gebhart/patrepeval huggingface dataset:
In vitro and in vivo antitumor effect of a trivalent bispecific antibody targeting ErbB2 and CD16 (2008)

In order to optimize the structure of bispecific antibody (BsAb) and minimize its toxicity, we developed a trivalent anti-ErbB2/anti-CD16 BsAb. This BsAb possesses three antigen binding sites, two antigen binding sites in the form of scFvs targeting the tumor cells overexpressing ErbB2 and a monovalent Fab fragment redirecting NK cells. Critical for this BsAb is its capacity to trigger cytotoxicity of the effector cells in vitro and in vivo. In the present study, we demonstrated that the BsAb is capable of binding to ErbB2 extracellular domain on SKBR3 cells and effectively direct the cytotoxic activities of effector cells to SKBR3 cells even at a low concentration. The BsAb was more effective to SKBR3 cells than to MCF-7 cells, indicating that the killing of tumor cells was dependent on the density of ErbB2 molecules on cell surface. Furthermore, the BsAb was more potent than anti-ErbB2 single chain antibody (scFv)-Fc fusion proteins in the cytotoxicity assay and in SKOV3 xenograft animals. Improved efficacy demonstrates that the BsAb may be valuable to be further modified and optimized for the treatment of malignant cells in a minimal residual disease.
Thrombin Preconditioning Attenuates Brain Edema Induced by Erythrocytes and Iron (2003)

Pretreatment with a low intracerebral dose of thrombin reduces brain edema after hemorrhagic and thrombo-embolic stroke. We have termed this phenomena thrombin preconditioning (TPC) or thrombin-induced brain tolerance. Red blood cell lysis and iron overload contribute to delayed edema formation after intracerebral hemorrhage. The present study examined whether TPC can attenuate the brain edema induced by lysed red blood cells or iron. It also examined whether TPC is associated with increasing hypoxia inducible factor-1alpha (HIF-1alpha) levels and alterations in two HIF-1alpha target genes, transferrin (Tf) and transferrin receptor (TfR), within the brain. Brain edema was measured by wet/dry weight method. HIF-1alpha, Tf, and TfR were measured by Western blot analysis and immunohistochemistry. We found that TPC reduces the edema induced by infusion of lysed red blood cells and iron. Thrombin increases HIF-1alpha levels through p44/42 mitogen activated protein kinases pathway. Thrombin also increases Tf and TfR levels in the brain. These results indicate that HIF-1alpha and its target genes may be involved in thrombin-induced brain tolerance.
Unification of the ferritin family of proteins. (1992)

Ferritin is the iron-storage protein of eukaryotic organisms. The nucleotide sequence encoding Azotobacter vinelandii bacterioferritin, a hemoprotein, was determined. The deduced amino acid sequence reveals a high degree of identity with Escherichia coli bacterioferritin and a striking similarity to eukaryotic ferritins. Moreover, derivation of a global alignment shows that virtually all key residues specifying the unique structural motifs of eukaryotic ferritin are conserved or conservatively substituted in the A. vinelandii sequence. The alignment suggests specific methionine residues as heme-binding ligands in bacterioferritins. The overall sequence similarity with conservation of key structural residues implies that all ferritins form a unified family of proteins. The results implicate ferritins as proteins potentially common to all aerobic organisms and as such useful in taxonomic classification, evolutionary analysis, and environmental monitoring.
A system for monitoring temperature distribution in bed and its application to the assessment of body movement (1993)

For the assessment of body movements during sleep, a system for monitoring the temperature in bed was developed. The system consists of 16 temperature sensors and a data logger with a memory card. Fifteen of the temperature sensors were arranged in line 6 cm apart on a flat cable. The temperatures at these 15 points in the bed, and the room temperature measured by the additional sensor, were stored on the memory card at predetermined intervals. The data were transferred into a microcomputer and analysed. Changes in posture and body movement were recognizable from the changes in the temperature profile, and well visualized using a three-dimensional display of the successive temperature profiles in the bed. The time of body movement was estimated from the derivative of the temperature profile. Comparison between this estimation and the video recording showed good agreement. The linear arrangement of the sensors provides a high-resolution temperature profile during sleep.
Clustering of the trp genes in Burkholderia (formerly Pseudomonas) cepacia (1995)

