gebhart/patrepeval huggingface dataset:
Clinical experience with a collagen impregnated woven Dacron graft. (1995)

Vascular grafts continue to evolve. Recent developments have been aimed at decreasing porosity, increasing strength of prosthesis, increasing ease of handling and suturing and optimising flow characteristics. This study describes results with a recently developed collagen impregnated polyester prosthesis Hemashield Woven Double Velour, which does not require pre-clotting. Between January 1988 and December, 1991 such prostheses were used in 90 patients at Papworth Hospital. Fifty-eight, were used to replace the ascending aorta, 10 for the arch of the aorta and 28 for the descending aorta seven of whom were for coarctation and four for traumatic transections. In 60 cases the underlying disease was a dissected or ruptured aorta requiring emergency operation. There were 66 survivors with X-ray and CT follow-up of 6-52 months. Median blood loss was 630 ml range 380-1800 ml. There was no leakage from any of the grafts during surgery despite full perioperative heparinisation. For emergency/elective operations (N = 60/30) early mortality was 25%/10% (15/3) and late mortality 5%/6.6% (3/2). Of 15 patients who had interposition grafts for Type A dissection CT scans at 5-47 months showed one with chronic dissection proximal to the repair and 11 with persistent distal dissection. There was no evidence of late bleeding, seroma impaired healing or thickened neointima formation. It is concluded that there are no clinical disadvantages associated with collagen impregnation to set against the notable convenience of initial impermeability.
Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss (2002)

The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis, and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. The pathogenesis of fetal loss and tissue injury in APS is incompletely understood, but is thought to involve platelet and endothelial cell activation as well as procoagulant effects of aPL antibodies acting directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation in the placenta leads to fetal death in utero. We hypothesized that aPL antibodies activate complement in the placenta, generating split products that mediate placental injury and lead to fetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. We found that inhibition of the complement cascade in vivo, using the C3 convertase inhibitor complement receptor 1-related gene/protein y (Crry)-Ig, blocks fetal loss and growth retardation. Furthermore, mice deficient in complement C3 were resistant to fetal injury induced by aPL antibodies. While antigenic epitopes recognized by aPL antibodies are important in the pathogenesis of APS, our data show that in vivo complement activation is required for aPL antibody-induced fetal loss and growth retardation.
Structure of an Escherichia coli tRNA operon containing linked genes for arginine, histidine, leucine, and proline tRNAs (1984)

A plasmid containing a gene for the most abundant Escherichia coli leucine isoacceptor tRNA, tRNALeu1 (anticodon CAG) was isolated from the Clarke-Carbon bank of cloned E. coli DNA. The clone contains a 12.3-kilobase DNA insert which was mapped by F' DNA hybridization analysis to the region 82 to 89 min on the chromosome. The cloned tDNALeu corresponds to the minor of two chromosomal regions containing different amounts of DNA complementary to tRNALeuCAG . Sequencing of the tDNA region revealed it to contain a multimeric transcription unit consisting of four different tRNA genes. The genes are in the arrangement 5'-leader- tRNAArgCCG -57 base pairs- tRNAHisGUG -20 base pairs- tRNALeuCAG -42 base pairs- tRNAProUGG -3'. Coordinate expression of the component tRNAs in vivo and the absence of intercistronic promoters indicated that all four tDNAs reside in the same operon. The tDNA sequence is bounded by a promoter element showing good agreement with the procaryotic consensus sequence and a GC-rich stem-loop element that corresponds to a rho-independent terminator. The promoter region contains a GC-rich sequence that agrees with a suggested consensus stringency control element and two domains possessing dyad symmetry which flank the Pribnow box and include the putative stringency control region.
A flexible bioluminescent‐quantitative polymerase chain reaction assay for analysis of competitive PCR amplicons (1999)

