gebhart/patrepeval huggingface dataset:
System-Dependent Outcomes during the Evaluation of Drug Candidates as Inhibitors of Cytochrome P450 (CYP) and Uridine Diphosphate Glucuronosyltransferase (UGT) Enzymes: Human Hepatocytes versus Liver Microsomes versus Recombinant Enzymes (2010)

The ability of a drug to cause clinically significant drug-drug interactions due to direct or metabolism-dependent inhibition of cytochrome P450 (CYP) can generally be predicted from in vitro studies with human liver microsomes (HLM) or recombinant CYP enzymes, as recommended by the FDA and other regulatory agencies. This review highlights some examples of system-dependent inhibition of CYP and uridine diphosphate glucuronosyltransferase (UGT) enzymes. In the case of CYP enzymes, examples are presented where in vitro studies with HLM under-predict or over-predict the degree of inhibition observed in the clinic and where the correct prediction comes from studies with human hepatocytes. Studies with HLM under-predict the ability of gemfibrozil and bupropion to cause clinically significant inhibition of CYP2C8 and CYP2D6, respectively, and over-predict the ability of ezetimibe to cause clinically significant inhibition of CYP3A4. Gemfibrozil and bupropion represent examples of glucuronidation-dependent and reduction-dependent activation to metabolites that inhibit CYP2C8 and CYP2D6, respectively, whereas ezetimibe represents an example of glucuronidation-dependent protection against metabolism-dependent inhibition of CYP3A4. This article illustrates why, when drug candidates are extensively metabolized by non-CYP enzymes, it would be prudent to use human hepatocytes in addition to HLM or recombinant enzymes to evaluate their ability to inhibit CYP enzymes.
P‐49: Integrated DisplayPort TCON Device with Vibrant Picture Quality Features (2009)

Abstract DisplayPort is the next generation digital video interface. It simplifies connectors and allows for sleeker displays and notebooks by removing the need for LVDS electronics. Integrating the DisplayPort interface into a Timing Controller (TCON) device, reduces the system cost. Vibrant Picture Quality and power reduction features can be integrated in the same device, bringing optimal picture quality to monitors and televisions.
Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid. (1990)

Grilled ground beef contains factors that inhibit the initiation of mouse epidermal carcinogenesis by 7,12-dimethylbenz(a)anthracene. Previously we isolated an active principal and characterized it as an isomeric mixture of conjugated dienoic derivatives of linoleic acid (CLA). We now show that synthetic CLA inhibits the initiation of mouse forestomach tumorigenesis by benzo(a)pyrene. Four and 2 days prior to p.o. treatment with benzo(a)pyrene, female ICR mice were given (a) CLA in olive oil, (b) linoleic acid in olive oil, or (c) olive oil alone or plus 0.85% saline (control groups). Three days later the cycle was repeated for a total of 4 times. At 30 wk of age, the mice were sacrificed. In three independent experiments, mice treated with CLA developed only about half as many neoplasms/animal as mice in the control groups (P less than 0.025); in two of the experiments tumor incidence was also reduced (P less than 0.05). There were no significant differences in food intake or body weight among the groups. High-performance liquid chromatography/gas chromatography analysis established that, following intubation, only the c-9, t-11 CLA isomer was incorporated into forestomach phospholipids. In studies aimed at elucidating the mechanism of action, we found that CLA is an effective antioxidant. Under the conditions of the test CLA was more potent than alpha-tocopherol and almost as effective as butylated hydroxytoluene. These observations indicate that CLA might serve as an in situ defense mechanism against membrane attack by free radicals and may, at least in part, explain the anticarcinogenic properties of CLA.
Waves in fluids (1966)

Preface Prologue 1. Sound waves 2. One-dimensional waves in fluids 3. Water waves 4. Internal waves Epilogue Bibliography Notation list Author index Subject index.
Effect of acidification of canned tomatoes on quality and shelf life (1976)

The review included a discussion of the reasons why acidification of canned tomatoes is sometimes desirable from a microbiological point of view, the possible Changes in the pH of tomatoes as a result of the breeding of new varieties, and the methods and suitable acids for acidification. Acidification does cause some minor differences in the chemical components of the canned product, but the differences appear to be inconsequential. Although can corrosion may be accelerated slightly, this again does not seem to be of practical importance. The can manufacturers recommend the same type of can whether or not tomatoes are acidified. Flavor studies almost invariably have indicated that tomatoes are as acceptable as nonacidified tomatoes at least down to pH 4.1 to 4.0. In fact, most studies show that acidified tomatoes are somewhat more acceptable. Reasons are suggested as to why outbreaks of botulism have occurred from home‐canned tomatoes, although the pH appears to have been below 4.5, and as to why outbreaks have not occurred commercially, although at times the pH may have approached 4.8.
Functional integration of multiple genes into the genome of the oleaginous yeast<i>Rhodosporidium toruloides</i> (2014)

