gebhart/patrepeval huggingface dataset:
Characterization of Rac and Cdc42 Activation in Chemoattractant-stimulated Human Neutrophils Using a Novel Assay for Active GTPases (1999)

A major function of Rac2 in neutrophils is the regulation of oxidant production important in bacterial killing. Rac and the related GTPase Cdc42 also regulate the dynamics of the actin cytoskeleton, necessary for leukocyte chemotaxis and phagocytosis of microorganisms. Although these GTPases appear to be critical downstream components of chemoattractant receptor signaling in human neutrophils, the pathways involved in direct control of Rac/Cdc42 activation remain to be determined. We describe an assay that measures the formation of Rac-GTP and Cdc42-GTP based on their specific binding to the p21-binding domain of p21-activated kinase 1. A p21-binding domain glutathione S-transferase fusion protein specifically binds Rac and Cdc42 in their GTP-bound forms both in vitro and in cell samples. Binding is selective for Rac and Cdc42 versus RhoA. Using this assay, we investigated Rac and Cdc42 activation in neutrophils and differentiated HL-60 cells. The chemoattractant fMet-Leu-Phe and the phorbol ester phorbol myristate acetate stimulate formation of Rac-GTP and Cdc42-GTP with distinct time courses that parallel cell activation. We also show that the signaling pathways leading to Rac and Cdc42 activation in HL-60 cells involve G proteins sensitive to pertussis toxin, as well as tyrosine kinase and phosphatidylinositol 3-kinase activities.
ANTIBODY-MEDIATED REJECTION OF THE KIDNEY AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION (SPKT): ALEMTUZUMAB IS NOT SUPERIOR TO BASILIXIMAB AS INDUCTION TREATMENT (2008)

Pascual, J1; Pirsch, J D.1; Torrealba, J R.2; Odorico, J S.1; Djamali, A3; Becker, Y T.1; Leverson, G1; Knechtle, S J.1; Sollinger, H W.1; Samaniego, M D.3 Author Information
Purification and characterization of morphinone reductase from Pseudomonas putida M10 (1994)

The NADH-dependent morphinone reductase from Pseudomonas putida M10 catalyses the reduction of morphinone and codeinone to hydromorphone and hydrocodone respectively. Morphinone reductase was purified from crude cell extracts to apparent homogeneity in a single affinity-chromatography step using Mimetic Yellow 2. The purified enzyme was a dimeric flavoprotein with two identical subunits of M(r) 41,100, binding non-covalently one molecule of FMN per subunit. The N-terminal sequence was PDTSFSNPGLFTPLQ. Morphinone reductase was active against morphinone, codeinone, neopinone and 2-cyclohexen-1-one, but not against morphine, codeine or isocodeine. The apparent Km values for codeinone and 2-cyclohexen-1-one were 0.26 mM and 5.5 mM respectively. The steroids progesterone and cortisone were potent competitive inhibitors; the apparent K1 for cortisone was 35 microM. The pH optimum for codeinone reduction was 8.0 in phosphate buffer. No reverse reaction could be detected, and NADPH could not be used as a reducing substrate in place of NADH. Morphinone reductase activity was strongly inhibited by 0.01 mM CuSO4 and p-hydroxymercuribenzoate, suggesting the presence of a vital thiol group. Steady-state kinetic studies suggested a Ping Pong (substituted enzyme) kinetic mechanism; however, product-inhibition patterns were inconsistent with a classical Ping Pong mechanism. Morphinone reductase may, like several other flavoprotein dehydrogenases, operate by a hybrid two-site Ping Pong mechanism.
The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas (2012)

To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome segregation defects, telomere shortening, and massive melanoma cell apoptosis. These findings suggest that DDX11 could be an important candidate for molecular targeted therapy for advanced melanoma.
The Role of Tec Family Kinases in Inflammatory Processes (2007)

