gebhart/patrepeval huggingface dataset:
Specificity of Alternative Splice Form Detection Using RT-PCR with a Primer Spanning the Exon Junction (2003)

A recently described strategy for splice variant specific detection by RT-PCR is based on the use of a primer spanning the junction between exons of the alternative splice form. However, this reaction may generate false-positive results in the presence of excess principal transcript. In this report, transcript variant 3 of T cell immune regulator gene 1 was used as a model to demonstrate a new method to ensure PCR specificity. Our approach permits the determination of detection specificity considering the full-length transcript amount. Furthermore, we demonstrated that the addition of a few molecules of a specific template dramatically increases the specificity of the reaction and allows for the detection of the alternative form, even in the presence of large amounts of the principal transcript. Competitor DNA for the alternative splice form is suggested as the specific template to achieve the detection specificity. Thus, we describe a simple strategy to avoid nonspecific amplifications for RT-PCR using a primer spanning the exon junction.
An Integrated Pipeline for de Novo Assembly of Microbial Genomes (2012)

Remarkable advances in DNA sequencing technology have created a need for de novo genome assembly methods tailored to work with the new sequencing data types. Many such methods have been published in recent years, but assembling raw sequence data to obtain a draft genome has remained a complex, multi-step process, involving several stages of sequence data cleaning, error correction, assembly, and quality control. Successful application of these steps usually requires intimate knowledge of a diverse set of algorithms and software. We present an assembly pipeline called A5 (Andrew And Aaron's Awesome Assembly pipeline) that simplifies the entire genome assembly process by automating these stages, by integrating several previously published algorithms with new algorithms for quality control and automated assembly parameter selection. We demonstrate that A5 can produce assemblies of quality comparable to a leading assembly algorithm, SOAPdenovo, without any prior knowledge of the particular genome being assembled and without the extensive parameter tuning required by the other assembly algorithm. In particular, the assemblies produced by A5 exhibit 50% or more reduction in broken protein coding sequences relative to SOAPdenovo assemblies. The A5 pipeline can also assemble Illumina sequence data from libraries constructed by the Nextera (transposon-catalyzed) protocol, which have markedly different characteristics to mechanically sheared libraries. Finally, A5 has modest compute requirements, and can assemble a typical bacterial genome on current desktop or laptop computer hardware in under two hours, depending on depth of coverage.
Fast computation of the continuous wavelet transform through oblique projections (2002)

We introduce a fast simple method for computing the real continuous wavelet transform (CWT). The approach achieves O(N) complexity per scale and the filter coefficients can be analytically obtained by a simple integration. Our method is to use P wavelets per octave and to approximate them with their oblique projection onto a space defined by a compact scaling function. The wavelet templates are expanded to larger sizes (octaves) using the two-scale relation and zero padded filtering. Error bounds are presented to justify the use of an oblique projection over an orthogonal one.
ANTITUBERCULOUS IMMUNITY IN MICE VACCINATED WITH KILLED TUBERCLE BACILLI (1953)

The resistance of white mice to tuberculous infection could be increased by preliminary vaccination with small amounts of tubercle bacilli killed by contact with 2 per cent phenol. Vaccine prepared from a variant strain of human tubercle bacilli unable to multiply in vivo (H37Ra) proved as active as vaccines prepared from either virulent or attenuated strains. The immunity induced by phenol-killed bacilli persisted for several weeks. Under the conditions of the experiments, however, it was never able to bring about the death of the virulent bacilli used for the challenge infection, even when the infective inoculum was very small. Its protective effect could be detected (a) by the increased survival time of mice infected with a very large dose of virulent bacilli, and particularly (b) by the lower numbers of bacilli present in the organs of mice sacrificed at various periods of time after injection of sublethal infective doses. Under the proper conditions of vaccination the immunity produced in mice by phenol-killed cells of avirulent bacilli was of the same order as that produced by BCG. The protective antigen proved to be susceptible to heat, particularly at acid reactions. It retained its activity when the bacilli were disintegrated and rendered non-acid-fast by grinding with concentrated phenol. It remained in the insoluble cellular debris when the bacilli were extracted with 88 per cent phenol. Reasons are presented to support the view that the antigenic components present in the tubercle bacilli (avirulent as well as virulent) killed with phenol play a significant part in several manifestations of increased resistance to tuberculosis.
Charge transport in mixed CdSe and CdTe colloidal nanocrystal films (2010)

