gebhart/patrepeval huggingface dataset:
Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis (2000)

The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism are available. While polyclonal antibodies against whole C. parvum reduce infection, their efficacy and predictability are suboptimal. We hypothesized that passive immunization against cryptosporidiosis could be improved by using neutralizing monoclonal antibodies (MAbs) targeting functionally defined antigens on the infective stages. We previously reported that the apical complex and surface-exposed zoite antigens CSL, GP25-200, and P23 are critical in the infection process and are therefore rational targets. In the present study, a panel of 126 MAbs generated against affinity-purified CSL, GP25-200, and P23 was characterized to identify the most efficacious neutralizing MAb formulation targeting each antigen. To identify neutralizing MAbs, sporozoite infectivity following exposure to individual MAbs was assessed by enzyme-linked immunosorbent assay. Of 126 MAbs evaluated, 47 had neutralizing activity. These were then evaluated individually in oocyst-challenged neonatal mice, and 14 MAbs having highly significant efficacy were identified for further testing in formulations. Epitope specificity assays were performed to determine if candidate MAbs recognized the same or different epitopes. Formulations of two or three neutralizing MAbs, each recognizing distinct epitopes, were then evaluated. A formulation of MAbs 3E2 (anti-CSL [alphaCSL]), 3H2 (alphaGP25-200), and 1E10 (alphaP23) provided highly significant additive efficacy over that of either individual MAbs or combinations of two MAbs and reduced intestinal infection by 86 to 93%. These findings indicate that polyvalent neutralizing MAb formulations targeting epitopes on defined antigens may provide optimal passive immunization against cryptosporidiosis.
Characterization of 2′-Fluoro-RNA Aptamers That Bind Preferentially to Disease-associated Conformations of Prion Protein and Inhibit Conversion (2003)

We have isolated artificial ligands or aptamers for infectious prions in order to investigate conformational aspects of prion pathogenesis. The aptamers are 2'-fluoro-modified RNA produced by in vitro selection from a large, randomized library. One of these ligands (aptamer SAF-93) had more than 10-fold higher affinity for PrPSc than for recombinant PrPC and inhibited the accumulation of PrPres in near physiological cell-free conversion assay. To understand the molecular basis of these properties and to distinguish specific from non-specific aptamer-PrP interactions, we studied deletion mutants of bovine PrP in denatured, alpha-helix-rich and beta-sheet-rich forms. We provide evidence that, like scrapie-associated fibrils (SAF), the beta-oligomer of PrP bound to SAF-93 with at least 10-fold higher affinity than did the alpha-form. This differential affinity could be explained by the existence of two binding sites within the PrP molecule. Site 1 lies within residues 23-110 in the unstructured N terminus and is a nonspecific RNA binding site found in all forms of PrP. The region between residue 90 and 110 forms a hinge region that is occluded in the alpha-rich form of PrP but becomes exposed in the denatured form of PrP. Site 2 lies in the region C-terminal of residue 110. This site is beta-sheet conformation-specific and is not recognized by control RNAs. Taken together, these data provide for the first time a specific ligand for a disease conformation-associated site in a region of PrP critical for conformational conversion. This aptamer could provide tools for the further analysis of the processes of PrP misfolding during prion disease and leads for the development of diagnostic and therapeutic approaches to TSEs.
Heat-stable antigen is a costimulatory molecule for CD4 T cell growth. (1992)

