gebhart/patrepeval huggingface dataset:
Identification and characterization of highly conserved antigenic determinants in the laminin molecule. (1990)

1. Fragments P1 and E8, the result of two different enzymatic digestions of the laminin molecule, represent interaction sites of laminin with specific cell receptors. By using negative and positive affinity purification of a rabbit antiserum against mouse laminin we have generated antibodies to these two fragments. 2. Antibodies against P1 were able to immunoprecipitate fragment E8 from elastase-digested laminin. By liquid phase competition experiments we demonstrated that the epitopes shared by P1 and E8 are a minor portion of the antigenic determinants of P1. When we checked for the presence of these shared epitopes in the human laminin molecule, they were the major fraction of the interspecies antigenic conservation. 3. A similar approach using polyclonal antibodies against human laminin has confirmed these results. 4. The shared epitopes present in both mouse and human laminin molecules seem to be spatially determined, because antibodies against these sites did not bind to fully denatured laminin. 5. Since human and mouse laminin bind to cell receptors and to other extracellular matrix proteins from both species, we conclude that these antigenic determinants may represent the actual sites for at least some of these interactions.
Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin (2005)

The only endogenous protein inhibitor known for metallocarboxypeptidases (MCPs) is latexin, a 25-kDa protein discovered in the rat brain. Latexin, alias endogenous carboxypeptidase inhibitor, inhibits human CPA4 (hCPA4), whose expression is induced in prostate cancer cells after treatment with histone deacetylase inhibitors. hCPA4 is a member of the A/B subfamily of MCPs and displays the characteristic alpha/beta-hydrolase fold. Human latexin consists of two topologically equivalent subdomains, reminiscent of cystatins, consisting of an alpha-helix enveloped by a curved beta-sheet. These subdomains are packed against each other through the helices and linked by a connecting segment encompassing a third alpha-helix. The enzyme is bound at the interface of these subdomains. The complex occludes a large contact surface but makes rather few contacts, despite a nanomolar inhibition constant. This low specificity explains the flexibility of latexin in inhibiting all vertebrate A/B MCPs tested, even across species barriers. In contrast, modeling studies reveal why the N/E subfamily of MCPs and invertebrate A/B MCPs are not inhibited. Major differences in the loop segments shaping the border of the funnel-like access to the protease active site impede complex formation with latexin. Several sequences ascribable to diverse tissues and organs have been identified in vertebrate genomes as being highly similar to latexin. They are proposed to constitute the latexin family of potential inhibitors. Because they are ubiquitous, latexins could represent for vertebrate A/B MCPs the counterparts of tissue inhibitors of metalloproteases for matrix metalloproteinases.
Power-aware routing in mobile ad hoc networks (1998)

b this paper we present a case for using new power-aware metn.cs for determining routes in wireless ad hoc networks. We present five ~erent metriw based on battery power consumption at nodw. We show that using th=e metrics in a shortest-cost routing algorithm reduces the cost/packet of routing packets by 5-30% over shortwt-hop routing (this cost reduction is on top of a 40-70% reduction in energy consumption obtained by using PAMAS, our MAC layer prtocol). Furthermore, using these new metrics ensures that the mean time to node failure is increased si~cantly. An interesting property of using shortest-cost routing is that packet delays do not increase. Fintiy, we note that our new metrim can be used in most tradition routing protocols for ad hoc networks.
Protection against Respiratory Syncytial Virus Infection by DNA Immunization (1998)

