Miracle-dz/UniFAR-FTUs huggingface dataset:
A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H‐2b mice: Fine specificity and T cell receptor Vβ expression of encephalitogenic T cells

A predominant response to myelin oligodendrocyte glycoprotein (MOG) was recently observed in patients with multiple sclerosis (MS). To study the possible pathogenic role of T cell response to MOG in MS, we have investigated the encephalitogenic potential of MOG. Synthetic MOG peptides, pMOG 1‐21, 35–55, 67–87, 104–117 and 202–218, representing predicted T cell epitopes, were injected into C57BL/6J and C3H.SW (H‐2b) mice. The mice developed significant specific T cell responses to pMOG 1–21, pMOG 35–55 and pMOG 104–117. However, pMOG 35–55 was the only MOG peptide which could induce neurological impairment. The highly reproducible disease was chronic, with ascending paralysis and neuropathology comparable with those observed in experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein or proteolipid protein, except that in H‐2b mice the disease was consistently non‐remitting. These features differ markedly from those which we recently observed in PL (H‐2u) mice with pMOG 35–55‐induced disease. In PL mice, pMOG 35–55‐induces atypical chronic relapsing EAE, the expression and progression of which are unpredictable. Hence, in different mouse strains, the same MOG peptide can induce typical EAE characterized by ascending paralysis, or atypical EAE with unpredictable clinical signs. pMOG 35–55‐specific T cells from H‐2b mice recognized an epitope within amino acids 40–55 of the MOG molecule, and pMOG 40–55‐reactive T cell lines were encephalitogenic upon transfer into syngeneic recipients. The encephalitogenic pMOG 35–55‐reactive C57BL/6J T cell lines expressed Vβ1, Vβ6, Vβ8, Vβ14 and Vβ15 gene segments, and the pMOG 35–55‐reactive C3H.SW T cell lines expressed Vβ1, Vβ2, Vβ6, Vβ8, Vβ10, Vβ14, and Vβ15 gene segments. However, in both mouse strains, the utilization of the Vβ8 gene product was predominant (40–43 %). The highly reproducible encephalitogenic activity of pMOG 35–55 strongly suggests a pathogenic role for T cell reactivity to MOG in MS and supports the possibility that MOG may also be a primary target antigen in the disease.
An Automatically Mode-Matched MEMS Gyroscope With Wide and Tunable Bandwidth

This paper presents the architecture and experimental verification of the automatic mode-matching system that uses the phase relationship between the residual quadrature and drive signals in a gyroscope to achieve and maintain matched resonance mode frequencies. The system also allows adjusting the system bandwidth with the aid of the proportional-integral controller parameters of the sense-mode force-feedback controller, independently from the mechanical sensor bandwidth. This paper experimentally examines the bias instability and angle random walk (ARW) performances of the fully decoupled MEMS gyroscopes under mismatched (~ 100 Hz) and mode-matched conditions. In matched-mode operation, the system achieves mode matching with an error frequency separation between the drive and sense modes in this paper. In addition, it has been experimentally demonstrated that the bias instability and ARW performances of the studied MEMS gyroscope are improved up to 2.9 and 1.8 times, respectively, with the adjustable and already wide system bandwidth of 50 Hz under the mode-matched condition. Mode matching allows achieving an exceptional bias instability and ARW performances of 0.54 °/hr and 0.025 °/√hr, respectively. Furthermore, the drive and sense modes of the gyroscope show a different temperature coefficient of frequency (TCF) measured to be -14.1 ppm/°C and -23.2 ppm/°C, respectively, in a temperature range from 0 °C to 100 °C. Finally, the experimental data indicate and verify that the proposed system automatically maintains the frequency matching condition over a wide temperature range, even if TCF values of the drive and sense modes are quite different.
Topical term weighting based on extended random sets for relevance feature selection

It is challenging to discover relevant features from long documents that describe user information needs due to the nature of text where synonymy, polysemy noise, and high dimensionality are inherited problems. Traditional feature selection methods could not effectively deal with these problems, because they assume that documents describe one topic only. Topic-based techniques, such as Latent Dirichlet Allocation (LDA), relax this assumption. They have been developed on the basis that a document can exhibit multiple hidden topics. However, LDA does not show encouraging results in selecting relevant features, because LDA calculates the weight of terms based on their local documents and does not generalise it globally at the collection level. So as to address this problem, we propose an innovative and effective extended random set model to generalise LDA weight for local document terms. The model is used as a weighting scheme for topical terms. It can assign a more discriminately accurate weight to these terms based on their appearance in LDA topics and relevant documents. The experimental results, based on the standard RCV1 dataset, TREC topics, and five standard performance measures, show that the proposed model significantly outperforms eight state-of-the-art baseline models in information filtering.
Evidence for differences in the mechanism of cell cycle arrest between senescent and serum‐deprived human fibroblasts: Heterokaryon and metabolic inhibitor studies

It has previously been shown that serum‐deprived, early passage quiescent human diploid fibroblastlike (HDFL) cells are able to inhibit cycling cells from entry into DNA synthesis upon cell fusion. We have found that the degree of inhibition of DNA synthesis in the heterokaryon correlates with the duration of serum deprivation, which is consistent with the suggestion that serum‐deprived cells may enter progressively deeper stages of G0 as they increase their time in quiescence. In contrast to fusions with senescent cells, in heterokaryons between serum‐deprived early passage and cycling young cells transient inhibition of protein synthesis with cycloheximide or inhibition of RNA synthesis with 5–6‐dichloro‐1‐β‐D‐ribofuranosyl benzimidazole (DRB) did not stimulate nuclear [3H]‐thymidine incorporation. These results suggest that differences may exist in the mechanisms responsible for inhibiting cell cycle progression in senescent vs early passage quiescent HDFL cells.
In vivo photoacoustic therapy with cancer-targeted indocyanine green-containing nanoparticles.

AIM The objective of this work was to study the photoacoustic effect of a special nanoparticle for selective cancer cell killing both in vitro and in vivo. MATERIALS & METHODS The nanoparticles (NPs) consisting of indocyanine green (ICG), phospholipid-polyethylene glycol (PL-PEG) and folic acid (FA) were used as cancer-targeting nanoprobes. Cancer cells incubated with the ICG-PL-PEG-FA solution were exposed to laser pulses. Finally, tumors in mice were treated with photoacoustic technique. RESULTS High selectivity of the photoacoustic destruction of cancer cells was observed. The tumors in mice after photoacoustic treatment showed a much slower growth rate. CONCLUSION The destruction of the cells was due to the photoacoustic effect originating from the NPs. The ICG-PL-PEG NP-based photoacoustic therapy would be a safe and highly efficient cancer treatment technique.
A Case Report of Rash at Peritoneal Dialysis Exit Site

The International Society for Peritoneal Dialysis recommends the regular application of topical antibiotic-containing preparations in addition to a routine exit site care to reduce the risk of exit site infection (ESI). Among these prophylactic antimicrobial preparations, topical gentamicin is one of the widely used and effective antibiotics for prevention of ESI and peritonitis in peritoneal dialysis (PD) patients. Overall, topical gentamicin is well tolerated; however, its use can be associated with the development of allergic contact dermatitis (ACD). We describe a first reported case of PD catheter exit site contact ACD due to topical gentamicin mimicking ESI. The patient in this report developed worsening violaceous in color and pruritic rash surrounding the PD catheter exit site that appeared 3 weeks after the initiation of gentamicin cream. The association between development of rash and initiation of topical gentamicin led to a suspicion of local reaction to gentamicin rather than ESI. Skin biopsy confirmed ACD. Discontinuation of the provoking agent and subsequent treatment with topical hydrocortisone application led to a resolution of the exit site rash. Any rash at a PD catheter exit site should be considered infectious until proven otherwise. However, it is important to be aware of noninfectious etiologies of exit site rashes as the treatment of these 2 conditions differs.
Physiological Characteristics of Photoreceptors in the Lamprey, Lethenteron japonicum

