gebhart/patrepeval huggingface dataset:
Dronedarone: an amiodarone analogue (2004)

Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardiac side effects and this has driven development of amiodarone analogues. These analogues include short acting analogues (e.g., AT-2001) with similar acute effects to amiodarone, the thyroid receptor antagonist KB-130015 and dronedarone. Dronedarone, (SR-33589; Sanofi-Synthelabo), is a non-iodinated amiodarone derivative that inhibits Na +, K + and Ca 2+ currents. It is a potent inhibitor of the acetylcholine-activated K + current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K + currents and inhibits L-type calcium current. Dronedarone is an antagonist at alpha- and beta-adrenoceptors and unlike amiodarone, has little effect at thyroid receptors. Dronedarone is more potent than amiodarone in inhibiting arrhythmias and death in animal models of ischaemia- and reperfusion-induced arrhythmias. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) clinical trial, dronedarone 800 mg/day appeared to be effective and safe for the prevention of atrial fibrillation relapses after cardioversion. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) trial was stopped due to a potential increased risk of death in the dronedarone group. Trials of dronedarone in the maintenance of sinus rhythm in patients with atrial fibrillation and a safety and tolerability study in patients with an implantable cardioverter defibrillator are ongoing. Further experimental and clinical studies are required before we have a definitive answer to whether dronedarone has advantages over amiodarone and other amiodarone analogues.
A Novel Pathogenic Taxon of the Mycobacterium tuberculosis Complex, Canetti: Characterization of an Exceptional Isolate from Africa (1997)

In an attempt to characterize an unusual mycobacterial strain isolated from a 2-year-old Somali patient with lymphadenitis, we applied various molecular methods not previously used for the taxonomic classification of mycobacteria. This isolate, designated So93, did not differ from Mycobacterium tuberculosis in the biochemical tests and in its 16S rRNA sequence, but produced smooth and glossy colonies, which is highly exceptional for this species. This smooth phenotype was unstable and switched nonreversibly to a rough colony morphology with a low frequency. The two colony types were equally virulent for the guinea pig, exhibiting characteristic tuberculous disease. Both morphotypes had shorter generation times than the M. tuberculosis reference laboratory strain H37Rv and clinical isolates of M. tuberculosis and Mycobacterium bovis. Furthermore, the So93 isolate differed from all M. tuberculosis complex strains described thus far by having only a single copy of insertion sequence IS1081, an unusual composition of the direct repeat cluster, and a characteristic phenolic glycolipid and lipooligosaccharide. This glycolipid had previously been observed only in a smooth isolate of M. tuberculosis obtained in 1969 by Canetti in France. Analysis of the Canetti strain showed that it shared virtually all genetic properties characteristic of So93, distinguishing these two strains from the known M. tuberculosis complex taxa, M. tuberculosis, Mycobacterium africanum, M. bovis, and Mycobacterium microti. The natural reservoir, host range, and mode of transmission of the group of bacteria described in this paper are presently unknown. This study, partly based on not previously used molecular criteria, supports the idea that the established members within the M. tuberculosis complex and the newly described Canetti grouping should be regarded as a single species, which likely will be designated "M. tuberculosis".
Comparison of action of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in human breast cancer cells. (2000)

