Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-Dose Interleukin-2 Therapy Restores Regulatory T Cell Homeostasis in Patients with Chronic Graft-Versus-Host Disease

Regulatory T cell homeostasis is restored in patients with chronic graft-versus-host disease who receive low-dose interleukin-2 therapy. Restoring Balance to the Immune System Hematopoietic stem cell transplantation can be a lifesaving therapy for patients with certain types of cancers or other blood disorders. However, it’s rare to find a perfect match, and transplants frequently occur from donors who are antigenically different from the recipient. When this happens, the graft itself can attack the host as foreign tissue, a response called graft-versus-host disease (GVHD). Matsuoka et al. now report that daily low-dose interleukin-2 (IL-2) can expand regulatory T cells (Tregs) and improve chronic GVHD. The authors studied the effects of daily low-dose IL-2 on different subsets of CD4+ T cells in patients with chronic GVHD. Conventional T cells in these patients had altered phosphorylation of the signaling molecule signal transducer and activator of transcription 5 (Stat5) and a functional deficiency in IL-2. When this IL-2 deficiency was replaced with their therapy, Stat5 phosphorylation levels were selectively increased in Tregs but decreased conventional T cells. Indeed, although daily low-dose IL-2 had minimal effects on conventional T cells, it induced a series of changes to Treg homeostasis that likely led to the establishment of immune tolerance. CD4+Foxp3+ regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation. We recently reported that daily administration of low-dose interleukin-2 (IL-2) induces selective expansion of functional Tregs and clinical improvement of chronic graft-versus-host disease (GVHD). To define the mechanisms of action of IL-2 therapy, we examined the immunologic effects of this treatment on homeostasis of CD4+ T cell subsets after transplant. We first demonstrated that chronic GVHD is characterized by constitutive phosphorylation of signal transducer and activator of transcription 5 (Stat5) in conventional CD4+ T cells (Tcons) associated with elevated amounts of IL-7 and IL-15 and relative functional deficiency of IL-2. IL-2 therapy resulted in the selective increase of Stat5 phosphorylation in Tregs and a decrease of phosphorylated Stat5 in Tcons. Over an 8-week period, IL-2 therapy induced a series of changes in Treg homeostasis, including increased proliferation, increased thymic export, and enhanced resistance to apoptosis. Low-dose IL-2 had minimal effects on Tcons. These findings define the mechanisms whereby low-dose IL-2 therapy restores the homeostasis of CD4+ T cell subsets and promotes the reestablishment of immune tolerance.
FERMI DETECTION OF γ-RAY EMISSION FROM THE M2 SOFT X-RAY FLARE ON 2010 JUNE 12

The Geostationary Operational Environmental Satellite (GOES) M2-class solar flare, SOL2010-06-12T00:57, was modest in many respects yet exhibited remarkable acceleration of energetic particles. The flare produced an ∼50 s impulsive burst of hard X- and γ-ray emission up to at least 400 MeV observed by the Fermi Gamma-ray Burst Monitor and Large Area Telescope experiments. The remarkably similar hard X-ray and high-energy γ-ray time profiles suggest that most of the particles were accelerated to energies ≳300 MeV with a delay of ∼10 s from mildly relativistic electrons, but some reached these energies in as little as ∼3 s. The γ-ray line fluence from this flare was about 10 times higher than that typically observed from this modest GOES class of X-ray flare. There is no evidence for time-extended >100 MeV emission as has been found for other flares with high-energy γ-rays.
Regularized Least Squares Potential SVRs

In this paper, we propose a regularized least squares approach to potential SVRs. The proposed solution involves inverting a single matrix of small dimension. In the case of linear SVRs, the size of the matrix is independent of the number of data samples. Results involving benchmark data sets demonstrate the computational advantages of the proposal. In a recent publication, it has been highlighted that the margin in support vector machines (SVMs) is not scale invariant. This implies that an appropriate scaling can have an impact on the generalization performance of the SVM based regressor. Potential SVMs address this issue and suggest a new approach to regression
Factors Associated with Successful Export Performance: A Study of Thai International Service Firms

International service enterprises have become critical in the global market. As a result, there is an increasing need to investigate what factors contribute to creating successful firms. Meanwhile, creating and maintaining long-term relationships between service firm exporters and business clients are seen as an effective tool to enhance a firm’s performance. A proposed follow-up study will develop and empirically test a theoretical framework of the antecedents that cover organizational issues, plural forms of governance mechanism and performance implications of successful inter-firm relationships. This study is designed to extend previous research of the service sector in Thailand.
Do we need novel radiologic response criteria for brain tumor immunotherapy?

