Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges

Recent years have substantially broadened our view on the pathogenesis of multiple sclerosis (MS). While earlier concepts focused predominantly on T lymphocytes as the key cell type to mediate inflammatory damage within central nervous system (CNS) lesions, emerging evidence suggests that B lymphocytes may play a comparably important role both as precursors of antibody-secreting plasma cells and as antigen-presenting cells (APCs) for the activation of T cells. With greater appreciation of this pathogenic B-cell function in MS, B-cell-directed therapies, and in particular B-cell-depleting monoclonal antibodies targeting the CD20 molecule, have gained enormous interest over recent years. Clinical trials demonstrated that anti-CD20 treatment, which depletes immature and mature B cells but spares CD20 negative plasma cells, rapidly reduces formation of new inflammatory CNS lesions. While these findings clearly corroborate a pathogenic contribution of B cells, recent experimental but also clinical findings indicate that not all B cells contribute in an equally pathogenic manner and that certain subsets may in contrast mediate anti-inflammatory effects. In this review, we summarize current findings in support of pathogenic B-cell function in MS, including the encouraging clinical data which derived from anti-CD20 MS trials. Further, we review novel findings suggestive of regulatory properties of B-cell subsets which may be collaterally abolished by pan-CD20 depletion. In conclusion, we aim to provide an outlook on how this currently differentiating concept of pro- and anti-inflammatory B-cell function could be harnessed to further improve safety and effectiveness of B-cell-directed therapeutic approaches in MS.
Hospitalisation as an outcome measure in schizophrenia

Background People with schizophrenia comprise the majority of patients with severe mental illness recruited to recent mental health service studies of new teams (e.g. assertive outreach, crisis resolution). Reduction in hospitalisation has been the most consistent outcome measure in these studies, but results are inconsistent Aims To understand inconsistency of results from studies using hospitalisation as an outcome measure Method The advantages and disadvantages of hospitalisation are explored, including the ways in which it is recorded. Regional variation in outcomes and the impact of control services are reviewed Results Hospitalisation has face validity as an outcome but translates poorly between differing healthcare contexts. These variations can be exploited positively to distinguish potentially effective ingredients in community care (outreach, combined health and social care, team structure) from redundant components Conclusions Hospitalisation is a good proxy outcome measure in schizophrenia care in randomised controlled trials, but the dangers of extrapolating to new contexts require care
Interleukin-17A Gene Variability in Patients with Type 1 Diabetes Mellitus and Chronic Periodontitis: Its Correlation with IL-17 Levels and the Occurrence of Periodontopathic Bacteria

Interleukin-17 contributes to the pathogenesis of type 1 diabetes mellitus (T1DM) and chronic periodontitis (CP). We analyzed IL-17A −197A/G and IL-17F +7488C/T polymorphisms in T1DM and CP and determined their associations with IL-17 production and occurrence of periopathogens. Totally 154 controls, 125 T1DM, and 244 CP patients were genotyped using 5′ nuclease TaqMan® assays. Bacterial colonization was investigated by a DNA-microarray kit. Production of IL-17 after in vitro stimulation of mononuclear cells by mitogens and bacteria was examined by the Luminex system. Although no differences in the allele/genotype frequencies between patients with CP and T1DM + CP were found, the IL-17A −197 A allele increased the risk of T1DM (P < 0.05). Levels of HbA1c were significantly elevated in carriers of the A allele in T1DM patients (P < 0.05). Production of IL-17 by mononuclear cells of CP patients (unstimulated/stimulated by Porphyromonas gingivalis) was associated with IL-17A A allele (P < 0.05). IL-17A polymorphism increased the number of Tannerella forsythia and Treponema denticola in patients with CP and T1DM + CP, respectively (P < 0.05). IL-17A gene variability may influence control of T1DM and the “red complex” bacteria occurrence in patients with CP and T1DM + CP. Our findings demonstrated the functional relevance of the IL-17A polymorphism with higher IL-17 secretion in individuals with A allele.
Colloids, nanoparticles, and materials for imaging, delivery, ablation, and theranostics by focused ultrasound (FUS)

