gebhart/patrepeval huggingface dataset:
Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat (2006)

Cold exposure induces brown adipocytes in retroperitoneal fat (RP) of adult A/J mice but not in C57BL/6J (B6) mice. In contrast, induction of the mitochondrial uncoupling protein 1 gene (Ucp1) in interscapular brown adipose tissue (iBAT) shows no strain dependence. We now show that unlike iBAT, in which Ucp1 was expressed in the fetus and continued throughout life, in RP, Ucp1 was transiently expressed between 10 and 30 days of age and then disappeared. Similar to the lack of genetic variation in the expression of Ucp1 in iBAT during cold induction of adult mice, no genetic variation in Ucp1 expression in iBAT was detected during development. In contrast, UCP1-positive multilocular adipocytes, together with corresponding increases in Ucp1 expression, appeared in RP at 10 days of age in A/J and B6 mice, but with much higher expression in A/J mice. At 20 days of age, brown adipocytes represent the major adipocyte present in RP of A/J mice. The disappearance of brown adipocytes by 30 days of age suggested that tissue remodeling occurred in RP. Genetic variability in Ucp1 expression could not be explained by variation in the expression of selective transcription factors and signaling molecules of adipogenesis. In summary, the existence of genetic variability between A/J and B6 mice during the development of brown adipocyte expression in RP, but not in iBAT, suggests that developmental mechanisms for the brown adipocyte differentiation program are different in these adipose tissues.
Effects of the Novel Antiepileptic Drug Levetiracetam on Spontaneous Recurrent Seizures in the Rat Pilocarpine Model of Temporal Lobe Epilepsy (2002)

The data demonstrate that interesting results can be obtained by drug testing in epileptic rats, giving a more realistic prediction of clinical efficacy than results from drug testing in animal models with elicited seizures. Thus, although drug trials in rats with spontaneous recurrent seizures are laborious and time-consuming, such trials should be added to the preclinical characterization of novel AEDs.
Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation. (1993)

The synthesis and posttranslational modification of lysosomal acid alpha-glucosidase were studied in a cell-free translation system and in mammalian cells transfected with acid alpha-glucosidase cDNA constructs. The newly synthesized precursor, sequestered in the endoplasmic reticulum, was demonstrated to be membrane-bound by lack of signal peptide cleavage, and to be catalytically inactive. Sugar chain modification was shown to occur in the Golgi complex and to be dependent on the rate of transport. From the trans-Golgi network different routes were found to be followed by acid alpha-glucosidase. A fraction of precursor molecules, proteolytically released from the membrane anchor, appeared to enter the secretory pathway and was recovered from the cell culture medium in a catalytically active form. A second fraction was transported to the lysosomes and was trimmed in a stepwise process at both the amino- and carboxyl-terminal ends. The intramolecular cleavage sites were determined. Involvement of thiol proteinases was demonstrated. Specificity for the natural substrate glycogen was gained during the maturation process. The phosphomannosyl receptor is assumed to be instrumental in the lysosomal targeting of acid alpha-glucosidase, but a phosphomannosyl receptor-independent transport of membrane-bound precursor molecules to the lysosomes, either directly or via the plasma membrane, cannot be excluded.
Chromium(III) picolinate produces chromosome damage in Chinese hamster ovary cells. (1995)

Chromium(III) complexes currently being sold as dietary supplements were tested for their ability to cause chromosomal aberrations in Chinese hamster ovary cells. Complexes were tested in soluble and particulate forms. Chromium picolinate was found to produce chromosome damage 3-fold to 18-fold above control levels for soluble doses of 0.050, 0.10, 0.50, and 1.0 mM after 24 h treatment. Particulate chromium picolinate doses of 8.0 micrograms/cm2 (corresponding to a 0.10 mM solublized dose) and 40 micrograms/cm2 (0.50 mM) produced aberrations 4-fold and 16-fold above control levels, respectively. Toxicity was measured as a decrease in plating efficiency relative to controls. The above treatments produced > or = 86% survival for all doses except 1.0 mM chromium picolinate, which produced 69 +/- 10% survival. Chromium nicotinate, nicotinic acid, and chromium(III) chloride hexahydrate did not produce chromosome damage at equivalent nontoxic doses. Damage was inferred to be caused by the picolinate ligand because picolinic acid in the absence of chromium was clastogenic. Data are evaluated in terms of their relevance to human exposure based on pharmacokinetic modeling of tissue accumulation and are discussed in terms of literature reporting toxic effects of picolinic acid.
Dual roles of yeast Rad51 N-terminal domain in repairing DNA double-strand breaks (2020)

