To address the problem that it is easy to form coverage blind areas when wireless sensor networks are randomly deployed, an improved coverage optimization algorithm based on improved Salpa swarm Intelligent algorithm (ATSSA) is proposed for wireless sensor networks. Firstly, the pop-ulation is initialized using tent chaotic sequence to enhance the optimization ability of the algo-rithm. Secondly, the T-distribution mutation is added to the update formula of the leaders for improving the ability to jump out of the local optimal value. Finally, an adaptive formula for updating the position of the follower is proposed, which not only guarantees the local searching ability of the algorithm in the late iteration period, but also improves the global searching ability of the algorithm in the early iteration period. The experimental results show that ATSSA algorithm can improve the coverage of the wireless sensor networks and reduce deployment costs com-pared with other algorithms, when it is used in the wireless sensor networks.

In statistics and probability theory, one of the most important statistics is the sums of random variables. After introducing a probability distribution, determining the sum of n independent and identically distributed random variables is one of the interesting topics for authors. This paper presents the probability density functions for the sum of n independent and identically distributed random variables such as Shanker, Akash, Ishita, Pranav, Rani, and Ram Awadh. In order to determine all aforementioned distributions, the problem-solving methods are applied which is based on the change-of-variables technique.

The intercomparison among different atmospheric monitoring systems is key for instrument calibration and validation. Common cases involve satellites, radiosonde, radio occultation (e.g. GNSS-RO) and atmospheric model outputs (e.g. ERA5 reanalysis). Since instruments and/or measures are not perfectly collocated, the miss-collocation uncertainty must be considered in the related intercomparison uncertainty budgets.

Adaptive T cell immunotherapy holds great promise for the successful treatment of leukemia as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system allowing deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in Primary Sjogren’s syndrome (pSS). The aim of this research was to assess the imbalance of subsets within CD8+ cells in peripheral blood. We examined blood samples from 34 patients with pSS and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA, and CD45. For immunophenotyping of ‘polarized’ CD8+ T cell subsets we used the following monoclonal antibodies:CXCR5, CCR6,CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, Rheumatoid factor, the Schirmer test, and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS.

Immune surveillance and adaptive immune responses, involving continuously circulating and tissue-resident T-lymphocytes, provide host defense against infectious agents and possible malignant transformation while avoiding autoimmune tissue damage. Activation, migration, and deployment of T-cells to affected tissue sites are crucial for mounting an adaptive immune response. An effective adaptive immune defense depends on the ability of T-cells to dynamically reprogram their metabolic requirements in response to environmental cues. Inability of the T-cells to adapt to specific metabolic demands may skew cells to become either hyporesponsive creating immunocompromised conditions or hyperactive causing autoimmune tissue destruction. Here, we review maladaptive T-cell metabolic fitness that can cause autoimmune diseases and discuss how T-cell metabolic programs can potentially be modulated to achieve therapeutic benefits.

This study introduces a new discrete distribution which is a weighted version of Poisson-Lindley distribution. The weighted distribution is obtained using the negative binomial weight function and can be fitted to count data with over-dispersion. The p.m.f., p.g.f. and simulation procedure of the new weighted distribution, namely weighted negative binomial Poisson-Lindley (WNBPL), are provided. The maximum likelihood method for parameter estimation is also presented. The WNBPL distribution is fitted to several insurance datasets, and is compared to the Poisson and negative binomial distributions in terms of several statistical tests.

A toy model for the distribution of the impact factor (IF) of a journal is proposed. The model demonstrates the presence of a heavy tail for the IF distribution, which occurs due to some random non-scientific circumstances. Therefore, the use of IF as an indicator of the quality of scientific papers seems to be inadequate.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Since its conception with the smallpox vaccination, worldwide-used vaccines have thwarted multiple pandemics including the recent COVID-19 outbreak. Insightful studies uncovered complexities of different functional networks of CD4 T cells [T helper 1 (Th1); Th2, Th17] and CD8 T cells (T cytotoxic; Tc) as well as B cells (BIgM, BIgG, BIgA and BIgE) subsets during response to vaccination. Both T and B cell subsets forge central, peripheral and tissue-resident subsets during vaccination. It also became apparent that each vaccination formed the network of T regulatory subsets, namely CD4+CD25+Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+Foxp3− T regulatory 1 (Tr1) as well as many others, are shaping the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on presenting how pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work revealed that the Treg/Tr1 involvement evoked different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response by increasing a dose, changing the delivery route and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Ra chain) or anti-PD-1 (programmed cell death protein) monoclonal antibody (mAb) to decrease Tregs and boost the T/B cell immune response. All these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals as well as organ transplant patients.

For bounded unit interval, we propose a new Kumaraswamy generalized (G) family of distributions from a new generator which could be an alternate to the Kumaraswamy-G family proposed earlier by Cordeiro and de-Castro in 2011. This new generator can also be used to develop alternate G-classes such as beta-G, McDonald-G, Topp-Leone-G, Marshall-Olkin-G and Transmuted-G for bounded unit interval. Some mathematical properties of this new family are obtained and maximum likelihood method is used for estimating the family parameters. We investigate the properties of one special model called a new Kumaraswamy-Weibull (NKwW) distribution. Parameter estimation is dealt and maximum likelihood estimators are assessed through simulation study. Two real life data sets are analyzed to illustrate the importance and flexibility of this distribution. In fact, this model outperforms some generalized Weibull models such as the Kumaraswamy-Weibull, McDonald-Weibull, beta-Weibull, exponentiated-generalized Weibull, gamma-Weibull, odd log-logistic-Weibull, Marshall-Olkin-Weibull, transmuted-Weibull, exponentiated-Weibull and Weibull distributions when applied to these data sets. The bivariate extension of the family is proposed and the estimation of parameters is given. The usefulness of the bivariate NKwW model is illustrated empirically by means of a real-life data set.

It has been empirically observed that the upper tail of the firm size distribution follows either the Pareto distribution or the Zipf distribution, with both patterns being explained by Gibrat’s law (Gabaix, 1999). This article analyzed firm revenue data from China, spanning from 2005 to 2013, to examine the whole range of the firm size distribution. Our empirical analysis revealed that firm revenue data over these years is well fitted by a three-parameter generalized Pareto distribution, with the fitted parameters indicating a dichotomy: The size distribution of large-sized firms, namely the upper tail, is asymptotically characterized by a Pareto distribution or a Zipf distribution, whereas the size distribution of smaller and medium-sized firms is approximated by an exponential distribution. This finding suggests that Gibrat’s law should be extended to account for the emergence of a generalized Pareto distribution.

Cancer metastasis into the brain constitutes one of the most severe but not uncommon development of cancer growth. Several factors control how cancer types interact with the brain to establish metastasis These factors include system of migration, system of infiltration of the blood-brain barrier and the interaction with host cells (e.g., neurons, astrocytes) and the immune system fight against metastasis in the brain. Although, brain radiotherapy is the main treatment procedure carried out to treat, new therapies are emerging that constitute a glimpse of hope for increasing the diminutive life expectancy currently forecasted to cancer patients who are facing the prospectus of brain metastasis. However applying these therapeutic strategies has been has not been effective. Thus there is a need for better understanding of the metastasis process in order to suggest novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the various process that they undergo including EMT, penetration of the ECM, intravasation, extravasation and infiltration of the blood brain barrier ending up with colonization and angiogenesis. In each phase, we focus on molecules that could potentially be drug target candidates.

