gebhart/patrepeval huggingface dataset:
Nitazoxanide: a new broad spectrum antiparasitic agent (2004)

Nitazoxanide (Alinia, Romark Laboratories) was synthesized based on the structure of niclosamide. In vitro studies have demonstrated activity against a broad range of parasites as well as some bacteria. Three controlled trials demonstrated efficacy in cryptosporidiosis, however, the efficacy in advanced AIDS patients (CD4 cell counts = 50) at approved doses was limited. Trials have also demonstrated efficacy comparable to metronidazole (Flagyl, GD Searle and Co.) in giardiasis with fewer side effects. Nitazoxanide is also effective versus intestinal helminths and tapeworms as well as in chronic fascioliasis. Side effects in clinical trials have been similar to placebo. Nitazoxanide is the first agent proven to be effective in cryptosporidiosis. It has also proven efficacy in giardiasis. Nitazoxanide is efficacious again intestinal helminths. Additional indications may be developed in the future.
The Status of Bedside Ultrasonography Training in Emergency Medicine Residency Programs (2003)

Abstract Bedside ultrasonography (BU) is rapidly being incorporated into emergency medicine (EM) training programs and clinical practice. In the past decade, several organizations in EM have issued position statements on the use of this technology. Program training content is currently driven by the recently published “Model of the Clinical Practice of Emergency Medicine,” which includes BU as a necessary skill. Objective: The authors sought to determine the current status of BU training in EM residency programs. Methods: A survey was mailed in early 2001 to all 122 Accreditation Council for Graduate Medical Education (ACGME)‐accredited EM residency programs. The survey instrument asked whether BU was currently being taught, how much didactic and hands‐on training time was incorporated into the curriculum, and what specialty representation was present in the faculty instructors. In addition, questions concerning the type of tests performed, the number considered necessary for competency, the role of BU in clinical decision making, and the type of quality assurance program were included in the survey. Results: A total of 96 out of 122 surveys were completed (response rate of 79%). Ninety‐one EM programs (95% of respondents) reported they teach BU, either clinically and/or didactically, as part of their formal residency curriculum. Eighty‐one (89%) respondents reported their residency program or primary hospital emergency department (ED) had a dedicated ultrasound machine. BU was performed most commonly for the following: the FAST scan (focused abdominal sonography for trauma, 79/87%); cardiac examination (for tamponade, pulseless electrical activity, etc., 65/71%); transabdominal (for intrauterine pregnancy, ectopic pregnancy, etc., 58/64%); and transvaginal (for intrauterine pregnancy, ectopic pregnancy, etc., 45/49%). One to ten hours of lecture on BU was provided in 43%, and one to ten hours of hands‐on clinical instruction was provided in 48% of the EM programs. Emergency physicians were identified as the faculty most commonly involved in teaching BU to EM residents (86/95%). Sixty‐one (69%) programs reported that EM faculty and/or residents made clinical decisions and patient dispositions based on the ED BU interpretation alone. Fourteen (19%) programs reported that no formal quality assurance program was in place. Conclusions: The majority of ACGME‐accredited EM residency programs currently incorporate BU training as part of their curriculum. The majority of BU instruction is done by EM faculty. The most commonly performed BU study is the FAST scan. The didactic component and clinical time devoted to BU instruction are variable between programs. Further standardization of training requirements between programs may promote increasing standardization of BU in future EM practice.
Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy (2005)

Mechanisms regulating thrombus stabilization remain largely unknown. Here, we report that loss of any 1 of the Gas6 receptors (Gas6-Rs), i.e., Tyro3, Axl, or Mer, or delivery of a soluble extracellular domain of Axl that traps Gas6 protects mice against life-threatening thrombosis. Loss of a Gas6-R does not prevent initial platelet aggregation but impairs subsequent stabilization of platelet aggregates, at least in part by reducing "outside-in" signaling and platelet granule secretion. Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. Blocking the Gas6-R-alphaIIbbeta3 integrin cross-talk might be a novel approach to the reduction of thrombosis.
Multivariate Calibration for the Determination of Total Azadirachtin-Related Limonoids and Simple Terpenoids in Neem Extracts Using Vanillin Assay (2001)

