gebhart/patrepeval huggingface dataset:
Growth-stimulatory monoclonal antibodies against human insulin-like growth factor I receptor. (1992)

Monoclonal antibodies (mAbs) against purified human placental insulin-like growth factor I (IGF-I) receptors were prepared and characterized. Three IgG mAbs were specific for the human IGF-I receptor and displayed negligible crossreactivity with the human insulin receptor. They stimulated 125I-labeled IGF-I (125I-IGF-I) or 125I-IGF-II binding to purified human placental IGF-I receptors and to IGF-I receptors expressed in NIH 3T3 cells in contrast to the well-studied mAb alpha IR-3, which inhibits 125I-IGF-I or 125I-IGF-II binding to both forms of IGF-I receptors. The mAbs introduced in this study stimulated DNA synthesis in NIH 3T3 cells expressing human IGF-I receptors approximately 1.5-fold above the basal level and the IGF-I- or IGF-II-stimulated level. In contrast, alpha IR-3 inhibited both basal and IGF-I or IGF-II-stimulated DNA synthesis by approximately 30%. Inhibition of IGF-II-stimulated DNA synthesis by alpha IR-3 was as potent as its inhibition of IGF-I-stimulated DNA synthesis, although IGF-II binding to the IGF-I receptors was not inhibited by IGF-II as potently as was IGF-I. With the purified IGF-I receptors, both inhibitory and stimulatory mAbs were shown to activate autophosphorylation of the IGF-I receptor beta subunit and to induce microaggregation of the receptors. These results suggest that conformational changes resulting from receptor dimerization in the presence of either type of mAb may affect the signal-transducing function of the IGF-I receptor differently. These additional mAbs and alpha IR-3 immunoprecipitated nearly 90% of IGF-I binding activity from Triton X-100-solubilized human placental membranes, indicating that IGF-I receptor reactive with these mAbs is the major form of the IGF-I receptor in human placenta.
Proteomic Profile of Uterine Luminal Fluid from Early Pregnant Ewes (2010)

Embryonic development is a time-sensitive period that requires a synchronized uterine environment, which is created by the secretion of proteins from both the embryo and uterus. Numerous studies have identified uterine luminal proteins and related these to specific adaptations during early pregnancy (EP). However, no study has yet utilized LC-MS/MS to identify the signature profile of proteins in the uterine lumen during EP. In this study, uterine luminal fluid from nonpregnant (NP; n = 3) and EP (n = 3; gestational day 16) ewes were analyzed by LC-MS/MS and validated by Western immunoblotting. We identified a unique signature profile for EP luminal fluid; 15 proteins related to specific aspects of embryonic development including growth and remodeling, immune system regulation, oxidative stress balance, and nutrition were significantly altered (up to 65-fold of NP) in EP profile. Specific uterine remodeling proteins such as transgelin (P = 0.008) and placental proteins like PP9 (P = 0.02) were present in EP luminal fluid but were barely detectable in the NP flushings. Direct correlations (R(2) = 0.84, P = 0.01) were observed between proteomics and immunoblotting. These data provide information on dynamic physiological processes associated with EP at the level of the uterus and conceptus and may potentially demonstrate a signature profile associated with embryonic well-being.
Preemptive priority-based scheduling: an appropriate engineering approach (1995)

Introduction Recent developments in the analysis of fixed-priority preemptive scheduling have made significant enhancements to the models introduced by Lui and Layland in their seminal 1973 paper [33]. These developments, taken together, now represent a body of analysis that forms the basis for an engineering approach to the design, verification, and implementation of hard real-time systems. In this chapter we review much of this analysis in order to support the thesis that safety critical realtime systems can, and should, be built using these techniques. Preemptive priority-based scheduling prescribes a run-time environment in which tasks, with a priority attribute, are dispatched in priority order. Priorities are, essentially, static. Processes are either runnable, in which case they are held on a notional (priority-ordered) run queue; delayed, in which case they are held Sec. 10.1 Introduction 223 on a notional delay queue; or suspended, in which
A Critical Assessment of Recent Work on the Application of Gas/Particle Partitioning Theories to Cigarette Smoke (2000)

