Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Characterization of NocR as a Positive Transcriptional Regulator of the β-Lactam Nocardicin A in Nocardia uniformis

ABSTRACT Nocardicin A is a monocyclic β-lactam isolated from the actinomycete Nocardia uniformis, which shows moderate activity against a broad spectrum of gram-negative bacteria. Within the biosynthetic gene cluster of nocardicin A, nocR encodes a 583-amino-acid protein with high similarity to a class of transcriptional regulators known as streptomyces antibiotic regulatory proteins. Insertional inactivation of this gene resulted in a mutant showing morphology and growth characteristics similar to the wild type, but one that did not produce detectable levels of nocardicin A or the early precursor p-hydroxybenzoyl formate. Similar disruptions of nocD, nocE, and nocO yielded mutants that maintained production of nocardicin A at levels similar to the wild-type strain. In trans complementation of the nocR::apr mutant partially restored the wild-type phenotype. Transcriptional analysis of the nocR::apr mutant using reverse transcription-PCR found an absence of mRNA transcripts for the early-stage nocardicin A biosynthetic genes. In addition, transcription of the genes responsible for the biosynthesis of the nonproteinogenic p-hydroxyphenylglycine (pHPG) precursor was attenuated on the nocR disruption mutant. NocR was heterologously expressed and purified from Escherichia coli as an N-terminal maltose binding protein-tagged fusion protein. DNA binding assays demonstrated that NocR is a DNA binding protein, targeting the 126-bp intergenic region between nocF and nocA. Within this intergenic region is the likely binding motif, a direct hexameric repeat, TGATAA, with a 5-bp spacer. These experiments establish NocR as a positive transcriptional regulator of the nocardicin A biosynthetic pathway, coordinating the initial steps of nocardicin A biosynthesis to the production of its pHPG precursor.
Rad54p Is a Chromatin Remodeling Enzyme Required for Heteroduplex DNA Joint Formation with Chromatin*

In eukaryotic cells, the repair of DNA double-strand breaks by homologous recombination requires a RecA-like recombinase, Rad51p, and a Swi2p/Snf2p-like ATPase, Rad54p. Here we find that yeast Rad51p and Rad54p support robust homologous pairing between single-stranded DNA and a chromatin donor. In contrast, bacterial RecA is incapable of catalyzing homologous pairing with a chromatin donor. We also show that Rad54p possesses many of the biochemical properties of bona fideATP-dependent chromatin-remodeling enzymes, such as ySWI/SNF. Rad54p can enhance the accessibility of DNA within nucleosomal arrays, but it does not seem to disrupt nucleosome positioning. Taken together, our results indicate that Rad54p is a chromatin-remodeling enzyme that promotes homologous DNA pairing events within the context of chromatin.
Oxidative/Nitrative Stress and Inflammation Drive Progression of Doxorubicin-Induced Renal Fibrosis in Rats as Revealed by Comparing a Normal and a Fibrosis-Resistant Rat Strain

Chronic renal fibrosis is the final common pathway of end stage renal disease caused by glomerular or tubular pathologies. Genetic background has a strong influence on the progression of chronic renal fibrosis. We recently found that Rowett black hooded rats were resistant to renal fibrosis. We aimed to investigate the role of sustained inflammation and oxidative/nitrative stress in renal fibrosis progression using this new model. Our previous data suggested the involvement of podocytes, thus we investigated renal fibrosis initiated by doxorubicin-induced (5 mg/kg) podocyte damage. Doxorubicin induced progressive glomerular sclerosis followed by increasing proteinuria and reduced bodyweight gain in fibrosis-sensitive, Charles Dawley rats during an 8-week long observation period. In comparison, the fibrosis-resistant, Rowett black hooded rats had longer survival, milder proteinuria and reduced tubular damage as assessed by neutrophil gelatinase-associated lipocalin (NGAL) excretion, reduced loss of the slit diaphragm protein, nephrin, less glomerulosclerosis, tubulointerstitial fibrosis and matrix deposition assessed by periodic acid–Schiff, Picro-Sirius-red staining and fibronectin immunostaining. Less fibrosis was associated with reduced profibrotic transforming growth factor-beta, (TGF-β1) connective tissue growth factor (CTGF), and collagen type I alpha 1 (COL-1a1) mRNA levels. Milder inflammation demonstrated by histology was confirmed by less monocyte chemotactic protein 1 (MCP-1) mRNA. As a consequence of less inflammation, less oxidative and nitrative stress was obvious by less neutrophil cytosolic factor 1 (p47phox) and NADPH oxidase-2 (p91phox) mRNA. Reduced oxidative enzyme expression was accompanied by less lipid peroxidation as demonstrated by 4-hydroxynonenal (HNE) and less protein nitrosylation demonstrated by nitrotyrosine (NT) immunohistochemistry and quantified by Western blot. Our results demonstrate that mediators of fibrosis, inflammation and oxidative/nitrative stress were suppressed in doxorubicin nephropathy in fibrosis-resistant Rowett black hooded rats underlying the importance of these pathomechanisms in the progression of renal fibrosis initiated by glomerular podocyte damage.
Social Learning and Corporate Peer Effects