A comprehensive heuristic analysis of the Pollard's Rho Method (PRM) is given. The analysis is based on ultimate periods and tails distribution of sequences. If $n$ is the composite number to be factored, then an improved version of PRM is developed which has an expected run time of $O(\sqrt[8]{n}\ln n)$ on a multi-core architecture which utilized a clever way of evaluating polynomials.

A new 2 parameter unit Weibull distribution is defined on the unit interval (0,1). The methodology of deducing its PDF, some of its properties and related functions are discussed. The paper is supplied by many figures illustrating the new distribution and how this can make it illegible to fit a wide range of skewed data. The new distribution holds a name (Attia) as a nickname.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the key focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection in pre-clinical models and human trials. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses delivered by replication-deficient vector ChAdOx1. It focuses T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the beta-coronavirus family.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

A new compounded distribution called the Topp-Leone-Lomax Poisson is developed. The statistical properties of this model are derived. The model parameters are estimated via the maximum likelihood technique. The performance of the estimation techniques was assessed by means of simulation studies. The new model was exposed to three data sets and compared to other models within the same class and the evidence supports the importance of the new model in data modelling.

CAR-T therapy has achieved considerable treatment success in hematologic tumors by using patient derived autologous αβ T cells. There is an impetus to broaden the applicability of this approach by using a third-party donor derived CAR-T cell product which has a potent anti-tumor function but a constrained GVHD property. In this study, CAR-T cells were prepared from Vγ9Vδ2 T cells expanded by using a novel prodrug PTA and their anti-tumor functions were assessed in conjunction with persistency, localization, and phenotype. γδ T cells were successfully transduced with a CAR specific to CEA with signaling domains of CD3ζ and CD28 (CEA.CAR-γδ T cells), and exhibited potent tumor killing function in vitro. In a xenograft mouse model, CEA.CAR-γδ T cells suppressed CEA+ tumor growth though a limited time window. CEA.CAR-γδ T cells persisted and accumulated in the tumor even after tumor progression, however, ex vivo analysis revealed that those recovered at different time points from PBMC, spleen and tumors gradually lost tumor reactivity as assessed by IFN-γ production. Provision of GITR co-stimulation enhanced anti-tumor function of CEA.CAR-γδ T cells, the result of which imposes additional measurers to be adopted in CAR-γδ T cells for an allogeneic adoptive immunotherapy.

Long non-coding RNA (lncRNA) aberrant expression have been found in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped in transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated in pediatric ALL and uc.112 expression was higher in T-ALL compared to patients with B-ALL and in patients with hyperdiploid karyotype. These findings suggest a potential role of this uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

SStatistical characteristics of the wind speed in Samaria region of Israel have been analyzed by processing 11 years of wind data provided by the Israeli Meteorological Service, recorded at 10 m height above the ground. The cumulative mean wind speed at measurement height was shown to be 4.53 m/s with standard deviation of 2.32 m/s. Prevailing wind direction is shown to be char-acterized by cumulative mean azimuth of 226° with standard deviation of 79.76°. The results were extrapolated to 70-meter height in order to estimate wind characteristics at hub height of a me-dium-scale wind turbine. Moreover, Weibull distribution parameters were calculated annually, monthly and seasonally, demonstrating a good match with histogram-based statistical repre-sentations. Shape parameter of the Weibull distribution was shown to reside within a narrow range of 1.93 to 2.15, allowing us to assume a Rayleigh distribution, thus simplifying wind tur-bines energy yield calculations. The novelty of the current paper is related to gathering wind statistics for a certain area (Samaria) we are not aware of any published statistics regarding wind velocity and direction in this area. The data may be interesting for potential regional wind energy development in which the obtained Weibull distribution can be used in calculations of expected power generation of particular turbines with known power dependence on velocity. We also point out that the fact that realistic wind velocity statistics is well described by an analytic formula (Weibull distribution) is not trivial, and in fact the fit may have been poor.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

The immune system’s evolution is crucial for its role in fighting pathogens and involvement in autoimmune and neurodegenerative diseases. The GFI1 gene family controls the function of immune cells, including neutrophils in the innate immune system and CD4+ T cells in the adaptive immune system. GFI1 consists of two members, GFI1A and GFI1B. GFI1A is vital for myeloid and lymphoid differentiation, while GFI1B is crucial for generating red blood cells and platelets. Both genes share a repressor SNAG protein and C2H2 zinc finger domains, though the peptide sequences between these domains remain uncharacterized. Using a comprehensive phylogenetic approach, we traced the evolutionary history of the GFI1 gene family, revealing its early presence in invertebrates. Two rounds of genome duplication led to GFI1A and GFI1B. Despite positive selection, the family retained structural conservation. We identified new motifs in the less-characterized middle regions, such as the SPOP-binding motif in GFI1A, potentially regulating cytokine production, and the FEDFW motif, possibly involved in neutrophil recruitment. These motifs are unique to GFI1A in higher vertebrates. In GFI1B, we discovered a unique EPLRP motif, a Separase cleavage site linked to sister chromatid separation. Our results indicate that GFI1 has evolved new functions to adapt to the complexity of the vertebrate immune system. This highlights the evolutionary significance of GFI1 in immune responses and suggests potential therapeutic applications, especially in diseases related to immune function.

T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for optimization of their use with combination or consolidation strategies, which necessitates prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in current knowledge and suggest that insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

Hamacher operation which is generalization of the Algebraic and Einstein operation, can widely provide a large number of arithmetical operation with respect to uncertainty information, and Heronian mean can deal with correlations of the input arguments or different criteria and don’t make calculation redundancy, meanwhile, the normal intuitionistic fuzzy numbers (NIFNs) can depict distinctively normal distribution information in practical decision making. In this paper, a multi-criteria group decision-making (MCGDM) problem is researched under the NIFNs environment, and a new MCGDM approach is introduced on the basis of the Hamacher operation. Firstly, according to Hamacher t-conorm and t-norm, some operational laws of NIFNs are presented. Secondly, it is noticed that Heronian mean can’t only once take into account mutual relation between attribute values once, but also consider the correlation between input argument and itself. Therefore, we develop some operators and study their properties in order to aggregate normal intuitionistic fuzzy numbers information, these operators include Hamacher Heronian mean (NIFHHM), Hamacher weighted Heronian mean (NIFHWHM), Hamacher geometric Heronian mean (NIFHGHM) and Hamacher weighted geometric Heronian mean (NIFHWGHM). Furthermore, we apply the proposed operators to the MCGDM problem and present a new method. The main characteristics of this new method involve that: (1) it is suitable to make decision under the normal intuitionistic fuzzy numbers environment and more reliable and reasonable to aggregate the normal distribution information. (2) it utilizes Hamacher operation which can provide more reliable and flexible decision-making results and offer an effective and powerful mathematic tool for the MAGDM under uncertainty. (3) it uses the Heronian mean operator which can considers relationships between the input arguments or the attributes and don’t brings subsequently about redundancy. Lastly, an application is given for showing the feasibility and effectiveness of the presented method in this paper.