The new anticancer agent poly(L-glutamic acid)-paclitaxel (PG-TXL) is a conjugate of paclitaxel and the water-soluble polyglutamate carrier. The observation that PG-TXL appears to possess antitumor activity superior to free paclitaxel in preclinical studies suggests that PG-TXL might possess favorable pharmacokinetic properties and/or have a mechanism of action different from that of paclitaxel. The purpose of this study was to compare the pharmacological action of PG-TXL and free paclitaxel in a panel of breast cancer cell lines with emphasis on their ability to induce apoptosis, their effects on cell cycle progression, and their cellular uptake. Morphological analysis and biochemical characterizations demonstrated that both compounds have similar abilities to induce apoptosis in cells expressing wild-type p53 (MCF-7) or mutant p53 (MDA-MB435 and MDA-MB453). Although MCF-7 cells were less sensitive to each compound than MDA-MB435 and MDA-MB453 cells, transfection experiments demonstrated that p53 did not appear to play a significant role in drug-induced cell death with either agent. Flow cytometry analysis further revealed that both free paclitaxel and PG-TXL induced a characteristic G2/M arrest in the cell cycle, consistent with the disturbance of microtubule polymerization as their mechanism of action. Western blot analysis showed that paclitaxel and PG-TXL downregulated HER2/neu expression in a similar fashion. HPLC analysis revealed that paclitaxel was released from the PG-TXL conjugate in vitro. The released paclitaxel, not the glutamic acid polymer, was subsequently transported into the cells. These results suggest that PG-TXL exerts its anticancer activity by continuous release of free paclitaxel, and that the favorable pharmacokinetics and drug distribution of the PG-TXL conjugate in vivo are likely the main factors contributing to its superior anticancer activity.
Galactose oxidase-glucan binding domain fusion proteins as targeting inhibitors of dental plaque bacteria (1997)

In order to inhibit the growth of bacteria present in the human oral cavity, a novel system which targets antimicrobial agents to dental plaque has been developed. This system involves a hybrid protein consisting of a peptide expressing the bactericidal properties of galactose oxidase (GAO) fused to the glucan binding domain (GBD) of the Streptococcus mutans glucosyltransferase-S enzyme. A gene encoding GAO from the fungus Fusarium sp. has been inserted into an Escherichia coli expression vector and fused to sequences encoding the GBD, which binds to the glucans synthesized by oral streptococci. Bacterial extracts expressing the hybrid protein were tested for their ability to target the GAO activity to an in vitro plaque model consisting of streptococcal cells bound to microtiter plate wells. The binding of the hybrid protein to the streptococcal cells through its GBD and the dependence of binding on the production of glucans by bacteria were demonstrated. Furthermore, killing of three different species of oral streptococci by bound hybrid protein in conjunction with the galactose-lactoperoxidase-iodide cytotoxic system has been demonstrated. These results suggest a novel strategy for controlling dental plaque formation as well as dental caries in humans.
Genetic dissection of the learning/memory gene dunce of Drosophila melanogaster. (1993)

The dunce (dnc) gene of Drosophila melanogaster codes for cAMP phosphodiesterase (PDE) and is required for normal learning/memory and for female fertility. The expression of the gene is elevated in mushroom bodies, brain structures implicated in olfactory learning and memory. In this study several chromosomal deletions and inversions that remove increasingly larger portions of the dnc gene from its 5' end and progressively more of the five known transcription start sites (tss) were used to assess the functions of the various transcriptional units. Surprisingly, the dnc PDE activity, female fertility, mushroom body expression, learning, and memory were unaffected by the removal of tss1 and tss2. tss3 was required for elevated mushroom body expression but not for female fertility nor initial learning. tss4 contributed to learning and the female fertility function, whereas tss5 contributed to female fertility. The results indicate that the structural complexity of the gene is of biological significance, with individual transcriptional units serving different biological functions.
Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX (1992)

