gebhart/patrepeval huggingface dataset:
Linkage Map of Escherichia coli K-12, Edition 10: The Physical Map (1998)

A physical map, EcoMap10, of the now completely sequenced Escherichia coli chromosome is presented. Calculated genomic positions for the eight restriction enzymes BamHI, HindIII, EcoRI, EcoRV, BglI, KpnI, PstI, and PvuII are depicted. Both sequenced and unsequenced Kohara/Isono miniset clones are aligned to this calculated restriction map. DNA sequence searches identify the precise locations of insertion sequence elements and repetitive extragenic palindrome clusters. EcoGene10, a revised set of genes and functionally uncharacterized open reading frames (ORFs), is also depicted on EcoMap10. The complete set of unnamed ORFs in EcoGene10 are assigned provisional names beginning with the letter "y" by using a systematic nomenclature.
Transcription of the interleukin 4 gene is regulated by multiple promoter elements. (1993)

Activation of T helper cell 1 (Th1) and Th2 results in transcription of the interleukin 2 (IL-2) and IL-4 cytokine genes, respectively. Whereas many of the regulatory elements and factors responsible for IL-2 transcription in T cells are well defined, little is known about parallel mechanisms that drive transcription of the IL-4 gene. Here we have analyzed the murine IL-4 promoter, both in vivo and in a Th2 clone. 3 kb of IL-4 upstream sequence is shown to be sufficient to achieve tissue-specific and inducible expression of a thymidine kinase reporter gene in vivo in a manner that mirrors the expression of endogenous IL-4. Tissue-specific and inducible expression is also demonstrated in a Th2 clone, but not in a B cell line. Deletional and mutational analysis of the IL-4 promoter demonstrated that sequences from -100 to -28 were necessary for a transcriptional response to Concanavalin A or anti-CD3 monoclonal antibody. An overlapping, yet smaller region, spanning the sequences from -60 to -28 bp was shown to be required for the response to ionomycin. Mutation of an 8-bp region from -43 to -35 of the IL-4 promoter completely abrogated IL-4 gene transcription in response to all stimuli tested. In addition, our results show that the effects of the immunosuppressive agent Cyclosporin A map to the same DNA sequences as the positive control elements. These results identify DNA sequences that are functionally important for the control of IL-4 gene transcription both in vivo and in vitro. Although these sequences are highly conserved in the human and murine IL-4 genes, they are largely not present in the IL-2 enhancer complex. Thus, cytokine-specific cis-acting elements may be one mechanism by which these two cytokine genes are differentially regulated.
Conversion of Escherichia coli pyruvate oxidase to an ‘α-ketobutyrate oxidase’ (2000)

Escherichia coli pyruvate oxidase (PoxB), a lipid-activated homotetrameric enzyme, is active on both pyruvate and 2-oxobutanoate ('alpha-ketobutyrate'), although pyruvate is the favoured substrate. By localized random mutagenesis of residues chosen on the basis of a modelled active site, we obtained several PoxB enzymes that had a markedly decreased activity with the natural substrate, pyruvate, but retained full activity with 2-oxobutanoate. In each of these mutant proteins Val-380 had been replaced with a smaller residue, namely alanine, glycine or serine. One of these, PoxB V380A/L253F, was shown to lack detectable pyruvate oxidase activity in vivo; this protein was purified, studied and found to have a 6-fold increase in K(m) for pyruvate and a 10-fold lower V(max) with this substrate. In contrast, the mutant had essentially normal kinetic constants with 2-oxobutanoate. The altered substrate specificity was reflected in a decreased rate of pyruvate binding to the latent conformer of the mutant protein owing to the V380A mutation. The L253F mutation alone had no effect on PoxB activity, although it increased the activity of proteins carrying substitutions at residue 380, as it did that of the wild-type protein. The properties of the V380A/L253F protein provide new insights into the mode of substrate binding and the unusual activation properties of this enzyme.
Molecular genetics of papillary thyroid carcinoma: great expectations... (2007)

