. Exposure to LPS resulted in a dose- and time-dependent increase in CD40 expression. Further studies using immunoblotting and pharmacological inhibitors revealed that mitogen-activated protein kinases (MAPKs) and NFκB were activated by LPS exposure and involved in LPS-induced CD40 expression. Activation of MAPKs was not responsible for LPS-induced NFκB activation. TLR4 was expressed on THP-1 cells and pretreatment of cells with a Toll-like receptor 4 (TLR4) neutralizing antibody (HTA125) significantly blunted LPS-induced MAPK and NFκB activation and ensuing CD40 expression. Additional studies with murine macrophages expressing wild type and mutated TLR4 showed that TLR4 was implicated in LPS-induced ERK and NFκB activation, and CD40 expression. Moreover, blockage of MAPK and NFκB activation inhibited LPS-induced TLR4 expression. In summary, LPS-induced CD40 expression in monocytic cells involves MAPKs and NFκB
14 CFR 35.40 - Functional test.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used in...
Narcissistic Personality Inventory : Structure of the adapted Dutch version

NARCIS (Netherlands)

Barelds, Dick P. H.; Dijkstra, Pieternel

The present study examined the structure of a Dutch adaptation of the 40-item Narcissistic Personality Inventory (Raskin & Terry, 1988) in a community sample (n = 460) and a student sample (n = 515). Altering the response format of the NPI to a Likert-scale had no apparent effect on the responses.
9 CFR 3.40 - Terminal facilities.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Terminal facilities. 3.40 Section 3.40... Pigs and Hamsters Transportation Standards § 3.40 Terminal facilities. No person subject to the Animal... animal holding areas of a terminal facility where shipments of live guinea pigs or hamsters are...
GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

Directory of Open Access Journals (Sweden)

Fuka Aizawa

2016-12-01

Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.
Genotype x environment interaction and growth stability of several elm clones resistant to Dutch elm disease

Science.gov (United States)

Alberto Santini; Francesco Pecori; Alessia L. Pepori; Luisa Ghelardini

2012-01-01

The elm breeding program carried out in Italy at the Institute of Plant Protection - Consiglio Nazionale delle Ricercje (CNR) during the last 40 years aimed to develop Dutch elm disease (DED)-resistant elm selections specific to the Mediterranean environment. The need for genotypes adapted to Mediterranean conditions was evident from the poor performance of the Dutch...
40 CFR 721.8145 - Propane,1,1,1,2,2,3,3-heptafluoro-3-methoxy-.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Propane,1,1,1,2,2,3,3-heptafluoro-3-methoxy-. 721.8145 Section 721.8145 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... significant new uses are: (i) Industrial, commercial, and consumer activities. Requirements as specified § 721...
15 CFR 8c.40 - Employment.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Employment. 8c.40 Section 8c.40... BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF COMMERCE § 8c.40 Employment... discrimination in employment under any program or activity conducted by the agency. The definitions, requirements...
Modulation of neuronal differentiation by CD40 isoforms

International Nuclear Information System (INIS)

Hou Huayu; Obregon, Demian; Lou, Deyan; Ehrhart, Jared; Fernandez, Frank; Silver, Archie; Tan Jun

2008-01-01

Neuron differentiation is a complex process involving various cell-cell interactions, and multiple signaling pathways. We showed previously that CD40 is expressed and functional on mouse and human neurons. In neurons, ligation of CD40 protects against serum withdrawal-induced injury and plays a role in survival and differentiation. CD40 deficient mice display neuron dysfunction, aberrant neuron morphologic changes, and associated gross brain abnormalities. Previous studies by Tone and colleagues suggested that five isoforms of CD40 exist with two predominant isoforms expressed in humans: signal-transducible CD40 type I and a C-terminal truncated, non-signal-transducible CD40 type II. We hypothesized that differential expression of CD40 isoform type I and type II in neurons may modulate neuron differentiation. Results show that adult wild-type, and CD40 -/- deficient mice predominantly express CD40 type I and II isoforms. Whereas adult wild-type mice express mostly CD40 type I in cerebral tissues at relatively high levels, in age and gender-matched CD40 -/- mice CD40 type I expression was almost completely absent; suggesting a predominance of the non-signal-transducible CD40 type II isoform. Younger, 1 day old wild-type mice displayed less CD40 type I, and more CD40 type II, as well as, greater expression of soluble CD40 (CD40L/CD40 signal inhibitor), compared with 1 month old mice. Neuron-like N2a cells express CD40 type I and type II isoforms while in an undifferentiated state, however once induced to differentiate, CD40 type I predominates. Further, differentiated N2a cells treated with CD40 ligand express high levels of neuron specific nuclear protein (NeuN); an effect reduced by anti-CD40 type I siRNA, but not by control (non-targeting) siRNA. Altogether these data suggest that CD40 isoforms may act in a temporal fashion to modulate neuron differentiation during brain development. Thus, modulation of neuronal CD40 isoforms and CD40 signaling may represent
40 CFR 464.40 - Applicability; description of the zinc casting subcategory.

Science.gov (United States)

2010-07-01

... casting subcategory. 464.40 Section 464.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS METAL MOLDING AND CASTING POINT SOURCE CATEGORY Zinc Casting Subcategory § 464.40 Applicability; description of the zinc casting subcategory. The provisions of this...
41 CFR 109-40.103-3 - International transportation.

Science.gov (United States)

2010-07-01

... transportation. 109-40.103-3 Section 109-40.103-3 Public Contracts and Property Management Federal Property..., TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.103-3 International transportation. See 4 CFR 52.2 for a certificate required in nonuse of U.S. flag vessels or U.S...
Ox-LDL increases OX40L in endothelial cells through a LOX-1-dependent mechanism

Energy Technology Data Exchange (ETDEWEB)

Dong, Q.; Xiang, R.; Zhang, D.Y.; Qin, S. [Department of Cardiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing (China)

2013-09-19

Oxidative low-density lipoprotein (Ox-LDL) is a key risk factor for the development of atherosclerosis, and it can stimulate the expression of a variety of inflammatory signals. As a new and highly sensitive inflammation index, OX40L may be a key to understanding the mechanisms that regulate interactions between cells within the vessel wall and inflammatory mediators during the development of atherosclerosis. To investigate whether Ox-LDL regulates OX40L expression through an oxidized LDL-1 receptor (LOX-1)-mediated mechanism, we investigated the effect of different concentrations of Ox-LDL (50, 100, 150 µg/mL) on endothelial cell proliferation and apoptosis. Stimulation with Ox-LDL increased OX40L protein 1.44-fold and mRNA 4.0-fold in endothelial cells, and these effects were inhibited by blocking LOX-1. These results indicate that LOX-1 plays an important role in the chronic inflammatory process in blood vessel walls. Inhibiting LOX-1 may reduce blood vessel inflammation and provide a therapeutic option to limit atherosclerosis progression.
Ox-LDL increases OX40L in endothelial cells through a LOX-1-dependent mechanism

International Nuclear Information System (INIS)

Dong, Q.; Xiang, R.; Zhang, D.Y.; Qin, S.

2013-01-01

Oxidative low-density lipoprotein (Ox-LDL) is a key risk factor for the development of atherosclerosis, and it can stimulate the expression of a variety of inflammatory signals. As a new and highly sensitive inflammation index, OX40L may be a key to understanding the mechanisms that regulate interactions between cells within the vessel wall and inflammatory mediators during the development of atherosclerosis. To investigate whether Ox-LDL regulates OX40L expression through an oxidized LDL-1 receptor (LOX-1)-mediated mechanism, we investigated the effect of different concentrations of Ox-LDL (50, 100, 150 µg/mL) on endothelial cell proliferation and apoptosis. Stimulation with Ox-LDL increased OX40L protein 1.44-fold and mRNA 4.0-fold in endothelial cells, and these effects were inhibited by blocking LOX-1. These results indicate that LOX-1 plays an important role in the chronic inflammatory process in blood vessel walls. Inhibiting LOX-1 may reduce blood vessel inflammation and provide a therapeutic option to limit atherosclerosis progression
Targeting outpatient drug safety: recommendations of the Dutch HARM-Wrestling Task Force.

NARCIS (Netherlands)

Warle-van Herwaarden, M.F.; Kramers, C.; Sturkenboom, M.C.; Bemt, P.M. van den; Smet, P.A.G.M. de

2012-01-01

BACKGROUND: Two Dutch observational studies (HARM [Hospital Admissions Related to Medication] and IPCI [Integrated Primary Care Information]) have shown that approximately 5% of all unplanned hospital admissions are associated with adverse drug events (ADEs), of which 40-46% are potentially
In silico Analysis of osr40c1 Promoter Sequence Isolated from Indica Variety Pokkali

Directory of Open Access Journals (Sweden)

W.S.I. de Silva

2017-07-01

Full Text Available The promoter region of a drought and abscisic acid (ABA inducible gene, osr40c1, was isolated from a salt-tolerant indica rice variety Pokkali, which is 670 bp upstream of the putative translation start codon. In silico promoter analysis of resulted sequence showed that at least 15 types of putative motifs were distributed within the sequence, including two types of common promoter elements, TATA and CAAT boxes. Additionally, several putative cis-acing regulatory elements which may be involved in regulation of osr40c1 expression under different conditions were found in the 5′-upstream region of osr40c1. These are ABA-responsive element, light-responsive elements (ATCT-motif, Box I, G-box, GT1-motif, Gap-box and Sp1, myeloblastosis oncogene response element (CCAAT-box, auxin responsive element (TGA-element, gibberellin-responsive element (GARE-motif and fungal-elicitor responsive elements (Box E and Box-W1. A putative regulatory element, required for endosperm-specific pattern of gene expression designated as Skn-1 motif, was also detected in the Pokkali osr40c1 promoter region. In conclusion, the bioinformatic analysis of osr40c1 promoter region isolated from indica rice variety Pokkali led to the identification of several important stress-responsive cis-acting regulatory elements, and therefore, the isolated promoter sequence could be employed in rice genetic transformation to mediate expression of abiotic stress induced genes.
GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

Science.gov (United States)

Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

2016-12-01

The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

40 CFR 440.40 - Applicability; description of the mercury ore subcategory.

Science.gov (United States)

2010-07-01

... mercury ore subcategory. 440.40 Section 440.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORE MINING AND DRESSING POINT SOURCE CATEGORY Mercury Ore Subcategory § 440.40 Applicability; description of the mercury ore subcategory. The provisions of subpart D...
On the Correct Application of the 100-40-40 Rule for Combining Responses Due to three Directions of Earthquake Loading

International Nuclear Information System (INIS)

Nie, J.; Morante, R.; Miranda, M.; Braverman, J.

2010-01-01

The 100-40-40 rule is often used with the response spectrum analysis method to determine the maximum seismic responses from structural responses resulting from the three spatial earthquake components. This rule has been referenced in several recent Design Certification applications of nuclear power plants, and appears to be gaining in popularity. However, this rule is described differently in ASCE 4-98 and Regulatory Guide 1.92, consequently causing confusion on correct implementation of this rule in practice. The square root of the sum of the squares method is another acceptable spatial combination method and was used to justify the adequacy of the 100-40-40 rule during the development of the Regulatory Guide 1.92. The 100-40-40 rule, when applied correctly, is almost always conservative compared to the SRSS method, and is only slightly unconservative in rare cases. The purpose of this paper is to describe in detail the proper application of the 100-40-40 rule, as prescribed in ASCE 4-98 and in Regulatory Guide 1.92, and to clarify the confusion caused by the two different formats of this rule.
On the Correct Application of the 100-40-40 Rule for Combining Responses Due to three Directions of Earthquake Loading

Energy Technology Data Exchange (ETDEWEB)

Nie, J.; Morante, R.; Miranda, M., Braverman, J.

2010-07-18

The 100-40-40 rule is often used with the response spectrum analysis method to determine the maximum seismic responses from structural responses resulting from the three spatial earthquake components. This rule has been referenced in several recent Design Certification applications of nuclear power plants, and appears to be gaining in popularity. However, this rule is described differently in ASCE 4-98 and Regulatory Guide 1.92, consequently causing confusion on correct implementation of this rule in practice. The square root of the sum of the squares method is another acceptable spatial combination method and was used to justify the adequacy of the 100-40-40 rule during the development of the Regulatory Guide 1.92. The 100-40-40 rule, when applied correctly, is almost always conservative compared to the SRSS method, and is only slightly unconservative in rare cases. The purpose of this paper is to describe in detail the proper application of the 100-40-40 rule, as prescribed in ASCE 4-98 and in Regulatory Guide 1.92, and to clarify the confusion caused by the two different formats of this rule.
Sensitivity and responsiveness of the health-related quality of life in stroke patients-40 (HRQOLISP-40) scale.

Science.gov (United States)

Vincent-Onabajo, Grace O; Owolabi, Mayowa O; Hamzat, Talhatu K

2014-01-01

To investigate the sensitivity and responsiveness of the Health-Related Quality of Life in Stroke Patients-40 (HRQOLISP-40) scale in evaluating stroke patients from onset to 12 months. Fifty-five patients with first-incidence stroke were followed-up for 12 months. The HRQOLISP-40 scale was used to assess health-related quality of life (HRQOL) while stroke severity was assessed with the Stroke Levity Scale. Sensitivity to change was assessed by analyzing changes in the HRQOLISP-40 scores between pairs of months with paired samples t-test. Standardized effect size (SES) and standardized response mean (SRM) were used to express responsiveness. Overall HRQOL and domains in the physical sphere of the HRQOLISP-40 were sensitive to change at different time intervals in the first 12 months post-stroke. Marked responsiveness (SES and SRM >0.7) was demonstrated by the overall scale, and the physical, psycho-emotional and cognitive domains at varying time intervals. For instance, SRM was greater than 0.7 between 1 and 6, 3 and 12, 1 and 9, and 1 and 12 months for both the physical and psycho-emotional domains. The HRQOLISP-40 is a sensitive and responsive stroke-specific quality of life measure that can be used to evaluate the outcome of stroke rehabilitation. Enhancing the health-related quality of life (HRQOL) of stroke survivors can be regarded as the ultimate goal of stroke rehabilitation. Sensitive and responsive stroke-specific HRQOL measures are required for use in evaluative studies, and clinical trials and practice. The Health-Related Quality of Life in Stroke Patients-40 (HRQOLISP-40) is a sensitive and responsive stroke-specific scale.
Data Analysis Details (DS): SE40_DS1 [Metabolonote[Archive

Lifescience Database Archive (English)

Full Text Available tware without cut off value and peaks are extracted from the text files by PowerFT ...SE40_DS1 PowerGet analysis for detection of all peaks Raw data files are converted to text file by MSGet sof
48 CFR 9904.403-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.403-40 Section 9904.403-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.403-40 Fundamental requirement. (a)(1) Home office...
Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1–40-induced toxicity

Directory of Open Access Journals (Sweden)

Yongjie Li

2015-01-01

Full Text Available Amyloid beta-peptides (Aβ are known to undergo active transport across the blood-brain barrier, and cerebral amyloid angiopathy has been shown to be a prominent feature in the majority of Alzheimer׳s disease. Quercetin is a natural flavonoid molecule and has been demonstrated to have potent neuroprotective effects, but its protective effect on endothelial cells under Aβ-damaged condition is unclear. In the present study, the protective effects of quercetin on brain microvascular endothelial cells injured by fibrillar Aβ1–40 (fAβ1–40 were observed. The results show that fAβ1–40-induced cytotoxicity in human brain microvascular endothelial cells (hBMECs can be relieved by quercetin treatment. Quercetin increases cell viability, reduces the release of lactate dehydrogenase, and relieves nuclear condensation. Quercetin also alleviates intracellular reactive oxygen species generation and increases superoxide dismutase activity. Moreover, it strengthens the barrier integrity through the preservation of the transendothelial electrical resistance value, the relief of aggravated permeability, and the increase of characteristic enzyme levels after being exposed to fAβ1–40. In conclusion, quercetin protects hBMECs from fAβ1–40-induced toxicity.
Accumulation and translocation peculiarities of "1"3"7Cs and "4"0K in the soil – plant system

International Nuclear Information System (INIS)

Marčiulionienė, Danutė; Lukšienė, Benedikta; Jefanova, Olga

2015-01-01

Long-term investigations (1996–2008) were conducted into the "1"3"7Cs and "4"0K in the soil of forests, swamps and meadows in different regions of Lithuania, as well as in the plants growing in these media. The "1"3"7Cs and "4"0K activity concentrations, the "1"3"7Cs/"4"0K activity concentration ratio and accumulation, and translocation in the system, i.e. from the soil to plant roots to above-ground plant part of these radionuclides, were evaluated after gamma-spectrometric measurements using a high purity germanium (HPGe) detector. Based on the obtained data, it can be asserted that in the tested plant species, the "1"3"7Cs and "4"0K accumulation, the transfer from soil to roots and translocation within the plants depend on the plant species and environmental ecological conditions. The "1"3"7Cs/"4"0K activity concentration ratios in the same plant species in different regions of Lithuania are different and this ratio depends on the biotope (forest, swamp or meadow) in which the plant grows and on the location of the growing region. Based on the determined trends of statistically reliable inverse dependence between the activity concentrations in both soil and plants, it can be stated that the exchange of "1"3"7Cs and "4"0K in plants and soil is different. Different accumulations and translocations of investigated radionuclides in the same plant species indicate diverse biological metabolism of "1"3"7Cs and its chemical analogue "4"0K in plants. A competitive relationship exists between "1"3"7Cs and "4"0K in plants as well as in the soil. - Highlights: • Investigations of "1"3"7Cs and "4"0K were performed in different ecological conditions. • The data indicate a diverse biological metabolism of "1"3"7Cs and "4"0K in plant species. • A pronounced association between "1"3"7Cs and "4"0K in soil and plants is not statistically significant. • A competitive relationship exists between "1"3"7Cs and "4"0K in plants as well as in the soil. • The ratio of "1
48 CFR 9904.412-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... in current and future cost accounting periods. (b) Measurement of pension cost. (1) For defined.... 9904.412-40 Section 9904.412-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.412-40 Fundamental requirement. (a) Components of pension...
A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40

Directory of Open Access Journals (Sweden)

Nipaporn Ngernyuang

2018-02-01

Full Text Available The heparin-binding glycoprotein YKL-40 (CHI3L1 is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R and lysine (K (RRDK; residues 144–147; but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334–345 that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A substituted for K or R (K337A, K342A, R344A, led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.
6 CFR 15.40 - Employment.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Employment. 15.40 Section 15.40 Domestic... Employment. No qualified individual with a disability shall, on the basis of that disability, be subjected to discrimination in employment under any program or activity conducted by the Department. The definitions...
Low incidence of germline mutation in BRCA1 Exon 11 among early-onset and familial Filipino breast cancer patients

International Nuclear Information System (INIS)

Nato, Alejandro Q. Jr; Deocaris, Custer C.; Sajise, Sheila C.

2002-01-01

Breast cancer susceptibility gene, type 1 (BRCA1) has been thought to be responsible for about 45% of families with multiple breast carcinoma cases and for more than 80% of hereditary breast and ovarian cancer (HBOC) families. About 61-75% of the reported distinct alterations that result in truncated protein products have been found in exon 11 which comprises 61% (3427bp) of the coding sequence of BRCA1(5592bp). Protein truncation test (PTT) has become a popular method as an efficient means of screening mutations in a coding sequence that lead to a truncated protein product. In this study, 34 early-onset and/or familial breast cancer (FBC) patients were investigated. Twenty-six patients are early-onset B(o)C cases (diagnosed≤40 years old), 14 of which have familiality of the disease. Among the 8 patients that have been diagnosed above 40 years old, 7 have familial clustering. Through radioactive PTT analysis of the 34 BC cases in a 5-20% denaturing gradient polyacrylamide gel, we found only one mutation in exon 11 having a 29.7 kDa truncated protein product. Our results corroborate the findings of a recently reported study of unselected incident breast cancer cases in the Philippines where the prevalence of BRCA1 mutation is also low. This would, however, be the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. (author)
Plasma YKL-40

DEFF Research Database (Denmark)

Jensen, Peter; Wiell, C; Milting, K

2013-01-01

Background Plasma YKL-40 is an inflammatory biomarker. No useful biomarker exists in patients with psoriasis or psoriatic arthritis. Objective To measure YKL-40 and high-sensitivity C-reactive protein (hs-CRP) in patients with psoriasis or psoriatic arthritis before and during treatment. Methods......-CRP at inclusion and during 48 weeks of adalimumab treatment. The patients with psoriatic arthritis were divided into responders and non-responders. Results In patients with psoriasis, the baseline median PASI score was 10.8 and baseline YKL-40 was 45 μg/L. Seventeen per cent had elevated plasma YKL-40 compared...
Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.

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Alexandra V Stavropoulou

Full Text Available Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24. In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6% of familial cancer cases and in 27/592 (4.6% of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%. The majority of BRCA1 carriers (71.2% presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.
Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis—Experience from two prospective cohorts

DEFF Research Database (Denmark)

Kornblit, Brian; Hellemann, Dorthe; Munthe-Fog, Lea

2013-01-01

YKL-40, derived from the CHI3L1 gene, has been associated with outcome of infectious and inflammatory diseases. We hypothesized that plasma YKL-40 concentrations and CHI3L1 genotype could be used as prognostic biomarkers in the assessment of systemic inflammatory response syndrome (SIRS) and sepsis....... The objective of the study was to assess the prognostic value of plasma YKL-40 and CHI3L1 genotype in patients with SIRS and sepsis. Plasma YKL-40 and CHI3L1 genotype (rs4950928) were analyzed at time of admission to intensive care units (ICU), in two prospective cohorts of consecutive SIRS patients (cohort 1...
Increased expression of OX40 is associated with progressive disease in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

Science.gov (United States)

Saito, Mineki; Tanaka, Reiko; Arishima, Shiho; Matsuzaki, Toshio; Ishihara, Satoshi; Tokashiki, Takashi; Ohya, Yusuke; Takashima, Hiroshi; Umehara, Fujio; Izumo, Shuji; Tanaka, Yuetsu

2013-05-07

OX40 is a member of the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells and promotes the development of effector and memory T cells. Although OX40 has been reported to be a target gene of human T-cell leukemia virus type-1 (HTLV-1) viral transactivator Tax and is overexpressed in vivo in adult T-cell leukemia (ATL) cells, an association between OX40 and HTLV-1-associated inflammatory disorders, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), has not yet been established. Moreover, because abrogation of OX40 signals ameliorates chronic inflammation in animal models of autoimmune disease, novel monoclonal antibodies against OX40 may offer a potential treatment for HTLV-1-associated diseases such as ATL and HAM/TSP. In this study, we showed that OX40 was specifically expressed in CD4+ T cells naturally infected with HTLV-1 that have the potential to produce pro-inflammatory cytokines along with Tax expression. We also showed that OX40 was overexpressed in spinal cord infiltrating mononuclear cells in a clinically progressive HAM/TSP patient with a short duration of illness. The levels of the soluble form of OX40 (sOX40) in the cerebrospinal fluid (CSF) from chronic progressive HAM/TSP patients or from patients with other inflammatory neurological diseases (OINDs) were not different. In contrast, sOX40 levels in the CSF of rapidly progressing HAM/TSP patients were higher than those in the CSF from patients with OINDs, and these patients showed higher sOX40 levels in the CSF than in the plasma. When our newly produced monoclonal antibody against OX40 was added to peripheral blood mononuclear cells in culture, HTLV-1-infected T cells were specifically removed by a mechanism that depends on antibody-dependent cellular cytotoxicity. Our study identified OX40 as a key molecule and biomarker for rapid progression of HAM/TSP. Furthermore, blocking OX40 may have potential in therapeutic intervention for
22 CFR 171.40 - Purpose and scope.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose and scope. 171.40 Section 171.40... PUBLIC Ethics in Government Act Provisions § 171.40 Purpose and scope. This subpart sets forth the... 2634, require that high-level Federal officials disclose publicly their personal financial interests. ...
Impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) on prostate-specific antigen (PSA) testing by Dutch general practitioners

NARCIS (Netherlands)

Van der Meer, Saskia; Kollen, Boudewijn J.; Hirdes, Willem H.; Steffens, Martijn G.; Hoekstra-Weebers, Josette E. H. M.; Nijman, Rien M.; Blanker, Marco H.

Objective To determine the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) publication in 2009 on prostate-specific antigen (PSA) level testing by Dutch general practitioners (GPs) in men aged 40 years. Materials and Methods Retrospective study with a Dutch insurance
40 CFR Table 3 to Subpart Dd of... - Tank Control Levels for Tanks at Existing Affected Sources as Required by 40 CFR 63.685(b)(1)

Science.gov (United States)

2010-07-01

... Existing Affected Sources as Required by 40 CFR 63.685(b)(1) 3 Table 3 to Subpart DD of Part 63 Protection... Hazardous Air Pollutants from Off-Site Waste and Recovery Operations Pt. 63, Subpt. DD, Table 3 Table 3 to Subpart DD of Part 63—Tank Control Levels for Tanks at Existing Affected Sources as Required by 40 CFR 63...
40 CFR 407.40 - Applicability; description of the frozen potato products subcategory.

Science.gov (United States)

2010-07-01

... frozen potato products subcategory. 407.40 Section 407.40 Protection of Environment ENVIRONMENTAL... PROCESSING POINT SOURCE CATEGORY Frozen Potato Products Subcategory § 407.40 Applicability; description of the frozen potato products subcategory. The provisions of this subpart are applicable to discharges...

SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells.

Science.gov (United States)

Mortera-Blanco, Teresa; Dimitriou, Marios; Woll, Petter S; Karimi, Mohsen; Elvarsdottir, Edda; Conte, Simona; Tobiasson, Magnus; Jansson, Monika; Douagi, Iyadh; Moarii, Matahi; Saft, Leonie; Papaemmanuil, Elli; Jacobsen, Sten Eirik W; Hellström-Lindberg, Eva

2017-08-17

Mutations in the RNA splicing gene SF3B1 are found in >80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients and were also present in downstream myeloid and erythroid progenitor cells. While in agreement with previous studies, little or no evidence for clonal ( SF3B1 mutation) involvement could be found in mature B cells, consistent involvement at the pro-B-cell progenitor stage was established, providing definitive evidence for SF3B1 mutations targeting lymphomyeloid HSCs and compatible with mutated SF3B1 negatively affecting lymphoid development. Assessment of stem cell function in vitro as well as in vivo established that only HSCs and not investigated progenitor populations could propagate the SF3B1 mutated clone. Upon transplantation into immune-deficient mice, SF3B1 mutated MDS-RS HSCs differentiated into characteristic ring sideroblasts, the hallmark of MDS-RS. Our findings provide evidence of a multipotent lymphomyeloid HSC origin of SF3B1 mutations in MDS-RS patients and provide a novel in vivo platform for mechanistically and therapeutically exploring SF3B1 mutated MDS-RS. © 2017 by The American Society of Hematology.
Calibration and Validation of the Dutch-Flemish PROMIS Pain Interference Item Bank in Patients with Chronic Pain.

Science.gov (United States)

Crins, Martine H P; Roorda, Leo D; Smits, Niels; de Vet, Henrica C W; Westhovens, Rene; Cella, David; Cook, Karon F; Revicki, Dennis; van Leeuwen, Jaap; Boers, Maarten; Dekker, Joost; Terwee, Caroline B

2015-01-01

The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT) model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA). Items were calibrated using the graded response model (GRM), an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF) for language (Dutch vs. English) was examined. Reliability was evaluated based on standard errors and Cronbach's alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF), good reliability (Cronbach's alpha = 0.98), and good construct validity (Pearson correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed.
Calibration and Validation of the Dutch-Flemish PROMIS Pain Interference Item Bank in Patients with Chronic Pain.

Directory of Open Access Journals (Sweden)

Martine H P Crins

Full Text Available The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA. Items were calibrated using the graded response model (GRM, an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF for language (Dutch vs. English was examined. Reliability was evaluated based on standard errors and Cronbach's alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986. Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44. The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF, good reliability (Cronbach's alpha = 0.98, and good construct validity (Pearson correlations between 0.62 and 0.75. A computer adaptive test (CAT and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed.
40 CFR 270.1 - Purpose and scope of these regulations.

Science.gov (United States)

2010-07-01

... Overview and definitions 40 CFR part 260 3001 Identification and listing of hazardous waste 40 CFR part 261... hazardous waste management units must have permits during the active life (including the closure period) of... of a permit for the active life of a hazardous waste management facility or unit does not affect the...
Transcriptional activation by the E1A regions of adenovirus types 40 and 41

NARCIS (Netherlands)

Loon, A.E. van; Gilardi, P.; Perricaudet, M.; Rozijn, Th. H.; Sussenbach, J.S.

In order to establish whether the poor growth of the two fastidious adenoviruses types 40 and 41 (Ad40 and Ad41) in HeLa cells is due to a reduced trans-activation by the early region to (E1A), we have determined the trans-activating effect of this region on the expression of the chloramphenicol
How cholesterol constrains glycolipid conformation for optimal recognition of Alzheimer's beta amyloid peptide (Abeta1-40).

Science.gov (United States)

Yahi, Nouara; Aulas, Anaïs; Fantini, Jacques

2010-02-05

Membrane lipids play a pivotal role in the pathogenesis of Alzheimer's disease, which is associated with conformational changes, oligomerization and/or aggregation of Alzheimer's beta-amyloid (Abeta) peptides. Yet conflicting data have been reported on the respective effect of cholesterol and glycosphingolipids (GSLs) on the supramolecular assembly of Abeta peptides. The aim of the present study was to unravel the molecular mechanisms by which cholesterol modulates the interaction between Abeta(1-40) and chemically defined GSLs (GalCer, LacCer, GM1, GM3). Using the Langmuir monolayer technique, we show that Abeta(1-40) selectively binds to GSLs containing a 2-OH group in the acyl chain of the ceramide backbone (HFA-GSLs). In contrast, Abeta(1-40) did not interact with GSLs containing a nonhydroxylated fatty acid (NFA-GSLs). Cholesterol inhibited the interaction of Abeta(1-40) with HFA-GSLs, through dilution of the GSL in the monolayer, but rendered the initially inactive NFA-GSLs competent for Abeta(1-40) binding. Both crystallographic data and molecular dynamics simulations suggested that the active conformation of HFA-GSL involves a H-bond network that restricts the orientation of the sugar group of GSLs in a parallel orientation with respect to the membrane. This particular conformation is stabilized by the 2-OH group of the GSL. Correspondingly, the interaction of Abeta(1-40) with HFA-GSLs is strongly inhibited by NaF, an efficient competitor of H-bond formation. For NFA-GSLs, this is the OH group of cholesterol that constrains the glycolipid to adopt the active L-shape conformation compatible with sugar-aromatic CH-pi stacking interactions involving residue Y10 of Abeta(1-40). We conclude that cholesterol can either inhibit or facilitate membrane-Abeta interactions through fine tuning of glycosphingolipid conformation. These data shed some light on the complex molecular interplay between cell surface GSLs, cholesterol and Abeta peptides, and on the influence
How cholesterol constrains glycolipid conformation for optimal recognition of Alzheimer's beta amyloid peptide (Abeta1-40.

