Miracle-dz/UniFAR-FTUs huggingface dataset:
Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.
Notch3 Mutations in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a Mendelian Condition Causing Stroke and Vascular Dementia

ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited condition whose key features include recurrent subcortical ischemic events, migraine attacks and vascular dementia in association with diffuse white‐matter abnormalities seen on neuroimaging. Pathologic examination shows multiple small deep cerebral infarcts, a leukoencephalopathy and a nonatherosclerotic nonamyloid angiopathy involving mainly the media of small cerebral arteries. To progress in understanding the pathophysiological mechanisms of this condition, we undertook the identification of the mutated gene. We mapped the CADASIL gene on chromosome 19p13.1. More than 120 families have been referred to our lab. Genetic linkage analysis of 33 of these families allowed us to reduce the size of the genetic interval to less than 1 cM and to demonstrate the genetic homogeneity of this condition. In the absence of any candidate gene, we undertook positional cloning of this gene. We identified, within the CADASIL critical region, the human Notch3 gene, whose sequence analysis revealed deleterious mutations in CADASIL families co‐segregating with the affected phenotype. These data establish that this gene causes CADASIL. Identification of the CADASIL gene will provide a valuable diagnostic tool for clinicians and could be used to estimate the prevalence of this underdiagnosed condition. It should help in the understanding of pathophysiological mechanisms of CADASIL and vascular dementia.
Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel

Background Poly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been demonstrated to be biocompatible and thermosensitive. In this study, its potential efficacy and mechanisms of preventing postsurgical abdominal adhesions were investigated. Results PECE hydrogel was transformed into gel state from sol state in less than 20 seconds at 37°C. None of the animals treated with the hydrogel (n = 15) developed adhesions. In contrast, all untreated animals (n = 15) had adhesions that could only be separated by sharp dissection (P < 0.001). The hydrogel adhered to the peritoneal wounds, gradually disappeared from the wounds within 7 days, and transformed into viscous fluid, being completely absorbed within 12 days. The parietal and visceral peritoneum were remesothelialized in about 5 and 9 days, respectively. The hydrogel prevented the formation of fibrinous adhesion and the invasion of fibroblasts. Also, along with the hydrogel degradation, a temporary inflammatory cell barrier was formed which could effectively delay the invasion of fibroblasts during the critical period of mesothelial regeneration. Conclusion The results suggested that PECE hydrogel could effectively prevent postsurgical intra-abdominal adhesions, which possibly result from the prevention of the fibrinous adhesion formation and the fibroblast invasion, the promotion of the remesothelialization, and the hydroflotation effect.
Cirrhotic patients with minimal hepatic encephalopathy have increased capacity to eliminate superoxide and peroxynitrite in lymphocytes, associated with cognitive impairment

Abstract Patients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxide (plumbagin) or nitric oxide (NOR-1) to assess the capacity to eliminate them. Under basal conditions, MHE patients show reduced superoxide and peroxynitrite levels and increased nitric oxide (NO) and nitrotyrosine levels. In patients without MHE plumbagin strongly increases cellular superoxide, moderately peroxynitrite and reduces NO levels. In MHE patients, plumbagin increases slightly superoxide and strongly peroxynitrite levels and affects slightly NO levels. NOR-1 increases NO levels much less in patients with than without MHE. These data show that the mechanisms and the capacity to eliminate cellular superoxide, NO and peroxynitrite are enhanced in MHE patients. Superoxide elimination is enhanced through reaction with NO to form peroxynitrite which, in turn, is eliminated by enhanced reaction with biological molecules, which could contribute to cognitive impairment in MHE. The data show that basal free radical levels do not reflect the oxidative stress status in MHE.
Is there a relationship between 3‐hydroxy‐3‐methylglutaryl coenzyme a reductase activity and forebrain pathology in the PKU mouse?

