gebhart/patrepeval huggingface dataset:
Effects of cytidine-5' diphosphocholine on norepinephrine, dopamine and serotonin synthesis in various regions of the rat brain. (1979)

Administered intravenously to rats, CDPcholine, significantly increases the level and the synthesis rate of dopamine, and the level of tyrosine in the corpus striatum (maximum effect for 50 mg/kg, one hour after administration). CDPcholine decreases the level of serotonin and tryptophan and the synthesis rate of serotonin in the midbrain + hypothalamus and in the brain stem. The increase of the striatum dopamine level and the decrease of the brain stem and midbrain serotonin level are correlated with the recognized antiparkinson and neurostimulant action of this nucleotide.
Kinetic and Chemical Mechanism of Mycobacterium tuberculosis 1-Deoxy-d-xylulose-5-phosphate Isomeroreductase (2004)

1-Deoxy-D-xylulose-5-phosphate (DXP) isomeroreductase catalyzes the isomerization and reduced nicotinamide adenine dinucleotide phosphate- (NADPH-) dependent reduction of DXP to generate 2-C-methylerythritol 4-phosphate (MEP) in the first committed step of the MEP pathway of isoprenoid biosynthesis. We have cloned the gene encoding the Mycobacterium tuberculosis DXP isomeroreductase, expressed the protein in Escherichia coli, and purified the enzyme to homogeneity using conventional column chromatography methods. DXP isomeroreductase is a metal ion-activated enzyme displaying superior specificity for Co(2+), good specificity for Mn(2+), and poor specificity for Mg(2+). Although NADPH is preferred over reduced nicotinamide adenine dinucleotide (NADH) about 100-fold as evaluated by the relative k(cat)/K(m) values, the maximum turnover numbers are similar, suggesting that the 2'-phosphate of NADPH contributes predominantly to binding and not to catalysis. While k(cat) was independent of pH in the region 6.0 <or= pH <or= 8.75, k(cat)/K(act)(Mn)2+ decreased at low pH as two enzymatic groups with pK(a) values of 7.4 are protonated. These groups likely represent carboxylate groups that coordinate the divalent metal ion in the active site. The results also support an electrostatic role for the divalent metal ion in catalysis. The results of product inhibition studies and isotope effects suggest that the enzyme utilizes a steady-state random mechanism. Significant isotope effects were observed with [4S-(2)H]NAD(P)H, establishing that the enzyme promotes transfer of the C(4)-proS hydride of the reduced pyridine nucleotide. The magnitude of these primary deuterium kinetic isotope effects varied with metal ion and reduced pyridine nucleotide identities. The results are discussed in terms of significant differences in the commitment factors for the various metal ions and pyridine nucleotides.
Dual‐color flow cytometric detection of fluorescent proteins using single‐laser (488‐nm) excitation (1998)

The ability to analyze independently the expression of multiple reporter gene constructs within single cells is a potentially powerful application of flow cytometry. In this paper, we explore the simultaneous detection of two variants of the reporter molecule, green fluorescent protein (GFP) that both fluoresce when excited with 488-nm light. One of these, enhanced GFP (EGFP) (excitation max. 490 nm; >90% efficiency at 488 nm), has been widely used for studies that involve flow cytometric detection of reporter gene expression. As a partner for EGFP, we employed a recently described variant termed enhanced yellow fluorescent protein (EYFP) (excitation max. 513 nm; ≈35% efficiency at 488 nm). Using 488-nm excitation, EYFP fluorescence could be readily detected following expression of the gene in murine fibroblasts and this signal was comparable in intensity to that obtained from EGFP. Importantly, we describe an optical filter configuration that permits the fluorescence signals from both proteins to be distinguished by flow cytometry, despite their similar emission maxima. This filter configuration employed a 510/20-nm bandpass filter for EGFP detection, a 550/30-nm bandpass filter for EYFP detection, and a 525-nm short-pass dichroic mirror to separate the two signals. With these filters, expression of either reporter protein could be detected, alone or in combination, within a mixed population of cells over a broad range of signal intensities. Cytometry 31:147–152, 1998. © 1998 Wiley-Liss, Inc.
Selective Radiation Resistance of Immunologically Induced T Cells as the Basis for Irradiation-Induced T-Cell-Mediated Regression of Immunogenic Tumor (1991)