We find that firms are more likely to split their stock if their peer firms have recently done so. The effect is comparable to an increase of 40–50% in the share price. Splitting probability is also increasing in the announcement returns of peer splits. These results are consistent with social learning from peers’ actions and outcomes. The unique features of the setting and various further tests render alternative explanations unlikely. We find no clear benefit in following successful peer splitters. Firms are sometimes suspected to succumb to imitation, and the effect we show could be a case in point.
The Effect of Melatonin on Climacteric Symptoms in Menopausal Women; A Double-Blind, Randomized Controlled, Clinical Trial

Abstract Background Menopause is one of the most critical periods of woman’s life. With reducing of ovarian estrogen; women are more prone to psychological and physical symptoms. The present study aimed to investigate the effect of melatonin on the climacteric symptoms. Methods The present double blind, placebo randomized controlled clinical trial was conducted on 240 menopausal women (40 - 60 years old) referring to the gynecology clinics of Shiraz University of Medical Sciences (January - November 2012). The participants were randomly divided into two groups through sortition. Demographic characteristics, Goldberg’s general health questionnaire (GHQ), Greene Climacteric Scale and level of Follicle Stimulating Hormone (FSH) were determined for both groups before the intervention. The intervention group received one 3mg melatonin tablet each night for 3 months and the control group received the placebo in the same period. Changes of climacteric symptoms and drug complications were measured 1, 2 and 3 months after the intervention Results We analyzed the data of 99 postmenopausal women in the intervention group and 101 postmenopausal women in the control group. In the melatonin group, the climacteric symptoms score decreased from 35.73+11.6 to 17.09+10.22 during the 3-month study period and regardless of time, a significant difference was observed between the two groups (P<0.001). In addition, a significant difference was found between the two groups regarding various dimensions of the climacteric symptoms over time (P<0.001). No significant difference was found regarding side effects between the two groups (P= 0.135). Conclusion The study findings showed that using melatonin improved the climacteric symptoms.
Mighty Invisible Manipulators: How Hidden Influences Can Explain Everything

At first she did not understand what was written, and slowly read the letter aloud, sentence by sentence, until she reached the signature . Éline . It was Éline who had written that, her own little Éline . How could that be? And yet the hand-writing, although a little shaky, certainly looked like her daughter’s writing . It must be that those madwomen out there had held her hand and dictated those monstrous phrases that she surely didn’t mean one word of . (Daudet, 1888: 201).
Dietary glycaemic index and glycaemic load in Danish children in relation to body fatness

The aim of this study was to describe dietary glycaemic index (GI) and glycaemic load (GL) values in the diets of Danish children, and to examine the associations between dietary GI, GL and body fatness. Data were collected during 1997–8 as part of the European Youth Heart Study. The study population comprised 485 children aged 10 years and 364 children aged 16 years from Odense County, Denmark. Dietary GI and GL were estimated using international food tables, and the associations between energy-adjusted dietary GI, GL and body fatness were analysed by multiple linear regression. The mean daily dietary GI value was 85 (SD 6·9) with a range of 62–111. No significant differences were found between age groups and gender. The daily dietary GL was higher among boys aged 16, with a GL of 330 (sd 95) (P<0·05), compared with girls or younger boys. Dietary GL was higher among 10-year-old boys than girls (250 (sd 81) v. 230 (sd 66) P<0·05), whereas dietary GL among 16-year-old girls was 230 (sd 56). Neither dietary GI nor GL was associated with the sum of four skinfolds (ΣSF) among girls or among 10-year-old boys. Among 16-year-old boys, significant associations were observed between dietary GI and ΣSF (β+0·60, SE+0·21, P=0·006), and between dietary GL and ΣSF (β+0·15, SE+0.06, P=0·009). In conclusion, dietary GI and GL were positively associated with body fatness among Danish boys aged 16 years, whereas no associations were found among girls or younger boys.
Top-k Reliability Search on Uncertain Graphs

