Guadecitabine, in combination with Cyclophosphamide, promotes anti- cancer immunity in BALB/c mice bearing 4T1 mouse mammary carcinoma

Background: The extremely high mortality rate of patients diagnosed with triple negative breast cancer makes it one of the deadliest forms of cancer. Due to the heterogenous nature of tumors, complete clearance is not achieved and clonal selection occurs resulting in tumor cells evading the immune system. I aim to design a therapeutic intervention that is able to elicit an effective immune response against the tumor and instill immunological memory to eradicate primary and metastatic lesions. I hypothesize that the combination of Guad and Cyp will synergize and promote anticancer immunity via increased expression of neo-tumor antigens and depletion of MDSCs and T-regs. Methods: Guadecitabine (Guad), is a second-generation DNA methyltransferase inhibitor (DMNTi) that has been reported to increase antigenicity and deplete myeloid-derived suppressor cells (MDSC’s). Cyclophosphamide (Cyp) is a chemotherapy that has been shown to deplete regulatory T-cells (T-regs). Both MDSD’s and T-regs suppress antitumor immunity. BALB/c mice were challenged with 4T1 tumor cells subcutaneously in the mammary fat pad region. 4T1-bearing mice were administered low-dose Guad and Cyp for ten consecutive days. Tumor growth curves, tumor-infiltrating lymphocytes (TILs) were measured and MDSC’s and T- regs levels were assessed by flow cytometry. Results: Results from this experiment showed significant synergy between Guad and Cyp with both drugs reducing the tumor size over monotherapy. Conclusions: Further analysis of the data along with future experiments will elucidate if this synergy is driven by the depletion of MDSC’s and T-regs alone or the increase in tumor antigenicity inducing increased numbers of TILs.https://scholarscompass.vcu.edu/gradposters/1078/thumbnail.jp

Euclid: Testing the Copernican principle with next-generation surveys

Context. The Copernican principle, the notion that we are not at a special location in the Universe, is one of the cornerstones of modern cosmology. Its violation would invalidate the Friedmann-Lemaître-Robertson-Walker metric, causing a major change in our understanding of the Universe. Thus, it is of fundamental importance to perform observational tests of this principle. Aims. We determine the precision with which future surveys will be able to test the Copernican principle and their ability to detect any possible violations. Methods. We forecast constraints on the inhomogeneous Lemaître-Tolman-Bondi (LTB) model with a cosmological constant Λ, basically a cosmological constant Λ and cold dark matter (CDM) model but endowed with a spherical inhomogeneity. We consider combinations of currently available data and simulated Euclid data, together with external data products, based on both Λ CDM and Λ LTB fiducial models. These constraints are compared to the expectations from the Copernican principle. Results. When considering the Λ CDM fiducial model, we find that Euclid data, in combination with other current and forthcoming surveys, will improve the constraints on the Copernican principle by about 30%, with ±10% variations depending on the observables and scales considered. On the other hand, when considering a Λ LTB fiducial model, we find that future Euclid data, combined with other current and forthcoming datasets, will be able to detect gigaparsec-scale inhomogeneities of contrast -0.1. Conclusions. Next-generation surveys, such as Euclid, will thoroughly test homogeneity at large scales, tightening the constraints on possible violations of the Copernican principl

Aplicación y evaluación de un programa cognitivo conductual pacientes con trastornos depresivos que asisten a la clínica de diabetes del Hospital Regional Anita Moreno de Los Santos, 2015

