Miracle-dz/UniFAR-FTUs huggingface dataset:
Attosecond single-cycle undulator light: a review

Research at modern light sources continues to improve our knowledge of the natural world, from the subtle workings of life to matter under extreme conditions. Free-electron lasers, for instance, have enabled the characterization of biomolecular structures with sub-ångström spatial resolution, and paved the way to controlling the molecular functions. On the other hand, attosecond temporal resolution is necessary to broaden our scope of the ultrafast world. Here we discuss attosecond pulse generation beyond present capabilities. Furthermore, we review three recently proposed methods of generating attosecond x-ray pulses. These novel methods exploit the coherent radiation of microbunched electrons in undulators and the tailoring of the emitted wavefronts. The computed pulse energy outperforms pre-existing technologies by three orders of magnitude. Specifically, our simulations of the proposed Soft X-ray Laser at MAX IV (Lund, Sweden) show that a pulse duration of 50–100 as and a pulse energy up to 5 J is feasible with the novel methods. In addition, the methods feature pulse shape control, enable the incorporation of orbital angular momentum, and can be used in combination with modern compact free-electron laser setups.
RNA element discovery from germ cell to blastocyst

Abstract Recent studies have shown that tissue-specific transcriptomes contain multiple types of RNAs that are transcribed from intronic and intergenic sequences. The current study presents a tool for the discovery of transcribed, unannotated sequence elements from RNA-seq libraries. This RNA Element (RE) discovery algorithm (REDa) was applied to a spectrum of tissues and cells representing germline, embryonic, and somatic tissues and examined as a function of differentiation through the first set of cell divisions of human development. This highlighted extensive transcription throughout the genome, yielding previously unidentified human spermatogenic RNAs. Both exonic and novel X-chromosome REs were subject to robust meiotic sex chromosome inactivation, although an extensive de-repression occurred in the post-meiotic stages of spermatogenesis. Surprisingly, 2.4% of the 10,395 X chromosome exonic REs were present in mature sperm. Transcribed genomic repetitive sequences, including simple centromeric repeats, HERVE and HSAT1, were also shown to be associated with RE expression during spermatogenesis. These results suggest that pervasive intergenic repetitive sequence expression during human spermatogenesis may play a role in regulating chromatin dynamics. Repetitive REs switching repeat classes during differentiation upon fertilization and embryonic genome activation was evident.
Reduced delivery of epididymal adipocyte‐derived exosomal resistin is essential for melatonin ameliorating hepatic steatosis in mice

Adipocyte‐derived exosomes (Exos) serve as bioinformation‐containing messengers in cell‐to‐cell communications, and numerous reports demonstrate that resistin, an adipokine, is strongly associated with hepatic steatosis and other fatty liver diseases, suggesting that adipose dysfunction‐generated altered pattern of exosomal cytokines may contribute to shaping the physiological activities in liver. Admittedly, melatonin‐mediated positive effects on various tissues/organs have been respectively reported, but regulatory mechanisms of melatonin on the crosstalk between adipose tissue and liver have been investigated rarely. Overall, we hypothesize that the crosstalk originating from adipose tissue may be another worthy regulatory pathway for melatonin ameliorating of hepatic steatosis. Here, we first found the amount of adipocyte‐derived exosomal resistin to be significantly decreased by melatonin supplementation. Compared to mice with ExosHFD or Exosresistin treatment, ExosMT remarkably ameliorated hepatic steatosis. Further test demonstrated that resistin was a pivotal cytokine which repressed phosphorylation of 5′ adenosine monophosphate‐activated protein kinase α (pAMPKα Thr172) to trigger endoplasmic reticulum (ER) stress, resulting in hepatic steatosis, whereas ExosMT reversed these risks in hepatocytes. In adipocytes, we identified melatonin to reduce the production of resistin through the brain and muscle arnt‐like protein 1 (Bmal1) transcriptional inhibition. Notably, we also confirmed that melatonin enhanced N6‐Methyladenosine (m6A) RNA demethylation to degrade resistin mRNA in adipocytes. Overall, melatonin decreases traffic volume of adipocyte‐generated exosomal resistin from adipocytes to hepatocytes, which further alleviates ER stress‐induced hepatic steatosis. Our findings illustrate a novel melatonin‐mediated regulatory pathway from adipocytes to hepatocytes, indicating that adipocyte‐derived exosome is a new potential target for treating obesity and related hepatorenal syndrome.
Maternal hemodynamic responses to two different types of moderate physical exercise during pregnancy: a randomized clinical trial

