Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of Autoantigen-Specific Th2 and Tr1 Regulatory T Cells and Modulation of Autoimmune Diabetes1

Autoantigen-based immunotherapy can modulate autoimmune diabetes, perhaps due to the activation of Ag-specific regulatory T cells. Studies of these regulatory T cells should help us understand their roles in diabetes and aid in designing a more effective immunotherapy. We have used class II MHC tetramers to isolate Ag-specific T cells from nonobese diabetic (NOD) mice and BALB/c mice treated with glutamic acid decarboxylase 65 peptides (p206 and p221). Based on their cytokine secretion profiles, immunization of NOD mice with the same peptide induced different T cell subsets than in BALB/c mice. Treatment of NOD mice induced not only Th2 cells but also IFN-γ/IL-10-secreting T regulatory type 1 (Tr1) cells. Adoptive transfer experiments showed that isolated tetramer+ T cells specific for p206 or p221 could inhibit diabetes development. These cells were able to suppress the in vitro proliferation of other NOD mouse T cells without cell-cell contact. They performed their regulatory functions probably by secreting cytokines, and Abs against these cytokines could block their suppressive effect. Interestingly, the presence of both anti-IL-10 and anti-IFN-γ could enhance the target cell proliferation, suggesting that Tr1 cells play an important role. Further in vivo experiments showed that the tetramer+ T cells could block diabetogenic T cell migration into lymph nodes. Therefore, treatment of NOD mice with autoantigen could induce Th2 and Tr1 regulatory cells that can suppress the function and/or block the migration of other T cells, including diabetogenic T cells, and inhibit diabetes development.
P-glycoprotein function and expression during obstructive cholestasis in rats

Objectives The present study was aimed at evaluation of in vivo biliary and renal excretion of rhodamine 123 (Rho123), a P-glycoprotein (P-gp) substrate, in rats during either acute or chronic cholestasis induced by bile duct obstruction (BDO). Methods The Rho123 clearance study was performed either one (BDO1) or seven (BDO7) days after BDO. Bile flow was reconstituted, and bile and urine were collected after steady-state plasma concentration of Rho123 was attained. Tissue expression of P-gp was evaluated by quantitative immunohistochemistry, and immunoblotting. Results Significant up-regulation of the liver P-gp protein was observed in acute and chronic cholestasis. Primary periportal location of P-gp was enlarged also to pericentral areas. In the kidneys, immunohistochemistry showed pancellular increase in P-gp after 1 day of BDO, which subsided after 7 days of BDO. Nevertheless, biliary and renal clearances (CLBile and CLR) of Rho123 did not reflect the induction of P-gp expression. While CLBile was reduced one day after cholestasis and restored on the seventh day, the CLR was preserved in BDO1 group and reduced in BDO7 group without change in glomerular filtration rate. In parallel, biliary and renal clearances of conjugated bilirubin were significantly reduced in both cholestatic groups compared with controls. Conclusion These findings suggest that extrahepatic cholestasis causes time-dependent changes in elimination of Rho123 which do not exactly reflect alteration of P-gp expression in the rat liver and kidney. These data may help to explain impaired elimination of P-gp substrates after short-term cholestasis that may commonly occur in clinical practice.
A Medical Claim Fraud/Abuse Detection System based on Data Mining: A Case Study in Chile

This paper describes an effective medical claim fraud/abuse detection system based on data mining used by a Chilean private health insurance company. Fraud and abuse in medical claims have become a major concern within health insurance companies in Chile the last years due to the increasing losses in revenues. Processing medical claims is an exhausting manual task carried out by a few medical experts who have the responsibility of approving, modifying or rejecting the subsidies requested within a limited period from their reception. The proposed detection system uses one committee of multilayer perceptron neural networks (MLP) for each one of the entities involved in the fraud/abuse problem: medical claims, affiliates, medical professionals and employers. Results of the fraud detection system show a detection rate of approximately 75 fraudulent and abusive cases per month, making the detection 6.6 months earlier than without the system. The application of data mining to a real industrial problem through the implementation of an automatic fraud detection system changed the original non-standard medical claims checking process to a standardized process helping to fight against new, unusual and known fraudulent/abusive behaviors.
Sex Differences in Blood Pressure Response to Intermittent Hypoxia in Rats