Optimal induction of clonal expansion by normal CD4 T cells requires a ligand that can engage the T cell receptor as well as functionally defined costimulatory activity on the same antigen-presenting cell surface. While the presence of effective costimulation induces proliferation, T cell receptor ligation in its absence renders T cells inactive or anergic. The molecular basis of this costimulatory activity remains to be defined. Here we describe a monoclonal antibody that can block the costimulatory activity of splenic accessory cells. Treatment with this antibody not only blocks the proliferation of CD4 T cells to a T cell receptor ligand, but also induces T cell nonresponsiveness to subsequent stimulation. Sequence analysis of the antigen recognized by this antibody indicates that it recognizes a protein that is identical to heat-stable antigen. Gene transfer experiments directly demonstrate that this protein has costimulatory activity. Thus, heat-stable antigen meets the criteria for a costimulator of T cell clonal expansion.
9-Borabicyclo[3.3.1]nonane as a convenient selective hydroborating agent (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT9-Borabicyclo[3.3.1]nonane as a convenient selective hydroborating agentEvord F. Knights and Herbert C. BrownCite this: J. Am. Chem. Soc. 1968, 90, 19, 5281–5283Publication Date (Print):September 1, 1968Publication History Published online1 May 2002Published inissue 1 September 1968https://pubs.acs.org/doi/10.1021/ja01021a047https://doi.org/10.1021/ja01021a047research-articleACS PublicationsRequest reuse permissionsArticle Views1210Altmetric-Citations62LEARN 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
Analysis of the Methanobrevibacter ruminantium draft genome: understanding methanogen biology to inhibit their action in the rumen (2008)

Methane is produced in the foregut (rumen) of ruminants by methanogens, which act as terminal reducers of carbon in the rumen system. The multistep methanogenesis pathway is well elucidated, mainly from the study of non-rumen methanogens, but the adaptations that allow methanogens to grow and persist in the rumen are not well understood. The Pastoral Greenhouse Gas Research Consortium is sequencing the genome of Methanobrevibacter ruminantium, a prominent methanogen in New Zealand ruminants, as part of a project to mitigate greenhouse gases. The genome is ~3.0 Mb in size with a guanine–cytosine (GC) content of 33.68%. All of the components of the methanogenesis pathway have been identified and comparison of these gene sequences with those from Methanothermobacter thermoautotrophicus and Methanosphaera stadtmanae indicates that methanogenesis gene organisation is conserved within the Methanobacteriales. The genome of M. ruminantium contains a prophage sequence (designated φmru) with distinct functional modules encoding phage integration, DNA replication and packaging, capsid proteins and lysis functions. A low GC region found at the distal end of the phage sequence harbours a putative DNA restriction/modification system which might provide additional protection against foreign DNA. The genome also contains many large surface proteins with characteristics that indicate that they may mediate association with other rumen microbes. Approximately half of the genes identified within the genome have no known function. Determining the function of these new genes will assist in defining the role of M. ruminantium in methane formation in the rumen and help identify means to control methane emissions from ruminant animals.
Vascular Endothelial Junction-associated Molecule, a Novel Member of the Immunoglobulin Superfamily, Is Localized to Intercellular Boundaries of Endothelial Cells (2000)

During the process of lymphocyte homing to secondary lymphoid organs, such as lymph nodes and tonsils, lymphocytes interact with and cross a specialized microvasculature, known as high endothelial venules. There is a great deal of information available about the first steps in the homing cascade, but molecular understanding of lymphocyte transmigration through the intercellular junctions of high endothelial venules is lacking. In analyzing expressed sequence tags from a cDNA library prepared from human tonsillar high endothelial cells, we have identified a cDNA encoding a novel member of the immunoglobulin superfamily. The protein, which we have termed VE-JAM ("vascular endothelial junction-associated molecule"), contains two extracellular immunoglobulin-like domains, a transmembrane domain, and a relatively short cytoplasmic tail. VE-JAM is prominently expressed on high endothelial venules but is also present on the endothelia of other vessels. Strikingly, it is highly localized to the intercellular boundaries of high endothelial cells. VE-JAM is most homologous to a recently identified molecule known as Junctional Adhesion Molecule, which is concentrated at the intercellular boundaries of both epithelial and endothelial cells. Because the Junctional Adhesion Molecule has been strongly implicated in the processes of neutrophil and monocyte transendothelial migration, an analogous function of VE-JAM during lymphocyte homing is plausible.
Functional Human Antigen-Specific T Cells Produced In Vitro Using Retroviral T Cell Receptor Transfer into Hematopoietic Progenitors (2007)

