gebhart/patrepeval huggingface dataset:
Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment (2014)

This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).
Readily Available Biaryl P,N Ligands for Asymmetric Catalysis (2004)

A short and modular synthesis of novel P,N ligands (pinap; see scheme; X=O or NH) is presented. A covalently bound chiral group allows the separation of the atropisomeric diastereomers, thus avoiding resolution involving chiral Pd–amine complexes. The utility of the ligands is demonstrated for three reactions catalyzed by different transition metals; in each case products are obtained with high enantiomeric excess (up to 99 % ee).
Design and construction of a microscope-based Raman system (1995)

A relatively inexpensive micro-Raman system featuring confocal imaging, holographic optics, and CCD detection is described in detail. The construction of a confocal filter is discussed, along with the depth of field and spatial rejection expected. Limitations of the system such as low-frequency signal rejection by the holographic optics and wavelength calibration are also discussed. Spectra are shown giving examples of the capabilities of the system and the signal-to-noise ratio expected for typical liquid and solid samples.
NAD+/NADH and/or CoQ/CoQH2 ratios from plasma membrane electron transport may determine ceramide and sphingosine‐1‐phosphate levels accompanying G1 arrest and apoptosis (2005)

To elucidate possible biochemical links between growth arrest from antiproliferative chemotherapeutic agents and apoptosis, our work has focused on agents (EGCg, capsaicin, cis platinum, adriamycin, anti-tumor sulfonylureas, phenoxodiol) that target tNOX. tNOX is a cancer-specific cell surface NADH oxidase (ECTO-NOX protein), that functions in cancer cells as the terminal oxidase for plasma membrane electron transport. When tNOX is active, coenzyme Q(10) (ubiquinone) of the plasma membrane is oxidized and NADH is oxidized at the cytosolic surface of the plasma membrane. However, when tNOX is inhibited and plasma membrane electron transport is diminished, both reduced coenzyme Q(10) (ubiquinol) and NADH would be expected to accumulate. To relate inhibition of plasma membrane redox to increased ceramide levels and arrest of cell proliferation in G(1) and apoptosis, we show that neutral sphingomyelinase, a major contributor to plasma membrane ceramide, is inhibited by reduced glutathione and ubiquinone. Ubiquinol is without effect or stimulates. In contrast, sphingosine kinase, which generates anti-apoptotic sphingosine-1-phosphate, is stimulated by ubiquinone but inhibited by ubiquinol and NADH. Thus, the quinone and pyridine nucleotide products of plasma membrane redox, ubiquinone and ubiquinol, as well as NAD(+) and NADH, may directly modulate in a reciprocal manner two key plasma membrane enzymes, sphingomyelinase and sphingosine kinase, potentially leading to G(1) arrest (increase in ceramide) and apoptosis (loss of sphingosine-1-phosphate). As such, the findings provide potential links between coenzyme Q(10)-mediated plasma membrane electron transport and the anticancer action of several clinically-relevant anticancer agents.
Modulation of epidermal tumor development caused by targeted overexpression of epidermis-type 12S-lipoxygenase. (2002)

In contrast to other 12S-lipoxygenase (LOX) isoforms expressed in the skin of mice, epidermis-type (e) 12S-LOX was found to be transcriptionally down-regulated in the course of epidermal tumor development in NMRI mice. This may indicate that this enzyme is related to antitumorigenic rather than protumorigenic effects. To test this hypothesis, two transgenic mouse lines were generated that differentially expressed e12S-LOX under the control of the bovine keratin 6 promoter known to be constitutively up-regulated in mouse skin tumors. As compared with the wild-type, low transgene expression correlated with a decreased skin tumor response paralleled by an up-regulation of leukocyte-type 12S-LOX and an accumulation of the linoleic acid derivative 13S-hydroxyoctadecadienoic acid. In contrast, high transgene expression coincided with an increased tumor response paralleled by a strong keratin 6 promoter-driven up-regulation of the transgenic e12S-LOX and an accumulation of the arachidonic acid derivative 12S-hydroxyeicosatetraenoic acid as the predominant LOX product. These results indicate a complex interaction between different LOX isoforms and an opposite role of arachidonic acid and linoleic acid products in the modulation of skin carcinogenesis.
Half-sandwich imido complexes of niobium and tantalum (1992)