Chromosomal location of trp genes of a strain Burkholderia cepacia (formerly Pseudomonas cepacia) has been determined by transduction using a generalized transducing phage CP75 and by molecular analysis for a cosmid plasmid clone with trp genes isolated from a genomic gene library of the strain. The trp genes were classified into three linkage groups and they all were closely linked on a short chromosomal region probably in the order (trpA, trpB, trpF)-(trpC, trpD)-trpE.
Purification and Sequence Analysis of the mRNA Coding for an Immunoglobulin Heavy Chain (1976)

A mutant cell line (IF2) derived from the mouse myeloma MOPC 21 has been used for the isolation and sequence analysis of H-chain mRNA. The IF2 cells synthesise an H-chain of reduced size in which the CH1 homology region is missing. Sizing of the IF2 H-chain mRNA and wild-type H-chain mRNA revealed that the deletion is expressed at the mRNA level. The mutant H-chain mRNA sedimented at 16-S, enabling effective resolution from 18-S ribosomal RNA. In experiments using IF2 cells labelled with [32P]phosphate, the 16-S mRNA was purified by oligo(T)-cellulose chromatography. Polyacrylamide gel analysis of the poly(A)-containing fraction showed the presence of a single radioactive band. Comparison of the mobility of this band relative to markers of known molecular weight revealed that the molecule contained about 1600 nucleotides. Digestion of the 32-P-labelled mRNA with T1 ribonuclease and two-dimensional fractionation of the resulting oligonucleotides yielded a 'finger-print' suitable for a preliminary sequence analysis. By using the established amino acid sequence of the IF2 H-chain and a knowledge of the genetic code, 14 oligonucleotides were assigned within the constant region and four within the variable region of the IF2 H-chain. This sequence data accounts for 19.5% of the coding region. Several other oligonucleotides, which could not be assigned within the coding region but which occurred in approximately molar yield, have also been partially characterised. These oligonucleotides are presumably derived from the untranslated regions of mRNA.
Diversity in unity: The biochemical composition of the endothelial cell surface varies between the vascular beds (2002)

The vascular endothelium represents a population of squamous epithelial cells characterized by a particular histological localization (intima of blood vessels) and by several physiological functions such as the transport of substances between blood and tissues, the modulation of the vascular tone, the control of blood coagulation and that of the leukocyte extravasation. In spite of all these elements in common and of an identical embryonic origin, endothelial cells show definite morphological and physiological variations that divide them into types and subtypes, each specifically associated to various categories of organs. Even within the vasculature of the same organ, there are clear segmental (arterial/capillary/venous) differentiations of the endothelial cells. While the morphological and physiological differences between endothelial cells are well documented, there are very few data on the biochemistry underlying this heterogeneity. This work presents several data suggesting that, at present, the domain is ripe for a comprehensive analysis of this biochemical diversity, at least in what concerns the luminal aspect of the endothelial plasmalemma, a compartment of crucial importance in the biology and pathology of the cardiovascular system.
World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Eating Disorders (2011)

Additional research is needed for the improvement of the treatment of eating disorders. Especially for anorexia nervosa there is a need for further pharmacological treatment strategies.
Both a precursor and a mature population of dendritic cells can bind HIV. However, only the mature population that expresses CD80 can pass infection to unstimulated CD4+ T cells (1995)

