gebhart/patrepeval huggingface dataset:
Zonisamide: a new antiepileptic drug. (1999)

Zonisamide (ZNS) is a relatively new antiepileptic medication currently available in Japan. Attempts to market the drug in the United States were thwarted by reports of nephrolithiasis by European and American investigators. However, successful marketing of the drug in Japan has resulted in a renewed interest in bringing the drug to the United States. Japanese experience with ZNS showed a broad spectrum of efficacy in the treatment of seizures, including infantile spasms and myoclonic seizures. A neuroprotective role and an antimanic effect have also been reported. The exact antiepileptic mechanism of action of ZNS is not known, but it has dose-dependent sodium channel blocking and T-type calcium channel blocking properties and free radical scavenging actions. Recommended initial adult dosage in Japan is 100-200 mg/d, increased if necessary to 200-400 mg/d, up to a maximum of 600 mg/d. In children, initial dosage is 2-4 mg/kg/d, increased if necessary to 4-8 mg/kg/d up to a maximum of 12 mg/kg/d. The recommended therapeutic plasma ZNS concentration is 10-20 mg/L. Adverse events, most notably drowsiness, loss of appetite, gastrointestinal problems, and CNS toxicity, have been noted with plasma ZNS concentrations of > 30 mg/L. A drug rash also has been reported.
A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA (2019)

The increasing importance of in vitro-transcribed (IVT) mRNA for synthesizing the encoded therapeutic protein in vivo demands the manufacturing of pure mRNA products. The major contaminant in the IVT mRNA is double-stranded RNA (dsRNA), a transcriptional by-product that can be removed only by burdensome procedure requiring special instrumentation and generating hazardous waste. Here we present an alternative simple, fast, and cost-effective method involving only standard laboratory techniques. The purification of IVT mRNA is based on the selective binding of dsRNA to cellulose in an ethanol-containing buffer. We demonstrate that at least 90% of the dsRNA contaminants can be removed with a good, >65% recovery rate, regardless of the length, coding sequence, and nucleoside composition of the IVT mRNA. The procedure is scalable; purification of microgram or milligram amounts of IVT mRNA is achievable. Evaluating the impact of the mRNA purification in vivo in mice, increased translation could be measured for the administered transcripts, including the 1-methylpseudouridine-containing IVT mRNA, which no longer induced interferon (IFN)-α. The cellulose-based removal of dsRNA contaminants is an effective, reliable, and safe method to obtain highly pure IVT mRNA suitable for in vivo applications.
Yeast Strain Improvement by Protoplast Fusion and Transformation (1983)

Yeasts are fungi that exist predominantly in the unicellular state. The study of yeasts has contributed much to our knowledge of cellular and molecular biology. In addition, these lower eukaryotes are an extremely important group of industrial micro-organisms. Of particular importance is the yeast Saccharomyces cerevisiae, which is used in the baking, brewing and alcohol production industries. The breeding of industrial yeasts to meet both product and process requirements is currently an active area of research. The techniques available for yeast strain improvement include the traditional methods of sexual hybridization and mutagenesis, and the new procedures of protoplast fusion and transformation. This review is concerned with the nature and application of the new methods to the genetic manipulation of yeasts for strain improvement and the study of molecular and cellular biology.
Astrocyte calcium signals at Schaffer collateral to CA1 pyramidal cell synapses correlate with the number of activated synapses but not with synaptic strength (2010)