Aequorin-based flash-type bioluminescent methods can detect nucleic acid molecules in the attomolar range (10–18) enabling improved monitoring of the polymerase chain reaction (PCR) at cycles previously considered too low for product detection. The high sensitivity of bioluminescence (BL) was used to examine the efficiency of the PCR and to assess the effect of substrate variation during the linear phase of amplification. Primer efficiency was dependent on initial template concentration, in a manner indicative of a two-component reaction. However, the rate of amplicon formation was significantly impaired at low template levels and could not be overcome by excess primer. The PCR was directly dependent upon nucleotide concentration, which was independent of template concentration. Conditions were identified for optimal linear amplification and detection using BL. Accurate quantitative analysis was performed using competitive coamplification of a specific target standard sequence containing identical target primer recognition sites and novel internal sequences. Quantitation was most accurate when target molecule was similar in concentration to the internal standard. The Bioluminescent Quantitative-PCR (BLQ-PCR) assay has the potential to eliminate processing variability. We demonstrated high quantitative potential with a broad dynamic range. Overall, the BLQ-PCR assay is flexible and a viable alternative to contemporary Q-PCR techniques. J. Clin. Lab. Anal. 13:40–47, 1999. © 1999 Wiley-Liss, Inc.
Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice (2005)

Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly expressed in adipose tissue and liver. Several recent studies demonstrated that ANGPTL4 is the target gene of peroxisome proliferation activators, the agonists of which are widely used as the antidiabetic and lipid-lowering drugs. Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Adenovirus-mediated expression of ANGPTL4 potently decreased blood glucose and improved glucose tolerance, whereas it induced hyperlipidemia, fatty liver, and hepatomegaly in C57 mice. In db/db diabetic mice, ANGPTL4 treatment reduced hyperglycemia to a normal level, and markedly alleviated glucose intolerance and hyperinsulinemia. Ex vivo studies on primary rat hepatocytes revealed that ANGPTL4 significantly decreased hepatic glucose production and enhanced insulin-mediated inhibition of gluconeogenesis. Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance. In patients with type 2 diabetes, serum levels of ANGPTL4 were significantly lower than those in healthy subjects, suggesting that the decreased ANGPTL4 could be a causative factor of this disease. These results collectively indicate that ANGPTL4 exerts distinct effects on glucose and lipid metabolism, and that its beneficial effect on glucose homeostasis might be useful for the treatment of diabetes.
Reactions of hydrazonoyl halides with imidazoles and benzimidazoles (1979)

Hydrazonoyl halides upon reaction with N-methylimidazole and N-substituted benzimidazoles yield ring opened 1 : 1 adducts. The action of aqueous sodium hydroxide on these adducts leads to the formation of pyrazin-2-one or quinoxalin-2-one derivatives via ring expansion.
Molecular cloning of gene sequences regulated by tumor promoters and mitogens through protein kinase C. (1987)

cDNA clones representing genes whose expression is modulated by treatment with mitogens and tumor promoters were isolated and characterized. TPA-S1 corresponds to an mRNA species whose abundance was increased markedly within 1 h of exposure to the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), and TPA-R1 represents an mRNA that was decreased in TPA-treated cells. The induction of TPA-S1 was blocked by actinomycin D but was not affected by cycloheximide, and it was specific for phorbol esters with tumor-promoting activity. The role of protein kinase C in the induction of TPA-S1 is supported by the following lines of evidence. (i) Agents that activated protein kinase C (TPA, platelet-derived growth factor, and diacylglycerol) also increased TPA-S1 mRNA levels. (ii) A potent PKC inhibitor blocked the induction of TPA-S1. (iii) Down-regulation of PKC activity, by treatment of cells with TPA for 24 h, resulted in a loss of responsiveness to TPA-S1 induction by subsequent TPA treatment. DNA sequence analysis of TPA-S1 predicts a cysteine-rich, secreted protein with a molecular weight of 22.6 X 10(3) that exhibits homology with sequences representing a protein with human erythroid-potentiating activity and protease inhibitory activity.
Specific and complete human genome amplification with improved yield achieved by phi29 DNA polymerase and a novel primer at elevated temperature (2009)

