Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth and Adult Height in Patients with Crohn's Disease Treated with Anti-Tumor Necrosis Factor α Antibodies

Inflammation contributes to growth failure associated with inflammatory bowel diseases. Anti-TNFα therapy induces sustained remission and short-term improvements in height velocity and/or height standard deviation score (H-SDS) patients with Crohn’s disease. The purpose of this study was to evaluate growth and adult height in patients with Crohn’s disease taking maintenance infliximab or adalimumab therapy.This university-hospital based retrospective study included 61 patients, with a median follow-up of 2.6 years (2.0; 3.3). 38 patients (62%) reached their adult height. H-SDS was collected at diagnosis and together with disease activity markers (Harvey-Bradshaw Index, albumin, and C-reactive protein) at treatment initiation (baseline), and follow-up completion. Wilcoxon’s signed-rank test was chosen for comparisons. Median H-SDS decreased from diagnosis to baseline (-0.08 [-0.73; +0.77] to -0.94 [-1.44; +0.11], p<0.0001) and then increased to follow-up completion (-0.63 [-1.08; 0.49], p = 0.003 versus baseline), concomitantly with an improvement in disease activity. Median adult H-SDS was within the normal range (-0.72 [-1.25; +0.42]) but did not differ from baseline H-SDS and was significantly lower than the target H-SDS (-0.09 [-0.67; +0.42], p = 0.01). Only 2 (6%) males had adult heights significantly below their target heights (10.5 and -13.5 cm [-1.75 and -2.25 SD]). In conclusion, anti-tumor necrosis factor α (TNF) therapy prevented loss of height without fully restoring the genetic growth potential in this group of patients with CD. Earlier treatment initiation might improve growth outcomes in these patients.
Pyrimidine Salvage in Trypanosoma brucei Bloodstream Forms and the Trypanocidal Action of Halogenated Pyrimidines

African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host. However, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine-based chemotherapy. Detailed characterization of pyrimidine transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high-affinity uracil transporter (designated TbU3) that is clearly distinct from the procyclic pyrimidine transporters. This transporter had low affinity for uridine and 2′deoxyuridine and was the sole pyrimidine transporter expressed in these cells. In addition, thymidine was taken up inefficiently through a P1-type nucleoside transporter. Of importance, the anticancer drug 5-fluorouracil was an excellent substrate for TbU3, and several 5-fluoropyrimidine analogs were investigated for uptake and trypanocidal activity; 5F-orotic acid, 5F-2′deoxyuridine displayed activity in the low micromolar range. The metabolism and mode of action of these analogs was determined using metabolomic assessments of T. brucei clonal lines adapted to high levels of these pyrimidine analogs, and of the sensitive parental strains. The analysis showed that 5-fluorouracil is incorporated into a large number of metabolites but likely exerts toxicity through incorporation into RNA. 5F-2′dUrd and 5F-2′dCtd are not incorporated into nucleic acids but act as prodrugs by inhibiting thymidylate synthase as 5F-dUMP. We present the most complete model of pyrimidine salvage in T. brucei to date, supported by genome-wide profiling of the predicted pyrimidine biosynthesis and conversion enzymes.
Sorafenib reveals efficacy in sequential treatment of metastatic renal cell cancer

Metastatic renal cell carcinoma (mRCC) is a highly vascularized tumor with a generally poor prognosis. It is largely resistant to conventional cancer treatment, including most schemes of hormonal and cytokine therapy as well as to modern chemotherapy. Although IFN-α has been the first choice in mRCC treatment strategies for more than a decade, recent recommendations of the European Association of Urology focus on so-called molecular-targeted therapies, with multikinase inhibitors, such as sorafenib and sunitinib, blocking the progression of cell proliferation and tumor angiogenesis, as preferential therapy. Sorafenib targets the VEGF receptor, the PDGF receptor β and, finally, Raf kinase, and is approved for patients who have either received cytokines or are unsuitable for such a therapy. Although targeted therapies reveal superior efficacy compared with previous cytokine-based approaches, they do not cure patients with metastatic disease. Therefore, following tumor progression, most patients require a second-line or sequential therapy during the further progress of the disease. Owing to the fact that optimal sequencing of these new agents has not been fully elucidated, some recent mainly retrospective studies compared the sequence of sorafenib and sunitinib in order to assess the best clinical benefit in mRCC patients. Apparently, no cross-resistance could be observed in any trial, and most results demonstrated a superior efficacy of a sequence strategy when sorafenib was applied as first-line treatment. Regarding current investigations, the aim of the present article is to address and critically discuss the clinical data concerning the efficacy of sorafenib as part of a sequential treatment of mRCC.
Driver's reaction time under emergency braking a car - research in a driving simulator