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

The innate and adaptive immune systems collaborate to detect SARS-CoV-2 infection, minimize the viral spread, and kill infected cells, ultimately leading to the resolution of the infection. The adaptive immune system develops a memory of previous encounters with the virus, providing enhanced responses when rechallenged by the same pathogen. Such immunological memory is the basis of vaccine function. Here, we review the current knowledge on the immune response to SARS-CoV-2 infection and vaccination, focusing on the pivotal role of T cells in establishing protective immunity against the virus. After providing an overview of the immune response to SARS-CoV-2 infection, we describe the main features of SARS-CoV-2-specific CD4+ and CD8+ T cells, including cross-reactive T cells, generated in patients with different degrees of COVID-19 severity, and of Spike-specific CD4+ and CD8+ T cells induced by vaccines. Finally, we discuss T cell responses to SARS-CoV-2 variants and hybrid immunity and conclude by highlighting possible strategies to improve the efficacy of COVID-19 vaccination.

In this article we introduce an extension of the Akash distribution. We use the slash 1 methodology to make the kurtosis of the Akash distribution more flexible. We study the general 2 density of this new distribution, some properties, moments, coefficients of asymmetry and kurtosis. 3 Statistical inference is performed using the methods of moments and maximum likelihood via the 4 EM algorithm. A simulation study is carried out to observe the behavior of the maximum likelihood 5 estimator. An application to a real data set with high kurtosis is considered, where it is shown that 6 the new distribution fits better than other extensions of the Akash distribution.

This paper presents a novel statistical model i.e. the Laplace-Rician distribution, for the characterisation of synthetic aperture radar (SAR) images. Since accurate statistical models lead to better results in applications such as target tracking, classification, or despeckling, characterising SAR images of various scenes including urban, sea surface, or agricultural, is essential. The proposed Laplace-Rician model is investigated for SAR images of several frequency bands and various scenes in comparison to state-of-the-art statistical models that include K, Weibull, and Lognormal. The results demonstrate the superior performance and flexibility of the proposed model for all frequency bands and scenes.

This study has developed a Matlab application for simulating statistical models project (SMp) probabilistic distributions that are similar to binomial and Poisson, which were created by mathematical procedures. The simulated distributions are graphically compared with these popular distributions. The application allows to obtain many probabilistic distributions, and shows the trend (τ ) for n trials with success probability p, i.e. the maximum probability as τ=np. While the Poisson distribution PD(x;µ) is a unique probabilistic distribution, where PD=0 in x=+∞, the application simulates many SMp(x;µ,Xmax) distributions, where µ is the Poisson parameter and value of x with generally the maximum probability, and Xmax is the upper limit of x with SMp(x;µ,Xmax) ≥ 0 and limit of the stochastic region of a random discrete variable. It is shown that by simulation via, one can get many and better probabilistic distributions than by mathematical one.

This study has developed a Matlab application for simulating statistical models project (SMp) probabilistic distributions that are similar to binomial and Poisson, which were created by mathematical procedures. The simulated distributions are graphically compared with these legendary distributions. The application allows to obtain many probabilistic distributions, and shows the trend (τ ) for n trials with success probability p, i.e. the maximum probability as τ=np. While the Poisson distribution PD(x;µ) is a unique probabilistic distribution, where PD=0 in x=+∞, the application simulates many SMp(x;µ,Xmax) distributions, where µ is the Poisson parameter and value of x with generally the maximum probability, and Xmax is upper limit of x with SMp(x;µ,Xmax) ≥ 0 and limit of the stochastic region of the random discrete variable X. It is shown that by simulation via, one can get many and better probabilistic distributions than by mathematical one.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using HPV16E6E7 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+T cell response with minimally a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.

The importance of continuously emerging new distribution is a mandate to understand the world and environment surrounding us. In this paper, the author will discuss a new distribution defined on the interval (0,1) as regards the methodology of deducing its PDF, some of its properties and related functions. A simulation and real data analysis will be highlighted.

This paper presents a hybrid probability distribution known as the FCD, which is based on the hazard functions of the Fréchet and Chen distributions. A notable characteristic of the FCD is its ability to model monotonic (increasing and decreasing) and non-monotonic (bathtub-shaped) behaviors, commonly linked to electrical and electronic device failure times in reliability analysis. The paper explores the statistical properties relevant to the reliability analysis of these devices. It proposes a Maximum Likelihood Estimator (MLE) and Bayesian Analysis equations for estimating the parameters of the FCD. Three case studies of electronic device lifetimes with varying behaviors were analyzed to validate the proposed methodology. The FCD was compared to other distributions with similar characteristics, and the results from each case study demonstrated that the proposed distribution yields competitive outcomes, closely reflecting the behavior of the devices analyzed, making it a valuable option for reliability engineering practitioners in warranty and maintenance time evaluations

The two-parameter distribution introduced by Kumaraswamy (1980) is a very flexible alternative to the Beta distribution with the same (0,1) support. Originally proposed in the field of hydrology, it has subsequently received a good deal of positive attention in both the theoretical and applied statistics literatures. Interestingly, the problem of testing formally for the appropriateness of the Kumaraswamy distribution appears to have received little or no attention to date. To fill this gap, in this paper we apply the “biased transformation” methodology proposed by Raschke (2009) to several standard goodness-of-fit tests based on the empirical distribution function. A simulation study reveals that these (modified) tests perform well in the context of the Kumaraswamy distribution, in terms of both low size distortion, and respectable power. In particular, the “biased transformation” Anderson-Darling test dominates the other tests that are considered.

In recent decades, there have been numerous endeavors to develop a novel category of survival distributions possessing enhanced flexibility through the extension of existing distributions. This article constructs and validates the statistical properties of a novel survival distribution in order to obtain an alternative distribution that is suitable for analyzing survival data by presenting the novel mixture of the Fréchet distribution along with statistical properties such as the probability density function (PDF), cumulative distribution function (CDF), rth ordinary moment, skewness, kurtosis, moment-generating function, mean, variance, mode, survival function, hazard function, and asymptotic behavior, as well as constructing the estimators of the unknown parameter by employing the expectation-maximization (EM) algorithm, and simulated annealing. Additionally, the performance of the proposed estimators was compared with bias, mean squared errors (MSE), and simulated variances, and given an illustrative example of the proposed distribution to the survival data set in order to show that the proposed distribution is appropriate for the right-skewed data. This will be extremely advantageous in survival analysis.

The increasing demand for higher inclusion cleanliness levels motivates the control over the formation and evolution of inclusions in the steel production process. In this work, the evolution of the chemical composition and size distribution of inclusions throughout a slab production process of Al-killed steel, including ladle furnace (LF) treatment and continuous casting (CC), was followed. The initial solid Al2O3 and Al2O3-MgO inclusions were modified to liquid Al2O3-CaO-MgO inclusions during LF treatment. The evolution of the size distributions during LF treatment was associated with the growth and removal of inclusions, as new inclusions were not created after the deoxidation process, according to a population density function (PDF) analysis. Additionally, the size distributions tended to be similar as the LF treatment progressed regardless of their initial features, whereas they differed during CC. Analysis of the upper tails of the distributions through generalized extreme values theory showed that inclusion distributions shifted from larger to smaller sizes as the process progressed. There were great changes in the distributions of large inclusions throughout the LF treatment and between the end of the LF treatment and the start of the CC process. Additionally, distributions of large inclusions differed at the end of the LF treatment, whereas such differences decreased as CC progressed.

Developments of new probability models for data analysis are keen interest of importance for all fields. The log-Dagum distribution has a prominent role in the theory and practice of statistics. In this article, a new family of continuous distributions generated from a log Dagum random variable called the log-Dagum Weibull distribution is proposed. The key properties of the proposed distribution are derived. Its density function can be symmetrical, left-skewed, right-skewed and reversed-J shaped and can have increasing, decreasing, bathtub hazard rates shaped. The model parameters are estimated by the method of maximum likelihood and illustrate its importance by means of applications to real data sets.