Factor IX is a multidomain protein and is the proenzyme of a serine protease, factor IXa, essential for hemostasis. In this report, we describe the molecular basis of hemophilia B (deficiency of factor IX activity) in five patients who have neither deletions nor rearrangements of the factor IX gene. By enzymatic amplification and sequencing of all exons and promoter regions, the following causative mutation in the protease domain of factor IX was identified in each patient: IXSchmallenberg: nucleotide 31,215G----T, Ser365Ile; IXVarel: nucleotide 31,214A----G, Ser365Gly; IXMechtal: nucleotide 31,211G----C, Asp364His; IXDreihacken: nucleotide 30,864G----A, Arg248Gln; and IXMonschau: nucleotide 30,855A----T, Glu245Val. In IXVarel, nucleotide 31,213T was also replaced by C, which results in a silent mutation (GAT- ---GAC) at Asp-364. Thus, this patient has a double base-pair substitution of TA to CG at nucleotides 31,213 and 31,214 but only a single amino acid change of Ser-365 to Gly. This patient also developed an antibody to factor IX during replacement therapy, which suggests that deletion of the factor IX gene is not necessary for development of the antibody in hemophilia B patients. The levels of plasma factor IX antigen in the patients ranged from 40% to 100% except for IXDreihacken (Arg248Gln), in which case it was approximately 4% of normal. The Ser365Gly and Ser365Ile mutants are nonfunctional because of lack of the active site serine residue. Mutant Asp364His is inactive because it cannot form the hydrogen bond between the carboxylate group of Asp-364 and the alpha-amino group of Val-181 generated after activation. As observed in other homologous serine proteases, this hydrogen bond is essential for maintaining the correct active site conformation in normal factor IXa (IXaN). Purified Arg248Gln had approximately 41% and Glu245Val had approximately 17% of the activity of normal factor IX (IXN) in a partial thromboplastin time (aPTT) assay. In immunodot blot experiments, the isolated Glu245Val mutant did and the Arg248Gln mutant did not bind to an anti-IXN monoclonal antibody that has been shown previously to inhibit the interaction of factor VIIIa with factor IXaN. We have recently shown that a high-affinity calcium binding site exists in the protease domain of IXN; among the proposed Ca(2+)-binding ligands is the carboxyl group of Glu-245. Further, a part of the epitope for the above antibody was shown to be contained in the 231 to 265 residue segment of factor IX.(ABSTRACT TRUNCATED AT 400 WORDS).
Inkjet-printing- and electroless-plating- based fabrication of RF circuit structures on high-frequency substrates (2009)

In this paper, a method to fabricate radio frequency (RF) circuit structures is described. This method involves inkjet printing of a silver nanoparticle-based ink on a functional substrate material to create the seed track (i.e., the seed layer), onto which copper is subsequently deposited by an electroless plating method, to obtain the desired thickness and conductivity of the RF structures. This process combination was validated by fabricating an S-band filter on a high-frequency substrate and comparing the RF performance of this filter with that of a filter fabricated using the conventional lithography-based method. The adhesion of the circuit structures to the substrate was qualitatively ascertained by the scotch tape test method. The performance of the inkjet-printed-electroless-plated filter was comparable to that of the conventional filter, thus proving the suitability of this novel method for practical RF applications.
Evaluation of EML4-ALK Fusion Proteins in Non–Small Cell Lung Cancer Using Small Molecule Inhibitors (2011)

The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene resulting from an inversion within chromosome 2p occurs in approximately 5% of non-small cell lung cancer and is mutually exclusive with Ras and EGFR mutations. In this study, we have used a potent and selective ALK small molecule inhibitor, NPV-TAE684, to assess the oncogenic role of EML4-ALK in non-small cell lung cancer (NSCLC). We show here that TAE684 inhibits proliferation and induces cell cycle arrest, apoptosis, and tumor regression in two NSCLC models that harbor EML4-ALK fusions. TAE684 inhibits EML4-ALK activation and its downstream signaling including ERK, AKT, and STAT3. We used microarray analysis to carry out targeted pathway studies of gene expression changes in H2228 NSCLC xenograft model after TAE684 treatment and identified a gene signature of EML4-ALK inhibition. The gene signature represents 1210 known human genes, and the top biologic processes represented by these genes are cell cycle, DNA synthesis, cell proliferation, and cell death. We also compared the effect of TAE684 with PF2341066, a c-Met and ALK small molecule inhibitor currently in clinical trial in cancers harboring ALK fusions, and demonstrated that TAE684 is a much more potent inhibitor of EML4-ALK. Our data demonstrate that EML4-ALK plays an important role in the pathogenesis of a subset of NSCLC and provides insight into the mechanism of EML4-ALK inhibition by a small molecule inhibitor.
LibGuides: Education: Education (2010)

Here you will find resources that will lead you to information about Education Search for sources on General Education
Evaluation of the sedative and cardiovascular effects of intramuscular administration of dexmedetomidine with and without concurrent atropine administration in dogs (2011)

Administration of atropine at 0.02 mg/kg, IM, with dexmedetomidine at 10 μg/kg, IM, resulted in an increase in mean arterial blood pressure and heart rate; deleterious cardiac arrhythmias were also observed. Use of atropine with dexmedetomidine is not recommended in dogs.
SPECIFIC RADIOIMMUNOASSAY OF CYCLO (HIS-PRO), A BIOLOGICALLY ACTIVE METABOLITE OF THYROTROPIN-RELEASING HORMONE (1981)