Whole genome amplification (WGA) is a practical solution to eliminate molecular analysis limitations associated with genomic DNA (gDNA) quantity. Different methods have been developed to amplify the whole genome, including primer extension preamplification (PEP), degenerate oligonucleotide primed PCR (DOP-PCR), and multiple displacement amplification (MDA). Each of these methods has its own merits and limitations. Effects of primer length and composition on amplification quality and quantity were explored in this study at two different temperatures (30°C & 40°C). New primer designs combined with elevated amplification temperature has significantly improved MDA as measured by amplification yield, genome coverage, and allele drop out (ADO) analysis. A remarkable finding was the comprehensive amplification, at 30°C & 40°C, of the human whole genome via the use of GGGCAGGA*N*G hotspot recombination consensus primer. Amplification was characterized by Affymetrix 10K SNP chip analysis. Finally, the use of new primer designs has suppressed the template-independent DNA amplification (TIDA) both at 30°C and 40°C. The use of new primers in this study combined with elevated incubation temperatures in MDA has remarkably improved the specificity, amplification yield, and suppressed TIDA.
Modulation of crystal formation by bone phosphoproteins: structural specificity of the osteopontin-mediated inhibition of hydroxyapatite formation (1994)

Osteopontin is a phosphorylated sialoprotein containing a conserved sequence of contiguous aspartic acid residues. This protein is expressed at high levels in mineralized tissues and has previously been shown to inhibit the in vitro formation of hydroxyapatite (HA). In the present study, protein modification and model compound studies have been used to identify the structural features of osteopontin that are responsible for its crystal-modulating properties. Using metastable calcium phosphate solutions buffered by autotitration, osteopontin caused half-maximal inhibition of HA formation at a concentration (IC50) of 0.06 microgram/ml. The hen egg yolk phosphoprotein phosvitin was a much weaker inhibitor, while dextran sulphate had no effect. The synthetic polypeptide poly(aspartic acid) was almost as effective an inhibitor of HA formation as osteopontin (IC50 0.11 microgram/ml), whereas poly(glutamic acid) was more than a thousand times less potent (IC50 155 micrograms/ml). In a steady-state agarose gel system, much higher polypeptide concentrations were required for inhibition of HA formation, but a similar relative order of inhibitory effectiveness was observed. Treatment of osteopontin with alkaline phosphatase removed 84% of the covalently bound phosphate and reduced its HA-inhibiting activity by more than 40-fold. Treatment with glycine ethyl ester in the presence of carbodi-imide modified 86% of the carboxylate groups in osteopontin and reduced its inhibitory activity by 6-fold. These findings indicate that osteopontin is a potent inhibitor of HA formation. This activity requires phosphate and carboxylate groups, possibly including the conserved sequence of contiguous aspartic acid residues. Osteopontin may act as an inhibitor of phase separation in physiological fluids of high supersaturation.
Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders (2008)

Despite the great number of observations being made concerning cellular and the molecular dysfunctions associated with autism spectrum disorders (ASD), the basic central mechanism of these disorders has not been proposed in the major scientific literature. Our review brings evidence that most heterogeneous symptoms of ASD have a common set of events closely connected with dysregulation of glutamatergic neurotransmission in the brain with enhancement of excitatory receptor function by pro-inflammatory immune cytokines as the underlying mechanism. We suggest that environmental and dietary excitotoxins, mercury, fluoride, and aluminum can exacerbate the pathological and clinical problems by worsening excitotoxicity and by microglial priming. In addition, each has effects on cell signaling that can affect neurodevelopment and neuronal function. Our hypothesis opens the door to a number of new treatment modes, including the nutritional factors that naturally reduce excitotoxicity and brain inflammation.
A fast rate-optimized motion estimation algorithm for low-bit-rate video coding (1999)