Previous reports have suggested that elevated levels of phenylalanine inhibit cholesterol synthesis. The goals of this study were to investigate if perturbations in cholesterol synthesis exist in the PAHenu2 genetic mouse model for phenylketonuria (PKU), and if so, initiate studies determining if they might underlie the white matter pathology that exists in PKU forebrain. Gross sections and electron microscopy showed that select tracts were hypomyelinated in adult PKU mouse forebrain but not hindbrain. The activity of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGR), the rate controlling enzyme in the cholesterol biosynthetic pathway, was examined in isolated microsomes from forebrain, hindbrain, and liver to assess if perturbations in cholesterol biosynthesis were occurring. HMGR activity was normal in unaffected PKU hindbrain and was increased 2–4‐fold in PKU liver compared to control. HMGR activity in the forebrain, however, was decreased by 30%. Because normal numbers of MBP‐expressing glia (oligodendrocytes) were present, but the number of glia expressing HMGR was reduced by 40% in the hypomyelinated tracts, the decreased HMGR activity seemed to result from a down‐regulation of HMGR expression in affected oligodendrocytes. Exposure of an oligodendrocyte‐like glioma cell line to physiologically relevant elevated levels of Phe resulted in a 30% decrease in cholesterol synthesis, a 28% decrease in microsomal HMGR activity, and a 28% decrease in HMGR protein levels. Measurement of HMGR activity after addition of exogenous Phe to control brain microsomes revealed that Phe is a noncompetitive inhibitor of HMGR; physiologically relevant elevated levels of exogenous Phe inhibited HMGR activity by 30%. Taken together, these data suggest that HMGR is moderately inhibited in the PKU mouse. Unlike other cell types in the body, a subset of oligodendrocytes in the forebrain seems to be unable to overcome this inhibition. We speculate that this may be the cause of the observed pathology in PKU brain. J. Neurosci. Res. 61:549–563, 2000. © 2000 Wiley‐Liss, Inc.
Characterization of in situ Deformation Texture in Superelastic Nitinol

This dissertation is motivated by the increasing usage of Nitinol in biomedical implant devices as well as the disturbing numbers of device failures as reported in the literature. Given the recent awareness of the complex in vivo loading conditions experience by the devices, combined with the lack of commercial finite element analysis program capable of accurate lifetime prediction for such devices, it is imperative to understand the fundamental mechanism of the underlying phase transformation behind the superelastic mechanical properties of Nitinol. Macroscopic multi-mode fatigue is examined through classical continuum mechanics. It is found that normalization of the dissimilar mechanical behaviors of superelastic Nitinol under multi-modes loading is possible through Coffin-Manson approach. The influence of austenitic texture under in situ multi-mode monotonic and fatigue loading is explored with micro-X-ray Diffraction. It appears that the martensitic transformation propagation occurs in competing pathways between the grain boundary and grain with favorable transformation orientations. It is found that initial austenitic textures as well as loading modes favors different propagation paths. The resulting evolution of austenite texture may explain the fatigue degradation of Nitinol. Austenite texture sharpness as well as grain boundary density is found to have negative influence on the fatigue lifetime of Nitinol. The results determined through this research can be used to derive a better constitutive relation as well as methods for better fatigue lifetime prediction.
Extrahepatic Manifestations and Autoantibodies in Patients with Hepatitis C Virus Infection

Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy

Cancer-related metabolism has recently emerged as one of the “hallmarks of cancer”. It has several important features, including altered metabolism of glucose and glutamine. Importantly, altered cancer metabolism connects different biochemical pathways into the one fine-tuned metabolic network, which stimulates high proliferation rates and plasticity to malignant cells. Among the keystones of cancer metabolism are one-carbon metabolism and nucleotide biosynthesis, which provide building blocks to anabolic reactions. Accordingly, the importance of these metabolic pathways for anticancer therapy has well been documented by more than fifty years of clinical use of specific metabolic inhibitors – methotrexate and nucleotides analogs. In this review we discuss one-carbon metabolism and nucleotide biosynthesis as common and specific features of many, if not all, tumors. The key enzymes involved in these pathways also represent promising anti-cancer therapeutic targets. We review different aspects of these metabolic pathways including their biochemistry, compartmentalization and expression of the key enzymes and their regulation at different levels. We also discuss the effects of known inhibitors of these pathways as well as the recent data on other enzymes of the same pathways as perspective pharmacological targets.
Pediatricians' Response to the Demand for School Health Programming

