gebhart/patrepeval huggingface dataset:
Are Individual Differences in Sleep and Circadian Timing Amplified by Use of Artificial Light Sources? (2017)

Within the human population, there is large interindividual variability in the timing of sleep and circadian rhythms. This variability has been attributed to individual differences in sleep physiology, circadian physiology, and/or light exposure. Recent experimental evidence suggests that the latter is necessary to evoke large interindividual differences in sleep and circadian timing. We used a validated model of human sleep and circadian physiology to test the hypothesis that intrinsic differences in sleep and circadian timing are amplified by self-selected use of artificial light sources. We tested the model under 2 conditions motivated by an experimental study (Wright et al., 2013): (1) a "natural" light cycle, and (2) a "realistic" light cycle that included attenuation of light due to living indoors when natural light levels are high and use of electric light when natural light levels are low. Within these conditions, we determined the relationship between intrinsic circadian period (within the range of 23.7-24.6 h) and timing of sleep onset, sleep offset, and circadian rhythms. In addition, we simulated a work week, with fixed wake time for 5 days and free sleep times on weekends. Under both conditions, a longer intrinsic period resulted in later sleep and circadian timing. Compared to the natural condition, the realistic condition evoked more than double the variation in sleep timing across the physiological range of intrinsic circadian periods. Model predictions closely matched data from the experimental study. We found that if the intrinsic circadian period was long (>24.2 h) under the realistic condition, there was significant mismatch in sleep timing between weekdays and weekends, which is known as social jetlag. These findings indicate that individual tendencies to have very delayed schedules can be greatly amplified by self-selected modifications to the natural light/dark cycle. This has important implications for therapeutic treatment of advanced or delayed sleep phase disorders.
Identification of differences in the specificity‐determining residues of antibodies that recognize antigens of different size: implications for the rational design of antibody repertoires (2004)

Studies of antibodies of known three-dimensional structure have revealed that insertion and deletion of amino acids at the hypervariable loops change the canonical structures, thus generating differences in the antigen-binding site topography. Such differences determine the size of the antigen with which the antibody interacts. Here, 59 unique antibodies determined at a resolution of 3.0 A or below, including 19 in complex with proteins, 18 with peptides and 22 with haptens, were analyzed to identify and characterize differences in the residues that are directly involved in the interaction with antigen, so-called specificity-determining residues (SDRs). It was found that antibodies use a similar number of SDRs to recognize proteins and peptides but contact haptens with five SDRs less. By using a score of SDR usage, differences in the location of the SDRs, depending on the type of antigen recognized, were then identified with precision. An analysis of the surface generated by the SDRs usage indicates that the differences found correlate well with the size of the antigen. Anti-protein antibodies have the largest SDR surface, with SDRs of high usage located in the edge of the surface. The SDR surface of anti-hapten antibodies is the smallest, with hot spots of contacts in the interior of the binding surface and buried in the V(L):V(H) interface. The SDR surface of anti-peptide antibodies has a size in between anti-protein and anti-hapten antibodies, with the SDRs of high usage located in the interior of the antigen-binding site but do not buried as in anti-hapten antibodies. These findings led to a fine-tuning of the model correlating differences in the antigen-binding site topography with its preference to recognize antigens of different size. Therefore, it is discussed how this knowledge should help to design antibody repertoires biased toward the recognition of antigens of predefined size.
Some Nitrogen Substituted Barbituric Acids and their Derivatives1 (1936)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSome Nitrogen Substituted Barbituric Acids and their Derivatives1Dorothy Nightingale and Claude H. AlexanderCite this: J. Am. Chem. Soc. 1936, 58, 5, 794–796Publication Date (Print):May 1, 1936Publication History Published online1 May 2002Published inissue 1 May 1936https://pubs.acs.org/doi/10.1021/ja01296a033https://doi.org/10.1021/ja01296a033research-articleACS PublicationsRequest reuse permissionsArticle Views144Altmetric-Citations4LEARN 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 Get e-Alerts
Construction and expression in the yeast Pichia pastoris of functionally active soluble forms of the human costimulatory molecules B7‐1 and B7‐2 and the B7 counter‐receptor CTLA‐4 (1997)