Directory of Open Access Journals (Sweden)

Nouara Yahi

Full Text Available Membrane lipids play a pivotal role in the pathogenesis of Alzheimer's disease, which is associated with conformational changes, oligomerization and/or aggregation of Alzheimer's beta-amyloid (Abeta peptides. Yet conflicting data have been reported on the respective effect of cholesterol and glycosphingolipids (GSLs on the supramolecular assembly of Abeta peptides. The aim of the present study was to unravel the molecular mechanisms by which cholesterol modulates the interaction between Abeta(1-40 and chemically defined GSLs (GalCer, LacCer, GM1, GM3. Using the Langmuir monolayer technique, we show that Abeta(1-40 selectively binds to GSLs containing a 2-OH group in the acyl chain of the ceramide backbone (HFA-GSLs. In contrast, Abeta(1-40 did not interact with GSLs containing a nonhydroxylated fatty acid (NFA-GSLs. Cholesterol inhibited the interaction of Abeta(1-40 with HFA-GSLs, through dilution of the GSL in the monolayer, but rendered the initially inactive NFA-GSLs competent for Abeta(1-40 binding. Both crystallographic data and molecular dynamics simulations suggested that the active conformation of HFA-GSL involves a H-bond network that restricts the orientation of the sugar group of GSLs in a parallel orientation with respect to the membrane. This particular conformation is stabilized by the 2-OH group of the GSL. Correspondingly, the interaction of Abeta(1-40 with HFA-GSLs is strongly inhibited by NaF, an efficient competitor of H-bond formation. For NFA-GSLs, this is the OH group of cholesterol that constrains the glycolipid to adopt the active L-shape conformation compatible with sugar-aromatic CH-pi stacking interactions involving residue Y10 of Abeta(1-40. We conclude that cholesterol can either inhibit or facilitate membrane-Abeta interactions through fine tuning of glycosphingolipid conformation. These data shed some light on the complex molecular interplay between cell surface GSLs, cholesterol and Abeta peptides, and on the
Choline Modulation of the Aβ P1-40 Channel Reconstituted into a Model Lipid Membrane

Directory of Open Access Journals (Sweden)

Daniela Meleleo

2010-01-01

Full Text Available Nicotinic acetylcholine receptors (AChRs, implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh and in palmitoyl-oleoyl-phosphatidylcholine (POPC:Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8 M added to the cis- or trans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs.
40 CFR 422.40 - Applicability; description of the defluorinated phosphate rock subcategory.

Science.gov (United States)

2010-07-01

... defluorinated phosphate rock subcategory. 422.40 Section 422.40 Protection of Environment ENVIRONMENTAL... Defluorinated Phosphate Rock Subcategory § 422.40 Applicability; description of the defluorinated phosphate rock... phosphate rock by application of high temperature treatment along with wet process phosphoric acid, silica...
Corrosion resistance of amorphous and crystalline Pd40Ni40P20 alloys in aqueous solutions

DEFF Research Database (Denmark)

Wu, Y.F.; Chiang, Wen-Chi; Chu, J.

2006-01-01

The corrosion behaviors of amorphous and crystalline Pd40Ni40P20 alloys in various aqueous solutions are reported in this paper. The corrosion resistance of crystalline (annealed) Pd40Ni40P20 is better than that of amorphous Pd40Ni40P20 in various corrosive solutions, due to crystalline Pd40Ni40P20...... and mainly consists of inert Pd5P2, NI3P, Ni2Pd2P and noble Pd phases. These inert and noble properties result in a higher corrosion resistance in crystalline Pd40Ni40P20....
40 CFR 98.40 - Definition of the source category.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Definition of the source category. 98... (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Electricity Generation § 98.40 Definition of the source... category does not include portable equipment, emergency equipment, or emergency generators, as defined in...
Exploring the common molecular basis for the universal DNA mutation bias: Revival of Loewdin mutation model

International Nuclear Information System (INIS)

Fu, Liang-Yu; Wang, Guang-Zhong; Ma, Bin-Guang; Zhang, Hong-Yu

2011-01-01

Highlights: → There exists a universal G:C → A:T mutation bias in three domains of life. → This universal mutation bias has not been sufficiently explained. → A DNA mutation model proposed by Loewdin 40 years ago offers a common explanation. -- Abstract: Recently, numerous genome analyses revealed the existence of a universal G:C → A:T mutation bias in bacteria, fungi, plants and animals. To explore the molecular basis for this mutation bias, we examined the three well-known DNA mutation models, i.e., oxidative damage model, UV-radiation damage model and CpG hypermutation model. It was revealed that these models cannot provide a sufficient explanation to the universal mutation bias. Therefore, we resorted to a DNA mutation model proposed by Loewdin 40 years ago, which was based on inter-base double proton transfers (DPT). Since DPT is a fundamental and spontaneous chemical process and occurs much more frequently within GC pairs than AT pairs, Loewdin model offers a common explanation for the observed universal mutation bias and thus has broad biological implications.
40 CFR 721.10012 - Manganate (MnO21-), calcium (2:1).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Manganate (MnO21-), calcium (2:1). 721... Substances § 721.10012 Manganate (MnO21-), calcium (2:1). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as manganate (MnO2 1 -), calcium (2:1) (PMN P...
40 CFR Table 1 to Subpart Xx of... - Hazardous Air Pollutants

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Hazardous Air Pollutants 1 Table 1 to Subpart XX of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Operations Pt. 63, Subpt. XX, Table 1 Table 1 to Subpart XX of Part 63—Hazardous Air Pollutants Hazardous air...
40 CFR 205.54-1 - Low speed sound emission test procedures.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Low speed sound emission test procedures. 205.54-1 Section 205.54-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205...
7 CFR 15b.40 - Food services.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Food services. 15b.40 Section 15b.40 Agriculture... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Other Aid, Benefits, or Services § 15b.40 Food services. (a) Recipients which provide food services shall serve special meals, at no extra charge, to persons whose...
Ühetaoline mõistekasutus karistusõiguses. Riigikohtu otsus 3-1-1-40-12 / Jaan Sootak

Index Scriptorium Estoniae

Sootak, Jaan, 1948-

2012-01-01

Karistusseadustiku § 266 (omavoliline sissetung) koosseisutunnuste – valdus, võõras asi, sissetungimise ebaseaduslikkus – käsitlusest Riigikohtu otsuses 3-1-1-40-12. Süülise hädaseisundi olemusest ja selle õiguslikest tagajärgedest
Ferromagnetic resonance studies on (Co40Fe40B20)x(SiO2)1-x granular magnetic films

International Nuclear Information System (INIS)

Yildiz, F.; Kazan, S.; Aktas, B.; Tarapov, S.I.; Tagirov, L.; Granovsky, B.

2006-01-01

Magnetic properties of granular (Co 40 Fe 40 B 20 ) x (SiO 2 ) 1-x thin films (x=0.37-0.53) have been studied by ferromagnetic resonance (FMR) technique. Samples have been prepared by ion-beam deposition of Co-Fe-B particles and SiO 2 on sitall ceramic substrate. The FMR measurements have been done for different orientations of DC magnetic field with respect to the sample plane. It was found that the deduced value of effective magnetization from FMR data of the thin granular film is reduced by the volume-filling factor of the bulk saturation magnetization. The overall magnetization changes from 152 to 515G depending on the ratio of the magnetic nanoparticles in the SiO 2 matrix. From angular measurements an induced in-plane uniaxial anisotropy has been obtained due to the preparation of the film conditions as well
Mechanisms of Nifedipine-Downregulated CD40L/sCD40L Signaling in Collagen Stimulated Human Platelets.

Directory of Open Access Journals (Sweden)

Tso-Hsiao Chen

Full Text Available The platelet-derived soluble CD40L (sCD40L release plays a critical role in the development of atherosclerosis. Nifedipine, a dihydropyridine-based L-type calcium channel blocker (CCB, has been reported to have an anti-atherosclerotic effect beyond its blood pressure-lowering effect, but the molecular mechanisms remain unclear. The present study was designed to investigate whether nifedipine affects sCD40L release from collagen-stimulated human platelets and to determine the potential role of peroxisome proliferator-activated receptor-β/-γ (PPAR-β/-γ. We found that treatment with nifedipine significantly inhibited the platelet surface CD40L expression and sCD40L release in response to collagen, while the inhibition was markedly reversed by blocking PPAR-β/-γ activity with specific antagonist such as GSK0660 and GW9662. Meanwhile, nifedipine also enhanced nitric oxide (NO and cyclic GMP formation in a PPAR-β/-γ-dependent manner. When the NO/cyclic GMP pathway was suppressed, nifedipine-mediated inhibition of sCD40L release was abolished significantly. Collagen-induced phosphorylation of p38MAPK, ERK1/2 and HSP27, matrix metalloproteinase-2 (MMP-2 expression/activity and reactive oxygen species (ROS formation were significantly inhibited by nifedipine, whereas these alterations were all attenuated by co-treatment with PPAR-β/-γ antagonists. Collectively, these results demonstrate that PPAR-β/-γ-dependent pathways contribute to nifedipine-mediated downregulation of CD40L/sCD40L signaling in activated platelets through regulation of NO/ p38MAPK/ERK1/2/HSP27/MMP-2 signalings and provide a novel mechanism regarding the anti-atherosclerotic effect of nifedipine.
40 CFR 1.47 - Office of Solid Waste and Emergency Response.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Office of Solid Waste and Emergency... ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.47 Office of Solid Waste and Emergency Response. The Office of Solid Waste and Emergency Response (OSWER), under the supervision of the Assistant...

Nanocrystallization in amorphous Fe40Ni40(Si+B)19Mo1-2 ribbons

International Nuclear Information System (INIS)

Saiseng, S.; Winotai, P.; Nilpairuch, S.; Limsuwan, P.; Tang, I.M.

2004-01-01

Cut Fe 40 Ni 40 (Si+B) 19 Mo 1-2 ribbons were annealed for 2 h at various temperatures between 350 deg. C and 600 deg. C. XRD and Mossbauer effect spectroscopy (ME) measurements were then performed on all of the ribbons. The magnetic properties of several ribbons were measured using a vibrating sample magnetometer (VSM). A differential thermal analysis scan (over the range 20-800 deg. C) of the as-cast ribbon showed two phase transitions; the first at 454 deg. C and the second at 525 deg. C. Both the XRD and ME spectra of the as cast, the 350 deg. C and 400 deg. C annealed ribbons showed that they were amorphous. The ME spectra of the 450 deg. C, 475 deg. C and 500 deg. C annealed ribbons showed that these ribbons contained α-Fe, α-Fe(Si) and t-Fe 2 B nanocrystallites. For the ribbons annealed above 550 deg. C, crystallites of t-Fe 2 B, t-Fe 3 B, t-Fe 5 SiB 2 and FCC-FeNi appeared, with the α-Fe and α-Fe(Si) crystallites disappearing. The sextets of all of the Fe compounds appeared in the ME spectra of the 525 deg. C annealed ribbon. The VSM measurements supported the picture of a two-stage phase transitions; amorphous phase→a nanocrystalline phase (Fe-containing nanocrystallites in an amorphous matrix) at 454 deg. C and then a second transition, the nanocrystalline phase→a disordered alloy containing Fe-B and Fe-Ni crystallites at 525 deg. C
Immune regulation by CD40-CD40-l interactions - 2; Y2K update.

Science.gov (United States)

van Kooten, C

2000-11-01

CD40 is a cell surface receptor, which belongs to the TNF-R family, and which was first identified and functionally characterized on B lymphocytes. However, in recent years it has become clear that CD40 is expressed much broader, including expression on monocytes, dendritic cells, endothelial cells and epithelial cells. Therefore it is now thought that CD40 plays a more general role in immune regulation. The present paper reviews recent developments in this field of research, with main emphasis on CD40 signal transduction and on in vivo functions of CD40/CD40-L interactions.
Interaction of monomeric Ebola VP40 protein with a plasma membrane: A coarse-grained molecular dynamics (CGMD) simulation study.

Science.gov (United States)

Mohamad Yusoff, Mohamad Ariff; Abdul Hamid, Azzmer Azzar; Mohammad Bunori, Noraslinda; Abd Halim, Khairul Bariyyah

2018-06-01

Ebola virus is a lipid-enveloped filamentous virus that affects human and non-human primates and consists of several types of protein: nucleoprotein, VP30, VP35, L protein, VP40, VP24, and transmembrane glycoprotein. Among the Ebola virus proteins, its matrix protein VP40 is abundantly expressed during infection and plays a number of critical roles in oligomerization, budding and egress from the host cell. VP40 exists predominantly as a monomer at the inner leaflet of the plasma membrane, and has been suggested to interact with negatively charged lipids such as phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and phosphatidylserine (PS) via its cationic patch. The hydrophobic loop at the C-terminal domain has also been shown to be important in the interaction between the VP40 and the membrane. However, details of the molecular mechanisms underpinning their interactions are not fully understood. This study aimed at investigating the effects of mutation in the cationic patch and hydrophobic loop on the interaction between the VP40 monomer and the plasma membrane using coarse-grained molecular dynamics simulation (CGMD). Our simulations revealed that the interaction between VP40 and the plasma membrane is mediated by the cationic patch residues. This led to the clustering of PIP 2 around the protein in the inner leaflet as a result of interactions between some cationic residues including R52, K127, K221, K224, K225, K256, K270, K274, K275 and K279 and PIP 2 lipids via electrostatic interactions. Mutation of the cationic patch or hydrophobic loop amino acids caused the protein to bind at the inner leaflet of the plasma membrane in a different orientation, where no significant clustering of PIP 2 was observed around the mutated protein. This study provides basic understanding of the interaction of the VP40 monomer and its mutants with the plasma membrane. Copyright © 2018 Elsevier Inc. All rights reserved.
22 CFR 40.92 - Aliens unlawfully present.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Aliens unlawfully present. 40.92 Section 40.92... UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.92 Aliens unlawfully present. (a) 3-year bar. An alien described in INA 212(a)(9)(B)(i)(I) shall be ineligible for a...
The multi-functionality of CD40L and its receptor CD40 in atherosclerosis

NARCIS (Netherlands)

Lievens, Dirk; Eijgelaar, Wouter J.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Lutgens, Esther

2009-01-01

Disrupting the CD40-CD40L co-stimulatory pathway reduces atherosclerosis and induces a stable atherosclerotic plaque phenotype that is low in inflammation and high in fibrosis. Therefore, inhibition of the CD40-CD40L pathway is an attractive therapeutic target to reduce clinical complications of
Mutations causative of familial hypercholesterolaemia

DEFF Research Database (Denmark)

Benn, Marianne; Watts, Gerald F; Tybjærg-Hansen, Anne

2016-01-01

causing mutations in 98 098 participants from the general population, the Copenhagen General Population Study. METHODS AND RESULTS: We genotyped for LDLR[W23X;W66G;W556S] and APOB[R3500Q] accounting for 38.7% of pathogenic FH mutations in Copenhagen. Clinical FH assessment excluded mutation information......-cholesterol concentration to discriminate between mutation carriers and non-carriers was 4.4 mmol/L. CONCLUSION: Familial hypercholesterolaemia-causing mutations are estimated to occur in 1:217 in the general population and are best identified by a definite or probable phenotypic diagnosis of FH based on the DLCN criteria....... The prevalence of the four FH mutations was 0.18% (1:565), suggesting a total prevalence of FH mutations of 0.46% (1:217). Using the Dutch Lipid Clinic Network (DLCN) criteria, odds ratios for an FH mutation were 439 (95% CI: 170-1 138) for definite FH, 90 (53-152) for probable FH, and 18 (13-25) for possible FH...
Involvement and Influence of Healthcare Providers, Family Members, and Other Mutation Carriers in the Cancer Risk Management Decision-Making Process of BRCA1 and BRCA2 Mutation Carriers.

Science.gov (United States)

Puski, Athena; Hovick, Shelly; Senter, Leigha; Toland, Amanda Ewart

2018-03-29

Deciding between increased cancer screening or prophylactic surgery and the timing of such procedures can be a difficult and complex process for women with BRCA mutations. There are gaps in our understanding of involvement of others in the decision-making process for women with BRCA mutations. This study evaluated the management decision-making process of women with BRCA mutations, focusing on the involvement of others. Grounded theory was used to analyze and code risk management decision-making information from interviews with 20 BRCA mutation carriers. Unaffected at-risk participants with a BRCA mutation, those under age 40, and those with no children described having a difficult time making risk management decisions. Physicians were an integral part of the decision-making process by providing decisional support and management recommendations. Family members and other mutation carriers filled similar yet distinct roles by providing experiential information as well as decisional and emotional support for carriers. Participants described genetic counselors as short-term providers of risk information and management recommendations. The study findings suggest that unaffected at-risk women, women under 40, and those who do not have children may benefit from additional support and information during the decision-making process. Genetic counselors are well trained to help women through this process and connect them with resources, and may be under-utilized in long-term follow-up for women with a BRCA mutation.
Going Dutch

Energy Technology Data Exchange (ETDEWEB)

Hoorn, C.

2002-09-07

The proposal by the Dutch to extract natural gas from the 40 billion cubic metres beneath the Wadden Sea has been cited as a serious cause for concern by environmentalists. The new right wing government is less concerned than was the recently ousted left wing government and stands to gain directly through increased revenue. The Wadden Sea is a vast area of tidal channels, mudflats, shifting sandbanks, salt marshes, wet meadows and dunes, and provides a safe haven for numerous protected plants and animals. It is also a sanctuary for migrating birds and a feeding ground for herring, sole and plaice. Subsidence is cited by the environmentalists as a major potential problem and pollution is said to be always a risk.
Going Dutch

International Nuclear Information System (INIS)

Hoorn, C.

2002-01-01

The proposal by the Dutch to extract natural gas from the 40 billion cubic metres beneath the Wadden Sea has been cited as a serious cause for concern by environmentalists. The new right wing government is less concerned than was the recently ousted left wing government and stands to gain directly through increased revenue. The Wadden Sea is a vast area of tidal channels, mudflats, shifting sandbanks, salt marshes, wet meadows and dunes, and provides a safe haven for numerous protected plants and animals. It is also a sanctuary for migrating birds and a feeding ground for herring, sole and plaice. Subsidence is cited by the environmentalists as a major potential problem and pollution is said to be always a risk
40 CFR 427.40 - Applicability; description of the asbestos paper (elastomeric binder) subcategory.

Science.gov (United States)

2010-07-01

... asbestos paper (elastomeric binder) subcategory. 427.40 Section 427.40 Protection of Environment... SOURCE CATEGORY Asbestos Paper (Elastomeric Binder) Subcategory § 427.40 Applicability; description of the asbestos paper (elastomeric binder) subcategory. The provisions of this subpart are applicable to...
22 CFR 226.40 - Purpose of procurement standards.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose of procurement standards. 226.40 Section 226.40 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.40 Purpose...
SERUM ANALYSIS OF AMYLOID BETA-PROTEIN 1-40 IN HEALTHY SUBJECTS, AUTISTIC CHILDREN AND ALZHEIMER’S PATIENTS

Directory of Open Access Journals (Sweden)

Vijendra K. SINGH

2008-06-01

Full Text Available Amyloid beta-protein1-40 (AP40 is a low molecular weight peptide produced throughout life during normal cell metabolism and neurodegenerative diseases. Owing to its neurotrophic and neurotoxic effects, the present study was conducted to evaluate serum levels of AP40 in healthy subjects, autistic children and Alzheimer’s disease patients. Serum AP40 was measured by enzyme-linked immunosorbent assay (ELISA. AP40 was significantly higher in normal children compared to normal older controls, in normal children compared to autistic children, and in autistic children compared to Alzheimer’s patients (p value was less than 0.05 for all groups. This finding suggests an age-related decline of serum AP40 in normal aging, as well as in autism and Alzheimer’s disease. This decline may result from abnormal processing of amyloid beta-protein precursor (APP during normal aging and age-related diseases such as autism in children and Alzheimer’s disease in elderly. Possible explanations for this decline may include age-related increased interactions of AP40 with cytoskeletal proteins for brain tissue deposition, increased serine proteases for APP metabolism or hyperimmune reaction (antibodies to AP40 for removal of circulating AP40. To conclude, the AP40 metabolism declines with normal aging and in addition to its role in Alzheimer’s disease this protein might also be a contributing factor in autism.
40 CFR 406.40 - Applicability; description of the bulgur wheat flour milling subcategory.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the bulgur wheat flour milling subcategory. 406.40 Section 406.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Bulgur...
28 CFR 16.40 - General provisions.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false General provisions. 16.40 Section 16.40 Judicial Administration DEPARTMENT OF JUSTICE PRODUCTION OR DISCLOSURE OF MATERIAL OR INFORMATION..., commission, service, or administration of the Department of Justice. (2) Request for access to a record means...
Silent hepatitis E virus infection in Dutch blood donors, 2011 to 2012

NARCIS (Netherlands)

Slot, E.; Hogema, B. M.; Riezebos-Brilman, A.; Kok, T. M.; Molier, M.; Zaaijer, H. L.

2013-01-01

In Europe, the dynamics of endemic hepatitis E virus (HEV) infection remain enigmatic. We studied the presence of silent HEV infection among Dutch blood donors. Using donations collected throughout the Netherlands in 2011 and 2012, 40,176 donations were tested for HEV RNA in 459 pools of 48 or 480
40 CFR 273.2 - Applicability-batteries.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Applicability-batteries. 273.2 Section...) STANDARDS FOR UNIVERSAL WASTE MANAGEMENT General § 273.2 Applicability—batteries. (a) Batteries covered under 40 CFR part 273. (1) The requirements of this part apply to persons managing batteries, as...
Effects of missense mutations in sortase A gene on enzyme activity in Streptococcus mutans.

Science.gov (United States)

Zhuang, P L; Yu, L X; Tao, Y; Zhou, Y; Zhi, Q H; Lin, H C

2016-04-11

Streptococcus mutans (S. mutans) is the major aetiological agent of dental caries, and the transpeptidase Sortase A (SrtA) plays a major role in cariogenicity. The T168G and G470A missense mutations in the srtA gene may be linked to caries susceptibility, as demonstrated in our previous studies. This study aimed to investigate the effects of these missense mutations of the srtA gene on SrtA enzyme activity in S. mutans. The point mutated recombinant S.mutans T168G and G470A sortases were expressed in expression plasmid pET32a. S. mutans UA159 sortase coding gene srtA was used as the template for point mutation. Enzymatic activity was assessed by quantifying increases in the fluorescence intensity generated when a substrate Dabcyl-QALPNTGEE-Edans was cleaved by SrtA. The kinetic constants were calculated based on the curve fit for the Michaelis-Menten equation. SrtA△N40(UA159) and the mutant enzymes, SrtA△N40(D56E) and SrtA△N40(R157H), were expressed and purified. A kinetic analysis showed that the affinity of SrtA△N40(D56E) and SrtA△N40(R157H) remained approximately equal to the affinity of SrtA△N40(UA159), as determined by the Michaelis constant (K m ). However, the catalytic rate constant (k cat ) and catalytic efficiency (k cat /K m ) of SrtA△N40(D56E) were reduced compared with those of SrtA△N40(R157H) and SrtA△N40(UA159), whereas the k cat and k cat /K m values of SrtA△N40(R157H) were slightly lower than those of SrtA△N40(UA159). The findings of this study indicate that the T168G missense mutation of the srtA gene results in a significant reduction in enzymatic activity compared with S. mutans UA159, suggesting that the T168G missense mutation of the srtA gene may be related to low cariogenicity.
Female contraception over 40

DEFF Research Database (Denmark)

2009-01-01

BACKGROUND: The majority of women 40-49 years of age need an effective method of contraception because the decline in fertility with age is an insufficient protection against unwanted pregnancy. Although pregnancy is less likely after the age of 40 years, the clinical and social consequences...... is insufficient for contraceptive purposes. Thus a family planning method is needed. Sterilization is by far the most common method in several countries. Copper intrauterine devices and hormone intrauterine systems have similar effectiveness, with fewer than 1% failures in the first year of typical use. Special...
Precise determination of 40Ti mass by measuring the 40Sc isospin analogue state

International Nuclear Information System (INIS)

Liu Weiping; Hellstroem, M.; Collatz, R.; Benlliure, J.; Cortina, G.D.; Farget, F.; Grawe, H.; Hu, Z.; Iwasa, N.; Pfuetzner, M.; Roeckl, E.; Chulkov, L.; Piechaczek, A.; Raabe, R.; Reusen, I.; Vancraeynest, G.; Woehr, A.

2001-01-01

The mass of 40 Ti has been determined by using the isobaric multiplet mass equation method. The experimental data of the 40 Ti β-decay were used to determine the level of the isospin analogue state of 40 Sc. The ground-state mass excess and the Q EC value for 40 Ti were determined to be -9060 +- 12 keV and 11466 +- 13 keV, respectively
27 CFR 27.40 - Distilled spirits.

Science.gov (United States)

2010-04-01

... OF THE TREASURY LIQUORS IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER Tax On Imported Distilled Spirits, Wines, and Beer Distilled Spirits § 27.40 Distilled spirits. (a) A tax is imposed on all... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Distilled spirits. 27.40...

40 CFR 35.6290 - Program income.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Program income. 35.6290 Section 35.6290... Administration Requirements Under A Cooperative Agreement § 35.6290 Program income. The recipient must comply with the requirements regarding program income described in 40 CFR 31.25. Recoveries of Federal cost...
24 CFR 107.40 - Compliance meeting.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Compliance meeting. 107.40 Section... NONDISCRIMINATION AND EQUAL OPPORTUNITY IN HOUSING UNDER EXECUTIVE ORDER 11063 § 107.40 Compliance meeting. (a... allegedly in violation (respondent) shall be sent a Notice of Compliance Meeting and requested to attend a...
40 CFR 76.5 - NOX emission limitations for Group 1 boilers.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false NOX emission limitations for Group 1 boilers. 76.5 Section 76.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.5 NOX emission limitations...
Serum YKL-40 in risk assessment for colorectal cancer

DEFF Research Database (Denmark)

Johansen, Julia Sidenius; Christensen, Ib Jarle; Jørgensen, Lars Nannestad

2015-01-01

The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred.......05-1.40; P = 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P = 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful...
40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic...
Efficient Identification of Causal Mutations through Sequencing of Bulked F2 from Two Allelic Bloomless Mutants of Sorghum bicolor

Directory of Open Access Journals (Sweden)

Yinping Jiao

2018-01-01

Full Text Available Sorghum (Sorghum bicolor Moench, L. plant accumulates copious layers of epi-cuticular wax (EW on its aerial surfaces, to a greater extent than most other crops. EW provides a vapor barrier that reduces water loss, and is therefore considered to be a major determinant of sorghum's drought tolerance. However, little is known about the genes responsible for wax accumulation in sorghum. We isolated two allelic mutants, bloomless40-1 (bm40-1 and bm40-2, from a mutant library constructed from ethyl methane sulfonate (EMS treated seeds of an inbred, BTx623. Both mutants were nearly devoid of the EW layer. Each bm mutant was crossed to the un-mutated BTx623 to generated F2 populations that segregated for the bm phenotype. Genomic DNA from 20 bm F2 plants from each population was bulked for whole genome sequencing. A single gene, Sobic.001G228100, encoding a GDSL-like lipase/acylhydrolase, had unique homozygous mutations in each bulked F2 population. Mutant bm40-1 harbored a missense mutation in the gene, whereas bm40-2 had a splice donor site mutation. Our findings thus provide strong evidence that mutation in this GDSL-like lipase gene causes the bm phenotype, and further demonstrate that this approach of sequencing two independent allelic mutant populations is an efficient method for identifying causal mutations. Combined with allelic mutants, MutMap provides powerful method to identify all causal genes for the large collection of bm mutants in sorghum, which will provide insight into how sorghum plants accumulate such abundant EW on their aerial surface. This knowledge may facilitate the development of tools for engineering drought-tolerant crops with reduced water loss.
Characteristics of gene mutation in Chinese patients with hereditary hemochromatosis

Directory of Open Access Journals (Sweden)

LYU Tingxia

2016-08-01

Full Text Available ObjectiveTo investigate the characteristics of gene mutation in Chinese patients with hereditary hemochromatosis (HH. MethodsA total of 9 patients with HH who visited Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2015 were enrolled. The genomic DNA was extracted, and PCR amplification and Sanger sequencing were performed for all the exons of four genotypes of HH, i.e., HFE (type Ⅰ, HJV (type ⅡA, HAMP (type ⅡB, TFR2 (type Ⅲ, and SLC40A1 (type Ⅳ to analyze gene mutations. A total of 50 healthy subjects were enrolled as control group to analyze the prevalence of identified gene mutations in a healthy population. ResultsOf all patients, 2 had H63D mutation of HFE gene in type Ⅰ HH, 1 had E3D mutation of HJV gene in type ⅡA HH, 2 had I238M mutation of TFR2 gene in type Ⅲ HH, and 1 had IVS 3+10 del GTT splice mutation of SLC40A1 gene in type Ⅳ HH. No patients had C282Y mutation of HFE gene in type Ⅰ HH which was commonly seen in European and American populations. Five patients had no missense mutation or splice mutation. In addition, it was found in a family that a HH patient had E3D mutation of HJV gene, H63D mutation of HFE gene, and I238M mutation of TFR2 gene, but the healthy brother and sister carrying two of these mutations did not had the phenotype of HH. ConclusionHH gene mutations vary significantly across patients of different races, and non-HFE-HH is dominant in the Chinese population. There may be HH genes which are different from known genes, and further investigation is needed.
40x40: Curriculum for Academic Excellence and Holistic Development

Science.gov (United States)

Cárdenas, Alejandra Natalia

2016-01-01

The arts school partnerships under the policy "40x40" in Bogotá-Colombia are an example of the international interest in new ways to redress social and educational disadvantages. The main purpose of the policy is to improve education by gradually extending school daytime. This vignette explores three important issues for the…
39 CFR 3050.40 - Additional financial reporting.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Additional financial reporting. 3050.40 Section... financial reporting. (a) In general. The Postal Service shall file with the Commission: (1) Within 40 days...), beginning with the annual report for fiscal year 2010. (c) Financial reporting. The reports required by...
40 CFR 257.1 - Scope and purpose.