Respiratory syncytial virus (RSV) remains a major cause of morbidity and mortality in infants and the elderly and is a continuing challenge for vaccine development. A murine T helper cell (Th) type 2 response associates with enhanced lung pathology, which has been observed in past infant trials using formalin-inactivated RSV vaccine. In this study, we have engineered an optimized plasmid DNA vector expressing the RSV fusion (F) protein (DNA-F). DNA-F was as effective as live RSV in mice at inducing neutralizing antibody and cytotoxic T lymphocyte responses, protection against infection, and high mRNA expression of lung interferon gamma after viral challenge. Furthermore, a DNA-F boost could switch a preestablished anti-RSV Th2 response towards a Th1 response. Critical elements for the optimization of the plasmid constructs included expression of a secretory form of the F protein and the presence of the rabbit beta-globin intron II sequence upstream of the F-encoding sequence. In addition, anti-F systemic immune response profile could be modulated by the route of DNA-F delivery: intramuscular immunization resulted in balanced responses, whereas intradermal immunization resulted in a Th2 type of response. Thus, DNA-F immunization may provide a novel and promising RSV vaccination strategy.
Metallothionein Gene from Tetrahymena thermophila with a Copper-Inducible-Repressible Promoter (2006)

We describe a novel metallothionein gene from Tetrahymena thermophila that has a strong copper-inducible promoter. This promoter can be turned on and off rapidly, making it a useful system for induction of ectopic gene expression in Tetrahymena and enhancing its applications in cell and molecular biology, as well as biotechnology.
A Quantum Approximate Optimization Algorithm (2014)

We introduce a quantum algorithm that produces approximate solutions for combinatorial optimization problems. The algorithm depends on a positive integer p and the quality of the approximation improves as p is increased. The quantum circuit that implements the algorithm consists of unitary gates whose locality is at most the locality of the objective function whose optimum is sought. The depth of the circuit grows linearly with p times (at worst) the number of constraints. If p is fixed, that is, independent of the input size, the algorithm makes use of efficient classical preprocessing. If p grows with the input size a different strategy is proposed. We study the algorithm as applied to MaxCut on regular graphs and analyze its performance on 2-regular and 3-regular graphs for fixed p. For p = 1, on 3-regular graphs the quantum algorithm always finds a cut that is at least 0.6924 times the size of the optimal cut.
Synthesis and antiviral activity of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (1992)

A number of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and tested in vitro for anti-herpes and anti-human immunodeficiency virus (HIV) activity. Among these analogues, (R)-2'-methyl-PMEG [(R)-3] and 2',2'-dimethyl-PMEG (7) demonstrated potent anti-HIV activity in the XTT assay with EC50 values of 1.0 and 2.6 microM, respectively. The corresponding (S)-2'-methyl-PMEG [(S)-3] was found to be less potent against HIV. In addition, the (R) and (S) enantiomers of 9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine (HPMPG, 8) were prepared for comparison of biological activity, and shown to be active and equipotent against herpesviruses, but inactive against HIV.
A Unique Sequence Motif in the 54-kDa Subunit of the Chloroplast Signal Recognition Particle Mediates Binding to the 43-kDa Subunit (2005)

Chloroplasts contain a novel type of signal recognition particle (cpSRP) that consists of two proteins, cpSRP54 and cpSRP43. cpSRP is involved in the post-translational targeting of the nuclear encoded light-harvesting chlorophyll-binding proteins (LHCPs) to the thylakoid membrane by forming a soluble cpSRP.LHCP transit complex in the stroma. Despite high sequence homology between chloroplast and cytosolic SRP54 proteins, the 54-kDa subunit of cpSRP is unique in its ability to bind cpSRP43. In this report, we identified a 10-amino acid long segment of cpSRP54 that forms the cpSRP43-binding site. This segment is located at position 530-539 close to the C terminus of cpSRP54. In addition, we demonstrate that arginine at position 537 is essential for binding cpSRP43 and that mutation of arginine 536 drastically reduced cpSRP43 binding. Mutations within the cpSRP43-binding site of cpSRP54 that reduced or completely abolished cpSRP complex formation also did inhibit transit complex formation and integration of LHCP into the thylakoid membrane, reflecting the importance of these residues for LHCP targeting. Alignment studies revealed that the cpSRP43-binding site is conserved in chloroplast SRP54 proteins and is not present in any SRP54 subunit of cytosolic SRPs.
Activation of Anopheles gambiae mosquitoes by carbon dioxide and human breath (1995)

