Miracle-dz/UniFAR-FTUs huggingface dataset:
Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells

Murine epidermal Langerhans cells (LC) have been shown to internalize Leishmania major, a cause of human cutaneous leishmaniasis, and to stimulate a vigorous parasite‐specific T cell response. The present study emphasizes the critical role of LC in leishmaniasis by documenting directly that LC have the ability to transport L. major from the skin to the draining lymph node (LN). This was revealed by irreversible labeling of LC with a fluorescent cell linker and in vivo tracking. In contrast, no migration to the LN was seen with L. major‐infected macrophages. These findings were consistent with the results of mixed labeling immunohistology showing that early in infection the expression of parasite antigen in the LN draining the lesion was confined to dendritic cells and could not be detected in macrophages. Furthermore, dendritic cells in LN draining the site of cutaneous infection stimulated L. mayor‐primed T cells in vitro and, most notably, were able to activate unprimed T cells capable of mediating parasite‐specific delayed‐type hypersensitivity reactivity in vivo. Taken together, the results indicate that LC capture L. major in the skin and transport it to the regional LN for initiation of the specific T cell immune response.
Introduction to the Special Section: Linking the MMPI–2–RF to Contemporary Models of Psychopathology

ABSTRACT This special section considers 9 independent articles that seek to link the Minnesota Multiphasic Personality Inventory–2–Restructured Form (MMPI–2–RF; Ben-Porath & Tellegen, 2008/2011) to contemporary models of psychopathology. Sellbom (this issue) maps the Specific Problems scales onto hierarchical psychopathology structures, whereas Romero, Toorabally, Burchett, Tarescavage, and Glassmire (this issue) and Shkalim, Almagor, and Ben-Porath (this issue) show evidence of linking the instruments' scales to diagnostic representations of common higher order psychopathology constructs. McCord, Achee, Cannon, Harrop, and Poynter (this issue) link the MMPI–2–RF scales to psychophysiological constructs inspired by the National Institute of Mental Health (NIMH) Research Domain Criteria. Sellbom and Smith (this issue) find support for MMPI–2–RF scale hypotheses in covering personality psychopathology in general, whereas Klein Haneveld, Kamphuis, Smid, and Forbey (this issue) and Kutchen et al. (this issue) demonstrate the utility of the MMPI–2–RF in capturing contemporary conceptualizations of the psychopathic personality. Finally, Franz, Harrop, and McCord (this issue) and Rogers et al. (this issue) mapped the MMPI–2–RF scales onto more specific transdiagnostic constructs reflecting interpersonal functioning and suicide behavior proneness, respectively.
D-Amphetamine and Antipsychotic Drug Effects on Latent Inhibition in Mice Lacking Dopamine D 2 Receptors

C Bay-Richter, MJ O’Callaghan , N Mathur, CMP O’Tuathaigh, DM Heery, KCF Fone, JL Waddington and PM Moran* School of Psychology, University of Nottingham, Nottingham, UK; Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, St Stephens Green, Dublin, Ireland; School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK; School of Biomedical Sciences, University of Nottingham, Nottingham, UK
Effects of dietary supplementation of pioglitazone or walnut meal on metabolic profiles and oxidative status in dairy cows with high pre-calving BCS

This research paper addresses the hypothesis that dietary pioglitazone (PGT), as synthetic and specific ligand for PPAR-γ or walnut meal (WM) as a natural ligand for PPAR-γ, affect plasma metabolites and reduce the oxidative status in high body condition score (BCS) dairy cows (≥4 BCS). Total of 36 multiparous Holstein cows were randomly assigned to one of the dietary treatments: 1- Control (basal diet; CTR), 2- Walnut meal (9·45% walnut meal of DMI; WM), and 3- Pioglitazone (6 mg/kg BW; PGT). The experimental diets were fed from parturition time to 21 d postpartum. Results showed that the PGT supplementation increased dry matter intake (DMI) (22·95 kg/d) compared to the CTR (21·45 kg/d) and WM (21·78 kg/d) groups. Results showed that milk yield and milk composition were not affected by the experimental diets. Body condition score losses tended to be higher in the CTR group compared to the PGT and WM cows. The PGT group had higher plasma insulin compared to the CTR group (11·84 vs. 10·68 mIU/l), and WM cows had intermediate plasma insulin. The PGT cows had lower plasma non esterified fatty acid (NEFA) and tended to have lower β-hydroxy butyric acid (BHBA) than the CTR group. Feeding pioglitazone decreased plasma malondialdehyde (MDA) and increased plasma total antioxidant capacity (TAC) and superoxide dismutase (SOD) compared to the CTR and WM groups. It was concluded that dietary pioglitazone had positive effects on DMI, BCS change, blood metabolites and oxidative status in fresh dairy cows with high pre-calving BCS. The anti-oxidant effects of walnut meal were not supported by the present data.
Additive manufacturing of metallic components by selective electron beam melting — a review