The basidiomycetous yeast Rhodosporidium toruloides represents an excellent producer for microbial lipids and carotenoids. However, further rational engineering of this unconventional yeast remains challenging partially because of the absence of efficient and reliable transformation method. In this study, we developed an Agrobacterium-mediated transformation (ATMT) protocol for effective gene integration into the R. toruloides genome. Both haploid and diploid strains were successfully modified, and the integration was confirmed by colony PCR, Western blot analysis and genome walking. We further demonstrated that multiple genes could be integrated by consecutive ATMT, leading to engineered strains simultaneously resistant to multiple antibiotics. Our results provided a practical method for functional integration and expression of exogenous genes in R. toruloides, which should facilitate the development of genetic tools and the construction of superior strains to produce biofuel molecules and biochemicals.
급성기 노인전문병동에 입원한 노인성 질환 환자에서 관찰되는 빈혈의 임상적 의의 (2007)

목적: 노인 환자에서 흔히 관찰되는 빈혈과 노인의 신체적인 기능, 정서적인 기능, 영양상태와의 상관관계를 알아보고 빈혈의 동반 유무가 급성 질환으로 입원한 노인 환자의 예후에 영향을 미치는 가를 알아보고자 본 연구를 수행하였다. 방법: 2004년 5월부터 2005년 4월까지 분당 서울대학교 병원 급성기 노인전문 병동에 입원한 431명의 환자 중 의학적 평가, 기능평가, 영양상태평가, 인지기능평가, 정서상태 평가 등을 포함한 노인 포괄평가가 가능한 환자 308명을 대상으로 입원 당시 혈색소치와 포괄적 노인평가 항목과의 통계적 분석을 시행하였으며 환자의 입원 기간 및 입원 기간 중의 노인 증후군의 발생 빈도를 비교하였다. 결과: 빈혈군이 정상군에 비해 보다 고령이고 남성이 많았으며 영양 결핍과 기능 의존 상태인 특성을 관찰할 수 있었다. 이러한 특성으로 인해 빈혈군에서 입원기간 중 섬망의 발생이 보다 많았고 입원 기간의 유의한 연장이 관찰되었다. 그러나 입원 기간에 영향 미치는 여러 인자 중 빈혈이 독립적인 위험 인자인지를 알아보기 위한 다변량 분석에서 유의한 상관관계는 없었다. 결론: 빈혈은 신체적인 기능, 영양 상태와 밀접한 상관관계가 있으며 전반적인 환자의 상태를 반영해 주는 지표로 생각되나 그 자체가 독립적으로 환자의 입원 기간을 연장시키는 위험인자는 아닐 것으로 생각된다. 향후 노인 환자에서 빈혈의 임상적 의의와 그 치료적 접근에 관해서는 추가적인 임상연구가 수행되어야 할 것으로 생각된다.
Defibrotide: Properties and clinical use of an old/new drug (2013)

The drug named defibrotide (DFT) has been studied for many years. It has been shown to possess many activities: profibrinolytic, antithrombotic-thrombolytic, antiischemic (heart, liver, kidney, skin, brain), antishock, antiatherosclerotic, antirejection and anti-angiogenic. The previously displayed activities, as antithrombotic, profibrinolytic and anti-inflammatory, suggested its use in vascular disorders, as in the treatment of peripheral obliterative arterial disease and in thrombophlebitis. Some years after, the use of DFT in hepatic veno-occlusive disease has been also proposed. Even if DFT was considered for long time a multi-target drug, now it could be considered on the whole as a drug able to protect endothelium against activation. The present work reviews the more important experimental and clinical studies performed to detect DFT effects.
Significant Association of KIR2DL3-HLA-C1 Combination with Cerebral Malaria and Implications for Co-evolution of KIR and HLA (2012)

