gebhart/patrepeval huggingface dataset:
The Key Sigma Factor of Transition Phase, SigH, Controls Sporulation, Metabolism, and Virulence Factor Expression in Clostridium difficile (2011)

Toxin synthesis in Clostridium difficile increases as cells enter into stationary phase. We first compared the expression profiles of strain 630E during exponential growth and at the onset of stationary phase and showed that genes involved in sporulation, cellular division, and motility, as well as carbon and amino acid metabolism, were differentially expressed under these conditions. We inactivated the sigH gene, which encodes an alternative sigma factor involved in the transition to post-exponential phase in Bacillus subtilis. Then, we compared the expression profiles of strain 630E and the sigH mutant after 10 h of growth. About 60% of the genes that were differentially expressed between exponential and stationary phases, including genes involved in motility, sporulation, and metabolism, were regulated by SigH, which thus appears to be a key regulator of the transition phase in C. difficile. SigH positively controls several genes required for sporulation. Accordingly, sigH inactivation results in an asporogeneous phenotype. The spo0A and CD2492 genes, encoding the master regulator of sporulation and one of its associated kinases, and the spoIIA operon were transcribed from a SigH-dependent promoter. The expression of tcdA and tcdB, encoding the toxins, and of tcdR, encoding the sigma factor required for toxin production, increased in a sigH mutant. Finally, SigH regulates the expression of genes encoding surface-associated proteins, such as the Cwp66 adhesin, the S-layer precursor, and the flagellum components. Among the 286 genes positively regulated by SigH, about 40 transcriptional units presenting a SigH consensus in their promoter regions are good candidates for direct SigH targets.
Gut microbiome in type 1 diabetes: A comprehensive review (2018)

Type 1 diabetes (T1D) is an autoimmune disease, which is characterized by the destruction of islet β cells in the pancreas triggered by genetic and environmental factors. In past decades, extensive familial and genome-wide association studies have revealed more than 50 risk loci in the genome. However, genetic susceptibility cannot explain the increased incidence of T1D worldwide, which is very likely attributed by the growing impact of environmental factors, especially gut microbiome. Recently, the role of gut microbiome in the pathogenesis of T1D has been uncovered by the increasing evidence from both human subjects and animal models, strongly indicating that gut microbiome might be a pivotal hub of T1D-triggering factors, especially environmental factors. In this review, we summarize the current aetiological and mechanism studies of gut microbiome in T1D. A better understanding of the role of gut microbiome in T1D may provide us with powerful prognostic and therapeutic tools in the near future.
Kinetics of Human Factor VII Activation (1996)

In this study the activation of human factor VII by a variety of potential activators in the presence and absence of mixed phospholipid vesicles [25% phosphatidylserine (PS), 75% phosphatidylcholine (PC)] is evaluated. At the plasma concentration of factor VII, 10 nM, the activation rate of the zymogen by 0.05 nM factor Xa is anionic phospholipid (PCPS) dependent and achieves a maximum value of 18 pM/s at 5-20 microM PCPS; further increases in the levels of PCPS decrease the activation rate of factor VII. The maximum activation rate of factor VII (10 nM) by the factor VIIa-tissue factor complex (0.1 nM), 0.76 pM/s, is achieved at 200 microM PCPS. No detectable activation of 10 nM factor VII is observed under similar conditions when either thrombin (0.1 nM) or factor IXa (0.1 nM) is used as an activator. Factor VIIa (10 nM) and factor XIa (1 nM) are not observed to activate factor VII at detectable rates. The observed Michaelis-Menten constants (KM) for factor VII activation in the presence of PCPS at optimal concentrations vary from 1.2 microM for factor Xa to 3.2 microM for the factor VIIa-tissue factor complex. The highest catalytic constant (kcat) value (15.2 s-1) is observed for factor Xa-PCPS. The factor VIIa-tissue factor complex, factor IXa, and thrombin kcat values are 1.4, 0.32, and 0.061 s-1, respectively. Tissue factor does not increase the factor VII activation rate by factor Xa, factor IXa, or thrombin. Factor VIIIa in the presence of PCPS has no effect on factor VII activation by factor IXa. In contrast, factor Va decreases the factor VII activation rate by factor Xa, reaching saturation at concentrations consistent with complete prothrombinase complex formation. The formed prothrombinase complex activates factor VII at approximately 30% the rate of factor Xa bound to phospholipids. These data allow us to conclude that the predominant physiological factor VII activator is, most likely, membrane-bound factor Xa.
BACE1 Function and Inhibition: Implications of Intervention in the Amyloid Pathway of Alzheimer’s Disease Pathology (2017)