Selective electron beam melting (SEBM) belongs to the additive manufacturing technologies which are believed to revolutionise future industrial production. Starting from computer-aided designed data, components are built layer by layer within a powder bed by selectively melting the powder with a high power electron beam. In contrast to selective laser melting (SLM), which can be used for metals, polymers and ceramics, the application field of the electron beam is restricted to metallic components since electric conductivity is required. On the other hand, the electron beam works under vacuum conditions, can be moved at extremely high velocities and a high beam power is available. These features make SEBM especially interesting for the processing of high-performance alloys. The present review describes SEBM with special focus on the relationship between process characteristics, material consolidation and the resulting materials and component properties.
Quasi-Interleaved Current Control for Switch-Linear Hybrid Envelope-Tracking Power Supply

An envelope-tracking (ET) technique can greatly enhance the efficiency of the power amplifier in wireless communication system. Among the structures of the ET power supply, the switch-linear hybrid (SLH) structure can obtain both high-tracking bandwidth and high efficiency. An implementation of series–parallel-form SLH ET power supply is proposed in this paper, which includes one multilevel converter, one linear amplifier, and two buck converters. The two buck converters adopt current sensor-less prediction control and are operated at critical conduction mode (CRM). In order to ensure the operation of CRM and provide as much load current as possible, a quasi-interleaved current control scheme is proposed for the two buck converters. Moreover, a peak current restriction method is proposed to prevent the output current of the two interleaved buck converters from excessively exceeding the load current, avoiding the increase of the power loss in the linear amplifier. Finally, a prototype is fabricated with the specifications as 5-MHz tracking bandwidth, 9.6–26.4-V output voltage, and 20-W average output power. The overall measured efficiency is 81.0%, and the normalized-mean-square error is 0.28% when tracking the envelope of wideband code division multiple access signal.
Feasibility of HIV Pre-Exposure Prophylaxis as Part of Routine Care in Toronto, Canada

INTRODUCTION The use of HIV Pre-Exposure Prophylaxis (PrEP) with oral tenofovir disproxil fumarate (TDF)/emtricitabine (FTC) (coformulated as Truvada) is effective in the prevention of HIV transmission through both sexual and injection drug exposures. The US Food and Drug Administration first approved TDF/FTC for PrEP in 2012, with comprehensive clinical practice guidelines released by the US Public Health Service in 2014. Currently, PrEP is not approved for this purpose by Health Canada and is prescribed off label. There are no published data about the use of PrEP in routine clinical practice in Canada, and little data of this sort have emerged from elsewhere. We aim to describe our experience with the use of PrEP in a cohort of Canadian patients receiving care in Toronto, Canada. We describe patient demographics, comorbidities, incidence of HIV, and other sexually transmitted infections (STIs), rates of follow-up, and reasons for discontinuation.
Establishing in vitro in vivo correlations to screen monoclonal antibodies for physicochemical properties related to favorable human pharmacokinetics