Glial cells respond to neuronal activity by transient increases in their intracellular calcium concentration. At hippocampal Schaffer collateral to CA1 pyramidal cell synapses, such activity-induced astrocyte calcium transients modulate neuronal excitability, synaptic activity, and LTP induction threshold by calcium-dependent release of gliotransmitters. Despite a significant role of astrocyte calcium signaling in plasticity of these synapses, little is known about activity-dependent changes of astrocyte calcium signaling itself. In this study, we analyzed calcium transients in identified astrocytes and NG2-cells located in the stratum radiatum in response to different intensities and patterns of Schaffer collateral stimulation. To this end, we employed multiphoton calcium imaging with the low-affinity indicator dye Fluo-5F in glial cells, combined with extracellular field potential recordings to monitor postsynaptic responses to the afferent stimulation. Our results confirm that somata and processes of astrocytes, but not of NG2-cells, exhibit intrinsic calcium signaling independent of evoked neuronal activity. Moderate stimulation of Schaffer collaterals (three pulses at 50 Hz) induced calcium transients in astrocytes and NG2-cells. Astrocyte calcium transients upon this three-pulse stimulation could be evoked repetitively, increased in amplitude with increasing stimulation intensity and were dependent on activation of metabotropic glutamate receptors. Activity-induced transients in NG2-cells, in contrast, showed a rapid run-down upon repeated three-pulse stimulation. Theta burst stimulation and stimulation for 5 min at 1 Hz induced synaptic potentiation and depression, respectively, as revealed by a lasting increase or decrease in population spike amplitudes upon three-pulse stimulation. Synaptic plasticity was, however, not accompanied by corresponding alterations in the amplitude of astrocyte calcium signals. Taken together, our results suggest that the amplitude of astrocyte calcium signals reflects the number of activated synapses but does not correlate with the degree of synaptic potentiation or depression at Schaffer collateral to CA1 pyramidal cell synapses.
Francisella tularensis Live Vaccine Strain Induces Macrophage Alternative Activation as a Survival Mechanism (2008)

Francisella tularensis (Ft), the causative agent of tularemia, elicits a potent inflammatory response early in infection, yet persists within host macrophages and can be lethal if left unchecked. We report in this study that Ft live vaccine strain (LVS) infection of murine macrophages induced TLR2-dependent expression of alternative activation markers that followed the appearance of classically activated markers. Intraperitoneal infection with Ft LVS also resulted in induction of alternatively activated macrophages (AA-Mphi). Induction of AA-Mphi by treatment of cells with rIL-4 or by infection with Ft LVS promoted replication of intracellular Ftn, in contrast to classically activated (IFN-gamma plus LPS) macrophages that promoted intracellular killing of Ft LVS. Ft LVS failed to induce alternative activation in IL-4Ralpha(-/-) or STAT6(-/-) macrophages and prolonged the classical inflammatory response in these cells, resulting in intracellular killing of Ft. Treatment of macrophages with anti-IL-4 and anti-IL-13 Ab blunted Ft-induced AA-Mphi differentiation and resulted in increased expression of IL-12 p70 and decreased bacterial replication. In vivo, Ft-infected IL-4Ralpha(-/-) mice exhibited increased survival compared with wild-type mice. Thus, redirection of macrophage differentiation by Ft LVS from a classical to an alternative activation state enables the organism to survive at the expense of the host.
Chlamydia pneumoniae in children with acute respiratory tract infections (1998)

Children seeking medical attention for acute respiratory tract infections were investigated for evidence of Chlamydia pneumoniae infection. Blood samples were obtained from 367 children. Nasopharyngeal or throat swabs for PCR analysis (polymerase chain reaction) were taken from 360 children. Serology was found to be useful for diagnosis of infection only in children aged > 5 y. Using PCR, a prevalence of 8 and 10% of C. pneumoniae was found in male and female children aged < 2 y; 17 and 19%, respectively, in the age group 2-4 y and 32 and 21%, respectively, in the age group 5-16 y. We conclude that Chlamydia pneumoniae is a common finding in young children with respiratory tract infections. Younger children were more often found to have a moderate disease, but may have been ill for a long period.
Ultrasensitive vector bending sensor based on multicore optical fiber (2016)

In this Letter, we demonstrate a compellingly simple directional bending sensor based on multicore optical fibers (MCF). The device operates in reflection mode and consists of a short segment of a three-core MCF that is fusion spliced at the distal end of a standard single mode optical fiber. The asymmetry of our MCF along with the high sensitivity of the supermodes of the MCF make the small bending on the MCF induce drastic changes in the supermodes, their excitation, and, consequently, on the reflected spectrum. Our MCF bending sensor was found to be highly sensitive (4094 pm/deg) to small bending angles. Moreover, it is capable of distinguishing multiple bending orientations.
A fluoroquinolone (DR-3355) protects human lymphocyte cell lines from HIV-1-induced cytotoxicity (1990)