We have generated soluble recombinant forms of the costimulatory molecules B7-1 and B7-2, and their counter-receptor CTLA-4 using a yeast Pichia pastoris expression system. Fragments comprising the extracellular domains of human B7-1, B7-2, and CTLA-4 molecules were expressed at high levels and could be purified from culture supernatants following a simple one-step purification protocol. The recombinant proteins retained their functionality and specific binding to their natural counterparts could be demonstrated by FACS analysis. In T cell proliferation assays costimulatory activity of immobilized B7-1 and B7-2 proteins in the presence of an anti-CD3 antibody was observed with the B7-1 protein being more potent than B7-2.
Apolipoprotein B and apolipoprotein A‐I: risk indicators of coronary heart disease and targets for lipid‐modifying therapy (2004)

Although LDL cholesterol (LDL-C) is associated with an increased risk of coronary heart disease, other lipoproteins and their constituents, apolipoproteins, may play an important role in atherosclerosis. Elevated levels of apolipoprotein (apo) B, a constituent of atherogenic lipoproteins, and reduced levels of apo A-I, a component of anti-atherogenic HDL, are associated with increased cardiac events. Apo B, apo A-I and the apo B/apo A-I ratio have been reported as better predictors of cardiovascular events than LDL-C and they even retain their predictive power in patients receiving lipid-modifying therapy. Measurement of these apolipoproteins could improve cardiovascular risk prediction.
Gene transfer using human polyomavirus BK virus-like particles expressed in insect cells (2001)

The major structural protein (VP1) of the BK polyomavirus (BKV) was expressed in the recombinant baculovirus expression system. Recombinant BKV VP1 was shown to self-assemble into virus-like particles (VLPs) with a diameter of 45-50 nm. As for other polyomaviruses, BKV VP1 has the capacity to bind to exogenous DNA. Furthermore, the potential of BKV VP1 VLPs was investigated for gene transfer into COS-7 cells using three methods for the formation of pseudo-virions: disassembly/reassembly, osmotic shock and direct interaction between VLPs and reporter plasmid DNA. The latter method was shown to be the most efficient when using linearized plasmid. Gene transfer efficiency with BKV pseudo-virions was of the same order as that observed with human papillomavirus type 16 L1 protein VLPs. In addition, it is demonstrated that cellular entry of BKV pseudo-virions is dependent on cell surface sialic acid.
Glucoamylase Activity in Industrial Enzyme Preparations Using Colorimetric Enzymatic Method: Collaborative Study (1995)

Fifteen laboratories participated in a collaborative study to validate a colorimetric assay for the determination of glucoamylase in industrial enzyme preparations. All laboratories received 12 samples as blind duplicates provided by 3 industrial producers. Each sample was analyzed once a day for 3 days. Results from one laboratory were excluded from the statistical analysis. Performance of the method was calculated according to the AOAC guidelines. For all 15 laboratories the repeatability relative standard deviation (RSDr) values ranged from 0.89 to 2.37%, and the reproducibility relative standard deviation (RSDR) values ranged from 7.92 to 9.86. After excluding outliers the RSDr values ranged from 0.74 to 2.24%, and RSDR values ranged from 3.46 to 8.92. The colorimetric enzymatic method for determination of glucoamylase activity in industrial enzyme preparations has been adopted first action by AOAC INTERNATIONAL.
A novel anti-inflammatory drug, SDZ ASM 981, for the topical and oral treatment of skin diseases:in vivopharmacology (1997)