Two-component and multivariate calibration techniques were developed for the simultaneous quantification of total azadirachtin-related limonoids (AZRL) and simple terpenoids (ST) in neem extracts using vanillin assay. A mathematical modeling method was also developed to aid in the analysis of the spectra and to simplify the calculations. The mathematical models were used in a two-component calibration (using azadirachtin and limonene as standards) for samples containing mainly limonoids and terpenoids (such as neem seed kernel extracts). However, for the extracts from other parts of neem, such as neem leaf, a multivariate calibration was necessary to eliminate the possible interference from phenolics and other components in order to obtain the accurate content of AZRL and ST. It was demonstrated that the accuracy of the vanillin assay in predicting the content of azadirachtin in a model mixture containing limonene (25% w/w) can be improved from 50% overestimation to 95% accuracy using the two-component calibration, while predicting the content of limonene with 98% accuracy. Both calibration techniques were applied to estimate the content of AZRL and ST in different parts of the neem plant. The results of this study indicated that the relative content of limonoids was much higher than that of the terpenoids in all parts of the neem plant studied.
Selective expression of foreign genes in glioma cells: Use of the mouse myelin basic protein gene promoter to direct toxic gene expression (1993)

We have previously demonstrated that retrovirus-mediated genes were transferred to mouse glioma cells in a meningeal gliomatosis model (Yamada et al.: Japanese Journal of Cancer Research 83:1244-1247, 1992). This retrovirus vector contains the Escherichia coli. beta-galactosidase (beta-gal) gene as a marker for integration of the lacZ gene, which is controlled by the SV40 early promoter. We investigated whether lacZ genes could be specifically controlled in mouse glioma cells by glial-specific promoters, including the 2.5 kb 5' flanking region of the mouse glial fibrillary acidic protein (GFAP) gene, the 1.3 kb 5' flanking region of the myelin basic protein (MBP) gene, and the 1.5 kb 5' flanking region of the myelin proteolipid protein (PLP) gene. Psi-2 packaging cells were transfected with each retrovirus vector (GFAP promoter-, MBP promoter-, and PLP promoter-lacZ) and the infectious virus particles were recovered from the supernatants. Blue staining for beta-gal was detected in various fibroblast, myeloma, and glioma cell lines transduced with the retrovirus BAG vector. On the other hand, blue staining was only detected in glioma cells after transduction with the lacZ gene-bearing retrovirus controlled by glial-specific promoters. The strongest promoter activity was detected after transduction with the retrovirus in which the MBP promoter controlled the lacZ gene. Mouse glioma cells transduced with retrovirus containing the MBP promoter directing the herpes simplex virus type 1 thymidine kinase (HTK) gene were extremely sensitive to ganciclovir, while the parental cells and cells transduced with retrovirus containing the lacZ gene were not sensitive to ganciclovir.(ABSTRACT TRUNCATED AT 250 WORDS)
Opposing Roles of Syndecan-1 and Syndecan-2 in Polyethyleneimine-mediated Gene Delivery (2008)

Polyethyleneimines (PEIs) are efficient non-viral vectors for gene transfer. Heparan sulfate proteoglycans have been proposed to be the cell-surface receptors for PEI.DNA complexes (polyplexes). Here, we investigated if syndecan-1 (SDC1) and syndecan-2 (SDC2) are involved in PEI-mediated transfection. Following addition of polyplexes to HEK293 cells, green fluorescent protein-tagged SDCs rapidly formed clusters with PEI that were dependent of lipid raft integrity. However, although SDC1 overexpression slightly enhanced PEI-mediated gene expression, SDC2 dramatically inhibited it. Confocal microscopy analysis showed that SDC1.polyplex endocytosis occurred within minutes after addition of polyplexes, whereas SDC2.polyplex endocytosis took hours. Expression of SDC1 cytoplasmic deletion mutants revealed that the SDC1 cytoplasmic tail is required for gene expression, but not for clustering or endocytosis, whereas overexpression of SDC1/SDC2 chimeras showed that the SDC2 ectodomain is responsible for the inhibitory effect on gene transfer. This study provides evidence that SDCs may have opposing effects on PEI-mediated transfection.
Presence and Significance of Two Diastereomers ofβ-Methyl-γ-octalactone in Aged Distilled Liquors (1974)