Intermittent hypoxia is used to mimic the arterial hypoxemia that occurs during sleep apnea. The present study examined the blood pressure and heart rate responses to exposure to intermittent hypoxia in male rats and in female rats before and after ovariectomy. Rats were instrumented with telemetry transmitters and blood pressure, heart rate, and activity measured during 7 days of exposure to intermittent hypoxia (3 minutes of normoxia [21% oxygen] alternating with 3 minutes 10% oxygen between 8 am and 4 pm, remainder of day at normoxia). Blood pressure increased in males, females, and ovariectomized females in response to 7 days of intermittent hypoxia during the hours of exposure to hypoxia. Blood pressure increased less in intact females (average change in blood pressure 1.6±0.6 mm Hg, n=11) than in females studied after ovariectomy (5.1±1.1 mm Hg, n=6) or males (5.4±1.0 mm Hg, n=10). This elevated blood pressure persisted throughout the remainder of the day when the animals were not exposed to intermittent hypoxia and remained significantly attenuated in female rats. Ovariectomy abolished the protection against the elevated blood pressure response to intermittent hypoxia in females. Heart rate increased only in males, and only during the period of the day associated with intermittent hypoxia. Female rats were protected against this tachycardia independent of the ovarian hormones. These results indicate that females are protected from the hypertensive and tachycardia effects of intermittent hypoxia.
Unsuspected Dengue as a Cause of Acute Febrile Illness in Children and Adults in Western Nicaragua

Background Dengue is an emerging infectious disease of global significance. Suspected dengue, especially in children in Nicaragua’s heavily-urbanized capital of Managua, has been well documented, but unsuspected dengue among children and adults with undifferentitated fever has not. Methodology/Principal Findings To prospectively study dengue in semi-urban and rural western Nicaragua, we obtained epidemiologic and clinical data as well as acute and convalescent sera (2 to 4 weeks after onset of illness) from a convenience sample (enrollment Monday to Saturday daytime to early evening) of consecutively enrolled patients (n = 740) aged ≥ 1 years presenting with acute febrile illness. We tested paired sera for dengue IgG and IgM and serotyped dengue virus using reverse transcriptase-PCR. Among 740 febrile patients enrolled, 90% had paired sera. We found 470 (63.5%) were seropositive for dengue at enrollment. The dengue seroprevalance increased with age and reached >90% in people over the age of 20 years. We identified acute dengue (serotypes 1 and 2) in 38 (5.1%) patients. Only 8.1% (3/37) of confirmed cases were suspected clinically. Conclusions/Significance Dengue is an important and largely unrecognized cause of fever in rural western Nicaragua. Since Zika virus is transmitted by the same vector and has been associated with severe congenital infections, the population we studied is at particular risk for being devastated by the Zika epidemic that has now reached Central America.
Depersonalization Disorder in Former Addicts (Prevalence of Depersonalization-Derealization Disorder in Former Addicts)

Many former addicts who have not been taking drugs for a while suffer from the so-called depersonalizationderealization disorder (DPD-DR) –a peculiar sensation of unreality and strangeness towards the environment, something like “living in a permanent dream”. It is not an altered conscious state but a different conscience of the world which makes the individual become a virtual spectator of a life that sometimes looks real to them, and sometimes looks illusory. Nearly all studies on the depersonalization-addiction binomial refer to current drug addicts, but there are no studies on former addicts. Objective: To find out the prevalence of depersonalization-derealization disorder in former addicts. Method: 68 former addicts were compared with 59 individuals from the control group. CDS (Cambridge Depersonalization Scale) scale, version CDS-11, and DES (Dissociative Experiences Scale by Bernstein & Putnam) scale were applied. Results: Nearly 25% of drug-free addicts (former addicts) suffer or have suffered from severe depersonalization disorder (DES scale). If we consider mild depersonalization disorder, the number rises up to 43.55% (DES scale) and 19.38% (CDS-11 scale). It should be noted that DPD-DR prevalence in the general population is 1.5%. Conclusions: Depersonalization-derealization disorder is a surprise both for former addicts and their relatives, as well as for the clinical staff, who is usually unaware of this phenomenon and can mistake it for nostalgia towards the consumption environment. Who knows how many drug-free or former addicts have been victims of a mistake by their therapist? DPD-DR can be overcome through an adequate intervention in 3-6 months from onset. We think healthcare professionals should be well aware of this phenomenon.
What will I like best when I'm all grown up? Preschoolers' understanding of future preferences.

