The Influence of Schema and Cultural Difference on L1 and L2 Reading

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Yang, Shi-sheng

2010-01-01

Reading in L1 shares numerous basic elements with reading in L2, and the processes also differ greatly. Intriguing questions involve whether there are two parallel cognitive processes at work, or whether there are processing strategies that accommodate both L1 and L2. This paper examines how reading in L1 is different from and similar to reading…

An automated and efficient conformation search of L-cysteine and L,L-cystine using the scaled hypersphere search method

Science.gov (United States)

Kishimoto, Naoki; Waizumi, Hiroki

2017-10-01

Stable conformers of L-cysteine and L,L-cystine were explored using an automated and efficient conformational searching method. The Gibbs energies of the stable conformers of L-cysteine and L,L-cystine were calculated with G4 and MP2 methods, respectively, at 450, 298.15, and 150 K. By assuming thermodynamic equilibrium and the barrier energies for the conformational isomerization pathways, the estimated ratios of the stable conformers of L-cysteine were compared with those determined by microwave spectroscopy in a previous study. Equilibrium structures of 1:1 and 2:1 cystine-Fe complexes were also calculated, and the energy of insertion of Fe into the disulfide bond was obtained.

Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.

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Paola R Luz

Full Text Available BACKGROUND: L-ficolin (encoded by FCN2 binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system. METHODS: We investigated L-ficolin levels in 160 T. cruzi infected patients with chronic Chagas disease and 71 healthy individuals, and FCN2 polymorphisms (-986 G>A, -602 G>A, and -4 A>G in the promoter and A258S in exon 8 in 243 patients, being 88 indeterminate (asymptomatic, 96 with cardiac, 23 with digestive and 33 with cardiodigestive manifestations (two were unspecified and 305 controls (135 for A258S. RESULTS: Patients presented lower L-ficolin plasma levels than controls (p<0.0001. Among the different groups of cardiac commitment, individuals with moderate forms had higher L-ficolin levels than the severe forms (P = 0.039. Lower L-ficolin levels were found associated with the 258S variant in the patients (P = 0.034. We found less -4A/G heterozygotes in the cardiac patients, than in the controls (OR = 0.56 [95% CI = 0.33-0.94], P = 0.034. Heterozygote -4A/G genotypes with the 258S variant and 258SS homozygotes were nevertheless more frequent among cardiodigestive patients than in controls (OR = 14.1 [95% CI = 3.5-56.8], P = 0.0001 and in indeterminate patients (OR = 3.2 [95% CI = 1.1-9.4], P = 0.037. We also found an association of the allelic frequency of the 258S variant with cardiodigestive Chagas disease compared to controls (OR = 2.24 [95% CI = 1.1-4.5], P = 0.037. Thus, decreased patient levels of L-ficolin reflect not only protein consumption due to the disease process, but also the higher frequency of the 258S variant in patients with cardiodigestive symptoms. CONCLUSION: The very first study on Brazilian cohort associates both L-ficolin plasma levels and FCN2 variants to Chagas disease and subsequent disease progression. The prognostic value of L-ficolin levels and the FCN2*A258S polymorphism

Metacognitive Online Reading Strategy Use: Readers' Perceptions in L1 and L2

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Taki, Saeed

2016-01-01

This study aimed to explore whether first-language (L1) readers of different language backgrounds would employ similar metacognitive online reading strategies and whether reading online in a second language (L2) could be influenced by L1 reading strategies. To this end, 52 Canadian college students as English L1 readers and 38 Iranian university…

A Prerequisite to L1 Homophone Effects in L2 Spoken-Word Recognition

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Nakai, Satsuki; Lindsay, Shane; Ota, Mitsuhiko

2015-01-01

When both members of a phonemic contrast in L2 (second language) are perceptually mapped to a single phoneme in one's L1 (first language), L2 words containing a member of that contrast can spuriously activate L2 words in spoken-word recognition. For example, upon hearing cattle, Dutch speakers of English are reported to experience activation…

L2 Word Recognition: Influence of L1 Orthography on Multi-Syllabic Word Recognition

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Hamada, Megumi

2017-01-01

L2 reading research suggests that L1 orthographic experience influences L2 word recognition. Nevertheless, the findings on multi-syllabic words in English are still limited despite the fact that a vast majority of words are multi-syllabic. The study investigated whether L1 orthography influences the recognition of multi-syllabic words, focusing on…

Discourse Connectives in L1 and L2 Argumentative Writing

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Hu, Chunyu; Li, Yuanyuan

2015-01-01

Discourse connectives (DCs) are multi-functional devices used to connect discourse segments and fulfill interpersonal levels of discourse. This study investigates the use of selected 80 DCs within 11 categories in the argumentative essays produced by L1 and L2 university students. The analysis is based on the International Corpus Network of Asian…

L1 track triggering with associative memory for the CMS HL-LHC tracker

International Nuclear Information System (INIS)

Sabes, D.

2014-01-01

One of the proposed solutions currently under study in Compact Muon Solenoid (CMS) collaboration [1] to reconstruct tracks at the first level trigger (L1) for the High Luminosity - Large Hadron Collider (HL-LHC) is based on the usage of Associative Memory [2] (AM) chips. The tracker information is first reduced to suppress low p T tracks and sent to boards equipped with AM chips. Each AM compares the tracker information with pre-calculated expectations (pattern matching) in a very short time (order of a μs), therefore providing a solution to the challenging computational problem of pattern recognition in a very busy environment. Associated to fast track fit methods, like the Hough transform, the AM approach should be able to fulfil the very demanding requirements of L1 tracking. The proposed architecture for the AM-based L1 track reconstruction system will be presented, together with the latest results obtained using a complete software emulation of this system

Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China.

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Yaofei Yue

Full Text Available HPV account for most of the incidence of cervical cancer. Approximately 90% of anal cancers and a smaller subset (<50% of other cancers (oropharyngeal, penile, vaginal, vulvar are also attributed to HPV. The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers type restricted protection. The L2 protein is a promising candidate for a broadly protective HPV vaccine. In our previous study, we found the most prevalent high-risk HPV infectious serotypes were HPV-16 and HPV-58 among women of Southwest China. To explore gene polymorphisms and intratypic variations of HPV-16 and HPV-58 L1/L2 genes originating in Southwest China, HPV-16 (L1: n = 31, L2: n = 28 and HPV-58 (L1: n = 21, L2: n = 21 L1/L2 genes were sequenced and compared to others described and submitted to GenBank. Phylogenetic trees were then constructed by Neighbor-Joining and the Kimura 2-parameters methods (MEGA software, followed by an analysis of the diversity of secondary structure. Then selection pressures acting on the L1/L2 genes were estimated by PAML software. Twenty-nine single nucleotide changes were observed in HPV-16 L1 sequences with 16/29 non-synonymous mutations and 13/29 synonymous mutations (six in alpha helix and two in beta turns. Seventeen single nucleotide changes were observed in HPV-16 L2 sequences with 8/17 non-synonymous mutations (one in beta turn and 9/17 synonymous mutations. Twenty-four single nucleotide changes were observed in HPV-58 L1 sequences with 10/24 non-synonymous mutations and 14/24 synonymous mutations (eight in alpha helix and four in beta turn. Seven single nucleotide changes were observed in HPV-58 L2 sequences with 4/7 non-synonymous mutations and 3/7 synonymous mutations. The result of selective pressure analysis showed that most of these mutations were of positive selection. This study may help understand the intrinsic geographical relatedness and biological differences of HPV-16/HPV-58 and

L1-L2 Transfer in the Narrative Styles of Chinese EFL Learners' Written Personal Narratives

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Su, I-Ru; Chou, Yi-Chun

2016-01-01

Most of the research on second language (L2) narratives has focused on whether or how L2 learners carry their L1 narrative styles into L2 narration; few studies have explored whether L2 learners' knowledge of the L2 also in turn affects their L1 narrative performance. The present study attempted to probe the issue of cultural transfer in narrative…

L1/L2 Differences in the Acquisition of Form-Meaning Pairings in a Second Language

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McManus, Kevin

2015-01-01

This paper examines the impact of L1/L2 form-meaning differences in the domain of aspect to investigate whether L2 learners are able to acquire properties of the L2 that are different from the L1. Oral data were collected from English- and German-speaking university learners of French L2 (n = 75) at two different levels of proficiency. The results…

Vibrational spectroscopic and theoretical study of 3,5-dimethyl-1-thiocarboxamide pyrazole (L) and the complexes Co2L2Cl4, Cu2L2Cl4 and Cu2L2Br2

International Nuclear Information System (INIS)

Nemcsok, Denes; Kovacs, Attila; Szecsenyi, Katalin Meszaros; Leovac, Vukadin M.

2006-01-01

In the present paper we report a joint experimental and theoretical study of 3,5-dimethyl-1-thiocarboxamide pyrazole (L) and its complexes Co 2 L 2 Cl 4 , Cu 2 L 2 Cl 4 and Cu 2 L 2 Br 2 . DFT computations were used to model the structural and bonding properties of the title compounds as well as to derive a reliable force field for the normal coordinate analysis of L. The computations indicated the importance of hydrogen bonding interactions in stabilising the global minimum structures on the potential energy surfaces. In contrast to the S-bridged binuclear Cu 2 L 2 Br 2 complex found in the crystal, our computations predicted the formation of (CuLBr) 2 dimers in the isolated state stabilized by very strong (53 kJ/mol) N-H...Br hydrogen bonding interactions. On the basis of FT-IR and FT-Raman experiments and the DFT-derived scaled quantum mechanical force field we carried out a complete normal coordinate analysis of L. The FT-IR spectra of the three complexes were interpreted using the present assignment of L, literature data and computed results

How Does L1 and L2 Exposure Impact L1 Performance in Bilingual Children? Evidence from Polish-English Migrants to the United Kingdom

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Ewa Haman

2017-09-01

Full Text Available Most studies on bilingual language development focus on children’s second language (L2. Here, we investigated first language (L1 development of Polish-English early migrant bilinguals in four domains: vocabulary, grammar, phonological processing, and discourse. We first compared Polish language skills between bilinguals and their Polish non-migrant monolingual peers, and then investigated the influence of the cumulative exposure to L1 and L2 on bilinguals’ performance. We then examined whether high exposure to L1 could possibly minimize the gap between monolinguals and bilinguals. We analyzed data from 233 typically developing children (88 bilingual and 145 monolingual aged 4;0 to 7;5 (years;months on six language measures in Polish: receptive vocabulary, productive vocabulary, receptive grammar, productive grammar (sentence repetition, phonological processing (non-word repetition, and discourse abilities (narration. Information about language exposure was obtained via parental questionnaires. For each language task, we analyzed the data from the subsample of bilinguals who had completed all the tasks in question and from monolinguals matched one-on-one to the bilingual group on age, SES (measured by years of mother’s education, gender, non-verbal IQ, and short-term memory. The bilingual children scored lower than monolinguals in all language domains, except discourse. The group differences were more pronounced on the productive tasks (vocabulary, grammar, and phonological processing and moderate on the receptive tasks (vocabulary and grammar. L1 exposure correlated positively with the vocabulary size and phonological processing. Grammar scores were not related to the levels of L1 exposure, but were predicted by general cognitive abilities. L2 exposure negatively influenced productive grammar in L1, suggesting possible L2 transfer effects on L1 grammatical performance. Children’s narrative skills benefitted from exposure to two languages

Comparing L1 and L2 Texts and Writers in First-Year Composition

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Eckstein, Grant; Ferris, Dana

2018-01-01

Scholars have at various points discussed the needs of second language (L2) writers enrolled in "mainstream" composition courses where they are mixed with native (L1) English speakers. Other researchers have investigated the experiences of L2 writers in mainstream classes and the perceptions of their instructors about their abilities and…

GAS2L1 Is a Centriole-Associated Protein Required for Centrosome Dynamics and Disjunction.

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Au, F.K.; Jia, Y.; Jiang, K.; Grigoriev, I.S.; Hau, B.K.; Shen, Y.; Du, S.; Akhmanova, A.S.; Qi, R.Z.

2017-01-01

Mitotic spindle formation and chromosome segregation require timely separation of the two duplicated centrosomes, and this process is initiated in late G2 by centrosome disjunction. Here we report that GAS2L1, a microtubule- and actin-binding protein, associates with the proximal end of mature

Characterization and immunogenicity of rLipL32/1-LipL21-OmpL1/2 fusion protein as a novel immunogen for a vaccine against Leptospirosis

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Zhao Xin

2015-01-01

Full Text Available Vaccination is an effective strategy to prevent leptospirosis, a global zoonotic disease caused by infection with pathogenic Leptospira species. However, the currently used multiple-valence vaccine, which is prepared with whole cells of several Leptospira serovars, has major side effects, while its cross-immunogenicity among different Leptospira serovars is weak. LipL32, LipL21 and 2 OmpL1 have been confirmed as surface-exposed antigens in all pathogenic Leptospira strains, but their immunoprotective efficiency needs to be improved. In the present study, we generated a fusion gene lipL32/1-lipL21-ompL1/2 using primer-linking PCR and an engineered E. coli strain to express the recombinant fusion protein rLipL32/1-LipL21-OmpL1/2 (rLLO. Subsequently, the expression conditions were optimized using a central composite design that increased the fusion protein yield 2.7-fold. Western blot assays confirmed that rLLO was recognized by anti-rLipL32/1, anti-rLipL21, and anti-rOmpL1/2 sera as well as 98.5% of the sera from leptospirosis patients. The microscopic agglutination test (MAT demonstrated that rLLO antiserum had a stronger ability to agglutinate the strains of different Leptospira serovars than the rLipL32/1, rLipL21, and rOmpL1/2 antisera. More importantly, tests in hamsters showed that rLLO provided higher immunoprotective rates (91.7% than rLipL32/1, rLipL21 and rOmpL1/2 (50.0-75.0%. All the data indicate that rLLO, a recombinant fusion protein incorporating three antigens, has increased antigenicity and immunoprotective effects, and so can be used as a novel immunogen to develop a universal genetically engineered vaccine against leptospirosis.

Simulation of LOFT anticipated-transient experiments L6-1, L6-2, and L6-3 using TRAC-PF1/MOD1

International Nuclear Information System (INIS)

Sahota, M.S.

1984-01-01

Anticipated-transient experiments L6-1, L6-2, and L6-3, performed at the Loss-of-fluid Test (LOFT) facility, are analyzed using the latest released version of the Transient Reactor Analysis Code (TRAC-PF1/MOD1). The results are used to assess TRAC-PF1/MOD1 trip and control capabilities, and predictions of thermal-hydraulic phenomena during slow transients. Test L6-1 simulated a loss-of-stream load in a large pressurized-water reactor (PWR), and was initiated by closing the main steam-flow control valve (MSFCV) at its maximum rate, which reduced the heat removal from the secondary-coolant system and increased the primary-coolant system pressure that initiated a reactor scram. Test L6-2 simulated a loss-of-primary coolant flow in a large PWR, and was initiated by tripping the power to the primary-coolant pumps (PCPs) allowing the pumps to coast down. The reduced primary-coolant flow caused a reactor scram. Test L6-3 simulated an excessive-load increase incident in a large PWR, and was initiated by opening the MSFCV at its maximum rate, which increased the heat removal from the secondary-coolant system and decreased the primary-coolant system pressure that initiated a reactor scram. The TRAC calculations accurately predict most test events. The test data and the calculated results for most parameters of interest also agree well

The Status of the Auxiliary "Do" in L1 and L2 English Negative Clauses

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Perales, Susana

2010-01-01

This paper addresses the issue of whether negative sentences containing auxiliary "do" in L1 and L2 English share the same underlying syntactic representation. To this end, I compare the negative sentences produced by 77 bilingual (Spanish/Basque) L2 learners of English with the corresponding data available for L1 acquirers reported on in Schutze…

Cognitive Style and Reading Comprehension in L1 and L2.

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Vivaldo-Lima, Javier

This paper presents the results of a research study carried out with Mexican college students to analyze the relationship between readers' cognitive styles (field dependent/independent) and their performance at different levels of written discourse processing in Spanish (L1) and English (L2). The sample for the study included 452 undergraduate…

Pragmatic assessment of schizophrenic bilinguals' L1 and L2 use ...

African Journals Online (AJOL)

This paper reports on a study investigating the pragmatic skills and deficits of schizophrenic bilinguals in their spontaneous first language (L1) and second language (L2) speech. Smit (2009) (see also Smit et al., this volume) argues that the locus of deficits in schizophrenic speech is semantics and suggests that a next step ...

β-L-Arabinofuranosylation Conducted by 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl Trichloroacetimidate.

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Li, Hong-Zhan; Ding, Jie; Cheng, Chun-Ru; Chen, Yue; Liang, Xing-Yong

2018-05-02

We describe a β-L-arabinofuranosylation method by employing the 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl trichloroacetimidate 10 as a donor. This approach allows a wide range of acceptor substrates, especially amino acid acceptors, to be used. Stereoselective synthesis of β-(1,4)-L-arabinofuranosyl-(2S, 4R)-4-hydroxy-L-proline (β-L-Araf-L-Hyp 4 ) and its dimer is achieved readily by this method. Both the stereoselectivities and yields of the reactions are excellent. To demonstrate the utility of this methodology, the preparation of a trisaccharide in a one-pot manner was carried out. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gestational diabetes mellitus is associated with TCF7L2 gene polymorphisms independent of HLA-DQB1*0602 genotypes and islet cell autoantibodies

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Papadopoulou, A.; Lynch, K. F.; Shaat, N.; Håkansson, R.; Ivarsson, S. A.; Berntorp, K.; Agardh, C. D.; Lernmark, Å

2011-01-01

Aims To test whether the TCF7L2 gene was associated with gestational diabetes, whether the association between TCF7L2 and gestational diabetes was independent of HLA-DQB1*0602 and islet cell autoantibodies, as well as maternal age, number of pregnancies, family history of diabetes and the HLA-DQB1 genotypes, and to test whether the distribution of HLA-DQB1 alleles was affected by country of birth. Methods We genotyped the rs7903146, rs12255372 and rs7901695 single nucleotide polymorphisms of the TCF7L2 gene in 826 mothers with gestational diabetes and in 1185 healthy control subjects in the Diabetes Prediction in Skåne Study. The mothers were also typed for HLA-DQB1 genotypes and tested for islet cell autoantibodies against GAD65, insulinoma-associated antigen-2 and insulin. Results The heterozygous genotypes CT, GT and TC of the rs7903146 (T is risk for Type 2 diabetes), rs12255372 (T is risk for Type 2 diabetes) and rs7901695 (C is risk for Type 2 diabetes), respectively, as well as the homozygous genotypes TT, TT and CC of the rs7903146, rs12255372 and rs7901695, respectively, were strongly associated with gestational diabetes (P gestational diabetes in mothers born in Sweden (P = 0.010). Conclusions The TCF7L2 was associated with susceptibility for gestational diabetes independently of the presence of HLA-DQB1*0602 and islet cell autoantibodies and other factors such as maternal age, number of pregnancies, family history of diabetes and other HLA-DQ genotypes. The HLA-DQB1*0602 was negatively associated with gestational diabetes in mothers born in Sweden. PMID:21672010

The Design of Morphological/Linguistic Data in L1 and L2 ...

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user

learners' MA of an L1 or L2 can be measured (and, as an extension to this, that users' and .... and they could activate these strategies and skills when confronted with new .... cussion of a wide range of morphological phenomena in English.

CLPTM1L is overexpressed in lung cancer and associated with apoptosis.

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Zhenhua Ni

Full Text Available CLPTM1L is believed to be associated with lung cancer. However, there is little information regarding its expression and function. Here using immunohistochemistry, we found that CLPTM1L expression was markedly increased in lung cancer tissues relative to normal tissues, especially in lung adenocarcinoma. CLPTM1L expression was not found to be associated with stages, smoking status, lymph node metastasis, or T lymphocyte infiltration but with differentiation stage. We found CLPTM1L to be enriched in the mitochondrial compared with plasma membrane protein extracts. CLPTM1L-EGFP transfection showed that the molecule product was expressed in cytoplasm and indicated the mitochondrial localization stained with mitochondrial marker MitoTracker. CLPTM1L transferred lung cancer cell line 95-D showed no growth inhibition or cell apoptosis, but it did show inhibited sensitivity to cis-diamminedichloroplatinum(II (cisplatin, CDDP. Knockdown of CLPTM1L by RNAi did not interfere with cell proliferation but it did increase cell sensitivity to CDDP and activation of caspase-9 and caspase-3/7. These data indicate CLPTM1L is a mitochondria protein and that it may be associated with anti-apoptotic mechanism which affects drug-resistance in turn.

Reading in L2 (English) and L1 (Persian): An Investigation into Reverse Transfer of Reading Strategies

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Talebi, Seyed Hassan

2012-01-01

This study investigates the effect of reading strategies instruction in L2 (English) on raising reading strategies awareness and use and reading ability of Iranian EFL learners in L2 (English) and L1 (Persian) as a result of transfer of reading strategies from L2 to L1. To this purpose, 120 students of intermediate and advanced English proficiency…

Verbal Inflectional Morphology in L1 and L2 Spanish: A Frequency Effects Study Examining Storage versus Composition.

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Bowden, Harriet Wood; Gelfand, Matthew P; Sanz, Cristina; Ullman, Michael T

2010-02-17

This study examines the storage vs. composition of Spanish inflected verbal forms in L1 and L2 speakers of Spanish. L2 participants were selected to have mid-to-advanced proficiency, high classroom experience, and low immersion experience, typical of medium-to-advanced foreign language learners. Participants were shown the infinitival forms of verbs from either Class I (the default class, which takes new verbs) or Classes II and III (non-default classes), and were asked to produce either first-person singular present-tense or imperfect forms, in separate tasks. In the present tense, the L1 speakers showed inflected-form frequency effects (i.e., higher frequency forms were produced faster, which is taken as a reflection of storage) for stem-changing (irregular) verb-forms from both Class I (e.g., pensar-pienso) and Classes II and III (e.g., perder-pierdo), as well as for non-stem-changing (regular) forms in Classes II/III (e.g., vender-vendo), in which the regular transformation does not appear to constitute a default. In contrast, Class I regulars (e.g., pescar-pesco), whose non-stem-changing transformation constitutes a default (e.g., it is applied to new verbs), showed no frequency effects. L2 speakers showed frequency effects for all four conditions (Classes I and II/III, regulars and irregulars). In the imperfect tense, the L1 speakers showed frequency effects for Class II/III (-ía-suffixed) but not Class I (-aba-suffixed) forms, even though both involve non-stem-change (regular) default transformations. The L2 speakers showed frequency effects for both types of forms. The pattern of results was not explained by a wide range of potentially confounding experimental and statistical factors, and does not appear to be compatible with single-mechanism models, which argue that all linguistic forms are learned and processed in associative memory. The findings are consistent with a dual-system view in which both verb class and regularity influence the storage vs

Requirements for an "ideal" bilingual L1 →L2 translation- oriented ...

African Journals Online (AJOL)

The major aim of this article is to outline the requirements for an "ideal" bilingual L1 →L2 dictionary of the general vocabulary specifically designed for the purposes of professional translation. The article challenges three commonly accepted beliefs: (a) a bilingual dictionary equals a translation dictionary; (b) a bilingual ...

L2 Word Recognition: Influence of L1 Orthography on Multi-syllabic Word Recognition.

Science.gov (United States)

Hamada, Megumi

2017-10-01

L2 reading research suggests that L1 orthographic experience influences L2 word recognition. Nevertheless, the findings on multi-syllabic words in English are still limited despite the fact that a vast majority of words are multi-syllabic. The study investigated whether L1 orthography influences the recognition of multi-syllabic words, focusing on the position of an embedded word. The participants were Arabic ESL learners, Chinese ESL learners, and native speakers of English. The task was a word search task, in which the participants identified a target word embedded in a pseudoword at the initial, middle, or final position. The search accuracy and speed indicated that all groups showed a strong preference for the initial position. The accuracy data further indicated group differences. The Arabic group showed higher accuracy in the final than middle, while the Chinese group showed the opposite and the native speakers showed no difference between the two positions. The findings suggest that L2 multi-syllabic word recognition involves unique processes.

The impact of language co-activation on L1 and L2 speech fluency.

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Bergmann, Christopher; Sprenger, Simone A; Schmid, Monika S

2015-10-01

Fluent speech depends on the availability of well-established linguistic knowledge and routines for speech planning and articulation. A lack of speech fluency in late second-language (L2) learners may point to a deficiency of these representations, due to incomplete acquisition. Experiments on bilingual language processing have shown, however, that there are strong reasons to believe that multilingual speakers experience co-activation of the languages they speak. We have studied to what degree language co-activation affects fluency in the speech of bilinguals, comparing a monolingual German control group with two bilingual groups: 1) first-language (L1) attriters, who have fully acquired German before emigrating to an L2 English environment, and 2) immersed L2 learners of German (L1: English). We have analysed the temporal fluency and the incidence of disfluency markers (pauses, repetitions and self-corrections) in spontaneous film retellings. Our findings show that learners to speak more slowly than controls and attriters. Also, on each count, the speech of at least one of the bilingual groups contains more disfluency markers than the retellings of the control group. Generally speaking, both bilingual groups-learners and attriters-are equally (dis)fluent and significantly more disfluent than the monolingual speakers. Given that the L1 attriters are unaffected by incomplete acquisition, we interpret these findings as evidence for language competition during speech production. Copyright © 2015. Published by Elsevier B.V.

L1 influence in the L2 acquisition of isiXhosa verb placement by ...

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1. Introduction. In second language (L2) acquisition research conducted within ..... versus Afrikaans-speaking beginner learners of isiXhosa, with regard to verb ..... Language contact within one home is also illustrated by the case of the four L1 ...

Exact solutions of sl-boson system in U(2l + 1) reversible O(2l + 2) transitional region

CERN Document Server

Zhang Xin

2002-01-01

Exact eigen-energies and the corresponding wavefunctions of the interacting sl-boson system in U(2l + 1) reversible O(2l +2) transitional region are obtained by using an algebraic Bethe Ansatz with the infinite dimensional Lie algebraic technique. Numerical algorithm for solving the Bethe Ansatz equations by using mathematical package is also outlined

L2-L1 Translation Priming Effects in a Lexical Decision Task: Evidence From Low Proficient Korean-English Bilinguals

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Yoonhyoung Lee

2018-03-01

Full Text Available One of the key issues in bilingual lexical representation is whether L1 processing is facilitated by L2 words. In this study, we conducted two experiments using the masked priming paradigm to examine how L2-L1 translation priming effects emerge when unbalanced, low proficiency, Korean-English bilinguals performed a lexical decision task. In Experiment 1, we used a 150 ms SOA (50 ms prime duration followed by a blank interval of 100 ms and found a significant L2-L1 translation priming effect. In contrast, in Experiment 2, we used a 60 ms SOA (50 ms prime duration followed by a blank interval of 10 ms and found a null effect of L2-L1 translation priming. This finding is the first demonstration of a significant L2-L1 translation priming effect with unbalanced Korean-English bilinguals. Implications of this work are discussed with regard to bilingual word recognition models.

PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

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Nguyen, Bella Hai; Montgomery, Renn; Fadia, Mitali; Wang, Jiali; Ali, Sayed

2018-02-01

There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time. © 2017 John Wiley & Sons Australia, Ltd.

Synthesis, crystal structure and properties of [Co(L2](ClO42 (L=1,3-bis(1H-benzimidazol-2-yl-2-oxapropane

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Tavman Aydin

2015-01-01

Full Text Available The reaction of 1,3-bis(1H-benzimidazol-2-yl-2-oxapropane (L with Co(ClO42•6H2O in absolute ethanol produces di[1,3-bis(1H-benzimidazol-2-yl-2-oxapropane-k2N,N’]cobalt(IIdiperchlorate chelate complex ([Co(L2](ClO42, 1. The complex 1 was characterized by elemental analysis, magnetic moment, molar conductivity, thermogravimetric analysis, FT-IR, UV-visible, mass spectrometry, and its solid state structure was determined by single crystal X-ray diffraction. According to the thermogravimetric analysis data, there is no any water coordinated or uncoordinated in 1 as well as elemental analysis. The complex 1 has 1:2 M:L ionic characteristic according to the molar conductivity. In the complex, the distances between the cobalt and the ethereal oxygen atoms (Co1-O2: 2.805(3; Co2-O1: 2.752(2 Å show the semi-coordination bonding and the Co(II ion is six-coordinated with a N4O2 ligand set, resulting in a distorted octahedron.

Neural overlap of L1 and L2 semantic representations in speech: A decoding approach.

Science.gov (United States)

Van de Putte, Eowyn; De Baene, Wouter; Brass, Marcel; Duyck, Wouter

2017-11-15

Although research has now converged towards a consensus that both languages of a bilingual are represented in at least partly shared systems for language comprehension, it remains unclear whether both languages are represented in the same neural populations for production. We investigated the neural overlap between L1 and L2 semantic representations of translation equivalents using a production task in which the participants had to name pictures in L1 and L2. Using a decoding approach, we tested whether brain activity during the production of individual nouns in one language allowed predicting the production of the same concepts in the other language. Because both languages only share the underlying semantic representation (sensory and lexical overlap was maximally avoided), this would offer very strong evidence for neural overlap in semantic representations of bilinguals. Based on the brain activation for the individual concepts in one language in the bilateral occipito-temporal cortex and the inferior and the middle temporal gyrus, we could accurately predict the equivalent individual concepts in the other language. This indicates that these regions share semantic representations across L1 and L2 word production. Copyright © 2017 Elsevier Inc. All rights reserved.