A variety of different cell lineages of the hematopoietic system are activated during inflammatory processes. These cells not only contribute to the beneficial outcome of an immune response, but can also cause pathology such as autoimmunity as a consequence of extended or uncontrolled reactions. Therefore, an understanding of the basic mechanisms that lead to immune cell activation and the identification of key molecular players will also lead to strategies towards therapeutic manipulation of extended immune reactions. Members of the Tec kinase family (Bmx, Btk, Itk, Rlk and Tec) constitute an important class of non-receptor protein tyrosine kinases that are primarily expressed in the hematopoietic system. They are activated upon a variety of signals and are important participants of major signal transduction pathways in immunological processes. Hence, deficiencies in Tec family kinases cause several immunological defects, both in man and mice. Since Tec family kinases have been shown to function as modulators of immune cell activation, they may provide attractive drug targets for the manipulation of the immune response. In this review, we summarize recent data from studies about the activities of Tec family kinases in inflammatory cells and their role in in vivo models of infection, inflammation and autoimmune diseases. Keywords: Tec family kinases, inflammation, mouse models, immunity, Th1/Th2
Solubilization of Membrane-bound Rod Phosphodiesterase by the Rod Phosphodiesterase Recombinant δ Subunit (1996)

Retinal rod and cone phosphodiesterases are oligomeric enzymes that consist of a dimeric catalytic core (alpha'2 in cones and alphabeta in rods) with inhibitory subunits (gamma) that regulate their activity. In addition, a 17-kDa protein referred to as the delta subunit co-purifies with the rod soluble phosphodiesterase and the cone phosphodiesterase. We report here partial protein sequencing of the rod delta subunit and isolation of a cDNA clone encoding it. The predicted amino acid sequence is unrelated to any other known protein. Of eight bovine tissue mRNA preparations examined by Northern analysis, the strongest delta subunit-specific signal was present in the retina. A less intense signal was seen in the brain and adrenal mRNA. In bovine retinal sections, rod delta subunit anti-peptide antibodies label rod but not cone outer segments. delta subunit, added back to washed outer segment membranes, solubilizes a large fraction of the membrane-bound phosphodiesterase, indicating that this subunit binds to the classical membrane associated phosphodiesterase. The subunit forms a tight complex with native, but not trypsin-released phosphodiesterase, suggesting that the isoprenylated carboxyl termini of the catalytic subunits may be involved in binding of the delta subunit to the phosphodiesterase holoenzyme.
[The latest review of therapeutic angiogenesis using angiogenic growth factors to peripheral arterial diseases]. (2002)

Therapeutic angiogenesis using angiogenic growth factors is expected to be a new treatment of patients with severe ischemic diseases. Indeed, human gene therapy for peripheral arterial disease(PAD) using VEGF gene demonstrated the beneficial effects. In contrast, we have reported the potent angiogenic activity of hepatocyte growth factor (HGF) in animal study and we planned gene therapy for ASO and Buerger disease using HGF gene (TREAT-HGF). In a prospective, open-labeled clinical trial, we investigated the safety and biological efficiency of this gene therapy in patients with peripheral arterial disease(PAD) who had failed conventional therapy.
Elevation of transforming growth factor alpha and its relationship to the epidermal growth factor and alpha-fetoprotein levels in patients with hepatocellular carcinoma. (1987)

A radioimmunoassay for transforming growth factor alpha (TGF-alpha) using synthetic rat sarcoma transforming growth factor and its rabbit polyclonal antibody has been developed. Using radioimmunoassays, the urinary TGF-alpha and epidermal growth factor (EGF) concentrations in 31 patients with hepatocellular carcinoma (HCC), 15 probable HCC, four metastatic liver cancer, and 33 age, sex-matched healthy controls were determined. For the first time, we have shown that the average TGF-alpha concentration for HCC patients was 21.5 +/- 20.3 micrograms per g creatinine, significantly higher than that of healthy subjects, 4.9 +/- 2.8 micrograms per g creatinine (P less than 0.001). There was no statistical difference in the level of EGF between HCC patients and controls (40.9 +/- 29.3 versus 46.2 +/- 16.6 micrograms per g creatinine; P greater than 0.05). The ratio of EGF/TGF-alpha between HCC patients (3.37 +/- 4.42) and controls (15.5 +/- 13.0) was significantly different (P less than 0.001). Among patients, 65% (20 of 31) of HCC cases and 87% (13 of 15) of probable HCC cases showed a marked elevation of TGF-alpha levels. We found only 16% (five of 31) of HCC cases with increased EGF level. EGF excretion was inversely age related. Serum total protein concentration and alkaline phosphatase activity were positively correlated to EGF concentration (r = 0.522, P less than 0.01 and rt = 0.393, P less than 0.05, respectively). There was no correlation between biochemical functions of liver and TGF-alpha concentration in HCC patients. Our results also suggested that TGF-alpha may be a useful complementary tumor marker for management of patients with clinical manifestation of HCC who have low alpha-fetoprotein levels.
Dynamic Combinatorial Libraries Based on Hydrogen‐Bonded Molecular Boxes (2006)