Alzheimer's disease (AD) is a fatal progressive neurodegenerative disorder characterized by increasing loss in memory, cognition, and function of daily living. Among the many pathologic events observed in the progression of AD, changes in amyloid β peptide (Aβ) metabolism proceed fastest, and precede clinical symptoms. BACE1 (β-secretase 1) catalyzes the initial cleavage of the amyloid precursor protein to generate Aβ. Therefore inhibition of BACE1 activity could block one of the earliest pathologic events in AD. However, therapeutic BACE1 inhibition to block Aβ production may need to be balanced with possible effects that might result from diminished physiologic functions BACE1, in particular processing of substrates involved in neuronal function of the brain and periphery. Potentials for beneficial or consequential effects resulting from pharmacologic inhibition of BACE1 are reviewed in context of ongoing clinical trials testing the effect of BACE1 candidate inhibitor drugs in AD populations.
THE EFFICACY OF A SINGLE DOSE OF INTRAVENOUS FERRIC CARBOXYMALTOSE (FERINJECT®) ON ANAEMIA IN A PRE‐DIALYSIS POPULATION OF CHRONIC KIDNEY DISEASE PATIENTS (2009)

Anaemia due to chronic kidney disease (CKD) is common and may be managed with erythropoiesis stimulating agents and/or iron preparations. Iron preparations may be administered orally, intravenously or by intramuscular injection. Oral preparations pose a significant tablet burden on patients who are often taking multiple medications and may have undesirable gastrointestinal side effects. The existing intravenous preparation Venofer requires multiple doses of drug (typically 100-200 mg) at multiple clinic visits. The preparation Cosmofer may be given as a single dose, but this requires four to six hours to administer. For these reasons, their use in pre-dialysis patients remains limited in practice. The new intravenous iron preparation Ferric Carboxymaltose (Ferinject) may be given as a single dose of up to 1000 mg (but not exceeding 15 mg/kg/week) as an infusion over 6-15 minutes. This offers a significant advance in the management of these patients. We describe our initial experience with using this drug in a non-dialysis patient population with chronic kidney disease.
Structure of human factor VIIa and its implications for the triggering of blood coagulation (1999)

Factor VIIa (EC 3.4.21.21 ) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade. On injury, factor VIIa forms a complex with its allosteric regulator, tissue factor, and initiates blood clotting. Although the structure of the binary complex has already been determined [Banner, D. W., D’Arcy, A., Chène, C., Winkler, F. K., Guha, A., Konigsberg, W. H., Nemerson, Y. &amp; Kirchhofer, D. (1996) Nature (London) 380, 41–46], the conformational effects of cofactor binding to factor VIIa are not known in detail because of a lack of structural information on free factor VIIa. Here we report the structure of γ-carboxyglutamic acid-domainless human coagulation factor VIIa at a resolution of 2.8 Å. The molecule adopts an extended conformation within the crystal similar to that previously observed for the full-length protein in complex with tissue factor. Detailed comparison of free and tissue factor-bound factor VIIa reveals several structural differences. The binding mode of the active-site inhibitor d -Phe-Phe-Arg methyl ketone differs in the two structures, suggesting a role for the cofactor in substrate recognition. More importantly, a surface-exposed α-helix in the protease domain (residues 307–312), which is located at the cofactor recognition site, is distorted in the free form of factor VIIa. This subtle structural difference sheds light on the mechanism of the dramatic tissue factor-induced enhancement of factor VIIa activity.
Immunopharmacologic Analysis of an Autologous, Hapten-Modified Human Melanoma Vaccine (2003)

This study underscores the importance of the immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to other cancer vaccine technologies.
Exopolysaccharide Production by Four Cyanobacterial Isolates and Preliminary Identification of These Isolates (2007)