Female Anopheles gambiae Giles mosquitoes were observed individually in a cage within a wind tunnel and their responses to pulses of carbon dioxide recorded on video tape. The range of concentrations tested revealed an 'activation' threshold concentration of carbon dioxide in the region of 0.01% above background. At this concentration, approximately 60% of the mosquitoes took off and flew upwind. Pulses of human breath, diluted with wind tunnel air to reproduce equivalent concentrations of carbon dioxide, elicited similar levels of response and the same 'activation' threshold concentration. These findings are discussed in relation to the activation of host-seeking mosquitoes.
Validation of short‐term handling and storage conditions for marrow and peripheral blood stem cell products (2010)

Seventy-two-hour storage of BM, PBSC, and PBMNC products at refrigerated temperature maintains optimal cell viability and recovery. Anticoagulation with ACD-A is preferred over heparin to reduce lactic acid accumulation in the product media.
Inhibitors of Endocannabinoid Degradation: Potential Therapeutics for Neurological Disorders (2003)

Joint benefits: Selective inhibitors of endocannabinoid degradation have been developed, among them the shown carbamate, which exhibit anxiolytic and analgesic properties in laboratory animals.
Inflammasome-regulated Cytokines Are Critical Mediators of Acute Lung Injury (2012)

The inflammasome pathway and its downstream cytokines play critical roles in ARDS development.
Synthesis of (2R,4'R,8'R)-.alpha.-tocopheryl acetate (vitamin E acetate) using [3,3] sigmatropic rearrangement (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of (2R,4'R,8'R)-.alpha.-tocopheryl acetate (vitamin E acetate) using [3,3] sigmatropic rearrangementKa-Kong Chan, Anthony C. Specian Jr., and Gabriel SaucyCite this: J. Org. Chem. 1978, 43, 18, 3435–3440Publication Date (Print):September 1, 1978Publication History Published online1 May 2002Published inissue 1 September 1978https://pubs.acs.org/doi/10.1021/jo00412a001https://doi.org/10.1021/jo00412a001research-articleACS PublicationsRequest reuse permissionsArticle Views606Altmetric-Citations45LEARN 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
Conformationally Constrained Anesthetic Steroids That Modulate GABAA Receptors (2000)

Various cyclic ether and other 3 alpha-hydroxyandrostane derivatives bearing a conformationally constrained hydrogen-bonding moiety were prepared. Their anesthetic potency and their binding affinity for GABA(A) receptors, measured by intravenous administration to mice and inhibition of [(35)S]TBPS binding to rat whole brain membranes, were compared with that of known anesthetic 3 alpha-hydroxypregnan-20-ones. Synthetic steroids with similar in vitro and in vivo activities to the endogenous 3 alpha-hydroxypregnan-20-ones all had an ether oxygen on the beta-face of the steroid D-ring. These results suggest that for optimal GABA(A) receptor modulation, the hydrogen bond-accepting substituent should be near perpendicular to the plane of the D-ring on the beta-face of the steroid.
Targeted Therapy of Advanced Gallbladder Cancer and Cholangiocarcinoma with Aggressive Biology: Eliciting Early Response Signals from Phase 1 trials (2013)

The PFS in phase I trials was similar to that of the first, second, and last-line therapy (P=0.95, 0.98, 0.76, respectively) with FDA-approved agents given in the advanced setting, emphasizing a role for targeted agents in a clinical trials setting as potentially valuable therapeutic options for these patients.
Identification of potential substrate-binding sites in yeast and human acyl-CoA sterol acyltransferases by mutagenesis of conserved sequences (2001)