This article describes two different types of dynamic combinatorial libraries of host and guest molecules. The first part of this article describes the encapsulation of alizarin trimer 2a3 by dynamic mixtures of up to twenty different self-assembled molecular receptors together with the amplification and selection of the best binder. Receptors (1a-d)3.(DEB)6 are formed by the self-assembly of six diethyl barbiturate (DEB) and calix[4]arene dimelamine derivatives 1a-d by using hydrogen bonds. The largest amplification factor (2.8) for a host assembly (1a3.(DEB)6) was observed after the addition of 2a to four-component library 1a(n).1b(3-n).(DEB)6 (n=0-3). Addition of 2a to twenty-component library 1a(n).1b(m).1c(o).1d(3-(n+m+o)).(DEB)6 (n, m, o=0-3; (n+m+o)<or=3) also showed amplification of receptor 1a3.(DEB)6. The second part of this article describes the complexation of libraries of different alizarin-like guest molecules (2a-d) and the self-assembled receptor 1a3.(DEB)6. This receptor is able to template the formation of the best-fitting guest trimer.
Minimal Reaction Sets for Escherichia coli Metabolism under Different Growth Requirements and Uptake Environments (2001)

A computational procedure for identifying the minimal set of metabolic reactions capable of supporting various growth rates on different substrates is introduced and applied to a flux balance model of the Escherichia coli metabolic network. This task is posed mathematically as a generalized network optimization problem. The minimal reaction sets capable of supporting specified growth rates are determined for two different uptake conditions: (i) limiting the uptake of organic material to a single organic component (e.g., glucose or acetate) and (ii) allowing the importation of any metabolite with available cellular transport reactions. We find that minimal reaction network sets are highly dependent on the uptake environment and the growth requirements imposed on the network. Specifically, we predict that the E. coli network, as described by the flux balance model, requires 224 metabolic reactions to support growth on a glucose-only medium and 229 for an acetate-only medium, while only 122 reactions enable growth on a specially engineered growth medium.
Using Eye Movements To Evaluate Effects of Driver Age on Risk Perception in a Driving Simulator (2005)

Novice drivers (16-year-olds with < or = 6 months' driving experience) have the highest crash involvement rates per 100 million vehicle miles (161 million vehicle km). In the past, this was attributed to greater risk taking or poorly developed psychomotor skills. More recently, however, their high crash involvement rate has been hypothesized to be attributable largely to their relative inability to acquire and assess information in inherently risky situations. The current study seeks to evaluate this hypothesis by recording eye movements while 72 participants (24 novice drivers, 24 younger drivers, and 24 older drivers) drove through 16 risky scenarios in an advanced driving simulator. There were significant age-related differences in driver scanning behavior, consistent with the hypothesis that novice drivers' scanning patterns reflect their failure to acquire information about potential risks and their consequent failure to deal with these risks. Actual or potential applications of this research include modification of these scenarios for display on a PC as a basis for a training module that would enable novice drivers to recognize risky scenarios before they encounter them on the road, in the hope of reducing their high fatality rate.
Natural Language Access to Enterprise Data (2014)

This article describes USI Answers — a natural language question‐answering system for enterprise data. We report on the progress toward the goal of offering easy access to enterprise data to a large number of business users, most of whom are not familiar with the specific syntax or semantics of the underlying data sources. Additional complications come from the nature of the data, which comes both as structured and unstructured. The proposed solution allows users to express questions in natural language, makes apparent the system's interpretation of the query, and allows easy query adjustment and reformulation. The application is in use by more than 1500 users from Siemens Energy. We evaluate our approach on a data set consisting of feet data.
Studies of Nucleoside Transporters Using Novel Autofluorescent Nucleoside Probes (2006)

