gebhart/patrepeval huggingface dataset:
CTLA-4 and PD-1 Pathways (2015)

The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets, resulting in increased activation of the immune system, has led to new immunotherapies for melanoma, non–small cell lung cancer, and other cancers. Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma. Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. The roles of CTLA-4 and PD-1 in inhibiting immune responses, including antitumor responses, are largely distinct. CTLA-4 is thought to regulate T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in an immune response, primarily in peripheral tissues. The clinical profiles of immuno-oncology agents inhibiting these 2 checkpoints may vary based on their mechanistic differences. This article provides an overview of the CTLA-4 and PD-1 pathways and implications of their inhibition in cancer therapy.
C1q (C1) Receptor on Human Platelets: Inhibition of Collagen-Induced Platelet Aggregation by C1q (C1) Molecules (1976)

Hemolytically active human C1q incubated with EA before the addition of complement inhibited the immune hemolysis. On the contrary, heat-inactivated preparation (30 min 56 degrees C) was ineffective. Preincubation of EA with bovine collagen also resulted in a decreased hemolysis. When aggregation was measured by a turbidimetric method in citrated human platelet-rich plasma, it was found that hemolytically active human C1q (C1) alone does not induce platelet aggregation. However, in its presence the platelets failed to aggregate or exhibited a significantly reduced aggregation response to bovine collagen. The inhibition by C1q depended on the preincubation time with platelets. Heat treatment (30 min 56 degrees C) destroyed the inhibitory action of C1q (C1). The effect of C1q proved to be highly specific because different C1q preparations at their inhibitory doses in collagen-induced platelet aggregation did not influence the response to other aggregating agents (bovine thrombin, ADP, horse anti-human thymocyte globulin, goat anti-baboon platelet antiserum). The results prove that collagen and C1q are capable of binding to the same site(s); namely, to those of EA and human platelets; furthermore, they suggest the presence of a receptor for C1q (C1) on human platelets.
Autologous cell transplantation and cardiac tissue engineering: Potential applications in heart failure (2003)

The promising concept of cell transplantation and cardiac tissue engineering has been developed in the last few years and focused on strategies attempting to replace dysfunctional, necrotic, and/or apoptotic cardiomyocytes with new cells of mesodermal origin. Transplantation of autologous cells minimizes the risk of neoplasia and avoids immune rejection associated with allogenic or xenogenic cells and recent data hold enormous hopes for short term clinical practices. Tissue engineering represents another promising approach that makes possible the creation of new functional tissues to replace the lost or failing one. Three-dimensional polymeric scaffolds provide the mechanical support for the candidate cells until the formation of cardiac-like tissue prior to surgical repair of the infarcted myocardium. For ultimate clinical applications, further investigations have to select the appropriate cell types, to determine the sufficient number of grafted cells and to provide the long term evaluation of these strategies in the global improvements of cardiac function (neoangiogenesis, synchronous contraction and extracellular matrix remodelling).
B Cells in Autoimmune Diseases (2012)

The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell mediated. This new understanding of the role of B cells opened up novel therapeutic options for the treatment of autoimmune diseases. This paper includes an overview of the different functions of B cells in autoimmunity; the involvement of B cells in systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes; and current B-cell-based therapeutic treatments. We conclude with a discussion of novel therapies aimed at the selective targeting of pathogenic B cells.
Variation in TCF7L2 Influences Therapeutic Response to Sulfonylureas (2007)

TCF7L2 variants influence therapeutic response to sulfonylureas but not metformin. This study establishes that genetic variation can alter response to therapy in type 2 diabetes.
The effect of polymer surface on the wetting and adhesion of liquid systems (2007)

Abstract Young's equation describes the wetting phenomenon in terms of the contact angle between a liquid and a solid surface. However, the contact angle is not the only parameter that defines liquid–solid interactions, an additional parameter related to the adhesion between the liquid drop and the solid surface is also of importance in cases where liquid sliding is involved. It is postulated that wetting which is related to the contact angle, and interfacial adhesion, which is related to the sliding angle, are interdependent phenomena and have to be considered simultaneously. A variety of models that relate the sliding angle to the forces developed along the contact periphery between a liquid drop and a solid surface have been proposed in the literature. Here, a modified model is proposed that quantifies the drop-sliding phenomenon, based also on the interfacial adhesion that develops across the contact area of the liquid/solid interface. Consequently, an interfacial adhesion strength parameter can be defined depending on the mass of the drop, the contact angle and the sliding angle. To verify the proposed approach the adhesion strength parameter has been calculated, based on experimental results, for a number of polymer surfaces and has been correlated with their composition and structure. The interaction strength parameter can be calculated for any smooth surface from measurements of the contact and the sliding angles. Keywords: MOLECULAR BONDINGMOLECULAR STRUCTUREWETTINGCONTACT ANGLESLIDING ANGLEINTERFACIAL ADHESIONPOLYMER SURFACES
SOS - STAN'S OWN SERVER: AN NFS FILE SERVER FOR THE IBM PC (1988)

