gebhart/patrepeval huggingface dataset:
Statins and ezetimibe modulate plasma proprotein convertase subtilisin kexin-9 (PCSK9) levels. (2009)

PCSK9 is a natural inhibitor of the LDL receptor. Gain-of-function mutations may cause the familial hypercholesterolemia phenotype, whereas loss-of-function variants associate with reduced LDL-C levels and lower coronary risk. Statins up-regulate PCSK9 in hepatocytes. We developed an assay to measure total PCSK9 in human plasma and evaluated the effect of statins and ezetimibe on PCSK9 in vivo and in vitro. In 254 normal subjects, the mean plasma PCSK9 was 89 +/- 32 ng/ml. PCSK9 levels correlated with plasma cholesterol, LDL-C, triglycerides, fasting glucose, age and body mass index. Sequencing PCSK9 from subjects at the extremes of plasma distribution revealed new variants. In 200 hypercholesterolemic patients, circulating PCSK9 was higher than in controls, increased with increasing statin dose, and further increased when ezetimibe was added. However, ezetimibe treatment of HepG2 (hepatocytes) and Caco-2 (enterocytes) cells caused a slight increase in PCSK9 and NPC1L1 mRNA, but no significant rise in PCSK9 protein secretion, suggesting that these transformed cells are not ideal model cell lines.
The Calpain System (2003)

The calpain system originally comprised three molecules: two Ca2+-dependent proteases, mu-calpain and m-calpain, and a third polypeptide, calpastatin, whose only known function is to inhibit the two calpains. Both mu- and m-calpain are heterodimers containing an identical 28-kDa subunit and an 80-kDa subunit that shares 55-65% sequence homology between the two proteases. The crystallographic structure of m-calpain reveals six "domains" in the 80-kDa subunit: 1). a 19-amino acid NH2-terminal sequence; 2). and 3). two domains that constitute the active site, IIa and IIb; 4). domain III; 5). an 18-amino acid extended sequence linking domain III to domain IV; and 6). domain IV, which resembles the penta EF-hand family of polypeptides. The single calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent. Since 1989, cDNA cloning has identified 12 additional mRNAs in mammals that encode polypeptides homologous to domains IIa and IIb of the 80-kDa subunit of mu- and m-calpain, and calpain-like mRNAs have been identified in other organisms. The molecules encoded by these mRNAs have not been isolated, so little is known about their properties. How calpain activity is regulated in cells is still unclear, but the calpains ostensibly participate in a variety of cellular processes including remodeling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis. Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage in response to events such as myocardial infarcts, stroke, and brain trauma.
A Hybrid Classical/Quantum Approach for Large-Scale Studies of Quantum Systems with Density Matrix Embedding Theory (2016)

Determining ground state energies of quantum systems by hybrid classical/quantum methods has emerged as a promising candidate application for near-term quantum computational resources. Short of large-scale fault-tolerant quantum computers, small-scale devices can be leveraged with current computational techniques to identify important subspaces of relatively large Hamiltonians. Inspired by the work that described the merging of dynamical mean-field theory (DMFT) with a small-scale quantum computational resource as an impurity solver [Bauer et al., arXiv:1510.03859v2], we describe an alternative embedding scheme, density matrix embedding theory (DMET), that naturally fits with the output from the variational quantum eigensolver and other hybrid approaches. This approach is validated using a quantum abstract machine simulator [Smith et al., arXiv:1608.03355] that reproduces the ground state energy of the Hubbard model converged to the infinite limit.
N-Dialkylaminoalkylbiphenylamines as antimalarial and antischistosomal agents (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-Dialkylaminoalkylbiphenylamines as antimalarial and antischistosomal agentsWarren G. Duncan and David W. HenryCite this: J. Med. Chem. 1969, 12, 1, 25–29Publication Date (Print):January 1, 1969Publication History Published online1 May 2002Published inissue 1 January 1969https://doi.org/10.1021/jm00301a007RIGHTS & PERMISSIONSArticle Views87Altmetric-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 InReddit PDF (635 KB) Get e-Alerts Get e-Alerts
Delay performance of some scheduling strategies in an input queuing ATM switch with multiclass bursty traffic (1996)