Background/Aim: Maternal hemodynamic responses (heart rate, systolic and diastolic blood pressure) were compared during two types of moderate-intensity physical exercise. Methods: A randomized clinical trial compared 120 pregnant women performing physical exercise on a treadmill (n=64) or stationary bicycle (n=56). In 44 of these women (n=23 treadmill; n=21 bicycle), blood pressure was monitored for 24 hours following exercise. Repeated-measures analysis compared maternal heart rate, systolic and diastolic blood pressure before, during and in the 24 hours following exercise in both groups. Results: Maternal heart rate increased significantly (p<0.001) with both types of exercise (from 84 at rest to 112 bpm on the treadmill and from 87 at rest to 107 bpm on the bicycle), without exceeding the limit of 140 bpm. Systolic pressure increased from 110 at rest to 118 mmHg on the bicycle (p=0.06) and from 112 at rest to 120 mmHg on the treadmill (p=0.02). Systolic pressure dropped steadily following exercise, reaching its lowest level (104 mmHg) after 14 hours, increasing thereafter and returning to pre-exercise levels by the 19th hour. Diastolic pressure increased during exercise irrespective of the type of exercise (p=0.27), from 70 at rest to 75 mmHg on the bicycle (p=0.39) and from 70 at rest to 76 mmHg on the treadmill (p=0.18), with the lowest level (59 mmHg) being at the 13th hour. Conclusions: A slight increase in blood pressure levels was found during exercise; however, this was not clinically significant and was followed by a substantial hypotensive effect that lasted around 19 hours. Register: Clinical Trials NCT01383889.
From confusion noise to active learning : playing on label availability in linear classification problems

Les travaux presentes dans cette these relevent de l'etude des methodes de classification lineaires, c'est a dire l'etude de methodes ayant pour but la categorisation de donnees en differents groupes a partir d'un jeu d'exemples, prealablement etiquetes, disponible en amont et appeles ensemble d'apprentissage. En pratique, l'acquisition d'un tel ensemble d'apprentissage peut etre difficile et/ou couteux, la categorisation d'un exemple etant de fait plus ardu que l'obtention de dudit exemple. Cette disparite entre la disponibilite des donnees et notre capacite a constituer un ensemble d'apprentissage etiquete a ete un des problemes centraux de l'apprentissage automatique et ce manuscrit s’interesse a deux solutions usuellement considerees pour contourner ce probleme : l'apprentissage en presence de donnees bruitees et l'apprentissage actif.
Safety and Tolerability of Omalizumab: A Randomized Clinical Trial of Humanized Anti‐IgE Monoclonal Antibody in Systemic Lupus Erythematosus

Autoreactive IgE antibodies have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesize that omalizumab, a monoclonal antibody binding IgE, may improve SLE activity by reducing type I interferon (IFN) production by hampering plasmacytoid dendritic cells and basophil activation. This study was undertaken to assess the safety, tolerability, and clinical efficacy of omalizumab in mild to moderate SLE.
A Lipidomics Study Reveals Lipid Signatures Associated with Early Allograft Dysfunction in Living Donor Liver Transplantation

Liver transplantation has become the ultimate treatment for patients with end stage liver disease. However, early allograft dysfunction (EAD) has been associated with allograft loss or mortality after transplantation. We aim to utilize a metabolomic platform to identify novel biomarkers for more accurate correlation with EAD using blood samples collected from 51 recipients undergoing living donor liver transplantation (LDLT) by 1H-nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography coupled with mass spectrometry (LC-MS). Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were used to search for a relationship between the metabolomic profiles and the presence of EAD.Cholesteryl esters (CEs), triacylglycerols (TGs), phosphatidylcholines (PCs) and lysophosphatidylcholine (lysoPC) were identified in association with EAD and a combination of cholesterol oleate, PC (16:0/16:0), and lysoPC (16:0) gave an optimal area under the curve (AUC) of 0.9487 and 0.7884 in the prediction of EAD and in-hospital mortality, respectively after LDLT. Such biomarkers may add as a potential clinical panel for the prediction of graft function and mortality after LDLT.
Better Ask Than Tell: Responses to mHealth Interrogative Reminders and Associations With Colorectal Cancer Screening Subsequent Uptake in a Prospective Cohort Intervention

Background Text message (short message service, SMS) interrogative reminders were adopted in population screening for the early detection of colorectal cancer (CRC). Objective This study aims to examine responses to text message (SMS) reminders and associate responses with senders’ characteristics, message type (interrogative/declarative), and subsequent screening uptake. Methods We conducted a prospective cohort intervention. Text message (SMS) reminders to undergo CRC screening, randomized into interrogative and declarative phrasing, were sent to nonadherent 40,000 women and men (age 50-74 years) at CRC average risk. We analyzed recipient responses by message phrasing, recipient characteristics, and for content, the latter predicting subsequent CRC screening per program database. Results While interrogative text message (SMS) reminders elicited 7.67% (1475/19,227) responses, declarative ones elicited 0.76% (146/19,262) responses. Text message (SMS) responses were content analyzed and grouped into attitudes toward CRC screening (1237/1512, 81.8% positive) and intention to screen (1004/1512, 62.6%). Text message (SMS) respondents screened significantly more than nonrespondents after 6 months (415/1621, 25.6% vs 3322/36,868, 9.0%; χ12=487.5, P<.001); 1 year (340/1621, 21.0% vs 4711/36,868; χ12=91.5, P<.001); and 2 years (225/1621, 13.9% vs 3924/36,868; χ12=16.9, P<.001) following the reminders. In a multivariable logistic regression among text message (SMS) respondents, screening after 6 months was significantly predicted by older age, past sporadic screening, attitudes, and intentions. Conclusions Interrogative text message (SMS) reminders reached previously uninvolved sectors in the CRC target population—men, sporadic-screenees, and the “never-tested” before. This novel application resulted in a population-level, incrementally enhanced screening. Asking patients about their future health behavior may be relevant for enhancing other health behaviors in preventive medicine and clinical settings.
Two‐Terminal Multibit Optical Memory via van der Waals Heterostructure

2D van der Waals (vdWs) heterostructures exhibit intriguing optoelectronic properties in photodetectors, solar cells, and light‐emitting diodes. In addition, these materials have the potential to be further extended to optical memories with promising broadband applications for image sensing, logic gates, and synaptic devices for neuromorphic computing. In particular, high programming voltage, high off‐power consumption, and circuital complexity in integration are primary concerns in the development of three‐terminal optical memory devices. This study describes a multilevel nonvolatile optical memory device with a two‐terminal floating‐gate field‐effect transistor with a MoS2/hexagonal boron nitride/graphene heterostructure. The device exhibits an extremely low off‐current of ≈10−14 A and high optical switching on/off current ratio of over ≈106, allowing 18 distinct current levels corresponding to more than four‐bit information storage. Furthermore, it demonstrates an extended endurance of over ≈104 program–erase cycles and a long retention time exceeding 3.6 × 104 s with a low programming voltage of −10 V. This device paves the way for miniaturization and high‐density integration of future optical memories with vdWs heterostructures.
Change in the incidence and severity of Retinopathy of Prematurity (ROP) in a Neonatal Intensive Care Unit in Northern India after 20 years: Comparison of two similar prospective cohort studies

ABSTRACT Purpose: To report the change in incidence and severity of retinopathy of prematurity (ROP) in the neonatal unit of a tertiary hospital after a 20-year period. Methods: A prospective cohort study of one-year duration was conducted between July 2013 and June 2014 in the neonatal intensive care unit (NICU) of a tertiary hospital. Inborn babies with birth weight ≤1700 g and gestational age ≤37 weeks were included. Change in incidence and severity of ROP were compared to a similar study in the same NICU between January and December 1993. Results: The 2013 study included higher numbers of newborn infants than the 1993 study (293 vs. 157). The mean (SD) birth weight and gestational age of the infants in the 2013 study were significantly lower than the 1993 study [1288.6 (229.8) vs. 1378.1 (232.6) g); p = 0.0001 and 31.7 (2.1) vs. 32.2 (2.31) weeks; p = 0.04]. Nevertheless, the overall incidence of ROP decreased from 49% to 26.6% (p < 0.001) after the 20-year interval. The incidence of stage 3 ROP decreased non-significantly from 24.7% to 12.8% (p = 0.058). Multivariate logistic regression analysis showed that birth weight ≤1250 g and belonging to the 1993 cohort were independently associated with an increased risk of ROP after adjusting for covariates (p = 0.013). Conclusion: The incidence of ROP improved significantly over a 20-year period in association with improved NICU management strategies despite an increase in the number of eligible neonates with lower birth weights and gestational ages.
Potency of descending pain modulatory system is linked with peripheral sensory dysfunction in fibromyalgia

Abstract Fibromyalgia (FM) is characterized by chronic widespread pain whose pathophysiological mechanism is related to central and peripheral nervous system dysfunction. Neuropathy of small nerve fibers has been implicated due to related pain descriptors, psychophysical pain, and neurophysiological testing, as well as skin biopsy studies. Nevertheless, this alteration alone has not been previously associated to the dysfunction in the descending pain modulatory system (DPMS) that is observed in FM. We hypothesize that they associated, thus, we conducted a cross-sectional exploratory study. To explore small fiber dysfunction using quantitative sensory testing (QST) is associated with the DPMS and other surrogates of nociceptive pathways alterations in FM. We run a cross-sectional study and recruited 41 women with FM, and 28 healthy female volunteers. We used the QST to measure the thermal heat threshold (HTT), heat pain threshold (HPT), heat pain tolerance (HPT), heat pain tolerance (HPTo), and conditional pain modulation task (CPM-task). Algometry was used to determine the pain pressure threshold (PPT). Scales to assess catastrophizing, anxiety, depression, and sleep disturbances were also applied. Serum brain-derived neurotrophic factor (BDNF) was measured as a marker of neuroplasticity. We run multivariate linear regression models by group to study their relationships. Samples differed in their psychophysical profile, where FM presented lower sensitivity and pain thresholds. In FM but not in the healthy subjects, regression models revealed that serum BDNF was related to HTT and CPM-Task (Hotelling Trace = 1.80, P < .001, power = 0.94, R2 = 0.64). HTT was directly related to CPM-Task (B = 0.98, P = .004, partial-&eegr;2 = 0.25), and to HPT (B = 1.61, P = .008, partial &eegr;2 = 0.21), but not to PPT. Meanwhile, BDNF relationship to CPM-Task was inverse (B = –0.04, P = .043, partial-&eegr;2 = 0.12), and to HPT was direct (B = –0.08, P = .03, partial-&eegr;2 = 0.14). These findings high spot that in FM the disinhibition of the DPMS is positively correlated with the dysfunction in peripheral sensory neurons assessed by QST and conversely with serum BDNF.
An amylopullulanase (ApuNP1) from Geobacillus thermoleovorans NP1: biochemical characterization and its potential industrial applications

Abstract An amylopullulanase was produced by Geobacillus thermoleovorans NP1. The optimum enzyme production occurred at 45°C and pH 7.0 (12 hr). NP1 amylopullulanase (ApuNP1) exhibited the maximal activity at 50°C and pH 6.0 and was stable between 30–50°C, and pH 3.0–12.0 for 24 hr. The enzyme showed two bands with molecular weights of 112 and 107 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The amylopullulanase retained 100% of its activity in the presence of 10 mM of Ca2+, Ba2+, Zn2+, Mg2+, Cu2+, EDTA, and PMSF. While the enzyme showed resistance to 5% of TritonX-100, Tween 20, and Tween 80, the activity was inhibited by 5% β-mercaptoethanol and H2O2. While the hydrolysis products of pullulan were maltose, maltotriose, and maltodextrin, the starch was hydrolyzed to maltose, maltotriose, and maltodextrin units. This shows that NP1 pullulanase is a type II pullulanase (amylopullulanase). After the liquefaction assay, 12% glucose content was measured with a refractometer in the presence of 20% starch. According to the wash performance tests, the mixture of ApuNP1 and 1% detergent removed almost all of the stains. This novel thermo-acidic amylopullulanase has a potency to be used in detergent, starch, food, baking, textile, and cosmetic industries.
B‐factor Guided Proline Substitutions in Chromobacterium violaceum Amine Transaminase: Evaluation of the Proline Rule as a Method for Enzyme Stabilization

Biocatalysis is attracting interest in the chemical industry as a sustainable alternative in large‐scale chemical transformations. However, low operational stability of naturally evolved enzymes is a challenge and major efforts are required to engineer protein stability, usually by directed evolution. The development of methods for protein stabilization based on rational design is of great interest, as it would minimize the efforts needed to generate stable enzymes. Here we present a rational design strategy based on proline substitutions in flexible areas of the protein identified by analyzing B‐factors. Several proline substitutions in the amine transaminase from Chromobacterium violaceum were shown to have a positive impact on stability with increased half‐life at 60 °C by a factor of 2.7 (variant K69P/D218P/K304P/R432P) as well as increased melting temperature by 8.3 °C (variant K167P). Finally, the presented method utilizing B‐factor analysis in combination with the proline rule was deemed successful at increasing the stability of this enzyme.
Drug-Eluting Stents Versus Bare-Metal Stents in Saphenous Vein Graft Intervention: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Percutaneous coronary intervention with drug-eluting stents (DES) has been increasingly used for revascularization of saphenous vein graft stenosis without strong clinical evidence favoring their use. Randomized controlled trials comparing DES versus bare-metal stents (BMS) in saphenous vein graft–percutaneous coronary intervention have been inconclusive. Methods and Results: We performed a comprehensive literature search through May 15, 2018, for all eligible studies comparing DES versus BMS in patients with saphenous vein graft stenosis in PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov. Clinical outcomes included all-cause mortality, cardiovascular mortality, major adverse cardiovascular events, myocardial infarction, stent thrombosis, and target vessel revascularization. Six randomized controlled trials were eligible and included 1582 patients, of whom 797 received DES and 785 received BMS. The follow-up period ranged from 18 months to 60 months. There was no statistically significant difference between DES and BMS for all-cause mortality (risk ratio [RR],1.11; 95% CI, 0.0.77–1.62; P=0.57), cardiovascular mortality (RR, 1.00; 95% CI, 0.64–1.57; P=0.99), major adverse cardiovascular events (RR, 0.83; 95% CI, 0.63–1.10; P=20), target vessel revascularization (RR, 0.73; 95% CI, 0.48–1.11; P=0.14), myocardial infarction (RR, 0.74; 95% CI, 0.48–1.16; P=0.19), or stent thrombosis (RR, 1.06; 95% CI, 0.42–2.65; P=0.90). Conclusions: In patients undergoing percutaneous coronary intervention for saphenous vein graft lesions, our results showed that there was no significant difference between DES and BMS for mortality, major adverse cardiovascular events, target vessel revascularization, myocardial infarction, or stent thrombosis.
The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.

Mycobacterium tuberculosis, responsible tuberculosis (TB), remains the leading cause of mortality among infectious diseases worldwide from a single infectious agent, with an estimated 1.7 million deaths in 2016. Biotin is an essential cofactor in M. tuberculosis that is required for lipid biosynthesis and gluconeogenesis. M. tuberculosis relies on de novo biotin biosynthesis to obtain this vital cofactor since it cannot scavenge sufficient biotin from a mammalian host. The biotin biosynthetic pathway in M. tuberculosis has been well studied and rigorously genetically validated providing a solid foundation for medicinal chemistry efforts. This review examines the mechanism and structure of the enzymes involved in biotin biosynthesis and ligation, summarizes the reported genetic validation studies of the pathway, and then analyzes the most promising inhibitors and natural products obtained from structure-based drug design and phenotypic screening.
Radioprotective Activity and Preliminary Mechanisms of N-oxalyl-d-phenylalanine (NOFD) In Vitro

The radiation-induced damage to the human body is primarily caused by excessive reactive oxygen species (ROS) production after irradiation. Therefore, the removal of the increase of ROS caused by ionizing radiation (IR) has been the focus of research on radiation damage protective agents. Hypoxia inducible factor (HIF) is a transcription factor in human and plays an important role in regulating the body metabolism. Factor inhibiting HIF (FIH) is an endogenous inhibitor factor of HIF protein under normoxia conditions. It has been shown that the high expression of HIF protein has a certain repair effect on radiation-induced intestinal injury and hematopoietic system damage in mice; however, it is not clear about the effect of HIF on the level of ROS after radiation. In this study, the role of N-oxalyl-d-phenylalanine (NOFD), an FIH inhibitor, for its effect on alleviating ROS level is investigated in the cells. Our results indicate that pretreatment with NOFD can mitigate ROS level and alleviate IR-induced DNA damage and apoptosis in vitro. Therefore, HIF can be used as a target on scavengers. Furthermore, in order to explore the relevant mechanism, we also test the expression of relevant HIF downstream genes in the cells, finding that Notch-2 gene is more sensitive to NOFD treatment. This experiment result is used to support the subsequent mechanism experiments.