Uncertain graphs have been widely used to represent graph data with inherent uncertainty in structures. Reliability search is a fundamental problem in uncertain graph analytics. This paper studies a new problem, the top-k reliability search problem on uncertain graphs, that is, finding k vertices v with the highest reliabilities of connections from a source vertex s to v. Note that the existing algorithm for the threshold-based reliability search problem is inefficient for the top-k reliability search problem. We propose a new algorithm to efficiently solve the top-k reliability search problem. The algorithm adopts two important techniques, namely the BFS sharing technique and the offline sampling technique. The BFS sharing technique exploits overlaps among different sampled possible worlds of the input uncertain graph and performs a single BFS on all possible worlds simultaneously. The offline sampling technique samples possible worlds offline and stored them using a compact structure. The algorithm also takes advantages of bit vectors and bitwise operations to improve efficiency. Moreover, we generalize the top-k reliability search problem to the multi-source case and show that the multi-source case of the problem can be equivalently converted to the single-source case of the problem. Extensive experiments carried out on both real and synthetic datasets verify that the optimized algorithm outperforms the baselines by 1 - 2 orders of magnitude in execution time while achieving comparable accuracy. Meanwhile, the optimized algorithm exhibits linear scalability with respect to the size of the input uncertain graph.
Productive Programming of GPU Clusters with OmpSs

Clusters of GPUs are emerging as a new computational scenario. Programming them requires the use of hybrid models that increase the complexity of the applications, reducing the productivity of programmers. We present the implementation of OmpSs for clusters of GPUs, which supports asynchrony and heterogeneity for task parallelism. It is based on annotating a serial application with directives that are translated by the compiler. With it, the same program that runs sequentially in a node with a single GPU can run in parallel in multiple GPUs either local (single node) or remote (cluster of GPUs). Besides performing a task-based parallelization, the runtime system moves the data as needed between the different nodes and GPUs minimizing the impact of communication by using affinity scheduling, caching, and by overlapping communication with the computational task. We show several applications programmed with OmpSs and their performance with multiple GPUs in a local node and in remote nodes. The results show good tradeoff between performance and effort from the programmer.
0 Ju l 2 00 3 Consciousness : The rules of engagement

We examine the role of a conscious observer in a typical quantum mechanical measurement. Four rules are given that govern stochastic choice and state reduction in several cases of continuous and intermittent observation. It is found that consciousness always accompanies a state reduction leading to observation, but its presence is not sufficient to ‘cause’ a reduction. The distinction is clarified and codified by the rules that are given below. This is the first of several papers that lead to an experimental test of the rules, and of the “parallel principle” that is described elsewhere.
Determination of Helicobacter pylori Virulence Genes in Gastric Biopsies by PCR

