gebhart/patrepeval huggingface dataset:
QPSOBT: One codon usage optimization software for protein heterologous expression (2010)

QPSOBT is a codon usage optimization software based on the Quantum-behaved Particle Swarm Optimization (QPSO) algorithm. It can design synthetic genes of multikilobase sequences for protein heterologous expression rapidly. The program runs on .NET platform. Compared to the existing codon optimization software and web services, QPSOBT is able to generate better results when DNA/RNA sequence length is less than 6 kb which is a commonly-used range, especially when some restriction sites need to be removed. QPSOBT is freely available (www.sigcib.org/qpsobt.html).

	 

	Key words: Codon usage, quantum-behaved particle swarm, optimization, protein expression.
Adenosine limits the therapeutic effectiveness of anti-CTLA4 mAb in a mouse melanoma model. (2014)

Combination therapies for melanoma that target immune-regulatory networks are entering clinical practice, and more are under investigation in preclinical or clinical studies. Adenosine plays a key role in regulating melanoma progression. We investigated the effectiveness of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (mAb) in combination with either modulators of adenosine receptors (AR) activation or an inhibitor of adenosine production in a murine model of melanoma. We found that treatment with APCP, selective inhibitor of the adenosine-generating nucleotidase CD73, enhanced the activity of anti-CTLA4 mAb, by improving tumor immune response. Blockade of the adenosine A2a receptor (A2aR), which plays a critical role in the regulation of T-cell functions, significantly reduced melanoma growth. Most importantly, combination therapy including an A2aR antagonist with anti-CTLA4 mAb markedly inhibited tumor growth and enhanced anti-tumor immune responses. Targeting A3R and CTLA4 was not as effective in limiting melanoma growth as targeting A2aR. These data suggest that the efficacy of anti-CTLA4 melanoma therapy may be improved by targeting multiple mechanisms of immune suppression within tumor tissue, including CD73 or A2a receptor.
Chemoenzymatic Synthesis of Biotinylated Nucleotide Sugars as Substrates for Glycosyltransferases (2001)

The enzymatic oxidation of uridine 5'-diphospho-alpha-D-galactose (UDP-Gal) and uridine 5'-diphospho-N-acetyl-alpha-D-galactosamine (UDP-GalNAc) with galactose oxidase was combined with a chemical biotinylation step involving biotin-epsilon-amidocaproylhydrazide in a one-pot synthesis. The novel nucleotide sugar derivatives uridine 5'-diphospho-6-biotin-epsilon-amidocaproylhydrazino-alpha-D-galactose (UDP-6-biotinyl-Gal) and uridine 5'-diphospho-6-biotin-epsilon-amidocaproylhydrazino-N-acetyl-alpha-D-galactosamine (UDP-6-biotinyl-GalNAc) were synthesized on a 100-mg scale and characterized by mass spectrometry (fast atom bombardment and matrix-assisted laser desorption/ionization time of flight) and one/two dimensional NMR spectroscopy. It could be demonstrated for the first time, by use of UDP-6-biotinyl-Gal as a donor substrate, that the human recombinant galactosyltransferases beta3Gal-T5, beta4Gal-T1, and beta4Gal-T4 mediate biotinylation of the neoglycoconjugate bovine serum albumin-p-aminophenyl N-acetyl-beta-D-glucosaminide (BSA-(GlcNAc)17) and ovalbumin. The detection of the biotin tag transferred by beta3Gal-T5 onto BSA-(GlcNAc)17 with streptavidin-enzyme conjugates gave detection limits of 150 pmol of tagged GlcNAc in a Western blot analysis and 1 pmol of tagged GlcNAc in a microtiter plate assay. The degree of Gal-biotin tag transfer onto agalactosylated hybrid N-glycans present at the single glycosylation site of ovalbumin was dependent on the Gal-T used (either beta3Gal-T5, beta4Gal-T4, or beta4Gal-T1), which indicates that the acceptor specificity may direct the transfer of the Gal-biotin tag. The potential of this biotinylated UDP-Gal as a novel donor substrate for human galactosyltransferases lies in the targeting of distinct acceptor structures, for example, under-galactosylated glycoconjugates, which are related to diseases, or in the quality control of glycosylation of recombinant and native glycoproteins.
Melatonin (2006)

