Miracle-dz/UniFAR-FTUs huggingface dataset:
Negative regulation of the adeno-associated virus (AAV) P5 promoter involves both the P5 rep binding site and the consensus ATP-binding motif of the AAV Rep68 protein

Transcript levels from the P5 promoter of adeno-associated virus type 2 (AAV) are negatively regulated by the AAV Rep78 and Rep68 proteins in the absence of helper virus. We have identified a Rep-responsive negative cis element of the P5 promoter between the P5 TATA box and transcription start site by using 5' and 3' deletions of the P5 promoter fused to the chloramphenicol acetyltransferase gene. This element contains four imperfect GAGC repeats similar to the Rep recognition sequences (RRSs) in the AAV inverted terminal repeats and in the AAV preferred integration locus in chromosome 19. Band shift analyses showed that human 293 cell nuclear extracts containing Rep68 or Rep68/K340H, a putative nucleoside triphosphate (NTP)-binding-site mutant of Rep68, formed Rep-specific complexes with this P5 RRS DNA. Within the P5 RRS, mutation of a cytosine at position 273 in the AAV sequence to guanine abolished Rep68 binding to the DNA. A mutation in the P5 RRS within a full-length AAV genome, which abolished Rep binding, resulted in a 40 to 50% reduction in the ability of wild-type Rep68 to inhibit the accumulation of P5 transcripts in vivo. In contrast, the Rep68/K340H mutant was unable to down-regulate this mutated promoter. These results indicate that there are at least two mechanisms involved in the negative regulation of P5 transcript levels by Rep68; one involves Rep68 binding to the P5 RRS, and another requires the region of Rep68 containing the consensus NTP-binding motif. Furthermore, our studies of AAV genomes containing mutated RRS- and/or YY1-binding elements suggest that transcription factor YY1 binding to the transcription start site of P5 interferes with Rep68 repression of the P5 promoter.
Modulation of cytotoxicity and cellular pharmacology of 1,2-diaminocyclohexane platinum (IV) complexes mediated by axial and equatorial ligands.

Isomers (R,R-, S,S-, and cis-) of 1,2-diaminocyclohexane (DACH) platinum(IV) complexes with selected axial and equatorial ligands were synthesized and evaluated for in vitro antitumor activity, cellular uptake, and total DNA-Pt adducts. L1210 cells, sensitive to cis-diamminedichloroplatinum(II) (CDDP) and tetraplatin (L1210/0), 160-fold resistant to CDDP [L1210/diamminedichloroplatinum (DDP)], or 70-fold resistant to tetraplatin (L1210/DACH), were used in conjunction with compounds having the general structure DACH-Pt(IV)-X2Y2, where X and Y are axial and equatorial ligands and X2Y2 are specifically Cl2Cl2,Ac2Cl2, (TFA)2Cl2, (OH)2Cl2, and Cl2CBDCA (Cl, chloro; Ac, acetato; TFA, trifluoroacetato; OH, hydroxo; CBDCA, 1,1-cyclobutanedicarboxylato). Comparison of cytotoxicities between isomers of Cl2Cl2,Ac2Cl2, or Cl2CBDCA indicated that R,R-isomers were the most effective against all three cell lines. The relatively lower activity of the S,S- and cis-isomers was cell line dependent: against L1210/DACH, both isomers of Cl2Cl2 were only 2- to 3-fold less effective, and this contrasted with 7- and 26-fold lower cytotoxicities, respectively, against L1210/DDP. Cross-resistance factors in the L1210/DDP and L1210/DACH lines depended on both isomeric form and the nature of axial or equatorial ligand. The L1210/DDP cells were 6- to 9-fold cross-resistant to the R,R-isomer, 8- to 15-fold to S,S-isomer, and 13- to 38-fold to cis-isomer. The L1210/DACH line was only 4- to 7-fold cross-resistant to the three isomers of Ac2Cl2 but cross-resistance to the isomers was 47- to 79-fold for Cl2Cl2 and 22- to 56-fold for Cl2CBDCA complexes. Compared with CDDP, accumulation (2 h at 100 microM drug concentration) of Ac2Cl2 in the three L1210 cell lines was 26-50%, while uptake of Cl2Cl2 and (TFA)2Cl2 was 100-170% and 320-570%, respectively. The greatest DNA binding was seen with Cl2Cl2 in all cell lines, followed by (TFA)2Cl2, CDDP, and Ac2Cl2. DNA binding correlated directly with potency (1/concentration producing 50% inhibition) in the L1210/0 model (r = 0.973, P < 0.016) but not in the L1210/DDP and L1210/DACH models. Accumulation and DNA-binding studies indicated that binding efficiency to DNA was: Cl2Cl2 > Ac2Cl2 > CDDP > (TFA)2Cl2. In a nonreducing environment, the Pt(IV) complexes (20 microM) did not react with salmon sperm DNA. Reduced glutathione (100 microM), as a reducing agent, rendered full binding capacity to Cl2Cl2; binding was 25-30% of the expected maximum for (TFA)2Cl2, while Ac2Cl2 remained inert. (ABSTRACT TRUNCATED AT 400 WORDS)
Connectedness at the End of Life Among People Admitted to Inpatient Palliative Care