Extract. The paper presents results of research on the reaction time of drivers of motor vehicles in case of accident risk. These studies have been conducted in an autoPW driving simulator research project N509 016 31/1251. During a simulated pre-accident situation, a test driver, as he was trying to avoid a collision with an obstacle, has been forced to perform a braking manoeuvre. 107 people of different age and driving experience have been studied. Various scenarios describing risk situations (the speed of a car driven by a tested driver, the distance between the vehicles at the initial moment) have been considered.Reaction times were determined at the controls of the vehicle and they have been presented in a time to collision function. The presented results provide important information on the analysed subject (for instance reaction time dependence on risk time). They have also confirmed the usefulness of this type of simulation studies in connection with the possibility of fairly accurate reproduction of the environment appearance and an event scenario in relation to possible real situations.
Recognition of Fibrotic Infarct Density by the Pattern of Local Systolic-Diastolic Myocardial Electrical Impedance

Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (<10% fibrosis), heterogeneous scar (10–50%) and dense scar (>50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 Ω·cm vs. 10 ± 1 Ω·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 Ω·cm, 225 ± 25 Ω·cm, and 162 ± 6 Ω·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of myocardial fibrosis can be detected in vivo by local measurement of phasic systolic-diastolic bioimpedance spectrum. Once this new bioimpedance method could be used via a catheter-based device, it would be of potential clinical applicability for the recognition of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.
MiR‐335 overexpression impairs insulin secretion through defective priming of insulin vesicles

MicroRNAs contribute to the maintenance of optimal cellular functions by fine‐tuning protein expression levels. In the pancreatic β‐cells, imbalances in the exocytotic machinery components lead to impaired insulin secretion and type 2 diabetes (T2D). We hypothesize that dysregulated miRNA expression exacerbates β‐cell dysfunction, and have earlier shown that islets from the diabetic GK‐rat model have increased expression of miRNAs, including miR‐335‐5p (miR‐335). Here, we aim to determine the specific role of miR‐335 during development of T2D, and the influence of this miRNA on glucose‐stimulated insulin secretion and Ca2+‐dependent exocytosis. We found that the expression of miR‐335 negatively correlated with secretion index in human islets of individuals with prediabetes. Overexpression of miR‐335 in human EndoC‐βH1 and in rat INS‐1 832/13 cells (OE335) resulted in decreased glucose‐stimulated insulin secretion, and OE335 cells showed concomitant reduction in three exocytotic proteins: SNAP25, Syntaxin‐binding protein 1 (STXBP1), and synaptotagmin 11 (SYT11). Single‐cell capacitance measurements, complemented with TIRF microscopy of the granule marker NPY‐mEGFP demonstrated a significant reduction in exocytosis in OE335 cells. The reduction was not associated with defective docking or decreased Ca2+ current. More likely, it is a direct consequence of impaired priming of already docked granules. Earlier reports have proposed reduced granular priming as the cause of reduced first‐phase insulin secretion during prediabetes. Here, we show a specific role of miR‐335 in regulating insulin secretion during this transition period. Moreover, we can conclude that miR‐335 has the capacity to modulate insulin secretion and Ca2+‐dependent exocytosis through effects on granular priming.
SVM based prediction of RNA‐binding proteins using binding residues and evolutionary information

RNA‐binding proteins (RBPs) play crucial role in transcription and gene‐regulation. This paper describes a support vector machine (SVM) based method for discriminating and classifying RNA‐binding and non‐binding proteins using sequence features. With the threshold of 30% interacting residues, RNA‐binding amino acid prediction method PPRINT achieved the Matthews correlation coefficient (MCC) of 0.32. BLAST and PSI‐BLAST identified RBPs with the coverage of 32.63 and 33.16%, respectively, at the e‐value of 1e‐4. The SVM models developed with amino acid, dipeptide and four‐part amino acid compositions showed the MCC of 0.60, 0.46, and 0.53, respectively. This is the first study in which evolutionary information in form of position specific scoring matrix (PSSM) profile has been successfully used for predicting RBPs. We achieved the maximum MCC of 0.62 using SVM model based on PSSM called PSSM‐400. Finally, we developed different hybrid approaches and achieved maximum MCC of 0.66. We also developed a method for predicting three subclasses of RNA binding proteins (e.g., rRNA, tRNA, mRNA binding proteins). The performance of the method was also evaluated on an independent dataset of 69 RBPs and 100 non‐RBPs (NBPs). An additional benchmarking was also performed using gene ontology (GO) based annotation. Based on the hybrid approach a web‐server RNApred has been developed for predicting RNA binding proteins from amino acid sequences (http://www.imtech.res.in/raghava/rnapred/). Copyright © 2010 John Wiley & Sons, Ltd.
`Are You Going Home Already?'