In vitro production of human T cells with known Ag specificity is of major clinical interest for immunotherapy against tumors and infections. We have performed TCRalphabeta gene transfer into human hemopoietic progenitors from postnatal thymus or umbilical cord blood, and subsequently cultured these precursors on OP9 stromal cells expressing the Notch human ligand Delta-like1. We report here that fully mature, functional T cells with controlled Ag specificity are obtained from such cultures. Using vectors encoding TCRalphabeta-chains directed against melanoma (MART-1), viral (CMV), and minor histocompatibility (HA-2) Ags, we show that the obtained Ag-specific T cells exert cytolytic activity against their cognate Ag and expand in vitro upon specific TCR stimulation. Therapeutic applications may arise from these results because they provide a way to produce large numbers of autologous mature Ag-specific T cells in vitro from undifferentiated hemopoietic progenitors.
Synthetic studies relevant to biosynthetic research on vitamin B12. Part 10. Construction of the east and west building blocks for synthesis of isobacteriochlorins (1992)

Studies with model compounds have led to the development of effective methods for (a) linking the pyrrolic rings to the reduced rings present in the isobacteriochlorin system (e.g.4) and (b) for introducing the carbon at C-5 required to complete the macrocycle. In the course of this work, many new pyrrolic systems have been prepared and characterised.
Silicate Phosphors for White LEDs Identified through Combinatorial Chemistry (2006)

In order to develop red, green, blue phosphors that emit efficiently under the excitation range, combinatorial chemistry was used based on silicate materials. We attempted to develop white UV light emitting diodes (LEDs) by combining them with an LED chip . Quaternary and ternary combinatorial libraries were developed to synthesize, process, and screen for silicate materials. Our combinatorial chemistry system consists of solution-based combinatorial synthesis and characterization, enabling the swift scanning of luminance. As a consequence of the combinatorial approach, several red, green, and blue candidates were found to show high luminance under the excitation range.
Effects of prior bevacizumab (B) use on outcomes from the VELOUR study: A phase III study of aflibercept (Afl) and FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin regimen. (2012)

3505 Background: Aflibercept (Afl; also known as VEGF Trap) is a recombinant human fusion protein that acts as a decoy receptor and prevents the interaction of vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF) with their receptors. In the phase III VELOUR study, Afl + FOLFIRI improved overall survival (OS) compared with FOLFIRI + placebo (pbo) in mCRC (ECCO 2011, abstract 6LBA). We report outcomes from a pre-specified subgroup analysis by prior B use. Methods: Pts with mCRC and progression during or after oxaliplatin were randomized 1:1 to receive either FOLFIRI + pbo or FOLFIRI + Afl 4 mg/kg IV Q2W with stratification by ECOG performance score (PS, 0 v 1 v 2) and prior B. OS and progression-free survival (PFS) in the prior B-treated pts are reported as median estimate and hazard ratios (HRs); 95.34% CI for OS and 95% CI for PFS. Results: Of the 1226 pts in the overall study, 187 in the pbo and 186 in the Afl group were stratified to prior B. The 2 arms were well balanced: median age 60 yrs; male 58%; PS 0-1 97%; and 55% &gt;1 metastatic organ. Although not powered for survival, Afl produced a consistent trend towards prolonged OS and PFS, regardless of prior B use, with no evidence of interaction (OS, P=0.7231; PFS, P=0.6954). The incidence of treatment-emergent adverse events in the Afl arm was similar in pts with prior B (100%) to those without (98.9%), with a similar incidence of grade 3/4 events (82.5% and 83.9%, respectively). Conclusions: Results of this pre-specified subgroup analysis indicate that adding Afl to FOLFIRI resulted in a consistent trend of increased OS and PFS, regardless of prior B use. Prior treatment with B did not appear to impact the safety profile of Afl. [Table: see text]
Schistosome Invasion of Human Skin and Degradation of Dermal Elastin Are Mediated by a Single Serine Protease (2000)

