gebhart/patrepeval huggingface dataset:
Structure and nucleotide sequence of the heavy chain gene of HLA-DR. (1983)

We have used a 175-nucleotide-long primer extension product corresponding to the 5' end of HLA-DR alpha-chain mRNA to isolate a genomic clone from a human DNA library. The entire HLA-DR alpha gene is contained in two contiguous EcoRI fragments spanning about 7.5 kilobases (kb); most of the sequence has been determined. The 5' end of the gene is contained in a 4.4-kb fragment, and the coding segments and the 3' untranslated region are contained in a 3.1-kb fragment. The gene is split into five exons. The 5' untranslated region, the leader peptide, and the first two NH2-terminal amino acids are fused into the first exon. Exons 2 and 3 represent two extracellular coding domains of mature p34. The transmembrane domain, cytoplasmic domain, and part of the 3' untranslated region are merged into a fourth exon. The rest of the 3' untranslated region is in exon 5. The predicted amino acid sequence of mature p34, as deduced from its gene structure, has 229 residues and reveals a single potential disulfide loop (between cysteine residues 107 and 163) as well as a 22-amino acid residue membrane integrated segment (residues 193-214). Fifteen amino acids (residues 215-229) reside on the cytoplasmic side of the plasma membrane. There is considerable amino acid sequence homology between the second external domains of p34 and p29, as well as the immunoglobulin-like third domain of HLA-B7, and beta 2-microglobulin and the homologous constant region domains of the light and heavy chains of immunoglobulins.
Rate-distortion optimized sender-driven streaming over best-effort networks (2002)

This paper addresses the problem of streaming packetized media over a lossy packet network, in a rate-distortion optimized way. Out of all the packets that a sender could transmit at a given transmission opportunity, we show how the sender should compute which packets, if any, to transmit in order to meet an average rate constraint while minimizing the average end-to-end distortion. Experimental results show that our system has steady-state gains of 3-7 dB or more over systems that are not rate-distortion optimized.
Galactose-Modified Cationic Liposomes as a Liver-Targeting Delivery System for Small Interfering RNA (2011)

We have developed a galactose-modified cationic liposome for delivery of small interfering RNA (siRNA) to the liver. The liposomes were designed to be transported into hepatocytes via the asialoglycoprotein receptor, which recognizes galactose residues. The liposomes contained a novel galactose-modified lipid, 1,2-dioleoyl-sn-glycerol-3-phosphatidyl-N-(1-deoxylactito-1-yl)ethanolamine (GDOPE). Delivery of siRNA to hepatocytes by the liposomes was evaluated by measuring the gene-silencing activity of liposome : siRNA complexes in two human hepatoma cell lines. A formulation with a cationic lipid : GDOPE ratio of 3 : 5 by weight, LIC-G5, showed the strongest activity. In mice, intravenous injection of LIC-G5 complexed with (3)H-labeled siRNA led to accumulation of radioactivity in the liver. When the hepatic cellular uptake was determined after intravenous injection into mice followed by collagenase liver perfusion, the distribution of siRNA to parenchymal cells was 1.9 times higher when LIC-G5 rather than nongalactosylated LIC was used as the carrier. The concentration of siRNA accumulated was 45 µg/ml, 30 times the concentration that produced strong gene silencing in vitro and therefore presumably sufficient for a therapeutic effect. Because increasing the cationic-lipid content of a liposome carrier generally enhances the uptake of siRNA by the liver at the expense of increased cell toxicity, we used only a moderate amount of cationic lipid in our galactose-modified carrier. LIC-G5 enhanced the uptake of siRNA by the liver without cytotoxic effects and is a promising candidate delivery system for liver-targeted siRNA therapy.
Advances in Development of Phosphatidylinositol 3-Kinase Inhibitors (2009)

