Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular ATP Induces a Distorted Maturation of Dendritic Cells and Inhibits Their Capacity to Initiate Th1 Responses1

Dendritic cells (DCs) express functional purinergic receptors, but the effects of purine nucleotides on DC functions have been marginally investigated. In this study, we report on the ability of micromolar concentrations of ATP to affect the maturation and Ag-presenting function of monocyte-derived DCs in vitro. Chronic stimulation (24 h) of DCs with low, noncytotoxic ATP doses increased membrane expression of CD54, CD80, CD86, and CD83, slightly reduced the endocytic activity of DCs, and augmented their capacity to promote proliferation of allogeneic naive T lymphocytes. Moreover, ATP enhanced LPS- and soluble CD40 ligand-induced CD54, CD86, and CD83 expression. On the other hand, ATP markedly and dose-dependently inhibited LPS- and soluble CD40 ligand-dependent production of IL-1α, IL-1β, TNF-α, IL-6, and IL-12, whereas IL-1 receptor antagonist and IL-10 production was not affected. As a result, T cell lines generated from allogeneic naive CD45RA+ T cells primed with DCs matured in the presence of ATP produced lower amounts of IFN-γ and higher levels of IL-4, IL-5, and IL-10 compared with T cell lines obtained with LPS-stimulated DCs. ATP inhibition of TNF-α and IL-12 production by mature DCs was not mediated by PGs or elevation of intracellular cAMP and did not require ATP degradation. The inability of UTP and the similar potency of ADP to reproduce ATP effects indicated that ATP could function through the P2X receptor family. These results suggest that extracellular ATP may serve as an important regulatory signal to dampen IL-12 production by DCs and thus prevent exaggerated and harmful immune responses.
Image Denoising via Collaborative Dual-Domain Patch Filtering

In this paper, we propose a novel image denoising algorithm exploiting features from both spatial as well as transformed domain. We implement intensity-invariance based improved grouping for collaborative support-agnostic sparse reconstruction. For collaboration firstly, we stack similar-structured patches via intensity-invariant correlation measure. The grouped patches collaborate to yield desirable sparse estimates for noise filtering. This is because similar patches share the same support in the transformed domain, such similar supports can be used as probabilities of active taps to refine the sparse estimates. This ultimately produces a very useful patch estimate thus increasing the quality of recovered image by discarding the noise-causing components. A region growing based spatially developed post-processor is then applied to further enhance the smooth regions by extracting the spatial domain features. We also extend our proposed method for denoising of color images. Comparison results with the state-of-the-art algorithms in terms of peak signal-to-noise ratio (PNSR) and structural similarity (SSIM) index from extensive experimentations via a broad range of scenarios demonstrate the superiority of our proposed algorithm.
Superflares on the late-type giant KIC 2852961

The most powerful superflares reaching 10$^{39}$erg bolometric energy are from giant stars. The mechanism behind flaring is supposed to be the magnetic reconnection, which is closely related to magnetic activity including starspots. However, it is poorly understood, how the underlying magnetic dynamo works and how the flare activity is related to the stellar properties which eventually control the dynamo action. We analyse the flaring activity of KIC 2852961, a late-type giant star, in order to understand how the flare statistics are related to that of other stars with flares and superflares and what the role of the observed stellar properties in generating flares is. We search for flares in the full Kepler dataset of the star by an automated technique together with visual inspection. We set a final list of 59 verified flares during the observing term. We calculate flare energies for the sample and perform a statistical analysis. The stellar properties of KIC 2852961 are revised and a more consistent set of parameters are proposed. The cumulative flare energy distribution can be characterized by a broken power-law, i.e. on the log-log representation the distribution function is fitted by two linear functions with different slopes, depending on the energy range fitted. We find that the total flare energy integrated over a few rotation periods correlates with the average amplitude of the rotational modulation due to starspots. Flares and superflares seem to be the result of the same physical mechanism at different energetic levels, also implying that late-type stars in the main sequence and flaring giant stars have the same underlying physical process for emitting flares. There might be a scaling effect behind generating flares and superflares in the sense that the higher the magnetic activity the higher the overall magnetic energy released by flares and/or superflares.
RESEARCH Integrative Cardiovascular Physiology and Pathophysiology Chronic exposure to water-pipe smoke induces cardiovascular dysfunction in mice