Dendritic cells (DC) are the principle APC involved in primary immune responses; their major function is to obtain Ag in tissues, migrate to lymphoid organs, and activate T cells. DC are also the first immune cells to arrive at sites of inflammation on mucous membranes, the major site of sexual transmission of HIV. We have demonstrated previously that three populations of cells that can develop a dendritic morphology are present in peripheral blood. Two of these populations can express CD83, a marker of DC, and appear to be at different stages of maturation: 1) a precursor population and 2) a mature immunostimulatory DC. Precursor-derived DC express high levels of CD86 (B7-2) and HLA-DR but no CD80 (B7-1), whereas mature DC have high levels of expression of all three markers. Mature DC in peripheral blood bind HIV to their surface and induce infection when added to autologous CD4+ T cells in the absence of added stimuli, such as mitogens. These mature DC, when isolated directly from peripheral blood, appear to be conjugated to T cells, and these conjugates are infected easily and productively with HIV. These findings suggest a role for DC in early HIV infection in which they bind virus and interact with T cells locally or after migrating to a lymphoid organ, thus establishing a productive infection. Furthermore, they likely play a role in the propagation of HIV infection by activating T cells in the presence of HIV, which leads to viral replication and immune cell destruction.
Carbon nanotube-based synthetic gecko tapes (2007)

We have developed a synthetic gecko tape by transferring micropatterned carbon nanotube arrays onto flexible polymer tape based on the hierarchical structure found on the foot of a gecko lizard. The gecko tape can support a shear stress (36 N/cm(2)) nearly four times higher than the gecko foot and sticks to a variety of surfaces, including Teflon. Both the micrometer-size setae (replicated by nanotube bundles) and nanometer-size spatulas (individual nanotubes) are necessary to achieve macroscopic shear adhesion and to translate the weak van der Waals interactions into high shear forces. We have demonstrated for the first time a macroscopic flexible patch that can be used repeatedly with peeling and adhesive properties better than the natural gecko foot. The carbon nanotube-based tape offers an excellent synthetic option as a dry conductive reversible adhesive in microelectronics, robotics, and space applications.
ChemInform Abstract: (S)‐2‐Chloropropanoyl Chloride. A Convenient Reagent for the Determination of the Enantiomeric Composition of α‐Substituted . alpha.‐Hydroxy Acids. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The Natural Tumor Suppressor Protein Maspin and Potential Application in Non Small Cell Lung Cancer (2010)

The grim prognosis of lung cancer, that has an overall 10-15% survival at 5 years, remains in the US the leading cause of cancer mortality, provides a compelling rationale for studying the molecular basis of this malignancy. Surmising the common, general association with smoking, lung cancers differ at the microscopic, anatomical, epidemiological and clinical level and harbor complex genetic and epigenetic alterations. Currently, lung cancer is divided into small cell lung carcinoma (SCLC) and non small cell lung carcinoma (NSCLC) for the purpose of clinical management. (NSCLC) constitutes 80-85% of lung cancers and is further divided into histological subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, etc. The ultimate goal for lung cancer research is to develop a strategy to block the tumor progression and improve the prognosis of lung cancer. This goal can realistically be achieved only when the biological complexity of this disease is taken into account. To this end, identification and understanding of molecular markers that are mechanistically involved in tumor progression is needed. Our recent studies suggest histological subtype-dependent distinct correlations between the expression and/or subcellular localization of tumor suppressive maspin with the progression and prognosis of NSCLC. Maspin is an epithelial specific member of the serine protease inhibitor (serpin) superfamily but recently identified as an endogenous inhibitor of histone deacetylase 1 (HDAC1). This novel biochemical activity coincides with a consensus emerged recently from the evidence that nuclear maspin confers better differentiated epithelial phenotypes, decreased tumor angiogenesis, increased tumor sensitivity to drug-induced apoptosis, and a more favorable prognosis. In the current review, we discuss the evidence that maspin may be a marker that stratifies the progression and prognosis of different subtypes of NSCLC.
Platelet-derived growth factor. Isolation by a large-scale procedure and analysis of subunit composition (1981)