SOS is a file server written to run on the IBM PC or compatibles.It conforms to Sun Microsystem's Network File System {NFS) .protocolversion 2. This paper discusses the SOS implementation and includes notes on portability, for programmers who wish to uriderstand or modify it.
Primary astrocytes retrovirally transduced with a tyrosine hydroxylase transgene driven by a glial‐specific promoter elicit behavioral recovery in experimental Parkinsonism (2000)

We used a retroviral-mediated gene transfer system to transduce primary rat astrocytes with a transgene in which the activity of a tyrosine hydroxylase (TH) cDNA is under the transcriptional control of a human promoter of the glial fibrillary acidic protein (GFAP). The engineered cells were tested for their therapeutic efficacy in a rodent model of Parkinson's disease (PD). The method is based both on the properties of astrocytes, as well as on those of the promoter. Astrocytes are an integral part of the neural tissue, have a long life span, are more resistant to oxidative stress than neurons, and possess an efficient secretory system. The GFAP promoter is active throughout postnatal life, and its activity is up-regulated by many insults to the brain, including PD. Transduced astrocytes were implanted into the striata of rats lesioned with 6-hydroxydopamine (6-OHDA), and the efficacy of grafted cells tested. Implanted astrocytes induced a significant reduction in the turning behavior that occurs in response to apomorphine for at least 4 weeks after grafting, and transgenic mRNA and protein could be detected in implanted brains. These results indicate that the gFa2-TH construct can be readily adapted to be used with a retroviral gene transfer system to obtain nontumorigenic cells that sustain a sufficient level of transgene activity to enable therapeutic effectiveness for prolonged periods. These results further endorse the use of astrocytes for gene therapy in the central nervous system. J. Neurosci. Res. 59:39–46, 2000 © 2000 Wiley-Liss, Inc.
DNA Polymerase β:  Structure−Fidelity Relationship from Pre-Steady-State Kinetic Analyses of All Possible Correct and Incorrect Base Pairs for Wild Type and R283A Mutant (1997)

The kinetic parameters (kpol, Kd app) for all possible correct and incorrect pairing between the A, T, G, and C bases were determined for wild-type (WT) rat DNA polymerase beta (pol beta) and the R283A mutant under pre-steady-state kinetic assay conditions. The base substitution fidelities of these two proteins were then determined for all 12 possible mispairs representing the first complete fidelity analysis of polymerases using pre-steady-state kinetics. The results led to several significant findings: (i) For both WT and R283A, the fidelity is determined primarily by kpol (decreases for the incorporation of incorrect nucleotides) and to a small extent by Kd app (increases for the incorporation of incorrect nucleotides). (ii) In general, the fidelity for the Y.X (incorporation of dXTP opposite template dYMP) mismatch is different from that for the X.Y mismatch, reflecting the asymmetry of the active site. (iii) The fidelity of R283A is reduced in all 12 mispairs compared to that of WT. The extent of decrease varies from 200-fold for the A.G mispair to 2.5-fold for the T.C mispair. In general, the differences in fidelity between the mutant and WT are greater for purine.purine mismatches (up to 200-fold) than purine.pyrimidine, pyrimidine. purine, or pyrimidine.pyrimidine mismatches (up to 19-fold). (iv) Overall, the decreases in the fidelity of the R283A mutant are caused mainly by changes in the values of kpol; the kpol values of correct incorporations decrease to a greater extent for the R283A mutant with respect to WT than those of incorrect incorporations. With the exception of G.C, the values of Kd app for the WT and R283A mutant remain constant for correct pairings and vary by less than a factor of 4 for incorrect pairings. (v) For WT pol beta, the Kd app of G.C (8.6 microM) is distinctly smaller than that of other correct base pairs (41-108 microM). For the R283A mutant, the kpol of G.C is higher by a factor of 15-17.
"Ideal" behavior of the open circuit voltage of semiconductor/liquid junctions (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT"Ideal" behavior of the open circuit voltage of semiconductor/liquid junctionsMary L. Rosenbluth and Nathan S. LewisCite this: J. Phys. Chem. 1989, 93, 9, 3735–3740Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 May 1989https://pubs.acs.org/doi/10.1021/j100346a072https://doi.org/10.1021/j100346a072research-articleACS PublicationsRequest reuse permissionsArticle Views949Altmetric-Citations89LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. (1990)

