gebhart/patrepeval huggingface dataset:
Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions (1992)

Previous kinetic studies have identified a high-affinity (S)-warfarin 7-hydroxylase present in human liver microsomes which appears to be responsible for the termination of warfarin's biological activity. Inhibition of the formation of (S)-7-hydroxywarfarin, the inactive, major metabolite of racemic warfarin in humans, is known to be the cause of several of the drug interactions experienced clinically upon coadministration of warfarin with other therapeutic agents. In order to identify the specific form(s) of human liver cytochrome P-450 involved in this particular toxicity, we have determined the metabolic profiles of 11 human cytochrome P-450 forms expressed in HepG2 cells toward both (R)- and (S)-warfarin. Of the 11 forms examined only 2C9 displayed the regioselectivity and stereoselectivity appropriate for the high-affinity human liver microsomal (S)-7-hydroxylase. We further compared Michaelis-Menten and sulfaphenazole inhibition constants for (S)-warfarin 7-hydroxylation catalyzed by cDNA-expressed 2C9 and by human liver microsomes. Similar kinetic constants were obtained for each enzyme source. It is concluded that 2C9 is likely to be a principal form of human liver P-450 which modulates the in vivo anticoagulant activity of the drug. It is further concluded that those drug interactions with warfarin that arise as a result of decreased clearance of the biologically more potent S-enantiomer may have as their common basis the inhibition of P-450 2C9.
Small incision trabeculotomy combined with phacoemulsification and intraocular lens implantation (1993)

Cataract surgeons frequently face the challenge of treating an open-angle glaucoma patient presenting for cataract surgery and intraocular lens implantation. It seems logical to treat both problems during the same surgical procedure if it can be done without jeopardizing the results of either. We present a short historic overview of the trabeculotomy procedure in adults, together with our technique using the new Fukasaku modification of the instrumentation (probes and forceps) and report 50 consecutive cases with a 100% three-month follow-up. The mean preoperative intraocular pressure was 19.3 mm Hg (range 16.0 to 37.0 mm Hg); three months after surgery it was 14.2 mm Hg (range 6.0 to 24.0 mm Hg). The mean preoperative pressure-reducing medications were 2.3 drugs per patient, and the postoperative mean was 0.7. Except for three cases of small postoperative hyphemas, no other complications were encountered during the study.
ISOLATION AND ANALYTICAL CHARACTERIZATION OF LOCAL MALAYSIAN LEECH SALIVA EXTRACTS (2011)

Leech saliva contains biologically active compounds that are mainly proteins and peptides. In this study a modified and smooth extraction method of saliva was used without leeches' scarification. UV and Bradford Assay protein methods showed that the saliva extract contains high concentrations of proteins. RP-HPLC chromatogram revealed that more than 30 different peaks were observed in leech saliva extract. Gel electrophoresis revealed the existence of proteins and peptides with different molecular weights. The gel showed up to 25 different bands. Comparison of gel electrophoresis data with protein database revealed the closeness of four molecular weights to known proteins from Hirudinaria leech family. Other proteins detected by gel electrophoresis may be related to completely new biologically active proteins and peptides in the saliva extract or to a modification (isoforms) of the existing ones or finally to a mixture of both. ABSTRAK: Air liur pacat secara biologinya mengandungi sebahagian besar campuran aktif protein dan peptida. Dalam kajian ini, kaedah pengestrakan air liur pacat yang telah diubah suai digunakan tanpa perlu membunuh pacat. Kaedah protein Cerakin UV dan Bradford menunjukkan air liur pacat yang diekstrak mengandungi konsentrasi protein yang tinggi. Kromatogram RP-HPLC memperlihatkan lebih daripada 30 puncak berbeza diperolehi semasa air liur pacat diekstrak. Gel elektroforesis memperlihatkan kewujudan protein dan peptida dengan berat molekul yang berbeza. Gel menunjukkan hingga 25 jalur yang berbeza. Perbandingan data menggunakan gel elektroforesis seiring dengan pangkalan data protein memperlihatkan persamaan empat berat molekul, dengan protein yang yang dikenali daripada keluarga pacat Hirudinaria. Jenis protein lain yang dikesan dengan menggunakan gel elektrofosis mungkin juga berkait secara biologinya dengan protein dan peptida aktif yang baru, dalam ekstrak air liur atau pengubahsuaian (beberapa jenis yang berbeza daripada protein yang sama) daripada yang sedia ada ataupun gabungan kedua-duanya.
Combination of Empagliflozin and Linagliptin as Second-Line Therapy in Subjects With Type 2 Diabetes Inadequately Controlled on Metformin (2015)

Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated.
HOLOGRAPHIC SOLAR CONCENTRATOR FOR TERRESTRTAL PHOTOVOLTAICS (2005)

This paper describes theoretical and experimental work performed on these high efficiency holographic concentrating and spectral splitting photovoltaic systems. The theoretical system efficiency was calculated to be 41% for a GaAs-InGaAs tandem cell when the hologram was recorded at 632.8 nm. A prototype system was used to demonstrate that it maintained a fairly constant efficiency over a period of 15 minutes without a heatsink; whereas the efficiency of a Fresnel system, using the same aperture and cell, dropped a factor of two within 30 seconds when used without a heatsink. Finally, a cost analysis of this system estimates it to generate power for 5.7 c per kWh when production levels reach 20 MW per year capacity.
Protein adsorption on histidyl-aminohexyl-Sepharose 4B. II. Application to the negative one-step affinity purification of human beta2-microglobulin and immunoglobulin G. (2001)

The adsorption of two human proteins, beta2-microglobulin and Immunoglobulin G, from uremic patient's blood ultrafiltrate and plasma, respectively, was investigated on the histidyl-aminohexyl-Sepharose 4B adsorbent. Both target proteins could be adsorbed on the gel through a low affinity for immobilized histidine ligand. However, a fine adjustment of the operating conditions (ionic strength, buffer, pH) prevented their adsorption and thus allowed their "negative affinity" purification (purity estimated by silver nitrate SDS-PAGE) by the removal of the contaminating proteins. This simple and efficient method provides purification under gentle chromatographic conditions and a further characterization of both molecules.
[Cognitive dysfunction and antiepileptic drugs]. (2011)

Cognition is a complex mental function that involves attention, concentration, recognition, judgment, and memory and relates to emotion to some extent. Cognitive dysfunction in epilepsy probably results from various factors such as frequent seizures themselves, an underlying brain lesion, and antiepileptic drugs (AEDs). However, the contribution of these factors remains ambiguous in many cases. From the therapeutic perspective, simplifying the use of AEDs, avoiding polypharmacy, and avoiding overdosing are important in almost all cases. Most classical AEDs (PB, PHT, CBZ, and SV) have some untoward effect on cognition, particularly, PB. On the other hand, many new drugs (GBP, LTG, and LEV) do not have such effects but they do affect emotions. TPM seems to have some untoward effect on cognition and emotion.
Glyceraldehyde-3-phosphate Dehydrogenase Is Phosphorylated by Protein Kinase Cι/λ and Plays a Role in Microtubule Dynamics in the Early Secretory Pathway (2002)

The small GTPase Rab2 immunolocalizes to vesicular tubular clusters (VTCs) that function as transport complexes carrying cargo between the endoplasmic reticulum and the Golgi complex. Our previous studies showed that Rab2 promotes vesicle formation from VTCs and that the released vesicles are enriched in beta-coat protein, protein kinase C iota/lambda (PKCiota/lambda), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the recycling protein p53/gp58. Because PKCiota/lambda kinase activity was necessary for vesicle formation, a search was initiated to identify the substrate(s) that potentiate Rab2 function within VTCs. In this study, we found that PKCiota/lambda phosphorylates GAPDH. Moreover, GAPDH interacts directly with the PKCiota/lambda regulatory domain. Based on numerous observations that show (beta-COP) GAPDH associates with cytoskeletal elements, we examined the role of phospho-GAPDH in promoting microtubule (MT) binding to membrane. Using a quantitative microsomal binding assay, we found that membrane association of beta-tubulin was dependent on phospho-GAPDH and was blocked by reagents that interfere with Rab2-dependent GAPDH membrane recruitment or with PKCiota/lambda kinase activity. Furthermore, normal rat kidney cells transfected with a constitutively activated form of Rab2 (Q65L) or with our anti-GAPDH polyclonal antibody displayed a dramatic change in MT organization. These combined results suggest that Rab2 stimulated PKCiota/lambda and GAPDH recruitment to VTCs, and the subsequent PKCiota/lambda phosphorylation of GAPDH ultimately influences MT dynamics in the early secretory pathway.
Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5 (2000)