四海洋的 cyanobacterial 孤立，说出 104， 109， 113 和 115，从水兵，离开中国的海岸的水能免除大量 exopolysaccharide (EPS ) 到媒介。在在四的生产孤立的 EPS 上的媒介的不同部件的效果被调查。Underthe 最佳的状况， EPS 释放了由孤立 104,109,113 和 115 到达 7.48gL ~(-1), 8.33gL ~(-1), 18.26 gL~(-1), 和 6.78gL ~( 在 14d 以内的 -1) 分别地。为 cyanobacteria 基于常规鉴定方法，这些孤立被分到类 Cyanothece。
Design and applications of modified oligonucleotides (2003)

Oligonucleotides have a wide range of applications in fields such as biotechnology, molecular biology, diagnosis and therapy. However, the spectrum of uses can be broadened by introducing chemical modifications into their structures. The most prolific field in the search for new oligonucleotide analogs is the antisense strategy, where chemical modifications confer appropriate characteristics such as hybridization, resistance to nucleases, cellular uptake, selectivity and, basically, good pharmacokinetic and pharmacodynamic properties. Combinatorial technology is another research area where oligonucleotides and their analogs are extensively employed. Aptamers, new catalytic ribozymes and deoxyribozymes are RNA or DNA molecules individualized from a randomly synthesized library on the basis of a particular property. They are identified by repeated cycles of selection and amplification, using PCR technologies. Modified nucleotides can be introduced either during the amplification procedure or after selection.
A NIMA-related Kinase, Fa2p, Localizes to a Novel Site in the Proximal Cilia ofChlamydomonasand Mouse Kidney Cells (2004)

Polycystic kidney disease and related syndromes involve dysregulation of cell proliferation in conjunction with ciliary defects. The relationship between cilia and cell cycle is enigmatic, but it may involve regulation by the NIMA-family of kinases (Neks). We previously showed that the Nek Fa2p is important for ciliary function and cell cycle in Chlamydomonas. We now show that Fa2p localizes to an important regulatory site at the proximal end of cilia in both Chlamydomonas and a mouse kidney cell line. Fa2p also is associated with the proximal end of centrioles. Its localization is dynamic during the cell cycle, following a similar pattern in both cell types. The cell cycle function of Fa2p is kinase independent, whereas its ciliary function is kinase dependent. Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression.
Information Storage and Retrieval (1997)

Overview. Document and Query Forms. Query Structures. The Matching Process. Text Analysis. User Profiles and Their Use. Multiple Reference Point Systems. Retrieval Effectiveness Measures. Effectiveness Improvement Techniques. Alternative Retrieval Techniques. Output Presentation. Document Access. The Ectosystem and Policy Issues. Appendices. Glossary. Index.
Enigma: An Image Retrieval System (1992)

The paper presents the functionality of a system which retrieves images on the basis of automatically generated indexes (i.e. semantic image representations, obtained by automatic image analysis, indicating the content of the images). The system consists of two parts: an off-line indexing part and an on-line image retrieval part. The indexing component is used to automatically generate semantic representations of images so that the image retrieval component can use this information to enable image retrieval. The man-machine communication of the image retrieval component is based on an iconical graphical query language to accomplish geographical query specification for image access. Experiments have been carried out on three different sets of images from the following domains: MRI images of the chest, electronic schemas and topographic maps. The experiments show encouraging results especially for domains which have a high degree of formality in their pictorial expression, such as electr...
Characterization of thin-oxide MNOS memory transistors (1972)