Sublethal, whole-body gamma-irradiation of immunocompetent, but not T cell deficient, mice bearing an established immunogenic tumor results in T-cell-mediated complete tumor regression and in long-term host survival. This striking T-cell-dependent immunotherapeutic action of irradiation was paradoxically associated with the destruction of over 90% of host T cells and with a state of severe immunodepression as evidenced by the inability of irradiated mice to reject a tumor allograft. Furthermore, whereas exposure to 500 rads caused regression of a syngeneic tumor implanted 6 days before irradiation, it caused enhanced growth of a different syngeneic tumor growing on the same animal and implanted 1 day before. This ability of irradiation to cause regression of a 6 day tumor, but accelerated growth of a 1 day tumor, was also seen when the tumors were implanted in the reverse order. This means that, between days 1 and 6 of a tumor growth, tumor-specific T cells are converted from a radiosensitive to a highly radioresistant state, almost certainly because of having been activated and inducted into the antitumor immune response. This explanation for the selective radioresistance of effector T cells is based on publications showing that activated, in contrast to resting, T cells are highly radioresistant. Thus irradiation-induced, T-cell-mediated tumor regression depends not only on the destruction of radiosensitive suppressor T cells but also on the selective sparing of radioresistant activated effector T cells that are needed to destroy the tumor in the absence of suppression.
Doubly fed induction generator usingback-to-back PWM convertersand its application to variable-speed wind-energy generation (1996)

The paper describes the engineering and design of a doubly fed induction generator (DFIG), using back-to-back PWM voltage-source converters in the rotor circuit. A vector-control scheme for the supply-side PWM converter results in independent control of active and reactive power drawn from the supply, while ensuring sinusoidal supply currents. Vector control of the rotor-connected converter provides for wide speed-range operation; the vector scheme is embedded in control loops which enable optimal speed tracking for maximum energy capture from the wind. An experimental rig, which represents a 7.5 kW variable speed wind-energy generation system is described, and experimental results are given that illustrate the excellent performance characteristics of the system. The paper considers a grid-connected system; a further paper will describe a stand-alone system.
Isolation and characterization of OmpC porin mutants with altered pore properties (1988)

The LamB protein is normally required for the uptake of maltodextrins. Starting with a LamB- OmpF- strain, we have isolated mutants that will grow on maltodextrins. The mutation conferring the Dex+ phenotype in the majority of these mutants has been mapped to the ompC locus. These mutants, unlike LamB- OmpF- strains, grew on maltotriose and maltotetraose, but not on maltopentaose, and showed a significantly higher rate of [14C]maltose uptake than the parent strain did. In addition, these mutants showed increased sensitivity to certain beta-lactam antibiotics and sodium dodecyl sulfate, but did not exhibit an increase in sensitivity to other antibiotics and detergents. The nucleotide sequence of these mutants has been determined. In all cases, residue 74 (arginine) of the mature OmpC protein was affected. The results suggest that this region of the OmpC protein is involved in the pore domain and that the alterations lead to an increased pore size.
Pharmacokinetics of Adenoviral Vector-Mediated Gene Delivery to Vascular Smooth Muscle Cells: Modulation by Poloxamer 407 and Implications for Cardiovascular Gene Therapy (1995)

