gebhart/patrepeval huggingface dataset:
T cell adhesion to intercellular adhesion molecule-1 (ICAM-1) is controlled by cell spreading and the activation of integrin LFA-1 (1996)

Many leukocyte integrins require activation before they can adhere to their ligands. For example, stimulation of T cells enables the integrin LFA-1 to bind to ligand. This study compares two well known protocols for inducing T cell LFA-1 mediated adhesion to intercellular adhesion molecule-1 (ICAM)-1. We how that treatment with high concentrations of the divalent cation Mg2+ induces a high affinity state of LFA-1, which is reflected in the binding of soluble ICAM-1 and correlates with the expression of the epitope recognized by mAb 24. The second stimulation protocol with the phorbol ester phorbol-12,13-dibutyrate (PDBu) does not induce a high affinity state of LFA-1, and in this situation, adhesion is dependent on cell spreading and intracellular events involving protein kinase C, [Ca2+]i, and actin polymerization. These low affinity LFA-1 receptors are responsible for the initial contact with immobilized ligand because, unlike the Mg2+-stimulated receptors, adhesion is not blocked by soluble ICAM-1. Finally, we used a third method of inducing LFA-1-mediated adhesion by stimulation of T cells through the TCR/CD3 complex. This procedure, which is considered to be a more physiologic trigger for LFA-1 activation, resembles the phorbol ester protocol in that high affinity LFA-1 receptors are not induced and cell adhesion depends on involvement of the cytoskeleton and cell spreading.
Genomic Prediction of Locoregional Recurrence After Mastectomy in Breast Cancer (2006)

Using gene expression profiles to develop prediction tree models effectively identifies breast cancer patients who are at higher risk for LR recurrence. This gene expression-based predictive index can be used to select patients for PMRT.
Thyroid Disease and Lipids (2002)

The composition and the transport of lipoproteins are seriously disturbed in thyroid diseases. Overt hypothyroidism is characterized by hypercholesterolaemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B (apo A) because of a decreased fractional clearance of LDL by a reduced number of LDL receptors in the liver. The high-density lipoprotein (HDL) levels are normal or even elevated in severe hypothyroidism because of decreased activity of cholesteryl-ester transfer protein (CETP) and hepatic lipase (HL), which are enzymes regulated by thyroid hormones. The low activity of CETP, and more specifically of HL, results in reduced transport of cholesteryl esters from HDL(2) to very low-density lipoproteins (VLDL) and intermediate low-density lipoprotein (IDL), and reduced transport of HDL(2) to HDL(3). Moreover, hypothyroidism increases the oxidation of plasma cholesterol mainly because of an altered pattern of binding and to the increased levels of cholesterol, which presents a substrate for the oxidative stress. Cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Hypothyroidism is often accompanied by diastolic hypertension that, in conjunction with the dyslipidemia, may promote atherosclerosis. However, thyroxine therapy, in a thyrotropin (TSH)-suppressive dose, usually leads to a considerable improvement of the lipid profile. The changes in lipoproteins are correlated with changes in free thyroxine (FT(4)) levels. Hyperthyroidism exhibits an enhanced excretion of cholesterol and an increased turnover of LDL resulting in a decrease of total and LDL cholesterol, whereas HDL are decreased or not affected. The action of thyroid hormone on Lp(a) lipoprotein is still debated, because both decrease or no changes have been reported. The discrepancies are mostly because of genetic polymorphism of apo(a) and to the differences between the various study groups. Subclinical hypothyroidism (SH) is associated with lipid disorders that are characterized by normal or slightly elevated total cholesterol levels, increased LDL, and lower HDL. Moreover, SH has been associated with endothelium dysfunction, aortic atherosclerosis, and myocardial infarction. Lipid disorders exhibit great individual variability. Nevertheless, they might be a link, although it has not been proved, between SH and atherosclerosis.
Pharmacology of Recombinant Hirudin (2002)

Hirudin is the anticoagulative product of the salivary glands of the medical leech Hirudo medicinalis. It is characterized by a direct, bifunctional inhibition mechanism and a high, exclusive specificity and a strong ability to bind to thrombin (tight binding). Further characteristics are the organic-chemical structure of hirudin (peptide), which allows only parenteral administration; the missing metabolism in the organism; and the exclusive glomerular filtration of hirudin in kidneys as the effective elimination mechanism. Recombinant hirudin (r-hirudin) is a product of genetic engineering that is identical to the hirudin found in nature and has the same biochemical and pharmacological characteristics as natural hirudin.
Comparative studies on properties of unfractionated and low molecular weight heparin. (1990)

