gebhart/patrepeval huggingface dataset:
Membranes Activate Tumor- and Virus-Specific Precursor Cytotoxic T Lymphocytes In Vivo and Stimulate Tumor-Specific T Lymphocytes In Vitro (1994)

Plasma membranes contain the entire antigenic repertoire of a cell in the form of processed antigens presented as peptides by major histocompatibility complex (MHC) class I molecules. We report here that plasma membranes but not internal membranes of cognate tumors stimulate murine fibrosarcoma and human melanoma-specific cytotoxic T lymphocyte (CTL) clones in vitro in an antigen-specific. MHC class I-restricted manner. Although stimulation of CTLs by class I-peptide complexes on reconstituted membranes has been documented before, this is the first demonstration of stimulation of cloned CTLs by natural, endogenously processed MHC class I-peptide complexes on plasma membranes. In addition to their ability to stimulate CTLs in vitro, immunization of syngeneic mice with membranes derived from ultraviolet-induced tumor cells, SV40 transformed fibroblasts, or influenza-infected fibroblasts elicits an antigen-specific, MHC class I restricted primary CTL response. To the best of our knowledge, this is also the first demonstration of the ability of cellular membranes to prime an MHC class I-restricted CTL responses in vivo. The ability of membranes to prime a CTL response in vivo suggests that they may be used as T-cell vaccines against tumors or infectious viruses. This approach circumvents the difficulties in generation of human tumor cell lines and identification of CTL-recognized determinants for vaccination and avoids some of the risks associated with whole-cell vaccination such as inoculation of patients with immunosuppressive factors, transforming DNA, or infectious viruses.
Adsorption-Driven Heat Pumps: The Potential of Metal–Organic Frameworks (2015)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAdsorption-Driven Heat Pumps: The Potential of Metal–Organic FrameworksMartijn F. de Lange†‡, Karlijn J. F. M. Verouden†, Thijs J. H. Vlugt‡, Jorge Gascon†, and Freek Kapteijn*†View Author Information† Catalysis Engineering, Chemical Engineering Department, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands‡ Engineering Thermodynamics, Process & Energy Department, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft, The Netherlands*E-mail: [email protected]Cite this: Chem. Rev. 2015, 115, 22, 12205–12250Publication Date (Web):October 23, 2015Publication History Received2 February 2015Published online23 October 2015Published inissue 25 November 2015https://pubs.acs.org/doi/10.1021/acs.chemrev.5b00059https://doi.org/10.1021/acs.chemrev.5b00059review-articleACS PublicationsCopyright © 2015 American Chemical SocietyRequest reuse permissionsArticle Views11179Altmetric-Citations403LEARN 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 SUBJECTS:Adsorption,Energy,Materials,Metal organic frameworks,Stability Get e-Alerts
Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis (2014)

The composition of tumor-targeted T cell infiltrates is a major prognostic factor in colorectal cancer (CRC) outcome; however, the functional role of these populations in prolonging patient survival remains unclear. Here, we evaluated 190 patients with CRC for the presence of functionally active tumor-infiltrating lymphocytes (TILs), the tumor specificity of these TILs, and the correlation between patient TILs and long-term survival. Using intracytoplasmic cytokine staining in conjunction with HLA multimers loaded with tumor peptide and antigen-specific cytokine secretion assays, we determined that TNF-&amp;alpha; expression delineates a population of tumor antigen-specific (TA-specific) cytotoxic T lymphocytes (CTLs) present within tumors from patients with CRC. Upregulation of TNF-&amp;alpha; expression in TILs strongly correlated with an increase in the total amount of intratumoral TNF-&amp;alpha;, which is indicative of tumor-specific CTL activity. Moreover, a retrospective multivariate analysis of 102 patients with CRC, which had multiple immune parameters evaluated, revealed that increased TNF-&amp;alpha; concentration was an independent prognostic factor. Together, these results indicate that the prognostic impact of T cell infiltrates for CRC maybe largely based on subpopulations of active TA-specific T cells within the tumor, suggesting causal implication for these cells in patient survival. Additionally, these results support the use of intratumoral TNF-&amp;alpha;, which is indicative of T cell function, as a prognostic parameter for CRC.
Cell size as a determinant of the clone-forming ability of human keratinocytes. (1985)