The significance of connectedness for well-being is well known. At the end of life however, illness and body decline may challenge a person’s ability of staying and feeling connected. The aim of this phenomenological study was to interpret meanings of connectedness, through narrative interviews with persons admitted to inpatient palliative care in Sweden. Results involving connectedness through the body, connectedness to, and uncanniness toward other patients, and connectedness to significant others and society are discussed. The study underscores the importance of connectedness until death. However, in inpatient palliative care this is complex. Patients can cocreate or challenge each other’s sense of connectedness through the symbolism of illness and diseased bodies. Moreover, the capability of connectedness is influenced by illness, spatiality, atmosphere, activities, and resources in the care place.
Cost-effectiveness of a preferred intensity exercise programme for young people with depression compared with treatment as usual: an economic evaluation alongside a clinical trial in the UK

Objectives To assess the cost-effectiveness of preferred intensity exercise programme for young people with depression compared with a treatment as usual control group. Design A ‘within trial’ cost-effectiveness and cost-utility analysis conducted alongside a randomised controlled trial. The perspective of the analysis was the UK National Health Service and social services. Setting The intervention was provided in a community leisure centre setting. Participants 86 young people aged 14–17 years attending Tier 2 and Tier 3 CAMHS (Child and Adolescent Mental Health Services) outpatient services presenting with depression. Interventions The intervention comprised 12 separate sessions of circuit training over a 6-week period. Sessions were supervised by a qualified exercise therapist. Participants also received treatment as usual. The comparator group received treatment as usual. Results We found improvements in the Children’s Depression Inventory-2 (CDI-2) and estimated cost-effectiveness at £61 per point improvement in CDI-2 for the exercise group compared with control. We found no evidence that the exercise intervention led to differences in quality-adjusted life years (QALY). QALYs were estimated using the EQ-5D-5L (5-level version of EuroQol-5 dimension). Conclusions There is evidence that exercise can be an effective intervention for adolescents with depression and the current study shows that preferred intensity exercise could also represent a cost-effective intervention in terms of the CDI-2. Trial registration number NCT01474837.
Improving Vehicular Traffic Simulations Using Real-Time Information on Environmental Conditions

This contribution illustrates the benefit of incorporating real-time environmental data into highway traffic information systems and describes the modelling and integration of weather conditions into a complex microscopic traffic simulation. Using stationary measured weather data as an example, the achieved results show the potential extended Floating Car Data (xFCD) - submitted to the traffic information system by cellular communication - can have for traffic simulation. Therefore, an estimation about the expected communication network load is given, when xFCD equipped vehicles have become prevalent.
Comparison of the O’Brien Filter Test and the PFA-100 Platelet Analyzer in the Laboratory Diagnosis of von Willebrand’s Disease