Species restrictions in immune cell interactions have been demonstrated both in Ag-specific responses of T lymphocytes and the phenomenon of natural attachment. To determine the possible contribution of adhesion receptors to these restrictions, we have studied binding between the murine and human homologues of LFA-1 (CD11a/CD18) and ICAM employing purified human LFA-1 and ICAM-1 (CD54) bound to solid substrates. Murine cell lines bind to purified human LFA-1 through ICAM-1 and at least one other counter-receptor. This provides evidence for multiple counter-receptors for LFA-1 in the mouse as well as in the human. In contrast to binding of murine ICAM-1 to human LFA-1, murine LFA-1 does not bind to human ICAM-1. The species specificity maps to the LFA-1 alpha subunit, because mouse x human hybrid cells expressing the human alpha subunit associated with a mouse beta subunit bind to human ICAM-1, whereas those with a human beta subunit associated with a murine alpha subunit do not. Increased adhesiveness for ICAM-1 stimulated by phorbol esters could be demonstrated for hybrid LFA-1 molecules with human alpha and murine beta subunits.
Single amino acid changes in the human immunodeficiency virus type 1 matrix protein block virus particle production (1994)

The matrix protein of human immunodeficiency virus type 1 is encoded by the amino-terminal portion of the Gag precursor and is postulated to be involved in a variety of functions in the virus life cycle. To define domains and specific amino acid residues of the matrix protein that are involved in virus particle assembly, we introduced 35 amino acid substitution mutations in the human immunodeficiency virus type 1 matrix protein. Using reverse transcriptase and radioimmunoprecipitation analyses and transmission electron microscopy, we assessed the mutants for their ability to form virus particles and to function in the infection process. This study has identified several domains of the matrix protein in which single amino acid substitutions dramatically reduce the efficiency of virus particle production. These domains include the six amino-terminal residues of matrix, the region of matrix between amino acids 55 and 59, and the region between amino acids 84 and 95. Single amino acid substitutions in one of these domains (between matrix amino acids 84 and 88) result in a redirection of the majority of virus particle formation to sites within cytoplasmic vacuoles.
Anterior expandable strut cage replacement for osteoporotic thoracolumbar vertebral collapse (2006)

An expandable titanium cage strut seems useful in vertebral body replacement in patients with osteoporotic thoracolumbar collapse. Favorable results were obtained in cases of Type I collapse (wedge type) in which the middle and posterior columns remained comparatively intact.
Distributed Hierarchical Control Architecture for Transient Dynamics Improvement in Power Systems (2013)

In this paper, a novel distributed hierarchical control architecture is proposed for large-scale power systems. The newly proposed architecture facilitates faster and more accurate frequency restoration during primary frequency control, by providing decentralized robust control to several selected pilot generators in each area. At the local level, these decentralized robust controllers are designed to quickly damp oscillations and restore frequency after large faults and disturbances in the system. Incorporating this supplementary governor control helps the system reach the nominal frequency without necessarily requiring secondary frequency control. Thus, at the area level, automatic generation control (AGC) actions are alleviated in terms of conducting frequency restoration. Moreover, at the area level, AGC coordinates with the decentralized robust controllers to successfully perform tie-line power balancing, while efficiently damping low-frequency inter-area oscillations. The interaction of local and area controllers is validated through detailed simulations.
Enhancing the copy number of episomal plasmids in Saccharomyces cerevisiae for improved protein production (2012)

2 μm-based episomal expression vectors are widely used in Saccharomyces cerevisiae for recombinant protein production and synthetic pathway optimization. In this study, we report a new approach to increase the plasmid copy number (PCN) and thus improve the expression of plasmid-encoded proteins. This was achieved by combining destabilization of the marker protein with decreasing the marker gene transcription level. Destabilization of the marker protein alone by fusing a ubiquitin/N-degron tag (ubi-tag) to the N-terminus of the Ura3 marker protein could increase the PCN and activity of LacZ expressed from the same vector. When arginine was exposed at the N-terminus of the marker protein after cleavage of ubiquitin, the PCN and LacZ activity were increased by 70-80%. Replacement of the native URA3 promoter with the HXT1, KEX2 or URA3-d promoter resulted in an increase in the PCN and LacZ activity by about 30-100%. Combining the ubi-tag and promoter modification of the marker gene, increased the PCN and LacZ activity by threefold. We also demonstrated that this new expression vectors can be used to increase enzyme activity by improving patchoulol production by threefold.
Paracrine Mechanisms of Mesenchymal Stem Cell-Based Therapy: Current Status and Perspectives (2013)

