gebhart/patrepeval huggingface dataset:
THE EARLY RELEASE OF INTERLEUKIN-2, TUMOR NECROSIS FACTOR-α AND INTERFERON-γ AFTER ISCHEMIA REPERFUSION INJURY IN THE LUNG ALLOGRAFT (1994)

A period of cold and warm ischemia is obligatory when performing lung transplantation. Subtle ischemia-reperfusion injury induced in the course of transplantation can pass undetected or cause a short phase of reversible lung dysfunction. We hypothesized that ischemia-reperfusion injury may result in the local release of cytokines that have the capability to mediate acute lung injury early following transplantation. To test this hypothesis, 10 mongrel dogs were subjected to left lung allotransplantation. As performed in the clinical setting, donor lungs were preserved with Eurocollins solution and stored at 4°C for 4 hr, which was followed by 1 hr of warm ischemia. Recipients received standard immunosuppression of cyclosporine, azathioprine, and low dose steroids. Bronchoalveolar lavage (BAL) and open lung biopsies were performed before operation and at approximately 1 hr, 4 hr, 24 hr, and 1 week after transplantation. A significant increase in BAL IL-2 levels was observed 4 hr after surgery (0 hr: 349±138 pg/ml; 4 hr: 757±284 pg/ml) (mean ± SEM) (P<0.05) which subsequently decreased 24 hr (320±168 pg/ml) after transplantation. BAL TNF-α levels were significantly increased 1 hr after transplantation (P<0.05) (0 hr: 3.4±0.65 pg/ml; 1 hr: 13.3±8.0 pg/ ml) returning to baseline after 24 hr (5.8±2.8 pg/ml). BAL IFN-γ levels also significantly increased 1 and 4 hr after transplantation (0 hr: 7.2±2.1 pg/ml; 1 hr: 68.2±49.2 pg/ml; 4 hr: 301±131 pg/ml) (P<0.05). This decreased back to baseline after 24 hr and 1 week (5.2±1.2 pg/ml and 9.7±7.9 pg/ml, respectively). There were no changes detected in plasma levels of cytokines. Histology showed evidence of grade 1–2 rejection after 1 week. We conclude that subjection of a lung allograft to standard periods of cold-warm ischemia will result in a temporary early elevation of IL-2, TNF-α, and IFN-γ detectable only in the bronchoalveolar compartment. Such local increase in cytokines in the lung allograft may play an important role in the development of early allograft dysfunction.
Potential Nectin-1 Binding Site on Herpes Simplex Virus Glycoprotein D (2004)

Four glycoproteins (gD, gB, gH, and gL) are essential for herpes simplex virus (HSV) entry into cells. An early step of fusion requires gD to bind one of several receptors, such as nectin-1 or herpesvirus entry mediator (HVEM). We hypothesize that a conformational change in gD occurs upon receptor binding that triggers the other glycoproteins to mediate fusion. Comparison of the crystal structures of gD alone and gD bound to HVEM reveals that upon HVEM binding, the gD N terminus transitions from a flexible stretch of residues to a hairpin loop. To address the contribution of this transition to the ability of gD to trigger fusion, we attempted to "lock" the gD N terminus into a looped conformation by engineering a disulfide bond at its N and C termini. The resulting mutant (gD-A3C/Y38C) failed to trigger fusion in the absence of receptor, suggesting that formation of the loop is not the sole fusion trigger. Unexpectedly, although gD-A3C/Y38C bound HVEM, it failed to bind nectin-1. This was due to the key role played by Y38 in interacting with nectin-1. Since tyrosines are often "hot spot" residues at the center of protein-protein interfaces, we mutated residues that surround Y38 on the same face of gD and tested their binding and functional properties. Our results suggest that this region of gD is important for nectin-1 interaction and is distinct from but partially overlaps the site of HVEM binding. Unique gD mutants with altered receptor usage generated in this study may help dissect the roles played by various HSV receptors during infection.
Platelet Functions in Recombinant Hirudin-Anticoagulated Blood (1990)