Papillary thyroid carcinoma (PTC) is the most prevalent type of endocrine cancer and, in recent epidemiological surveys, one of the types of human cancer whose incidence is growing. Despite the favourable outcome and long survival rates of most patients, some tumours display an aggressive behaviour and may progress to the highly aggressive and lethal, anaplastic thyroid carcinoma. In recent years, several progresses have been made on the molecular characterization of PTC, in general, and in the genetic alterations underlying the histotype diversity of this type of cancer, in particular. This holds true regarding alterations on nuclear DNA as well as mitochondrial DNA. In this review we have summarized the most recent findings in the genetic characterization of PTC, giving a particular emphasis to the genotype-phenotype associations, the prognosis implications, and the diagnostic and therapeutic value of the newly identified genetic markers.
The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro (2015)

Although bone responds to its mechanical environment, the cellular and molecular mechanisms underlying the response of the skeleton to mechanical unloading are not completely understood. Osteocytes are the most abundant but least understood cells in bones and are thought to be responsible for sensing stresses and strains in bone. Sclerostin, a product of the SOST gene, is produced postnatally primarily by osteocytes and is a negative regulator of bone formation. Recent studies show that SOST is mechanically regulated at both the mRNA and protein levels. During prolonged bed rest and immobilization, circulating sclerostin increases both in humans and in animal models, and its increase is associated with a decrease in parathyroid hormone. To investigate whether SOST/sclerostin up-regulation in mechanical unloading is a cell-autonomous response or a hormonal response to decreased parathyroid hormone levels, we subjected osteocytes to an in vitro unloading environment achieved by the NASA rotating wall vessel system. To perform these studies, we generated a novel osteocytic cell line (Ocy454) that produces high levels of SOST/sclerostin at early time points and in the absence of differentiation factors. Importantly, these osteocytes recapitulated the in vivo response to mechanical unloading with increased expression of SOST (3.4 ± 1.9-fold, p < 0.001), sclerostin (4.7 ± 0.1-fold, p < 0.001), and the receptor activator of nuclear factor κΒ ligand (RANKL)/osteoprotegerin (OPG) (2.5 ± 0.7-fold, p < 0.001) ratio. These data demonstrate for the first time a cell-autonomous increase in SOST/sclerostin and RANKL/OPG ratio in the setting of unloading. Thus, targeted osteocyte therapies could hold promise as novel osteoporosis and disuse-induced bone loss treatments by directly modulating the mechanosensing cells in bone.
A Reductionist View of Alzheimer's Disease (1996)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Reductionist View of Alzheimer's DiseasePeter T. LansburyView Author Information Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Cite this: Acc. Chem. Res. 1996, 29, 7, 317–321Publication Date (Web):July 11, 1996Publication History Received16 October 1995Published online11 July 1996Published inissue 11 July 1996https://pubs.acs.org/doi/10.1021/ar950159uhttps://doi.org/10.1021/ar950159uresearch-articleACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views626Altmetric-Citations92LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Central nervous system,Genetics,Nanofibers,Nucleation,Peptides and proteins Get e-Alerts
Induction of Cell Proliferation by Fibroblast and Insulin-Like Growth Factors in Pure Rat Inner Ear Epithelial Cell Cultures (1997)

