gebhart/patrepeval huggingface dataset:
Abstract 3665: Enzymatic depletion of pericellular HA from tumor cell surface sensitizes Erbitux dependent immune cell-mediated cytotoxicity (2011)

Abstract Hyaluronan (HA), a ubiquitous high-molar-mass linear glycosaminoglycan (GAG) plays a critical role in cell adhesion, motility, growth and differentiation. HA accumulation is associated with many human cancers. Human tumor cells can form HA rich pericellular matrix which might favor tumor growth by preventing the access of host immune cells to malignant cells. Monoclonal antibody (MAb) based therapeutics are emerging as an important component of therapy for human malignancies. Despite the very high specificity of monoclonal antibodies, resistance to MAb therapy is common. Antibody Dependent Cell-mediated Cytotoxicity (ADCC) is an important effector for the clinical efficacy of MAbs and relies on effective interaction between the Fc domain of antigen bound antibody and FcγRIII positive immune cells. We hypothesize that pericellular HA coating may contribute to resistance of HA-rich malignant cells to MAb mediated therapy by preventing efficient access of effector cells to their tumor targets. Enzymatic depletion of HA with PEGPH20 hyaluronidase could potentially sensitize such tumors to MAb mediated therapy. remove ell surface and ated therapy by preventing tumor cells contact EGFR positive breast carcinoma cell line MDA-MB-231luc and genetically engineered HAS2 over expressing MDA-MB-231HAS2 were used to investigate the role of HA-rich pericellular matrix in inhibition of ADCC. ADCC assay was performed by incubating Calcein AM labeled monolayer cells with monoclonal antibody (1h at 37°C) followed by co-incubation of recombinant human IL-2 (rhIL-2) activated human peripheral blood mononuclear cells (PBMC, 5h at 37°C, 5% CO2) with or without PEGPH20. Live cells from each treatment were assessed by fluorescence readings at Ex/Em 488nm/537nm (SpectraMax M2e plate reader) at the end of the assay. Percentages of cell killing were calculated against control. The student's t test was used to compare the difference between treatments. Particle exclusion assay demonstrated that HAS2 over expressing MDA-MB-231HAS2 cells formed a pericellular coat that inhibited access of the rhIL-2 activated PBMC to tumor cells. Incubation with PEGPH20 removed the HA-rich pericellular matrix and promoted contact of PBMC to tumor cells. Incubation of Erbitux with rhIL-2 activated PBMC induced a dose dependent killing of both MDA-MB-231luc and MDA-MB-231HAS2 cells. PEGPH20 increased ADCC by 10% on MDA-MB-231luc (HAlow) and 25% on MDA-MB-231HAS2 (HAhigh) tumor cells. Our results show that the HA-rich pericellular matrix on adherent tumor cells inhibits ADCC and PEGPH20 depletion of this coat sensitizes the tumor cells to ADCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3665. doi:10.1158/1538-7445.AM2011-3665
Dendritic Cells Are Resistant to Apoptosis Through the Fas (CD95/APO-1) Pathway (1999)

Immunoregulation of lymphocytes and macrophages in the peripheral immune system is achieved in part by activation-induced cell death. Members of the TNF receptor family including Fas (CD95) are involved in the regulation of activation-induced cell death. To determine whether activation-induced cell death plays a role in regulation of dendritic cells (DCs), we examined interactions between Ag-presenting murine DCs and Ag-specific Th1 CD4+ T cells. Whereas mature bone marrow- or spleen-derived DCs expressed high levels of Fas, these DCs were relatively insensitive to Fas-mediated killing by the agonist mAb, Jo-2, as well as authentic Fas ligand expressed on the CD4+ T cell line, A.E7. The insensitivity to Fas-mediated apoptosis was not affected by priming with IFN-gamma and/or TNF-alpha or by blocking the DC survival signals TNF-related activation-induced cytokine and CD40L. However, apoptosis could be induced with C2-ceramide, suggesting that signals proximal to the generation of ceramide might mediate resistance to Fas. Analysis of protein expression of several anti-apoptotic mediators revealed that expression of the intracellular inhibitor of apoptosis Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein was significantly higher in Fas-resistant DCs than in Fas-sensitive macrophages, suggesting a possible role for Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein in DC resistance to Fas-mediated apoptosis. Our results demonstrate that murine DCs differ significantly from other APC populations in susceptibility to Fas-mediated apoptosis during cognate presentation of Ag. Because DCs are most notable for initiation of an immune response, resistance to apoptosis may contribute to this function.
ANTIGEN RECOGNITION AND THE IMMUNE RESPONSE (1972)