A direct tunneling theory is formulated and applied to high-speed thin-oxide complementary metal-nitride-oxide-silicon (MNOS) memory transistors. Charge transport in the erase/write mode of operation is interpreted in terms of the device threshold voltage shift. The threshold voltage shift in the erase/write mode is related to the amplitude and time duration of the applied gate voltage over the full range of switching times. MNOS memory devices ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X_{o}=25 \Aring, X_{N} = 335 \Aring</tex> ) exhibit a <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\Delta V_{th} = \plusmn3</tex> V for an erase/write <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t_{p} = 100</tex> ns, which corresponds to an initial oxide field strength <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">E_{ox}= 1.2 \times 10^{7}</tex> V/cm. The direct tunneling theory is applied to the charge retention or memory mode in which charge is transported to and from the Si-SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> interface states. The rate of charge loss to interface states is influenced by electrical stress which alters the interface state characteristics. We discuss the fabrication of complementary high-speed MNOS memory transistors and the experimental test procedures to measure charge transport and storage in these devices.
Evaluation of Newly Isolated Klebsiella pneumoniae Strains for the Co-Production of 3-hydroxypropionic acid and 1,3-propanediol from Glycerol (2016)

Co-production of 3-hydroxypropionic acid (3-HP) and 1,3-propanediol (1,3-PDO) was suggested as an innovative strategy to overcome several limitations occurring in the single production of 3-HP from glycerol. In this study, two new isolates of Klebsiella pneumoniae, which produce less lipopolysaccharide (LPS) thus considered less pathogenic than K. pneumoniae DSM 2026, were compared and evaluated for their potential for the co-production of 3-HP and 1,3-PDO. The newly isolated strains showed significantly faster sedimentation rate than DSM, which should be beneficial for downstream processing. Analysis of genome sequences of the isolates confirmed the presence of all genes necessary for glycerol assimilation, 1,3-PDO production and biosynthesis of coenzyme <TEX>$B_{12}$</TEX>. Co-production yield was highest under anaerobic condition while cell growth was highest under aerobic condition. Both strains showed similarly good performance for the co-production although J2B gave the slightly higher co-production yield of 0.80 mol/mol than GSC021 (0.75 mol/mol). The evaluation of the newly developed strains presented here should be useful in designing similar evaluation experiments for other microorganisms.
Functions of CD40 and Its Ligand, gp39 (CD40L) (1996)

Initially, a role for the interaction between CD40, expressed on B cells, and gp39 (CD40L), expressed on activated T cells, has been defined in humoral immunity. CD40-CD40L interaction is an essential signal for B cell proliferation, expression of activation markers, immunoglobulin production, and isotype switching. CD40-CD40L interaction is also required for formation of B memory cells and germinal centers, and signaling through CD40 prevents apoptosis of germinal center B cells. Defective expression of CD40L in humans leads to an inability to produce isotypes other than IgM (hyper IgM syndrome), and to an absence of germinal centers. More recent evidence indicates an expansion of the role of the CD40-CD40L axis in cellular interactions beyond antibody formation. Induced expression of CD40 on monocytes can lead to CD40L-activated monocyte effector mechanisms. In addition, CD40-CD40L interactions are crucially involved in development of autoimmune disease in a number of animal models. CD40-CD40L interactions also impact on growth regulation of certain carcinomas. Manipulation of CD40L has also been used to develop novel strategies for long-term antigen-specific tolerization of peripheral T cells. Finally, the CD40-CD40L axis is involved in thymic selection. Following is a comprehensive overview of CD40L-CD40 interactions in physiological and pathogenic cellular responses and a discussion of the therapeutic ramifications of these interactions.
Six-month partial suppression of Huntingtin is well tolerated in the adult rhesus striatum (2012)