Spectral L2/L1 norm: A new perspective for spectral kurtosis for characterizing non-stationary signals

Science.gov (United States)

Wang, Dong

2018-05-01

Thanks to the great efforts made by Antoni (2006), spectral kurtosis has been recognized as a milestone for characterizing non-stationary signals, especially bearing fault signals. The main idea of spectral kurtosis is to use the fourth standardized moment, namely kurtosis, as a function of spectral frequency so as to indicate how repetitive transients caused by a bearing defect vary with frequency. Moreover, spectral kurtosis is defined based on an analytic bearing fault signal constructed from either a complex filter or Hilbert transform. On the other hand, another attractive work was reported by Borghesani et al. (2014) to mathematically reveal the relationship between the kurtosis of an analytical bearing fault signal and the square of the squared envelope spectrum of the analytical bearing fault signal for explaining spectral correlation for quantification of bearing fault signals. More interestingly, it was discovered that the sum of peaks at cyclic frequencies in the square of the squared envelope spectrum corresponds to the raw 4th order moment. Inspired by the aforementioned works, in this paper, we mathematically show that: (1) spectral kurtosis can be decomposed into squared envelope and squared L2/L1 norm so that spectral kurtosis can be explained as spectral squared L2/L1 norm; (2) spectral L2/L1 norm is formally defined for characterizing bearing fault signals and its two geometrical explanations are made; (3) spectral L2/L1 norm is proportional to the square root of the sum of peaks at cyclic frequencies in the square of the squared envelope spectrum; (4) some extensions of spectral L2/L1 norm for characterizing bearing fault signals are pointed out.

Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

Science.gov (United States)

Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

2018-03-01

Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

Characterization Results for the L(2, 1, 1-Labeling Problem on Trees

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Zhang Xiaoling

2017-08-01

Full Text Available An L(2, 1, 1-labeling of a graph G is an assignment of non-negative integers (labels to the vertices of G such that adjacent vertices receive labels with difference at least 2, and vertices at distance 2 or 3 receive distinct labels. The span of such a labelling is the difference between the maximum and minimum labels used, and the minimum span over all L(2, 1, 1-labelings of G is called the L(2, 1, 1-labeling number of G, denoted by λ2,1,1(G. It was shown by King, Ras and Zhou in [The L(h, 1, 1-labelling problem for trees, European J. Combin. 31 (2010 1295–1306] that every tree T has Δ2(T − 1 ≤ λ2,1,1(T ≤ Δ2(T, where Δ2(T = maxuv∈E(T(d(u + d(v. And they conjectured that almost all trees have the L(2, 1, 1-labeling number attain the lower bound. This paper provides some sufficient conditions for λ2,1,1(T = Δ2(T. Furthermore, we show that the sufficient conditions we provide are also necessary for trees with diameter at most 6.

l1- and l2-Norm Joint Regularization Based Sparse Signal Reconstruction Scheme

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Chanzi Liu

2016-01-01

Full Text Available Many problems in signal processing and statistical inference involve finding sparse solution to some underdetermined linear system of equations. This is also the application condition of compressive sensing (CS which can find the sparse solution from the measurements far less than the original signal. In this paper, we propose l1- and l2-norm joint regularization based reconstruction framework to approach the original l0-norm based sparseness-inducing constrained sparse signal reconstruction problem. Firstly, it is shown that, by employing the simple conjugate gradient algorithm, the new formulation provides an effective framework to deduce the solution as the original sparse signal reconstruction problem with l0-norm regularization item. Secondly, the upper reconstruction error limit is presented for the proposed sparse signal reconstruction framework, and it is unveiled that a smaller reconstruction error than l1-norm relaxation approaches can be realized by using the proposed scheme in most cases. Finally, simulation results are presented to validate the proposed sparse signal reconstruction approach.

L2 Acquisition of Prosodic Properties of Speech Rhythm: Evidence from L1 Mandarin and German Learners of English

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Li, Aike; Post, Brechtje

2014-01-01

This study examines the development of speech rhythm in second language (L2) learners of typologically different first languages (L1s) at different levels of proficiency. An empirical investigation of durational variation in L2 English productions by L1 Mandarin learners and L1 German learners compared to native control values in English and the…

Input frequencies in processing of verbal morphology in L1 and L2: Evidence from Russian

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Tatiana Chernigovskaya

2011-02-01

Full Text Available In this study we take a usage-based perspective on the analysis of data from the acquisition of verbal morphology by Norwegian adult learners of L2 Russian, as compared to children acquiring Russian as an L1. According to the usage-based theories, language learning is input-driven and frequency of occurrence of grammatical structures and lexical items in the input plays a key role in this process. We have analysed to what extent the acquisition and processing of Russian verbal morphology by children and adult L2 learners is dependent on the input factors, in particular on type and token frequencies. Our analysis of the L2 input based on the written material used in the instruction shows a different distribution of frequencies as compared to the target language at large. The results of the tests that elicited present tense forms of verbs belonging to four different inflectional classes (-AJ-, -A-, -I-, and -OVA- have demonstrated that for both Russian children and L2 learners type frequency appears to be an important factor, influencing both correct stem recognition and generalisations. The results have also demonstrated token frequency effects. For L2 learners we observed also effects of formal instruction and greater reliance on morphological cues. In spite of the fact that L2 learners did not match completely any of the child groups, there are many similarities between L1 and L2 morphological processing, the main one being the role of frequency.

Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

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Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

2018-04-01

Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

L(2,1)-labelling of Circular-arc Graph

OpenAIRE

Paul, Satyabrata; Pal, Madhumangal; Pal, Anita

2014-01-01

An L(2,1)-labelling of a graph $G=(V, E)$ is $\\lambda_{2,1}(G)$ a function $f$ from the vertex set V (G) to the set of non-negative integers such that adjacent vertices get numbers at least two apart, and vertices at distance two get distinct numbers. The L(2,1)-labelling number denoted by $\\lambda_{2,1}(G)$ of $G$ is the minimum range of labels over all such labelling. In this article, it is shown that, for a circular-arc graph $G$, the upper bound of $\\lambda_{2,1}(G)$ is $\\Delta+3\\omega$, ...

Effect of L1-ORF2 on senescence of GES-1 cells and its molecular mechanisms

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Ying-nan LI

2016-06-01

Full Text Available Objective 　To investigate the effect of long interspersed nuclear elements 1 open reading frame 2(L1-ORF2 gene on the senescence of GES-1 cells and its mechanism of molecular regulation. Methods 　Cell culture of high glucose was used to construct stable model of senescent GES-1 cells. L1-ORF2 siRNA vector was constructed and then transfected into normal GES1 and senescent ones with liposome transfection reagents for transient expression. Forty eight hours after transfection, cell growth curves were drawn to show the speed of cell proliferation, flow cytometry was used to analyze the cell cycle, β-galactosidase staining to detect cell aging and Western blotting to detect the expressions of L1-ORF2, P53 and P21proteins. Results 　Senescent GES-1 cell model and L1-ORF2 siRNA vector were constructed. Compared with negative control group, the L1-ORF2 expression decreased in normal and senescent GES-1 cells transfected with L1-ORF2 siRNA vector. There was a faster proliferation of senescent GES1 cells (P<0.05 and lower ratio of β-galactosidase (56% vs 69%, P<0.05 and G0/G1 phase (34.2% vs 39.3%, P<0.05 in senescent GES-1 cells transfected with L1-ORE2 siRNA vector than those transfected with negative control vector, while there was no obvious difference between normal GES-1 cells transfected with L1-ORF2 siRNA vector and negative control vector (P＞0.05. P53 protein was expressed only in senescent GES-1 cell, while P21 protein was expressed in both normal and senescent GES-1 cells, and the latter had a higher expression level (P<0.05. The GES-1 cells transfected with L1-ORF2 siRNA vector showed lower expressions of P53 and P21 proteins than those transfected with negative control vector (P<0.05. Conclusions 　L1-ORF2-siRNA vector could down-regulate the expression of L1-ORF2 protein in normal and senescent GES-1 cells and promote the proliferation of senescent GES-1 cells. P21 and P53 proteins participate in the process of L1-ORF2 regulating

Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4

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Shinji Yamada

2018-03-01

Full Text Available Programmed cell death-ligand 1 (PD-L1, which is a ligand of programmed cell death-1 (PD-1, is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1 expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb, L1Mab-4 (IgG2b, kappa, using cell-based immunization and screening (CBIS method and investigated hPD-L1 expression in oral cancers. L1Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 in flow cytometry and stained oral cancers in a membrane-staining pattern. L1Mab-4 stained 106/150 (70.7% of oral squamous cell carcinomas, indicating the very high sensitivity of L1Mab-4. These results indicate that L1Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers. Keywords: Programmed cell death-ligand 1, Monoclonal antibody, Oral cancer

Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice.

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Winchenbach, Jan; Düking, Tim; Berghoff, Stefan A; Stumpf, Sina K; Hülsmann, Swen; Nave, Klaus-Armin; Saher, Gesine

2016-01-01

Background: Studying astrocytes in higher brain functions has been hampered by the lack of genetic tools for the efficient expression of inducible Cre recombinase throughout the CNS, including the neocortex. Methods: Therefore, we generated BAC transgenic mice, in which CreERT2 is expressed under control of the Aldh1l1 regulatory region. Results: When crossbred to Cre reporter mice, adult Aldh1l1-CreERT2 mice show efficient gene targeting in astrocytes. No such Cre-mediated recombination was detectable in CNS neurons, oligodendrocytes, and microglia. As expected, Aldh1l1-CreERT2 expression was evident in several peripheral organs, including liver and kidney. Conclusions: Taken together, Aldh1l1-CreERT2 mice are a useful tool for studying astrocytes in neurovascular coupling, brain metabolism, synaptic plasticity and other aspects of neuron-glia interactions.

Association of the TCF7L2 rs12255372 (G/T variant with type 2 diabetes mellitus in an Iranian population

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Faranak Mahmoudi Alami

2012-01-01

Full Text Available In various populations worldwide, common variants of the TCF7L2 (Transcription factor 7-like 2 gene are associated with the risk of type 2 diabetes mellitus (T2DM. The aim was to investigate the association between rs12255372 (G/T polymorphism in the TCF7L2 gene and T2DM in an Iranian population. 236 unrelated patients with T2DM, and 255 normoglycemic controls without diabetes were studied. The PCR-RFLP method was used for genotyping rs12255372 (G/T polymorphism, and the SPSS version 18.0 for Windows for statistical analysis. The minor T allele of TCF7L2 rs12255372 was found to significantly increase the risk of T2DM, with an allelic odds ratio (OR of 1.458 (95% CI 1.108-1.918, p = 0.007. A significant difference in TT genotype was observed between T2DM patients and normoglycemic controls (OR 2.038, 95% CI 1.147-3.623; p = 0.014. On assuming dominant and recessive models, ORs of 1.52 [95% CI (1.05-2.21 p = 0.026] and 1.74 [95% CI (1.01-3.00 p = 0.043] were obtained, respectively, thereby implying that the co-dominant model would best fit the susceptible gene effect. This study further confirms the TCF7L2 gene as enhancing susceptibility to the development of T2DM.

Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice [version 1; referees: 2 approved

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Jan Winchenbach

2016-12-01

Full Text Available Background: Studying astrocytes in higher brain functions has been hampered by the lack of genetic tools for the efficient expression of inducible Cre recombinase throughout the CNS, including the neocortex. Methods: Therefore, we generated BAC transgenic mice, in which CreERT2 is expressed under control of the Aldh1l1 regulatory region. Results: When crossbred to Cre reporter mice, adult Aldh1l1-CreERT2 mice show efficient gene targeting in astrocytes. No such Cre-mediated recombination was detectable in CNS neurons, oligodendrocytes, and microglia. As expected, Aldh1l1-CreERT2 expression was evident in several peripheral organs, including liver and kidney. Conclusions: Taken together, Aldh1l1-CreERT2 mice are a useful tool for studying astrocytes in neurovascular coupling, brain metabolism, synaptic plasticity and other aspects of neuron-glia interactions.

Morphological Family Size effects in L1 and L2 processing: An electrophysiological study

NARCIS (Netherlands)

Mulder, K.; Schreuder, R.; Dijkstra, A.F.J.

2013-01-01

The present study examined Morphological Family Size effects in first and second language processing. Items with a high or low Dutch (L1) Family Size were contrasted in four experiments involving Dutch–English bilinguals. In two experiments, reaction times (RTs) were collected in English (L2) and

Discussion on the method to increase the successful rate of L5/S1 intervertebral disc puncture

International Nuclear Information System (INIS)

Zhong Xianyi; Li Liangjun; Yu Chengxin

2007-01-01

Objective: To study the effective methods of L 5 /S 1 intervertebral disc puncture without drilling to solve the barriers from iliaca. Methods: (1) puncturing with belly-buttock sticking out: to enlarge waist sacro-iliaca angle to move the puncture point up; (2) puncturing through intervertebral edge: puncturing through L 5 to 1/3 intervertebral disc to make the puncture point move Up; (3) puncturing through L 5 /S 1 intervertebral disc with the self-made puncture location instrument. Results with the methods, 280 cases with L 5 /S 1 intervertebral disc protrusion have been successfully punctured, with successful rate 100%. Conclusion: These methods are ideal and easy to use to treat L 5 /S 1 intervertebral disc protrusion puncture, and worth popularizing. (authors)

TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes.

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Redondo, Maria J; Geyer, Susan; Steck, Andrea K; Sosenko, Jay; Anderson, Mark; Antinozzi, Peter; Michels, Aaron; Wentworth, John; Xu, Ping; Pugliese, Alberto

2018-02-01

The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 ( TCF7L2 ) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data ( n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders. The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old ( n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones ( n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) ( P = 0.008) and lower mean glucose AUC ( P = 0.0127). The results were similar for the rs7901695 SNP. In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms. © 2017 by the American Diabetes Association.

The transcription factor 7-like 2 (TCF7L2 polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC Study

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Boerwinkle Eric

2010-05-01

Full Text Available Abstract Background Transcription factor 7-like 2 (TCF7L2 has emerged as a consistently replicated susceptibility gene for type 2 diabetes, however, whether the TCF7L2 gene also has similar effects on the retinal microvasculature is less clear. We therefore aimed to investigate the association between the transcription factor 7-like 2 (TCF7L2 rs7903146 polymorphism and retinal microvascular phenotypes in the Atherosclerosis Risk in Communities (ARIC Study (1993-1995. Methods This was a population-based, cross-sectional study of 10,320 middle-aged African American (n = 2,199 and Caucasian (n = 8,121 men and women selected from four United States communities to examine the association between TCF7L2 rs7903146 polymorphism and retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, arteriolar and venular calibers. Photographs on one randomly selected eye were graded for presence of retinal microvascular signs and used to measure retinal vessel calibres. Results After adjusting for age, sex, study center, mean arterial blood pressure, total serum cholesterol, triglycerides, and other covariates, few associations of TCF7L2 rs7903146 and retinal microvascular signs were noted. TCF7L2 rs7903146 T risk allele was significantly associated with focal arteriolar narrowing in Caucasians with hypertension [odds ratio (ORCT vs. CC (95% CI = 1.25 (1.09-1.44; ORTT vs. CC = 1.56 (1.18-2.06; P = 0.002] and in Caucasians without diabetes [OR CT vs. CC = 1.18 (1.06-1.32; OR TT vs. CC = 1.40 (1.12, 1.75; P = 0.003]. No significant association of the TCF7L2 rs7903146 polymorphism and retinal vascular signs was noted among African American individuals. Conclusions TCF7L2 rs7903146 is not consistently associated with retinal microvascular signs. However, we report an association between the TCF7L2 rs7903146 polymorphism and focal arteriolar narrowing in Caucasians with hypertension or without diabetes. Further research in other

Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations.

Science.gov (United States)

Sanna-Cherchi, Simone; Khan, Kamal; Westland, Rik; Krithivasan, Priya; Fievet, Lorraine; Rasouly, Hila Milo; Ionita-Laza, Iuliana; Capone, Valentina P; Fasel, David A; Kiryluk, Krzysztof; Kamalakaran, Sitharthan; Bodria, Monica; Otto, Edgar A; Sampson, Matthew G; Gillies, Christopher E; Vega-Warner, Virginia; Vukojevic, Katarina; Pediaditakis, Igor; Makar, Gabriel S; Mitrotti, Adele; Verbitsky, Miguel; Martino, Jeremiah; Liu, Qingxue; Na, Young-Ji; Goj, Vinicio; Ardissino, Gianluigi; Gigante, Maddalena; Gesualdo, Loreto; Janezcko, Magdalena; Zaniew, Marcin; Mendelsohn, Cathy Lee; Shril, Shirlee; Hildebrandt, Friedhelm; van Wijk, Joanna A E; Arapovic, Adela; Saraga, Marijan; Allegri, Landino; Izzi, Claudia; Scolari, Francesco; Tasic, Velibor; Ghiggeri, Gian Marco; Latos-Bielenska, Anna; Materna-Kiryluk, Anna; Mane, Shrikant; Goldstein, David B; Lifton, Richard P; Katsanis, Nicholas; Davis, Erica E; Gharavi, Ali G

2017-11-02

Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10 -5 for novel LOF, increased to p = 4.1 × 10 -6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10 -7 ). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus

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Gu Harvest F

2010-07-01

Full Text Available Abstract Background MCF2L2, ADIPOQ and SOX2 genes are located in chromosome 3q26-27, which is linked to diabetic nephropathy (DN. ADIPOQ and SOX2 genetic polymorphisms are found to be associated with DN. In the present study, we first investigated the association between MCF2L2 and DN, and then evaluated effects of these three genes on the development of DN. Methods A total of 1177 type 1 diabetes patients with and without DN from the GoKinD study were genotyped with TaqMan allelic discrimination. All subjects were of European descent. Results Leu359Ile T/G variant in the MCF2L2 gene was found to be associated with DN in female subjects (P = 0.017, OR = 0.701, 95%CI 0.524-0.938 but not in males. The GG genotype carriers among female patients with DN had tendency decreased creatinine and cystatin levels compared to the carriers with either TT or TG genotypes. This polymorphism MCF2L2-rs7639705 together with SNPs of ADIPOQ-rs266729 and SOX2-rs11915160 had combined effects on decreased risk of DN in females (P = 0.001. Conclusion The present study provides evidence that MCF2L2, ADIPOQ and SOX2 genetic polymorphisms have effects on the resistance of DN in female T1D patients, and suggests that the linkage with DN in chromosome 3q may be explained by the cumulated genetic effects.

Electrode Potentials of l-Tryptophan, l-Tyrosine, 3-Nitro-l-tyrosine, 2,3-Difluoro-l-tyrosine, and 2,3,5-Trifluoro-l-tyrosine.

Science.gov (United States)

Mahmoudi, Leila; Kissner, Reinhard; Nauser, Thomas; Koppenol, Willem H

2016-05-24

Electrode potentials for aromatic amino acid radical/amino acid couples were deduced from cyclic voltammograms and pulse radiolysis experiments. The amino acids investigated were l-tryptophan, l-tyrosine, N-acetyl-l-tyrosine methyl ester, N-acetyl-3-nitro-l-tyrosine ethyl ester, N-acetyl-2,3-difluoro-l-tyrosine methyl ester, and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester. Conditional potentials were determined at pH 7.4 for all compounds listed; furthermore, Pourbaix diagrams for l-tryptophan, l-tyrosine, and N-acetyl-3-nitro-l-tyrosine ethyl ester were obtained. Electron transfer accompanied by proton transfer is reversible, as confirmed by detailed analysis of the current waves, and because the slopes of the Pourbaix diagrams obey Nernst's law. E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) at pH 7 are 0.99 ± 0.01 and 0.97 ± 0.01 V, respectively. Pulse radiolysis studies of two dipeptides that contain both amino acids indicate a difference in E°' of approximately 0.06 V. Thus, in small peptides, we recommend values of 1.00 and 0.96 V for E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH), respectively. The electrode potential of N-acetyl-3-nitro-l-tyrosine ethyl ester is higher, while because of mesomeric stabilization of the radical, those of N-acetyl-2,3-difluoro-l-tyrosine methyl ester and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester are lower than that of tyrosine. Given that the electrode potentials at pH 7 of E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) are nearly equal, they would be, in principle, interchangeable. Proton-coupled electron transfer pathways in proteins that use TrpH and TyrOH are thus nearly thermoneutral.

SO(2 ell + 1) contains ? contains SO/sub L/(3) in group chains for L-S coupling

International Nuclear Information System (INIS)

Wu, Z.Y.; Sun, C.P.; Zhang, L.; Li, B.F.

1986-01-01

Racah pointed out in his 1949 article that there exists a proper subgroup of SO(7) which properly contains SO/sub L/(3) in group chains for L-S coupling. This paper investigates whether such a proper subgroup exists for SO(2l + 1) which contains SO/sub L/(3) for an arbitrary l and concludes that this subgroup exists only for the case in which l is equal to 3. 4 references

Targeting immune co-stimulatory effects of PD-L1 and PD-L2 might represent an effective therapeutic strategy in stroke

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Sheetal eBodhankar

2014-08-01

Full Text Available Stroke outcome is worsened by the infiltration of inflammatory immune cells into ischemic brains. Our recent study demonstrated that PD-L1- and to a lesser extent PD-L2-deficient mice had smaller brain infarcts and fewer brain-infiltrating cells vs. WT mice, suggesting a pathogenic role for PD-Ligands in experimental stroke. We sought to ascertain PD-L1 and PD-L2-expressing cell types that affect T-cell activation, post-stroke in the context of other known co-stimulatory molecules. Thus, cells from male WT and PD-L-deficient mice undergoing 60 min of middle cerebral artery occlusion (MCAO followed by 96h of reperfusion were treated with neutralizing antibodies to study co-stimulatory and co-inhibitory interactions between CD80, CTLA-4, PD-1 and PD-Ls that regulate CD8+ and CD4+ T-cell activation. We found that antibody neutralization of PD-1 and CTLA-4 signaling post-MCAO resulted in higher proliferation in WT CD8+ and CD4+ T-cells, confirming an inhibitory role of PD-1 and CTLA-4 on T-cell activation. Also, CD80/CD28 interactions played a prominent regulatory role for the CD8+ T-cells and the PD-1/PD-L2 interactions were dominant in controlling the CD4+ T-cell responses in WT mice after stroke. A suppressive phenotype in PD-L1-deficient mice was attributed to CD80/CTLA-4 and PD-1/PD-L2 interactions. PD-L2 was crucial in modulating CD4+ T-cell responses, whereas PD-L1 regulated both CD8+ and CD4+ T-cells. To establish the contribution of PD-L1 and PD-L2 on regulatory B-cells (Bregs, infarct volumes were evaluated in male PD-L1- and PD-L2-deficient mice receiving IL-10+ B-cells 4h post-MCAO. PD-L2- but not PD-L1-deficient recipients of IL-10+ B-cells had markedly reduced infarct volumes, indicating a regulatory role of PD-L2 on Bregs. These results imply that PD-L1 and PD-L2 differentially control induction of T- and Breg-cell responses after MCAO, thus suggesting that selective targeting of PD-L1 and PD-L2 might represent a valuable therapeutic

Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression

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Duan Rui-Dong

2010-04-01

Full Text Available Abstract Background Curcumin is a polyphenol and the one of the principle curcuminoids of the spice turmeric. Its antioxidant, anti-cancer and anti-inflammatory effects have been intensively studied. Previous in vivo studies showed that administration of curcumin also decreased cholesterol levels in the blood, and the effects were considered to be related to upregulation of LDL receptor. However, since plasma cholesterol levels are also influenced by the uptake of cholesterol in the gut, which is mediated by a specific transporter Niemann-Pick Cl-like 1 (NPC1L1 protein, the present study is to investigate whether curcumin affects cholesterol uptake in the intestinal Caco-2 cells. Methods Caco-2 cells were cultured to confluence. The micelles composed of bile salt, monoolein, and 14C-cholesterol were prepared. We first incubated the cells with the micelles in the presence and absence of ezetimibe, the specific inhibitor of NPC1L1, to see whether the uptake of the cholesterol in the cells was mediated by NPC1L1. We then pretreated the cells with curcumin at different concentrations for 24 h followed by examination of the changes of cholesterol uptake in these curcumin-treated cells. Finally we determined whether curcumin affects the expression of NPC1L1 by both Western blot analysis and qPCR quantification. Results We found that the uptake of radioactive cholesterol in Caco-2 cells was inhibited by ezetimibe in a dose-dependent manner. The results indicate that the uptake of cholesterol in this study was mediated by NPC1L1. We then pretreated the cells with 25-100 μM curcumin for 24 h and found that such a treatment dose-dependently inhibited cholesterol uptake with 40% inhibition obtained by 100 μM curcumin. In addition, we found that the curcumin-induced inhibition of cholesterol uptake was associated with significant decrease in the levels of NPC1L1 protein and NPC1L1 mRNA, as analyzed by Western blot and qPCR, respectively. Conclusion

Development of Isocratic RP-HPLC Method for Separation and Quantification of L-Citrulline and L-Arginine in Watermelons

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Rasdin Ridwan

2018-01-01

Full Text Available Watermelons (Citrullus lanatus are known to have sufficient amino acid content. In this study, watermelons grown and consumed in Malaysia were investigated for their amino acid content, L-citrulline and L-arginine, by the isocratic RP-HPLC method. Flesh and rind watermelons were juiced, and freeze-dried samples were used for separation and quantification of L-citrulline and L-arginine. Three different mobile phases, 0.7% H3P04, 0.1% H3P04, and 0.7% H3P04 : ACN (90 : 10, were tested on two different columns using Zorbax Eclipse XDB-C18 and Gemini C18 with a flow rate of 0.5 mL/min and a detection wavelength at 195 nm. Efficient separation with reproducible resolution of L-citrulline and L-arginine was achieved using 0.1% H3P04 on the Gemini C18 column. The method was validated and good linearity of L-citrulline and L-arginine was obtained with R2 = 0.9956, y=0.1664x+2.4142 and R2=0.9912, y=0.4100x+3.4850, respectively. L-citrulline content showed the highest concentration in red watermelon of flesh and rind juice extract (43.81 mg/g and 45.02 mg/g, whereas L-arginine concentration was lower than L-citrulline, ranging from 3.39 to 11.14 mg/g. The isocratic RP-HPLC method with 0.1% H3P04 on the Gemini C18 column proved to be efficient for separation and quantification of L-citrulline and L-arginine in watermelons.

Delayed vertebral diagnosed L4 pincer vertebral fracture, L2-L3 ruptured vertebral lumbar disc hernia, L5 vertebral wedge fracture - Case report

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Balasa D

2016-08-01

Full Text Available An association between delayed ruptured lumbar disc hernia, L5 vertebral wedge fracture and posttraumaticL4 pincer vertebral fracture (A2.3-AO clasification at different levels is a very rare entity. We present the case of a 55 years old male who falled down from a bicycle. 2 months later because of intense and permanent vertebral lumbar and radicular L2 and L3 pain (Visual Scal Autologus of Pain7-8/10 the patient came to the hospital. He was diagnosed with pincer vertebral L4 fracture (A2.3-AO clasification and L2-L3 right ruptured lumbar disc hernia in lateral reces. The patient was operated (L2-L3 right fenestration, and resection of lumbar disc hernia, bilateral stabilisation, L3-L4-L5 with titan screws and postero-lateral bone graft L4 bilateral harvested from iliac crest.

Comparing Hypertext Reading in L1 and L2: The Case of Filipino Adults

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Gruspe, Michael Angelo M.; Marinas, Christian Joshua L.; Villasin, Marren Nicole F.; Villanueva, Ariel Josephe Therese R.; Vizconde, Camilla J.

2015-01-01

This research probed into the reading experiences of adult readers in their first language (L1) and second language (L2). Qualitative in nature, the investigation focused on twelve (12) adult readers , six (6) males and six (6) females, whose first language is Filipino. Data were gathered through interviews and focus-group discussions. Based on…

Quantitative and Qualitative Aspects of L1 (Swedish) and L2 (English) Idiom Comprehension

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Karlsson, Monica

2013-01-01

In the present investigation, 15 first term university students were faced with 80 context-based idioms in English (L2) and Swedish (L1) respectively, 30 of which were in the source domain of animals, commonly used in both languages, and asked to explain their meaning. The idioms were of varying frequency and transparency. Three main research…

Data of evolutionary structure change: 1AIFL-2AI0L [Confc[Archive

Lifescience Database Archive (English)

Full Text Available /ss_2> 0 n> 1AIF L...n> 1AIFLn> VSSSI----SSSNL 2AI0 Ln> 2AI0L...1AIFL-2AI0L 1AIF 2AI0 L L DIQLTQSPAFMAASPGEKVTITCSVSSSI----SSSNLH...line> SER CA 273 SER CA 260 ASN CA 337 LEU CA 408

L1000CDS2: LINCS L1000 characteristic direction signatures search engine.