water-pipe smoke induces cardiovascular tobacco smoking is becoming prevalent in all over the world including Western countries. There are limited data on the cardiovascular effects of water-pipe smoke (WPS), in particular following chronic exposure. Here, we assessed the chronic cardiovascular effects of nose-only WPS exposure in C57BL/6 mice. The duration of the session was 30 minutes/day, 5 days/week for 6 consecutive months. Control mice were exposed to air. WPS signiﬁcantly increased systolic blood pressure. The relative heart weight and plasma concentrations of troponin-I and B-type natriuretic peptide were increased in mice exposed to WPS. Arterial blood gas analysis showed that WPS caused a signiﬁcant decrease in Pa O 2 and an increase in Pa CO 2 . WPS signiﬁcantly shortened the thrombotic occlusion time in pial arterioles and venules and increased the number of circulating platelet. Cardiac lipid peroxidation, measured as thiobarbituric acid-reactive substances, was signiﬁcantly increased, while superoxide dismutase activity, total nitric oxide activity, and glutathione concentration were reduced by WPS exposure. Likewise, immunohistochemical analysis of the heart revealed an increase in the expression of inducible nitric oxide synthase and cytochrome c by cardiomyocytes of WPS-exposed mice. Moreover, hearts of WPS-exposed mice showed the presence of focal interstitial ﬁbrosis. WPS exposure signiﬁcantly increased heart DNA damage assessed by Comet assay. We conclude that chronic nose-only exposure to WPS impairs cardiovascular homeostasis. Our ﬁndings provide evidence that long-term exposure to WPS is harmful to the cardiovascular system and supports interventions to control the spread of WPS, particularly amid youths.
Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer’s disease and frontotemporal dementia

OBJECTIVES The diagnosis of Alzheimer’s disease (AD) is now reliant on the use of NINCDS-ADRDA criteria. Other diseases causing dementia are being increasingly recognised—for example, frontotemporal dementia (FTD). Historically, these disorders have not been clearly demarcated from AD. This study assesses the capability of the NINCDS-ADRDA criteria to accurately distinguish AD from FTD in a series of pathologically proved cases. METHODS The case records of 56 patients (30 with AD, 26 with FTD) who had undergone neuropsychological evaluation, brain imaging, and ultimately postmortem, were assessed in terms of whether at initial diagnosis the NINCDS-ADRDA criteria were successful in diagnosing those patients who had AD and excluding those who did not. RESULTS (1) The overall sensitivity of the NINCDS-ADRDA criteria in diagnosing “probable” AD from 56 patients with cortical dementia (AD and FTD) was 0.93. However, the specificity was only 0.23; most patients with FTD also fulfilled NINCDS-ADRDA criteria for AD. (2) Cognitive deficits in the realms of orientation and praxis significantlyincreased the odds of a patient having AD compared with FTD, whereas deficits in problem solving significantlydecreased the odds. Neuropsychological impairments in the domains of attention, language, perception, and memory as defined in the NINCDS-ADRDA statement did not contribute to the clinical differentiation of AD and FTD. CONCLUSION NINCDS-ADRDA criteria fail accurately to differentiate AD from FTD. Suggestions to improve the diagnostic specificity of the current criteria are made.
Adjunctive perampanel in adolescents with inadequately controlled partial‐onset seizures: A randomized study evaluating behavior, efficacy, and safety

The noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist perampanel was shown in phase III trials to be an effective and well‐tolerated adjunctive treatment for partial‐onset seizures. In adolescents, it is necessary to characterize cognitive, neuropsychological, and behavioral side effects of antiepileptic drugs (AEDs). The current analysis focuses on behavioral outcomes, efficacy, and safety of perampanel in adolescents.
Advanced stage and unfavorable Hodgkin's disease in the Chinese—a 20‐year experience

