Miracle-dz/UniFAR-FTUs huggingface dataset:
The human cationic host defense peptide LL‐37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system

The human cathelicidin LL‐37 is a cationic host defense peptide (antimicrobial peptide) expressed primarily by neutrophils and epithelial cells. This peptide, up‐regulated under conditions of inflammation, has immunomodulatory and antimicrobial functions. We demonstrate that LL‐37 is a potent inhibitor of human neutrophil apoptosis, signaling through P2X7 receptors and G‐protein‐coupled receptors other than the formyl peptide receptor‐like‐1 molecule. This process involved modulation of Mcl‐1 expression, inhibition of BID and procaspase‐3 cleavage, and the activation of phosphatidylinositol‐3 kinase but not the extracellular signal‐regulated kinase 1/2 mitogen‐activated protein kinase pathway. In contrast to the inhibition of neutrophil apoptosis, LL‐37 induced apoptosis in primary airway epithelial cells, demonstrating alternate consequences of LL‐37‐mediated modulation of apoptotic pathways in different human primary cells. We propose that these novel immunomodulatory properties of LL‐37 contribute to peptide‐mediated enhancement of innate host defenses against acute infection and are of considerable significance in the development of such peptides and their synthetic analogs as potential therapeutics for use against multiple antibiotic‐resistant infectious diseases.
Carbon/epoxy filament wound composite drive shafts under torsion and compression

Composite cylinders to be used as half shafts must satisfy several requirements, such as critical speed, critical buckling torque, and load carrying ability. This study focused on the investigation of carbon fiber reinforced epoxy composite cylinders produced by filament winding to be used as half shafts. A preliminary torsional test in a [±45]5 cylinder was performed and three other laminates were chosen for the study: [±22/±45], [±89/±45], and [±45/±45]. Radial and longitudinal compression tests were performed. Mechanical analysis has been carried out using analytical and numerical approaches, and good correlation was found between them and the experimental values. The [±45/±45] cylinder showed the best performance under torsional loading, as expected, as well as radial and longitudinal compression, but not critical buckling torque.
Learning orthopaedics: Assessing medical students' experiences of interprofessional training in an orthopaedic clinical education ward

Interprofessional training is becoming commonplace in undergraduate medical education. Orthopaedics is considered to be a setting that offers good opportunities for interprofessional training. Curriculum overload is a common problem, which has to be addressed with respect to content. The aim of this study was to assess medical students' experiences of interprofessional care during their orthopaedic training. Over a two-week period, medical, nursing, physiotherapy and occupational therapy students trained together in teams in an orthopaedic ward (Clinical Education Ward, CEW). A questionnaire was distributed to assess the impact of this new curriculum on medical students. A patient-satisfaction questionnaire was also administered to assess patients' satisfaction with the treatment provided by students at the CEW. In general, the medical students were satisfied with the interprofessional course in the CEW. Of the 178 medical students who took the course, 134 (75%) responded to the questionnaire. Total time devoted to orthopaedics was reported to be between 7 – 44% (mean). The total time regarding medical tasks was reported to be between 57 – 71% (mean). Results from the patient-satisfaction questionnaire showed that patients perceived CEW as highly satisfactory. The medical students reported generally satisfactory experiences of interprofessional orthopaedic training in general. In an interprofessional training context, professional supervision and role modeling takes on added importance, and may be regarded as essential ingredients in helping students to learn effectively within an authentic clinical setting.
Oligomerization of 10,16-Dihydroxyhexadecanoic Acid and Methyl 10,16-Dihydroxyhexadecanoate Catalyzed by Lipases