The half-sandwich methylimido complexes [Nb(η-C5R5)(NMe)Cl2](R = H 1a, or Me 1b) have been prepared by treatment of [Nb(η-C5R5)Cl4] with NMe(SiMe3)2 in acetonitrile. The sterically hindered alkyl- and aryl-imido analogues [Nb(η-C5H5)(NR)Cl2](R = But1c, or C6H3Pri2-2,6 1d), [Nb(η-C5Me5)(N-C6H3Pri2-2,6)Cl2]1e and the tantalum compound [Ta(η-C5Me5)(N-C6H3Pri2-2,6)Cl2]1f are obtained by treatment of [M(η-C5R5)Cl4] with two equivalents of NHR(SiMe3) in chlorocarbon solvent. Crystal structures of 1a, 1c, 1d and 1f show that these complexes are mononuclear with quasi-linear imido ligands. The metal–nitrogen bond distances range from 1.744(3) to 1.780(5)Å consistent with pseudo triple bonds. Compounds 1a–1e react with tertiary phosphines to give eighteen-electron adducts of the type [Nb(η-C5H5)(NR)Cl2(PR′3)]2a–2e. The crystal structure of [Nb(η-C5H5)(NMe)Cl2(PMe3)] shows a distorted four-legged piano-stool geometry in which the phosphine binds cis to the methylimido and cis to one of the chloride ligands. Alkoxide and aryloxide derivatives of the type [Nb(η-C5R5)(NR′)(OR″)2] may be prepared via reactions of the dichlorides 1 with 2 equivalents of LiOR″ in Et2O. Fenske–Hall quantum-chemical calculations indicate that there exists a close relationship between the Nb(η-C5H5)(NR) fragment and the bent metallocene moiety M(η-C5H5)2 for the Group 4 elements.
Genes duplicated by polyploidy show unequal contributions to the transcriptome and organ-specific reciprocal silencing (2003)

Most eukaryotes have genomes that exhibit high levels of gene redundancy, much of which seems to have arisen from one or more cycles of genome doubling. Polyploidy has been particularly prominent during flowering plant evolution, yielding duplicated genes (homoeologs) whose expression may be retained or lost either as an immediate consequence of polyploidization or on an evolutionary timescale. Expression of 40 homoeologous gene pairs was assayed by cDNA-single-stranded conformation polymorphism in natural (1- to 2-million-yr-old) and synthetic tetraploid cotton (Gossypium) to determine whether homoeologous gene pairs are expressed at equal levels after polyploid formation. Silencing or unequal expression of one homoeolog was documented for 10 of 40 genes examined in ovules of Gossypium hirsutum. Assays of homoeolog expression in 10 organs revealed variable expression levels and silencing, depending on the gene and organ examined. Remarkably, silencing and biased expression of some gene pairs are reciprocal and developmentally regulated, with one homoeolog showing silencing in some organs and the other being silenced in other organs, suggesting rapid subfunctionalization. Duplicate gene expression was examined in additional natural polyploids to characterize the pace at which expression alteration evolves. Analysis of a synthetic tetraploid revealed homoeolog expression and silencing patterns that sometimes mirrored those of the natural tetraploid. Both long-term and immediate responses to polyploidization were implicated. Data suggest that some silencing events are epigenetically induced during the allopolyploidization process.
Mechanism of electrical conductivity of transparentInGaZnO4 (2000)

The electronic structure of ${\mathrm{InGaZnO}}_{4},$ which has a layered structure with alternating laminated layers of ${\mathrm{InO}}_{2}$ and ${\mathrm{GaZnO}}_{2},$ was calculated in order to investigate the mechanism of electrical conductivity. In the crystal structure obtained through relaxation calculations using classical two-center potentials, the Ga ion in the ${\mathrm{GaZnO}}_{2}$ layer has pentagonal coordination forming a bipyramid with five oxygen ions, while the Zn ion in the same layer has tetrahedral coordination, losing a bond with the oxygen at the top of one pyramid. The molecular orbitals of model clusters for the relaxed structure, which were calculated by the discrete variational $X\ensuremath{\alpha}$ method using a model cluster, show strong two-dimensional structures. The electronic states at the edge of the conduction band are the result of overlapping between In $5s$ orbitals, and delocalize in the ${\mathrm{InO}}_{2}$ layer. The energy in the Ga $4s$ and Zn $4s$ states in the ${\mathrm{GaZnO}}_{2}$ layer was too large to be doped with electrons. The In $5s$ states are considered to be conduction paths for carrier electrons. A very high conductivity can be expected in the case where dopant ions are introduced into the ${\mathrm{GaZnO}}_{2}$ layers.
Beta blocker eye drops for treatment of acute migraine. (2014)