Widespread poverty is the most serious threat and social problem that Bangladesh faces. Regional vulnerability to climate change threatens to escalate the magnitude of this poverty. It is essential that projections of poverty be made while bearing in mind the effects of climate change. The main purpose of this paper is to investigate the agrarian sub-national regional analysis of climate change vulnerability in Bangladesh under various climate change scenarios and its potential impact on poverty. This study is relevant to socio-economic research on climate change vulnerability and agriculture risk management and has the potential to contribute new insights to the complex interactions in household income and climate change risks to agricultural communities in Bangladesh and South Asia. The current study uses analysis of variance, cluster analysis, decomposition of variance and log-normal distribution to estimate the parameters of income variability that ascertain vulnerability levels and help us to understand the poverty levels that climate change could potentially incur. It is found that the income share in income sources revealed that income category shares across the various regions of Bangladesh are far from uniform. The variance decomposition of income showed that agricultural income in Mymensingh and Rangpur is the main cause of income difference. Moreover, large variance of agricultural income in the regions is induced by gross income from rice production. Additionally, constant reduction of rice yield due to climate change in Bangladesh is not such a severe problem for farmers, however, the extreme events like flood, flash flood, drought, sea level rise, and greenhouse gas emission based on RCPs could increase the poverty rates in Mymensingh, Rajshahi, Barisal, and Khulna regions that would be highly affected by unexpected yield loss due to extreme climatic events. Therefore, research and development of adaptation measures to climate change for regions where farmers are largely dependent on agricultural income is important.

It is quite easy to stochastically distort an original count variable to obtain a new count variable with relatively more variability than in the original variable. Many popular overdispersion models (variance greater than mean) can indeed be obtained by mixtures, compounding or randomlystopped sums. There is no analogous stochastic mechanism for the construction of underdispersed count variables (variance less than mean), starting from an original count distribution of interest. This work proposes a generic method to stochastically distort an original count variable to obtain a new count variable with relatively less variability than in the original variable. The proposed mechanism, termed condensation, attracts probability masses from the quantiles in the tails of the original distribution and redirect them toward quantiles around the expected value. If the original distribution can be simulated, then the simulation of variates from a condensed distribution is straightforward. Moreover, condensed distributions have a simple mean-parametrization, a characteristic useful in a count regression context. An application to the negative binomial distribution resulted in a distribution allowing under, equi and overdispersion. In addition to graphical insights, fields of applications of special cases of condensed Poisson and condensed negative binomial distributions were pointed out as an indication of the potential of condensation for a flexible analysis of count data

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

Inflammatory bowel diseases (IBD) involve chronic inflammation of the gastrointestinal tract, where effector CD4+ T-cells play a central role. Thereby, the recruitment of T-cells into the colonic mucosa represents a key process in IBD. We recently found that CCR9 and DRD5 might form a heteromeric complex on the T-cell surface. The increase of CCL25 production and the reduction in dopamine levels associated with colonic inflammation represent a dual signal stimulating the CCR9:DRD5 heteromer, which promotes the recruitment of CD4+ T-cells into the colonic lamina propria. Here, we aimed to analysing the molecular requirements involved in the heteromer assembly as well as to determining the underlying cellular mechanisms involved in the colonic tropism given by the stimulation of the CCR9:DRD5 complex. The results show that dual stimulation of the CCR9:DRD5 heteromer potentiates the phosphorylation of the myosin light chain 2 (MLC2) and the migration speed in confined microchannels. Accordingly, disrupting the CCR9:DRD5 assembly induced a sharp reduction in the pMLC2 in vitro, decreased the migratory speed in confined microchannels and dampened the recruitment of CD4+ T-cells into the inflamed colonic mucosa. Furthermore, in silico analysis confirmed that the interface of interaction of CCR9:DRD5 is formed by the transmembrane segments 5 and 6 from each protomer. Our findings demonstrated that the CCR9:DRD5 heteromeric complex plays a fundamental role in the migration of CD4+ T-cells into the colonic mucosa upon inflammation. Thereby, disassembling the formation of the CCR9:DRD5 represents an important therapeutic opportunity to treat IBD.

Recently, a concept known as μTRISTAN, which involves the acceleration of μ+, has been proposed. This initiative has led to considerations of a new design for a neutrino factory. Additionally, leveraging the polarization of μ+, measurements of T violation in neutrino oscillations are also being explored. In this paper, we present analytical expressions for T violation in neutrino oscillations within the framework of standard three flavor neutrino oscillations, a scenario involving nonstandard interactions, and a case of unitarity violation. We point out that examining the energy spectrum of T violation may be useful for probing new physics effects.

Trichinella spp. are etiological zoonotic agents spread throughout the world affecting mammals, birds, and rep-tiles, involved in the evolution of the two cycles, domestic and sylvatic. The pine marten (Martes martes) is a mammal carnivorous nocturnal from the family Mustelidae. In Romania, this host is widespread in all the forests of the country. The pine marten has an extremely voracious appetite, feeding on fruit but also on a variety of small animals, including rodents such as mice or rats. The aim of the study was identification and molecular characterization of Trichinella larvae isolated from the muscles of tree martens from different counties of Romania. The muscle samples were examined by artificial digestion, and the larvae were processed by multiplex PCR. Trichinella britovi, a species frequently identified in wild carnivores in temperate zones, has been confirmed. Although T. britovi has been reported in Romania to several host animals, this study confirms for the first time its presence in the pine marten, a result which undoubtedly underlines the fact that the parasitic reserve in the sylvatic environment is maintained at a consistent level, and the knowledge of these vector hosts remains a permanent concern of the specialists.

The immune response is crucial in Pregnancy Loss (RPL), which affects 1-2% of women. In RPL, peripheral blood lymphocytes and local immune cells are activated with a concomitant decrease in the leukocyte tolerogenic response in the uterus and decidua. IL-17 plays an essential role in T cell activation, weakening tolerogenic responses of the T cells. The report aims to analyze the IL-17 genetic polymorphism, circulating IL-17 lymphocyte populations, the reaction upon lymphocyte priming, the amount of cytokine in serum, and the number of T-reg cells in a group of 50 RPL and 50 normal women from the admixed Venezuelan population. No differences were observed in the genetic polymorphisms rs2275913 and rs763780. A significant decrease (P<0.001) was observed in RPL patients compared to controls in the IL-17+ cell populations CD3+, CD8+, CD56+, and CD4CD25 FoxP3, but not in the CD4IL17+ cells. The response upon cell priming was significantly decreased (P<0.001) in all subpopulations of RPL as compared to controls. It is concluded that despite the increase in IL-17A in the serum of patients, the number of circulating IL-17 cells and the lymphocyte response to stimulation was significantly decreased (p<0.001). No differences in the genetic polymorphism compared to controls suggest that biological factors influence IL-17 levels in RPL patients, which must be carefully studied.

Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15%-20% of HIV-related mortality. A complication of initiating Antiretroviral therapy (ART) following opportunistic infection is Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS afflicts 10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4⁺ and CD8⁺ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8⁺ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2⁺/IL-17⁺ CD4⁺ T cells in patients with CM-IRIS. Moreover, CD8⁺ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.

The aim of this 9th expository article is to conclude a study on domination in two fuzzy models, including t−norm fuzzy graphs and fuzzy graphs. All parts are twofold even if we don’t men- tion, directly. I.e., all results depicts some properties about fuzzy graph and t−norm fuzzy graph.

