gebhart/patrepeval huggingface dataset:
Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor (2016)

Adoptive immunotherapy with regulatory T cells (Tregs) is a promising treatment for allograft rejection and graft-versus-host disease (GVHD). Emerging data indicate that, compared with polyclonal Tregs, disease-relevant antigen-specific Tregs may have numerous advantages, such as a need for fewer cells and reduced risk of nonspecific immune suppression. Current methods to generate alloantigen-specific Tregs rely on expansion with allogeneic antigen-presenting cells, which requires access to donor and recipient cells and multiple MHC mismatches. The successful use of chimeric antigen receptors (CARs) for the generation of antigen-specific effector T cells suggests that a similar approach could be used to generate alloantigen-specific Tregs. Here, we have described the creation of an HLA-A2-specific CAR (A2-CAR) and its application in the generation of alloantigen-specific human Tregs. In vitro, A2-CAR-expressing Tregs maintained their expected phenotype and suppressive function before, during, and after A2-CAR-mediated stimulation. In mouse models, human A2-CAR-expressing Tregs were superior to Tregs expressing an irrelevant CAR at preventing xenogeneic GVHD caused by HLA-A2+ T cells. Together, our results demonstrate that use of CAR technology to generate potent, functional, and stable alloantigen-specific human Tregs markedly enhances their therapeutic potential in transplantation and sets the stage for using this approach for making antigen-specific Tregs for therapy of multiple diseases.
A recombinant vaccinia virus expressing human prostate‐specific antigen (PSA): Safety and immunogenicity in a non‐human primate (1995)

Prostate-specific antigen (PSA) is a serine protease secreted by prostatic epithelial cells and is widely used as a marker for prostate cancer. The tissue specificity of PSA makes it a potential target for active specific immunotherapy, especially in prostate cancer patients who have undergone prostatectomy and in whom the only PSA-expressing tissue in the body resides in metastatic deposits. We report here the cloning, construction and immunological consequences of immunization of rhesus monkeys with a recombinant vaccinia virus expressing human PSA (designated rV-PSA). The prostate gland of the rhesus is structurally and functionally similar to the human prostate. While rodent and other mammalian species do not share homology with human PSA, there is 94% homology between the amino acid sequences of rhesus and human PSA. Immunization of rhesus monkeys with wild-type vaccinia virus or rV-PSA elicited the usual low-grade constitutional symptoms of vaccinia virus infection. There was no evidence of any adverse effects in any immunized monkeys. A short-lived PSA-specific IgM antibody response was noted in all rV-PSA immunized monkeys regardless of dose level. All monkeys receiving the 10(8)pfu dose of rV-PSA demonstrated PSA-specific T-cell responses that were maintained up to 270 days. No differences in anti-PSA immune responses or toxicity were observed in animals that received prostatectomy prior to immunization. Our results thus demonstrate the safety and immunogenicity of rV-PSA in a non-human primate and have implications for potential specific immunotherapy protocols using PSA as a target.
A robust low rate voice codec for wireless communications (2002)

The design, implementation and performance of a high quality low bit rate speech codec for wireless communication is presented. The codec is based on the CELP model. Generalized analysis-by-synthesis, algebraic fixed codebooks, and multistage LSF techniques are used, resulting in robustness to transmission errors and high quality across changing speech levels and background noise conditions. The bit allocations for the quantization of LSF, pitch and the excitation are chosen in a mode specific manner based on a robust mode classification scheme. A 4.8 kb/s version has been implemented and subjective tests show speech quality that is equivalent to or better than most cellular standard codecs. Performance is also consistent across speech levels and transmission errors.
Efficient Synthesis and Characterization of Novel Bibenzimidazole Oligomers and Polymers as Potential Conjugated Chelating Ligands (2005)