Considers an N/spl times/N nonblocking, space division, input queuing ATM cell switch, and a class of Markovian models for cell arrivals on each of its inputs. The traffic at each input comprises geometrically distributed bursts of cells, each burst destined for a particular output. The inputs differ in the burstiness of the offered traffic, with burstiness being characterized in terms of the average burst length. We analyze burst delays where some inputs receive traffic with low burstiness and others receive traffic with higher burstiness. Three policies for head-of-the-line contention resolution are studied: two static priority policies [shorter-expected-burst-length-first (SEBF), longer-expected-burst-length-first (LEBF)] and random selection (RS). Direct queuing analysis is used to obtain approximations for asymptotic high and low priority mean burst delays with the priority policies. Simulation is used for obtaining mean burst delays for finite N and for the random selection policy. As the traffic burstiness increases, the asymptotic analysis can serve as a good approximation only for large switch sizes. Qualitative performance comparisons based on the asymptotic analysis are, however, found to continue to hold for finite switch sizes. It is found that the SEBF policy yields the best delay performance over a wide range of loads, while RS lies in between. SEBF drastically reduces the delay of the less bursty traffic while only slightly increasing the delay of the more bursty traffic. LEBF causes severe degradation in the delay of less bursty traffic, while only marginally improving the delays of the more bursty traffic. RS can be an adequate compromise if there is no prior knowledge of input traffic burstiness.
5′-Terminal sequences of eucaryotic mRNA can be cloned with high efficiency (1981)

A method for cloning mRNAs has been used which results in a high yield of recombinants containing complete 5'-terminal mRNA sequences. It is not dependent on self-priming to generate double-stranded DNA and therefore the S1 nuclease digestion step is not required. Instead, the cDNA is dCMP-tailed at its 3'-end with terminal deoxynucleotidyl transferase (TdT). The synthesis of the second strand is primed by oligo(dG) hybridized to the 3'-tail. Double-stranded cDNA is subsequently tailed with dCTP and annealed to dGMP-tailed vector DNA. This approach overcomes the loss of the 5'-terminal mRNA sequences and the problem of artifacts which may be introduced into cloned cDNA sequences. Chicken lysozyme cDNA was cloned into pBR322 by this procedure with a transformation efficiency of 5 x 10(3) recombinant clones per ng of ds-cDNA. Sequence analysis revealed that at least nine out of nineteen randomly isolated plasmids contained the entire 5'-untranslated mRNA sequence. The data strongly support the conclusion that the 5'-untranslated region of the lysozyme mRNA is heterogeneous in length.
cDNA and protein sequence of polymorphic macaque albumins that differ in bilirubin binding. (1993)

The rhesus monkey, Macaca mulatta, exhibits a geographically restricted polymorphism of serum albumins Mac A and Mac B that is recognized by electrophoresis and is associated with a difference in bilirubin-binding parameters. To identify the basis of the polymorphism, the cDNA and protein sequences of serum albumin from M. mulatta were determined. Screening of a lambda gt11 rhesus liver cDNA library yielded a 1988-bp cDNA sequence that encodes the complete amino acid sequence of mature albumin, the entire propeptide, and part of the prepropeptide. Isoelectric focusing and amino-terminal protein sequencing of CNBr fragments of albumin from A/A and B/B homozygotes were performed, and the structural difference was localized to a CNBr fragment (MCB3) spanning residues 124-264. Sequence analysis of lysyl endopeptidase peptides of MCB3 established that Mac A albumin has a glutamine residue at position 188 while the Mac B albumin has a glutamic residue at the same position. PCR amplification, subcloning, and DNA sequence analysis of clones from A/A and B/B homozygotes confirmed the protein sequence data and the codon difference of CAA versus GAA, respectively. Comparison of macaque and human serum albumin shows a 93.5% identity at the amino acid level. In human serum albumin, Glu188 is located close to the IIA binding pocket for ligands, probably including bilirubin. Derivatives of coumarin compete more efficiently with bilirubin for binding sites on the Mac A albumin than on the Mac B albumin. In regions where coumarin-containing plants are important food resources, Mac B albumin may confer a selective advantage because bilirubin is less readily displaced from it.
Impact of Organizational Control and Reward Systems on Service Quality: An Empirical Study (2013)