This review focuses on different materials and contrast agents that sensitize imaging and therapy with Focused Ultrasound (FUS). At high intensities, FUS is capable of selectively ablating tissue with focus on the millimeter scale, presenting an alternative to surgical intervention or management of malignant growth. At low intensities, FUS can be also used for other medical applications such as local delivery of drugs and blood brain barrier opening (BBBO). Contrast agents offer an opportunity to increase selective acoustic absorption or facilitate destructive cavitation processes by converting incident acoustic energy into thermal and mechanical energy. First, we review the history of FUS and its effects on living tissue. Next, we present different colloidal or nanoparticulate approaches to sensitizing FUS, for example using microbubbles, phase-shift emulsions, hollow-shelled nanoparticles, or hydrophobic silica surfaces. Exploring the science behind these interactions, we also discuss ways to make stimulus-responsive, or “turn-on” contrast agents for improved selectivity. Finally, we discuss acoustically-active hydrogels and membranes. This review will be of interest to those working in materials who wish to explore new applications in acoustics and those in acoustics who are seeking new agents to improve the efficacy of their approaches.
Detection and expression of enterotoxin genes in endophytic strains of Bacillus cereus

Aims: The aim of this study was to determine whether endophytic Bacillus cereus isolates from agronomic crops possessed genes for the nonhaemolytic enterotoxin (Nhe) and haemolysin BL (HBL) and, therefore, have the potential to cause diarrhoeal illness in humans.
Incidence of psychotic illness in London: comparison of ethnic groups

Abstract Objective: To compare annual incidences of20psychosis in people from different ethnic groups as defined in the 1991 census. Setting: Catchment area of district psychiatric20hospital. Design - All people aged 16 to 54 years who made contact with a wide range of community and hospital services between 1 July 1991 and 30 June 1992 were20screened for psychotic symptoms. Patients with such symptoms were interviewed face to face to collect information on demography, ethnic group,20psychiatric history and symptoms, drug use, and how care had been sought. A key informant, usually a close relative, was also interviewed. Main outcome measures: Age standardised incidence of schizophrenia and non-affective psychosis according to the ninth edition of the International Classification of Diseases in each ethnic group. Results - Ninety three patients took part, of whom 38 were assigned a certain or very likely diagnosis of schizophrenia (15 in white population, 14 in black,20seven in Asian, and two in others). The age standardised annual incidence of schizophrenia was 2.2 (95% confidence interval 1.5 to 2.9) per 10 000 of the population. The incidence ratio for schizophrenia in all ethnic minority groups compared with the white population was 3.6 (1.9 to 7.1); the corresponding figure for non- affective psychosis was 3.7 (2.2 to 6.2). Conclusions: Raised incidences of schizophrenia were not specific to the African Caribbeans, which suggests that the current focus on schizophrenia in20this population is misleading. Members of all ethnic minority groups were more likely to develop a psychosis but not necessarily schizophrenia. The personal and social pressures of belonging to any ethnic minority group in Britain are important determinants in the excess of psychotic disorders found.
Unbiased estimation of odds ratios: combining genomewide association scans with replication studies

Odds ratios or other effect sizes estimated from genome scans are upwardly biased, because only the top‐ranking associations are reported, and moreover only if they reach a defined level of significance. No unbiased estimate exists based on data selected in this fashion, but replication studies are routinely performed that allow unbiased estimation of the effect sizes. Estimation based on replication data alone is inefficient in the sense that the initial scan could, in principle, contribute information on the effect size. We propose an unbiased estimator combining information from both the initial scan and the replication study, which is more efficient than that based just on the replication. Specifically, we adjust the standard combined estimate to allow for selection by rank and significance in the initial scan. Our approach explicitly allows for multiple associations arising from a scan, and is robust to mis‐specification of a significance threshold. We require replication data to be available but argue that, in most applications, estimates of effect sizes are only useful when associations have been replicated. We illustrate our approach on some recently completed scans and explore its efficiency by simulation. Genet. Epidemiol. 33:406–418, 2009. © 2009 Wiley‐Liss, Inc.
Person Identification Based on Hand Tremor Characteristics