CAR-T cell therapy has emerged as a groundbreaking approach in cancer treatment, leveraging the immune system to target and eliminate cancer cells. While currently focused on hematologic malignancies, the future holds promise for expanding CAR-T cell therapy to diverse cancers, enhancing its efficacy, and improving safety profiles. Recent advances in tumor immunology have propelled CAR-T cell therapy as a game-changer in treating diseases such as relapsed/refractory B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). Six CAR-T cell products have received FDA approval for treating R/R B cell malignancies. However, challenges persist, including complications like cytokine release syndrome (CRS), coagulopathy, and cytopenias. Strategies to mitigate these complications involve targeting distinct antigens with dual- or multi-targeted CAR-T cells and enhancing immunogenicity. Additionally, γδ CAR-T cells show promise in recognizing antigen- negative leukemia cells in an MHC-independent manner while reducing the risk of inducing graft-versus-host disease (GVHD). As CAR-T cell therapy continues to evolve through innovation and discovery, it holds the potential to revolutionize cancer treatment, offering new hope to patients and reshaping the landscape of oncology with its precision and efficacy.

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to 10e8 CAR T cells/ Kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here we tested CD8/4-1BB compared to CD28-based anti-CAIX CAR PBMCs cells-releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a 10e7 CAR PBMCs cells/ Kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, T cell exhaustion status in peripheral CD4 T cells, additionally to CD8 was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon administration of 10e7 CAR PMBCs cells/Kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors.

The availability rating of any system is the probability that it will be able to operate for a given time in other words, to restore the system in the case of a system failure, or during the failure it is a measure of the availability index of resource system. We aimed to complete the study for the reasons as below. The rating and upgrading of underground mine radio communication system availability is to ensure operation reliability of the underground mine and to establish reliable radio communication system for miner’s safety during failure. Therefore, our study is contributed to reveal system availability rating of single resource (with two parallel connections) system and two resources (with three parallel connections) system. The study is related to not only practical contribution but also reliability engineering theory. To achieve this result, we have used Exponential, Weibull, and Poisson distributions. The readiness rating of single resource (with two parallel connections) and two resources (with three parallel connections) systems were calculated using Matlab software and the simulation results were introduced. This result confirms that any system has a resource system, which increases its readiness rating. The study was in examples of single resource radio communication system on the two shafts of the underground mine and two resource radio communication system for three shafts. During the initial system reliability enhancement study, the readiness of the dual resource system was assessed. The rating shows a 99 percent result, which is very meaningless for systems with more than two n-resources and we have revealed that it can show more than 100 percent result. In the process of the study on system reliability improvement the rating availability of system which has two resources was 99 % result. It is very meaningless for systems with more than two n-resources or more than 100% result.

The present paper investigates flaw strength distributions established using various flexural tests on batches of SiC bar test specimens: 4-point bending as well as 3-point bending with different span lengths. Flaw strength is given by the elemental stress operating on the critical flaw at fracture of a test specimen. Fracture inducing flaws and their locations are identified by fractography. A single population of pores was found to dominate fracture. The construction of diagrams of p-quantile vs elemental strengths was aimed at assessing the Gaussian nature of flaw strengths. Then, empirical cumulative distributions of strengths were constructed using the normal distribution function. Weibull cumulative probability distributions were derived from the mean and the standard deviation using the first moment equation. Agreement was obtained between both Weibull and normal flaw strengths distributions. The cumulative distributions for the different bending tests were predicted satisfactorily from the flaw strength density function using the elemental strength model. Flaw strength distributions that include potential weaker flaws encountered in larger test pieces are extrapolated using the p-quantile diagrams. Implications are discussed about the pertinence of an intrinsically representative flaw strength distribution, about failure predictions, about size effects, and about the significance of flaw spatial distributions.

Two extensions of the generalized double Lomax distribution are introduced - the spliced-scale generalized double Lomax distribution and the exponentiated generalized double Lomax distribution. Their properties are studied. Usefulness of the new distributions is shown by fitting them to stock returns datasets.

The decapod fauna in intertidal rocky shore in continental Chile has high species diversity mainly in northern and central Chile due high productivity of these coast due influence of cold Humboldt stream. One of the abundant species in these ecosystems is decapod Cyclograpsus cinereus Dana, 1851. The aim of the present study was determine the spatial distribution pattern of C. cinereus along rocky shore in Antofagasta bay, north of Chile between spring and summer 2018-2020. Data was obtained counting individuals from random quadrants in intertidal zones, to the obtained data was applied the variance mean ratio for determine if the specimens have random, aggregate or uniform distribution, that are associated to Poisson, negative binomial or positive binomial distributions respectively. Data obtained revealed the existence of associated distribution with respective negative binomial distribution pattern in 16 observations, and uniform distribution for 3 observations. The sites corresponds to rocky shores in urban zones, and in a protected zone, and the density does not have significant differences for both kind of sites. The observed data about aggregated pattern agree with observations for decapods for rocky shore in central and southern Chile, specifically in interpretative probabilistic models.

In this research first, a sequence of properties called delta is assigned to each prime number and then examined. Deltas are only dependent on the distribution of prime numbers, so the results obtained for the delta distribution can be considered as a proxy for the distribution of prime numbers. The first observation was that these properties are not unique and different prime numbers may have the same value of delta of a given order. It was found that a small number of deltas cover a large portion of prime numbers, so by recognizing repetitive deltas, the next prime numbers can be predicted with a certain probability, but the most important observation of this study is the normal distribution of deltas. This research has not tried to justify the obtained observations and instead of answering the questions, it seeks to ask the right question.

The asymmetric bimodal exponential power (ABEP) distribution is an extension of the generalized gamma distribution to the real line via adding two parameters which fit the shape of peakedness in bimodality on real line. The special values of peakedness parameters of the distribution are combination of half Laplace and half normal distributions on real line. The distribution has two parameters fitting the height of bimodality, so capacity of bimodality is enhanced by using these parameters. Adding a skewness parameter is considered to model asymmetry in data. The location-scale form of this distribution is proposed. The Fisher information matrix of these parameters in ABEP is obtained explicitly. Properties of ABEP are examined. Real data examples are given to illustrate the modelling capacity of ABEP. The replicated artificial data from maximum likelihood estimates of parameters of ABEP and distributions having an algorithm for artificial data generation procedure are provided to test the similarity with real data.

In this paper we consider type II bivariate generalized power series Poisson distribution as a compound Poisson distribution with bivariate generalized power series compounding distribution. We obtain some properties, p.m.f. and conditional distributions. In addition we also give a brief discussion about the multivariate extension of this case. Then we introduce type II bivariate generalized power series Poisson process and consider a bivariate risk model with type II bivariate generalized power series Poisson model as the counting process. For this model we derive distribution of the time to ruin and bounds for the probability of ruin. We obtain partial integro-differential equation for the ruin probabilities and express its bivariate transform through two univariate boundary transforms,where one of the initial capitals is fixed at zero.