This study explores the influence of the organizational control and reward systems on the commitment and service quality of staff. A group of front-line service staffs handling sales tasks served as a sample to test the hypothesized model. Results using a structural equation model indicated that service staffs who operate under a behavior-based control system have higher organizational and professional commitment, and thus produce a higher service quality compared with those who work under an outcome-based control system. Moreover, a higher fixed salary percentage leads to higher professional commitment of service staffs. Organizational and professional commitments positively influence service quality. The implications of the findings are considered and suggestions for future research are provided.
The Effect of Magnesium Supplementation in Increasing Doses on the Control of Type 2 Diabetes (1998)

Mg depletion is common in poorly controlled patients with type 2 diabetes, especially in those with neuropathy or coronary disease. More prolonged use of Mg in doses that are higher than usual is needed to establish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications.
Adenovirus Vectors and Subviral Particles for Protein and Peptide Delivery (2012)

Adenovirus vectors belong to the most frequently used vector type in gene therapy approaches. In addition, adenovirus vector particles and adenovirus subviral particles offer a great potential for the direct delivery of proteins into cells. In this review we discuss this potential and the technology of adenovirus as a protein delivery platform for applications ranging from vaccination to gene therapy.
Zinc binding to the HCCH motif of HIV-1 virion infectivity factor induces a conformational change that mediates protein–protein interactions (2006)

Virion infectivity factor (Vif) is an accessory protein encoded by HIV-1 and is critical for viral infection of the host CD4(+) T cell population. Vif induces ubiquitination and subsequent degradation of Apo3G, a cytosolic cytidine deaminase that otherwise targets the retroviral genome. Interaction of Vif with the cellular Cullin5-based E3 ubiquitin ligase requires a conserved BC box and upstream residues that are part of the conserved H-(Xaa)(5)-C-(Xaa)(17-18)-C-(Xaa)(3-5)-H (HCCH) motif. The HCCH motif is involved in stabilizing the Vif-Cullin 5 interaction, but the exact role of the conserved His and Cys residues remains elusive. In this report, we find that full-length HIV-1 Vif, as well as a HCCH peptide, is capable of binding to zinc with high specificity. Zinc binding induces a conformational change that leads to the formation of large protein aggregates. EDTA reversed aggregation and regenerated the apoprotein conformation. Cysteine modification studies with the HCCH peptide suggest that C114 is critical for stabilizing the fold of the apopeptide, and that C133 is located in a solvent-exposed region with no definite secondary structure. Selective alkylation of C133 reduced metal-binding specificity of the HCCH peptide, allowing cobalt to bind with rates comparable to that with zinc. This study demonstrates that the HCCH motif of HIV-1 Vif is a unique metal-binding domain capable of mediating protein-protein interactions in the presence of zinc and adds to a growing list of examples in which metal ion binding induces protein misfolding and/or aggregation.
New members of the chemokine receptor gene family (1996)

Chemokines are relatively small peptides with potent chemoattractant and activation activities for leukocytes. Several chemokine receptors have been cloned and characterized and all are members of the G protein-coupled receptor superfamily. Using degenerate oligonucleotides and polymerase chain reaction, we have identified seven novel receptors. Two of these sequences are presented here for the first time. We have shown, with gene mapping studies, that receptors with the highest sequence similarity are closely linked on human chromosomes. This close genetic association suggests a functional relationship as well.
Surgical treatment of atrial fibrillation; a systematic review☆ (2004)