Skeletal muscle differentiation is controlled by interactions between myocyte enhancer factor-2 (MEF2) and myogenic basic helix-loop-helix transcription factors. Association of MEF2 with histone deacetylases (HDAC) -4 and -5 results in repression of MEF2 target genes and inhibition of myogenesis. Calcium/calmodulin-dependent protein kinase (CaMK) signaling promotes myogenesis by disrupting MEF2-HDAC complexes and stimulating HDAC nuclear export. To further define the mechanisms that confer CaMK responsiveness to HDAC4 and -5, we performed yeast two-hybrid screens to identify HDAC-interacting factors. These screens revealed interactions between HDAC4 and members of the 14-3-3 family of proteins, which function as signal-dependent intracellular chaperones. HDAC4 binds constitutively to 14-3-3 in yeast and mammalian cells, whereas HDAC5 binding to 14-3-3 is largely dependent on CaMK signaling. CaMK phosphorylates serines -259 and -498 in HDAC5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to HDAC5 is required for CaMK-dependent disruption of MEF2-HDAC complexes and nuclear export of HDAC5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.
Matching fibres for low loss coupling into fibre amplifiers (1990)

Fibre amplifier gain may be greatly increased by reducing the field spot size. However, the resulting mismatch between the fields in the amplifier and standard fibre leads to large splicing losses which reduce the amplifier efficiency. We show theoretically that total splice loss may be greatly reduced by using one or more intermediate fibres.
Antisense therapy of MAdCAM-1 for trinitrobenzenesulfonic acid-induced murine colitis (2006)

Background: Anti-a 4 integrin reagent, natalizumab, which is 1 of the most promising antiadhesion monoclonal antibodies, has been introduced into clinical trials against inflammatory bowel disease (IBD). Lethal consequences such as progressive multifocal leukoencephalopathy have recently been reported in patients using natalizumab, making it critical to determine which selective adhesion molecule in the a 4 integrinsYdependent pathway should be targeted for inhibition and the minimal spectrum of activity required for the valid treatment of IBD. Mucosal addressin cell adhesion molecule (MAdCAM)-1 is known to be restrictedly expressed in gut-associated lymphoid tissues, and its expression dramatically increases in IBD. This study aimed to reevaluate the effectiveness of MAdCAM-1 inhibition and to determine the feasibility of anti-MAdCAM-1 strategy.
Recent developments in micromilling using focused ion beam technology (2004)

The application of focused ion beam (FIB) technology in microfabrication has become increasingly popular. Its use in microfabrication has advantages over contemporary photolithography or other micromachining technologies, such as small feature resolution, the ability to process without masks and being accommodating for a variety of materials and geometries. An overview of the recent development in FIB microfabrication technology is given. The emphasis will be on direct milling, or maskless techniques, and this can distinguish the FIB technology from the contemporary photolithography process and provide a vital alternative to it. After an introduction to the technology and its FIB principles, the recent developments in using milling techniques for making various high-quality devices and high-precision components at the micrometer scale are examined and discussed. Finally, conclusions are presented to summarize the reviewed work and to suggest the areas for improving the FIB milling technology and for future research.
Neurofilament heavy chain-like messenger RNA and protein are present in benign prostate and down-regulated in prostatic carcinoma. (1997)