Science.gov (United States)

Duan, Qiaonan; Reid, St Patrick; Clark, Neil R; Wang, Zichen; Fernandez, Nicolas F; Rouillard, Andrew D; Readhead, Ben; Tritsch, Sarah R; Hodos, Rachel; Hafner, Marc; Niepel, Mario; Sorger, Peter K; Dudley, Joel T; Bavari, Sina; Panchal, Rekha G; Ma'ayan, Avi

2016-01-01

The library of integrated network-based cellular signatures (LINCS) L1000 data set currently comprises of over a million gene expression profiles of chemically perturbed human cell lines. Through unique several intrinsic and extrinsic benchmarking schemes, we demonstrate that processing the L1000 data with the characteristic direction (CD) method significantly improves signal to noise compared with the MODZ method currently used to compute L1000 signatures. The CD processed L1000 signatures are served through a state-of-the-art web-based search engine application called L1000CDS 2 . The L1000CDS 2 search engine provides prioritization of thousands of small-molecule signatures, and their pairwise combinations, predicted to either mimic or reverse an input gene expression signature using two methods. The L1000CDS 2 search engine also predicts drug targets for all the small molecules profiled by the L1000 assay that we processed. Targets are predicted by computing the cosine similarity between the L1000 small-molecule signatures and a large collection of signatures extracted from the gene expression omnibus (GEO) for single-gene perturbations in mammalian cells. We applied L1000CDS 2 to prioritize small molecules that are predicted to reverse expression in 670 disease signatures also extracted from GEO, and prioritized small molecules that can mimic expression of 22 endogenous ligand signatures profiled by the L1000 assay. As a case study, to further demonstrate the utility of L1000CDS 2 , we collected expression signatures from human cells infected with Ebola virus at 30, 60 and 120 min. Querying these signatures with L1000CDS 2 we identified kenpaullone, a GSK3B/CDK2 inhibitor that we show, in subsequent experiments, has a dose-dependent efficacy in inhibiting Ebola infection in vitro without causing cellular toxicity in human cell lines. In summary, the L1000CDS 2 tool can be applied in many biological and biomedical settings, while improving the extraction of

Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2

International Nuclear Information System (INIS)

Ullrich, Nina D.; Koschak, Alexandra; MacLeod, Kenneth T.

2007-01-01

Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca 2+ channel (Ca v 1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca 2+ current, I CaL . The effect of oestrogen on I CaL was measured in Ca v 1.2-transfected HEK-293 cells using the whole-cell patch-clamp technique. The current revealed typical activation and inactivation profiles of nifedipine- and cadmium-sensitive I CaL . Oestrogen (50 μM) rapidly reduced I CaL by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca 2+ channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I CaL through direct interaction of the steroid with the channel protein

The Role of L1 Conceptual and Linguistic Knowledge and Frequency in the Acquisition of L2 Metaphorical Expressions

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Türker, Ebru

2016-01-01

This study investigates how figurative language is processed by learners of a second language (L2). With an experiment testing L2 comprehension of figurative expressions in three categories, each combining shared and unshared first language (L1) and L2 lexical representations and conceptual representations in a different way, the study…

Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

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Maher, Christina M; Thomas, Jeffrey D; Haas, Derick A; Longen, Charles G; Oyer, Halley M; Tong, Jane Y; Kim, Felix J

2018-02-01

posits Sigma1 modulators as novel therapeutic agents in PD-L1/PD-1 blockade strategies that regulate the tumor immune microenvironment. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/2/243/F1.large.jpg Mol Cancer Res; 16(2); 243-55. ©2017 AACR . ©2017 American Association for Cancer Research.

Isothermal (vapour + liquid) equilibrium for the binary {l_brace}1,1,2,2-tetrafluoroethane (R134) + propane (R290){r_brace} and {l_brace}1,1,2,2-tetrafluoroethane (R134) + isobutane (R600a){r_brace} systems

Energy Technology Data Exchange (ETDEWEB)

Dong Xueqiang [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Graduate University of Chinese Academy of Sciences, Beijing 100039 (China); Gong Maoqiong, E-mail: gongmq@mail.ipc.ac.c [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Liu Junsheng [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Graduate University of Chinese Academy of Sciences, Beijing 100039 (China); Wu Jianfeng, E-mail: jfwu@mail.ipc.ac.c [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China)

2010-09-15

(Vapour + liquid) equilibrium (VLE) data for the binary systems of {l_brace}1,1,2,2-tetrafluoroethane (R134) + propane (R290){r_brace} and {l_brace}1,1,2,2-tetrafluoroethane (R134) + isobutane (R600a){r_brace} were measured with a recirculation method at the temperatures ranging from (263.15 to 278.15) K and (268.15 to 288.15) K, respectively. All of the data were correlated by the Peng-Robinson (PR) equation of state (EoS) with the Huron-Vidal (HV) mixing rules utilizing the non-random two-liquid (NRTL) activity coefficient model. Good agreement can be found between the experimental data and the correlated results. Azeotropic behaviour can be found at the measured temperature ranges for these two mixtures.

Cyclophilins facilitate dissociation of the human papillomavirus type 16 capsid protein L1 from the L2/DNA complex following virus entry.

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Bienkowska-Haba, Malgorzata; Williams, Carlyn; Kim, Seong Man; Garcea, Robert L; Sapp, Martin

2012-09-01

Human papillomaviruses (HPV) are composed of the major and minor capsid proteins, L1 and L2, that encapsidate a chromatinized, circular double-stranded DNA genome. At the outset of infection, the interaction of HPV type 16 (HPV16) (pseudo)virions with heparan sulfate proteoglycans triggers a conformational change in L2 that is facilitated by the host cell chaperone cyclophilin B (CyPB). This conformational change results in exposure of the L2 N terminus, which is required for infectious internalization. Following internalization, L2 facilitates egress of the viral genome from acidified endosomes, and the L2/DNA complex accumulates at PML nuclear bodies. We recently described a mutant virus that bypasses the requirement for cell surface CyPB but remains sensitive to cyclosporine for infection, indicating an additional role for CyP following endocytic uptake of virions. We now report that the L1 protein dissociates from the L2/DNA complex following infectious internalization. Inhibition and small interfering RNA (siRNA)-mediated knockdown of CyPs blocked dissociation of L1 from the L2/DNA complex. In vitro, purified CyPs facilitated the dissociation of L1 pentamers from recombinant HPV11 L1/L2 complexes in a pH-dependent manner. Furthermore, CyPs released L1 capsomeres from partially disassembled HPV16 pseudovirions at slightly acidic pH. Taken together, these data suggest that CyPs mediate the dissociation of HPV L1 and L2 capsid proteins following acidification of endocytic vesicles.

Analyzing the Pattern of L1 Sounds on L2 Sounds Produced by Javanese Students of Stkip PGRI Jombang

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Daning Hentasmaka

2015-07-01

Full Text Available The studyconcerns on an analysis on the tendency of first language (L1 sound patterning on second language (L2 sounds done by Javanese students.Focusing on the consonant sounds, the data were collected by recording students’ pronunciationof English words during the pronunciation test. The data then analysed through three activities: data reduction, data display, and conclusion drawing/ verification. Theresult showedthatthe patterning of L1 sounds happened on L2 sounds especially on eleven consonant sounds: the fricatives [v, θ, ð, ʃ, ʒ], the voiceless stops [p, t, k], and the voiced stops [b, d, g].Thosepatterning case emergedmostlyduetothe difference in the existence of consonant sounds and rules of consonant distribution. Besides, one of the cases was caused by the difference in consonant clusters between L1 and L2

ANALYZING THE PATTERN OF L1 SOUNDS ON L2 SOUNDS PRODUCED BY JAVANESE STUDENTS OF STKIP PGRI JOMBANG

Directory of Open Access Journals (Sweden)

Daning Hentasmaka

2015-07-01

Full Text Available The studyconcerns on an analysis on the tendency of first language (L1 sound patterning on second language (L2 sounds done by Javanese students.Focusing on the consonant sounds, the data were collected by recording students’ pronunciationof English words during the pronunciation test. The data then analysed through three activities: data reduction, data display, and conclusion drawing/ verification. Theresult showedthatthe patterning of L1 sounds happened on L2 sounds especially on eleven consonant sounds: the fricatives [v, θ, ð, ʃ, ʒ], the voiceless stops [p, t, k], and the voiced stops [b, d, g].Thosepatterning case emergedmostlyduetothe difference in the existence of consonant sounds and rules of consonant distribution. Besides, one of the cases was caused by the difference in consonant clusters between L1 and L2.

Neurocognitive Development and Predictors of L1 and L2 Literacy Skills in Dyslexia: A Longitudinal Study of Children 5-11 Years Old.

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Helland, Turid; Morken, Frøydis

2016-02-01

The aim of this study was to find valid neurocognitive precursors of literacy development in first language (L1, Norwegian) and second language (L2, English) in a group of children during their Pre-literacy, Emergent Literacy and Literacy stages, by comparing children with dyslexia and a typical group. Children who were 5 years old at project start were followed until the age of 11, when dyslexia was identified and data could be analysed in retrospect. The children's neurocognitive pattern changed both by literacy stage and domain. Visuo-spatial recall and RAN appeared as early precursors of L1 literacy, while phonological awareness appeared as early precursor of L2 English. Verbal long term memory was associated with both L1 and L2 skills in the Literacy stage. Significant group differences seen in the Pre-literacy and Emergent literacy stages decreased in the Literacy stage. The developmental variations by stage and domain may explain some of the inconsistencies seen in dyslexia research. Early identification and training are essential to avoid academic failure, and our data show that visuo-spatial memory and RAN could be suitable early markers in transparent orthographies like Norwegian. Phonological awareness was here seen as an early precursor of L2 English, but not of L1 Norwegian. © 2015 The Authors. Dyslexia published by John Wiley & Sons Ltd.

The Effects of Giving and Receiving Marginal L1 Glosses on L2 Vocabulary Learning by Upper Secondary Learners

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Samian, Hosein Vafadar; Foo, Thomas Chow Voon; Mohebbi, Hassan

2016-01-01

This paper reports the findings of a study that investigated the effect of giving and receiving marginal L1 glosses on L2 vocabulary learning. To that end, forty nine Iranian learners of English were assigned to three different experimental conditions including marginal L1 glosses Giver (n = 17), marginal L1 glosses Receiver (n = 17), and no…

RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

Science.gov (United States)

Galloway, Alison; Saveliev, Alexander; Łukasiak, Sebastian; Hodson, Daniel J; Bolland, Daniel; Balmanno, Kathryn; Ahlfors, Helena; Monzón-Casanova, Elisa; Mannurita, Sara Ciullini; Bell, Lewis S; Andrews, Simon; Díaz-Muñoz, Manuel D; Cook, Simon J; Corcoran, Anne; Turner, Martin

2016-04-22

Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-μ at the pre-BCR checkpoint. Copyright © 2016, American Association for the Advancement of Science.

Dialogic spaces of knowledge construction in research article Conclusion sections written by English L1, English L2 and Spanish L1 writers

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Elena Sheldon

2018-04-01

Full Text Available While vast research efforts have been directed to the identification of moves and their constituent steps in research articles (RA, less attention has been paid to the social negotiation of knowledge, in particular in the Conclusion section of RAs. In this paper, I examine the Conclusion sections of RAs in English and Spanish, including RA Conclusions written in English by Spanish-background speakers in the field of applied linguistics. This study brings together two complementary frameworks, genre-based knowledge and evaluative stance, drawing on Swales’s (1990, 2004 move analysis framework and on the engagement system in Martin and White’s (2005 Appraisal framework. The results indicate that the English L1 group negotiates a consistent space for readers to approve or disapprove the writers’ propositions. However, the Spanish L1 group aligns with readers, using a limited space through contracting resources, which may be because this group addresses a smaller audience in comparison to the English L1 group which addresses an international readership. On the other hand, the English L2 group tends to move towards English rhetorical international practice, but without fully abandoning their SpL1. These results contribute to gaining a better understanding of how successful scholarly writing in English is achieved, and offers important insights for teaching multilingual researchers.

Gene structure of the pregnancy-associated glycoprotein-like (PAG-L) in the Eurasian beaver (Castor fiber L.).

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Lipka, Aleksandra; Majewska, Marta; Panasiewicz, Grzegorz; Bieniek-Kobuszewska, Martyna; Szafranska, Bozena

2017-09-01

The pregnancy-associated glycoprotein-like family (PAG-L) is a large group of chorionic products, expressed in the pre-placental trophoblast and later in the post-implantational chorionic epithelium, and are involved in proper placenta development and embryo-maternal interaction in eutherians. This study describes identification of the PAG-L family in the genome of the Eurasian beaver (Castor fiber L.), named CfPAG-L. We identified 7657 bp of the CfPAG-L gDNA sequence (Acc. No. KX377932), encompassing nine exons (1-9) and eight introns (A-H). The length of the CfPAG-L exons (59-200 bp) was equivalently similar to the only known counterparts of bPAG1, bPAG2, and pPAG2. The length of the CfPAG-L introns ranged 288-1937 bp and was completely different from previously known PAG introns. The exonic CfPAG-L regions revealed 50.3-72.9% homology with equivalent segments of bPAG1 and pPAG2 structure. The intronic CfPAG-L regions alignments revealed a lack of homology. Within the entire CfPAG-L gene, 31 potential single nucleotide variants (SNV: 7 transversions and 24 transitions) were predicted. The identified exonic polymorphic loci did not affect the amino acid sequence of the CfPAG-L polypeptide precursor. This is the first report describing the CfPAG-L gene sequence, structural organization, and SNVs in the Eurasian beaver, one of the largest rodents.

A Novel Role of IGF1 in Apo2L/TRAIL-Mediated Apoptosis of Ewing Tumor Cells

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Frans van Valen

2012-01-01

Full Text Available Insulin-like growth factor 1 (IGF1 reputedly opposes chemotoxicity in Ewing sarcoma family of tumor (ESFT cells. However, the effect of IGF1 on apoptosis induced by apoptosis ligand 2 (Apo2L/tumor necrosis factor (TNF- related apoptosis-inducing ligand (TRAIL remains to be established. We find that opposite to the partial survival effect of short-term IGF1 treatment, long-term IGF1 treatment amplified Apo2L/TRAIL-induced apoptosis in Apo2L/TRAIL-sensitive but not resistant ESFT cell lines. Remarkably, the specific IGF1 receptor (IGF1R antibody α-IR3 was functionally equivalent to IGF1. Short-term IGF1 incubation of cells stimulated survival kinase AKT and increased X-linked inhibitor of apoptosis (XIAP protein which was associated with Apo2L/TRAIL resistance. In contrast, long-term IGF1 incubation resulted in repression of XIAP protein through ceramide (Cer formation derived from de novo synthesis which was associated with Apo2L/TRAIL sensitization. Addition of ceramide synthase (CerS inhibitor fumonisin B1 during long-term IGF1 treatment reduced XIAP repression and Apo2L/TRAIL-induced apoptosis. Noteworthy, the resistance to conventional chemotherapeutic agents was maintained in cells following chronic IGF1 treatment. Overall, the results suggest that chronic IGF1 treatment renders ESFT cells susceptible to Apo2L/TRAIL-induced apoptosis and may have important implications for the biology as well as the clinical management of refractory ESFT.

Delayed vertebral diagnosed L4 pincer vertebral fracture, L2-L3 ruptured vertebral lumbar disc hernia, L5 vertebral wedge fracture - Case report

OpenAIRE

Balasa D; Schiopu M; Tunas A; Baz R; Hancu Anca

2016-01-01

An association between delayed ruptured lumbar disc hernia, L5 vertebral wedge fracture and posttraumaticL4 pincer vertebral fracture (A2.3-AO clasification) at different levels is a very rare entity. We present the case of a 55 years old male who falled down from a bicycle. 2 months later because of intense and permanent vertebral lumbar and radicular L2 and L3 pain (Visual Scal Autologus of Pain7-8/10) the patient came to the hospital. He was diagnosed with pincer vertebral L4 fracture (A2....

Semantic Categorization of Placement Verbs in L1 and L2 Danish and Spanish

Science.gov (United States)

Cadierno, Teresa; Ibarretxe-Antuñano, Iraide; Hijazo-Gascón, Alberto

2016-01-01

This study investigates semantic categorization of the meaning of placement verbs by Danish and Spanish native speakers and two groups of intermediate second language (L2) learners (Danish learners of L2 Spanish and Spanish learners of L2 Danish). Participants described 31 video clips picturing different types of placement events. Cluster analyses…

L[subscript 1] and L[subscript 2] Spoken Word Processing: Evidence from Divided Attention Paradigm

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Shafiee Nahrkhalaji, Saeedeh; Lotfi, Ahmad Reza; Koosha, Mansour

2016-01-01

The present study aims to reveal some facts concerning first language (L[subscript 1]) and second language (L[subscript 2]) spoken-word processing in unbalanced proficient bilinguals using behavioral measures. The intention here is to examine the effects of auditory repetition word priming and semantic priming in first and second languages of…

L1 Differences and L2 Similarities: Teaching Verb Tenses in English

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Collins, Laura

2007-01-01

In making decisions regarding the focus for grammar teaching, ESL instructors may take into consideration errors that appear to result from the influence of their students' first language(s) (L1). There is also evidence from language acquisition research suggesting that for some grammatical features, learners of different L1 backgrounds may face…

L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis

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Jaroslav Zelenka

2015-01-01

Full Text Available A moderate elevation of reactive oxygen species (ROS production and a mild inhibition of mitochondrial respiratory chain have been associated with a health promotion and a lifespan extension in several animal models of aging. Here, we tested whether this phenomenon called mitohormesis could be mediated by L-lactate. The treatment with 5 mM L-lactate significantly increased H2O2 production and slightly inhibited the respiration in cultured skin fibroblasts and in isolated mitochondria. The L-lactate exposure was associated with oxidation of intracellular glutathione, phosphorylation of 5′AMP-activated protein kinase (AMPK, and induction of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α transcription. A replicative aging of fibroblasts (L0 with a constant (LC, or intermittent 5 mM L-lactate (LI in media showed that the high-passage LI fibroblasts have higher respiration, lower H2O2 release, and lower secretion of L-lactate compared to L0 and LC. This protection against mitochondrial dysfunction in LI cells was associated with lower activity of mechanistic target of rapamycin complex 1 (mTORC1, less signs of cellular senescence, and increased autophagy compared to L0 and LC. In conclusion, we demonstrated that intermittent but not constant exposure to L-lactate triggers mitohormesis, prevents aging-associated mitochondrial dysfunction, and improves other markers of aging.

Informational Packaging, Level of Formality, and the Use of Circumstance Adverbials in L1 and L2 Student Academic Presentations

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Zareva, Alla

2009-01-01

The analysis of circumstance adverbials in this paper was based on L1 and L2 corpora of student presentations, each of which consisting of approximately 30,000 words. The overall goal of the investigation was to identify specific functions L1 and L2 college students attributed to circumstance adverbials (the most frequently used adverbial class in…

Weak or no association of TCF7L2 variants with Type 2 diabetes risk in an Arab population

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Al-Daghri Nasser

2008-07-01

Full Text Available Abstract Background The rs7903146 and rs12255372 variants of TCF7L2 have been strongly associated with type 2 diabetes (T2D risk in most populations studied to date. Meta-analysis of 27 different studies has resulted in a global OR of 1.46 [1.42–1.51] (rs7903146 variant. Thus far, despite a high incidence of T2D, the role of this variant in Arabs has not been established. Methods We performed a case-control association study using 522 Saudi T2D patients (WHO criteria, and 346 controls (age > 60; fasting plasma glucose Results For rs7903146, the T allele frequency of the cases (0.415 was not different from that observed in the controls (0.405. The crude odds ratio (OR was 1.04 with a 95% CI of 0.86–1.27 (P = 0.675. For rs12255372, the T allele frequency of the cases (0.368 was not different from that observed in the controls (0.355. Retrospective power calculations based upon an OR of 1.46 reported in a comprehensive meta-analysis of TCF7L2 risk, indicated this study was sufficiently powered (96.92%; α = 0.05 to detect an effect of similar magnitude to that reported for rs7903146. Conclusion Our study is consistent with weak or no association of T2D in Arabs with the two TCF7L2 variants, however it cannot rule out an effect of other SNPs in this gene. Future studies in this population are required to confirm our findings and may indicate the presence of yet to be defined genetic risk factors for T2D.

Crystallization and preliminary X-ray crystallographic analysis of highly thermostable L2 lipase from the newly isolated Bacillus sp. L2

International Nuclear Information System (INIS)

Shariff, Fairolniza Mohd; Rahman, Raja Noor Zaliha Raja Abd.; Ali, Mohd Shukuri Mohamad; Chor, Adam Leow Thean; Basri, Mahiran; Salleh, Abu Bakar

2010-01-01

Thermostable recombinant L2 lipase from thermophilic Bacillus sp. L2 has been crystallized by using counter-diffusion method and diffracted to 2.7 Å resolution. The crystal belongs to the primitive orthorhombic space group P2 1 2 1 2 1 with unit-cell parameters a = 87.44, b = 94.90, c = 126.46 Å. Purified thermostable recombinant L2 lipase from Bacillus sp. L2 was crystallized by the counter-diffusion method using 20% PEG 6000, 50 mM MES pH 6.5 and 50 mM NaCl as precipitant. X-ray diffraction data were collected to 2.7 Å resolution using an in-house Bruker X8 PROTEUM single-crystal diffractometer system. The crystal belonged to the primitive orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 87.44, b = 94.90, c = 126.46 Å. The asymmetric unit contained one single molecule of protein, with a Matthews coefficient (V M ) of 2.85 Å 3 Da −1 and a solvent content of 57%

Embodiment and second-language: automatic activation of motor responses during processing spatially associated L2 words and emotion L2 words in a vertical Stroop paradigm.

Science.gov (United States)

Dudschig, Carolin; de la Vega, Irmgard; Kaup, Barbara

2014-05-01

Converging evidence suggests that understanding our first-language (L1) results in reactivation of experiential sensorimotor traces in the brain. Surprisingly, little is known regarding the involvement of these processes during second-language (L2) processing. Participants saw L1 or L2 words referring to entities with a typical location (e.g., star, mole) (Experiment 1 & 2) or to an emotion (e.g., happy, sad) (Experiment 3). Participants responded to the words' ink color with an upward or downward arm movement. Despite word meaning being fully task-irrelevant, L2 automatically activated motor responses similar to L1 even when L2 was acquired rather late in life (age >11). Specifically, words such as star facilitated upward, and words such as root facilitated downward responses. Additionally, words referring to positive emotions facilitated upward, and words referring to negative emotions facilitated downward responses. In summary our study suggests that reactivation of experiential traces is not limited to L1 processing. Copyright © 2014 Elsevier Inc. All rights reserved.

Unconscious motivation. Part II: Implicit attitudes and L2 achievement

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Ali H. Al-Hoorie

2016-12-01

Full Text Available This paper investigates the attitudinal/motivational predictors of second language (L2 academic achievement. Young adult learners of English as a foreign language (N = 311 completed several self-report measures and the Single-Target Implicit Association Test. Examination of the motivational profiles of high and low achievers revealed that attachment to the L1 community and the ought-to L2 self were negatively associated with achievement, while explicit attitudes toward the L2 course and implicit attitudes toward L2 speakers were positively associated with it. The relationship between implicit attitudes and achievement could not be explained either by social desirability or by other cognitive confounds, and remained significant after controlling for explicit self-report measures. Explicit–implicit congruence also revealed a similar pattern, in that congruent learners were more open to the L2 community and obtained higher achievement. The results also showed that neither the ideal L2 self nor intended effort had any association with actual L2 achievement, and that intended effort was particularly prone to social desirability biases. Implications of these findings are discussed.

Critical contrastive rhetoric: The influence of L2 letter writing instruction on L1letter writing

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Mehrnoosh Fakharzadeh

2014-08-01

Full Text Available The present study employed critical contrastive rhetoric to investigate the L2 to L1 transfer of organizational pattern and directness level of speech acts in business complaint letters. By examining the L1 complaint letters of 30 tourism university students in two phases of study, pre and post instruction of English complaint letter, the study revealed that the rhetorical organization of Persian letters are in a state of hybridity. The post instruction comparison of letters, however, showed a tendency towards applying English conventions both in organization and directness level of complaint speech act in the L1 complaint letters. The results also revealed that after instruction the expert in the field of tourism viewed some letters as inappropriate in terms of politeness which is reflected through some lexical items.

Measurement of neutralizing serum antibodies of patients vaccinated with human papillomavirus L1 or L2-based immunogens using furin-cleaved HPV Pseudovirions.

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Joshua W Wang

Full Text Available Antibodies specific for neutralizing epitopes in either Human papillomavirus (HPV capsid protein L1 or L2 can mediate protection from viral challenge and thus their accurate and sensitive measurement at high throughput is likely informative for monitoring response to prophylactic vaccination. Here we compare measurement of L1 and L2-specific neutralizing antibodies in human sera using the standard Pseudovirion-Based Neutralization Assay (L1-PBNA with the newer Furin-Cleaved Pseudovirion-Based Neutralization Assay (FC-PBNA, a modification of the L1-PBNA intended to improve sensitivity towards L2-specific neutralizing antibodies without compromising assay of L1-specific responses. For detection of L1-specific neutralizing antibodies in human sera, the FC- PBNA and L1-PBNA assays showed similar sensitivity and a high level of correlation using WHO standard sera (n = 2, and sera from patients vaccinated with Gardasil (n = 30 or an experimental human papillomavirus type 16 (HPV16 L1 VLP vaccine (n = 70. The detection of L1-specific cross-neutralizing antibodies in these sera using pseudovirions of types phylogenetically-related to those targeted by the L1 virus-like particle (VLP vaccines was also consistent between the two assays. However, for sera from patients (n = 17 vaccinated with an L2-based immunogen (TA-CIN, the FC-PBNA was more sensitive than the L1-PBNA in detecting L2-specific neutralizing antibodies. Further, the neutralizing antibody titers measured with the FC-PBNA correlated with those determined with the L2-PBNA, another modification of the L1-PBNA that spacio-temporally separates primary and secondary receptor engagement, as well as the protective titers measured using passive transfer studies in the murine genital-challenge model. In sum, the FC-PBNA provided sensitive measurement for both L1 VLP and L2-specific neutralizing antibody in human sera. Vaccination with TA-CIN elicits weak cross-protective antibody in a

L2 Working Memory Capacity and L2 Reading Skill.

Science.gov (United States)

Harrington, Mike; Sawyer, Mark

1992-01-01

Examines the sensitivity of second-language (L2) working memory (ability to store and process information simultaneously) to differences in reading skills among advanced L2 learners. Subjects with larger L2 working memory capacities scored higher on measures of L2 reading skills, but no correlation was found between reading and passive short-term…

Neurocognitive Development and Predictors of L1 and L2 Literacy Skills in Dyslexia: A Longitudinal Study of Children 5–11 Years Old

Science.gov (United States)

Morken, Frøydis

2015-01-01

The aim of this study was to find valid neurocognitive precursors of literacy development in first language (L1, Norwegian) and second language (L2, English) in a group of children during their Pre‐literacy, Emergent Literacy and Literacy stages, by comparing children with dyslexia and a typical group. Children who were 5 years old at project start were followed until the age of 11, when dyslexia was identified and data could be analysed in retrospect. The children's neurocognitive pattern changed both by literacy stage and domain. Visuo‐spatial recall and RAN appeared as early precursors of L1 literacy, while phonological awareness appeared as early precursor of L2 English. Verbal long term memory was associated with both L1 and L2 skills in the Literacy stage. Significant group differences seen in the Pre‐literacy and Emergent literacy stages decreased in the Literacy stage. The developmental variations by stage and domain may explain some of the inconsistencies seen in dyslexia research. Early identification and training are essential to avoid academic failure, and our data show that visuo‐spatial memory and RAN could be suitable early markers in transparent orthographies like Norwegian. Phonological awareness was here seen as an early precursor of L2 English, but not of L1 Norwegian. © 2015 The Authors. Dyslexia published by John Wiley & Sons Ltd. PMID:26511662

A novel PKD2L1 C-terminal domain critical for trimerization and channel function.

Science.gov (United States)

Zheng, Wang; Hussein, Shaimaa; Yang, JungWoo; Huang, Jun; Zhang, Fan; Hernandez-Anzaldo, Samuel; Fernandez-Patron, Carlos; Cao, Ying; Zeng, Hongbo; Tang, Jingfeng; Chen, Xing-Zhen

2015-03-30

As a transient receptor potential (TRP) superfamily member, polycystic kidney disease 2-like-1 (PKD2L1) is also called TRPP3 and has similar membrane topology as voltage-gated cation channels. PKD2L1 is involved in hedgehog signaling, intestinal development, and sour tasting. PKD2L1 and PKD1L3 form heterotetramers with 3:1 stoichiometry. C-terminal coiled-coil-2 (CC2) domain (G699-W743) of PKD2L1 was reported to be important for its trimerization but independent studies showed that CC2 does not affect PKD2L1 channel function. It thus remains unclear how PKD2L1 proteins oligomerize into a functional channel. By SDS-PAGE, blue native PAGE and mutagenesis we here identified a novel C-terminal domain called C1 (K575-T622) involved in stronger homotrimerization than the non-overlapping CC2, and found that the PKD2L1 N-terminus is critical for dimerization. By electrophysiology and Xenopus oocyte expression, we found that C1, but not CC2, is critical for PKD2L1 channel function. Our co-immunoprecipitation and dynamic light scattering experiments further supported involvement of C1 in trimerization. Further, C1 acted as a blocking peptide that inhibits PKD2L1 trimerization as well as PKD2L1 and PKD2L1/PKD1L3 channel function. Thus, our study identified C1 as the first PKD2L1 domain essential for both PKD2L1 trimerization and channel function, and suggest that PKD2L1 and PKD2L1/PKD1L3 channels share the PKD2L1 trimerization process.

l=1,2 high-beta stellarator

International Nuclear Information System (INIS)

Bartsch, R.R.; Cantrell, E.L.; Gribble, R.F.; Klare, K.A.; Kutac, K.J.; Miller, G.; Siemon, R.E.