The main monomer of tomato cuticle, 10,16-dihydroxyhexadecanoic acid (10,16-DHPA) and its methyl ester derivative (methyl-10,16-dihydroxyhexadecanote; methyl-10,16-DHHD), were used to study their oligomerization reactions catalyzed by five lipases: Candida antarctica lipase B (CAL-B), Rhizomucor miehei lipase (RM), Thermomyces lanuginosus lipase (TL), Pseudomonas cepacia lipase (PCL) and porcine pancreatic lipase (PPL). For 10,16-DHPA, optimum yields were obtained at 60 °C using toluene and 2-methyl-2-butanol (2M2B) as solvent, while for methyl-10,16-DHHD the bests yields were obtained in toluene and acetonitrile. Both reactions leaded to linear polyesters according to the NMR and FT-IR analysis, and there was no data indicating the presence of branched polymers. Using optimized conditions, poly(10,16-DHPA) and poly(methyl-10,16-DHHD) with Mw = 814 and Mn = 1,206 Da, and Mw = 982 and Mn = 860 Da, respectively, were formed according to their MALDI-TOF MS and ESI-MS data. The self-assembly of the polyesters obtained were analyzed by AFM.
Person Authentication Using Brainwaves (EEG) and Maximum A Posteriori Model Adaptation

In this paper, we investigate the use of brain activity for person authentication. It has been shown in previous studies that the brainwave pattern of every individual is unique and that the electroencephalogram (EEG) can be used for biometric identification. EEG-based biometry is an emerging research topic and we believe that it may open new research directions and applications in the future. However, very little work has been done in this area and was focusing mainly on person identification but not on person authentication. Person authentication aims to accept or to reject a person claiming an identity, i.e., comparing a biometric data to one template, while the goal of person identification is to match the biometric data against all the records in a database. We propose the use of a statistical framework based on Gaussian mixture models and maximum a posteriori model adaptation, successfully applied to speaker and face authentication, which can deal with only one training session. We perform intensive experimental simulations using several strict train/test protocols to show the potential of our method. We also show that there are some mental tasks that are more appropriate for person authentication than others
Detection of colorectal adenoma and cancer based on transthyretin and C3a‐desArg serum levels

Colorectal cancer is the second leading cause of cancer death, and it develops from benign colorectal adenomas in over 95% of patients. Early detection of these cancer precursors by screening tests and their removal can potentially eradicate more than 95% of colorectal cancers before they develop. To discover sensitive and specific biomarkers for improvement of pre‐clinical diagnosis of colorectal adenoma and cancer, we analysed in two independent studies (n = 87 and n = 83 patients) serum samples from colorectal cancer (stage III), colorectal adenoma and control patients using SELDI‐TOF‐MS. Extensive statistical analysis was performed to establish homogeneous patient groups based on their clinical data. Two biomarkers that were each able to distinguish control patients from either colorectal adenoma or colorectal cancer patients (p<0.001) were identified as transthyretin (pre‐albumin) and C3a‐desArg by MS/MS and were further validated by antibody‐based assays (radial immunodiffusion, ELISA). A combination of both proteins clearly indicated the presence of colorectal adenoma or carcinoma. Using a cut‐off of <0.225 g/L for transthyretin and >1974 ng/mL for C3a‐desArg, we found a sensitivity and specificity for colorectal adenoma of 96% and 70%, respectively.
Mechanisms of the Incretin Effect in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes

The incretin effect on insulin secretion was investigated in 8 subjects with type 2 diabetes (T2D) and 8 with normal glucose tolerance (NGT), using 25, 75, and 125 g oral glucose tolerance tests (OGTT) and isoglycemic intravenous glucose infusions (IIGI). The ß-cell response was evaluated using a model embedding a dose-response (slope = glucose sensitivity), an early response (rate sensitivity), and potentiation (time-related secretion increase). The incretin effect, as OGTT/IIGI ratio, was calculated for each parameter. In NGT, the incretin effect on total secretion increased with dose (1.3±0.1, 1.7±0.2, 2.2±0.2 fold of IIGI, P<0.0001), mediated by a dose-dependent increase of the incretin effect on glucose sensitivity (1.9±0.4, 2.4±0.4, 3.1±0.4, P = 0.005), and a dose-independent enhancement of the incretin effect on rate sensitivity (894 [1145], 454 [516], 783 [1259] pmol m−2 L mmol−1 above IIGI; median [interquartile range], P<0.0001). The incretin effect on potentiation also increased (0.97±0.06, 1.45±0.20, 1.24±0.16, P<0.0001). In T2D, the incretin effect on total secretion (1.0±0.1, 1.1±0.1, 1.3±0.1, P = 0.004) and glucose sensitivity (1.2±0.2, 1.3±0.2, 2.0±0.2, P = 0.005) were impaired vs NGT; however, the incretin effect on rate sensitivity increased already at 25 g (269 [169], 284 [301], 193 [465] pmol m−2 L mmol−1 above IIGI; negligible IIGI rate sensitivity in T2D prevented the calculation of the fold increment). OGTT did not stimulate potentiation above IIGI (0.94±0.04, 0.89±0.06, 1.06±0.09; P<0.01 vs NGT). In the whole group, the incretin effect was inversely associated with total secretion during IIGI, although systematically lower in T2D. In conclusion, 1) In NGT, glucose sensitivity and potentiation mediate the dose-dependent incretin effect increase; 2) In T2D, the incretin effect is blunted vs NGT, but rate sensitivity is enhanced at all loads; 3) Relatively lower incretin effect in NGT is associated with higher secretion during IIGI, suggesting that the reduced incretin effect does not result from ß-cell dysfunction.
Periodic orbits associated with the libration Points of the Homogeneous rotating Gravitating Triaxial Ellipsoid

We present computational results for the families of periodic orbits that emanate from the five libration points of the homogeneous gravitating triaxial ellipsoid rotating around its small axis, as well as for various secondary bifurcating families. Possible applications of our results include research on the motion of stars and clusters in elliptical galaxies, and the design of space missions to the vicinity of small bodies (asteroids) and their libration points. The numerical continuation and bifurcation algorithms employed in our study are based on boundary value techniques, as implemented in the AUTO software tool.
Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi. org/10.7554/eLife.00049. 001
Control of Sulfide Production in High Salinity Bakken Shale Oil Reservoirs by Halophilic Bacteria Reducing Nitrate to Nitrite

Microbial communities in shale oil fields are still poorly known. We obtained samples of injection, produced and facility waters from a Bakken shale oil field in Saskatchewan, Canada with a resident temperature of 60°C. The injection water had a lower salinity (0.7 Meq of NaCl) than produced or facility waters (0.6–3.6 Meq of NaCl). Salinities of the latter decreased with time, likely due to injection of low salinity water, which had 15–30 mM sulfate. Batch cultures of field samples showed sulfate-reducing and nitrate-reducing bacteria activities at different salinities (0, 0.5, 0.75, 1.0, 1.5, and 2.5 M NaCl). Notably, at high salinity nitrite accumulated, which was not observed at low salinity, indicating potential for nitrate-mediated souring control at high salinity. Continuous culture chemostats were established in media with volatile fatty acids (a mixture of acetate, propionate and butyrate) or lactate as electron donor and nitrate or sulfate as electron acceptor at 0.5 to 2.5 M NaCl. Microbial community analyses of these cultures indicated high proportions of Halanaerobium, Desulfovermiculus, Halomonas, and Marinobacter in cultures at 2.5 M NaCl, whereas Desulfovibrio, Geoalkalibacter, and Dethiosulfatibacter were dominant at 0.5 M NaCl. Use of bioreactors to study the effect of nitrate injection on sulfate reduction showed that accumulation of nitrite inhibited SRB activity at 2.5 M but not at 0.5 M NaCl. High proportions of Halanaerobium and Desulfovermiculus were found at 2.5 M NaCl in the absence of nitrate, whereas high proportions of Halomonas and no SRB were found in the presence of nitrate. A diverse microbial community dominated by the SRB Desulfovibrio was observed at 0.5 M NaCl both in the presence and absence of nitrate. Our results suggest that nitrate injection can prevent souring provided that the salinity is maintained at a high level. Thus, reinjection of high salinity produced water amended with nitrate maybe be a cost effective method for souring control.
Compound Embedding Features for Semi-supervised Learning

