Chromatin regulation and immune escape

Antigens expressed by cancer cells target them for elimination by tumor-infiltrating T cells (1). But, despite T cell recognition, advanced malignancies are often fatally progressive. T cell inhibitory (checkpoint) receptors, including programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4), contribute to immune suppression and dysfunction in tumors. Checkpoint inhibitors (CPIs) developed to block these pathways and derepress T cell activity have considerably improved outcomes for various cancer types. However, beyond certain rare and highly sensitive tumors (2), responses remain limited to a fraction of patients, and both primary and acquired resistance are frequently observed. Although much work has focused on defining and overcoming T cell–intrinsic inhibitory mechanisms, such as checkpoint expression, less is known about what regulates tumor cell sensitivity to T cell attack. On pages 801 and 770 of this issue, Miao et al. (3) and Pan et al. (4), respectively, find that chromatin remodeling pathways contribute to cancer cell immune resistance through control of interferon-stimulated gene (ISG) expression. This has implications for our understanding of why CPIs fail and suggests that targeting these pathways may enhance tumor immunotherapy

Constraining dark matter interactions mediated by a light scalar with white dwarfs

Observations of white dwarfs in dark matter-rich environments can provide strong limits on the strength of dark matter interactions. Here we apply the recently improved formalism of the dark matter capture rate in white dwarfs to a general model in which dark matter interacts with the white dwarf ion components via a light scalar mediator. We compute the dark matter capture rate in the optically thin limit in a cold white dwarf from the globular cluster Messier. We then estimate the threshold cross-section, which significantly varies as a function of the light scalar mediator mass $m_\phi$ in the range of 0.05\, m_\chim_\chi. We also show that the bounds obtained from the dark matter capture in a white dwarf from the globular cluster Messier 4 are complementary to direct detection experiments and particularly strong in the sub-GeV regime.Comment: 6 pages, 2 figure

Methodological Proposal to Evaluate the Alternative of Outsourcing the Transportation Fleet of a Company

Abstract The companies have different solutions to transport their merchandise to the customer: have their own fleet, outsource the excess when the transport capacity is exceeded by the demand (mixed system) and the complete subcontracting of all the transport operations. Outsourcing is one of the solutions, in different areas of administration and especially in transportation. Then, being a strategic decision, it is pertinent to ask the questions: should it be externalized? and when?. The answer depends on factors that must be evaluated in each case. To make the decision, it is necessary first to evaluate if transport is a "key success factor" and it is a "basic competence" for the company. It is essential before defining what type of solution to give to the transport and depending on it, when it should be taken to make the business gain a competitive advantage. The proposed methodology distinguishes the relevant factors that allow a successful outsourcing, which are: people, infrastructure, ICTs, logistics management and business strategy, which will allow the development and growth of the business. Likewise, tools for business analysis, management, project evaluation and decision making, play a fundamental role in the qualitative and quantitative study of the proposed methodology, a decision model that allows the evaluation of the fleet's externalization, through the possible transport management solutions. Finally, a map of the evaluation process is proposed, integrating the tools defined for the diagnosis, evaluation and definition of the decision

Exploring the dark sectors via the cooling of white dwarfs

As dense and hot bodies with a well-understood equation of state, white dwarfs offer a unique opportunity to investigate new physics. In this paper, we examine the role of dark sectors, which are extensions of the Standard Model of particle physics that are not directly observable, in the cooling process of white dwarfs. Specifically, we examine the role of a dark photon, within the framework of a three-portal Model, in enhancing the neutrino emission during the cooling process of white dwarfs. We compare this scenario to the energy release predicted by the Standard Model. By analyzing the parameter space of dark sectors, our study aims to identify regions that could lead to significant deviations from the expected energy release of white dwarfs.Comment: 9 pages, 5 figure

Nivel de satisfacción de las mujeres, en la atención del parto vaginal en la sala de puerperio fisiológico del Hospital Bertha Calderon Roque en el período de Abril–Agosto del 2014

La satisfacción de la mujer con la experiencia delnacimiento de su hijo es un indicador importante en la calidad de los servicios de atención obstétricos. El presente estudio se realizó bajo el marco conceptual de Mackey Childbirth Scale 1998). El cual considera cinco componentes de la satisfacción: ella misma, hijo, enfermera, médico y acompañante.El objetivo del presente trabajo fue determinar la satisfacción materna con la experiencia del nacimiento de su hijo considerando a la parturienta como un todo en su evaluación integral.Se realizó un estudio descriptivo de corte trasversal, con muestreo probabilístico en las salas de puerperio fisiológico mediato del Hospital Bertha Calderón, se contó con una población a estudio de 240 puérperas, como instrumento de medición se tomó en cuenta la escala antes descrita. Para su análisis estadístico se interpretó en porcentajes y frecuencias.Entre los hallazgos encontrados en este estudio se encontró el principal grupo etario que dio a luz fue las edades comprendidas entre 21 y 25 años, con escolaridad secundaria, unión estable de ocupación de ama de casa. Como tal se logró apreciar que las pacientes clasifican su experiencia de parto como positiva durante su proceso de parto vaginal

A monolithic conservative level set method with built-in redistancing

We introduce a new level set method for representing evolving interfaces. In the case of divergence-free velocity fields, the new method satisfies a conservation principle. Conservation is important for many applications such as modeling two-phase incompressible flow. In the present implementation, the conserved quantity is defined as the integral of a smoothed characteristic function. The new approach embeds level sets into a volume of fluid formulation. The evolution of an approximate signed distance function is governed by a conservation law for its (smoothed) sign. The non-linear level set transport equation is regularized by adding a flux correction term that assures a non-singular Jacobian and penalizes deviations from a distance function. The result is a locally conservative level set method with built-in elliptic redistancing. The continuous model is monolithic in the sense that the level set transport model, the volume of fluid law of mass conservation, and the minimization problem that preserves the approximate distance function property are incorporated into a single equation. There is no need for any extra stabilization, artificial compression, flux limiting, redistancing, mass correction, and other numerical fixes which are commonly used in level set or volume of fluid methods. In addition, there is just one free parameter that controls the strength of regularization and penalization in the model. The accuracy and conservation properties of the monolithic finite element / level set method are illustrated by the results of numerical studies for passive advection of free interfaces