Objective. Because of the broad and increasing interest in school health, the American Academy of Pediatrics (AAP) surveyed its members to determine their awareness of school health education/programs, their level of participation, their desire to participate, and their resource needs to participate more effectively. Methods. Self-administered questionnaires were mailed to a randomized representative sample of AAP members (N= 1602). Overall response rate was 64.5%. Some responses were stratified for analysis by gender; age (>45 years or ≤45 years); practice area (urban, suburban, or rural); practice setting (solo, group, or hospital); and type of practice (general versus specialty). χ2 Tests were used to compare responses. Results. Greater than half of the pediatricians who responded to the questionnaire were aware of school health education curriculum on risky adolescent behaviors in their community, counseling services (58%), school nursing services (63%), and screening services (71%); however, more than half were not aware of curriculum on injury/violence prevention, fitness, or whether a school health advisory council was available. Most pediatricians supported comprehensive school health education (pregnancy prevention, 82%; violence prevention, 77%; mental health, 56%). Also, respondents supported services (counseling, 76%; nutrition, 65%; screening/referral, 58%; school-based primary care, 58%). Although 22% of AAP pediatricians are currently working with local school programs, >70% wanted to become involved or more involved and needed information on how they may be able to participate. Only 25% believed they were adequately prepared. Two thirds believed school-based clinics were one of the best ways to reach underserved children and adolescents and should include preteens. Conclusion. AAP pediatricians want to become more involved with comprehensive school health programs. The ways in which they want to participate vary substantially. Most pediatricians thought they needed additional education. The AAP has developed recommendations for graduate medical education and continuing medical education for pediatricians to participate in integrated school health services.
CUDL Language Semantics: Authority Links

Conceptual Universal Database Language (CUDL) is a new language designed to manage dynamic database environments, which conform to the Frame DataBase model (FDB). FDB is a generic database model (oversubscribe both the Entity-Attribute-Value and the Nested Relational). CUDL is not only an FDB database language but it is mainly an agent that provides an abstraction level superior to the logical level. CUDL permits the users to conceive a database schema where single fields (tags) accept repetitions (list of values), entertain subfields and also permit to entertain an entire table in the place of a single field. In this paper we explain the advanced power of the FDB CUDL that emanates from particular improvements to specific parts of the generic FDB model. More precisely, we investigate ameliorations to the “authority links” set of FDB and explain the outgrowth of these ameliorations, to define easily unambiguous and robust relationships between database entities. We also present the novel ability of the model to manipulate data normalizations and data explanations.
Calcineurin inhibitor‐sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicity

Abstract: Background: The calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, have had a revolutionary effect on the overall success of renal transplantation through reduction in early immunologic injury and acute rejection rates. However, the CNIs have a significant adverse impact on renal function and cardiovascular disease, and extended long‐term graft survival has not been achieved. The recognition of these effects sparked interest in CNI‐sparing strategies. Strategies to limit CNI exposure include CNI minimization, avoidance, and withdrawal. We sought to review the impact of CNI‐sparing strategies in kidney, liver, and heart transplantation.
Agent Technologies for Virtual Enterprises in the One-of-a-Kind-Production Industry

One-of-a-kind-products (OKP) virtual enterprises are highly individualized and perform unique projects. Structural and behavioral modeling are important aspects of the use of agents to support their information systems. This paper discusses business processes in the OKP environment in relation to the collaboration/cooperation mechanisms enacted between people and information systems in a distributed virtual enterprise (VE). The Agent-Object-Relationship (AOR) language and modeling methods are introduced for giving details about structure, interaction, and behavior. As an example, a generic model of a multi-agent system is mapped onto the virtual enterprise model.
Experimental Investigation of Performance and Emissions in Light Duty Diesel Engine under Different Loads using Diesel-Biodiesel Fuel Blends

