gebhart/patrepeval huggingface dataset:
Abstract 2999: NKG2A checkpoint receptor expression on tumor-infiltrating CD8+ T cells restrains efficacy of immunotherapy (2017)

Abstract The inhibitory receptor CD94-NKG2A is expressed on subsets of NK cells and cytotoxic CD8+ T cells, but not CD4+ T helper cells. It’s ligand is the non-classical MHC class I molecule HLA-E, commonly over-expressed in human cancers. We previously demonstrated that high HLA-E expression in ovarian carcinoma and NSCLC may neutralize the survival benefit of T cell infiltration, suggesting that NKG2A could represent an immune checkpoint that tumors may exploit for immune evasion. We thus examined NKG2A expression on human and mouse Tumor Infiltrating Lymphocyte (TIL) populations and tested blockade of this receptor in mouse tumor models. Multicolor flow cytometry analysis showed higher frequency of NKG2A+CD8+ T cells in TIL samples obtained from biopsies of human head- and neck- carcinomas (n=17) compared to peripheral blood CD8+ T cells. Frequency of NKG2A+ TIL was higher in patients with measurable immune reactivity to HPV16-viral antigens than in patients without tumor immunity (14.8% vs 4.7%, respectively). Interestingly, only subsets of the NKG2A+ T cells co-expressed other inhibitory receptors, including PD-1 and TIM3, suggesting the existence of a ‘dedicated’ T cell subset for NKG2A. In our mouse tumor models we observed similar findings and, moreover, demonstrated that therapeutic vaccines comprising tumor antigens increased the frequency of NKG2A+-positive CD8+ TIL up to 80%. Similarly, expression of Qa-1, the mouse homologue of HLA-E, on tumor cells also increased after therapeutic vaccination. As a proof of concept that the NKG2A - Qa-1 axis limits the efficacy of immunotherapy, NKG2A blocking antibodies were applied in the TC-1 model together with therapeutic peptide vaccination. Combination treatment with vaccine and NKG2A blockade significantly improved the therapeutic efficacy compared to the vaccine alone, both in terms of survival (P&amp;lt;0.05, median survival 44 vs 31 days) as well as overall response rate, defined as decreased tumor size of more than 30% (93.8% vs 43.8%, respectively). Similar results were obtained in Qa-1-deficient mice, suggesting that Qa-1 on tumor cells is of importance. In conclusion, inhibitory receptor NKG2A is enriched on CD8+ TIL and functions as an immune checkpoint that restrains therapeutic efficacy of a cancer vaccine. Citation Format: Thorbald van Hall, Nadine van Montfoort, Sytse Piersma, Marjolein Sluijter, Marij J. Welters, Pascale André, Nicolai Wagtmann, Sjoerd H. van der Burg. NKG2A checkpoint receptor expression on tumor-infiltrating CD8+ T cells restrains efficacy of immunotherapy [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 2999. doi:10.1158/1538-7445.AM2017-2999
Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHuman very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modificationVassilis I. Zannis and Jan L. BreslowCite this: Biochemistry 1981, 20, 4, 1033–1041Publication Date (Print):February 17, 1981Publication History Published online1 May 2002Published inissue 17 February 1981https://doi.org/10.1021/bi00507a059Request reuse permissionsArticle Views373Altmetric-Citations400LEARN 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 InReddit PDF (4 MB) Get e-Alertsclose Get e-Alerts
Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice (2016)

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.
Annexin II is a major component of fusogenic endosomal vesicles. (1993)

We have used an in vitro assay to follow the proteins transferred from a donor to an acceptor upon fusion of early endosomes. The acceptor was a purified early endosomal fraction immunoisolated on beads and the donor was a metabolically-labeled early endosomal fraction in suspension. In the assay, both fractions were mixed in the presence of unlabeled cytosol, and then the beads were retrieved and washed. The donor proteins transferred to the acceptor were identified by two-dimensional gel electrophoresis and autoradiography. Approximately 50 major proteins were transferred and this transfer fulfilled all criteria established for endosome fusion in vitro. However, only a small subset of proteins was efficiently transferred, if donor endosomes were briefly sonicated to generate small (0.1 micron diam) vesicles before the assay. These include two acidic membrane proteins, and three alkaline peripheral proteins exposed on the cytoplasmic face of the membrane. Partial sequencing and Western blotting indicated that one of the latter components is annexin II, a protein known to mediate membrane-membrane interactions. Immunogold labeling of cryosections confirmed that annexin II is present on early endosomes in vivo. These data demonstrate that annexin II, together with the other four proteins we have identified, is a major component of fusogenic endosomal vesicles, suggesting that these proteins are involved in the binding and/or fusion process.
Multidrug Resistance in Chinese Hamster Cells: Effect of Liposome-Encapsulated Doxorubicin (1989)