We report the influence of trap states on charge transport through films of mixed CdTe and CdSe nanocrystals (NCs) between lateral electrodes, through layered films of CdTe and CdSe NCs in a layered geometry, and through films of CdTe/CdSe nanobarbells in a layered geometry. We find that an electron trapping state on the surface of the CdTe NCs dominates the conduction in all devices studied. X-ray photoelectron spectroscopy and thermal activation studies implicate unpassivated or oxidized Te as the electron-trapping site.
Genetic characterization and expression in heterologous hosts of the 3-(3-hydroxyphenyl)propionate catabolic pathway of Escherichia coli K-12 (1997)

We report the complete nucleotide sequence of the gene cluster encoding the 3-(3-hydroxyphenyl)propionate (3-HPP) catabolic pathway of Escherichia coli K-12. Sequence analysis revealed the existence of eight genes that map at min 8 of the chromosome, between the lac and hemB regions. Six enzyme-encoding genes account for a flavin-type monooxygenase (mhpA), the extradiol dioxygenase (mhpB), and the meta-cleavage pathway (mhpCDFE). The order of these catabolic genes, with the sole exception of mhpF, parallels that of the enzymatic steps of the pathway. The mhpF gene may encode the terminal acetaldehyde dehydrogenase (acylating) not reported previously in the proposed pathway. Enzymes that catalyze the early reactions of the pathway, MhpA and MhpB, showed the lowest level of sequence similarity to analogous enzymes of other aromatic catabolic pathways. However, the genes mhpCDFE present the same organization and appear to be homologous to the Pseudomonas xyl, dmp, and nah meta-pathway genes, supporting the hypothesis of the modular evolution of catabolic pathways and becoming the first example of this type of catabolic module outside the genus Pseudomonas. Two bacterial interspersed mosaic elements were found downstream of the mhpABCDFE locus and flank a gene, orfT, which encodes a protein related to the superfamily of transmembrane facilitators that might be associated with transport. All of the genes of the 3-HPP cluster are transcribed in the same direction, with the sole exception of mhpR. Inducible expression of the mhp catabolic genes depends upon the presence, in the cis or trans position, of a functional mhpR gene, which suggests that the mhpR gene product is the activator of the 3-HPP biodegradative pathway. The primary structure of MhpR revealed significant similarities to that of members of the IclR subfamily of transcriptional regulators. A 3-HPP catabolic DNA cassette was engineered and shown to be functional not only in enteric bacteria (E. coli and Salmonella typhimurium) but also in Pseudomonas putida and Rhizobium meliloti, thus facilitating its potential application to improve the catabolic abilities of bacterial strains for degradation of aromatic compounds.
Molecular aspects of primary immunodeficiencies: lessons from cytokine and other signaling pathways (2002)

JAK-STAT signaling in human diseaseNumerous examples indicate that mammalian development can be entirely normal in the absence of the immune system; indeed, prior to birth, individuals with even very severe immunodeficiencies are developmentally unaffected.Perhaps it is not surprising, therefore, that more than 95 different primary immunodeficiency syndromes have been identified, encompassing defects in lymphocytes, phagocytes, and complement proteins.Indeed, within the past several years, more than 70 separate genes have been identified whose mutations cause immunodeficiency.These discoveries have been made both by using candidate gene approaches and by positional cloning.In some cases, the generation of gene-targeted mice preceded the identification of human mutations, whereas in other cases, the reverse was true.Therapy for these disorders, ranging from replacement therapy to bone marrow transplantation and gene therapy, has also moved at a rapid pace.This field therefore provides outstanding examples of the power of molecular medicine, with tremendous opportunities for interplay between basic and clinical science.Many of the processes that govern development of lymphoid and hematopoietic cells are now understood in some detail.We know that the growth and development of hematopoietic precursors, which develop in the fetal liver and bone marrow, are dependent upon a panoply of cytokines.In addition, lymphocytes require appropriate signals from antigen receptors to mature properly (Figure 1).Additionally, other receptors and counter-receptors on lymphoid and antigen-presenting cells are critical for initiating immune responses (Figure 2).We will provide examples in which mutations affect each of these steps and consequently result in immunodeficiency (Table 1).Several excellent reviews provide comprehensive discussion of the genetic basis of primary immunodeficiencies (1, 2).Our goal is not to summarize this field in its entirety; rather, a major focus of this review will be the role of cytokines and their receptors in the pathogenesis of primary immunodeficiencies.Additionally, the identification of new genes associated with immunodeficiency disorders, insights from patient-derived mutations, the heterogeneity of clinical presentations, the significance of revertants, and advances in gene therapy will be highlighted.To an extent, the areas emphasized are also a reflection of our interests, but in general the lessons are applicable to most of the diseases encompassed by primary immunodeficiencies.
Mesoporous Carbon Materials: Synthesis and Modification (2008)