We could not identify any significant difference in the postoperative SR conversion rates between the classical 'cut and sew' and the alternative sources of energy, which were used to treat atrial fibrillation.
Photochemical Release of Amines by C,N-Bond Cleavage (2003)

A method for the photorelease of primary and secondary amines using coumarin as chromophore was developed. This mild C,N-bond cleavage reactions liberates the amine not only in solution but also on solid support
Influence of culture conditions on the N‐glycosylation of a monoclonal antibody specific for recombinant hepatitis B surface antigen (2004)

MAbs (monoclonal antibodies) are becoming increasingly important as diagnostic tools for pharmaceutical biotechnology, and hence it is crucial that they are produced under controlled conditions to assure their consistency and reproducibility, not only in terms of protein sequence and bioactivity, but also in terms of post‐translational modifications, e.g. for N‐glycosylation. Hybridoma CB.Hep‐1, which secretes an IgG2b mAb, was cultured in vivo in ascites and in vitro in static‐flask, spinner‐flask, dialysis‐membrane and perfusion systems using protein‐free, low‐serum‐containing medium (1% foetal‐calf serum) and high‐serum‐containing medium (8% foetal‐calf serum). These CB.Hep‐1 mAbs were fully characterized, and insignificant differences in the affinity constant were observed. Glycosylation profiling was performed by labelling the N‐glycans released by peptide N ‐glycosidase F with either of the fluorophore tags 8‐aminonaphthalene‐1,3,6‐trisulphonic acid and 4‐aminobenzoic acid. The mAb produced in vivo showed two major biantennary‐complex‐type N‐glycans: monogalactosylated, core‐fucosylated and agalactosylated, core‐fucosylated. The mAbs produced in vitro in static flasks and spinner flasks were not significantly influenced by the serum content in the culture media and showed a higher degree of N‐glycan galactosylation compared with those produced in mouse‐ascites, hollow‐fibre and membrane systems. The monogalactosylated, core‐fucosylated structure was the most abundant N‐glycan except for those produced in ascites and hollow fibres, where the agalactosylated, core‐fucosylated glycoform was the major specie. MAbs produced in high‐cellular‐yield systems displayed greater galactosylation heterogeneity influenced by changes in culture media.
Synthesis and Structure of Steroidal 4-Pregneno [3,2-c]Pyrazoles. A Novel Class of Potent Anti-Inflammatory Steroids (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and Structure of Steroidal 4-Pregneno [3,2-c]Pyrazoles. A Novel Class of Potent Anti-Inflammatory SteroidsRalph. Hirschmann, N. G. Steinberg, Paul. Buchschacher, J. H. Fried, G. J. Kent, Max. Tishler, and S. L. SteelmanCite this: J. Am. Chem. Soc. 1963, 85, 1, 120–122Publication Date (Print):January 1, 1963Publication History Published online1 May 2002Published inissue 1 January 1963https://pubs.acs.org/doi/10.1021/ja00884a034https://doi.org/10.1021/ja00884a034research-articleACS PublicationsRequest reuse permissionsArticle Views189Altmetric-Citations48LEARN 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
Two Classes of Plant cDNA Clones Differentially Complement Yeast Calcineurin Mutants and Increase Salt Tolerance of Wild-type Yeast (1996)