Abstract In the August 1997 issue of Environmental Science&amp;Technology (ES&amp;T), PANKOW and co-workers at the Oregon Graduate Institute reported that the addition of ammonia-containing additives to cigarette tobacco increased the amount of unprotonated nicotine in cigarette mainstream smoke (MSS) and thus increased the bioavailability of nicotine to the smoker. Articles about PANKOW's work also appeared in other publications along with allegations that ammonia-containing additives are used to manipulate nicotine deliveries. However, initial review of PANKOW's research and that reported on environmental tobacco smoke (ETS) in an earlier paper showed that potentially serious issues existed with PANKOW's experimental data and conclusions. Consequently, a critical assessment of PANKOW's research and the underlying theories of gas/particle partitioning was undertaken. This assessment confirmed that PANKOW and his co-workers made a number of errors not only in their determinations of the gas/particle partitioning coefficients for nicotine in MSS and ETS but also in the interpretations of the data. During the preparation of this assessment, data from other researchers became public. These data showed that there was no correlation between tobacco ammonia (including residual ammonia from the use of ammonia-containing additives) and MSS ammonia deliveries and MSS smoke pH, and that the amount of unprotonated nicotine in the undiluted MSS of a full flavor (FF) American filter cigarette was less than 0.1%. These new data fully substantiated the findings of this assessment, and it can be safely concluded that the assertions made by PANKOW and his co-workers were incorrect. However, this assessment also showed that there is significant merit in the application of PANKOW's theory of absorptive partitioning for the estimation of the gas/particle partitioning of semivolatile components in MSS and ETS. Application of PANKOW's theory along with data from recent tobacco related conferences has allowed estimation of the gas/particle partition coefficient for nicotine in cigarette MSS and also has allowed approximation of values for the activity coefficient of nicotine in mainstream particulate matter.
The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia (2011)

An important mediator of cytokine signaling implicated in regulation of hematopoiesis is the PI3K/protein kinase B (PKB/c-Akt) signaling module. Constitutive activation of this signaling module has been observed in a large group of leukemias. Because activation of this signaling pathway has been demonstrated to be sufficient to induce hematologic malignancies and is thought to correlate with poor prognosis and enhanced drug resistance, it is considered to be a promising target for therapy. A high number of pharmacologic inhibitors directed against either individual or multiple components of this pathway have already been developed to improve therapy. In this review, the safety and efficacy of both single and dual-specificity inhibitors will be discussed as well as the potential of combination therapy with either inhibitors directed against other signal transduction molecules or classic chemotherapy.
Automation of Workplace Lifting Hazard Assessment for Musculoskeletal Injury Prevention (2014)

Our results suggest that it may be possible to produce reasonable estimates of posture and temporal elements of tasks such as task frequency in an automated fashion, although these findings should be confirmed in a larger study. Further work is needed to incorporate force assessments and address workplace feasibility challenges. We anticipate that this approach could ultimately be used to perform large-scale musculoskeletal exposure assessment not only for research but also to provide real-time feedback to workers and employers during work method improvement activities and employee training.
The Biochemistry of Vision (1953)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen (2010)

Erythropoiesis in Rac1(-/-);Rac2(-/-) mice is characterized by abnormal burst-forming unit-erythroid colony morphology and decreased numbers of megakaryocyte-erythrocyte progenitors, erythroid colony-forming units, and erythroblasts in the bone marrow. In contrast, splenic erythropoiesis is increased. Combined Rac1 and Rac2 deficiency compromises proliferation of the megakaryocyte-erythrocyte progenitor population in the bone marrow, while it allows increased survival and proliferation of megakaryocyte-erythrocyte progenitors in the spleen. Conclusions These data suggest that Rac1 and Rac2 GTPases are essential for normal bone marrow erythropoiesis but that they are dispensable for erythropoiesis in the spleen, implying different signaling pathways for homeostatic and stress erythropoiesis.
Mutational Activation of the K-rasOncogene (1987)

To define the role of cellular oncogenes in human cancers, we studied the prevalence of mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. The K-ras gene was found to be activated by point mutations in codon 12 in 5 of 10 adenocarcinomas. Two of these tumors were less than 2 cm in size and had not metastasized. No ras gene mutations were observed in 15 squamous-cell carcinomas, 10 large-cell carcinomas, 1 carcinoid, 2 metastatic adenocarcinomas from primary tumors outside the lung, and 1 small-cell carcinoma. An approximately 20-fold amplification of the unmutated K-ras gene was observed in a tumor that proved to be a solitary lung metastasis of a rectal carcinoma. We conclude that mutational K-ras activation may be an important early event in the pathogenesis of adenocarcinoma of the lung but that amplification of ras genes or mutational activation of H-ras or N-ras does not play a major part in non-small-cell lung cancer.
Viral Late Domains (2002)