Proliferation of supporting cells in the inner ear is the early major event occurring during hair cell regeneration after acoustic trauma or aminoglycoside treatment. In the present study, we examined the possible influence of 30 growth factors on the proliferation of pure rat utricular epithelial cells in culture. Utricular epithelial sheets were separated and partially dissociated from early postnatal rats via a combined enzymatic and mechanical method. The cultured utricular epithelial cells expressed exclusively epithelial cell antigens, but not fibroblast, glial, or neuronal antigens. With tritiated thymidine incorporation assays, we found that several fibroblast growth factor (FGF) family members, insulin-like growth factor-1 (IGF-1), IGF-2, transforming growth factor-alpha (TGF-alpha), and epidermal growth factor (EGF), stimulated proliferation of the utricular epithelial cells. In contrast, neurotrophins and other growth factors did not elicit any detectable mitogenic effects. Among all of the growth factors examined, FGF-2 was the most potent mitogen. When FGF-2 was added in combination with IGF-1 or TGF-alpha to the medium, combined effects were seen. These results were confirmed with BrdU immunocytochemistry. Thus, the present culture system provides a rapid and reliable assay system to screen novel growth factors involved in proliferation of mammalian inner ear supporting cells. Furthermore, immunostainings revealed that the cultured utricular epithelial cells expressed FGF and IGF-1 receptors, and utricular hair cells produced FGF-2 in vivo. The addition of neutralizing antibodies against FGF-2 or IGF-1 to the cultures significantly inhibited the utricular epithelial cell proliferation. This work suggests that FGF-2 and IGF-1 may regulate the proliferation step during hair cell development and regeneration.
Enhanced sensitivity due to current redistribution in the Hall effect of semiconductor-metal hybrid structures (2005)

Experimental and theoretical studies have shown that nonmagnetic semiconductor-metal hybrid structures can exhibit a very large magnetoresistance effect, the so-called extraordinary magnetoresistance (EMR) effect. The EMR can be useful in magnetic-field sensors and read heads. We show that the sensitivity of a linear hybrid structure can be further enlarged by using an optimized configuration of current leads and voltage probes. Strikingly, we find that the EMR and the Hall effect cooperate and thereby improve the performance. Our findings also explain the origin of the recently reported sensitivity increase in a nanostructured EMR device obtained via interchanging one lead and one probe [J. Moussa et al., J. Appl. Phys. 94, 1110 (2003)].
Surveillance for Neuraminidase Inhibitor Resistance among Human Influenza A and B Viruses Circulating Worldwide from 2004 to 2008 (2008)

The surveillance of seasonal influenza virus susceptibility to neuraminidase (NA) inhibitors was conducted using an NA inhibition assay. The 50% inhibitory concentration values (IC(50)s) of 4,570 viruses collected globally from October 2004 to March 2008 were determined. Based on mean IC(50)s, A(H3N2) viruses (0.44 nM) were more sensitive to oseltamivir than A(H1N1) viruses (0.91 nM). The opposite trend was observed with zanamivir: 1.06 nM for A(H1N1) and 2.54 nM for A(H3N2). Influenza B viruses exhibited the least susceptibility to oseltamivir (3.42 nM) and to zanamivir (3.87 nM). To identify potentially resistant viruses (outliers), a threshold of a mean IC(50) value + 3 standard deviations was defined for type/subtype and drug. Sequence analysis of outliers was performed to identify NA changes that might be associated with reduced susceptibility. Molecular markers of oseltamivir resistance were found in six A(H1N1) viruses (H274Y) and one A(H3N2) virus (E119V) collected between 2004 and 2007. Some outliers contained previously reported mutations (e.g., I222T in the B viruses), while other mutations [e.g., R371K and H274Y in B viruses and H274N in A(H3N2) viruses) were novel. The R371K B virus outlier exhibited high levels of resistance to both inhibitors (>100 nM). A substantial variance at residue D151 was observed among A(H3N2) zanamivir-resistant outliers. The clinical relevance of newly identified NA mutations is unknown. A rise in the incidence of oseltamivir resistance in A(H1N1) viruses carrying the H274Y mutation was detected in the United States and in other countries in the ongoing 2007 to 2008 season. As of March 2008, the frequency of resistance among A(H1N1) viruses in the United States was 8.6% (50/579 isolates). The recent increase in oseltamivir resistance among A(H1N1) viruses isolated from untreated patients raises public health concerns and necessitates close monitoring of resistance to NA inhibitors.
Platelets as Immune Cells (2007)