HIV-1 infection of human CD4+ lymphocyte cell lines results in cell death. Treatment, but not pretreatment, of infected cells, with a fluoroquinolone antibiotic, DR-3355, protects a significant subfraction of cells from HIV-1-mediated cytolysis. All surviving cells have lost expression of the CD4 antigen, but do (MT-4) or do not (CEM) express viral antigens and produce infective virus. The rescued CEM and MT-4 cells are phenotypically stable and do not require continuous exposure to the drug for survival.
Negative symptoms of schizophrenia: a problem that will not go away (2006)

The description of new methods for measuring these devastating symptoms, coupled with the ongoing development of novel antipsychotics and agents that augment antipsychotics have fuelled renewed interest in the evaluation of negative symptoms and optimism that better treatments for negative symptoms can be found.
Analysis of two cycloplatinated compounds derived from N-(4-methoxyphenyl)-.alpha.-benzoylbenzylidenamine. Comparison of the activity of these compounds with other isostructural cyclopalladated compounds (1993)

In the present paper we report the synthesis, structural characterization, biochemical properties, and antiproliferative activity of two organo-cis-platinum cyclometalated compounds of formula [M(4-OMeC6H4N=C(COC6H5)C6H4)X]2, where M = Pt and X=Cl (4) or OAc (5). The IR and 1H and 13C NMR data of the chloro-bridged compound 4 showed that it has a planar structure. As indicated by IR and 1H and 13C NMR, the acetate-bridged compound 5 has an open-book shape structure. This structure was further confirmed by X-ray diffraction. The comparison of the biochemical properties and antiproliferative activity of these compounds relative to the isostructural palladium compounds [Pd(4-OMeC6H4N=C(COC6H5)C6H4)X]2 [X = AcO (1) and (2) or Cl (3)] indicated that the activity of compounds 4 and 5 is higher than that of the corresponding isostructural compounds 3 and 1-2, respectively, since their ID50 are 2-9-fold lower. It seems that there are not differences in the antiproliferative activity of all these compounds against leukemia HL-60 cells or mammary cancer MDA-MB 468 cells. Compounds 4 and 5 modify also the DNA structure of the oc and ccc forms of plasmid DNA. The acetate-bridged compound 5 showed the highest antiproliferative activity which is even higher than that of cis-DPP. Our data indicate that the Pt(II) compounds are more active than those having Pd(II) as the metal center.
Drop volume of commercial anti-glaucoma eye drops (1993)

Seventy six bottles of 19 different brands of anti- glaucoma eye drops (pilocarpine 1, 2, 4 % and timolol 0.25, 0.5 %) were tested for total volume, total number of drops, drop volume, drops/ml, and duration of therapy, by using a 10 ml glass cylinder with 0.1 ml graduations and a mechanical counter. The range of the drop volume for pilocarpine 1% was 55.3 - 55.4 'l: pilocarpine 2% was 41 .O - 54.4 'l; pilocarpine 4% was 47.8 - 47.8 'l and timolol 0.25% was 38.7 - 55.2 'l; timolol 0.5% was 35.9 - 55.6 'l. Ten out of 19 brands of antiglaucoma eye drops had total volume less than the labelled amount. The drop volume of the commercial anti- glaucoma eye drops is more than optimal.
Reversal of Decreased Human Adipose Tissue Lipoprotein Lipase and Hypertriglyceridemia after Treatment of Hypothyroidism (1976)