Regional in vivo delivery of therapeutic genes to the cardiovascular system at sites of localized vascular disease is feasible by catheter-mediated delivery of recombinant adenoviral vectors. Vascular smooth muscle cell (SMC) proliferation, which follows angioplasty and contributes to restenosis, is one process that may be amenable to such a gene therapy strategy. The clinical utility of localized delivery strategies such as this critically depends upon successful gene transfer to sufficient numbers of vascular cells, locally, within a clinically acceptable time period. Relatively limited information is available concerning the kinetics of gene transfer by first-generation, replication-deficient, recombinant adenovirus (Av1) vectors. In this context, we evaluated the pharmacokinetics of adenoviral vector-mediated gene delivery to vascular SMC using an Av1 reporter vector (Av1LacZ4) expressing a nuclear-targeted beta-galactosidase (beta-Gal) reporter. Bovine aortic SMC were exposed to Av1LacZ4 for various times at a range of concentrations and multiplicities of infection (MOI). After exposure, cells were washed and evaluated for transduction at 48 hr by X-Gal staining. Transduction occurred with a rate constant typically determined in the range of 10(-10) to 10(-11) events.ml/cell.virion.min. The rate of transduction was directly dependent on virion concentration, but not substantially on the virion-to-cell ratio. Relatively low fractions of the total input vector were found to be consumed, even after prolonged adsorption times. We hypothesized that the cellular transduction rate (and thus overall efficiency) would be improved by agents that could maintain a prolonged, high pericellular vector concentration. To evaluate this, cells were exposed to the vector in the presence of 15 grams/dl poloxamer 407, a viscous biocompatibile polyol, for various times followed by washout and evaluation as described above. Both cells and vector remained viable under these conditions, and poloxamer was found to increase the apparent transduction rate 10-fold or more (1-5 x 10(-9) transduction events.ml/cell.virion.min), with remarkable increases in numbers of cells transduced even after brief exposure periods. These observations demonstrate that the pharmacokinetics of adenoviral-mediated gene delivery to vascular SMC can be modulated by agents such as poloxamer 407, which may improve gene delivery by maintaining high pericellular concentrations of vector. Such modulation may permit achievement of desired levels of gene transfer while requiring lower total viral dosage and exposure time, and in turn may have important implications for in vivo gene delivery to vascular tissues.
2‐methoxyestradiol inhibits atorvastatin‐induced rounding of human vascular smooth muscle cells (2009)

The cardiovascular benefits of statins, including atorvastatin (ATV), have been reported to be gender-dependent, but the underlying mechanism is unclear. In this study we examine whether estrogen and its metabolite, 2-methoxyestradiol (2ME), affect the rounding response of human vascular smooth muscle cells (SMCs) induced by ATV. Twenty-four hour treatment with ATV (10-100 microM) induced rounding of cultured human SMCs. Addition of 2ME (1-20 microM), but not 17beta-estradiol, for 2 h induced re-spreading of rounded cells. Our further studies showed that the effects of 2ME were mimicked by microtubule-disrupting drugs and inhibited by taxol. Inhibition of RhoA and ROCK (Rho-kinase) by C3-toxin and H-1152, respectively, blocked 2ME effects. 2ME effects were also blocked by treatment with either actin-interfering drugs, such as cytochalasin D and jasplakinolide, or myosin inhibitor blebbistatin. ML-7 and -9, the inhibitors for myosin light chain kinase, inhibited 2ME effect as well. ATV treatment induced a decrease of F-actin content and Thr18/Ser19 dual phosphorylation of myosin regulatory light chain (MRLC), which was rescued by 2ME or mevalonate. The rescue effects of 2ME on F-actin content and MRLC dual phosphorylation were abolished by taxol or H-1152. In addition, kinesin Eg5 inhibitor monastrol and dynein inhibitor erythro-9-3-(2-hydroxynonyl) adenine (EHNA) significantly blocked 2ME effects. Finally, our results revealed that 2ME inhibited the migration of SMCs induced by ATV (0.1 microM) in wound healing assay and Boyden chamber assay. In summary, our data show that 2ME, but not estrogen, inhibits ATV-induced rounding of human SMCs through induction of microtubule disassembly and activation of the Rho-ROCK-actinomyosin pathway.
<title>Monolithic integration of InGaAs/InP JFET/detectors for NIR imaging applications</title> (1996)

Monolithic arrays of InP JFET switches and InGaAs detectors have been demonstrated with unprecedented JFET leakages below 20 pA. Improvements in the JFET dark current resulted from reduced device geometry along with the use of a novel reversed bias p-n junction. Successful devices have been made both with OMVPE and gas source MBE crystal. Other impressive results with column-switched 16 X 16 element arrays include detector leakages below 1 nA, 70 percent quantum efficiency from 1.0 - 1.65 micrometers and ON/OFF ratios beyond 70 db.
Accelerated Monte Carlo models to simulate fluorescence spectra from layered tissues (2003)