We report seven cases of successful treatment of acute migraine symptoms using beta blocker eye drops. The literature on beta blockers for acute migraine is reviewed. Oral beta blocker medication is not effective for acute migraine treatment. This is likely due to a relatively slow rate of achieving therapeutic plasma levels when taken orally. Topical beta blocker eye drops achieve therapeutic plasma levels within minutes of ocular administration which may explain their apparent effectiveness in relief of acute migraine symptoms.
Preparation and polypeptide composition of chlorophyll‐free plasma membranes from leaves of light‐grown spinach and barley (1984)

Chlorophyf l‐free preparations of plasma membranes from leaves of barley (Hordeum vulgare L. cv. Kristina) and spinach (Spinada oleracea L. cv. Viking II) were obtained by partition in an aqueous dextran‐polyethylene glycol two‐phase system. CJlu‐can synthetase II (EC 2.4,1.34), a marker for the plasma membrane, was highly enriched in both preparations. Silicotungstic acid, a specific stain for the plasma membrane, indicated a purity close to 100% for the barley preparation. Both plasma membrane preparations contained a light‐reducible b‐cytochrome, as shown by low temperature spectroscopy. The plasma membranes had a tow protein content compared to the bulk of intracellular membranes. The polypeptide composition of the barley and spinach plasma membranes showed striking similarities, with.the most prominent polypeptides in the 49‐58 kdalton region, and some further prominent bands in the 30 kcialton region. Some high molecular weight polypeptides in the 73‐110 kdalton region were also typical for the plasma membranes compared to the microsomal fractions.
Nanotube Radio (2007)

We have constructed a fully functional, fully integrated radio receiver from a single carbon nanotube. The nanotube serves simultaneously as all essential components of a radio: antenna, tunable band-pass filter, amplifier, and demodulator. A direct current voltage source, as supplied by a battery, powers the radio. Using carrier waves in the commercially relevant 40-400 MHz range and both frequency and amplitude modulation techniques, we demonstrate successful music and voice reception.
Successful Maintenance Immunotherapy by BCG of Non‐Hodgkin's Malignant Lymphomas: Results of a Controlled Trial* (1979)

Forty-eight patients less than 65 years old, suffering non-Hodgkin's malignant lymphomas with one or more criteria of poor prognosis, were priorly placed in complete remission by an association of chemo + radio + chemotherapy. They were then randomized to receive either BCG in weekly scarifications for 3 years or no further treatment. Five patients were excluded (four after pathological reassessment); 43 are thus evaluable. There were 13 relapses out of 23 control patients and three relapses out of 20 treated patients (0.01 less than P less than 0.025). This difference is more distinct for clinical stages I and II (0.01 less than P less than 0.025) than for stages III and IV (not significant). Eight patients died in the control group whereas there was only one death in the treated group (0.025 less than P less than 0.05). These results indicate than BCG is useful in maintaining remission in about 40% of the cases and also in increasing their survival, especially in patients with clinical stages I or II.
A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors (1995)

A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel (11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 microM and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA2 = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent -2-enyl]-4-(2- hydroxyphenyl)-1,3-dioxan-2-yl]-benzyl]oxy]phenyl]-7-(3-pyridyl)he pt-6- enoic acid (110) was both an antagonist (pA2 = 6.7) and a synthase inhibitor (IC50 = 0.02 microM). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio > 64 (rat, 3 h) and > 59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).
Selective functional, regional, and neuronal vulnerability in frontotemporal dementia (2008)

Integrative approaches to selective vulnerability may help clarify neurodegenerative disease pathogenesis.
Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12. (1979)

A herpes simplex virus DNA fragment that is produced by digestion with BamHI endonuclease and carries the thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene has been cloned in Escherichia coli. A recombinat plasmid, pFG5, has been analyzed extensively and a detailed restriction map is presented. pFG5 DNA efficiently transforms TK- mouse L cells. The TK coding sequence in the cloned fragment has been localized and a smaller recombinant plasmid, pAG0, also carrying an active TK gene, has been constructed to serve as a more convenient vector for transfer, into TK- cells, of genes previously cloned in E. coli.
A microfabricated device for sizing and sorting DNA molecules (1999)