Highly toxic DNA double-strand breaks (DSBs) readily trigger the DNA damage response (DDR) in cells, which delays cell cycle progression to ensure proper DSB repair. In Saccharomyces cerevisiae, mitotic S phase (20-30 min) is lengthened upon DNA damage. During meiosis, Spo11-induced DSB onset and repair lasts up to 5 h. We report that the NH2-terminal domain (NTD; residues 1-66) of Rad51 has dual functions for repairing DSBs during vegetative growth and meiosis. Firstly, Rad51-NTD exhibits autonomous expression-enhancing activity for high-level production of native Rad51 and when fused to exogenous β-galactosidase in vivo. Secondly, Rad51-NTD is an S/T-Q cluster domain (SCD) harboring three putative Mec1/Tel1 target sites. Mec1/Tel1-dependent phosphorylation antagonizes the proteasomal degradation pathway, increasing the half-life of Rad51 from ∼30 min to ≥180 min. Our results evidence a direct link between homologous recombination and DDR modulated by Rad51 homeostasis.
Review of Chemical Sensors for In-Situ Monitoring of Volatile Contaminants (2001)

Sandia National Laboratories has sponsored an LDRD (Laboratory Directed Research and Development) project to investigate and develop micro-chemical sensors for in-situ monitoring of subsurface contaminants. As part of this project, a literature search has been conducted to survey available technologies and identify the most promising methods for sensing and monitoring subsurface contaminants of interest. Specific sensor technologies are categorized into several broad groups, and these groups are then evaluated for use in subsurface, long-term applications. This report introduces the background and specific scope of the problem being addressed by this LDRD project, and it provides a summary of the advantages and disadvantages of each sensor technology identified from the literature search.
Molecular beam epitaxy grown PbSnTe buried quantum-well diode lasers with PbEuSeTe confinement layers (1991)

Buried quantum-well (BQW) lasers were fabricated in a two-stage MBE growth sequence. The first growth stage included a 1.3- mu m-thick p-PbTe:Tl buffer grown on top of a p-type
Redox Regulation of the DNA Binding Activity in Transcription Factor PEBP2 (1997)

Transcription factor PEBP2/CBF consists of a DNA binding subunit, alpha, and a regulatory subunit, beta. The alpha subunit has an evolutionarily conserved 128-amino acid region termed "Runt domain" that is responsible for both DNA binding and heterodimerization with the beta subunit. The Runt domain in all mammalian submembers of the alpha subunit contains two conserved cysteine residues, and its DNA binding activity undergoes redox regulation. To investigate the mechanism of this redox regulation, we performed site-directed mutagenesis of the two conserved cysteines in the Runt domain of the mouse PEBP2alphaA homolog. Substitution of Cys-115 to serine resulted in a partially impaired DNA binding, which remained highly sensitive to a thiol-oxidizing reagent, diamide. Conversely, the corresponding substitution of Cys-124 caused an increased DNA binding concomitant with an increased resistance to diamide. In contrast, substitution of either cysteine to aspartate was destructive to DNA binding to marked extents. These results have revealed that both Cys-115 and Cys-124 are responsible for the redox regulation in their own ways with low and high oxidizabilities, respectively. We have also found that two cellular thiol-reactive proteins, thioredoxin and Ref-1, work effectively and synergistically for activation of the Runt domain. Interestingly, the beta subunit further enhanced the activation by these proteins and reciprocally prevented the oxidative inactivation by diamide. These findings collectively suggest the possibility that the Runt domain's function in vivo could be dynamically regulated by the redox mechanism with Trx, Ref-1, and the beta subunit as key modulators.
Introduction to neuropsychology (1983)