Phosphatidylinositol 3-kinases (PI3Ks) are a class of lipid kinases that phosphorylate phosphatidylinositol 4,5-bisphosphate (PIP2) at the 3-OH of the inositol ring to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which in turn activates Akt and the downstream effectors like mTOR, and therefore play important roles in cell growth, survival, etc. The phosphatase and tensin homolog deleted in chromosome ten (PTEN), acts as the catalytic antagonist of PI3K by dephosphorylating PIP3 to PIP2. PI3K has become an important drug target for cancer therapy, since gain-of-function mutations of PIK3CA encoding PI3Kalpha, as well as loss-of-function mutations of PTEN, have been frequently found in human cancers. The pharmaceutical development of PI3K inhibitors has made a great leap forward during the last 3 years. While PI3Kbeta, delta and gamma isoform-specific PI3K inhibitors (TGX-221, IC87114 and AS-605240) have been developed for therapy of coronary heart disease, asthma, and glomerulonephritis, respectively, a promising PI3Kalpha specific inhibitor is not yet available. Correspondingly, almost all of the promising PI3K inhibitors under development for caner therapy, such as NVP-BEZ235, GDC-0941 and ZSTK474, are pan-PI3K isoform inhibitors. Each of these pan-PI3K inhibitors seems to induce a common G1 phase arrest. All have shown favorable in vivo anticancer efficacies and low toxicities, and therefore most have entered evaluation in clinical trials. P-Akt and p-S6 have been reported to be feasible pharmacodynamic biomarkers for monitoring the efficacy of these agents. In the process of discovery of these and other PI3K inhibitors, detailed structure-activity relationship studies were carried out. This review summarizes key advances in the development of PI3K inhibitors, which is preceded by an introduction of PI3K family and their functions.
Generation of a continuum extending to the midinfrared by pumping ZBLAN fiber with an ultrafast 1550-nm source (2005)

Pulses from a commercial erbium-doped fiber laser are coupled into a standard silica fiber and a standard fluoride fiber connected in series. By cascaded Raman soliton self-shifting, a continuum extending to a wavelength of /spl sim/3 μm is generated. The total average power emitted in the 1.8-3.4-μm range is 5 mW. Throughout the 1.4-2.9-μm range, the average spectral power is /spl sim/4 μW/nm and higher, corresponding at 2.9 μm to a spectral radiance approximately 4600 times that of a 3000 K blackbody.
Expression of human alpha 1-antitrypsin cDNA in the yeast Saccharomyces cerevisiae. (1984)

Nucleotide sequences coding either for the precursor or the mature form of human alpha 1-antitrypsin have been placed under the control of the yeast ARG3 expression signals. Recombinant plasmids pRIT10782 and pRIT10787 express the precursor or the mature alpha 1-antitrypsin species, respectively, in two different yeast strains, with yields ranging between 0.3 and 1% of total soluble proteins. The alpha 1-antitrypsin synthesized in yeasts was specifically recognized by polyclonal and monoclonal antibodies raised against human alpha 1-antitrypsin. In addition, it was shown to be biologically active in its mature form only, with optimal activity in a peptidase-deficient yeast strain.
Body Composition Variation and Impact of Low Skeletal Muscle Mass in Patients With Advanced Medullary Thyroid Carcinoma Treated With Vandetanib: Results From a Placebo-Controlled Study (2013)

Muscle and adipose tissues are restored after only 3 months of vandetanib treatment. Patients with low muscle mass had high vandetanib serum concentration and high incidence of toxicities.
Transforming growth factor-beta 1 inhibits the production of IL-8 and the transmigration of neutrophils through activated endothelium (1996)