There is a need for safe and effective therapies for inflammatory skin diseases. Current topical and systemic treatment of psoriasis is effective but suffers from side-effects or is inconvenient. The therapeutic armamentarium for atopic dermatitis is very limited and far from satisfactory. In vivo preclinical data are presented for SDZ ASM 981, a novel ascomycin macrolactam derivative with high anti-inflammatory activity. Anti-inflammatory activity was observed in mouse, rat and pig models of allergic contact dermatitis. In the pig model, topical SDZ ASM 981 was as effective as the ultrapotent corticosteroid clobetasol-17-propionate, and when compared with a series of commercial topical corticosteroid preparations, 0.1% SDZ ASM 981 had equivalent efficacy to clobetasol-17-propionate (0.05%), the most potent product on the market. Unlike the corticosteroid, however, SDZ ASM 981 did not cause skin atrophy in pigs. SDZ ASM 981 potently inhibited allergic contact dermatitis in mice and rats when given systemically, and oral treatment was more effective than cyclosporin A in rats. Furthermore, SDZ ASM 981 has a low potential for affecting systemic immune responses, as demonstrated in rat models of localized graft vs. host reaction and allogeneic kidney transplantation. Preclinical results suggest that SDZ ASM 981 has the potential to be a well-tolerated and effective drug for topical as well as oral treatment of inflammatory skin diseases.
Regulation of DNA replication in S phase nuclei by ATP and ADP pools (1979)

Synchronized 3T6 (mouse fibroblast) ghost monolayers (isolated nuclei) were utilized to study the effects of ATP and ADP levels on DNA replication in vitro. A system yielding discontinuous semiconservative DNA replication (without any detectable repair) in synchronized S phase nuclei has been developed. Lack of initiation of new sites has been observed in isolated S phase 3T6 nuclei without the presence of cytoplasmic material; DNA synthesis is comprised only of elongation at sites where initiation had previously taken place. DNA synthesis in S phase nuclei proceeded optimally at an ATP concentration of 4-5 mM. High ATP levels as well as high ATP/ADP ratios (produced by an ATP-regenerating system at a variety of ATP concentrations) yielded marked inhibition of [(3)H]dTTP incorporation. The cellular and nuclear pools of ATP and ADP in intact synchronized 3T6 cells were accurately determined by high-pressure liquid chromatography. A good correlation with the studies on isolated nuclei has been observed. Whereas total cellular ATP pools increase during the progression of 3T6 cells from G(1) to S phase of the cell cycle, nuclear ATP pools do not increase, and the nuclear ATP/ADP ratios decrease once the cells enter the S phase of their cycle. These experiments suggest that nuclear ATP pools and ATP/ADP ratios act as S phase controls, regulating DNA elongation at sites where its synthesis has previously been initiated by cytoplasmic factors.
Apolipoprotein E–low density lipoprotein receptor interaction: influences of basic residue and amphipathic α-helix organization in the ligand (2000)

Conserved lysines and arginines within amino acids 140-150 of apolipoprotein (apo) E are crucial for the interaction between apoE and the low density lipoprotein receptor (LDLR). To explore the roles of amphipathic alpha-helix and basic residue organization in the binding process, we performed site-directed mutagenesis on the 22-kDa fragment of apoE (amino acids 1-191). Exchange of lysine and arginine at positions 143, 146, and 147 demonstrated that a positive charge rather than a specific basic residue is required at these positions. Consistent with this finding, substitution of neutral amino acids for the lysines at positions 143 and 146 reduced the binding affinity to about 30% of the wild-type value. This reduction corresponds to a decrease in free energy of binding of approximately 600 cal/mol, consistent with the elimination of a hydrogen-bonded ion pair (salt bridge) between a lysine on apoE and an acidic residue on the LDLR. Binding activity was similarly reduced when K143 and K146 were both mutated to arginine (K143R + K146R), indicating that more than the side-chain positive charge can be important.Exchanging lysines and leucines indicated that the amphipathic alpha-helical structure of amino acids 140-150 is critical for normal binding to the low density lipoprotein receptor.
Consumer Preference for a No‐Choice Option (1997)