Mesenchymal stem cells (MSCs) are one of a few stem cell types to be applied in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair. In addition to their multipotent differentiation potential, a strong paracrine capacity has been proposed as the principal mechanism that contributes to tissue repair. Apart from cytokine/chemokine secretion, MSCs also display a strong capacity for mitochondrial transfer and microvesicle (exosomes) secretion in response to injury with subsequent promotion of tissue regeneration. These unique properties of MSCs make them an invaluable cell type to repair damaged tissues/organs. Although MSCs offer great promise in the treatment of degenerative diseases and inflammatory disorders, there are still many challenges to overcome prior to their widespread clinical application. Particularly, their in-depth paracrine mechanisms remain a matter for debate and exploration. This review will highlight the discovery of the paracrine mechanism of MSCs, regulation of the paracrine biology of MSCs, important paracrine factors of MSCs in modulation of tissue repair, exosome and mitochondrial transfer for tissue repair, and the future perspective for MSC-based therapy.
Recapitulating complex biological signaling environments using a multiplexed, DNA-patterning approach (2020)

Elucidating how the spatial organization of extrinsic signals modulates cell behavior and drives biological processes remains largely unexplored because of challenges in controlling spatial patterning of multiple microenvironmental cues in vitro. Here, we describe a high-throughput method that directs simultaneous assembly of multiple cell types and solid-phase ligands across length scales within minutes. Our method involves lithographically defining hierarchical patterns of unique DNA oligonucleotides to which complementary strands, attached to cells and ligands-of-interest, hybridize. Highlighting our method's power, we investigated how the spatial presentation of self-renewal ligand fibroblast growth factor-2 (FGF-2) and differentiation signal ephrin-B2 instruct single adult neural stem cell (NSC) fate. We found that NSCs have a strong spatial bias toward FGF-2 and identified an unexpected subpopulation exhibiting high neuronal differentiation despite spatially occupying patterned FGF-2 regions. Overall, our broadly applicable, DNA-directed approach enables mechanistic insight into how tissues encode regulatory information through the spatial presentation of heterogeneous signals.
On the Specificity of Bacteriophage-Induced Hydroxymethylcytosine Glucosyltransferases. 2. Specificities of Hydroxymethyleytosine alpha- and beta-Glucosyltransferases Induced by Bacteriophage T4 (1967)

Glucose-less DNA of the T-even bacteriophage type was glucosylated in vitro by the T4-specific hydroxymethylcytosine α- and β-glucosyltransferases separately and by mixtures of the two enzymes in the presence of varying concentrations of Mg++ ions. The α- and β-glucose content of the glucosylated 5-hydroxymethylcytosine residues in the recovered DNA was analyzed. The results indicate that the 5-hydroxymethylcytosine-α-glucosyltransferase is not capable of glucosylating hydroxymethyldeoxyctidine nucleotide, whereas the β-glucosyltransferase will react with such 5-hydroxymethyldeoxycytidine nucleotide, whereas the β-glucosyltransferase will react with such 5-hydroxymethylcytosine residues. 5-Hydroxymethyldeoxycytidine nucleotides in all the other sequences examined are susceptible to both enzymes. In the presence of both transferases the ratio of α- and β-glucose residues introduced in vitro can be influenced by changing the Mg++ content of the incubation mixture. This situation applies to 5-hydroxymethylcytosine residues generally and to the 5-hydroxymethylcytosine nucleotides present in some specific sequences. The proportion of α- and β-glucosides in T4 DNA produced in vivo has been found to remain constant irrespective of the Mg++ content of the growth medium.
Code generators (1990)

Code generators, which take a programmer's inputs in the form of some abstraction, design, or direct interaction with the system and write out a source program that implements the details of the application, are reviewed. After a brief overview, four separate presentations cover examples of such systems from four domains. The Tags tools uses abstraction to specify real-time control systems. In this tool, the details of synchronization code are hidden from the designer, but some functionality must still be provided in detail. Microstep is a similar kind of tool for data-processing applications. One can view both Tags and Microstep as high-level specification languages. PSG generates programming environments, i.e. one gives it a nonprocedural specification of a language's syntax and it generates an integrated programming environment for that language. While one must specify the environment in detailed form, the actual code generation is hidden. Escort is a similar system specialized for telecommunications applications. It lets one build, execute, and test specifications for telecommunication systems. Both PSG and Escort illustrate the power of domain-specific tools.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>