Modeling Monty Hall in IF logic

We provide a game-theoretical solution to the Monty Hall problem, and its representation in IF-logic, a system of logic which is an extension of first-order logic with Independent Quantifiers. This solution has been originally proposed by Allen Mann, but here we focus more on the game-theoretical aspects and the philosophical significance.Peer reviewe

Strategi Branding Baran Energy sebagai Merek Energi Baru Terbarukan di Indonesia

Oleh : Velica Halim Saat ini, Indonesia memiliki ketergantungan energi fosil yang kian menipis tiap tahunnya. Penggunaan energi baru terbarukan (EBT) dapat menjadi solusi untuk mengatasi hal tersebut. Salah satu merek EBT hadir di Indonesia yakni Baran Energy dengan mengembangkan produk energy storage system (Baran Power). Tujuan penelitian ini untuk mengetahui bagaimana strategi branding Baran Energy dari aspek identitas merek dan komunikasi merek. Penelitian ini menggunakan jenis penelitian kualitatif bersifat deskriptif dengan metode studi kasus. Penelitian ini dilakukan dengan indepth interview, observasi, dan studi pustaka. Metode triangulasi yang digunakan guna menunjukkan keabsahan data pada peneltian. Hasil penelitian menunjukkan bahwa Baran Energy melakukan startegi branding melalui identitas merek dan komunikasi merek sebagai merek EBT di Indonesia. Namun, tahapan proses membangun identitas merek belum dilakukan secara maksimal oleh Baran Energy. Komunikasi merek yang dilakukan Baran Energy melalui public relations, promosi penjualan, events, media sosial dan media online

Robert Bosch GMBH, Guadalajara

En este proyecto PAP estaré colaborando con la empresa Robert Bosch GmbH como becario de desarrollo de software embebido. Las actividades que llevaré a cabo consistirán en soporte al equipo encargado del módulo de diagnóstico de su producto DASy. Además de las actividades específicas asignadas por este equipo, parte fundamental del proyecto consistirá en el aprendizaje y familiarización con las tecnologías y estándares utilizados en la industria automotriz. El producto DASy es un sistema de computo que busca soportar la gran variedad de aplicaciones de tipo ADAS que han tenido un auge de desarrollo en los últimos años. El equipo de diagnóstico tiene la responsabilidad de habilitar las actividades diagnóstico, a la medida del proyecto del cliente, particularmente al implementar los servicios UDS, así como elementos que interactúan con estos servicios (rutinas, DiDs). Mis actividades de soporte se enfocarán en la elaboración de los requerimientos de servicios UDS, apoyo en la implementación de DiDs y elaboración de documentación interna para el equipo. Entre los temas en lo que me estaré formando, los principales para apoyar a las actividades que desarrollare son la especificación de UDS y AUTOSAR. Otros temas que también estaré cubriendo serán protocolos de comunicación y practica de programación en lenguaje C++.ITESO, A.C

Safety and efficacy of Tet-regulated IL-12 expression in cancer-specific T cells

We explored whether engineering of T cell specificity and effector function improves immunotherapy of solid tumors. Although IL-12 can enhance cancer immunity, a strategy of safe IL-12 delivery without toxicity is currently lacking. We engineered T cells to express IL-12 controlled by the NFAT promoter responsive to TCR stimulation, or by the Tet-On promoter responsive to doxycycline. In vivo, NFAT-engineered T cells caused lethal toxicity, while Tet-engineered T cells were safe in the absence of doxycycline. Combining gene transfer of the melanoma-specific TRP2-TCR with Tet-IL-12 engineering revealed that temporal induction of IL-12 was essential to inhibit the growth of B16F10 melanoma tumors. Induced IL-12 increased the number of tumor-infiltrating T cells and also prevented the down-modulation of the TRP2-TCR and the associated up-regulation of the PD1 marker that was observed in the absence of IL-12. In addition, temporal induction of IL-12 expression also increased the number of plasmacytoid DC in the tumor micro-environment. We show that repeated induction of IL-12 can be used to enhance control of tumor growth without encountering systemic toxicity. The observation that TCR engineering combined with Tet-regulated IL-12 expression can achieve tumor immunity without the side effects that are usually associated with the in vivo use of IL-12 warrants translation of this concept into the clinic

Expression of a dominant T-cell receptor can reduce toxicity and enhance tumor protection of allogeneic T-cell therapy

