Search results for: Yukli Freedman

Authors: Yong H Sheng, Beatriz Garcillán, Eden Whitlock, Yukli Freedman, SiLing Yang, M Arifur Rahman, Nicholas Weber, Fabienne Mackay

Abstract:

Chronic lymphocytic leukemia (CLL) is closely associated with immune dysfunction, yet the mechanisms underlying this immune deficiency remain poorly understood. Transmembrane Activator and CAML Interactor (TACI), a receptor known for its role in IL-10 regulation and autoimmunity, to the best of our knowledge has not been investigated in the context of anti-tumor immunity or its impact on CLL progression. This study addresses the gap by exploring the role of TACI in regulating CLL cells within the tumor microenvironment and its broader effects on disease progression and immune competence. We utilized the Eµ-TCL1 mouse model to generate CLL mice deficient in TACI and examined the consequences of TACI loss in adoptive transfer models over a five-week period. Comprehensive transcriptomic analysis, including RNA sequencing and microarray, was employed to determine TACI’s influence on the CLL gene expression profile. Additionally, we studied TACI’s direct role in CLL cell migration and immune modulation using patient-derived CLL cells in culture and Patient-Derived Xenograph (PDX) models. Our findings demonstrate that TACI signaling plays a pivotal role in promoting CLL progression and immune suppression. Loss of TACI signaling significantly inhibited CLL development and enhanced immune functionality. When TACI+/+ or TACI-/- TCL1 CLL cells were transferred into wild-type recipient mice, those receiving TACI-deficient cells showed reduced disease progression and lower incidence of CLL. Mice with TACI-/- CLL cells exhibited normalized serum levels of pro-inflammatory cytokines IL-6 and IL-10, restored proportions of T-cell subsets, and improved immune compartment function compared to counterparts with TACI+/+ CLL cells. Mechanistically, TACI-deficient CLL cells expressed significantly lower levels of IL-10, TNF, and inhibitory receptors such as PD-L1 and PD-L2. These cells also display restored circulating immunoglobulin levels and responses to T cell-dependent antigens, highlighting a recovery of immune competence. Further mechanistic studies revealed that TACI signaling drives CLL cell migration and homing to the spleen, where these cells actively establish an immunosuppressive microenvironment that supports immune evasion and tumor growth. Patient-derived CLL cells and PDX models confirmed TACI’s direct role in enhancing CLL cell migration and fostering immune suppression, emphasizing its critical function in the tumor microenvironment. By disrupting TACI signaling, we observed a reduction in CLL-associated immune suppression and tumor progression, offering a promising therapeutic avenue. This study establishes, for the first time, that targeting TACI disrupts key mechanisms underlying CLL progression while preserving vital immune functions. Unlike existing treatments that often impair immunity and lead to infection-related complications, TACI inhibition offers the dual benefit of controlling disease and maintaining immune homeostasis. These findings provide a strong rationale for developing therapeutic strategies that inhibit TACI as a means to improve outcomes in CLL patients. Beyond its implications for CLL, this research underscores the broader importance of TACI in regulating immune-tumor interactions, paving the way for future studies into its role in other malignancies.

Keywords: chronic lymphocytic leukemia, TACI, IL-10, immune suppression

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Authors: J. Urban, Á. S. Botella, L. E. Robaina, A. Bárta, P. Souček, P. Císař, Š. Papáček, L. M. Domínguez

Abstract:

Skin coloration in fish is of great physiological, behavioral and ecological importance and can be considered as an index of animal welfare in aquaculture as well as an important quality factor in the retail value. Currently, in order to compare color in animals fed on different diets, biochemical analysis, and colorimetry of fished, mildly anesthetized or dead body, are very accurate and meaningful measurements. The noninvasive method using digital images of the fish body was developed as a standalone application. This application deals with the computation burden and memory consumption of large input files, optimizing piece wise processing and analysis with the memory/computation time ratio. For the comparison of color distributions of various experiments and different color spaces (RGB, CIE L*a*b*) the comparable semi-equidistant binning of multi channels representation is introduced. It is derived from the knowledge of quantization levels and Freedman-Diaconis rule. The color calibrations and camera responsivity function were necessary part of the measurement process.