Porous carbon materials are of interest in many applications because of their high surface area and physicochemical properties. Conventional syntheses can only produce randomly porous materials, with little control over the pore-size distributions, let alone mesostructures. Recent breakthroughs in the preparation of other porous materials have resulted in the development of methods for the preparation of mesoporous carbon materials with extremely high surface areas and ordered mesostructures, with potential applications as catalysts, separation media, and advanced electronic materials in many scientific disciplines. Current syntheses can be categorized as either hard-template or soft-template methods. Both are examined in this Review along with procedures for surface functionalization of the carbon materials obtained.
Commercial Mushrooms and Bean Sprouts Are a Source of Pseudomonas aeruginosa (2005)

Although Pseudomonas aeruginosa is widely reported to be ubiquitous in the environment, attempts to reliably isolate this opportunistic pathogen from environmental sources have often had limited success. In many cases, if present, P. aeruginosa is not detectable in quantifiable amounts and requires
Novel 2-Aminotetralin and 3-AminoChroman Derivatives as Selective Serotonin 5-HT7 Receptor Agonists and Antagonists (2004)

The understanding of the physiological role of the G-protein coupled serotonin 5-HT(7) receptor is largely rudimentary. Therefore, selective and potent pharmacological tools will add to the understanding of serotonergic effects mediated through this receptor. In this report, we describe two compound classes, chromans and tetralins, encompassing compounds with nanomolar affinity for the 5-HT(7) receptor and with good selectivity. Within theses classes, we have discovered both agonists and antagonists that can be used for further understanding of the pharmacology of the 5-HT(7) receptor.
Review of Tropospheric Bomb 14C Data for Carbon Cycle Modeling and Age Calibration Purposes (2004)

Comprehensive published radiocarbon data from selected atmospheric records, tree rings, and recent organic matter were analyzed and grouped into 4 different zones (three for the Northern Hemisphere and one for the whole Southern Hemisphere). These 14 C data for the summer season of each hemisphere were employed to construct zonal, hemispheric, and global data sets for use in regional and global carbon model calculations including calibrating and comparing carbon cycle models. In addition, extended monthly atmospheric 14 C data sets for 4 different zones were compiled for age calibration purposes. This is the first time these data sets were constructed to facilitate the dating of recent organic material using the bomb 14 C curves. The distribution of bomb 14 C reflects the major zones of atmospheric circulation.
Hepatic stellate cells, liver innate immunity, and hepatitis C virus (2013)

Chronic hepatitis C virus (HCV) infection can cause liver damage, ranging from mild to more severe conditions, such as fibrosis and cirrhosis. Hepatic stellate cell (HSC) activation is a key event in HCV-induced liver fibrosis. HSCs express several HCV coreceptors that interact with HCV proteins, promoting liver fibrogenesis. In addition, HSCs have the ability to engulf apoptotic bodies of hepatocytes induced by HCV and trigger a profibrogenic response. Recent studies have suggested that HSCs may play a novel role in the liver innate immunity. HSCs enhanced differentiation and accumulation of regulatory T cells. HSCs-activated natural killer cells could produce γ-interferon that inhibits HCV replication. Importantly, HSCs possess functional Toll-like receptor-3 and retinoic acid-inducible gene I that can be activated by their ligands (poly I :C, 5'ppp-dsRNA), leading to the induction of interferon and inhibition of HCV replication in hepatocytes. These new observations highlight the importance of HSCs in liver immunity against HCV, which is the focus of this review paper.
Methicillin-resistant Staphylococcus pseudintermedius isolated from canine pyoderma in North China (2012)

