Miracle-dz/UniFAR-FTUs huggingface dataset:
Human B- and T-cell responses after immunization with a hexavalent PorA meningococcal outer membrane vesicle vaccine

The PorA protein from Neisseria meningitidis, a potential vaccine candidate, induces human bactericidal antibodies which are serosubtype specific. We developed a hexavalent PorA outer membrane vesicle vaccine based on reference strain H44/76. This vaccine contains the six most prevalent PorA serosubtypes as found in many countries. We previously reported on the immune responses of 20 adult volunteers after a single immunization with this vaccine. In this study, the B- and T-cell responses in three adult volunteers were studied after three consecutive immunizations (0, 2, and 11 months). The first immunization induced a strong B-cell response resulting in high immunoglobulin G levels in an outer membrane vesicle enzyme-linked immunosorbent assay. At least a fourfold increase in bactericidal activity was observed against the majority (four to six) of the vaccine antigens compared to prevaccination titers. Immunodominance was observed for one or two of the PorAs in the bactericidal assay with a set of six isogenic H44/76-derived PorA target strains. These strains carry the individual PorAs as present in the vaccine. The second and third immunizations did not induce a further increase in the immune responses. A decline in time with respect to PorA-specific antibodies was observed after each immunization. These observations were reflected by the T-cell proliferation responses. Two additional sets of isogenic H44/76-derived mutant strains were used to study the specificity and/or cross-reactivity of the induced bactericidal antibodies. These target strains differ only in expressing mutant family variants of either PorA P1.7,16 or P1.5,10, both present in the PorA vesicle vaccine. The bactericidal antibody responses found were directed predominantly against the P1.7 (loop 1 of P1.7,16) and the P1.10 (loop 4 of P1.5,10) epitopes. This indicates that different portions of PorA were involved in the induction of bactericidal antibodies depending upon the PorA serosubtype.
Dynamics of Chytridiomycosis during the Breeding Season in an Australian Alpine Amphibian

Understanding disease dynamics during the breeding season of declining amphibian species will improve our understanding of how remnant populations persist with endemic infection, and will assist the development of management techniques to protect disease-threatened species from extinction. We monitored the endangered Litoria verreauxii alpina (alpine treefrog) during the breeding season through capture-mark-recapture (CMR) studies in which we investigated the dynamics of chytridiomycosis in relation to population size in two populations. We found that infection prevalence and intensity increased throughout the breeding season in both populations, but infection prevalence and intensity was higher (3.49 and 2.02 times higher prevalence and intensity, respectively) at the site that had a 90-fold higher population density. This suggests that Bd transmission is density-dependent. Weekly survival probability was related to disease state, with heavily infected animals having the lowest survival. There was low recovery from infection, especially when animals were heavily infected with Bd. Sympatric amphibian species are likely to be reservoir hosts for the disease and can play an important role in the disease ecology of Bd. Although we found 0% prevalence in crayfish (Cherax destructor), we found that a sympatric amphibian (Crinia signifera) maintained 100% infection prevalence at a high intensity throughout the season. Our results demonstrate the importance of including infection intensity into CMR disease analysis in order to fully understand the implications of disease on the amphibian community. We recommend a combined management approach to promote lower population densities and ensure consistent progeny survival. The most effective management strategy to safeguard the persistence of this susceptible species might be to increase habitat area while maintaining a similar sized suitable breeding zone and to increase water flow and area to reduce drought.
GENDER DIFFERENCES IN DOMAIN SPECIFIC SELF-ESTEEM OF ADOLESCENTS

The objective of the present study was to investigate the role of gender in determining the level of domain specific self-esteem in student adolescents of ages between 13 to 18 years. 512 randomly selected school/ college going adolescents (males=273 & females=239) from educational organizations situated in urban area of KarachiPakistan were assessed through a group administration of Pakistani version of Adolescent form (Imran & Ahmad, 2011) of Culture Free Self-esteem Inventories-3 (CFSEI-3; Battle, 2002). t-test was computed for the analysis that shows significant gender differences in the domains of personal (t = 4.52, p< .001), social (t = 2.53, p< .01) and academic (t = - 5.81, p< .001) self-esteem, while no gender differences have been found in general, parent/home and overall self-esteem. Findings of the present research may also have significant implication in the future interventions for enhancing adolescent’s feeling of self-worth and competence, which lead them towards achievement of positive self-growth and better utilization of their potentials.
Rasagiline for the treatment of Parkinson’s disease: an update