A central mechanism of inflammation is the activation of vascular endothelium by the inflammatory cytokines TNF-alpha and IL-1. These cytokines induce the expression of adhesion molecules, the elaboration of chemokines, and the transendothelial migration of white cells. TGF-beta 1 has anti-inflammatory properties, is expressed in the vessel wall, and has previously been shown to inhibit leukocyte adhesiveness to the endothelium at least in part by inhibiting the expression of E-selectin. We now show that TGF-beta 1 also inhibits the migration of neutrophils through endothelial monolayers activated by TNF-alpha. At a dose of 10 U/ml TNF-alpha, the transmigration of neutrophils was inhibited 42.7 +/- 7.9% (n = 8) by 0.2 ng/ml TGF-beta 1. Furthermore, TGF-beta 1 inhibited, in a time- and dose-dependent fashion, the elaboration of IL-8 by TNF-activated endothelial cells by between 33 and 78% (TNF doses from 100 down to 0.1 U/ml) and the elaboration of mRNA for IL-8 by 69%. TGF-beta 1 treatment did not significantly alter the TNF-induced IL-8 mRNA stability, suggesting that the mechanism of action of TGF-beta 1 is on gene transcription. Neutrophil transmigration through cytokine-activated endothelium involves both IL-8-dependent and IL-8-independent mechanisms. Using an anti-IL-8 Ab, we show that TGF-beta 1 inhibits only the IL-8-dependent pathway, but does not affect the IL-8-independent transendothelial migration mechanism. These and our previous results show that TGF-beta1, achieves its anti-inflammatory properties by inhibiting the expression of at least two genes, E-selectin and IL-8, which are essential in the inflammatory pathway.
Vibration control of a coordinate measuring machine (2003)

A comparative study of two vibration reduction schemes, the command preshaping technique and the feedforward control technique, is presented. The objective is to drive the end-point of a coordinate measuring machine along a commanded trajectory without any oscillations at the end-point. This is achieved by designing appropriate controllers for the system based on a robust control scheme. This scheme consists of two nested feedback loops-an inner loop to control the motor position and an outer loop to control the position of the end-point. The controllers based on the two vibration reduction schemes are designed for the outer loop to make the system vibration-free. It is shown that the command preshaping scheme is a special case of the feedforward control scheme. The design method is illustrated with a numerical example.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Trapping the tetrahedral intermediate in the alkaline phosphatase reaction by substitution of the active site serine with threonine (2006)

We report here the construction of a mutant version of Escherichia coli alkaline phosphatase (AP) in which the active site Ser was replaced by Thr (S102T), in order to investigate whether the enzyme can utilize Thr as the nucleophile and whether the rates of the critical steps in the mechanism are altered by the substitution. The mutant AP with Thr at position 102 exhibited an approximately 4000-fold decrease in k(cat) along with a small decrease in Km. The decrease in catalytic efficiency of approximately 2000-fold was a much smaller drop than that observed when Ala or Gly were substituted at position 102. The mechanism by which Thr can substitute for Ser in AP was further investigated by determining the X-ray structure of the S102T enzyme in the presence of the Pi (S102T_Pi), and after soaking the crystals with substrate (S102T_sub). In the S102T_Pi structure, the Pi was coordinated differently with its position shifted by 1.3 A compared to the structure of the wild-type enzyme in the presence of Pi. In the S102T_sub structure, a covalent Thr-Pi intermediate was observed, instead of the expected bound substrate. The stereochemistry of the phosphorus in the S102T_sub structure was inverted compared to the stereochemistry in the wild-type structure, as would be expected after the first step of a double in-line displacement mechanism. We conclude that the S102T mutation resulted in a shift in the rate-determining step in the mechanism allowing us to trap the covalent intermediate of the reaction in the crystal.
Safety, tolerability, and feasibility of high-dose naltrexone in alcohol dependence: an open-label study (2011)

High-dose naltrexone may serve as a viable treatment option for alcohol-dependent patients with prominent alcohol craving. Further controlled studies are needed to confirm our findings.
Gene Therapy for Prostate Cancer by Controlling Adenovirus E1a and E4 Gene Expression with PSES Enhancer (2005)