Lampreys are among the most basal vertebrates, and similar to jawed vertebrates, they have two types of photoreceptors: long photoreceptors (LP; putative cones) and short photoreceptors (SP; putative rods). It is intriguing to examine the physiological properties of vision in these animals. Although there is an accumulating body of histological and biochemical studies of photoreceptors of the lamprey Lethenteron japonicum, many physiological characteristics of this species have not been described. In the present study, single-cell recordings of photoreceptors in the upstream migrant lamprey were performed to investigate the physiological properties of SP and LP of the lamprey Lethenteron japonicum. It was found that the sensitivity in LP at 560 nm was 2000 photons µm-2, whereas that in SP at 520 nm was 67 photons µm-2, which is approximately a 30-fold difference. Moreover, the response kinetics of LP was remarkably faster than those of SP, which is consistent with previous studies of other Northern hemisphere lampreys. Unexpectedly, the amplitude of single-photon response in the lamprey SP was approximately 0.12 pA, less than 1% of the circulating current. The small amplitude in lamprey SP may degrade the ability to detect single photons of this species. The spectral sensitivity analysis revealed that approximately 30% of all the chromophores are composed of A2 retinal, which may account for the relatively low amplitude of single-photon response in SP.
Metabolic dysregulation and late-life depression: a prospective study

Background Depression is associated with the metabolic syndrome (MS). We examined whether metabolic dysregulation predicted the 2-year course of clinical depression. Method A total of 285 older persons (⩾60 years) suffering from depressive disorder according to DSM-IV-TR criteria was followed up for 2 years. Severity of depression was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Metabolic syndrome was defined according the National Cholesterol Education Programme (NCEP-ATP III). We applied logistic regression and linear mixed models adjusted for age, sex, years of education, smoking, alcohol use, physical activity, somatic co-morbidity, cognitive functioning and drug use (antidepressants, anti-inflammatory drugs) and severity of depression at baseline. Results MS predicted non-remission at 2 years (odds ratioper component = 1.26, 95% confidence interval 1.00–1.58), p = 0.047), which was driven by the waist circumference and HDL cholesterol. MS was not associated with IDS sum score. Subsequent analyses on its subscales, however, identified an association with the somatic symptom subscale score over time (interaction time × somatic subscale, p = 0.005), driven by higher waist circumference and elevated fasting glucose level. Conclusions Metabolic dysregulation predicts a poor course of late-life depression. This finding supports the concept of ‘metabolic depression’, recently proposed on population-based findings of a protracted course of depressive symptoms in the presence of metabolic dysregulation. Our findings seem to be driven by abdominal obesity (as indicated by the waist circumference) and HDL cholesterol dysregulation.
Worker Mobility and the Diffusion of Knowledge

We develop a theory of teams to measure the way knowledge diffuses across workers. We extend the sequential auctions framework to allow for workers to influence each other's knowledge. Workers can search on-the-job and leave their team to start a new team, carrying some of their knowledge with them. In contrast to standard sorting models, a firm's type is no longer exogenous; it is coworker human capital. Using a new methodology, we estimate the knowledge diffusion process and the degree of worker complementarities in production with micro wage data and job mobility patterns from the LEHD. Our estimated parameters imply both positive peer effects and strong production complementarities.
In Vivo Detection of Peripherin-Specific Autoreactive B Cells during Type 1 Diabetes Pathogenesis

Autoreactive B cells are essential for the pathogenesis of type 1 diabetes. The genesis and dynamics of autoreactive B cells remain unknown. In this study, we analyzed the immune response in the NOD mouse model to the neuronal protein peripherin (PRPH), a target Ag of islet-infiltrating B cells. PRPH autoreactive B cells recognized a single linear epitope of this protein, in contrast to the multiple epitope recognition commonly observed during autoreactive B cell responses. Autoantibodies to this epitope were also detected in the disease-resistant NOR and C57BL/6 strains. To specifically detect the accumulation of these B cells, we developed a novel approach, octameric peptide display, to follow the dynamics and localization of anti-PRPH B cells during disease progression. Before extended insulitis was established, anti-PRPH B cells preferentially accumulated in the peritoneum. Anti-PRPH B cells were likewise detected in C57BL/6 mice, albeit at lower frequencies. As disease unfolded in NOD mice, anti-PRPH B cells invaded the islets and increased in number at the peritoneum of diabetic but not prediabetic mice. Isotype-switched B cells were only detected in the peritoneum. Anti-PRPH B cells represent a heterogeneous population composed of both B1 and B2 subsets. In the spleen, anti-PRPH B cell were predominantly in the follicular subset. Therefore, anti-PRPH B cells represent a heterogeneous population that is generated early in life but proliferates as diabetes is established. These findings on the temporal and spatial progression of autoreactive B cells should be relevant for our understanding of B cell function in diabetes pathogenesis.
Isocitrate Dehydrogenase (IDH) Mutations Promote a Reversible ZEB1/MicroRNA (miR)-200-dependent Epithelial-Mesenchymal Transition (EMT)*

Background: Isocitrate dehydrogenase (IDH) mutations occur in diverse tumor types, leading to production of the oncometabolite 2-hydroxyglutarate (2-HG). Results: High 2-HG levels lead to a reversible epithelial-mesenchymal transition (EMT) phenotype, which is dependent on ZEB1/miR-200. Conclusion: Mutant IDH reversibly disrupts normal epithelial morphology through EMT induction, a possible tumorigenic mechanism. Significance: This is the first report of a reversible mutant IDH-dependent signaling phenotype. Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH and 2-HG alter signaling pathways to promote cancer, however, remains unclear. Additionally, there exist relatively few cell lines with IDH mutations. To examine the effect of endogenous IDH mutations and 2-HG, we created a panel of isogenic epithelial cell lines with either wild-type IDH1/2 or clinically relevant IDH1/2 mutations. Differences were noted in the ability of IDH mutations to cause robust 2-HG accumulation. IDH1/2 mutants that produce high levels of 2-HG cause an epithelial-mesenchymal transition (EMT)-like phenotype, characterized by changes in EMT-related gene expression and cellular morphology. 2-HG is sufficient to recapitulate aspects of this phenotype in the absence of an IDH mutation. In the cells types examined, mutant IDH-induced EMT is dependent on up-regulation of the transcription factor ZEB1 and down-regulation of the miR-200 family of microRNAs. Furthermore, sustained knockdown of IDH1 in IDH1 R132H mutant cells is sufficient to reverse many characteristics of EMT, demonstrating that continued expression of mutant IDH is required to maintain this phenotype. These results suggest mutant IDH proteins can reversibly deregulate discrete signaling pathways that contribute to tumorigenesis.
Understanding the main organisational antecedents of employee participation in continuous improvement

Purpose Companies use continuous improvement (CI) as a strategy to achieve business excellence and innovation. Yet CI initiatives fail mostly due to a lack of employee engagement. The paper aims to discuss this issue. Design/methodology/approach Based on the CI literature and the technology acceptance model (TAM), a comprehensive model called continuous improvement acceptance mode (CIAM) was developed to understand the main organisational antecedents that predict employee intention to participate in CI. The CIAM is based on structural equation modelling using partial least squares and it was validated in a large manufacturing plant in Europe. Findings Emulating the findings of the TAM, this study shows that employee intention to participate can be predicted by two variables called ease of participating and usefulness of participating. The CIAM then relates these constructs with relevant CI enablers found in the CI literature. Practical implications The CIAM could help academics and practitioners to better understand employee participation in CI activities, allowing CI systems to be better designed and achieve long-term sustainability. Originality/value The CIAM presents new variables and interactions that help to understand employee participation in CI activities. Some of these variables and interactions have received scant attention in the CI literature and thus they are worth investigating in greater depth in the future.
TLR2‐mediated leukocyte trafficking to the developing brain