A Chinese hamster cell line (LZ), selected for multidrug resistance (MDR), exhibits a 3,000-fold resistance to doxorubicin, compared to parental V-79 cells. These drug resistant cells have amplified MDR genes, overexpress P-glycoprotein, and in the presence of doxorubicin show reduced intracellular drug accumulation. Using liposome-encapsulated doxorubicin (Rahman et al. Cancer Res. 45:796-803; 1985), we observed partial reversal of the resistance of LZ cells to this drug and a higher intracellular drug accumulation, compared to free drug. Parental V-79 cells, however, did not exhibit differences in survival or in drug accumulation when treated with encapsulated or free doxorubicin. Comparison of the effect of liposome-encapsulated doxorubicin with that of verapamil in reversing drug resistance showed that the liposomal preparation was as effective as verapamil used at its maximum clinically relevant concentration (1.5 microM). These results suggest that the use of liposomes as carriers of anticancer drugs may offer a strategy for overcoming MDR in tumor cells.
Improving Data Center Energy Efficiency With Advanced Thermal Management (2017)

Experimental investigation of data center cooling and computational energy efficiency improvement through advanced thermal management was performed. A chiller-less data center liquid cooling system was developed that transfers the heat generated from computer systems to the outdoor ambient environment while eliminating the need for energy-intensive vapor-compression refrigeration. This liquid cooling system utilizes a direct-attach cold-plate approach that enables the use of warm water at temperature a few degrees above outdoor ambient to achieve lower chip junction temperatures than refrigerated air. Using this approach, we demonstrated a cooling energy reduction by over 90% and computational energy reduction of up to 14% compared to traditional refrigerated air cooled data centers. To enable future computational efficiency improvements through high-density 3-D-chip stacking, we developed a 3-D compatible chip-embedded two-phase liquid cooling technology where a dielectric coolant is pumped through microscale cavities to provide thermal management of chips within the stack. In two-phase cooling, liquid is converted to vapor, which increases the capacity to remove heat, while the dielectric fluid enables integration with chip electrical interconnects. A test vehicle simulating an eight-core microprocessor was fabricated with embedded cooling channels. Results demonstrate that this volumetrically efficient cooling solution compatible with 3-D chip stacks can manage three times the core power density of today's high-power processor while maintaining the device temperature well within limits.
Methylene Derivatives as Intermediates in Polar Reactions. IX. The Concerted Mechanism for α-Eliminations of Haloforms<sup>1</sup> (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMethylene Derivatives as Intermediates in Polar Reactions. IX. The Concerted Mechanism for α-Eliminations of Haloforms1Jack Hine and Paul B. LangfordCite this: J. Am. Chem. Soc. 1957, 79, 20, 5497–5500Publication Date (Print):October 1, 1957Publication History Published online1 May 2002Published inissue 1 October 1957https://pubs.acs.org/doi/10.1021/ja01577a046https://doi.org/10.1021/ja01577a046research-articleACS PublicationsRequest reuse permissionsArticle Views175Altmetric-Citations43LEARN 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
Improved method for chick whole-embryo culture using a filter paper carrier (2001)

We describe a simple method of chick whole-embryo culture, which uses a filter paper carrier to hold the early blastoderm and vitelline membranes under tension while the embryo grows on a substratum of agar-albumen. This is a quick and efficient means of setting up cultures of chick embryos beginning at pre-primitive streak stages to stage 10 (stages X--XIV, Eyal-Giladi and Kochav [1976] Dev Biol 49:321-337; stages 1--10, Hamburger and Hamilton [1951] J Morphol 88:49--92). This is an improvement on the original method of New, which used a glass ring and watch glass (New [1955] Exp Morphol 3:320--331). Our modification of New's method, which we call EC (Early Chick, pronounced EASY) culture, facilitates several manipulations in early chick embryos, including microsurgery, grafting, bead implantation, microinjection, and electroporation. Using the EC method, embryos at stage 8 and older can be readily cultured either dorsal-side up (in contrast to New's method) or ventral-side up, as desired; embryos younger than stage 8 can be culture only ventral-side up (as with New's method). We also discuss some alternative methods for setting up these cultures.
Field Plot Techniques for Selecting Increased Once-over Harvest Yields in Pickling Cucumbers1 (1978)