Two efficient Monte Carlo models are described, facilitating predictions of complete time-resolved fluorescence spectra from a light-scattering and light-absorbing medium. These are compared with a third, conventional fluorescence Monte Carlo model in terms of accuracy, signal-to-noise statistics, and simulation time. The improved computation efficiency is achieved by means of a convolution technique, justified by the symmetry of the problem. Furthermore, the reciprocity principle for photon paths, employed in one of the accelerated models, is shown to simplify the computations of the distribution of the emitted fluorescence drastically. A so-called white Monte Carlo approach is finally suggested for efficient simulations of one excitation wavelength combined with a wide range of emission wavelengths. The fluorescence is simulated in a purely scattering medium, and the absorption properties are instead taken into account analytically afterward. This approach is applicable to the conventional model as well as to the two accelerated models. Essentially the same absolute values for the fluorescence integrated over the emitting surface and time are obtained for the three models within the accuracy of the simulations. The time-resolved and spatially resolved fluorescence exhibits a slight overestimation at short delay times close to the source corresponding to approximately two grid elements for the accelerated models, as a result of the discretization and the convolution. The improved efficiency is most prominent for the reverse-emission accelerated model, for which the simulation time can be reduced by up to two orders of magnitude.
Residues 17–20 and 30–35 of beta‐amyloid play critical roles in aggregation (2003)

We examined the effects of co-incubating nine different Abeta peptide fragments with full-length Abeta1-40 (Abeta40) on protein aggregation. Six fragments enhanced aggregation of Abeta40 (Abeta1-28, 12-28, 17-28, 10-20, 25-35 and 17-40), while three others did not (Abeta1-11, 1-16, and 20-29). All of the peptides that enhanced aggregation contained either residues 17-20 or 30-35, indicating the importance of these regions for promoting aggregation of full-length Abeta. Abeta25-35 in particular increased both the rate and extent of aggregation of Abeta40 considerably as indicated by fluorescence staining. Atomic force microscope imaging (AFM) indicates the increase in fluorescence staining with Abeta25-35 is primarily due to increased formation of oligomers and protofibrils rather than formation of large amyloid fibrils. AFM images of Abeta25-35 when incubated alone also indicate formation of aggregates and long thin filaments. The increase in formation of the small toxic oligomeric morphology of Abeta40, along with formation of Abeta25-35 oligomers and thin filaments, represent two different potential pathways for Abeta25-35 toxicity. The critical roles of residues 17-20 and 30-35 of Abeta provide further insight into mechanism that underlie the formation of toxic aggregates in Alzheimer Disease (AD) and suggest targets for the design of beta-sheet breakers to modulate the aggregation and inhibit toxicity of full-length Abeta.
Localization of a Breast Cancer Susceptibility Gene, BRCA2 , to Chromosome 13q12-13 (1994)

A small proportion of breast cancer, in particular those cases arising at a young age, is due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. A genomic linkage search was performed with 15 high-risk breast cancer families that were unlinked to the BRCA1 locus on chromosome 17q21. This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13. Preliminary evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer.
A new upper bound for error-correcting codes (1962)

By refining Hamming's geometric sphere-packing model a new upper bound for nonsystematic binary error-correcting codes is found. Only combinatorial arguments are used. Whereas Hamming's upper bound estimate for <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">e</tex> -error-correcting codes involved a count of all points <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\leq e</tex> Hamming distance from the set of code points, the model is extended here to include consideration of points which are <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;e</tex> distance away from the code set. The percentage improvement from Hamming's bounds is sometimes quite sizable for cases of two or more errors to be corrected. The new bound improves on Wax's bounds in all but four of the cases he lists.
The expression of a novel, epithelium-specific ets transcription factor is restricted to the most differentiated layers in the epidermis (1997)