A plethora of biometric measures have been proposed in the past. In this paper we introduce a new potential biometric measure: the human tremor. We present a new method for identifying the user of a handheld device using characteristics of the hand tremor measured with a smartphone built-in inertial sensors (accelerometers and gyroscopes). The main challenge of the proposed method is related to the fact that human normal tremor is very subtle while we aim to address real-life scenarios. To properly address the issue, we have relied on weighted Fourier linear combiner for retrieving only the tremor data from the hand movement and random forest for actual recognition. We have evaluated our method on a database with 10 000 samples from 17 persons reaching an accuracy of 76%.
Association between HSV-2 and HIV-1 viral load in semen, cervico-vaginal secretions and genital ulcers of Thai men and women

We studied the association between herpes simplex virus type-2 (HSV-2) and HIV-1 viralload in plasma, semen, cervico-vaginal secretions and genital ulcers. Forty-seven (68%) men and 57 (80%) women were HSV-2 antibody positive, of whom 12 (26%, 95% confidence interval [CI] 20, 32) and five (8%, 95% CI 4, 12), respectively, had HSV-2 genital shedding detected by polymerase chain reaction. The mean HIV-1 seminal and cervico-vaginal viral loads did not differ significantly according to the presence of HSV-2 shedding. Eleven men and 15 women presented with genital ulcers; all ulcers were due to HSV-2. Ten men and nine women were followed up over six days: the mean (95% CI) HIV-1 log viral load copies/mL in the genital ulcers at baseline and final visits were 2.5 (2.3, 2.7) and 3.1 (2.0, 4.2) for men and 3.0 (2.6, 3.4) and 2.7 (2.3, 3.1) for women. These findings do not support the hypothesis that HSV-2 increases the HIV-1 viral load in genital secretions.
Rethinking FTP: Aggressive block reordering for large file transfers

Whole-file transfer is a basic primitive for Internet content dissemination. Content servers are increasingly limited by disk arm movement, given the rapid growth in disk density, disk transfer rates, server network bandwidth, and content size. Individual file transfers are sequential, but the block access sequence on a content server is effectively random when many slow clients access large files concurrently. Although larger blocks can help improve disk throughput, buffering requirements increase linearly with block size. This article explores a novel block reordering technique that can reduce server disk traffic significantly when large content files are shared. The idea is to transfer blocks to each client in any order that is convenient for the server. The server sends blocks to each client opportunistically in order to maximize the advantage from the disk reads it issues to serve other clients accessing the same file. We first illustrate the motivation and potential impact of aggressive block reordering using simple analytical models. Then we describe a file transfer system using a simple block reordering algorithm, called Circus. Experimental results with the Circus prototype show that it can improve server throughput by a factor of two or more in workloads with strong file access locality.
miR‐134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene

Head and neck squamous cell carcinoma (HNSCC) is a prevalent disease worldwide, and the survival of HNSCC has not improved significantly over the last few decades. MicroRNAs (miRNAs) have an important regulatory role during carcinogenesis. Our study investigated the pathogenic implications of miR‐134 in head and neck carcinogenesis. The clinicopathologic implications of miR‐134 in HNSCC were investigated using expression assays and the functional role of miR‐134 in HNSCC pathogenesis was determined using ectopic expression, knockdown and reporter assay experiments. Xenographic tumorigenesis and orthotopic nodal metastasis were assayed in mouse models. In situ hybridization and immunohistochemistry were used to detect the expression of miR‐134 and the WWOX gene in human HNSCC. The results indicated that miR‐134 was upregulated in HNSCC tissues relative to control mucosa. High expression of miR‐134 was associated with nodal metastasis and mortality of patients. Decreased plasma miR‐134 levels after tumor ablation indicated a better prognosis for patients. Multivariate analysis showed that high miR‐134 expression in HNSCC was an independent predictor of poor survival. Ectopic miR‐134 expression significantly enhanced in vitro oncogenic phenotypes and the orthotopic growth and metastasis of HNSCC cells. miR‐134 targeted WW domain‐containing oxidoreductase (WWOX) gene and cell invasion enhanced by miR‐134 expression was abrogated by ectopic WWOX expression in HNSCC cells. miR‐134 expression was reversely associated with the WWOX expression in HNSCC tissues. Evidences from our study substantiated that miR‐134 expression contributes to head and neck carcinogenesis by targeting the WWOX.
Phosphorylation of the Vesicle-Tethering Protein P115 by a Casein Kinase II–Like Enzyme Is Required for Golgi Reassembly from Isolated Mitotic Fragments