Abstract Three harvest methods and 3 plot sizes for estimating yields in pickling cucumbers (Cucumis sativus L.) were examined. The correlation between dollar values for a simulated once-over harvest and successive harvest were low (r &lt; .16). Correlation between once-over harvest value and fruit number was .84, while correlation between once-over harvest value and mature fruit number was only .36. The correlation of .84 was high enough to warrant use of fruit number as a primary trait in selection for increased value. Use of fruit number as an estimate of yield would eliminate the grading and weighing processes needed to compute value. An efficient plot size for estimating mean differences between lines was 3.6m 2 .
Experimental and theoretical study of photoenolization mechanism for 1-methylanthraquinone (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExperimental and theoretical study of photoenolization mechanism for 1-methylanthraquinoneN. P. Gritsan, I. V. Khmelinski, and O. M. UsovCite this: J. Am. Chem. Soc. 1991, 113, 25, 9615–9620Publication Date (Print):December 1, 1991Publication History Published online1 May 2002Published inissue 1 December 1991https://pubs.acs.org/doi/10.1021/ja00025a029https://doi.org/10.1021/ja00025a029research-articleACS PublicationsRequest reuse permissionsArticle Views167Altmetric-Citations34LEARN 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
Prognostic Values of CD38<sup>+</sup>CD101<sup>+</sup>PD1<sup>+</sup>CD8<sup>+</sup> T Cells in Pancreatic Cancer (2019)

Programmed death-1 (PD-1), a key immune checkpoint molecule, has been developed as an oncotherapy target for various carcinomas. However, treatment with anti-PD-1 elicited only a minimal effect in pancreatic ductal adenocarcinoma (PDAC). Subsequent studies revealed the existence of a subset of PD-1<sup>+</sup> T cells coexpressing CD38 and CD101, representing a fixed dysfunctional subpopulation that are not able to be rescued by anti-PD-1 immunotherapy. However, whether this subpopulation of PD-1 expressing CD8<sup>+</sup> T cells could be useful in predicting PDAC stage or prognosing survival is unknown. In this study, we used flow cytometry and immunofluorescence assay to analyze the expression of CD38 and CD101 in 183 clinical PDAC samples, including 84 of peripheral blood and 99 of surgical tissues. High coexpression of CD38/CD101 on peripheral PD-1<sup>+</sup>CD8<sup>+</sup> T cells or tumor-infiltrating lymphocytes (TILs) was found to be most significantly correlated with Tumor/Node/Metastasis (T/N/M) classification and clinical stage, in contrast PD-1<sup>+</sup>CD8<sup>+</sup> T cells could not correlate with T classification. CD38/CD101 co-repression on TILs also correlated with the poor survival in these PDAC patient samples. Our data suggest that CD38/CD101 might represent a more helpful biomarker than PD-1 alone for diagnosis and prognosis of PDAC.
THE HYDROGENATION OF AROMATIC KETONES WITH HYDROGEN AND COPPER-CHROMIUM OXIDE CATALYST (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE HYDROGENATION OF AROMATIC KETONES WITH HYDROGEN AND COPPER-CHROMIUM OXIDE CATALYSTDOROTHY NIGHTINGALE and HERSCHEL D. RADFORDCite this: J. Org. Chem. 1949, 14, 6, 1089–1093Publication Date (Print):November 1, 1949Publication History Published online1 May 2002Published inissue 1 November 1949https://pubs.acs.org/doi/10.1021/jo01158a018https://doi.org/10.1021/jo01158a018research-articleACS PublicationsRequest reuse permissionsArticle Views309Altmetric-Citations9LEARN 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
Families of Neural Adhesion Molecules (2007)