Two diastereomers of β-methyl-γ-octalactone were identified as aging aroma substances from the neutral ethyl acetate extract of aged brandy. It was shown by means of gas liquid chromatography that they were derived from the oak barrels and were accumulated in the distilled liquor during the aging process. The organoleptic threshold of cis-lactone was 0.79 ppm and that of trans-lactone was 0.067 ppm. The aroma of cis-lactone was more fragrant than that of trans-lactone. The amount of β-methyl-γ-octalactone in various wood powders was determined comparatively, and the precursor of the lactone was identified in oak wood. Moreover, a positive correlation between the organoleptic evaluation of whisky and the amount of trans-lactone was recognized.
Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system (2011)

Alveolar type II (ATII) cell apoptosis and depressed fibrinolysis that promotes alveolar fibrin deposition are associated with acute lung injury (ALI) and the development of pulmonary fibrosis (PF). We therefore sought to determine whether p53-mediated inhibition of urokinase-type plasminogen activator (uPA) and induction of plasminogen activator inhibitor-1 (PAI-1) contribute to ATII cell apoptosis that precedes the development of PF. We also sought to determine whether caveolin-1 scaffolding domain peptide (CSP) reverses these changes to protect against ALI and PF. Tissues as well as isolated ATII cells from the lungs of wild-type (WT) mice with BLM injury show increased apoptosis, p53, and PAI-1, and reciprocal suppression of uPA and uPA receptor (uPAR) protein expression. Treatment of WT mice with CSP reverses these effects and protects ATII cells against bleomycin (BLM)-induced apoptosis whereas CSP fails to attenuate ATII cell apoptosis or decrease p53 or PAI-1 in uPA-deficient mice. These mice demonstrate more severe PF. Thus p53 is increased and inhibits expression of uPA and uPAR while increasing PAI-1, changes that promote ATII cell apoptosis in mice with BLM-induced ALI. We show that CSP, an intervention targeting this pathway, protects the lung epithelium from apoptosis and prevents PF in BLM-induced lung injury via uPA-mediated inhibition of p53 and PAI-1.
Bayesian Compressive Sensing Via Belief Propagation (2009)

Compressive sensing (CS) is an emerging field based on the revelation that a small collection of linear projections of a sparse signal contains enough information for stable, sub-Nyquist signal acquisition. When a statistical characterization of the signal is available, Bayesian inference can complement conventional CS methods based on linear programming or greedy algorithms. We perform asymptotically optimal Bayesian inference using belief propagation (BP) decoding, which represents the CS encoding matrix as a graphical model. Fast computation is obtained by reducing the size of the graphical model with sparse encoding matrices. To decode a length-N signal containing <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">K</i> large coefficients, our CS-BP decoding algorithm uses O(K log(N)) measurements and O(N log <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (N)) computation. Finally, although we focus on a two-state mixture Gaussian model, CS-BP is easily adapted to other signal models.
Load Balancing Routing of Fault Tolerant QoS-Guaranteed VPNs (2007)

As both end-to-end network reliability and performance becomes a growing concern for large distributed organizations, carriers face an increasing pressure to offer enhanced network services with higher quality of service (QoS). Such premier services are exemplified by wide-area virtual private networks (VPN) with QoS guarantees, or QVPNs, for which users can specify bandwidth, latency, and reliability requirements. From a carrier's standpoint, the primary challenge is to set up fault-tolerant routes for each QVPN request across its network with user-specified reliability and performance guarantees and, at the same time, maximize the total number of QVPNs that its network can support at any instant. We propose a fault tolerant load balancing routing (FTLBR) algorithm to select fault-tolerant routes for QVPNs. FTLBR maintains network-wide load balance while selecting primary and backup routes for QVPNs and performs resource sharing along backup routes to achieve an overall high network resource utilization efficiency. FTLBR is able to avoid formation of bottleneck links during primary-backup route selection by employing a simple quantitative metric that effectively captures network-wide load balance. Simulation results show that FTLBR can support significantly higher number of QVPNs when compared with existing traffic engineering algorithms.
Alternative therapies in critical care areas: The limitations and benefits (2007)