Cerebral malaria is a major, life-threatening complication of Plasmodium falciparum malaria, and has very high mortality rate. In murine malaria models, natural killer (NK) cell responses have been shown to play a crucial role in the pathogenesis of cerebral malaria. To investigate the role of NK cells in the developmental process of human cerebral malaria, we conducted a case-control study examining genotypes for killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) class I ligands in 477 malaria patients. We found that the combination of KIR2DL3 and its cognate HLA-C1 ligand was significantly associated with the development of cerebral malaria when compared with non-cerebral malaria (odds ratio 3.14, 95% confidence interval 1.52-6.48, P = 0.00079, corrected P = 0.02). In contrast, no other KIR-HLA pairs showed a significant association with cerebral malaria, suggesting that the NK cell repertoire shaped by the KIR2DL3-HLA-C1 interaction shows certain functional responses that facilitate development of cerebral malaria. Furthermore, the frequency of the KIR2DL3-HLA-C1 combination was found to be significantly lower in malaria high-endemic populations. These results suggest that natural selection has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria high-endemic populations because of the propensity of interaction between KIR2DL3 and C1 to favor development of cerebral malaria. Our findings provide one possible explanation for KIR-HLA co-evolution driven by a microbial pathogen, and its effect on the global distribution of malaria, KIR and HLA.
Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells (2003)

Schwann cells lacking the tumor-suppressor-protein merlin tend in man to build benign tumors (schwannoma). We observed that characteristic features of these cells which are relevant to tumorigenicity resemble those described in cells with high Rac activity. Moreover this small GTPase also phosphorylates merlin via PAK activation. We hypothesized that merlin deficiency might cause an activation of Rac and its dependent signaling pathways, in particular the pro-tumorigenic JNK pathway. We show an enhanced activation of Rac1 in primary human schwannoma cells, find both Rac and its effector PAK at the membrane where they colocalize, and describe increased levels of phosphorylated JNK in the nucleus of these cells. Further we describe regulation at post-transcriptional level with upregulated protein, but not mRNA levels for Rac1, and JNK1/2. We conclude that merlin regulates Rac activation, and suggest that this is important for human schwannoma cell dedifferentiation.
N-terminal brain natriuretic propeptide levels correlate with procalcitonin and C-reactive protein levels in septic patients (2006)

The aim of this study was to find the relationship between N-terminal brain natriuretic propeptide (NT-proBNP), procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations in septic patients. This was a prospective study, performed at Medical University Hospital No. 5 in łódź. Twenty patients with sepsis and severe sepsis were included in the study. N-terminal brain natriuretic propeptide, procalcitonin and C-reactive protein concentrations, and survival were evaluated. In the whole studied group (128 measurements), the mean NT-proBNP, procalcitonin and C-reactive protein concentrations were, respectively: 140.80+/-84.65 pg/ml, 22.32+/-97.41 ng/ml, 128.51+/-79.05 mg/l. The correlations for the NT-proBNP level and procalcitonin and C-reactive protein levels were 0.3273 (p<0.001) and 0.4134 (p<0.001), respectively. NT-proBNP levels correlate with PCT and CRP levels in septic patients. In the survivor subgroup, the mean NT-proBNP plasma concentrations were significantly lower than in the non-survivor subgroup.
Identification and quantitation of free ceramides in human platelets (1972)

Free ceramides were isolated from human platelets. Their structures were unequivocally determined by gas-liquid chromatography-mass spectrometry of the trimethylsilyl ether derivatives. The major components were N-(palmitoyl) sphingosine, N-(stearoyl) sphingosine, N-(eicosanoyl) sphingosine, N-(docosanoyl) sphingosine, N-(tetracosanoyl) sphingosine, and N-(tetracosenoyl) sphingosine. Sphinganine-and sphingadienine-containing ceramides as well as ceramides containing other unsaturated acids were also present. The amount of ceramides was determined by quantitative gas-liquid chromatography, using radioactive ceramide as internal standard and synthetic crystalline ceramides for comparison of peak areas. The concentration of ceramides was found to be 1.31 micro g/10(9) platelets or 0.47 micro g/mg of platelet protein.
GROWTH AND DEPTH-DEPENDENCE OF SATURATION MAGNETIZATION OF IRON NITRIDE THIN FILMS ON <font>MgO</font> SUBSTRATE (2012)