ABSTRACT Implementation of in vitro assays that correlate with in vivo human pharmacokinetics (PK) would provide desirable preclinical tools for the early selection of therapeutic monoclonal antibody (mAb) candidates with minimal non-target-related PK risk. Use of these tools minimizes the likelihood that mAbs with unfavorable PK would be advanced into costly preclinical and clinical development. In total, 42 mAbs varying in isotype and soluble versus membrane targets were tested in in vitro and in vivo studies. MAb physicochemical properties were assessed by measuring non-specific interactions (DNA- and insulin-binding ELISA), self-association (affinity-capture self-interaction nanoparticle spectroscopy) and binding to matrix-immobilized human FcRn (surface plasmon resonance and column chromatography). The range of scores obtained from each in vitro assay trended well with in vivo clearance (CL) using both human FcRn transgenic (Tg32) mouse allometrically projected human CL and observed human CL, where mAbs with high in vitro scores resulted in rapid CL in vivo. Establishing a threshold value for mAb CL in human of 0.32 mL/hr/kg enabled refinement of thresholds for each in vitro assay parameter, and using a combinatorial triage approach enabled the successful differentiation of mAbs at high risk for rapid CL (unfavorable PK) from those with low risk (favorable PK), which allowed mAbs requiring further characterization to be identified. Correlating in vitro parameters with in vivo human CL resulted in a set of in vitro tools for use in early testing that would enable selection of mAbs with the greatest likelihood of success in the clinic, allowing costly late-stage failures related to an inadequate exposure profile, toxicity or lack of efficacy to be avoided.
Discovery of Hydrocarbon-Stapled Short α-Helical Peptides as Promising Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Fusion Inhibitors

The hexameric α-helical coiled-coil formed between the C-terminal and N-terminal heptad repeat (CHR and NHR) regions of class I viral fusion proteins plays an important role in mediating the fusion of the viral and cellular membranes and provides a clear starting point for molecular mimicry that drives viral fusion inhibitor design. Unfortunately, such peptide mimicry of the short α-helical region in the CHR of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein has been thwarted by the loss of the peptide’s native α-helical conformation when taken out of the parent protein structure. Here, we describe that appropriate all-hydrocarbon stapling of the short helical portion-based peptide to reinforce its bioactive secondary structure remarkably improves antiviral potency. The resultant stapled peptide P21S10 could effectively inhibit infection by MERS-CoV pseudovirus and its spike protein-mediated cell–cell fusion; additionally, P21S10 exhibits improved pharmacokinetic properties than HR2P-M2, suggesting strong potential for development as an anti-MERS-CoV therapeutic.
Subspecialty approach for the management of acute cholecystitis: an alternative to acute surgical unit model of care

Acute cholecystitis is a common condition. Recent studies have shown an association between creation of an acute surgical unit (ASU) and improved outcomes. This study aimed to evaluate the outcomes of a subspecialty based approach to the management of acute cholecystitis as an alternative to the traditional ‘generalist’ general surgery approach or the ASU model.
Influence of frailty on the quality of life patients qualified for pacemaker implantation

AIMS AND OBJECTIVES An important question is whether frailty syndrome affects the assessment of quality of life or whether frailty syndrome may reduce the benefits of a cardiac pacemaker implantation. BACKGROUND Frailty syndrome is known risk factor for quality of life evaluation after selected cardiology invasive procedures. DESIGN The study was designed as single-centre prospective study. METHODS The study included 171 patients aged ≥60 years who were qualified for pacemaker implantation. Quality of life was evaluated twice-before and 6 months after implantation using MLHF questionnaire. A frailty syndrome evaluation using the Tilburg Frailty Indicator (TFI) was performed prior to pacemaker implantation. A DDDR pacemaker was implanted in each patient. RESULTS Frailty syndrome was identified in half of the patients with indications for cardiac pacemaker implantation. There was an improvement in quality of life in the six months after pacemaker implantation in all of the robust and frailty syndrome-affected patients that were included into the study-in general, physical and emotional domains. CONCLUSION Implantation of cardiac pacemaker influences the compensation quality of life evaluation in patients with sinus node dysfunction. Presence of frailty influences worse quality of life of patients when evaluated before cardiac pacemaker implantation. RELEVANCE TO CLINICAL PRACTICE Frailty should be evaluated in all older patients qualified for pacemaker implantation to evaluate high-risk group, optimise therapeutic approach and to intense education activities for patients and family.
[Heart failure in nursing home residents].

