gebhart/patrepeval huggingface dataset:
Tyrosine Kinases as Targets for Anti-Inflammatory Therapy (2007)

Tyrosine kinases play key roles in cell proliferation, differentiation, survival, cell migration, tissue development, and cell metabolisms. Mutation and /or truncation in tyrosine kinases result in their constitutive activation independent of ligand stimulation. The constitutively activated tyrosine kinase often triggers cancer development. Furthermore, it is well documented that overexpression of tyrosine kinases is involved in malignancy. In inflammatory lesion, tyrosine kinases are also activated via over-production of growth factors and/or cytokines from tissues. Several recent studies have demonstrated that targeting tyrosine kinases in inflammatory disease may lead to an useful therapy. In this review, we describe tyrosine kinases that are or may be involved in inflammatory disease such as stem cell factor (SCF) receptor (c-Kit), platelet derived growth factor (PDGF) receptors, macrophage colony stimulating factor (M-CSF) receptor (c-Fms), Trk receptors, vascular endothelial growth factor (VEGF) receptors, fibroblast growth factor (FGF) receptors, epidermal growth factor (EGF) receptors, macrophage stimulating protein receptor (Ron), Janus kinases (Jak), and spleen tyrosine kinase (Syk)/zeta-chain associated protein kinase of 70 kDa (ZAP-70). In addition we describe potential tools and methods that can be applied for therapy, such as small molecule kinase inhibitors, antibodies, small peptides, or truncated receptors. Since inflammatory diseases are generally complex host reactions for a long term, and tyrosine kinases are important for maintenance of cell homeostasis, a successful tyrosine kinase targeting therapy will require many further studies. Keywords: Receptor tyrosine kinase, cytoplasmic tyrosine kinase, growth factors and cytokines, inflammatory disease, therapeutic targets, small molecule kinase inhibitors, inhibitory antibodies
Evaluation of ‘In-Car’ Countermeasures to Sleepiness: Cold Air and Radio (1998)

The efficacy of putative "in-car" countermeasures to driver sleepiness is unknown. Sixteen young adult drivers within the normal range for the Epworth Sleepiness Scale (ESS), had their sleep restricted to 5 hours the night before, and drove an interactive car simulator in the afternoon for 2.5 hours, under monotonous conditions. After 30 minutes of driving they were exposed to: (1) cold air to the face (AIR) from the vehicle's air conditioning vents, (2) listening to the vehicle's radio/tape (RADIO) according to subjects' choice, or (3) NIL treatment. The active treatments typified those experienced under real driving conditions. Drifting over lane markings were "incidents." EEGs were recorded and spectrally analyzed in the alpha and theta range. Subjects responded to the Karolinska Sleepiness Scale (KSS) every 200 seconds. Overall, RADIO and AIR had no significant effects on incidents, although there was a trend for RADIO to reduce incidents, particularly during the first 30 minutes, when AIR also had some effect. KSS scores were significantly lower for RADIO for most of the drive, whereas AIR had only transient and non-significant effects. The EEG showed no significant effects of the active treatments. Compared with other countermeasures such as caffeine and a brief nap, which we have previously shown to be more effective (using the same equipment and protocols), AIR and RADIO are at best only temporary expedients to reduce driver sleepiness, perhaps enabling drivers to find a suitable place to stop, take a break and avail themselves of caffeine and a nap.
Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma (2008)