Journal Article Consumer Preference for a No-Choice Option Get access Ravi Dhar Ravi Dhar Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Consumer Research, Volume 24, Issue 2, September 1997, Pages 215–231, https://doi.org/10.1086/209506 Published: 01 September 1997 Article history Received: 01 March 1996 Revision received: 01 December 1996 Published: 01 September 1997
Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model (2009)

Growing evidence indicates antibody-dependent cellular cytotoxicity (ADCC) contributes to the clinical response to monoclonal antibody (mAb) therapy of lymphoma. Recent in vitro analysis suggests C3b can inhibit mAb-induced natural killer (NK)-cell activation and ADCC. Further studies were conducted to assess the effect of C3 depletion on mAb-induced NK activation and therapy of lymphoma. Normal human serum inhibited the ability of rituximab-coated lymphoma cells to activate NK cells as previously reported. Serum did not inhibit NK-cell activation when it was preincubated with cobra venom factor (CVF) to deplete C3. Similar results were found when transudative pleural fluid or nonmalignant ascites was used as surrogates for extravascular fluid, suggesting the inhibitory effect of complement may be present in the extravascular compartment, in which many malignant lymphocytes reside. In vivo, C3 was depleted before mAb treatment in a syngeneic murine model of lymphoma. Survival of lymphoma-bearing mice after treatment with CVF plus mAb and with a human C3 derivative with CVF-like functions (HC3-1496) plus mAb was both superior to that of mAb alone. These studies show that complement depletion enhances NK-cell activation induced by rituximab-coated target cells and improves the efficacy of mAb therapy in a murine lymphoma model.
Tetracycline can inhibit tRNA binding to the ribosomal P site as well as to the A site (1986)

A and P sites of Escherichia coli ribosomes were titrated with AcPhe-tRNAPhe, in the absence or presence of tetracycline. The P-site location of the bound AcPhe-tRNA was assessed by means of a quantitative puromycin reaction. The results demonstrate that, in agreement with the generally held view, tetracycline exclusively inhibits the A-site binding, if the statistical number of bound acyl-tRNA molecules per ribosome does not exceed about 0.5. However, above this value the P site becomes sensitive to tetracycline as well. It follows that the tightly coupled 70S ribosomes used in functional studies appear to be functionally heterogeneous, i.e. those P sites which cannot be affected by tetracycline are preferentially occupied by AcPhe-tRNA, whereas higher concentrations of this tRNA species are required to fill tetracycline-sensitive P sites. Furthermore, the results imply that under tRNA saturation conditions the tetracycline inhibition cannot be used as an indicator for the site location of bound tRNA.
Biochemical Characterization and Structural Analysis of a Highly Proficient Cocaine Esterase, (2002)

The bacterial cocaine esterase, cocE, hydrolyzes cocaine faster than any other reported cocaine esterase. Hydrolysis of the cocaine benzoyl ester follows Michaelis-Menten kinetics with k(cat) = 7.8 s(-1) and K(M) = 640 nM. A similar rate is observed for hydrolysis of cocaethylene, a more potent cocaine metabolite that has been observed in patients who concurrently abuse cocaine and alcohol. The high catalytic proficiency, lack of observable product inhibition, and ability to hydrolyze both cocaine and cocaethylene make cocE an attractive candidate for rapid cocaine detoxification in an emergency setting. Recently, we determined the crystal structure of this enzyme, and showed that it is a serine carboxylesterase, with a catalytic triad formed by S117, H287, and D259 within a hydrophobic active site, and an oxyanion hole formed by the backbone amide of Y118 and the Y44 hydroxyl. The only enzyme previously known to use a Tyr side chain to form the oxyanion hole is prolyl oligopeptidase, but the Y44F mutation of cocE has a more deleterious effect on the specificity rate constant (k(cat)/K(M)) than the analogous Y473F mutation of prolyl oligopeptidase. Kinetic studies on a series of cocE mutants both validate the proposed mechanism, and reveal the relative contributions of active site residues toward substrate recognition and catalysis. Inspired by the anionic binding pocket of the cocaine binding antibody GNC92H2, we found that a Q55E mutation within the active site of cocE results in a modest (2-fold) improvement in K(M), but a 14-fold loss of k(cat). The pH rate profile of cocE was fit to the ionization of two groups (pK(a1) = 7.7; pK(a2) = 10.4) that likely represent titration of H287 and Y44, respectively. We also describe the crystal structures of both S117A and Y44F mutants of cocE. Finally, urea denaturation studies of cocE by fluorescence and circular dichroism show two unfolding transitions (0.5-0.6 M and 3.2-3.7 M urea), with the first transition likely representing pertubation of the active site.
Recent Advances in Design and Fabrication of Electrochemical Supercapacitors with High Energy Densities (2013)