[Structure: see text]. A simple and mild condensation route for the synthesis of novel bibenzimidazole oligomers and polymers is reported here using methyl 2,2,2-trichloroacetimidate as a key starting material. The dimer, trimer, tetramer, and polymers of bibenzimidazole were synthesized as a new series of potential conjugated chelating ligands for metallopolymer studies. The polymers show a maximum absorption at around 400 nm. The optical band gap of the polymer was estimated to be 2.68 eV.
Imidazo[1,2-b]pyridazines, Novel Nucleus with Potent and Broad Spectrum Activity against Human Picornaviruses:  Design, Synthesis, and Biological Evaluation (2003)

A novel structural class of picornavirus inhibitors comprising an imidazo[1,2-b]pyridazine nucleus was discovered. 2-Aminoimidazo[1,2-b]pyridazines (6d, (E/Z)-7b, (E)-7d, (Z)-7d, (E/Z)-8b, (E)-10b, (E)-13a, (Z)-13a, (E)-13b, (Z)-13b, (E)-13c, and (Z)-13c) were designed and synthesized in an effort to identify potent broad spectrum antirhinoviral agents. A practical synthetic route to this chemical scaffold has been developed. The target compounds were evaluated in a plaque reduction assay and in a cytopathic effect assay. Our preliminary SAR studies highlight the minimum structural features required for antirhinovirus activity. Our data suggest that the nature of the linker between the phenyl and the imidazopyridazine moieties has a significant influence on the activity of these compounds. Oximes are slightly better than vinyl carboxamides at this position. The oximes are the most potent analogues against human rhinovirus 14 (HRV-14), and at the concentrations evaluated, no apparent cellular toxicity is noted. Furthermore, the E geometry appears to be a key element for activity; the Z isomer leads to a considerable loss in potency. Of particular interest, analogue 7b exhibits potent broad-spectrum antirhinoviral and antienteroviral activity when evaluated against a panel of seven additional rhino- and enteroviruses. The chemistry and the biological evaluations are discussed.
Permercuration of Ferrocenes and Ruthenocenes. New Approaches to Complexes Bearing Perhalogenated Cyclopentadienyl Ligands (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPermercuration of Ferrocenes and Ruthenocenes. New Approaches to Complexes Bearing Perhalogenated Cyclopentadienyl LigandsYoung-Hee Han, Mary Jane Heeg, and Charles H. WinterCite this: Organometallics 1994, 13, 8, 3009–3019Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/om00020a017https://doi.org/10.1021/om00020a017research-articleACS PublicationsRequest reuse permissionsArticle Views382Altmetric-Citations46LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Analysis, design, and optimization of the LCC resonant inverter as a high-intensity discharge lamp ballast (1998)

A complete study of the clamped-mode (CM) series-parallel (LCC) resonant inverter together with some of the control-to-output characteristics are presented in this paper. Also, a new control method for the CM LCC resonant inverter is introduced. With this method, the inverter is forced to operate with optimum commutations and without handling reactive energy, thus minimizing both switching and conduction losses. The corresponding design procedure is illustrated with a design example. Finally, some experimental results obtained from a prototype at the laboratory are also shown to validate the analysis and evaluate the proposed control method.
Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy (2011)

Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.
Lamprey: tracking users on the World Wide Web. (1996)

Tracking individual web sessions provides valuable information about user behavior. This information can be used for general purpose evaluation of web-based user interfaces to biomedical information systems. To this end, we have developed Lamprey, a tool for doing quantitative and qualitative analysis of Web-based user interfaces. Lamprey can be used from any conforming browser, and does not require modification of server or client software. By rerouting WWW navigation through a centralized filter, Lamprey collects the sequence and timing of hyperlinks used by individual users to move through the web. Instead of providing marginal statistics, it retains the full information required to recreate a user session. We have built Lamprey as a standard Common Gateway Interface (CGI) that works with all standard WWW browsers and servers. In this paper, we describe Lamprey and provide a short demonstration of this approach for evaluating web usage patterns.
Cleavage and inactivation of human C1 inhibitor by the human leukocyte proteinase, proteinase 3 (1993)