Over the past decade there has been increasing interest in the use of complementary therapies in health care settings (Hill, 1995). Although holistic techniques designed to reduce stress and anxiety, such as massage and aromatherapy, are viewed within the realm of nursing, such techniques are infrequently used and inadequately evaluated in critical care settings (Hobbs and Davies, 1998). This article aims to review the available literature on the effects of massage in critical care areas
Traveling-Wave Bulk Electroconvection Induced across a Temperature Gradient (1967)

If a temperature gradient is imposed on a slightly conducting liquid, a gradient in natural electrical conductivity generally results. It is shown that if the liquid is then subjected to a wave of electric field traveling perpendicular to the temperature and conductivity gradients, charges are induced in the liquid bulk. These charges relax to form a traveling wave which interacts with the imposed field to pump the liquid. The sign of the conductivity gradient determines whether the liquid is pumped in the same direction or a direction opposite to that of the traveling wave. Equations are given for the velocity profile in plane flow, showing the effect of fluid properties as well as of the frequency, wavelength, and potential of the traveling wave. Experiments support the significance of the theory. Observations of a type of bulk Rayleigh-Taylor instability are discussed.
Sequence and Organization of pXO1, the Large Bacillus anthracis Plasmid Harboring the Anthrax Toxin Genes (1999)

The Bacillus anthracis Sterne plasmid pXO1 was sequenced by random, "shotgun" cloning. A circular sequence of 181,654 bp was generated. One hundred forty-three open reading frames (ORFs) were predicted using GeneMark and GeneMark.hmm, comprising only 61% (110,817 bp) of the pXO1 DNA sequence. The overall guanine-plus-cytosine content of the plasmid is 32.5%. The most recognizable feature of the plasmid is a "pathogenicity island," defined by a 44.8-kb region that is bordered by inverted IS1627 elements at each end. This region contains the three toxin genes (cya, lef, and pagA), regulatory elements controlling the toxin genes, three germination response genes, and 19 additional ORFs. Nearly 70% of the ORFs on pXO1 do not have significant similarity to sequences available in open databases. Absent from the pXO1 sequence are homologs to genes that are typically required to drive theta replication and to maintain stability of large plasmids in Bacillus spp. Among the ORFs with a high degree of similarity to known sequences are a collection of putative transposases, resolvases, and integrases, suggesting an evolution involving lateral movement of DNA among species. Among the remaining ORFs, there are three sequences that may encode enzymes responsible for the synthesis of a polysaccharide capsule usually associated with serotype-specific virulent streptococci.
Disruption of the erp/mkp-1 gene does not affect mouse development: normal MAP kinase activity in ERP/MKP-1-deficient fibroblasts. (1996)

Externally regulated phosphatase (ERP or MKP-1) is a dual specificity phosphatase that has been implicated in the dephosphorylation of mitogen activated protein kinases (MAP kinases). MAP kinase is activated in response to external signals and in turn phosphorylates proteins essential to the regulation of cell growth. To study the role of ERP/MKP-1 protein in mammalian development and its function in signal transduction we have generated mice, embryonic stem (ES), cells and mouse embryo fibroblasts (MEFs) that are deficient in the ERP/MKP-1 protein. ERP/MKP-1-deficient mice are born at normal frequency, are fertile and present no phenotypic or histologic abnormalities. MAP kinase activity and the induction of c-fos mRNA is unaltered in MEFs lacking the ERP/MKP-1 protein, indicating no alteration of the MAP kinase pathway. In addition, ERP/MKP-1 deficient MEFs grow and enter DNA synthesis at the same rate as control cells. Our results demonstrate that the activity of ERP/MKP-1 is not essential for embryo development and indicate that the lack of ERP/MKP-1 activity can be compensated by other phosphatases in vivo.
Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-β Promoter in the Toll-Like Receptor Signaling (2002)