Science.gov (United States)

2010-07-01

... disposal of solid waste by underground well injection subject to the regulations (40 CFR part 146) for the Underground Injection Control Program (UICP) under the Safe Drinking Water Act, as amended, 42 U.S.C. 3007 et... intended for return to the mine site. (3) The criteria do not apply to the land application of domestic...
29 CFR 18.40 - Motion for summary decision.

Science.gov (United States)

2010-07-01

... OFFICE OF ADMINISTRATIVE LAW JUDGES General § 18.40 Motion for summary decision. (a) Any party may, at... that a party is entitled to summary decision. The administrative law judge may deny the motion whenever... 29 Labor 1 2010-07-01 2010-07-01 true Motion for summary decision. 18.40 Section 18.40 Labor...
46 CFR 2.20-40 - Chief engineer's reports.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Chief engineer's reports. 2.20-40 Section 2.20-40... INSPECTIONS Reports and Forms § 2.20-40 Chief engineer's reports. (a) Repairs to boilers and pressure vessels. The chief engineer is required to report any repairs to boilers or unfired pressure vessels in...
Reisifirmade TOP 40 aastal 2002

Index Scriptorium Estoniae

2003-01-01

Reisifirmade TOP 40 aastal 2002. Reisifirmade TOP-i esikümme. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Reisifirmade üldandmed. Reisifirmade finantsandmed. Tehnilise käibe alusel arvutatud edetabelid: Reisifirmade TOP 25; Käibe TOP 40; Rentaabluse TOP 10; Käibe kasvu TOP 10
Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

OpenAIRE

Teruel, María; Simeón Aznar, Carmen Pilar; Broen, Jasper C.; Vonk, Madelon C.; Carreira, Patricia; Camps García, María Teresa; García-Portales, Rosa; Delgado-Frías, Esmeralda; Gallego, Maria; Espinosa Garriga, Gerard; Spanish Scleroderma Group; Beretta, Lorenzo; Airó, Paolo; Lunardi, Claudio; Riemekasten, Gabriela

2012-01-01

Introduction: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). Methods: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genot...
Prognostic value of p53 mutations in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy

Energy Technology Data Exchange (ETDEWEB)

Ito, Tomohiro; Kaneko, Kazuhiro; Makino, Reiko; Ito, Hiroaki; Konishi, Kazuo; Kurahashi, Toshinori; Kitahara, Tadashi; Mitamura, Keiji [Showa Univ., Tokyo (Japan). School of Medicine

2001-05-01

A significant correlation has been found between p53 mutation and response to chemotherapy or radiotherapy. To determine the prognostic value of p53 mutation in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy, p53 mutation was analyzed using the biopsied specimens taken for diagnosis. Concurrent chemoradiotherapy was performed for 40 patients with severe dysphagia caused by esophageal squamous cell carcinoma associated with T3 or T4 disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil, combined with an infusion of cisplatinum. Radiation treatment of the mediastinum was administered concomitantly with chemotherapy. The p53 gene mutation was detected by fluorescence-based polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) methods. DNA sequences were determined for DNA fragments with shifted peaks by SSCP methods. Of the 40 patients, 15 had T3 disease and 25 had T4 disease; 11 patients had M1 lymph node (LYM) disease. Of the 40 patients, 13 (33%) achieved a complete response. The median survival time was 14 months, and the 2-year survival rate was 20%. Among the 40 tumor samples, p53 mutation was detected in 24 tumors (60%). The survival rate in the 24 patients with p53 mutation did not differ significantly from that in the 16 patients without p53 mutation. In contrast, the 15 patients with T3 disease survived longer than the 25 patients with T4 disease (P=0.016); however, the survival rate in the 11 patients with M1 LYM disease did not differ significantly from that in the 29 patients without M1 LYM disease. Concurrent chemoradiotherapy is potentially curative for locally advanced esophageal carcinoma, but p53 genetic abnormality has no impact on prognosis. (author)
Prognostic value of p53 mutations in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy

International Nuclear Information System (INIS)

Ito, Tomohiro; Kaneko, Kazuhiro; Makino, Reiko; Ito, Hiroaki; Konishi, Kazuo; Kurahashi, Toshinori; Kitahara, Tadashi; Mitamura, Keiji

2001-01-01

A significant correlation has been found between p53 mutation and response to chemotherapy or radiotherapy. To determine the prognostic value of p53 mutation in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy, p53 mutation was analyzed using the biopsied specimens taken for diagnosis. Concurrent chemoradiotherapy was performed for 40 patients with severe dysphagia caused by esophageal squamous cell carcinoma associated with T3 or T4 disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil, combined with an infusion of cisplatinum. Radiation treatment of the mediastinum was administered concomitantly with chemotherapy. The p53 gene mutation was detected by fluorescence-based polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) methods. DNA sequences were determined for DNA fragments with shifted peaks by SSCP methods. Of the 40 patients, 15 had T3 disease and 25 had T4 disease; 11 patients had M1 lymph node (LYM) disease. Of the 40 patients, 13 (33%) achieved a complete response. The median survival time was 14 months, and the 2-year survival rate was 20%. Among the 40 tumor samples, p53 mutation was detected in 24 tumors (60%). The survival rate in the 24 patients with p53 mutation did not differ significantly from that in the 16 patients without p53 mutation. In contrast, the 15 patients with T3 disease survived longer than the 25 patients with T4 disease (P=0.016); however, the survival rate in the 11 patients with M1 LYM disease did not differ significantly from that in the 29 patients without M1 LYM disease. Concurrent chemoradiotherapy is potentially curative for locally advanced esophageal carcinoma, but p53 genetic abnormality has no impact on prognosis. (author)
Age-Related Hearing Impairment (ARHI) associated with GJB2 single mutation IVS1+1G>A in the Yakut population isolate in Eastern Siberia.

Science.gov (United States)

Barashkov, Nikolay A; Teryutin, Fedor M; Pshennikova, Vera G; Solovyev, Aisen V; Klarov, Leonid A; Solovyeva, Natalya A; Kozhevnikov, Andrei A; Vasilyeva, Lena M; Fedotova, Elvira E; Pak, Maria V; Lekhanova, Sargylana N; Zakharova, Elena V; Savvinova, Kyunney E; Gotovtsev, Nyurgun N; Rafailo, Adyum M; Luginov, Nikolay V; Alexeev, Anatoliy N; Posukh, Olga L; Dzhemileva, Lilya U; Khusnutdinova, Elza K; Fedorova, Sardana A

2014-01-01

Age-Related Hearing Impairment (ARHI) is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene) and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia). This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz) and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs = 0.499, p = 0.006860 for males and rs = 0.427, p = 0.000277 for females). Moreover, the average hearing thresholds on high frequency (8.0 kHz) in individuals with genotype IVS1+1G>A/wt (both sexes) were significantly worse than in individuals with genotype wt/wt (pA/wt was estimated to be ∼40 years (rs = 0.504, p = 0.003). These findings demonstrate that the single IVS1+1G>A mutation (GJB2) is associated with age-related hearing impairment (ARHI) of the IVS1+1G>A carriers in the Yakuts.
Age-Related Hearing Impairment (ARHI associated with GJB2 single mutation IVS1+1G>A in the Yakut population isolate in Eastern Siberia.

Directory of Open Access Journals (Sweden)

Nikolay A Barashkov

Full Text Available Age-Related Hearing Impairment (ARHI is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia. This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs = 0.499, p = 0.006860 for males and rs = 0.427, p = 0.000277 for females. Moreover, the average hearing thresholds on high frequency (8.0 kHz in individuals with genotype IVS1+1G>A/wt (both sexes were significantly worse than in individuals with genotype wt/wt (pA/wt was estimated to be ∼40 years (rs = 0.504, p = 0.003. These findings demonstrate that the single IVS1+1G>A mutation (GJB2 is associated with age-related hearing impairment (ARHI of the IVS1+1G>A carriers in the Yakuts.
Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells

Directory of Open Access Journals (Sweden)

Tibullo eDaniele

2015-10-01

Full Text Available Osteolytic bone disease is a common manifestation of multiple myeloma (MM that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients.It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases CHIT1 and YKL40 is associated with osteoclast (OCs differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib’s concentration (BO (2.5 nM and 5nM on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to BO was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disc assay resorption pits. Silencing chitinase proteins in U266 cell line with specific siRNAs, resulted in pits number reduction on dentine discs. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients.
Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells.

Science.gov (United States)

Tibullo, Daniele; Di Rosa, Michelino; Giallongo, Cesarina; La Cava, Piera; Parrinello, Nunziatina L; Romano, Alessandra; Conticello, Concetta; Brundo, Maria V; Saccone, Salvatore; Malaguarnera, Lucia; Di Raimondo, Francesco

2015-01-01

Osteolytic bone disease is a common manifestation of multiple myeloma (MM) that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients. It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases chitotriosidase (CHIT1) and YKL40 is associated with osteoclast (OCs) differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib's concentration (2.5 and 5 nM) on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to bortezomib (BO) was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP, and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disk assay resorption pits. Silencing chitinase proteins in U266 cell line with specific small interfering RNA, resulted in pits number reduction on dentine disks. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients.

46 CFR 12.40-11 - Citizenship and identity.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Citizenship and identity. 12.40-11 Section 12.40-11... Passenger Vessels § 12.40-11 Citizenship and identity. (a) In lieu of the requirements of § 10.221 of this... and identity requirements of this subpart, an applicant must present an unexpired passport issued by...
Study of a clusters in 40Ca and 40Ar through nuclear break-up

International Nuclear Information System (INIS)

Lefebvre, Laurent

2013-01-01

Nuclei are complex self-bound systems formed by nucleons. Conjointly to a mean-field picture in which nucleons can be regarded as independent particles, few nucleons might self-organize into compact objects, called clusters, inside the nucleus. It is theoretically predicted that it should manifest itself most strikingly for N = Z nuclei close to the emission thresholds and has been studied extensively in this region. We propose to study α-clusterization in the ground state of the N = Z 40 20 Ca 20 nucleus and the N (different of) Z 40 18 Ar 22 nucleus. We have studied the nuclear break-up of 40 Ca when the 40 Ar projectile passes by. If α clusters are preformed in 40 Ca, the probability of α-emission through nuclear break-up will be enhanced as compared to 40 Ar N (different of) Z nuclei.The nuclear break-up of 40 Ca was studied with an 40 Ar beam produced at GANIL at 35 MeV/A. The SPEG spectrometer was used to detect the heavy projectile with accurate resolution. The MUST2 Silicon detectors were placed around the target to measure the emitted α and the EXL calorimeter prototype was used to identify the γ rays from the decay of the residual 36 Ar and 36 S. A theoretical approach based on Time-Dependent Schroedinger Equation (TDSE) theory has been used to reproduce some experimental results like angular distributions. From the data analysis, we reconstructed excitation energy spectra and angular distributions which are compared to TDSE theory to extract some spectroscopic factors S α . These factors show that there is no more clusterization state in the ground state of the 40 Ca than in the ground state of 40 Ar. (author)
40 CFR 155.40 - General.

Science.gov (United States)

2010-07-01

... does not apply to products whose sale or distribution is authorized under FIFRA section 5 or section 18... STANDARDS AND REGISTRATION REVIEW Registration Review Procedures § 155.40 General. (a) Purpose. These regulations establish procedures for the registration review program required in FIFRA section 3(g...
40 CFR 442.40 - Applicability.

Science.gov (United States)

2010-07-01

... TRANSPORTATION EQUIPMENT CLEANING POINT SOURCE CATEGORY Tanks Transporting Food Grade Cargos § 442.40 Applicability. This subpart applies to discharges resulting from the cleaning of tank trucks, intermodal tank containers, rail tank cars, tank barges and ocean/sea tankers which have been used to transport food grade...
Majutusasutuste TOP 40 aastal 2002

Index Scriptorium Estoniae

2003-01-01

Majutusasutuste TOP 40 aastal 2002. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Majutusasutuste üldandmed. Majutusasutuste finantsandmed
Nuclear Data Sheets for A=40

Energy Technology Data Exchange (ETDEWEB)

Chen, Jun

2017-02-15

The experimental nuclear structure data and decay data are evaluated for the known nuclides of mass 40 (Mg, Al, Si, P, S, Cl, Ar, K, Ca, Sc, Ti). Detailed evaluated nuclear structure information is presented with the best values recommended for level energies, half-lives, γ-ray energies and intensities, decay properties (energies, intensities and placement of radiations), and other spectroscopic data. The {sup 40}Ca and {sup 40}K nuclides remain as the most extensively studied from many different reactions and decays; no excited states are known in {sup 40}Mg, {sup 40}Al, {sup 40}P and {sup 40}Ti. This work supersedes the earlier full evaluation of A=40 by J. Cameron and B. Singh (2004Ca38).
Identification of excess 40Ar by the 40Ar/39Ar age spectrum technique

International Nuclear Information System (INIS)

Lanphere, M.A.; Dalrymple, G.B.

1976-01-01

40 Ar/ 39 Ar incremental heating experiments on igneous plagioclase, biotite, and pyroxene that contain known amounts of excess 40 Ar indicate that saddle-shaped age spectra are diagnostic of excess 40 Ar in igneous minerals as well as in igneous rocks. The minima in the age spectra approach but do not reach the crystallization age. Neither the age spectrum diagram nor the 40 Ar/ 36 Ar versus 39 Ar/ 36 Ar isochron diagram reliably reveal the crystallization age in such samples. (Auth.)
40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Early election for Group 1, Phase II boilers. 76.8 Section 76.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1...
40 CFR 412.40 - Applicability.

Science.gov (United States)

2010-07-01

... CONCENTRATED ANIMAL FEEDING OPERATIONS (CAFO) POINT SOURCE CATEGORY Swine, Poultry, and Veal Calves § 412.40 Applicability. This subpart applies to operations defined as concentrated animal feeding operations (CAFOs... lbs. or more; 10,000 swine each weighing less than 55 lbs.; 30,000 laying hens or broilers if the...
40 CFR 164.40 - Qualifications and duties of Administrative Law Judge.

Science.gov (United States)

2010-07-01

... Administrative Law Judge. 164.40 Section 164.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Judicial Ethics of the American Bar Association. (d) Power. Subject to review, as provided elsewhere in... Law Judge, the Administrator or the Environmental Appeals Board. [38 FR 19371, July 20, 1973, as...
Combined Analysis of CSF Tau, Aβ42, Aβ1–42% and Aβ1–40ox% in Alzheimer's Disease, Dementia with Lewy Bodies and Parkinson's Disease Dementia

Directory of Open Access Journals (Sweden)

Mirko Bibl

2010-01-01

Full Text Available We studied the diagnostic value of CSF Aβ42/tau versus low Aβ1–42% and high Aβ1–40ox% levels for differential diagnosis of Alzheimer's disease (AD and dementia with Lewy bodies (DLB, respectively. CSF of 45 patients with AD, 15 with DLB, 21 with Parkinson's disease dementia (PDD, and 40 nondemented disease controls (NDC was analyzed by Aβ-SDS-PAGE/immunoblot and ELISAs (Aβ42 and tau. Aβ42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers were Aβ1–42% and Aβ1–40ox% for AD and DLB, respectively. AD and DLB could be differentiated by both Aβ1–42% and Aβ1–40ox% with an accuracy of 80% at minimum. Thus, we consider Aβ1–42% and Aβ1–40ox% to be useful biomarkers for AD and DLB, respectively. We propose further studies on the integration of Aβ1–42% and Aβ1–40ox% into conventional assay formats. Moreover, future studies should investigate the combination of Aβ1–40ox% and CSF alpha-synuclein for the diagnosis of DLB.
ROMI 4.0: Rough mill simulator 4.0 users manual

Science.gov (United States)

R. Edward Thomas; Timo Grueneberg; Urs. Buehlmann

2015-01-01

The Rough MIll simulator (ROMI Version 4.0) is a computer software package for personal computers (PCs) that simulates current industrial practices for rip-first, chop-first, and rip and chop-first lumber processing. This guide shows how to set up the software; design, implement, and execute simulations; and examine the results. ROMI 4.0 accepts cutting bills with as...
41 CFR 109-40.103-2 - Disqualification and suspension of carriers.

Science.gov (United States)

2010-07-01

... suspension of carriers. 109-40.103-2 Section 109-40.103-2 Public Contracts and Property Management Federal... AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.103-2 Disqualification and suspension of carriers. Disqualification and suspension are...
Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog.

Science.gov (United States)

Dowling, Geraldine; Kavanagh, Pierce V; Talbot, Brian; O'Brien, John; Hessman, Gary; McLaughlin, Gavin; Twamley, Brendan; Brandt, Simon D

2017-03-01

2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy. Increasing popularity and off-label use as a cognitive enhancer has resulted in a reputation as an intelligence boosting 'wonder drug'. Common alternatives available from online shops and other retail outlets include 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide (adrafinil), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}acetamide (CRL-40,940), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide (CRL-40,941), and N-methyl-4,4-difluoro-modafinil (modafiendz), respectively. Gas chromatography-mass spectrometry (GC-MS) is a common tool used in forensic and clinical analysis but there is a potential for inducing analysis-related ambiguities. This study reports on the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940, and CRL-40,941 due to exposure to the heated GC injection port dissolved in a variety of solvents. Key degradation products common to modafinil, modafinic acid, and adrafinil analysis included diphenylmethanol and 1,1,2,2-tetraphenylethane (TPE), the latter of which was verified by its synthesis and characterization by x-ray crystallography. The investigated compounds were also characterized by 1 H and 13 C NMR. Diphenylmethane and thiobenzophenone were also identified in some instances. TPE formation was suggested to involve the generation of a benzhydrylium ion and its reaction with the sulfoxide oxygen of the parent compound to give an oxysulfonium intermediate. Correspondingly, the fluorinated TPE analogue was formed during heat-induced degradation of modafiendz, CRL-40,940 and CRL-40,941, respectively. When a mixture of modafinil (non-fluorinated) and modafiendz (fluorinated) were subjected to GC analysis, 4,4'-(2,2-diphenylethane-1,1-diyl)bis(fluorobenzene) was detected as a third cross reaction product in addition to the two expected TPE analogues. These observations served as a reminder that the seemingly straightforward
40 CFR 443.40 - Applicability; description of the linoleum and printed asphalt felt subcategory.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Applicability; description of the linoleum and printed asphalt felt subcategory. 443.40 Section 443.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS EFFLUENT LIMITATIONS GUIDELINES FOR EXISTING SOURCES AND STANDARDS OF PERFORMANC...
CD40-CD40L interactions partly participate in the endothelial cel

African Journals Online (AJOL)

Jane

2011-10-17

Oct 17, 2011 ... therapies for its advantages, for instance they can carry. *Corresponding author. ... Vascular endothelial cells (ECs) represent the natural barrier between the blood ..... the kinetics of CD40L-, interleukin 1-, or tumor necrosis.
75 FR 52292 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Science.gov (United States)

2010-08-25

... Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for all Diamond Aircraft Industries GmbH Models DA 40 and DA 40F... received information from Diamond Aircraft Industries GmbH that the Models DA 40 and DA 40F airplanes have...
The clinical investigation of OX40/OX40L from lymphocytes of patients with Graves' disease after 131I therapy

International Nuclear Information System (INIS)

Shi Bimin; Du Xuan; Wang Qin

2013-01-01

Objective To investigate the clinical value and the expression of OX40/OX40L from lymphocytes of patients with Graves' disease (GD) before and after 131 I therapy.Methods The expression of OX40/OX40L on T,B lymphocytes and the percentage of lymphocyte subsets were analyzed using immunofluorescence staining and flow cytometry in 32 patients with GD before and after 131 I therapy.Twenty-five healthy subjects were considered as the control group.The data between GD patients and controls were compared with two-sample t test.The correlation between the expression of OX40/OX40L and the function of thyroid (FT3,FT4 and TRAb level) was performed with linear correlation analysis.Results Compared with the healthy subjects,the percentage of CD4+ T cells and ratio of CD4+/CD8+ were decreased ((34.36 ±6.73)% vs (45.60-±5.72)%,t=2.634; 1.24±0.26 vs 1.84±0.37,t=2.125,both P<0.05).Whereas the percentage of CD19+ B cells in patients with GD were significantly higher than that in healthy subjects ((21.42 ±3.92)% vs (15.35 ± 3.15)%,t =2.653,P<0.05).The expression of OX40 increased in CD4+ T lymphocytes ((12.92 ± 2.26) %) and OX40L expression was up-regulated in CD19+ B lymphocytes ((15.33 ± 3.75)%) of patients with GD,compared with the healthy subjects ((4.19 ±1.45) % and (8.64 ± 1.73) %,respectively,t =2.112 and 2.467,both P<0.05).The expression of OX40 in CD4+ T lymphocytes ((7.65 ± 1.64) %) and OX40L in CD19+ B lymphocytes ((11.50 ±2.72)%) were increased after 131 I therapy(t =2.795,2.393,both P<0.05).The thyroid functions of 32 GD patients were improved.The levels of FT3,FT4 and TRAb decreased significantly after 131 I treatment (from 20.79 ±6.05 to 4.53 ± 2.54,from 49.65 ± 10.12 to 13.69 ± 4.35,and from 24.78 ± 8.46 to 11.74 ±6.19,respectively; t =2.219,2.441 and 2.293,all P<0.05).The levels of FT3 and FT4 were positively correlated with the percentage of OX40 expression in CD4+ T lymphocytes (r =0.65 and 0.73,both P<0.05).TRAb was positively correlated
Association between simian virus 40 and non-Hodgkin lymphoma

Science.gov (United States)

Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

2002-01-01

BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.
Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage.

Science.gov (United States)

Zhang, Can; Browne, Andrew; Kim, Doo Yeon; Tanzi, Rudolph E

2010-02-01

Alzheimer's disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid beta-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than approximately 80% of all FAD mutations. All PSEN1 FAD mutations can increase the Abeta42:Abeta40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of beta-secretase-derived secreted form of APP (sAPPbeta), could bind the death receptor, DR6, and lead to neurodegeneration. Here we asked whether PSEN1 FAD mutations lead to neurodegeneration by modulating sAPPbeta levels. All four different PSEN1 FAD mutations tested (in three mammalian cell lines) did not alter sAPPbeta levels. Therefore PS1 mutations do not appear to contribute to AD pathogenesis via altered production of sAPPbeta.

Reconstitution of wild type viral DNA in simian cells transfected with early and late SV40 defective genomes.

Science.gov (United States)

O'Neill, F J; Gao, Y; Xu, X

1993-11-01

The DNAs of polyomaviruses ordinarily exist as a single circular molecule of approximately 5000 base pairs. Variants of SV40, BKV and JCV have been described which contain two complementing defective DNA molecules. These defectives, which form a bipartite genome structure, contain either the viral early region or the late region. The defectives have the unique property of being able to tolerate variable sized reiterations of regulatory and terminus region sequences, and portions of the coding region. They can also exchange coding region sequences with other polyomaviruses. It has been suggested that the bipartite genome structure might be a stage in the evolution of polyomaviruses which can uniquely sustain genome and sequence diversity. However, it is not known if the regulatory and terminus region sequences are highly mutable. Also, it is not known if the bipartite genome structure is reversible and what the conditions might be which would favor restoration of the monomolecular genome structure. We addressed the first question by sequencing the reiterated regulatory and terminus regions of E- and L-SV40 DNAs. This revealed a large number of mutations in the regulatory regions of the defective genomes, including deletions, insertions, rearrangements and base substitutions. We also detected insertions and base substitutions in the T-antigen gene. We addressed the second question by introducing into permissive simian cells, E- and L-SV40 genomes which had been engineered to contain only a single regulatory region. Analysis of viral DNA from transfected cells demonstrated recombined genomes containing a wild type monomolecular DNA structure. However, the complete defectives, containing reiterated regulatory regions, could often compete away the wild type genomes. The recombinant monomolecular genomes were isolated, cloned and found to be infectious. All of the DNA alterations identified in one of the regulatory regions of E-SV40 DNA were present in the recombinant
Cyclophilin 40 facilitates HSP90-mediated RISC assembly in plants.

Science.gov (United States)

Iki, Taichiro; Yoshikawa, Manabu; Meshi, Tetsuo; Ishikawa, Masayuki

2012-01-18

Posttranscriptional gene silencing is mediated by RNA-induced silencing complexes (RISCs) that contain AGO proteins and single-stranded small RNAs. The assembly of plant AGO1-containing RISCs depends on the molecular chaperone HSP90. Here, we demonstrate that cyclophilin 40 (CYP40), protein phosphatase 5 (PP5), and several other proteins with the tetratricopeptide repeat (TPR) domain associates with AGO1 in an HSP90-dependent manner in extracts of evacuolated tobacco protoplasts (BYL). Intriguingly, CYP40, but not the other TPR proteins, could form a complex with small RNA duplex-bound AGO1. Moreover, CYP40 that was synthesized by in-vitro translation using BYL uniquely facilitated binding of small RNA duplexes to AGO1, and as a result, increased the amount of mature RISCs that could cleave target RNAs. CYP40 was not contained in mature RISCs, indicating that the association is transient. Addition of PP5 or cyclophilin-binding drug cyclosporine A prevented the association of endogenous CYP40 with HSP90-AGO1 complex and inhibited RISC assembly. These results suggest that a complex of AGO1, HSP90, CYP40, and a small RNA duplex is a key intermediate of RISC assembly in plants.
22 CFR 92.40 - Authentication of foreign extradition papers.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication of foreign extradition papers. 92.40 Section 92.40 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES NOTARIAL AND RELATED SERVICES Specific Notarial Acts § 92.40 Authentication of foreign extradition papers. Foreign...
Induction of host defences by Rhizobium during ineffective nodulation of pea (Pisum sativum L.) carrying symbiotically defective mutations sym40 (PsEFD), sym33 (PsIPD3/PsCYCLOPS) and sym42.

Science.gov (United States)

Ivanova, Kira A; Tsyganova, Anna V; Brewin, Nicholas J; Tikhonovich, Igor A; Tsyganov, Viktor E

2015-11-01

Rhizobia are able to establish a beneficial interaction with legumes by forming a new organ, called the symbiotic root nodule, which is a unique ecological niche for rhizobial nitrogen fixation. Rhizobial infection has many similarities with pathogenic infection and induction of defence responses accompanies both interactions, but defence responses are induced to a lesser extent during rhizobial infection. However, strong defence responses may result from incompatible interactions between legumes and rhizobia due to a mutation in either macro- or microsymbiont. The aim of this research was to analyse different plant defence reactions in response to Rhizobium infection for several pea (Pisum sativum) mutants that result in ineffective symbiosis. Pea mutants were examined by histochemical and immunocytochemical analyses, light, fluorescence and transmission electron microscopy and quantitative real-time PCR gene expression analysis. It was observed that mutations in pea symbiotic genes sym33 (PsIPD3/PsCYCLOPS encoding a transcriptional factor) and sym40 (PsEFD encoding a putative negative regulator of the cytokinin response) led to suberin depositions in ineffective nodules, and in the sym42 there were callose depositions in infection thread (IT) and host cell walls. The increase in deposition of unesterified pectin in IT walls was observed for mutants in the sym33 and sym42; for mutant in the sym42, unesterified pectin was also found around degrading bacteroids. In mutants in the genes sym33 and sym40, an increase in the expression level of a gene encoding peroxidase was observed. In the genes sym40 and sym42, an increase in the expression levels of genes encoding a marker of hypersensitive reaction and PR10 protein was demonstrated. Thus, a range of plant defence responses like suberisation, callose and unesterified pectin deposition as well as activation of defence genes can be triggered by different pea single mutations that cause perception of an otherwise
Increased YKL-40 expression in patients with carotid atherosclerosis

DEFF Research Database (Denmark)

Michelsen, Axel Gottlieb; Rathcke, C.N.; Skjelland, M.

2010-01-01

atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. Results: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid...... atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4...
SERUM YKL-40 CORRELATES WITH SERUM INTERLEUKIN-6 IN MULTIPLE MYELOMA

DEFF Research Database (Denmark)

Mylin, Anne Kjærsgaard; Andersen, Niels Frost; Johansen, Julia S.

2007-01-01

Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including angiogenesis. YKL-40 expression is seeen in vascular smooth muscle cells, and the protein is suggested to function......, but S-YKL-40 show a strong positive correlation with S-IL-6 consistent with a possible IL-6 mediated regulation of YKL-40 secretion demonstrated in previous studies. Table 1 Normal S-YKL-40 N Median (range) Elevated S-YKL-40 N Median (range) p-value S-IL-6, ng/L PB 23 3 (1...
Molecular mechanism and function of CD40/CD40L engagement in the immune system.

Science.gov (United States)

Elgueta, Raul; Benson, Micah J; de Vries, Victor C; Wasiuk, Anna; Guo, Yanxia; Noelle, Randolph J

2009-05-01

During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.
Could You Buy Me a Beer? Measuring Secondary Supply of Alcohol in Dutch On-Premise Outlets.

Science.gov (United States)

Roodbeen, Ruud T J; Geurtsen, Suzie; Schelleman-Offermans, Karen

2018-01-01

Alcohol is largely available for Dutch minors through on-premise secondary supply, which occurs when an adult furnishes an alcoholic drink to a minor in an on-premise outlet. Vendors allowing this secondary supply on their premises are in violation of the Dutch Licensing and Catering Act (legal age limit is 18 years old for the sale and possession of alcohol). Using existing mystery shopping protocols as a standard, our study objective was the development and field testing of a novel procedure, measuring vendors' compliance with secondary supply. Using a newly developed mystery shopping procedure, transfers of alcohol between young adult buyers and minors were staged in 109 Dutch on-premise outlets (cafes and bars) to measure vendors' compliance with secondary supply. In accordance with the Dutch Licensing and Catering Act, 29% of the vendors disallowed the secondary supply of alcohol to minors (32 of 109 attempts). During 40 attempts (of 109 attempts; 37%), the vendor asked for the identification document (ID) of the minor. Compliance after the ID was requested was 80% (32 of 40 attempts). During 8 attempts (20%), the minors were served even after the ID of the minor was requested. Mystery shopping is a suitable methodology for measuring compliance with secondary supply. Results show that alcohol is largely available for Dutch minors through secondary supply. Governments that intend to formulate and evaluate enforcement policies aimed at curbing high alcohol availability for minors are advised to use this novel procedure for monitoring compliance and to use these results for agenda setting and benchmarking.
28 CFR 40.3 - Communication of procedures.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Communication of procedures. 40.3 Section... Standards for Inmate Grievance Procedures § 40.3 Communication of procedures. The written grievance... inmate and employee shall, upon arrival at the institution, receive written notification and an oral...
40 CFR 6.207 - Environmental impact statements.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Environmental impact statements. 6.207... ACTIONS EPA's NEPA Environmental Review Procedures § 6.207 Environmental impact statements. (a) The Responsible Official will prepare an environmental impact statement (EIS) (see 40 CFR 1508.11) for major...
Decay of quadrupole-octupole 1- states in 40Ca and 140Ce

Science.gov (United States)

Derya, V.; Tsoneva, N.; Aumann, T.; Bhike, M.; Endres, J.; Gooden, M.; Hennig, A.; Isaak, J.; Lenske, H.; Löher, B.; Pietralla, N.; Savran, D.; Tornow, W.; Werner, V.; Zilges, A.