1978-01-01

The final scyllac experiments are described. These experiments utilized a feedback-stabilized, l=1,2 high-beta stellarator configuration and like the previous feedback-stabilization experiments were carried out in a toroidal sector, rather than a complete torus. The energy confinement time, obtained from excluded flux measurements, agrees with a two-dimensional calculation of particle end loss from a straight theta pinch. Because simple end loss was dominant, the energy confinement time was independent of whether equilibrium adjustment or feedback stabilization fields were applied. The dynamical characteristics of the toroidal equilibrium were improved by elimination of the l=0 field used previously, as expected from theory. A modal rather than local feedback control algorithm was used. Although feedback clearly decreased the m=1 motion of the plasma, the experimental test of modal feedback, which is expected from theory to be superior to local feedback, is considered inconclusive because of the limitations imposed by the sector configuration

Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders.

Science.gov (United States)

Carpenter, Danielle; Walker, Susan; Prescott, Natalie; Schalkwijk, Joost; Armour, John Al

2011-08-18

Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders

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Carpenter Danielle

2011-08-01

Full Text Available Abstract Background Copy number variation (CNV contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. Results We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Conclusions Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

Parity violations in electron-nucleon scattering and the SU(2)sub(L)xSU(2)sub(R)xU(1)sub(L+R) electroweak symmetry

International Nuclear Information System (INIS)

Rajpoot, S.

1981-07-01

The SU(2)sub(L) x SU(2)sub(R) x U(1)sub(L+R) model of electroweak interactions is described with the most general gauge couplings gsub(L), gsub(R) and gsub(L+R). The case in which neutrino neutral current interactions are identical to the standard SU(2)sub(L) x U(1)sub(L+R) model is discussed in detail. It is shown that with the weak angle lying in the experimental range sin 2 thetaSUB(w)=0.23+-0.015 and 1 2 /gsub(R) 2 <3 it is possible to explain the amount of parity violation observed at SLAC and at the same time predict values of the ''weak charge'' in bismuth to lie in the range admitted by the controversal data from different experiments. (author)

ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner

OpenAIRE

Suk, Fat-Moon; Chang, Chi-Ching; Lin, Ren-Jye; Lin, Shyr-Yi; Liu, Shih-Chen; Jau, Chia-Feng; Liang, Yu-Chih

2018-01-01

ZFP36 family members include ZFP36, ZFP36L1, and ZFP36L2, which belong to CCCH-type zinc finger proteins with two tandem zinc finger (TZF) regions. Whether ZFP36L1 and ZFP36L2 have antiproliferative activities similar to that of ZFP36 is unclear. In this study, when ZFP36L1 or ZFP36L2 was overexpressed in T-REx-293 cells, cell proliferation was dramatically inhibited and the cell cycle was arrested at the G1 phase. The levels of cell-cycle-related proteins, including cyclin B, cyclin D, cycli...

The Level of Autoantibodies Targeting Eukaryote Translation Elongation Factor 1 α1 and Ubiquitin-Conjugating Enzyme 2L3 in Nondiabetic Young Adults

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Eunhee G. Kim

2016-01-01

Full Text Available BackgroundThe prevalence of novel type 1 diabetes mellitus (T1DM antibodies targeting eukaryote translation elongation factor 1 alpha 1 autoantibody (EEF1A1-AAb and ubiquitin-conjugating enzyme 2L3 autoantibody (UBE2L3-AAb has been shown to be negatively correlated with age in T1DM subjects. Therefore, we aimed to investigate whether age affects the levels of these two antibodies in nondiabetic subjects.MethodsEEF1A1-AAb and UBE2L3-AAb levels in nondiabetic control subjects (n=150 and T1DM subjects (n=101 in various ranges of age (18 to 69 years were measured using an enzyme-linked immunosorbent assay. The cutoff point for the presence of each autoantibody was determined based on control subjects using the formula: [mean absorbance+3×standard deviation].ResultsIn nondiabetic subjects, there were no significant correlations between age and EEF1A1-AAb and UBE2L3-AAb levels. However, there was wide variation in EEF1A1-AAb and UBE2L3-AAb levels among control subjects <40 years old; the prevalence of both EEF1A1-AAb and UBE2L3-AAb in these subjects was 4.4%. When using cutoff points determined from the control subjects <40 years old, the prevalence of both autoantibodies in T1DM subjects was decreased (EEFA1-AAb, 15.8% to 8.9%; UBE2L3-AAb, 10.9% to 7.9% when compared to the prevalence using the cutoff derived from the totals for control subjects.ConclusionThere was no association between age and EEF1A1-AAb or UBE2L3-AAb levels in nondiabetic subjects. However, the wide variation in EEF1A1-AAb and UBE2L3-AAb levels apparent among the control subjects <40 years old should be taken into consideration when determining the cutoff reference range for the diagnosis of T1DM.

Long-term convergence of speech rhythm in L1 and L2 English

NARCIS (Netherlands)

Quené, H; Orr, Rosemary

2014-01-01

When talkers from various language backgrounds use L2 English as a lingua franca, their accents of English are expected to converge, and talkers’ rhythmical patterns are predicted to converge too. Prosodic convergence was studied among talkers who lived in a community where L2 English is used

COMPARISON OF 16S rRNA-PCR-RFLP, LipL32-PCR AND OmpL1-PCR METHODS IN THE DIAGNOSIS OF LEPTOSPIROSIS

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Tülin GÜVEN GÖKMEN

Full Text Available SUMMARY Leptospirosis is still one of the most important health problems in developing countries located in humid tropical and subtropical regions. Human infections are generally caused by exposure to water, soil or food contaminated with the urine of infected wild and domestic animals such as rodents and dogs. The clinical course of leptospirosis is variable and may be difficult to distinguish from many other infectious diseases. The dark-field microscopy (DFM, serology and nucleic acid amplification techniques are used to diagnose leptospirosis, however, a distinctive standard reference method is still lacking. Therefore, in this study, we aimed to determine the presence of Leptospira spp., to differentiate the pathogenic L. interrogans and the non-pathogenic L. biflexa, and also to determine the sensitivity and specificity values of molecular methods as an alternative to conventional ones. A total of 133 serum samples, from 47 humans and 86 cattle were evaluated by two conventional tests: the Microagglutination Test (MAT and the DFM, as well as three molecular methods, the 16S rRNA-PCR followed by Restriction Fragment Lenght Polymorphism (RFLP of the amplification products 16S rRNA-PCR-RFLP, LipL32-PCR and OmpL1-PCR. In this study, for L. interrogans, the specificity and sensitivity rates of the 16S rRNA-PCR and the LipL32-PCR were considered similar (100% versus 98.25% and 100% versus 98.68%, respectively. The OmpL1-PCR was able to classify L. interrogans into two intergroups, but this PCR was less sensitive (87.01% than the other two PCR methods. The 16S rRNA-PCR-RFLP could detect L. biflexa DNA, but LipL32-PCR and OmpL1-PCR could not. The 16S rRNA-PCR-RFLP provided an early and accurate diagnosis and was able to distinguish pathogenic and non-pathogenic Leptospira species, hence it may be used as an alternative method to the conventional gold standard techniques for the rapid disgnosis of leptospirosis.

Turbulence, raindrops and the l{sup 1/2} number density law

Energy Technology Data Exchange (ETDEWEB)

Lovejoy, S [Department of Physics, McGill University, 3600 University street, Montreal, Quebec, H3A 2T8 (Canada); Schertzer, D [Universite Paris-Est, ENPC/CEREVE, 77455 Marne-la-Vallee Cedex 2 (France)], E-mail: lovejoy@physics.mcgill.ca

2008-07-15

Using a unique data set of three-dimensional drop positions and masses (the HYDROP experiment), we show that the distribution of liquid water in rain displays a sharp transition between large scales which follow a passive scalar-like Corrsin-Obukhov (k{sup -5/3}) spectrum and a small-scale statistically homogeneous white noise regime. We argue that the transition scale l{sub c} is the critical scale where the mean Stokes number (= drop inertial time/turbulent eddy time) St{sub l} is unity. For five storms, we found l{sub c} in the range 45-75 cm with the corresponding dissipation scale St{sub {eta}} in the range 200-300. Since the mean interdrop distance was significantly smaller ({approx} 10 cm) than l{sub c} we infer that rain consists of 'patches' whose mean liquid water content is determined by turbulence with each patch being statistically homogeneous. For l>l{sub c}, we have St{sub l}<1 and due to the observed statistical homogeneity for l{sub c}, we argue that we can use Maxey's relations between drop and wind velocities at coarse grained resolution l{sub c}. From this, we derive equations for the number and mass densities (n and {rho}) and their variance fluxes ({psi} and {chi}). By showing that {chi} is dissipated at small scales (with l{sub {rho}}{sub ,diss}{approx}l{sub c}) and {psi} over a wide range, we conclude that {rho} should indeed follow Corrsin-Obukhov k{sup -5/3} spectra but that n should instead follow a k{sup -2} spectrum corresponding to fluctuations scaling as {delta}{rho}{approx}l{sup 1/3} and {delta}n{approx}l{sup 1/2}. While the Corrsin-Obukhov law has never been observed in rain before, its discovery is perhaps not surprising; in contrast the {delta}n{approx}l{sup 1/2} number density law is quite new. The key difference between the {delta}{rho}, {delta}n laws is the fact that the microphysics (coalescence, breakup) conserves drop mass, but not numbers of particles. This implies that the timescale for the transfer of the

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

DEFF Research Database (Denmark)

Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L

2017-01-01

bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well...

PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5-Dependent Mechanism.

Science.gov (United States)

McKay, Jerome T; Haro, Marcela A; Daly, Christina A; Yammani, Rama D; Pang, Bing; Swords, W Edward; Haas, Karen M

2017-09-15

B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2 -/- ) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2 -/- mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae , but not PC-negative nontypeable Haemophilus influenzae , relative to wild-type mice. PD-L2 -/- mice had significantly increased PC-specific CD138 + splenic plasmablasts bearing a B-1a phenotype, and produced PC-reactive Abs largely of the T15 Id. Importantly, PC-reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated that B cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition to increased PC-specific IgM, naive PD-L2 -/- mice and irradiated chimeras reconstituted with PD-L2 -/- B cells had significantly higher levels of IL-5, a potent stimulator of B-1 cell Ab production. PD-L2 mAb blockade of wild-type B-1 cells in culture significantly increased CD138 and Blimp1 expression and PC-specific IgM, but did not affect proliferation. PD-L2 mAb blockade significantly increased IL-5 + T cells in culture. Both IL-5 neutralization and STAT5 inhibition blunted the effects of PD-L2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural Ab production by B-1 cells. These findings have broad implications for the development of therapeutic strategies aimed at altering natural Ab levels critical for protection against infectious disease, autoimmunity, allergy, cancer, and atherosclerosis. Copyright © 2017 by The American Association of Immunologists, Inc.

Listeria monocytogenes serovar 4a is a possible evolutionary intermediate between L. monocytogenes serovars 1/2a and 4b and L. innocua.

Science.gov (United States)

Chen, Jianshun; Jiang, Lingli; Chen, Xueyan; Luo, Xiaokai; Chen, Yang; Yu, Ying; Tian, Guoming; Liu, Dongyou; Fang, Weihuan

2009-03-01

The genus Listeria consists of six closely related species and forms three phylogenetic groups: L. monocytogenes- L. innocua, L. ivanovii-L. seeligeri-L. welshimeri, and L. grayi. In this report, we attempted to examine the evolutionary relationship in the L. monocytogenes-L. innocua group by probing the nucleotide sequences of 23S rRNA and 16S rRNA, and the gene clusters lmo0029-lmo0042, ascBdapE, rplS-infC, and prs-ldh in L. monocytogenes serovars 1/2a, 4a, and 4b, and L. innocua. Additionally, we assessed the status of L. monocytogenes-specific inlA and inlB genes and 10 L. innocua-specific genes in these species/serovars, together with phenotypic characterization by using in vivo and in vitro procedures. The results indicate that L. monocytogenes serovar 4a strains are genetically similar to L. innocua in the lmo0035-lmo0042, ascB-dapE, and rplS-infC regions and also possess L. innocua-specific genes lin0372 and lin1073. Furthermore, both L. monocytogenes serovar 4a and L. innocua exhibit impaired intercellular spread ability and negligible pathogenicity in mouse model. On the other hand, despite resembling L. monocytogenes serovars 1/2a and 4b in having a nearly identical virulence gene cluster, and inlA and inlB genes, these serovar 4a strains differ from serovars 1/2a and 4b by harboring notably altered actA and plcB genes, displaying strong phospholipase activity and subdued in vivo and in vitro virulence. Thus, by possessing many genes common to L. monocytogenes serovars 1/2a and 4b, and sharing many similar gene deletions with L. innocua, L. monocytogenes serovar 4a represents a possible evolutionary intermediate between L. monocytogenes serovars 1/2a and 4b and L. innocua.

Data of evolutionary structure change: 1AIFA-2AI0L [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 2> 0 n> 1AIF n>A ...n>1AIFAn> VSSSI----SSSNL...n> 2AI0 n>L 2AI...1AIFA-2AI0L 1AIF 2AI0 A L DIQLTQSPAFMAASPGEKVTITCSVSSSI----SSSNLH...SER CA 251 SER CA 276 SER CA 258 ASN CA 337 LEU CA 410

L 1 Generalized Procrustes 2D Shape Alignment

DEFF Research Database (Denmark)

Larsen, Rasmus

2008-01-01

on the orientation of the coordinate system, i.e. it is not rotationally invariant. However, by simultaneously minimizing the city block distances in a series of rotated coordinate systems we are able to approximate the circular equidistance curves of Euclidean distances with a regular polygonal equidistance curve...... to the precision needed. Using 3 coordinate systems rotated 30 degrees we get a 12 sided regular polygon, with which we achieve deviations from Euclidean distances less than 2 % over all directions. This new formulation allows for minimization in the L1-norm using LP. We demonstrate that the use of the L1-norm...

L = ± 1 stellarator

International Nuclear Information System (INIS)

Kikuchi, T.; Shiina, S.; Saito, K.; Gesso, H.; Aizawa, M.; Kawakami, I.

1985-01-01

We report the magnetic field configuration of helical magnetic axis stellarator. The magnetic field configuration is composed of large l=1 field and small l=-1 and l=0(bumpy) fields. The large l=1 field (combined with the small l=-1 field) is used to form helical magnetic axis with the helical curvature much larger than the toroidal curvature, which provides the high limiting values of β. The small l=-1 field, furthermore, as well as the large l=1 field reduces the Pfirsch-Schlueter currents by combining with l=0 field. Therefore, the large l=1 field and the combination of three field components may be favourable for the increase of limiting β value

Bi-allelic Mutations in PKD1L1 Are Associated with Laterality Defects in Humans.

Science.gov (United States)

Vetrini, Francesco; D'Alessandro, Lisa C A; Akdemir, Zeynep C; Braxton, Alicia; Azamian, Mahshid S; Eldomery, Mohammad K; Miller, Kathryn; Kois, Chelsea; Sack, Virginia; Shur, Natasha; Rijhsinghani, Asha; Chandarana, Jignesh; Ding, Yan; Holtzman, Judy; Jhangiani, Shalini N; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Hanchard, Neil A; Harel, Tamar; Rosenfeld, Jill A; Belmont, John W; Lupski, James R; Yang, Yaping

2016-10-06

Disruption of the establishment of left-right (L-R) asymmetry leads to situs anomalies ranging from situs inversus totalis (SIT) to situs ambiguus (heterotaxy). The genetic causes of laterality defects in humans are highly heterogeneous. Via whole-exome sequencing (WES), we identified homozygous mutations in PKD1L1 from three affected individuals in two unrelated families. PKD1L1 encodes a polycystin-1-like protein and its loss of function is known to cause laterality defects in mouse and medaka fish models. Family 1 had one fetus and one deceased child with heterotaxy and complex congenital heart malformations. WES identified a homozygous splicing mutation, c.6473+2_6473+3delTG, which disrupts the invariant splice donor site in intron 42, in both affected individuals. In the second family, a homozygous c.5072G>C (p.Cys1691Ser) missense mutation was detected in an individual with SIT and congenital heart disease. The p.Cys1691Ser substitution affects a highly conserved cysteine residue and is predicted by molecular modeling to disrupt a disulfide bridge essential for the proper folding of the G protein-coupled receptor proteolytic site (GPS) motif. Damaging effects associated with substitutions of this conserved cysteine residue in the GPS motif have also been reported in other genes, namely GPR56, BAI3, and PKD1 in human and lat-1 in C. elegans, further supporting the likely pathogenicity of p.Cys1691Ser in PKD1L1. The identification of bi-allelic PKD1L1 mutations recapitulates previous findings regarding phenotypic consequences of loss of function of the orthologous genes in mice and medaka fish and further expands our understanding of genetic contributions to laterality defects in humans. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus.

Science.gov (United States)

Fufaa, Gudeta D; Weil, E Jennifer; Nelson, Robert G; Hanson, Robert L; Bonventre, Joseph V; Sabbisetti, Venkata; Waikar, Sushrut S; Mifflin, Theodore E; Zhang, Xiaoming; Xie, Dawei; Hsu, Chi-Yuan; Feldman, Harold I; Coresh, Josef; Vasan, Ramachandran S; Kimmel, Paul L; Liu, Kathleen D

2015-01-01

Kidney injury molecule 1 (KIM-1), liver fatty acid-binding protein (L-FABP), N-acetyl-β-D-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) are urinary biomarkers of renal tubular injury. We examined their association with incident end-stage renal disease (ESRD) and all-cause mortality in American Indians with type 2 diabetes. Biomarker concentrations were measured in baseline urine samples in 260 Pima Indians who were followed for a median of 14 years. HRs were reported per SD of creatinine (Cr)-normalised log-transformed KIM-1, NAG and NGAL, and for three categories of L-FABP. During follow-up, 74 participants developed ESRD and 101 died. Median concentrations of KIM-1/Cr, NAG/Cr and NGAL/Cr and the proportion of detectable L-FABP were highest in those with macroalbuminuria (p associated with ESRD (HR 1.59, 95% CI 1.20, 2.11) and mortality (HR 1.39, 95% CI 1.06, 1.82); L-FABP/Cr was inversely associated with ESRD (HR [for highest vs lowest tertile] 0.40, 95% CI 0.19, 0.83). Addition of NGAL/Cr to models that included albuminuria and glomerular filtration rate increased the c-statistic for predicting ESRD from 0.828 to 0.833 (p = 0.001) and for death from 0.710 to 0.722 (p = 0.018). Addition of L-FABP/Cr increased the c-statistic for ESRD from 0.828 to 0.832 (p = 0.042). In Pima Indians with type 2 diabetes, urinary concentrations of NGAL and L-FABP are associated with important health outcomes, but they are unlikely to add to risk prediction with standard markers in a clinically meaningful way given the small increase in the c-statistic.

The Use of Paraphrase in Summary Writing: A Comparison of L1 and L2 Writers

Science.gov (United States)

Keck, Casey

2006-01-01

Paraphrasing is considered by many to be an important skill for academic writing, and some have argued that the teaching of paraphrasing might help students avoid copying from source texts. Few studies, however, have investigated the ways in which both L1 and L2 academic writers already use paraphrasing as a textual borrowing strategy when…

[Construction and application of prokaryotic expression system of Leptospira interrogans lipL32/1-lipL41/1 fusion gene].

Science.gov (United States)

Luo, Dong-jiao; Yan, Jie; Mao, Ya-fei; Li, Shu-ping; Luo, Yi-hui; Li, Li-wei

2005-01-01

To construct lipL32/1-lipL41/1 fusion gene and its prokaryotic expression system and to determine frequencies of carrying and expression of lipL32 and lipL41 genes in L.interrogans wild strains and specific antibody levels in sera from leptospirosis patients. lipL32/1-lipL41/1 fusion gene was constructed using linking primer PCR method and the prokaryotic expression system of the fusion gene done with routine techniques. SDS-PAGE was used to examine expression of the target recombinant protein rLipL32/1-rLipL41/1. Immunogenicity of rLipL32/1-rLipL41/1 was identified by Western blot. PCR and MAT were performed to detect carrying and expression of lipL32 and lipL41 genes in 97 wild L.interrogans strains. Antibodies against products of lipL32 and lipL41 genes in serum samples from 228 leptospirosis patients were detected by ELISA method. The homogeneity of nucleotide and putative amino acid sequence of lipL32/1-lipL41/1 fusion gene were 99.9 % and 99.8 % in comparison with the reported sequences. Expression output of the target recombinant protein rLipL32/1-rLipL41/1, mainly present in inclusion body, accounted for 10 % of the total bacterial proteins. Both the rabbit antisera against rLipL32/1 and rLipL41/1 could combine to rLipL32/1-rLipL41/1. 97.9 % and 87.6 % of the L.interrogans wild strains had lipL32 and lipL41 genes, respectively. 95.9 % and 84.5 % of the wild strains were positive for MAT with titers of 1:4 - 1:128 using rabbit anti-rLipL32s or anti-rLipL41s sera, respectively. 94.7 % - 97.4 % of the patients'serum samples were positive for rLipL32s antibodies, while 78.5 % - 84.6 % of them were rLipL41s antibodies detectable. lipL32/1-jlipL41/1 fusion gene and its prokaryotic expression system were successfully constructed. The expressed fusion protein had qualified immunogenicity. Both the lipL32 and lipL41 genes are extensively carried and frequently expressed by different serogroups of L.interrogans, and their expression products exhibit cross-antigenicity.

Acquiring native-like intonation in Dutch and Spanish : Comparing the L1 and L2 of native speakers and second language learners

NARCIS (Netherlands)

van Maastricht, L.J.; Swerts, M.G.J.; Krahmer, E.J.

2013-01-01

ACQUIRING NATIVE-LIKE INTONATION IN DUTCH AND SPANISH Comparing the L1 and L2 of native speakers and second language learners Introduction Learning more about the interaction between the native language (L1) and the target language (L2) has been the aim of many studies on second language acquisition

La norma L1 como alternativa a la norma L2 en el ajuste de la regresión

Directory of Open Access Journals (Sweden)

Carlos N. Bouza

2002-01-01

Full Text Available En este trabajo analizamos el desarrollo y los conceptos de las normas L1 y L2 y se comparan con algunos ejemplos. Por una parte la norma L1 es óptima bajo los supuestos de que los errores tienen la distribución de Laplace. Esta fue propuesta mucho antes que el MC, pero las facilidades de cómputo de éstos últimos le dieron primacía. Actualmente va adquiriendo gran importancia para las aplicaciones económicas, dado que en general los problemas de finanzas y de series temporales incumplen con las hipótesis usadas en el teorema de Gauss-Markoff. El uso de la norma L2, es el método de universal aceptación en el ajuste de la regresión. Sin embargo su optimalidad solo es válida bajo una serie de supuestos que no se cumplen en general (Teorema de Gaus- Markoff. Por lo tanto, norma L1 aparece como una alternativa mejor que la L2 en muchas aplicaciones dada su robustez ante las observaciones atípicas.

L1 and L2 sub-shell fluorescence yields for elements with 64 ≤ Z ≤ 70

International Nuclear Information System (INIS)

Kumar, Anil; Puri, Sanjiv

2010-01-01

The L 1 and L 2 sub-shell fluorescence yields have been deduced for elements with 64 ≤ Z ≤ 70 from the L k (k = l, α, β 1,4 , β 3,6 , β 2,15,9,10,7 , γ 1,5 and γ 2,3,4 ) X-ray production cross sections measured at 22.6 keV incident photon energy using a spectrometer involving a disc type radioisotope of Cd 109 as a photon source and a Peltier cooled X-ray detector. The incident photon intensity, detector efficiency and geometrical factor have been determined from the K X-ray yields emitted from elemental targets with 20 ≤ Z ≤ 42 in the same geometrical setup and from knowledge of the K shell cross sections. The present deduced ω 1 (exp) values, for elements with 64 ≤ Z ≤ 70, are found to be in good agreement with those tabulated by Campbell (J.L. Campbell, Atom. Data Nucl. Data Tables 95 (2009) 115), where as these are, on an average, higher by 19% and 24% than those based on the Dirac-Hartree-Slater model (S. Puri et al., X-ray Spectrometry 22 (1993) 358) and the semi-empirical values compiled by Krause (M.O. Krause, J. Phys. Chem. Ref. Data 8 (1979) 307), respectively. The present deduced ω 2 (exp) values are found to be in good agreement with those based on the Dirac-Hartree-Slater model and are higher by up to ∼13% than the semi-empirical values for the elements under investigation.

L 1 and L 2 sub-shell fluorescence yields for elements with 64 ⩽ Z ⩽ 70

Science.gov (United States)

Kumar, Anil; Puri, Sanjiv

2010-05-01

The L 1 and L 2 sub-shell fluorescence yields have been deduced for elements with 64 ⩽ Z ⩽ 70 from the L k( k = l, α, β1,4, β3,6, β2,15,9,10,7, γ1,5 and γ2,3,4) X-ray production cross sections measured at 22.6 keV incident photon energy using a spectrometer involving a disc type radioisotope of Cd 109 as a photon source and a Peltier cooled X-ray detector. The incident photon intensity, detector efficiency and geometrical factor have been determined from the K X-ray yields emitted from elemental targets with 20 ⩽ Z ⩽ 42 in the same geometrical setup and from knowledge of the K shell cross sections. The present deduced ω1(exp) values, for elements with 64 ⩽ Z ⩽ 70, are found to be in good agreement with those tabulated by Campbell (J.L. Campbell, Atom. Data Nucl. Data Tables 95 (2009) 115), where as these are, on an average, higher by 19% and 24% than those based on the Dirac-Hartree-Slater model (S. Puri et al., X-ray Spectrometry 22 (1993) 358) and the semi-empirical values compiled by Krause (M.O. Krause, J. Phys. Chem. Ref. Data 8 (1979) 307), respectively. The present deduced ω2(exp) values are found to be in good agreement with those based on the Dirac-Hartree-Slater model and are higher by up to ˜13% than the semi-empirical values for the elements under investigation.

IRS1, TCF7L2, ADRB1, PPARG, and HHEX Polymorphisms Associated with Atherogenic Risk in Mexican Population

Directory of Open Access Journals (Sweden)

B. I. Estrada-Velasco

2013-01-01

Full Text Available Objective. We aimed to explore the association between polymorphisms of IRS1 (rs1801278, TCF7L2 (rs7903146 and rs12255372, ADRB1 (rs1801253, PPARG (rs1801282, and HHEX (rs5015480 genes with atherogenic risk (AI = Total cholesterol/HDL in MetS, T2D, and healthy populations from the Mexican Social Security Institute. Methodology and Results. Four hundred thirty-five MetS, 517 T2D, and 547 healthy individuals were selected. The association between the SNPs and the atherogenic index was evaluated by multiple linear regression and multinomial logistic regression models. The ADRB1 gene showed a statistically significant association with high-risk atherogenic index, OR=2.94 (IC 95% 1.64–5.24; P<0.0001 for the Arg/Gly variant, under the dominant model an OR=2.96 (IC 95% 1.67–5.25; P<0.0001, and under the Log additive model an OR=2.52 (IC 95% 1.54–4.15; P<0.0001. Conclusions. The Arg389Gly polymorphism of the ADRB1 gene may be a worthy biological marker to predict the risk of developing cardiovascular diseases given a high-risk atherogenic index.

HPTLC methods for the Rapid Determination of Adhatoda vasica L. Glycyrrhiza glabbra L., Phyllanthus embelica L. and Camellia sinensis L. in a polyherbal formulation (INSTY)

International Nuclear Information System (INIS)

Sheikh, Z. A.; Zahoor, A.; Shafiq, K.; Usmanghani, K.; Khan, S. S.; Khan, A.

2015-01-01

An Insty Granule is a polyherbal formulation, and it is widely used to treat upper respiratory tract infections. It contains expectorant, anti-inflammatory, mucolytic and anti-pyretic properties. The major active constituents are vasicine, gallic acid, caffeine and glycyrrhizin. Insty a poly herbal formulation of eight herbs were investigated for its phytochemical evaluation. Biomarkers of about four herbs both qualitatively and quantitatively were investigated. Methods: The solvent systems used were ethyl acetate, chloroform, ethanol, ammonia (6: 3: 1: 1) for vasicin, ethyl acetate, chloroform, formic acid (12: 15: 3) for gallic acid, ethyl acetate, methanol, water (100: 13.5: 10) for caffeine, and methanol, water, acetic acid (70: 30: 0.5) for glycyrrhizin. Results: The methods showed a good linear relationship (r/sup 2/ = 0.999) in the concentration range 25-1500 ng per spot. It was found to be linear, accurate, precise, specific, robust and can be applied for quality control and standardization. Conclusion: In present study rapid and inexpensive qualification methods for the quality control of Adhatoda vasica L. Glycyrrhiza glabbra L., Phyllanthus embelica L. and Camellia sinensis L. on thin layer chromatography (TLC) were developed and validated on silica gel. HPTLC is most suitable technique because of quantification of number of samples at low operating cost, easy sample preparation, short analysis time and analytical assurance. (author)

JNK1 Controls Dendritic Field Size in L2/3 and L5 of the Motor Cortex, Constrains Soma Size and Influences Fine Motor Coordination

Directory of Open Access Journals (Sweden)

Emilia eKomulainen

2014-09-01

Full Text Available Genetic anomalies on the JNK pathway confer susceptibility to autism spectrum disorders, schizophrenia and intellectual disability. The mechanism whereby a gain or loss of function in JNK signaling predisposes to these prevalent dendrite disorders, with associated motor dysfunction, remains unclear. Here we find that JNK1 regulates the dendritic field of L2/3 and L5 pyramidal neurons of the mouse motor cortex (M1, the main excitatory pathway controlling voluntary movement. In Jnk1-/- mice, basal dendrite branching of L5 pyramidal neurons is increased in M1, as is cell soma size, whereas in L2/3, dendritic arborization is decreased. We show that JNK1 phosphorylates rat HMW-MAP2 on T1619, T1622 and T1625 (Uniprot P15146 corresponding to mouse T1617, T1620, T1623, to create a binding motif, that is critical for MAP2 interaction with and stabilization of microtubules, and dendrite growth control. Targeted expression in M1 of GFP-HMW-MAP2 that is pseudo-phosphorylated on T1619, T1622 and T1625 increases dendrite complexity in L2/3 indicating that JNK1 phosphorylation of HMW-MAP2 regulates the dendritic field. Consistent with the morphological changes observed in L2/3 and L5, Jnk1-/- mice exhibit deficits in limb placement and motor coordination, while stride length is reduced in older animals. In summary, JNK1 phosphorylates HMW-MAP2 to increase its stabilization of microtubules while at the same time controlling dendritic fields in the main excitatory pathway of M1. Moreover, JNK1 contributes to normal functioning of fine motor coordination. We report for the first time, a quantitative sholl analysis of dendrite architecture, and of motor behavior in Jnk1-/- mice. Our results illustrate the molecular and behavioral consequences of interrupted JNK1 signaling and provide new ground for mechanistic understanding of those prevalent neuropyschiatric disorders where genetic disruption of the JNK pathway is central.

