ICAM- melanoma cells are relatively resistant to CD3-mediated T-cell lysis

Abstract The primary activation pathway of T cells is via the T-cell receptor (TCR)/CD3 complex, which is functionally interrelated with various accessory molecules. We examined the contribution of the lymphocyte-function-associated antigenI/intercellular adhesion molecule I (LFA-I/ICAM-I) interaction to CD3/TCR-mediated lysis by cytotoxic T lymphocytes (CTL). We used ICAM-I-or+ tumor cell lines as target cells and anti-CD3- or anti-LFA-I containing hetero-cross-linked monoclonal antibody (MAb) to bridge CTL and target cells and simultaneously to activate CTL. The ICAM-I- melanoma-derived cell line lgR39 was relatively resistant to CD3-mediated lysis by both TCRαβ+ and TCRγdL+ CTL, when compared with ICAM-I+ cell lines. Induction of ICAM-I on the membrane of lgR39 cells by tumor necrosis factor (TNF) rendered these cells more susceptible to CD3-mediated lysis. Anti-ICAM-I MAb inhibited this TNF-enhanced susceptibility to lysis, directly demonstrating that the induction of ICAM-I was critical in the TNF-induced increase in susceptibility to lysis of lgR39 cells. CTL formed less efficient conjugates with the ICAM-I- cells as compared to ICAM-I+ cells. Both spontaneous and CD3-induced conjugate formation as well as CD3-mediated lysis of ICAM-I- tumor cells by CTL were enhanced by the addition of anti-LFA-I containing heterocross-linked MAb, thereby mimicking the LFA-I/ICAM-I interaction between CTL and target cells. Soluble anti-CD18 MAb inhibited CD3-mediated lysis of ICAM-I- target cells by CTL without affecting their conjugate formation. Anti-LFA-I MAb added after conjugate formation still inhibited lysis of both ICAM-I+or- tumor cells. Taken together, these findings suggest that the LFA-I/ICAM-I interaction co-activates CD3/TCR-mediated lysis by CTL through both an enhanced CTL-target cell binding and the delivery of post-conjugate costimulatory signals

Ramond-Ramond Fields, Fractional Branes and Orbifold Differential K-Theory

We study D-branes and Ramond-Ramond fields on global orbifolds of Type II string theory with vanishing H-flux using methods of equivariant K-theory and K-homology. We illustrate how Bredon equivariant cohomology naturally realizes stringy orbifold cohomology. We emphasize its role as the correct cohomological tool which captures known features of the low-energy effective field theory, and which provides new consistency conditions for fractional D-branes and Ramond-Ramond fields on orbifolds. We use an equivariant Chern character from equivariant K-theory to Bredon cohomology to define new Ramond-Ramond couplings of D-branes which generalize previous examples. We propose a definition for groups of differential characters associated to equivariant K-theory. We derive a Dirac quantization rule for Ramond-Ramond fluxes, and study flat Ramond-Ramond potentials on orbifolds.Comment: 46 pages; v2: typos correcte

Mindfulness-based stress reduction as supportive therapy in cancer care: systematic review

Aim: This paper reports a systematic review and critical appraisal of the evidence on the effectiveness of Mindfulness-Based Stress Reduction for cancer supportive care. Background: The experience of cancer can have a negative impact on both psychological and physical health and on quality of life. Mindfulness-Based Stress Reduction is a therapy package that has been used with patients with a variety of conditions. In order to draw conclusions on its effectiveness for cancer patients, the evidence requires systematic assessment. Methods: A comprehensive search of major biomedical and specialist complementary medicine databases was conducted. Additionally, efforts were made to identify unpublished and ongoing research. Relevant research was categorized by study type and appraised according to study design. Clinical commentaries were obtained for each study and included in the review. Results: Three randomized controlled clinical trials and seven uncontrolled clinical trials were found. A lack of relevant qualitative research studies was identified. Studies report positive results, including improvements in mood, sleep quality and reductions in stress. A dose-response effect has been observed between practice of Mindfulness-Based Stress Reduction and improved outcome. A number of methodological limitations were identified. Modifications to the traditional Mindfulness-Based Stress Reduction programme make comparison between studies difficult and a lack of controlled studies precludes any firm conclusion on efficacy. Conclusion: Mindfulness-Based Stress Reduction has potential as a clinically valuable self-administered intervention for cancer patients. Further research into its efficacy, feasibility and safety for cancer patients in the nursing context is recommended

Luminescence spectra and kinetics of disordered solid solutions

We have studied both theoretically and experimentally the luminescence spectra and kinetics of crystalline, disordered solid solutions after pulsed excitation. First, we present the model calculations of the steady-state luminescence band shape caused by recombination of excitons localized in the wells of random potential induced by disorder. Classification of optically active tail states of the main exciton band into two groups is proposed. The majority of the states responsible for the optical absorption corresponds to the group of extended states belonging to the percolation cluster, whereas only a relatively small group of “radiative” states forms the steady-state luminescence band. The continuum percolation theory is applied to distinguish the “radiative” localized states, which are isolated in space and have no ways for nonradiative transitions along the tail states. It is found that the analysis of the exciton-phonon interaction gives the information about the character of the localization of excitons. We have shown that the model used describes quite well the experimental cw spectra of CdS(1−c)Sec and ZnSe(1−c)Tec solid solutions. Further, the experimental results are presented for the temporal evolution of the luminescence band. It is shown that the changes of band shape with time come from the interplay of population dynamics of extended states and spatially isolated “radiative” states. Finally, the measurements of the decay of the spectrally integrated luminescence intensity at long delay times are presented. It is shown that the observed temporal behavior can be described in terms of relaxation of separated pairs followed by subsequent exciton formation and radiative recombination. Electron tunneling processes are supposed to be responsible for the luminescence in the long-time limit at excitation below the exciton mobility edge. At excitation by photons with higher energies the diffusion of electrons can account for the observed behavior of the luminescence

A Historiometric Examination of Machiavellianism and a New Taxonomy of Leadership

Although researchers have extensively examined the relationship between charismatic leadership and Machiavellianism (Deluga, 2001; Gardner & Avolio, 1995; House & Howell, 1992), there has been a lack of investigation of Machiavellianism in relation to alternative forms of outstanding leadership. Thus, the purpose of this investigation was to examine the relationship between Machiavellianism and a new taxonomy of outstanding leadership comprised of charismatic, ideological, and pragmatic leaders. Using an historiometric approach, raters assessed Machiavellianism via the communications of 120 outstanding leaders in organizations across the domains of business, political, military, and religious institutions. Academic biographies were used to assess twelve general performance measures as well as twelve general controls and five communication specific controls. The results indicated that differing levels of Machiavellianism is evidenced across the differing leader types as well as differing leader orientation. Additionally, Machiavellianism appears negatively related to performance, though less so when type and orientation are taken into account.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The Importance of Context in Managerial Work: The Case of Senior Hotel Managers in Greece

Qualitative research on the interplay between context and hospitality managerial work has not been previously addressed in the literature. Based on the works of Johns (2006) and Dierdorff et al. (2009), this research suggests that luxury senior hotel managers (GMs and department managers) are to a certain degree recipients of contextual/cultural influences, depending on the ownership status of the hotel. It is also argued that managerial work is shaped and exercised by a set of moderating factors, which are unique for each individual. Overall, the aim of this research is to increase the level of awareness and trigger further research in this topic area. © 2014 Copyright © Taylor & Francis Group, LLC

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog