Miracle-dz/UniFAR-FTUs huggingface dataset:
Site-specific recruitment of epigenetic factors with a modular CRISPR/Cas system

AbSTRACT Dissecting the complex network of epigenetic modifications requires tools that combine precise recognition of DNA sequences with the capability to modify epigenetic marks. The CRISPR/Cas system has been proven to be a valuable addition to existing methodologies that fulfill these tasks. So far, sequence-specific editing of epigenetic modifications such as DNA methylation and histone posttranslational modifications relied on direct fusions of enzymatically inactivated Cas9 (dCas9) with epigenetic effectors. Here, we report a novel, modular system that facilitates the recruitment of any GFP-tagged protein to desired genomic loci. By fusing dCas9 to a GFP-binding nanobody (GBP) we demonstrate that prevalent epigenetic modifications at mouse major satellite repeats can be erased or set de novo by recruiting GFP-coupled catalytic domains of TET1 and DNMT3A, respectively. Furthermore, we construct an inducible expression system that enables a temporally controlled expression of both GBP-dCas9 and the effector protein. Thus, our approach further expands the CRISPR/Cas toolbox for site-specific manipulation of epigenetic modifications with a modular and easy-to-use system.
Serum Glycan Signatures of Gastric Cancer

Glycomics, a comprehensive study of glycans expressed in biologic systems, is emerging as a simple yet highly sensitive diagnostic tool for disease onset and progression. This study aimed to use glycomics to investigate glycan markers that would differentiate patients with gastric cancer from those with nonatrophic gastritis. Patients with duodenal ulcer were also included because they are thought to represent a biologically different response to infection with Helicobacter pylori, a bacterial infection that can cause either gastric cancer or duodenal ulcer. We collected 72 serum samples from patients in Mexico City that presented with nonatrophic gastritis, duodenal ulcer, or gastric cancer. N-glycans were released from serum samples using the generic method with PNGase F and were analyzed by matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron resonance mass spectrometry. The corresponding glycan compositions were calculated based on accurate mass. ANOVA-based statistical analysis was performed to identify potential markers for each subgroup. Nineteen glycans were significantly different among the diagnostic groups. Generally, decreased levels of high-mannose–type glycans, glycans with one complex type antenna, bigalactosylated biantennary glycans, and increased levels of nongalactosylated biantennary glycans were observed in gastric cancer cases. Altered levels of serum glycans were also observed in duodenal ulcer, but differences were generally in the same direction as gastric cancer. Serum glycan profiles may provide biomarkers to differentiate gastric cancer cases from controls with nonatrophic gastritis. Further studies will be needed to validate these findings as biomarkers and identify the role of protein glycosylation in gastric cancer pathology. Cancer Prev Res; 7(2); 226–35. ©2013 AACR.
Identification of holocarboxylase synthetase chromatin binding sites in human mammary cell lines using the DamID technology

Holocarboxylase synthetase (HCS) is a chromatin protein that is essential for mediating the covalent binding of biotin to histones. Biotinylation of histones plays crucial roles in the repression of genes and repeats in the human genome. We tested the feasibility of DNA adenine methyltransferase identification (DamID) technology to map HCS binding sites in human mammary cell lines. Full-length HCS was fused to Dam for subsequent transfection into breast cancer (MCF-7) and normal breast (MCF-10A) cells. HCS docking sites in chromatin were identified by using the unique adenine methylation sites established by Dam in the fusion construct; docking sites were unambiguously identified using methylation sensitive digestion, cloning, and sequencing. Fifteen novel HCS binding sites were identified in the two cell lines and the following four out of the 15 overlapped between MCF-7 and MCF-10A cells: inositol polyphosphate-5-phosphatase A, corticotropin hormone precursor, ribosome biogenesis regulatory protein, and leptin precursor. We conclude that DamID is a useful technology to map HCS binding sites in human chromatin and propose that the entire set of HCS binding sites could be mapped by combining DamID with microarray technology.
New and old agents in the management of diabetic nephropathy

Purpose of reviewDiabetic nephropathy is a long-standing complication of diabetes mellitus and is responsible for more than 40% of end-stage renal disease cases in developed countries. Unfortunately, conventional renin–angiotensin–aldosterone system (RAAS) inhibitor medications only partially protect against the development and progression of diabetic nephropathy. Moreover, RAAS inhibitors have failed as primary prevention therapy in type 1 diabetes. Thus, agents targeting alternative pathogenic mechanisms leading to diabetic nephropathy have been intensively investigated, which is the topic of this review. Recent findingsPromising emerging agents have targeted neurohormonal activation (alternative components of the RAAS and neprilysin inhibition), tubuloglomerular feedback mechanisms (sodium glucose cotransporter 2 inhibition and incretin-based therapy) and renal inflammation/fibrosis. SummaryEvidence demonstrating the potential of these agents to protect and prevent progression of diabetic nephropathy is summarized in this review. There are dedicated clinical trials ongoing with these therapies, which have the potential to change the clinical practice.
Task Assignment and Path Planning for Multiple Autonomous Underwater Vehicles Using 3D Dubins Curves †

This paper investigates the task assignment and path planning problem for multiple AUVs in three dimensional (3D) underwater wireless sensor networks where nonholonomic motion constraints of underwater AUVs in 3D space are considered. The multi-target task assignment and path planning problem is modeled by the Multiple Traveling Sales Person (MTSP) problem and the Genetic Algorithm (GA) is used to solve the MTSP problem with Euclidean distance as the cost function and the Tour Hop Balance (THB) or Tour Length Balance (TLB) constraints as the stop criterion. The resulting tour sequences are mapped to 2D Dubins curves in the X−Y plane, and then interpolated linearly to obtain the Z coordinates. We demonstrate that the linear interpolation fails to achieve G1 continuity in the 3D Dubins path for multiple targets. Therefore, the interpolated 3D Dubins curves are checked against the AUV dynamics constraint and the ones satisfying the constraint are accepted to finalize the 3D Dubins curve selection. Simulation results demonstrate that the integration of the 3D Dubins curve with the MTSP model is successful and effective for solving the 3D target assignment and path planning problem.
Avian Influenza Viruses Infect Primary Human Bronchial Epithelial Cells Unconstrained by Sialic Acid α2,3 Residues

Avian influenza viruses (AIV) are an important emerging threat to public health. It is thought that sialic acid (sia) receptors are barriers in cross-species transmission where the binding preferences of AIV and human influenza viruses are sias α2,3 versus α2,6, respectively. In this study, we show that a normal fully differentiated, primary human bronchial epithelial cell model is readily infected by low pathogenic H5N1, H5N2 and H5N3 AIV, which primarily bind to sia α2,3 moieties, and replicate in these cells independent of specific sias on the cell surface. NHBE cells treated with neuraminidase prior to infection are infected by AIV despite removal of sia α2,3 moieties. Following AIV infection, higher levels of IP-10 and RANTES are secreted compared to human influenza virus infection, indicating differential chemokine expression patterns, a feature that may contribute to differences in disease pathogenesis between avian and human influenza virus infections in humans.
A Content Analysis of Testosterone Websites: Sex, Muscle, and Male Age-Related Thematic Differences

Male testosterone supplementation is a large and growing industry. How is testosterone marketed to male consumers online? The present exploratory study entailed a content coding analysis of the home pages of 49 websites focused on testosterone supplementation for men in the United States. Four hypotheses concerning anticipated age-related differences in content coding were also tested: more frequent longevity content toward older men, and more frequent social dominance/physical formidability, muscle, and sex content toward younger men. Codes were created based on inductive observations and drawing upon the medical, life history, and human behavioral endocrinology literatures. Approximately half (n = 24) of websites were oriented toward younger men (estimated audience of men 40 years of age or younger) and half (n = 25) toward older men (estimated audience over 40 years of age). Results indicated that the most frequent content codes concerned online sales (e.g., product and purchasing information). Apart from sales information, the most frequent codes concerned, in order, muscle, sex/sexual functioning, low T, energy, fat, strength, aging, and well-being, with all four hypotheses also supported. These findings are interpreted in the light of medical, evolutionary life history, and human behavioral endocrinology approaches.
Self-Contained Resonant Rectifier for Piezoelectric Sources Under Variable Mechanical Excitation

A rectification scheme is proposed for increasing the available output power of electrical generators that have a high output capacitance. The proposed rectifier could be useful in increasing the output power of piezoelectric generators (PZG) that convert mechanical vibrations into electrical power. The improvement is achieved by a resonant circuit that self commutates the voltage across the output terminals of the PZG and thereby eliminates the shunting of the output current by the output capacitor. A low-consumption circuit synchronously controls the operation of the resonant rectifier by detecting voltage transitions across the generator. The presented resonant rectifier was experimentally verified by connecting it to a PZG as well as to a PZG emulator. The results show that, under constant harmonic excitation, the proposed circuit can significantly increase the extracted power by up to 230% as compared to a conventional bridge rectifier. The feasibility of using the proposed topology as a self-powered system driven by variable excitation was investigated experimentally as well. In particular, the system was driven by two types of excitation source: amplitude modulated and frequency modulated. It was found that the proposed circuit increases the extracted power by 160% and 172% for AM and FM excitations, respectively.
The effect of progesterone use in the first trimester on fetal nuchal translucency

Objective: To evaluate the possible association between progesterone use in the first trimester of pregnancy and fetal nuchal translucency (NT). Material and Methods: This is an observational case-control study, which was conducted with patients who underwent nuchal scans between March 2015 and February 2016 and consequently delivered live and healthy babies. The study group was composed of assisted reproductive technology pregnancies and used intravaginal progesterone 180 mg/day until gestational week 12. The control group comprised pregnant women who became pregnant spontaneously without using any progesterone preparation in the first trimester. Results: One hundred sixty-four (57.5%) of 285 patients were in the control group and 121 (42.5%) were in the progesterone group. Age, bodyweight, gravidity, and parity number of previous births and abortus, gestational week, crown-rump lengths, free β-human chorionic gonadotropin, pregnancy-associated plasma protein A, and NT values of the progesterone and control groups were recorded and we investigated whether there was a statistically significant difference between the two groups in terms of these parameters; maternal weight was found to be higher in the progesterone group than in the control group and the difference between the groups was statistically significant (p=0.019 and p=0.025). Whether the difference in NT was caused by the effect of maternal weight was investigated using the covariance analysis test and maternal weight was not found to be statistically significant in the model (p=0.284). Conclusion: Fetal NT was increased in the progesterone group compared with the untreated group in healthy pregnancies.
Involvement of melastatin type transient receptor potential 7 channels in ginsenoside Rd-induced apoptosis in gastric and breast cancer cells

Ginsenoside, one of the active ingredients of Panax ginseng, has a variety of physiologic and pharmacologic effects. The purpose of this study was to explore the effects of ginsenoside Rd (G-Rd) on melastatin type transient receptor potential 7 (TRPM7) channels with respect to the proliferation and survival of AGS and MCF-7 cells (a gastric and a breast cancer cell line, respectively). AGS and MCF-7 cells were treated with different concentrations of G-Rd, and caspase-3 activities, mitochondrial depolarizations, and sub-G1 fractions were analyzed to determine if cell death occurred by apoptosis. In addition, human embryonic kidney (HEK) 293 cells overexpressing TRPM7 channels were used to confirm the role of TRPM7 channels. G-Rd inhibited the proliferation and survival of AGS and MCF-7 cells and enhanced caspase-3 activity, mitochondrial depolarization, and sub-G1 populations. In addition, G-Rd inhibited TRPM7-like currents in AGS and MCF-7 cells and in TRPM7 channel overexpressing HEK 293 cells, as determined by whole cell voltage-clamp recordings. Furthermore, TRPM7 overexpression in HEK 293 cells promoted G-Rd induced cell death. These findings suggest that G-Rd inhibits the proliferation and survival of gastric and breast cancer cells by inhibiting TRPM7 channel activity.
Fiction Reading Has a Small Positive Impact on Social Cognition: A Meta-Analysis

Scholars from both the social sciences and the humanities have credited fiction reading with a range of positive real-world social effects. Research in psychology has suggested that readers may make good citizens because fiction reading is associated with better social cognition. But does fiction reading causally improve social cognition? Here, we meta-analyze extant published and unpublished experimental data to address this question. Multilevel random-effects meta-analysis of 53 effect sizes from 14 studies demonstrated that it does: compared to nonfiction reading and no reading, fiction reading leads to a small, statistically significant improvement in social-cognitive performance (g = .15–.16). This effect is robust across sensitivity analyses and does not appear to be the result of publication bias. We recommend that in future work, researchers use more robust reading manipulations, assess whether the effects transfer to improved real-world social functioning, and investigate mechanisms.
Lung Injury Prevention with Aspirin (LIPS-A): a protocol for a multicentre randomised clinical trial in medical patients at high risk of acute lung injury

Introduction Acute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI. Methods and analysis LIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy.
Problem features vs. algorithm performance on rugged multi-objective combinatorial fitness landscapes

In this paper, we attempt to understand and to contrast the impact of performance of randomized search heuristics for black-box multiobjective combinatorial optimization problems. At first, we measure the performance of two conventional dominance-based approaches with unbounded archive on a benchmark of enumerable binary optimization problems with tunable ruggedness, objective space dimension, and objective correlation (ρMNK-landscapes). Precisely, we investigate the expected runtime required by a global evolutionary optimization algorithm with an ergodic variation operator (GSEMO) and by a neighborhood-based local search heuristic (PLS), to identify a -approximation of the Pareto set. Then, we define a number of problem features characterizing the fitness landscape, and we study their intercorrelation and their association with algorithm runtime on the benchmark instances. At last, with a mixed-effects multi-linear regression we assess the individual and joint effect of problem features on the performance of both algorithms, within and across the instance classes defined by benchmark parameters. Our analysis reveals further insights into the importance of ruggedness and multi-modality to characterize instance hardness for this family of multi-objective optimization problems and algorithms.
Airspeed control of electric airplane based on 2-quadrant thrust control and verification with towing test using electric vehicle

Electrical airplanes (EAs) have become practical in the recent years. Considering the increase of demand on smaller aircraft and the attention to environmental issues, the demand on small EAs is expected to grow in the coming decade. However, the accident rate of small aircrafts is higher than that of larger aircrafts, so ensuring higher safety of EA is very urgent. Modeling and thrust control of EAs have been proposed previously by the authors' research group. However, this model and control method is not suitable when the propeller revolution speed is near and below zero. In this paper, the improved thrust control method based on new EA propeller plant is proposed. This method is necessary for design of airspeed control method, which can be expected to improve the safety of EA. A towing test method which allows plane's dynamical experiment on ground is also proposed. Real flight experiment was the only conventional method test a plane's dynamics. However, the test piece needs to be a complete airplane to conduct a real flight. Moreover, it is impossible to observe the response a particular input without interferes from other factors. The proposed method allows component technology to be tested in dynamical situations. The effectiveness of the proposed methods is verified through simulations and experiments.
A 2014 Medical Informatics Perspective on Clinical Decision Support Systems: Do We Hit The Ceiling of Effectiveness?

Summary Objective: To summarize recent research and propose a selection of best papers published in 2013 in the field of computer-based decision support in health care. Method: Two literature reviews were performed by the two section editors from bibliographic databases with a focus on clinical decision support systems (CDSSs) and computer provider order entry in order to select a list of candidate best papers to be peer-reviewed by external reviewers. Results: The full review process highlighted three papers, illustrating current trends in the domain of clinical decision support. The first trend is the development of theoretical approaches for CDSSs, and is exemplified by a paper proposing the integration of family histories and pedigrees in a CDSS. The second trend is illustrated by well-designed CDSSs, showing good theoretical performances and acceptance, while failing to show a clinical impact. An example is given with a paper reporting on scorecards aiming to reduce adverse drug events. The third trend is represented by research works that try to understand the limits of CDSS use, for instance by analyzing interactions between general practitioners, patients, and a CDSS. Conclusions: CDSSs can achieve good theoretical results in terms of sensibility and specificity, as well as a good acceptance, but evaluations often fail to demonstrate a clinical impact. Future research is needed to better understand the causes of this observation and imagine new effective solutions for CDSS implementation.
Advantage of Completely Laparoscopic Gastrectomy With Linear Stapled Reconstruction: A Long-term Follow-up Study

Background:Completely laparoscopic gastrectomy with intracorporeal anastomosis was introduced to achieve safer anastomosis and smaller scars. Although several reports have shown the feasibility of linear-stapled anastomosis, there are no studies of a large number of patients assessing the long-term complications and functional outcomes. Methods:This retrospective study included 345 patients who had intended to undergo completely laparoscopic distal or total gastrectomy with linear-stapled anastomosis between September 2005 and January 2012. This study evaluated both the short- and long-term complications, as well as the endoscopic findings, changes in body weight and serum albumin. Results:Completely laparoscopic gastrectomy was successfully achieved in 342 patients (99.1%). Short-term complications occurred in 59 patients (17.3%). Reconstruction-related complications were observed in 19 patients (5.6%). Three patients with anastomotic leakage required reoperation. No patient experienced anastomotic stenosis over a mean follow-up period of 29.6 months. Two patients underwent an emergency operation for an internal hernia after total gastrectomy. Adhesive intestinal obstruction was observed in 5 patients (1.5%), but all were resolved without surgical intervention. Body weight loss at 2 years after distal and total gastrectomy was 7.2% and 13.9%, which were similar to previous reports of open surgery. Conclusions:Completely laparoscopic gastrectomy with linear-stapled anastomosis is a feasible choice for gastric cancer patients with some potential long-term advantages such as less anastomotic stenosis and fewer adhesive intestinal obstructions.