Miracle-dz/UniFAR-FTUs huggingface dataset:
TNF induces increased production of extracellular amyloid-  - and  -synuclein-containing aggregates by human Alzheimer(cid:146)s

In addition to increased aberrant protein aggregation, inflammation has been proposed as a key element in the pathogenesis and progression of Alzheimer(cid:146)s disease. How inflammation interacts with other disease pathways and how protein aggregation increases during disease are not clear. We used single molecule imaging approaches and membrane permeabilisation assays to determine the effect of chronic exposure to TNF, a master proinflammatory cytokine, on protein aggregation in human induced pluripotent stem cell-derived neurons harbouring monogenic Alzheimer(cid:146)s disease mutations. We report that exposure of Alzheimer(cid:146)s disease, but not control, neurons to TNF induces substantial production of extracellular protein aggregates. Aggregates from Alzheimer(cid:146)s disease neurons are composed of amyloid-  and α-synuclein and induce significant permeabilisation of lipid membranes in an assay of pathogenicity. These findings provide support for a causal relationship between two crucial processes in Alzheimer(cid:146)s disease pathogenesis, and suggest that targeting inflammation, particularly TNF, may have beneficial downstream effects on ameliorating aberrant protein aggregation and under these conditions. Together, these results suggest that TNF augments the secretion of extracellular Aβ and  -synuclein containing aggregates from PSEN1 mutant neurons that have the
and human (HPV) linear array for HPV

Human papillomavirus (HPV) is causally associated with anal cancer, as HPV DNA is detected in up to 90% of anal intraepithelial Human papillomavirus (HPV) is causally associated with anal cancer, as HPV DNA is detected in up to 90% of anal intraepithelial neoplasias and anal cancers. With the gradual increase of anal cancer rates, there is a growing need to establish reliable and clinically relevant methods to detect anal cancer precursors. In resource-limited settings, HPV DNA detection is a potentially relevant tool for anal cancer screening. Here, we evaluated the performance of the Hybribio GenoArray (GA) for genotyping HPV in anal samples, against the reference standard Roche Linear Array (LA). Anal swab samples were obtained from sexually active men who have sex with men. Following DNA extraction, each sample was genotyped using GA and LA. The overall interassay agreement, type-speciﬁc, and single and multiple genotype agreements were evaluated by kappa statistics and McNemar’s (cid:2) 2 tests. Using GA and LA, 68% and 76% of samples were HPV DNA positive, respectively. There was substantial interassay agreements for the detection of all HPV genotypes ( (cid:3) (cid:4) 0.70, 86% agreement). Although LA was able to detect more genotypes per sample, the interassay agreement was acceptable ( (cid:3) (cid:4) 0.53, 63% agreement). GA had poorer speciﬁc detection of HPV genotypes 35, 42, and 51 ( (cid:3) < 0.60). In conclusion, GA and LA showed good interassay agreement for the detection of most HPV genotypes in anal samples. However, the detection of HPV DNA in up to 76% of anal samples warrants further evaluation of its clinical signiﬁcance.
MINIREVIEW Frequency, Causes, and New Challenges of Indeterminate Results in Western Blot Conﬁrmatory Testing for Antibodies to Human Immunodeﬁciency Virus (cid:1)

More than 2 decades of developments in the ﬁeld have led to a wide variety of test kits available for addressing the different needs of surveillance, diagnosis, and monitoring of human immunodeﬁciency virus (HIV) infection and antiretroviral therapy (20, 23). These test kits are based on different technologies, including immunoassays and molecular testing. Typically, enzyme-linked immunosorbent assays (ELISAs) and rapid tests for detecting anti-HIV antibodies are used for blood screening and/or surveillance purposes. The former include third-generation ELISAs that utilize the antigen sand-wich design for improved sensitivity, while the latter term refers to immunochromatographic tests or other simple antibody tests requiring less than 30 min of assay time. Since the viral capsid (core) p24 protein can be detected earlier than anti-HIV antibodies (93), attempts had also been made to develop a new generation of ELISA capable of simultaneously detecting the p24 antigen and anti-HIV antibodies (34, 52, 76, 101, 103). Signiﬁcant reductions of the window period were achieved, which is ideal for blood screening and surveillance (102), but users were also advised to be mindful of possible limitations when utilizing such a combination assay (52, 81, 83). With speciﬁc panels, a delay in detection by a fourth-generation ELISA was evident compared with a dedicated p24 antigen assay (81). This shortcoming of fourth-generation ELISAs is understandable,
Assessment of Student Performance in the Context of Active Learning