Incubation of highly purified human C1 inhibitor with equally pure human leukocyte proteinase 3, resulted in a dose- and time-dependent inactivation of C1 inhibitor hemolytic activity. Furthermore, this inactivation was accompanied by proteinase 3-dependent cleavage of the C1 inhibitor into an 83,000 molecular weight fragment. The formation of the 83,000 molecular weight fragment followed a time course which was similar to that observed for the inactivation of hemolytic activity. Within 120 minutes more than 90% of the hemolytic activity was lost. This inactivation of C1 inhibitor appeared to be selective as purified human C1q was not degraded in a similar time period. Moreover, when 100 micrograms IgG, isolated from each of 21 Wegener's granulomatosis patients with cytoplasmic anti-nuclear antibodies immunofluorescent titers to proteinase 3 greater then 1:64, was incubated with 3 milliunits of proteinase 3, little to no cleavage of C1 inhibitor was observed. In contrast, 100 micrograms of IgG isolated from 14 normal donors was ineffective in affording protection to C1 inhibitor upon incubation with proteinase 3. Our results suggest that neutrophil infiltration and activation could lead to local complement consumption at the tissue sites.
Abstract 2659: MT-4019: a de-immunized engineered toxin body targeting CD38 for multiple myeloma (2017)

Abstract Molecular Templates is developing engineered toxin bodies (ETBs), potent recombinant immunotoxins that combine the specificity of an antibody fragment with the powerful direct cytotoxicity of the Shiga-like toxin A subunit (SLTA). ETBs can induce their own internalization, route through the cell in a predictable manner, enzymatically and irreversibly destroy ribosomes to shutdown protein synthesis and induce apoptosis of tumor cells. This mechanism of action is distinct from that of other therapeutics, making ETBs an attractive treatment for patients who have become resistant to chemotherapy and other treatments. Safety and efficacy in refractory non-Hodgkin’s lymphoma patients has been observed in a phase I study with Molecular Template’s first-generation CD20-targeting compound, MT-3724. CD38 is a surface receptor that is highly expressed on malignant plasma cells. CD38 is a clinically validated target of monoclonal antibodies for treatment of multiple myeloma and is known to persist after failure of antibody treatment. MT-4019 is a CD38-targeted next-generation ETB, utilizing a modified SLTA. The SLTA subunit of the next-generation ETB scaffold has been modified through proprietary genetic engineering to systematically and comprehensively reduce B cell and CD4+T cell epitopes, as well as to dampen the innate response by decreasing binding to TLR-4. This de-immunized next-generation scaffold retains the potency and specificity of an ETB containing an unmodified SLTA. Pre-clinical studies in rodents and non-human primate models have demonstrated the tolerability of MT-4019, along with a decreased anti-drug antibody response. Additionally, in the non-human primate model, MT-4019 showed reduced neutrophil and monocyte activation as compared to an ETB with an unmodified SLTA subunit, indicating that SLTA modification also exhibits a diminished innate immune response. Molecular Template’s ETB technology has resulted in potent, targeted therapeutic agents that have a unique mechanism of action in the field of oncology. MT-3724, a first-generation CD20-targeted ETB, has shown promising clinical results in the refractory setting for non-Hodgkin’s lymphoma. The next-generation scaffold, as exemplified in the CD38-targeted MT-4019, retains potent and specific direct cell kill activities, and additionally reduces the innate and adaptive immune response to the therapeutic. MT-4019 is a promising lead and is under further development to enable clinical studies in multiple myeloma. Citation Format: Garrett L. Robinson, Sangeetha Rajagopalan, Brigitte Brieschke, Jane Neill, Jennifer Erdman, Rodney Flores, Jensing Liu, Jack P. Higgins, Erin K. Willert. MT-4019: a de-immunized engineered toxin body targeting CD38 for multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2659. doi:10.1158/1538-7445.AM2017-2659
Spike protein-nucleocapsid interactions drive the budding of alphaviruses (1992)