Aquatic larvae (cercariae) of the trematode parasite Schistosoma mansoni rapidly penetrate human skin by degrading host proteins including elastin. Two serine proteases, one chymotrypsin-like and the second trypsin-like, have been proposed to be involved. To evaluate the relative roles of these two proteases in larval invasion, both were purified, identified by sequence, and then biochemically characterized. The trypsin-like activity was resolved into two distinct serine proteases 76% similar in predicted amino acid sequence. Southern blot analysis, genomic polymerase chain reaction, and immunolocalization demonstrated that the trypsin-like proteases are in fact not from the schistosome, but are released with larvae from the snail host Biomphalaria glabrata. Invasion inhibition assays using selective inhibitors confirmed that the chymotrypsin-like protease is the enzyme involved in skin penetration. Its ability to degrade skin elastin was confirmed, and the three sites of cleavage within elastin help define a new family of elastases.
The Impact of Centering First-Level Predictors on Individual and Contextual Effects in Multilevel Data Analysis (2005)

There is no single best answer to the question of whether to use group-mean centering or grand-mean centering. The theory and specific questions to be answered should be the researcher's guide to selecting which centering approach to use. Understanding the implications of first-level centering is essential to interpreting second-level coefficients correctly.
Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity (2000)

In this study, we use a mouse insertional mutant to delineate gene activities that shape the distal limb skeleton. A recessive mutation that results in brachydactyly was found in a lineage of transgenic mice. Sequences flanking the transgene insertion site were cloned, mapped to chromosome 3, and used to identify the brachydactyly gene as the type IB bone morphogenetic protein receptor, BmprIB (ALK6). Expression analyses in wild-type mice revealed two major classes of BmprIB transcripts. Rather than representing unique coding RNAs generated by alternative splicing of a single pro-mRNA transcribed from one promoter, the distinct isoforms reflect evolution of two BmprIB promoters: one located distally, driving expression in the developing limb skeleton, and one situated proximally, initiating transcription in neural epithelium. The distal promoter is deleted in the insertional mutant, resulting in a regulatory allele (BmprIB(Tg)) lacking cis-sequences necessary for limb BmprIB expression. Mutants fail to generate digit cartilage, indicating that BMPRIB is the physiologic transducer for the formation of digit cartilage from the skeletal blastema. Expansion of BmprIB expression into the limb through acquisition of these distal cis-regulatory sequences appears, therefore, to be an important genetic component driving morphological diversity in distal extremities. GDF5 is a BMP-related signal, which is also required for proper digit formation. Analyses incorporating both Gdf5 and BmprIB(Tg) alleles revealed that BMPRIB regulates chondrogenesis and segmentation through both GDF5-dependent and -independent processes, and that, reciprocally, GDF5 acts through both IB and other type I receptors. Together, these findings provide in vivo support for the concept of combinatorial BMP signaling, in which distinct outcomes result both from a single receptor being triggered by different ligands and from a single ligand binding to different receptors.
Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction (2010)

galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.
Flow cytometric analysis of agonist-induced annexin V, factor Va and factor Xa binding to human platelets (1998)

Activated platelets provide a procoagulant surface for the assembly and expression of prothrombinase complex. Expression of activity is associated with the binding of the protease factor Xa (FXa) and the co-factor Va (FVa) to the procoagulant surface. A flow cytometric methodology to measure annexin V-FITC as well as FVa and FXa binding to ionophore A 23187 activated platelets is described. Annexin V-FITC was used to determine platelet exposure of phosphatidylserine. The binding was calcium-dependent and excess of unlabelled annexin V (10-fold) prevented the binding of the labelled protein. The binding of FVa and FXa to platelets was measured using specific FITC-labelled monoclonal antibodies. The FITC labelled antibodies were displaced by 10-to 20-fold excess of unlabelled antibodies. Binding was strictly Ca2+-dependent. Fixation of platelets by formaldehyde caused artificial binding of annexin V, FVa and FXa as well, irrespective of the platelet activation status. Using gel-filtered platelets, the binding of FVa increased with alpha -granule secretion but the amount of stored FVa was not sufficient to saturate the available platelet binding sites. Exogenous FVa was needed for maximal FVa binding to occur. No binding of FXa from internal platelet stores was observed. Addition of exogenous FVa and FXa resulted in FXa binding to the platelet surface. The methodology might be of use for the study of platelets from patients with bleeding disorders.
A Direct Route to 3‐(D‐Ribofuranosyl)pyridine Nucleosides (1991)