Geração de Isolinhas, com dados obtidos por levantamento GPS/L1L2, mediante a técnica de Redes Neurais Artificiais = Generation of Isolines using GPS/L1L2 data and Artificial Neural Network technique

Directory of Open Access Journals (Sweden)

Elaine Cristine Barros de Souza

2006-07-01

Full Text Available O objetivo deste trabalho é mostrar uma alternativa para o processo deinterpolação empregado em Modelagem Digital do Terreno. Utilizando-se dados de levantamentos GPS coletados por meio de posicionamento relativo cinemático realizou-se um processo de interpolação por meio de Redes Neurais Artificiais (RNA. Os resultados foram comparados com os dados obtidos usando-se o algoritmo de interpolação Inverso doQuadrado de uma Distância (IQD para avaliar o comportamento das grades geradas por meio de análises qualitativas (isolinhas e MDT e quantitativas (resíduos. Conclui-se que o método testado é viável se comparado com o algoritmo IQD e, portanto, o uso de RNA apresenta-se adequado para a interpolação de dados GPS provenientes do processamento de fase das portadoras L1 e L2.The objective of this work is to show an alternative for theinterpolation process used in Digital Terrain Modeling. GPS surveying data of a kinematic relative positioning were interpolated by means of Artificial Neural Networks (ANN algorithm. The performance of the generated gridding was compared to the Inverse Square Distance interpolation algorithm data by means of qualitative (isolines and DTM and quantitative (residuals analyses. In conclusion, the tested method is viable if compared to the algorithm Inverse of the Square of a Distance. Therefore, the use of ANN is suitable for the interpolation of GPS data obtained from the L1 and L2 carriers phase processing.

Phonetic Encoding of Coda Voicing Contrast under Different Focus Conditions in L1 vs. L2 English.

Science.gov (United States)

Choi, Jiyoun; Kim, Sahayng; Cho, Taehong

2016-01-01

This study investigated how coda voicing contrast in English would be phonetically encoded in the temporal vs. spectral dimension of the preceding vowel (in vowel duration vs. F1/F2) by Korean L2 speakers of English, and how their L2 phonetic encoding pattern would be compared to that of native English speakers. Crucially, these questions were explored by taking into account the phonetics-prosody interface, testing effects of prominence by comparing target segments in three focus conditions (phonological focus, lexical focus, and no focus). Results showed that Korean speakers utilized the temporal dimension (vowel duration) to encode coda voicing contrast, but failed to use the spectral dimension (F1/F2), reflecting their native language experience-i.e., with a more sparsely populated vowel space in Korean, they are less sensitive to small changes in the spectral dimension, and hence fine-grained spectral cues in English are not readily accessible. Results also showed that along the temporal dimension, both the L1 and L2 speakers hyperarticulated coda voicing contrast under prominence (when phonologically or lexically focused), but hypoarticulated it in the non-prominent condition. This indicates that low-level phonetic realization and high-order information structure interact in a communicatively efficient way, regardless of the speakers' native language background. The Korean speakers, however, used the temporal phonetic space differently from the way the native speakers did, especially showing less reduction in the no focus condition. This was also attributable to their native language experience-i.e., the Korean speakers' use of temporal dimension is constrained in a way that is not detrimental to the preservation of coda voicing contrast, given that they failed to add additional cues along the spectral dimension. The results imply that the L2 phonetic system can be more fully illuminated through an investigation of the phonetics-prosody interface in connection

English Language Learners' Nonword Repetition Performance: The Influence of Age, L2 Vocabulary Size, Length of L2 Exposure, and L1 Phonology.

Science.gov (United States)

Duncan, Tamara Sorenson; Paradis, Johanne

2016-02-01

This study examined individual differences in English language learners' (ELLs) nonword repetition (NWR) accuracy, focusing on the effects of age, English vocabulary size, length of exposure to English, and first-language (L1) phonology. Participants were 75 typically developing ELLs (mean age 5;8 [years;months]) whose exposure to English began on average at age 4;4. Children spoke either a Chinese language or South Asian language as an L1 and were given English standardized tests for NWR and receptive vocabulary. Although the majority of ELLs scored within or above the monolingual normal range (71%), 29% scored below. Mixed logistic regression modeling revealed that a larger English vocabulary, longer English exposure, South Asian L1, and older age all had significant and positive effects on ELLs' NWR accuracy. Error analyses revealed the following L1 effect: onset consonants were produced more accurately than codas overall, but this effect was stronger for the Chinese group whose L1s have a more limited coda inventory compared with English. ELLs' NWR performance is influenced by a number of factors. Consideration of these factors is important in deciding whether monolingual norm referencing is appropriate for ELL children.

L2TTMON Monitoring Program for L2 Topological Trigger in H1 Experiment - User's Guide

International Nuclear Information System (INIS)

Banas, E.; Ducorps, A.

1999-01-01

Monitoring software for the L2 Topological Trigger in H1 experiment consists of two parts working on two different computers. The hardware read-out and data processing is done on a fast FIC 8234 computer working with the OS9 real time operating system. The Macintosh Quadra is used as a Graphic User Interface for accessing the OS9 trigger monitoring software. The communication between both computers is based on the parallel connection between the Macintosh and the VME crate, where the FIC computer is placed. The special designed protocol (client-server) is used to communicate between both nodes. The general scheme of monitoring for the L2 Topological Trigger and detailed description of using of the monitoring software in both nodes are given in this guide. (author)

Development and implementation of a novel assay for L-2-hydroxyglutarate dehydrogenase (L-2-HGDH) in cell lysates: L-2-HGDH deficiency in 15 patients with L-2-hydroxyglutaric aciduria

DEFF Research Database (Denmark)

Kranendijk, M; Salomons, G S; Gibson, K M

2009-01-01

L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by mutations in the gene encoding L-2-hydroxyglutarate dehydrogenase. An assay to evaluate L-2-hydroxyglutarate dehydrogenase (L-2-HGDH) activity in fibroblast, lymphoblast and/or lymphoc...

HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations.

Science.gov (United States)

Aulicino, Paula C; Rocco, Carlos A; Mecikovsky, Debora; Bologna, Rosa; Mangano, Andrea; Sen, Luisa

2010-01-01

Patterns and pathways of HIV type-1 (HIV-1) antiretroviral (ARV) drug resistance-associated mutations in clinical isolates are conditioned by ARV history and factors such as viral subtype and fitness. Our aim was to analyse the frequency and association of ARV drug resistance mutations in a group of long-term vertically infected patients from Argentina. Plasma samples from 71 patients (38 children and 33 adolescents) were collected for genotypic HIV-1 ARV resistance testing during the period between February 2006 and October 2008. Statistically significant pairwise associations between ARV resistance mutations in pol, as well as associations between mutations and drug exposure, were identified using Fisher's exact tests with Bonferroni and false discovery rate corrections. Phylogenetic analyses were performed for subtype assignment. In protease (PR), resistance-associated mutations M46I/L, I54M/L/V/A/S and V82A/F/T/S/M/I were associated with each other and with minor mutations at codons 10, 24 and 71. Mutations V82A/F/T/S/M/I were primarily selected by the administration of ritonavir (RTV) in an historical ARV regimen. In reverse transcriptase, thymidine analogue mutation (TAM)1 profile was more common than TAM2. The non-nucleoside K103N+L100I mutations were observed at high frequency (15.5%) and were significantly associated with the nucleoside mutation L74V in BF recombinants. Associations of mutations at PR sites reflect the frequent use of RTV at an early time in this group of patients and convergent resistance mechanisms driven by the high exposure to protease inhibitors, as well as local HIV-1 diversity. The results provide clinical evidence of a molecular interaction between K103N+L100I and L74V mutations at the reverse transcriptase gene in vivo, limiting the future use of second-generation non-nucleoside reverse transcriptase inhibitors such as etravirine.

Experiment prediction for LOFT nuclear experiments L5-1/L8-2

International Nuclear Information System (INIS)

Chen, T.H.; Modro, S.M.

1982-01-01

The LOFT Experiments L5-1 and L8-2 simulated intermediate break loss-of-coolant accidents with core uncovery. This paper compares the predictions with the measured data for these experiments. The RELAP5 code was used to perform best estimate double-blind and single-blind predictions. The double-blind calculations are performed prior to the experiment and use specified nominal initial and boundary conditions. The single-blind calculations are performed after the experiment and use measured initial and boundary conditions while maintaining all other parameters constant, including the code version. Comparisons of calculated results with experimental results are discussed; the possible causes of discrepancies are explored and explained. RELAP5 calculated system pressure, mass inventory, and fuel cladding temperature agree reasonably well with the experiment results, and only slight changes are noted between the double-blind and single-blind predictions

Getting Things Done in the L1 and L2: Bilingual Immigrant Women's Use of Communication Strategies in Entrepreneurial Contexts

Science.gov (United States)

Collier, Shartriya

2010-01-01

The article examines the communication strategies of four bilingual, immigrant women entrepreneurs within the context of their businesses. The analysis revealed that L1 and L2 use is crucial to the business success of the participants. L1 conversations consisted of largely private speech and directives. The women positioned themselves as…

Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2

DEFF Research Database (Denmark)

Hawthorne, Felicia; Feng, Sheng; Metlapally, Ravikanth

2013-01-01

PURPOSE: Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21-23 by four independent linkage studies. METHODS: We performed a genetic association study...... statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10(-6)); rs7134216, in the 3' untranslated region (UTR) of DEPDC4 (P = 5.4 × 10(-7)); and rs17306116, an intronic SNP within PPFIA2 (P Independently conducted whole genome expression array analyses identified...... protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR). CONCLUSIONS: In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs...

Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

DEFF Research Database (Denmark)

Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda

2018-01-01

Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unkn...... expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.......Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression...... is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. Materials and methods: We...

Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.

Science.gov (United States)

Su, Qiang; Hu, Feizhuo; Liu, Yuxia; Ge, Xiaofei; Mei, Changlin; Yu, Shengqiang; Shen, Aiwen; Zhou, Qiang; Yan, Chuangye; Lei, Jianlin; Zhang, Yanqing; Liu, Xiaodong; Wang, Tingliang

2018-03-22

PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of π-π interactions, suggesting a potential PKD2L1 gating mechanism.

FROM ENGLISH AS L1 TO PORTUGUESE AS L3 THROUGH SPANISH AS L2: TRANSFERS IN VERB REGENCY/TRANSITIVITY, WITH SPECIAL EMPHASIS ON PREPOSITIONS

OpenAIRE

RENATA DE OLIVEIRA RAZUK

2008-01-01

Do Inglês L1 ao Português L3 passando pelo Espanhol L2: transferências em regência/transitividade verbal, com foco nas preposições transita por temas pouco explorados - não só pela combinação de línguas adotada, como também pela especificidade do fenômeno analisado e pelo tópico gramatical escolhido -, contribuindo para o desenvolvimento de uma área de pesquisa extremamente recente e promissora: a aquisição de terceira língua. Os estudos em AL3 ainda estão mui...

Search for Associated Higgs Boson Production WH→WWW*→l±νl'±ν'+X in pp Collisions at √(s)=1.96 TeV

International Nuclear Information System (INIS)

Abazov, V. M.; Piegaia, R.; Abbott, B.; Gutierrez, P.; Hall, I.; Jain, S.; Kopal, M.; Pompos, A.; Severini, H.; Skubic, P.; Strauss, M.; Abolins, M.; Benitez, J. A.; Brock, R.; Dyer, J.; Edmunds, D.; Hauser, R.; Kalk, J. R.; Kozminski, J.; Linnemann, J.

2006-01-01

We present a search for associated Higgs boson production in the process pp→WH→WWW*→l ± νl '± ν ' +X in final states containing two like-sign isolated electrons or muons (e ± e ± , e ± μ ± , or μ ± μ ± ). The search is based on D0 run II data samples corresponding to integrated luminosities of 360-380 pb -1 . No excess is observed over the predicted standard model background. We set 95% C.L. upper limits on σ(pp→WH)xBr(H→WW*) between 3.2 and 2.8 pb for Higgs boson masses from 115 to 175 GeV

Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression.

Science.gov (United States)

Feng, Dan; Ohlsson, Lena; Duan, Rui-Dong

2010-04-19

Curcumin is a polyphenol and the one of the principle curcuminoids of the spice turmeric. Its antioxidant, anti-cancer and anti-inflammatory effects have been intensively studied. Previous in vivo studies showed that administration of curcumin also decreased cholesterol levels in the blood, and the effects were considered to be related to upregulation of LDL receptor. However, since plasma cholesterol levels are also influenced by the uptake of cholesterol in the gut, which is mediated by a specific transporter Niemann-Pick Cl-like 1 (NPC1L1) protein, the present study is to investigate whether curcumin affects cholesterol uptake in the intestinal Caco-2 cells. Caco-2 cells were cultured to confluence. The micelles composed of bile salt, monoolein, and 14C-cholesterol were prepared. We first incubated the cells with the micelles in the presence and absence of ezetimibe, the specific inhibitor of NPC1L1, to see whether the uptake of the cholesterol in the cells was mediated by NPC1L1. We then pretreated the cells with curcumin at different concentrations for 24 h followed by examination of the changes of cholesterol uptake in these curcumin-treated cells. Finally we determined whether curcumin affects the expression of NPC1L1 by both Western blot analysis and qPCR quantification. We found that the uptake of radioactive cholesterol in Caco-2 cells was inhibited by ezetimibe in a dose-dependent manner. The results indicate that the uptake of cholesterol in this study was mediated by NPC1L1. We then pretreated the cells with 25-100 muM curcumin for 24 h and found that such a treatment dose-dependently inhibited cholesterol uptake with 40% inhibition obtained by 100 muM curcumin. In addition, we found that the curcumin-induced inhibition of cholesterol uptake was associated with significant decrease in the levels of NPC1L1 protein and NPC1L1 mRNA, as analyzed by Western blot and qPCR, respectively. Curcumin inhibits cholesterol uptake through suppression of NPC1L1

Proton induced L{sub 1}, L{sub 2}, L{sub 3}-sub-shell X-ray production cross sections of Hf and Au

Energy Technology Data Exchange (ETDEWEB)

Bertol, A.P.L., E-mail: anapaula.bertol@gmail.com [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Hinrichs, R. [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Geociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Vasconcellos, M.A.Z. [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

2015-11-15

Experimental data for proton induced X-ray production cross sections of L-sub-shells of Hf and Au were obtained, in order to contribute to the existing data sets and to support refinements of the ECPSSR theory. X-ray emissions of mono-elemental 10 nm films of Hf and Au were excited with 0.7–1.5 MeV protons. The measured L-line spectra were fitted assuming Gaussian shapes and constraining peak positions and line widths. The transition energy values used to establish peak positions were based on values proposed in the literature, while the line widths were matched to the detector resolution, obtained independently. The intensity of each line was obtained from the adjusted areas, without the use of emission rates. The line intensities were summed in α, β, γ, and ℓ groups to validate the measurements by comparison with existing data, and in L{sub 1}, L{sub 2}, L{sub 3}-sub-shells for comparison with ECPSSR-UA theory. Ratios of the emission rates of lines of the same sub-shell were obtained and compared with the data from the literature.

RELATIONSHIP AMONG BRAIN HEMISPHERIC DOMINANCE, ATTITUDE TOWARDS L1 AND L2, GENDER, AND LEARNING SUPRASEGMENTAL FEATURES

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Mohammad Hadi Mahmoodi

2016-07-01

Full Text Available Oral skills are important components of language competence. To have good and acceptable listening and speaking, one must have good pronunciation, which encompasses segmental and suprasegmental features. Despite extensive studies on the role of segmental features and related issues in listening and speaking, there is paucity of research on the role of suprasegmental features in the same domain. Conducting studies which aim at shedding light on the issues related to learning suprasegmental features can help language teachers and learners in the process of teaching/learning English as a foreign language. To this end, this study was designed to investigate the relationship among brain hemispheric dominance, gender, attitudes towards L1 and L2, and learning suprasegmental features in Iranian EFL learners. First, 200 Intermediate EFL learners were selected from different English language teaching institutes in Hamedan and Isfahan, two provinces in Iran, as the sample. Prior to the main stage of the study, Oxford Placement Test (OPT was used to homogenize the proficiency level of all the participants. Then, the participants were asked to complete the Edinburgh Handedness Questionnaire to determine their dominant hemisphere. They were also required to answer two questionnaires regarding their attitudes towards L1 and L2. Finally, the participants took suprasegmental features test. The results of the independent samples t-tests indicated left-brained language learners’ superiority in observing and learning suprasegmental features. It was also found that females are better than males in producing suprasegmental features. Furthermore, the results of Pearson Product Moment Correlations indicated that there is significant relationship between attitude towards L2 and learning suprasegmental features. However, no significant relationship was found between attitude towards L1 and learning English suprasegmental features. The findings of this study can

Analysis of LOFT loss-of-coolant experiments L2-2, L2-3, and L3-0

International Nuclear Information System (INIS)

Leach, L.P.; Linebarger, J.H.

1979-01-01

A summary of results from Loss-of-Coolant Experiments (LOCE) L2-2, L2-3, and L3-0, conducted in the Loss-of-Fluid Test (LOFT) facility, and conclusions from posttest analyses of the experimental data are presented. LOCEs L2-2 and L2-3 were nuclear large break experiments and were dominated by a core-wide fuel rod cladding rewet, which limited the maximum fuel temperature. Analytical models only conservatively predicted the measured fuel rod temperatures and will require improvements to provide best estimate predictions in this area. Analysis of a large commercial pressurized water reactor (PWR) indicates that the cladding rewet observed in LOFT is also likely to occur in a large PWR, and that, therefore, safety analysis calculations of large loss-of-coolant accidents (LOCA) are more conservative than previously thought. LOCE L3-0 was an isothermal small break (top of pressurizer) experiment and illustrated that the pressurizer fills after the primary system fluid saturates someplace other than the pressurizer itself, that the indicated pressurizer level is higher than the actual level, and that additional model development and assessment work is necessary in order to predict small LOCAs as accurately as large LOCAs

Context affects L1 but not L2 during bilingual word recognition: an MEG study.

Science.gov (United States)

Pellikka, Janne; Helenius, Päivi; Mäkelä, Jyrki P; Lehtonen, Minna

2015-03-01

How do bilinguals manage the activation levels of the two languages and prevent interference from the irrelevant language? Using magnetoencephalography, we studied the effect of context on the activation levels of languages by manipulating the composition of word lists (the probability of the languages) presented auditorily to late Finnish-English bilinguals. We first determined the upper limit time-window for semantic access, and then focused on the preceding responses during which the actual word recognition processes were assumedly ongoing. Between 300 and 500 ms in the temporal cortices (in the N400 m response) we found an asymmetric language switching effect: the responses to L1 Finnish words were affected by the presentation context unlike the responses to L2 English words. This finding suggests that the stronger language is suppressed in an L2 context, supporting models that allow auditory word recognition to be affected by contextual factors and the language system to be subject to inhibitory influence. Copyright © 2015 Elsevier Inc. All rights reserved.

Using a Shared L1 to Reduce Cognitive Overload and Anxiety Levels in the L2 Classroom

Science.gov (United States)

Bruen, Jennifer; Kelly, Niamh

2017-01-01

This paper considers the attitudes and behaviours of university language lecturers and their students regarding the use of the L1 in the higher education L2 classroom. A case study of one Irish higher education institution was carried out and qualitative interviews conducted with six lecturers in Japanese and six in German. The results indicated…

Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis

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Peng-Fei Wang

2017-10-01

Full Text Available Background: Treatment of cancers with programmed cell death protein 1 (PD-1 pathway inhibitors can lead to immune-related adverse events (irAEs, which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs.Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence.Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC, colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis, endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency, digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin, respiratory system (pneumonitis, lung infiltration, and interstitial lung disease, and urinary system (increased creatinine, nephritis, and renal failure. In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73–32.61; I2, 92.80 in any grade and 6.10% (95% CI, 4.85–7.64; I2, 52.00 in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%.Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.

ATG16L1

DEFF Research Database (Denmark)

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris

2015-01-01

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1...... (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong...... association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus...

Synthesis and characterization of iron(III), manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) complexes of salicylidene-N-anilinoacetohydrazone (H2L1) and 2-hydroxy-1-naphthylidene-N-anilinoacetohydrazone (H2L2).

Science.gov (United States)

AbouEl-Enein, S A; El-Saied, F A; Kasher, T I; El-Wardany, A H

2007-07-01

Salicylidene-N-anilinoacetohydrazone (H(2)L(1)) and 2-hydroxy-1-naphthylidene-N-anilinoacetohydrazone (H(2)L(2)) and their iron(III), manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) complexes have been synthesized and characterized by IR, electronic spectra, molar conductivities, magnetic susceptibilities and ESR. Mononuclear complexes are formed with molar ratios of 1:1, 1:2 and 1:3 (M:L). The IR studies reveal various modes of chelation. The electronic absorption spectra and magnetic susceptibility measurements show that the iron(III), nickel(II) and cobalt(II) complexes of H(2)L(1) have octahedral geometry. While the cobalt(II) complexes of H(2)L(2) were separated as tetrahedral structure. The copper(II) complexes have square planar stereochemistry. The ESR parameters of the copper(II) complexes at room temperature were calculated. The g values for copper(II) complexes proved that the Cu-O and Cu-N bonds are of high covalency.

Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype

DEFF Research Database (Denmark)

Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet

2011-01-01

A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer As...

A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L

Science.gov (United States)

Drappier, Melissa; Elliott, Ruth; Zhang, Rong; Weiss, Susan R.; Silverman, Robert H.

2018-01-01

The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A. PMID:29652922

A Renewable and Ultrasensitive Electrochemiluminescence Immunosenor Based on Magnetic RuL@SiO2-Au~RuL-Ab2 Sandwich-Type Nano-Immunocomplexes

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Ning Gan

2011-08-01

Full Text Available An ultrasensitive and renewable electrochemiluminescence (ECL immunosensor was developed for the detection of tumor markers by combining a newly designed trace tag and streptavidin-coated magnetic particles (SCMPs. The trace tag (RuL@SiO2-Au~RuL-Ab2 was prepared by loading Ru(bpy32+(RuL-conjuged secondary antibodies (RuL-Ab2 on RuL@SiO2 (RuL-doped SiO2 doped Au (RuL@SiO2-Au. To fabricate the immunosensor, SCMPs were mixed with biotinylated AFP primary antibody (Biotin-Ab1, AFP, and RuL@SiO2-Au~RuL-Ab2 complexes, then the resulting SCMP/Biotin-Ab1/AFP/RuL@SiO2-Au~RuL-Ab2 (SBAR sandwich-type immunocomplexes were absorbed on screen printed carbon electrode (SPCE for detection. The immunocomplexes can be easily washed away from the surface of the SPCE when the magnetic field was removed, which made the immunosensor reusable. The present immunosensor showed a wide linear range of 0.05–100 ng mL–1 for detecting AFP, with a low detection limit of 0.02 ng mL–1 (defined as S/N = 3. The method takes advantage of three properties of the immunosensor: firstly, the RuL@SiO2-Au~RuL-Ab2 composite exhibited dual amplification since SiO2 could load large amount of reporter molecules (RuL for signal amplification. Gold particles could provide a large active surface to load more reporter molecules (RuL-Ab2. Accordingly, through the ECL response of RuL and tripropylamine (TPA, a strong ECL signal was obtained and an amplification analysis of protein interaction was achieved. Secondly, the sensor is renewable because the sandwich-type immunocomplexes can be readily absorbed or removed on the SPCE’s surface in a magnetic field. Thirdly, the SCMP modified probes can perform the rapid separation and purification of signal antibodies in a magnetic field. Thus, the present immunosensor can simultaneously realize separation, enrichment and determination. It showed potential application for the detection of AFP in human sera.

Evaluation of Extraction and Degradation Methods to Obtain Chickpeasaponin B1 from Chickpea (Cicer arietinum L.)

OpenAIRE

Kun Cheng; Hua Gao; Rong-Rong Wang; Yang Liu; Yu-Xue Hou; Xiao-Hong Liu; Kun Liu; Wei Wang

2017-01-01

The objective of this research is to implement extraction and degradation methods for the obtainment of 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1) from chickpea. The effects of microwave-assisted extraction (MAE) processing parameters—such as ethanol concentration, solvent/solid ratio, extraction temperature, microwave irradiation power, and irradiation time—were evaluated. Using 1g of material with 8 mL of 70% aqueous ethanol and an extraction t...

Type 2 diabetes gene TCF7L2 polymorphism is not associated with fetal and postnatal growth in two birth cohort studies

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Hofman Albert

2009-07-01

Full Text Available Abstract Background An inverse association between birth weight and the risk of developing type 2 diabetes (T2D in adulthood has been reported. This association may be explained by common genetic variants related to insulin secretion and resistance, since insulin is the most important growth factor in fetal life. The objective of this study was to examine whether T2D gene polymorphism TCF7L2 rs7903146 is associated with growth patterns from fetal life until infancy. Methods This study was performed in two independent birth cohort studies, one prospective population-based (Generation R, and one of subjects born small-for-gestational-age (SGA cohort. Fetal growth was assessed by ultrasounds in second and third trimesters of pregnancy in Generation R. Growth in infancy was assessed in both cohorts at birth and at 6, 12 and 24 months postnatally. TCF7L2 genotype was determined in 3,419 subjects in Generation R and in 566 subjects in the SGA cohort. Results Minor allele frequency did not differ significantly (p = 0.47 between Generation R (T-allele: 28.7% and the SGA cohort (T-allele: 29.8%. No differences at birth were found in gestational age or size (head circumference, length, weight between the genotypes in either cohort. TCF7L2 genotype was also not associated with any pre- or postnatal growth characteristic in either Generation R or the SGA cohort. Conclusion We found no evidence for an association between TCF7L2 genotype and fetal and early postnatal growth. Furthermore, this TCF7L2 polymorphism was not associated with an increased risk of SGA.

Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype

DEFF Research Database (Denmark)

Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet

2011-01-01

for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling......A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer......10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11...

Full-Length Sequence of Mouse Acupuncture-Induced 1-L (Aig1l Gene Including Its Transcriptional Start Site

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Mika Ohta

2011-01-01

Full Text Available We have been investigating the molecular efficacy of electroacupuncture (EA, which is one type of acupuncture therapy. In our previous molecular biological study of acupuncture, we found an EA-induced gene, named acupuncture-induced 1-L (Aig1l, in mouse skeletal muscle. The aims of this study consisted of identification of the full-length cDNA sequence of Aig1l including the transcriptional start site, determination of the tissue distribution of Aig1l and analysis of the effect of EA on Aig1l gene expression. We determined the complete cDNA sequence including the transcriptional start site via cDNA cloning with the cap site hunting method. We then analyzed the tissue distribution of Aig1l by means of northern blot analysis and real-time quantitative polymerase chain reaction. We used the semiquantitative reverse transcriptase-polymerase chain reaction to examine the effect of EA on Aig1l gene expression. Our results showed that the complete cDNA sequence of Aig1l was 6073 bp long, and the putative protein consisted of 962 amino acids. All seven tissues that we analyzed expressed the Aig1l gene. In skeletal muscle, EA induced expression of the Aig1l gene, with high expression observed after 3 hours of EA. Our findings thus suggest that the Aig1l gene may play a key role in the molecular mechanisms of EA efficacy.

Network-Based Logistic Classification with an Enhanced L1/2 Solver Reveals Biomarker and Subnetwork Signatures for Diagnosing Lung Cancer

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Hai-Hui Huang

2015-01-01

Full Text Available Identifying biomarker and signaling pathway is a critical step in genomic studies, in which the regularization method is a widely used feature extraction approach. However, most of the regularizers are based on L1-norm and their results are not good enough for sparsity and interpretation and are asymptotically biased, especially in genomic research. Recently, we gained a large amount of molecular interaction information about the disease-related biological processes and gathered them through various databases, which focused on many aspects of biological systems. In this paper, we use an enhanced L1/2 penalized solver to penalize network-constrained logistic regression model called an enhanced L1/2 net, where the predictors are based on gene-expression data with biologic network knowledge. Extensive simulation studies showed that our proposed approach outperforms L1 regularization, the old L1/2 penalized solver, and the Elastic net approaches in terms of classification accuracy and stability. Furthermore, we applied our method for lung cancer data analysis and found that our method achieves higher predictive accuracy than L1 regularization, the old L1/2 penalized solver, and the Elastic net approaches, while fewer but informative biomarkers and pathways are selected.