We have developed a radioimmunoassay that can detect 10 pg cyclo (His-Pro) in rat brain perchloric acid extracts. The normal rat brain concentration of cyclo (His-Pro) ranged from 35-61 pmole/brain. The elution profiles of cyclo (His-Pro)-like immunoreactivity and radioactive cyclo (His-Pro) following gel filtration and ion-exchange chromatography were similar.
Application of Encoded Multi-source Waveform Inversion to Marine-streamer Acquisition Based on the Global Correlation (2011)

The conventional multi-source inversion cannot be applied to the marine-streamer acquisition data because of the mismatch of acquisition geometries of the observed and modelled data. To make the inversion applicable to the marine-streamer acquisition, we use an objective function based on the global correlation between the observed and modelled data. The new residual seismogram based on the global correlation attenuates modeled data not supported by the observed data configuration, and thus, can be applied to multi-source marine-streamer acquisition, included blended sources. Furthermore, our method also employs the back-propagation algorithm (or Born approximation algorithm) similar to reverse-time migration based on the adjoint-state of wave equation to efficiently calculate the gradient. In the numerical examples the multi-source inversion based on the global correlation objective function resulted in a better inversion for the marine-streamer acquisition than the conventional approach.
Workload analysis of a large-scale key-value store (2012)

Key-value stores are a vital component in many scale-out enterprises, including social networks, online retail, and risk analysis. Accordingly, they are receiving increased attention from the research community in an effort to improve their performance, scalability, reliability, cost, and power consumption. To be effective, such efforts require a detailed understanding of realistic key-value workloads. And yet little is known about these workloads outside of the companies that operate them. This paper aims to address this gap.
Genetic and biochemical characterization of the oligopeptide transport system of Lactococcus lactis (1993)

The nucleotide sequence of a chromosomal DNA fragment of Lactococcus lactis subsp. lactis SSL135, previously implicated in peptide utilization, has been determined. The genes oppDFBCA, encoding the oligopeptide transport system (Opp), and that encoding the endopeptidase PepO were located on this 8.9-kb DNA fragment. The oppDFBCA and pepO genes are probably organized in an operon. Analysis of the deduced amino acid sequences of the genes indicated that the oligopeptide transport system consists of two ATP-binding proteins OppD and OppF, two integral membrane proteins OppB and OppC, and a substrate-binding protein OppA. On the basis of the homology of OppF and OppD of L. lactis with other ABC (ATP-binding cassette) transporter proteins, the L. lactis Opp system can be classified as a member of this group. Two integration mutants, one defective in OppA and the other defective in PepO, were constructed. Growth of these mutants in a chemically defined medium with oligopeptides showed that the transport system, but not the endopeptidase, is essential for the utilization of peptides longer than three residues. Uptake of the pentapeptide Leu-enkephalin in glycolyzing lactococcal cells was followed by rapid hydrolysis of the peptide intracellularly. Importantly, extracellular hydrolysis of Leu-enkephalin is not observed. The OppA-deficient mutant was unable to transport Leu-enkephalin. Growth experiments with pasteurized milk revealed that transport of oligopeptides forms an essential part of the proteolytic system in lactococci.
Repellency of Essential Oils to Mosquitoes (Diptera: Culicidae) (1999)

The repellency of different concentrations (5, 10, 25, 50, 75, and 100%) and combinations of 5 essential oils (Bourbon geranium, cedarwood, clove, peppermint, and thyme) to Aedes aegypti (L.) and Anopheles albimanus Wiedemann when applied to human skin was determined in laboratory tests. Cedarwood oil failed to repel mosquitoes and only high concentrations of peppermint oil repelled Ae. aegypti. None of the oils tested prevented mosquito bite when used at the 5 or 10% concentration. Thyme and clove oils were the most effective mosquito repellents and provided 1 1/2 to 3 1/2 h of protection, depending on oil concentration. Clove oil (50%) combined with geranium oil (50%) or with thyme oil (50%) prevented biting by An. albimanus for 1 1/4 to 2 1/2 h. The potential for using essential oils as topical mosquito repellents may be limited by user acceptability; clove, thyme, and peppermint oils can be irritating to the skin, whereas both human subjects in this study judged the odor of clove and thyme oils unacceptable at concentrations > or = 25%.
Gaussian Processes for Signal Strength-Based Location Estimation (2006)