To solve data sparsity problem, recently there has been a trend in discriminative methods of NLP to use representations of lexical items learned from unlabeled data as features. In this paper, we investigated the usage of word representations learned by neural language models, i.e. word embeddings. The direct usage has disadvantages such as large amount of computation, inadequacy with dealing word ambiguity and rare-words, and the problem of linear non-separability. To overcome these problems, we instead built compound features from continuous word embeddings based on clustering. Experiments showed that the compound features not only improved the performances on several NLP tasks, but also ran faster, suggesting the potential of embeddings.
Subunit Organization of Mcm2-7 and the Unequal Role of Active Sites in ATP Hydrolysis and Viability

ABSTRACT The Mcm2-7 (minichromosome maintenance) complex is a toroidal AAA+ ATPase and the putative eukaryotic replicative helicase. Unlike a typical homohexameric helicase, Mcm2-7 contains six distinct, essential, and evolutionarily conserved subunits. Precedence to other AAA+ proteins suggests that Mcm ATPase active sites are formed combinatorially, with Walker A and B motifs contributed by one subunit and a catalytically essential arginine (arginine finger) contributed by the adjacent subunit. To test this prediction, we used copurification experiments to identify five distinct and stable Mcm dimer combinations as potential active sites; these subunit associations predict the architecture of the Mcm2-7 complex. Through the use of mutant subunits, we establish that at least three sites are active for ATP hydrolysis and have a canonical AAA+ configuration. In isolation, these five active-site dimers have a wide range of ATPase activities. Using Walker B and arginine finger mutations in defined Mcm subunits, we demonstrate that these sites similarly make differential contributions toward viability and ATP hydrolysis within the intact hexamer. Our conclusions predict a structural discontinuity between Mcm2 and Mcm5 and demonstrate that in contrast to other hexameric helicases, the six Mcm2-7 active sites are functionally distinct.
Host-Feeding Patterns of Native Culex pipiens and Invasive Aedes albopictus Mosquitoes (Diptera: Culicidae) in Urban Zones from Barcelona, Spain

ABSTRACT The feeding patterns of haematophagous arthropods are of major importance in the amplification and transmission of infectious disease agents to vertebrate hosts, including humans. The establishment of new vector populations in nonnative range might alter transmission networks. The Asian tiger mosquito Aedes albopictus (Skuse) represents an example of how an invasive species can alter the risk of viral transmission to humans. Blood meal molecular identification from two sympatric mosquito species (the invasive Ae. albopictus and the native Culex pipiens) was carried out by polymerase chain reaction-based methods. Samples were collected in Barcelona metropolitan area, Spain, from June to October 2009 as part of a monitoring-control program. Blood meals were identified to the species level in 30 Ae. albopictus and 43 Cx. pipiens. Ae. albopictus acquired blood exclusively from human hosts (100%), whereas Cx. pipiens fed on a diversity of avian and mammalian hosts, including 35.7% of blood meals from humans. Based on mosquito diet, our results suggest that the Ae. albopictus invasion in Spain might increase the risk of virus transmission to humans and could support local outbreaks of imported tropical viruses such as dengue and chikungunya. However, in the studied area, the presence of this invasive species would have a negligible effect on the transmission of zoonotic agents such as West Nile virus. However, Cx. pipiens could amplify and transmit West Nile virus, but avian contribution to its diet was lower than that reported in North America. Feeding patterns of these mosquito species may help to understand the flavivirus outbreaks recently reported in southwestern Europe.
Anthrolysin O and Other Gram-positive Cytolysins Are Toll-like Receptor 4 Agonists