The growing adherence to the use of active learning methodologies brought to light the discussion of the challenge related to the forms of student assessment used and the performance measurement, expressed by the grades. In this type of approach, team projects are very common, where students are expected to collaborate equitably. For these cases, the forms of assessment practiced involve individual and group assessments, concomitantly or not. For both cases, the challenge remains to extract the contribution of each student from the work developed and express it through evaluations (grades). Given the above, this paper aims to bring a discussion about the theme and the proposal of alternatives that best suit the context of active learning. As a result, in addition to an extensive literature review, presenting the challenges experienced by professors, an evaluation model for Industrial Engineering courses is presented.
I NTRA - AND I NTER -I NDUSTRY P RODUCTIVITY S PILLOVERS IN OECD M ANUFACTURING : A S PATIAL E CONOMETRIC P ERSPECTIVE

We adopt a spatial econometric approach to estimate intra- and inter-industry productivity spillovers in total factor productivity transmitted through input-output relations in a sample of 13 OECD countries and 15 manufacturing industries. Both R&D spillovers as well as remainder, input-output-related linkage effects are accounted for, the latter of which we model by a spatial regressive error process. We find that knowledge spillovers occur both horizontally and vertically, whereas remainder spillovers are primarily of intra-industry type. Notably, these intra-industry remainder spillovers turn out economically more significant than R&D spillovers.
Extreme operator-valued continuous maps

Let . oq~(H) denote the space of operators on a Hilbert space H. We show that the extreme points of the unit ball of the space of continuous functions C(K, .LP(H)) (K-compact Hausdorff) are precisely the functions with extremal values. We show also that these extreme points are (a) strongly exposed if and only if dim H< ~ and card K<,~, (b) exposed if and only if / / is separable and K carries a strictly positive measure.
Inhibition of dental caries around composite resin containing ursolic acid

Recurrent caries formation around existing restorations represents the primary reason for replacement of composite resin restorations. Use of the antimicrobial restorative material to inhibit the bacterial biofilm formation can be one way to prevent the recurrent caries around restoration. The aim of this study is to compare the degree of caries-like lesion formation around experimental composite containing different concentrations of ursolic acid. containing antibacterial substances. Caries-like lesions were produced on the experimental teeth using S. mutans-induced artificial caries system. Specimens were incubated in a mixture of saliva and medium containing 1% carbohydrate at 37 ℃ for 5 days. Demineralization of dental enamel around the margins of restorations were analyzed with quantitative light-induced fluorescence(QLF). The demineralized specimens were photographed with QLF-D Biluminator TM 2 the fluorescence images of white spot area 1mm around the restorations were analyzed using image analysis software evaluate the effect of ursolic acid-containing composite resins on inhibition of artificial caries around the restorations formed by S. biofilm. interactions between oral bacteria. Attempts are required to mimic the diverse conditions present in the oral cavity which may affect dental caries development. This study evaluated the degree of outer lesion formation in the enamel around the restorations of composite resin containing ursolic acid. However, the secondary caries lesion consists of outer lesion as well as wall lesion, which is a narrower defect in the enamel or dentin along the cavity wall-restoration interface. Further investigation about the wall lesion around the restoration will allow the direct effect of ursolic acid-containing composite on inhibiting secondary caries to be understood.
Cotinine Selectively Activates a Subpopulation of (cid:1) 3/ (cid:1) 6 (cid:2) 2* Nicotinic Receptors in Monkey Striatum