Platelet-derived growth factor was purified from fresh platelets by a large-scale procedure not involving the use of SDS (sodium dodecyl sulphate). The product, 0.5 mg of platelet-derived growth factor, obtained from about 3 x 10(13) platelets migrated as a single component in analytical gel electrophoresis in the presence of SDS and showed no inhomogeneity on sedimentation-equilibrium analysis in the ultracentrifuge. It had a high specific activity, 2 ng of platelet-derived growth factor/ml (70pM) being equivalent to 1% (v/v) human serum in an assay for multiplication-stimulating activity. Amino acid analysis revealed that platelet-derived growth factor contains all the common amino acids, except tryptophan, but no hexosamine. The molecular weight of platelet-derived growth factor, as determined by sedimentation-equilibrium analysis, was about 33 000. A similar value was obtained by gel electrophoresis in SDS under non-reducing conditions. In the presence of reducing agents the factor molecule was converted into two distinct components of lower molecular weight (17 000 and 14 000 respectively), as demonstrated by protein staining. The molecular model implicated by these findings is that platelet-derived growth factor consists of two different polypeptides chains, linked by disulphide bridges.
HEAVY-HYDROGEN DRUGS TURN HEADS, AGAIN (2009)

RETURN TO ISSUEPREVNewsNEXTHEAVY-HYDROGEN DRUGS TURN HEADS, AGAINFirms seek to improve drug candidates by selective DEUTERIUM SUBSTITUTIONAMANDA YARNELLView Author Information C&EN BOSTONCite this: Chem. Eng. News 2009, 87, 25, 36–39Publication Date (Print):June 22, 2009Publication History Published online14 November 2010Published inissue 22 June 2009https://pubs.acs.org/doi/10.1021/cen-v087n025.p036https://doi.org/10.1021/cen-v087n025.p036newsACS PublicationsCopyright © 2009 AMERICAN CHEMICAL SOCIETYArticle Views124Altmetric-Citations38LEARN 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 options SUBJECTS:Hydrogen,Hydrogen isotopes,Pharmaceuticals Get e-Alerts
A Selective and Brain Penetrant p38αMAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction (2019)

The p38αMAPK is a serine/threonine protein kinase and a key node in the intracellular signaling networks that transduce and amplify stress signals into physiological changes. A preponderance of preclinical data and clinical observations established p38αMAPK as a brain drug discovery target involved in neuroinflammatory responses and synaptic dysfunction in multiple degenerative and neuropsychiatric brain disorders. We summarize the discovery of highly selective, brain-penetrant, small molecule p38αMAPK inhibitors that are efficacious in diverse animal models of neurologic disorders. A crystallography and pharmacoinformatic approach to fragment expansion enabled the discovery of an efficacious hit. The addition of secondary pharmacology screens to refinement delivered lead compounds with improved selectivity, appropriate pharmacodynamics, and efficacy. Safety considerations and additional secondary pharmacology screens drove optimization that delivered the drug candidate MW01-18-150SRM (MW150), currently in early stage clinical trials.
Hydrogenation of Fats and Oils: Theory and Practice (1994)

Discusses vegetable and other oils, and considers the hydrogenation technique in detail. Topics covered include the hydrogenation reaction; hydrogenation process techniques; the hydrogenation plant; hydrogen; catalysts; hydrogenation methods; safety; and quality and control. Gives direct practical advice as well as explanations why changes occur as they do. Written for production staff who need advice on specific problems and to provide directions for development personnel
Purification and properties of the α‐acetolactate decarboxylase from Lactococcus lactis subsp. lactis NCDO 2118 (1994)

alpha-Acetolactate decarboxylase from Lactococcus lactis subsp. lactis NCDO 2118 was expressed at low levels in cell extracts and was also unstable. The purification was carried out from E. coli in which the enzyme was expressed 36-fold higher. The specific activity was 24-fold enhanced after purification. The main characteristics of alpha-acetolactate decarboxylase were: (i) activation by the three branched chain amino acids leucine, valine and isoleucine; (ii) allosteric properties displayed in absence and Michaelis kinetics in the presence of leucine. The enzyme is composed of six identical subunits of 26,500 Da.
Abstract B045: Antigen-free cancer vaccine to treat poorly immunogenic tumors (2019)