Beyond an eminent role in hemostasis and thrombosis, platelets are characterized by expert functions in assisting and modulating inflammatory reactions and immune responses. This is achieved by the regulated expression of adhesive and immune receptors on the platelet surface and by the release of a multitude of secretory products including inflammatory mediators and cytokines, which can mediate the interaction with leukocytes and enhance their recruitment. In addition, platelets are characterized by an enormous surface area and open canalicular system, which in concert with specialized recognition receptors may contribute to the engulfment of serum components, antigens, and pathogens. Platelet-dependent increases in leukocyte adhesion may not only account for an exacerbation of atherosclerosis, for arterial repair processes, but also for lymphocyte trafficking during adaptive immunity and host defense. This review compiles a selection of platelet-derived tools for bridging inflammation and vascular disease and highlights the molecular key components governing platelet-mediated mechanisms operative in immune surveillance, vascular remodeling, and atherosclerosis.
Inhibition of Tau Polymerization by Its Carboxy-Terminal Caspase Cleavage Fragment (2003)

Abnormal aggregation of the microtubule-associated protein, tau, occurs in many neurodegenerative diseases, making it important to understand the mechanisms of tau polymerization. Previous work has indicated that the C-terminal region of tau inhibits polymerization in vitro, and a growing body of evidence implicates caspase cleavage of tau at Asp 421 in the C-terminus as an important inducer of tau polymerization in Alzheimer's disease. In the present study, we provide evidence that the C-terminal peptide fragment produced by caspase cleavage inhibits tau polymerization, suggesting that caspase cleavage of tau enhances its polymerization by removing the inhibitory control element. Moreover, we provide evidence that the peptide assumes an alpha-helical configuration and inhibits tau assembly by interacting with residues 321-375 in the microtubule binding repeat region. These findings indicate that formation of the fibrillar pathologies during the course of Alzheimer's disease may be driven or sustained by apoptotic events leading to caspase activation.
Gene Silencing Activity of siRNAs with a Ribo-difluorotoluyl Nucleotide (2006)

Recently, chemically synthesized short interfering RNA (siRNA) duplexes have been used with success for gene silencing. Chemical modification is desired for therapeutic applications to improve biostability and pharmacokinetic properties; chemical modification may also provide insight into the mechanism of silencing. siRNA duplexes containing the 2,4-difluorotoluyl ribonucleoside (rF) were synthesized to evaluate the effect of noncanonical nucleoside mimetics on RNA interference. 5'-Modification of the guide strand with rF did not alter silencing relative to unmodified control. Internal uridine to rF substitutions were well-tolerated. Thermal melting analysis showed that the base pair between rF and adenosine (A) was destabilizing relative to a uridine-adenosine pair, although it was slightly less destabilizing than other mismatches. The crystal structure of a duplex containing rFoA pairs showed local structural variations relative to a canonical RNA helix. As the fluorine atoms cannot act as hydrogen bond acceptors and are more hydrophobic than uridine, there was an absence of a well-ordered water structure around the rF residues in both grooves. siRNAs with the rF modification effectively silenced gene expression and offered improved nuclease resistance in serum; therefore, evaluation of this modification in therapeutic siRNAs is warranted.
In-flight experiment for combined planar antennas and solar cells (SOLANT) (2009)

An in-flight experiment to validate advanced solar antenna structures (SOLANT) in space is presented. Two different antennas have been designed and manufactured, one for global positioning system (GPS) reception and one for S-band beacon transmission. Both units use slot aperture radiators embedded in identical mechanical structures. The GPS antenna has been designed to generate an omni-directional radiation pattern with right-handed circular polarisation thus fulfilling NavStar specifications. The S-band beacon antenna is based on a four-element circularly polarised array providing 6 dBic of gain. These antennas are integrated within two solar panels, which form the upper layer of the antenna structure. The two panels are identical, make use of gallium arsenide (GaAs) solar cells arranged in two strings and provide a peak power of 10 W each. The SOLANTs were launched, fixed to a Cosmos payload adapter and remained operative for 2 years, well beyond their expected lifetime. This study summarises the design and performance tests performed prior the launch and during the orbital operation.
Differentiation of Pluripotent Embryonic Stem Cells Into Cardiomyocytes (2002)