Early phase studies of glioma vaccines have shown encouraging preliminary clinical activity. However, as the therapeutic basis of immunotherapy involves the induction of an inflammatory response in the lesion, it is often challenging to properly evaluate radiological responses. Long-term survival and/or regression are sometimes seen after initial imaging changes that can suggest immunotherapy failure, which highlights the limitations of conventional response evaluation approaches and calls attention to the need for more therapeutically relevant strategies to provide a reliable assessment of response to brain tumor immunotherapy. As our knowledge of immunologic science has evolved [1], and novel immunomodulatory agents have become available, we have begun to face unique challenges in the radiologic evaluation of patients, given that inflammatory responses induced by vaccine strategies can mimic radiologic features of tumor progression [2]. A series of published studies of vaccination in brain tumor patients has suggested that the incidence of ‘tumor pseudoprogression’ following vaccine treatments is not insignificant, which may result in the possible unnecessary withdrawal of patients from these studies. Conversely, objective tumor regressions have been reported following postvaccine chemotherapy [3–5], which complicates the determination of whether efficacy resulted from a delayed response to the immune therapy, a direct effect of the chemotherapeutic agent, or a combination of both. In this regard, Wheeler et al. reported that vaccinated patients receiving subsequent chemotherapy exhibited significantly longer times to tumor recurrence after chemotherapy, relative to their own previous recurrence times [5]. Furthermore, they demonstrated a correlation between vaccine responses and time-to-progression (TTP) spanning chemo therapy [4]. These findings imply that the biological status of these tumors at the time of switching from immunotherapy to chemotherapy may not represent pure tumor progression, but rather an effect of vaccine-induced immune responses within the persisting tumors. Indeed, we recently reported pathological evidence of pseudoprogression in a patient who participated in our Phase I/II vaccine study using type-1 polarizing dendritic cells and a potent immunoadjuvant, polyinosinic-polycytidylic acid (poly[I:C]) stabilized by lysine and carboxymethylcellulose (poly-ICLC) [6]. Following vaccination, this patient demonstrated enlargement of the gadolinium-enhanced lesion on MRI scans, and thus underwent craniotomy. However, the resected tissue revealed no evidence of a mitotically active tumor, and remarkable infiltration of CD68 macro phages and CD8 T cells. This implies that MRI-based evaluation of TTP requires careful interpretation Hideho Okada
Pilot feasibility of an mHealth system for conducting ecological momentary assessment of mood-related symptoms following traumatic brain injury

Abstract Objective: This study assessed pilot feasibility and validity of a mobile health (mHealth) system for tracking mood-related symptoms after traumatic brain injury (TBI). Design: A prospective, repeated measures design was used to assess compliance with daily ecological momentary assessments (EMA) conducted via a smartphone application over an 8-week period. Methods: An mHealth system was developed specifically for individuals with TBI and utilized previously validated tools for depressive and anxiety symptoms (Patient Health Questionnaire-9, Generalized Anxiety Disorder-7). Feasibility was assessed in 20 community-dwelling adults with TBI via an assessment of compliance, satisfaction and usability of the smartphone applications. The authors also developed and implemented a clinical patient safety management mechanism for those endorsing suicidality. Results: Participants correctly completed 73.4% of all scheduled assessments, demonstrating good compliance. Daily assessments took <2 minutes to complete. Participants reported high satisfaction with smartphone applications (6.3 of 7) and found them easy to use (6.2 of 7). Comparison of assessments obtained via telephone-based interview and EMA demonstrated high correlations (r = 0.81–0.97), supporting the validity of conducting these assessments via smartphone application in this population. Conclusions: EMA conducted via smartphone demonstrates initial feasibility among adults with TBI and presents numerous opportunities for long-term monitoring of mood-related symptoms in real-world settings.
Dynamics of post‐translational modifications and protein stability in the stroma of Chlamydomonas reinhardtii chloroplasts