To determine whether adipose tissue lipoprotein lipase (LPL) plays a role in the regulation of triglyceride (TG) metabolism in hypothyroidism, the activity of the enzyme was measured in the subcutaneous adipose tissue of six hypothyroid patients before and during therapy with L-thyroxine. The activity of the activated form of the enzyme, measured as heparin elutable LPL, was lower in hypothyroid patients (1.54 +/- 0.93; mU/10(6) cells; mean +/- SD) than in controls (3.26 +/- 1.49; P less than .02) and increased (163 +/- 89%; P less than .01) with treatment to levels comparable to the controls. The total activity of LPL, measured in ammonium hydroxide extracts of acetone ether tissue powders, was in the low normal range in the hypothyroid patients (0.68 +/- 0.42), but not significantly different from normal (1.10 +/- 0.58) and did not increase significantly (92 +/- 105%), with treatment. Plasma post heparin lipolytic activity (PHLA) was low in hypothyroidism and increased (111 +/- 78%; P less than .05) with treatment. These increases in PHLA correlated with the increases in the activity of heparin elutable LPL (r = .88, P less than .05). In all patients fasting plasma TG levels decreased (-43 +/- 25%; P less than .02) after treatment. Serial determination of heparin elutable LPL activity, PHLA, and plasma TG during L-thyroxine treatment revealed a correlation between the per cent changes in PHLA and heparin elutable LPL activity (r = .68, P less than .05), an inverse correlation between plasma TG levels and heparin elutable LPL (r = -0.53,P less than .05) and no correlation between plasma TG and PHLA (r = -0.05). These results suggest that the low PHLA and hypertriglyceridemia of hypothyroidism are related to low adipose tissue LPL activity. All these parameters return to normal after treatment with L-thyroxine and attainment of euthyroidism.
The molecular structure of the Toll-like receptor 3 ligand-binding domain (2005)

Innate immunity is the first line of defense against invading pathogens. Toll-like receptors (TLRs) act as sentinels of the innate immune system, sensing a variety of ligands from lipopolysaccharide to flagellin to dsRNA through their ligand-binding domain that is composed of leucine-rich repeats (LRRs). Ligand binding initiates a signaling cascade that leads to the up-regulation of inflammation mediators. In this study, we have expressed and crystallized the ectodomain (ECD) of human TLR3, which recognizes dsRNA, a molecular signature of viruses, and have determined the molecular structure to 2.4-A resolution. The overall horseshoe-shaped structure of the TLR3-ECD is formed by 23 repeating LRRs that are capped at each end by specialized non-LRR domains. The extensive beta-sheet on the molecule's concave surface forms a platform for several modifications, including insertions in the LRRs and 11 N-linked glycans. The TLR3-ECD structure indicates how LRR loops can establish distinct pathogen recognition receptors.
Facile stereoselective reductions of enediones and cage diketones suing sodium borohydride-cerium(III) chloride (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFacile stereoselective reductions of enediones and cage diketones suing sodium borohydride-cerium(III) chlorideAlan P. Marchand, William D. LaRoe, G. V. Madhava Sharma, Suresh Chander Suri, and D. Sivakumar ReddyCite this: J. Org. Chem. 1986, 51, 9, 1622–1625Publication Date (Print):May 1, 1986Publication History Published online1 May 2002Published inissue 1 May 1986https://pubs.acs.org/doi/10.1021/jo00359a054https://doi.org/10.1021/jo00359a054research-articleACS PublicationsRequest reuse permissionsArticle Views744Altmetric-Citations84LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A hybrid distributed slot assignment TDMA channel access protocol (2002)

A distributed hybrid channel access protocol for a network of partially connected tactical users is presented. The protocol defines a random access time slotted nonpersistent carrier-sense multiple access (CSMA) protocol for rapid network access for low-volume bursty traffic and a reservation time-division multiple processor (TDMA) protocol for efficient forwarding of high-volume periodic traffic. The TDMA protocol organizes the network users into communications groups (CGs) of fully connected nodes and allocates slots to be shared by CG members using a variation of the mini-slotted alternating priorities (MSAP) protocol to provide hidden terminal collision-free communication between the members of a CG. A node may be a member of several overlapping CGs to support efficient relaying of traffic. Both protocols use a mechanism for higher priority traffic to capture a channel slot by preempting the transmission of lower priority traffic.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Renal Infarction with Absolute Ethanol (1980)