LMW heparin (FR-860) produced by depolymerization of unfractionated heparin with dinitric acid was used to investigate clinical effects in healthy volunteers. The results were as follows: 1. Subjective symptoms, physiologic studies, blood examinations, blood chemistry, and urinary chemistry tests were not changed. 2. Two of five volunteers who received unfractionated heparin (H-25) and two of five who received LMW heparin (F-50) manifested petechiae at the injection sites. These bleedings were dose dependent. 3. The effect on APTTs and thrombin times was less evident with F-25 and F-35 than with H-25; F-50 showed greater prolongation than H-25. 4. The half-life of LMW heparin was 1.5 to 1.8 hours; unfractionated heparin had 0.68 hours. 5. No changes were observed in the levels of AT III, fibrinogen, and FDP. 6. Platelet aggregation rates induced by 1.0 microM ADP were less affected by LMW heparin than by unfractionated heparin. 7. Platelet factor 4 levels increased markedly, but to a lesser extent with LMW heparin than with unfractionated heparin. These results are due to its mobilization from the vessel wall. No changes were observed in beta-thromboglobulin levels. 8. Fatty acid analysis (LPL and HTGL) was less affected by LMW heparin than by unfractionated heparin.
IL-2 down-regulates the expression of TCR and TCR-associated surface molecules on CD8+ T cells (2001)

CD8(+) T cells are known to down-regulate the TCR complex upon ligation with its cognate MHC class I-peptide complex. In the present report, we demonstrate that stimulation of CD8(+) T cells with cytokines also leads to down-regulation of the TCR complex and TCR-associated surface molecules. A significant reduction of TCRalpha beta, CD3, CD8alpha and CD8beta surface expression was observed when CD8(+) T cells were cultured in IL-2 and to a lesser extent in IL-4 or IL-15. The down-regulation was apparent after 2 days of culture and was observed at IL-2 concentrations as low as 10 U/ml. Using TCR transgenic mice, we found that the down-regulation was associated with a decreased affinity of CD8(+) T cells to MHC class I-peptide complexes, as determined by MHC class I tetramer staining. Furthermore, the antigen-specific proliferation of IL-2-pre-activated CD8(+) T cells was significantly reduced compared to naive CD8(+) T cells or to CD8(+) T cells previously stimulated with peptide-pulsed dendritic cells. Moreover, only CD8alpha(high) but not CD8alpha(low) cells sorted from IL-2-activated CD8(+) T cells proliferated in response to specific antigen, although both subsets proliferated equally well to IL-2. Taken together, these data suggest that the down-regulation of TCR components and a subsequent decrease in affinity towards MHC class I-peptide complexes may be a mechanism by which TCR-dependent proliferation of non-specifically activated CD8(+) T cells is avoided.
Improved insulin-sensitivity in mice heterozygous for PPAR-γ deficiency (2000)

The thiazolidinedione class of insulin-sensitizing, antidiabetic drugs interacts with peroxisome proliferator-activated receptor gamma (PPAR-gamma). To gain insight into the role of this nuclear receptor in insulin resistance and diabetes, we conducted metabolic studies in the PPAR-gamma gene knockout mouse model. Because homozygous PPAR-gamma-null mice die in development, we studied glucose metabolism in mice heterozygous for the mutation (PPAR-gamma(+/-) mice). We identified no statistically significant differences in body weight, basal glucose, insulin, or FFA levels between the wild-type (WT) and PPAR-gamma(+/-) groups. Nor was there a difference in glucose excursion between the groups of mice during oral glucose tolerance test, but insulin concentrations of the WT group were greater than those of the PPAR-gamma(+/-) group, and insulin-induced increase in glucose disposal rate was significantly increased in PPAR-gamma(+/-) mice. Likewise, the insulin-induced suppression of hepatic glucose production was significantly greater in the PPAR-gamma(+/-) mice than in the WT mice. Taken together, these results indicate that - counterintuitively - although pharmacological activation of PPAR-gamma improves insulin sensitivity, a similar effect is obtained by genetically reducing the expression levels of the receptor.
Plasma membrane localization signals in the light chain of botulinum neurotoxin (2004)

Botulinum neurotoxin (BoNT) is a potent biological substance used to treat neuromuscular and pain disorders. Both BoNT type A and BoNT type E display high-affinity uptake into motor neurons and inhibit exocytosis through cleavage of the synaptosome-associated protein of 25 kDa (SNAP25). The therapeutic effects of BoNT/A last from 3 to 12 months, whereas the effects of BoNT/E last less than 4 weeks. Using confocal microscopy and site-specific mutagenesis, we have determined that the protease domain of BoNT/A light chain (BoNT/A-LC) localizes in a punctate manner to the plasma membrane, colocalizing with the cleaved product, SNAP25(197). In contrast, the short-duration BoNT/E serotype is cytoplasmic. Mutations in the BoNT/A-LC have revealed sequences at the N terminus necessary for plasma membrane localization, and an active dileucine motif in the C terminus that is likely involved in trafficking and interaction with adaptor proteins. These data support sequence-specific signals as determinants of intracellular localization and as a basis for the different durations of action in these two BoNT serotypes.
Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration (2008)

Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based immunity. In vivo, the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state. Depending on their cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E2 (PGE2) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter.
Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents. (1989)

More than 20 different cDNA clones encoding DNA-damage-inducible transcripts in rodent cells have recently been isolated by hybridization subtraction (A. J. Fornace, Jr., I. Alamo, Jr., and M. C. Hollander, Proc. Natl. Acad. Sci. USA 85:8800-8804, 1988). In most cells, one effect of DNA damage is the transient inhibition of DNA synthesis and cell growth. We now show that five of our clones encode transcripts that are increased by other growth cessation signals: growth arrest by serum reduction, medium depletion, contact inhibition, or a 24-h exposure to hydroxyurea. The genes coding for these transcripts have been designated gadd (growth arrest and DNA damage inducible). Two of the gadd cDNA clones were found to hybridize at high stringency to transcripts from human cells that were induced after growth cessation signals or treatment with DNA-damaging agents, which indicates that these responses have been conserved during mammalian evolution. In contrast to results with growth-arrested cells that still had the capacity to grow after removal of the growth arrest conditions, no induction occurred in HL60 cells when growth arrest was produced by terminal differentiation, indicating that only certain kinds of growth cessation signals induce these genes. All of our experiments suggest that the gadd genes are coordinately regulated: the kinetics of induction for all five transcripts were similar; in addition, overexpression of gadd genes was found in homozygous deletion c14CoS/c14CoS mice that are missing a small portion of chromosome 7, suggesting that a trans-acting factor encoded by a gene in this deleted portion is a negative effector of the gadd genes. The gadd genes may represent part of a novel regulatory pathway involved in the negative control of mammalian cell growth.
Late-binding (2007)

Conventional load/store queues (LSQs) are an impediment to both power-efficient execution in superscalar processors and scaling tolarge-window designs. In this paper, we propose techniques to improve the area and power efficiency of LSQs by allocating entries when instructions issue ("late binding"), rather than when they are dispatched. This approach enables lower occupancy and thus smaller LSQs. Efficient implementations of late-binding LSQs, however, require the entries in the LSQ to be unordered with respect to age. In this paper, we show how to provide full LSQ functionality in an unordered design with only small additional complexity and negligible performance losses. We show that late-binding, unordered LSQs work well for small-window superscalar processors, but can also be scaled effectively to large, kilo-window processors by breaking the LSQs into address-interleaved banks. To handle the increased overflows, we apply classic network flow control techniques to the processor micronetworks, enabling low-overhead recovery mechanisms from bank overflows. We evaluate three such mechanisms: instruction replay, skid buffers, an dvirtual-channel buffering in the on-chip memory network. We show that for an 80-instruction window, the LSQ can be reduced to 32 entries. For a 1024-instruction window, the unordered, late-binding LSQ works well with four banks of 48 entries each. By applying a Bloom filter as well, this design achieves full hardware memory disambiguation for a 1,024 instruction window while requiring low average power per load and store access of 8 and 12 CAM entries, respectively.
Identification of Bacillus thuringiensis Delta-Endotoxin Cry1C Domain III Amino Acid Residues Involved in Insect Specificity (1999)

Cry1C domain III amino acid residues involved in specificity for beet armyworm (Spodoptera exigua) were identified. For this purpose, intradomain III hybrids between Cry1E (nontoxic) and Cry1E-Cry1C hybrid G27 (toxic) were made. Crossover points of these hybrids defined six sequence blocks containing between 1 and 19 of the amino acid differences between Cry1E and G27. Blocks B, C, D, and E of G27 were shown to be required for optimal activity against S. exigua. Block E was also required for optimal activity against the tobacco hornworm (Manduca sexta), whereas block D had a negative effect on toxicity for this insect. The mutagenesis of individual amino acids in block B identified Trp-476 as the only amino acid in this block essential, although not sufficient by itself, for full S. exigua activity. In block D, we identified a seven-amino-acid insertion in G27 that was not in Cry1E. The deletion of either one of two groups of four consecutive amino acids in this insertion completely abolished activity against S. exigua but resulted in higher activity against M. sexta. Alanine substitutions of the first group had little effect on toxicity, whereas alanine substitutions of the second group had the same effect as its deletion. These results identify groups of amino acids as well as some individual residues in Cry1C domain III, which are strongly involved in S. exigua-specific activity as well as sometimes involved in M. sexta-specific activity.
Mitoxantrone—A Hypomethylating Agent? (2003)