2016-03-01

Background: Two-phonon excitations originating from the coupling of two collective one-phonon states are of great interest in nuclear structure physics. One possibility to generate low-lying E 1 excitations is the coupling of quadrupole and octupole phonons. Purpose: In this work, the γ -decay behavior of candidates for the (21+⊗31-)1- state in the doubly magic nucleus 40Ca and in the heavier and semimagic nucleus 140Ce is investigated. Methods: (γ ⃗,γ') experiments have been carried out at the High Intensity γ -ray Source (HI γ S ) facility in combination with the high-efficiency γ -ray spectroscopy setup γ3 consisting of HPGe and LaBr3 detectors. The setup enables the acquisition of γ -γ coincidence data and, hence, the detection of direct decay paths. Results: In addition to the known ground-state decays, for 40Ca the decay into the 31- state was observed, while for 140Ce the direct decays into the 21+ and the 02+ state were detected. The experimentally deduced transition strengths and excitation energies are compared to theoretical calculations in the framework of EDF theory plus QPM approach and systematically analyzed for N =82 isotones. In addition, negative parities for two J =1 states in 44Ca were deduced simultaneously. Conclusions: The experimental findings together with the theoretical calculations support the two-phonon character of the 11- excitation in the light-to-medium-mass nucleus 40Ca as well as in the stable even-even N =82 nuclei.
40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Global Warming Potentials A Table A-1 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt. A, Table A-1 Table A-1 to Subpart A of Part 98—Global Warming...
40Ar/39Ar age calibration against counted annuallayers

DEFF Research Database (Denmark)

Storey, Michael; Stecher, Ole

2008-01-01

The 40Ar/39Ar method, based on the decay of the naturally occurring radioactive isotope 40K, is capable of producing ages with precision better than ± 0.1 %. However, accuracy is limited to no better than 1 % mainly due to the relatively large uncertainty in the 40K decay constants. One approach...... worth exploring for an improved absolute age basis for the 40Ar/39Ar system is through cross-calibration with counted annual layers (e.g. tree rings, varves and ice cores). North Atlantic Ash Zone (NAAZ) II is found within the dated part of the annual Greenland ice core record. NAAZ II has been...... correlated to the Icelandic peralkaline rhyolitic Thorsmörk ignimbrite. We will present preliminary 40Ar/39Ar results on the age of this eruption...
WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity.

Science.gov (United States)

Li, Qiuhong; Chang, Leifu; Aibara, Shintaro; Yang, Jing; Zhang, Ziguo; Barford, David

2016-09-20

The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C.
The GFDL global atmosphere and land model AM4.0/LM4.0: 1. Simulation characteristics with prescribed SSTs

Science.gov (United States)

Zhao, M.; Golaz, J.-C.; Held, I. M.; Guo, H.; Balaji, V.; Benson, R.; Chen, J.-H.; Chen, X.; Donner, L. J.; Dunne, J. P.; Dunne, Krista A.; Durachta, J.; Fan, S.-M.; Freidenreich, S. M.; Garner, S. T.; Ginoux, P.; Harris, L. M.; Horowitz, L. W.; Krasting, J. P.; Langenhorst, A. R.; Liang, Z.; Lin, P.; Lin, S.-J.; Malyshev, S. L.; Mason, E.; Milly, Paul C.D.; Ming, Y.; Naik, V.; Paulot, F.; Paynter, D.; Phillipps, P.; Radhakrishnan, A.; Ramaswamy, V.; Robinson, T.; Schwarzkopf, D.; Seman, C. J.; Shevliakova, E.; Shen, Z.; Shin, H.; Silvers, L.; Wilson, J. R.; Winton, M.; Wittenberg, A. T.; Wyman, B.; Xiang, B.

2018-01-01

In this two‐part paper, a description is provided of a version of the AM4.0/LM4.0 atmosphere/land model that will serve as a base for a new set of climate and Earth system models (CM4 and ESM4) under development at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL). This version, with roughly 100 km horizontal resolution and 33 levels in the vertical, contains an aerosol model that generates aerosol fields from emissions and a “light” chemistry mechanism designed to support the aerosol model but with prescribed ozone. In Part 1, the quality of the simulation in AMIP (Atmospheric Model Intercomparison Project) mode—with prescribed sea surface temperatures (SSTs) and sea‐ice distribution—is described and compared with previous GFDL models and with the CMIP5 archive of AMIP simulations. The model's Cess sensitivity (response in the top‐of‐atmosphere radiative flux to uniform warming of SSTs) and effective radiative forcing are also presented. In Part 2, the model formulation is described more fully and key sensitivities to aspects of the model formulation are discussed, along with the approach to model tuning.
Postmortem diagnosis of Marfan syndrome in a case of sudden death due to aortic rupture: Detection of a novel FBN1 frameshift mutation.

Science.gov (United States)

Wang, Yunyun; Chen, Shu; Wang, Rongshuai; Huang, Sizhe; Yang, Mingzhen; Liu, Liang; Liu, Qian

2016-04-01

To investigate the sudden death of a 36-year-old Chinese man, a medicolegal autopsy was performed, combining forensic pathological examinations and genetic sequencing analysis to diagnose the cause of death. Genomic DNA samples were extracted from blood and subjected to high-throughput sequencing. Major findings included a dilated aortic root with a ruptured and dissected aorta and consequent tamponade of the pericardial sac. Moreover, arachnodactyly and other skeletal deformities were noted. By sequencing the fibrillin-1 gene (FBN1), five genetic variations were found, including four previously known single nucleotide polymorphisms (SNPs) and a novel frameshift mutation, leading to the diagnosis of Marfan syndrome. The frameshift mutation (c.4921delG, p.glu1641llysFsX9) detected in exon 40 led to a stop codon after the next 8 amino acids. The four SNPs included a splice site mutation (c.3464-5 G>A, rs11853943), a synonymous mutation (p.Asn625Asn, rs25458), and two missense mutations (p.Pro1148Ala, rs140598; p.Cys472Tyr, rs4775765). Genetic screening was recommended for the relatives as it was reported that the father and brother of the deceased had died at the ages of 40 and 25, respectively, from sudden cardiac failure. The son of the deceased lacked the relevant mutations. This report emphasizes the important contribution of medicolegal postmortem analysis on the molecular pathogenesis study of Marfan syndrome and early diagnosis of at-risk relatives. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Distribution of ultraviolet-induced lesions in Simian Virus 40 DNA

International Nuclear Information System (INIS)

Bourre, F.; Renault, G.; Sarasin, A.; Seawell, P.C.

1985-01-01

In order to analyze the molecular mechanisms of mutagenesis in mammalian cells, we devised an analytical assay using Simian Virus 40 as biological probe. To study the possible correlations between the distribution of the lesions on the treated DNA and the distribution of mutations, we have located and quantified the lesions induced by ultraviolet light (254 nm) on a SV40 DNA fragment. At a fluence of 2,000J/m 2 , our results show that the formation frequency of thymine-thymine dimers (TT) is three to four times higher than the formation frequency of the other types of dimers (TC, CT, CC). On the other hand, the formation frequency of a dimer is influenced by the adjacent sequence. In particular, a pyrimidine in the 5' position of a thymine-thymine dimer enhances its formation frequency. At the dose used the formation frequency of the pyrimidine (6-4) pyrimidone photoproducts is twenty times less than the formation frequency of pyrimidine dimers. This paper shows the distribution of the major lesions induced by UV-light on a defined fragment of SV40 genome after UV irradiation. This work is necessary to get an insight in the molecular mechanisms of UV-mutagenesis
30 CFR 49.40 - Requirements for large coal mines.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Requirements for large coal mines. 49.40 Section 49.40 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.40 Requirements for large coal...
22 CFR 192.40 - Eligibility for benefits.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Eligibility for benefits. 192.40 Section 192.40 Foreign Relations DEPARTMENT OF STATE HOSTAGE RELIEF VICTIMS OF TERRORISM COMPENSATION Educational... programs of the Department of Veterans' Affairs under chapter 35 of title 38, United States Code). (b) A...
32 CFR 651.40 - Introduction.

Science.gov (United States)

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Introduction. 651.40 Section 651.40 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Environmental Impact Statement § 651.40 Introduction. (a) An...

FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.

Science.gov (United States)

Park, Myoung-Ja; Taki, Tomohiko; Oda, Megumi; Watanabe, Tomoyuki; Yumura-Yagi, Keiko; Kobayashi, Ryoji; Suzuki, Nobuhiro; Hara, Junichi; Horibe, Keizo; Hayashi, Yasuhide

2009-04-01

Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).
Genome Plasticity and Polymorphisms in Critical Genes Correlate with Increased Virulence of Dutch Outbreak-Related Coxiella burnetii Strains

Directory of Open Access Journals (Sweden)

Runa Kuley

2017-08-01

Full Text Available Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of Q fever. During 2007–2010 the largest Q fever outbreak ever reported occurred in The Netherlands. It is anticipated that strains from this outbreak demonstrated an increased zoonotic potential as more than 40,000 individuals were assumed to be infected. The acquisition of novel genetic factors by these C. burnetii outbreak strains, such as virulence-related genes, has frequently been proposed and discussed, but is not proved yet. In the present study, the whole genome sequence of several Dutch strains (CbNL01 and CbNL12 genotypes, a few additionally selected strains from different geographical locations and publicly available genome sequences were used for a comparative bioinformatics approach. The study focuses on the identification of specific genetic differences in the outbreak related CbNL01 strains compared to other C. burnetii strains. In this approach we investigated the phylogenetic relationship and genomic aspects of virulence and host-specificity. Phylogenetic clustering of whole genome sequences showed a genotype-specific clustering that correlated with the clustering observed using Multiple Locus Variable-number Tandem Repeat Analysis (MLVA. Ortholog analysis on predicted genes and single nucleotide polymorphism (SNP analysis of complete genome sequences demonstrated the presence of genotype-specific gene contents and SNP variations in C. burnetii strains. It also demonstrated that the currently used MLVA genotyping methods are highly discriminatory for the investigated outbreak strains. In the fully reconstructed genome sequence of the Dutch outbreak NL3262 strain of the CbNL01 genotype, a relatively large number of transposon-linked genes were identified as compared to the other published complete genome sequences of C. burnetii. Additionally, large numbers of SNPs in its membrane proteins and predicted virulence-associated genes were identified
VBDO Responsible Supply Chain Benchmark 2012. A comparative investigation into CSR in the supply chain of 40 multinationals

Energy Technology Data Exchange (ETDEWEB)

Bres, C.; Cotterell, P.; Kaya, R.; Verbunt, S.

2012-11-15

This benchmark is a qualitative (partly quantitative), comparative investigation among 40 Dutch publicly listed companies, aiming to inform stakeholders on responsible supply chain management. These stakeholders are company executives, investors, academia, NGOs, government and society at large. Rather than concentrate on the nature of a company's activities, this benchmark focuses on the company's supply chain governance and management thereof. This makes it possible to compare, to a reasonable degree, the responsible supply chain policies of companies across different sectors.
7 CFR 932.40 - Accounting.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 932.40 Section 932.40 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Expenses and Assessments § 932.40 Accounting. (a) If, at the end of a fiscal year, the...
34 CFR 361.40 - Reports.

Science.gov (United States)

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Reports. 361.40 Section 361.40 Education Regulations of... Requirements for Vocational Rehabilitation Services Administration § 361.40 Reports. (a) The State plan must assure that the designated State agency will submit reports, including reports required under sections 13...
Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates.

Science.gov (United States)

Mulu, Andargachew; Maier, Melanie; Liebert, Uwe Gerd

2015-12-01

Although biochemical analysis of HIV-1 integrase enzyme suggested the use of integrase inhibitors (INIs) against HIV-1C, different viral subtypes may favor different mutational pathways potentially leading to varying levels of drug resistance. Thus, the aim of this study was to search for the occurrence and natural evolution of integrase polymorphisms and/or resistance mutations in HIV-1C Ethiopian clinical isolates prior to the introduction of INIs. Plasma samples from chronically infected drug naïve patients (N = 45), of whom the PR and RT sequence was determined previously, were used to generate population based sequences of HIV-1 integrase. HIV-1 subtype was determined using the REGA HIV-1 subtyping tool. Resistance mutations were interpreted according to the Stanford HIV drug resistance database ( http://hivdb.stanford.edu ) and the updated International Antiviral Society (IAS)-USA mutation lists. Moreover, rates of polymorphisms in the current isolates were compared with South African and global HIV-1C isolates. All subjects were infected with HIV-1C concordant to the protease (PR) and reverse transcriptase (RT) regions. Neither major resistance-associated IN mutations (T66I/A/K, E92Q/G, T97A, Y143HCR, S147G, Q148H/R/K, and N155H) nor silent mutations known to change the genetic barrier were observed. Moreover, the DDE-catalytic motif (D64G/D116G/E152 K) and signature HHCC zinc-binding motifs at codon 12, 16, 40 and 43 were found to be highly conserved. However, compared to other South African subtype C isolates, the rate of polymorphism was variable at various positions. Although the sample size is small, the findings suggest that this drug class could be effective in Ethiopia and other southern African countries where HIV-1C is predominantly circulating. The data will contribute to define the importance of integrase polymorphism and to improve resistance interpretation algorithms in HIV-1C isolates.
41 CFR 109-40.5101 - Policy.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Policy. 109-40.5101... MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.51-Price-Anderson Coverage Certifications for Nuclear Shipments § 109-40.5101 Policy. Upon request of a carrier, an appropriate certification will be...
Selective removal of U(VI) from low concentration wastewater by functionalized HKUST-1@H3PW12O40

International Nuclear Information System (INIS)

Hui Zhang; Jinhua Xue; Nan Hu; Jing Sun; Dexin Ding; Yongdong Wang; Le Li

2016-01-01

The adsorption of U(VI) from low concentration solution by HKUST-1@H 3 PW 12 O 40 was studied as a function of various experimental parameters including pH, interfering ions, contact time, initial uranium concentration and temperature by batch experiments. Equilibrium data were found to fit with Langmuir isotherm model better than Freundlich isotherm model. The kinetic adsorption was fitted by the pseudo-second-order model well. Thermodynamic data from the adsorption experiments indicate that adsorption process is spontaneous and endothermic. HKUST-1@H 3 PW 12 O 40 can selectively adsorb U(VI) from multi-metal ion solutions and the adsorption capacity of HKUST-1@H 3 PW 12 O 40 don't decrease significantly after three cycles of desorption-reuse. The results show that HKUST-1@H 3 PW 12 O 40 is suitable for removal of U(VI) from low concentration solutions. (author)
Industry 4.0: The Digital German Ideology

Directory of Open Access Journals (Sweden)

Christian Fuchs

2018-02-01

Full Text Available Especially in Germany, a vivid public debate about “industry 4.0” has developed in recent years. It advances the argument that industry 4.0 is the fourth industrial revolution that follows on from technological revolutions brought about by water and steam power (industrial revolution 1.0, electric power (industrial revolution 2.0, and computing/computerised automation (industrial revolution 3.0. In 1845/46, Marx and Engels wrote The German Ideology. 170 years later, we live in the time of digital capitalism that has its own peculiar forms of ideology. This paper argues that “industry 4.0” is the new German ideology, the digital German ideology. Image: By ChristophRoser, AllAboutLean.com, CC BY-SA 4.0, via Wikimedia Commons
12 CFR 334.40 - Scope.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Scope. 334.40 Section 334.40 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY FAIR CREDIT REPORTING Duties of Furnishers of Information § 334.40 Scope. This subpart applies to a financial institution or...
36 CFR 228.40 - Authority.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Authority. 228.40 Section 228.40 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials § 228.40 Authority. Authority for the disposal of mineral materials is provided by the...
45 CFR 606.40 - Employment.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Employment. 606.40 Section 606.40 Public Welfare... § 606.40 Employment. No qualified individual with handicaps shall, on the basis of handicap, be subjected to discrimination in employment under any program or activity conducted by the Foundation. The...
29 CFR 801.40 - General.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false General. 801.40 Section 801.40 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR OTHER LAWS APPLICATION OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 Enforcement § 801.40 General. (a) Whenever the Secretary believes...
40 CFR 262.58 - International agreements.

Science.gov (United States)

2010-07-01

... universal waste management standards of 40 CFR Part 273, or subject to State requirements analogous to 40... waste meets the Federal definition of hazardous waste in 40 CFR 261.3 and is subject to either the Federal RCRA manifesting requirements at 40 CFR part 262, subpart B, the universal waste management...
Monomeric Aβ(1-40) and Aβ(1-42) Peptides in Solution Adopt Very Similar Ramachandran Map Distributions That Closely Resemble Random Coil.

Science.gov (United States)

Roche, Julien; Shen, Yang; Lee, Jung Ho; Ying, Jinfa; Bax, Ad

2016-02-09

The pathogenesis of Alzheimer's disease is characterized by the aggregation and fibrillation of amyloid peptides Aβ(1-40) and Aβ(1-42) into amyloid plaques. Despite strong potential therapeutic interest, the structural pathways associated with the conversion of monomeric Aβ peptides into oligomeric species remain largely unknown. In particular, the higher aggregation propensity and associated toxicity of Aβ(1-42) compared to that of Aβ(1-40) are poorly understood. To explore in detail the structural propensity of the monomeric Aβ(1-40) and Aβ(1-42) peptides in solution, we recorded a large set of nuclear magnetic resonance (NMR) parameters, including chemical shifts, nuclear Overhauser effects (NOEs), and J couplings. Systematic comparisons show that at neutral pH the Aβ(1-40) and Aβ(1-42) peptides populate almost indistinguishable coil-like conformations. Nuclear Overhauser effect spectra collected at very high resolution remove assignment ambiguities and show no long-range NOE contacts. Six sets of backbone J couplings ((3)JHNHα, (3)JC'C', (3)JC'Hα, (1)JHαCα, (2)JNCα, and (1)JNCα) recorded for Aβ(1-40) were used as input for the recently developed MERA Ramachandran map analysis, yielding residue-specific backbone ϕ/ψ torsion angle distributions that closely resemble random coil distributions, the absence of a significantly elevated propensity for β-conformations in the C-terminal region of the peptide, and a small but distinct propensity for αL at K28. Our results suggest that the self-association of Aβ peptides into toxic oligomers is not driven by elevated propensities of the monomeric species to adopt β-strand-like conformations. Instead, the accelerated disappearance of Aβ NMR signals in D2O over H2O, particularly pronounced for Aβ(1-42), suggests that intermolecular interactions between the hydrophobic regions of the peptide dominate the aggregation process.
Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

DEFF Research Database (Denmark)

Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo

2014-01-01

Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy...... and safety of sugammadex 4.0 mg kg-1 for reversal of deep rocuronium-induced NMB in Chinese and Caucasian patients. Methods: This was an open-label, multicenter, prospective Phase III efficacy study in adult American Society of Anesthesiologists Class 1-3 patients scheduled for surgery under general...... anesthesia and requiring deep NMB. All patients received intravenous propofol and opioids for induction and maintenance of anesthesia, and a single intubation dose of rocuronium 0.6 mg/kg, with maintenance doses of 0.1-0.2 mg/kg as required. Sugammadex 4.0 mg/kg was administered after the last dose...
34 CFR 300.40 - State.

Science.gov (United States)

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false State. 300.40 Section 300.40 Education Regulations of... SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH DISABILITIES General Definitions Used in This Part § 300.40 State. State means each of the 50 States, the District of...
40 years Gorleben... and no end; 40 Jahre Gorleben... und kein Ende

Energy Technology Data Exchange (ETDEWEB)

NONE

2017-04-15

The brochure on 40 years Gorleben discusses the following issues: anti-nuclear messages, the Gorleben-moment, the next 40 years, double risk, radioactive waste on the Neckar river, the Castor, escape from the cost, nuclear power in Bulgaria, Germany's most hazardous nuclear power plant.
Attitudes and perceptions of Dutch veterinarians on their role in the reduction of antimicrobial use in farm animals

NARCIS (Netherlands)

Speksnijder, David C.; Jaarsma, Debbie A C; Verheij, Theo J M; Wagenaar, Jaap A.

2015-01-01

Little is known about attitudes of veterinarians towards antibiotic use and reduction opportunities, and their interaction with farmers herein. Therefore, a questionnaire was developed and sent out to Dutch farm animal veterinarians. The response rate was 40%. Categorical Principal Component
Attitudes and perceptions of Dutch veterinarians on their role in the reduction of antimicrobial use in farm animals

NARCIS (Netherlands)

Speksnijder, David C.; Jaarsma, Debbie A.C.; Verheij, Theo J.M.; Wagenaar, Jaap A.

2015-01-01

Little is known about attitudes of veterinarians towards antibiotic use and reduction opportunities, and their interaction with farmers herein. Therefore, a questionnaire was developed and sent out to Dutch farm animal veterinarians. The response rate was 40%. Categorical Principal Component

46 CFR 39.40-1 - General requirements for vapor balancing-TB/ALL.

Science.gov (United States)

2010-10-01

... Section 39.40-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS... to control vapor emissions during a lightering or topping-off operation which does not use vapor... compressor or blower to assist vapor transfer without approval from the Commandant (CG-522). (d) Vapor...
21 CFR 606.40 - Facilities.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Facilities. 606.40 Section 606.40 Food and Drugs... GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS Plant and Facilities § 606.40 Facilities. Facilities shall be maintained in a clean and orderly manner, and shall be of suitable size, construction and...
A family with hereditary hemochromatosis carrying HFE gene splice site mutation: a case report

Directory of Open Access Journals (Sweden)

NING Huibin

2017-01-01

Full Text Available ObjectiveTo investigate a new type of HFE gene mutation in a family with hereditary hemochromatosis (HH. MethodsThe analysis of HFE gene was performed for one patient with a confirmed diagnosis of HH and five relatives. Blood genomic DNA was extracted and PCR multiplication was performed for the exon and intron splice sequences of related HFE, HJV, HAMP, transferrin receptor 2 (TfR2, and SLC40A1 genes. After agarose gel electrophoresis and purification, bi-directional direct sequencing was performed to detect mutation sites. ResultsThe proband had abnormal liver function and increases in serum iron, total iron binding capacity, serum ferritin, and transferrin saturation, as well as T→C homozygous mutation in the fourth base of intron 2 in the intervening sequence of the exon EXON2 of HFE gene (IVs 2+4T→C, C/C homozygous, splicing, abnormal. There were no abnormalities in HJV, HAMP, TfR2, and SLC40A1 genes. The proband′s son had the same homozygous mutation, three relatives had heterozygous mutations, and one relative had no abnormal mutations. ConclusionGene detection plays an important role in the diagnosis of hemochromatosis, and IVs 2+4T→C mutation may be a new pathogenic mutation for HH in China.
Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Ohkawa, Mayumi [Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Ohno, Yoshiya [Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-shi, Hyogo 650-8530 (Japan); Masuko, Kazue; Takeuchi, Akiko; Suda, Kentaro; Kubo, Akihiro; Kawahara, Rieko; Okazaki, Shogo [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan); Tanaka, Toshiyuki [Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-shi, Hyogo 650-8530 (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8502 (Japan); Seki, Masayuki; Enomoto, Takemi [Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Yagi, Hideki [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan); Hashimoto, Yoshiyuki [Tohoku University, Sendai (Japan); Masuko, Takashi, E-mail: masuko@phar.kindai.ac.jp [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan)

2011-03-25

Highlights: {yields} We established LAT1 amino-acid transporter-disrupted DT40 cells. {yields} LAT1-disrupted cells showed slow growth and lost the oncogenicity. {yields} siRNA and mAb inhibited human tumor growth in vitro and in vivo. {yields} LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1{sup -/-}) cell clones, derived from a heterozygous LAT1{sup +/-} clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1{sup -/-} DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1{sup -/-} cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1{sup -/-} DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1{sup -/-} DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1{sup +/-} DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.
Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

International Nuclear Information System (INIS)

Ohkawa, Mayumi; Ohno, Yoshiya; Masuko, Kazue; Takeuchi, Akiko; Suda, Kentaro; Kubo, Akihiro; Kawahara, Rieko; Okazaki, Shogo; Tanaka, Toshiyuki; Saya, Hideyuki; Seki, Masayuki; Enomoto, Takemi; Yagi, Hideki; Hashimoto, Yoshiyuki; Masuko, Takashi

2011-01-01

Highlights: → We established LAT1 amino-acid transporter-disrupted DT40 cells. → LAT1-disrupted cells showed slow growth and lost the oncogenicity. → siRNA and mAb inhibited human tumor growth in vitro and in vivo. → LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1 -/- ) cell clones, derived from a heterozygous LAT1 +/- clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1 -/- DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1 -/- cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1 -/- DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1 -/- DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1 +/- DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.
BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history.

Directory of Open Access Journals (Sweden)

Gaik Theng Toh

Full Text Available BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised. METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (40 years and no reported family history. Mutational analysis of BRCA1 and BRCA2 was conducted by full sequencing of all exons and intron-exon junctions. CONCLUSIONS: Here, we report a total of 14 BRCA1 and 17 BRCA2 sequence alterations, of which eight are novel (3 BRCA1 and 5 BRCA2. One deleterious BRCA1 mutation and 2 deleterious BRCA2 mutations, all of which are novel mutations, were identified in 3 of 37 individuals. This represents a prevalence of 2.7% and 5.4% respectively, which is consistent with other studies in other Asian ethnic groups (4-9%.
Soft spin-dipole resonances in 40Ca

International Nuclear Information System (INIS)

Stuhl, L; Krasznahorkay, A; Csatlós, M; Gulyás, J; Marketin, T; Litvinova, E; Adachi, T; Fujita, H; Hatanaka, K; Hirota, K; Ong, H J; Ishikawa, D; Matsubara, H; Algora, A; Estevez, E; Molina, F; Daeven, J; Guess, C; Meharchand, R; Fujita, Y

2012-01-01

High resolution experimental data has been obtained for the 40,42,44,48 Ca( 3 He,t)Sc charge exchange reaction at 420 MeV beam energy, which favors the spin-isospin excitations. The measured angular distributions were analyzed for each state separately, and the relative spin dipole strength has been extracted for the first time. The low-lying spin-dipole strength distribution in 40 Sc shows some interesting periodic gross feature. It resembles to a soft, damped multi-phonon vibrational band with hω= 1.8 MeV, which might be associated to pairing vibrations around 40 Ca.
Intracistronic complementation in the simian virus 40 A gene.

Science.gov (United States)

Tornow, J; Cole, C N

1983-01-01

A set of eight simian virus 40 mutants was constructed with lesions in the A gene, which encodes the large tumor (T) antigen. These mutants have small deletions (3-20 base pairs) at either 0.497, 0.288, or 0.243 map units. Mutants having both in-phase and frameshift mutations at each site were isolated. Neither plaque formation nor replication of the mutant DNAs could be detected after transfection of monkey kidney cells. Another nonviable mutant, dlA2459, had a 14-base-pair deletion at 0.193 map unit and was positive for viral DNA replication. Each of the eight mutants were tested for ability to form plaques after cotransfection with dlA2459 DNA. The four mutants that had in-phase deletions were able to complement dlA2459. The other four, which had frameshift deletions, did not. No plaques were formed after cotransfection of cells with any other pair of group A mutants. This suggests that the defect in dlA2459 defines a distinct functional domain of simian virus 40 T antigen. Images PMID:6312452
Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12).

NARCIS (Netherlands)

Pennings, R.J.E.; Topsakal, V.; Astuto, L.M.; Brouwer, A.P.M. de; Wagenaar, M.; Huygen, P.L.M.; Kimberling, W.J.; Deutman, A.F.; Kremer, J.M.J.; Cremers, C.W.R.J.

2004-01-01

OBJECTIVE: To describe the findings of audiovestibular and ophthalmologic examinations in four families with mutations in the CDH23 gene. STUDY DESIGN: Family study. SETTING: Tertiary referral center. PATIENTS: Four DFNB12 patients from a large consanguineous Dutch family and six patients from three
Mutation effect of streptomyces kitasatoensis after exposure to heavy ions radiation

International Nuclear Information System (INIS)

Liu Jing; Chen Jihong; Wang Shuyang; Li Wenjian

2011-01-01

To define the optimum dose of heavy ion beams for selecting high productive strains, we should study mortality and mutation effects of Streptomyces kitasatoensis irradiated by heavy ion beams in different doses. In this research, spores of Streptomyces kitasatoensis were irradiated by heavy ion beams with different doses. And survival rate, mortality rate, positive mutation and negative mutation were analyzed statistically. The results showed that high mortality rate appeared from 5 Gy and then the mortality rate curve became gently. Compared the positive and negative mutations in different doses, highest positive mutation was obtained in 40 Gy, while the negative mutation was lower in this dose, and the survival rate was 0.92%. So we defined that optimum dose of heavy ions radiation for Streptomyces kitasatoensis selection was 40 Gy in this experiment. (authors)
40 CFR 180.565 - Thiamethoxam; tolerances for residues.

Science.gov (United States)

2010-07-01

... Mustard, seed 0.02 Nut, tree, group 14 0.02 Onion, dry bulb 0.03 Papaya 0.40 Peppermint, tops 1.5... apple 0.40 Sunflower 0.02 Tomato, paste 0.80 Vegetable, cucurbit, group 9 0.2 Vegetable, fruiting, group...
Random integration of SV40 in SV40-transformed, immortalized human fibroblasts.