L-Tyrosine-p-azobenzenearsonate (RAT) induces cellular immunity without humoral antibody in guinea pigs. Asymmetric bifunctional antigens composed of one RAT moiety and one dinitrophenyl (DNP) group separated by flexible spacers induce anti-RAT cellular immunity and an anti-DNP humoral response. Symmetrical bifunctional antigens of similar design but comprised of two RAT determinants induce cellular immunity without demonstrable anti-RAT antibody. However, when the flexible spacer is replaced by a rigid decaproline chain, humoral anti-RAT responses are provoked. Since RAT contains both electropositive (azo) and electronegative (arsonate) centers, the failure of bifunctional RAT compounds with flexible spacers to induce humoral immunity might be ascribed either to intramolecular stacking, which compromises their bifunctional character, or to interaction of both determinants with receptors on the same cell surface, which would fail to satisfy the requirement for cooperation. In order to distinguish between these alternatives, symmetrical bifunctional antigens composed of two L-tyrosine-p-azophenyltrimethylammonium (TAT) determinants separated by flexible or rigid spacers were synthesized. TAT is immunogenic and does not cross-react with RAT. Furthermore, it contains only electropositive centers and consequently bifunctional molecules do not undergo intramolecular stacking. Immunization with either flexibly or rigidly spaced bifunctional TAT antigens raised anti-TAT antibody. These results conclusively demonstrate that "self-help," cooperation between bone marrow-derived and thymus-derived lymphocytes of identical or similar specificity, can occur, provided the determinants on the antigen are prevented from associating with each other.
Inhibition of oncostatin M in osteoarthritic synovial fluid enhances GAG production in osteoarthritic cartilage repair (2013)

Mediators in the synovial fluid are thought to play a major role in osteoarthritic cartilage turnover. The purpose of the current study was to investigate the role of oncostatin M (OSM) in osteoarthritis (OA) by evaluating the presence of the cytokine and its receptors in the OA joint and interfering with its activity in synovial fluid co-cultured with cartilage explants. OSM levels were increased in the synovial fluid of osteoarthritic patients compared to healthy donors. Immunohistochemistry confirmed the presence of both the leukaemia inhibitory factor (LIF) and OSM receptors for OSM throughout the whole depth of osteoarthritic cartilage and synovial tissue, whereas in healthy cartilage their presence seemed more restricted to the superficial zone. Blocking OSM activity, using an activity inhibiting antibody, in 25 % osteoarthritic synovial fluid added to OA cartilage explant cultures increased glycosaminoglycan (GAG) content from 18.6 mg/g to 24.3 mg/g (P < 0.03) and total production from 7.0 mg/g to 11.9 mg/g (P < 0.003). However, OSM exogenously added to cartilage explant cultures reflecting low and high concentrations in the synovial fluid (5 and 50 pg/mL) did not affect cartilage matrix turnover, suggesting that factors present in the synovial fluid act in concert with OSM to inhibit GAG production. The current study indicates the potential to enhance cartilage repair in osteoarthritis by modulating the joint environment by interfering with OSM activity.
Transparent-refresh DRAM (TReD) using dual-port DRAM cell (2003)