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an 'internal sleep facilitator' promotes sleep, and melatonin's sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a 'photoperiodic molecule' in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.
Antibodies Made to Order (1985)

Sur la preparation et les applications therapeutiques d'anticorps chimeriques dont les regions variables sont d'origine murine et les regions constantes sont d'origine humaine
Tissue-Specific Gene Expression Identifies a Gene in the Lysogenic Phage Gifsy-1 That Affects Salmonella enterica Serovar Typhimurium Survival in Peyer's Patches (2000)

In vivo expression technology was used to identify Salmonella enterica serovar Typhimurium genes that are transcriptionally induced when the bacteria colonize the small intestines of mice. These genes were subsequently screened for those that are transcriptionally inactive during the systemic stages of disease. This procedure identified gipA, a gene that is specifically induced in the small intestine of the animal. The gipA gene is carried on the lambdoid phage Gifsy-1. Consistent with the expression profile, the sole defect conferred by a gipA null mutation is in growth or survival in a Peyer's patch. The gipA strain is wild type in its ability to initially colonize the small intestine and invade the intestinal epithelium. The mutant also survives and propagates at wild-type levels during the systemic stages of disease. The gipA open reading frame is homologous to a family of putative insertion sequence elements, although our evidence shows that transposition is not required for gipA function in the Peyer's patch. These results suggest that the bacteria sense and respond to the particular environment of the Peyer's patch, a critical site for the replication of Salmonella serovar Typhimurium.
Proteomics Reveals that Proteins Expressed During the Early Stage of Bacillus Anthracis Infection are Potential Targets for the Development of Vaccines and Drugs (2004)

Abstract In this review, we advance a new concept in developing vaccines and/or drugs to target specific proteins expressed during the early stage of Bacillus anthracis (anthrax) infection and address existing challenges to this concept. Three proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase) initially identified by proteomics in our laboratory were found to have differential expressions during anthrax spore germination and early outgrowth. Other studies of different bacillus strains indicate that these three proteins are involved in either germination or cytotoxicity of spores, suggesting that they may serve as potential targets for the design of anti-anthrax vaccines and drugs.
821. Hydrolysis of sodium silicate: ultracentrifugation in chloride solutions (1965)

J. Aveston, J. Chem. Soc., 1965, 4444 DOI: 10.1039/JR9650004444
Long-Term Survival After Resection for Ductal Adenocarcinoma of the Pancreas Is It Really Improving? (1995)

Five-year survival for patients undergoing pancreatic resection for lesions deemed to be clinically "curable" intraoperatively and histologically reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately 7%. Survival is greater (23%) in the subset of patients with negative nodes and no duodenal or perineural invasions. Pathologic review of all patients with pancreatic ductal cancer adenocarcinoma is mandatory if survival data are to be meaningful.
Optimization Of Multi-ring Sensing Electrode Set (2005)

The potential generated in a set of concentric ring electrodes by a moving dipole layer has been simulated by a linear finite element model. The wavefront was represented by rectangular charged elements with the charge concentrated at the center of each element. The results were described in a previous paper. The model was refined to reflect the solid angle described by the corners of the finite element and the center of the element on the ring of interest. This corrected the potential while the dipole layer was near the center of the sensing electrodes. The model confirmed that the far-field dependence of both bipolar and tripolar rings was a function of r-4. As expected, the tripolar configuration is more spatially sensitive with a smaller amplitude. When signal amplitude is more important than spatial specificity then the bipolar configuration appears superior.
Invariant optical-pattern recognition based on a contour bank (1994)

We propose a new optical pattern-recognition method that is invariant to shift, rotation, and scale changes. By means of a zero-order circular-harmonic filter the input object can be transformed into a correlation peak whose outline retains a shape similar to the outline of the input object. After multilevel thresholding and binarization, a bank composed of many contours with different sizes is formed. The invariant recognition can be obtained by a small contour line being taking as a reference and its second-order circular-harmonic component being taken as a filter. In addition to the scale invariance the correlation peak is superior to the classical circular-harmonic filter and the phase-only circular-harmonic filter in terms of peak intensity, half-maximum width, and peak-to-sidelobe ratio.
Spatiotemporal information preservation in turbulent vapor plumes (2018)