Introduction: Rasagiline is a potent, selective, irreversible Monoamine Oxidase-B (MAO-B) inhibitor, developed to prolong the action of dopamine in the brain. It has been demonstrated that rasagiline can improve motor and some non-motor symptoms (NMS) in both early and advanced Parkinson’s disease (PD) patients, and it also exhibits neuroprotective and antiapoptotic properties. Areas covered: The objective of this review, performed by a Medline search on the most recent papers investigating the therapeutic effects of rasagiline, is to describe the role of rasagiline in the schedule of treatment of early and advanced PD patients. It will then focus on its role in treating NMS, fatigue, early morning off and cognitive decline, which heavily affect quality of life for PD patients. Expert opinion: Rasagiline is an efficacious, well-tolerated, easy to use drug. The drug has been extensively studied and has proven its efficacy in monotherapy and in combination with any other antiparkinsonian therapy. It proved to be efficacious in reducing ‘off’ time and in improving early morning ‘off’ but also some NMS, thus enhancing the therapeutic approach to PD.
A sea urchin gene encoding dystrophin-related proteins.

The gene which is defective in Duchenne muscular dystrophy (DMD) is the largest known gene. The product of the gene in muscle, dystrophin, is a 427 kDa protein. The same gene encodes at least six additional products: two non-muscle dystrophin isoforms transcribed from promoters located in the 5'-end region of the gene and four smaller proteins transcribed from internal promoters located further downstream. Several other genes, encoding evolutionarily related proteins, have been identified. These include a structurally very similar gene in vertebrates encoding utrophin (DRP1), which is closely related to dystrophin, and a number of small and simple genes in vertebrates or invertebrates encoding proteins similar to some of the small products of the DMD gene. We have isolated a sea urchin gene showing very strong sequence and structural homology with the DMD and utrophin genes. Sequence and intron/exon structure similarities suggest that this gene is related to a precursor of both the DMD gene and the gene encoding utrophin. The sea urchin gene has the unique complex structure of the DMD gene. There is at least one, and possibly more, product(s) transcribed from internal promoters, as well as a large product of >300 kDa containing at least three of the four major domains of dystrophin. The small product seems to be evolutionarily related to Dp116, one of the small products of the human DMD gene. Partial characterization of this gene helped us to construct an evolutionary tree connecting the vertebrate dystrophin gene family with related genes in invertebrates. The constructed evolutionary tree also implies that the vertebrate small and simple structured gene encoding a Dp71-like protein, called DRP2 , evolved from the dystrophin/utrophin ancestral large and complex gene by a duplication of only a small part of the gene.
Addicting drugs utilize a synergistic molecular mechanism in common requiring adenosine and Gi-βγ dimers

The mesolimbic dopamine system and cAMP-dependent/protein kinase A (PKA) pathways are strongly implicated in addictive behaviors. Here we determine the role of dopamine D2 receptors (D2) in PKA signaling responses to δ-opioid (DOR) and cannabinoid (CB1) receptors. We find in NG108-15/D2 cells and in cultured primary neurons that a brief exposure to saturating concentrations of DOR and CB1 agonists increases cAMP, promotes PKA Cα translocation and increases cAMP-dependent gene expression. Activation of PKA signaling is mediated by Gi-βγ dimers. Importantly, subthreshold concentrations of DOR or CB1 agonists with D2 agonists, which are without effect when added separately, together activate cAMP/PKA signaling synergistically. There is also synergy between DOR or CB1 with ethanol, another addicting agent. In all instances, synergy requires adenosine activation of adenosine A2 receptors and is mediated by βγ dimers. Synergy by this molecular mechanism appears to confer hypersensitivity to opioids and cannabinoids while simultaneously increasing the sensitivity of D2 signaling when receptors are expressed on the same cells. This mechanism may account, in part, for drug-induced activation of medium spiny neurons in the nucleus accumbens.
Voltage Coordination in Multi-Area Power Systems via Distributed Model Predictive Control

This paper proposes a coordination paradigm for properly coordinating local control actions, taken by many communicating control agents (CAs), in order to maintain multi-area power system voltages within acceptable bounds. The proposed control scheme is inspired by distributed model predictive control (DMPC), and relies on the communication of planned local control actions among neighboring CAs, each possibly operated by an independent transmission system operator (TSO). Each CA, knowing a local model of its own area, as well as reduced-order QSS models of its immediate neighboring areas, and assuming a simpler equivalent PV models for its remote neighbors, performs a greedy local optimization over a finite window in time, communicating its planned control input sequence to its immediate neighbors only. The good performance of the proposed real-time model-based feedback coordinating controller, following major disturbances, is illustrated using time-domain simulation of the well-known realistic Nordic32 test system, assuming worst-case conditions.
The neuromuscular differential diagnosis of joint hypermobility

Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers–Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult‐onset inherited myopathies also present with joint hypermobility in the context of often only mild‐to‐moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers–Danlos syndrome, Marfan syndrome and Loeys‐Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers–Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1‐ and SEPN1‐related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders. © 2015 Wiley Periodicals, Inc.
A repetitive based controller for a shunt active filter to compensate for reactive power and harmonic distortion

This paper presents a repetitive-based controller for a single phase active filter to compensate for reactive power and current harmonic distortion, i.e., to guarantee a power factor close to unity. The topology selected for the active filter consists of a single phase full-bridge Voltage Source Inverter (VSI). The controller is based on a frequency domain description of the periodic disturbances. Adaptation is then introduced to cope with uncertainties in the disturbance signals and system parameters. A first observation is that the adaptations are reduced to a bank of resonant filters by means of suitable rotations, which are tuned at the frequencies of the harmonics under compensation. The second observation is that there exists an equivalent expression for such a bank of resonators in terms of a single delay line. Moreover, we show that this new expression for the controller, which belongs to the family of repetitive schemes, has a relatively simple implementation. The proposed control scheme has been experimentally tested in a 1.5 KVA prototype and the results are presented here.
Effects of shear stress on endothelial cells: go with the flow

Haemodynamic forces influence the functional properties of vascular endothelium. Endothelial cells (ECs) have a variety of receptors, which sense flow and transmit mechanical signals through mechanosensitive signalling pathways to recipient molecules that lead to phenotypic and functional changes. Arterial architecture varies greatly exhibiting bifurcations, branch points and curved regions, which are exposed to various flow patterns. Clinical studies showed that atherosclerotic plaques develop preferentially at arterial branches and curvatures, that is in the regions exposed to disturbed flow and shear stress. In the atheroprone regions, the endothelium has a proinflammatory phenotype associated with low nitric oxide production, reduced barrier function and increased proadhesive, procoagulant and proproliferative properties. Atheroresistant regions are exposed to laminar flow and high shear stress that induce prosurvival antioxidant signals and maintain the quiescent phenotype in ECs. Indeed, various flow patterns contribute to phenotypic and functional heterogeneity of arterial endothelium whose response to proatherogenic stimuli is differentiated. This may explain the preferential development of endothelial dysfunction in arterial sites with disturbed flow.
Improved and Promising Identification of Human MicroRNAs by Incorporating a High-Quality Negative Set

MicroRNA (miRNA) plays an important role as a regulator in biological processes. Identification of (pre-) miRNAs helps in understanding regulatory processes. Machine learning methods have been designed for pre-miRNA identification. However, most of them cannot provide reliable predictive performances on independent testing data sets. We assumed this is because the training sets, especially the negative training sets, are not sufficiently representative. To generate a representative negative set, we proposed a novel negative sample selection technique, and successfully collected negative samples with improved quality. Two recent classifiers rebuilt with the proposed negative set achieved an improvement of ~6 percent in their predictive performance, which confirmed this assumption. Based on the proposed negative set, we constructed a training set, and developed an online system called miRNApre specifically for human pre-miRNA identification. We showed that miRNApre achieved accuracies on updated human and non-human data sets that were 34.3 and 7.6 percent higher than those achieved by current methods. The results suggest that miRNApre is an effective tool for pre-miRNA identification. Additionally, by integrating miRNApre, we developed a miRNA mining tool, mirnaDetect, which can be applied to find potential miRNAs in genome-scale data. MirnaDetect achieved a comparable mining performance on human chromosome 19 data as other existing methods.
Offspring sex varies with maternal investment ability: empirical demonstration based on cross-fostering

Despite decades of interest, adaptive explanations for biased offspring sex ratios in mammals remain contentious, largely because direct tests of the underlying fitness assumptions of adaptive hypotheses are rarely conducted. These tests are complicated by the difficulty of manipulating offspring sex prior to significant maternal investment owing to the biological constraints of viviparity. We test the adaptive advantage of sex allocation through cross-fostering offspring by sex in tammar wallabies. We examine whether offspring sex is correlated with maternal investment ability (i.e. Trivers–Willard hypothesis, TWH). In addition, we test the assumption that maternal investment has a greater influence on the fitness of sons than of daughters. We failed to find statistical support for maternal investment ability influencing a son's weaning success or body size more than a daughter's, although this result was probably owing to small sample sizes. In support of the TWH, females that gave birth to a son had higher investment ability (likelihood of weaning an offspring) regardless of the sex of offspring fostered.
Effect of early enteral nutrition after hepatectomy in hepatocellular carcinoma patients