Inflammation is a significant risk factor for brain injury in the perinatal period. In this study, we tested the hypothesis that activation of peripheral TLR induces inflammation in the brain, including leukocyte trafficking. Postnatal day 8 mice were injected intraperitoneally with a TLR1/2 (Pam3CSK4, P3C), TLR2/6 (FSL‐1) or TLR4 (LPS) agonist, and the peripheral and central cytokine and chemokine response was determined. Infiltration of immune cells to the CSF and brain was examined by flow cytometry, and brain permeability was investigated by radioactively labeled sucrose. We report that peripheral administration of P3C to neonatal mice induces significant influx of leukocytes, mainly neutrophils and monocytes, to the CSF and brain. Infiltration of leukocytes was TLR2 and MyD88 dependent, but largely absent after administration of LPS or FSL‐1. PC3‐mediated accumulation of immune cells in the brain was observed in classic CNS‐leukocyte gateways, the subarachnoid space and choroid plexus, as well as in the median eminence. Although P3C and LPS induced a similar degree of peripheral inflammatory responses, P3C provoked a distinct brain chemokine response and increased permeability, in particular, of the blood‐CSF barrier. Collectively, our results do not support the hypothesis that TLR activation, in general, induces immune cell infiltration to the brain. Instead, we have discovered a specific TLR2‐mediated mechanism of CNS inflammation and leukocyte invasion into the neonatal brain. This interaction between peripheral and central immune responses is to a large extent via the blood‐CSF barrier.
European comparisons between mental health services

When developing accessible, affordable and effective mental health systems, exchange of data between countries is an important moving force towards better mental health care. Unfortunately, health information systems in most countries are weak in the field of mental health, and comparability of data is low. Special international data collection exercises, such as the World Health Organization (WHO) Atlas Project and the WHO Baseline Project have provided valuable insights in the state of mental health systems in countries, but such single-standing data collections are not sustainable solutions. Improvements in routine data collection are urgently needed. The European Commission has initiated major improvements to ensure harmonized and comprehensive health data collection, by introducing the European Community Health Indicators set and the European Health Interview Survey. However, both of these initiatives lack strength in the field of mental health. The neglect of the need for relevant and valid comparable data on mental health systems is in conflict with the importance of mental health for European countries and the objectives of the ‘Europe 2020’ strategy. The need for valid and comparable mental health services data is today addressed only by single initiatives, such as the Organisation for Economic Co-operation and Development work to establish quality indicators for mental health care. Real leadership in developing harmonized mental health data across Europe is lacking. A European Mental Health Observatory is urgently needed to lead development and implementation of monitoring of mental health and mental health service provision in Europe.
Volatile compounds in health and disease

Purpose of reviewTo summarize the recent progress made in noninvasive monitoring of volatile compounds in exhaled breath and above biological liquids, as they are becoming increasingly important in assessing the nutritional and clinical status and beginning to provide support to conventional clinical diagnostics and therapy. To indicate the potential of these developments in medicine and the specific areas which are currently under investigation. Recent findingsThe significance of the following breath gases and their concentrations are reported: acetone and the influence of diet; ammonia confirmed as an indicator of dialysis efficacy; hydrogen and the 13CO2/12CO2 ratio (following the ingestion of 13C-labeled compounds) as related to gastric emptying and bowel transit times; hydrogen cyanide released by Pseudomonas and its detection in breath of children with cystic fibrosis; and multiple trace compounds in breath of patients with specific pathophysiological conditions and ‘metabolic profiling’. SummaryAdvanced analytical methods, especially exploiting mass spectrometry, are moving breath analysis towards the clinical setting; some trace gas metabolites are already being exploited in diagnosis and therapy. Much effort is being given to the search for biomarkers of tumours in the body. HCN as an indicator of the presence of Pseudomonas in the airways has real potential in therapeutically alleviating the symptoms of cystic fibrosis.
Moving beyond ‘more crop per drop’: insights from two decades of research on agricultural water productivity

ABSTRACT Concern over increasing water scarcity has led to the introduction of the concept of agricultural water productivity and an emphasis on interventions to achieve ‘more crop per drop’. Yet, a strong debate continues on how the concept is to be defined and used. Drawing largely from the irrigation literature, the origins of the concept and its methodological developments are reviewed, and its use in applied work over two decades is discussed. Based on this analysis of conceptual and applied research, key insights into the concept’s contributions and limitations are presented, as well as opportunities for further refinements.