To better understand nucleoside transport processes and intracellular fates of nucleosides, we have developed a pair of fluorescent nucleoside analogues, FuPmR and dFuPmR, that differ only in the sugar moiety (ribofuranosyl versus 2'-deoxy, respectively), for real-time analysis of nucleoside transport into living cells by confocal microscopy. The binding and transportability of the two compounds were assessed for five recombinant human nucleoside transporters (hENT1/2, hCNT1/2/3) produced in Saccharomyces cerevisiae and/or oocytes of Xenopus laevis. The ribosyl derivative (FuPmR) was used to demonstrate proof of principle in live cell imaging studies in 11 cultured human cancer cell lines with different hENT1 activities. The autofluorescence emitted from FuPmR enabled direct visualization of its movement from the extracellular medium into the intracellular compartment of live cells, and this process was blocked by inhibitors of hENT1 (nitrobenzylmercaptopurine ribonucleoside, dipyridamole, and dilazep). Quantitative analysis of fluorescence signals revealed two stages of FuPmR uptake: a fast first stage that represented the initial uptake rate (i.e., transport rate) followed by a slow long-lasting second stage. The accumulation of FuPmR and/or its metabolites in nuclei and mitochondria was also visualized by live cell imaging. Measurements of fluorescence intensity increases in nuclei and mitochondria revealed rate-limited processes of permeant translocation across intracellular membranes, demonstrating for the first time the intracellular distribution of nucleosides and/or nucleoside metabolites in living cells. The use of autofluorescent nucleosides in time-lapse confocal microscopy is a novel strategy to quantitatively study membrane transport of nucleosides and their metabolites that will provide new knowledge of nucleoside biology.
One Model To Learn Them All (2017)

Deep learning yields great results across many fields, from speech recognition, image classification, to translation. But for each problem, getting a deep model to work well involves research into the architecture and a long period of tuning. We present a single model that yields good results on a number of problems spanning multiple domains. In particular, this single model is trained concurrently on ImageNet, multiple translation tasks, image captioning (COCO dataset), a speech recognition corpus, and an English parsing task. Our model architecture incorporates building blocks from multiple domains. It contains convolutional layers, an attention mechanism, and sparsely-gated layers. Each of these computational blocks is crucial for a subset of the tasks we train on. Interestingly, even if a block is not crucial for a task, we observe that adding it never hurts performance and in most cases improves it on all tasks. We also show that tasks with less data benefit largely from joint training with other tasks, while performance on large tasks degrades only slightly if at all.
Acute myocardial infarction as the presenting symptom of acute myeloblastic leukemia with extreme hyperleukocytosis (2002)

Abstract This case report deals with an unusual leukostatic complication in a 56‐year‐old woman with acute myeloblastic leukemia (AML) and extreme hyperleukocytosis (316 × 10 9 /L) who presented with acute myocardial infarction (MI). After leukopheresis the patient achieved hemodynamic stabilization and rapid neurologic recovery of encephalopathy that had also developed after the infarction. Considering the central role of WBC in the remodeling of post MI myocardial tissue, it was obvious that administration of chemotherapy with its subsequent inevitable pancytopenia could impose an increased risk for further cardiac complications including myocardial rupture. Nevertheless, cytarabine‐based induction chemotherapy was initiated 3 days after admission, and she achieved prolonged complete remission. Coronary angiography disclosed segmental atherosclerosis, but the only significant obstruction was in the right coronary artery. The patient died with relapsed leukemia 7 years later without recurrence of any cardiac symptoms or signs. Autopsy disclosed segmental coronary atherosclerosis involving the LAD (60% obstruction), suggesting that atherosclerosis was a predisposing risk factor. Additional compromise to blood perfusion due to leukostasis had led to this unusual complication of AML involving a major vessel. This is the first documented case of leukostasis causing coronary artery occlusion as well as the first report of successful induction chemotherapy for AML during a myocardial infarction. Am. J. Hematol. 71:47–49, 2002. © 2002 Wiley‐Liss, Inc.
Adhesion to Bone Marrow Stroma Inhibits Apoptosis of Chronic Lymphocytic Leukemia Cells (1999)