We used polarized neutron reflectometry (PNR) to investigate the depth-dependent saturation magnetization (4πM s ) of bi-layer structured Fe–N/Fe grown on MgO substrates, which were prepared by a facing target sputtering method followed by a subsequent annealing process to purposely study the N inter-diffusive effect. It is observed that by tuning the Fe layer thickness from 2 nm to 5 nm, the magnetic properties of the resulting product varies substantially. According to X-ray diffraction, an additional peak, indexed to Fe 16 N 2 (004) , was developed in the sample with thinner (2 nm) underlayer. Its corresponding PNR study shows a 4πM s of up to 2.82 T towards the substrate interface, which is 14% higher than the known limit ( Fe 65 Co 35 ~ 4πM s = 2.45 T ). We attribute this giant magnetization to the presence of chemically ordered Fe 1 N 2 . We have seen evidence that the high M s is favorably stabilized due to the lattice misfit. The thickness range is consistent with the strained region of the films. This depth-dependent saturation magnetization analysis can shed a light to help understand the previous magnetization reports by classical magnetometry methods for the samples prepared using the same underlayer.
Pharmacokinetic and thrombolytic properties of cysteine-linked polyethylene glycol derivatives of staphylokinase (2000)

Recombinant staphylokinase (SakSTAR) variants obtained by site-directed substitution with cysteine, in the core (lysine 96 [Lys96], Lys102, Lys109, and/or Lys135) or the NH(2)-terminal region that is released during activation of SakSTAR (serine 2 [Ser2] and/or Ser3), were derivatized with thiol-specific (ortho-pyridyl-disulfide or maleimide) polyethylene glycol (PEG) molecules with molecular weights of 5,000 (P5), 10,000 (P10), or 20,000 (P20). The specific activities and thrombolytic potencies in human plasma were unaltered for most variants derivatized with PEG (PEGylates), but maleimide PEG derivatives had a better temperature stability profile. In hamsters, SakSTAR was cleared at 2.2 mL/min; variants with 1 P5 molecule were cleared 2-to 5-fold; variants with 2 P5 or 1 P10 molecules were cleared 10-to 30-fold; and variants with 1 P20 molecule were cleared 35-fold slower. A bolus injection induced dose-related lysis of a plasma clot, fibrin labeled with 125 iodine ((125)I-fibrin plasma clot), and injected into the jugular vein. A 50% clot lysis at 90 minutes required 110 microg/kg SakSTAR; 50 to 110 microg/kg of core-substitution derivatives with 1 P5; 25 microg/kg for NH(2)-terminal derivatives with 1 P5; 5 to 25 microg/kg with derivatives with 2 P5 or 1 P10; and 7 microg/kg with P20 derivatives. Core substitution with 1 or 2 P5 molecules did not significantly reduce the immunogenicity of SakSTAR in rabbits. Derivatization of staphylokinase with a single PEG molecule allows controllable reduction of the clearance while maintaining thrombolytic potency at a reduced dose. This indicates that mono-PEGylated staphylokinase variants may be used for single intravenous bolus injection.
3. Some Matrix Problems (1994)

3.1 Minimizing Condition Number by Scaling The condition number of a matrix , with , is the ratio of its largest and smallest singular values, i.e., κ (M) ≜ λmax ( MT M) λmin ( MT M) 1/2 for M full-rank, and otherwise. For square invertible matrices this reduces to . We consider the problem: minimizeκ (LMR) subject toL∈ Rp×p ,diagonal and nonsingularR∈ Rq×q ,diagonal and nonsingular 3.1 where L and R are the optimization variables, and the matrix is given. We will show that this problem can be transformed into a GEVP. We assume without loss of generality that and M is full-rank.
RNA interference modulates replication of dengue virus in Drosophila melanogaster cells (2010)

These findings indicate that DENV can replicate in Drosophila S2 cells and that the RNAi pathway plays a role in modulating DENV replication in these cells. S2 cells offer a useful cell culture model for evaluation of the interaction between DENV and the RNAi response.
TRACEY ROSE: POSTAPARTHEID PLAYGROUND (2004)

Research Article| May 01 2004 TRACEY ROSE: POSTAPARTHEID PLAYGROUND Kellie Jones Kellie Jones Kellie Jones is an Assistant Professor of History of Art and African American Studies at Yale University. Search for other works by this author on: This Site Google Nka (2004) 2004 (19): 26–31. https://doi.org/10.1215/10757163-19-1-26 Cite Icon Cite Share Icon Share Twitter Permissions Search Site Citation Kellie Jones; TRACEY ROSE: POSTAPARTHEID PLAYGROUND. Nka 1 May 2004; 2004 (19): 26–31. doi: https://doi.org/10.1215/10757163-19-1-26 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search Books & JournalsAll JournalsNka Search Advanced Search The text of this article is only available as a PDF. Copyright © 2004 Nka: Journal of Contemporary African Art2004 Article PDF first page preview Close Modal Issue Section: Articles You do not currently have access to this content.
High-quality InP surface corrugations for 1.55 μm InGaAsP DFB lasers fabricated using electron-beam lithography (1982)