A novel memory circuit, the transparent-refresh DRAM (TReD), is proposed to make a dynamic random-access memory (DRAM) virtually refresh-free, and a test device is successfully fabricated. The TReD uses dual-port dynamic RAM cells, one port of which is assigned for a refresh operation and the other port is assigned for a normal read/write operation. Using the configuration, users of the RAM are freed from a cumbersome refresh control without access-time degradation. The TReD cell size is about 1/2.5 of a 4-transistor SRAM (static RAM) cell, so that it can provide very-high-density RAM macros, which is functionally static. As a dual-port memory, the proposed dual-port DRAM cell size is 1/5 of the dual-port SRAM cell, and is suitable for large-scale dual-port memory macros in ASIC (application-specific integrated circuit) environments.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone? (2015)

An analysis of chemical reactions used in current medicinal chemistry (2014), three decades ago (1984), and in natural product total synthesis has been conducted. The analysis revealed that of the current most frequently used synthetic reactions, none were discovered within the past 20 years and only two in the 1980s and 1990s (Suzuki-Miyaura and Buchwald-Hartwig). This suggests an inherent high bar of impact for new synthetic reactions in drug discovery. The most frequently used reactions were amide bond formation, Suzuki-Miyaura coupling, and SNAr reactions, most likely due to commercial availability of reagents, high chemoselectivity, and a pressure on delivery. We show that these practices result in overpopulation of certain types of molecular shapes to the exclusion of others using simple PMI plots. We hope that these results will help catalyze improvements in integration of new synthetic methodologies as well as new library design.
Immune-Neuro-Endocrine Interactions: Facts and Hypotheses (1996)

THE existence of mechanisms that provide immunity to an infective agent was inferred from empirical observations obtained through the ingenuity and deductive capacity of early investigators. The first procedures for vaccinations and serotherapy resulted from these observations. The implementation of these procedures, probably the most important contribution of immunology to medical science, was, at first, based on a very rudimentary knowledge of the immune system. During the first half of the 20th century, this rather primitive knowledge coincided with evidence showing that the endocrine and nervous systems integrate and regulate different bodily functions. Therefore, based on some supportive data, it was considered that immune mechanisms may also be influenced by these systems. However, at the beginning of the second half of the 20th century, most efforts were directed at understanding the molecular and cellular basis of the immune response and the mechanisms of acquisition of immunological diversity and self-tolerance.
Molecular interaction between human tumor marker protein p150, the largest subunit of eIF3, and intermediate filament protein K7 (2001)

The human tumor marker protein p150 was identified as the largest subunit of eukaryotic translation initiation factor 3 (eIF3) (also known as p170/p180). Its expression level is not only upregulated in many transformed cell lines, but also in several human cancers including breast, cervical, esophageal, and stomach carcinomas. The function of p150 in cancer and initiation of translation are not well understood. Using the yeast two-hybrid genetic screen, we found that a portion of p150 interacts with hPrt1, another subunit of eIF3, and cytokeratin 7, an intermediate filament protein. The interactions between p150 and hPrt1, and between p150 and cytokeratin 7 were verified both in vivo and in vitro. The interaction site for hPrt1 was mapped to the carboxyl half of the coiled-coil region of the p150 protein between amino acids 664-835. The expression of hPrt1 was clearly upregulated in cancer tissue, similarly to that of p150. By contrast, no substantial difference in the expression level of cytokeratin 7 was observed between cancer and normal breast tissue, suggesting that cytokeratin 7 expression is not co-regulated with p150. Taken together, our studies suggest a new role for p150 in translation initiation, possibly by acting as an adapter molecule between the translation initiation apparatus and the cytoskeleton structure in the cell.
Inhibition of Pulmonary Fibrosis by the Chemokine IP-10/CXCL10 (2004)