OBJECTIVE To determine the prevalence of heart failure (HF) in nursing home residents and to gain insight into the clinical characteristics of residents with heart failure. DESIGN Multi-centre, observational, cross-sectional study. METHOD 501 nursing home residents aged 65 years and over, in a department for chronic somatic diseases or a psychogeriatric department, participated in this study. The diagnosis of HF and the related characteristics were based on data collected from clinical examinations for heart failure (including history, physical examination, ECG, cardiac markers and echocardiography), patient records and questionnaires. A panel of two cardiologists and an internist-geriatrician made the final diagnosis of HF. RESULTS The prevalence of HF in nursing home residents was 33%. Dyspnoea, oedema and a history of cardiac disease were more common in residents with heart failure. Diabetes mellitus and chronic obstructive pulmonary disease also appeared to be more prevalent in this group. In 54% of the residents with HF, the diagnosis had not previously been made. Diagnosis of HF was not confirmed by the expert panel in 31% of residents with a history of HF. CONCLUSION Heart failure does indeed appear to be very prevalent in nursing home residents. Heart failure had not been previously diagnosed in many cases but also a previous diagnosis of heart failure could be disproved in many participants. It is therefore important that the diagnostic process for heart failure in nursing home residents be improved.
Signaling pathways regulating the expression of Prx1 and Prx2 in the chick mandibular mesenchyme

Prx1 and Prx2 are members of the aristaless‐related homeobox genes shown to play redundant but essential roles in morphogenesis of the mandibular processes. To gain insight into the signaling pathways that regulate expression of Prx genes in the mandibular mesenchyme, we used the chick as a model system. We examined the patterns of gene expression in the face and the roles of signals derived from the epithelium on the expression of Prx genes in the mandibular mesenchyme. Our results demonstrated stage‐dependent roles of mandibular epithelium on the expression of Prx in the mandibular mesenchyme and provide evidence for positive roles of members of the fibroblast and hedgehog families derived from mandibular epithelium on the expression of Prx genes in the mandibular mesenchyme. Our studies suggest that endothelin‐1 signaling derived from the mesenchyme is involved in restricting the expression of Prx2 to the medial mandibular mesenchyme. Developmental Dynamics 237:3115–3127, 2008. © 2008 Wiley‐Liss, Inc.
Yield of Endoscopic Ultrasound in Children and Adolescent With Acute Recurrent Pancreatitis

Objectives: Endoscopic ultrasound (EUS) is an established tool for evaluation of adults with acute recurrent pancreatitis (ARP) whereas data in pediatrics is limited. Our study assessed the role of EUS in identifying etiology including changes of chronic pancreatitis (CP) in children and adolescents with ARP. Methods: Children with ARP (≥2 episodes of acute pancreatitis [AP]) were prospectively evaluated with a detailed clinical proforma and EUS. Subjects with known etiology of ARP or CP on ultrasonography/computed tomography and magnetic resonance cholangiopancreatography (MRCP, Cambridge grade ≥3) were excluded. Parenchymal and ductal changes on EUS as per minimal standards terminology (MST) features were noted. Results: Thirty-two children (22 boys, age 14 [8–18] years) with ARP (median of 3 [2–5] episodes of AP) were enrolled. EUS was safe and technically successful in all. Gall bladder sludge was found in 1 (3%) case and none had other pancreatobiliary structural abnormalities. EUS diagnosis of CP (≥4 features) was made in 10/32 (31%) cases. Subjects with CP on EUS had a longer disease duration than those without CP (45 [10–97] vs 22 [8–78] months; P = ns). MRCP was normal in 28 and showed pancreas divisum in 1 case. Three cases had equivocal (Cambridge II) changes at initial MRCP and 2 of them had repeat MRCP, which showed definite (Cambridge IV) CP. All these 3 cases had CP on EUS. Conclusions: EUS diagnosed CP (≥4 features) in 31% and biliary abnormality in 3% children with ARP. EUS is safe, sensitive, and useful for early diagnosis of CP in children with ARP.
Mechanical properties of concrete containing recycled steel fibres