In this research, the performance characteristics and exhaust emissions of an air-cooled single-cylinder diesel engine were investigated using different mixtures of biodiesel fuel derived from castor oil. The evaluations were carried out at different engine loads (0, 25, 50, 75 and 100%) and engine constant speed of 1950 rpm. For all of the investigated loads, the generated power by the engine using the different biofuel mixturesincreased.The specific fuel consumptiondecreased for biodiesel blendsin low loads compared to diesel fuel. The lowest emissions of CO pollutant for all of the evaluated mixtures were observed at middle engine loads and the emissions for biodiesel mixtures were lower than those of pure diesel fuel. Emissions of CO2 for all of the evaluated mixtures were lower than those of pure diesel and the highest decrease (8.5%) was observed for B15 mixture. Compared with pure diesel fuel, the emission of NOx for B5 and B10 mixtures increased insignificantly, whilst the emission decreased for B15 and B20 mixtures. The emissions of unburnedhydrocarbons by the engine decreased by 21% compared to pure diesel engine.
NeuroControl of movement: system identification approach for clinical benefit

Progress in diagnosis and treatment of movement disorders after neurological diseases like stroke, cerebral palsy (CP), dystonia and at old age requires understanding of the altered capacity to adequately respond to physical obstacles in the environment. With posture and movement disorders, the control of muscles is hampered, resulting in aberrant force generation and improper impedance regulation. Understanding of this improper regulation not only requires the understanding of the role of the neural controller, but also attention for: (1) the interaction between the neural controller and the “plant”, comprising the biomechanical properties of the musculaskeletal system including the viscoelastic properties of the contractile (muscle) and non-contractile (connective) tissues: neuromechanics; and (2) the closed loop nature of neural controller and biomechanical system in which cause and effect interact and are hence difficult to separate. Properties of the neural controller and the biomechanical system need to be addressed synchronously by the combination of haptic robotics, (closed loop) system identification (SI), and neuro-mechanical modeling. In this paper, we argue that assessment of neuromechanics in response to well defined environmental conditions and tasks may provide for key parameters to understand posture and movement disorders in neurological diseases and for biomarkers to increase accuracy of prediction models for functional outcome and effects of intervention.
Mutational Analysis of CD28 in Coeliac Disease

Background: Coeliac disease shows a strong genetic predisposition involving HLA-DQ2 and non-HLA components. The CD28 cell surface molecule, encoded by CD28, represents a potential candidate coeliac disease susceptibility gene. Furthermore, some studies have demonstrated linkage to the CD28/CTLA4 gene region. To investigate whether germline mutations in CD28 contribute to coeliac disease susceptibility, we have carried out a comprehensive analysis of the gene in Swedish patients with biopsyproven disease. Methods: Blood samples were collected from 52 children with biopsy proven coeliac disease attending one Swedish centre. DNA was extracted from lymphocytes and all exons and intronexon boundaries of CD28 were screened for mutations. Analysis of CD28 was undertaken by a combination of conformation specific gel electrophoresis and direct sequencing. Results: Three sequence variants were identified: a synonymous G → A substitution at position 3 of codon 35 encoding alanine, a synonymous G → A substitution at position 3 of codon 70 encoding glycine, and a T → C substitution at nucleotide +17 of intron 3. No pathogenic variants were detected. Conclusions: There is no evidence from this study that mutations in CD28 , which lead to an altered protein, contribute to coeliac disease susceptibility.
A Bayesian Stochastic Machine for Sound Source Localization

Compared to conventional processors, stochastic computing architectures have strong potential to speed up computation time and to reduce power consumption. We present such an architecture, called Bayesian Machine (BM), dedicated to solving Bayesian inference problems. Given a set of noisy signals provided by low-level sensors, a BM estimates the posterior probability distribution of an unknown target information. In the present study, a BM is used to solve a sound source localization (SSL) problem: the BM computes the probability distribution of the position of a sound source given acoustic signals captured by a set of microphones. Assuming free field wave propagation (no reverberations), we express the SSL problem as the maximization of a likelihood function fed with audio features provided by the time-frequency (TF) analysis of the captured audio waves. The proposed BM uses bitwise parallel sampling to fuse the resulting multi-channel information. As the number of channels to fuse is large, the standard BM architecture encounters the so-called ``time dilution problem" (long delays are necessary to obtain valid samples). We tackle this problem by using max-normalization of the distributions combined with a periodic re-sampling of the bit streams after processing a reasonably small subset of evidences. Finally, we compare the localization performance of the proposed machine with the results obtained using a standard version of the machine. The re-sampling leads to an impressive acceleration factor of 10³ in the computation.