We retrospectively analyzed 57 patients with advanced stage (stage III/IV) or unfavorable (presence of B symptoms or bulky disease) Hodgkin's disease from January 1977 to December 1997. There were 29 male and 28 female patients. The median age was 27 years old (range, 13–59). Lactate dehydrogenase levels ranged from 104 units/l to 2320 units/l (median, 433). Eighteen (31.6%), 13 (22.8%), and 26 (45.6%) patients had stage II bulky, stage III, and stage IV disease, respectively. Twenty‐five (44%) patients had B symptoms. One (1.8%), 3 (5.3%), 36 (63.2%), and 17 (29.8%) had lymphocyte predominant, lymphocyte depleted, nodular sclerosis, and mixed cellularity histology, respectively. Chemotherapy regimens included mechlorethamine, vincristine, procarbazine, prednisone (MOPP) (n = 9), adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) (n = 23), MOPP alternating with ABVD (n = 13), and COPP‐ABV hybrid (n = 12). Complete remission was achieved in 47 (82.4%) patients. Eleven patients (23%) relapsed after the first complete remission and four (36%) attained a second complete remission with salvage chemotherapy. Projected overall survival was 69.0% at 10 years and 20 years. Disease‐free survival rates were 71% at 10 years and 20 years. Of the potential prognostic factors analyzed (age, sex, stage, lactate dehydrogenase, serum albumin level, regimen, B symptoms and bulky disease) by using the Cox regression model, only a low albumin level was found to adversely affect overall survival (P = 0.003). In conclusion, despite the relative low incidence of Hodgkin's disease in Hong Kong Chinese, the treatment outcomes in patients with advanced stage or unfavorable Hodgkin's disease is comparable to Caucasian patients. Am. J. Hematol. 61: 159–163, 1999. © 1999 Wiley‐Liss, Inc.
A Suffix Tree Based Handwritten Chinese Address Recognition System

The main contribution of the paper is that it presents a suffix tree based data structure for automatic handwritten Chinese address reading. Since lots of papers have discussed the destination address block (DAB) location for Chinese, we will not extend it in this paper. Instead, we pay more attention to improve the address matching performance after DAB location. As some conventional methods, the extracted text lines are pre-segmented into a series of radicals. We then build a hierarchical structure of sub-strings from the recognized characters of valid radical combinations. Coarse address candidates are selected at the same time. In address maching, we incorporate postcode information to filter redundant addresses. The pre- segmented radicals are compared with candidate address and a cost function combining recognition and structrual cost is evaluated for final decision. In the system, character segmentation, recognition, string searching and matching are considered synchronously by taking advantage of lexicon knowledge. Suffix tree can greatly facilitate the substring generation process and enable the matching process to start from any character to collect potentially bitty information. Therefore, our algorithms is more robust to the intervening noises and irregular writing styles. Finallly, we test 1,000 handwritten Chinese envelopes and achieve a correct rate of 85.30% in 3.0 seconds per mail averagely.
Review of methods used for quantifying excess water in over‐hydrated skin using evaporimetry

Background: Advances in diapers and skin barrier products are often aimed at reducing water penetration of the skin to prevent diaper dermatitis and evaporimetry has commonly been measured to quantify excess water in the skin. The aim of this study was to critically review the methods used to measure water vapour flux density (WVFD) using evaporimetry in order to identify a standardised methodology.
Generation of Sequence-specific, High Affinity Anti-DNA Antibodies*

By taking advantage of the extreme stability of a protein-DNA complex, we have obtained two highly specific monoclonal antibodies against a predetermined palindromic DNA sequence corresponding to the binding site of the E2 transcriptional regulator of the human papillomavirus (HPV-16). The purified univalent antibody fragments bind to a double-stranded DNA oligonucleotide corresponding to the E2 binding site in solution with dissociation constants in the low and subnanomolar range. This affinity matches that of the natural DNA binding domain and is severalfold higher than the affinity of a homologous bovine E2 C-terminal domain (BPV-1) for the same DNA. These antibodies discriminate effectively among a number of double- and single-stranded synthetic DNAs with factors ranging from 125- to 20,000-fold the dissociation constant of the specific DNA sequence used in the immunogenic protein-DNA complex. Moreover, they are capable of fine specificity tuning, since they both bind less tightly to another HPV-16 E2 binding site, differing in only 1 base pair in a noncontact flexible region. Beyond the relevance of obtaining a specific anti-DNA response, these results provide a first glance at how DNA as an antigen is recognized specifically by an antibody. The accuracy of the spectroscopic method used for the binding analysis suggests that a detailed mechanistic analysis is attainable.
Current pre-clinical and clinical advances in the BCR-ABL1-positive and -negative chronic myeloproliferative neoplasms