Lack of knowledge to properly dispose or to turn used tyres into useful recycled materials may become hazardous to the environment. A study by Economic Planning Unit (EPU) and Danish International Development Agency (Danida) in 2003 reported 19.7 millions or 157,000 tonnes tyres were junk by us annually. Two years later, it has been reported an increasing to 180,000 tonnes tyres are tossed per year or 500 tonnes per day. Therefore, innovative and creative technique to properly dispose used tyres is very important and also to encourage public on the development of new market for used tyres. Initiative has been taken by researchers at Universiti Teknologi Malaysia to use steel fibres recovered by tyre recycling process in concrete mixtures. The mechanical properties of recycled steel fibres (RSFs) was determined which include its diameter, and tensile strength while the length is fixed to 60±5 mm. Furthermore, these RSFs were added in the concrete mixture and tested for cube compressive strength (fcu), tensile splitting strength (fct), and flexural strength (fcf). The volume of RSFs were 0% (as control batch), 0.3%, and 0.7%. The aim of this research is to investigate the effect of recycled steel fibre on the properties of concrete in comparison with plain concrete. The usage of recycled steel fibre in concrete has shown satisfactory results on the improvement of its mechanical properties. Besides, the successful on using recycled steel fibre in concrete later not only develop new market on used tyres but also contribute to the sustainable development of building construction.
Consolidating Concurrency Control and Consensus for Commits under Conflicts

Conventional fault-tolerant distributed transactions layer a traditional concurrency control protocol on top of the Paxos consensus protocol. This approach provides scalability, availability, and strong consistency. When used for wide-area storage, however, this approach incurs cross-data-center coordination twice, in serial: once for concurrency control, and then once for consensus. In this paper, we make the key observation that the coordination required for concurrency control and consensus is highly similar. Specifically, each tries to ensure the serialization graph of transactions is acyclic. We exploit this insight in the design of Janus, a unified concurrency control and consensus protocol. Janus targets one-shot transactions written as stored procedures, a common, but restricted, class of transactions. Like MDCC [16] and TAPIR [51], Janus can commit unconflicted transactions in this class in one round-trip. Unlike MDCC and TAPIR, Janus avoids aborts due to contention: it commits conflicted transactions in this class in at most two round-trips as long as the network is well behaved and a majority of each server replica is alive. We compare Janus with layered designs and TAPIR under a variety of workloads in this class. Our evaluation shows that Janus achieves ∼5× the throughput of a layered system and 90% of the throughput of TAPIR under a contention-free microbenchmark. When the workloads become contended, Janus provides much lower latency and higher throughput (up to 6:8×) than the baselines.
Efficacy of three interventions at mitigating the adverse effects of muscle fatigue on postural control

This study evaluated the efficacy of three interventions at reducing the adverse effects of muscle fatigue on postural control. The first provided rest breaks according to perceived decrements in postural stability, while the other two involved auditory stimulations (static pure tone and moving conversation). Sixteen participants performed repetitive box handling (lifting + lowering) over 1.5 h to induce muscle fatigue mainly in the lumbar extensors. Trials of quiet upright stance were completed at 10-min intervals, during which the interventions (or a control condition) were applied. Postural control was assessed using perceived stability (PS) and several measures derived from centre-of-pressure (COP) time series. Allowance of rest breaks did not significantly affect any of the objective measures, though a trend indicated an offset to fatigue-induced decreases in PS. Both the static pure tone and moving conversation led to significant changes in the dependent measures indicating a mitigation of fatigue-induced postural instability. Practitioner Summary: We examined the effects of three control strategies on postural control in the presence of muscle fatigue induced by a simulated occupational task. The findings can facilitate the development of future strategies or practical interventions to reduce falling risk and prevent falls.
R&D and Credit Rationing in SMEs

type="main" xml:id="ecin12080-abs-0001"> We study the effects of credit rationing on research and development (R&D) investment using survey and accounting data on a large representative sample of manufacturing small- and medium-sized enterprises (SMEs). Our econometric model accounts for the endogeneity of our credit rationing indicator and employs an innovative theory-based identification strategy. We find that credit rationing has a significantly negative effect on both the probability to set up R&D activities and on the level of R&D spending (conditioned on the R&D decision), but the overall estimated reduction in R&D spending is largely to be associated with the first effect. ( JEL G21, D82, O32, C35)
Czech speech rhythm and the rhythm class hypothesis

While a number of languages have been classified as either syllable- or stress-timed, the case of Czech remains unclear. In this paper we make predictions about Czech rhythm on the basis of our analysis of syllable complexity in recorded samples of Czech. The results on syllable complexity show mixed features. This is reflected in the classification of Czech rhythm using rhythm measures based on durational variability of consonantal and vocalic intervals.