The nicotine metabolite cotinine is an abundant long-lived bio- active compound that may contribute to the overall physiolog-ical effects of tobacco use. Although its mechanism of action in the central nervous system has not been extensively investi-gated, cotinine is known to evoke dopamine release in the nigrostriatal pathway through an interaction at nicotinic receptors (nAChRs). Because considerable evidence now demon- strates the presence of multiple nAChRs in the striatum, the present experiments were done to determine the subtypes through which cotinine exerts its effects in monkeys, a species that expresses similar densities of striatal (cid:1) 4 (cid:2) 2* (nAChR containing the (cid:1) 4 and (cid:2) 2 subunits, but not (cid:1) 3 or (cid:1) 6) and (cid:1) 3/ (cid:1) 6 (cid:2) 2* (nAChR composed of the (cid:1) 3 or (cid:1) 6 subunits and (cid:2) 2) nAChRs. Competition binding studies showed that cotinine interacts with both (cid:1) 4 (cid:2) 2* and (cid:1) 3/ (cid:1) 6 (cid:2) 2* nAChR subtypes in the caudate, with cotinine IC 50 values for inhibition of 5-[ 125 I]iodo-3-[2( S )-azeti-nylmethoxy]pyridine-2HCl and 125 I- (cid:1) -conotoxinMII binding in the micromolar range. This interaction at the receptor level is of functional significance because cotinine stimulated both (cid:1) 4 (cid:2) 2* and (cid:1) 3/ (cid:1) 6 (cid:2) 2* nAChR [ 3 H]dopamine release from caudate synaptosomes. Our results unexpectedly showed that nicotine evokes [ 3 H]dopamine release from two (cid:1) 3/ (cid:1) 6 (cid:2) 2* nAChR populations, one of which was sensitive to cotinine and the other was not. This cotinine-insensitive subtype was only present in the medial caudate and was preferentially lost with 1-methyl-4-phe- nyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal damage. In contrast, cotinine and nicotine elicited equivalent levels of (cid:1) 4 (cid:2) 2* nAChR-mediated dopamine release. These data demonstrate that cotinine functionally discriminates between two (cid:1) 3/ (cid:1) 6 (cid:2) 2* nAChRs in monkey striatum, with the cotinine-insensitive (cid:1) 3/ (cid:1) 6 (cid:2) 2* nAChR preferentially vulnerable to nigrostriatal damage. (cid:2) release suggests that the decrease is due to a loss of cotinine-insensitive This with 125 I- -conotoxin-MII
Parity and BRCA1/2-associated breast cancer risk linked to hormone-responsive p27 + luminal epithelial progenitors

This is the author’s version of a work that was accepted for publication in Cell Stem Cell. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cell Stem Cell, [VOL 13, ISSUE 1, (2013)] DOI: 10.1016/j.stem. 2013.05. 004
HIV-infected individuals with high coping self-efﬁcacy are less likely to report depressive symptoms: a cross-sectional study from Denmark § International Journal of Infectious Diseases

Objectives: Having effective ways to cope helps HIV-infected individuals maintain good psychological and physical well-being. This study investigated the relationship between coping self-efﬁcacy levels, as determined by the Coping Self-Efﬁcacy Scale (CSE), HIV status disclosure, and depression in a Danish cohort. Methods: In 2008, the CSE was administered to 304 HIV-infected individuals to measure their conﬁdence in their ability to cope with HIV infection. HIV status disclosure was assessed on a three-point scale: living openly with the disease, partly openly, or secretly. The Beck Depression Inventory (BDI) was used to assess depression prevalence and severity. Results: The CSE score was signiﬁcantly related to depression (Spearman’s rho = (cid:2) 0.71; the test of H 0 : BDI and coping, probability > t = 0.0001). There was a signiﬁcant relationship between higher CSE scores and living openly with HIV. The risk of depression was four times higher in HIV-infected individuals who did not disclose their HIV status (i.e. who lived ‘secretly’; odds ratio = 4.1) than in individuals who lived openly. Conclusion: Those with low CSE scores were more likely to report living secretly with HIV and to be depressed. Disclosing HIV may constitute a social stressor, and a lack of coping self-efﬁcacy may increase the likelihood of non-disclosure and depression. Interventions that enhance self-efﬁcacy may help in managing the demands of daily life with HIV, increase disclosure, and reduce depression. (cid:2) 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. All rights reserved.
PHARMACOVIGILANCE PROFILE OF DERMATOLOGICAL ADVERSE DRUG REACTION REPORTS COLLECTED FROM A TERTIARY CARE TEACHING HOSPITAL OF BANARAS HINDU UNIVERSITY, VARANASI

Introduction: Drugs can cure, suppress or prevent a disease and are usually beneficial to humans. However, they can also produce undesirable / harmful effects, which are known as adverse drug reactions. These are important cause of morbidity, hospitalization, increased health expenditure and even death. Cutaneous adverse drug reactions are among the most frequent adverse drug reactions. Active search is essential for identification of these, as patients may tend to downplay the causal association between drug use and the subsequent cutaneous manifestation. Objective: To observe the types of drug induced dermatological drug reactions in the patients attending to out patients department of Dermatology in a tertiary care teaching hospital, Banaras Hindu University, Varanasi, and find out the incidence, causal relationship with final outcome of skin drug reactions. Patients and Methods: A prospective study involved 200 patients attending to the Dermatology Outpatient department was observed during the period of one year to find the patients with Dermatological ADRs using self-reporting method for selection of cases in the adverse drug reaction monitoring form by CDSCO, India. Causality was assessed using WHO-UMC Causality assessment Scale. Results were analysed using suitable statistical methods. Results and Discusions: Skin reactions are the most common manifestations of adverse drug reactions. The pattern of adverse drug reactions and the drugs causing them is remarkably different in our population. Knowledge of these drug eruptions, the causative drugs and the prognostic indicators is essential for clinicians for diagnosis and prevention of adverse drug reactions. It is recommended to advise patients to carry a card or an emergency identification of offending drugs in their wallets that list the drug allergies and/or intolerances.
Relationship to Alpha^antitrypsin Phenotype

Hepatic explant specimens from 171 patients with cirrhosis were examined to determine the incidence of periodic acid-Schiff (PAS)-positive diastase-resistant globules (PDRGs) in end-stage hepatic disease and whether the globules bear a specific relation ship to the alpha 1 -antitrypsin (A 1 AT) phenotype or to causes of hepatic disease other than A^T deficiency. PAS-positive diastase-resistant globules were detected in 17 (10%) of the hepatic explant specimens, and the globules in all of these cases were strongly immunoreactive for AjAT. In the 17 patients with PDRGs, the cir rhosis was attributed preoperatively to AjAT deficiency (3 patients), ethanol abuse, viral hepatitis, or both (10 patients), cryp togenic cirrhosis (3 patients), and autoimmune hepatitis (1 patient). The AjAT isoelectric phenotypes classified according to ^ the protease inhibitor (Pi) nomenclature for 16 of these patients were as follows: Pi ZZ (3 patients), Pi SS (1 patient), Pi MZ (8 patients), and Pi MM (4 patients). Because PDRGs were seen in a variety of A 1 AT phenotypes, serum electrophoretic analysis, not histologic examination, is required for the correct diagnosis of an AjAT abnormality. Furthermore, although PDRGs were seen in a variety of hepatic diseases, the majority of patients with globules had an undetected A 1 AT abnormality. Accordingly, on identifica tion of hepatocytic PDRGs, the clinician should be alerted to the possibility of an unsuspected A 1 AT abnormality even in the presence of other causes of hepatic disease. (Key words: Alpha 1 antitrypsin; Hepatic disease; Hepatic transplantation) Am J Clin Pathol 1997;107:692-697.
University of Birmingham Investigating predictors and moderators of burnout in staff working in services for people with intellectual disabilities

Objectives Understanding predictors of burnout could potentially aid interventions for staff working in services for people with intellectual disabilities (ID). This study sought to understand predictors of burnout for staff specifically focusing on the moderating effect of emotional intelligence (EI) and self-efficacy. Methods 86 staff members working in services for people with ID completed a series of questionnaires about their experiences of violence, burnout (emotional exhaustion, depersonalisation and reduced personal accomplishment), self-efficacy and EI. Results
Upgraded Tango Tree to solve the Dictionary Problem and its Applications