The paper deals with the Compound Inverse Rayleigh distribution, shown to constitute a proper model for the characterization of the probability distribution of extreme values of wind-speed, a topic which is gaining growing interest in the field of renewable generation assessment, both in view of wind power production evaluation and the wind-tower mechanical reliability and safety. The first part of the paper illustrates such model starting from its origin as a generalization of the Inverse Rayleigh model - already proven to be a valid model for extreme wind-speeds - by means of a continuous mixture generated by a Gamma distribution on the scale parameter, which gives rise to its name. Moreover, its validity to interpret different field data is illustrated, also by means of numerous numerical examples based upon real wind speed measurements. Then, a novel Bayes approach for the estimation of such extreme wind-speed model is proposed. The method relies upon the assessment of prior information in a practical way, that should be easily available to system engineers. In practice, the method allows to express one’s prior beliefs both in terms of parameters, as customary, and/or in terms of probabilities. The results of a large set of numerical simulations – using typical values of wind-speed parameters - are reported to illustrate the efficiency and the accuracy of the proposed method. The validity of the approach is also verified in terms of its robustness with respect to significant differences compared to the assumed prior information.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

Wireless Sensor Networks are at the center of scientific interest thanks to the ever growing range of their applications. The main weakness of Wireless Sensor Networks is the restricted lifetime of their sensor nodes due to limited energy capacity. The extension of the lifespan of sensor nodes is pursued in various ways. One of them, is the usage of protocols that achieve energy efficient routing. LEACH is one of the pioneering protocols of this type and has numerous descendants. This research article focuses on energy efficient routing protocols that are based on LEACH. Specifically, a study of LEACH along with many of its successors is provided. In addition, a novel protocol of this kind, named T-LEACHSAS is proposed. This protocol is actually an extension of T-LEACH, which is one of the most well-known descending protocols of LEACH. The performance of T-LEACHSAS is compared against that of T-LEACH via simulation tests that validate the protocols' strengths and weaknesses in various scenarios. Finally, concluding remarks are indicated.

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

This paper explores the feasibility of applying Bayesian statistical methods to study the distortion patterns induced by carburizing heat treatment. By establishing posterior and predictive distribution models for torsion bar dimensions, we aim to accurately understand and predict the expansion behavior, thus enhancing control over carburizing-induced dimensional changes. Bayesian methods allow for the integration of prior knowledge and real-time data, providing a more comprehensive understanding of the distortion phenomena. This approach not only improves the precision of dimensional predictions but also contributes to optimizing the overall manufacturing process, ensuring that the torsion bars meet the rigorous standards required for high-performance applications in demanding industrial environments.

Cotton cultivation and sustaining its productivity is challenging in temperate arid regions around the globe. Exploring suitable cotton cultivation areas to improve productivity in such climatic regions is essential. Thus, this study explores the ecologically suitable areas of cotton cultivation using the Maxent model, having 375 distribution points of long-staple cotton and various factors, including 19 climatic factors, 2 terrain factors, and 6 soil factors in Xinjiang. The area under the curve (AUC) of the predicted results was greater than 0.9, indicating that the model's predictions had fairly high accuracy. However, the main environmental factors that affect cotton's growth are the lowest temperature in the coldest month, the hottest month, the precipitation in the driest season, and the monthly average temperature difference. Further, the temperature factors contribute 71%, while the contribution ratio of terrain and soil factors is only 22%. The research shows that the current planting area is consistent with the predicted area in many areas of the study. Still, some areas, such as the Turpan region, northwest of Bayingolin Mongol Autonomous Prefecture, are supposed to be suitable for planting cotton, but it is not planted. The current potential distribution area of long-staple cotton is mainly located in Aksu Prefecture and the northern part of the Kashgar Prefecture region. The climatic prediction shows that the growing area of long-staple cotton may expand to southern Altay, central Aksu, and Bortala Mongol Autonomous Prefecture. This study will be helpful for cotton cultivation suitability areas in Xinjiang and other regions with similar environments.

In this paper a more flexible extension of the Fréchet distribution is introduced. The new distribution is defined by means of the stochastic representation as the quotient of two independent random variables, a Fréchet distribution and the power of a random variable with uniform distribution in the interval (0,1). We will call this new extension the Slash Fréchet distribution and one of its main characteristics is that its tails are heavier than the Fréchet distribution. The general density of this distribution and some basic properties are determined. Its moments, skewness coefficients and kurtosis are calculated. In addition, the estimation of the model parameters is obtained by the method of moments and maximum likelihood. Finally, two applications with real data are performed by fitting the new model and comparing it with the Fréchet distribution.

The goal of clustering is to identify common structures in a data set by forming groups of homogeneous objects. The observed characteristics of many economic time series motivated the development of classes of distributions that can accommodate properties such as heavy tails and skewness. Thanks to its flexibility, the Skewed Exponential Power Distribution (also called Skewed Generalized Error Distribution) ensures a unified and general framework for clustering possibly skewed and heavy tailed time series. This paper develops a clustering procedure of model-based type, assuming that the time series are generated by the same underlying probability distribution but with different parameters. Moreover, we propose to optimally combine the estimated parameters to form the clusters with an entropy weighing $k$-means approach. The usefulness of the proposal is showed by means of application to financial time series, demonstrating also how the obtained clusters can be used to form portfolio of stocks.

Background: Emerging data indicate that radiotherapy can modulate antitumour immune responses. Regulatory T cells (Tregs) are a key immunosuppressive subpopulation of interest. We aimed to evaluate the impact of conventional fractionated radiotherapy on circulating Treg levels in melanoma patients and to determine the correlation between these changes and survival. Understanding radiotherapy–immunity interactions may facilitate personalized combination therapies. Methods: Peripheral blood samples from 32 melanoma patients were analysed to quantify Tregs before and 1-3 months after regional lymph node radiotherapy using flow cytometry. Tregs were characterized as CD4+/CD25+/CD127-. Total CD4+ T cells were also evaluated. Changes were compared to those in a control group of 30 tumor-free patients. Overall survival was correlated with T-cell subset dynamics induced by radiotherapy. Results: At baseline, the median percentage of Tregs was not significantly lower in melanoma patients than in controls (7.4% vs 8.32%, p=0.17). Radiotherapy markedly increased the median Treg count to 10.01% (p=0.0008), with a concomitant increase in total CD4+ cells (to 11.71%, p=0.001), indicating systemic expansion. Patients exhibiting coordinated increases in Treg and CD4+ T cells after treatment had a significantly improved prognosis compared with nonresponders (median OS 27.8 vs 13.1 months, p=0.001). Conclusions: Our study demonstrated the significant effects of standard fractionated radiotherapy on systemic Treg levels in melanoma patients. Radiation-induced changes in T-cell subset proportions hold prognostic value. Monitoring of circulating lymphocyte subsets could facilitate personalized combination therapies.

Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the ‘dependence’ on the normal cells. This article illustrates the benefits of new, functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in cancer stem cells’ metabolism. This theory highlights the mitochondria in cancer biology and explains how targeted anti-mitochondrial treatments can improve oncological outcomes.