The neural cell adhesion molecules L1 and N-CAM share a common carbohydrate epitope that is recognized by the monoclonal antibodies L2 and HNK-1. The L2/HNK-1 epitope is also present on the myelin-associated glycoprotein (MAG) and secreted J1 glycoprotein, both of which have been identified as cell adhesion molecules. Each of the four adhesion molecules is differentially expressed during development on distinct cell types. Expression of the L2/HNK-1 epitope is regulated independently of the protein backbone, is phylogenetically conserved, and plays a role in cell-cell and, particularly, cell-substrate interactions. Another set of glycoproteins shares a common carbohydrate epitope designated L3. This epitope is present on the novel adhesion molecule on glia (AMOG), L1 and MAG, but not on J1 and N-CAM. As in the L2/HNK-1 family, the number of glycoproteins expressing this epitope is not yet known. It is therefore possible that heterogeneities in carbohydrate structures are associated with different sets of adhesion molecules and may have functional implications.
Internal ribosome entry site-based vectors for combined gene therapy (2015)

Gene therapy appears as a promising strategy to treat incurable diseases. In particular, combined gene therapy has shown improved therapeutic efficiency. Internal ribosome entry sites (IRESs), RNA elements naturally present in the 5' untranslated regions of a few mRNAs, constitute a powerful tool to co-express several genes of interest. IRESs are translational enhancers allowing the translational machinery to start protein synthesis by internal initiation. This feature allowed the design of multi-cistronic vectors expressing several genes from a single mRNA. IRESs exhibit tissue specificity, and drive translation in stress conditions when the global cell translation is blocked, which renders them useful for gene transfer in hypoxic conditions occurring in ischemic diseases and cancer. IRES-based viral and non viral vectors have been used successfully in preclinical and clinical assays of combined gene therapy and resulted in therapeutic benefits for various pathologies including cancers, cardiovascular diseases and degenerative diseases.
An 8Kx8 bit static MOS RAM fabricated by n-MOS/n-well CMOS technology (1980)

A 64 kbit fully static MOS RAM which contains about 402500 elements on the chip area of 5.44/spl times/5.80 mm has been designed. The memory cell is a basic cross-coupled flip-flop with four n-MOSFETs and two polysilicon load resistors. The memory cell size is decreased to 16/spl times/19 /spl mu/m (304 /spl mu/m/SUP 2/) by using advanced n-MOS technology with double-level polysilicon films and photolithography of 2 /spl mu/m dimensions. By applying n-well CMOS technology fabricated on a high-resistivity p-type silicon substrate to peripheral circuits of the RAM, high performance characteristics with high speed access times and low power dissipation are obtained. The RAM is designed for single 5 V operation. Address and chip select access times are typically 80 ns. Power dissipation in the active and standby mode is typically 300 and 75 mW, respectively.
Molecular and immunological characterization of ADP-ribosylarginine hydrolases. (1992)

Mono-ADP-ribosylation is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the forward and reverse reactions, respectively.Hydrolase activities were present in a variety of animal species, with the highest specific activities found in rat and mouse brain, spleen, and testis.Rat and mouse hydrolases were dithiothreitol-and Mg2+-dependent, whereas the bovine and guinea pig enzymes were dithiothreitol-independent.A rat brain hydrolase was purified -20,000-fold and represented the major -39-kDa protein on denaturing gels.Immunoaffinity-purified rabbit polyclonal antibodies reacted with 39-kDa proteins from turkey erythrocytes and rat, mouse, and calf brains.A rat brain cDNA library was screened using oligonucleotide and polymerase chain reactiongenerated cDNA probes.Inserts from two overlapping clones yielded a composite sequence that included a 108%-base pair open reading frame, which contained amino acid sequences found in the purified hydrolase.A hydrolase fusion protein, synthesized in Escherichia coli, reacted with anti-39-kDa polyclonal antibodies and exhibited M8+-and dithiothreitol-dependent hydrolase activity.A coding region cDNA hybridized readily to a 1.7-kilobase band in rat and mouse poly(A)+ RNA, but poorly to bovine, chicken, rabbit, and human poly(A)+ RNA.The immunological and molecular biological data are consistent with partial conservation of hydrolase structure across animal species.ADP-ribosylation is a post-translational modification of proteins, which participates in normal eukaryotic cell physiology and in the pathogenesis of disease (1-6).Several bac-
An improved model of experimentally induced ocular hypertension in the rabbit. (1976)

A model of experimentally induced ocular hypertension for the evaluation of antiglaucoma drugs in the unanesthetized rabbit is described. It is based on the intravenous infusion of suitable amounts of 5 per cent glucose solution, and advantageously substitutes the oral water load. The method is sensitive to drugs acting both on the outflow facility (2 per cent pilocarpine) and an aqueous humor formation (10 per cent guanethidine).