The influence of genetically engineered recombinant hirudin (r-hirudin) on platelet functions was studied. Depending on the concentration, r-hirudin inhibits the thrombin-induced aggregation and 14C-serotonin secretion to the same extent as native hirudin. Comparative studies in blood anticoagulated by r-hirudin, heparin or citrate show a significantly lower spontaneous platelet aggregation in r-hirudinized blood. The extent of the ADP-induced aggregation is nearly the same in r-hirudinized, heparinized or citrated plasma. In r-hirudinized plasma, however, aggregation is reversible. In contrast to heparinized or citrated plasma, adrenaline causes only a very slight aggregation in r-hirudinized plasma. ADP- or adrenaline-induced secretion of 14C-serotonin do not occur in r-hirudinized plasma. The collagen- as well as the PAF-induced aggregation and 14C-serotonin release in hirudinized plasma do not differ significantly from those in heparinized or citrated plasma. r-Hirudin is a suitable anticoagulant for studying platelet functions because it does not produce any alterations in platelet reactions and does not provoke any changes in the ionized calcium concentration in blood.
A case for direct-mapped caches (1988)

Direct-mapped caches are defined, and it is shown that trends toward larger cache sizes and faster hit times favor their use. The arguments are restricted initially to single-level caches in uniprocessors. They are then extended to two-level cache hierarchies. How and when these arguments for caches in uniprocessors apply to caches in multiprocessors are also discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Human Articular Cartilage: Influence of Aging and Early Symptomatic Degeneration on the Spatial Variation of T2—Preliminary Findings at 3 T (2000)

Aging is associated with an asymptomatic increase in T2 of the transitional zone of articular cartilage. Preliminary results indicate this diffuse increase in T2 in senescent cartilage is different in appearance than the focally increased T2 observed in damaged articular cartilage.
Gene Expression Profiling Reflects Physiological Processes in Salt Acclimation of Synechocystis sp. Strain PCC 6803 (2004)

The kinetics of genome-wide responses of gene expression during the acclimation of cells of Synechocystis sp. PCC 6803 to salt stress were followed by DNA-microarray technique and compared to changes in main physiological parameters. During the first 30 min of salt stress, about 240 genes became induced higher than 3-fold, while about 140 genes were repressed. However, most changes in gene expression were only transient and observed among genes for hypothetical proteins. At 24 h after onset of salt stress conditions, the expression of only 39 genes remained significantly enhanced. Among them, many genes that encode proteins essential for salt acclimation were detected, while only a small number of genes for hypothetical proteins remained activated. Following the expression of genes for main functions of the cyanobacterial cell, i.e. PSI, PSII, phycobilisomes, and synthesis of compatible solutes, such as ion homeostasis, distinct kinetic patterns were found. While most of the genes for basal physiological functions were transiently repressed during the 1st h after the onset of salt stress, genes for proteins specifically related to salt acclimation were activated. This gene expression pattern reflects well the changes in main physiological processes in salt-stressed cells, i.e. transient inhibition of photosynthesis and pigment synthesis as well as immediate activation of synthesis of compatible solutes. The results clearly document that following the kinetics of genome-wide expression, profiling can be used to envisage physiological changes in the cyanobacterial cell after certain changes in growth conditions.
Novel Polymerization of α‐Olefins with the Catalyst System Nickel/Aminobis(imino)phosphorane (1985)

A new type of linking of α-olefins upon polymerization has been achieved by catalysis with nickel(0) complexes and [X2NP(NX)2], X = Me3Si. 2,ω-linking leads to polymers with methyl branches at well-defined intervals; products of type 1 are obtained from linear α-olefins.
Erythropoietin and interleukin-2 activate distinct JAK kinase family members. (1994)

The erythropoietin (EPO) receptor and the interleukin-2 (IL-2) receptor beta-chain subunit are members of the cytokine receptor superfamily. They have conserved primary amino acid sequences in their cytoplasmic domains and activate phosphorylation of common substrates, suggesting common biochemical signaling mechanisms. We have generated a cell line, CTLL-EPO-R, that contains functional cell surface receptors for both EPO and IL-2. CTLL-EPO-R cells demonstrated similar growth kinetics in EPO and IL-2. Stimulation with EPO resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK2. In contrast, stimulation with IL-2 or the related cytokine IL-4 resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK1 and an additional 116-kDa protein. This 116-kDa protein was itself immunoreactive with a polyclonal antiserum raised against JAK2 and appears to be a novel member of the JAK kinase family. Immune complex kinase assays confirmed that IL-2 and IL-4 activated JAK1 and EPO activated JAK2. These results demonstrate that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R cells and that the EPO and IL-2 receptors interact with distinct JAK kinase family members within the same cellular background.
LCW-Based Agent Planning for the Semantic Web (2002)