IL FENOMENO DELL’ALTERNANZA L1/L2 NELL’INSEGNAMENTO DELL’ITALIANO COME LINGUA STRANIERA. ANALISI DI UN CORPUS DI INTERAZIONI DIDATTICHE

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Paola Arrigoni

2012-02-01

Full Text Available La modalità plurilingue della comunicazione in classi di lingua straniera può rientrare tra le strategie pedagogiche a disposizione dell’insegnante per il raggiungimento di precisi scopi didattici e formativi. Partendo da una breve analisi sul significato di parlante plurilingue e plurilinguismo stesso, in questo articolo si è voluto esaminare come si attua una educazione al plurilinguismo in contesti formativi e, in particolare, se e come l’utilizzo della L1 può costituire uno strumento di supporto all’insegnamento e all’apprendimento di una lingua straniera. A questo scopo sono stati analizzati i dati raccolti presso l’Università di Coventry durante corsi di italiano L2 per studenti anglofoni. I fenomeni di contatto linguistico L1/L2 più frequenti e significativi sono stati suddivisi in base al parlante e alle loro funzioni.   The phenomena of l1/l2 alternation in the teaching of italian as a foreign language. analysis of a corpus of didactic interactions Multilingual communication in foreign language classrooms can be considered as one of the teacher’s pedagogical  strategies to achieve specific educational aims. Through a brief analysis of the meaning of multilingual speakers and multilingualism, this article examines how an education to multilingualism in teaching contexts is carried out and, in particular, if and how the use of the L1 can be a helpful tool for the foreign language teaching and learning. For this purpose the data collected at Coventry University during Italian (L2 classrooms for English students were examined. The more common and meaningful phenomena of linguistic contact between L1 and L2 were grouped according to the speaker and to their functions.

Improved l1-SPIRiT using 3D walsh transform-based sparsity basis.

Science.gov (United States)

Feng, Zhen; Liu, Feng; Jiang, Mingfeng; Crozier, Stuart; Guo, He; Wang, Yuxin

2014-09-01

l1-SPIRiT is a fast magnetic resonance imaging (MRI) method which combines parallel imaging (PI) with compressed sensing (CS) by performing a joint l1-norm and l2-norm optimization procedure. The original l1-SPIRiT method uses two-dimensional (2D) Wavelet transform to exploit the intra-coil data redundancies and a joint sparsity model to exploit the inter-coil data redundancies. In this work, we propose to stack all the coil images into a three-dimensional (3D) matrix, and then a novel 3D Walsh transform-based sparsity basis is applied to simultaneously reduce the intra-coil and inter-coil data redundancies. Both the 2D Wavelet transform-based and the proposed 3D Walsh transform-based sparsity bases were investigated in the l1-SPIRiT method. The experimental results show that the proposed 3D Walsh transform-based l1-SPIRiT method outperformed the original l1-SPIRiT in terms of image quality and computational efficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of SES in Chinese (L1) and English (L2) Word Reading in Chinese-Speaking Kindergarteners

Science.gov (United States)

Liu, Duo; Chung, Kevin K. H.; McBride, Catherine

2016-01-01

The present study investigated the relationships between socioeconomic status (SES) and word reading in both Chinese (L1) and English (L2), with children's cognitive/linguistic skills considered as mediators and/or moderators. One hundred ninety-nine Chinese kindergarteners in Hong Kong with diverse SES backgrounds participated in this study. SES…

L1 and L2 Picture Naming in Mandarin-English Bilinguals: A Test of Bilingual Dual Coding Theory

Science.gov (United States)

Jared, Debra; Poh, Rebecca Pei Yun; Paivio, Allan

2013-01-01

This study examined the nature of bilinguals' conceptual representations and the links from these representations to words in L1 and L2. Specifically, we tested an assumption of the Bilingual Dual Coding Theory that conceptual representations include image representations, and that learning two languages in separate contexts can result in…

Corrosion inhibition of iron in 0.5 mol L-1 H2SO4 by halide ions

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Jeyaprabha C.

2006-01-01

Full Text Available The inhibition effect of halide ions such as iodide, bromide and chloride ions on the corrosion of iron in 0.5 mol L-1 H2SO4 and the adsorption behaviour of these ions on the electrode surface have been studied by polarization and impedance methods. It has been found that the inhibition of nearly 90% has been observed for iodide ions at 2.5 10-3 mol L-1, for bromide ions at 10 10-3 mol L-1 and 80% for chloride ions at 2.5 10-3 mol L-1. The inhibition effect is increased with increase of halide ions concentration in the case of I- and Br- ions, whereas it has decreased in the case of Cl- ion at concentrations higher than 5 10-3 mol L-1. The double layer capacitance values have decreased considerably in the presence of halide ions which indicate that these anions are adsorbed on iron at the corrosion potential.

Polarographic study of Cd(2), Pb(2), Hg(1) in anhydrous acetic acid; Etude polarographique de Cd(2), Pb(2), Hg(1) dans l'acide acetique anhydre

Energy Technology Data Exchange (ETDEWEB)

Conesa-Botta, M C [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1966-07-01

Anhydrous acetic acid is a solvent which can be compared to water as far as its behaviour towards acid-base reactions is concerned. It is in fact, like water both a proton acceptor (basic) - and as such it can provoke the dissociation of acids - and a proton donor (acid). This amphoteric behaviour is characterized by the equilibrium: 2 H O Ac {r_reversible} Ac OH{sub 2}{sup +} + Ac O{sup -} with K{sub i} = |Ac O H{sub 2}|{sup +} |Ac O{sup -}| = 10{sup -14.5} analogue to 2 H{sub 2}O {r_reversible} H{sub 3}O{sup +} + HO{sup -} with K{sub i} = |H{sub 3}O{sup +}| |HO{sup -}| = 10{sup -14} The acid-base reactions can in principle be characterized by a pH scale based on a definition similar to that for the pH scale in aqueous solutions. The essential difference however between aqueous and acetic acid solutions is due to the fact that acetic acid has a low dielectric constant. {epsilon} = 6.1 (at 25 deg. C) The ions therefore remain associated, almost completely, in the form of ion-pairs produced as a result of the strong electrostatic interactions. This phenomenon requires us to modify the reasoning usually applied to aqueous solutions. The new general methods of reasoning have been established and discussed by G. CHARLOT and B. TREMILLON. We will make use of them for the particular case under consideration. In the first part, we have employed the polarographic method for the study of the acetic complexes of two elements: cadmium(II) and lead (II). In the second part we have tried to show that mercurous halides are formed in acetic acid; we have attempted to determine their stability. (author) [French] L'acide acetique anhydre est un solvant qui peut etre rapproche de l'eau par son comportement envers les reactions acides-bases. Il est en effet, comme l'eau, a la fois accepteur de protons (basique) - et comme tel agit sur la dissociation des acides - et donneur de protons (acide). Ce pouvoir amphotere est caracterise par l'equilibre: 2 H O Ac {r_reversible} Ac OH{sub 2

L2, the minor capsid protein of papillomavirus

Energy Technology Data Exchange (ETDEWEB)

Wang, Joshua W. [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21287 (United States); Roden, Richard B.S., E-mail: roden@jhmi.edu [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21287 (United States); Department of Oncology, The Johns Hopkins University, Baltimore, MD 21287 (United States); Department of Gynecology and Obstetrics, The Johns Hopkins University, Baltimore, MD 21287 (United States)

2013-10-15

The capsid protein L2 plays major roles in both papillomavirus assembly and the infectious process. While L1 forms the majority of the capsid and can self-assemble into empty virus-like particles (VLPs), L2 is a minor capsid component and lacks the capacity to form VLPs. However, L2 co-assembles with L1 into VLPs, enhancing their assembly. L2 also facilitates encapsidation of the ∼8 kbp circular and nucleosome-bound viral genome during assembly of the non-enveloped T=7d virions in the nucleus of terminally differentiated epithelial cells, although, like L1, L2 is not detectably expressed in infected basal cells. With respect to infection, L2 is not required for particles to bind to and enter cells. However L2 must be cleaved by furin for endosome escape. L2 then travels with the viral genome to the nucleus, wherein it accumulates at ND-10 domains. Here, we provide an overview of the biology of L2. - Highlights: • L2 is the minor antigen of the non-enveloped T=7d icosahedral Papillomavirus capsid. • L2 is a nuclear protein that can traffic to ND-10 and facilitate genome encapsidation. • L2 is critical for infection and must be cleaved by furin. • L2 is a broadly protective vaccine antigen recognized by neutralizing antibodies.

L2, the minor capsid protein of papillomavirus

International Nuclear Information System (INIS)

Wang, Joshua W.; Roden, Richard B.S.

2013-01-01

The capsid protein L2 plays major roles in both papillomavirus assembly and the infectious process. While L1 forms the majority of the capsid and can self-assemble into empty virus-like particles (VLPs), L2 is a minor capsid component and lacks the capacity to form VLPs. However, L2 co-assembles with L1 into VLPs, enhancing their assembly. L2 also facilitates encapsidation of the ∼8 kbp circular and nucleosome-bound viral genome during assembly of the non-enveloped T=7d virions in the nucleus of terminally differentiated epithelial cells, although, like L1, L2 is not detectably expressed in infected basal cells. With respect to infection, L2 is not required for particles to bind to and enter cells. However L2 must be cleaved by furin for endosome escape. L2 then travels with the viral genome to the nucleus, wherein it accumulates at ND-10 domains. Here, we provide an overview of the biology of L2. - Highlights: • L2 is the minor antigen of the non-enveloped T=7d icosahedral Papillomavirus capsid. • L2 is a nuclear protein that can traffic to ND-10 and facilitate genome encapsidation. • L2 is critical for infection and must be cleaved by furin. • L2 is a broadly protective vaccine antigen recognized by neutralizing antibodies

Impact of L1 Use in L2 English Writing Classes

African Journals Online (AJOL)

This experimental study endeavored to assess the impact of L1 use in .... Two sections were selected using simple ... practice. In all the four writing practice activities, the experimental group ..... during the pre-test, but this was not true for.

Experiment prediction for LOFT nuclear experiments L5-1 and L8-2

International Nuclear Information System (INIS)

Chen, T.H.; Modro, S.M.

1983-01-01

The LOFT Experiments L5-1 and L8-2 simulated intermediate break loss-of-coolant accidents with core uncovery. This paper compares the predictions with the measured data for these experiments. The RELAP5 code was used to perform best estimate double-blind and single-blind predictions. The double-blind calculations are performed prior to the experiment and use specified nominal initial and boundary conditions. The single-blind calculations are performed after the experiment and use measured initial and boundary conditions while maintaining all other parameters constant, including the code version. Comparisons of calculated results with experimental results are discussed; the possible causes of discrepancies are explored and explained. RELAP5 calculated system pressure, mass inventory, and fuel cladding temperature agree reasonably well with the experiment results, and only slight changes are noted between the double-blind and single-blind predictions

hnRNP L regulates differences in expression of mouse integrin alpha2beta1.

Science.gov (United States)

Cheli, Yann; Kunicki, Thomas J

2006-06-01

There is a 2-fold variation in platelet integrin alpha2beta1 levels among inbred mouse strains. Decreased alpha2beta1 in 4 strains carrying Itga2 haplotype 2 results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype 1 and a 21 CA repeat sequence at this position (CA21) express twice the level of platelet alpha2beta1 and exhibit an equivalent gain of platelet function in vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an increased proportion of alternatively spliced product. The splicing enhancer activity of CA21 in vivo is abolished by prior treatment with hnRNP L-specific siRNA. Thus, decreased surface alpha2beta1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1.

Comparative studies of the endonucleases from two related Xenopus laevis retrotransposons, Tx1L and Tx2L: target site specificity and evolutionary implications.

Science.gov (United States)

Christensen, S; Pont-Kingdon, G; Carroll, D

2000-01-01

In the genome of the South African frog, Xenopus laevis, there are two complex families of transposable elements, Tx1 and Tx2, that have identical overall structures, but distinct sequences. In each family there are approximately 1500 copies of an apparent DNA-based element (Tx1D and Tx2D). Roughly 10% of these elements in each family are interrupted by a non-LTR retrotransposon (Tx1L and Tx2L). Each retrotransposon is flanked by a 23-bp target duplication of a specific D element sequence. In earlier work, we showed that the endonuclease domain (Tx1L EN) located in the second open reading frame (ORF2) of Tx1L encodes a protein that makes a single-strand cut precisely at the expected site within its target sequence, supporting the idea that Tx1L is a site-specific retrotransposon. In this study, we express the endonuclease domain of Tx2L (Tx2L EN) and compare the target preferences of the two enzymes. Each endonuclease shows some preference for its cognate target, on the order of 5-fold over the non-cognate target. The observed discrimination is not sufficient, however, to explain the observation that no cross-occupancy is observed - that is, L elements of one family have never been found within D elements of the other family. Possible sources of additional specificity are discussed. We also compare two hypotheses regarding the genome duplication event that led to the contemporary pseudotetraploid character of Xenopus laevis in light of the Tx1L and Tx2L data.

Sensitivity to TOP2 targeting chemotherapeutics is regulated by Oct1 and FILIP1L.

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Huarui Lu

Full Text Available Topoisomerase II (TOP2 targeting drugs like doxorubicin and etoposide are frontline chemotherapeutics for a wide variety of solid and hematological malignancies, including breast and ovarian adenocarcinomas, lung cancers, soft tissue sarcomas, leukemias and lymphomas. These agents cause a block in DNA replication leading to a pronounced DNA damage response and initiation of apoptotic programs. Resistance to these agents is common, however, and elucidation of the mechanisms causing resistance to therapy could shed light on strategies to reduce the frequency of ineffective treatments. To explore these mechanisms, we utilized an unbiased shRNA screen to identify genes that regulate cell death in response to doxorubicin treatment. We identified the Filamin A interacting protein 1-like (FILIP1L gene as a crucial mediator of apoptosis triggered by doxorubicin. FILIP1L shares significant similarity with bacterial SbcC, an ATPase involved in DNA repair. FILIP1L was originally described as DOC1, or "down-regulated in ovarian cancer" and has since been shown to be downregulated in a wide variety of human tumors. FILIP1L levels increase markedly through transcriptional mechanisms following treatment with doxorubicin and other TOP2 poisons, including etoposide and mitoxantrone, but not by the TOP2 catalytic inhibitors merbarone or dexrazoxane (ICRF187, or by UV irradiation. This induction requires the action of the OCT1 transcription factor, which relocalizes to the FILIP1L promoter and facilitates its expression following doxorubicin treatment. Our findings suggest that the FILIP1L expression status in tumors may influence the response to anti-TOP2 chemotherapeutics.

Langue et culture : l'indispensable association dans l'enseignement du FLE à des arabophones

Directory of Open Access Journals (Sweden)

Dupont Ilham

2014-07-01

Parmi ces sources, nous trouvons la « nativisation », la « dénativisation », la période intermédiaire de « l'interlangue » (l'apprenant substitue ses propres connaissances à celles de la langue apprise et évolue dans une période transitoire jusqu'à ne plus y faire référence et la proximité interlinguistique parmi les langues connues par l'apprenant (transferts. Une source importante d'erreurs, notamment lexicales, vient de la confrontation entre L1 et L2 dans l'esprit de l'apprenant. Ces erreurs sont majoritairement dues à la méconnaissance ou à l'insuffisance de connaissance du contexte culturel de la langue apprise. Il est évident qu'une simple conversation entre deux personnes ayant la même culture peut être incompréhensible ou même inaccessible à un étranger. Notre travail met ainsi en exergue que langue et culture sont intimement liés et que l'acquisition de l'une ne peut se faire sans la compréhension de l'autre. Selon le concept de la « lexiculture », leur enseignement doit donc être simultané ce qui présente en outre, de nombreux avantages. L'étudiant est motivé à apprendre car il comprend la langue qu'il peut pratiquer concrètement. Le contact entre les deux cultures (L1 et L2, comme par un effet de miroir, va lui permettre aussi de se situer par rapport à un autre univers culturel.

Lexical statistics of competition in L2 versus L1 listening

NARCIS (Netherlands)

Cutler, A.

2005-01-01

Spoken-word recognition involves multiple activation of alternative word candidates and competition between these alternatives. Phonemic confusions in L2 listening increase the number of potentially active words, thus slowing word recognition by adding competitors. This study used a 70,000-word

FIMP and muon (g−2) in a U(1){sub L{sub μ−L{sub τ}}} model

Energy Technology Data Exchange (ETDEWEB)

Biswas, Anirban [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India); Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India); Choubey, Sandhya [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India); Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India); Department of Theoretical Physics, School of Engineering Sciences, KTH Royal Institute of Technology, AlbaNova University Center, 106 91 Stockholm (Sweden); Khan, Sarif [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India); Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India)

2017-02-23

The tightening of the constraints on the standard thermal WIMP scenario has forced physicists to propose alternative dark matter (DM) models. One of the most popular alternate explanations of the origin of DM is the non-thermal production of DM via freeze-in. In this scenario the DM never attains thermal equilibrium with the thermal soup because of its feeble coupling strength (∼ 10{sup −12}) with the other particles in the thermal bath and is generally called the Feebly Interacting Massive Particle (FIMP). In this work, we present a gauged U(1){sub L{sub μ−L{sub τ}}} extension of the Standard Model (SM) which has a scalar FIMP DM candidate and can consistently explain the DM relic density bound. In addition, the spontaneous breaking of the U(1){sub L{sub μ−L{sub τ}}} gauge symmetry gives an extra massive neutral gauge boson Z{sub μτ} which can explain the muon (g−2) data through its additional one-loop contribution to the process. Lastly, presence of three right-handed neutrinos enable the model to successfully explain the small neutrino masses via the Type-I seesaw mechanism. The presence of the spontaneously broken U(1){sub L{sub μ−L{sub τ}}} gives a particular structure to the light neutrino mass matrix which can explain the peculiar mixing pattern of the light neutrinos.

Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

Directory of Open Access Journals (Sweden)

Kihyuck Kwak

Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type

Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

Science.gov (United States)

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-01-01

INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with l-ascorbic acid 1 2 3 4

OpenAIRE

Wade, Kaitlin H; Forouhi, Nita G; Cook, Derek G; Johnson, Paul; McConnachie, Alex; Morris, Richard W; Rodriguez, Santiago; Ye, Zheng; Ebrahim, Shah; Padmanabhan, Sandosh; Watt, Graham; Bruckdorfer, K Richard; Wareham, Nick J; Whincup, Peter H; Chanock, Stephen

2014-01-01

Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation.\\ud \\ud Objectives:We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed...

The Effects of L2 Experience on L3 Perception

Science.gov (United States)

Onishi, Hiromi

2016-01-01

This study examines the influence of experience with a second language (L2) on the perception of phonological contrasts in a third language (L3). This study contributes to L3 phonology by examining the influence of L2 phonological perception abilities on the perception of an L3 at the beginner level. Participants were native speakers of Korean…

Crystal structure of l-leucyl-l-isoleucine 2,2,2-trifluoroethanol monosolvate

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Carl Henrik Görbitz

2016-05-01

Full Text Available Hydrophobic dipeptides with either l-Leu or l-Phe constitute a rather heterogeneous group of crystal structures. Some form materials with large water-filled channels, but there is also a pronounced tendency to incorporate organic solvent molecules, which then act as acceptors for one of the three H atoms of the charged N-terminal amino group. l-Leu-l-Ile has uniquely been obtained as two distinct hydrates, but has so far failed to co-crystallize with a simple alcohol. The present structure of C12H24N2O3·CF3CH2OH, which crystallizes with two dipeptide and two solvent molecules in the asymmetric unit, demonstrates that when 2,2,2-trifluoroethanol is used as a solvent, its high capacity as a hydrogen-bond donor leads to formation of an alcohol solvate.

Mechanism for the decrease in the FIP1L1-PDGFRalpha protein level in EoL-1 cells by histone deacetylase inhibitors.

Science.gov (United States)

Ishihara, Kenji; Kaneko, Motoko; Kitamura, Hajime; Takahashi, Aki; Hong, Jang Ja; Seyama, Toshio; Iida, Koji; Wada, Hiroshi; Hirasawa, Noriyasu; Ohuchi, Kazuo

2008-01-01

Acetylation and deacetylation of proteins occur in cells in response to various stimuli, and are reversibly catalyzed by histone acetyltransferase and histone deacetylase (HDAC), respectively. EoL-1 cells have an FIP1L1-PDGFRA fusion gene that causes transformation of eosinophilic precursor cells into leukemia cells. The HDAC inhibitors apicidin and n-butyrate suppress the proliferation of EoL-1 cells and induce differentiation into eosinophils by a decrease in the protein level of FIP1L1-PDGFRalpha without affecting the mRNA level for FIP1L1-PDGFRA. In this study, we analyzed the mechanism by which the protein level of FIP1L1-PDGFRalpha is decreased by apicidin and n-butyrate. EoL-1 cells were incubated in the presence of the HDAC inhibitors apicidin, trichostatin A or n-butyrate. The protein levels of FIP1L1-PDGFRalpha and phosphorylated eIF-2alpha were determined by Western blotting. Actinomycin D and cycloheximide were used to block RNA synthesis and protein synthesis, respectively, in the chasing experiment of the amount of FIP1L1-PDGFRalpha protein. When apicidin- and n-butyrate-treated EoL-1 cells were incubated in the presence of actinomycin D, the decrease in the protein level of FIP1L1-PDGFRalpha was significantly enhanced when compared with controls. In contrast, the protein levels were not changed by cycloheximide among these groups. Apicidin and n-butyrate induced the continuous phosphorylation of eIF-2alpha for up to 8 days. The decrease in the level of FIP1L1-PDGFRalpha protein by continuous inhibition of HDAC may be due to the decrease in the translation rate of FIP1L1-PDGFRA. Copyright 2008 S. Karger AG, Basel.

MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer.

Science.gov (United States)

Momose, Kota; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-07-01

Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD-L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair-deficient tumors are associated with improved survival, although they are not sensitive to 5-fluorouracil-based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5-year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (PMLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD-L1 expression.

Heads or tails: L1 insertion-associated 5' homopolymeric sequences

Directory of Open Access Journals (Sweden)

Meyer Thomas J

2010-02-01

Full Text Available Abstract Background L1s are one of the most successful autonomous mobile elements in primate genomes. These elements comprise as much as 17% of primate genomes with the majority of insertions occurring via target primed reverse transcription (TPRT. Twin priming, a variant of TPRT, can result in unusual DNA sequence architecture. These insertions appear to be inverted, truncated L1s flanked by target site duplications. Results We report on loci with sequence architecture consistent with variants of the twin priming mechanism and introduce dual priming, a mechanism that could generate similar sequence characteristics. These insertions take the form of truncated L1s with hallmarks of classical TPRT insertions but having a poly(T simple repeat at the 5' end of the insertion. We identified loci using computational analyses of the human, chimpanzee, orangutan, rhesus macaque and marmoset genomes. Insertion site characteristics for all putative loci were experimentally verified. Conclusions The 39 loci that passed our computational and experimental screens probably represent inversion-deletion events which resulted in a 5' inverted poly(A tail. Based on our observations of these loci and their local sequence properties, we conclude that they most probably represent twin priming events with unusually short non-inverted portions. We postulate that dual priming could, theoretically, produce the same patterns. The resulting homopolymeric stretches associated with these insertion events may promote genomic instability and create potential target sites for future retrotransposition events.

Search for the Higgs boson produced in association with Z-->l+l in pp collisions at sqrt[s]=1.96 TeV.

Science.gov (United States)

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Copic, K; Cordelli, M; Cortiana, G; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kusakabe, Y; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, E; Lee, S W; Leone, S; Lewis, J D; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlok, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-12-19

We present a search for the Higgs boson in the process qq-->ZH-->l;{+}l;{-}bb[over ]. The analysis uses an integrated luminosity of 1 fb;{-1} of pp[over ] collisions produced at sqrt[s]=1.96 TeV and accumulated by the upgraded Collider Detector at Fermilab (CDF II). We employ artificial neural networks both to correct jets mismeasured in the calorimeter and to distinguish the signal kinematic distributions from those of the background. We see no evidence for Higgs boson production, and set 95% C.L. upper limits on sigma{ZH}B(H-->bb[over ]), ranging from 1.5 to 1.2 pb for a Higgs boson mass (m{H}) of 110 to 150 GeV/c(2).

Path covering number and L(2,1)-labeling number of graphs

OpenAIRE

Lu, Changhong; Zhou, Qing

2012-01-01

A {\\it path covering} of a graph $G$ is a set of vertex disjoint paths of $G$ containing all the vertices of $G$. The {\\it path covering number} of $G$, denoted by $P(G)$, is the minimum number of paths in a path covering of $G$. An {\\sl $k$-L(2,1)-labeling} of a graph $G$ is a mapping $f$ from $V(G)$ to the set ${0,1,...,k}$ such that $|f(u)-f(v)|\\ge 2$ if $d_G(u,v)=1$ and $|f(u)-f(v)|\\ge 1$ if $d_G(u,v)=2$. The {\\sl L(2,1)-labeling number $\\lambda (G)$} of $G$ is the smallest number $k$ suc...

Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer.

Science.gov (United States)

Cho, Jong Ho; Zhou, Wei; Choi, Yoon-La; Sun, Jong-Mu; Choi, Hyejoo; Kim, Tae-Eun; Dolled-Filhart, Marisa; Emancipator, Kenneth; Rutkowski, Mary Anne; Kim, Jhingook

2018-01-01

Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC). We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR -mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis. All patients had ≥1 EGFR mutation-54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1-positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1-positive groups (TPS ≥ 1%) compared with the PD-L1-negative group (median, 35 months). PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR -mutant NSCLC.

Association between Virulence Factors and TRAF1/4-1BB/Bcl-xL Expression in Gastric Mucosa Infected with Helicobacter pylori

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Fen Wang

2015-01-01

Full Text Available Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1, tumor necrosis factor receptor superfamily member 9 (4-1BB, and B-cell lymphoma-extra large (Bcl-xL in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM patients, and 28 gastric carcinoma (Ca patients. The expression of  TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P<0.05 compared with CG. There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P<0.05. Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P<0.05. Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue.

Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.

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Lee, Hyun Tae; Lee, Ju Yeon; Lim, Heejin; Lee, Sang Hyung; Moon, Yu Jeong; Pyo, Hyo Jeong; Ryu, Seong Eon; Shin, Woori; Heo, Yong-Seok

2017-07-17

In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.

Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

Science.gov (United States)

Chung, Jee-Eun; Lee, Kyung Eun; Chang, Byung Chul; Gwak, Hye Sun

2018-01-30

The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02±1.56 vs. 5.96±2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses. Copyright © 2017. Published by Elsevier B.V.

Pyrazole complexes of rhenium. Synthesis and crystal structure of trans-[Re(O)(OMe)L4]Br2 · L · 4H2O (L - 3,5-dimethylpyrazole)

International Nuclear Information System (INIS)

Sokolov, M.N.; Fedorova, N.Eh.; Fedorov, V.E.; Virovets, A.V.; Nun'es, P.

2002-01-01

The first rhenium (V) mononuclear complex featuring composition [Re(O)(OMe)L 4 ]Br 2 (L = 3,5-dimethylpyrazole), which is resistant to hydrolysis in neutral aqueous solution, along with its molecular adduct of the composition [Re(O)(OMe)L 4 ]Br 2 · L · 4H 2 O were synthesized. The reaction products were characterized by the methods of elementary analysis, absorption spectroscopy in visible, UV and IR ranges, mass spectrometry. Besides, the adduct structure was studied by the method of X-ray diffraction analysis. It was ascertained that the adduct is crystallized in tetragonal crystal system with unit cell parameters as follows: a = 14.912 (3), c = 17.108 (4) A, sp. gr. I4/m, Z = 4. In the complex molecule linear grouping Re(O)(OMe)] 2+ (Re-O-C angle being equal to 180 deg) is coordinated by four L ligand molecules [ru

Mixed Total Variation and L1 Regularization Method for Optical Tomography Based on Radiative Transfer Equation

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Jinping Tang

2017-01-01

Full Text Available Optical tomography is an emerging and important molecular imaging modality. The aim of optical tomography is to reconstruct optical properties of human tissues. In this paper, we focus on reconstructing the absorption coefficient based on the radiative transfer equation (RTE. It is an ill-posed parameter identification problem. Regularization methods have been broadly applied to reconstruct the optical coefficients, such as the total variation (TV regularization and the L1 regularization. In order to better reconstruct the piecewise constant and sparse coefficient distributions, TV and L1 norms are combined as the regularization. The forward problem is discretized with the discontinuous Galerkin method on the spatial space and the finite element method on the angular space. The minimization problem is solved by a Jacobian-based Levenberg-Marquardt type method which is equipped with a split Bregman algorithms for the L1 regularization. We use the adjoint method to compute the Jacobian matrix which dramatically improves the computation efficiency. By comparing with the other imaging reconstruction methods based on TV and L1 regularizations, the simulation results show the validity and efficiency of the proposed method.