The proteome of any system is a dynamic entity dependent on the intracellular concentration of the entire set of expressed proteins. In turn, this whole protein concentration will be reliant on the stability/turnover of each protein as dictated by their relative rates of synthesis and degradation. In this study, we have investigated the dynamics of the stromal proteome in the model organism Chlamydomonas reinhardtii by characterizing the half‐life of the whole set of proteins. 2‐DE stromal proteins profiling was set up and coupled with MS analyses. These identifications featuring an average of 26% sequence coverage and eight non‐redundant peptides per protein have been obtained for 600 independent samples related to 253 distinct spots. An interactive map of the global stromal proteome, of 274 distinct protein variants is now available on‐line at http://www.isv. cnrs‐gif.fr/gel2dv2/. N‐α‐terminal‐Acetylation (NTA) was noticed to be the most frequently detectable post‐translational modification, and new experimental data related to the chloroplastic transit peptide cleavage site was obtained. Using this data set supplemented with series of pulse‐chase experiments, elements directing the relationship between half‐life and N‐termini were analyzed. Positive correlation between NTA and protein half‐life suggests that NTA could contribute to protein stabilization in the stroma.
A Study on Factors of Education's Outcome using Decision Trees

In order to manage the lectures efficiently in the university and improve the educational outcome, the process is needed that make diagnosis of the present educational outcome of each classes on a lecture and find factors of educational outcome. In most studies for finding the factors of the efficient lecture, statistical methods such as association analysis, regression analysis are used usually, and recently decision tree analysis is employed, too. The decision tree analysis have the merits that is easy to understand a result model, and to be easy to apply for the decision making, but have the weaknesses that is not strong for characteristic of input data such as multicollinearity. This paper indicates the weaknesses of decision tree analysis, and suggests the experimental solution using multiple decision tree algorithm to supplement these problems. The experimental result shows that the suggested method is more effective in finding the reliable factors of the educational outcome.
Characterizing the conformational ensemble of monomeric polyglutamine

Studies of synthetic polyglutamine peptides in vitro have established that polyglutamine peptides aggregate via a classic nucleation and growth mechanism. Chen and colleagues [Proc Natl Acad Sci U S A 2002;99:11884–11889] have found that monomeric polyglutamine, which is a disordered statistical coil in solution, is the critical nucleus for aggregation. Therefore, nucleation of β‐sheet–rich aggregates requires an initial disorder to order transition, which is a highly unfavorable thermodynamic reaction. The questions of interest to us are as follows: What are the statistical fluctuations that drive β‐sheet formation in monomeric polyglutamine? How do these fluctuations vary with chain length? And why is this process thermodynamically unfavorable, that is, why is monomeric polyglutamine disordered? To answer these questions we use multiple molecular dynamics simulations to provide quantitative characterization of conformational ensembles for two short polyglutamine peptides. We find that the ensemble for polyglutamine is indeed disordered. However, the disorder is inherently different from that of denatured proteins and the average compactness and magnitude of conformational fluctuations increase with chain length. Most importantly, the effective concentration of sidechain primary amides around backbone units is inherently high and peptide units are solvated either by hydrogen bonds to sidechains or surrounding water molecules. Due to the multiplicity of backbone solvation modes the probability associated with any specific backbone conformation is small, resulting in a conformational entropy bottleneck which makes β‐sheet formation in monomeric polyglutamine thermodynamically unfavorable. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Coarse‐grained molecular dynamics simulations of protein–ligand binding

Coarse‐grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein–ligand binding processes. We chose two protein–ligand systems, the levansucrase–sugar (glucose or sucrose), and LinB–1,2‐dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand‐binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse‐grained (CG) ligand molecules revealed potential ligand‐binding sites on the protein surfaces other than the real ligand‐binding sites. The ligands bound most strongly to the real ligand‐binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase–sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand‐binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein–ligand binding processes. © 2014 Wiley Periodicals, Inc.
Expert Assessment Of The Environmental Risk Of Technogenic Nature – An Element Of The Environmental Pollution Liability Insurance Of The Industrial Enterprises

The article deals with the issues of insuring the environmental pollution risk in economic enterprises. In addition, the research outlines the structure of the environment with reference to the operations of enterprises with hazardous waste production; it also analyses the elements of the environment and the risk factors, which determine the risk situations in the industrial enterprises. Finally, the article discusses the primary role of environmental pollution liability insurance within the concept of risk management in the industrial enterprises.
A data‐centric framework for debugging highly parallel applications

Contemporary parallel debuggers allow users to control more than one processing thread while supporting the same examination and visualisation operations of that of sequential debuggers. This approach restricts the use of parallel debuggers when it comes to large scale scientific applications run across hundreds of thousands compute cores. First, manually observing the runtime data to detect error becomes impractical because the data is too big. Second, performing expensive but useful debugging operations becomes infeasible as the computational codes become more complex, involving larger data structures, and as the machines become larger. This study explores the idea of a data‐centric debugging approach, which could be used to make parallel debuggers more powerful. It discusses the use of ad hoc debug‐time assertions that allow a user to reason about the state of a parallel computation. These assertions support the verification and validation of program state at runtime as a whole rather than focusing on that of only a single process state. Furthermore, the debugger's performance can be improved by exploiting the underlying parallel platform because the available compute cores can execute parallel debugging functions, while a program is idling at a breakpoint. We demonstrate the system with several case studies and evaluate the performance of the tool on a 20 000 cores Cray XE6. Copyright © 2013 John Wiley & Sons, Ltd.
Administration of distillate thyme leaves into the diet of Segureña ewes: effect on lamb meat quality.