Keratinocytes isolated from human epidermis and subsequently cultured may form clones if they are 11 micron or less in diameter but are irreversibly committed to further enlargement and terminal differentiation if they are 12 micron or more in diameter. When a founding cell of 11 micron or less forms a small rapidly growing clone in culture, the cells of that clone are able to found new colonies even when their diameter is as great as 20 micron. As the clone becomes larger and grows more slowly, the maximal size of its clonogenic cells is reduced toward that of the epidermis. A cultured cell of up to 20 micron in diameter can, when it divides, give rise to clonogenic progeny smaller than itself, thus reversing the process of enlargement. Cells larger than 20 micron cannot divide and therefore cannot be rescued from terminal differentiation. It is concluded that when keratinocytes multiply rapidly, they extend reversibly the maximal size at which they are capable of generating clones into the range usually characteristic of terminally differentiating cells. It is proposed that this mechanism enables the keratinocyte to accommodate an increased rate of multiplication to its need to attain a large size during terminal differentiation.
A Quest for Structure: Jointly Learning the Graph Structure and Semi-Supervised Classification (2019)

Semi-supervised learning (SSL) is effectively used for numerous classification problems, thanks to its ability to make use of abundant unlabeled data. The main assumption of various SSL algorithms is that the nearby points on the data manifold are likely to share a label. Graph-based SSL constructs a graph from point-cloud data as an approximation to the underlying manifold, followed by label inference. It is no surprise that the quality of the constructed graph in capturing the essential structure of the data is critical to the accuracy of the subsequent inference step [6]. How should one construct a graph from the input point-cloud data for graph-based SSL? In this work we introduce a new, parallel graph learning framework (called PG-learn) for the graph construction step of SSL. Our solution has two main ingredients: (1) a gradient-based optimization of the edge weights (more specifically, different kernel bandwidths in each dimension) based on a validation loss function, and (2) a parallel hyperparameter search algorithm with an adaptive resource allocation scheme. In essence, (1) allows us to search around a (random) initial hyperparameter configuration for a better one with lower validation loss. Since the search space of hyperparameters is huge for high-dimensional problems, (2) empowers our gradient-based search to go through as many different initial configurations as possible, where runs for relatively unpromising starting configurations are terminated early to allocate the time for others. As such, PG-learn is a carefully-designed hybrid of random and adaptive search. Through experiments on multi-class classification problems, we show that PG-learn significantly outperforms a variety of existing graph construction schemes in accuracy (per fixed time budget for hyperparameter tuning), and scales more effectively to high dimensional problems.
Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma (2015)

Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL), both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life.
Trp2 Peptide Vaccine Adjuvanted with (R)-DOTAP Inhibits Tumor Growth in an Advanced Melanoma Model (2011)

Previously we have shown cationic lipid (R)-DOTAP as the immunologically active enantiomer of the DOTAP racemic mixture, initiating complete tumor regression in an exogenous antigen model (murine cervical cancer model). Here, we investigate the use of (R)-DOTAP as an efficacious adjuvant delivering an endogenous antigen in an aggressive murine solid tumor melanoma model. (R)-DOTAP/Trp2 peptide complexes showed decreasing size and charge with increasing peptide concentration, taking a rod shape at highest concentrations. The particles were stable for 2 weeks at 4 °C. A dose of 75 nmol of Trp2 (formulated in (R)-DOTAP) was able to show statistically significant tumor growth delay compared to lower doses of 5 and 25 nmol, which were no different than untreated tumors. (R)-DOTAP/Trp2 (75 nmol) treated mice also showed increased T cell IFN-γ secretion after restimulation with Trp2, as well as CTL activity in vivo. This vaccination group also showed the highest population of functionally active tumor-infiltrating lymphocytes, indicated by IFN-γ secretion after restimulation with Trp2. Thus, (R)-DOTAP has shown the ability to break tolerance as an adjuvant. Its activity to enhance immunogenicity of other tumor associated antigens should be studied further.
In Vitro Stimulation and Expansion of Human Tumour‐Reactive CD8+ Cytotoxic T Lymphocytes by Anti‐CD3/CD28/CD137 Magnetic Beads (2011)

Abstract Adoptive immunotherapy with tumour‐reactive CD8 + cytotoxic T lymphocytes (CTLs) requires efficient in vitro approaches allowing the expansion of CTLs to large numbers prior infusion. Here, we investigated the antigen‐independent activation and the expansion of human T cells in peripheral blood mononuclear cells (PBMCs) and in tumour‐reactive CTLs using Dynabeads coated with monoclonal antibodies to CD3 and to the costimulatory molecules CD28 and CD137 (4‐1BB). T cells in PBMCs showed an increased expansion rate of 15‐ to 17‐fold during a 2‐week culture period using antibody‐conjugated beads with interleukin‐2 (IL‐2) added versus IL‐2 alone. No significant difference between CD3/CD28 beads and CD3/CD28/CD137 beads was observed ( P = 0.4). In contrast, expansion of tumour‐reactive CD8 + CTLs over 2 weeks was more efficient using CD3/CD28/CD137 beads (14.4‐fold ±1.2) compared with CD3/CD28 beads (10.6‐fold ±0.7) ( P = 0.03) and matched well to the control arm using weekly stimulation with tumour cells. Although all modes of in vitro stimulation decreased the expression of central memory markers CD62L and CCR7 on CTLs, bead‐activated cultures expressed consistently higher levels than tumour‐stimulated cultures. CTLs analysed after bead‐induced expansion versus weekly tumour stimulation showed equal IFN‐γ production in ELISPOT assay. Furthermore, cytotoxicity assays demonstrated an either unchanged or slightly reduced capability of tumour cell lysis for antigen‐independent stimulated CTLs versus those that maintained on weekly tumour stimulation, regardless of which type of beads was used. Our data suggest that the conjugation of anti‐CD137 antibodies to conventional CD3/CD28 beads results in a minor but significant increase in the expansion capacity for tumour‐reactive CD8 + CTLs.
Clindamycin lotion alone versus combination lotion of clindamycin phosphate plus tretinoin versus combination lotion of clindamycin phosphate plus salicylic acid in the topical treatment of mild to moderate acne vulgaris: A randomized control trial (2009)