Science.gov (United States)

Hara, H; Kaji, H

1987-02-01

We have studied the relationship between immortalization of SV40-transformed human embryonic fibroblasts and their SV40 integration sites. From several independently transformed cell pools, we have isolated clones which do not harbor unintegrated SV40 DNA. We have analysed whole-cell DNA from these clones, using the Southern blot method. Our results suggest that no specific integration sites in the cellular genome exist which are a prerequisite for the immortalization process. Although some integration sites were found to be predominant in pre-crisis clones, they could not be detected in the post-crisis clones. This suggests that none of these predominating sites is selected for during the crisis period.
IDH Mutations: Genotype-Phenotype Correlation and Prognostic Impact

Directory of Open Access Journals (Sweden)

Xiao-Wei Wang

2014-01-01

Full Text Available IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1R132H, IDH1nonR132H, and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1nonR132H in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated—which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.
40 years of multi-faceted change in the Dutch Tax and Customs Administration

DEFF Research Database (Denmark)

Rukanova, Boriana; Stijn, Eveline van; Henriksen, Helle Zinner

2006-01-01

perceived as key components of a solution. Thus, we see that many ICT-driven change efforts have taken and continue to take place under the header of eGovernment. These changes are not always successful, however, and not yet wellunderstood. In this article, we provide an interpretive longitudinal account...... of the strategic IS efforts at the Dutch Tax and Customs Administration (DTCA). Instead of focusing on IS that supports the government itself or the relations between governments and citizens, we seek to contribute to the sparse literature that is specifically directed at the interactions between EU initiatives...
Blockade of OX40/OX40 ligand to decrease cytokine messenger RNA expression in acute renal allograft rejection in vitro.

Science.gov (United States)

Wang, Y-L; Li, G; Fu, Y-X; Wang, H; Shen, Z-Y

2013-01-01

The aim of this study was to investigate cytokine messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) from renal recipients experiencing acute rejection by blocking OX40-OX40L interactions with recombinant human OX40-Fc fusion protein (rhOX40Fc) in vitro. PBMCs were isolated from 20 recipients experiencing acute rejection episodes (rejection group) and 20 recipients with stable graft function (stable group). Levels of Th1 (interferon [IFN]-γ) and Th2 (interleukin [IL]-4) mRNA expressions by PBMCs were measured using real-time reverse transcriptase-polymerase chain reactions. IFN-γ mRNA expression levels were significantly higher in the rejection than the stable group (P rejection group, rhOX40Fc reduced significantly the expression of IFN-γ and IL-4 mRNA by anti-CD3-monoclonal antibody stimulated PBMCs (P type cytokines. Copyright © 2013 Elsevier Inc. All rights reserved.
40 CFR Table 1 to Subpart C - VOC Content Limits by Product Category

Science.gov (United States)

2010-07-01

... (weight-percent VOC) Air fresheners: Single-phase 70 Double-phase 30 Liquids/pump sprays 18 Solids/gels 3... 40 Protection of Environment 5 2010-07-01 2010-07-01 false VOC Content Limits by Product Category 1 Table 1 to Subpart C Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
9 CFR 113.40 - Dog safety tests.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...
46 CFR 32.40-35 - Hospital space-T/ALL.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Hospital space-T/ALL. 32.40-35 Section 32.40-35 Shipping... REQUIREMENTS Accommodations for Officers and Crew § 32.40-35 Hospital space—T/ALL. (a) Each vessel which in the... crew of 12 or more, must be provided with a hospital space. This space must be situated with due regard...
VBDO Responsible Supply Chain Benchmark 2012. A comparative investigation into CSR in the supply chain of 40 multinationals

Energy Technology Data Exchange (ETDEWEB)

Bres, C.; Cotterell, P.; Kaya, R.; Verbunt, S.

2012-11-15

This benchmark is a qualitative (partly quantitative), comparative investigation among 40 Dutch publicly listed companies, aiming to inform stakeholders on responsible supply chain management. These stakeholders are company executives, investors, academia, NGOs, government and society at large. Rather than concentrate on the nature of a company's activities, this benchmark focuses on the company's supply chain governance and management thereof. This makes it possible to compare, to a reasonable degree, the responsible supply chain policies of companies across different sectors.
Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced?

Science.gov (United States)

van Tilborg, Theodora C; Derks-Smeets, Inge A P; Bos, Anna M E; Oosterwijk, Jan C; van Golde, Ron J; de Die-Smulders, Christine E; van der Kolk, Lizet E; van Zelst-Stams, Wendy A G; Velthuizen, Maria E; Hoek, Annemieke; Eijkemans, Marinus J C; Laven, Joop S E; Ausems, Margreet G E M; Broekmans, Frank J M

2016-11-01

Do BRCA1/2 mutation carriers have a compromised ovarian reserve compared to proven non-carriers, based on serum anti-Müllerian hormone (AMH) levels? BRCA1/2 mutation carriers do not show a lower serum AMH level in comparison to proven non-carriers, after adjustment for potential confounders. It has been suggested that the BRCA genes play a role in the process of ovarian reserve depletion, although previous studies have shown inconsistent results regarding the association between serum AMH levels and BRCA mutation status. Hence, it is yet unclear whether BRCA1/2 mutation carriers may indeed be at risk of a reduced reproductive lifespan. STUDY DESIGN, SIZE, DURATION: A multicenter, cross-sectional study was performed between January 2012 and February 2015 in 255 women. We needed to include 120 BRCA1/2 mutation carriers and 120 proven non-carriers to demonstrate a difference in AMH levels of 0.40 µg/l (SD ± 0.12 µg/l, two-sided alpha-error 0.05, power 80%). Healthy women aged 18-45 years who were referred to the Clinical Genetics Department and applied for predictive BRCA1/2 testing because of a familial BRCA1/2 mutation were asked to participate. A cross-sectional assessment was performed by measuring serum AMH levels and filling out a questionnaire. Multivariate linear regression analyses adjusted for age, current smoking and current hormonal contraceptive use were performed on log-transformed serum AMH levels. Out of 823 potentially eligible women, 421 (51.2%) were willing to participate, and of those, 166 (39%) did not meet our inclusion criteria. Two hundred and fifty-five women were available for analyses; 124 BRCA1/2 mutation carriers and 131 proven non-carriers. The median [range] AMH level in carriers was 1.90 µg/l [0.11-19.00] compared to 1.80 µg/l [0.11-10.00] in non-carriers (P = 0.34). Adjusted linear regression analysis revealed no reduction in AMH level in the carriers (relative change = 0.98 (95%CI, 0.77-1.22); P = 0.76). Participants

33 CFR 138.40 - Forms.

Science.gov (United States)

2010-07-01

...) § 138.40 Forms. All forms referred to in this subpart may be obtained from NPFC by requesting them in writing at the address given in § 138.45(a) or by clicking on the Forms link at the NPFC E-COFR Web site... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Forms. 138.40 Section 138.40...
40 CFR 180.472 - Imidacloprid; tolerances for residues.

Science.gov (United States)

2010-07-01

... 1.5 Grape, raisin 1.5 Guava 1.0 Herbs subgroup 19A, dried herbs 48 Herbs subgroup 19-A, fresh herbs... Kava, leaves 4.0 Kava, roots 0.40 Leaf petioles subgroup 4B 6.0 Leafy greens subgroup 4A 3.5 Lettuce, head 3.5 Lettuce, leaf 3.5 Lingonberry 3.5 Longan 3.0 Lychee 3.0 Mango 1.0 Milk 0.10 Mustard, black...
Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

Directory of Open Access Journals (Sweden)

Jalkh Nadine

2012-06-01

Full Text Available Abstract Breast cancer is the most prevalent malignancy in women in Western countries, currently accounting for one third of all female cancers. Familial aggregation is thought to account for 5–10 % of all BC cases, and germline mutations in BRCA1 and BRCA2 account for less of the half of these inherited cases. In Lebanon, breast cancer represents the principal death-causing malignancy among women, with 50 % of the cases diagnosed before the age of 50 years. In order to study BRCA1/2 mutation spectra in the Lebanese population, 72 unrelated patients with a reported family history of breast and/or ovarian cancers or with an early onset breast cancer were tested. Fluorescent direct sequencing of the entire coding region and intronic sequences flanking each exon was performed. A total of 38 BRCA1 and 40 BRCA2 sequence variants were found. Seventeen of them were novel. Seven confirmed deleterious mutations were identified in 9 subjects providing a frequency of mutations of 12.5 %. Fifteen variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases. In conclusion, this study represents the first evaluation of the deleterious and unclassified genetic variants in the BRCA1/2 genes found in a Lebanese population with a relatively high risk of breast cancer.
Assessment of 40K levels in foodstuffs by gamma spectrometry

International Nuclear Information System (INIS)

Chinnaesakki, S.; Sartandel, S.J.; Bara, S.V.; Krishna, N.S.; Vinod Kumar, A.; Tripathi, R.M.; Puranik, V.D.

2012-01-01

Potassium-40 ( 40 K) is a naturally occurring radioactive isotope of potassium. Radioactive potassium-40 comprises a very small fraction(0.012%) of naturally occurring potassium, which is an element found in large amounts throughout nature. The half-life of 40 K is 1.3 billion years, and it decays to calcium-40 ( 40 Ca) by emitting a beta particle (89 %) and to the argon-40 ( 40 Ar) gas by electron capture with the emission of an energetic gamma ray of energy 1460 keV (10.7%). Humans require potassium to sustain biological processes, with most including 40 K being almost completely absorbed upon ingestion, moving quickly from the gastrointestinal tract to the blood stream (ANL-EVS, 2007). The body content of potassium is under homeostatic control. The total annual effective dose due to inhalation and ingestion of terrestrial radionuclides is assessed to be 0.29 mSv, of which 0.17mSv is due to 40 K and 0.12 mSv to the long-lived radionuclides in the uranium and thorium series (UNSCEAR 2008). Hence, measurement of 40 K in foodstuff is very much essential. This paper discusses the measurement of 40 K in foodstuffs samples collected in and around the new Bhabha Atomic Research Centre campus, Vishakhapatnam, Andhra Pradesh. This study was carried out as part of the baseline radiological monitoring
Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency.

Science.gov (United States)

Murray, Anna; Schoemaker, Minouk J; Bennett, Claire E; Ennis, Sarah; Macpherson, James N; Jones, Michael; Morris, Danielle H; Orr, Nick; Ashworth, Alan; Jacobs, Patricia A; Swerdlow, Anthony J

2014-01-01

Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population. The prevalence of FMR1 expansion mutations in early menopause (between the ages of 40 and 45 years) has not been published. We studied FMR1 CGG repeat number in more than 2,000 women from the Breakthrough Generations Study who underwent menopause before the age of 46 years. We determined the prevalence of premutation (55-200 CGG repeats) and intermediate (45-54 CGG repeats) alleles in women with primary ovarian insufficiency (n = 254) and early menopause (n = 1,881). The prevalence of the premutation was 2.0% in primary ovarian insufficiency, 0.7% in early menopause, and 0.4% in controls, corresponding to odds ratios of 5.4 (95% confidence interval = 1.7-17.4; P = 0.004) for primary ovarian insufficiency and 2.0 (95% confidence interval = 0.8-5.1; P = 0.12) for early menopause. Combining primary ovarian insufficiency and early menopause gave an odds ratio of 2.4 (95% confidence interval = 1.02-5.8; P = 0.04). Intermediate alleles were not significant risk factors for either early menopause or primary ovarian insufficiency. FMR1 premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of primary ovarian insufficiency and early menopause.
Benchmarking ENDF/B-VII.1, JENDL-4.0 and JEFF-3.1

International Nuclear Information System (INIS)

Van Der Marck, S. C.

2012-01-01

Three nuclear data libraries have been tested extensively using criticality safety benchmark calculations. The three libraries are the new release of the US library ENDF/B-VII.1 (2011), the new release of the Japanese library JENDL-4.0 (2011), and the OECD/NEA library JEFF-3.1 (2006). All calculations were performed with the continuous-energy Monte Carlo code MCNP (version 4C3, as well as version 6-beta1). Around 2000 benchmark cases from the International Handbook of Criticality Safety Benchmark Experiments (ICSBEP) were used. The results were analyzed per ICSBEP category, and per element. Overall, the three libraries show similar performance on most criticality safety benchmarks. The largest differences are probably caused by elements such as Be, C, Fe, Zr, W. (authors)
25 CFR 225.40 - Government employees cannot acquire minerals agreements.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Government employees cannot acquire minerals agreements. 225.40 Section 225.40 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS OIL AND GAS, GEOTHERMAL, AND SOLID MINERALS AGREEMENTS Minerals Agreements § 225.40 Government...
Serum YKL-40 and colorectal cancer

DEFF Research Database (Denmark)

Cintin, C; Johansen, J S; Christensen, Ib Jarle

1999-01-01

related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three......YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been...
Variations of CHI3L1, levels of the encoded glycoprotein YKL-40 and prediction of fatal and non-fatal ischemic stroke

DEFF Research Database (Denmark)

Rathcke, Camilla Noelle; Thomsen, Stine Brinkloev; Linneberg, Allan

2012-01-01

BACKGROUND: Polymorphisms of CHI3L1 are associated with inter-individual YKL-40 levels and YKL-40 is associated with an increased mortality and is elevated in patients with cardiovascular disease. We investigated the association between single nucleotide polymorphisms (SNPs) of CHI3L1, serum YKL-40...... levels and all-cause and cardiovascular mortality and first-time incidence of myocardial infarction, ischemic heart disease (IHD) and stroke. METHODOLOGY/PRINCIPAL FINDINGS: 12 SNPs of CHI3L1 were genotyped and serum YKL-40 was measured in 2656 Danes representative of the general population. Median...
Positive magnetoresistance in Co40Fe40B20/SiO2/Si heterostructure

KAUST Repository

Zhang, Y.

2016-07-20

Current-perpendicular-to-plane electronic transport properties and magnetoresistance of amorphous Co40Fe40B20/SiO2/Si heterostructures are investigated systematically. A backward diode-like rectifying behavior was observed due to the formation of a Schottky barrier between Co40Fe40B20 and Si. The junction resistance shows a metal-insulator transition with decreasing temperature in both the forward and reverse ranges. A large positive magnetoresistance (MR) of ∼2300% appears at 200 K. The positive MR can be attributed to the magnetic-field-controlled impact ionization process of carriers. MR shows a temperature-peak-type character under a constant bias current, which is related to the spin-dependent barrier in the Si near the interface. © CopyrightEPLA, 2016.
Positive magnetoresistance in Co40Fe40B20/SiO2/Si heterostructure

KAUST Repository

Zhang, Y.; Mi, W. B.; Zhang, Xixiang

2016-01-01

Current-perpendicular-to-plane electronic transport properties and magnetoresistance of amorphous Co40Fe40B20/SiO2/Si heterostructures are investigated systematically. A backward diode-like rectifying behavior was observed due to the formation of a Schottky barrier between Co40Fe40B20 and Si. The junction resistance shows a metal-insulator transition with decreasing temperature in both the forward and reverse ranges. A large positive magnetoresistance (MR) of ∼2300% appears at 200 K. The positive MR can be attributed to the magnetic-field-controlled impact ionization process of carriers. MR shows a temperature-peak-type character under a constant bias current, which is related to the spin-dependent barrier in the Si near the interface. © CopyrightEPLA, 2016.
Neutron-induced mutation experiments. Comprehensive report, March 1, 1977-August 31, 1980

International Nuclear Information System (INIS)

Abrahamson, S.

1981-02-01

Neutron-induced X-linked lethal mutations were induced in Drosophila melanogaster oogonia at energies of .43, .66, 2, and 6 MeV. The 37 irradiations were carried out at the RARAF facility at Brookhaven National Laboratory. RBE's (relative to x-ray data similarly collected) were calculated to be .43 MeV to 4.8; .66 MeV to 4.0; 2 MeV to 3.2; and 6 MeV to 2.9. The dose/frequency response curves for all energies best fit a linear rather than a linear-quadratic model following regression analyses. Control data for specific locus mutations (420,000 tests) were gathered. This data, combined with other data (both X-linked lethal and specific locus) has been used to estimate the number of loci on the X-chromosome of Drosophila which can mutate to recessive lethals
19 CFR 115.40 - Technical requirements for containers.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Technical requirements for containers. 115.40...; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS Procedures for Approval of Containers After Manufacture § 115.40 Technical requirements for...
2 CFR 215.40 - Purpose of procurement standards.

Science.gov (United States)

2010-01-01

... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Purpose of procurement standards. 215.40 Section 215.40 Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET CIRCULARS AND GUIDANCE Reserved UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION...
Evaluation of a nationwide mass media campaign aimed at prevention of weight gain in Dutch young adults

NARCIS (Netherlands)

B.M. Wammes (Birgitte)

2007-01-01

textabstractThe prevalence of overweight and obesity is increasing rapidly. In the Netherlands, the prevalence of obesity has roughly doubled over the last decade and now more than 40% of the Dutch adult population is overweight and more than 10% obese. To promote weight-gain preventive actions
40 CFR 40.115-4 - Municipality.

Science.gov (United States)

2010-07-01

... 208 of the act. (b) Under the Resource Conservation and Recovery Act, a city, town, borough, county... subdivision thereof. (c) In all other cases, a city, town, borough, county, parish, district, or other public... DEMONSTRATION GRANTS § 40.115-4 Municipality. (a) Under the Federal Water Pollution Control Act, a city, town...
49 CFR 40.271 - How are alcohol testing problems corrected?

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false How are alcohol testing problems corrected? 40.271 Section 40.271 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Alcohol Testing § 40.271 How are alcohol testing...
49 CFR 40.205 - How are drug test problems corrected?

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false How are drug test problems corrected? 40.205 Section 40.205 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.205 How are drug test problems...
Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells.

Science.gov (United States)

Fonseca, Ana Catarina R G; Ferreiro, Elisabete; Oliveira, Catarina R; Cardoso, Sandra M; Pereira, Cláudia F

2013-12-01

Neurovascular dysfunction arising from endothelial cell damage is an early pathogenic event that contributes to the neurodegenerative process occurring in Alzheimer's disease (AD). Since the mechanisms underlying endothelial dysfunction are not fully elucidated, this study was aimed to explore the hypothesis that brain endothelial cell death is induced upon the sustained activation of the endoplasmic reticulum (ER) stress response by amyloid-beta (Aβ) peptide, which deposits in the cerebral vessels in many AD patients and transgenic mice. Incubation of rat brain endothelial cells (RBE4 cell line) with Aβ1-40 increased the levels of several markers of ER stress-induced unfolded protein response (UPR), in a time-dependent manner, and affected the Ca(2+) homeostasis due to the release of Ca(2+) from this intracellular store. Finally, Aβ1-40 was shown to activate both mitochondria-dependent and -independent apoptotic cell death pathways. Enhanced release of cytochrome c from mitochondria and activation of the downstream caspase-9 were observed in cells treated with Aβ1-40 concomitantly with caspase-12 activation. Furthermore, Aβ1-40 activated the apoptosis effectors' caspase-3 and promoted the translocation of apoptosis-inducing factor (AIF) to the nucleus demonstrating the involvement of caspase-dependent and -independent mechanisms during Aβ-induced endothelial cell death. In conclusion, our data demonstrate that ER stress plays a significant role in Aβ1-40-induced apoptotic cell death in brain endothelial cells suggesting that ER stress-targeted therapeutic strategies might be useful in AD to counteract vascular defects and ultimately neurodegeneration. © 2013.
YKL-40 levels are independently associated with albuminuria in type 2 diabetes

DEFF Research Database (Denmark)

Røndbjerg, Anne K; Omerovic, Emina; Vestergaard, Henrik

2011-01-01

YKL-40 is involved in inflammation and endothelial dysfunction, and is increased in patients with type 1 diabetes, with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. YKL-40 is associated with atherosclerosis and an increased cardiovascular morta...... mortality in the general population. In the present study YKL-40 levels were examined in patients with type 2 diabetes (T2D) with increasing levels of albuminuria, known to be associated with an increased risk of cardiovascular disease.......YKL-40 is involved in inflammation and endothelial dysfunction, and is increased in patients with type 1 diabetes, with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. YKL-40 is associated with atherosclerosis and an increased cardiovascular...

40 CFR 261.40 - Conditional Exclusion for Used, Intact Cathode Ray Tubes (CRTs) Exported for Recycling.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Conditional Exclusion for Used, Intact Cathode Ray Tubes (CRTs) Exported for Recycling. 261.40 Section 261.40 Protection of Environment...) Exported for Recycling. Used, intact CRTs exported for recycling are not solid wastes if they meet the...
YKL-40 - an emerging biomarker in cardiovascular disease and diabetes

Directory of Open Access Journals (Sweden)

Rathcke Camilla

2009-01-01

Full Text Available Abstract Several inflammatory cytokines are involved in vascular inflammation resulting in endothelial dysfunction which is the earliest event in the atherosclerotic process leading to manifest cardiovascular disease. YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction by promoting chemotaxis, cell attachment and migration, reorganization and tissue remodelling as a response to endothelial damage. YKL-40 protein expression is seen in macrophages and smooth muscle cells in atherosclerotic plaques with the highest expression seen in macrophages in the early lesion of atherosclerosis. Several studies demonstrate, that elevated serum YKL-levels are independently associated with the presence and extent of coronary artery disease and even higher YKL-40 levels are documented in patients with myocardial infarction. Moreover, elevated serum YKL-40 levels have also been found to be associated with all-cause as well as cardiovascular mortality. Finally, YKL-40 levels are elevated both in patients with type 1 and type 2 diabetes, known to be at high risk for the development of cardiovascular diseases, when compared to non-diabetic persons. A positive association between elevated circulating YKL-40 levels and increasing levels of albuminuria have been described in patients with type 1 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. This review describes the present knowledge about YKL-40 and discusses its relation to endothelial dysfunction, atherosclerosis, cardiovascular disease and diabetes and look ahead on future perspectives of YKL-40 research.
Spin dipole and quadrupole resonances in 40Ca

International Nuclear Information System (INIS)

Baker, F.T.; Love, W.G.; Bimbot, L.; Fergerson, R.W.; Glashausser, C.; Green, A.; Jones, K.; Nanda, S.

1989-01-01

Angular distributions of the double differential cross section d 2 σ/dΩ dE(σ) and the spin-flip probability S nn have been measured for inclusive proton inelastic scattering from 40 Ca at 319 MeV. Excitation energies (ω) up to about 40 MeV have been investigated over the angular range from 3.5 degree to 12 degree in the laboratory (0.3 to 0.9 fm -1 ). Here, multipole decompositions of angular distributions of σS nn for the 40 Ca(rvec p,rvec p ') reaction at 319 MeV have been performed in order to compare ΔS=1 strength observed with sum rules. In contrast to the well-known quenching of Gamow-Teller and M1 resonances, the spin-dipole resonance has a total measured strength which is larger than that predicted by the energy-weighted sum rule. The spin-dipole strength distribution supports asymmetric widths predicted by calculations including 2p-2h mixing. The spin-quadrupole resonance is observed near ω=35 MeV and its total strength for ω<40 MeV estimated
Determination of K-40 in croquettes

International Nuclear Information System (INIS)

Escalona L, M. I.; Campillo R, G. E.; Vega C, H. R.; Garcia S, E.

2017-10-01

The health of the pets depends on several factors; one of the most important is the quality of their diet. The dog (Canis lupus familiaris) is a carnivorous mammal of the family of canines that is part of the most accepted pets. For the feeding of these pets is common to use industrial foods such as croquettes that offer many advantages, however they also contribute to the intake of radioisotopes that can affect their health. Potassium is an essential element for health, naturally there are 3 isotopes: K-39, K-40 and K-41. The K-40 is radioactive with 1,248 x 10 9 years of half-life that when decaying emits beta particles and photons of 1.42 MeV. In this work, potassium 40 activity was determined in croquette brands: Dog Chow, Canine Power and Exceed; KCl was used as a standard and dehydrated pea was used as control. The croquettes and peas were ground and weighed 160 grams of each sample, of KCl and pea, which were placed in Marinelli containers that were measured with a spectrometric system for γ rays and with a Nal(Tl) scintillator of 7.62 cm in diameter and 7.62 cm in height. It was found that the average activity of K-40 in all the measured brands is 5.0 ± 0.3 Bq per croquettes gram. (Author)
Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility.

Science.gov (United States)

Melikian, George L; Rhee, Soo-Yon; Taylor, Jonathan; Fessel, W Jeffrey; Kaufman, David; Towner, William; Troia-Cancio, Paolo V; Zolopa, Andrew; Robbins, Gregory K; Kagan, Ron; Israelski, Dennis; Shafer, Robert W

2012-05-01

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.
22 CFR 40.24 - Prostitution and commercialized vice.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Prostitution and commercialized vice. 40.24... Certain Crimes § 40.24 Prostitution and commercialized vice. (a) Activities within 10 years preceding visa... United States solely, principally, or incidentally to engage in prostitution, or has engaged in...
Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect.

Science.gov (United States)

Barashkov, Nikolay A; Dzhemileva, Lilya U; Fedorova, Sardana A; Teryutin, Fedor M; Posukh, Olga L; Fedotova, Elvira E; Lobov, Simeon L; Khusnutdinova, Elza K

2011-09-01

Hereditary forms of hearing impairment (HI) caused by GJB2 (Cx26) mutations are the frequent sensory disorders registered among newborns in various human populations. In this study, we present data on the molecular, audiological and population features of autosomal recessive deafness 1A (DFNB1A) associated with the donor splicing site IVS1+1G>A mutation of GJB2 gene in Yakut population isolate of the Sakha Republic (Yakutia) located in Eastern Siberia (Russian Federation). The Yakut population exhibits high frequency of some Mendelian disorders, which are rare in other populations worldwide. Mutational analysis of GJB2 gene in 86 unrelated Yakut patients with congenital HI without other clinical features has been performed. In this study, we registered a large cohort of Yakut patients homozygous for the IVS1+1G>A mutation (70 unrelated deaf subjects in total). Detailed audiological analysis of 40 deaf subjects with genotype IVS1+1G>A/IVS1+1G>A revealed significant association of this genotype with mostly symmetrical bilateral severe to profound HI (85% severe-to-profound HI versus 15% mild-to-moderate HI, PA mutation (11.7%) has been found in Yakut population. Reconstruction of 140 haplotypes with IVS1+1G>A mutation demonstrates the common origin of all mutant chromosomes found in Yakuts. The age of mutation was estimated to be approximately 800 years. These findings characterize Eastern Siberia as the region with the most extensive accumulation of the IVS1+1G>A mutation in the world as a result of founder effect.
Overexpression of chitinase like protein YKL-40 in leukemia patients

Directory of Open Access Journals (Sweden)

Anil K. Hurmale

2013-01-01

Full Text Available YKL-40 is a member of mammalian chitanase (CHI3L1, expressed and secreted by several types of solid tumor cells, inflammatory cells and stem cells. The precise physiological role of YKL-40 in cancer is still not clear and it is suggested that it play a role in cancer cell proliferation, differentiation, metastatic potential, cell attachment and migration, reorganization and tissue remodeling.The aim of the study was to check the appearance of YKL-40 in leukemic cells and over-expression of YKL-40 in the plasma of leukemia patients in comparison to healthy controls, and find whether YKL-40 could serve as a peripheral biomarker for leukemia. The study was conducted between July 2012 and March 2013 and included 67 volunteers, 55 having leukemia at the stage of diagnosis ofthe disease and 12 normal healthy volunteers. YKL-40 levels were determined in all plasma samples using the YKL-40 enzyme-linked immunosorbent assay (ELISA kit and expression of YKL-40 was observed by using immunocytochemical (ICC analysis. YKL-40 plasma levels differed significantly between patients with leukemia and the normal healthy volunteers (P=<0.001 and YKL-40 was positively expressed in all four types of leukemia (AML, ALL, CLL and CML specimens.
22 CFR 40.61 - Aliens present without admission or parole.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Aliens present without admission or parole. 40.61 Section 40.61 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH... Immigration Violators § 40.61 Aliens present without admission or parole. INA 212(a)(6)(A)(i) does not apply...
Industry 4.0 implies lean manufacturing: Research activities in industry 4.0 function as enablers for lean manufacturing

Directory of Open Access Journals (Sweden)

Adam Sanders

2016-09-01

Full Text Available Purpose: Lean Manufacturing is widely regarded as a potential methodology to improve productivity and decrease costs in manufacturing organisations. The success of lean manufacturing demands consistent and conscious efforts from the organisation, and has to overcome several hindrances. Industry 4.0 makes a factory smart by applying advanced information and communication systems and future-oriented technologies. This paper analyses the incompletely perceived link between Industry 4.0 and lean manufacturing, and investigates whether Industry 4.0 is capable of implementing lean. Executing Industry 4.0 is a cost-intensive operation, and is met with reluctance from several manufacturers. This research also provides an important insight into manufacturers’ dilemma as to whether they can commit into Industry 4.0, considering the investment required and unperceived benefits. Design/methodology/approach: Lean manufacturing is first defined and different dimensions of lean are presented. Then Industry 4.0 is defined followed by representing its current status in Germany. The barriers for implementation of lean are analysed from the perspective of integration of resources. Literatures associated with Industry 4.0 are studied and suitable solution principles are identified to solve the abovementioned barriers of implementing lean. Findings: It is identified that researches and publications in the field of Industry 4.0 held answers to overcome the barriers of implementation of lean manufacturing. These potential solution principles prove the hypothesis that Industry 4.0 is indeed capable of implementing lean. It uncovers the fact that committing into Industry 4.0 makes a factory lean besides being smart. Originality/value: Individual researches have been done in various technologies allied with Industry 4.0, but the potential to execute lean manufacturing was not completely perceived. This paper bridges the gap between these two realms, and identifies
22 CFR 40.71 - Documentation requirements for immigrants.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Documentation requirements for immigrants. 40... NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Documentation Requirements § 40.71 Documentation requirements for immigrants. INA 212(a)(7)(A) is not applicable at the time of...
22 CFR 40.9 - Classes of inadmissible aliens.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Classes of inadmissible aliens. 40.9 Section 40.9 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND... inadmissible aliens. Subparts B through L describe classes of inadmissible aliens who are ineligible to receive...
40 CFR 35.6270 - Standards for financial management systems.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Standards for financial management... § 35.6270 Standards for financial management systems. (a) Accounting system standards—(1) General. The... of the adequacy of the financial management system as described in 40 CFR 31.20(c). (2) Allowable...
Cone structure in patients with usher syndrome type III and mutations in the Clarin 1 gene.