MyD88 is a Toll/IL-1 receptor (TIR) domain-containing adapter common to signaling pathways via Toll-like receptor (TLR) family. However, accumulating evidence demonstrates the existence of a MyD88-independent pathway, which may explain unique biological responses of individual TLRs, particularly TLR3 and TLR4. TIR domain-containing adapter protein (TIRAP)/MyD88 adapter-like, a second adapter harboring the TIR domain, is essential for MyD88-dependent TLR2 and TLR4 signaling pathways, but not for MyD88-independent pathways. Here, we identified a novel TIR domain-containing molecule, named TIR domain-containing adapter inducing IFN-beta (TRIF). As is the case in MyD88 and TIRAP, overexpression of TRIF activated the NF-kappaB-dependent promoter. A dominant-negative form of TRIF inhibited TLR2-, TLR4-, and TLR7-dependent NF-kappaB activation. Furthermore, TRIF, but neither MyD88 nor TIRAP, activated the IFN-beta promoter. Dominant-negative TRIF inhibited TLR3-dependent activation of both the NF-kappaB-dependent and IFN-beta promoters. TRIF associated with TLR3 and IFN regulatory factor 3. These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway.
Scalable, Electrochemical Oxidation of Unactivated C–H Bonds (2017)

A practical electrochemical oxidation of unactivated C-H bonds is presented. This reaction utilizes a simple redox mediator, quinuclidine, with inexpensive carbon and nickel electrodes to selectively functionalize "deep-seated" methylene and methine moieties. The process exhibits a broad scope and good functional group compatibility. The scalability, as illustrated by a 50 g scale oxidation of sclareolide, bodes well for immediate and widespread adoption.
32. Purines, pyrimidines, and glyoxalines. Part VII. New syntheses of 2-thiouracils and 2-thiothymines (1958)

G. Shaw and R. N. Warrener, J. Chem. Soc., 1958, 153 DOI: 10.1039/JR9580000153
Cellular genomic reporter assays for screening and evaluation of inducers of fetal hemoglobin (2003)

Reactivation of fetal hemoglobin (HbF) expression using pharmacological agents represents a potential strategy for the therapy of beta-thalassemia, sickle cell disease, HbE and other beta-hemoglobinopathies. However, the drugs currently available have low efficacy and specificity and are associated with high toxicity. We describe the development of stable cellular genomic reporter assays (GRAs) based on the green fluorescence protein (EGFP) gene under the Ggamma-globin promoter in the intact human beta-globin locus. We show that human erythroleukemic cell lines stably transfected with a Ggamma-EGFP beta-globin locus construct can maintain a uniform basal level of EGFP expression over long periods of continuous culture and that induction of EGFP expression parallels the induction of the endogenous globin genes. We compared the EGFP-induction potency of a number of chemotherapeutic agents, including histone deacetylase inhibitors and DNA-binding agents. We show that hydroxyurea and butyrate result in moderate levels of induction (70-80%) but with an additive inductive effect. Among the DNA-binding agents tested, cisplatin was the most potent inducer of HbF expression, (442+/-32%), a level which is comparable to hemin (764+/-145%). These results indicate that cellular GRAs containing Ggamma-EGFP-modified beta-globin locus constructs can be used to develop novel inducers of HbF synthesis for the therapy of beta-hemoglobinopathies.
The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor. (1992)

The high affinity IgE receptor (Fc epsilon RI) is a tetrameric hetero-oligomer composed of an alpha chain, a beta chain, and two disulfide-linked gamma chains. The beta chain contains four transmembrane (TM) segments and long cytoplasmic domains that are thought to play an important role in intracellular signaling. We now report the structural characterization and the sequence of the complete human beta gene and cDNA. The gene spans approximately 10 kilobases and contains seven exons. There is a single transcription initiation site preceded by a TATA box. The first exon codes for the 5'-untranslated region and a portion of the N-terminal cytoplasmic tail. TM-1 is encoded in exons 2 and 3, TM-2 in exons 3 and 4, TM-3 in exon 5, and TM-4 in exon 6. The seventh and final exon encodes the end of the C-terminal cytoplasmic tail and the 3'-untranslated sequence. The human beta gene appears to be a single copy gene. Two corresponding transcripts, detected as a doublet around 3.9 kilobases, are present in cells of mast cell and basophil lineage from different individuals, but not in the other hematopoietic cells tested here. The human beta protein is homologous to rodent beta. The consensus amino acid sequences of human, mouse, and rat beta show 69% identical residues. Analysis of the surface expression of transfected receptors indicates that human alpha gamma and alpha beta gamma complexes are expressed with comparable efficiency. Human beta interacts with human alpha more efficiently than does rat beta, and both rat and mouse beta interact with their corresponding alpha more efficiently than does human beta, demonstrating a species specificity of the alpha/beta interaction.