Direct synthesis of L1 type Fe-Pt nanoparticles using microwave-polyol method

International Nuclear Information System (INIS)

Minami, Rumiko; Kitamoto, Yoshitaka; Chikata, Tsukasa; Kato, Shunsaku

2005-01-01

We report the synthesis of Fe-Pt nanoparticles with microwave irradiation during polyol-reduction reaction. Chemically ordered Fe-Pt nanoparticles with L1 structure are fabricated at 250 deg. C using a microwave-polyol method without any post-synthesis treatments. Moessbauer analyses reveal the nanoparticles have partially ordered L1 structure. The partially ordered Fe-Pt nanoparticles exhibit coercivity of 3.4 kOe, saturation magnetization of 49 emu/g, and anisotropy field of 83 kOe at room temperature

Taxonomies in L1 and L2 Reading Strategies: A Critical Review of Issues Surrounding Strategy-Use Definitions and Classifications in Previous Think-Aloud Research

Science.gov (United States)

Alkhaleefah, Tarek A.

2016-01-01

Considering the various classifications of L1 and L2 reading strategies in previous think-aloud studies, the present review aims to provide a comprehensive look into those various taxonomies reported in major L1 and L2 reading studies. The rationale for this review is not only to offer a comprehensive overview of the different classifications in…

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

Science.gov (United States)

Sandford, Andrew J; Malhotra, Deepti; Boezen, H Marike; Siedlinski, Mateusz; Postma, Dirkje S; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Biswal, Shyam

2012-08-01

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

Reproducibility of repeated measures of deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) binding in the human brain

International Nuclear Information System (INIS)

Logan, Jean; Fowler, Joanna S.; Volkow, Nora D.; Wang, Gene-Jack; MacGregor, Robert R.; Shea, Colleen

2000-01-01

The purpose of this study was to assess the reproducibility of repeated positron emission tomography (PET) measures of brain monoamine oxidase B (MAO B) using deuterium-substituted [ 11 C]L-deprenyl ([ 11 C]L-deprenyl-D2) in normal subjects and to validate the method used for estimating the kinetic constants from the irreversible 3-compartment model applied to the tracer binding. Five normal healthy subjects (age range 23-73 years) each received two PET scans with [ 11 C]L-deprenyl-D2. The time interval between scans was 7-27 days. Time-activity data from eight regions of interest and an arterial plasma input function was used to calculate λk 3 , a model term proportional to MAO B, and K 1 , the plasma to brain transfer constant that is related to blood flow. Linear (LIN) and nonlinear least-squares (NLLSQ) estimation methods were used to calculate the optimum model constants. A comparison of time-activity curves for scan 1 and scan 2 showed that the percent of change for peak uptake varied from -18.5 to 15.0% and that increases and decreases in uptake on scan 2 were associated with increases and decreases in the value of the arterial input of the tracer. Calculation of λk 3 showed a difference between scan 1 and scan 2 in the global value ranging between -6.97 and 4.5% (average -2.1±4.7%). The average percent change for eight brain regions for the five subjects was -2.84±7.07%. Values of λk 3 for scan 1 and scan 2 were highly correlated (r 2 =0.98; p 1 showed a significant correlation between scan 1 and scan 2 (r 2 =0.61; p 11 C]L-deprenyl-D2 varied between scan 1 and scan 2, driven by the differences in arterial tracer input. Application of a 3-compartment model to regional time-activity data and arterial input function yielded λk 3 values for scan 1 and scan 2 with an average difference of -2.84 ± 7.07%. Linear regression applied to values of λk 3 from the LIN and NLLSQ methods validated the use of the linear method for calculating λk 3

hnRNP L regulates differences in expression of mouse integrin α2β1

Science.gov (United States)

Cheli, Yann; Kunicki, Thomas J.

2006-01-01

There is a 2-fold variation in platelet integrin α2β1 levels among inbred mouse strains. Decreased α2β1 in 4 strains carrying Itga2 haplotype 2 results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype 1 and a 21 CA repeat sequence at this position (CA21) express twice the level of platelet α2β1 and exhibit an equivalent gain of platelet function in vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an increased proportion of alternatively spliced product. The splicing enhancer activity of CA21 in vivo is abolished by prior treatment with hnRNP L–specific siRNA. Thus, decreased surface α2β1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1. PMID:16455949

Efficacy L-Arginine In Patients With Nonalcoholic Steatohepatitis Associated With Metabolic Syndrome

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Oleksandr Fediv

2015-01-01

Full Text Available Abstract Background and Purpose Recent research in the field of hematology indicate that among the many pathogenic mechanisms of development and progression of nonalcoholic steatohepatitis NASH which occurs on the background of the metabolic syndrome an important role is played by endothelial dysfunction and violations of haemocoagulation. The aim of this research was to study the effectiveness of L-arginine as it corrects endothelial dysfunction and disorders of homeostasis haemocoagulation link in patients with NASH associated with the metabolic syndrome. Subjects and Methods 128 patients with nonalcoholic steatohepatitis associated with metabolic syndrome were examined. Some patients 63 persons received standard treatment according to national guidelines. To another group 65 patients on the background of basic therapy L-arginine hydrochloride followed by transition to oral form of L-arginine aspartate was administered. Blood levels of stable nitrogen monoxide metabolites nitrites nitrates endothelin-1 and plasma recalcification time prothrombin time thrombin time activated partial thromboplastin time fibrinogen plasma level activity of antithrombin III and coagulation factor XIII potential activity of plasminogen plasma fibrinolytic blood activity were studied. Results Originally significantly increased levels of endothelin-1 decreased after the therapy in all studied groups but more noticeable changes in the group with L-arginine appointment were observed p0.05. In the studied groups normalization of stable nitrogen monoxide metabolites after treatment was also noticed. Significant p0.05 increase in all haemocoagulation time characteristics and activities of antithrombin-III and factor XIII was found. The positive effect of L-arginine on blood fibrinolytic activity was noted. Discussion and Conclusion Combined therapy of nonalcoholic steatohepatitis associated with metabolic syndrome with a differentiated degreeal L-arginine assignment by

Lexical knowledge of Serbian L1 English L2 learners: Reception vs. production

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Danilović-Jeremić Jelena

2015-01-01

Full Text Available The acquisition of lexical knowledge in a second/foreign language is often investigated by means of vocabulary size tests which assess two aspects of the learners' competence: reception and production. Estimates of these two dimensions, as well as the (potential gap between them, have important pedagogical implications in that they indicate the degree to which the learners can comprehend or use the language autonomously. Therefore, the aim of this paper is to explore the vocabulary size of three generations of B2-level L2 learners (CEFR, first-year students majoring in English at the Faculty of Philology and Arts in Kragujevac, Serbia, by means of Vocabulary Levels Tests (Laufer & Nation, 1999; Nation, 1990. The results of the statistical analyses show that the receptive vocabulary of Serbian L2 learners is much more developed than their productive vocabulary, and that the gap between lexical production and reception changes depending on the frequency of the lexemes and the proficiency level of L2 learners. The findings imply that, at the primary and secondary level of education, more attention should be paid to the development of productive lexical knowledge which is crucial not only for success in English degree courses but communication in English in general.

Identification of a new DPY19L2 mutation and a better definition of DPY19L2 deletion breakpoints leading to globozoospermia.

Science.gov (United States)

Ghédir, Houda; Ibala-Romdhane, Samira; Okutman, Ozlem; Viot, Géraldine; Saad, Ali; Viville, Stéphane

2016-01-01

The purpose of this study was to analyze DPY19L2 sequence variants to investigate the mechanism leading to the entire DPY19L2 deletion in a large cohort of infertile globozoospermic patients. An improved analysis of the DPY19L2 deletion breakpoints (BPs) allowed us to identify two BPs located in a small 1 kb region and to more precisely localize the BPs reported previously. Three genes [spermatogenesis associated 16 (SPATA16), protein interacting with PRKCA (PICK1) and DPY19L2] were previously correlated with globozoospermia, but a homozygous deletion of the entire DPY19L2 was identified as the most frequent alteration causing this phenotype. In addition, several point mutations in this gene were reported. In previous work, we have identified nine BPs for the DPY19L2 deletion clustered in two hotspot regions, while others reported a total of five BPs. We screened for the DPY19L2 deletion and for mutations in the DPY19L2, SPATA16 and PICK1 genes in a cohort of 21 Tunisian globozoospermic patients. In order to characterize the DPY19L2 deletion BPs, we sequenced a 2 kb fragment on low copy repeat (LCR) 1 and LCR2 in Tunisian fertile controls to distinguish between single-nucleotide polymorphisms (SNPs) and LCR-specific markers. Molecular analyses performed on 18 genetically independent individuals showed that 11 (61.1%) were homozygous for the DPY19L2 deletion, 2 (11.1%) were homozygous for the non-synonymous mutation (p.R298C) in exon 8, 1 patient (5.6%) was homozygous for a new splice-site mutation at the junction exon-intron 16 [c.1579_1580+4delAGGTAAinsTCAT] and no DPY19L2, SPATA16 or PICK1 mutations were identified for 4 patients (22.2%). By defining 15 specific LCR markers, we characterized 2 BPs for the DPY19L2 deletion in 11 patients showing the homozygous deletion. Using 20 non-LCR-specific SNPs, we identified 8 distinct haplotypes. A limitation of this study is the small number of patients owing to the rarity of this form of male infertility. Our data showed

Learner-Generated Noticing Behavior by Novice Learners: Tracing the Effects of Learners' L1 on Their Emerging L2

Science.gov (United States)

Park, Eun Sung

2013-01-01

This study examines novice learners' self-generated input noticing approaches and strategies. It is motivated by previous research on input enhancement which yielded insights that learners are naturally prone to notice certain aspects of L2 input on their own without any external means to channel their attention. Two L1 groups (Japanese and…

Prognostic Value of PD-L1 in Breast Cancer: A Meta-Analysis.

Science.gov (United States)

Wang, Changjun; Zhu, Hanjiang; Zhou, Yidong; Mao, Feng; Lin, Yan; Pan, Bo; Zhang, Xiaohui; Xu, Qianqian; Huang, Xin; Sun, Qiang

2017-07-01

Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value. © 2017 Wiley Periodicals, Inc.

Sp1 and CREB regulate basal transcription of the human SNF2L gene

International Nuclear Information System (INIS)

Xia Yu; Jiang Baichun; Zou Yongxin; Gao Guimin; Shang Linshan; Chen Bingxi; Liu Qiji; Gong Yaoqin

2008-01-01

Imitation Switch (ISWI) is a member of the SWI2/SNF2 superfamily of ATP-dependent chromatin remodelers, which are involved in multiple nuclear functions, including transcriptional regulation, replication, and chromatin assembly. Mammalian genomes encode two ISWI orthologs, SNF2H and SNF2L. In order to clarify the molecular mechanisms governing the expression of human SNF2L gene, we functionally examined the transcriptional regulation of human SNF2L promoter. Reporter gene assays demonstrated that the minimal SNF2L promoter was located between positions -152 to -86 relative to the transcription start site. In this region we have identified a cAMP-response element (CRE) located at -99 to -92 and a Sp1-binding site at -145 to -135 that play a critical role in regulating basal activity of human SNF2L gene, which were proven by deletion and mutation of specific binding sites, EMSA, and down-regulating Sp1 and CREB via RNAi. This study provides the first insight into the mechanisms that control basal expression of human SNF2L gene

L2 Milestone 5433: Characterization of Dynamic Behavior of AM and Conventionally Processed Stainless Steel (316L and 304L)

Energy Technology Data Exchange (ETDEWEB)

Gray, George Thompson [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Livescu, Veronica [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rigg, P. A. [Washington State Univ., Pullman, WA (United States). Inst. for Shock Physics; Trujillo, Carl Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cady, Carl McElhinney [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chen, Shuh-Rong [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Carpenter, John S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lienert, Thomas J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Fensin, Saryu Jindal [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Knapp, Cameron M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Beal, Roberta Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Morrow, Benjamin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dippo, Olivia F. [Univ. of California, San Diego, CA (United States); Jones, David Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Martinez, Daniel Tito [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Valdez, James Anthony [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-09-26

For additive manufacturing (AM) of metallic materials, the certification and qualification paradigm needs to evolve as there currently exists no broadly accepted “ASTM- or DIN-type” additive manufacturing certified process or AM-material produced specifications. Accordingly, design, manufacture, and thereafter implementation and insertion of AM materials to meet engineering applications requires detailed quantification of the constitutive (strength and damage) properties of these evolving materials, across the spectrum of metallic AM methods, in comparison/contrast to conventionally-manufactured metals and alloys. This report summarizes the 316L SS research results and presents initial results of the follow-on study of 304L SS. For the AM-316L SS investigation, cylindrical samples of 316L SS were produced using a LENS MR-7 laser additive manufacturing system from Optomec (Albuquerque, NM) equipped with a 1kW Yb-fiber laser. The microstructure of the AM-316L SS was characterized in both the “as-built” Additively Manufactured state and following a heat-treatment designed to obtain full recrystallization to facilitate comparison with annealed wrought 316L SS. The dynamic shock-loading-induced damage evolution and failure response of all three 316L SS materials was quantified using flyer-plate impact driven spallation experiments at peak stresses of 4.5 and 6.35 GPa. The results of these studies are reported in detail in the first section of the report. Publication of the 316L SS results in an archival journal is planned. Following on from the 316L SS completed work, initial results on a study of AM 304L SS are in progress and presented herein. Preliminary results on the structure/dynamic spallation property behavior of AM-304L SS fabricated using both the directed-energy LENS and an EOS powder-bed AM techniques in comparison to wrought 304L SS is detailed in this Level 2 Milestone report.

Pseudolisthesis secondary to small L5

International Nuclear Information System (INIS)

Bagheri, Mohammad Hadi; Hosseini, Mehrdad Mohammad; Foroughi, Amin Aboulhassani

2011-01-01

Rationale and objective: Small AP diameter of L5 can mimic spondylolisthesis in lumbosacral MRI. The aim of the present study was to evaluate the prevalence of small L5 mimicking spondylolisthesis in lumbosacral MRI of the patients referred to an imaging center by any symptoms. Association between small anteroposterior diameter of L5 and presence and absence of unilateral or bilateral spondylolysis at L5 were also evaluated. Materials and methods: 2000 lumbosacral MRI of the patients referred to an imaging center for any reasons were evaluated. The posterior step of L5 was measured and the cases with posterior step of more than 2 mm were selected. These cases were evaluated for presence or absence of spondylolysis. Results: Small anteroposterior diameters of L5 were detected in 38 cases (2%), mimicking the spondylolisthesis in lumbosacral MRI. The prevalence of small L5 in lumbosacral MRI of the patients referred by any symptoms was about 2%. In these selected cases, 6 (15.8%) show unilateral spondylolysis and 5 (13.1%) show bilateral spondylolysis. Conclusion: Pseudospondylolisthesis secondary to small AP diameter of L5 has prevalence of about 2% in lumbosacral MRI of cases referred for any reasons and can be overlooked in reporting of LS MRI. There was an association between small anteroposterior diameter of L5 and presence of spondylolysis at L5.

Measurements of Development in L2 Written Production: The Case of L2 Chinese

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Jiang, Wenying

2013-01-01

This study investigates measures for second language (L2) writing development. A T-unit, which has been found the most satisfactory unit of analysis for measuring L2 development in English, is extended to measure L2 Chinese writing development through a cross-sectional design in this study. Data were collected from three L2 Chinese learner groups…

Learners’ L1 Use in a Task-based Classroom

DEFF Research Database (Denmark)

Bao, Rui; Du, Xiangyun

2015-01-01

, but with only a very small amount oc- curring for off-task talk across tasks. L1 use mainly occurred in learners’ efforts to mediate completion of the tasks. The findings highlight the role of L1 in foreign language learning and suggest that L1 use is associated with a number of factors, such as task types......’ extensive L1 use and off-task talk. Informed by sociocultural theory, this study explored the extent to which L1s and their func- tions were used when performing tasks. The subjects were beginner-level lower-secondary school learners of Chinese. The data shows that learners have a high amount of L1 use...

The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts.

Science.gov (United States)

Sista, P; Wasikowski, B; Lecocq, P; Pattery, T; Bacheler, L

2008-08-01

The HIV-1 protease mutation I50 L causes atazanavir resistance but increases susceptibility to other PIs. Predicted phenotypic FC values were obtained from viral genotypes, using the virtual Phenotype-LM bioinformatics tool (powering vircoTYPE). To evaluate I50 L's effect on susceptibility to 8 PIs, in a large genotype database. I50 L containing routine clinical isolate samples in Virco's genotype database were paired with samples having like patterns (or profiles) of IAS-USA-defined primary PI mutations, but lacking I50 L. Using vircoTYPE (version 4.1), the median predicted FC for each mutational profile was determined. I50 L-associated shifts in FC were evaluated using drug-specific CCOs. We selected 307 and 37098 samples with and without I50 L. These corresponded to 31 mutation patterns of > or =3 samples each. I50 L caused resistance to atazanavir in all 31 mutation contexts, but was associated with higher susceptibility for other PIs. The largest I50 L-associated shifts in median predicted FC were: 1.2 to 42.4 (atazanavir), 10.2 to 3.2 (amprenavir), 3.3 to 0.5 (darunavir), 13 to 0.5 (indinavir), 34.9 to 1.3 (lopinavir), 22.3 to 1.3 (nelfinavir), 5.2 to 0.3 (saquinavir) and 29.9 to 5.2 (tipranavir). The PI mutation I50 L causes clinically relevant resistance and increased susceptibility to atazanavir and other PIs respectively.

Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions

Science.gov (United States)

Schulz, Florian; Lutz, David; Rusche, Norman; Bastús, Neus G.; Stieben, Martin; Höltig, Michael; Grüner, Florian; Weller, Horst; Schachner, Melitta; Vossmeyer, Tobias; Loers, Gabriele

2013-10-01

The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1 sequence of the third fibronectin type III domain of murine L1 was identified and conjugated to gold nanoparticles (AuNPs) to obtain constructs that interact homophilically with the extracellular domain of L1 and trigger the cognate beneficial L1-mediated functions. Covalent conjugation was achieved by reacting mixtures of two cysteine-terminated forms of this L1 peptide and thiolated poly(ethylene) glycol (PEG) ligands (~2.1 kDa) with citrate stabilized AuNPs of two different sizes (~14 and 40 nm in diameter). By varying the ratio of the L1 peptide-PEG mixtures, an optimized layer composition was achieved that resulted in the expected homophilic interaction of the AuNPs. These AuNPs were stable as tested over a time period of 30 days in artificial cerebrospinal fluid and interacted with the extracellular domain of L1 on neurons and Schwann cells, as could be shown by using cells from wild-type and L1-deficient mice. In vitro, the L1-derivatized particles promoted neurite outgrowth and survival of neurons from the central and peripheral nervous system and stimulated Schwann cell process formation and proliferation. These observations raise the hope that, in combination with other therapeutic approaches, L1 peptide-functionalized AuNPs may become a useful tool to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1

l-2-Nitrimino-1,3-diazepane-4-carboxylic acid

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Harutyun A. Karapetyan

2008-05-01

Full Text Available The cyclic form of l-nitroarginine, C6H10N4O4, crystallizes with two independent molecules in the asymmetric unit. According to the geometrical parameters, similar in both molecules, the structure corresponds to that of l-2-nitrimino-1,3-diazepane-4-carboxylic acid; there are, however, conformational differences between the independent molecules, one of them being close to a twisted chair while the other might be described as a rather flattened boat. All six active H atoms in the two molecules are involved in hydrogen bonds, two of which are intramolecular and four intermolecular, forming an infinite chain of molecules along the b axis.

Nephrogenic diabetes insipidus in a patient with L1 syndrome: a new report of a contiguous gene deletion syndrome including L1CAM and AVPR2.

Science.gov (United States)

Knops, Noël B B; Bos, Krista K; Kerstjens, Mieke; van Dael, Karin; Vos, Yvonne J

2008-07-15

We report on an infant boy with congenital hydrocephalus due to L1 syndrome and polyuria due to diabetes insipidus. We initially believed his excessive urine loss was from central diabetes insipidus and that the cerebral malformation caused a secondary insufficient pituitary vasopressin release. However, he failed to respond to treatment with a vasopressin analogue, which pointed to nephrogenic diabetes insipidus (NDI). L1 syndrome and X-linked NDI are distinct clinical disorders caused by mutations in the L1CAM and AVPR2 genes, respectively, located in adjacent positions in Xq28. In this boy we found a deletion of 61,577 basepairs encompassing the entire L1CAM and AVPR2 genes and extending into intron 7 of the ARHGAP4 gene. To our knowledge this is the first description of a patient with a deletion of these three genes. He is the second patient to be described with L1 syndrome and NDI. During follow-up he manifested complications from the hydrocephalus and NDI including global developmental delay and growth failure with low IGF-1 and hypothyroidism. 2008 Wiley-Liss, Inc.

ɛ '/ ɛ anomaly and neutron EDM in SU(2) L × SU(2) R × U(1) B- L model with charge symmetry

Science.gov (United States)

Haba, Naoyuki; Umeeda, Hiroyuki; Yamada, Toshifumi

2018-05-01

The Standard Model prediction for ɛ '/ ɛ based on recent lattice QCD results exhibits a tension with the experimental data. We solve this tension through W R + gauge boson exchange in the SU(2) L × SU(2) R × U(1) B- L model with `charge symmetry', whose theoretical motivation is to attribute the chiral structure of the Standard Model to the spontaneous breaking of SU(2) R × U(1) B- L gauge group and charge symmetry. We show that {M_W}{_R}study a correlation between ɛ ' /ɛ and the neutron EDM. We confirm that the model can solve the ɛ ' /ɛ anomaly without conflicting the current bound on the neutron EDM, and further reveal that almost all parameter regions in which the ɛ ' /ɛ anomaly is explained will be covered by future neutron EDM searches, which leads us to anticipate the discovery of the neutron EDM.

TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate

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Kabagambe Edmond K

2009-10-01

Full Text Available Abstract Background Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2 gene polymorphisms (rs12255372 and rs7903146, consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate. Methods Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 ± 16 y were included. All participants suspended use of lipid-lowering drugs for three weeks and were then given 160 mg/day of fenofibrate for three weeks. Inflammatory markers and lipids were measured before and after fenofibrate. ANOVA was used to test for differences across TCF7L2 genotypes. Results Under the additive or dominant model, there were no significant differences (P > 0.05 in the concentrations of inflammatory markers (hsCRP, IL-2, IL-6, TNF-α and MCP-1 across TCF7L2 genotypes in the period before or after treatment. For both rs12255372 and rs7903146, homozygote T-allele carriers had significantly higher (P Conclusion Overall these data show no association between TCF7L2 polymorphisms and the inflammatory markers suggesting that the effects of TCF7L2 on diabetes may not be via inflammation.

Development and validation of an UFLC-MS/MS method for enantioselectivity determination of d,l-thero-methylphenidate, d,l-thero-ethylphenidate and d,l-thero-ritalinic acid in rat plasma and its application to pharmacokinetic study.

Science.gov (United States)

Zhang, Chenghao; Luo, Huafei; Wu, Yubo; Zhang, Junyun; Zhang, Furong; Lin, Guobei; Wang, Hao

2016-02-01

A chiral UFLC-MS/MS method was established and validated for quantifying d-threo-methylphenidate (d-threo-MPH), l-threo-methylphenidate (l-threo-MPH), d-threo-ethylphenidate (d-threo-EPH), l-threo-ethylphenidate (l-threo-EPH) and d,l-threo-ritalinic acid (d,l-threo-RA) in rat plasma over the linearity range of 1-500ng/mL. Chiral separation was performed on an Astec Chirobiotic V2 column (5μm, 250×2.1mm) with isocratic elution using methanol containing 0.003% ammonium acetate (w/v) and 0.003% trifluoroacetic acid (v/v) at a flow of 0.3mL/min. All analytes and IS were extracted from rat plasma by a one-step liquid-liquid extraction (LLE) method. The intra- and inter-run accuracies were within 85-115%, and the intra- and inter-run precision were <10% for all analytes. Extraction recoveries were 55-62% for d-threo-MPH, 54-60% for l-threo-MPH, 55-60% for d-threo-EPH, 53-57% for l-threo-EPH and 25-30% for d,l-threo-RA. The validated UFLC-MS/MS method successfully applied to the pharmacokinetic interaction study of oral d-threo-MPH and l-threo-MPH (alone or in combination) in female Sprague Dawley rats. The EPH was not detected in rat plasma following oral administrated MPH without EtOH. As far as it is known to the authors, this study is the first one step liquid-liquid extraction method to extract and UFLC-MS/MS method to quantify d-threo-MPH, l-threo-MPH, d-threo-EPH, l-threo-EPH and d,l-threo-RA simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians.

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Srinivasan Pugazhendhi

Full Text Available Inflammatory bowel disease (IBD is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs in the autophagy related 16 like 1 (ATG16L1 gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn's disease (CD, 249 patients with ulcerative colitis (UC and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D' = 0.76-1.0 and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10-6 for CD and 0.002 for UC. SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.

Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

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Kumar Sudhesh

2008-02-01

Full Text Available Abstract Background Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2 gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods We genotyped four single nucleotide polymorphisms (SNPs of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372 in 831 subjects with diabetes and 437 control subjects. Results The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3. For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7. Conclusion Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups.

Localization and role of NPC1L1 in cholesterol absorption in human intestine.

Science.gov (United States)

Sané, Alain Théophile; Sinnett, Daniel; Delvin, Edgard; Bendayan, Moise; Marcil, Valérie; Ménard, Daniel; Beaulieu, Jean-François; Levy, Emile

2006-10-01

Recent studies have documented the presence of Niemann-Pick C1-Like 1 (NPC1L1) in the small intestine and its capacity to transport cholesterol in mice and rats. The current investigation was undertaken to explore the localization and function of NPC1L1 in human enterocytes. Cell fractionation experiments revealed an NPC1L1 association with apical membrane of the enterocyte in human jejunum. Signal was also detected in lysosomes, endosomes, and mitochondria. Confirmation of cellular NPC1L1 distribution was obtained by immunocytochemistry. Knockdown of NPC1L1 caused a decline in the ability of Caco-2 cells to capture micellar [(14)C]free cholesterol. Furthermore, this NPC1L1 suppression resulted in increased and decreased mRNA levels and activity of HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and of ACAT, the key enzyme in cholesterol esterification, respectively. An increase was also noted in the transcriptional factor sterol-regulatory element binding protein that modulates cholesterol homeostasis. Efforts were devoted to define the impact of NPC1L1 knockdown on other mediators of cholesterol uptake. RT-PCR evidence is presented to show the significant decrease in the levels of scavenger receptor class B type I (SR-BI) with no changes in ABCA1, ABCG5, and cluster determinant 36 in NPC1L1-deficient Caco-2 cells. Together, our data suggest that NPC1L1 contributes to intestinal cholesterol homeostasis and possibly cooperates with SR-BI to mediate cholesterol absorption in humans.

On the Role of L1 Markedness and L2 Input Robustness in Determining Potentially Fossilizable Language Forms in Iranian EFL Learners' Writing

Science.gov (United States)

Nushi, Musa

2016-01-01

Han's (2009, 2013) selective fossilization hypothesis (SFH) claims that L1 markedness and L2 input robustness determine the fossilizability (and learnability) of an L2 feature. To test the validity of the model, a pseudo-longitudinal study was designed in which the errors in the argumentative essays of 52 Iranian EFL learners were identified and…

Detention of HPV L1 Capsid Protein and hTERC Gene in Screening of Cervical Cancer

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Huang Bin

2013-06-01

Full Text Available   Objective(s: To investigate the expression of human papilloma virus (HPV L1 capsid protein, and human telomerase RNA component (hTERC in cervical cancer and the role of detection of both genes in screening of cervical cancer.   Materials and Methods: A total of 309 patients were recruited and cervical exfoliated cells were collected. Immunocytochemistry was employed to detect HPV L1 capsid protein, and fluorescent in situ hybridization (FISH was performed to detect the hTERC. Results: The expression of HPV L1 capsid protein reduced with the increase of the histological grade of cervical cells and was negatively related to the grade of cervical lesions. However, the expression of hTERC increased with the increase of the histological grade and positively associated with the grade of cervical lesions. The proportion of patients with L1(-/hTERC(+ was higher in patients with histological grade of CIN2 or higher than that in those with histological grade of CIN1. The L1(+/hTERC(- and L1(-/hTERC(- were negatively related to the grade of cervical lesions. L1(-/hTERC(+ was positively associated with the grade of cervical lesions. The L1/hTERC ratio increased. The negative predictive value of both HPV L1 and hTERC was higher than that of HPV L1 or hTERC, but there was no marked difference in the screening efficacy of cervical cancer among HPV L1, hTERC and HPV L1+hTERC. Conclusion: HPV L1 capsid protein and hTERC gene may serve as markers for the early diagnosis and prediction of cervical lesions. The increase in L1/hTERC ratio reflects the progression of cervical lesions to a certain extent.

Helical magnetic axis configuration combined with l = 1 and weak l = -1 torsatron fields

International Nuclear Information System (INIS)

Kikuchi, Hitoshi; Saito, Katsunori; Gesso, Hirokazu; Shiina, Shoichi

1989-01-01

The superposition of a relatively weak l = -1 torsatron field on a main l = 1 torsatron field leads to the improvement of the confinement properties due to the formation of a local magnetic well, which results from the local curvature of the helical magnetic axis with a larger excursion in the major radius direction. This l±1 helical magnetic axis system has a comparatively simple, compact coil structure. Here the vacuum configuration properties of l = ±1 system are described. (author)

Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity

NARCIS (Netherlands)

Rocker, N. de; Vergult, S.; Koolen, D.A.; Jacobs, E.; Hoischen, A.; Zeesman, S.; Bang, B.; Bena, F.; Bockaert, N.; Bongers, E.M.H.F.; Ravel, T. de; Devriendt, K.; Giglio, S.; Faivre, L.; Joss, S.; Maas, S.; Marle, N.; Novara, F.; Nowaczyk, M.J.; Peeters, H.; Polstra, A.; Roelens, F.; Rosenberg, C.; Thevenon, J.; Tumer, Z.; Vanhauwaert, S.; Varvagiannis, K.; Willaert, A.; Willemsen, M.H.; Willems, M.; Zuffardi, O.; Coucke, P.; Speleman, F.; Eichler, E.E.; Kleefstra, T.; Menten, B.