In recent years, tremendous research effort has been aimed at increasing the energy density of supercapacitors without sacrificing high power capability so that they reach the levels achieved in batteries and at lowering fabrication costs. For this purpose, two important problems have to be solved: first, it is critical to develop ways to design high performance electrode materials for supercapacitors; second, it is necessary to achieve controllably assembled supercapacitor types (such as symmetric capacitors including double‐layer and pseudo‐capacitors, asymmetric capacitors, and Li‐ion capacitors). The explosive growth of research in this field makes this review timely. Recent progress in the research and development of high performance electrode materials and high‐energy supercapacitors is summarized. Several key issues for improving the energy densities of supercapacitors and some mutual relationships among various effecting parameters are reviewed, and challenges and perspectives in this exciting field are also discussed. This provides fundamental insight into supercapacitors and offers an important guideline for future design of advanced next‐generation supercapacitors for industrial and consumer applications.
Mucosal Immunization with Iron Receptor Antigens Protects against Urinary Tract Infection (2009)

Uncomplicated infections of the urinary tract, caused by uropathogenic Escherichia coli, are among the most common diseases requiring medical intervention. A preventive vaccine to reduce the morbidity and fiscal burden these infections have upon the healthcare system would be beneficial. Here, we describe the results of a large-scale selection process that incorporates bioinformatic, genomic, transcriptomic, and proteomic screens to identify six vaccine candidates from the 5379 predicted proteins encoded by uropathogenic E. coli strain CFT073. The vaccine candidates, ChuA, Hma, Iha, IreA, IroN, and IutA, all belong to a functional class of molecules that is involved in iron acquisition, a process critical for pathogenesis in all microbes. Intranasal immunization of CBA/J mice with these outer membrane iron receptors elicited a systemic and mucosal immune response that included the production of antigen-specific IgM, IgG, and IgA antibodies. The cellular response to vaccination was characterized by the induction and secretion of IFN-gamma and IL-17. Of the six potential vaccine candidates, IreA, Hma, and IutA provided significant protection from experimental infection. In immunized animals, class-switching from IgM to IgG and production of antigen-specific IgA in the urine represent immunological correlates of protection from E. coli bladder colonization. These findings are an important first step toward the development of a subunit vaccine to prevent urinary tract infections and demonstrate how targeting an entire class of molecules that are collectively required for pathogenesis may represent a fundamental strategy to combat infections.
Is an Effective HIV Vaccine Feasible? (2005)

In the 2 decades since researchers identified HIV as the cause of AIDS, more money has been spent on the search for a vaccine against the virus than on any vaccine effort in history. The U.S. National Institutes of Health alone invests nearly $500 million each year, and more than 50 different preparations have entered clinical trials. Yet an effective AIDS vaccine, which potentially could thwart millions of new HIV infections each year, remains a distant dream.
Daily versus As-Needed Corticosteroids for Mild Persistent Asthma (2005)

It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen. Further studies are required to determine whether this novel approach to treatment should be recommended.