Differences in gene expression between benign and malignant human prostate specimens were investigated using the differential display technique. RNA samples from paired benign and malignant areas microdissected from opposite sides of the same prostate gland were used for reverse transcription PCR. A 477-bp band was identified that was consistently present in benign prostate but absent or diminished in intensity in malignant tissue. This band was cloned, and the sequence demonstrated 99% identity with a region in the fourth exon of the human neurofilament heavy chain gene (NF-H). Northern blotting with a cDNA probe derived from this band confirmed the presence of a similarly sized message of approximately 3.9 kb in both prostate and brain, and reverse transcription PCR using primers specific to an upstream region of exon 4 confirmed NF-H-like mRNA expression in benign prostatic tissue. Immunostaining with a monoclonal antibody to NF-H showed a positive reaction in benign prostatic epithelial cells but complete absence of staining in prostatic cancer cells. These data demonstrate the presence of a NF-H-like gene product in normal prostatic epithelial cells that is down-regulated or absent in prostatic carcinomas.
Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2 (2006)

Eye development initiates as an evagination of the early neural plate, before the closure of the neural tube. Structural malformations of the eye such as anophthalmia and microphthalmia arise very early in development. It is not surprising therefore that three of the genes currently identified to play a significant role in these developmental eye anomalies are also major players in brain development and regionalization. However, as has been emerging for a high proportion of transcriptional regulators studied, these genes have evolved to play multiple roles throughout development, and perhaps even in adult tissue maintenance. This complex spatiotemporal expression pattern requires elaborate regulatory systems which we are beginning to unravel. A major component of these complex regulatory networks is a series of cis-acting elements, highly conserved through evolution, which spread large distances from the coding region of each gene. We describe how cross regulation for PAX6, SOX2 and perhaps OTX2 has now been uncovered, pointing to the mechanisms that can fine-tune the expression of such essential developmental components. These interactions also help us understand why there is significant phenotypic overlap between mutations at these three loci.
Molecular Characterization of the First Two Enzymes of the Pentose-phosphate Pathway of Trypanosoma brucei (2000)

Trypanosomatids are parasitic protists that have part of their glycolytic pathway sequestered inside peroxisome-like organelles: the glycosomes. So far, at least one enzyme of the pentose-phosphate pathway has been found to be associated partially with glycosomes. Here, we describe how two genes from Trypanosoma brucei, coding for the first two enzymes of the pentose-phosphate pathway, i.e. glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase, were identified by in silico screening of trypanosome genome project data bases. These genes were cloned and sequenced. Analysis of the lactonase sequence revealed that it contained a C-terminal peroxisome targeting signal in agreement with its subcellular localization in the bloodstream form trypanosome (15% glycosomal and 85% cytosolic). However, the dehydrogenase sequence did not reveal any targeting signal, despite its localization inside glycosomes. The corresponding enzymes have been overexpressed in Escherichia coli and purified, and their biochemical characteristics have been determined.
Distributed Transactions for Google App Engine: Optimistic Distributed Transactions built upon Local Multi-Version Concurrency Control (2011)

Massively scalable web applications encounter a fundamental tension in computing between "performance" and "correctness": performance is often addressed by using a large and therefore distributed machine where programs are multi-threaded and interruptible, whereas correctness requires data invariants to be maintained with certainty. A solution to this problem is "transactions" [Gray-Reuter]. Some distributed systems such as Google App Engine [http://code.google.com/appengine/docs/] provide transaction semantics but only for functions that access one of a set of predefined local regions of the database: a "Local Transaction" (LT) [http://code.google.com/appengine/docs/python/datastore/transactions.html]. To address this problem we give a "Distributed Transaction" (DT) algorithm which provides transaction semantics for functions that operate on any set of objects distributed across the machine. Our algorithm is in an "optimistic" [http://en.wikipedia.org/wiki/Optimistic_concurrency_control] style. We assume Sequential [Time-]Consistency [http://en.wikipedia.org/wiki/Sequential_consistency] for Local Transactions.
DMD-based LED-illumination Super-resolution and optical sectioning microscopy (2013)