Summary Von Willebrand’s disease (vWD) is the most common congenital haemorrhagic diathesis, characterized by the quantitative or qualitative disorder of von Willebrand factor (vWF). A number of methods have been used for the diagnosis of the disease, and the bleeding time determination is widely accepted as a screening test in spite of its low sensitivity. Our aim was to evaluate and compare the performance of two high shear systems (the O’Brien filter test and the PFA-100 device) in the screening and diagnosis of vWD. Thirty patients (n=13 type 1 with mild symptoms, n = 9 type 1 with severe symptoms, n = 2 type 2A, n = 3 type 2B and n = 3 type 3 vWD) and twenty controls were investigated. In mild vWD the platelet retention in the second phase of the filter test with citrated blood showed the highest sensitivity (91.6%). The sensitivity of the PFA-100 method with collagen-epinephrine cartridges in this group was 76.9%, while the bleeding time was prolonged only in 15.4% of the cases. In severe type 1, in type 2A and type 3 all functional tests reflected the bleeding tendency of the patients. In type 2B disease the bleeding time was prolonged only when the patient was thrombocytopenic, but both high shear systems revealed the disease independently of the presence of thrombocytopenia. The overall sensitivity of the bleeding time determination was 50% compared to the 80-90% sensitivity of the O’Brien filter test and the PFA-100 system. The sensitivity values of the filter test and the PFA-100 device with collagen-epinephrine cartridges were in the same range, but the collagen-ADP cartridges showed a lower (65.5%) sensitivity, though the results were specific and had high positive predictive value. We conclude that both high shear systems are suitable for the screening of vWD, and that they are superior to the traditional bleeding time determination in case of mild disease or type 2B vWD.
Identification of selective norbornane-type aspartate analogue inhibitors of the glutamate transporter 1 (GLT-1) from the chemical universe generated database (GDB).

A variety of conformationally constrained aspartate and glutamate analogues inhibit the glutamate transporter 1 (GLT-1, also known as EAAT2). To expand the search for such analogues, a virtual library of aliphatic aspartate and glutamate analogues was generated starting from the chemical universe database GDB-11, which contains 26.4 million possible molecules up to 11 atoms of C, N, O, F, resulting in 101026 aspartate analogues and 151285 glutamate analogues. Virtual screening was realized by high-throughput docking to the glutamate binding site of the glutamate transporter homologue from Pyrococcus horikoshii (PDB code: 1XFH ) using Autodock. Norbornane-type aspartate analogues were selected from the top-scoring virtual hits and synthesized. Testing and optimization led to the identification of (1R*,2R*,3S*,4R*,6R*)-2-amino-6-phenethyl-bicyclo[2.2. 1]heptane-2,3-dicarboxylic acid as a new inhibitor of GLT-1 with IC(50) = 1.4 μM against GLT-1 and no inhibition of the related transporter EAAC1. The systematic diversification of known ligands by enumeration with help of GDB followed by virtual screening, synthesis, and testing as exemplified here provides a general strategy for drug discovery.
Gender Diversity in Top Management and Its Impact on Firm’s Financial Performance in the Case of Ethiopian Financial Institution

ii Acknowledgement.iii Table of contents. iv List of tables. vii List of figures. vii CHAPTER ONE INTRODUCTION.1 1.1. Background of the study.1 1.2. Statement of the problem.4 1.3. Objective of the study.6 1.4. Research questions.7 1.5. Hypothesis.7 1.6. Significance of the study . 8 1.7. scope of the study.9 1.8. Limitation of the study.9 1.9Organization of the study.9 CHAPTER TWO LITERATURE REVIEW.10 2.
Interactive Plant Modeling Based on Fractal

Plant modeling is challenging because of its complexity. The difficult problem is that the system how to present the sufficient and effective parameters for user to control the models. To address this problem, we design an interactive system for generating all kinds of plants. We first consider the plant models composed by two units: the leaf and branch unit. Then we use fractal method to draw the branches based on the branch segment generated by the branch units. Finally we use the several branches to shape the plantpsilas overall silhouette and density with the global method. The user can change the attribute value of the two units and the parameters of recursion by the interactive interface. The manipulation is simply and the results look more naturally. Our system also supports large numbers of leaves model, the user can chose one of them or add some new models in them.
Conservative Politicians and Voting on Same-sex Marriage