Three experiments investigated 3-, 4-, and 5-year-olds' (N = 240) understanding that their future or "grown-up" preferences may differ from their current ones (self-future condition). This understanding was compared to children's understanding of the preferences of a grown-up (adult-now condition) or the grown-up preferences of a same-aged peer (peer-future condition). Children's performance across all three conditions improved significantly with age. Moreover, children found it significantly more difficult to reason about their own future preferences than they did to reason either about an adult's preferences or the future preferences of a peer. These results have important implications for theories about future thinking and perspective-taking abilities, more broadly.
Striated domains: self-organizing ordered assemblies of transmembrane α-helical peptides and lipids in bilayers

Abstract This review summarizes the knowledge on striated domains, which are ordered assemblies of transmembrane peptides and lipids under gel-state conditions. The structure, mechanism of function and utility of this system as a model for domain formation is described, resulting in a molecular description of the domains and a discussion on the relevance of these insights for the function/formation and structure of similar domains in biological membranes.
Strong T-Perfection of Bad-K4-Free Graphs

We show that each graph not containing a bad subdivision of -K4 as a subgraph is strongly t-perfect. Here a graph G=(V,E) is strongly t-perfect if, for each weight function $w:V\to\mathbb{Z}_+$, the maximum weight of a stable set is equal to the minimum (total) cost of a family of vertices, edges, and circuits covering any vertex v at least w(v) times. By definition, the cost of a vertex or edge is 1, and the cost of a circuit C is $\lfloor\frac{1}{2}|VC|\rfloor$. A subdivision of K4 is called bad if each triangle has become an odd circuit and if it is not obtained by making the edges in a 4-circuit of K4. evenly subdivided, while the other two edges are not subdivided. The theorem generalizes earlier results of Gerards [J. Combin. Theory Ser. B, 47 (1989), pp. 330--348] on the strong t-perfection of odd-K4-free graphs and of Gerards and Shepherd [SIAM J. Discrete Math., 11 (1998), pp. 524--545] on the t-perfection of bad-K4-free graphs.
New Cell Growth

Background: Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. Results: Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion: VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods. It is freely-available online at the URL: http://www.jenner. ac.uk/VaxiJen. Published: 05 January 2007 BMC Bioinformatics 2007, 8:4 doi:10.1186/1471-2105-8-4 Received: 24 August 2006 Accepted: 05 January 2007 This article is available from: http://www.biomedcentral. com/1471-2105/8/4 © 2007 Doytchinova and Flower; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
SINR in Wireless Networks and the Two-Parameter Poisson-Dirichlet Process

Stochastic geometry models of wireless networks based on Poisson point processes are increasingly being developed with a focus on studying various signal-to-interference-plus-noise ratio (SINR) values. We show that the SINR values experienced by a typical user with respect to different base stations of a Poissonian cellular network are related to a specific instance of the so-called two-parameter Poisson-Dirichlet process. This process has many interesting properties as well as applications in various fields. We give examples of several results proved for this process that are of immediate or potential interest in the development of analytic tools for cellular networks. Some of them simplify or are akin to certain results that are being developed in the network literature. By doing this we hope to motivate further research and use of Poisson-Dirichlet processes in this new setting.
Myogenic Differential Methylation: Diverse Associations with Chromatin Structure

Employing a new algorithm for identifying differentially methylated regions (DMRs) from reduced representation bisulfite sequencing profiles, we identified 1972 hypermethylated and 3250 hypomethylated myogenic DMRs in a comparison of myoblasts (Mb) and myotubes (Mt) with 16 types of nonmuscle cell cultures. DMRs co-localized with a variety of chromatin structures, as deduced from ENCODE whole-genome profiles. Myogenic hypomethylation was highly associated with both weak and strong enhancer-type chromatin, while hypermethylation was infrequently associated with enhancer-type chromatin. Both myogenic hypermethylation and hypomethylation often overlapped weak transcription-type chromatin and Polycomb-repressed-type chromatin. For representative genes, we illustrate relationships between DNA methylation, the local chromatin state, DNaseI hypersensitivity, and gene expression. For example, MARVELD2 exhibited myogenic hypermethylation in transcription-type chromatin that overlapped a silenced promoter in Mb and Mt while TEAD4 had myogenic hypomethylation in intronic subregions displaying enhancer-type or transcription-type chromatin in these cells. For LSP1, alternative promoter usage and active promoter-type chromatin were linked to highly specific myogenic or lymphogenic hypomethylated DMRs. Lastly, despite its myogenesis-associated expression, TBX15 had multiple hypermethylated myogenic DMRs framing its promoter region. This could help explain why TBX15 was previously reported to be underexpressed and, unexpectedly, its promoter undermethylated in placentas exhibiting vascular intrauterine growth restriction.
Effects of Direct and Indirect Cross-Group Friendships on Judgments of Catholics and Protestants in Northern Ireland: The Mediating Role of an Anxiety-Reduction Mechanism