In mammals, the esterification of sterols by ACAT plays a critical role in eukaryotic lipid homeostasis. Using the predominant isoform of the yeast ACAT-related enzyme family, Are2p, as a model, we targeted phylogenetically conserved sequences for mutagenesis in order to identify functionally important motifs. Deletion, truncation, and missense mutations implicate a regulatory role for the amino-terminal domain of Are2p and identified two carboxyl-terminal motifs as required for catalytic activity. A serine-to-leucine mutation in the (H/Y)SF motif (residues 338-340), unique to sterol esterification enzymes, nullified the activity and stability of yeast Are2p. Similarly, a tyrosine-to-alanine change in the FYxDWWN motif of Are2p (residues 523-529) produced an enzyme with decreased activity and apparent affinity for oleoyl-CoA. Mutagenesis of the tryptophan residues in this motif completely abolished activity. In human ACAT1, mutagenesis of the corresponding motifs (residues 268-270, and 403-409, respectively) also nullified enzymatic activity. On the basis of their critical roles in enzymatic activity and their sequence conservation, we propose that these motifs mediate sterol and acyl-CoA binding by this class of enzymes.
An Erythropoietin Fusion Protein Comprised of Identical Repeating Domains Exhibits Enhanced Biological Properties (1999)

The hematopoietic growth factor erythropoietin (Epo) initiates its intracellular signaling cascade by binding to and inducing the homodimerization of two identical receptor molecules. We have now constructed and expressed in COS cells a cDNA encoding a fusion protein consisting of two complete human Epo domains linked in tandem by a 17-amino acid flexible peptide. On SDS-polyacrylamide gel electrophoresis, the Epo-Epo fusion protein migrated as a broad band with an average apparent molecular mass of 76 kDa, slightly more than twice the average apparent molecular mass of Epo, 37 kDa. Enzymatic N-deglycosylation resulted in an Epo-Epo species that migrated on SDS-polyacrylamide gel electrophoresis as a narrow band with an average apparent molecular mass of 39 kDa. The specific activity of the Epo-Epo fusion protein in vitro (1,007 IU/microgram; 76 IU/pmol) was significantly greater than that of Epo (352 IU/microgram; 13 IU/pmol). Moreover, secretion of Epo-Epo by COS cells was 8-fold greater than that of Epo. Subcutaneous administration of a single dose of Epo-Epo to mice resulted in a significant increase in red blood cell production within 7 days. In contrast, administration of an equivalent dose of conventional recombinant Epo was without effect. The pharmacokinetic behavior of Epo-Epo differed significantly from that of Epo. The results suggest that Epo-Epo may have important biological and therapeutic advantages.
Comparative effects of cholic, chenodeoxycholic, and ursodeoxycholic acids on micellar solubilization and intestinal absorption of cholesterol (1981)

Cholesterol absorption was studied in mice receiving cholic, chenodeoxycholic, or ursodeoxycholic acids (0.2% of the diet) for 2 months. Cholesterol absorption was greater with cholic acid (79%) than with chenodeoxycholic acid feeding (60%) and the lowest levels were observed during ursodeoxycholic acid feeding (37%). Under the three diets, bile acid pool and bile acid secretion were not different. Biliary cholesterol secretion was increased by cholic acid. The bile acid fed represents at least 80% of total bile acids. Micellar solubilization of oleic acid and cholesterol in the presence of each tauro-conjugated bile salt (10 mM) was determined in vitro by the coprecipitation method. Whatever the pH conditions, taurochenodeoxycholate solubilized significantly more cholesterol and more oleic acid than taurocholate. Tauroursodeoxycholate had the poorest detergent properties for both lipids. The differences between the three bile salts for cholesterol solubilization were enlarged by lowering pH and by high oleic acid concentration. Therefore the decrease in cholesterol absorption observed during ursodeoxycholic acid feeding could be explained by the poor detergent properties of this bile salt species. On the other hand, there is no relationship between the detergent properties of taurochenodeoxycholate and taurocholate and their effects on cholesterol absorption in mice. These results suggest that, in this particular case, micellar solubilization is not the rate limiting step in cholesterol absorption.
Comparison of histologic and quantitative techniques in evaluation of therapy for experimental Pneumocystis carinii pneumonia (1987)