Our data suggested that the efficacy of CS lotion was significantly more than C lotion with respect to the TLC and ASI, although there was no significant difference between CS and CT lotion.
A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination (2016)

The presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35-40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity.
Functional translation of a calculus of capabilities (2008)

Reasoning about imperative programs requires the ability to track aliasing and ownership properties. We present a type system that provides this ability, by using regions, capabilities, and singleton types. It is designed for a high-level calculus with higher-order functions, algebraic data structures, and references (mutable memory cells). The type system has polymorphism, yet does not require a value restriction, because capabilities act as explicit store typings. We exhibit a type-directed, type-preserving, and meaning-preserving translation of this imperative calculus into a pure calculus. Like the monadic translation, this is a store-passing translation. Here, however, the store is partitioned into multiple fragments, which are threaded through a computation only if they are relevant to it. Furthermore, the decomposition of the store into fragments can evolve dynamically to reflect ownership transfers. The translation offers deep insight about the inner workings and soundness of the type system. If coupled with a semantic model of its target calculus, it leads to a semantic model of its imperative source calculus. Furthermore, it provides a foundation for our long-term objective of designing a system for specifying and certifying imperative programs with dynamic memory allocation.
Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor (2002)

The product of the von Hippel-Lindau gene, pVHL, targets the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF) for polyubiquitination in the presence of oxygen. The binding of pVHL to HIF is governed by the enzymatic hydroxylation of conserved prolyl residues within peptidic motifs present in the HIFalpha family members. By using a biochemical purification strategy, we have identified a human homolog of Caenorhabditis elegans Egl9 as a HIF prolyl hydroxylase. In addition, we studied the activity of a structurally diverse collection of low molecular weight inhibitors of procollagen prolyl 4-hydroxylase as potential inhibitors of the HIF hydroxylase. A model compound of this series stabilized HIF in a variety of cells, leading to the increased production of its downstream target, vascular endothelial growth factor.
Synthesis, Biological Evaluation, and Molecular Modeling of Ribose-Modified Adenosine Analogues as Adenosine Receptor Agonists (2005)

A number of 3'-C-methyl analogues of selective adenosine receptor agonists such as CPA, CHA, CCPA, 2'-Me-CCPA, NECA, and IB-MECA was synthesized to further investigate the subdomain of the receptor that binds the ribose moiety of the ligands. Affinity data at A(1), A(2A), and A(3) receptors in bovine brain membranes showed that the 3'-C-modification in adenosine resulted in a decrease of the affinity at all three receptor subtypes. When this modification was combined with N(6)-substitution with groups that induce high potency and selectivity at A(1) receptor, the affinity and selectivity were increased. However, all 3'-C-methyl derivatives proved to be very less active than the corresponding 2'-C-methyl analogues. The most active compound was found to be 3'-Me-CPA which displayed a K(i) value of 0.35 microM at A(1) receptor and a selectivity for A(1) vs A(2A) and A(3) receptors higher than 28-fold. 2'-Me-CCPA was confirmed to be the most selective, high affinity agonist so far known also at human A(1) receptor with a K(i) value of 3.3 nM and 2903- and 341-fold selective vs human A(2A) and A(3) receptors, respectively. In functional assay, 3'-Me-CPA, 3'-Me-CCPA, and 2-Cl-3'-Me-IB-MECA inhibited forskolin-stimulated adenylyl cyclase activity with IC(50) values ranging from 0.3 to 4.9 microM, acting as full agonists. A rhodopsin-based model of the bovine A(1)AR was built to rationalize the higher affinity and selectivity of 2'-C-methyl derivatives of N(6)-substituted-adenosine compared to that of 3'-C-methyl analogues. In the docking exploration, it was found that 2'-Me-CCPA was able to form a number of interactions with several polar residues in the transmembrane helices TM-3, TM-6, and TM-7 of bA(1)AR which were not preserved in the molecular dynamics simulation of 3'-Me-CCPA/bA(1)AR complex.
Cytomegalovirus Studies of Autopsy Tissue: II. Incidence of Inclusion Bodies and Related Pathologic Data (1975)