Science.gov (United States)

Ratnam, Kavitha; Västinsalo, Hanna; Roorda, Austin; Sankila, Eeva-Marja K; Duncan, Jacque L

2013-01-01

To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost. Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations. These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3. clinicaltrials.gov Identifier: NCT00254605.
Cone Structure in Patients With Usher Syndrome Type III and Mutations in the Clarin 1 Gene

Science.gov (United States)

Ratnam, Kavitha; Västinsalo, Hanna; Roorda, Austin; Sankila, Eeva-Marja K.; Duncan, Jacque L.

2015-01-01

Objective To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). Methods High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. Results CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost. Conclusions Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations. Clinical Relevance These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3. Trial Registration clinicaltrials.gov Identifier: NCT00254605 PMID:22964989
Core Follow Calculation for Palo Verde Unit 1 in Cycles 1 through 4 using DeCART2D/MASTER4.0 Code System

International Nuclear Information System (INIS)

Jeong, Hee Jeong; Choi, Yonghee; Kim, Sungmin; Lee, Kyunghoon

2017-01-01

To verify and validate the DeCART2D/MASTER4.0 design system, core follow calculations of Palo Verde Unit 1(PV-1) in cycles 1 through 4 are performed. The calculation results are compared with the measured data and will be used in the generation of bias and uncertainty factors in the DeCART2D/MASTER4.0 design system. The DeCART2D/MASTER codes system has been developed in KAERI for the PWR (Pressurized water reactors) core design including SMRs (Small Modular Reactors). Core follow calculations of Pale Verde Unit 1 in Cycles 1 through 4 have been performed. Reactivities, assembly powers and startup parameters such as EPC, RW, ITC and IBW are compared with the measured data. This work will be used in the generation of bias and uncertainty factors in DeCART2D/MASTER4.0 design system.
Involvement of nuclear factor κB in platelet CD40 signaling

International Nuclear Information System (INIS)

Hachem, Ahmed; Yacoub, Daniel; Zaid, Younes; Mourad, Walid; Merhi, Yahye

2012-01-01

Highlights: ► sCD40L induces TRAF2 association to CD40 and NF-κB activation in platelets. ► IκBα phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. ► IκBα is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-κB). Given that platelets contain NF-κB, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of IκBα, which are abolished by CD40L blockade. Inhibition of IκBα phosphorylation reverses sCD40L-induced IκBα phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on IκBα phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of IκBα phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-κB activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo-inflammatory disorders.
22 CFR 40.91 - Certain aliens previously removed.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certain aliens previously removed. 40.91... IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.91 Certain aliens previously removed. (a) 5-year bar. An alien who has been found inadmissible, whether as a result...
7 CFR 953.40 - Marketing policy.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing policy. 953.40 Section 953.40 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... STATES Order Regulating Handling Regulations § 953.40 Marketing policy. Prior to or at the same time...
46 CFR 151.40-5 - Construction.

Science.gov (United States)

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Construction. 151.40-5 Section 151.40-5 Shipping COAST... LIQUID HAZARDOUS MATERIAL CARGOES Temperature or Pressure Control Installations § 151.40-5 Construction. Construction of machinery or equipment, such as heat exchangers, condensers, piping, etc., associated with...

YKL-40 in patients with end-stage renal disease receiving haemodialysis

DEFF Research Database (Denmark)

Nielsen, Ture Lange; Plesner, Louis Lind; Warming, Peder Emil

2018-01-01

PURPOSE: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40. METHODS: Patients >18 years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after...... a single HD treatment. RESULTS: A total of 306 patients were included. Median serum YKL-40 concentration was 238 µgL-1(IQR: 193-291 µgL-1) before HD treatment and 198 µgL-1(IQR: 147-258 µgL-1) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality...
High luminance LCD projection TV, 40ZIP; Kokido ekisho projection terebi 40ZIP

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

A 40 type LCD projection TV was commercialized which utilized the characteristics of a `large screen`, `saved space` and `light weight` incident to an LCD projection system and which succeeded `a television benign to people`, the concept of a flat wide television FACE{sub TM}. The main features are as follows:(1) A bright-in-every-corner and high-definition picture realized by employing a 2.7 type low temperature polysilicon LCD panel, high performance optical unit, wide angle of visibility, and high contrast screen. (2) A slim design for a 40 type large screen (compared with conventional models at Toshiba) having a depth comparable to that of 14 type and a mass equivalent to that of 25 type.(3) A PC input terminal most suitable for presentation. (translated by NEDO)
Cost-effectiveness of different strategies to prevent breast and ovarian cancer in German women with a BRCA 1 or 2 mutation.

Science.gov (United States)

Müller, Dirk; Danner, Marion; Rhiem, Kerstin; Stollenwerk, Björn; Engel, Christoph; Rasche, Linda; Borsi, Lisa; Schmutzler, Rita; Stock, Stephanie

2018-04-01

Women with a BRCA1 or BRCA2 mutation are at increased risk of developing breast and/or ovarian cancer. This economic modeling study evaluated different preventive interventions for 30-year-old women with a confirmed BRCA (1 or 2) mutation. A Markov model was developed to estimate the costs and benefits [i.e., quality-adjusted life years (QALYs), and life years gained (LYG)] associated with prophylactic bilateral mastectomy (BM), prophylactic bilateral salpingo-oophorectomy (BSO), BM plus BSO, BM plus BSO at age 40, and intensified surveillance. Relevant input data was obtained from a large German database including 5902 women with BRCA 1 or 2, and from the literature. The analysis was performed from the German Statutory Health Insurance (SHI) perspective. In order to assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed. With costs of €29,434 and a gain in QALYs of 17.7 (LYG 19.9), BM plus BSO at age 30 was less expensive and more effective than the other strategies, followed by BM plus BSO at age 40. Women who were offered the surveillance strategy had the highest costs at the lowest gain in QALYs/LYS. In the probabilistic sensitivity analysis, the probability of cost-saving was 57% for BM plus BSO. At a WTP of 10,000 € per QALY, the probability of the intervention being cost-effective was 80%. From the SHI perspective, undergoing BM plus immediate BSO should be recommended to BRCA 1 or 2 mutation carriers due to its favorable comparative cost-effectiveness.
40 CFR 763.92 - Training and periodic surveillance.

Science.gov (United States)

2010-07-01

... forms. (ii) Information on the health effects associated with asbestos exposure. (iii) Locations of ACBM... 40 CFR part 763, subpart G, and in 40 CFR part 61, subpart M, and OSHA regulations contained in 29... surveillance. (1) At least once every 6 months after a management plan is in effect, each local education...
Transformation and radiosensitivity of human diploid skin fibroblasts transfected with SV40 T-antigen mutants defective in RB and P53 binding domains

International Nuclear Information System (INIS)

LingNah Su; Little, J.B.

1992-01-01

A series of human diploid fibroblast cell clones were developed by DNA transfection with either wild-type SV40 T-antigen (SV40T) or T-antigen mutants defective in its various functional domains. Cell clones expressing the wild-type SV40 T were significantly radioresistant as compared with clones transfected with the neo gene only (D o 192 ± 13 vs 127 ± 19). This radioresistance persisted in post-crisis, immortalized cell lines. A series of mutants with point or deletion mutations within each functionally active domain of SV40 T were also examined for their ability to alter radiosensitivity and induce morphological transformation. Cell clones transfected with T-antigen mutants defective in nuclear localization or origin binding showed increased radioresistance similar to clones transfected with wild-type T-antigen, and expressed morphological changes characteristic of SV40 T-transfected cells. (author)
40 CFR 430.00 - Applicability.

Science.gov (United States)

2010-07-01

... Contained in the July 1, 1997 Edition of 40 CFR Parts 425 Through 699 Final codified subpart Final... sulfite mills where blow pit pulp washing techniques are used (Ja) and pulp and paper at papergrade...
Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population

DEFF Research Database (Denmark)

Lagerstedt-Robinson, Kristina; Rohlin, Anna; Aravidis, Christos

2016-01-01

Lynch syndrome caused by constitutional mismatch‑repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2...... Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large...... deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder...
Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit.

Science.gov (United States)

van Rijssen, L Bengt; Koerkamp, Bas G; Zwart, Maurice J; Bonsing, Bert A; Bosscha, Koop; van Dam, Ronald M; van Eijck, Casper H; Gerhards, Michael F; van der Harst, Erwin; de Hingh, Ignace H; de Jong, Koert P; Kazemier, Geert; Klaase, Joost; van Laarhoven, Cornelis J; Molenaar, I Quintus; Patijn, Gijs A; Rupert, Coen G; van Santvoort, Hjalmar C; Scheepers, Joris J; van der Schelling, George P; Busch, Olivier R; Besselink, Marc G

2017-10-01

Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade ≥ III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
40 CFR 424.40 - Applicability; description of the covered calcium carbide furnaces with wet air pollution control...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERROALLOY MANUFACTURING POINT SOURCE...
40 CFR 5.500 - Employment.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Employment. 5.500 Section 5.500... in Employment in Education Programs or Activities Prohibited § 5.500 Employment. (a) General. (1) No... subjected to discrimination in employment, or recruitment, consideration, or selection therefor, whether...
46 CFR 80.40 - Civil penalty.

Science.gov (United States)

2010-10-01

... 46 Shipping 3 2010-10-01 2010-10-01 false Civil penalty. 80.40 Section 80.40 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS DISCLOSURE OF SAFETY STANDARDS AND COUNTRY OF REGISTRY § 80.40 Civil penalty. For each violation of the regulations in this part, the owner, operator...
46 CFR 111.40-7 - Location.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Location. 111.40-7 Section 111.40-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Panelboards § 111.40-7 Location. Each panelboard must be accessible but not in a bunker or a cargo hold...
46 CFR 32.40-50 - Heating and cooling-T/ALL.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Heating and cooling-T/ALL. 32.40-50 Section 32.40-50... REQUIREMENTS Accommodations for Officers and Crew § 32.40-50 Heating and cooling—T/ALL. (a) All manned spaces must be adequately heated and cooled in a manner suitable to the purpose of the space. (b) The heating...
22 CFR 40.68 - Aliens subject to INA 222(g).

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Aliens subject to INA 222(g). 40.68 Section 40... § 40.68 Aliens subject to INA 222(g). An alien who, under the provisions of INA 222(g), has voided a... new nonimmigrant visa unless the alien complies with the requirements in 22 CFR 41.101 (b) or (c...
Involvement of nuclear factor {kappa}B in platelet CD40 signaling

Energy Technology Data Exchange (ETDEWEB)

Hachem, Ahmed [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Yacoub, Daniel [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Zaid, Younes [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Mourad, Walid [Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Merhi, Yahye, E-mail: yahye.merhi@icm-mhi.org [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada)

2012-08-17

Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Given that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo
Associations of moderate and severe overweight with self-reported illness and medical care in Dutch adults

NARCIS (Netherlands)

Seidell, J C; de Groot, L.C.; van Sonsbeek, J L; Deurenberg, P.; Hautvast, J.G.A.J.

Data on height, weight, illness, medical care consumption, and demographic variables for 19,126 Dutch adults aged 20 years or older were obtained from three annual Health Interview Surveys. Data on severely overweight (Body Mass Index 30.0-40.0 kg/m2) and moderately overweight (BMI 25.0-29.9 kg/m2)
SERUM YKL-40 IS ASSOCIATED WITH BONE DISEASE IN MULTIPLE MYELOMA

DEFF Research Database (Denmark)

Mylin, Anne Kjærsgaard; Abildgaard, Niels; Johansen, Julia S.

2007-01-01

Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix, in angiogen...... Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix...... and followed for up to 30 months. Skeletal related events (SRE) were registered and subdivided in vertebral fractures and osteolytic events including non-vertebral fractures. Results. 57% of the patients had a S-YKL-40 elevated above the upper limit in an age specific 90 per cent reference range for healthy...... adults. Patients with elevated S-YKL-40 had a higher total X-ray score (p=0.005) and higher levels of S-CTX-MMP (p=0.003), U-PYD (p=0.004) and U-DPD (p=0.002), while U-NTX-1 and the markers of bone formation did not differ from the levels seen in patients with normal S-YKL-40. During follow-up 21...
Relationship Between Mutations In BRCA1 And BRCA2 Genes And Breast Cancer Prevalence Among Egyptian Women

International Nuclear Information System (INIS)

ELMAGHRABY, T.K.

2009-01-01

Breast cancer represents the most common cancer of women in the world and it is a biologically heterogeneous disease influenced by complex interactions between multiple genetic and environmental risk factors. In Egypt, breast cancer is classified as the first rank cancer case among women. The present study included 55 patients with breast cancer from Upper Egypt of which 40 patients had sporadic and 15 had familial breast cancers. Mutations in DNA of exons 10 and 11 of BRCA1 and BRCA2 were detected by single strand conformation polymorphisms (SSCPs) and sequencing. Moreover, BRCA1 protein expression was detected by immunostaining technique and correlation between risk factors and incidence rate of breast cancer. The results revealed 5 mutations (unclassified variants); three mutations (60%) were recorded internationally in Breast Information Cancer (BIC), one of them was 1767 C→T(550 Asn→His) and previously recorded in the Arabic world and the other 2 novel mutations were 1663 T→ C(479 Asp→Gly) and del AG 6079. The results obtained in the present study also demonstrated that the increase of the negative immunostaining of ''BRCA1'' protein in the tumour cells of BRCA1 mutation carriers was comparable to familial and sporadic breast cancer non-carrier. Accurate estimation of the relative frequency of BRCA1 and BRCA2 mutations in Egyptian breast cancer patients could not be deduced from the results of this relatively small pilot study. More studies with larger numbers of patients are needed to clarify the relation between BRCA1 and BRCA2 gene mutations and the prediction of breast cancer in Egypt.
CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent.

Science.gov (United States)

D'Souza, Lucas; Gupta, Sneh Lata; Bal, Vineeta; Rath, Satyajit; George, Anna

2017-12-01

B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses. We report that CD73 expression identifies a subset of antigen-experienced IgM + cells that share attributes of functional B-cell memory. This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice and in mixed marrow chimeras made with mutant and wild-type marrow, the proportion of CD73 + IgM memory is restored in the T-cell-deficient donor compartment but not in the CD40-deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age-associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC-associated memory generation during B-cell differentiation, CD40-signalling can influence the composition of the unswitched memory B-cell pool. They also raise the possibility that a fraction of ABCs may represent T-cell-dependent IgM memory. © 2017 John Wiley & Sons Ltd.
40 CFR 52.2420 - Identification of plan.

Science.gov (United States)

2010-07-01

..., Hazardous waste, Household waste, Industrial waste, Junkyard, Open burning, Open pit incinerator, Refuse... 4/17/95 4/21/00, 65 FR 21315 120-04-3911. Article 40Emission Standards for Open Burning (Rule 4-40.../00, 65 FR 21315 120-04-4002. 5-40-5620 Open burning prohibitions 10/18/06 3/19/09, 74 FR 11661 5-40...

Germline PMS2 mutation screened by mismatch repair protein immunohistochemistry of colorectal cancer in Japan.

Science.gov (United States)

Sugano, Kokichi; Nakajima, Takeshi; Sekine, Shigeki; Taniguchi, Hirokazu; Saito, Shinya; Takahashi, Masahiro; Ushiama, Mineko; Sakamoto, Hiromi; Yoshida, Teruhiko

2016-11-01

Germline PMS2 gene mutations were detected by RT-PCR/direct sequencing of total RNA extracted from puromycin-treated peripheral blood lymphocytes (PBL) and multiplex ligation-dependent probe amplification (MLPA) analyses of Japanese patients with colorectal cancer (CRC) fulfilling either the revised Bethesda Guidelines or being an age at disease onset of younger than 70 years, and screened by mismatch repair protein immunohistochemistry of formalin-fixed paraffin embedded sections. Of the 501 subjects examined, 7 (1.40%) showed the downregulated expression of the PMS2 protein alone and were referred to the genetic counseling clinic. Germline PMS2 mutations were detected in 6 (85.7%), including 3 nonsense and 1 frameshift mutations by RT-PCR/direct sequencing and 2 genomic deletions by MLPA. No mutations were identified in the other MMR genes (i.e. MSH2, MLH1 and MSH6). The prevalence of the downregulated expression of the PMS2 protein alone was 1.40% among the subjects examined and IHC results predicted the presence of PMS2 germline mutations. RT-PCR from puromycin-treated PBL and MLPA may be employed as the first screening step to detect PMS2 mutations without pseudogene interference, followed by the long-range PCR/nested PCR validation using genomic DNA. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Properties of mouse CD40: differential expression of CD40 epitopes on dendritic cells and epithelial cells

NARCIS (Netherlands)

van den Berg, T. K.; Hasbold, J.; Renardel de Lavalette, C.; Döpp, E. A.; Dijkstra, C. D.; Klaus, G. G.

1996-01-01

In this study we describe the tissue distribution of mouse CD40 using two monoclonal antibodies (mAb) against different epitopes of the molecule. In lymphoid tissues CD40 was expressed by B lymphocytes. Most B cells in typical B-cell compartments were CD40-positive, including germinal centre B
40 CFR 26.1124 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false [Reserved] 26.1124 Section 26.1124 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical...-nursing Adults § 26.1124 [Reserved] ...
Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection.

Science.gov (United States)

Palmer, Clovis S; Duette, Gabriel A; Wagner, Marc C E; Henstridge, Darren C; Saleh, Suah; Pereira, Candida; Zhou, Jingling; Simar, David; Lewin, Sharon R; Ostrowski, Matias; McCune, Joseph M; Crowe, Suzanne M

2017-10-01

High glucose transporter 1 (Glut1) surface expression is associated with increased glycolytic activity in activated CD4+ T cells. Phosphatidylinositide 3-kinases (PI3K) activation measured by p-Akt and OX40 is elevated in CD4+Glut1+ T cells from HIV+ subjects. TCR engagement of CD4+Glut1+ T cells from HIV+ subjects demonstrates hyperresponsive PI3K-mammalian target of rapamycin signaling. High basal Glut1 and OX40 on CD4+ T cells from combination antiretroviral therapy (cART)-treated HIV+ patients represent a sufficiently metabolically active state permissive for HIV infection in vitro without external stimuli. The majority of CD4+OX40+ T cells express Glut1, thus OX40 rather than Glut1 itself may facilitate HIV infection. Furthermore, infection of CD4+ T cells is limited by p110γ PI3K inhibition. Modulating glucose metabolism may limit cellular activation and prevent residual HIV replication in 'virologically suppressed' cART-treated HIV+ persons. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
40 CFR 761.306 - Sampling 1 meter square surfaces by random selection of halves.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Sampling 1 meter square surfaces by...(b)(3) § 761.306 Sampling 1 meter square surfaces by random selection of halves. (a) Divide each 1 meter square portion where it is necessary to collect a surface wipe test sample into two equal (or as...
50 CFR 300.40 - Civil penalties.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Civil penalties. 300.40 Section 300.40... South Pacific Tuna Fisheries § 300.40 Civil penalties. The procedures of 15 CFR part 904 apply to the assessment of civil penalties, except as modified by the requirements of section 8 of the Act. ...
Social neighborhood environment and sports participation among Dutch adults: does sports location matter?

Science.gov (United States)

Kramer, D; Stronks, K; Maas, J; Wingen, M; Kunst, A E

2015-04-01

Studies on the relation between the social neighborhood environment and sports participation have produced inconsistent results. Use of generic sports outcomes may have obscured associations only apparent for sports at certain locations. This study aims to assess the association between the social neighborhood environment and three location-specific sports outcomes. Repeated cross-sectional data on sports participation (any type of sports, sports at indoor sports clubs, sports at outdoor sports clubs, sports on streets) were obtained from 20 600 adults using the Dutch national health survey 2006-2009. Data on neighborhood social safety and social capital were obtained using the Dutch Housing Research 2006. Over 40% of Dutch adults participated in any type of sports. Indoor sports clubs were most popular. Multilevel logistic regression analyses revealed that neighborhood social safety was positively associated with sports at indoor sports clubs [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.06-1.48), but not with the other sports outcomes. Contrary, neighborhood social capital was positively associated with sports on streets only (OR = 1.69, 95% CI = 1.17-2.44). The results suggest that a positive social neighborhood environment enhances sports participation, but that this impact depends on the location of the sports activity. This study highlights the importance of using location-specific sports outcomes when assessing environmental determinants. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Laterality related to the successive selection of Dutch national youth soccer players.

Science.gov (United States)

Verbeek, Jan; Elferink-Gemser, Marije T; Jonker, Laura; Huijgen, Barbara C H; Visscher, Chris

2017-11-01

In the general population, estimates of left-foot preference are around 20%. In soccer, specific tasks create positional demands, requiring 40% of the players to be left-footed. Whether and how this is related to the selection of players is unknown. To examine the successive selection of soccer players for Dutch national youth teams in relation to foot preference, 280 youth players (age = 16.2 ± 1.08 years) were monitored from the U16 through the U19 teams over the last 5 years. No difference in successive selection between left- and right-footed players was found (p soccer teams.
40 CFR 63.110 - Applicability.

Science.gov (United States)

2010-07-01

... of 40 CFR parts 260 through 272. The owner or operator shall keep a record of the information used to... 272. (f) Overlap with the Vinyl Chloride NESHAP. (1) After the compliance dates specified in § 63.100...
YKL-40 tissue expression and plasma levels in patients with ovarian cancer

International Nuclear Information System (INIS)

Høgdall, Estrid VS; Christensen, Lise H; Ringsholt, Merete; Høgdall, Claus K; Christensen, Ib Jarle; Johansen, Julia S; Kjaer, Susanne K; Blaakaer, Jan; Ostenfeld-Møller, Lene; Price, Paul A

2009-01-01

YKL-40 (chitinase-3-like-1) is a member of 'mammalian chitinase-like proteins'. The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004). YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC
Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain.

Science.gov (United States)

Laskowski, Roman A; Tyagi, Nidhi; Johnson, Diana; Joss, Shelagh; Kinning, Esther; McWilliam, Catherine; Splitt, Miranda; Thornton, Janet M; Firth, Helen V; Wright, Caroline F

2016-03-01

We present a generic, multidisciplinary approach for improving our understanding of novel missense variants in recently discovered disease genes exhibiting genetic heterogeneity, by combining clinical and population genetics with protein structural analysis. Using six new de novo missense diagnoses in TBL1XR1 from the Deciphering Developmental Disorders study, together with population variation data, we show that the β-propeller structure of the ubiquitous WD40 domain provides a convincing way to discriminate between pathogenic and benign variation. Children with likely pathogenic mutations in this gene have severely delayed language development, often accompanied by intellectual disability, autism, dysmorphology and gastrointestinal problems. Amino acids affected by likely pathogenic missense mutations are either crucial for the stability of the fold, forming part of a highly conserved symmetrically repeating hydrogen-bonded tetrad, or located at the top face of the β-propeller, where 'hotspot' residues affect the binding of β-catenin to the TBLR1 protein. In contrast, those altered by population variation are significantly less likely to be spatially clustered towards the top face or to be at buried or highly conserved residues. This result is useful not only for interpreting benign and pathogenic missense variants in this gene, but also in other WD40 domains, many of which are associated with disease. © The Author 2016. Published by Oxford University Press.
A COMPARISON OF THE CAPITAL STRUCTURES OF THE TOP 40MULTINATIONAL ENTITIES AND THE TOP 40 JSE-LISTED ENTITIES

Directory of Open Access Journals (Sweden)

Lana H. Harmse

2017-01-01

Full Text Available The strategies and policies of multinational entities (MNEscentre onthe focalgoal of any company, which isto maximise profits and shareholder wealth.Management aims for an optimum ownership structure by implementing variousstrategies. One of these strategies is the debt-to-equity ratio (the capital structure.Previous studiesconductedonvariouscountries’locally-listed entities confirmthat the capital structure of an entity has an impact on the value ofthat entity.Thisthen raisesan interesting question as to whetherthecapital structures ofthetop 40Johannesburg Stock Exchange (JSE-listedentitiesare similar to those ofthe top40 global MNEs.Based on market capitalisation on 31December2014, this studysought to compare the capital structures,using the debt-to-equity ratio,ofthe top40JSE-listed entitieswith those ofthe top 40globalMNEs on the Fortune 500list.Independent t-testswere performed on thedebt-to-equity ratios of thetop 40JSE-listed entities and the top 40globalMNEsas a group.Both independent t-tests and the Mann-Whitney testswereperformedonthedebt-to-equity ratiosofapplicable entities of the group divided into threeselectedindustries. The resultsof theindependent t-testindicateastatistical andpractically significant differencebetween the top 40 JSE-listed entities and the top 40 global MNEs’ capitalstructures.The resultsof the Mann-Whitney testsindicatethat if the financialindustry is excluded,there isnostatistical orpractically significant differencebetween the capital structures of the top 40 JSE-listed entities and the top 40MNEs.However, based on the effect size there is a practical visible difference.
40 CFR 1051.1 - Does this part apply for my vehicles or engines?

Science.gov (United States)

2010-07-01

... (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM RECREATIONAL ENGINES AND VEHICLES Overview and Applicability § 1051.1 Does this part apply for my vehicles or engines? (a) The regulations in this part 1051... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Does this part apply for my vehicles...
40 CFR 63.138 - Process wastewater provisions-performance standards for treatment processes managing Group 1...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Process wastewater provisions-performance standards for treatment processes managing Group 1 wastewater streams and/or residuals removed from Group 1 wastewater streams. 63.138 Section 63.138 Protection of Environment ENVIRONMENTAL...
Availability of Dutch biomass for electricity and heat in 2020

International Nuclear Information System (INIS)

Koppejan, J.; Elbersen, W.; Meeusen, M.; Bindraban, P.

2009-11-01

Availability of biomass is an important factor in realizing the Dutch targets for renewable energy. This study maps the availability of Dutch biomass in the framework of alternative applications and sustainability requirements, today and in the future. The conclusion is drawn that there is approximately 13 to 16 million tons of dry biomass available for energy generation in the Netherlands in 2020. This is 30 to 40% of the amount of biomass that is annually used in the Netherlands, generating 53 to 94 PJ of final energy, avoiding 101 to 157 PJ of fossil energy. This availability of biomass and the energy that is generated from the biomass can increase further after 2020. In addition, biomass will also be imported, especially for combustion and co-firing in coal-fired power plants and for the production of transport fuels. [nl
Fix 40!

Index Scriptorium Estoniae

2008-01-01

Ansambel Fix peab 13. detsembril Tallinnas Saku Suurhallis oma 40. sünnipäeva. Kontserdi erikülaline on ansambel Apelsin, kaastegevad Jassi Zahharov ja HaleBopp Singers. Õhtut juhib Tarmo Leinatamm
The melatonin-MT1 receptor axis modulates tumor growth in PTEN-mutated gliomas.

Science.gov (United States)

Ma, Huihui; Wang, Zhen; Hu, Lei; Zhang, Shangrong; Zhao, Chenggang; Yang, Haoran; Wang, Hongzhi; Fang, Zhiyou; Wu, Lijun; Chen, Xueran

2018-02-19

More than 40% of glioma patients have tumors that harbor PTEN (phosphatase and tensin homologue deleted on chromosome ten) mutations; this disease is associated with poor therapeutic resistance and outcome. Such mutations are linked to increased cell survival and growth, decreased apoptosis, and drug resistance; thus, new therapeutic strategies focusing on inhibiting glioma tumorigenesis and progression are urgently needed. Melatonin, an indolamine produced and secreted predominantly by the pineal gland, mediates a variety of physiological functions and possesses antioxidant and antitumor properties. Here, we analyzed the relationship between PTEN and the inhibitory effect of melatonin in primary human glioma cells and cultured glioma cell lines. The results showed that melatonin can inhibit glioma cell growth both in culture and in vivo. This inhibition was associated with PTEN levels, which significantly correlated with the expression level of MT1 in patients. In fact, c-fos-mediated MT1 was shown to be a key modulator of the effect of melatonin on gliomas that harbor wild type PTEN. Taken together, these data suggest that melatonin-MT1 receptor complexes represent a potential target for the treatment of glioma. Copyright © 2018 Elsevier Inc. All rights reserved.
Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study

DEFF Research Database (Denmark)

Mitra, Anita V; Bancroft, Elizabeth K; Barbachano, Yolanda

2011-01-01

mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA >3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (± 5 years) who were negative for the familial mutation. RESULTS: In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2......Study Type - Diagnostic (validating cohort) Level of Evidence 1b OBJECTIVES: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening...... in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. MATERIALS AND METHODS: Men aged 40-69 years from families with BRCA1 or BRCA2...
40 CFR 36.640 - Employee.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Employee. 36.640 Section 36.640... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.640 Employee. (a) Employee means the employee of a recipient directly engaged in the performance of work under the award, including— (1...
40 CFR 27.21 - Discovery.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Discovery. 27.21 Section 27.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...

Health screenings for women ages 40 to 64

Science.gov (United States)

Health maintenance visit - women - ages 40 to 64; Physical exam - women - ages 40 to 64; Yearly exam - ... 64; Checkup - women - ages 40 to 64; Women's health - ages 40 to 64; Preventive care - women - ages ...
Health screenings for men ages 40 to 64

Science.gov (United States)

Health maintenance visit - men - ages 40 to 64; Physical exam - men - ages 40 to 64; Yearly exam - ... 64; Checkup - men - ages 40 to 64; Men's health - ages 40 to 64; Preventive care - men - ages ...
Resveratrol represses YKL-40 expression in human glioma U87 cells

International Nuclear Information System (INIS)

Zhang, Wei; Tamiya, Takashi; Murao, Koji; Zhang, Xiang; Matsumoto, Kensuke; Diah, Suwarni; Okada, Masaki; Miyake, Keisuke; Kawai, Nobuyuki; Fei, Zhou

2010-01-01

Glioblastoma multiforme (GBM) is the most malignant intracranial tumour that develops in both adults and children. Microarray gene analyses have confirmed that the human YKL-40 gene is one of the most over-expressed genes in these tumours but not in normal brain tissue. Clinical studies have shown that serum YKL-40 levels are positively correlated with tumour burden in addition to being an independent prognostic factor of a short relapse-free interval as well as short overall survival in patients with various cancers. Our previous study revealed that YKL-40 was closely correlated with the pathological grades of human primary astrocytomas and played a crucial role in glioma cell proliferation. Hence, YKL-40 could be an attractive target in the design of anti-cancer therapies. Cell viability and invasion assays were performed to detect the cell proliferation and invasive ability of U87 cells induced by resveratrol (3, 5, 4'-trihydroxystilbene; Res) or YKL-40 small-interfering RNAs (siRNAs). In addition, the luciferase assay, real-time RT-PCR, western blotting, and ELISA were used to measure YKL-40 promoter activity, mRNA, and protein expression, respectively. The expressions of phosphor-ERK1/2 and ERK1/2 were determined by western blotting. Res inhibited U87 cell proliferation and invasion in vitro and repressed YKL-40 in U87 cells by decreasing the activity of its promoter and reducing mRNA transcription and protein expression in vitro. YKL-40 siRNA treatment also impaired the invasiveness of U87 cells. When U87 cells were cultured with 20 μM PD98059 (an ERK1/2 inhibitor) alone, with 20 μM PD98059 and 100 μM Res, or with 100 μM Res alone for 48 h, YKL-40 protein expression decreased most significantly in the Res-treated group. PD98059 partially reversed the decrease of YKL-40 protein expression induced by Res. Furthermore, phosphor-ERK1/2 expression was reduced by Res treatment in a time-dependent manner. We demonstrated for the first time that Res
40 keV atomic resolution TEM

International Nuclear Information System (INIS)

Bell, David C.; Russo, Christopher J.; Kolmykov, Dmitry V.