Drawing on Weberian theory of social closure, this article explores how the long hours culture fostered in so many British organizations may act as a means of social closure to exclude women managers from senior positions. The research, conducted in eight different divisions of two UK companies, an airline and a merchant bank, shows that access to the resource of time is vital to be a successful manager. Women are less likely to have equal access to time because of the gendered division of domestic labour, and indeed men's time is often made available to them by their partners at home. At a time when women can offer almost everything that men can in terms of ability, skills and experience, time becomes the differentiating feature which makes men more likely to achieve promotion. The research shows the convergence of patriarchal and organizational desires/interests.
ExoMol: molecular line lists for exoplanet and other atmospheres

The discovery of extrasolar planets is one of the major scientific advances of the last two decades. Hundreds of planets have now been detected and astronomers are beginning to characterize their composition and physical characteristics. To do this requires a huge quantity of spectroscopic data most of which are not available from laboratory studies. The ExoMol project will offer a comprehensive solution to this problem by providing spectroscopic data on all the molecular transitions of importance in the atmospheres of exoplanets. These data will be widely applicable to other problems and will be used for studies on cool stars, brown dwarfs and circumstellar environments. This paper lays out the scientific foundations of this project and reviews previous work in this area. A mixture of first principles and empirically tuned quantum mechanical methods will be used to compute comprehensive and very large rotation–vibration and rotation–vibration– electronic line lists. Methodologies will be developed for treating larger molecules such as methane and nitric acid. ExoMol will rely on these developments and the use of state-of-the-art
Cellular basis of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.
Strengthening of Timber Bridges

Most timber bridges in the Province of Manitoba are constructed with sawn Douglas Fir stringers, which are simply-supported with spans ranging from 6 to 10 m. Due to an increase in the allowable gross vehicle weight, most of these bridge stringers may require flexural and/or shear strengthening to increase their load-carrying capacity. This paper presents an innovative approach for the use of fibre reinforced polymers (FRP) for strengthening these bridges. The FRPs have a high strength-to-weight ratio and are non-corrosive. This enables engineers to strengthen old timber bridges without increasing the self-weight of the structure. An experimental program was undertaken at the University of Manitoba to study the behaviour of creosote-treated old Douglas Fir beams strengthened by glass fibre reinforced polymer (GFRP). Halfscale and full-scale timber beams were tested to examine the effectiveness of the technique and to determine the ultimate capacity and ductility of GFRP-strengthened timber bridge girders. The GFRP was bonded to the timber using epoxy. Twenty-two beams were tested using three GFRP reinforcement ratios and plain timber beams as control beams. The proposed technique has proven that the ductility will be dramatically improved and the flexural strength may be increased by 25 to 50 percent. Full-scale tests on three beams of 10 m span confIrmed that using GFRP is a feasible technique for strengthening timber bridges.
Ethical Leaders and Their Followers: The Transmission of Moral Identity and Moral Attentiveness

In the expanding field of ethical leadership research, little attention has been paid to the association between ethical leadersâ€™ ethical characteristics (beyond personality) and perceived ethical leadership, and, more importantly, the potential influence of ethical leadership on followersâ€™ ethical characteristics. In this study, we tested a theoretical model based upon social cognitive theory (Bandura, 1986) to examine leadersâ€™ moral identity and moral attentiveness as antecedents of perceived ethical leadership, and follower moral identity and moral attentiveness as outcomes of ethical leadership. Based upon data from 89 leaders and 460 followers in China, collected at two points in time, we found that leadersâ€™ moral identity and moral attentiveness are associated with followerâ€™s perceptions of ethical leadership. Ethical leadership is, in turn, associated with their followersâ€™ moral identity and moral attentiveness. We found furthermore that ethical leadership mediates the effect of leadersâ€™ moral identity on followersâ€™ moral identity, but not the effect of leadersâ€™ moral attentiveness on followersâ€™ moral attentiveness. We discuss the findings, theoretical contributions, practical implications, and future research.
What Motivates Librarians to Share Knowledge?