Domains have been identified in the Gag proteins of a number of retroviruses, and in the matrix proteins of the rhabdoviruses and filoviruses, that play a critical role in the pinching off of virus particles from the plasma membrane. These sequences are collectively termed late or L domains to reflect their function late in the virus budding process. One of the intriguing features of these L domains is that they all contain highly conserved motifs known to mediate protein-protein interactions between cellular proteins. Three classes of motifs have been defined in viral L domains: PTAP, PPXY, and YXXL. In each case, the integrity of these motifs appears to be essential for L domain activity, suggesting that L domains function by interacting with a host factor(s). This minireview summarizes the present state of our knowledge concerning viral L domain function and describes recent tantalizing clues regarding the identity of the cellular partners with which L domains interact.
Effects of Reversible Renal Denervation on Haemodynamic and Excretory Functions of the Ipsilateral and Contralateral Kidney in the Cat (1986)

In anaesthetized cats reversible denervation of one kidney was performed by cooling of the left renal nerves to 3 degrees C for 16 min. The response of the left (ipsilateral) kidney was compared with the response of the right (contralateral) kidney twice in the same animal: (1) when the right kidney was still innervated, and (2) after it had been surgically denervated. Left renal nerve cooling did not cause any changes in arterial pressure. In the left kidney, blood flow, vascular conductance, sodium and water excretions increased, and renin release decreased. Simultaneously in the contralateral kidney, no haemodynamic changes were observed, glomerular filtration was only transiently decreased, whereas sodium and water excretion significantly decreased and renin release increased. When left renal nerve cooling was repeated after surgical denervation of the right kidney, similar changes were observed in the left (ipsilateral) kidney, whereas all contralateral effects were abolished. These experiments suggest that tonically active afferent fibres from one kidney exert a reflex inhibitory action on sympathetic activity directed to the contralateral kidney controlling tubular sodium reabsorption and renin release.
On-Resin Click-Glycoconjugationof Peptoids (2009)

Peptoids are unnatural peptide-like oligomers having the side-chain attached to the glycine nitrogen. In order to investigate how such oligomers are affected upon glycoconjugation, a series of glycosylated peptoids has been synthesized. The conjugation between glycosyl residue and peptoid was achieved by azide + alkyne [3+2] cycloaddition (click reaction). The glycosylated peptoids were obtained by either stepwise assembly from sarcosine and glycosylated monomers or global on-resin click glycoconjugation. CD spectroscopic studies were performed on both unglycosylated and glycosylated peptoids with varying chain-length, revealing length and substituent dependences. Additionally, three peptoids were tested for antifreeze activity.
The comparative efficacy and toxicity of second‐line drugs in rheumatoid arthritis results of two metaanalyses (1990)

We performed 2 metaanalyses of placebo-controlled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid arthritis (RA). For the efficacy study, we applied a set of inclusion criteria and focused on trials which provided information on tender joint count, erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials that contained 117 treatment groups of interest, and for each drug, we combined the treatment groups. For each outcome, results showed that AUR tended to be weaker than other second-line drugs. The results of the 3 outcome measures were synthesized into a composite measure of outcomes, and AUR was significantly weaker than MTX (P = 0.006), injectable gold (P less than 0.0001), DP (P less than 0.0001), and SSZ (P = 0.009) and was slightly, but not significantly, weaker than antimalarial agents (P = 0.11). We also found heterogeneity among antimalarial agents, in that patients treated with chloroquine did better than those treated with hydroxychloroquine. We found little difference in efficacy between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial should contain at least 170 patients per treatment group to successfully differentiate between more effective and less effective (e.g., AUR) second-line drugs. None of the reported interdrug comparative trials we reviewed were this large. For the toxicity study, our inclusion criteria captured RA trials which reported the proportion of patients who discontinued therapy because of drug toxicity and the total proportion who dropped out. We found 71 clinical trials that contained 129 treatment groups. The average proportion who dropped out and the average proportion who dropped out because of drug toxicity were computed for each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of them did so because of drug toxicity. Injectable gold had higher toxicity rates (P less than 0.05) and higher total dropout rates (P less than 0.01) than any other drug; 30% of gold-treated patients dropped out because of side effects versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low rates of toxicity; the rate for MTX was imprecise because of discrepancies between trials. Thus, of the commonly used second-line drugs, AUR is the weakest, and injectable gold is the most toxic. Agents introduced in the future will be compared with these drugs.(ABSTRACT TRUNCATED AT 400 WORDS)
Acute d-serine treatment produces antidepressant-like effects in rodents (2011)