Though it has been remarkable to have witnessed the major advances in the understanding of the molecular pathogenesis of the chronic myeloproliferative neoplasms (MPN) over the past three decades, many challenges remain. The advances began with the identification of the BCR-ABL1 gene in chronic myeloid leukemia (CML) in 1985, leading to the introduction of ABL1 tyrosine kinase inhibitors (TKIs), and the JAK2V617F mutation in polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) in 2005, leading to the JAK inhibitors.1–3 CML is now arguably the most successfully treated human malignancy. Despite these remarkable achievements, the quest for cure, functionally defined as treatment-free remission after discontinuation of TKI therapy, remains difficult.4 In the BCR-ABL1 negative MPNs, a similar degree of success has not been achieved, perhaps because of the rather surprising clonal complexity of these disorders and the increasing molecular evidence of the need for JAK2V617F mutation to cooperate with other genetic aberrations in the initiation and progression of the disease. This clonal complexity needs to be elucidated further in order to recognize clinically relevant candidate therapeutic targets. Herein, we review some of the topical challenges and successes in the biology and therapy of the MPNs that were discussed at the 7th post-American Society of Hematology CML-MPN workshop, which took place in Atlanta on December 11–12, 2012, and up-dated prior to this publication.
Arabidopsis Branched-Chain Aminotransferase 3 Functions in Both Amino Acid and Glucosinolate Biosynthesis1[W][OA]

In Arabidopsis thaliana, transamination steps in the leucine biosynthetic and catabolic pathways and the methionine (Met) chain elongation cycle of aliphatic glucosinolate formation are catalyzed by branched-chain aminotransferases (BCATs) that are encoded by a small gene family of six members. One member of this family, the plastid-located BCAT3, was shown to participate in both amino acid and glucosinolate metabolism. In vitro activity tests with the recombinant protein identified highest activities with the 2-oxo acids of leucine, isoleucine, and valine, but also revealed substantial conversion of intermediates of the Met chain elongation pathway. Metabolite profiling of bcat3-1 single and bcat3-1/bcat4-2 double knockout mutants showed significant alterations in the profiles of both amino acids and glucosinolates. The changes in glucosinolate proportions suggest that BCAT3 most likely catalyzes the terminal steps in the chain elongation process leading to short-chain glucosinolates: the conversion of 5-methylthiopentyl-2-oxo and 6-methylthiohexyl-2-oxo acids to their respective Met derivatives, homomethionine and dihomo-methionine, respectively. The enzyme can also at least partially compensate for the loss of BCAT4, which catalyzes the initial step of Met chain elongation by converting Met to 4-methylthio-2-oxobutanoate. Our results show the interdependence of amino acid and glucosinolate metabolism and demonstrate that a single enzyme plays a role in both processes.
Distribution of the rol gene encoding the regulator of lipopolysaccharide O-chain length in Escherichia coli and its influence on the expression of group I capsular K antigens

The rol (cld) gene encodes a protein involved in the expression of lipopolysaccharides in some members of the family Enterobacteriaceae. Rol interacts with one or more components of Rfc-dependent O-antigen biosynthetic complexes to regulate the chain length of lipopolysaccharide O antigens. The Rfc-Rol-dependent pathway for O-antigen synthesis is found in strains with heteropolysaccharide O antigens, and, consistent with this association, rol-homologous sequences were detected in chromosomal DNAs from 17 different serotypes with heteropolysaccharide O antigens. Homopolymer O antigens are synthesized by a pathway that does not involve either Rfc or Rol. It was therefore unexpected when a survey of Escherichia coli strains possessing mannose homopolymer O8 and O9 antigens showed that some strains contained rol. All 11 rol-positive strains coexpressed a group IB capsular K antigen with the O8 or O9 antigen. In contrast, 12 rol-negative strains all produced group IA K antigens in addition to the homopolymer O antigen. Previous research from this and other laboratories has shown that portions of the group I K antigens are attached to lipopolysaccharide lipid A-core, in a form that we have designated K(LPS). By constructing a hybrid strain with a deep rough rfa defect, it was shown that the K40 (group IB) K(LPS) antigen exists primarily as long chains. However, a significant amount of K40 antigen was surface expressed in a lipid A-core-independent pathway. The typical chain length distribution of the K40 antigen was altered by introduction of multicopy rol, suggesting that the K40 group IB K antigen is equivalent to a Rol-dependent O antigen. The prototype K30 (group IA) K antigen is expressed as short oligosaccharides (primarily single repeat units) in K(LPS), as well as a high-molecular-weight lipid A-core-independent form. Introduction of multicopy rol into the K30 strain generated a novel modal pattern of K(LPS) with longer polysaccharide chains. Collectively, these results suggested that group IA K(LPS) is also synthesized by a Rol-dependent pathway and that the typically short oligosaccharide K(LPS) results from the absence of Rol activity in these strains.
Antimicrobial resistance and disease control: making One Health work