Due to the lack of specificity for tumor antigens, allogeneic T-cell therapy is associated with graft-versus-host disease. Enhancing the anti-tumor specificity while reducing the graft-versus-host disease risk of allogeneic T cells has remained a research focus. In this study, we demonstrate that the introduction of ‘dominant’ T-cell receptors into primary murine T cells can suppress the expression of endogenous T-cell receptors in a large proportion of the gene-modified T cells. Adoptive transfer of allogeneic T cells expressing a ‘dominant’ T-cell receptor significantly reduced the graft-versus-host toxicity in recipient mice. Using two bone marrow transplant models, enhanced anti-tumor activity was observed in the presence of reduced graft-versus-host disease. However, although transfer of T-cell receptor gene-modified allogeneic T cells resulted in the elimination of antigen-positive tumor cells and improved the survival of treated mice, it was associated with accumulation of T cells expressing endogenous T-cell receptors and the development of delayed graft-versus-host disease. The in vivo deletion of the engineered T cells, mediated by endogenous mouse mammary tumor virus MTV8 and MTV9, abolished graft-versus-host disease while retaining significant anti-tumor activity of adoptively transferred T cells. Together, this study shows that the in vitro selection of allogeneic T cells expressing high levels of a ‘dominant’ T-cell receptor can lower acute graft-versus-host disease and enhance anti-tumor activity of adoptive cell therapy, while the in vivo outgrowth of T cells expressing endogenous T-cell receptors remains a risk factor for the delayed onset of graft-versus-host disease

Hop Mice Display Synchronous Hindlimb Locomotion and a Ventrally Fused Lumbar Spinal Cord Caused by a Point Mutation in Ttc26

Identifying the spinal circuits controlling locomotion is critical for unravelling the mechanisms controlling the production of gaits. Development of the circuits governing left-right coordination relies on axon guidance molecules such as ephrins and netrins. To date, no other class of proteins have been shown to play a role during this process. Here, we have analyzed hop mice, which walk with a characteristic hopping gait using their hindlimbs in synchrony. Fictive locomotion experiments suggest that a local defect in the ventral spinal cord contributes to the aberrant locomotor phenotype. Hop mutant spinal cords had severe morphologic defects, including the absence of the ventral midline and a poorly defined border between white and gray matter. The hop mice represent the first model where, exclusively found in the lumbar domain, the left and right components of the central pattern generators (CPGs) are fused with a synchronous hindlimb gait as a functional consequence. These defects were associated with abnormal developmental processes, including a misplaced notochord and reduced induction of ventral progenitor domains. Whereas the underlying mutation in hop mice has been suggested to lie within the Ttc26 gene, other genes in close vicinity have been associated with gait defects. Mouse embryos carrying a CRISPR replicated point mutation within Ttc26 displayed an identical morphologic phenotype. Thus, our data suggest that the assembly of the lumbar CPG network is dependent on fully functional TTC26 protein

The S enantiomer of 2-hydroxyglutarate increases central memory CD8 populations and improves CAR-T therapy outcome

Cancer immunotherapy is advancing rapidly and gene-modified T cells expressing chimeric antigen receptors (CARs) show particular promise. A challenge of CAR-T cell therapy is that the ex vivo-generated CAR-T cells become exhausted during expansion in culture, and do not persist when transferred back to patients. It has become clear that naive and memory CD8 T cells perform better than the total CD8 T-cell populations in CAR-T immunotherapy because of better expansion, antitumor activity, and persistence, which are necessary features for therapeutic success and prevention of disease relapse. However, memory CAR-T cells are rarely used in the clinic due to generation challenges. We previously reported that mouse CD8 T cells cultured with the S enantiomer of the immunometabolite 2-hydroxyglutarate (S-2HG) exhibit enhanced antitumor activity. Here, we show that clinical-grade human donor CAR-T cells can be generated from naive precursors after culture with S-2HG. S-2HG-treated CAR-T cells establish long-term memory cells in vivo and show superior antitumor responses when compared with CAR-T cells generated with standard clinical protocols. This study provides the basis for a phase 1 clinical trial evaluating the activity of S-2HG-treated CD19-CAR-T cells in patients with B-cell malignancies

Redirection to the bone marrow improves T cell persistence and antitumor functions

A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15–dependent homeostatic expansion and promoted the differentiation of memory precursor–like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells