gebhart/patrepeval huggingface dataset:
Dynamic Regulation of LFA-1 Activation and Neutrophil Arrest on Intercellular Adhesion Molecule 1 (ICAM-1) in Shear Flow (2002)

Neutrophil recruitment during acute inflammation is triggered by G-protein-linked chemotactic receptors that in turn activate beta(2) integrin (CD18), deemed a critical step in facilitating cell capture and arrest under the shear force of blood flow. A conformational switch in the I domain allosteric site (IDAS) and in CD18 regulates LFA-1 affinity for endothelial ligands including intercellular adhesion molecule 1 (ICAM-1). We examined the dynamics of CD18 activation in terms of the efficiency of neutrophil capture of ICAM-1, and we correlated this with the membrane topography of 327C, an antibody that recognizes the active conformation of CD18 I-like domain. Adhesion increased in direct proportion to chemotactic stimulus rising 7-fold over a log range of interleukin-8 (IL-8). A threshold dose of approximately 75 pm IL-8, corresponding to ligation of only approximately 10-100 receptors, was sufficient to activate approximately 20,000 CD18 and a rapid boost in the capture efficiency on ICAM-1. This was accompanied by a rapid redistribution of active LFA-1, but not Mac-1, into membrane patches, a necessary component for optimum adhesion efficiency. Shear-resistant arrest on a monolayer of ICAM-1 was reversed within minutes of chemotactic stimulation correlating with a shift from high to low affinity CD18 and dispersal of patches of active CD18. Mobility of active CD18 into high avidity patches was dependent on phosphatidylinositol 3-kinase activity and not F-actin polymerization. The data reveal that the number of chemotactic receptors bound and the topography and lifetime of high affinity LFA-1 tightly regulate the efficiency of neutrophil capture on ICAM-1.
Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myelodysplastic syndromes (2004)

The findings suggest that different mechanisms are involved in the pathophysiology of AML and MDS. The concentration of sVEGFR1 and sVEGFR2 in plasma should be considered a significant factor in guiding antiangiogenic therapy for AML and MDS. They may play a role in the pharmacodynamics of therapeutic agents that are supposed to bind directly to these receptors.
Virtualizing Transactional Memory (2005)

Writing concurrent programs is difficult because of the complexity of ensuring proper synchronization. Conventional lock-based synchronization suffers from wellknown limitations, so researchers have considered non-blocking transactions as an alternative. Recent hardware proposals have demonstrated how transactions can achieve high performance while not suffering limitations of lock-based mechanisms. However, current hardware proposals require programmers to be aware of platform-specific resource limitations such as buffer sizes, scheduling quanta, as well as events such as page faults, and process migrations. If the transactional model is to gain wide acceptance, hardware support for transactions must be virtualized to hide these limitations in much the same way that virtual memory shields the programmer from platform-specific limitations of physical memory. This paper proposes Virtual Transactional Memory (VTM), a user-transparent system that shields the programmer from various platform-specific resource limitations. VTM maintains the performance advantage of hardware transactions, incurs low overhead in time, and has modest costs in hardware support. While manysystem-level challenges remain, VTM takes a step toward making transactional models more widely acceptable.
Transfection of CD14 into 70Z/3 cells dramatically enhances the sensitivity to complexes of lipopolysaccharide (LPS) and LPS binding protein. (1992)

Bacterial endotoxin (lipopolysaccharide [LPS]) causes fatal shock in humans and experimental animals. The shock is mediated by cytokines released by direct LPS stimulation of cells of monocytic origin (monocyte/macrophage [MO]). Recent studies have supported the concept that the plasma protein, LPS binding protein (LBP), plays an important role in controlling MO responses to LPS. Specifically, evidence has been presented to suggest that CD14, a membrane protein present in MO, serves as a receptor for complexes of LPS and the plasma protein LPS binding protein (LBP). In this function CD14 mediates attachment of LPS-bearing particles opsonized with LBP and appears to play an important role in regulating cytokine production induced by complexes of LPS and LBP. The CD14-, murine pre-B cell line 70Z/3 responds to LPS by synthesis of kappa light chains and consequent expression of surface IgM. To better understand the role of CD14 in controlling cellular responses to LPS, we investigated the effect of transfection of CD14 into 70Z/3 cells on LPS responsiveness. We report here that transfection of human or rabbit CD14 cDNA into 70Z/3 cells results in membrane expression of a glycosyl-phosphatidylinositol-anchored CD14. When LPS is complexed with LBP, CD14-bearing 70Z/3 cells bind more LPS than do the parental or 70Z/3 cells transfected with vector only. Remarkably, the expression of CD14 lowers the amount of LPS required to stimulate surface IgM expression by up to 10,000-fold when LPS dose-response curves in the CD14-, parental and CD14-bearing, transfected 70Z/3 cells are compared. In contrast, the response of CD14-bearing 70Z/3 cells and the parental 70Z/3 cell line (CD14-) to interferon gamma is indistinguishable. LPS stimulation of the parental and CD14-bearing 70Z/3 cells results in activation of NF-kB. These data provide evidence to support the concept that the LPS receptor in cells that constitutively express CD14 may be a multiprotein complex containing CD14 and membrane protein(s) common to a diverse group of LPS-responsive cells.
Chimaeric T-cell receptors specific to a B-lymphoma idiotype: a model for tumour immunotherapy (1995)

Conference Article| November 01 1995 Chimaeric T-cell receptors specific to a B-lymphoma idiotype: a model for tumour immunotherapy G. Gross; G. Gross ‡ *Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100 Israel Search for other works by this author on: This Site PubMed Google Scholar S. Levy; S. Levy †Division of Oncology M-207, Stanford University School of Medicine, Stanford, CA 94305, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar R. Levy; R. Levy †Division of Oncology M-207, Stanford University School of Medicine, Stanford, CA 94305, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar T. Waks; T. Waks *Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100 Israel Search for other works by this author on: This Site PubMed Google Scholar Z. Eshhar Z. Eshhar § *Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100 Israel §To whom correspondence should be addressed. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1995) 23 (4): 1079–1082. https://doi.org/10.1042/bst0231079 Article history Received: June 21 1995 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation G. Gross, S. Levy, R. Levy, T. Waks, Z. Eshhar; Chimaeric T-cell receptors specific to a B-lymphoma idiotype: a model for tumour immunotherapy. Biochem Soc Trans 1 November 1995; 23 (4): 1079–1082. doi: https://doi.org/10.1042/bst0231079 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: 38C13, mouse lymphoma expressing surface IgM, S1C5, anti-38C13 idiotype, cTCR, chimaeric T-cell receptor, MHC, major histocompatability This content is only available as a PDF. © 1995 Biochemical Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.
Prevalence of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations and polymorphisms in NNRTI-naïve HIV-infected patients (2002)

In contrast to resistance mutations, RT substitutions at positions involved in NNRTI resistance are frequent. They are not associated with a worse virologic outcome or with decreased phenotypic susceptibility to NNRTIs. It may be prudent not to rule out the use of NNRTIs in patients with small shifts in IC50 values or poorly understood mutations.
Trans Protein Splicing of Cyanobacterial Split Inteins in Endogenous and Exogenous Combinations (2007)

Inteins are autocatalytic protein domains that post-translationally excise from protein precursors and ligate their flanking regions with a peptide bond, in a process called protein splicing. Intein-containing DNA polymerases of cyanobacteria and nanoarchaea are naturally split into two separate genes at their intein domain. Such naturally occurring split inteins rapidly self-associate and reconstitute protein-splicing activity in trans. Here, we analyze the in vitro protein-splicing activity of three naturally split inteins from diverse cyanobacteria: Oscillatoria limnetica, Thermosynechococcus vulcanus, and Nostoc sp. PCC7120. N- and C-terminal halves of these split inteins were mixed in nine combinations, resulting in three endogenous (wild-type) and six exogenous combinations. Protein splicing was detected in all split-intein combinations, despite a 30-50% sequence variation between the homologous proteins. Splicing activity proceeded under a variety of conditions, including the presence of denaturants and reductants and high temperature, ionic strength, and viscosity. Still, in a high concentration of salt (2 M) or urea (6 M), specific combinations spliced significantly better than others. Additionally, copper ions were found to inhibit trans splicing in a reversible double-lock reaction. Our comparative analysis of naturally split inteins in endogenous and exogenous combinations demonstrates the modularity of trans protein-splicing elements and their robust activity. It suggests tight interactions between split-intein halves and conditions for modifying the specificity of intein parts. These results promote the biotechnological use of split inteins for controlled assembly of protein fragments either in vivo or in vitro and under moderate or extreme conditions.
The autonomic nervous system and sudden death. (1998)

The knowledge progressively accumulated on the relation between changes in autonomic activity and cardiac mortality, particularly in the setting of acute myocardial ischaemia, has turned during the last decade toward the potential prognostic value of markers of autonomic activity. Two of these markers, heart rate variability and baroreflex sensitivity, have gained progressive popularity. This chapter reviews some of the experimental observations that were instrumental for the novel clinical approach to post-myocardial infarction risk stratification based on the use of autonomic markers as risk stratifiers. It then focuses on clinical studies with special attention for a very recent multicentre prospective study (ATRAMI) carried out in almost 1300 post-myocardial infarction patients and aimed at the evaluation of the prognostic value of both heart rate variability and baroreflex sensitivity. Finally, some pathophysiological considerations are added to clarify the legitimacy, or lack of it, of the terminology currently used in clinical studies based on autonomic markers.
MESODERM-ECTODERM INTERACTION IN THE PRODUCTION OF THE AGOUTI PIGMENTATION PATTERN IN MICE (1972)

Alleles at the agouti locus in the mouse determine the synthesis of either phaeomelanin or eumelanin by follicular melanocytes by altering the hair follicle environment. The method of dermal-epidermal recombination of mouse skin from C57BL/6J a/a and C57BL/6J A(w-J)/A(w-J) embryos was used in this study to establish the precise site of agouti gene action within the hair follicle. The pigmentary pattern of hairs formed in the recombination skin grafts was specific for the genotype of the dermal (mesodermal) component of the hair follicle. The genotype of the epidermal (ectodermal) component had no influence on the type of hair pigmentary pattern. These results indicate that future studies on gene mechanisms should focus on the dermis as the determining factor in altering the hair follicle environment.
T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. (1987)