Abstract Certain chemotherapeutic drugs can elicit immunogenic death of tumor cells and enhance antitumor immune responses. Here we explore whether immunogenic chemotherapy can be utilized for the development of antigen-free cancer vaccines, by combining it with peritumorally injected biomaterial scaffolds that recruit dendritic cells (DCs) for subsequent antigen presentation and T-cell priming. Pore-forming alginate gels containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and a doxorubicin-iRGD conjugate were found to efficiently induce the apoptosis of 4T1 triple-negative breast cancer cells in vivo, while recruiting large numbers of DCs. The co-encapsulation of CpG oligodeoxynucleotides in the gel significantly enhanced the immunogenic death of 4T1 cells, increased systemic tumor-specific CD8+ T-cells and tumoral infiltration of CD8+ T-cells, repolarized tumor-associated macrophages towards an inflammatory M1-like phenotype, and resulted in significantly improved antitumor efficacy. This in situ antigen-free gel vaccine shows promise for the treatment of poorly immunogenic tumors, and more broadly, may serve as a facile platform to enable in situ personalized cancer vaccination without requiring identification of tumor-specific antigens and manufacturing of personalized vaccines. Citation Format: Miguel C. Sobral, Hua Wang, Alexander J. Najibi, Aileen Li, Catia S. Verbeke, David J. Mooney. Antigen-free cancer vaccine to treat poorly immunogenic tumors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B045.
'Pandemic Vaccine' Appears to Protect Only at High Doses (2005)

This week, a U.S. health official trumpeted apparently good news: An ongoing trial suggests that a vaccine can protect humans from H5N1, the bird flu strain many worry may evolve into a pandemic. But some flu experts found the glass half-empty. The vaccine seems to works only at doses so high that the world's flu vaccine factories could not churn out enough to combat a pandemic, they say. Based on the preliminary data, the current U.S. stockpile of the vaccine, produced by Sanofi Pasteur, is enough for only 450,000 people—not the more than 2 million the administration hoped it would protect.
Quantitative analysis of serum neutralization of human immunodeficiency virus type 1 from subtypes A, B, C, D, E, F, and I: lack of direct correlation between neutralization serotypes and genetic subtypes and evidence for prevalent serum-dependent infectivity enhancement (1996)

Human immunodeficiency virus type 1 (HIV-1) M group strains have been assigned to date to nine distinct genetic subtypes, designated A through I, according to phylogenetic analyses of nucleotide sequences of their env or gag genes. Whether there is any relationship between phylogenetic subtypes and the neutralization serotypes is not clear, yet defining the nature of any such relationship by mathematical means would be of major importance for the development of globally effective HIV-1 vaccines. We have therefore developed a quantitative method to analyze serum neutralization of HIV-1 isolates and to identify HIV-1 neutralization serotypes. This method involves calculations of the neutralization index, N(i), a newly defined parameter derived from plots generated from in vitro neutralization assays, calculations of pairwise serum-virus vector distances, and cluster analyses. We have applied this approach to analyze three independent neutralization matrices involving primary HIV-1 strains and sera from genetic subtypes A, B, C, D, E, F, and I. Detailed serum and HIV-1 isolate cluster analyses have shown that in general, the identified neutralization serotypes do not directly correlate with HIV-1 genetic subtypes. These results suggest that neutralization serotypes do not during natural HIV-1 infection are not governed by antibodies directed against simple epitopes within gp120 monomers. A significant proportion (28%) of 1,213 combinations of sera and HIV-1 isolates caused serum-dependent infectivity enhancement [negative N(i) values] rather than neutralization. We also noted that negative N(i) values tended to correlate better with certain HIV-1 isolates rather than with HIV-1-positive sera. Syncytium-inducing variants of HIV-1 were slightly more likely than non-syncytium-inducing variants to undergo serum-dependent infectivity enhancement, although the latter variants could clearly be susceptible to enhancement.