The Semantic Web has the potential to allow software agents to intelligently process and integrate the Web’s wealth of information. These agents must plan how to achieve their goals in light of the information available. However, because the Web is so vast and changes so rapidly, the agent cannot make a closed-world assumption. This condition makes it difficult for an agent to know when it has gathered all relevant information or when additional searches may be redundant. We propose to use local closed world (LCW) information to assist these agents. LCW information can be obtained by accessing sources that are described in a Semantic Web language with LCW extensions, or by executing operators that provide exhaustive information. In this paper, we demonstrate how two Semantic Web languages (DAML+OIL and SHOE) can be augmented with the ability to state LCW information. We also show that DAML+OIL can represent many kinds of LCW information even without additional language features. Finally, we describe how ordered task decomposition can be used with LCW information to efficiently plan in distributed information environments. 1
Solid phase synthesis of glycopeptide dendrimers with Tn antigenic structure and their biological activities. Part I (1999)

Multiple antigenic peptides containing dimeric Tn antigen [Ac-(Tn)2-γ-Abu]4-(Lys-X)2-Lys-β-Ala (V: X=0; VIII: X=γ-Abu) and [Ac-(Tn)2-γ-Abu]8-(Lys-X)4-(Lys-X)2-Lys-β-Ala (XI: X=0; XIV: X=γ-Abu), immobilized on biocompatible Tenta Gel S NH2 support were prepared by SPPS. Rosetting tests of V, VIII, XI and XIV showed positive reactions with anti-Tn (DAKO) and Tn+ erythrocytes, with anti-Tn/A (BRIC 66) and Tn+ and A erythrocytes, other combinations were negative. In all the animals immunized with XIV, we found a remarkable increase in the level of anti-Tn (titre 2000–64 000, score 105–167) and no change of anti-A levels (titre 8, score 13–17). Neither non-immune nor immune sera showed any reactivity with T+, Cad+ and blood group O erythrocytes. Immunized mice did not exhibit any sign of adverse reaction to the administered conjugates. Biological activities were correlated with molecular modelling and molecular dynamic calculations. The biological activities of these synthetic Tn antigen conjugates (good availability for the immunological interactions, highly specific immunogenicity, good biological tolerance) together with their precise chemical characterization seem to be a promising approach to preparation of anti-tumour vaccine and affinity purification of anti-Tn antibodies. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.
USE OF SPECTRAL ANALYSIS OF SURFACE WAVES METHOD FOR DETERMINATION OF MODULI AND THICKNESSES OF PAVEMENT SYSTEMS. (1983)

The spectal analysis of surface waves (SASW) method is a nondestructive method for determining moduli and thicknesses of pavement systems. By means of a transient impact on the surface of a pavement system (or soil deposit), a group of waves with different frequencies is transmitted to the medium. Seismic wave velocities and, eventually, elastic moduli and thicknesses of the various layers in the pavement system are determined from analysis of the phase information for each frequency determined between two receivers located on the surface. The method has several advantages: it is nondestructive, has a unique solution, and is capable of full automation. The results of three series of tests performed on TX-71 near Columbus, Texas, are presented. Testing was performed on an asphaltic concrete pavement, a continuously reinforced concrete pavement, and a natural soil occupying the median at the site. Elastic moduli determined by using the SASW method are compared with those determined by means of crosshole seismic tests and Dynaflect measurements. Moduli determined by the SASW method are in agreement with those from crosshole tests, whereas moduli back-calculated from Dynaflect measurements compare rather unfavorably with moduli determined by the other two methods.
Cross-linking of T3 (CD3) with T4 (CD4) enhances the proliferation of resting T lymphocytes. (1987)