Phospholipases are a family of lipid altering enzymes that can either reduce or increase bioactive lipid levels. Bioactive lipids elicit signaling responses, activate transcription factors, promote g-coupled protein activity, and modulate membrane fluidity that mediate cellular function. Phospholipases and the bioactive lipids they produce are important regulators on immune cell activity, dictating both pro-inflammatory and pro-resolving activity. During atherosclerosis, pro-inflammatory and pro-resolving activities govern atherosclerosis progression and regression respectively. This review will look at the interface of phospholipase activity, immune cell function, and atherosclerosis.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

Transient receptor potential vanilloid (TRPV) channels act as sensors of pain, temperature, and other external stimuli. We have recently shown that DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can modulate the activity of TRPV on human primary keratinocytes, suggesting their potential as a possible pain modulator [1]. CD4+ T lymphocytes also express TRPV channels, and we sought with special interest to examine the effect of DPV576 in modulating the functions of TRPV channel expression and secretion of cytokines on human CD4+ T lymphocytes. Human primary CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:25 and 1:100 dilutions for 24 hours in vitro. TRPV Receptor expression (TRPV1 and TRPV4) on CD4+ T cells was examined by flow cytometry. The capacity of DPV576 to modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also determined. Activation of CD4+ T cells was determined by production of cytokines TNF-α, IFN-γ, and IL-10 using specific ELISA kits. DPV576 treatment of CD4+ T cells that were activated with anti CD3/CD28, resulted in increased expression of TRPV1 channel but had no effect on TRPV4. This was accompanied by increased secretion of IFN-g and reduced expression of TRPV1 in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin, induced the production of both IFN-g and TNF-α, and enhanced the secretion of IL-10. We conclude that short term exposure to DPV576 inhibits the activity of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible beneficial use for pain management.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Extracellular vesicles (EV) are a very heterogeneous group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular communication, both locally and systemically, since they induce signals and transfer their contents (proteins, lipids, RNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. How-ever, cell surface receptor-induced EV release is limited to cells from the immune system, includ-ing T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptor for antigen and several bioactive molecules, including proapoptotic proteins. These EV are thus specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we discuss the generation of EV by T lymphocytes and some potential therapeutic approaches of these EV.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

The Amazon region has the most incredible diversity of freshwater stingrays; however, there are still places where information about this group is scarce. The present work aims to record the occurrence of freshwater stingrays in the Uatumã river basin, Amazonas, Brazil. For this, collections were carried out in three municipalities bathed by the Uatumã River, Presidente Figueiredo, Itapiranga and São Sebastião do Uatumã. The rays were collected through fishing using a hand net and, after capture, were identified through the pattern of the dorsal and ventral color of the disc, the absence or presence of the labial groove and the organization of the row of spines on the tail, too were also measured, weighed and sexed. In total, 69 specimens of Potamotrygonines were captured, 59 of which were from the genus Potamotrygon and ten individuals from the genus Paratrygon. The present study provides preliminary information on the characteristics of freshwater stingray species that may occur in the Uatumã River. Furthermore, new research is necessary to improve the identification of specimens to determine the diversity and elucidate aspects related to the biology of elasmobranchs in the Uatumã River Basin, Brazil.

Este estudio empleó el algoritmo MaxEnt para evaluar la distribución potencial de la serpiente de cascabel de cola larga, Crotalus stejnegeri , una especie amenazada endémica de México. Los resultados demuestran una buena fiabilidad del modelo, alcanzando un AUC de 0,879. Destacan una distribución potencial concentrada en las estribaciones de la Sierra Madre Occidental, principalmente en el centro-sur de Sinaloa, suroeste de Durango y norte de Nayarit, caracterizada por bosque seco tropical. La temperatura durante el trimestre más seco y la estacionalidad de la precipitación se identifican como factores determinantes, mientras que la baja idoneidad en Chihuahua sugiere una afinidad tropical de la especie. La variabilidad en las precipitaciones durante el trimestre más frío enfatiza la importancia de ampliar el número de registros de ocurrencia de la especie mediante una mayor exploración de campo dentro de su área de distribución. Estos hallazgos proporcionan información valiosa para los esfuerzos de conservación y subrayan áreas clave para futuras investigaciones.

This paper examines the regional changes of corn production and the relationship between ethanol production and corn production. The underlying hypothesis is that the rapid growth in ethanol production causes regional expansion of corn production outside the traditional regions. This paper introduces the information approach developed by entropy theory to describe these regional changes. The results support the hypothesis that ethanol production leads to expansion of corn production outside traditional corn producing regions.

Currently, there is no widely accepted consensus regarding a consistent thermodynamic framework within the special relativity paradigm. However, by postulating that the inverse temperature 4-vector, denoted as β, is future-directed and timelike, intriguing insights emerge. Specifically, it is demonstrated that the q-dependent Tsallis distribution can be conceptualized as a de-Sitterian deformation of the relativistic Maxwell-Jüttner distribution. In this context, the curvature of the de Sitter space-time is characterized by Λ/3, where Λ represents the cosmological constant within the ΛCDM standard model for Cosmology. For a simple gas composed of particles with proper mass m, and within the framework of quantum statistical de Sitterian considerations, the Tsallis parameter q exhibits a dependence on the cosmological constant given by q=1+ℓcΛ/n where ℓc=ℏ/mc is the Compton length of the particle and n is a positive numerical factor. This formulation establishes a novel connection between the Tsallis distribution, quantum statistics, and the cosmological constant, shedding light on the intricate interplay between relativistic thermodynamics and fundamental cosmological parameters.

In studies of dynamic stability and power quality, it is necessary to know the mechanical parameters that determine the transient response of a wind turbine. The exact value of these parameters is not as decisive as the power curve can be, but an estimate that is far from reality can distort or even invalidate the simulation results. Despite its importance, this information, especially the inertia, but also the stiffness and damping constant of the drive-train, is hardly available for the turbine model under investigation. In this work, the different bibliographical sources that provide values of blade inertia in kg·m2 will be reviewed, and above all, those that provide a distribution of masses along the span of the blade. With this, different reliable relations will be obtained that allow calculating the inertia of the turbine rotor, based on the mass and length of the blade. When the center of gravity is also available, a very correlated expression is provided to obtain the inertia. The even rarer references to the stiffness and damping constant of the drive-train will also be reviewed.

In this work, we explore the extreme searching of multidimensional functions by natural gradient descent based on Dirichlet and generalized Dirichlet distributions. The natural gradient is based on describing multidimensional surface with probability distributions, which allows us to reduce changing the accuracy of gradient and step-size. In this article, we propose an algorithm of natural gradient descent based on Dirichlet and generalized Dirichlet distributions. We demonstrate that the natural gradient descent with step-size adaptation with Dirichlet and generalized Dirichlet distributions has higher accuracy and does not take a large number of iterations for minimizing test functions than gradient descent and Adam.

This paper provides attempts to formalize Hayek’s theory of knowledge. It has been theoretically shown that exponential income distribution is a spontaneous order of the well-functioning market economy. We show that this theoretical result is supported by the empirical evidence from the United Kingdom and China. In particular, we empirically show how the income structure of China evolved towards an exponential distribution after the market-oriented economic reformation. Furthermore, we strictly prove that, if the income structure of an economy obeys an exponential distribution, the income summation over all households leads to an aggregate production function with Hicks-neutral-like technical progress, in which the technology factor is exactly equal to society’s information stock that is a result of combining all of decentralized decisions.