Semliki Forest virus (SFV) particles are released from infected cells by budding of nucleocapsids through plasma membrane regions that are modified by virus spike proteins. The budding process was studied with recombinant SFV genomes which lacked the nucleocapsid protein gene or, alternatively, the spike genes. No subviral particles were released from cells which expressed only the nucleocapsid protein or the spike proteins. Virus release was found to be strictly dependent on the coexpression of the nucleocapsid and the spike proteins. These results provide direct proof for the hypothesis that the alphavirus budding is driven by nucleocapsid-spike interactions. The importance of the viral 42S RNA for virus assembly and budding was investigated by using the heterologous vaccinia virus-T7 expression system for the synthesis of the SFV structural proteins. The results demonstrate that the viral genome is not absolutely required for formation of budding competent nucleocapsids, since small amounts of viruslike particles were assembled in the absence of 42S RNA.
Selective antibody‐mediated targeting of class I MHC to EGFR‐expressing tumor cells induces potent antitumor CTL activity in vitro and in vivo (2006)

Epidermal growth factor receptor (EGFR) is highly overexpressed in many tumor types. We present a new fusion molecule that can target solid tumors that express EGFR. The fusion molecule combines the advantage(s) of the well-established tumor targeting capabilities of high affinity recombinant fragments of antibodies with the known efficient, specific and potent killing ability of CD8 T lymphocytes directed against highly antigenic MHC/peptide complexes. A recombinant chimeric molecule was created by the genetic fusion of the scFv antibody fragment derived from the anti-EGFR monoclonal antibody C225, to monomeric single-chain HLA-A2 complexes containing immunodominant tumor or viral-specific peptides. The fusion protein can induce very efficiently CTL-dependent lysis of EGFR-expressing tumor cells regardless of the expression of self peptide-MHC complexes. Moreover, the molecule exhibited very potent antitumor activity in vivo in nude mice bearing preestablished human tumor xenografts. These in vitro and in vivo results indicate that recombinant scFv-MHC-peptide fusion molecules might represent a novel and powerful approach to immunotherapy of solid tumors, bridging antibody and T lymphocyte attack on cancer cells.
Effect of the Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody, AMG 145, in Homozygous Familial Hypercholesterolemia (2013)

This study demonstrates significant and dose-related LDL cholesterol lowering with a PCSK9 monoclonal antibody in homozygous familial hypercholesterolemia patients with defective LDL receptor activity but no reduction in those who were receptor negative.
Hugo Zapata siembra sus flores de piedra en China (2013)

La roca, elemento medular de la obra del artista colombiano Hugo Zapata, se presenta como el eje de la reflexión que en esta edición de Poliantea propone Juan Gustavo Cobo Borda. El escritor se aproxima al trabajo de Zapata y dilucida algunos de sus motivos y temas primordiales.
18F-FDG PET Database of Longitudinally Confirmed Healthy Elderly Individuals Improves Detection of Mild Cognitive Impairment and Alzheimer's Disease (2007)

Our longitudinally confirmed NL database constitutes reliable (18)F-FDG PET normative values for MCI and AD.
A data-driven spoken language understanding system (2004)

The paper presents a purely data-driven spoken language understanding (SLU) system. It consists of three major components, a speech recognizer, a semantic parser, and a dialog act decoder. A novel feature of the system is that the understanding components are trained directly from data without using explicit semantic grammar rules or fully-annotated corpus data. Despite this, the system is nevertheless able to capture hierarchical structure in user utterances and handle long range dependencies. Experiments have been conducted on the ATIS corpus and 16.1% and 12.6% utterance understanding error rates were obtained for spoken input using the ATIS-3 1993 and 1994 test sets. These results show that our system is comparable to existing SLU systems which rely on either handcrafted semantic grammar rules or statistical models trained on fully-annotated training corpora, but it has greatly reduced build cost.
Functional Analysis of CAR, the Target Sequence for the Rev Protein of HIV-1 (1989)