Research suggests that dysfunctional glutamatergic signalling may contribute to depression, a debilitating mood disorder affecting millions of individuals worldwide. Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects in approximately 70% of patients. Glutamate evokes the release of D-serine from astrocytes and neurons, which then acts as a co-agonist and binds at the glycine site on the NR1 subunit of NMDA receptors. Several studies have implicated glial deficits as one of the underlying facets of the neurobiology of depression. The present study tested the hypothesis that D-serine modulates behaviours related to depression. The behavioural effects of a single, acute D-serine administration were examined in several rodent tests of antidepressant-like effects, including the forced swim test (FST), the female urine sniffing test (FUST) following serotonin depletion, and the learned helplessness (LH) paradigm. D-serine significantly reduced immobility in the FST without affecting general motor function. Both D-serine and ketamine significantly rescued sexual reward-seeking deficits caused by serotonin depletion in the FUST. Finally, D-serine reversed LH behaviour, as measured by escape latency, number of escapes, and percentage of mice developing LH. Mice lacking NR1 expression in forebrain excitatory neurons exhibited a depression-like phenotype in the same behavioural tests, and did not respond to D-serine treatment. These findings suggest that D-serine produces antidepressant-like effects and support the notion of complex glutamatergic dysfunction in depression. It is unclear whether D-serine has a convergent influence on downstream synaptic plasticity cascades that may yield a similar therapeutic profile to NMDA antagonists like ketamine.
Dielectrophoretic isolation and detection of cfc‐DNA nanoparticulate biomarkers and virus from blood (2013)

Dielectrophoretic (DEP) microarray devices allow important cellular nanoparticulate biomarkers and virus to be rapidly isolated, concentrated, and detected directly from clinical and biological samples. A variety of submicron nanoparticulate entities including cell free circulating (cfc) DNA, mitochondria, and virus can be isolated into DEP high-field areas on microelectrodes, while blood cells and other micron-size entities become isolated into DEP low-field areas between the microelectrodes. The nanoparticulate entities are held in the DEP high-field areas while cells are washed away along with proteins and other small molecules that are not affected by the DEP electric fields. DEP carried out on 20 μL of whole blood obtained from chronic lymphocytic leukemia patients showed a considerable amount of SYBR Green stained DNA fluorescent material concentrated in the DEP high-field regions. Whole blood obtained from healthy individuals showed little or no fluorescent DNA materials in the DEP high-field regions. Fluorescent T7 bacteriophage virus could be isolated directly from blood samples, and fluorescently stained mitochondria could be isolated from biological buffer samples. Using newer DEP microarray devices, high-molecular-weight DNA could be isolated from serum and detected at levels as low as 8-16 ng/mL.
Loss measurement and analysis of high-silica reflection bending optical waveguides (1988)

Bending loss of high-silica single-mode bending optical waveguides using a waveguide side-wall as a reflecting facet is described theoretically and experimentally as a function of the bending angle. Two types of bending waveguides, which have the reflecting facet exposed to the air coated with a metal film, are treated. The causes of bending loss are discussed in terms of los due to the Goos-Hanchen effect and the perpendicularity and roughness of the reflecting facet.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis (2016)

Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of proteoglycans, resulting in disassembly of the extracellular matrix underlying endothelial and epithelial cells and associating with enhanced cell invasion and metastasis. Heparanase expression is induced in carcinomas and sarcomas, often associating with enhanced tumor metastasis and poor prognosis. In contrast, the function of heparanase in hematological malignancies (except myeloma) was not investigated in depth. Here, we provide evidence that heparanase is expressed by human follicular and diffused non-Hodgkin's B-lymphomas, and that heparanase inhibitors restrain the growth of tumor xenografts produced by lymphoma cell lines. Furthermore, we describe, for the first time to our knowledge, the development and characterization of heparanase-neutralizing monoclonal antibodies that inhibit cell invasion and tumor metastasis, the hallmark of heparanase activity. Using luciferase-labeled Raji lymphoma cells, we show that the heparanase-neutralizing monoclonal antibodies profoundly inhibit tumor load in the mouse bones, associating with reduced cell proliferation and angiogenesis. Notably, we found that Raji cells lack intrinsic heparanase activity, but tumor xenografts produced by this cell line exhibit typical heparanase activity, likely contributed by host cells composing the tumor microenvironment. Thus, the neutralizing monoclonal antibodies attenuate lymphoma growth by targeting heparanase in the tumor microenvironment.