gebhart/patrepeval huggingface dataset:
Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction (2000)

An extensive association analysis of a candidate gene for coronary heart disease, Cholesteryl Ester Transfer Protein (CETP) gene, was performed. Ten polymorphisms, out of which three were newly identified in regulatory regions, were investigated for association with myocardial infarction (MI) and 2 MI endophenotypes (CETP mass and HDL-cholesterol level) in 568 MI patients and 668 controls. The polymorphisms affecting codon 405 (Ile405Val) and the nucleotide 524 downstream from the stop codon (G+524T) were almost completely concordant and associated with plasma CETP mass (P < 0.001). The polymorphisms –629 (located in promoter), intron1 (Taq1B) and intron7 were almost completely concordant and associated with plasma CETP mass (P < 0.0001) and HDL-cholesterol levels (P < 0.0001). This latter association was not found in teetotalers and increased with the quantity of alcohol consumed. Heavy drinkers (>75g/day) homozygous for the –628A allele had a reduced risk of MI (OR = 0.33, P < 0.02). Subjects both homozygous for 451Arg and heterozygous for 373Pro had decreased plasma HDL-cholesterol levels and this effect increased with alcohol consumption. The results illustrate the complexity of polymorphism-phenotype associations. They suggest that the CETP gene may carry several functional polymorphisms. Observed interactions between alcohol consumption and polymorphisms associated with HDL-cholesterol level constitute concrete examples of gene-environment interactions. Furthermore, the pattern of association between HDL-cholesterol levels and the polymorphisms at codons 373 and 451 illustrated how two polymorphisms may be confounders (in the usual epidemiological sense) one for the other: their marginal effects are neutralized because of linkage disequilibrium and thus are not detectable by standard univariate association analysis. Genet. Epidemiol. 19:64–80, 2000. © 2000 Wiley-Liss, Inc.
Clinical Applications of Acute Intraoperative Arterial Elongation (1993)

This study reports four clinical cases in which acute intraoperative, extraluminal, arterial elongation was utilized. This technique was developed to facilitate end-to-end anastomoses across vascular defects traditionally bridged with vein grafts. In the reported cases, arterial defects, ranging from 17 to 25 mm, were closed primarily following the application of this technique. Follow-up, ranging from 3 to 34 months, has demonstrated patency in all cases. The authors believe this technique can be used clinically as a reliable alternative to vein grafting for the reconstruction of certain arterial defects.
Inducible Cre/loxP Recombination in the Mouse Proximal Tubule (2007)

Transgenic technologies in mice became invaluable experimental tools to identify the in vivo function of proteins. However, conventional knockout technology often results in embryonic lethality and because genes are frequently expressed in multiple cell types, the resulting knockout phenotypes can be complex and difficult or impossible to dissect. These issues are particularly important for gene-targeting strategies used to examine renal function. The kidney contains quite a number of different cell types, the function of many of which impacts that of other renal cells. To avoid these limitations conditional knockout strategies have been designed. As one important part of this system we describe the development of a mouse line expressing the tamoxifen-activatable Cre recombinase Cre-ER(T2) specifically in renal proximal tubules. The expression of Cre-ER(T2) is driven by a promoter fragment of the mouse gamma-glutamyl transpeptidase type II gene resulting in the generation of the activatable recombinase in S3 segments of the proximal tubules from which over 80% were positive for Cre activity. In combination with loxP-based conditional mutant mice as a second tool this tamoxifen-inducible Cre-ER(T2) line allows functional analysis of a variety of genes important for renal development and function in a precisely controlled spatiotemporal manner.
Nicotinic acid: an old drug with a promising future (2007)

