Identification of distinct markers to differentiate natural and induced T regulatory cells in cancer.

Regulatory T cells (Tregs) are a distinct subset of CD4+ T cells that play a vital role in maintaining immune homeostasis and peripheral tolerance, thereby preventing autoimmunity. Tregs are generally categorised into two main subsets; natural and induced Tregs. In cancer, Tregs are found extremely enriched in the tumour microenvironment and contribute to the inhibition of anti-tumour response and tumour progression. The origin of tumour-infiltrating Tregs (whether it is nTregs or iTregs) is still enigmatic, since there are no distinct biomarkers which can differentiate between the two subsets. Therefore, the aim of this study is to identify cell surface biomarkers that can differentiate phenotypic features of iTregs from nTregs in the context of cancer. With this aim, an in vitro murine model was successfully developed to generate CD4+CD25++Foxp3+ iTregs from purely sorted naïve CD4+CD25-Foxp3- T cells in the presence of TGF-β1. The induction of iTregs was assessed using flow cytometry. Methylation status of Foxp3-TSDR and Foxp3 stability was assessed. Naïve CD4+CD25-Foxp3- T cells and CD4+CD25+Foxp3+ nTregs were purely sorted using cell sorting. Five biologically different subsets of CD4+ cells including naïve CD4+CD25-Foxp3- T cells, activated CD4+CD25-Foxp3- T cells, naïve CD4+CD25+Foxp3+ nTregs, activated CD4+CD25+Foxp3+ nTregs and CD4+CD25++Foxp3+ iTregs were subjected to quantitative proteomic profiling using SWATH-MS. Subcellular fractionation methods were employed to isolate membrane and cytoplasmic proteins from each of the subsets. Quantitative proteomic data were analysed using artificial neural networks. The results revealed that 4 distinct membrane biomarkers (PLP2, ITIH4, HEM6 and MAVS) were differentially upregulated in iTregs compared to other subsets. EPHX1 (HYEP) was identified upregulated only in naïve nTregs and downregulated in iTregs and other subsets. The biomarkers were further tested. Pathway enrichment analysis of iTregs showed a distinct metabolic pathway enrichment in iTregs indicating a mechanistic insight into the iTreg development. Once validated in humans these proteins could be used as a biomarker for iTreg or as a drug target for the selective depletion for better immunotherapeutic outcome in cancer patients

On the generalized Hartley-Hilbert and Fourier-Hilbert transforms

In this paper, we discuss Hartley-Hilbert and Fourier-Hilbert transforms on a certain class of generalized functions. The extended transforms considered in this article are shown to be well-defined, one-to-one, linear and continuous mappings with respect to δ and Δ convergence. Certain theorems are also established

Striking enhancement at the site of radiation for nivolumab-induced Stevens-Johnson syndrome

Stevens-Johnson syndrome is a rare adverse cutaneous drug reaction characterized by epidermal detachment of <10% body surface area with an average mortality rate of 1-5%. The mechanism of SJS is not fully understood. Nivolumab is a monoclonal antibody directed against programmed cell death-1 protein (PD-1), a receptor with immune checkpoint inhibitory and antineoplastic activities. We present a case of SJS in a patient being treated with anti-PD-1 therapy nivolumab for metastatic squamous cell carcinoma of the oropharynx. This case is unusual because of the severe accentuation with striking enhancement at his prior radiation site and in the cutaneous region with heavier tumor burden from his metastatic disease. This reaction may give insight to the underlying pathophysiology of SJS, suggesting that immune checkpoint inhibitors can activate T-cells to target keratinocytes and that external factors may be involved in creating distinct epitopes for T-cell recognition. We hope this case adds to the body of knowledge in the pathogenesis of Stevens-Johnson syndrome and cutaneous adverse events seen with checkpoint inhibitors

Educational Dimension of Woman's Character in the Narration's of Prophets as Stated in the Holy Qur'an