2015-01-01

PURPOSE: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis. METHODS: In this study

A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria

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Farias Fabiana HG

2012-07-01

Full Text Available Abstract Background L-2-hydroxyglutaric aciduria is a metabolic repair deficiency characterized by elevated levels of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid. Neurological signs associated with the disease in humans and dogs include seizures, ataxia and dementia. Case presentation Here we describe an 8 month old Yorkshire terrier that presented with episodes of hyperactivity and aggressive behavior. Between episodes, the dog’s behavior and neurologic examinations were normal. A T2 weighted MRI of the brain showed diffuse grey matter hyperintensity and a urine metabolite screen showed elevated 2-hydroxyglutaric acid. We sequenced all 10 exons and intron-exon borders of L2HGDH from the affected dog and identified a homozygous A to G transition in the initiator methionine codon. The first inframe methionine is at p.M183 which is past the mitochondrial targeting domain of the protein. Initiation of translation at p.M183 would encode an N-terminal truncated protein unlikely to be functional. Conclusions We have identified a mutation in the initiation codon of L2HGDH that is likely to result in a non-functional gene. The Yorkshire terrier could serve as an animal model to understand the pathogenesis of L-2-hydroxyglutaric aciduria and to evaluate potential therapies.

Electrical sounding data inversion with minimum L-1 norm; Inversao de dados de sondagem eletrica minimizando a norma L1

Energy Technology Data Exchange (ETDEWEB)

Marinho, Jose Marcio Lins [Bahia Univ., Salvador, BA (Brazil). Inst. de Geociencias. Programa de Pesquisa e Pos-graduacao em Geociencias]|[Ceara Univ., Fortaleza, CE (Brazil). Dept. de Geologia; Lima, Olivar Antonio Lima de [Bahia Univ., Salvador, BA (Brazil). Inst. de Geociencias. Programa de Pesquisa e Pos-graduacao em Geociencias

1995-12-31

The steepest descent and the damped least squares are the most used methods for inverting electrical sounding data. Normally, such inversions are made in the apparent resistivity domain using the norm L{sub 2}. For one dimensional earth models we present a new inversion scheme based on the minimization of norm L{sub 1} applied in the logarithmic domain. In the steepest descent case, the implementation of the L{sub 1} norm consists essentially in computing partial derivatives of the objective function with respect to the model parameters. In the second case, referred here as the damped least absolute deviation, the implementation is done via an interactively reweighed least square procedure. Several inversions were done for the Schlumberger array using both theoretical and field data. The results are very promising and attest the robustness of the L{sub 1} norm. A comparative performance study of the both norms are in progress using more than 140 Schlumberger soundings obtained in a groundwater exploration program in the area of Itarema-Acarau, Ceara State, Brazil. (author). 9 refs., 3 figs

Technetium(I) complexes Tc(CO)3BrL2 (L = phosphine, pyridine, isocyanide)

International Nuclear Information System (INIS)

Lorenz, B.; Findeisen, M.; Olk, B.; Schmidt, K.

1988-01-01

Technetium pentacarbonyl bromide reacts with π-acceptor ligands L (L = phosphine, pyridine, isocyanide) to form disubstituted compounds of the type Tc(CO) 3 BrL 2 . The stereochemistry of the complexes was established by infrared and 1 H-NMR measurement. Chemical shifts and the half-widths of the 99 Tc-NMR signals are discussed. (author)

Association of anti-apoptotic Mcl-1L isoform expression with radioresistance of oral squamous carcinoma cells

International Nuclear Information System (INIS)

Palve, Vinayak C; Teni, Tanuja R

2012-01-01

Oral cancer is a common cancer and a major health problem in the Indian subcontinent. At our laboratory Mcl-1, an anti-apoptotic member of the Bcl-2 family has been demonstrated to be overexpressed in oral cancers and to predict outcome in oral cancer patients treated with definitive radiotherapy. To study the role of Mcl-1 isoforms in radiation response of oral squamous carcinoma cells (OSCC), we investigated in the present study, the association of Mcl-1 isoform expression with radiosensitivity of OSCC, using siRNA strategy. The time course expression of Mcl-1 splice variants (Mcl-1L, Mcl-1S & Mcl-1ES) was studied by RT-PCR, western blotting & immunofluorescence, post-irradiation in oral cell lines [immortalized FBM (radiosensitive) and tongue cancer AW8507 & AW13516 (radioresistant)]of relatively differing radiosensitivities. The effect of Mcl-1L knockdown alone or in combination with ionizing radiation (IR) on cell proliferation, apoptosis & clonogenic survival, was investigated in AW8507 & AW13516 cells. Further the expression of Mcl-1L protein was assessed in radioresistant sublines generated by fractionated ionizing radiation (FIR). Three to six fold higher expression of anti-apoptotic Mcl-1L versus pro-apoptotic Mcl-1S was observed at mRNA & protein levels in all cell lines, post-irradiation. Sustained high levels of Mcl-1L, downregulation of pro-apoptotic Bax & Bak and a significant (P < 0.05) reduction in apoptosis was observed in the more radioresistant AW8507, AW13516 versus FBM cells, post-IR. The ratios of anti to pro-apoptotic proteins were high in AW8507 as compared to FBM. Treatment with Mcl-1L siRNA alone or in combination with IR significantly (P < 0.01) increased apoptosis viz. 17.3% (IR), 25.3% (siRNA) and 46.3% (IR plus siRNA) and upregulated pro-apoptotic Bax levels in AW8507 cells. Combination of siRNA & IR treatment significantly (P < 0.05) reduced cell proliferation and clonogenic survival of radioresistant AW8507 & AW13516 cells

TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population

Directory of Open Access Journals (Sweden)

Mill JG

2008-12-01

Full Text Available Abstract Background Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. Methods We genotyped the single nucleotide polymorphisms (SNP rs7903146 of the TCF7L2 gene in 560 patients with known coronary disease enrolled in the MASS II (Medicine, Angioplasty, or Surgery Study Trial and in 1,449 residents of Vitoria, in Southeast Brazil. The associations of this gene variant to diabetes risk and metabolic characteristics in these two different populations were analyzed. To access the potential benefit of using this marker for diabetes risk prediction in the general population we analyzed the impact of this genetic variant on a validated diabetes risk prediction tool based on clinical characteristics developed for the Brazilian general population. Results SNP rs7903146 of the TCF7L2 gene was significantly associated with type 2 diabetes in the MASS-II population (OR = 1.57 per T allele, p = 0.0032, confirming, in the Brazilian population, previous reports of the literature. Addition of this polymorphism to an established clinical risk prediction score did not increased model accuracy (both area under ROC curve equal to 0.776. Conclusion TCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease. However, the inclusion of this polymorphism in a risk prediction tool developed for the general population resulted in no improvement of performance. This is the first study, to our knowledge, that has confirmed this recent association in a South American population and adds to the great consistency of this finding in studies around the world

Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade

Directory of Open Access Journals (Sweden)

Ikebuchi Ryoyo

2011-09-01

Full Text Available Abstract The inhibitory receptor programmed death-1 (PD-1 and its ligand, programmed death-ligand 1 (PD-L1 are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.

Intra-articular sodium hyaluronate 2 mL versus physiological saline 20 mL versus physiological saline 2 mL for painful knee osteoarthritis: a randomized clinical trial

DEFF Research Database (Denmark)

Lundsgaard, C.; Dufour, N.; Fallentin, E.

2008-01-01

, Knee Injury and Osteoarthritis Outcome Score (KOOS), Osteoarthritis Research Society International (OARSI) criteria, and global assessment of the patient's condition. Results: The mean age of the patients was 69.4 years; 55% were women. The effects of hyaluronate 2 mL, physiological saline 20 m......Objective: Methodological constraints weaken previous evidence on intra-articular viscosupplementation and physiological saline distention for osteoarthritis. We conducted a randomized, patient- and observer-blind trial to evaluate these interventions in patients with painful knee osteoarthritis....... Methods: We centrally randomized 251 patients with knee ostcoarthritis to four weekly intra-articular injections of sodium hyaluronate 2 mL (Hyalgan(R) 10.3 mg/mL) versus physiological saline 20 mL (distention) versus physiological saline 2 mL (placebo) and followed patients for 26 weeks. Inclusion...

L2 listening at work

DEFF Research Database (Denmark)

Øhrstrøm, Charlotte

This dissertation on adult second language (L2) learning investigates individual learners’ experiences with listening in Danish as an L2 in everyday situations at work. More specifically, the study explores when international employees, who work at international companies in Denmark with English...... as a corporate language, listen in Danish at work, how they handle these situations, what problems they experience, and why some situations are more difficult to listen in than others. The study makes use of qualitative research methods and theoretical aspects from psycholinguistic approaches as well as socially...

Varying the Lewis base coordination of the Y2N2 core in the reduced dinitrogen complexes {[(Me3Si)2N]2(L)Y}2(μ-η2:η2-N2) (L = benzonitrile, pyridines, triphenylphosphine oxide, and trimethylamine N-oxide).

Science.gov (United States)

Corbey, Jordan F; Farnaby, Joy H; Bates, Jefferson E; Ziller, Joseph W; Furche, Filipp; Evans, William J

2012-07-16

The effect of the neutral donor ligand, L, on the Ln(2)N(2) core in the (N═N)(2-) complexes, [A(2)(L)Ln](2)(μ-η(2):η(2)-N(2)) (Ln = Sc, Y, lanthanide; A = monoanion; L = neutral ligand), is unknown since all of the crystallographically characterized examples were obtained with L = tetrahydrofuran (THF). To explore variation in L, displacement reactions between {[(Me(3)Si)(2)N](2)(THF)Y}(2)(μ-η(2):η(2)-N(2)), 1, and benzonitrile, pyridine (py), 4-dimethylaminopyridine (DMAP), triphenylphosphine oxide, and trimethylamine N-oxide were investigated. THF is displaced by all of these ligands to form {[(Me(3)Si)(2)N](2)(L)Y}(2)(μ-η(2):η(2)-N(2)) complexes (L = PhCN, 2; py, 3; DMAP, 4; Ph(3)PO, 5; Me(3)NO, 6) that were fully characterized by analytical, spectroscopic, density functional theory, and X-ray crystallographic methods. The crystal structures of the Y(2)N(2) cores in 2-5 are similar to that in 1 with N-N bond distances between 1.255(3) Å and 1.274(3) Å, but X-ray analysis of the N-N distance in 6 shows it to be shorter: 1.198(3) Å.

Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

Science.gov (United States)

Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

2017-12-01

Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Effet de l'herbe de Guinée ( Panicum maximum Jacq.) associée à l ...

African Journals Online (AJOL)

Effet de l'herbe de Guinée ( Panicum maximum Jacq.) associée à l'herbe de lait ( Euphorbia heterophylla L.) ou aux feuilles de patate douce ( Ipomoea batatas (L.) Lam) sur la croissance des lapins ( Oryctolagus cuniculus L.)

Genotyping of a tri-allelic polymorphism by a novel melting curve assay in MTHFD1L: an association study of nonsyndromic Cleft in Ireland

LENUS (Irish Health Repository)

Minguzzi, Stefano

2012-04-20

AbstractBackgroundPolymorphisms within the MTHFD1L gene were previously associated with risk of neural tube defects in Ireland. We sought to test the most significant MTHFD1L polymorphisms for an association with risk of cleft in an Irish cohort. This required the development of a new melting curve assay to genotype the technically challenging MTHFD1L triallelic deletion\\/insertion polymorphism (rs3832406).MethodsMelting curve analysis was used to genotype the MTHFD1L triallelic deletion\\/insertion polymorphism (rs3832406) and a Single Nucleotide Polymorphism rs17080476 in an Irish cohort consisting of 981 Irish case-parent trios and 1,008 controls. Tests for association with nonsyndromic cleft lip with or without cleft palate and cleft palate included case\\/control analysis, mother\\/control analysis and Transmission Disequilibrium Tests of case-parent trios.ResultsA successful melting curve genotyping assay was developed for the deletion\\/insertion polymorphism (rs3832406). The TDT analysis initially showed that the rs3832406 polymorphism was associated with isolated cleft lip with or without cleft palate. However, corrected p-values indicated that this association was not significant.ConclusionsMelting Curve Analysis can be employed to successfully genotype challenging polymorphisms such as the MTHFD1L triallelic deletion\\/insertion polymorphism (DIP) reported here (rs3832406) and is a viable alternative to capillary electrophoresis. Corrected p-values indicate no association between MTHFD1L and risk of cleft in an Irish cohort.

Synthesis, structure, luminescent, and magnetic properties of carbonato-bridged Zn(II)2Ln(III)2 complexes [(μ4-CO3)2{Zn(II)L(n)Ln(III)(NO3)}2] (Ln(III) = Gd(III), Tb(III), Dy(III); L(1) = N,N'-bis(3-methoxy-2-oxybenzylidene)-1,3-propanediaminato, L(2) = N,N'-bis(3-ethoxy-2-oxybenzylidene)-1,3-propanediaminato).

Science.gov (United States)

Ehama, Kiyomi; Ohmichi, Yusuke; Sakamoto, Soichiro; Fujinami, Takeshi; Matsumoto, Naohide; Mochida, Naotaka; Ishida, Takayuki; Sunatsuki, Yukinari; Tsuchimoto, Masanobu; Re, Nazzareno

2013-11-04

Carbonato-bridged Zn(II)2Ln(III)2 complexes [(μ4-CO3)2{Zn(II)L(n)Ln(III)(NO3)}2]·solvent were synthesized through atmospheric CO2 fixation reaction of [Zn(II)L(n)(H2O)2]·xH2O, Ln(III)(NO3)3·6H2O, and triethylamine, where Ln(III) = Gd(III), Tb(III), Dy(III); L(1) = N,N'-bis(3-methoxy-2-oxybenzylidene)-1,3-propanediaminato, L(2) = N,N'-bis(3-ethoxy-2-oxybenzylidene)-1,3-propanediaminato. Each Zn(II)2Ln(III)2 structure possessing an inversion center can be described as two di-μ-phenoxo-bridged {Zn(II)L(n)Ln(III)(NO3)} binuclear units bridged by two carbonato CO3(2-) ions. The Zn(II) ion has square pyramidal coordination geometry with N2O2 donor atoms of L(n) and one oxygen atom of a bridging carbonato ion at the axial site. Ln(III) ion is coordinated by nine oxygen atoms consisting of four from the deprotonated Schiff-base L(n), two from a chelating nitrate, and three from two carbonate groups. The temperature-dependent magnetic susceptibilities in the range 1.9-300 K, field-dependent magnetization from 0 to 5 T at 1.9 K, and alternating current magnetic susceptibilities under the direct current bias fields of 0 and 1000 Oe were measured. The magnetic properties of the Zn(II)2Ln(III)2 complexes are analyzed on the basis of the dicarbonato-bridged binuclear Ln(III)-Ln(III) structure, as the Zn(II) ion with d(10) electronic configuration is diamagnetic. ZnGd1 (L(1)) and ZnGd2 (L(2)) show a ferromagnetic Gd(III)-Gd(III) interaction with J(Gd-Gd) = +0.042 and +0.028 cm(-1), respectively, on the basis of the Hamiltonian H = -2J(Gd-Gd)ŜGd1·ŜGd2. The magnetic data of the Zn(II)2Ln(III)2 complexes (Ln(III) = Tb(III), Dy(III)) were analyzed by a spin Hamiltonian including the crystal field effect on the Ln(III) ions and the Ln(III)-Ln(III) magnetic interaction. The Stark splitting of the ground state was so evaluated, and the energy pattern indicates a strong easy axis (Ising type) anisotropy. Luminescence spectra of Zn(II)2Tb(III)2 complexes were observed, while those

Aspergillus niger PA2: a novel strain for extracellular biotransformation of L-tyrosine into L-DOPA.

Science.gov (United States)

Agarwal, Pragati; Pareek, Nidhi; Dubey, Swati; Singh, Jyoti; Singh, R P

2016-05-01

L-DOPA (3,4-dihydroxyphenyl-L-alanine), an amino acid derivative is the most widely used drug of choice for the treatment of Parkinson's disease and other neurologic injuries. The present study deals with the elevated biochemical transformation of L-tyrosine to L-DOPA by Aspergillus niger PA2, a potent tyrosinase producer, isolated from decomposed food wastes. This appears to be the first report on A. niger as a notable extracellular tyrosinase producer. The extracellular tyrosinase activity produced remarkably higher levels of L-DOPA, i.e. 2.44 mg mL(-1) when the media was supplemented with 5 mg mL(-1) L-tyrosine. The optimum pH for tyrosinase production was 6.0, with the maximal L-DOPA production at the same pH. The product thus produced was analyzed by thin-layer chromatography, UV spectroscopy, high-performance liquid chromatography and Fourier transform infrared spectroscopy, that had denoted this to be L-DOPA. Kinetic parameters viz. Y p/s, Q s and Q p had further indicated the notable levels of production. Thus, Aspergillus niger PA2 could be a promising resource and may be further exploited for large-scale production of L-DOPA.

Power system state estimation using an iteratively reweighted least squares method for sequential L{sub 1}-regression

Energy Technology Data Exchange (ETDEWEB)

Jabr, R.A. [Electrical, Computer and Communication Engineering Department, Notre Dame University, P.O. Box 72, Zouk Mikhael, Zouk Mosbeh (Lebanon)

2006-02-15

This paper presents an implementation of the least absolute value (LAV) power system state estimator based on obtaining a sequence of solutions to the L{sub 1}-regression problem using an iteratively reweighted least squares (IRLS{sub L1}) method. The proposed implementation avoids reformulating the regression problem into standard linear programming (LP) form and consequently does not require the use of common methods of LP, such as those based on the simplex method or interior-point methods. It is shown that the IRLS{sub L1} method is equivalent to solving a sequence of linear weighted least squares (LS) problems. Thus, its implementation presents little additional effort since the sparse LS solver is common to existing LS state estimators. Studies on the termination criteria of the IRLS{sub L1} method have been carried out to determine a procedure for which the proposed estimator is more computationally efficient than a previously proposed non-linear iteratively reweighted least squares (IRLS) estimator. Indeed, it is revealed that the proposed method is a generalization of the previously reported IRLS estimator, but is based on more rigorous theory. (author)

Functional Crosstalk between the PP2A and SUMO Pathways Revealed by Analysis of STUbL Suppressor, razor 1-1.

Directory of Open Access Journals (Sweden)

Minghua Nie

2016-07-01

Full Text Available Posttranslational modifications (PTMs provide dynamic regulation of the cellular proteome, which is critical for both normal cell growth and for orchestrating rapid responses to environmental stresses, e.g. genotoxins. Key PTMs include ubiquitin, the Small Ubiquitin-like MOdifier SUMO, and phosphorylation. Recently, SUMO-targeted ubiquitin ligases (STUbLs were found to integrate signaling through the SUMO and ubiquitin pathways. In general, STUbLs are recruited to target proteins decorated with poly-SUMO chains to ubiquitinate them and drive either their extraction from protein complexes, and/or their degradation at the proteasome. In fission yeast, reducing or preventing the formation of SUMO chains can circumvent the essential and DNA damage response functions of STUbL. This result indicates that whilst some STUbL "targets" have been identified, the crucial function of STUbL is to antagonize SUMO chain formation. Herein, by screening for additional STUbL suppressors, we reveal crosstalk between the serine/threonine phosphatase PP2A-Pab1B55 and the SUMO pathway. A hypomorphic Pab1B55 mutant not only suppresses STUbL dysfunction, but also mitigates the phenotypes associated with deletion of the SUMO protease Ulp2, or mutation of the STUbL cofactor Rad60. Together, our results reveal a novel role for PP2A-Pab1B55 in modulating SUMO pathway output, acting in parallel to known critical regulators of SUMOylation homeostasis. Given the broad evolutionary functional conservation of the PP2A and SUMO pathways, our results could be relevant to the ongoing attempts to therapeutically target these factors.

Analysis list: Ash2l [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Ash2l Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ash2l.1.tsv... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ash2l.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ash2...l.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Ash2l.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

Orbit Determination of Spacecraft in Earth-Moon L1 and L2 Libration Point Orbits

Science.gov (United States)

Woodard, Mark; Cosgrove, Daniel; Morinelli, Patrick; Marchese, Jeff; Owens, Brandon; Folta, David

2011-01-01

The ARTEMIS mission, part of the THEMIS extended mission, is the first to fly spacecraft in the Earth-Moon Lissajous regions. In 2009, two of the five THEMIS spacecraft were redeployed from Earth-centered orbits to arrive in Earth-Moon Lissajous orbits in late 2010. Starting in August 2010, the ARTEMIS P1 spacecraft executed numerous stationkeeping maneuvers, initially maintaining a lunar L2 Lissajous orbit before transitioning into a lunar L1 orbit. The ARTEMIS P2 spacecraft entered a L1 Lissajous orbit in October 2010. In April 2011, both ARTEMIS spacecraft will suspend Lissajous stationkeeping and will be maneuvered into lunar orbits. The success of the ARTEMIS mission has allowed the science team to gather unprecedented magnetospheric measurements in the lunar Lissajous regions. In order to effectively perform lunar Lissajous stationkeeping maneuvers, the ARTEMIS operations team has provided orbit determination solutions with typical accuracies on the order of 0.1 km in position and 0.1 cm/s in velocity. The ARTEMIS team utilizes the Goddard Trajectory Determination System (GTDS), using a batch least squares method, to process range and Doppler tracking measurements from the NASA Deep Space Network (DSN), Berkeley Ground Station (BGS), Merritt Island (MILA) station, and United Space Network (USN). The team has also investigated processing of the same tracking data measurements using the Orbit Determination Tool Kit (ODTK) software, which uses an extended Kalman filter and recursive smoother to estimate the orbit. The orbit determination results from each of these methods will be presented and we will discuss the advantages and disadvantages associated with using each method in the lunar Lissajous regions. Orbit determination accuracy is dependent on both the quality and quantity of tracking measurements, fidelity of the orbit force models, and the estimation techniques used. Prior to Lissajous operations, the team determined the appropriate quantity of tracking

L1-norm locally linear representation regularization multi-source adaptation learning.

Science.gov (United States)

Tao, Jianwen; Wen, Shiting; Hu, Wenjun

2015-09-01

In most supervised domain adaptation learning (DAL) tasks, one has access only to a small number of labeled examples from target domain. Therefore the success of supervised DAL in this "small sample" regime needs the effective utilization of the large amounts of unlabeled data to extract information that is useful for generalization. Toward this end, we here use the geometric intuition of manifold assumption to extend the established frameworks in existing model-based DAL methods for function learning by incorporating additional information about the target geometric structure of the marginal distribution. We would like to ensure that the solution is smooth with respect to both the ambient space and the target marginal distribution. In doing this, we propose a novel L1-norm locally linear representation regularization multi-source adaptation learning framework which exploits the geometry of the probability distribution, which has two techniques. Firstly, an L1-norm locally linear representation method is presented for robust graph construction by replacing the L2-norm reconstruction measure in LLE with L1-norm one, which is termed as L1-LLR for short. Secondly, considering the robust graph regularization, we replace traditional graph Laplacian regularization with our new L1-LLR graph Laplacian regularization and therefore construct new graph-based semi-supervised learning framework with multi-source adaptation constraint, which is coined as L1-MSAL method. Moreover, to deal with the nonlinear learning problem, we also generalize the L1-MSAL method by mapping the input data points from the input space to a high-dimensional reproducing kernel Hilbert space (RKHS) via a nonlinear mapping. Promising experimental results have been obtained on several real-world datasets such as face, visual video and object. Copyright © 2015 Elsevier Ltd. All rights reserved.

Roles of linguistic knowledge, metacognitive knowledge and processing speed in L3, L2 and L1 reading comprehension: a structural equation modeling approach

NARCIS (Netherlands)

van Gelderen, A.; Schoonen, R.; de Glopper, K.; Hulstijn, J.; Snellings, P.; Simis, A.; Stevenson, M.

2003-01-01

In this article we present an analysis of the relationship between L3 reading comprehension and its constituent skills for bilingual Dutch students for whom English is a third language(L3) compared to monolingual Dutch students for whom English is a second language(L2). An analogous analysis is made

An L-stable method for solving stiff hydrodynamics

Science.gov (United States)

Li, Shengtai

2017-07-01

We develop a new method for simulating the coupled dynamics of gas and multi-species dust grains. The dust grains are treated as pressure-less fluids and their coupling with gas is through stiff drag terms. If an explicit method is used, the numerical time step is subject to the stopping time of the dust particles, which can become extremely small for small grains. The previous semi-implicit method [1] uses second-order trapezoidal rule (TR) on the stiff drag terms and it works only for moderately small size of the dust particles. This is because TR method is only A-stable not L-stable. In this work, we use TR-BDF2 method [2] for the stiff terms in the coupled hydrodynamic equations. The L-stability of TR-BDF2 proves essential in treating a number of dust species. The combination of TR-BDF2 method with the explicit discretization of other hydro terms can solve a wide variety of stiff hydrodynamics equations accurately and efficiently. We have implemented our method in our LA-COMPASS (Los Alamos Computational Astrophysics Suite) package. We have applied the code to simulate some dusty proto-planetary disks and obtained very good match with astronomical observations.

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

Science.gov (United States)

Anastasiadou, Eleni; Stroopinsky, Dina; Alimperti, Stella; Jiao, Alan L; Pyzer, Athalia R; Cippitelli, Claudia; Pepe, Giuseppina; Severa, Martina; Rosenblatt, Jacalyn; Etna, Marilena P; Rieger, Simone; Kempkes, Bettina; Coccia, Eliana M; Sui, Shannan J Ho; Chen, Christopher S; Uccini, Stefania; Avigan, David; Faggioni, Alberto; Trivedi, Pankaj; Slack, Frank J

2018-06-26

Cancer cells subvert host immune surveillance by altering immune checkpoint (IC) proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs in the context of its preferred host, the B lymphocyte and in derived lymphomas. Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III-expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancers, our findings may have important implications for combinatorial immunotherapy, which include IC inhibiting antibodies and miR-34a, for EBV-associated cancers.

Apolipoprotein L1 confers pH-switchable ion permeability to phospholipid vesicles.

Science.gov (United States)

Bruno, Jonathan; Pozzi, Nicola; Oliva, Jonathan; Edwards, John C

2017-11-03

Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility to some progressive kidney diseases. ApoL1 has been hypothesized to function like a pore-forming colicin and has been reported to have permeability effects on both intracellular and plasma membranes. Here, to gain insight into how ApoL1 may function in vivo , we used vesicle-based ion permeability, direct membrane association, and intrinsic fluorescence to study the activities of purified recombinant ApoL1. We found that ApoL1 confers chloride-selective permeability to preformed phospholipid vesicles and that this selectivity is strongly pH-sensitive, with maximal activity at pH 5 and little activity above pH 7. When ApoL1 and lipid were allowed to interact at low pH and were then brought to neutral pH, chloride permeability was suppressed, and potassium permeability was activated. Both chloride and potassium permeability linearly correlated with the mass of ApoL1 in the reaction mixture, and both exhibited lipid selectivity, requiring the presence of negatively charged lipids for activity. Potassium, but not chloride, permease activity required the presence of calcium ions in both the association and activation steps. Direct assessment of ApoL1-lipid associations confirmed that ApoL1 stably associates with phospholipid vesicles, requiring low pH and the presence of negatively charged phospholipids for maximal binding. Intrinsic fluorescence of ApoL1 supported the presence of a significant structural transition when ApoL1 is mixed with lipids at low pH. This pH-switchable ion-selective permeability may explain the different effects of ApoL1 reported in intracellular and plasma membrane environments. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.

Science.gov (United States)

Bardhan, Kankana; Anagnostou, Theodora; Boussiotis, Vassiliki A

2016-01-01

The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (T Regs ). These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) plays an important role in the induction and maintenance of peripheral tolerance and for the maintenance of the stability and the integrity of T cells. However, the PD-1:PD-L1/L2 pathway also mediates potent inhibitory signals to hinder the proliferation and function of T effector cells and have inimical effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events regulated by PD-1 engagement, and their consequences on the function of T effector cells.

The PD1: PD-L1/2 pathway from discovery to clinical implementation

Directory of Open Access Journals (Sweden)

Kankana Bardhan

2016-12-01

Full Text Available The immune system has the difficult challenge of discerning and defending against a diversity of microbial pathogens, while simultaneously avoiding self-reactivity. T lymphocytes function as effectors and regulators of the immune system. While central tolerance mechanism results in deletion of the majority of self-reactive T lymphocytes during thymic selection, a fraction of self reactive lymphocytes escapes to the periphery and retains the potential to inflict destructive autoimmune pathology. The immune system evolved various mechanisms to restrain such auto-reactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs. These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programmed cell death 1 (PD-1 receptor (CD279 and its ligands PD-L1 (B7-H1, CD274 and PD-L2 (B7-DC; CD273 plays a vital role in the induction and maintenance of peripheral tolerance and for the maintenance of T cell homeostasis. In contrast to its beneficial role in self-tolerance, the PD-1: PD-L1/L2 pathway mediates potent inhibitory signals that prevent the expansion and function of T effector cells and have detrimental effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events that are regulated by PD-1 triggering, and their consequences on the function of T effector cells.

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