Embryonic stem (ES) cells have been established as permanent lines of undifferentiated pluripotent cells from early mouse embryos. ES cells provide a unique system for the genetic manipulation and the creation of knockout strains of mice through gene targeting. By cultivation in vitro as 3D aggregates called embryoid bodies, ES cells can differentiate into derivatives of all 3 primary germ layers, including cardiomyocytes. Protocols for the in vitro differentiation of ES cells into cardiomyocytes representing all specialized cell types of the heart, such as atrial-like, ventricular-like, sinus nodal-like, and Purkinje-like cells, have been established. During differentiation, cardiac-specific genes as well as proteins, receptors, and ion channels are expressed in a developmental continuum, which closely recapitulates the developmental pattern of early cardiogenesis. Exploitation of ES cell-derived cardiomyocytes has facilitated the analysis of early cardiac development and has permitted in vitro "gain-of-function" or "loss-of-function" genetic studies. Recently, human ES cell lines have been established that can be used to investigate cardiac development and the function of human heart cells and to determine the basic strategies of regenerative cell therapy. This review summarizes the current state of ES cell-derived cardiogenesis and provides an overview of how genomic strategies coupled with this in vitro differentiation system can be applied to cardiac research.
Comparison of Azelastine Eye Drops with Levocabastine Eye Drops in the Treatment of Seasonal Allergic Conjunctivitis (2000)

SummaryA randomised, multicentre parallel group study was undertaken to compare the efficacy and safety of 0.05% azelastine eye drops (101 patients) in an open manner with 0.05% levocabastine eye drops (103 patients) and in a double-blind manner with placebo (103 patients) during a 14-day treatment period involving patients with seasonal allergic conjunctivitis. The three main eye symptoms, scored on a four-point scale, were itching, lacrimation and conjunctival redness; the primary efficacy variable was the responder rate on day 3. Responders were patients whose sum score of the three main eye symptoms decreased by at least three points from a baseline score of at least six points. In addition to these main symptoms, five other symptoms were recorded on days 0, 3, 7 and 14, and patients kept daily diaries of the three main eye symptoms and swollen eyelids. The responder rate after 3 days of treatment was 69% in patients treated with azelastine, 59% in patients treated with levocabastine and 51% in the placebo group. Only the difference in responder rates between azelastine and placebo eye drops was statistically significant (p = 0.02). The improvements in other ocular symptoms and entries in the patients’ diaries closely reflected the changes reported by the investigators. No serious adverse events occurred throughout the study. Nine patients (three in the azelastine, five in the levocabastine and one in the placebo group) terminated the study prematurely due to poor tolerability. Adverse drug reactions, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported in 37% of patients receiving azelastine eye drops, 31% of patients receiving levocabastine and 9% of placebo patients. Overall tolerability was assessed as very good or good in 86% of azelastine- and levocabastinetreated patients, and in 95% of the patients receiving placebo. The results of this study indicate that azelastine possesses a tolerability profile at least comparable to that of levocabastine eye drops, but additionally appears to have a slightly quicker onset of effect, and confirm the therapeutic potential of azelastine eye drops in the treatment of allergic conjunctivitis.
A perspective on multiaccess channels (1985)

The information theoretic approach and the collision resolution approach to multiaccess channels are reviewed in terms of the underlying communication problems that both are modeling. Some perspective on the strengths and weakness of these approaches is given, and the need of a more combined approach focused on coding and decoding techniques is argued.