Cytomegaloviruses (CMV) were recovered from lung tissue in 34 (6.8%) of 502 unselected autopsy cases. Inclusion bodies were detected in the lung in nine of these cases (26%) and in organs other than the lung in three others. Overall, the incidence of inclusion bodies in this series of 502 cases was 2.4%. Our data strongly indicate that virus isolation is more sensitive than histopathologic study in establishing the presence of CMV infection. However, CMV was not recovered from one kidney and one liver in which inclusion bodies were present, although the virus was isolated from lung. Four of five cases of renal allograft rejection were positive for both CMV and inclusion bodies. The incidence of CMV recovery and inclusion body detection in leukemia and lymphoma cases was more than twice that in cases with other diseases. CMV inclusion bodies with or without associated inflammation were found, in descending order of frequency, in the lung, kidney, liver, pancreas, adrenal gland, esophagus, prostate, testes, thyroid gland, parathyroid gland, stomach, small intestine, large intestine, and heart.
Neutrality of International Languages (2006)

This paper focuses on the neutrality of international languages. First, a derivation of the concept of “neutral language” from “inter- national communicative act” is provided; it is argued that an acceptable neutral language for international communication can only be an artificial language. Certain characterizations of consciously created languages are discussed. The paper distinguishes two types of neutrality: communicative neutrality and linguistic neutrality. All planned languages are communicatively neutral, but their linguistic neutrality varies, reflecting the diversity of language design principles. Given that absolute linguistic neutrality unattainable, it becomes reasonable to construct a language based on certain control languages plus linguistic universals. We introduce the term “deneutralization” to designate a process whereby a neutral language changes into an ordinary language. The paper also shows that Esperanto has not become deneutralized.
Chromophores in human skin (1997)

Human skin, especially the epidermis, contains several major solar ultraviolet-radiation- (UVR-) absorbing endogenous chromophores including DNA, urocanic acid, amino acids, melanins and their precursors and metabolites. The lack of solubility of melanins prevents their absorption spectra being defined by routine techniques. Indirect spectroscopic methods show that their spectral properties depend on the stimulus for melanogenesis. The photochemical consequences of UVR absorption by some epidermal chromophores are relatively well understood whereas we lack a detailed understanding of the consequent photobiological and clinical responses. Skin action spectroscopy is not a reliable way of relating a photobiological outcome to a specific chromophore but is important for UVR hazard assessment. Exogenous chromophores may be administered to the skin in combination with UVR exposure for therapeutic benefit, or as sunscreens for the prevention of sunburn and possibly skin cancer.
Simultaneous quantitative assessment of circulating cell-free mitochondrial and nuclear DNA by multiplex real-time PCR (2009)

Quantification of circulating nucleic acids in plasma and serum could be used as a non-invasive diagnostic tool for monitoring a wide variety of diseases and conditions. We describe here a rapid, simple and accurate multiplex real-time PCR method for direct synchronized analysis of circulating cell-free (ccf) mitochondrial (mtDNA) and nuclear (nDNA) DNA in plasma and serum samples. The method is based on one-step multiplex real-time PCR using a FAM-labeled MGB probe and primers to amplify the mtDNA sequence of the ATP 8 gene, and a VIC-labeled MGB probe and primers to amplify the nDNA sequence of the glycerinaldehyde-3-phosphate-dehydrogenase (GAPDH) gene, in plasma and serum samples simultaneously. The efficiencies of the multiplex assays were measured in serial dilutions. Based on the simulation of the PCR reaction kinetics, the relative quantities of ccf mtDNA were calculated using a very simple equation. Using our optimised real-time PCR conditions, close to 100% efficiency was obtained from the two assays. The two assays performed in the dilution series showed very good and reproducible correlation to each other. This optimised multiplex real-time PCR protocol can be widely used for synchronized quantification of mtDNA and nDNA in different samples, with a very high rate of efficiency.
High-accuracy laser mask repair technology using ps UV solid state laser (2002)

Laser Mask Repair System named LM700A has been developed to satisfy the increasing demands for higher accuracy with thigh throughput photomask repair system in recent semiconductor industry requirements. This paper introduces the basic configuration of the system, evaluated results for Chromium (Cr) binary masks and Molybdenum Silicide (MoSi) HalfTone (HT) phaseshift masks repairing performances, and the features of removing process using mid range (250ps) pulse duration ablation mechanism.