This study is the first report on MRSP from canine pyoderma in China. Further surveillance study is needed to gain more detailed data concerning this major clinical challenge in veterinary medicine.
Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region (2001)

There is currently no universally accepted numbering convention for the antiviral drug-related resistance mutations in the reverse transcriptase (rt) domain of the human hepatitis B virus (HBV) polymerase. The published inconsistencies have resulted from different HBV genotypes. A standardized numbering system for HBV polymerase is proposed. The new system is based on functional observations of HBV surface gene proteins (preS1, preS2, and HBsAg) and on the current convention used for human immunodeficiency virus type 1 (HIV-1) polymerase proteins (protease, rt, and integrase), in which the amino acid numbering restarts at the first codon position of each domain. The HBV polymerase protein can be divided into 4 domains (terminal protein, spacer, rt, ribonuclease H) and each of these can be numbered separately. In this proposal, the HBV rt domain starts with the highly conserved EDWGPCDEHG motif, contains 344 amino acids, and the lamivudine-related resistance mutations are found at amino acid rtL180M (previously amino acid 528, 526, 515, or 525) and rtM204V/I (previously 552, 550, 539, or 549). The new consensus rt domain numbering system is genotype independent and allows investigators to number any previously and newly discovered antiviral-related amino acid change in a standardized manner.
The ferro-, ferri- and antiferro-electric properties of a series of novel 2- or 3-substituted-alkyl 4-(4′-dodecyloxybiphenyl-4-carbonyloxy)-benzoate esters (1996)

Abstract This paper reports the synthesis of six chiral liquid crystalline 2- or 3-substituted-alkyl 4-(4′-dodecyloxybiphenyl-4-carbonyloxy)benzoates, their mesophase assignments and the phase transition temperatures. All six materials display S∗A followed by S∗C phases on cooling from their isotropic liquids. The magnitudes of switched tilt angle, spontaneous polarization, helical twist sense (L.H.) and direction of polarization (P s(−)) are given for the S∗C phases. Close inspection of the S∗C phases revealed that for the six compounds, two showed a ferrielectric (S∗C γ) and an antiferroelectric (S∗A) subphase, two showed only a ferrielectric subphase and one showed only an antiferroelectric subphase. The field-dependent behaviour of the switched tilt angle of the ferrielectric and antiferroelectric phases of some of the compounds is also presented.
Neutrophil Elastase Acts as a Biased Agonist for Proteinase-activated Receptor-2 (PAR2) (2011)

Human neutrophil proteinases (elastase, proteinase-3, and cathepsin-G) are released at sites of acute inflammation. We hypothesized that these inflammation-associated proteinases can affect cell signaling by targeting proteinase-activated receptor-2 (PAR(2)). The PAR family of G protein-coupled receptors is triggered by a unique mechanism involving the proteolytic unmasking of an N-terminal self-activating tethered ligand (TL). Proteinases can either activate PAR signaling by unmasking the TL sequence or disarm the receptor for subsequent enzyme activation by cleaving downstream from the TL sequence. We found that none of neutrophil elastase, cathepsin-G, and proteinase-3 can activate G(q)-coupled PAR(2) calcium signaling; but all of these proteinases can disarm PAR(2), releasing the N-terminal TL sequence, thereby preventing G(q)-coupled PAR(2) signaling by trypsin. Interestingly, elastase (but neither cathepsin-G nor proteinase-3) causes a TL-independent PAR(2)-mediated activation of MAPK that, unlike the canonical trypsin activation, does not involve either receptor internalization or recruitment of β-arrestin. Cleavage of synthetic peptides derived from the extracellular N terminus of PAR(2), downstream of the TL sequence, demonstrated distinct proteolytic sites for all three neutrophil-derived enzymes. We conclude that in inflammation, neutrophil proteinases can modulate PAR(2) signaling by preventing/disarming the G(q)/calcium signal pathway and, via elastase, can selectively activate the p44/42 MAPK pathway. Our data illustrate a new mode of PAR regulation that involves biased PAR(2) signaling by neutrophil elastase and a disarming/silencing effect of cathepsin-G and proteinase-3.
Activation of lecithin: cholesterol acyltransferase by human apolipoprotein A-IV. (1985)