Antimicrobial resistance and infectious disease control were the main themes at a One Health conference held in London last month. Hosted collaboratively by the Royal Society of Medicine and the Bella Moss Foundation, the meeting put particular emphasis on making the One Health concept work when dealing with resistance and disease control. Georgina Mills reports
Posttraumatic Growth in Women Survivors of Breast Cancer

Aim: The aim of the study was to understand the phenomenon of posttraumatic growth (PTG) in women survivors of breast cancer from an Indian perspective. Settings and Design: It was a mixed method, cross-sectional, and exploratory design wherein in-depth qualitative data covering a broader area of experiences were gathered from a sub-section of the larger quantitative sample (n = 50). The qualitative sample consisted of 15 Indian women from urban communities of Southern and Eastern India. Sampling method was purposive in nature. Subjects and Methods: Semi-structured interview schedule was developed by researchers based on a review of literature. In-depth interviews were audio recorded after their permissions were obtained and carried out at homes and offices of participants. All participants spoke English. Qualitative data were collected until no new phenomenological information emerged through the interviews. Data Management and Analysis: Descriptive phenomenological approach was utilized to analyze the interview data. It focuses on understanding one's life experience from the first person's point of view. Results: Consistent with other literature, PTG was evident in varying forms through positive changes in perspective toward life, better understanding of self, closer, and warmer relationships, and richer spiritual dimension of life. Conclusions: These findings have implications for promoting holistic cancer care and identifying ways to promote PTG through the initial stages of cancer care into survivorship trajectory.
BMI at Age 17 Years and Diabetes Mortality in Midlife: A Nationwide Cohort of 2.3 Million Adolescents

OBJECTIVE The sequelae of increasing childhood obesity are of major concern. We assessed the association of BMI in late adolescence with diabetes mortality in midlife. RESEARCH DESIGN AND METHODS The BMI values of 2,294,139 Israeli adolescents (age 17.4 ± 0.3 years), measured between 1967 and 2010, were grouped by U.S. Centers for Disease Control and Prevention age/sex percentiles and by ordinary BMI values. The outcome, obtained by linkage with official national records, was death attributed to diabetes mellitus (DM) as the underlying cause. Cox proportional hazards models were applied. RESULTS During 42,297,007 person-years of follow-up (median, 18.4 years; range <1–44 years) there were 481 deaths from DM (mean age at death, 50.6 ± 6.6 years). There was a graded increase in DM mortality evident from the 25th to the 49th BMI percentile group onward and from a BMI of 20.0–22.4 kg/m2 onward. Overweight (85th to 94th percentiles) and obesity (the 95th percentile or higher), compared with the 5th to 24th percentiles, were associated with hazard ratios (HRs) of 8.0 (95% CI 5.7–11.3) and 17.2 (11.9–24.8) for DM mortality, respectively, after adjusting for sex, age, birth year, height, and sociodemographic variables. The HR for the 50th through 74th percentiles was 1.6 (95% CI 1.1–2.3). Findings persisted in a series of sensitivity analyses. The estimated population-attributable fraction for DM mortality, 31.2% (95% CI 26.6–36.1%) for the 1967–1977 prevalence of overweight and obesity at age 17, rose to a projected 52.1% (95% CI 46.4–57.4%) for the 2012–2014 prevalence. CONCLUSIONS Adolescent BMI, including values within the currently accepted “normal” range, strongly predicts DM mortality up to the seventh decade. The increasing prevalence of childhood and adolescent overweight and obesity points to a substantially increased future adult DM burden.