Aim. The aim of this study was to identify the presence of H. pylori in biopsy specimens from symptomatic patients by PCR. In addition, the rate of cagA, vacA, iceA1, and iceA2 virulence genes was determined. Materials and Methods. One hundred antral gastric biopsy specimens were collected during endoscopy from patients suffering from gastroduodenal symptoms. The samples were collected by the gastroenterologists in their own clinics in Ramallah, Palestine. DNA was extracted from the biopsies and subsequently used for PCR identification of H. pylori and the virulence genes using specific primers. Results. The rate of positive H. pylori in the collected biopsies was 44%. The rates of the virulence genes in this sample: cagA, vacA, iceA1, and iceA2 were 65.9%, 40.9%, 63.6%, and 84.1%, respectively. Conclusion. The iceA2 gene was the most frequent in this study. Much research is necessary to determine the presence of an association of this gene with gastric pathology. Variation in the rates of the iceA gene in different countries is a strong indication of its geographical distribution. This study would provide important information regarding the prevalence of virulence genes (vacA, cagA, iceA1, and iceA2) in H. pylori strains in the sample tested in this country.
TLR2 Regulates Neutrophil Recruitment and Cytokine Production with Minor Contributions from TLR9 during Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to environmental antigens. The disease results in alveolitis, granuloma formation and may progress to a fibrotic chronic form, which is associated with significant morbidity and mortality. The severity of the disease correlates with a neutrophil rich influx and an IL-17 response. We used the Saccharopolyspora rectivirgula (SR) model of HP to determine whether Toll-like receptors (TLR) 2 and 9 cooperate in neutrophil recruitment and IL-17-associated cytokine production during the development of HP. Stimulation of bone marrow derived macrophages (BMDMs) from C57BL/6, MyD88-/- and TLR2/9-/- mice with SR demonstrate that SR is a strong inducer of neutrophil chemokines and growth factors. The cytokines induced by SR were MyD88-dependent and, of those, most were partially or completely dependent on TLRs 2 and 9. Following in vivo exposure to SR, CXCL2 production and neutrophil recruitment were reduced in TLR2-/- and TLR2/9-/- mice suggesting that the response was largely dependent on TLR2; however the reduction was greatest in the TLR2/9-/- double knockout mice indicating TLR9 may also contribute to the response. There was a reduction in the levels of pro-inflammatory cytokines TNFα and IL-6 as well as CCL3 and CCL4 in the BALF from TLR2/9-/- mice compared to WT and single knockout (SKO) mice exposed one time to SR. The decrease in neutrophil recruitment and TNFα production in the TLR2/9-/- mice was maintained throughout 3 weeks of SR exposures in comparison to WT and SKO mice. Both TLRs 2 and 9 contributed to the Th17 response; there was a decrease in Th17 cells and IL-17 mRNA in the TLR2/9-/- mice in comparison to the WT and SKO mice. Despite the effects on neutrophil recruitment and the IL-17 response, TLR2/9-/- mice developed granuloma formation similarly to WT and SKO mice suggesting that there are additional mediators and pattern recognition receptors involved in the disease.
Characterization of the Genomic Promoter of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus

ABSTRACT The genome of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) consists of two negative-sense, single-strand RNA segments designated L and S. Arenavirus genomes exhibit high sequence conservation at their 3′ ends. All arenavirus genomes examined to date have a conserved terminal sequence element (3′-terminal 20 nucleotides [nt]) thought to be a highly conserved viral promoter. Terminal complementarity between the 5′ and 3′ ends of the L and S RNAs predicts the formation of a thermodynamically stable panhandle structure that could contribute to the control of RNA synthesis. We investigated these issues by using a transcription- and replication-competent minireplicon system. A series of overlapping deletions spanning the 3′-terminal 20-nt region of an LCMV minigenome (MG) was generated, and the mutant MGs were analyzed for their activity as templates for RNA synthesis by the LCMV polymerase. The minimal LCMV genomic promoter was found to be contained within the 3′-terminal 19 nt. Substitution of C for G at the last 3′-end nucleotide position in the MG resulted in nondetection of RNA transcription or replication, whereas the addition of a C at the 3′ end did not have any significant affect on RNA synthesis mediated by the LCMV polymerase. All other mutations introduced within the 3′-terminal 19 nt of the MG resulted in undetectable levels of promoter activity. Deletions and nucleotide substitutions within the MG 5′ end that disrupted terminal complementarity abolished chloramphenicol acetyltransferase expression and RNA synthesis mediated by the LCMV polymerase. These findings indicate that both sequence specificity within the 3′-terminal 19 nt and the integrity of the predicted panhandle structure appear to be required for efficient RNA synthesis mediated by the LCMV polymerase.
On the frequency, intensity, and duration of starburst episodes triggered by galaxy interactions and mergers