Motion estimation is known to be the main bottleneck in real-time encoding applications, and the search for an effective motion estimation algorithm (in terms of computational complexity and compression efficiency) has been a challenging problem for years. This paper describes a new block-matching algorithm that is much faster than the full search algorithm and occasionally even produces better rate-distortion curves than the full search algorithms. We observe that a piecewise continuous motion field reduces the bit rate for differentially encoded motion vectors. Our motion estimation algorithm exploits the spatial correlations of motion vectors effectively in the sense of producing better rate-distortion curves. Furthermore, we incorporate such correlations in a multiresolution framework to reduce the computational complexity. Simulation shows that this method is successful because of the homogeneous and reliable estimation of the displacement vectors. In nine out of our ten benchmark simulations, the performance of the full search algorithm and that of our subblock multiresolution method is about the same. In one out of our ten benchmark simulations, our method has improvement.
Multiple-turnover cleavage of double-stranded DNA by sandwiched zinc-finger nuclease (2009)

To refine zinc-finger nuclease (ZFN) technology, we constructed a sandwiched ZFN, in which a DNA cleavage enzyme was sandwiched with two artificial zinc-finger proteins (AZPs). Because the sandwiched ZFN is designed to cleave the DNA between the two AZP-binding sites, the sandwiched ZFN is expected to bind preferentially to a DNA substrate rather than to cleavage products and thereby cleave it with multiple turnovers. To prove the concept, we sandwiched a staphylococcal nuclease (SNase), which cleaves DNA as a monomer, between two 3-finger AZPs. The AZP-sandwiched SNase cleaved large amounts of dsDNA site-specifically. Such multiple-turnover cleavage was not observed with control nucleases that possess a single AZP.
Regulation of human NAD(P)H:quinone oxidoreductase gene. Role of AP1 binding site contained within human antioxidant response element. (1992)

Deletion mutagenesis and transfection studies into hepatic (mouse hepatoma (Hepa-1) and human hepatoblastoma (Hep-G2)) and nonhepatic (HeLa) cells indicated that high levels of expression of the human NAD(P)H:quinone oxidoreductase gene in tumor cells and its induction by beta-naphthoflavone and 3-(2)-tert-butyl-4-hydroxyanisole are mediated by human antioxidant response element (hARE) located in the region between -470 and -445. The hARE, when attached to the thymidine kinase promoter and transfected into several mammalian cells, expressed high levels of the chloramphenicol acetyltransferase gene that was inducible by beta-naphthoflavone and 3-(2)-tert-butyl-4-hydroxyanisole. Nucleotide sequence analysis of the hARE revealed the presence of a recognition site for binding to the AP1 protein. Mutation of the AP1 binding site located within the hARE resulted in the loss of expression and induction upon transfection into various cell types. Band shift and competition assays with hARE and nuclear extracts from control and beta-naphthoflavone-treated Hepa-1, Hep-G2 and HeLa cells indicated specific interaction of regulatory protein(s) to the hARE. The supershift assays using antibodies against specific proteins of the AP1 family identified Jun-D and c-Fos as two members in the hARE-protein complex observed in band shift assays.
Ximelagatran vs Warfarin for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation (2005)

The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.
Antigen‐presenting cell exosomes are protected from complement‐mediated lysis by expression of CD55 and CD59 (2003)

Exosomes are secreted nanometer-sized vesicles derived from antigen-presenting cells, which have attracted recent interest as they likely play important roles in immune regulation, and their use as cell-free tools for immunotherapy has been proposed. Liposomes used clinically as transport vehicles can activate the complement system, leading to their rapid degradation and significant inflammatory toxicity. The use of isolated exosomes in therapy, therefore, may also elicit complement activation, reducing their potential efficacy. We have examined the expression and functional roles of the membrane regulators of complement (CD46, CD55 and CD59) on antigen-presenting cell-derived exosomes. Exosomes express the glycosylphosphatidylinositol (GPI)-anchored regulators CD55 and CD59, but not the transmembrane protein CD46. Antibody blocking of CD55 in the presence of sensitizing antibody (w6/32) and human serum resulted in increased C3b deposition and significantly increased exosome lysis. Blockade of CD59 also resulted in significant lysis, while blocking both CD55 and CD59 increased lysis still further. We conclude that exosomes express GPI-anchored complement regulators in order to permit their survival in the extracellular environment.
Targeting Alzheimer's disease genes with RNA interference: an efficient strategy for silencing mutant alleles (2004)