Recent evidence suggests that both direct and indirect friendship with outgroup members (knowledge of ingroup members’ friendship with outgroup members) can reduce prejudice toward the outgroup. Two surveys of cross-community relationships in Northern Ireland, using a student sample (N = 341) and a representative sample of the general population (N = 735), tested whether (a) direct and indirect friendships had generalized effects on both prejudice and perceived outgroup variability and (b) reduced anxiety about future encounters with outgroup members mediated such relationships. Structural equation modeling confirmed that, in both samples, direct and indirect cross-group friendships between Catholics and Protestants were associated with reduced prejudice toward the religious outgroup and increased perceived outgroup variability, via an anxiety-reduction mechanism. It is argued that emerging generalization hypotheses help to integrate both cognition and affect and interpersonal and intergroup approaches to contact.
Essential role for a long-term depression mechanism in ocular dominance plasticity

The classic example of experience-dependent cortical plasticity is the ocular dominance (OD) shift in visual cortex after monocular deprivation (MD). The experimental model of homosynaptic long-term depression (LTD) was originally introduced to study the mechanisms that could account for deprivation-induced loss of visual responsiveness. One established LTD mechanism is a loss of sensitivity to the neurotransmitter glutamate caused by internalization of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Although it has been shown that MD similarly causes a loss of AMPARs from visual cortical synapses, the contribution of this change to the OD shift has not been established. Using an herpes simplex virus (HSV) vector, we expressed in visual cortical neurons a peptide (G2CT) designed to block AMPAR internalization by hindering the association of the C-terminal tail of the AMPAR GluR2 subunit with the AP2 clathrin adaptor complex. We found that G2CT expression interferes with NMDA receptor (NMDAR)-dependent AMPAR endocytosis and LTD, without affecting baseline synaptic transmission. When expressed in vivo, G2CT completely blocked the OD shift and depression of deprived-eye responses after MD without affecting baseline visual responsiveness or experience-dependent response potentiation in layer 4 of visual cortex. These data suggest that AMPAR internalization is essential for the loss of synaptic strength caused by sensory deprivation in visual cortex.
What the SWIFT and TREVO II Trials Tell Us About the Role of Endovascular Therapy for Acute Stroke

The Solitaire With the Intention for Thrombectomy (SWIFT) trial1 and the TREVO II trial,2 published online in Lancet in August 2012, are important trials in the history of endovascular therapy for acute ischemic stroke for several reasons. First, both randomized trials compared a new technology, 2 versions of a stent-retriever, with a previously Food and Drug Administration-cleared technology, the Merci Retriever. The latest iteration of the Merci Retriever, which had been cleared for use since 2005, is a flexible nitinol wire with distal corkscrew-shaped coil loops with attached filaments. Stent-retriever technology is based on self-expanding stents that can be fully deployed and then retrieved about 5 minutes later, after migration of the thrombus through the stent struts.3 Retrievable stents were introduced in 2010 in experienced, high-volume comprehensive European stroke centers with increased rates of recanalization in a shorter time compared with intra-arterial thrombolysis.4 The Merci Retriever and retrievable stents are distal thrombectomy devices that require navigation of the device through and beyond the site of occlusion without image-guidance of a high-resolution biplane or 3D roadmap. In contrast, proximal thrombectomy devices allow a safe, image-guided approach to the site of occlusion and aspiration of the thrombus. These 2 randomized trials broke the trend of single-arm trials comparing a new technology with the intravenous heparin arm of the randomized PROACT II trial study, which was completed in 1998.5 The goal of past single-arm trials, used for both the Merci Retriever6,7 and Penumbra Aspiration System,8 was to obtain 510k clearance by the FDA, or regulatory approval in other countries, for thrombectomy in acute ischemic stroke. However, no randomized trial of these devices has demonstrated improved clinical outcome by a thrombectomy device compared with standard therapy, whether intravenous tissue-type plasminogen activator (tPA) within 3 and …
Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4 ± 7.40 yo) preimplant NT proBNP level is 5124.5 ± 4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87 ± 0.41, 0.63 ± 0.66, 99.00 ± 2.60, and 3.22 ± 3.79%, respectively. LVEF was improved (22 ± 5.68 versus 26.8 ± 7.93, p < 0.001) during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.