Commentary to: Mitoxantrone Mediates Demethylation and Re-Expression of Cyclin D2, Estrogen Receptor 14.3.3 Sigma In Breast Cancer Cells Belinda S. Parker, Suzanne M. Cutts, Abraham Nudelman, Ada Rephaeli, Don R. Phillips and Saraswati Sukumar
Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α‐chain CDR3 loop (2008)

A significant fraction of CD1d-restricted T cells express an invariant T cell receptor (TCR) alpha-chain. These highly conserved invariant NKT (iNKT) populations are important regulators of a wide spectrum of immune responses. The ability to directly identify and manipulate iNKT cells is essential to understanding their function and to exploit their therapeutic potential. To this end, we sought monoclonal and polyclonal antibodies specific for iNKT cells by immunizing CD1d KO mice, which lack iNKT cells, with a cyclic peptide modeled after the TCRalpha CDR3 loop. One mAb (6B11) was specific for cloned and primary human but not rodent iNKT cells and the human invariant TCRalpha, as shown by transfection and reactivity with human invariant TCRalpha transgenic T cells ex vivo and in situ. 6B11 was utilized to identify, purify, and expand iNKT cells from an otherwise minor component of human peripheral blood lymphocytes and to specifically identify human iNKT cells in tissue. Thus, we report a novel and general strategy for the generation of mAb specific for the CDR3 loop encoded by the TCR of interest. Specifically, an anti-Valpha24Jalpha18 CDR3 loop clonotypic TCR mAb is available for the enumeration and therapeutic manipulation of human and non-human primate iNKT populations.
Adaptive Dispatching Rule for Semiconductor Wafer Fabrication Facility (2012)

Uncertainty in semiconductor fabrication facilities (fabs) requires scheduling methods to attain quick real-time responses. They should be well tuned to track the changes of a production environment to obtain better operational performance. This paper presents an adaptive dispatching rule (ADR) whose parameters are determined dynamically by real-time information relevant to scheduling. First, we introduce the workflow of ADR that considers both batch and non-batch processing machines to obtain improved fab-wide performance. It makes use of such information as due date of a job, workload of a machine, and occupation time of a job on a machine. Then, we use a backward propagation neural network (BPNN) and a particle swarm optimization (PSO) algorithm to find the relations between weighting parameters and real-time state information to adapt these parameters dynamically to the environment. Finally, a real fab simulation model is used to demonstrate the proposed method. The simulation results show that ADR with constant weighting parameters outperforms the conventional dispatching rule on average; ADR with changing parameters tracking real-time production information over time is more robust than ADR with constant ones; and further improvements can be obtained by optimizing the weights and threshold values of BPNN with a PSO algorithm.
The PADS project (2011)

The goal of the PADS project, which started in 2001, is to make it easier for data analysts to extract useful information from ad hoc data files. This paper does not report new results, but rather gives an overview of the project and how it helps bridge the gap between the unmanaged world of ad hoc data and the managed world of typed programming languages and databases. In particular, the paper reviews the design of PADS data description languages, describes the generated parsing tools and discusses the importance of meta-data. It also sketches the formal semantics, discusses useful tools and how can they can be generated automatically from PADS descriptions, and describes an inferencing system that can learn useful PADS descriptions from positive examples of the data format.
Photostimulated luminescence and dynamics of AgI and Ag nanoclusters in zeolites (2002)

The photoluminescence and photostimulated luminescence of Ag and AgI nanoclusters formed in zeolite-Y are studied using fluorescence spectroscopy. The photoluminescence spectra of AgI nanoclusters show emission from both AgI as well as Ag nanoclusters which are present in small amounts in the AgI nanoclusters, while in the photostimulated luminescence, only the emission of Ag clusters is observed. While the photoluminescence from both Ag and AgI particles displays subnanosecond and microsecond lifetimes, the emission from photostimulated luminescence shows very short, picosecond lifetimes. A model which ascribes the photostimulated luminescence to recombination of electrons trapped in the zeolite with Ag in close proximity to the trap site is proposed. The appearance of strong photostimulated luminescence with short decays in these systems demonstrates that nanoparticles have potential for digital storage and medical radiology applications.
An architecture for a business and information system (1988)

The transaction-processing environment in which companies maintain their operational databases was the original target for computerization and is now well understood. On the other hand, access to company information on a large scale by an end user for reporting and data analysis is relatively new. Within IBM, the computerization of informational systems is progressing, driven by business needs and by the availability of improved tools for accessing the company data. It is now apparent that an architecture is needed to draw together the various strands of informational system activity within the company. IBM Europe, Middle East, and Africa (E/ME/A) has adopted an architecture called the E/ME/A Business Information System (EBIS) architecture as the strategic direction for informational systems. EBIS proposes an integrated warehouse of company data based firmly in the relational database environment. End-user access to this warehouse is simplified by a consistent set of tools provided by an end-user interface and supported by a business data directory that describes the information available in user terms. This paper describes the background and components of the architecture of EBIS.