The human brain is a fascinating and engimatic machine. Weighing only about 3 pounds (1.36 kilograms) and with a volume of about 1,250 cubic centimeters, it has the ability to monitor and control our basic life support systems, to maintain our posture and direct our movements, to receive and interpret information about the world around us, and to store information in a readily accessible form throughout our lives. It allows us to solve problems that range from the strictly practical to the highly abstract, to communicate with our fellow human beings through language, to create new ideas and imagine things that have never existed, to feel love and happiness and disappointment, and to experience an awareness of ourselves as individuals. Not only can the brain undertake such a variety of different functions, but it can do more or less all of them simultaneously. How this is achieved is one of the most challenging and exciting problems faced by contemporary science.
Epigenetic Control of the foxp3 Locus in Regulatory T Cells (2007)

Compelling evidence suggests that the transcription factor Foxp3 acts as a master switch governing the development and function of CD4(+) regulatory T cells (Tregs). However, whether transcriptional control of Foxp3 expression itself contributes to the development of a stable Treg lineage has thus far not been investigated. We here identified an evolutionarily conserved region within the foxp3 locus upstream of exon-1 possessing transcriptional activity. Bisulphite sequencing and chromatin immunoprecipitation revealed complete demethylation of CpG motifs as well as histone modifications within the conserved region in ex vivo isolated Foxp3(+)CD25(+)CD4(+) Tregs, but not in naïve CD25(-)CD4(+) T cells. Partial DNA demethylation is already found within developing Foxp3(+) thymocytes; however, Tregs induced by TGF-beta in vitro display only incomplete demethylation despite high Foxp3 expression. In contrast to natural Tregs, these TGF-beta-induced Foxp3(+) Tregs lose both Foxp3 expression and suppressive activity upon restimulation in the absence of TGF-beta. Our data suggest that expression of Foxp3 must be stabilized by epigenetic modification to allow the development of a permanent suppressor cell lineage, a finding of significant importance for therapeutic applications involving induction or transfer of Tregs and for the understanding of long-term cell lineage decisions.
Diagnostic Uses of the Vineland Adaptive Behavior Scales (1985)

This report presents an overview of the Vineland Adaptive Behavior Scales and two measures of cognitive ability: the Kaufman Assessment Battery for Children (i.e., sequential and simultaneous processing, levels of achievement) and the revised Peabody Picture Vocabulary Test (i.e., listening vocabulary). These three instruments are applied and directly compared to demonstrate the interplay between adaptive behavior and cognitive functioning in the broader context of a pediatric setting. Two hypothetical case histories are discussed, one in which the child's levels of adaptive functioning are adequate while cognitive functioning is low; and a second one in which the reverse phenomenon is true, namely, high levels of cognitive functioning are coupled with impairments in adaptive functioning. The direct comparisons between the various areas of functioning are made possible by large Vine/and standardization samples of children whose abilities were assessed by all three instruments.
Insights into the conformational flexibility of Bruton's tyrosine kinase from multiple ligand complex structures (2010)

Bruton's tyrosine kinase (BTK) plays a key role in B cell receptor signaling and is considered a promising drug target for lymphoma and inflammatory diseases. We have determined the X-ray crystal structures of BTK kinase domain in complex with six inhibitors from distinct chemical classes. Five different BTK protein conformations are stabilized by the bound inhibitors, providing insights into the structural flexibility of the Gly-rich loop, helix C, the DFG sequence, and activation loop. The conformational changes occur independent of activation loop phosphorylation and do not correlate with the structurally unchanged WEI motif in the Src homology 2-kinase domain linker. Two novel activation loop conformations and an atypical DFG conformation are observed representing unique inactive states of BTK. Two regions within the activation loop are shown to structurally transform between 3(10)- and α-helices, one of which collapses into the adenosine-5'-triphosphate binding pocket. The first crystal structure of a Tec kinase family member in the pharmacologically important DFG-out conformation and bound to a type II kinase inhibitor is described. The different protein conformations observed provide insights into the structural flexibility of BTK, the molecular basis of its regulation, and the structure-based design of specific inhibitors.
Tetramethylphosphonium Fluoride:  “Naked” Fluoride and Phosphorane (2003)