Abstract We examine whether conservative politicians are less likely to support same-sex marriage when they run for office in safe rather than in contested districts using new data based on a roll-call vote in the national German parliament. The results show that the margin of the majority for the incumbent in the previous election was a strong predictor for supporting same-sex marriage. When the majority increased by a 1 percentage point, the likelihood of voting in favour of same-sex marriage decreased by around 1.3 percentage points. We conjecture that politicians are election-motivated - even when submitting roll-call votes on a matter of conscience.
Complete mitochondrial genome of the sea anemone, Anthopleura midori (Actiniaria: Actiniidae)

Abstract Here we sequenced and characterized the complete mitochondrial genome (mitogenome) of Anthopleura midori from Weihai, China. This is the first species with sequenced mitogenome of genus Anthopleura. The A. midori mitogenome is 20 039 bp in length (GenBank accession no. KT989511). The overall base composition of the H-strand is 26.81% A, 17.45% C, 21.52% G, and 34.22% T. The base composition clearly showed the A–T skew. Similar to most other sea anemone in family Actiniidae, it contains 13 protein-coding genes, 2 rRNAs, 2 tRNAs, and some non-coding regions. The circular mitogenome codes entirely on the heavy strand and ND5 and COI genes were embedded by an intron. Phylogenetic analyses show that A. midori is related most closely to Phymanthus crucifer.
Impacts of load reduction offers on load profile

Demand Response (DR) has gained so much importance due to its effect on load profile characteristics. The focus of this paper is on impacts of flexible load participation in day-ahead energy market, in which bulk power consumers introduce their load reduction as generation. Based on costumer's characteristics, a model is developed for the demand side participation in aforementioned program. Effects of demand side cooperation and various incentive policies on load profile have been surveyed by the help of the proposed model. Moreover, results were compared for several cases in order to prioritize various strategies.
The Role of Inducible Nitric Oxide Synthase Inhibitor, Meropenem, and Taurine in Experimental Acute Necrotizing Pancreatitis

Introduction Translocation of bacteria from the gut is one of the most important factors in the development of septic complications and mortality in acute pancreatitis. Aims To investigate whether S-methylisothiourea (SMT), taurine (TAU), and meropenem (MER) could effect bacterial translocation and the course of acute necrotizing pancreatitis. Methodology Seventy male Sprague-Dawley rats were studied. Rats were randomly allocated into seven groups. Acute pancreatitis was induced in group II (MER), group III (TAU), group IV (TAU + MER), group V (TAU + SMT), group VI (TAU + MER + SMT), and group VII (positive control) by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham) received normal saline infusion into the common biliopancreatic duct as negative control. Rats were treated with drug combinations intraperitoneally for 48 hours after induction of pancreatitis. At the 48th hour of induction, all animals were killed, and specimens were collected. Results Bacterial translocation to peritoneum and pancreas in groups treated with MER were lower than in the other groups. Pancreatic tissue GSHpx and SOD levels were higher in all groups in comparison with levels in group VII. Pancreatic tissue MDA levels were also lower in all treatment groups except group II. The most favorable results were obtained in group VI (TAU + MER + SMT). Also, the lowest pathologic score between the groups in which acute pancreatitis developed was obtained in group VI. Conclusions Addition of TAU and SMT to the treatment protocol for acute pancreatitis seems to improve the pathologic score and oxidative stress parameters. Also, antibiotherapy with MER decreases the risk of bacterial translocation.
Textual Sentiment, Option Characteristics, and Stock Return Predictability

We distill sentiment from a huge assortment of NASDAQ news articles by means of machine learning methods and examine its predictive power in single-stock option markets and equity markets. We provide evidence that single-stock options react to contemporaneous sentiment. Next, examining return predictability, we discover that while option variables indeed predict stock returns, sentiment variables add further informational content. In fact, both in a regression and a trading context, option variables orthogonalized to public and sentimental news are even more informative predictors of stock returns. Distinguishing further between overnight and trading-time news, we find the first to be more informative. From a statistical topic model, we uncover that this is attributable to the differing thematic coverage of the alternate archives. Finally, we show that sentiment disagreement commands a strong positive risk premium above and beyond market volatility and that lagged returns predict future returns in concentrated sentiment environments.
Video foreground detection via sparse representation