Human plasma apoproteins (apo) A-I and A-IV both activate the enzyme lecithin:cholesterol acyltransferase (EC 2.3.1.43). Lecithin:cholesterol acyltransferase activity was measured by the conversion of [4-14C] cholesterol to [4-14C]cholesteryl ester using artificial phospholipid/cholesterol/[4-14C]cholesterol/apoprotein substrates. The substrate was prepared by the addition of apoprotein to a sonicated aqueous dispersion of phospholipid/cholesterol/[4-14C]cholesterol. The activation of lecithin:cholesterol acyltransferase by apo-A-I and -A-IV differed, depending upon the nature of the hydrocarbon chains of the sn-L-alpha-phosphatidylcholine acyl donor. Apo-A-I was a more potent activator than apo-A-IV with egg yolk lecithin, L-alpha-dioleoylphosphatidylcholine, and L-alpha-phosphatidylcholine substituted with one saturated and one unsaturated fatty acid regardless of the substitution position. When L-alpha-phosphatidylcholine esterified with two saturated fatty acids was used as acyl donor, apo-A-IV was more active than apo-A-I in stimulating the lecithin:cholesterol acyltransferase reaction. Complexes of phosphatidylcholines substituted with two saturated fatty acids served as substrate for lecithin:cholesterol acyltransferase even in the absence of any activator protein. Essentially the same results were obtained when substrate complexes (phospholipid-cholesterol-[4-14C]cholesterol-apoprotein) were prepared by a detergent dialysis procedure. Apo-A-IV-L-alpha-dimyristoylphosphatidylcholine complexes thus prepared were shown to be homogeneous particles by column chromatography and density gradient ultracentrifugation. It is concluded that apo-A-IV is able to facilitate the lecithin:cholesterol acyltransferase reaction in vitro.
Evolution in Reverse: Engineering a D‐Xylose‐Specific Xylose Reductase (2008)

Staying faithful: Xylose reductases (XRs) are highly promiscuous enzymes and are of great interest for the biosynthesis of xylitol—a very desirable sugar substitute. However, the expensive purification of the substrate D-xylose from the impurity L-arabinose plagues the industrial implementation of XRs. We have engineered a XR that preferentially reduces D-xylose over L-arabinose (see figure). This is one of the very few cases in which a promiscuous enzyme has been engineered to prefer one natural substrate over another. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2008/z700765_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Mechanisms by Which Both Heterozygous Peroxisome Proliferator-activated Receptor γ (PPARγ) Deficiency and PPARγ Agonist Improve Insulin Resistance (2001)

Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated transcription factor and a member of the nuclear hormone receptor superfamily that is thought to be the master regulator of fat storage; however, the relationship between PPARgamma and insulin sensitivity is highly controversial. We show here that supraphysiological activation of PPARgamma by PPARgamma agonist thiazolidinediones (TZD) markedly increases triglyceride (TG) content of white adipose tissue (WAT), thereby decreasing TG content of liver and muscle, leading to amelioration of insulin resistance at the expense of obesity. Moderate reduction of PPARgamma activity by heterozygous PPARgamma deficiency decreases TG content of WAT, skeletal muscle, and liver due to increased leptin expression and increase in fatty acid combustion and decrease in lipogenesis, thereby ameliorating high fat diet-induced obesity and insulin resistance. Moreover, although heterozygous PPARgamma deficiency and TZD have opposite effects on total WAT mass, heterozygous PPARgamma deficiency decreases lipogenesis in WAT, whereas TZD stimulate adipocyte differentiation and apoptosis, thereby both preventing adipocyte hypertrophy, which is associated with alleviation of insulin resistance presumably due to decreases in free fatty acids, and tumor necrosis factor alpha, and up-regulation of adiponectin, at least in part. We conclude that, although by different mechanisms, both heterozygous PPARgamma deficiency and PPARgamma agonist improve insulin resistance, which is associated with decreased TG content of muscle/liver and prevention of adipocyte hypertrophy.