Me(4)PF was investigated in the solid state, in the gas phase, and in solutions. Vibrational spectra of the solid and a single-crystal structure show an ionic tetramethylphosphonium fluoride. The compound crystallizes in the space group Pbca with a = 1016.0(1), b = 1018.0(1), c = 1205.8(4) pm, and Z = 8. The fluoride ion is nearly trigonal planar surrounded by three Me(4)P+ cations forming six H...F contacts between 218 and 240 pm. The compound is stable below 120 degrees C and sublimes in a vacuum. It possesses a phosphorane structure in the gas phase that was studied by electron diffraction and vibrational spectra, and additionally by theoretical calculations. The Me(4)PF molecule has a trigonal bipyramidal structure with one methyl group and the fluorine atom in axial positions and bond lengths of d(PC(eq)) = 182.6(4) pm, d(PC(ax)) = 188.4(8) pm, and d(PF) = 175.3(6) pm. The compound is remarkably soluble in acetonitrile, water, and alcohols, and slightly soluble in benzene, dimethyl ether, and diethyl ether. The solutions were studied by (1)H, (13)C, (19)F, and (31)P NMR spectroscopy. The hygroscopic Me(4)PF forms a tetrahydrate which crystallizes in the space group I4(1)/a with a = 1106.1(1) pm, c = 816.3(1) pm, and Z = 4. The fluoride ion in Me(4)PF.4 H(2)O is surrounded by four water molecules. These units form a three-dimensional network in which the Me(4)P+ cations are embedded without any contacts.
A class based language model for speech recognition (2002)

Class based language models are often used when there is insufficient data to generate a word based language model directly from the training data. In this approach, similar items are clustered into classes, an n-gram language model for the class tokens is generated, and then the probabilities for words in a class are distributed according to the smoothed relative unigram frequencies of the words. Classes expand to lists of single word tokens, that is, a class cannot represent a sequence of lexical tokens. We propose a more general mechanism for defining a language model class. In it, classes are expanded to word sequences through finite-state networks. This allows expansion to word sequences without requiring compound words in the lexicon. Where finite-state models are too brittle to represent sentence-level strings, they can represent class-level strings (dates, names and titles for example). We compared the perplexity on the ARPA Dec93 ATIS Test set and found that the new model reduced the perplexity by approximately 17 percent (relative).
A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances lung cancer susceptibility. (2001)