We investigate the intensity enhancement and the duration of starburst episodes triggered by major galaxy interactions and mergers. We analyze two large statistical datasets of numerical simulations. These have been obtained using two independent and different numerical techniques to model baryonic and dark matter evolution that are extensively compared for the first time. One is a Tree-SPH code, the other one is a grid-based N-body sticky-particles code. We show that, at low redshift, galaxy interactions and mergers in general trigger only moderate star formation enhancements. Strong starbursts where the star formation rate is increased by a factor greater than 5 are rare and found only in about 15% of major galaxy interactions and mergers. Merger-driven starbursts are also rather short-lived, with a typical duration of activity of a few 10 8 yr. These conclusions are found to be robust, independent of the numerical techniques and star formation models. At higher redshifts where galaxies contain more gas, gas inflow-induced starbursts are neither stronger nor longer than their local counterparts. In turn, the formation of massive gas clumps, results of local Jeans instability that can occur spontaneously in gas-rich disks or be indirectly favored by galaxy interactions, could play a more important role in determining the duration and intensity of star formation episodes.
NO . 14-9 COMPETING FOR ORDER FLOW IN OTC MARKETS

We develop a model of a two-sided asset market in which trades are intermediated by dealers and are bilateral. Dealers compete to attract order flow by posting the terms at which they execute trades, which can include prices, quantities, and execution times, and investors direct their orders toward dealers that offer the most attractive terms of trade. Equilibrium outcomes have the following properties. First, investors face a trade-off between trading costs and speeds of execution. Second, the asset market is endogenously segmented in the sense that investors with different asset valuations and different asset holdings will trade at different speeds and different costs. For example, under a Leontief technology to match investors and dealers, per unit trading costs decrease with the size of the trade, in accordance with the evidence from the market for corporate bonds. Third, dealers’ implicit bargaining powers are endogenous and typically vary across sub-markets. Finally, we obtain a rich set of comparative statics both analytically, by studying a limiting economy where trading frictions are small, and numerically. For instance, we find that the relationship between trading costs and dealers’ bargaining power can be hump-shaped. ∗Pierre Mabille and Semih Uslu provided expert research assistance. We’d like to thank the participants of the JMCB-SNB-Uni Bern 2013 Conference on Financial Frictions and Julien Hugonnier for comments that greatly improved the paper. †The views expressed here are those of the authors and do not necessarily reflect the views of the Federal Reserve Bank of Philadelphia or the Federal Reserve System. This paper is available free of charge at www.philadelphiafed. org/research-and-data/publications/working-papers/.
Target Genes of the MADS Transcription Factor SEPALLATA3: Integration of Developmental and Hormonal Pathways in the Arabidopsis Flower

The molecular mechanisms by which floral homeotic genes act as major developmental switches to specify the identity of floral organs are still largely unknown. Floral homeotic genes encode transcription factors of the MADS-box family, which are supposed to assemble in a combinatorial fashion into organ-specific multimeric protein complexes. Major mediators of protein interactions are MADS-domain proteins of the SEPALLATA subfamily, which play a crucial role in the development of all types of floral organs. In order to characterize the roles of the SEPALLATA3 transcription factor complexes at the molecular level, we analyzed genome-wide the direct targets of SEPALLATA3. We used chromatin immunoprecipitation followed by ultrahigh-throughput sequencing or hybridization to whole-genome tiling arrays to obtain genome-wide DNA-binding patterns of SEPALLATA3. The results demonstrate that SEPALLATA3 binds to thousands of sites in the genome. Most potential target sites that were strongly bound in wild-type inflorescences are also bound in the floral homeotic agamous mutant, which displays only the perianth organs, sepals, and petals. Characterization of the target genes shows that SEPALLATA3 integrates and modulates different growth-related and hormonal pathways in a combinatorial fashion with other MADS-box proteins and possibly with non-MADS transcription factors. In particular, the results suggest multiple links between SEPALLATA3 and auxin signaling pathways. Our gene expression analyses link the genomic binding site data with the phenotype of plants expressing a dominant repressor version of SEPALLATA3, suggesting that it modulates auxin response to facilitate floral organ outgrowth and morphogenesis. Furthermore, the binding of the SEPALLATA3 protein to cis-regulatory elements of other MADS-box genes and expression analyses reveal that this protein is a key component in the regulatory transcriptional network underlying the formation of floral organs.