We have demonstrated a microfabricated single-molecule DNA sizing device. This device does not depend on mobility to measure molecule size, is 100 times faster than pulsed-field gel electrophoresis, and has a resolution that improves with increasing DNA length. It also requires a million times less sample than pulsed-field gel electrophoresis and has comparable resolution for large molecules. Here we describe the fabrication and use of the single-molecule DNA sizing device for sizing and sorting DNA restriction digests and ladders spanning 2-200 kbp.
Eosinopenia as a Marker of Outcome in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. (2015)

We conclude that a significant relationship exists between eosinopenia and outcomes of patients with AECOPD. Thus, eosinopenia can be a useful, easy-to-measure, and inexpensive biomarker for predicting the prognosis of patients with AECOPD.
TOR controls translation initiation and early G1 progression in yeast. (1996)

Saccharomyces cerevisiae cells treated with the immunosuppressant rapamycin or depleted for the targets of rapamycin TOR1 and TOR2 arrest growth in the early G1 phase of the cell cycle. Loss of TOR function also causes an early inhibition of translation initiation and induces several other physiological changes characteristic of starved cells entering stationary phase (G0). A G1 cyclin mRNA whose translational control is altered by substitution of the UBI4 5' leader region (UBI4 is normally translated under starvation conditions) suppresses the rapamycin-induced G1 arrest and confers starvation sensitivity. These results suggest that the block in translation initiation is a direct consequence of loss of TOR function and the cause of the G1 arrest. We propose that the TORs, two related phosphatidylinositol kinase homologues, are part of a novel signaling pathway that activates eIF-4E-dependent protein synthesis and, thereby, G1 progression in response to nutrient availability. Such a pathway may constitute a checkpoint that prevents early G1 progression and growth in the absence of nutrients.
Scalable multi-access flash store for big data analytics (2014)

For many "Big Data" applications, the limiting factor in performance is often the transportation of large amount of data from hard disks to where it can be processed, i.e. DRAM. In this paper we examine an architecture for a scalable distributed flash store which aims to overcome this limitation in two ways. First, the architecture provides a high-performance, high-capacity, scalable random-access storage. It achieves high-throughput by sharing large numbers of flash chips across a low-latency, chip-to-chip backplane network managed by the flash controllers. The additional latency for remote data access via this network is negligible as compared to flash access time. Second, it permits some computation near the data via a FPGA-based programmable flash controller. The controller is located in the datapath between the storage and the host, and provides hardware acceleration for applications without any additional latency. We have constructed a small-scale prototype whose network bandwidth scales directly with the number of nodes, and where average latency for user software to access flash store is less than 70mus, including 3.5mus of network overhead.
Up-Regulation of Oxytocin Receptor Messenger Ribonucleic Acid and Protein by Estradiol in the Cervix of Ovariectomized Rat1 (1998)

Oxytocin receptor (OTR) regulation has been extensively studied in uterine myometrium and endometrium. However, studies in the cervix are limited. The present studies utilized in situ hybridization and immunocytochemistry to localize OTR mRNA and protein distribution in cervices of nonpregnant ovariectomized (OVX) rats and examined the effect of combined and independent treatments with estradiol and progesterone on cervical OTR. Thirteen nonpregnant rats were bilaterally OVX under general anesthesia. At least 7 days later, the rats were exposed to one of four different treatments 24 h prior to necropsy: 1) estradiol (50 microg, n = 4); 2) progesterone (10 mg, n = 3); 3) both estradiol (50 microg) and progesterone (10 mg) (n = 3); 4) corn oil vehicle (n = 3). After 24-h estradiol treatment, OTR mRNA increased significantly (p < 0.05) in smooth muscle cells of the rat cervix as a result of increased copy numbers of OTR mRNA per cell as well as an increased population of OTR mRNA-positive cells. Progesterone alone had no effect on OTR mRNA expression; however, progesterone combined with estradiol significantly inhibited the up-regulation of OTR mRNA by estradiol alone. The increase of OTR mRNA in cervical epithelial cells was minimal in all situations. Intensity of cervical OTR immunostaining in both the epithelial cells and cervical smooth muscle cells was also elevated after estradiol treatment. The anti-rat OTR antiserum used for immunocytochemistry was validated by Western blot analysis. In conclusion, OTR and OTR mRNA were localized in smooth muscle cells and in epithelial cells of rat cervix. Estradiol-dependent activation of OTR gene expression and active OTR synthesis in smooth muscle cells account for the increased OTR level in rat cervix in vivo, in which progesterone acted as an antagonist of estradiol on OTR gene expression.