Ets proteins have been implicated in the regulation of gene expression during a variety of biological processes, including growth control, differentiation, development and transformation. More than 35 related proteins containing the 'ets domain' have now been found which specifically interact with DNA sequences encompassing the core tetranucleotide GGAA. Although ets responsive genes have been identified in the epidermis, little is known about their distribution and function in this tissue. We have now demonstrated that epidermis and cultured epidermal keratinocytes synthesize numerous ets proteins. The expression of some of these proteins is regulated as a function of differentiation. Among these is a novel ets transcription factor with a dual DNA-binding specificity, which we have called jen. The expression of jen is not only epithelial specific, but it is the only ets protein so far described, and one of the very few transcription factors whose expression is restricted to the most differentiated epidermal layers. We show that two epidermal marker genes whose expression coincides with that of jen are transregulated by this protein in a complex mode which involves interactions with other transcriptional regulators such as Sp1 and AP1.
Determination of serum neutralization antibodies against seasonal influenza A strain H3N2 and the emerging strains 2009 H1N1 and avian H5N1 (2010)

Neutralizing activities against H5N1 and 2009 H1N1 were low in the general population. Therefore, public health agencies should design strategies for preventing potential H5N1 and 2009 H1N1 pandemics.
Prediction of fade durations due to rain in satellite communication systems (1997)

The paper discusses the prediction of long‐term fade duration statistics in slant paths, obtained from rain attenuation time series simulated with the synthetic storm technique (with input from 1‐min rain rate time series). The results of the prediction were tested against the experimental fade duration statistics collected at three sites of the Sirio experiment in Italy at 11.6 GHz. Predicted and measured statistics are very similar for fade durations longer than about 64–128 s, which represent a fundamental lower limit to fade duration prediction using 1‐min rain rate time series. The short durations have not been reproduced because they are mainly caused by tropospheric turbulence, not by the space‐time structure of rain, well described statistically by the synthetic storm technique. The prediction is not sensitive to rainstorm speed.
Distribution of Internal Elastic Lamina and External Elastic Lamina in the Internal Carotid Artery: Possible Relationship With Atherosclerosis (2010)

The intracranial internal carotid artery (ICA) is a muscular artery and lacks external elastic lamina (EEL). Stenosis of the intracranial ICA is relatively uncommon, but the most common site is the cavernous portion. The characteristics of the arterial wall structures were examined using serial 3-mm sections of 32 intracranial ICAs obtained from 50 cadavers to identify where the EEL disappeared. The portions of the ICA where the intima exhibited thickening were also determined. Both the internal elastic lamina (IEL) and EEL were observed in all 32 specimens of the petrous portion of the ICA. Only the IEL was observed in all 32 specimens of the intradural portion of the ICA. The EEL had disappeared in 31 of the 32 specimens of the horizontal segment of the cavernous portion of the ICA. Intimal thickening of the ICA was observed in 23 of 32 ICA specimens, and frequently appeared in the horizontal segment of the cavernous portion of the ICA. The EEL disappeared in the cavernous portion of the ICA, which is the most common site of stenosis of the intracranial ICA. Change in the elasticity of the arterial wall in the cavernous portion may be an important factor in the process of atherosclerosis in the intracranial ICA.
Mutations of PIK3CA in Anaplastic Oligodendrogliomas, High-Grade Astrocytomas, and Medulloblastomas (2004)

The phosphatidylinositol 3'-kinase pathway is activated in multiple advanced cancers, including glioblastomas, through inactivation of the PTEN tumor suppressor gene. Recently, mutations in PIK3CA, a member of the family of phosphatidylinositol 3'-kinase catalytic subunits, were identified in a significant fraction (25-30%) of colorectal cancers, gastric cancers, and glioblastomas and in a smaller fraction of breast and lung cancers. These mutations were found to cluster into two major "hot spots" located in the helical and catalytic domains. To determine whether PIK3CA is genetically altered in brain tumors, we performed a large-scale mutational analysis of the helical and catalytic domains. A total of 13 mutations of PIK3CA within these specific domains were identified in anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme, and medulloblastomas, whereas no mutations were identified in ependymomas or low-grade astrocytomas. These observations implicate PIK3CA as an oncogene in a wider spectrum of adult and pediatric brain tumors and suggest that PIK3CA may be a useful diagnostic marker or a therapeutic target in these cancers.