CD28 is a homodimeric glycoprotein expressed on the surface of a major subset of human T cells that has recently been identified as a member of the immunoglobulin supergene family. The binding of monoclonal antibodies to the CD28 antigen on purified T cells does not result in proliferation; however, previous studies have shown that the combination of CD28 stimulation and protein kinase C activation by phorbol myristate acetate (PMA) results in T-cell proliferation that is independent of both accessory cells and activation of the T-cell receptor-CD3 complex. In the present study, effects of stimulation by anti-CD28 on cell cycle progression and on the interleukin 2 (IL-2) and IL-2 receptor system have been investigated on primary cultures of purified peripheral-blood CD28+ T cells. There was no measurable effect on cell size or on DNA synthesis after stimulation of resting (G0) cells by CD28 alone. After 3 h of activation of T cells by PMA alone, a slight (8%) increase in cell volume occurred that did not progress to DNA synthesis. In contrast, T-cell stimulation by CD28 in combination with PMA resulted in a progressive increase in cell volume in approximately 100% of cells at 12 to 14 h after stimulation. Northern blot (RNA blot) analysis revealed that CD28 stimulation alone failed to cause expression of the alpha chain of the IL-2 receptor or of IL-2 mRNA, and in accord with previous studies, stimulation by PMA alone resulted in the accumulation of IL-2 receptor transcripts but no detectable IL-2 mRNA. In contrast, T-cell stimulation by the combination of CD28 and PMA resulted in the appearance of IL-2 transcripts and enhanced expression of IL-2 receptor mRNA. Functional studies revealed that the proliferation induced by CD28 and PMA stimulation was entirely resistant to cyclosporine, in contrast to T-cell activation induced by the CD3-T-cell receptor complex. Cyclosporine was found not to affect the accumulation of IL-2 mRNA after CD28 plus PMA stimulation, although there was no detectable IL-2 mRNA after stimulation by CD3 in the presence of the drug. Furthermore, stimulation by CD28 in combination with immobilized CD3 antibodies caused a striking enhancement of IL-2 mRNA expression that was, in part, resistant to the effects of cyclosporine. These studies indicate that the CD28 molecule synergizes with protein kinase C activation to induce IL-2 gene expression and demonstrate that stimulation by the CD28 pathway can cause vigorous T-cell proliferation even in the presence of cyclosporine and that cyclosporine does not prevent transcription of 16-2 mRNA, as has been suggested previously. Moreover, these findings suggest that a potential role for the CD28 molecule in vivo may be to augment IL-2 production after stimulation of the CD3-T-cell receptor molecular complex and thereby to amplify an antigen-specific immune response. Finally, these results provide further evidence that the CD28 molecule triggers T-cell proliferation in a manner that differs biochemically from CD3-T-cell receptor-induced proliferation.
Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. (1994)

To prepare for the DNA synthesis (S) phase of the cell cycle, transcription of many genes required for nucleotide biosynthesis increases. The promoters of several of these genes contain binding sites for the E2F family of transcription factors, and, in many cases, mutation of these sites abolishes growth-regulated transcription. The RNA levels of one family member, E2F1, increase about 15-fold at the G1/S-phase boundary and expression of E2F1 in quiescent cells activates transcription from some G1/S-phase-specific promoters, suggesting that E2F1 plays a critical role in preparing cells to enter S phase. To elucidate the signal transduction pathway leading to the activation of genes required for DNA synthesis, we are investigating the mechanism by which expression of E2F1 is regulated. To determine whether levels of E2F1 mRNA are controlled by changes in promoter activity, we have cloned and characterized the mouse E2F1 promoter. Sequence analysis revealed two sets of overlapping E2F-binding sites located between -12 and -40 relative to the transcription initiation site. We show that these sites bind cellular E2F and that an E2F1 promoter fragment can be activated up to 100-fold by coexpression of E2F proteins. We also show that the activity of this E2F1 promoter fragment increases approximately 80-fold at the G1/S-phase boundary and that this activation is, in part, regulated by G0-specific repression via the E2F sites. However, the E2F sites are not sufficient to mediate growth-regulated transcriptional activity; our results indicate that multiple DNA elements are required for transcription regulation of the E2F1 promoter at the G1/S-phase boundary.
Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis. (1999)

Both lymphotoxin-alpha (LTalpha)-deficient mice and alymphoplasia (aly) mice, a natural mutant strain, manifest a quite similar phenotype: lack of lymph nodes (LN) and Peyer's patches (PP), with disturbed spleen architecture. The mechanisms underlying the defective lymphoid organogenesis in these mice were investigated by generating aggregation chimeras; ex vivo fused morulae were implanted into pseudo-pregnant host females and allowed to develop to term. Chimeric mice between LTalpha-deficient mice and wild-type mice restored LN and PP almost completely, suggesting that LTalpha expressed by circulating bone marrow-derived cells is essential for lymphoid organogenesis as well as for organization of spleen architecture. By contrast, chimeric mice between aly mice and wild-type mice showed only limited restoration of LN and PP. This suggests that the putative aly gene product does not act as a circulating ligand for lymphoid organogenesis, like LTalpha. Rather, abnormal development of lymphoid organs in aly mice seems most likely due to the defective development of the incipient stromal cells of the LN and PP. Supporting this hypothesis, up-regulation of VCAM-1 on aly mouse embryonic fibroblasts by signals through LTbetaR, which is exclusively expressed by nonlymphoid cells, was disturbed. These studies demonstrate that LTalpha and the putative aly gene product together control lymphoid organogenesis with a close mechanistic relationship in their biochemical pathways through governing the distinct cellular compartments, the former acting as a circulating ligand and the latter as a LTbetaR-signaling molecule expressed by the stroma of the lymphoid organs.
Purification and characterization of endogenous peptides extracted from HLA‐DR isolated from the spleen of a patient with rheumatoid arthritis (1995)