The salt-sensitive phenotype of yeast cells deficient in the phosphoprotein phosphatase, calcineurin, was used to identify genes from the higher plant Arabidopsis thaliana that complement this phenotype. cDNA clones corresponding to two different sequences, designated STO (salt tolerance) and STZ (salt tolerance zinc finger), were found to increased tolerance of calcineurin mutants and of wild-type yeast to both Li+ and Na+ ions. STZ is related to Cys2/His2-type zinc-finger proteins found in higher plants, and STO is similar to the Arabidopsis CONSTANS protein in regions that may also be zinc fingers. Although neither protein has sequence similarity to any protein phosphatase, STO was able to at least partially compensate for all tested additional phenotypic effects of calcineurin deficiency, and STZ compensated for a subset of these effects. Salt tolerance produced by STZ appeared to be partially dependent on ENA1/PMR2, a P-type ATPase required for Li+ and Na+ efflux in yeast, whereas the effect of STO on salt tolerance was independent of ENA1/PMR2. STZ and STO were found to be expressed in Arabidopsis roots and leaves, whereas only STO message was detectable in flowers. An apparent increase in the level of STZ mRNA was observed in response NaCl exposure in Arabidopsis seedlings, but the level of STO mRNA was not altered by this treatment.
Phase transition of Potts model on a frustrated 3D lattice (2000)

We report here on Monte Carlo simulations of the q-state Potts model on a fully frustrated cubic geometry. Most investigations so far were restricted to the case of Ising, XY, or Heisenberg spins. Nothing is known about the fully frustrated Potts model and on the disorder effects in such systems. The effects of frustration and weak disorder on the q=3 and q=4 fully frustrated Potts system are studied in the present work.
Nanoparticles for Thermal Cancer Therapy (2009)

Advances in nanotechnology are enabling many new diagnostic and therapeutic approaches in cancer. In this review, examples where nanoparticles are employed to induce localized heating within tumors are explored. Approaches to nanoparticle-mediated thermal therapy include absorption of infrared light, radio frequency ablation, and magnetically-induced heating. These approaches have demonstrated high efficacy in animal models, and two are already in human clinical trials.
Alteration of channel activities and gating by mutations of slow ISK potassium channel. (1991)

ISK is a small membrane protein consisting of 129-130 amino acid residues with a single putative transmembrane domain and induces a very slow voltage-dependent K+ channel activity in the Xenopus oocyte expression system. We investigated the nature and structure-function relation of ISK by examining the effects of various mutations of ISK on the K+ channel activities measured in Xenopus oocytes. Deletion and truncation of the ISK protein indicated that the 63-amino acid sequence covering a transmembrane domain is sufficient for eliciting a K+ channel activity characteristic of ISK. Amino acid substitutions at a total of 31 positions within and surrounding the transmembrane domain caused different effects on the channel activity. A channel activity was enhanced by substitution of leucine with isoleucine at position 52 within the transmembrane domain, and the kinetic analysis of this mutation indicated that the enhancement of the channel activity is due to an alteration of a gating property of the ISK protein and thus supported the view that ISK forms an integral part of the K+ channel itself. The substitutions at many positions of the membrane-following region produced drastic reduction of the channel activity, and this is in marked contrast to the lack of effects of amino acid substitutions at the membrane-preceding region. Thus, the cytoplasmic portion immediately following the transmembrane domain plays a crucial role in inducing the channel activity of ISK.
The Host Response to Sepsis and Developmental Impact (2010)

Invasion of the human by a pathogen necessitates an immune response to control and eradicate the microorganism. When this response is inadequately regulated, systemic manifestations can result in physiologic changes described as "sepsis." Recognition, diagnosis, and management of sepsis remain among the greatest challenges shared by the fields of neonatology and pediatric critical care medicine. Sepsis remains among the leading causes of death in both developed and underdeveloped countries and has an incidence that is predicted to increase each year. Despite these sobering statistics, promising therapies derived from preclinical models have universally failed to obviate the substantial mortality and morbidity associated with sepsis. Thus, there remains a need for well-designed epidemiologic and mechanistic studies of neonatal and pediatric sepsis to improve our understanding of the causes (both early and late) of deaths attributed to the syndrome. In reviewing the definitions and epidemiology, developmental influences, and regulation of the host response to sepsis, it is anticipated that an improved understanding of this host response will assist clinician-investigators in identifying improved therapeutic strategies.