Chromosomal aneuploidy is the major reason why couples opt for prenatal diagnosis. Current methods for definitive diagnosis rely on invasive procedures, such as chorionic villus sampling and amniocentesis, and are associated with a risk of fetal miscarriage. Fetal DNA has been found in maternal plasma but exists as a minor fraction among a high background of maternal DNA. Hence, quantitative perturbations caused by an aneuploid chromosome in the fetal genome to the overall representation of sequences from that chromosome in maternal plasma would be small. Even with highly precise single molecule counting methods such as digital PCR, a large number of DNA molecules and hence maternal plasma volume would need to be analyzed to achieve the necessary analytical precision. Here we reasoned that instead of using approaches that target specific gene loci, the use of a locus-independent method would greatly increase the number of target molecules from the aneuploid chromosome that could be analyzed within the same fixed volume of plasma. Hence, we used massively parallel genomic sequencing to quantify maternal plasma DNA sequences for the noninvasive prenatal detection of fetal trisomy 21. Twenty-eight first and second trimester maternal plasma samples were tested. All 14 trisomy 21 fetuses and 14 euploid fetuses were correctly identified. Massively parallel plasma DNA sequencing represents a new approach that is potentially applicable to all pregnancies for the noninvasive prenatal diagnosis of fetal chromosomal aneuploidies.
Treatment of recalcitrant psoriatic arthritis with anti‐tumor necrosis factor‐α antibody (2002)

Currently available treatments for psoriatic arthritis are either not completely effective or toxic in some patients. As tumour necrosis factor (TNF)-alpha is involved in both the joint and skin involvement in psoriatic arthritis, blockade of TNF-alpha seems a reliable way to treat patients with this disease. We report two patients with progressive recalcitrant psoriatic arthritis treated with low-dose methotrexate (7.5 mg, once per week) in combination with intravenous chimeric monoclonal anti-TNF-alpha antibody (infliximab, 3 mg/kg body weight). Both showed a dramatic and rapid response in the reduction of pain, followed by improvement of laboratory and clinical signs of joint inflammation. Skin disease also responds after a short delay. The observation shows that infliximab is effective and well tolerated in patients with recalcitrant progressive psoriatic arthritis. Different kinetics of symptom release during treatment suggest a variable role for TNF-alpha in disease pathways of pain, joint inflammation and skin involvement.
Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors (2005)

Inhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA). Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication. With the use of reverse genetics technique, we investigated the effect of glycans attached at Asn 94a, 129, and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activity.
ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines: A Focused Update of the ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use (2010)

Abraham, Neena S MD, FACG, Chair; Hlatky, Mark A MD, FACC, FAHA, Vice Chair; Antman, Elliott M MD, FACC, FAHA; Bhatt, Deepak L MD, MPH, FACC, FAHA; Bjorkman, David J MD, MSPH, FACG; Clark, Craig B DO, FACC, FAHA; Furberg, Curt D MD, PhD, FAHA; Johnson, David A MD, FACG; Kahi, Charles J MD, MSc, FACG; Laine, Loren MD, FACG; Mahaffey, Kenneth W MD, FACC; Quigley, Eamonn M MD, FACG; Scheiman, James MD, FACG; Sperling, Laurence S MD, FACC, FAHA; Tomaselli, Gordon F MD, FACC, FAHA Author Information
Adult rabbit cardiomyocytes undergo hibernation-like dedifferentiation when co-cultured with cardiac fibroblasts (2001)

Objectives: Little is known about the causal factors which induce the typical structural changes accompanying cardiomyocyte dedifferentiation in vivo such as in chronic hibernating myocardium. For identifying important factors involved in cardiomyocyte dedifferentiation, as seen in chronic hibernation, an in vitro model mimicking those morphological changes, would be extremely helpful. Methods: Adult rabbit cardiomyocytes were co-cultured with cardiac fibroblasts. The typical changes induced by this culturing paradigm were investigated using morphometry, electron microscopy and immunocytochemical analysis of several structural proteins, which were used as dedifferentiation markers, i.e., titin, desmin, cardiotin and α-smooth muscle actin. Results: Close apposition of fibroblasts with adult rabbit cardiomyocytes induced hibernation-like dedifferentiation, similar to the typical changes seen in chronic hibernation in vivo. Both changes in ultrastructure and in the protein expression pattern of dedifferentiation markers as seen in chronic hibernating myocardium were seen in the co-cultured cardiomyocytes. Conclusion: Hibernation-like changes can be induced by co-culturing adult rabbit cardiomyocytes with fibroblasts. This cellular model can be a valuable tool in identifying and characterizing the pathways involved in the dedifferentiation phenotype in vivo, and already suggests that many of the structural changes accompanying dedifferentiation are not per se dependent on a decreased oxygen availability.
Detoxification of organophosphate pesticides using an immobilized phosphotriesterase from Pseudomonas diminuta (1991)