Abstract A route for synthesizing C ‐nucleosides with 2,6‐substituted pyridines as heterocyclic aglycones is described. Condensation of appropriately substituted lithiated pyridines with ribono‐1,4‐lactone derivatives yields hemiacetal 4a – g ( Table 1 ), which can be reduced by Et 3 SiH and BF 3 ·Et 2 O to the corresponding C ‐nucleoside (see Scheme 1 for 4d → β‐ D ‐ 5 ). Conditions are presented that optimize the amount of the 2,6‐dichloropyridine‐derived β‐ D ‐anomer β‐ D ‐ 5 formed ( Table 3 ). Aminolysis of β‐ D ‐ 5 yields the diaminonucleoside 14 ( Scheme 3 ).
Simulations of Slumping Propellant and Flexing Inhibitors in Solid Rocket Motors (2002)

We describe and present results from GEN2, the sec- ond-generation three-dimensional solid rocket motor simulation package developed at CSAR. The internal gas dynamics, propellant combustion, and structural re- sponse are fully coupled. In addition to several test cases, we simulate propellant slumping at a joint slot due to uneven gas pressure loads in the Titan IV SRMU. We also study the motion of a flexible inhibi- tor and its effect on the gas flow near a joint slot in a section of a typical large solid rocket motor.
Effective Elimination of Acute Myeloid Leukemic Cells by Recombinant Bispecific Antibody Derivatives Directed Against CD33 and CD16 (2010)

Single-chain Fv triplebodies (sctb), consisting of a single polypeptide chain with 3 single-chain antibody variable fragments connected in tandem, were generated as antileukemic agents. A CD19-specific sctb of this format has previously been shown to be superior to a bispecific single-chain Fv antibody fragment (bsscFv) for the elimination of leukemic B-lineage cells, but corresponding targeted agents for the treatment of acute myeloid leukemia are still lacking. For this purpose, both a bsscFv and a sctb specific for CD33 and the trigger molecule CD16 (FcgammaRIII) were produced. The sctb displayed 3.5-fold greater avidity for CD33 than the bsscFv 33xds16, whereas both had close to equal affinity for CD16. In antibody-dependent cellular cytotoxicity (ADCC) reactions with human mononuclear cells as effectors, both the bsscFv 33xds16 and the sctb induced lysis of tumor cells with half maximum effective concentrations (EC50) in the low picomolar range. It is interesting to note that the sctb promoted equal lysis of human leukemia-derived cell lines at 10 to 200-fold lower concentrations than the bsscFv. Both molecules mediated ADCC of primary patient cells. In conclusion, both the bsscFv 33xds16 and the sctb 33xds16x33 eliminated acute myeloid leukemia cells in ADCC reactions, but the novel sctb format showed significantly greater specific activity.
CANDIDATE RESISTANCE GENES FROM AN EST DATABASE PROVE A RICH SOURCE OF MARKERS FOR MAJOR GENES CONFERRING RESISTANCE TO IMPORTANT APPLE PESTS AND DISEASES (2003)

ISHS XXVI International Horticultural Congress: Genetics and Breeding of Tree Fruits and Nuts CANDIDATE RESISTANCE GENES FROM AN EST DATABASE PROVE A RICH SOURCE OF MARKERS FOR MAJOR GENES CONFERRING RESISTANCE TO IMPORTANT APPLE PESTS AND DISEASES
Stability-Indicating HPLC Methods for Drug Analysis (1999)

The contents are arranged as an A-Z list of over 500 drug monographs. Each monograph has a consistent structure comprising 28 elements.