The Holy Qur'an has addressed the needs of women and their status in a way never done before in any other religious text. Woman's exalted position in Islam is due, primarily, to her role as a child rearer. It is she who is considered the "first madrasah" (first school) by Islam, and it is from her that children will learn about their responsibility as future 'standard bearers' of Islam and society. The research examines stories and biographies of women in the Qur'an, narrated by various prophets (peace be upon them) through the ages. These stories have been drawn from sound Islamic sources. not the doubtful narrations of Israelite scriptures, showing, through their life stories, women's attitude nature, some positive and others negative. This provides an authentic and comprehensive view of Muslim women from the Qur'anic perspective. It puts forward an educational model for women to realize their true role in the challenging times in which we live. By studying the attitudes and dispositions of women in the Holy Qur'an and the Sunna of the Prophet Muhammad (peace and blessings be upon him) the research illustrates the merits. morals and role of women as educators in the family, as well as society. It also shows the extent to which a Muslim women can harm or benefit each member of her family. The study also shows the scope of educational techniques in the Holy Qur'an and their impact on the attitudes and character of women. It delineates the educational role of women and the features of women's character through investigation of previous religions and comparison with those in Islam. In this way, we can become more acquainted with the characteristics of women, her tasks, rights, duties and the type of work suited to her outside the family

Thinking Green: Analyzing EFL Textbooks in Light of Ecological Education Themes

The present study aimed at examining English as a Foreign Language (from now on as EFL) textbooks on ecological education key global themes in language teaching, since EFL teaching should not only be restricted to the development of learners’ language proficiency but also to empower them to improve thinking skills that can be worthwhile in ecological sustainability. The study followed a conceptual content analysis design where EFL materials were read recursively to match global themes. Themes were assessed against a developed content analysis checklist. For the purpose of analysis, data were gathered distinctly from 10th grade textbooks in the academic year 2013/2014. The examination of data was completed through descriptive and critical analysis. The study reported that only more than one third (34.57%; 33.33% respectively) of EFL textbook content involved types on sensitivity to ecological problems as well as ecological skills development. About 19.75% of the content reflected ecological knowledge. Another 12.35% of the content echoed ecological contribution themes. The study, however, came to a conclusion that entails that as given EFL textbook scarcity of global ecological themes, more responsibility of language teachers was emphasized in relation to raising students' awareness towards ecological themes by means of developing their language skills in meaningful theme-based communication. Keywords: Communicative competence, Ecological Education, EFL textbook, Jordan.

Combined effect of frustration and dimerization in ferrimagnetic chains and square lattice

Within the zero-temperature linear spin-wave theory we have investigated the effect of frustration and dimerization of a Heisenberg system with alternating spins $s_{1}$ and $s_{2}$ on one- and two-dimensional lattices. The combined effect most visibly appears in the elementary excitation spectra. In contrast to the ground state energy that decreases with dimerization and increases with frustration, the excitation energies are shown to be suppressed in energy by both dimerization and frustration. The threshold value of frustration that signals a transition from a classical ferrimagnetic state to a spiral state, decreases with dimerization, showing that dimerization further helps in the phase transition. The correlation length and sublattice magnetization decrease with both dimerization and frustration indicating the destruction of the long-range classical ferrimagnetic. The linear spin wave theory shows that in the case of a square lattice, dimerization initially opposes the frustration-led transition to a spiral magnetic state, but then higher magnitudes of lattice deformation facilitate the transition. It also shows that the transition to spiral state is inhibited in a square lattice beyond a certain value of dimerization.Comment: 8 pages, latex, 12 postscript figure

Wind Generation Impact on Symmetrical Fault Level at Grid Buses

This paper mainly aims at evaluating quantitatively the impact of wind turbine generators (WTGs) on fault level (FL) in case of a balanced fault occurring in the host grid (HG). This impact is not generic but it depends on the grid configuration, operation mode, and load profile; the impact may be positive for a network while it is negative for another one. Therefore, the impact will be estimated for a specific distribution network (DN). The grid faults and wind generations (WGs) are simulated by the simulation tool Power Factory DigSilent 14.0.506. The paper addresses the influence on FL of grid buses in general and particularly on FL of the point of common coupling (PCC). The effect of both penetration and dispersion levels of embedded WTGs on fault response is also investigated. Moreover, the influence of WG type on FL is assessed. It is concluded, among other points, that the FL at PCC could rise by about 150% and 17% due to embedded WG of type 1 and type 2 respectively, what it leads to the recommendation to avoid installing type 1 wind systems for new wind farm