2012-01-01

Here we present the first atomic resolution TEM imaging at 40 keV using an aberration-corrected, monochromated source TEM. Low-voltage High-Resolution Electron Microscopy (LVHREM) has several advantages, including increased cross-sections for inelastic and elastic scattering, increased contrast per electron and improved spectroscopy efficiency, decreased delocalization effects and reduced knock-on damage. Together, these often improve the contrast to damage ratio obtained on a large class of samples. Third-order aberration correction now allows us to operate the TEM at low energies while retaining atomic resolution, which was previously impossible. At low voltage the major limitation to resolution becomes the chromatic aberration limit. We show that using a source monochromator we are able to reduce the effect of chromatic aberration and achieve a usable high-resolution limit at 40 keV to less than 1 Å. We show various materials' examples of the application of the technique to image graphene and silicon, and compare atomic resolution images with electron multislice simulations. -- Highlights: ► We present the first atomic resolution images recorded at 40 keV using an aberration-corrected, monochromated TEM. ► We show information transfer measured to better than 1 Å. ► At 40 keV an aberration-corrected monochromated TEM is limited by fifth-order spherical aberration. ► We show that using a monochromator the effect of chromatic aberration is reduced to enable high resolution imaging. ► Low voltage high resolution electron microscopy will be beneficial for imaging the organic/inorganic materials interface.
40 CFR 180.482 - Tebufenozide; tolerances for residues.

Science.gov (United States)

2010-07-01

... stem, subgroup 5A 5.0 Brassica, leafy greens, subgroup 5B 10.0 Canola, refined oil 4.0 Canola, seed 2.0..., forage, fodder and hay, group 17 1.0 Vegetable, foliage of legume, group 7 0.20 [60 FR 29347, May 31... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Tebufenozide; tolerances for residues...
22 CFR 224.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Stays ordered by the Department of Justice. 224.40 Section 224.40 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT IMPLEMENTATION OF THE PROGRAM FRAUD CIVIL REMEDIES ACT § 224.40 Stays ordered by the Department of Justice. If at any time the...
49 CFR 31.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Stays ordered by the Department of Justice. 31.40 Section 31.40 Transportation Office of the Secretary of Transportation PROGRAM FRAUD CIVIL REMEDIES § 31.40 Stays ordered by the Department of Justice. If at any time the Attorney General or an Assistant...
6 CFR 13.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Stays ordered by the Department of Justice. 13.40 Section 13.40 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.40 Stays ordered by the Department of Justice. If at any time the Attorney...
40 CFR 426.55 - Standards of performance for new sources.

Science.gov (United States)

2010-07-01

... establish the quantity or quality of pollutants or pollutant properties, controlled by this section, which...— Metric units (g/kkg of product) TSS 0.70 0.70 Oil 1.40 1 .40 Phosphorus 0.05 .05 pH (1) (1) English units (lb/ton of product) TSS 0.0014 0.0014 Oil 0.0028 .0028 Phosphorus 0.0001 .0001 pH (1) (1) 1 Within the...
40 CFR Table 1 to Subpart Xxxx of... - Emission Limits for Tire Production Affected Sources

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Emission Limits for Tire Production Affected Sources 1 Table 1 to Subpart XXXX of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION.... 63, Subpt. XXXX, Table 1 Table 1 to Subpart XXXX of Part 63—Emission Limits for Tire Production...
Programming C# 40

CERN Document Server

Griffiths, Ian; Liberty, Jesse

2010-01-01

With its support for dynamic programming, C# 4.0 continues to evolve as a versatile language on its own. But when C# is used with .NET Framework 4, the combination is incredibly powerful. This bestselling tutorial shows you how to build web, desktop, and rich Internet applications using C# 4.0 with .NET's database capabilities, UI framework (WPF), extensive communication services (WCF), and more. In this sixth edition, .NET experts Ian Griffiths, Matthew Adams, and Jesse Liberty cover the latest enhancements to C#, as well as the fundamentals of both the language and framework. You'll learn
Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

NARCIS (Netherlands)

Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

2007-01-01

Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and
40 CFR 89.206 - Trading.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Trading. 89.206 Section 89.206... EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES Averaging, Banking, and Trading Provisions § 89.206 Trading. (a) Requirements for Tier 1 engines rated at or above 37 kW. (1) A nonroad...
40 CFR 89.205 - Banking.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Banking. 89.205 Section 89.205... EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES Averaging, Banking, and Trading Provisions § 89.205 Banking. (a) Requirements for Tier 1 engines rated at or above 37 kW. (1) A manufacturer...
40 CFR 90.205 - Banking.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Banking. 90.205 Section 90.205... EMISSIONS FROM NONROAD SPARK-IGNITION ENGINES AT OR BELOW 19 KILOWATTS Certification Averaging, Banking, and Trading Provisions § 90.205 Banking. (a)(1) Beginning August 1, 2007, a manufacturer of a Class I engine...
Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients

Science.gov (United States)

de Bot, Susanne T; Burggraaff, Rogier C; Herkert, Johanna C; Schelhaas, Helenius J; Post, Bart; Diekstra, Adinda; van Vliet, Reinout O; van der Knaap, Marjo S; Kamsteeg, Erik-Jan; Scheffer, Hans; van de Warrenburg, Bart P; Verschuuren-Bemelmans, Corien C; Kremer, Hubertus PH

2013-01-01

Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providing SPG11 mutation analysis, between 1 January 2009 and 1 January 2011. We identified nine different SPG11 mutations, four of which are novel, in nine index patients. Eighteen SPG11 patients from these nine families were studied by means of a retrospective chart analysis and additional interview/examination. Ages at onset were between 4 months and 14 years; 39% started with learning difficulties rather than gait impairment. Brain magnetic resonance imaging showed a thin corpus callosum and typical periventricular white matter changes in the frontal horn region (known as the ‘ears-of the lynx'-sign) in all. Most patients became wheelchair bound after a disease duration of 1 to 2 decades. End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures. Several patients died of complications between ages 30 and 48 years, 3–4 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span. PMID:23443022
CASMO5 JENDL-4.0 and ENDF/B-VII.1beta4 libraries

International Nuclear Information System (INIS)

Rhodes, J.; Gheorghiu, N.; Ferrer, R.

2012-01-01

This paper details the generation of neutron data libraries for the CASMO5 lattice physics code based on the recently released JENDL-4.0 and ENDF/B-VII.1beta4 nuclear data evaluations. This data represents state-of-the-art nuclear data for late-2011. The key features of the new evaluations are briefly described along with the procedure for processing of this data into CASMO5, 586-energy group neutron data libraries. Finally some CASMO5 results for standard UO 2 and MOX critical experiments for the two new libraries and the current ENDF/B-VII.0 CASMO5 library are presented including the B and W 1810 series, DIMPLE S06A, S06B, TCA reflector criticals with iron plates and the PNL-30-35 MOX criticals. The results show that CASMO5 with the new libraries is performing well for these criticals with a very slight edge in results to the JENDL-4.0 nuclear data evaluation over the ENDF/B-VII.1beta4 evaluation. Work is currently underway to generate a CASMO5 library based on the final ENDF/B-VII.R1 evaluation released Dec. 22, 2011. (authors)
A study of the face validity of the 40 item version of the Defense Style Questionnaire (DSQ-40).

Science.gov (United States)

Chabrol, Henri; Rousseau, Amélie; Rodgers, Rachel; Callahan, Stacey; Pirlot, Gérard; Sztulman, Henri

2005-11-01

There are few studies examining the face validity of the 40-item version of the Defense Style Questionnaire (DSQ-40). Moreover, the existing studies have provided conflicting results. The present study provides an in-depth examination of the face validity of the DSQ-40. Eight clinicians independently attributed each item of the DSQ-40 to a defense mechanism. The defense mechanisms listed in the DSM-IV Defensive Functioning Scale and their definitions were provided as a guide, along with the definition of those defense mechanisms investigated by the DSQ that are not included. It was further specified that the raters could attribute the items to defense mechanisms other than those listed or coping mechanisms. Twelve items out of 40 (30%) were attributed to the defense mechanisms they were supposed to investigate by fewer than four out of the eight raters. This result suggests that a substantial part of the DSQ-40 is lacking in face validity.
Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain.

Science.gov (United States)

Sartorius, Tina; Drescher, Andrea; Panse, Madhura; Lastovicka, Petr; Peter, Andreas; Weigert, Cora; Kostenis, Evi; Ullrich, Susanne; Häring, Hans-Ulrich

2015-01-01

Conjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs. After chronic application of CLAs C57BL/6J wild type (WT) and GPR40/FFAR1 (Ffar1(-/-)) knockout mice developed insulin resistance. Although CLAs accumulated in liver up to 46-fold genotype-independently, hepatic triglycerides augmented only in WT mice. This triglyceride deposition was not associated with increased inflammation. In contrast, in brain of CLA fed Ffar1(-/-) mice mRNA levels of TNF-α were 2-fold higher than in brain of WT mice although CLAs accumulated genotype-independently in brain up to 4-fold. Concomitantly, Ffar1(-/-) mice did not respond to intracerebroventricular (i.c.v.) insulin injection with an increase in cortical activity while WT mice reacted as assessed by radiotelemetric electrocorticography (ECoG) measurements. In vitro incubation of primary murine astrocytes confirmed that CLAs stimulate neuronal inflammation independent of GPR40/FFAR1. This study discloses that GPR40/FFAR1 indirectly modulates organ-specific effects of CLAs: the expression of functional GPR40/FFAR1 counteracts CLA-induced inflammation and insulin resistance in the brain, but favors the development of fatty liver. © 2015 S. Karger AG, Basel.
Assessment of serum levels of soluble CD40L in Egyptian children and adolescents with type 1 diabetes mellitus: Relationship to microalbuminuria and glycemic control

Directory of Open Access Journals (Sweden)

Kotb Abbass Metwalley

2013-01-01

Full Text Available Context: Soluble CD40 ligand (sCD40L is known to be elevated in different clinical situations including hypercholesterolemia, acute coronary syndromes, and type 2 diabetes mellitus (T2DM, Data about the relationship between type 1 diabetes mellitus (T1DM and sCD40L is limited. In addition, the potential role ofsCD40Lin the pathogenesis of vascular complications in children and adolescents with T1DM is to be clarified. Hence, the study aimed at assessment of sCD40L levels in children and adolescents with T1DM and correlation of these levels with glycemic control and microalbuminuria. Settings and Design: Cross-sectional controlled study. Materials and Methods: The study was performed in the Pediatric Endocrinology and Diabetes Unit, Assuit University Children Hospital, Assiut, Egypt. It included 70 children and adolescents with T1DM (mean age 14. 76 ± 2.21 years. Cases were further subdivided into 43 cases with normoalbuminuria and 27 cases with microalbuminuria according to presence or absence or microalbuminuria in fresh urine samples. Twentyfive healthy subjects, age- and sex-matched were included as control group (mean age = 13.62 ± 2.11 years. Studied cases were subjected to medical history, clinical examination, and laboratory assessment of fasting blood glucose (FBG, lipid profile, glycosylated hemoglobin (HbA1c, and sCD40L were performed. Results: Mean HbA1c and sCD40L were significantly higher in diabetic children (n = 70 compared to control (n = 25 (P < 0.001 for each. Mean HbA1c and sCD40L levels were significantly higher in microalbuminuric cases (n = 27 compared to normoalbuminuric cases (n = 43 (P < 0.05 and <0.01, respectively.We also observed a significant positive correlation between sCD40L levels and the age, diabetes duration, HbA1c, and urinary albumin creatinine ratio. Conclusions: The high serum sCD40L levels in children and adolescents with T1DM particularly in those with microalbminuria and its positive correlation with

A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia

Science.gov (United States)

Coutelier, Marie; Blesneac, Iulia; Monteil, Arnaud; Monin, Marie-Lorraine; Ando, Kunie; Mundwiller, Emeline; Brusco, Alfredo; Le Ber, Isabelle; Anheim, Mathieu; Castrioto, Anna; Duyckaerts, Charles; Brice, Alexis; Durr, Alexandra; Lory, Philippe; Stevanin, Giovanni

2015-01-01

Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs. PMID:26456284
Rrp12 and the Exportin Crm1 participate in late assembly events in the nucleolus during 40S ribosomal subunit biogenesis.

Science.gov (United States)

Moriggi, Giulia; Nieto, Blanca; Dosil, Mercedes

2014-12-01

During the biogenesis of small ribosomal subunits in eukaryotes, the pre-40S particles formed in the nucleolus are rapidly transported to the cytoplasm. The mechanisms underlying the nuclear export of these particles and its coordination with other biogenesis steps are mostly unknown. Here we show that yeast Rrp12 is required for the exit of pre-40S particles to the cytoplasm and for proper maturation dynamics of upstream 90S pre-ribosomes. Due to this, in vivo elimination of Rrp12 leads to an accumulation of nucleoplasmic 90S to pre-40S transitional particles, abnormal 35S pre-rRNA processing, delayed elimination of processing byproducts, and no export of intermediate pre-40S complexes. The exportin Crm1 is also required for the same pre-ribosome maturation events that involve Rrp12. Thus, in addition to their implication in nuclear export, Rrp12 and Crm1 participate in earlier biosynthetic steps that take place in the nucleolus. Our results indicate that, in the 40S subunit synthesis pathway, the completion of early pre-40S particle assembly, the initiation of byproduct degradation and the priming for nuclear export occur in an integrated manner in late 90S pre-ribosomes.
43 CFR 35.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Stays ordered by the Department of Justice. 35.40 Section 35.40 Public Lands: Interior Office of the Secretary of the Interior ADMINISTRATIVE REMEDIES FOR FRAUDULENT CLAIMS AND STATEMENTS § 35.40 Stays ordered by the Department of Justice. If at any...
10 CFR 13.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Stays ordered by the Department of Justice. 13.40 Section 13.40 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.40 Stays ordered by the Department of Justice. If at any time the Attorney General or an Assistant Attorney General designated by the...
22 CFR 35.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Stays ordered by the Department of Justice. 35.40 Section 35.40 Foreign Relations DEPARTMENT OF STATE CLAIMS AND STOLEN PROPERTY PROGRAM FRAUD CIVIL REMEDIES § 35.40 Stays ordered by the Department of Justice. If at any time the Attorney General or an...
45 CFR 79.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Stays ordered by the Department of Justice. 79.40 Section 79.40 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.40 Stays ordered by the Department of Justice. If at any time the Attorney General...
34 CFR 33.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Stays ordered by the Department of Justice. 33.40 Section 33.40 Education Office of the Secretary, Department of Education PROGRAM FRAUD CIVIL REMEDIES ACT § 33.40 Stays ordered by the Department of Justice. If at any time the Attorney General or an Assistant...
40 CFR 22.10 - Appearances.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Appearances. 22.10 Section 22.10 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL CONSOLIDATED RULES OF PRACTICE GOVERNING... and ethics required of practitioners before the courts of the United States. ...
KeyPathwayMiner 4.0

DEFF Research Database (Denmark)

Alcaraz, Nicolas; Pauling, Josch; Batra, Richa

2014-01-01

release of KeyPathwayMiner (version 4.0) that is not limited to analyses of single omics data sets, e.g. gene expression, but is able to directly combine several different omics data types. Version 4.0 can further integrate existing knowledge by adding a search bias towards sub-networks that contain...... (avoid) genes provided in a positive (negative) list. Finally the new release now also provides a set of novel visualization features and has been implemented as an app for the standard bioinformatics network analysis tool: Cytoscape. CONCLUSION: With KeyPathwayMiner 4.0, we publish a Cytoscape app...
ERA-40

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — ERA-40 project was to produce and promote the use of a comprehensive set of global analysis describing the state of the atmosphere and land and ocean-wave conditions...
Monomeric Aβ1–40 and Aβ1–42 Peptides in Solution Adopt Very Similar Ramachandran Map Distributions That Closely Resemble Random Coil

Science.gov (United States)

2016-01-01

The pathogenesis of Alzheimer’s disease is characterized by the aggregation and fibrillation of amyloid peptides Aβ1–40 and Aβ1–42 into amyloid plaques. Despite strong potential therapeutic interest, the structural pathways associated with the conversion of monomeric Aβ peptides into oligomeric species remain largely unknown. In particular, the higher aggregation propensity and associated toxicity of Aβ1–42 compared to that of Aβ1–40 are poorly understood. To explore in detail the structural propensity of the monomeric Aβ1–40 and Aβ1–42 peptides in solution, we recorded a large set of nuclear magnetic resonance (NMR) parameters, including chemical shifts, nuclear Overhauser effects (NOEs), and J couplings. Systematic comparisons show that at neutral pH the Aβ1–40 and Aβ1–42 peptides populate almost indistinguishable coil-like conformations. Nuclear Overhauser effect spectra collected at very high resolution remove assignment ambiguities and show no long-range NOE contacts. Six sets of backbone J couplings (3JHNHα, 3JC′C′, 3JC′Hα, 1JHαCα, 2JNCα, and 1JNCα) recorded for Aβ1–40 were used as input for the recently developed MERA Ramachandran map analysis, yielding residue-specific backbone ϕ/ψ torsion angle distributions that closely resemble random coil distributions, the absence of a significantly elevated propensity for β-conformations in the C-terminal region of the peptide, and a small but distinct propensity for αL at K28. Our results suggest that the self-association of Aβ peptides into toxic oligomers is not driven by elevated propensities of the monomeric species to adopt β-strand-like conformations. Instead, the accelerated disappearance of Aβ NMR signals in D2O over H2O, particularly pronounced for Aβ1–42, suggests that intermolecular interactions between the hydrophobic regions of the peptide dominate the aggregation process. PMID:26780756
SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma.

NARCIS (Netherlands)

Bayley, J.P.M.; Kunst, H.P.M.; Cascon, A.; Sampietro, M.L.; Gaal, J.; Korpershoek, E.; Hinojar-Gutierrez, A.; Timmers, H.J.L.M.; Hoefsloot, L.H.; Hermsen, M.A.; Suarez, C.; Hussain, A.K.; Vriends, A.H.; Hes, F.J.; Jansen, J.C.; Tops, C.M.; Corssmit, E.P.; Knijff, P. de; Lenders, J.W.M.; Cremers, C.W.R.J.; Devilee, P.; Dinjens, W.N.; Krijger, R.R. de; Robledo, M.

2010-01-01

BACKGROUND: Paragangliomas and phaeochromocytomas are neuroendocrine tumours associated frequently with germline mutations of SDHD, SDHC, and SDHB. Previous studies have shown the imprinted SDHAF2 gene to be mutated in a large Dutch kindred with paragangliomas. We aimed to identify SDHAF2 mutation
Dietary factors and Truncating APC Mutations in Sporadic Colorectal Adenomas

NARCIS (Netherlands)

Diergaarde, B.; Tiemersma, E.W.; Braam, H.; Muijen, van G.N.P.; Nagengast, F.M.; Kok, F.J.; Kampman, E.

2005-01-01

Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control
Dietary factors and truncating APC mutations in sporadic colorectal adenomas.

NARCIS (Netherlands)

Diergaarde, B.; Tiemersma, E.W.; Braam, H.; Muijen, G.N.P. van; Nagengast, F.M.; Kok, F.J.; Kampman, E.

2005-01-01

Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control
Training in the Industry 4.0 (in Spain and Italy

Directory of Open Access Journals (Sweden)

Djamil Tony Kahale Carrillo

2016-12-01

Full Text Available The Industry 4.0, known as the fourth industrial revolution, refers to an industrial revolution that is stimulated by the digital transformation and the introduction of the digital technology in the industry in general. The digital transformation supposes the whole challenge for the Spanish and Italian industry; nevertheless, it offers the opportunity to improve the competitive position on the international market.The reports indicate that the digitalization of the industry will suppose the disappearance of 7,1 million employments in 15 countries most industrialized of the world; as well as the creation of 2,1 million new positions for 2020. For this better competitive position of the activation of the Industry 4.0 there is needed that the workers have a training 4.0, provided that new professions based on the digitalization will be demanded.The present study offers a first definition of the Industry 4.0 and an analysis of the training policies for Industry 4.0 in Spain and Italy, concluding with some remarks.
Determination of {sup 40}K in water samples; Determinacion del {sup 40}K en muestras de agua

Energy Technology Data Exchange (ETDEWEB)

Delgado, C. E.; Miranda C, L.; Cuevas J, A. K.; Vega C, H. R., E-mail: rmfranccesco0223@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

2014-10-15

The natural water used for human consumption comes from different sources, which may contain suspended solids in varying proportions. In groundwater, the source of suspended solids is related to the dissolution of mineral strata by the waters and leaching of rocks. Also, the radioactivity could concentrate on the bodies of slow-moving water that eventually could present a risk to ecosystems, as well as for the consumer. The water usually contains several natural radionuclides as: tritium, radon, radio, uranium isotopes, etc. The objective of this study was to evaluate the concentration of {sup 40}K in water from different areas of Zacatecas state (Mexico). Four water samples were taken in triplicate from different areas; the {sup 40}K concentration was measured with a spectrum metric system of gamma radiation with NaI (Tl) scintillation detector of 7.62 cm. In the measuring process a standard was prepared using water and KCl analytic grade where the {sup 40}K concentration is 6.25 mol/Lt adding 250 mg/ml of potassium. Also the system was calibrated in energy using 3 point sources of {sup 137}Cs, diameter {sup 22}Na and 7.62 cm of height, using containers Marinelli and {sup 60}Co. In the obtained spectra was observed that the photon of 1.432 MeV that emits the {sup 40}K when decaying is the most important. The highest concentration was of 123 ± 5.2 Bq/lt and the lowest was of 9 ± 0.4 Bq/lt. Under the standards of drinking water, an amount of {sup 40}K deposits an effective dose which contributes to annual dose received by people. (Author)
The prevalence of BRCA1 mutations among young women with triple-negative breast cancer

International Nuclear Information System (INIS)

Young, SR; DeSai, Damini; Zandvakili, Inuk; Royer, Robert; Li, Song; Narod, Steven A; Pilarski, Robert T; Donenberg, Talia; Shapiro, Charles; Hammond, Lyn S; Miller, Judith; Brooks, Karen A; Cohen, Stephanie; Tenenholz, Beverly

2009-01-01

Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer. We studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT) and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE). All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing. Five deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%). Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer
29 CFR 22.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Stays ordered by the Department of Justice. 22.40 Section 22.40 Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.40 Stays ordered by the Department of Justice. If at any time the Attorney General or an Assistant Attorney General...
15 CFR 25.40 - Stays ordered by the Department of Justice.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Stays ordered by the Department of Justice. 25.40 Section 25.40 Commerce and Foreign Trade Office of the Secretary of Commerce PROGRAM Fraud Civil Remedies § 25.40 Stays ordered by the Department of Justice. If at any time the Attorney General...
Inkoopwijsheden: 40 stellingen uit inkoopproefschriften

NARCIS (Netherlands)

Schotanus, Fredo

2006-01-01

40 inkoopwijsheden opgesteld door 10 NEVI-inkooppromovendi in de afgelopen 10 jaren. Dat is wat de onderstaande lijst weergeeft, samengesteld door promovendus Fredo Schotanus. De lijst is gerangschikt naar datum en soms vertaald naar het Nederlands. De lijst is niet een top 40 lijst, maar geeft wel

27 CFR 40.201 - Inventories.

Science.gov (United States)

2010-04-01

... PROCESSED TOBACCO Operations by Manufacturers of Tobacco Products Inventories and Reports § 40.201 Inventories. Every manufacturer of tobacco products shall make true and accurate inventories on Form 5210.9... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Inventories. 40.201...
Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

Science.gov (United States)

Ali, Selman A; Ahmad, Murrium; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Choolun, Esther; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

2004-09-09

OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.
Hip Arthroscopy in Patients Age 40 or Older: A Systematic Review.

Science.gov (United States)

Horner, Nolan S; Ekhtiari, Seper; Simunovic, Nicole; Safran, Marc R; Philippon, Marc J; Ayeni, Olufemi R

2017-02-01

To (1) report clinical outcomes, complication rates, and total hip arthroplasty (THA) conversion rates for patients age 40 or older who underwent hip arthroscopy, and (2) report any age-related predictors of outcome identified in the literature. MEDLINE, EMBASE, and PubMed were searched for relevant studies and pertinent data were abstracted from eligible studies. No meta-analysis was performed because of heterogeneity amongst studies. Seventeen studies were included in this review comprising 16,327 patients, including 9,954 patients age 40 or older. All studies reported statistically significant improvements in outcomes after hip arthroscopy for femoral osteochondroplasty, labral repair, or unspecified indications. In patients 40 or older who underwent labral debridement, these improvements were not clinically significant. Obesity and osteoarthritic changes predicted poorer outcomes. Only 1 of 3 studies directly comparing the 2 groups found that patients 40 or older had a significantly less improvement in a standardized hip outcome score than patients under 40 after hip arthroscopy, but all found that patients 40 or older had significantly higher rates of THA conversion. The rate of conversion to THA was 18.1% for patients 40 or older, 23.1% for patients over 50, and 25.2% for patients over 60 with a mean of 25.0 months to THA. Indications for hip arthroscopy including femoral osteochondroplasty and labral repair resulted in clinically significant improvements in patients 40 or older in most research studies examined in this review, whereas labral debridement did not produce clinically significant improvements postoperatively in the same studies. In these studies, the rate of conversion to THA is higher than in patients under 40 and increases with each decade of life, with many individual studies showing a significant increase in the rate of THA conversion. Hip arthroscopy may be suitable for some patients 40 or older, but patient selection is key and patients
PRO40 is a scaffold protein of the cell wall integrity pathway, linking the MAP kinase module to the upstream activator protein kinase C.

Directory of Open Access Journals (Sweden)

Ines Teichert

2014-09-01

Full Text Available Mitogen-activated protein kinase (MAPK pathways are crucial signaling instruments in eukaryotes. Most ascomycetes possess three MAPK modules that are involved in key developmental processes like sexual propagation or pathogenesis. However, the regulation of these modules by adapters or scaffolds is largely unknown. Here, we studied the function of the cell wall integrity (CWI MAPK module in the model fungus Sordaria macrospora. Using a forward genetic approach, we found that sterile mutant pro30 has a mutated mik1 gene that encodes the MAPK kinase kinase (MAPKKK of the proposed CWI pathway. We generated single deletion mutants lacking MAPKKK MIK1, MAPK kinase (MAPKK MEK1, or MAPK MAK1 and found them all to be sterile, cell fusion-deficient and highly impaired in vegetative growth and cell wall stress response. By searching for MEK1 interaction partners via tandem affinity purification and mass spectrometry, we identified previously characterized developmental protein PRO40 as a MEK1 interaction partner. Although fungal PRO40 homologs have been implicated in diverse developmental processes, their molecular function is currently unknown. Extensive affinity purification, mass spectrometry, and yeast two-hybrid experiments showed that PRO40 is able to bind MIK1, MEK1, and the upstream activator protein kinase C (PKC1. We further found that the PRO40 N-terminal disordered region and the central region encompassing a WW interaction domain are sufficient to govern interaction with MEK1. Most importantly, time- and stress-dependent phosphorylation studies showed that PRO40 is required for MAK1 activity. The sum of our results implies that PRO40 is a scaffold protein for the CWI pathway, linking the MAPK module to the upstream activator PKC1. Our data provide important insights into the mechanistic role of a protein that has been implicated in sexual and asexual development, cell fusion, symbiosis, and pathogenicity in different fungal systems.
Biological activity of SV40 DNA

International Nuclear Information System (INIS)

Abrahams, P.J.

1978-01-01

This thesis deals with a study on the biological activity of SV40 DNA. The transforming activity of SV40 DNA and DNA fragments is investigated in order to define as precisely as possible the area of the viral genome that is involved in the transformation. The infectivity of SV40 DNA is used to study the defective repair mechanisms of radiation damages of human xeroderma pigmentosum cells. (C.F.)
Serum YKL-40 and gestational diabetes - an observational cohort study

DEFF Research Database (Denmark)

Gybel-Brask, Dorte; Johansen, Julia S; Christiansen, Ib J

2016-01-01

To examine serum YKL-40 in women developing gestational diabetes mellitus (GDM). In the present large observational cohort study of 1179 pregnant women, we determined serum YKL-40 four times during pregnancy (at gestational age 12, 20, 25, and 32 weeks). Pregnancy outcome was obtained from medical...... records. Sixty-eight women (5.8%) developed GDM. Serum YKL-40 increased from gestational age (GA) 12 weeks and the following weeks in the women who developed GDM and was independent of BMI, parity, and maternal age (OR = 2.69, 95% CI: 1.45-5.00, p = 0.002). No association was found between serum YKL-40...
YKL-40 tissue expression and plasma levels in patients with ovarian cancer

DEFF Research Database (Denmark)

Høgdall, Estrid V S; Ringsholt, Merete; Høgdall, Claus K

2009-01-01

survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. METHODS: YKL-40 protein expression was determined by immunohistochemistry...... in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. RESULTS: YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor...... stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40-3.25, p = 0.0004). CONCLUSION: YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic...
28 CFR 40.13 - Review by the Attorney General.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Review by the Attorney General. 40.13... Procedures for Obtaining Certification of a Grievance Procedure § 40.13 Review by the Attorney General. The Attorney General shall review and respond to each application as promptly as the circumstances, including...
42 CFR 84.40 - Quality control plans; filing requirements.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Quality control plans; filing requirements. 84.40... Control § 84.40 Quality control plans; filing requirements. As a part of each application for approval or... proposed quality control plan which shall be designed to assure the quality of respiratory protection...
40 CFR 52.1960 - Original Identification of plan section.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Original Identification of plan section... Original Identification of plan section. (a) This section identifies the original “State of Oklahoma Air... § 856.1(C) of the Oklahoma statutes to mean “original equipment manufacturer (OEM) or equivalent”. (40...
48 CFR 9905.505-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... paragraphs (a) through (d) of this subsection shall be subject to the same cost accounting principles.... 9905.505-40 Section 9905.505-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.505-40 Fundamental...
48 CFR 9904.406-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.406-40 Section 9904.406-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.406-40 Fundamental requirement. (a) A contractor shall...
48 CFR 9904.407-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.407-40 Section 9904.407-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.407-40 Fundamental requirement. Standard costs may be...
48 CFR 9905.501-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.501-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.501-40 Section 9905.501-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...
48 CFR 9905.502-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.502-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.502-40 Section 9905.502-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...
48 CFR 9905.506-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.506-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.506-40 Section 9905.506-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...
48 CFR 9904.404-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.404-40 Section 9904.404-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.404-40 Fundamental requirement. (a) The acquisition cost...
48 CFR 9904.409-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.409-40 Section 9904.409-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.409-40 Fundamental requirement. (a) The depreciable cost...
48 CFR 9904.408-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.408-40 Section 9904.408-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.408-40 Fundamental requirement. (a) The costs of...
48 CFR 9904.405-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.405-40 Section 9904.405-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.405-40 Fundamental requirement. (a) Costs expressly...

48 CFR 9904.401-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.401-40 Section 9904.401-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.401-40 Fundamental requirement. (a) A contractor's...
Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent mutations of UNC5C and prognostic importance of DNA repair gene mutations on survival.

Science.gov (United States)

Yap, Kai Lee; Kiyotani, Kazuma; Tamura, Kenji; Antic, Tatjana; Jang, Miran; Montoya, Magdeline; Campanile, Alexa; Yew, Poh Yin; Ganshert, Cory; Fujioka, Tomoaki; Steinberg, Gary D; O'Donnell, Peter H; Nakamura, Yusuke

2014-12-15

Because of suboptimal outcomes in muscle-invasive bladder cancer even with multimodality therapy, determination of potential genetic drivers offers the possibility of improving therapeutic approaches and discovering novel prognostic indicators. Using pTN staging, we case-matched 81 patients with resected ≥pT2 bladder cancers for whom perioperative chemotherapy use and disease recurrence status were known. Whole-exome sequencing was conducted in 43 cases to identify recurrent somatic mutations and targeted sequencing of 10 genes selected from the initial screening in an additional 38 cases was completed. Mutational profiles along with clinicopathologic information were correlated with recurrence-free survival (RFS) in the patients. We identified recurrent novel somatic mutations in the gene UNC5C (9.9%), in addition to TP53 (40.7%), KDM6A (21.0%), and TSC1 (12.3%). Patients who were carriers of somatic mutations in DNA repair genes (one or more of ATM, ERCC2, FANCD2, PALB2, BRCA1, or BRCA2) had a higher overall number of somatic mutations (P = 0.011). Importantly, after a median follow-up of 40.4 months, carriers of somatic mutations (n = 25) in any of these six DNA repair genes had significantly enhanced RFS compared with noncarriers [median, 32.4 vs. 14.8 months; hazard ratio of 0.46, 95% confidence interval (CI), 0.22-0.98; P = 0.0435], after adjustment for pathologic pTN staging and independent of adjuvant chemotherapy usage. Better prognostic outcomes of individuals carrying somatic mutations in DNA repair genes suggest these mutations as favorable prognostic events in muscle-invasive bladder cancer. Additional mechanistic investigation into the previously undiscovered role of UNC5C in bladder cancer is warranted. ©2014 American Association for Cancer Research.
Anti-CD40-mediated cancer immunotherapy

DEFF Research Database (Denmark)

Hassan, Sufia Butt; Sørensen, Jesper Freddie; Olsen, Barbara Nicola

2014-01-01

activation and thus enhancement of immune responses. Treatment with anti-CD40 monoclonal antibodies has been exploited in several cancer immunotherapy studies in mice and led to the development of anti-CD40 antibodies for clinical use. Here, Dacetuzumab and Lucatumumab are in the most advanced stage...... with other cancer immunotherapies, in particular interleukin (IL)-2. An in-depth analysis of this immunotherapy is provided elsewhere. In the present review, we provide an update of the most recent clinical trials with anti-CD40 antibodies. We present and discuss recent and ongoing clinical trials...... in this field, including clinical studies which combine anti-CD40 treatment with other cancer-treatments, such as Rituximab and Tremelimumab....
Deletion map of CYC1 mutants and its correspondence to mutationally altered iso-1-cytochromes c of yeast

International Nuclear Information System (INIS)

Sherman, F.; Jackson, M.; Liebman, S.W.; Schweingruber, A.M.; Stewart, J.W.

1975-01-01

Mutants arising spontaneously from sporulated cultures of certain strains of yeast, Saccharomyces cerevisiae, contained deletions of the CYC1 gene which controls the primary structure of iso-1-cytochrome c. At least 60 different kinds of deletions were uncovered among the 104 deletions examined and these ranged in length from those encompassing only two adjacent point mutants to those encompassing at least the entire CYC1 gene. X-ray-induced recombination rates of crosses involving these deletions and cyc1 point mutants resulted in the assignment of 211 point mutants to 47 mutational sites and made it possible to unambiguously order 40 of these 47 sites. Except for one mutant, cyc1-15, there was a strict colinear relationship between the deletion map and the positions of 13 sites that were previously determined by amino acid alterations in iso-1-cytochromes c from intragenic revertants
Replicative intermediates in UV-irradiated Simian virus 40

International Nuclear Information System (INIS)

Clark, J.M.; Hanawalt, P.C.

1984-01-01

The authors have used Simian virus 40 (SV40) as a probe to study the replication of UV-damaged DNA in mammalian cells. Viral DNA replication in infected monkey kidney cells was synchronized by incubating a mutant of SV40 (tsA58) temperature-sensitive for the initiation of DNA synthesis at the restrictive temperature and then adding aphidicolin to temporarily inhibit DNA synthesis at the permissive temperature while permitting pre-replicative events to occur. After removal of the drug, the infected cells were irradiated at 100 J/m 2 (254 nm) to produce 6-7 pyrimidine dimers per SV40 genome, and returned to the restrictive temperature to prevent reinitiation of replication from the SV40 origin. Replicative intermediates (RI) were labeled with [ 3 H]thymidine. The size distribution of daughter DNA strands in RI isolated shortly after irradiation was skewed towards lengths less than the interdimer spacing in parental DNA; this bias persisted for at least 1 h after irradiation, but disappeared within 3 h by which time the size of the newly-synthesized DNA exceeded the interdimer distance. Evidence was obtained for the generation at late times after irradiation, of Form I molecules in which the daughter DNA strand contain dimers. Thus DNA strand exchange as well as trans-dimer synthesis may be involved in the generation of supercoiled Form I DNA from 0V-damaged SV40 replicative intermediates. (Auth.)
Prevalence of- and risk factors for work disability in Dutch patients with inflammatory bowel disease.

Science.gov (United States)

Spekhorst, Lieke M; Oldenburg, Bas; van Bodegraven, Ad A; de Jong, Dirk J; Imhann, Floris; van der Meulen-de Jong, Andrea E; Pierik, Marieke J; van der Woude, Janneke C; Dijkstra, Gerard; D'Haens, Geert; Löwenberg, Mark; Weersma, Rinse K; Festen, Eleonora A M

2017-12-14

To determine the prevalence of work disability in inflammatory bowel disease (IBD), and to assess risk factors associated with work disability. For this retrospective cohort study, we retrieved clinical data from the Dutch IBD Biobank on July 2014, containing electronic patient records of 3388 IBD patients treated in the eight University Medical Centers in the Netherlands. Prevalence of work disability was assessed in 2794 IBD patients and compared with the general Dutch population. Multivariate analyses were performed for work disability (sick leave, partial and full disability) and long-term full work disability (> 80% work disability for > 2 years). Prevalence of work disability was higher in Crohn's disease (CD) (29%) and ulcerative colitis (UC) (19%) patients compared to the general Dutch population (7%). In all IBD patients, female sex, a lower education level, and extra-intestinal manifestations, were associated with work disability. In CD patients, an age > 40 years at diagnosis, disease duration > 15 years, smoking, surgical interventions, and anti-TNFα use were associated with work disability. In UC patients, an age > 55 years, and immunomodulator use were associated with work disability. In CD patients, a lower education level (OR = 1.62, 95%CI: 1.02-2.58), and in UC patients, disease complications (OR = 3.39, 95%CI: 1.09-10.58) were associated with long-term full work disability. The prevalence of work disability in IBD patients is higher than in the general Dutch population. Early assessment of risk factors for work disability is necessary, as work disability is substantial among IBD patients.
40 CFR 31.32 - Equipment.

Science.gov (United States)

2010-07-01

... awarding agency. (d) Management requirements. Procedures for managing equipment (including replacement... return. (e) Disposition. When original or replacement equipment acquired under a grant or subgrant is no... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Equipment. 31.32 Section 31.32...
40 CFR 36.655 - Individual.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Individual. 36.655 Section 36.655 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.655 Individual. Individual means a...
40 years of formal methods

DEFF Research Database (Denmark)

Bjørner, Dines; Havelund, Klaus

2014-01-01

In this "40 years of formal methods" essay we shall first delineate, Sect. 1, what we mean by method, formal method, computer science, computing science, software engineering, and model-oriented and algebraic methods. Based on this, we shall characterize a spectrum from specification-oriented met...
40 CFR 129.102 - Endrin.

Science.gov (United States)

2010-07-01

...—Environmental Protection Agency method specified in 40 CFR part 136, except that a 1-liter sample size is... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS TOXIC POLLUTANT EFFLUENT... production, preparation or processing of another synthetic organic substance. (2) Endrin Formulator means a...
40 CFR 26.102 - Definitions.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Definitions. 26.102 Section 26.102 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic EPA...) Human subject means a living individual about whom an investigator (whether professional or student...
40 CFR 5.540 - Advertising.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Advertising. 5.540 Section 5.540... in Employment in Education Programs or Activities Prohibited § 5.540 Advertising. A recipient shall not in any advertising related to employment indicate preference, limitation, specification, or...
40 CFR 721.4575 - L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6-(phenylamino...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-aspartic acid, N,Nâ²- [(1E) - 1,2... Substances § 721.4575 L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6... uses subject to reporting. (1) The chemical substance identified as l-aspartic acid, N,N′- [(1E) - 1,2...
40 CFR 262.80 - Applicability.

Science.gov (United States)

2010-07-01

... procedures if it meets the Federal definition of hazardous waste in 40 CFR 261.3 and it is subject to either the Federal manifesting requirements at 40 CFR Part 262, Subpart B, to the universal waste management... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS...
27 CFR 40.523 - Inventories.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Inventories. 40.523... PROCESSED TOBACCO Manufacture of Processed Tobacco Operations by Manufacturers of Processed Tobacco § 40.523 Inventories. Every manufacturer of processed tobacco must provide a true and accurate inventory on TTB F 5210...
BERN railway station: security assessment under a speed increase of trains from 30 to 40 km h-1

International Nuclear Information System (INIS)

Ribaux, C.; Capron, M.

1994-01-01

In the frame of the ''Rail 2000'' project, the CFF (Swiss Railways) would like to increase the speed of trains arriving in Bern station. On the eastern head, this speed would be raised from 30 to 40kmh -1 . The superstructure is formed by a three-storey building which rests on 450mm diameter steel columns.The aim of the present study was: - to determine the security loss of the station superstructure under a train impact on the columns at 40kmh -1 rather than at 30kmh -1 - to propose measures in order to get at 40kmh -1 the same security as at 30kmh -1 Four approaches are dealt with: (1)on the base of accidents statistics and of their cost; (2)review of possible dynamical approaches; (3)equivalent static load (from European railways codes); (4)energy in which, starting from its initial speed, the train loses energy on different obstacles (ballast, platform, protection devices, walls, train's own deformation) and the remaining energy is compared with the maximum energy that the column can dissipate by deformation.The conclusions are presented as a 'security plan' and the proposed protection costs are evaluated. ((orig.))
48 CFR 9904.411-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.411-40 Fundamental requirement. (a) The contractor shall... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9904.411-40 Section 9904.411-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...
48 CFR 9904.402-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402-40 Fundamental requirement. All costs incurred for... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9904.402-40 Section 9904.402-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...
48 CFR 9904.418-40 - Fundamental requirements.

Science.gov (United States)

2010-10-01

... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.418-40 Fundamental requirements. (a) A business unit... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirements. 9904.418-40 Section 9904.418-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...
48 CFR 9904.410-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.410-40 Section 9904.410-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.410-40 Fundamental requirement. (a) Business unit G&A...

Evaluation of 40K and studies of its variation in occupational radiation workers of TAPS 1-4

International Nuclear Information System (INIS)

Nagaraju, G.; Rao, D.D.; Baburajan, A.

2014-01-01

Tarapur Maharashtra Site consists of two units (TAPS 1 and 2) of 160 MW(e) BWRs and two units (TAPS 3 and 4) of 540 MW(e) PHWRs in operation. Monitoring and dose assessment of all radiation workers is a regulatory requirement as per radiation safety procedures of operating stations based on AERB guidelines. Internal contamination and committed effective dose (CED) due to internally deposited gamma radionuclides is evaluated based on whole body counting measurements. The predominant nuclides of potential internal contamination continued to be 60 Co, 134+137 Cs and 131 I. Apart from these, natural radionuclide 40 K is also detected in the body of occupational workers. It is one of the most important nutrients distributed throughout the body, mainly in muscle and is an essential element in life process. It is under close homeostatic control in the body and is not influenced by the environmental levels. The daily intake of natural radionuclides of uranium and thorium series is almost negligible compared with that of 40 K, a radioisotope of potassium present to the extent of 0.012 % of natural Potassium. It has a halflife of 1.28 x 10 9 Y and decays by beta emission and electron capture accompanied by 1.46 MeV gamma ray emission with 10.7 % abundance. The specific activity of potassium is 31.5 Bq 40 K per gram of potassium. The paper presents the analysis of 40 K concentration in the workers of vegetarian and Non-vegetarian diet categories
40 CFR 798.5265 - The salmonella typhimurium reverse mutation assay.

Science.gov (United States)

2010-07-01

... mean number of revertant colonies per plate and standard deviation shall be presented for test chemical... revertant colonies per plate, standard deviation. (vi) Dose-response relationship, if applicable. (g... Salmonella/ mammalian-microsome mutagenicity test,” Mutation Research 31:347-364 (1975). (2) de Serres, F.J...
Amyloid beta(1-40-induced astrogliosis and the effect of genistein treatment in rat: a three-dimensional confocal morphometric and proteomic study.

Directory of Open Access Journals (Sweden)

Maryam Bagheri

Full Text Available Astrocytes are highly involved in regulation and homeostasis of the extracellular environment in the healthy brain. In pathological conditions, these cells play a major role in the inflammatory response seen in CNS tissues, which is called reactive astrogliosis and includes hypertrophy and proliferation of astrocytes. Here, we performed 3D confocal microscopy to evaluate the morphological response of reactive astrocytes positive for glial fibrillary acidic protein (GFAP in rats, to the presence of Aβ(1-40 in the rat brain before and after treatment with genistein. In 50 astrocytes per animal, we measured the volume and surface area for the nucleus, cell body, the entire cell, the tissue covered by single astrocytes and quantified the number and length of branches, the density of the astrocytes and the intensity of GFAP immunoreactivity. Injecting Aβ(1-40 into the brain of rats caused astrogliosis indicated by increased values for all measured parameters. Mass spectrometric analysis of hippocampal tissue in Aβ(1-40-injected brain showed decreased amounts of tubulins, enolases and myelin basic protein, and increased amounts of dihydropyrimidinase-related protein 2. In Aβ(1-40-injected rats pretreated with genistein, GFAP intensity was decreased to the sham-operated group level, and Aβ(1-40-induced astrogliosis was significantly ameliorated.
Hydrogenation study of suction-cast Ti{sub 40}Zr{sub 40}Ni{sub 20} quasicrystal

Energy Technology Data Exchange (ETDEWEB)

Huang, Huogen; Li, Rong; Yin, Chen; Zheng, Shaotao; Zhang, Pengcheng [National Key Laboratory for Surface Physics and Chemistry, P.O. Box 718-35, Mian Yang 621907, Sichuan (China)

2008-09-15

Suction casting was predicted to be an usable method for improving the hydriding kinetics of Ti/Zr-based icosahedral quasicrystals (IQCs) in our previous work. To further determine it, a suction-cast Ti{sub 40}Zr{sub 40}Ni{sub 20} IQC alloy was used for hydrogenation studies by Pressure Composition Isotherm (PCI) and Temperature Programmed Desorption (TPD) techniques. The results showed that, this alloy absorbed hydrogen rapidly with obvious hydrogen pressure plateau and some reversibility, however, displayed very limited hydrogen capacity (about 0.7 wt.%) and low equilibrium pressure. After several hydrogenation/dehydrogenation cycles, the IQC structure transformed into two hydride phases, ZrH{sub 2-x} and one unknown, both of which decomposed at above 600 C, suggesting high thermo-stability for them. On the whole, indeed the suction-casting method can increase the hydrogen absorption rate of Ti/Zr-based IQCs, however, the hydrogenation properties of the Ti{sub 40}Zr{sub 40}Ni{sub 20} IQC alloy still need a mighty advancement. (author)
32 CFR 34.40 - Purpose of reports and records.

Science.gov (United States)

2010-07-01

... Requirements Reports and Records § 34.40 Purpose of reports and records. Sections 34.41 and 34.42 prescribe requirements for monitoring and reporting financial and program performance and for records retention. ... 32 National Defense 1 2010-07-01 2010-07-01 false Purpose of reports and records. 34.40 Section 34...
40 CFR 76.7 - Revised NOX emission limitations for Group 1, Phase II boilers.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Revised NOX emission limitations for Group 1, Phase II boilers. 76.7 Section 76.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.7 Revised NOX...
Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment

NARCIS (Netherlands)

Beelen, E. van; Oonk, A.M.M.; Leijendeckers, J.M.; Hoefsloot, E.H.; Pennings, R.J.E.; Feenstra, I.; Dieker, H.J.; Huygen, P.L.M.; Snik, A.F.M.; Kremer, H.; Kunst, H.P.M.

2016-01-01

OBJECTIVES: Mutations in EYA4 can cause nonsyndromic autosomal dominant sensorineural hearing impairment (DFNA10) or a syndromic variant with hearing impairment and dilated cardiomyopathy. A mutation in EYA4 was found in a Dutch family, causing DFNA10. This study is focused on characterizing the
Crystallization in Pd40Ni40P20 glass

DEFF Research Database (Denmark)

Jiang, Jianzhong; Saksl, K.; Nishiyama, N.

2002-01-01

Phase segregation and the effect of pressure on crystallization of bulk and ribbon Pd40Ni40P20 glasses have been studied by means of differential scanning calorimetry (DSC) and x-ray diffraction. The DSC measurements show only one glass transition event in the samples annealed at different...... temperatures in the supercooled liquid region. Phase analyses reveal at least five crystalline phases crystallized from the glass: monoclinic; body-centered tetragonal; orthorhombic; Ni2Pd2P and fcc-(Ni,Pd) solid solution phases. In the pressure range from 0 to 4.2 GPa, the crystallization temperature...... increases with pressure having a slope of 11 K/GPa. The eutectic crystallization reaction mode and crystalline phases formed are unchanged in the pressure range used. The enhancement of the crystallization temperature with increasing pressure in the glass can be explained by the suppression of atomic...
SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.

Science.gov (United States)

Inoue, D; Kitaura, J; Matsui, H; Hou, H-A; Chou, W-C; Nagamachi, A; Kawabata, K C; Togami, K; Nagase, R; Horikawa, S; Saika, M; Micol, J-B; Hayashi, Y; Harada, Y; Harada, H; Inaba, T; Tien, H-F; Abdel-Wahab, O; Kitamura, T

2015-04-01

Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (SETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-β signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS.
48 CFR 9904.415-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

... separately for purposes of measurement and assignment of such costs to cost accounting periods. However, if.... 9904.415-40 Section 9904.415-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.415-40 Fundamental requirement. (a) The cost of deferred...
48 CFR 9904.414-40 - Fundamental requirement.

Science.gov (United States)

2010-10-01

.... 9904.414-40 Section 9904.414-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.414-40 Fundamental requirement. (a) A contractor's... money rate shall be based on rates determined by the Secretary of the Treasury, pursuant to Public Law...
40Ar/39Ar age and thermal history of the Kirin chondrite

International Nuclear Information System (INIS)

Wang, S.; McDougall, I.; Tetley, N.; Harrison, T.M.

1980-01-01

The Kirin meteorite, a large (> 2800 kg) H5 chondrite, fell in Kirin Province, China in 1976. A sample from each of the two largest fragments (K-1. K-2) yield 40 Ar/ 39 Ar total fusion ages of 3.63 +- 0.02 b.y. and 2.78 +- 0.02 b.y. respectively. 40 Ar/ 40 Ar age spectra show typical diffusional argon loss profiles. Maximum apparent ages of 4.36 b.y. (K-1) and approx. 4.0 b.y. (K-2) are interpreted as possible minimum estimates for the age of crystallization of the parent body. (orig./ME)
CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity.

Science.gov (United States)

Zaccard, Colleen R; Watkins, Simon C; Kalinski, Pawel; Fecek, Ronald J; Yates, Aarika L; Salter, Russell D; Ayyavoo, Velpandi; Rinaldo, Charles R; Mailliard, Robbie B

2015-02-01

The ability of dendritic cells (DC) to mediate CD4(+) T cell help for cellular immunity is guided by instructive signals received during DC maturation, as well as the resulting pattern of DC responsiveness to the Th signal, CD40L. Furthermore, the professional transfer of antigenic information from migratory DC to lymph node-residing DC is critical for the effective induction of cellular immune responses. In this study we report that, in addition to their enhanced IL-12p70 producing capacity, human DC matured in the presence of inflammatory mediators of type 1 immunity are uniquely programmed to form networks of tunneling nanotube-like structures in response to CD40L-expressing Th cells or rCD40L. This immunologic process of DC reticulation facilitates intercellular trafficking of endosome-associated vesicles and Ag, but also pathogens such HIV-1, and is regulated by the opposing roles of IFN-γ and IL-4. The initiation of DC reticulation represents a novel helper function of CD40L and a superior mechanism of intercellular communication possessed by type 1 polarized DC, as well as a target for exploitation by pathogens to enhance direct cell-to-cell spread. Copyright © 2015 by The American Association of Immunologists, Inc.
Plasma YKL-40 in Inuit and Danes

DEFF Research Database (Denmark)

Nøjgaard, Camilla; Johansen, Julia S; Bjerregaard, Peter

2015-01-01

AIMS: The aim of the present study was to investigate whether there are differences in plasma levels of YKL-40 between Inuit in Greenland and in Denmark and in Danes, as well as to study the relationship between alcohol intake, plasma YKL-40 and other factors in Inuit. METHODS: Plasma YKL-40 levels...... were measured on 1645 people from The Greenland Population Study (a cross-sectional population study of Inuit from Denmark and West Greenland) and were compared with the plasma YKL-40 levels of 8899 people from The Copenhagen City Heart Study (a population-based, prospective study of the Danish general...... population). RESULTS: The plasma concentrations of YKL-40 were significantly (P = 0.001) lower in Inuit living in Greenland (median 46 µg/l, range 10-2164, n = 1164) compared with the plasma YKL-40 levels of Inuit living in Denmark (median 63 µg/l, range 20-2827, n = 481) and of Danes living in Denmark...
Decay of 1, 2 and 3-phonon states in 40Ca

International Nuclear Information System (INIS)

Fallot, M.; Scarpaci, J.A.; Frascaria, N.; Blumenfeld, Y.; Chbihi, A.; Chomaz, Ph.; Desesquelles, P.; Frankland, J.; Khan, E.; Laville, J.L.; Plagnol, E.; Pollacco, E.C.; Roussel-Chomaz, P.; Roynette, J.C.; Shrivastava, A.; Zerguerras, T.

2007-01-01

Inelastic scattering of 40 Ca on 40 Ca at 50 A.MeV has been measured in coincidence with protons at the GANIL facility using a very performant set-up. The SPEG spectrometer was associated with 240 CsI(Tl) scintillators of the INDRA 4π array, allowing for the measurement of complete decay events. The missing energy method was applied to these events to study the particle decay of collective states. For events with excitation energy between 42 and 55 MeV, a direct decay branch by three protons towards the low energy states of 37 Cl gives the first evidence for a 3-phonon giant resonance state. A significant direct decay branch by alpha-particles of the GQR is also measured for the first time
Study of giant multipole resonances in 40Ca

International Nuclear Information System (INIS)

Rost, H.

1979-01-01

In the present thesis giant resonance states in 40 Ca were studied by scattering of 104 MeV a particles on 40 Ca and by the reactions 39 K(p vector,p') 39 K and 39 K(p,α) 36 Ar. The scattered α-particles were measured at extreme forward angles (THETAsub(L) = 4 0 -16 0 C), because at forward angles the cross sections for the excitation of states with spin 0 and 1 strongly differ from those with higher spin. The aim of this experiment was first of all the study of the giant resonance region in 40 Ca on the contribution to 0 + or 1 - states. Beside the known electric giant quadrupole resonances at Esub(x) approx. equal to 18.5 MeV (25% EWSR) contributions of EO-strength at Esub(x) approx. equal to 21 MeV (6% EWSR) and indications to a (isoscalar) E1-strength at Esub(x) approx. equal to 14 MeV and Esub(x) approx. equal to 16 MeV were found. At the reactions 39 K(p vector,p') 39 K and 39 K(p,α) 36 Ar in the channels (p,p 0 ),(p,p 4 ), (p,αsub(o)), and (p,α 1 ) at incident energies at about 10 MeV (Esub(x)( 40 Ca) approx. equal to 18 MeV) resonant structures were observed. A scattering phase analysis performed for the elastic proton scattering didn't however yield quantitative results about the resonance parameter. An expansion of the cross sections by Legendre polynomials for the remaining reaction channel didn't allow a conclusion about the dominance of a certain L-value. The only indication to the connection of the observed resonant structures with the giant quadrupole resonance in 40 Ca is therefore the energetic position at about Esub(x) approx. equal to 18 MeV. Altogether the observed structures however were not very pronounced, so it can be concluded, that the excitation of the giant quadrupole resonance in 40 Ca by protons via the ground state of 39 K occurs not very strongly. (orig./HSI) [de
Meniscus suture repair: minimum 10-year outcomes in patients younger than 40 years compared with patients 40 and older.

Science.gov (United States)

Steadman, J Richard; Matheny, Lauren M; Singleton, Steven B; Johnson, Nicholas S; Rodkey, William G; Crespo, Bernardo; Briggs, Karen K

2015-09-01

Few studies have compared outcomes after meniscus suture repair in patients younger than 40 years versus patients 40 years and older. To document failure rates and long-term outcomes after meniscus suture repair by a single surgeon, using the inside-out technique, at a minimum 10-year follow-up in patients younger than 40 years versus those 40 years and older. Cohort study; Level of evidence, 3. This study included all patients 18 years or older who underwent meniscus suture repair with the inside-out technique by a single surgeon between January 1992 and December 2003. Patients were divided into 2 cohorts according to age: meniscus as repaired in the index surgery. Patients completed a subjective questionnaire at minimum of 10 years after arthroscopy. Outcomes measures included Lysholm, Tegner, and patient satisfaction with outcome. All data were collected prospectively. The surgeon performed 339 meniscus repairs between 1992 and 2003. The study included 181 knees in 178 patients, who had a mean age of 33 years (range, 18-70 years). Cohort 1 contained 136 knees; 16 patients (12%) were lost to follow-up and 47 (35%) underwent a subsequent knee arthroscopy. Cohort 2 contained 45 knees; 2 patients (4.4%) were lost to follow-up, 3 patients had a total knee arthroplasty, and 12 patients (28%) underwent a subsequent knee arthroscopy. In cohort 1, the meniscus repair failure rate was 5.5% (6/110), and in cohort 2 it was 5.3% (2/38) (P = .927). There was no significant difference in failure rate based on which meniscus was repaired (P = .257), concomitant anterior cruciate ligament (ACL) reconstruction (P = .092), or microfracture (P = .674). Average follow-up time for cohort 1 was 16.1 years (range, 10.0-21.9 years), with 82% follow-up (n = 73/89); average follow-up time for cohort 2 was 16.2 years (range, 10.1-21.0 years), with 93% follow-up (n = 28/30). There were no significant differences in outcomes scores after meniscus suture repair based on age cohort or meniscus
PROSA version 4.0 manual

International Nuclear Information System (INIS)

Bicking, U.; Golly, W.; Peter, N.; Seifert, R.

1991-05-01

This report includes a comprehensive manual of the computer program PROSA which illustrate the handling and functioning of PROSA. The manual PROSA 4.0 (FORTRAN 77) describes the PC Version of PROSA including its program moduls. The PROSA program package is a statistical tool to decide on the basis of statistical assumptions whether in a given sequence of material balance periods a loss of material might have occurred. The evaluation of the material balance data is based on statistical test procedures. In the present PROSA Version 4.0 the three tests CUMUF test, PAGE's test and GEMUF test are applied to a sequence of material balances. PROSA Version 4.0 supports a real sequential evaluation. That means, PROSA is not only able to evaluate a series of MUF values sequentially after the campaign has finished, but also real sequentially during the campaign. PROSA Version 4.0 is a menu-guided computer program. Data input can be performed either by diskette or by key-enter. Result output is primarily an information whether or not an alarm is indicated. This information can be displayed either numerically or graphically. Therefore, a comfortable graphical output utility is attached to PROSA 4.0. The program moduls are compiled and linked with the Ryan Mc-Farland Compiler. The PROSA graphical utility uses the PLOT88 Library of Plotworks, Inc. (orig./HP) [de
40 CFR 230.97 - Management.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Management. 230.97 Section 230.97... Losses of Aquatic Resources § 230.97 Management. (a) Site protection. (1) The aquatic habitats, riparian.... For government property, long-term protection may be provided through federal facility management...
40 CFR 162.151 - Definitions.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Definitions. 162.151 Section 162.151 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS STATE REGISTRATION... registered product. Pest problem means: (1) A pest infestation and its consequences, or (2) Any condition for...

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