Monoclonal antibodies reactive with defined T lymphocyte surface antigens were covalently coupled to protein A-Sepharose beads using the bifunctional imidoester, dimethyl pimelimidate. Sepharose-immobilized antibody reactive with T3 induced the proliferation of resting T lymphocytes in the presence of either recombinant interleukin 2 or phorbol myristate acetate. When monoclonal antibodies reactive with T3 and T4 were coupled to the same Sepharose bead (hereafter designated Sepharose (T3:T4)), proliferation was enhanced an average of three-fold. Similarly prepared Sepharose beads coupled to anti-T3 and anti-T8 also enhanced proliferation over that observed with anti-T3 alone. Sepharose (T3:T4) similarly increased the proliferation of T4+ lymphocytes and a T4+ clone but failed to enhance the proliferation of T8+ lymphocytes. The increased proliferation of T4+ lymphocytes resulted from a preferential activation of the T4+2H4- helper population over the T4+2H4+ suppressor-inducer population. The enhanced proliferation induced by Sepharose (T3:T4) could be completely inhibited by soluble anti-T4. These results suggest that perturbation of T3 may be a minimal signal for T cell activation and that the assembly of a multimeric complex including T3 and T4 may be required for optimal T cell activation.
The antigenicity of carcinoembryonic antigen in man (1975)

Binding of globulins to -125I CEA was detected in 10 of 24 sera from patients with cancer, 13 of 26 sera from blood donors, and 7 of 27 supernates of tumor-cell suspensions. Binding was predominantly by IgM in 10 of 14 sera tested by radioimmunoelectrophoresis. Binding was inhibited by 6 ng unlabelled CEA in one instance only, and by adsorption with blood group A erythrocytes in three cases. Binding was not increased in dialysed precipitates formed by ammonium sulfate at pH 2.5, while there was increased binding in precipitates of complexes of CEA and heterologous anti-CEA. These results confirm that human IgM binds to CEA, and in some cases binding appears to be mediated by antibodies to blood group A. However, the binding is weak and appears to be of low affinity. This suggests that binding of CEA by immunoglobulins represents cross-reactivity by antibodies to similar antigens, of which blood group A is one example.
Cetuximab in recurrent/metastatic (R&M) squamous cell carcinoma of the head and neck (SCCHN) refractory to first-line platinum-based therapies (2005)

5505 Background: Patients with R&M SCCHN have a poor prognosis. Patients failing first-line therapy have few therapeutic options. Cetuximab (Erbitux) is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR) which has shown second-line activity in SCCHN Methods: We present here a descriptive comparison of the intention-to-treat efficacy data from 330 patients treated with cetuximab (400 mg/m2 initial dose followed by 250 mg/m2/week) in 3 phase II studies (2 cetuximab plus platinum compound [at the same dose and schedule the patient progressed on] [n=96 and n=131] and 1 cetuximab monotherapy [n=103]) with historical data from a retrospective analysis in which 151 patients received various second-line treatments (Leon et al. Proc ASCO 2003). All patients had R&M SCCHN that had progressed on platinum-based therapy. Statistical analyses were not performed on these data. Results: The efficacy results are summarised in the table below. In all studies, cetuximab was well tolerated, the most common adverse event being skin reactions. In the monotherapy study, acne-like rash was reported in 69% of the cases (Grade 3/4 in 1%). When cetuximab was combined with platinum, acne-like rash was reported in 72%of the patients (Grade 3/4 in 3%). Severe hypersensitivity reactions were seen in between 0 and 3% of patients in the three studies. Conclusions: The median survival time of around 6 months achieved with cetuximab in platinum-refractory SCCHN is similar to that seen with first-line therapy and represents an increase in survival of 2.5 months compared with platinum-refractory historical controls. Based on these results cetuximab monotherapy seems to be a good option in patients with recurrent/metastatic SCCHN who have progressed on platinum-based chemotherapy. No significant financial relationships to disclose.
Discovery of CGS 27023A, a Non-Peptidic, Potent, and Orally Active Stromelysin Inhibitor That Blocks Cartilage Degradation in Rabbits (1997)

Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.
Multiplex PCR amplification from the CFTR gene using DNA prepared from buccal brushes/swabs (1993)