Keywords: color distribution, fish skin color, piecewise transformation, object to background segmentation

Procedia PDF Downloads 262

Authors: Mohammad Reza Boromand, Masoud Moradi, Amin Eskandari

Abstract:

The present study attempts to determine ranking of managerial parameters impacting upon performance of football referees in Iran. The population consisted of all referees in Leagues 1, 2 and 3 as well as super league of Iran (N=273), of which we selected 160 referees and assistant referees in 2013-2014. A research-designed questionnaire was used for data collection which was divided into two sections: (1) Demographic details (age range, Marital status, employment, refereeing experience, education level, refereeing level and proficiency) and (2) items related to parameters impacting upon performance of referees (structural parameters, operational parameters, environmental parameters, temporal parameters, economic parameters, facilities and tools, personal performance and performance evaluation). Internal consistency was calculated by Cronbach's alpha (r=0.85). For data analysis, we performed Freedman's Test and used SPSS software (α>0.05), along with descriptive statistics. The findings showed the following ranking for the above-mentioned managerial parameters: Facilities and tools, personal performance, economic parameters, structural parameters, operational parameters, environmental parameters, temporal parameters, and performance evaluation.

Keywords: Iran, football referees, managerial parameters, performance

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Authors: Khaidan Hatami, Mehran Nasiri

Abstract:

The aim of following research was the analysis between sport motivation and control center of football players of Iran. All the players employed in Iran’s football league are included in the population of the research. So, 360 players, every level 120 players ( Youth, U-21 and adults ) playing in Guilan, Kurdistan and Kermanshah province having professional football league in first and second level league were randomly and selectively taken and included the population. The current research is of descriptive and solidarity types. Instruments of measurement are three personal questionnaires, sport motivation (SMS) of Politer and partners (1995), control center of Berger (1986) which their valid content were confirmed by experts in sport management field. The internal stability of questions were analyzed by Alfa Cronbach respectively for sport obligation questionnaire (0.82) and control center (0.86) to analysis and evaluate data, Kolmogrouf-Smirnov, Spearman Correlation, Kruskal-Wallis test, Whitney U, Freedman and T-Wilcoxon were used in a meaningful level (P ≤ 0/05). The results showed positive and meaningful relation between control center of football players in youth, U-21 and adults and sport motivation of football players. So, it can be concluded, people with internal control against those with external one have more internal sport motivation and follow the team goals with more mental power. So, it’s recommended to coaches to use sport psychologist in their teams to internalize the people’s needs by scientific method by taking the mental issues and the type of control in people on life events.

Keywords: sport motivation, control center, internal, external football players

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Authors: Hamid Ahmadi, Amirreza Ghaffari

Abstract:

Fatigue life of tubular joints in offshore structures is not only dependent on the value of hot-spot stress, but is also significantly influenced by the through-the-thickness stress distribution characterized by the degree of bending (DoB). The DoB exhibits considerable scatter calling for greater emphasis in accurate determination of its governing probability distribution which is a key input for the fatigue reliability analysis of a tubular joint. Although the tubular X-joints are commonly found in offshore jacket structures, as far as the authors are aware, no comprehensive research has been carried out on the probability distribution of the DoB in tubular X-joints. What has been used so far as the probability distribution of the DoB in reliability analyses is mainly based on assumptions and limited observations, especially in terms of distribution parameters. In the present paper, results of parametric equations available for the calculation of the DoB have been used to develop probability distribution models for the DoB in the chord member of tubular X-joints subjected to four types of bending loads. Based on a parametric study, a set of samples was prepared and density histograms were generated for these samples using Freedman-Diaconis method. Twelve different probability density functions (PDFs) were fitted to these histograms. The maximum likelihood method was utilized to determine the parameters of fitted distributions. In each case, Kolmogorov-Smirnov test was used to evaluate the goodness of fit. Finally, after substituting the values of estimated parameters for each distribution, a set of fully defined PDFs have been proposed for the DoB in tubular X-joints subjected to bending loads.

Keywords: tubular X-joint, degree of bending (DoB), probability density function (PDF), Kolmogorov-Smirnov goodness-of-fit test

Procedia PDF Downloads 719