The effect of including thyme by-products from the distillation industry into the diet of pregnant ewes on the final quality of lamb meat was evaluated during meat storage in modified atmosphere. A total of 36 Segureña ewes were randomly assigned to three homogeneous groups. One group was fed a basal diet (BD) as control (C), whereas the diet of the other two groups was modified by substituting 10% (T 1) and 20% (T 2) of the BD with pellets made from 50% barley and 50% distilled thyme leaves (DTL). Meat spoilage (total viable, psychrotroph (PSY), moulds and yeasts, Enterobacteriaceae and lactic acid bacteria), thiobarbituric acid reactive substances (TBARS), colour (CIELab coordinates, metmyoglobin) and sensory characteristics of fresh lamb meat packed in modified atmosphere packaging (70% O2 : 30% CO2) were analysed after storage at 0, 7, 14 and 21 days. In general, the DTL-containing diet inhibited lipid and pigment oxidation in fresh lamb meat. Lower PSY counts and content of secondary oxidation product (TBARS) as a result of adding DTL to the ewe diet, whereas surface redness (a* values) was significantly higher on days 7 and 14. It can be concluded that thyme by-products from the distillation industry could be used as a source of natural antioxidant and antimicrobial in the feed for ewes.
The societal impact of governmental voluntary sustainable development programs: Case "the Commitment 2050"

This thesis aims at understanding the content and potential societal impact of governmental voluntary sustainable development program through a case entity “The Finland we want by 2050 – Society’s commitment to sustainable development”, focusing on business participants. Existing literature has focused mostly on evaluating issue or industry specific voluntary environmental or social programs. However, all-encompassing governmental voluntary programs that are open for all societal actors and cover all sustainability aspects are a new phenomenon that set a new ground for research. The research is an evaluative single case study that combines both qualitative and quantitative data and analysis methods. The primary data is collected from the program’s database containing 170 individual commitments out of which 42 were company commitments. The research is complemented by official documents and interviews with three company representatives, two representatives of the FNCSD and one third party representative. Individual operative commitments were analysed using an evaluation matrix. The findings in the study points out that the program is most likely to cause positive impact on society. However, due to insufficient information provided by the participants, the absolute impact couldn’t be measured. Majority of the participants used internally measurable indicators that could not be used for evaluating societal impact. This lead to suggestion that voluntary programs should have better indicators in order to measure societal impact. The study also showed that one third of the commitments did not have any impact through the program. This was caused by two types of commitments: those that existed before the participant joined the program and those that pledged to carry on business-as-usual activities as their commitment. In addition, the participants interpreted some of the program criteria and objectives differently. This caused variation in quality and difficulties for evaluating the impact of the program. The suggestion is that criteria for participants should be clearer in order to avoid openness for interpretation. The commitment 2050 proved capabilities in attracting SMEs to take public CSR actions instead of only including large companies that are traditionally more visible in CSR. Nevertheless, the commitment program attracted mostly companies that were already active in the field of CSR or sustainable development.
Input-Series–Output-Parallel-Connected Buck Rectifiers for High-Voltage Applications

This paper presents input-series-output-parallel (ISOP) configuration for single-phase front-end buck rectifiers (BRs). The configuration is especially suitable for traction applications, where the complete rectification system needs to withstand high ac voltages and supply medium-power loads. The primary rectification module of the proposed configuration is based on pulsewidth-modulated BR (current source inverter topology). The desired isolation, mandatory for ISOP connection, is provided at the dc stage through a medium-frequency/high-frequency transformer. Equal power sharing by modules is achieved from the ac side through input voltage and current sharing. The proposed control scheme is configured using two loops. While the outer loop regulates the output dc voltage and active wave shaping of the source current, the inner loop ensures stable voltage sharing. The performance of the proposed ISOP configuration is verified using numerical simulation. Experimental verification is achieved through a 2-kW grid-connected laboratory prototype.