In this article we propose a novel background model method based on sparse representation theory. In this framework the image is divided into N×N non-overlapping blocks, each block of a new input image has a sparse representation in the space spanned by background model. The sparse representation is achieved by solving an ℓ1-regularized least squares problem which is computed by the preconditioned conjugate gradients (PCG) algorithm. Then the block with large error vector is taken as the foreground region. The experimental results show that proposed algorithm produces more accurate and stable results.
Longin and GAF Domains: Structural Evolution and Adaptation to the Subcellular Trafficking Machinery

Endomembrane trafficking is one of the most prominent cytological features of eukaryotes. Given their widespread distribution and specialization, coiled‐coil domains, coatomer domains, small GTPases and Longin domains are considered primordial ‘building blocks’ of the membrane trafficking machineries. Longin domains are conserved across eukaryotes and were likely to be present in the Last Eukaryotic Common Ancestor. The Longin fold is based on the α‐β‐α sandwich architecture and a unique topology, possibly accounting for the special adaptation to the eukaryotic trafficking machinery. The ancient Per ARNT Sim (PAS) and cGMP‐specific phosphodiesterases, Adenylyl cyclases and FhlA (GAF) family domains show a similar architecture, and the identification of prokaryotic counterparts of GAF domains involved in trafficking provides an additional connection for the endomembrane system back into the pre‐eukaryotic world. Proteome‐wide, comparative bioinformatic analyses of the domains reveal three binding regions (A, B and C) mediating either specific or conserved protein–protein interactions. While the A region mediates intra‐ and inter‐molecular interactions, the B region is involved in binding small GTPases, thus providing an evolutionary connection among major building blocks in the endomembrane system. Finally, we propose that the peculiar interaction surface of the C region of the Longin domain allowed it to extensively integrate into the endomembrane trafficking machinery in the earliest stages of building the eukaryotic cell.
Resource Allocation for Energy Harvesting-Powered D2D Communication Underlaying Cellular Networks

Energy harvesting (EH)-powered wireless communications have attracted great attention from both industry and academia. However, the available energy, which relies on EH efficiency, will become another nonnegligible factor when we do research on EH-powered wireless communications. This paper studies the resource allocation problems in terms of spectrum and energy under EH-powered Device-to-Device (D2D) Communication underlaying Cellular Network (EH-DCCN). In this network, D2D pairs powered by EH are allowed to reuse the spectrum resources occupied by Cellular Users (CUs). To investigate the resource allocation problems, a sum-rate maximization problem of the whole cellular network with consideration of Quality of Service (QoS) and available energy constraints is formulated. The maximization problem is a nonconcave mixed-integer nonlinear programming (MINLP) problem, which has been proved to be NP-hard. To solve the problem, we first relax it with a concave lower bound on the original problem and then obtain the theoretical performance of the lower bound by Outer Approximation Algorithm. Moreover, a heuristic algorithm, an Energy-aware Space Matching approach (ESM), is proposed to acquire a suboptimal solution with low computational complexity. Finally, numerical simulation results indicate our considered resource allocation strategy is more effective than the strategy only based on channel state information under the EH-DCCN. Moreover, the performance in aspects of the sum rate and the matching probability shows that the ESM can approximately obtain the theoretical performance of the lower bound on the original problem under the scenarios with higher ratio of CU and EH-powered D2D numbers.
Genotype × Environmental Interaction on Seed Cotton Yield and Yield Components

Cotton yield and fibre quality parameters are dependent on the environment in which the crop is grown. A major challenge in crop genotype recommendations is genotype × environment interaction. The identification of cultivars with high adaptability and stability is one of the best ways to address this challenge. Genotype × Environmental interaction on Gosypium hirsutum was investigated. Ten genotypes were planted in a randomised complete block design with three replications. Collected data were subjected to Analysis of Variance (ANOVA) with genotype and location as factors. Additive Main Effect and Multiplicative Interaction model which combines standard analysis of variance with principal component analysis was used to investigate the genotype main effects, environment main effects and the GE interactions. Significant genotype × environment interactions existed for lint yield, boll weights, staple length, and fuzzy seed grade. There were no significant cultivar × site interactions on total seed cotton yield. Cotton cultivars respond differently to different growing conditions implying that, correct choice of varieties by growers for specific production conditions, must be a must to avoid losses due to genotype × environment interactions.