Extracellular matrix-degrading matrix metalloproteinase-1 (MMP-1) is one of the interstitial collagenases likely to be involved in tumor invasion and metastasis. MMP-1 may also contribute to tumor initiation and development by altering the cellular microenvironment that facilitates tumor formation. Recent studies have found that overexpression of MMP-1 is associated with the initial stages of cancer development in addition to promoting cellular invasion; however, preexisting oncogenic mutations or chemical carcinogens are required to initiate tumorigenesis as well. There is a single nucleotide polymorphism located in the promoter region of MMP-1 that partially regulates gene expression. The 2G/2G genotype enhances transcriptional activity and may be associated with an increased lung cancer risk. Using a case-control study, we tested the hypotheses that (a) individuals with the 2G/2G genotype may be at an increased risk for lung cancer; and (b) the risk should be greatly elevated in smoking individuals. PCR-RFLP was used to determine the MMP-1 genotypes in 456 lung-cancer cases and 451 frequency-matched controls of Caucasian ethnicity. Overall, there was a significant association between the 2G/2G genotype and lung cancer risk [odds ratio (OR), 1.76; 95% confidence interval (CI), 1.29-2.39]. In current smokers, the lung cancer risk associated with the 2G/2G genotype was significantly elevated (OR, 3.16; 95% CI, 1.87-5.35). However, this association was less evident in former smokers (OR, 1.23; 95% CI, 0.81-1.87) and absent in never smokers (OR, 1.09; 95% CI, 0.31-3.91). Similarly, this risk was more evident in heavy smokers (OR, 2.55; 95% CI, 1.61-4.03) than in light smokers (OR, 1.40; 95% CI, 0.84-2.32). Interestingly, men were observed to have a 2.15-fold increased lung cancer risk (OR, 2.15; 95% CI, 1.42-3.26) compared with women (OR, 1.34; 95% CI, 0.84-2.15). Furthermore, subjects with 2G/2G genotype developed lung cancer earlier (60.94 +/- 0.64 years old) than patients with 1G/1G and 1G/2G genotypes (62.91 +/- 0.59 years old; P = 0.024). Our data demonstrate that the 2G/2G genotype enhances lung cancer susceptibility especially in current smokers. To our knowledge, these results report the first molecular epidemiological evidence of the MMP-1 promoter polymorphism associated with the development of lung cancer in the presence of continuing carcinogenic exposure.
Structure Determination of Membrane Proteins by NMR Spectroscopy (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure Determination of Membrane Proteins by NMR SpectroscopyStanley J. Opella and Francesca M. MarassiView Author Information Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, and The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037 Cite this: Chem. Rev. 2004, 104, 8, 3587–3606Publication Date (Web):July 22, 2004Publication History Received9 March 2004Published online22 July 2004Published inissue 1 August 2004https://pubs.acs.org/doi/10.1021/cr0304121https://doi.org/10.1021/cr0304121research-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views3166Altmetric-Citations368LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Micelles,Nuclear magnetic resonance spectroscopy,Peptides and proteins,Protein structure,Vesicles Get e-Alerts
Sleep Spindle Activity is Associated with the Integration of New Memories and Existing Knowledge (2010)

Sleep spindle activity has been associated with improvements in procedural and declarative memory. Here, for the first time, we looked at the role of spindles in the integration of newly learned information with existing knowledge, contrasting this with explicit recall of the new information. Two groups of participants learned novel spoken words (e.g., cathedruke) that overlapped phonologically with familiar words (e.g., cathedral). The sleep group was exposed to the novel words in the evening, followed by an initial test, a polysomnographically monitored night of sleep, and a second test in the morning. The wake group was exposed and initially tested in the morning and spent a retention interval of similar duration awake. Finally, both groups were tested a week later at the same circadian time to control for possible circadian effects. In the sleep group, participants recalled more words and recognized them faster after sleep, whereas in the wake group such changes were not observed until the final test 1 week later. Following acquisition of the novel words, recognition of the familiar words was slowed in both groups, but only after the retention interval, indicating that the novel words had been integrated into the mental lexicon following consolidation. Importantly, spindle activity was associated with overnight lexical integration in the sleep group, but not with gains in recall rate or recognition speed of the novel words themselves. Spindle activity appears to be particularly important for overnight integration of new memories with existing neocortical knowledge.
Lightweight Directory Access Protocol (LDAP) Read Entry Controls (2006)

before and/or after the modifications are applied.These reads are done as an atomic part of the update operation.
Problems of North-South Economic Integration and Politics in Ireland: Southern Perspectives (1997)

North-South economic integration across the border in Ireland is being stimulated by wider transnational processes and European Union integration. But its meanings and extent, as elsewhere in the EU, are defined by state-centred structures and political ideologies. In Ireland, economic integration, and the lack of it, has been shaped by political Partition and the national conflict over Northern Ireland. This article discusses economic integration and politics from a Southern perspective, drawing on interviews with Dublin-based representatives of business organisations, professional associations and semi-state bodies. It mirrors earlier research in Belfast on the motivations and problems of cross-border integration, its institutional forms and future potential. Private firms, associations and other bodies have generally tried to circumvent rather than supersede North-South and national divisions. But the end result of trying to keep ‘economics’ separate from ‘politics’ is a very uneven and stunted form of integration which is sorely lacking in coherence, coordination, and accountability. It is concluded that overcoming these problems requires North-South political institutions and democratic involvement.