Second-order surface corrugations for 1.55 μm distributed feedback (DFB) lasers have been fabricated in InP with a high yield using electron beam exposed resist masks. Attractive features of this technique are its flexibility and variable mark/space ratio (for optimum DFB coupling strength). Diffraction experiments show these gratings to be of suitably high optical quality.
A durable gigawatt class solid state pulsed power system (2011)

A unique all solid-state pulsed power system has been tested at the Naval Research Laboratory that produced 200 kV, 4.5 kA, and 300 ns pulses, continuously for more than 11,500,000 shots into a resistive load at a repetition rate of 10 pps. The Marx has an efficiency of 80% based on calorimetric measurements. This pulser is used to evaluate components and advance solid state designs for a next generation solid-state pulsed power system to drive an electron beam pumped KrF laser system for inertial fusion energy. The solid state pulser, designed and constructed by PLEX LLC, consists of a 12 stage Marx, coupled with a 3rd harmonic stage to sharpen the Marx output waveforms, a main magnetic switch, a compact pulse forming line used as a transit time isolator, and a resistive load. Each Marx stage uses an APP Model S33A compact high voltage switch that consists of 12 series connected thyristors. A life test on individual thyristors showed operation of >; 300 M shots at 20 Hz without failure.
Development of in-situ second phase pinning structure in niobium-titanium based superconducting alloys (1991)

A niobium-based superconducting alloy which has a rare-earth second phase that segregates between the matrix dendrites during solidification has been developed. The second phase can be refined by conventional deformation without heat treatment so as to form an in-situ fiber network. In such an alloy, one has independent control of the second-phase volume fraction as well as the matrix composition. The development of the in-situ alloy along with early microstructural and critical current results on the first wires are reported. The in-situ second phase was found to be about 2- mu m thick and 8- mu m apart in a conventionally solidified 35Nb-50Ti-15Y alloy. This size and spacing are suitable for producing a flux line lattice (FLL) pinning morphology in the strain available in conventional conductor processing. The properties of the test alloy are shown to be satisfactory with respect to easy melting, high ductility, and nondegraded superconducting properties.
Eyes free dialing for cellular telephones (2002)

The authors describe a chip set that implements voice dialing for cellular telephones using isolated-word speaker-dependent speech-recognition algorithms. High recognition rates of over 98% in noisy car cabins are achieved using noise-immune techniques for preprocessing, feature extraction, template training, and template comparison. A unique work endpoint detector is realized with a modified dynamic time warping algorithm and a noise-robust voice-activated switch. The chip set supports up to two users and a vocabulary of 32 words. It incorporates speech synthesis for guiding, prompting, and verification by vocal feedback, and allows dialing digit by digit or speed dialing of up to 10 stored numbers invoked with user-defined phrases.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Selective fluorescent labeling of amino groups of bovine pancreatic tryspin inhibitor by reductive alkylation (1986)

Abstract Bovine pancreatic trypsin inhibitor (BPTI) was reductively alkylated with 2‐methoxy‐1‐naphthyl aldehyde and sodium cyanoborohydride (NaCNBH 3 ). All five possible derivatives, each labeled at one of the primary amino groups of BPTI, were obtained. The distribution of yields of the various derivatives can be controlled by changing the reaction conditions. Products were identified by high‐performance liquid chromatography (HPLC) tryptic peptide mapping. This procedure was used for the preparation of three pure 2‐methoxy‐1‐naphthyl‐methylenyl‐BPTI (MNA‐BPTI) derivatives. Purification was achieved by means of affinity chromatography and HPLC. The spectral characteristics of the probe, notably monoexponential decay with a lifetime of 6.8 ± 0.1 ns and moderate limiting fluorescence polarization, P = 0.3 ± 0.015, make it a very useful donor in energy‐transfer measurements.
Ball Detection Based on Color Information and Hough Transform (2009)

In this article, we present a ball detection algorithm based on color information and Hough transform. Our objective is to detect the color balls under complex environments and different illumination conditions. To do so, we firstly apply the multiscale Retinex algorithm to enhance the image. Then, an adaptive Hough transform is introduced to locate the position of the balls in order to reduce the influence of the complex environments. Thirdly, to detect the interested balls under different illumination conditions, we introduce color invariant model Grayworld normalization (GN) to overcome the influence of the illumination. Finally, to evaluate the proposed ball detection in practice, experiments have been carried out on 100 images taken from various illuminations. On the basis of the reported theory and experimental results, it is shown that high interested ball detection accuracy is achieved by our proposed method.