A purified phosphotriesterase was successfully immobilized onto trityl agarose in a fixed bed reactor. A total of up to 9200 units of enzyme activity was immobilized onto 2.0 mL of trityl agarose (65 micromol trityl groups/mL agarose), where one unit is the amount of enzyme required to catalyze the hydrolysis of one micromole of paraoxon in one min. The immobilized enzyme was shown to behave chemically and kinetically similar to the free enzyme when paraoxon was utilized as a substrate. Several organophosphate pesticides, methyl parathion, ethyl parathion, diazinon, and coumaphos were also hydrolyzed by the immobilized phosphotriesterase. However, all substrates exhibited an affinity for the trityl agarose matrix. For increased solubility and reduction in the affinity of these pesticides for the trityl agarose matrix, methanol/water mixtures were utilized. The effect of methanol was not deleterious when concentrations of less than 20% were present. However, higher concentrations resulted in elution of enzyme from the reactor. With a 10-unit reactor, a 1.0 mM paraoxon solution was hydrolyzed completely at a flow rate of 45 mL/h. Kinetic parameters were measured with a 0.1-unit reactor with paraoxon as a substrate at a flow rate of 22 mL/h. The apparent K(m) for the immobilized enzyme was 3-4 times greater than the K(m) (0.1 mM) for the soluble enzyme. Immobilization limited the maximum rate of substrate hydrolysis to 40% of the value observed for the soluble enzyme. The pH-rate profiles of the soluble and immobilized enzymes were very similar. The immobilization of phosphotriesterase onto trityl agarose provides an effective method esterase onto trityl agarose provides an effective method for hydrolyzing and thus detoxifyuing organophosphate pesticides and mammalian acetylcholinesterase inhinbitors.
Role of Renal Nerves in Mediating the Hypertensive Effects of Nitric Oxide Synthesis Inhibition (1996)

Recent studies suggest that enhanced renal sympathetic nervous activity plays an important role in mediating the renal hemodynamic and electrolyte excretion changes associated with acute inhibition of NO synthesis. The purpose of this study was to determine the importance of renal nerves in mediating the long-term hypertensive and renal actions of NO synthesis blockade. To achieve this goal, we infused N(G)-nitro-L-arginine methyl ester (L-NAME) at a rate of 25 microg/kg per minute for 2 weeks in control dogs and in bilaterally renal-denervated dogs. NO synthesis blockade in control dogs increased arterial pressure by 18%, from 94 +/- 3 to 111 +/- 4 mm Hg, and decreased heart rate from 74 +/- 4 to 57 +/- 4 beats per minute (bpm). L-NAME also decreased renal plasma flow from 195 +/- 18 to 166 +/- 18 mL/min while having no effect on glomerular filtration rate (67 +/- 7 versus 63 +/- 6 mL/min). In the renal-denervated dogs, inhibition of NO synthesis increased arterial pressure by 14%, from 92 +/- 4 to 105 +/- 5 mm Hg, and decreased heart rate from 80 +/- 4 to 65 +/- 5 bpm. Renal plasma flow in this group decreased from 195 +/- 20 to 165 +/- 20 mL/min, whereas glomerular filtration rate remained unchanged (66+/- 6 versus 64 +/- 6 mL/min). In addition, renal excretion of sodium and water in response to L-NAME was similar in each group. The results of this study indicate that the long-term hypertensive and renal effects of NO synthesis inhibition in the dog are not dependent on activation of the renal sympathetic nervous system.
Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. (1993)