Pneumocystis carinii pneumonia was induced in rats by the administration of corticosteroids, and histologic and quantitative techniques were compared in the evaluation of the severity of the disease and response to therapy. A highly significant correlation was found between the histologic score of the extent of alveolar involvement (the standard method of assessment) and the number of P. carinii cysts and nuclei in lung homogenates, lung weight, and lung weight/body weight ratio. Clear differences were noted between rats which responded well and rats which responded poorly to therapy by all techniques. Quantitation of P. carinii cysts and nuclei revealed a 10(4)-fold reduction in organism burden with successful treatment. Thus, these techniques should be helpful in the development of testing of new antimicrobial agents in the rat model of pneumocystosis.
RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis (2016)

Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation and disease progression. Therefore, the development of agents that overcome apoptosis dysregulation in tumor cells is an attractive therapeutic approach. Activation of the extrinsic apoptotic pathway is strongly dependent on death receptor (DR) hyperclustering on the cell surface. However, strategies to activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue an alternative approach for tumor-targeted induction of apoptosis, we engineered a bispecific antibody (BsAb), which simultaneously targets fibroblast-activation protein (FAP) on cancer-associated fibroblasts in tumor stroma and DR5 on tumor cells. We hypothesized that bivalent binding to both FAP and DR5 leads to avidity-driven hyperclustering of DR5 and subsequently strong induction of apoptosis in tumor cells but not in normal cells. Here, we show that RG7386, an optimized FAP-DR5 BsAb, triggers potent tumor cell apoptosis in vitro and in vivo in preclinical tumor models with FAP-positive stroma. RG7386 antitumor efficacy was strictly FAP dependent, was independent of FcR cross-linking, and was superior to conventional DR5 antibodies. In combination with irinotecan or doxorubicin, FAP-DR5 treatment resulted in substantial tumor regression in patient-derived xenograft models. FAP-DR5 also demonstrated single-agent activity against FAP-expressing malignant cells, due to cross-binding of FAP and DR5 across tumor cells. Taken together, these data demonstrate that RG7386, a novel and potent antitumor agent in both mono- and combination therapies, overcomes limitations of previous DR5 antibodies and represents a promising approach to conquer tumor-associated resistance to apoptosis. Mol Cancer Ther; 15(5); 946-57. ©2016 AACR.
Dropout as a Bayesian Approximation: Representing Model Uncertainty in\n Deep Learning (2015)

Deep learning tools have gained tremendous attention in applied machine\nlearning. However such tools for regression and classification do not capture\nmodel uncertainty. In comparison, Bayesian models offer a mathematically\ngrounded framework to reason about model uncertainty, but usually come with a\nprohibitive computational cost. In this paper we develop a new theoretical\nframework casting dropout training in deep neural networks (NNs) as approximate\nBayesian inference in deep Gaussian processes. A direct result of this theory\ngives us tools to model uncertainty with dropout NNs -- extracting information\nfrom existing models that has been thrown away so far. This mitigates the\nproblem of representing uncertainty in deep learning without sacrificing either\ncomputational complexity or test accuracy. We perform an extensive study of the\nproperties of dropout's uncertainty. Various network architectures and\nnon-linearities are assessed on tasks of regression and classification, using\nMNIST as an example. We show a considerable improvement in predictive\nlog-likelihood and RMSE compared to existing state-of-the-art methods, and\nfinish by using dropout's uncertainty in deep reinforcement learning.\n
The HLA dictionary 1999: a summary of HLA‐A, ‐B, ‐C, ‐DRB1/3/4/5, ‐DQB1 alleles and their association with serologically defined HLA‐A, ‐B, ‐C, ‐DR and ‐DQ antigens (1999)

This report presents serologic equivalents of 90 HLA-A, 190 HLA-B and 145 HLA-DRB1 alleles. The equivalents cover over 70% of the presently identified HLA-A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1997 and now also includes equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO HLA Nomenclature Committee, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and by individual laboratories. In addition, a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities and that often lack official WHO nomenclature. The provided equivalents will be useful in guiding searches for unrelated donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. Some guidelines are provided for the use of appropriate WHO HLA nomenclature for serological typings and for generic and allele specific typings obtained with molecular methods. The tables with HLA equivalents and the questionnaire for submission of serology on poorly identified alleles will also be available at the WMDA web page: www:bmdw.org/wmda.