Tau and amyloid precursor protein (APP) are key proteins in the pathogenesis of sporadic and inherited Alzheimer's disease. Thus, developing ways to inhibit production of these proteins is of great research and therapeutic interest. The selective silencing of mutant alleles, moreover, represents an attractive strategy for treating inherited dementias and other dominantly inherited disorders. Here, using tau and APP as model targets, we describe an efficient method for producing small interfering RNA (siRNA) against essentially any targeted region of a gene. We then use this approach to develop siRNAs that display optimal allele-specific silencing against a well-characterized tau mutation (V337M) and the most widely studied APP mutation (APPsw). The allele-specific RNA duplexes identified by this method then served as templates for constructing short hairpin RNA (shRNA) plasmids that successfully silenced mutant tau or APP alleles. These plasmids should prove useful in experimental and therapeutic studies of Alzheimer's disease. Our results suggest guiding principles for the production of allele-specific siRNA, and the general method described here should facilitate the production of gene-specific siRNAs.
Regression of Advanced Ovarian Carcinoma by Intraperitoneal Treatment With Autologous TLymphocytes Retargeted by a Bispecific Monoclonal Antibody (1995)

Improvement in systemic antitumor responses is needed before this approach can prove useful as adjunctive treatment following induction chemotherapy in patients with minimal residual disease.
Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo (2003)

The use of semiconductor nanocrystals (quantum dots) as fluorescent labels for multiphoton microscopy enables multicolor imaging in demanding biological environments such as living tissue. We characterized water-soluble cadmium selenide-zinc sulfide quantum dots for multiphoton imaging in live animals. These fluorescent probes have two-photon action cross sections as high as 47,000 Goeppert-Mayer units, by far the largest of any label used in multiphoton microscopy. We visualized quantum dots dynamically through the skin of living mice, in capillaries hundreds of micrometers deep. We found no evidence of blinking (fluorescence intermittency) in solution on nanosecond to millisecond time scales.
Dropspots: a picoliter array in a microfluidic device (2008)

We present a simple microfluidic device that uses an array of well-defined chambers to immobilize thousands of femtoliter- to picoliter-scale aqueous drops suspended in inert carrier oil. This device enables timelapse studies of large numbers of individual drops, while simultaneously enabling subsequent drop recovery.
Performance of Momguard, a new non-invasive prenatal testing protocol developed in Korea (2015)

Momguard is a reliable screening tool for detecting T21 and T18. For T13 and sex-chromosome anomalies, further prospective studies are necessary to confirm its utility.
Monoclonal antibodies to human melanoma-associated antigens: an amplified enzyme-linked immunosorbent assay for the detection of antigen, antibody, and immune complexes. (1983)

An amplified, indirect biotin-avidin micro-enzyme-linked immunosorbent assay was developed for the measurement of human melanoma-associated antigens, either free or circulating with associated immunoglobulin in patient sera. Parameters and specificity of detection were assessed using monoclonal antibody to human melanoma-associated antigens. The main advantages of the assay are its flexibility, through the use of indirect detection and a variety of formats, and its sensitivity, with a lower limit of antibody detection at 100 pg/well and a lower limit of soluble antigen detection at 10 pg/well. The assay was applied to cell surface antigen detection with monoclonal antibody 9.2.27 to a melanoma-associated antigen against a panel of glutaraldehyde-fixed cells, and gave similar binding specificity as assessed by a previous 125I-Protein A assay. Utilizing a unique "sandwich" format, aMr 100,000 melanoma-carcinoma-associated antigen was quantitated in melanoma patient sera and found highly elevated in Stage IV disease. The same sandwich format was also used to detect and determine the class of human immunoglobulin associated with circulating Mr 100,000 human melanoma-associated antigens in normal donor sera. Thus, the sensitivity and flexibility of this enzyme-linked immunosorbent assay system make it particularly suitable for numerous applications in the study of monoclonal antibody-defined tumor-associated antigens.