—In 1989 Wilber [2] conjecture a lower bound O (log n) for a query using any balanced existing binary search tree with static data. Later in 2004 Demaine et al., [1] Came up with new lower bound O (loglogn) called interleave lower bound and he also claimed that these two lower bound O (log n) and O (loglogn) acts as a good tight intervals for any binary search tree. Tango tree was recently introduced by Demaine et al . , [1], having O (loglogn) - competitive ratio. Tango tree [1] supports only lookup (search) operations, where most of the online algorithms (like dictionary problem, a cache problem, adaptive data compression, etc.,) need additions and removals of collections (key, value) too, which are not supported by tango trees [1]. In this paper, we propose a new upgraded version of tango tree which supports addition and removal of collections (key, value) dynamically without knowing the sequence before hand in O (loglogn) time. We show run-time analysis with experimental results. We also show theoretically how these algorithms achieve O (loglogn) -competitive dynamic interleave bound.
(2012) Neuroemulation: definition and key benefits for water resources research. Hydrological Sciences (3). pp. 407-423. ISSN 0262-6667

Neuroemulation is the art and science of using a neural network model to replicate the external behaviour of some other model and it is an activity that is distinct from neural-network-based simulation. Whilst is has become a recognised and established sub-discipline in many fields of study, it remains poorly defined in the field of water resources and its many potential benefits have not been adequately recognised to date. One reason for the lack of recognition of the field is the difficulty in identifying, collating and synthesising published neuro-emulation studies because simple database searching fails to identifying papers concerned with a field of study for which an agreed conceptual and terminological framework does not yet exist. Therefore, in this paper we provide a first attempt at defining this framework for use in water resources. We identify eight key benefits offered by neuro-emulation and exemplify these with relevant examples from the literature. The concluding section highlights a number of strategic research directions, related to the identified potential of neuroemulators in water resources modelling.
a half-space when the coating and substrate have similar material properties

This study investigates the buckling of a uni-axially compressed neo-Hookean thin ﬁlm bonded to a neo-Hookean substrate. Previous studies have shown that the elastic bifurcation is supercritical if r ≡ μ f /μ s > 1.74 and subcritical if r < 1.74, where μ f and μ s are the shear moduli of the ﬁlm and substrate, respectively. Moreover, existing numerical simulations of the fully nonlinear post-buckling behaviour have all been focused on the regime r > 1.74. In this paper, we consider instead a subset of the regime r < 1.74, namely when r is close to unity. Four near-critical regimes are considered. In particular, it is shown that, when r > 1 and the stretch is greater than the critical stretch (the subcritical regime), there exists a localized solution that
Cell Differentiation T Cells Reveals Functional Plasticity in Th Genetic Reprogramming of Primary Human

Activation of naive T cells through the TCR and cytokine signals directs their differentiation into effector or memory subsets with different cytokine proﬁles. Here, we tested the ﬂexibility of human Th1 or Th2 differentiation by forced expression of transcription factors T-bet and GATA-3. Ectopic expression of T-bet and GATA-3 in freshly isolated human T N cells resulted in their differentiation to a Th1 and Th2 phenotype, respectively, in the absence of polarizing cytokines. Introduction of GATA-3 into lineage-committed Th1 cells induced the expression of Th2-speciﬁc cytokines (IL-4 and IL-5) and chemotactic receptors (CCR4, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). However, these cells partially maintained their Th1-speciﬁc proﬁle (IFN- (cid:1) and IL-12R (cid:2) 2 expression). Conversely, expression of T-bet in lineage-committed Th2 cells caused a more profound switch to the Th1 phenotype, including the up-regulation of CXCR3 and down-regulation of CCR4 and CRTH2. Interestingly, similar to the naive T cell subset, central memory T cells were also largely programmed toward Th1 or Th2 effector cells upon expression of T-bet and GATA-3, respectively. However, expression of these transcription factors in effector memory T cells was much less inﬂuential on cytokine and chemokine receptor expression proﬁles. Our results reveal remarkable plasticity in the differentiation programs of human memory T cells. This ﬂexibility is progressively diminished as cells mature from naive to effector T cells. These ﬁndings have important implications in understanding the molecular mechanisms of human T cell differentiation and for devising novel therapeutic strategies aimed at immunomodulation of skewed effector T cell responses.