Introduction: Obstructive sleep apnea (OSA) is the most common sleep-breathing disorder. OSA is associated with cardiovascular diseases such as coronary artery disease (CAD) and arrhythmias with an increased risk of sudden cardiac death. Some changes in ECG markers are seen as an indicator of arrhythmogenicity, especially ventricular arrhythmias. The goal of this study was to investigate if OSA patients with CAD have QT dispersion and T peak to T end (TpTe) changes as a surrogate of arrhythmogenicity. Methods: We studied 75 patients with CAD who underwent polysomnographic studies. Patients were categorized into mild, moderate, and severe OSA according to the Apnea hypopnea index (AHI). Baseline ECG and echocardiography for assessing LV function and valvular heart disease were done for all of them. Results: Results showed that in patients with moderate and severe sleep apnea QT dispersion was higher in a group with more involvement of coronary artery disease, reduced ejection fraction, and a history of old MI. However, we didn’t find any significant statistical relationship between OSA and TpTe marker. Conclusion: Our results showed a positive relation between ECG arrhythmic indices such as QT dispersion and OSA severity in patients with CAD.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

This paper presents the five-parameter Exponentiated Weibull Weibull (EWW) distribution with Weibull base failure rate parameterization, developed to model the dropout times of students in an online class module. Parameters of the model were estimated using both Maximum Likelihood and Bayesian estimation procedures to determine the most effective estimation method. Simulation results indicate that, across various hazard types and censoring levels, Bayesian estimates are more accurate and precise than Maximum Likelihood estimates. Real-life data analysis of online students module presentation supports these findings, showing significantly lower standard deviations for Bayesian estimates compared to Maximum Likelihood estimates, highlighting the efficiency of Bayesian estimation for the EWW distribution. Additionally, a comparative goodness-of-fit analysis demonstrated that the EWW distribution better fits the student dropout times dataset than Weibull Weibull (WW), Weibull Exponential (WE), and Exponential Weibull (EW) distributions. The median dropout time estimated using the EWW distribution is 24 days, suggesting that instructors should closely monitor student attendance around this period.

Molecular-scale density fluctuations at equilibrium produce cavities in a liquid and can be analyzed to shed light on the statistics of the number of molecules occupying observation volumes of increasing radius. An information theory approach led to the conclusion that these probabilities should follow a Gaussian distribution function. This prediction has been confirmed by computer simulations in different liquid models if the size of the observation volume is not large. The reversible work of cavity creation is exactly linked to the probability of finding zero molecules in a given observation volume. The Gaussian formula for the latter probability is scrutinized to arrive at the enthalpy and entropy changes associated with cavity creation. The reversible work of cavity creation has a purely entropic origin due to the solvent-excluded volume effect produced by the inaccessibility of a given region of the configurational space. The consequent structural reorganization of liquid molecules leads to exactly compensating enthalpy and entropy changes. These results are in line with those obtained in a direct statistical mechanical study by Lee.

This work presents a new algorithm to resolve the problem of distribution network reconfiguration using the Tabu Search metaheuristic and voltage drop. The proposed method presents a different way to obtain the initial solution using the voltage drop, as well as a new way to generate a neighborhood of candidate solutions, based on randomness and the voltage drop, to perform a smooth and steady descent execution of the algorithm. The proposed algorithm has the main objective to reduce the active power losses in distribution networks, but it also achieves an refinement in the voltage profile. The proposed method was tested in two distribution systems, the 33-Bus and 94-Bus systems, commonly found and tested in the literature. The results of the tests show that the proposed method presents a low computational cost, achieves good solutions, and is better than the other methods found in the literature.

The purpose of this paper is to summarize and share the field experiment results of KEPCO's project consortium to create a TSO-DSO-DERA interaction scheme. The field experiment was conducted based on the prequalification algorithm proposed in the previous research from the same consortium and was designed to verify the validity of the algorithm under realistic grid conditions. In addition, during the course of the field experiment, it was found that points that were missed or not given much importance in the existing prequalification algorithm could affect the completeness of the overall system, and then practical improvements were made to improve it. The demonstration results confirm that the proposed algorithm is effective in real-world grid environments and can help DSOs ensure the reliability of the distribution system while supporting DERA's participation in the wholesale market using the proposed prequalification scheme.

The power function distribution is a flexible waiting time model that may provide better fit for some failure data. This paper presents the comparison of the maximum likelihood estimates and the Bayes estimates of two-parameter power function distribution. The Bayes estimates are obtained, using conjugate priors, under five loss functions consist of square error, precautionary, weighted, LINEX and DeGroot loss function. The Gibbs sampling algorithm is proposed to generate samples from posterior distributions and in result the Bayes estimates are computed. The comparison of the maximum likelihood estimates and the Bayes estimates are done through the root mean squared errors. One real-life data set is analyzed to illustrate the evaluation of proposed methods of estimation. Finally, results from the simulation are discussed to assess the performance behavior of the maximum likelihood estimates and the Bayes estimates.

This paper studies the goodness of fit test for the bivariate Hermite distribution. Specifically, we propose and study a Cramér-von Mises-type test based on the empirical probability generation function. The bootstrap can be used to consistently estimate the null distribution of the test statistics. A simulation study investigates the goodness of the bootstrap approach for finite sample sizes.

While lidar-based forest inventory methods have been widely demonstrated, prediction of tree diameters with lidar is not well understood. The performance metrics typically used in studies for prediction of diameters can be difficult to interpret and may not support comparative inferences between sampling designs or study areas. We evaluate a variety of lidar and k nearest neighbor (k-NN) strategies for prediction of tree diameter distributions using two indices which are easier to interpret and compare. The indices are based on the coefficient of determination (R²), and root mean square deviation (RMSD). These indices facilitate comparisons with alternative (non-lidar) inventory strategies, and with other project areas. We evaluate k nearest neighbors (k-NN) dbh density (relative frequency by dbh class) prediction strategies with lidar for 190 training plots distribute across the 800 km² Savannah River Site in South Carolina, USA. We evaluate the performance of k-NN with respect to distance metrics, number of neighbors, predictor sets, and response sets. Amongst the examined strategies we found Mahalanobis distance with k = 3 neighbors performed best according to a number of criteria.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

Lymphocyte collection by apheresis for CAR-T production usually does not include mobilized blood using Granulocyte Colony Stimulating Factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinic, makes necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent work that experimentally verifies the role and functionality of T and NK lymphocytes, and the generation of CAR-T, from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant and the different sub-populations remain stable. In addition, its expansion and proliferation rate are invariant regardless mobilization with G-CSF, as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

We propose that the coexistence of gapless Fermi arcs with the metal-insulator crossover of in-plane resistivity in strongly underdoped cuprates can be explained by the FL* fractionalized Fermi liquid nature of these systems and it is not due simply to disorder effects. The particle excitations of this FL* system derived from variants of the t-J model are: the gapless holon carrying charge with small Fermi momentum proportional to the doping, the gapful spinon carrying spin 1/2, gauge fluctuations coupling them and the hole as a spinon-holon bound state or resonance due to gauge binding with a Fermi surface respecting the topological Luttinger theorem. In our proposal Fermi arcs are determined by the hole resonance, whereas the metal-insulator crossover is dominated by spinon-spinon (with subleading holon-holon) gauge interactions and this dichotomy is able to explain their coexistence.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest into the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed the CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials that evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are undergoing. In this review, we summarize the current status of knowledge regarding the changes of CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biologic mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

The oncogenicity of the human cytomegalovirus (CMV) is debated to this day. In recent years, mounting evidence addresses an anti-cancer effect via T cell-mediated CMV-targeted tumor de-struction. However, the data mostly comes from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. This study examined the correlation between country-specific CMV seroprevalence (n=73) and age-standardized inci-dence rates for 34 tumors using data obtained from the International Agency for Research on Cancer of the World Health Organization. The association between CMV and cancer incidences in 10-year age increments was also analyzed. The study revealed a worldwide inverse correlation between CMV seroprevalence and incidences of 88.2% tumors. Notably, this inverse link persists for all cancers combined (Spearman’s ρ= -0.732, p= 0.001). An antithetical and significant correlation is also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, suggesting a common under-lying mechanism – CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, further in-depth investigation of host-virus interactions is warranted.