Estimating the location of a mobile device or a robot from wireless signal strength has become an area of highly active research. The key problem in this context stems from the complexity of how signals propagate through space, especially in the presence of obstacles such as buildings, walls or people. In this paper we show how Gaussian processes can be used to generate a likelihood model for signal strength measurements. We also show how parameters of the model, such as signal noise and spatial correlation between measurements, can be learned from data via hyperparameter estimation. Experiments using WiFi indoor data and GSM cellphone connectivity demonstrate the superior performance of our approach.
DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides. (1994)

Lipoprotein lipase (LPL) plays a critical role in the metabolism of lipoproteins because this enzyme hydrolyzes the triacylglycerides in chylomicrons and very low density lipoproteins. This process influences the production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. Accordingly, LPL qualifies as a candidate gene for understanding lipid metabolic disorders and atherosclerosis. Studies on the relationship between genetic variation at the LPL locus and lipid phenotypes have produced equivocal results to date. To help clarify this issue, we investigated 144 outwardly healthy male Mediterranean migrants (from Italy and Greece), age between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the following lipid and lipoprotein phenotypes: total plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triacylglycerides. A series of analysis of variance tests, controlling for age, body mass index, and ethnicity, showed that the HindIII polymorphism at the LPL locus is significantly associated with both triacylglyceride and HDL cholesterol concentrations in this sample. The PvUII polymorphism, however, showed no association with any lipid. Kruskal-Wallis tests confirmed the significance of the associations between the HindIII RFLP and both HDL (p = 0.008) and triacylglycerides (p = 0.03). When the sample was subdivided into subjects who exhibited primary hypertriacylglyceridemia and normolipidemics, a significant difference was observed in the frequency of HindIII (p < 0.05) but not PvuII genotypes. HindIII heterozygotes (H1,H2) were least and H2,H2 individuals were most at risk for triacylglyceridemia. Examination of the normolipidemic sample revealed some evidence for an independent effect of the PvuII polymorphism on both LDL cholesterol and total cholesterol levels.
Editor's Note (1989)

With this issue, Charles B. Metz will retire from the editorship of The Biological Bulletin after a successful 10-year tenure. Marine Biological Laboratory President and Director Harlyn O. Halvorson is pleased to announce that Michael J. Greenberg has agreed to serve a five-year term as Editor-in-Chief of the journal. Dr. Greenberg is currently the director of the University of Florida's Whitney Laboratory in St. Augustine, Florida. Please note that all manuscript correspondence should still be sent to the Managing Editor at the Marine Biological Laboratory, Woods Hole, Massachusetts 02543.
Genomic organization and expression of Campylobacter flagellin genes (1990)

Campylobacter coli VC167, which undergoes an antigenic flagellar variation, contains two full-length flagellin genes, flaA and flaB, that are located adjacent to one another in a tandem orientation and are 91.5% homologous. The gene product of flaB, which has an Mr of 58,946, has 93% sequence homology to the gene product of flaA, which has an Mr of 58,916 (S. M. Logan, T. J. Trust, and P. Guerry, J. Bacteriol. 171:3031-3038, 1989). Mutational analyses and primer extension experiments indicated that the two genes are transcribed under the control of distinct promoters but that they are expressed concomitantly in the same cell, regardless of the antigenic phase of flagella being produced. The flaA gene, which was expressed at higher levels than the flaB gene in both phases, was transcribed from a typical sigma 28-type promoter, whereas the flaB promoter was unusual. A mutant producing only the flaB gene product did not synthesize a flagellar filament and was nonmotile. Southern blot analysis indicated that flagellar antigenic variation involves a rearrangement of flagellin sequence information rather than the alternate expression of the two distinct genes.