Monitoring of airborne chemicals is essential for public safety and environmental applications, but the complex nature of stochastic airflow limits the accuracy of data acquired from chemical sensors, including the identity, concentration, and location of a chemical source. Here, we explore the limits on information retrieval in a turbulent environment using temporally modulated vapor plumes. By exploiting the physical and statistical properties of turbulent flow, we demonstrate higher classification rates (≥20 Hz) at lower chemical error rates (≤0.1%) than prior reports. Physical constraints on vapor sensing are explored, including finite spatial sampling, large path distances (≥3 m), dilute concentrations (≤1 ppb), dynamic wind velocities (V = 0–5 m/s), cross winds, and occluded airflows. Our results highlight the fact that as turbulence increases, smaller structures can be embedded in an air flow, which increases measurement variance, but also makes each plume more quickly and accurately identifiable. For a given wind velocity, there exists a modulation rate which optimizes the rate of preserved information. This raises interesting possibilities for the identification of optimally preserved patterns in a turbulent environment.
Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration (2014)

Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg.
Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles (2018)

The human lung harbors a large population of resident memory T cells (Trm cells). These cells are perfectly positioned to mediate rapid protection against respiratory pathogens such as influenza virus, a highly contagious respiratory pathogen that continues to be a major public health burden. Animal models show that influenza-specific lung CD8+ Trm cells are indispensable for crossprotection against pulmonary infection with different influenza virus strains. However, it is not known whether influenza-specific CD8+ Trm cells present within the human lung have the same critical role in modulating the course of the disease. Here, we showed that human lung contains a population of CD8+ Trm cells that are highly proliferative and have polyfunctional progeny. We observed that different influenza virus-specific CD8+ T cell specificities differentiated into Trm cells with varying efficiencies and that the size of the influenza-specific CD8+ T cell population persisting in the lung directly correlated with the efficiency of differentiation into Trm cells. To our knowledge, we provide the first ex vivo dissection of paired T cell receptor (TCR) repertoires of human influenza-specific CD8+ Trm cells. Our data reveal diverse TCR profiles within the human lung Trm cells and a high degree of clonal sharing with other CD8+ T cell populations, a feature important for effective T cell function and protection against the generation of viral-escape mutants.
Regulation of theEscherichia coli sheAgene and characterization of its encoded hemolytic activity (1998)

Escherichia coli K-12 carries the cryptic hemolysin gene sheA which is under the control of positive and negative transcriptional regulators. The objectives of the present study were to further analyze the regulation of the sheA gene in E. coli, to compare the sheA genes from E. coli K-12 and a pathogenic E. coli strain, and to characterize the SheA hemolytic activity. Northern blot analysis demonstrated that the transcriptional regulator SlyA activates the E. coli K-12 sheA gene. The main transcriptional start site of the sheA gene was 56 nucleotides upstream from the start codon as determined by primer extension analysis. The sheA genes from E. coli K-12 and a pathogenic E. coli strain were identical. SheA hemolytic activity was cell associated and Ca2+ independent.
Evaluation of Different Approaches for Fetal DNA Analysis from Maternal Plasma and Nucleated Blood Cells (1999)

One potential noninvasive approach for antenatal diagnosis is the use of fetal cells in maternal circulation as a source of fetal DNA (1). To date, fetal DNA has been extracted from maternal nucleated blood cells and amplified by nested PCR of Y-chromosome sequences from male fetuses (2)(3).

A recent study (4) demonstrated the presence of fetal DNA in maternal plasma. After a single PCR with a high number of cycles, detection of fetal DNA was possible in 24 (80%) of the 30 maternal plasma samples, using 10 μL of boiled plasma (4). When DNA extracted from a similar volume of whole blood was used, only 17% of the samples gave a Y-positive signal, suggesting an enrichment of fetal DNA in plasma compared with whole blood cells (4). The mechanism responsible for fetal DNA release in maternal circulation is unclear. It has been postulated that fetal cell lysis after physical and immunological damage, as well as developmentally regulated apoptosis of certain fetal tissues, may be responsible for this phenomenon (5). Furthermore, the release and clearance of fetal DNA from maternal plasma may be influenced by pathophysiological factors that are still to be determined.