Apoptosis is a morphologically and biochemically distinct form of cell death that occurs under a variety of physiological and pathological conditions. In the present study, the proteolytic cleavage of poly(ADP-ribose) polymerase (pADPRp) during the course of chemotherapy-induced apoptosis was examined. Treatment of HL-60 human leukemia cells with the topoisomerase II-directed anticancer agent etoposide resulted in morphological changes characteristic of apoptosis. Endonucleolytic degradation of DNA to generate nucleosomal fragments occurred simultaneously. Western blotting with epitope-specific monoclonal and polyclonal antibodies revealed that these characteristic apoptotic changes were accompanied by early, quantitative cleavage of the M(r) 116,000 pADPRp polypeptide to an M(r) approximately 25,000 fragment containing the amino-terminal DNA-binding domain of pADPRp and an M(r) approximately 85,000 fragment containing the automodification and catalytic domains. Activity blotting revealed that the M(r) approximately 85,000 fragment retained basal pADPRp activity but was not activated by exogenous nicked DNA. Similar cleavage of pADPRp was observed after exposure of HL-60 cells to a variety of chemotherapeutic agents including cis-diaminedichloroplatinum(II), colcemid, 1-beta-D-arabinofuranosylcytosine, and methotrexate; to gamma-irradiation; or to the protein synthesis inhibitors puromycin or cycloheximide. Similar changes were observed in MDA-MB-468 human breast cancer cells treated with trifluorothymidine or 5-fluoro-2'-deoxyuridine and in gamma-irradiated or glucocorticoid-treated rat thymocytes undergoing apoptosis. Treatment with several compounds (tosyl-L-lysine chloromethyl ketone, tosyl-L-phenylalanine chloromethyl ketone, N-ethylmaleimide, iodoacetamide) prevented both the proteolytic cleavage of pADPRp and the internucleosomal fragmentation of DNA. The results suggest that proteolytic cleavage of pADPRp, in addition to being an early marker of chemotherapy-induced apoptosis, might reflect more widespread proteolysis that is a critical biochemical event early during the process of physiological cell death.
High-resolution timing of cell cycle-regulated gene expression (2007)

The eukaryotic cell division cycle depends on an intricate sequence of transcriptional events. Using an algorithm based on maximum-entropy deconvolution, and expression data from a highly synchronized yeast culture, we have timed the peaks of expression of transcriptionally regulated cell cycle genes to an accuracy of 2 min (approximately equal to 1% of the cell cycle time). The set of 1,129 cell cycle-regulated genes was identified by a comprehensive analysis encompassing all available cell cycle yeast data sets. Our results reveal distinct subphases of the cell cycle undetectable by morphological observation, as well as the precise timeline of macromolecular complex assembly during key cell cycle events.
Burst synchronization for OFDM-based cellular systems with separate signaling channel (2002)

A novel burst synchronization scheme suitable for a high rate OFDM/TDMA/TDD (pico)cellular system with a centralized dynamic slot allocation MAC protocol is presented. The physical layer may have an optional low-rate separate signaling channel (SSC) used in the standby mode and implemented on a subset of OFDM subcarriers. A one-shot feedforward synchronization concept for the OFDM-based active transmission mode is designed using the functionality of the SSC and a special periodical OFDM preamble. Joint symbol and frequency synchronization as well as channel estimation can be achieved simultaneously. The synchronizer features low complexity and low processing delay. Simulations verify its robust operation for indoor channel power delay profiles at 5 GHz.
Analysis of somatic hypermutation in mouse Peyer's patches using immunoglobulin kappa light-chain transgenes. (1993)