Exposure of bone marrow–derived macrophages (BMDMs) to low concentrations of Bacillus anthracis lethal toxin (LT), whose catalytic subunit is lethal factor (LF), results in induction of a robust apoptotic response dependent on activation of Toll-like receptor (TLR)4. A similar TLR4-dependent apoptotic response is observed when BMDMs are infected with live B. anthracis (Sterne strain). However, TLR4 is considered to be a specific signaling receptor for lipopolysaccharide (LPS), a typical product of gram-negative bacteria, whereas B. anthracis is gram-positive. To understand how B. anthracis can activate TLR4, we analyzed its culture supernatants and found them to contain a potent TLR4-stimulating activity that can also induce apoptosis in macrophages in which the antiapoptotic p38 MAP kinase (whose activation is prevented by LF) was inhibited. Purification of this activity suggested it consists of anthrolysin O (ALO), a member of the cholesterol-dependent cytolysin (CDC) family. We show that recombinant ALO can activate TLR4 in a manner independent of LPS contamination and, together with LT, can induce macrophage apoptosis. We also provide genetic evidence that ALO is required for induction of macrophage apoptosis in response to infection with live B. anthracis and that other CDC family members share the ability to activate TLR4.
Effects of sex and COMT genotype on environmentally modulated cognitive control in mice

Cognitive functioning differs between males and females, likely in part related to genetic dimorphisms. An example of a common genetic variation reported to have sexually dimorphic effects on cognition and temperament in humans is the Val/Met polymorphism in catechol-O-methyltransferase (COMT). We tested male and female wild-type mice (+/+) and their COMT knockout littermates (+/− and −/−) in the five-choice serial reaction time task (5CSRTT) to investigate the effects of sex, COMT genotype, and their interactions with environmental manipulations of cognitive functions such as attention, impulsivity, compulsivity, motivation, and rule-reversal learning. No sex- or COMT-dependent differences were present in the basic acquisition of the five-choice serial reaction time task. In contrast, specific environmental manipulations revealed a variety of sex- and COMT-dependent effects. Following an experimental change to trigger impulsive responding, the sexes showed similar increases in impulsiveness, but males eventually habituated whereas females did not. Moreover, COMT knockout mice were more impulsive compared with wild-type littermates. Manipulations involving mild stress adversely affected cognitive performance in males, and particularly COMT knockout males, but not in females. In contrast, following amphetamine treatment, subtle sex by genotype and sex by treatment interactions emerged primarily limited to compulsive behavior. After repeated testing, female mice showed improved performance, working harder and eventually outperforming males. Finally, removing the food-restriction condition enhanced sex and COMT differences, revealing that overall, females outperform males and COMT knockout males outperform their wild-type littermates. These findings illuminate complex sex- and COMT-related effects and their interactions with environmental factors to influence specific executive cognitive domains.
Factors predicting the near-final height in growth hormone-treated children and adolescents with chronic kidney disease.

CONTEXT GH therapy is an accepted measure to increase adult height in young prepubertal patients suffering from growth failure related to chronic kidney disease (CKD). The impact of GH therapy on final height (FH) in CKD patients of pubertal age is unclear. OBJECTIVE This study set out to analyze near-FH in a cohort of GH-treated CKD patients. DESIGN, SETTINGS, AND PATIENTS Of 240 evaluable patients in the Pfizer International Growth Database (KIGS) with CKD, 39% were prepubertal and 61% were pubertal at baseline; 45% were on conservative treatment for CKD, 28% were on dialysis, and 27% were in the period after renal transplantation. MAIN OUTCOME MEASURES Near-FH, relation to pubertal stage, and factors predictive of growth response were the main outcome measures. RESULTS Mean height sd scores increased continuously during GH treatment until near-FH by 1.2 and 1.6 in boys and girls, respectively. Mean near-FH differed significantly from prepubertal patients showing severely delayed puberty (-3.6), late pubertal patients (-2.9), early pubertal patients (-2.2), and prepubertal patients with normal onset of puberty (-2.0). The initial degree of stunting, degree of bone age retardation, duration of GH therapy, time spent on conservative treatment/dialysis, pubertal delay (>2 sd), gender, and age at start of GH treatment were significant predictors of growth response to GH therapy, explaining between 33 and 61% of the overall variability. CONCLUSIONS Long-term GH therapy of CKD patients in prepubertal and pubertal age results in an increased adult height, but response is diminished in patients on dialysis and/or with severely delayed puberty.