PSES is a chimeric enhancer containing enhancer elements from prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) genes that are prevalently expressed in androgen-independent prostate cancers. PSES shows strong activity equivalent to cytomegalovirus (CMV) promoter, specifically in PSA/PSMA-positive prostate cancer cells, the major cell types in prostate cancer in the absence of androgen. We developed a recombinant adenovirus (AdE4PSESE1a) by placing adenoviral E1a and E4 genes under the control of the bidirectional enhancer PSES and enhanced green fluorescent protein gene for the purpose of intratumoral virus tracking under the control of CMV promoter. Because of PSES being very weak in nonprostatic cells, including HEK293 and HER911 that are frequently used to produce recombinant adenovirus, AdE4PSESE1a can only be produced in the HER911E4 cell line which expresses both E1 and E4 genes. AdE4PSESE1a showed similar viral replication and tumor cell killing activities to wild-type adenovirus in PSA/PSMA-positive prostate cancer cells. The viral replication and tumor cell killing activities were dramatically attenuated in PSA/PSMA-negative cells. To test whether AdE4PSESE1a could be used to target prostate tumors in vivo, CWR22rv s.c. tumors were induced in nude mice and treated with AdE4PSESE1a via intratumoral and tail vein injection. Compared to tumors treated with control virus, the growth of CWR22rv tumors was dramatically inhibited by AdE4PSESE1a via tail vein injection or intratumoral injection. These data show that adenoviral replication can be tightly controlled in a novel fashion by controlling adenoviral E1a and E4 genes simultaneously with a single enhancer.
Altered antioxidant defence in a mouse adriamycin model of glomerulosclerosis (2001)

The fast development of glomerulosclerosis combined with an altered antioxidant status makes this mouse adriamycin model a suitable alternative for the slower rat models.
Highly Efficient and Stable Red Phosphorescent Organic Light‐Emitting Diodes Using Platinum Complexes (2012)

Highly efficient and stable, red phosphorescent organic light-emitting diodes (OLEDs) are demonstrated using platinum complexes. The host/dopant combination is a crucial factor in obtaining high efficiency and stability. The OLEDs exhibit a maximum external quantum efficiency of about 20% and an expected half-life of about 10 000 h with an initial luminance of 1000 cd m−2.
High-resolution compact imaging holographic Bragg grating spectrometer (1998)

Summary form only given. Existing imaging spectrometers are based either on precision-ruled diffraction gratings or thin holographic gratings. Both rely on angular dispersion of the gratings and require sufficient length (1 m) to achieve high (i.e., subangstrom) resolution. As a result, these devices are bulky, expensive, and inconvenient in field conditions. Volume Bragg gratings, on the other hand, rely on spectral selectivity of thick holograms that produce a single diffraction order and suppress all higher orders. This means that long paths are not necessary to achieve high spectral resolution, which depends on the thickness of the grating instead.
Red blood cell-mimicking synthetic biomaterial particles (2009)

Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.
The Gonococcal Fur Regulon: Identification of Additional Genes Involved in Major Catabolic, Recombination, and Secretory Pathways (2002)

In this study, we have characterized the in vitro binding of Neisseria gonorrhoeae Fur to several well-defined iron transport genes, as well as to additional genes involved in major catabolic, secretory, and recombination pathways of gonococci. The gonococcal Fur protein was recombinantly expressed in Escherichia coli HBMV119. Fur was isolated from inclusion bodies and partially purified by ion-exchange chromatography. Gonococcal Fur was found to bind to the promoter/operator region of a gene encoding the previously identified Fur-regulated periplasmic binding protein (FbpA) in a metal ion-dependent fashion, demonstrating that purified Fur is functional. In silico analysis of the partially completed gonococcal genome (FA1090) identified Fur boxes in the promoters of several genes, including tonB, fur, recN, secY, sodB, hemO, hmbR, fumC, a hypothetical gene (Fe-S homolog), and the opa family of genes. By using purified gonococcal Fur, we demonstrate binding to the operator regions of tonB, fur, recN, secY, sodB, hemO, hmbR, fumC, the Fe-S homolog gene, and the opa gene family as determined by an electrophoretic mobility shift assay. While gonococcal Fur was demonstrated to bind to the promoter regions of all 11 opa genes (opaA through -K), we did not detect binding of purified E. coli Fur with 8 of the 11 opa members, indicating that target DNA sequence specificities between these two closely related proteins exist. Furthermore, we observed differences in the relative strengths of binding of gonococcal Fur for these different genes, which most likely reflect a difference in affinity between gonococcal Fur and its DNA targets. This is the first report that definitively demonstrates the binding of gonococcal Fur to its own promoter/operator region, as well as to the opa family of genes that encode surface proteins. Our results demonstrate that the gonococcal Fur protein binds to the regulatory regions of a broad array of genes and indicates that the gonococcal Fur regulon is larger than originally proposed.
Petri net modeling and one-wafer scheduling of single-arm tree-like multi-cluster tools (2015)