Nicotinic acid has been used for decades to treat dyslipidaemic states. In particular its ability to raise the plasma HDL cholesterol concentration has led to an increased interest in its pharmacological potential. The clinical use of nicotinic acid is somewhat limited due to several harmless but unpleasant side effects, most notably a cutaneous flushing phenomenon. With the recent discovery of a nicotinic acid receptor, it has become possible to better understand the mechanisms underlying the metabolic and vascular effects of nicotinic acid. Based on these new insights into the action of nicotinic acid, novel strategies are currently under development to maximize the pharmacological potential of this drug. The generation of both flush-reducing co-medications of nicotinic acid and novel drugs targeting the nicotinic acid receptor will provide future therapeutic options for the treatment of dyslipidaemic disorders.
Silicon Nanowire Array Photoelectrochemical Cells (2007)

Silicon nanowire arrays were grown by vapor−liquid−solid growth from SiH4 vapor at 500 °C, and tested as photocathodes in [Ru(bpy)3]2+ (bpy = 2,2'-bipyridyl)/acetonitrile solutions. Si nanowires were grown in anodic aluminum oxide membranes by first electroplating 50 μm long Co wires capped with 250 nm gold segments in the pores and then reacting with SiH4. The resulting Si nanowires protruded 10−15 μm beyond the top surface of the membrane but were degeneratively doped, most likely by Al from the membrane. Nanowires grown in the same manner on Si(111)/Au substrates could be controllably doped p-type by addition of trimethylboron. These p-Si nanowire arrays gave a photovoltage of 220 mV in [Ru(bpy)3]2+ solution when illuminated by white light.
Synthesis and central nervous system activity of quinazolones related to 2-methyl-3-(o-tolyl)-4(3H)-quinazolone (methaqualone) (1977)

A number of derivatives of 2-methyl-3-(o-tolyl)-4(3H)-quinazolone bearing new substituents on the 2-methyl group have been synthesized. It was established that most substitutions at this position reduce or remove the CNS depressant activity of methaqualone. From the series prepared only the 2-fluoromethyl derivative or certain isothiouronium salts, which could be hydrolyzed in vivo to the 2-mercaptomethyl derivative, showed activity of the same magnitude as methaqualone.
Extreme visualization (2008)

Database searches are usually performed with query languages and form fill in templates, with results displayed in tabular lists. However, excitement is building around dynamic queries sliders and other graphical selectors for query specification, with results displayed by information visualization techniques. These filtering techniques have proven to be effective for many tasks in which visual presentations enable discovery of relationships, clusters, outliers, gaps, and other patterns. Scaling visual presentations from millions to billions of records will require collaborative research efforts in information visualization and database management to enable rapid aggregation, meaningful coordinated windows, and effective summary graphics. This paper describes current and proposed solutions (atomic, aggregated, and density plots) that facilitate sense-making for interactive visual exploration of billion record data sets.
AAV Vector Integration Sites in Mouse Hepatocellular Carcinoma (2007)

Adeno-associated viruses (AAV) are promising gene therapy vectors that have little or no acute toxicity. We show that normal mice and mice with mucopolysaccharidosis VII (MPS VII) develop hepatocellular carcinoma (HCC) after neonatal injection of an AAV vector expressing b-glucuronidase. AAV proviruses were isolated from four tumors and were all located within a 6-kilobase region of chromosome 12. This locus encodes several imprinted transcripts, small nucleolar RNAs (snoRNAs), and microRNAs. Transcripts from adjacent genes encoding snoRNAs and microRNAs were overexpressed in tumors. Our findings implicate this locus in the development of HCC and raise concerns over the clinical use of AAV vectors.
Substrate and inhibitor specificity of glutamine cyclotransferase (QC). (1996)

This paper reports a systematic study of the substrate and inhibitor specificity of papaya latex glutamine cyclotransferase (QC). The results showed that the second amino acid residue in N-terminal glutaminyl peptides significantly accelerated papaya latex QC-catalyzed reactions while the third residue provided no further rate enhancement. Substrate binding was shown to be the main specificity-determining step. Fifteen proline derivatives and dipeptides containing an N-terminal proline were tested and found to inhibit papaya latex QC. This supports our previous molecular modeling study of the QC catalytic pathway which suggested a structure of the reaction intermediates similar to that of L-proline.
Ectopic Expression of the Serotonin 1c Receptor and the Triggering of Malignant Transformation (1989)