Huntington's disease is caused by expression of a mutant form of Huntingtin protein containing an expanded polyglutamine repeat. One possible treatment for Huntington's disease may be to reduce expression of mutant Huntingtin in the brain via RNA interference. Unless the therapeutic molecule is designed to be allele-specific, both wild-type and mutant protein will be suppressed by an RNA interference treatment. A key question is whether suppression of wild-type as well as mutant Huntingtin in targeted brain regions can be tolerated and result in a net benefit to patients with Huntington's disease. Whether Huntingtin performs essential functions in the adult brain is unclear. Here, we tested the hypothesis that the adult primate brain can tolerate moderately reduced levels of wild-type Huntingtin protein for an extended period of time. A serotype 2 adeno-associated viral vector encoding for a short hairpin RNA targeting rhesus huntingtin messenger RNA (active vector) was bilaterally injected into the striatum of four adult rhesus monkeys. Four additional animals received a comparable vector encoding a scrambled control short hairpin RNA (control vector). General health and motor behaviour were monitored for 6 months. Upon termination, brain tissues were sampled and assessed blindly for (i) huntingtin messenger RNA knockdown; (ii) Huntingtin protein expression; and (iii) neuropathological changes. Reduction in wild-type huntingtin messenger RNA levels averaging ∼30% was measured in the striatum of active vector recipients 6 months post-injection. A widespread reduction in Huntingtin protein levels was also observed by immunohistochemistry in these animals, with an average protein reduction of ∼45% relative to controls measured by western blot analysis in the putamen of active vector recipients. As with control vector recipients, no adverse effects were observed behaviourally, and no neurodegeneration was found on histological examination of active vector recipients. Our results suggest that long-term partial suppression of wild-type Huntingtin may be safe, and thus if a comparable level of suppression of mutant Huntingtin is beneficial, then partial suppression of both wild-type and mutant Huntingtin may result in a net benefit in patients with heterozygous Huntington's disease.
Hybrid two segments ring dielectric resonator antenna for ultrawideband application (2015)

In this article, a hybrid two segments ring dielectric resonator antenna with partial ground plane, for ultrawideband application is described. The proposed antenna structure consists of annular shape microstrip line along with two ring dielectric resonators having different permittivity. By applying the combination of shifted annular shape microstrip line (used as a radiator as well as to convert TM01δ mode to TE01δ mode) and two segments ring dielectric resonator, ultra wide bandwidth has been achieved. Prototype of proposed structure has been fabricated and tested. Measured results show good agreement with the simulated ones. The proposed antenna structure operates over a frequency range of 3.45-10.9 GHz with a fractional bandwidth of 103.83% and having better gain and radiation characteristics. © 2015 Wiley Periodicals, Inc. Int J RF and Microwave CAE 26:47–53, 2016.
Bacterial gene transfer by natural genetic transformation in the environment (1994)

Natural genetic transformation is the active uptake of free DNA by bacterial cells and the heritable incorporation of its genetic information. Since the famous discovery of transformation in Streptococcus pneumoniae by Griffith in 1928 and the demonstration of DNA as the transforming principle by Avery and coworkers in 1944, cellular processes involved in transformation have been studied extensively by in vitro experimentation with a few transformable species. Only more recently has it been considered that transformation may be a powerful mechanism of horizontal gene transfer in natural bacterial populations. In this review the current understanding of the biology of transformation is summarized to provide the platform on which aspects of bacterial transformation in water, soil, and sediments and the habitat of pathogens are discussed. Direct and indirect evidence for gene transfer routes by transformation within species and between different species will be presented, along with data suggesting that plasmids as well as chromosomal DNA are subject to genetic exchange via transformation. Experiments exploring the prerequisites for transformation in the environment, including the production and persistence of free DNA and factors important for the uptake of DNA by cells, will be compiled, as well as possible natural barriers to transformation. The efficiency of gene transfer by transformation in bacterial habitats is possibly genetically adjusted to submaximal levels. The fact that natural transformation has been detected among bacteria from all trophic and taxonomic groups including archaebacteria suggests that transformability evolved early in phylogeny. Probable functions of DNA uptake other than gene acquisition will be discussed. The body of information presently available suggests that transformation has a great impact on bacterial population dynamics as well as on bacterial evolution and speciation.
Molecular Identification of I1PP2A, a Novel Potent Heat-Stable Inhibitor Protein of Protein Phosphatase 2A (1996)

The amino acid sequences of two tryptic peptides derived from purified preparations of I1PP2A indicated that this potent heat-stable protein inhibitor of protein phosphatase 2A (PP2A) may be equivalent to putative histocompatibility leukocyte antigens class II-associated protein I (PHAP-I). Experiments using purified preparations of recombinant human PHAP-I confirmed that this protein inhibited PP2A. Half-maximal inhibition of the phosphatase occurred at about 4 nM PHAP-I, similar to the half-maximal inhibition obtained with purified preparations of bovine kidney I1PP2A. In addition, PHAP-I did not affect the activities of protein phosphatase 1, 2B, and 2C in a manner analogous to that of I1PP2A. Together, the results establish the identity of I1PP2A on a firm basis.