Traditionally, DNA used for PCR-based diagnostic analysis has originated from white cells fractionated from whole blood. Although this method yields substantial quantities of DNA, there are some drawbacks to the procedure, including the inconvenience of drawing blood, risk of exposure to blood-borne pathogens, liquid sample handling, and the somewhat involved extraction procedure. Alternatively, DNA for genetic diagnosis has been derived from finger stick blood samples, hair roots, cheek scrapings, and urine samples. Oral saline rinses have also been used extensively as a means of collecting buccal epithelial cells as a DNA source. However, this method still requires liquid sample handling. Herein, we present our results involving the rapid extraction of DNA from buccal cells collected on cytology brushes and swabs for use in PCR reactions, specifically the multiplex amplification of 5 exons within the CFTR gene. The quality of DNA isolated from buccal cells, collected in this manner, has been sufficient to reproducibly support multiplex amplification. Cheek cell samples and the DNA prepared from them as described here are highly stable. The success rate of PCR amplification on DNA prepared from buccal cells is 99%. In a blind study comparing the analysis of 12 mutations responsible for cystic fibrosis in multiplex products amplified with DNA from both blood and buccal cell samples from 464 individuals, there was 100% correlation of results for blood and cheek cell DNA, validating the use of DNA extracted from cheek cells collected on cytology brushes for use in genetic testing.
Enantioselective Total Synthesis of Quadrigemine C and Psycholeine (2002)

The first total syntheses of higher-order members of the polypyrrolidinoindoline alkaloid family are reported. The synthesis of quadrigemine C (1) and psycholeine (3) begins with synthetic meso-chimonanthine (4), which is synthesized from commercially available oxindole and isatin in 13 steps and 35% overall yield. Double Stille cross coupling of diiodide 7, available in three steps from 4, with vinylstannane 8 produces dibutenanilide 9. Double catalytic asymmetric Heck cyclization of 9 simultaneously installs the two peripheral quaternary stereocenters and desymmetrizes this advanced meso precursor to deliver the chiral, decacyclic intermediate 11 in 62% yield and 90% ee. In two additional steps, 11 is converted to 1, which upon treatment with acid generates 3. The synthesis of quadrigemine C (1), which rigorously confirms its relative and absolute configuration, was executed in 19 linear steps (2% overall yield) from commercially available starting materials.
Met and c-Src Cooperate to Compensate for Loss of Epidermal Growth Factor Receptor Kinase Activity in Breast Cancer Cells (2008)

Breast cancers are not responsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), although 30% of breast cancers overexpress EGFR. The mechanism of intrinsic resistance to EGFR TKIs in breast cancer is the focus of current studies. Here, we observed that EGFR remains tyrosine phosphorylated in breast cancer cells that proliferate in the presence of EGFR TKIs. In one such cell line, SUM229, inhibiting c-Src kinase activity with either a dominant-negative c-Src or a c-Src TKI decreased EGFR phosphorylation on Tyr(845), Tyr(992), and Tyr(1086) in the presence of EGFR TKIs. Conversely, overexpressing wild-type (wt) c-Src in the EGFR TKI-sensitive breast cancer cell line SUM149 increased EGFR kinase-independent EGFR tyrosine phosphorylation. In addition, in the presence of EGFR TKIs, inhibiting c-Src kinase activity decreased cell growth in SUM229 cells, and overexpressing wt-c-Src increased cell growth in SUM149 cells. We identified the receptor tyrosine kinase Met to be responsible for activating c-Src in SUM229 cells. Inhibiting Met kinase activity with a small molecule inhibitor decreased c-Src phosphorylation and kinase activation. In addition, inhibiting Met kinase activity in SUM229 cells decreased EGFR tyrosine phosphorylation and growth in the presence of EGFR TKIs. Stimulating Met kinase activity in SUM149 cells with hepatocyte growth factor increased EGFR tyrosine phosphorylation and cell growth in the presence of EGFR TKIs. These data suggest a Met/c-Src-mediated signaling pathway as a mediator of EGFR tyrosine phosphorylation and cell growth in the presence of EGFR TKIs.
Virtualizing Operating Systems for Seamless Distributed Environments (2000)

Applications and operating systems can be augmented with extra functionality by injecting additional middleware into the boundary layer between them, without tampering with their binaries. Using this scheme, we separate the physical resource bindings of the application and replace it with virtual bindings. This is called virtualization. We are developing a virtualizing Operating System (vOS) residing on top of Windows NT, that injects all applications with the virtualizing software. The vOS makes it possible to build communities of systems that cooperate to run applications and share resources non-intrusively while retaining complete application binary compatibility. In this paper, we describe the structure, architecture and operation of the virtualizing Operating System supporting our virtualization concepts and methodologies Keywords: Parallel/distributed computing systems, API Interception. 1. Introduction The promise of global, seamless distributed systems, constructed out of m...