ABSTRACT This study investigated the effects of social and individual factors of strength of ties, perceived benefits, extrinsic rewards, recognition, reciprocity, and perceived cost on sharability. A survey was sent to 170 librarians at special, public, and academic libraries across Kuwait; 139 responses were received for a response rate of 80%. It was found that the strength of ties and perceived benefits had a positive effect and perceived costs had a negative effect on sharability. The findings can help libraries identify the opportunities and barriers to motivate librarians to share their knowledge. This study is a useful contribution to knowledge management literature, especially concerning the library context.
Three-Level Single-Phase Bridgeless PFC Rectifiers

This paper presents new three-level unidirectional single-phase PFC rectifier topologies well suited for applications targeting high efficiency and/or high power density. The characteristics of a selected novel rectifier topology including its principles of operation, modulation strategy, feedback control scheme, and a power circuit design related analysis are presented. Finally, a 220-V/3-kW laboratory prototype is constructed and used in order to verify the characteristics of the new converter, which include remarkably low switching losses and single ac-side boost inductor, that allow for a 98.6% peak efficiency with a switching frequency of 140 kHz.
Allogeneic and autologous bone marrow transplantation for acute leukemia and malignant lymphoma: Current status

The current status of autologous and allogeneic marrow transplantation for acute leukemias and malignant lymphoma is reviewed and compared to the current status of conventional chemotherapy. Based on the reviewed literature, it is concluded that marrow transplantation and conventional chemoradiotherapy are not mutually exclusive and that for most young patients with acute hematological malignancies the question is not if, but rather when to intervene with a marrow transplant treatment. Thus marrow transplantation and conventional chemoradiotherapy can work as complimentary units in the complex therapeutic approach needed to cure most patients with hematological malignancies.
Delay-Constrained Capacity of the IEEE 802.11 DCF in Wireless Multihop Networks

Gamal et al. showed that the end-to-end delay is <inline-formula><tex-math notation="LaTeX">$n$</tex-math> <alternatives><inline-graphic xlink:type="simple" xlink:href="kim-ieq1-2457422.gif"/></alternatives></inline-formula> times the end-to-end throughput under the centralized TDMA scheduling <xref ref-type="bibr" rid="ref4">[4]</xref> where <inline-formula> <tex-math notation="LaTeX">$n$</tex-math><alternatives><inline-graphic xlink:type="simple" xlink:href="kim-ieq2-2457422.gif"/> </alternatives></inline-formula> is the number of nodes in the network, and defined this relationship as the optimal tradeoff between the end-to-end throughput and the end-to-end delay. The main purpose of this paper is to show whether this tradeoff relationship is established when IEEE 802.11 DCF is used. We mathematically express the end-to-end throughput and the end-to-end delay as a function of carrier sensing range and packet generation rate. We optimally control them in order to derive a delay-constrained capacity, the maximum value among the end-to-end throughput in which the end-to-end delay requirement is satisfied. As a result, we show that IEEE 802.11 DCF can establish the optimal tradeoff relationship in <xref ref-type="bibr" rid="ref4">[4]</xref>. This indicates that the optimally controlled parameters can compensate the loss from the difference between the centralized TDMA scheduling and IEEE 802.11 DCF.
The Oyster River Protocol: a multi-assembler and kmer approach for de novo transcriptome assembly

Characterizing transcriptomes in non-model organisms has resulted in a massive increase in our understanding of biological phenomena. This boon, largely made possible via high-throughput sequencing, means that studies of functional, evolutionary and population genomics are now being done by hundreds or even thousands of labs around the world. For many, these studies begin with a de novo transcriptome assembly, which is a technically complicated process involving several discrete steps. The Oyster River Protocol (ORP), described here, implements a standardized and benchmarked set of bioinformatic processes, resulting in an assembly with enhanced qualities over other standard assembly methods. Specifically, ORP produced assemblies have higher Detonate and TransRate scores and mapping rates, which is largely a product of the fact that it leverages a multi-assembler and kmer assembly process, thereby bypassing the shortcomings of any one approach. These improvements are important, as previously unassembled transcripts are included in ORP assemblies, resulting in a significant enhancement of the power of downstream analysis. Further, as part of this study, I show that assembly quality is unrelated with the number of reads generated, above 30 million reads. Code Availability: The version controlled open-source code is available at https://github.com/macmanes-lab/Oyster_River_Protocol. Instructions for software installation and use, and other details are available at http://oyster-river-protocol.rtfd. org/.