Pulmonary fibrosis is an enigmatic and devastating disease with few treatment options, now thought to result from abnormal wound healing in the lung in response to injury. We have previously noted a role for the chemokine interferon gamma-inducible protein of 10 kD (IP-10)/CXC chemokine ligand 10 in the regulation of cutaneous wound healing, and consequently investigated whether IP-10 regulates pulmonary fibrosis. We found that IP-10 is highly expressed in a mouse model of pulmonary fibrosis induced by bleomycin. IP-10-deficient mice exhibited increased pulmonary fibrosis after administration of bleomycin, suggesting that IP-10 limits the development of fibrosis in this model. Substantial fibroblast chemoattractant and proliferative activities were generated in the lung after bleomycin exposure. IP-10 significantly inhibited fibroblast responses to the chemotactic, but not the proliferative activity generated, suggesting that IP-10 may attenuate fibroblast accumulation in bleomycin-induced pulmonary fibrosis by limiting fibroblast migration. Consistent with this inhibitory activity of IP-10 on fibroblast migration, fibroblast accumulation in the lung after bleomycin exposure was dramatically increased in IP-10-deficient mice compared with wild-type mice. Conversely, transgenic mice overexpressing IP-10 were protected from mortality after bleomycin exposure, and demonstrated decreased fibroblast accumulation in the lung after challenge compared with wild-type mice. Our findings suggest that interruption of fibroblast recruitment may represent a novel therapeutic strategy for pulmonary fibrosis, which could have applicability to a wide range of fibrotic illnesses.
Cyclophilin A Mediates Vascular Remodeling by Promoting Inflammation and Vascular Smooth Muscle Cell Proliferation (2008)

In response to low flow, CyPA plays a crucial role in VSMC migration and proliferation, as well as inflammatory cell accumulation, thereby regulating flow-mediated vascular remodeling and intima formation.
Antitumor Imidazotetrazines. 41. Conjugation of the Antitumor Agents Mitozolomide and Temozolomide to Peptides and Lexitropsins Bearing DNA Major and Minor Groove-Binding Structural Motifs (2002)

Carboxylic acids derived from the amido groups of the antitumor agents mitozolomide and temozolomide have been conjugated to simple amino acids and peptides by carbodiimide coupling. Solid-state peptide synthesis has been applied to link the acids to DNA major groove-binding peptidic motifs known to adopt alpha-helical conformations. Attachment of the acids to pyrrole and imidazole polyamidic lexitropsins gave a series of potential DNA minor groove-binding ligands. In vitro biological evaluation of a limited number of these novel conjugates failed to demonstrate any enhanced growth-inhibitory activity compared to the unconjugated drugs; sites of alkylation at tracts of multiple guanines were also unaffected. Attachment of additional residues at C-8 of the imidazotetrazines did not perturb the chemistry of activation of the bicyclic nucleus, and biological sequelae can be rationalized by invoking the liberation of a common, diffusible, reactive chemical intermediate, the methanediazonium ion.
Stability of ondansetron hydrochloride and 12 medications in plastic syringes (1998)

The stability and compatibility of ondansetron hydrochloride with neostigmine methylsulfate, naloxone hydrochloride, midazolam hydrochloride, fentanyl citrate, alfentanil hydrochloride, atropine sulfate, morphine sulfate, meperidine hydrochloride, propofol, droperidol, metoclopramide monohydrochloride, and glycopyrrolate were studied. Ondansetron 1.33 or 1.0 mg/mL was combined with 0.9% sodium chloride injection and each of the 12 drugs in duplicate in plastic syringes (or glass for propofol). The syringes were stored at 21.8-23.4 or 4 degrees C in the dark, except for those containing propofol, which were stored at ambient temperature. Samples were removed at 0, 4, 8, and 24 hours for analysis by high-performance liquid chromatography and pH measurement; the propofol-containing samples were removed at 0, 1, 2, and 4 hours. Syringes were visually assessed for color and clarity, and particulate content was measured with a particle counter at the end of the study period. All solutions containing ondansetron retained more than 90% of their initial ondansetron concentration. Solutions containing each of the other drugs except droperidol retained more than 90% of their initial concentration of these drugs. The solutions containing droperidol retained more than 90% of their initial droperidol concentration for up to eight hours at ambient temperature but precipitated quickly at 4 degrees C. In combinations of ondansetron 1.33 or 1.0 mg/mL and 10 of 12 drugs, all drugs were stable for 24 hours in plastic syringes at 23 and 4 degrees C; ondansetron hydrochloride 1.0 mg/mL and propofol 1.0 and 5.0 mg/mL in admixtures were stable for 4 hours, and droperidol on its own and combined with ondansetron 1.0 mg/mL was stable for no more than 8 hours at ambient temperature.
Potential radiosensitizing agents. Dinitroimidazoles (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPotential radiosensitizing agents. DinitroimidazolesKrishna C. Agrawal, Kathleen B. Bears, Raj K. Sehgal, Joe N. Brown, Patricia E. Rist, and W. D. RuppCite this: J. Med. Chem. 1979, 22, 5, 583–586Publication Date (Print):May 1, 1979Publication History Published online1 May 2002Published inissue 1 May 1979https://pubs.acs.org/doi/10.1021/jm00191a025https://doi.org/10.1021/jm00191a025research-articleACS PublicationsRequest reuse permissionsArticle Views614Altmetric-Citations47LEARN 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
New information about the polymyxin/colistin class of antibiotics (2009)