Super-resolution three-dimensional (3D) optical microscopy has incomparable advantages over other high-resolution microscopic technologies, such as electron microscopy and atomic force microscopy, in the study of biological molecules, pathways and events in live cells and tissues. We present a novel approach of structured illumination microscopy (SIM) by using a digital micromirror device (DMD) for fringe projection and a low-coherence LED light for illumination. The lateral resolution of 90 nm and the optical sectioning depth of 120 μm were achieved. The maximum acquisition speed for 3D imaging in the optical sectioning mode was 1.6×10(7) pixels/second, which was mainly limited by the sensitivity and speed of the CCD camera. In contrast to other SIM techniques, the DMD-based LED-illumination SIM is cost-effective, ease of multi-wavelength switchable and speckle-noise-free. The 2D super-resolution and 3D optical sectioning modalities can be easily switched and applied to either fluorescent or non-fluorescent specimens.
The Heathrow broadband access system (2003)

The digital switched video fiber access system deployed at Heathrow, Florida, is described. The system principles and architecture, system design, and overall system performance are presented along with field results and experiences. The Heathrow broadband system has shown the technical feasibility of delivering very-high-quality video to residential customers via an all-digital switched design; it also has shown the dramatic quality improvement such an approach can offer when compared to analog/RF delivery via conventional cable systems. Further evolution of the base technology and the system topology for digital centrally switched systems will lead to a highly capable system, able to provide a common access vehicle for all service classes previously envisioned with a very high guaranteed delivery quality. With volume deployment such a system is projected to be economical, but this depends on the evolution of technology, especially in the area of low-cost optoelectronics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Bone morphogenetic protein 7: a novel treatment for chronic renal and bone disease (2004)

Bone morphogenetic protein 7 may be a powerful new therapeutic agent for chronic kidney disease, with the novel attribute of not only treating the kidney disease itself, but also directly inhibiting some of the most important complications of the disease state.
Resilience of the Internet to Random Breakdowns (2000)

A common property of many large networks, including the Internet, is that the connectivity of the various nodes follows a scale-free power-law distribution, P(k) = ck(-alpha). We study the stability of such networks with respect to crashes, such as random removal of sites. Our approach, based on percolation theory, leads to a general condition for the critical fraction of nodes, p(c), that needs to be removed before the network disintegrates. We show analytically and numerically that for alpha</=3 the transition never takes place, unless the network is finite. In the special case of the physical structure of the Internet (alpha approximately 2.5), we find that it is impressively robust, with p(c)>0.99.
Site of Alkylation of the Major Ribonuclease from Aspergillus saitoi with Iodoacetate (1986)

A base non-specific and adenylic acid preferential ribonuclease from Aspergillus saitoi (RNase M) was modified by [14C]iodoacetic acid. RNase M was inactivated with concomitant incorporation of about 1 mol equivalent of carboxymethyl group. Carboxymethylated RNase M (CM RNase M) thus obtained was reduced and carboxymethylated (RCM CM RNase M). From tryptic and chymotryptic digests of RCM CM RNase M, two carboxymethylated histidine-containing peptides labeled with radioactivity were isolated. The amino acid sequences of these two peptides were determined to be Thr-Ile-His-Gly-Leu-Trp-Pro-Asp-Asn-Cys-Asp-Gly-Ser-Tyr... and His-Gly-Thr-Cys-Ile-Asn-Thr-Ile-Asp-Pro-Ser-Cys-Tyr-Pro-Asp-Asp-Tyr-Ala. .... The distribution of the radioactivity on the former and latter peptides was 43% and 57%, respectively. The results indicated that two histidine residues are involved in the active site of RNase M, and the modification of either one of the two histidine residues inactivates RNase M. The CD spectrum of carboxymethylated RNase M indicated that some tryptophan residue(s) with a CD band at 287 nm is in the proximity of the active site histidine residues of RNase M.
Accelerating Applications by Mapping Critical Kernels on Coarse-Grain Reconfigurable Hardware in Hybrid Systems (2005)

In this paper, we propose a method for speeding-up applications by partitioning them between the reconfigurable hardware blocks of different granularity and mapping critical parts of applications on the coarse-grain reconfigurable hardware. The partitioning method consists of four steps; the intermediate representation creation, the kernel identification, the mapping onto coarse-grain reconfigurable blocks, and the mapping onto the FPGA hardware. The method is validated using five real-world applications, where the speedup relative to an all-FPGA solution ranges from 1.4 to 3.1.