Backgrounds/Aims To evaluate the effect of early enteral nutrition after hepatectomy in hepatocellular carcinoma (HCC) patients on postoperative gastrointestinal motility recovery and admission days, liver function and nutrition recovery, and postoperative complication. Methods From August 2010 to July 2011, 102 patients with primary HCC underwent hepatectomy. Forty two patients took a sip of water (SOW) at postoperative day (POD)#1, soft blended diet (SBD) at POD#2 (early diet group, ED group), otherwise 60 patients took a SOW at POD#3, SBD at POD#4 (conventional diet group, CD group). Postoperative flatus-pass day, stool-pass day, nausea, vomiting, admission days, immediate postoperative (POD#0) and POD#1, 3, 5, 7 profiles of albumin, prothrombin time (PT) INR, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), white blood cell (WBC), and POD#1, 3, 5, 7 profiles of C-reactive protein (CRP), and postoperative complications cases were compared between ED group and CD group. All clinical data were compared retrospectively. Results Flatus-pass days (p<0.01), stool-pass days (p<0.01) and postoperative admission days (p=0.012) were shorter in ED group. Total bilirubin levels were higher at POD#0, 1, 3 but lower or similar at POD#5, 7 in ED group. AST, ALT levels were higher at POD#0 but lower at POD#1, 3, 5. There were no significant differences in albumin, PT INR, WBC, CRP and postoperative complication rates. Conclusions ED group had no difference in nutritional recovery and postoperative complication rates compared to CD group but it has better gastrointestinal motility recovery, liver function recovery, and shorter postoperative admission days.
Zoledronic acid in breast cancer: latest findings and interpretations

The intravenous nitrogen-containing bisphosphonate zoledronic acid has been shown to block multiple steps in tumor metastasis (e.g. angiogenesis, invasion, adhesion, proliferation) in preclinical and translational studies. Moreover, clinical data from the ABCSG-12 and ZO-FAST trials demonstrate significantly improved disease-free survival with zoledronic acid in the adjuvant breast cancer setting. In contrast to these two trials, recent interim results from the AZURE trial do not show a benefit from adding zoledronic acid to adjuvant therapy in the overall patient population. However, subset analyses of AZURE data show that zoledronic acid significantly improved overall survival in women who were more than 5 years postmenopausal or older than 60 years at baseline. Similarly, subset analyses of the ABCSG-12 trial data demonstrate greater benefits from zoledronic acid treatment in patients who theoretically would have achieved more complete ovarian suppression. These observations, together with the AZURE postmenopausal data, suggest that the endocrine environment may affect the potential anticancer activity of zoledronic acid. Indeed, current data support the possibility that zoledronic acid might be most effective for improving disease-free survival in the adjuvant breast cancer setting in women who are postmenopausal or have endocrine therapy-induced menopause.
Dynamic changes in clonal architecture during disease progression in follicular lymphoma

Follicular lymphoma (FL) is typically a slow growing cancer that can be effectively treated. Some patients undergo transformation to diffuse large B cell lymphoma (DLBCL), which is frequently resistant to chemotherapy and is generally fatal. Targeted sequencing of DNA and RNA was applied to identify mutations and transcriptional changes that accompanied transformation in a cohort of 16 patients, including 14 with paired samples. In most cases we found mutations that were specific to the FL clone dominant at diagnosis, supporting the view that DLBCL does not develop directly from FL, but from an ancestral progenitor. We identified frequent mutations in TP53, cell cycle regulators (cyclins and cyclin-dependent kinases) and the PI3K pathway, as well as recurrent somatic copy number variants (SCNVs) on chromosome 3, 7 and 17p associated with transformation. An integrated analysis of RNA and DNA identified allele specific expression changes in oncogenes, including MYC, that could be attributed to structural rearrangements. By focusing on serial samples taken from two patients, we identified evidence of convergent tumour evolution, where clonal expansion was repeatedly associated with mutations targeting the same genes or pathways. Analysis of serial samples is a powerful way to identify core dependencies that support lymphoma growth.
Drug Pathways, Transitions and Decisions: The Experiences of Young People in an Inner-City Dublin Community

This paper reports on selected findings from an ethnographic study of drug use by young people in a Dublin inner-city community considered to be “high risk” for problem drug use. In-depth individual interviews and focus-group discussions were used to generate extensive data on the social and drug-related experiences of young people ages 15–19 years. Fifty-seven young people were interviewed individually, and a subsample of 24 took part in focus-group discussions. The paper explores young people's drug “journeys” and documents emerging drug pathways. It examines the processes relevant to young people's drug transitions, drawing attention to the role of risk perceptions and risk boundaries in decision-making about drugs. The findings highlight the role of social/contextual influences in the onward transitions to new drugs and suggest that drug choices are strongly mediated by young people's experience of, and interaction with, their social environment.