Selective renal artery catheterization was undertaken in a series of mongrel dogs. Absolute ethanol was injected on a dose/weight ratio. Venous blood ethanol levels were monitored. Pre- and postprocedure angiography was performed to evaluate the effectiveness of the injection. The dogs were subsequently sacrificed and pathologic examination performed. Renal infarction was produced in all animals. Systemic blood alcohol levels remained consistently below established criteria of toxic levels. No evidence of vascular damage in systemic arteries distal to the renal artery was found. Absolute ethanol is apparently a safe and effective method of producing permanent renal infarction.
Results of cardiac monitoring during phase I trials of a novel histone deacetylase (HDAC) inhibitor LBH589 in patients with advanced solid tumors and hematologic malignancies (2005)

3106 Introduction: LBH589 is a novel cinnamic acid hydroxamate that inhibits HDAC activity, IC50 of 0.03 μM, and inhibits hERG channel with an IC50 of 3.9 μM. Methods: In 2 phase I studies, LBH589 was administered as a 30 minute intravenous infusion on 2 schedules, days 1–3 and 8–10 of a 21 day cycle or days 1–3 and 15–17 of a 28 day cycle to adult pts with advanced solid malignancies (study 2101) or on a schedule of days 1–7 of a 21 day cycle to adult pts with hematologic malignancies (study 2102). Patients with impaired heart function were excluded, and drugs known to prolong QT interval were prohibited. Serial digital ECGs were performed at baseline (6 ECGs), and on days of dosing. ECG data were processed in a core lab by manual analysis. Results: 45 pts (median age: 60 yrs; 23 males, 22 females) were treated at 10 dose levels, range 1.2 - 20.0 mg/m2/day. PK analysis showed dose proportionality, T1/2 of 6 - 26 hr, and approximately 1.5 fold accumulation at steady state (day 3). PD analysis of PBL showed increased histone acetylation for 24 hours post-last dose at doses ≥ 4.8 mg.m2. A total of 1475 post-dose ECGs were performed. Central tendency analysis showed no change in QTcF on day 1; however, on day 3 of dosing, there was a dose related increase in QTcF of at most 20 msec. Frequency of outliers, QTcF > 500 msec and/or > 60 msec change from baseline, was 28% (12 pts) and occurred over a broad dose range, 4.8 mg/m2 - 20.0 mg/m2. Outlier ECGs occurred primarily on day 3 (7/12 pts) or later (3/12 pts) on days 4 or 5). Only 2 pts had outliers ECG on day 1. Six patients (14%) had QTc > 500 msec. Frquency of QTcF > 500 msec increased with dose. At doses ≤ 9 mg/m2, only 1 patient (1/33) had QTcF > 500 msec; while at doses > 9 mg/m2, 5 of 12 patients had QTcF > 500 msec. T wave and ST-T wave changes, primarily T wave flattening were frequently observed and were non-specific.Conclusions: LBH589 is a novel, potent HDAC inhibitor which was found to induce dose-related increases in QTcF of 20 msec or less at doses up to 20.0 mg/m2. Cardiac repolarization changes were delayed until day 3 perhaps due to a different mechanism effecting the hERG channel. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Isolation, characterization, and molecular cloning of a specific Mycobacterium tuberculosis antigen gene: identification of a species-specific sequence (1991)

A rabbit polyclonal antiserum exhibiting a specific recognition pattern for Mycobacterium tuberculosis proteins was used to screen an M. tuberculosis genomic library constructed in the expression vector lambda gt11. One clone, denominated C1:10, expressed M. tuberculosis-specific determinants as part of a large fusion protein with beta-galactosidase. The gene for this protein has been sequenced, and it encodes a protein of 134 amino acids (13.8 kDa) which did not display significant homology with any of the previously reported proteins in the data bases. Hybridization studies with restriction fragments of the cloned sequence revealed that it was not present in the genomes of related mycobacteria, namely, M. bovis, M. bovis BCG, M. flavescens, M. fortuitum, M. phlei, and M. vaccae. These findings suggest that we have detected a gene, or a fragment therefrom, unique for M. tuberculosis whose nucleotide and amino acid sequences could be useful tools in the design of an improved vaccine or a diagnostic method of greater accuracy for tuberculosis.