Expression of high levels of the structural proteins of the human immunodeficiency virus type 1 (HIV-1) requires the presence of the protein encoded by the rev open reading frame (Rev) and its associated target sequence CAR (cis anti-repression sequence) which is present in the env region of viral RNA. Extensive mutagenesis demonstrated that CAR has a complex secondary structure consisting of a central stem and five stem/loops. Disruption of any of these structures severely impaired the Rev response, but many of the stem/loops contain material that was unnecessary for Rev regulation and must be retained in these structures to avoid disturbing adjacent structures critical for CAR function. Probably no more than two of the described structural components are involved in sequence-specific recognition by regulatory proteins.
Factors associated with prolonged symptoms and severe disease due to Clostridium difficile (1999)

risk factors for severity of CDAD include functional disability, cognitive impairment, and recent endoscopy. Anticipation of severe CDAD may limit morbidity and mortality.
Calcium-activated, phospholipid-dependent protein kinase from rat brain. Subcellular distribution, purification, and properties. (1982)

in rat brain was investigated.Approximately one-third of the protein kinase was recovered in the soluble cytosol fraction, another one-third was in the crude mitochondrial fraction, and the rest was in nuclear and microsomal fractions.Upon further analysis of the crude mitochondrial fraction, most of the enzyme was found to be associated with synaptosomal membranes.The cytosol protein kinase was purified approximately 800- fold to apparent homogeneity by DEAE-cellulose and Sephadex G-150 column chromatographies, followed by isoelectrofocusing electrophoresis, blue-Sepharose CL-GB, and phenyl-Sepharose CG4B column chromatographies.The molecular weight of the protein kinase was about 77,000 as estimated by sucrose density gradient ultracentrifugation.The enzyme gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with M, -82,000, indicating that the enzyme is composed of one polypeptide chain.The enzyme was free of calmodulin.The protein kinase associated with membrane was solubilized with Triton X-100, and partially purified by DEAE-cellulose and Sephadex G-150 column chromatographies.The membraneassociated protein kinase thus obtained was indistinguishable from the cytosol protein kinase in physical, kinetic, and catalytic properties.Both enzymes were fully activated by diacylglycerol in the presence of phospholipid and less than micromolar concentrations of Ca2+.
Designing Fcabs: well-expressed and stable high affinity antigen-binding Fc fragments (2017)

Fc fragment with antigen-binding (Fcab) is a novel construct which can be selected to recognize specifically a wide variety of target proteins. We describe the selection and affinity maturation of Fcab clones targeting VEGF, an important pro-angiogenesis factor. To investigate the extent of engineering permissible to Fcabs we applied targeted mutagenesis to all three C-terminal loop structures and the C-terminus of the CH3 domain to isolate high-affinity binders by directed evolution and yeast display. The matured clone, CT6, binds to VEGF with low nanomolar affinity and inhibits VEGF-stimulated proliferation of human umbilical vein endothelial cells in vitro. Molecular dynamics simulations were performed to address flexibility of the molecular structure of CT6 and to approximate a structural ensemble in aqueous solution. Significantly higher RMSF levels of CT6 in comparison to wild-type Fc were limited to the elongated CD-loop in the CH3 domain, while the overall structural integrity was retained. This allowed the Fcab to replace the Fc portion of a mAb, in which both the CH3 and Fab are capable of antigen engagement: a construct called mAb2 was assembled with CT6 and the Fab of bevacizumab. This bispecific molecule showed more potent antagonistic activity than bevacizumab in vitro. Further evaluation for the potential of the CT6 Fcab in targeted therapy is warranted due to the possibility of being combined with other therapeutically meaningful targets.