Neurotransmitter receptors are usually restricted to neuronal cells, but the signaling pathways activated by these receptors are widely distributed in both neural and non-neural cells. The functional consequences of activating a brain-specific neurotransmitter receptor, the serotonin 5HT1c receptor, in the unnatural environment of a fibroblast were examined. Introduction of functional 5HT1c receptors into NIH 3T3 cells results, at high frequency, in the generation of transformed foci. Moreover, the generation and maintenance of transformed foci requires continued activation of the serotonin receptor. In addition, the injection of cells derived from transformed foci into nude mice results in the generation of tumors. The serotonin 5HT1c receptor therefore functions as a protooncogene when expressed in NIH 3T3 fibroblasts.
A proposal on digital watermark in document image communication and its application to realizing a signature (1990)

Abstract With the advance of telematic technology, increasing document image information utilized in the state of soft copy is expected. In these situations, copies of obtained document image information are made illegally with ease, and hence the validity authentication of the information itself and its provider becomes more necessary. Since document image information to be authenticated exists in a form which can be read at an unidentified number of receiver terminals, the realization of an authentication scheme where document image and signature are combined is necessary. This is characteristic of document image information including nature pictures and photographs. This paper proposes a new concept of signature, which is called “digital watermark” for document image communication. A digital watermark is the coding scheme in which secret information is embedded into a document image similar to a watermark. Image coding schemes already proposed are available to realize a digital watermark. We present a method of obtaining a digital watermark using a well‐known predictive coding algorithm. Also, we define a criterion for security and show to what extent the digital signature is safe using simulation results, where two or three illegal actions are considered.
Constitutive production of human interferons by mouse cells with bovine papillomavirus as a vector. (1984)

Mouse C127I cells were transformed with a chimeric plasmid consisting of bovine papillomavirus and human interferon (HuIFN) gene (either IFN-gamma or IFN-alpha 5) placed under the control of simian virus 40 early promoter. The transformed cells retained 30-50 copies each of the hybrid plasmid extrachromosomally and secreted a high level of HuIFNs constitutively up to 3-4 X 10(5) international units/ml. The secreted HuIFN-gamma had no detectable activity on mouse cells, whereas HuIFN-alpha 5 was slightly active on mouse cells. Each IFN was neutralized either by anti-HuIFN-gamma or anti-HuIFN-alpha antiserum. The partially purified 35S-labeled HuIFN-gamma produced by the transformed cells showed heterogeneous bands with apparent Mrs of 22,000-25,000 on NaDodSO4/polyacrylamide gel electrophoresis. This value is similar to that of natural IFN-gamma and larger than the molecular weight calculated from the amino acid sequence, which suggests that HuIFN-gamma secreted by transformed mouse cells was glycosylated. The 35S-labeled IFN-alpha 5, immunoprecipitated with anti-HuIFN-alpha antiserum from the supernatant of the transformed cells, had a molecular weight of mature protein. These results suggest that the bovine papillomavirus vector can be used to produce a large quantity of foreign proteins in mammalian cells.
LCNN: Lookup-Based Convolutional Neural Network (2017)

Porting state of the art deep learning algorithms to resource constrained compute platforms (e.g. VR, AR, wearables) is extremely challenging. We propose a fast, compact, and accurate model for convolutional neural networks that enables efficient learning and inference. We introduce LCNN, a lookup-based convolutional neural network that encodes convolutions by few lookups to a dictionary that is trained to cover the space of weights in CNNs. Training LCNN involves jointly learning a dictionary and a small set of linear combinations. The size of the dictionary naturally traces a spectrum of trade-offs between efficiency and accuracy. Our experimental results on ImageNet challenge show that LCNN can offer 3.2x speedup while achieving 55.1% top-1 accuracy using AlexNet architecture. Our fastest LCNN offers 37.6x speed up over AlexNet while maintaining 44.3% top-1 accuracy. LCNN not only offers dramatic speed ups at inference, but it also enables efficient training. In this paper, we show the benefits of LCNN in few-shot learning and few-iteration learning, two crucial aspects of on-device training of deep learning models.
Synthesis and Characterization of a Sulfhydryl-Reactive Rhenium Metal−Ligand Complex (2000)