It is very challenging to obtain a one-wafer cyclic schedule for the widely used multi-cluster tools in semiconductor manufacturing. This work studies the scheduling problem for a single-arm tree-like multi-cluster tool that is process-dominant. A resource-oriented Petri net (PN) model is developed to describe its operation behavior by explicitly modeling robot waiting. Based on it, sufficient and necessary conditions are for the first time established to find a one-wafer periodic schedule. By determining robot waiting time, efficient algorithms are proposed to find such a schedule with the minimal cycle time. An example is used to show its application.
Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organisation and synaptic structure (2002)

Deleterious mutations in RS1 encoding retinoschisin are associated with X-linked juvenile retinoschisis (RS), a common form of macular degeneration in males. The disorder is characterized by a negative electroretinogram pattern and by a splitting of the inner retina. To gain further insight into the function of the retinoschisin protein and its role in the cellular pathology of RS, we have generated knockout mice deficient in Rs1h, the murine ortholog of the human RS1 gene. We show that pathologic changes in hemizygous Rs1h(-/Y) male mice are evenly distributed across the retina, apparently contrasting with the macula-dominated features in human. Similar functional anomalies in human and Rs1h(-/Y) mice, however, suggest that both conditions are a disease of the entire retina affecting the organization of the retinal cell layers as well as structural properties of the retinal synapse.
Fetal blood group genotyping from DNA from maternal plasma: an important advance in the management and prevention of haemolytic disease of the fetus and newborn (2004)

The cloning of blood group genes and subsequent identification of the molecular bases of blood group polymorphisms has made it possible to predict blood group phenotypes from DNA with a reasonable degree of accuracy. The major application of this technology, which has now become the standard of care, is the determination of a fetal RHD genotype in women with anti-D, to assess whether the fetus is at risk of haemolytic disease of the fetus and newborn (HDFN). Initially, the procurement of fetal DNA required the invasive procedures of amniocentesis or chorionic villus sampling. Since the discovery of fetal DNA in maternal plasma in 1997, the technology of detecting an RHD gene in this very small quantity of fetal DNA has developed rapidly, so that non-invasive fetal D typing can now be provided as a diagnostic service for D-negative pregnant women with anti-D. Within a few years, it is probable that fetuses of all D-negative pregnant women will be tested for RHD, to establish whether the mother requires antenatal anti-D immunoglobulin prophylaxis.
Enantioselective binding of Casodex to the androgen receptor (1996)

1. The biologic activity of androgens is mediated through the formation of a non-covalent androgen receptor (AR)-steroid complex. Casodex and other antiandrogens inhibit formation of this complex and thus negate the role of endogenous steroids in androgen-dependent growth of prostate. 2. Casodex is currently available as a racemic mixture. The goal of this investigation was to determine the in vitro AR binding affinities of the individual isomers of Casodex. 3. The (R) or (S) isomers of Casodex were synthesized according to the general synthetic scheme proposed by Tucker et al. for (S)-Casodex, using (R) or (S)-proline as the chiral matrix respectively. 4. ARs were isolated from rat ventral prostate tissue by homogenization and differential centrifugation, and used as the receptor source. 5. AR binding studies were conducted by incubation of the cytosol with 1 nM 3H-mibolerone (a synthetic androgen) and increasing concentrations of each isomer (10(-12) - 10(-5) M). Bound radioligand was quantitated by liquid scintillation counting. 6. Ki for (R)-Casodex (11.0 +/- 1.5 nM) was about 30 times lower than that of (S)-Casodex (364 +/- 10 nM). Ki for the racemate was 20.2 +/- 2.0 nM. 7. This study demonstrated that (R)-Casodex has a higher binding affinity than its stereoisomer and suggests that the antiandrogenic activity of racemic Casodex is almost completely due to the (R)-isomer.