Infections by multidrug resistant Gram-negative bacilli (MDR-GNB) have become a major threat for patients hospitalized in intensive care units, representing a prevalent cause of morbimortality in the critically ill, since these microorganisms have developed resistance to most available antimicrobial agents. In this respect, very few therapeutic innovations have been developed in recent years, and it is not foreseen that any new drugs will be commercialized in the near future. Tigecycline represents an effective alternative in this setting, but lacks activity against Pseudomonas aeruginosa, and its use has not been validated for all organ-specific infections. Frequently, only old antibiotics like colistin remain a valid option. New pharmaceutical formulations and dosage regimens of polymyxins have considerably reduced the toxicity previously attributed to these antimicrobials, and have made it possible to reintroduce them into clinical practice. Nonetheless, the effectiveness of polymyxins is still suboptimal, and the expansion of heteroresistance and pan-drug-resistant strains of gram-negative bacilli is of concern. Improvements in dosing, alternative methods of administration and different synergic antimicrobial combinations have been proposed in recent literature, among other measures, to enhance the effectiveness of polymyxins. The latest data regarding polymyxins and their clinical use are discussed in this review.
Querying Web data - the WebQA approach (2003)

The common paradigm of searching and retrieving information on the Web is based on keyword-based search using one or more search engines, then browsing through the large number of returned URLs. This is significantly weaker than declarative querying that is supported by DBMSs. The lack of a schema and high volatility of the Web make "database-like" querying of Web data difficult. We report on our work in building a system, called WebQA, that provides a declarative query-based approach to Web data retrieval that uses question-answering technology in extracting information from Web sites that are retrieved by search engines. The approach consists of first using meta-search techniques in an open environment to gather candidate responses from search engines and other on-line databases, then using information extraction techniques to find the answer to a specific question from these candidates. A prototype system has been developed to test this approach. Testing includes evaluation of its performance as a question-answering system using a well-known evaluation system called TREC-9. Its accuracy using TREC-9 data for simple questions is high and its retrieval performance is good. The system employs an open system architecture allowing for on-going improvements.
Dendrite-Free Lithium Deposition via Self-Healing Electrostatic Shield Mechanism (2013)

Rechargeable lithium metal batteries are considered the "Holy Grail" of energy storage systems. Unfortunately, uncontrollable dendritic lithium growth inherent in these batteries (upon repeated charge/discharge cycling) has prevented their practical application over the past 40 years. We show a novel mechanism that can fundamentally alter dendrite formation. At low concentrations, selected cations (such as cesium or rubidium ions) exhibit an effective reduction potential below the standard reduction potential of lithium ions. During lithium deposition, these additive cations form a positively charged electrostatic shield around the initial growth tip of the protuberances without reduction and deposition of the additives. This forces further deposition of lithium to adjacent regions of the anode and eliminates dendrite formation in lithium metal batteries. This strategy may also prevent dendrite growth in lithium-ion batteries as well as other metal batteries and transform the surface uniformity of coatings deposited in many general electrodeposition processes.