We have exploited mice transgenic for an immunoglobulin kappa light chain in order to show that immunoglobulin genes in the B cells of Peyer's patches in unimmunized mice carry a high level of somatic mutations. Most of the mutations are found in the subpopulation of B cells which, based on peanut agglutinin binding, derive from the germinal centers. The number of mutations per clone and their distribution along the variable gene segment (indicative of untemplated point mutations) are very similar to those found in antigen-specific splenic B cells of normal mice after secondary immunization. The mutations accumulate mainly in complementarity-determining region 1, in particular in some specific codons (Ser-26, Ser-31, and Ser-77) which have been previously recognized as intrinsic hypermutational hotspots. These results suggest that, as in the spleen, somatic mutation occurs in B cells which have migrated to the germinal centers, probably as a consequence of stimulation by antigens present in the gut environment. Transgenic animals are increasingly being used to define the signals involved in hypermutation. However, their subsequent study is very time-consuming because it is based on immunization and analysis of hybridomas or antigen-selected cells. We propose that the use of Peyer's patches of unimmunized adult mice offers a reliable and simple approach to analyze hypermutation of transgenes.
The Social Structure of Tagging Internet Video on del.icio.us (2007)

The ability to tag resources with uncontrolled metadata or "folksonomies" is often characterized as one of the central features of "Web 2.0" applications. Folksonomies are said to support emergent classification, where the semantic value of the tags and their relation to one another is worked out through a negotiated process of users applying their selected tags and seeing what others have tagged the same way. Few studies exist to show how folksonomic tagging is actually done, and to what extent users share each other's tagging patterns. In this paper, we present the results of a social network analysis of two months worth of tagging Internet video on the social bookmarking system del.icio.us. The analysis reveals that specific videos are tagged in fairly coherent ways by a relatively tight group of users. However, contrary to our expectations, there does not appear to be much re-use of tags across different content, or even very many users tagging more than a few similar items. Overwhelmingly, specific clusters of tags and users are associated with individual video links. This result suggests that tagging bookmarks is highly local, and the overall collection of tags is unlikely to result in a coherent globally navigable classification system
Production Optimization at Connacher’s Pod One (Great Divide) Oil Sands Project (2011)

Abstract Connacher’s first oil sands project, the Pod One facility at Great Divide, has been operational since 2007. The successful SAGD project has produced approximately 7 million barrels of bitumen. During the past three and a half years, the impacts of certain predicted reservoir challenges and opportunities have become apparent. While the quality of the oil sands in this first phase of Pod One is generally good, Pad 101 South in particular has geological zones that affect SAGD operation. This includes a bitumen lean zone, and a gas cap overlying the main bitumen channel/s. Early field results matched with detailed simulations have shown positive results in maximizing well pair production. For the purposes of this paper a lean bitumen zone differs from an aquifer in two ways. The lean zone is not charged, and is limited in size. The operation is also complicated by the fact the gas bearing zone has been depleted through earlier production. Connacher’s operating practice at Great Divide attempts to achieve a pressure balance between the 3 zones (rich oil sands, lean zone, gas cap) to reduce steam loss and maximize production rates. Reducing the pressure encourages steam chamber development growth horizontally and ensures that steam contacts the highly saturated bitumen areas. How this is achieved with the highest positive impact on well productivity is illustrated with operational data and analysis including the results of simulations that recommended the optimum operating strategies.
A Mouse Gene Encoding an Oocyte Antigen Associated with Autoimmune Premature Ovarian Failure (1999)

Autoimmune premature ovarian failure causes young women to develop menopausal symptoms and infertility. A similar syndrome appears in mice with postthymectomy autoimmune premature ovarian failure. We demonstrate that these mice develop antibodies against a 125-kDa protein located in the oocyte cytoplasm (ooplasm). By screening a mouse ovarian complementary DNA expression library with autoimmune serum, we have identified a novel mouse gene with a 3.75-kb ovarian transcript, the expression of which is restricted to the oocyte. The longest open reading frame (3333 bp) encodes an oocyte-specific protein, designated OP1 (ooplasm-specific protein 1). The protein is composed of 1111 amino acids with a predicted molecular mass of 125,502 Da. Based on its primary structure, it appears to be novel and has no motifs to suggest a localization other than in the cytoplasm. The ability of immune serum from mice with ovarian autoimmunity to react specifically with recombinant OP1 raises the possibility that OP1 as an antigen may play a role in murine autoimmune premature ovarian failure.