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of monoclonal long-lived B cells which are apparently resistant to normal apoptotic regulation. Since bone marrow stromal cells play an essential role in B lymphopoiesis, we have investigated whether stromal cells influence B-CLL cell survival. Our results indicate that intimate contact with stromal cells reduces B-CLL cell apoptosis and prevents the loss of bcl-2 protein expression. Binding of B-CLL cells to stromal cells requires simultaneous action of beta1 and beta2 integrins. The interaction between B-CLL cells and other cell types seems important for their survival and may represent an important mechanism underlying accumulation of malignant cells in B-CLL patients.
Targeted Disruption of the CD18 or ICAM-1 Gene Inhibits Choroidal Neovascularization (2003)

These data suggest a nonredundant role for leukocyte adhesion to vascular endothelium in the development of laser-induced choroidal neovascularization.
Endovascular treatments for intracranial aneurysms (1996)

During the last 10 years, the development of flexible microcatheters which can navigate cerebral vessels to lesions deep within the brain, has allowed the treatment of an increasing range of intracranial pathologies, including aneurysms. Techniques to embolize aneurysms, either by occlusion of their parent artery or endosaccular packing with its preservation, have evolved largely in order to treat inoperable aneurysms. Endosaccular packing with thrombogenic coils has recently allowed embolization of smaller aneurysms to be performed in patients acutely ill after subarachnoid haemorrhage. The procedural morbidity associated with these endovascular treatments are less dependent on aneurysm site than conventional neurosurgical clipping and initial results are comparable. These developments are challenging current thinking on the surgical management of patients with intracranial aneurysms. This review describes the evolution and practice of current endovascular treatments and their possible implications for the future of neuroradiology.
Serum measurement of interleukin‐31 (IL‐31) in paediatric atopic dermatitis: elevated levels correlate with severity scoring (2010)

The results of this study confirm the importance of IL-31 in AD pathophysiology. Serum IL-31 level is an objective reliable marker of AD severity in children. It may represent a novel target for antipruritic drug development.
The Human purH Gene Product, 5-Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase (1996)

We report here the cloning and sequencing of the cDNA, purification, steady state kinetic analysis, and truncation mapping studies of the human 5-aminoimidazole- 4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICARFT/IMPCHase). These steps of de novo purine biosynthesis, respectively. In all species of both prokaryotes and eukaryotes studied, these two activities are present on a single bifunctional polypeptide encoded on the purH gene. The human purH cDNA is 1776 base pairs in length encoding for a 591-amino acid polypeptic (Mr = 64,425). The human and avian purH cDNAs are 75 and 81% similar on the nucleotide and amino acid sequence level, respectively. The Km values for AICAR and (6R,6S)10-formyltetrahydrofolate are 16.8 microM +/- 1.5 and 60.2 microM +/- 5.0, respectively, for the cloned, purified human enzyme. A 10-amino acid sequence within the COOH-terminal portion of human AICARFT/IMPCHase has some degree of homology to a previously noted "folate binding site." Site directed mutagenesis studies indicate that this sequence plays no role in enzymatic activity. We have constructed truncation mutants which demonstrate that each of the two enzyme activities can be expressed independent of the other. IMPCHase and AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406 amino acids, respectively. The truncation mutant possessing AICARFT activity displays steady state kinetic parameters identical to those of the holoenzyme.
(-)-2'-deoxy-3'-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro (1992)

The (-)-enantiomer of 2'-deoxy-3'-thiacytidine (3TC) was found to be a potent and selective inhibitor of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) in vitro. We determined its antiviral activity against a number of laboratory strains of HIV-1 and HIV-2 in a range of CD4-bearing lymphocyte cell lines (mean 50% inhibitory concentration [IC50] range, 4 nM to 0.67 microM). 3TC was also active against a range of HIV-1 strains in peripheral blood lymphocytes (mean IC50 range, 2.5 to 90 nM). The IC50 for cytotoxicity in seven lymphocyte cell cultures, including human peripheral blood lymphocytes, ranged from 0.5 to 6 mM. 3TC had no detectable antiviral activity against a range of other viruses or in cells chronically infected with HIV-1 or HIV-2. The effects of time of addition of the compound and varying the multiplicity of infection on the antiviral activity of 3TC were determined. The results showed that 3TC is a potent and selective inhibitor of HIV-1 and HIV-2 replication in vitro.