A composite structured/unstructured-mesh Euler method for complex airfoil shapes

A general two-dimensional Euler zonal method has been developed for computing flows about complex airfoil geometries such as multielement and iced airfoils. The method utilizes a composite structured and unstructured grid generated using conformal mapping and Delaunay triangulation, respectively. The finite-volume Euler method is then modified to couple solutions in the zones with structured and unstructured grids. Solutions about an iced airfoil and a multielement airfoil are given as examples of applications of the scheme

Emerging translational strategies and challenges for enhancing regulatory T cell therapy for graft-versus-host disease

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for many types of cancer. Genetic disparities between donor and host can result in immune-mediated attack of host tissues, known as graft versus host disease (GVHD), a major cause of morbidity and mortality following HSCT. Regulatory CD4+ T cells (Tregs) are a rare cell type crucial for immune system homeostasis, limiting the activation and differentiation of effector T cells (Teff) that are self-reactive or stimulated by foreign antigen exposure. Adoptive cell therapy (ACT) with Treg has demonstrated, first in murine models and now in patients, that prophylactic Treg infusion can also suppress GVHD. While clinical trials have demonstrated Treg reduce severe GVHD occurrence, several impediments remain, including Treg variability and practical need for individualized Treg production for each patient. Additionally, there are challenges in the use of in vitro expansion techniques and in achieving in vivo Treg persistence in context of both immune suppressive drugs and in lymphoreplete patients being treated for GVHD. This review will focus on 3 main translational approaches taken to improve the efficacy of tTreg ACT in GVHD prophylaxis and development of treatment options, following HSCT: genetic modification, manipulating TCR and cytokine signaling, and Treg production protocols. In vitro expansion for Treg ACT presents a multitude of approaches for gene modification to improve efficacy, including: antigen specificity, tissue targeting, deletion of negative regulators/exhaustion markers, resistance to immunosuppressive drugs common in GVHD treatment. Such expansion is particularly important in patients without significant lymphopenia that can drive Treg expansion, enabling a favorable Treg:Teff ratio in vivo. Several potential therapeutics have also been identified that enhance tTreg stability or persistence/expansion following ACT that target specific pathways, including: DNA/histone methylation status, TCR/co-stimulation signaling, and IL-2/STAT5 signaling. Finally, this review will discuss improvements in Treg production related to tissue source, Treg subsets, therapeutic approaches to increase Treg suppression and stability during tTreg expansion, and potential for storing large numbers of Treg from a single production run to be used as an off-the-shelf infusion product capable of treating multiple recipients

Agreement between DSM-IV and ICD-10 criteria for opioid use disorders in two Iranian samples

The aim of this study was to determine the agreement between the two systems in opioid users in the general population and a clinical sample. Two series of data were used in this study. The first was the data of 236 home-residing opioid abusers aged 15-64, who had previously participated in the Iran Mental Health Survey (IranMHS) in 2011, and the second was the data of 104 general psychiatry patients from inpatient or outpatient wards of two psychiatry hospitals in Tehran. Opioid use disorders were evaluated with CIDI-version 2.1. The disorders were assessed in all participants who used opioid substances for at least 5 times during the past 12. months. In the sample from the general population, the agreement between the two systems on the diagnosis of dependence was excellent (0.81). The agreement between the two systems on the diagnosis of abuse and harmful use was 0.41. In the clinical sample, the agreement between the two systems on the diagnosis of dependence or any opioid use disorder was 0.96 and 0.93, respectively. The agreement between abuse and harmful use was 0.9 and - 0.02 with and without regarding hierarchy, respectively. The inter-rater reliability of both DSM-IV and ICD-10 systems for all diagnosis was more than 0.95. The results of the diagnosis of dependence in the two systems had a weak concordance with treatment. The diagnostic criteria of DSM-IV and ICD-10 regarding dependence are very similar and the diagnosis produced by each system is concordant with the other system. However, the two systems have noticeable discrepancies in the diagnosis of abuse and harmful use. The discrepancies result from their conceptual differences and necessitate further revision in the definition of these disorders in the two systems. © 2013 Elsevier Ltd

Loss of expression of TGF-βs and their receptors in chronic skin lesions induced by sulfur mustard as compared with chronic contact dermatitis patients

<p>Abstract</p> <p>Background</p> <p>Sulfur mustard (SM) is a blister-forming agent that has been used as a chemical weapon. Sulfur mustard can cause damage in various organs, especially the skin, respiratory system, and eyes. Generally, the multiple complications of mustard gas result from its alkalizing potency; it reacts with cellular components like DNA, RNA, proteins, and lipid membranes.</p> <p>TGF-β is a multi-functional cytokine with multiple biological effects ranging from cell differentiation and growth inhibition to extracellular matrix stimulation, immunosuppression, and immunomodulation. TGF-β has 3 isoforms (TGF-β 1, 2, 3) and its signaling is mediated by its receptors: R1, R2 and intracellular Smads molecules.</p> <p>TGF-β has been shown to have anti-inflammatory effects. TGF-βs and their receptors also have an important role in modulation of skin inflammation, proliferation of epidermal cells, and wound healing, and they have been implicated in different types of skin inflammatory disorders.</p> <p>Methods</p> <p>Seventeen exposed SM individuals (48.47 ± 9.3 years), 17 chronic dermatitis patients (46.52 ± 14.6 years), and 5 normal controls (44.00 ± 14.6 years) were enrolled in this study.</p> <p>Evaluation of TGF-βs and their receptors expressions was performed by semiquantitative RT-PCR. Only TGF1was analyzed immunohistochemically.</p> <p>Results</p> <p>Our results showed significant decreases in the expression percentages of TGF-β 1, 2 and R1, R2 in chemical victims in comparison with chronic dermatitis and normal subjects and significant decreases in the intensity of R1 and R2 expressions in chemical victims in comparison with chronic dermatitis and normal controls. (P value < 0.05)</p> <p>Conclusions</p> <p>TGF-βs and their receptors appear to have a noticeable role in chronic inflammatory skin lesions caused by sulfur mustard.</p

Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects

Latent class analysis of DSM-5 criteria for opioid use disorders: Results from the Iranian National Survey on Mental Health

Background: Assessments of DSM-IV and DSM-5 criteria with sample populations of opioid users are limited. This study aimed to determine the number of latent classes in opioid users and assessment of the proposed revisions to the DSM-5 opioid use disorder (OUD) criteria. Methods: Data came from the 2011 Iranian National Mental Health Survey (IranMHS) on 7,886 participants aged 15-64 years living in Iran. We used the Composite International Diagnostic Interview (CIDI) version 2.1 in all respondents who indicated using opioids at least 5 times in the previous 12 months (n = 236). Results: A three-class model provided the best fit of all the models tested. Classes showed a spectrum of severity that was compatible with the DSM-5 classification. 'Legal problems' and 'desire to cut down' showed poor discrimination between classes. The weighted prevalence of OUD using DSM-5 was 20.7 higher than with DSM-IV. Conclusions: Results support the grouping based on severity of symptoms, combining abuse and dependence into a single diagnosis, omitting legal problems, and addition of craving as a new criterion. © 2015 S. Karger AG, Basel