We have purified HLA-DR from the spleen of a patient with rheumatoid arthritis. The patient had Felty's syndrome and was heterozygous for the DR4Dw4 antigen. We have isolated endogenous peptides from purified HLA-DR molecules. The peptides were purified by reverse phase HPLC and the major peaks were subjected to N-terminal sequencing. The peptides were derived from a variety of proteins: human serum albumin, human erythroid protein 4.1, 60S ribosomal proteins L31 and L35, VCAM-1, human immunoglobulin lambda chain and cathepsin-S. A peptide corresponding to the sequence of human serum albumin (HSA) residues 106-120 was synthesized and shown to bind to HLA-DR4Dw4 (IC50 = 1.41 microM). We have confirmed and refined current ideas about the structural motif for the binding of peptides to HLA-DR and HLA-DR4Dw4.
Association of an activation inducible serine kinase activity with CD5. (1993)

We show the association of a protein kinase activity with CD5 immunoprecipitates under different detergent conditions (1% digitonin, 1% Triton X-100). This association can be observed in all CD5+ cell types tested (PBMC, thymocytes, B cells from chronic lymphocytic leukemia, and some lymphoblastoid T cell lines as Jurkat, Molt-4, 8402). Phosphoaminoacid analysis of the in vitro phosphorylated proteins and Western blot analysis of the immunoprecipitates with an antiphosphotyrosine mAb show that, in contrast with other lymphocyte receptors (CD3, CD4, IL-2R), CD5 coimmunoprecipitates a serine kinase activity. Our results show also that preactivation of cells through the CD3/TCR complex induces a rapid (detectable in 1-3 min) and transient (returns to basal levels after 10-15 min) increase in the kinase activity associated with CD5 immunoprecipitates. This CD3-induced increase in CD5-associated kinase activity correlates with an increase in CD5 phosphorylation. Furthermore, activation with soluble anti-CD5 mAb induces also an increase in the kinase activity associated with this receptor. In contrast with the increase observed after activation with CD3, after activation with CD5 the increase in the kinase activity peaks after 10 min and is maintained for 1 h. These different kinetics suggest that there may exist different mechanisms that regulate this phenomenon.
Narrowband wavelength selective detector applicable SD-OCT based on Fabry-Perot tunable filter and balanced photoreceiver (2008)

We demonstrate a novel implementation of spectral domain OCT by using a proposed sweeping detector at 1320 nm wavelength range. A fiber pigtailed Fabry-Perot tunable filter is newly adapted to receive spectral interferometer information using a photo-receiver instead of using charged couple detector arrays. In order to show a possibility of the scheme in other view point, we have changed the position of the Fabry-Perot tunable filter of the interferometer. The combination of a super luminescent LED and a semiconductor optical amplifier was used as an optical source. Its output power is about 10 mW and the spectral bandwidth is about 60 nm. The filtered light after passing thorough the Fabry- Perot tunable filter has 0.15 nm instantaneous spectral linewidth with 1.3 mW average output power. The system with an axial resolution of 12 &mu;m performed OCT imaging of a cornea of a rat eye proving potential about the application of the proposed sweeping detector OCT.