The efficacy of the single PCR protocol on maternal plasma DNA has not yet been compared to established methodologies of nested amplification of DNA prepared from intact cells. The present work compares single PCR on plasma DNA with nested PCR on DNA extracted from plasma or nucleated blood cells. We collected 27 maternal blood samples at gestational ages ranging from the 7th to the 32nd weeks (16 male- and 11 female-bearing pregnancies). Nine, 14, and 4 samples were from the first (7–12 weeks), second (14–20 weeks), and third (27–32 weeks) trimesters. Fetal gender was unknown at the time of sampling and analysis and was verified …
Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk (2013)

The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events. (Funded by the National Institutes of Health and others.).
Stable Transduction of Actively Dividing Cells via a Novel Adenoviral/Episomal Vector (2000)

Many gene therapy indications would benefit from vectors capable of achieving efficient in vivo delivery and long-term transgene expression in either dividing or nondividing cells. Such vector systems are not yet available. To achieve both goals, we have used noncytotoxic E1- and E4-deleted adenoviral vectors as vehicles for delivering an Epstein-Barr virus-based self-replicating episome (replicon) via Cre/loxP site-specific recombination. Co-infection of human cells with a proreplicon-encoded and a Cre-expressing adenovirus resulted in efficient delivery and excision of a functional replicon in the absence of vector-induced cytotoxicity. In addition, replication and nuclear retention of the replicon in the cell progeny translated into a prolonged transgene expression in actively dividing cells, both in vitro and in vivo. Combining desired features from different viruses within a single hybrid vector system should expand the range of clinical indications currently amenable to gene transfer.
The range of PaO2 variation determines the severity of oxygen-induced retinopathy in newborn rats. (1995)

These results suggest that PaO2 fluctuation and degree of hypoxia may have more influence on proliferative retinal disease in newborn rats than the extended hyperoxia that has historically received greater attention. Experimental designs that address the inherent differences in pulmonary function between intrinsically healthy animals and compromised premature infants are of substantial value to our understanding of the pathogenesis of retinopathy of prematurity.
A bipolar four-quadrant analog quarter-square multiplier consisting of unbalanced emitter-coupled pairs and expansions of its input ranges (1994)

A bipolar four-quadrant analog multiplier based on the quarter-square technique, which is constituted from unbalanced emitter-coupled pairs, and some methods for extending the input voltage range, are described. The building blocks for the circuit consist of an unbalanced emitter-coupled pair with different emitter areas, an emitter-coupled pair with an input bias offset, and an unbalanced emitter-coupled pair with unbalanced emitter degeneration. A basic squaring circuit is realized from two identical unbalanced emitter-coupled pairs with emitter area ratio K and cross-coupled inputs and parallel-connected outputs. The quarter-square multipliers proposed in this paper can operate under low supply voltage (typically <3 V, and a minimum of 1 V). Therefore, the Gilbert multiplier, which has been the most popular analog multiplier in bipolar technology over the past few decades, can be replaced.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Elimination of Residual Natural Nucleotides from 3′- O -Modified-dNTP Syntheses by Enzymatic Mop-Up (1998)

Here, we describe a novel strategy called enzymatic "Mop-Up" that efficiently removes contaminating dNTPs from reverse-phase, high-performance liquid chromatography (RP-HPLC) purified 3'-O-modified dNTP syntheses. Enzymatic mop-up takes advantage of the high selectivity of DNA polymerases for the former nucleoside triphosphates over the latter nucleotide analogs. We demonstrate the selective removal of contaminating dATP and dTTP from RP-HPLC purified 3'-O-methyl-dATP and 3'-O-(2-nitrobenzyl)-dTTP syntheses, respectively. These data highlight the importance of natural nucleotide contamination when interpreting enzymatic incorporation data and provide an alternative hypothesis for the observed property of catalytic editing of DNA polymerases. Moreover, the effective removal of natural nucleotides from 3'-O-modified analogs addresses the important issue of nucleotide read-through for stop-start DNA sequencing strategies, such as the base addition sequencing scheme (BASS).