We describe the synthesis and spectral characterization of a rhenium metal-ligand complex. This complex reacts with sulfhydryl groups via an iodoacetamide side chain on the phenanthroline ligand and displays a high limiting anisotropy near 0.35 when excited at 442 nm. When covalently linked to human serum albumin, this complex displayed a mean decay time of about 1 micros. This decay time is appropriate for measuring rotational correlation times on the microsecond time scale as may occur for large macromolecular complexes.
Coenzyme Properties of NAD+ Bound to Different Matrices through the Amino Group in the 6‐Position (1976)

A method for the synthesis of N6-(2-aminoethyl)-NAD+ is given. The binding of this NAD+ derivative to different soluble and insoluble supports and the direct coupling of NAD+ to epoxyactivated Sepharose are described. Proofs are given that NAD+ is bound through the amino group in 6- position and the NAD+ derivative through the aliphatic amino group of the side chain. Non-enzymic reduction of the bound coenzyme to an almost quantitative extent is possible in all cases, but the enzymic reduction is largely influenced by the support. While N6-(2-aminoethyl)-NAD+ coupled to soluble dextran is nearly completely reducible by different dehydrogenases with a velocity of about 40% of that for free NAD+, the coenzyme bound to different insoluble matrices is very slowly reduced. Only 5% of the coenzyme derivative bound to BrCN-activated Sepharose are reducible, but 40% when it is bound through a spacer. From capacity determinations evidence is given that, even in this coenzyme gel, only those coenzyme molecules are useful in affinity chromatography which are on the surface of the gel grains; it is supposed that this may be due to the slow diffusion of an enzyme into the inner parts of an affinity gel.
Factor XI Deficiency (2009)

Severe factor XI (FXI) deficiency is an injury-related bleeding disorder common in Ashkenazi Jews and rare worldwide. In the past two decades, more than 180 mutations in the FXI gene have been reported in patients with FXI deficiency, five of which show a founder effect (Cys38Arg, Gln88Stop, Cys128Stop, Glu117stop, and Phe283Leu, the last two largely prevalent among Ashkenazi Jews). Inhibitors to FXI after exposure to plasma, FXI concentrates, or Rh immunoglobulin were described in patients with mutations resulting in null alleles. Treatment with low-dose recombinant activated factor VII in these patients appears promising. Survival advantages to patients with severe FXI have been recently reported. Herein, we present new observations related to clinic presentation, genotype-phenotype correlation, and treatment problems in patients with FXI deficiency.
Activating and inhibitory Fcγ receptors in immunotherapy: being the actor or being the target (2009)

Membrane Fcgamma receptors (FcgammaRs) can act either as potent activators of effector cell functions or as inhibitors of receptor-mediated cell activation following engagement by IgG antibodies bound to their target molecules. The remarkable ability of activating FcgammaRs to trigger antibody-dependent cellular cytotoxicity, cytokine release and phagocytosis/endocytosis followed by antigen presentation has stimulated the development of a number of therapeutic monoclonal antibodies whose Fc regions have been engineered to optimize their effector functions, mostly their killing activities. Conversely, the demonstration that inhibitory FcgammaRs can block or downmodulate effector functions has led to the concept that targeting these receptors is of interest in a number of pathologies. The use of bispecific antibodies leading to the crosslinking of FcgammaRIIB with activating receptors could induce immunomodulation in autoimmune or allergic diseases. Alternatively, the use of cytotoxic/antagonist anti-FcgammaRIIB antibodies could kill FcgammaRIIB-positive tumor cells or prevent the downmodulation of activating receptors. Thus, antibodies engineered to preferentially target activating or inhibitory FcgammaRs are currently being designed for therapeutic use.
Acute Palsy of the Recurrent Laryngeal Nerve Complicating Epstein-Barr Virus Infection (1996)

We report an 11-year-old boy with active Epstein-Barr virus (EBV) infection who developed acute aphonia and had signs and symptoms of recurrent laryngeal nerve palsy. The association of isolated recurrent laryngeal nerve palsy and EBV infection has not previously been reported. This case report expands the spectrum of neurologic complications of EBV infection, and suggests that infectious mononucleosis should be considered in the differential diagnosis of acute aphonia in children.
Defined Flanking Spacers and Enhanced Proteolysis Is Essential for Eradication of Established Tumors by an Epitope String DNA Vaccine (2001)

Loss of immunogenic epitopes by tumors has urged the development of vaccines against multiple epitopes. Recombinant DNA technologies have opened the possibility to develop multiepitope vaccines in a relatively rapid and efficient way. We have constructed four naked DNA-based multiepitope vaccines, containing CTL, Th cell, and B cell epitopes of the human papillomavirus type 16. Here we show that gene gun-mediated vaccination with an epitope-based DNA vaccine protects 100% of the vaccinated mice against a lethal tumor challenge. The addition of spacers between the epitopes was crucial for the epitope-induced tumor protection, as the same DNA construct without spacers was significantly less effective and only protected 50% of the mice. When tested for therapeutic potential, only the epitope construct with defined spacers significantly reduced the size of established tumors, but failed to induce tumor regression. Only after targeting the vaccine-encoded protein to the protein degradation pathway by linking it to ubiquitin, the vaccine-induced T cell-mediated eradication of 100% of 7-day established tumors in mice. The finding that defined flanking sequences around epitopes and protein targeting dramatically increased the efficacy of epitope string DNA vaccines against established tumors will be of importance for the further development of multiepitope DNA vaccines toward clinical application.
Submicron bipolar-CMOS technology using 16 GHz f/sub T/ double poly-Si bipolar devices (2003)

Submicrometer CMOS devices were integrated with self-aligned double-polysilicon bipolar devices, showing a cutoff frequency of 16 GHz and an ECL circuit speed of 65 ps/gate. It was found that an amorphous silicon film deposited at 575 degrees C and used as the base electrode improve the gate oxide breakdown voltage compared to a polysilicon film deposited at 600 degrees C. The PMOS FETs showed good short-channel behavior for effective channel lengths down to 0.6 mu m, while the NMOS FETs showed a hump in subthreshold current. This hump was eliminated by minimizing the overetch during the base polysilicon reactive-ion-etching process. Minimum-cell CMOS, BiCMOS and bipolar ECL (emitter-coupled logic) circuits were characterized as functions of loading capacitance, power dissipation, power supply voltage, and channel length of the MOS devices. The relative circuit speed improvements in the BiCMOS and CMOS circuits as the channel lengths were scaled from 0.8 mu m to 0.4 mu m were almost the same, while the BiCMOS circuit speed became slower than that of the CMOS when the power supply voltage was reduced below 3.3 V.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Towards gene therapy for deafness (2010)

Many hearing disorders are associated with the damage or loss of sensory hair cells (HC) which can produce a profound and irreversible deafness. Apoptosis pathway is reported to play an important role leading to rapid expansion of the HC lesion after exposure to intense noise. Furthermore, progress made over the last year in understanding molecular mechanisms involved in the proliferative and regenerative capacity of sensory cells in the mammalian inner ear has raised the possibility that targeted therapies might prevent the loss of these cells and preserve the patient's hearing. A first step towards the successful therapeutic exploitation is a better understanding of the different pathways that control survival and proliferation of sensory cells. In this review, we provide an overview of recent findings concerning the possibility to prevent apoptosis in auditory cells. We also show the current knowledge on the molecular mechanisms involved in the potential regenerative behavior of these cells and the progress of gene therapy to prevent deafness noise-induced.