Coat protein I (COPI) transport vesicles can be tethered to Golgi membranes by a complex of fibrous, coiled-coil proteins comprising p115, Giantin and GM130. p115 has been postulated to act as a bridge, linking Giantin on the vesicle to GM130 on the Golgi membrane. Here we show that the acidic COOH terminus of p115 mediates binding to both GM130 and Giantin as well as linking the two together. Phosphorylation of serine 941 within this acidic domain enhances the binding as well as the link between them. Phosphorylation is mediated by casein kinase II (CKII) or a CKII-like kinase. Surprisingly, the highly conserved NH2-terminal head domain of p115 is not required for the NSF (N-ethylmaleimide–sensitive fusion protein)–catalyzed reassembly of cisternae from mitotic Golgi fragments in a cell-free system. However, the ability of p115 to link GM130 to Giantin and the phosphorylation of p115 at serine 941 are required for NSF-catalyzed cisternal regrowth. p115 phosphorylation may be required for the transition from COPI vesicle tethering to COPI vesicle docking, an event that involves the formation of t-SNARE (trans–soluble NSF attachment protein [SNAP] receptor) complexes.
Measurement of radioactivity level of oil-contaminated soils around mechanic workshops for environmental impact assessment

ABSTRACT This study identified and quantified the naturally occurring radionuclides, evaluated the levels of radiological hazard indices using the radionuclide activity concentrations and assessed their contamination status of the soils around mechanic workshops in Akure, Nigeria. Samples of oil-contaminated and control soils were, respectively, collected from mechanic workshops areas and areas with little or no anthropogenic activities within Akure, Ondo State, Nigeria and the activity levels of the radionuclides were determined using gamma-ray spectrometry. The radionuclides obtained with reliable regularity are associated with the decay series of 238U and 232Th as well as the non-decay series 40K. The results showed that the mean activity concentrations of the radionuclides 232Th, 238U and 40K in the oil-contaminated soils were 0.89 ± 0.08, 132.13 ± 0.16, and 51.52 ± 0.06 Bq/Kg, respectively. The radiological assessments in terms of the mean values of absorbed dose rate were (63.93 nGy/hr), annual equivalent dose rate (0.55 mSv/yr), internal hazard index (0.72 Bq/Kg), external hazard index (0.37 Bq/Kg), annual gonadal dose equivalent (428.22 µsvy−1), representative gamma index (0.92), and radium equivalent (137.38 Bq/Kg). Thus, radiological assessment indicated that long-term exposure of the radionuclides might pose integral hazards to human health.
Energy optimal controller for electric vehicles on partially icy roads with heuristic skidding compensation

In this study, a mathematical model is constructed for an electric vehicle. An energy optimal controller is designed for the gross motion model of the vehicle moving on a positive constant slope road with some icy parts. The energy optimal controller takes torque, speed and battery constraints into account. The loss of control during skidding period is compensated with an additional control command based on heuristics. The compensation is based on an enrichment of applied control input throughout the sections before and after skidding in balance within the controller constraints. The energy consumption of the optimal controller is compared with a standard cruise controller throughout several scenarios. These scenarios include constant slope roads with fixed amount of continuous icy part. The scenarios are carefully chosen that both controllers can accomplish to reach the end. It has been shown that energy optimal controller satisfies at least ten percent energy efficiency with respect to cruise controller under the tested scenarios.
Cleft Lip and/or Palate: 10 Years Experience at a Pediatric Cleft Center in Southern Thailand

Objective: To study the clinical characteristics, demographic data, and associated congenital anomalies of pediatric patients with cleft lip and/or palate in Southern Thailand. Design: Retrospective, hospital-based study. Setting: Cleft Clinic Center, Songklanagarind Hospital Participants: Children with cleft lip and/or palate who were born or seen at Songklanagarind Hospital between January 1997 and December 2006. Main Outcome Measure: Clinical features including demographic data, types of cleft, associated anomalies, family history of clefts, and physical growth. Results: A total of 153 children were seen during the studied period, of whom 36 (23.5%) had isolated cleft lip, 32 (20.9%) had isolated cleft palate, and 85 (55.6%) had combined cleft lip and palate. Twenty-seven children (17.7%) had a family history of clefts. Congenital malformations (syndromic cleft) were found in 20 children (13%), and chromosomal abnormalities were found in four of these (20%). There were no significant differences among the three groups (isolated cleft lip, isolated cleft palate, and combined cleft lip and palate) in maternal and paternal ages, gestational age, birth weight, family history of cleft, or associated malformations. The physical growth parameters of children with nonsyndromic cleft were the same as in the general population. Children with syndromic cleft were significantly lighter at birth and had grown up significantly shorter and lighter, with smaller head circumference. Conclusions: Chromosomal abnormalities are commonly found in children with syndromic cleft. Children with nonsyndromic cleft have normal growth; whereas, those with syndromic cleft have some degree of prenatal and postnatal growth restriction.
Gene Network Analysis of Metallo Beta Lactamase Family Proteins Indicates the Role of Gene Partners in Antibiotic Resistance and Reveals Important Drug Targets

Metallo Beta (β) Lactamases (MBL) are metal dependent bacterial enzymes that hydrolyze the β‐lactam antibiotics. In recent years, MBL have received considerable attention because it inactivates most of the β‐lactam antibiotics. Increase in dissemination of MBL encoding antibiotic resistance genes in pathogenic bacteria often results in unsuccessful treatments. Gene interaction network of MBL provides a complete understanding on the molecular basis of MBL mediated antibiotic resistance. In our present study, we have constructed the MBL network of 37 proteins with 751 functional partners from pathogenic bacterial spp. We found 12 highly interconnecting clusters. Among the 37 MBL proteins considered in the present study, 22 MBL proteins are from B3 subclass, 14 are from B1 subclass and only one is from B2 subclass. Global topological parameters are used to calculate and compare the probability of interactions in MBL proteins. Our results indicate that the proteins associated within the network have a strong influence in antibiotic resistance mechanism. Interestingly, several drug targets are identified from the constructed network. We believe that our results would be helpful for researchers exploring MBL‐mediated antibiotic resistant mechanisms. J. Cell. Biochem. 117: 1330–1339, 2016. © 2015 Wiley Periodicals, Inc.
Bifurcation of the East India Coastal Current east of Sri Lanka

The East India Coastal Current (EICC) flows equatorward during October–December carrying low salinity water from the Bay of Bengal en route. Using results from a high resolution ocean general circulation model, satellite altimeter data, Argo float profiles and ocean color images we show that the EICC bifurcates east of Sri Lanka. One part continues along the coast of Sri Lanka but the major part of the EICC, called here as the East Sri Lanka Jet (ESLJ) flows eastward into the Bay of Bengal. As a result of this bifurcation, there is offshore transport of chlorophyll a rich low salinity water from the coast of Sri Lanka. Altimeter data from 1993–2004 show that the bifurcation occurred every year except during the Indian Ocean Dipole (IOD) years of 1994 and 1997. The bifurcation occurs when an anticyclonic eddy that propagates westward ahead of a downwelling Rossby wave front impinges on the Sri Lanka coast. This new finding suggests that the main route of the low salinity water from the Bay of Bengal into the southeastern Arabian Sea may not be along the coast around Sri Lanka but through the Winter Monsoon Current.