El presente estudio ha tenido como propósito esencial la aplicación y evaluación de un programa cognitivo conductual para el manejo de los síntomas depresivos en pacientes diabéticos que asisten a la consulta externa del hospital Regional Anita Moreno de Los Santos. A través de un diseño de investigación de pretest y postest, con un solo grupo, fue evaluada la efectividad de una intervención cognitivo conductual en un grupo aplicado a pacientes diabéticos que presentaban síntomas depresivos a causa de la enfermedad. El tratamiento fue ofrecido en doce sesiones, una vez por semana con una duración de dos horas cada sesión. Dentro de las técnicas y pruebas psicologías; se administra la escala de Beck, y se aplicaron entrevistas estructuradas, y hojas de registros para evaluar el avance de las terapias. Los resultados de la investigación señalan que el promedio de puntuación inicial fue 18 ± 4 y al final de 6 ± 2. El uso del estadístico t para muestras apareadas nos da un valor de 21.4, que mayor que el valor crítico de 1.76 para una p: 0.05 y gL: 14. Con base en lo anterior se rechaza la hipótesis nula y se concluye que la diferencia en las puntuaciones antes y después, es estadísticamente significativa. Además, se realizó el análisis de las diferencias de las respuestas por preguntas de la escala de Beck, en cual el valor fue de t de Student para cada pregunta aplicada a los 15 participantes antes y después de la terapia. (p: 0,05, valor crítico 1,76). Podemos evidenciar que entre mayor sea el valor del estadístico, mayor será la significancia del cambio en las preguntas del instrumento utilizado

ANÁLISIS DE INTERLENGUA EN UN CORPUS DE PORTUGUÉS ESCRITO DE ESTUDIANTES CASTELLANO HABLANTES UNIVERSITARIOS

[EN] This article presents the results of the analysis of errors and characteristics of the interlanguage produced by students of Portuguese as a foreign language at the National Autonomous University of Mexico. It is based on a corpus of 104 texts written by intermediate and advanced students. This study forms part of the triangulation of doctoral research on the subject of efficiency in the teaching of Portuguese.[ES] El presente artículo es el resultado del análisis de errores y fenómenos de interlengua producidos por estudiantes de portugués lengua extranjera de la Universidad Nacional Autónoma de México, en un corpus escrito de 104 redacciones de alumnos de niveles intermedio y avanzado. Este estudio forma parte de la triangulación de una investigación doctoral sobre eficiencia en la enseñanza del portugués.Camarena Ortiz, ED. (2011). ANÁLISIS DE INTERLENGUA EN UN CORPUS DE PORTUGUÉS ESCRITO DE ESTUDIANTES CASTELLANO HABLANTES UNIVERSITARIOS. Revista de Lingüística y Lenguas Aplicadas. 6:71-82. doi:10.4995/rlyla.2011.8947182

Self-pulsing dynamics of ultrasound in a magnetoacoustic resonator

A theoretical model of parametric magnetostrictive generator of ultrasound is considered, taking into account magnetic and magnetoacoustic nonlinearities. The stability and temporal dynamics of the system is analized with standard techniques revealing that, for a given set of parameters, the model presents a homoclinic or saddle--loop bifurcation, which predicts that the ultrasound is emitted in the form of pulses or spikes with arbitrarily low frequency.Comment: 5 pages, 5 figure

The Copernican principle in light of the latest cosmological data

We pursue a program to confront observations with inhomogeneous extensions of the FLRW metric. The main idea is to test the Copernican principle (CP) rather than assuming it a priori. We consider the CDM model endowed with a spherical LTB inhomogeneity around us, that is, we assume isotropy and test the hypothesis of homogeneity. We confront the LTB model with the latest available data from cosmic microwave background, BAO, type Ia supernovae, local H0, cosmic chronometers, Compton y-distortion, and kinetic Sunyaev-Zeldovich effect. We find that these data can constrain tightly this extra inhomogeneity, almost to the cosmic variance level: on scales 100 Mpc structures can have a small non-Copernican effective contrast of just δL 0.01. Furtheore, the constraints on the standard CDM parameters are not weakened after marginalizing over the parameters that model the local structure, to which we assign ignorance priors. In other words, dropping the CP assumption does not imply worse constraints on the cosmological parameters. This positive result confis that the present and future data can be meaningfully analyzed within the framework of inhomogeneous cosmology. © 2021 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society

Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation

As part of PsychENCODE, we developed a three-dimensional (3D) epigenomic map of primary cultured neuronal cells derived from olfactory neuroepithelium (CNON). We mapped topologically associating domains and high-resolution chromatin interactions using Hi-C and identified regulatory elements using chromatin immunoprecipitation and nucleosome positioning assays. Using epigenomic datasets from biopsies of 63 living individuals, we found that epigenetic marks at distal regulatory elements are more variable than marks at proximal regulatory elements. By integrating genotype and metadata, we identified enhancers that have different levels corresponding to differences in genetic variation, gender, smoking, and schizophrenia. Motif searches revealed that many CNON enhancers are bound by neuronal-related transcription factors. Last, we combined 3D epigenomic maps and gene expression profiles to predict enhancer-target gene interactions on a genome-wide scale. This study not only provides a framework for understanding individual epigenetic variation using a primary cell model system but also contributes valuable data resources for epigenomic studies of neuronal epithelium

Late-transition versus smooth H(z)-deformation models for the resolution of the Hubble crisis

Gravitational transitions at low redshifts (zt < 0.1) have been recently proposed as a solution to the Hubble and growth tensions. Such transitions would naturally lead to a transition in the absolute magnitude M of type Ia supernovae (SnIa) at zt (Late M Transitions - LMT) and possibly in the dark energy equation of state parameter w (Late w − M Transitions - LwMT). Here, we compare the quality of fit of this class of models to cosmological data, with the corresponding quality of fit of the cosmological constant model (ΛCDM) and some of the best smooth H(z) deformation models (wCDM, CPL, PEDE). We also perform model selection via the Akaike Information Criterion and the Bayes factor. We use the full CMB temperature anisotropy spectrum data, the baryon acoustic oscillations (BAO) data, the Pantheon SnIa data, the SnIa absolute magnitude M as determined by Cepheid calibrators and the value of the Hubble constant H0 as determined by local SnIa calibrated using Cepheids. We find that smooth H(z) deformation models perform worse than transition models for the following reasons: 1) They have a worse fit to low-z geometric probes (BAO and SnIa data); 2) They favor values of the SnIa absolute magnitude M that are lower as compared to the value Mc obtained with local Cepheid calibrators at z < 0.01; 3) They tend to worsen the Ωm,0−σ8,0 growth tension. We also find that the w−M transition model (LwMT) does not provide a better quality of fit to cosmological data than a pure M transition model (LMT) where w is fixed to the ΛCDM value w = −1 at all redshifts. We conclude that the LMT model has significant statistical advantages over smooth late-time H(z) deformation models in addressing the Hubble crisis

Plan de negocios para implementar una escuela de manejo con simuladores

La implementaci?n de una escuela de manejo cuya ense?anza se imparte principalmente mediante el uso de simuladores, tiene como ventaja que esta forma de aprendizaje radica en que los alumnos podr?n familiarizarse con los veh?culos y experimentar escenarios complejos de conducci?n, sin correr riesgos de accidentes por nerviosismo o imprudencia del conductor o peat?n. Este aprendizaje se complementa con una cantidad reducida de pr?ctica de manejo en veh?culos reales y horas de instrucci?n de la normativa de tr?nsito. Como valor agregado, se integra una moderna aula virtual con videos did?cticos, plataforma web y gesti?n de reservas, y durante las clases se da ?nfasis sobre las consecuencias de conducir ebrios o bajo los efectos de alguna sustancia alucin?gena mediante el uso de unas gafas. Todo ello, a diferencia de una escuela de manejo convencional, donde la metodolog?a empleada expone al aprendiz a posibles accidentes, adem?s de que las escuelas de manejo convencionales presentan como principales deficiencias el impartir instrucci?n sin tener en cuenta la condici?n y los objetivos del usuario, as? como la falta de innovaci?n en sus procesos y deficiente metodolog?a en la ense?anza, lo cual no permite generar confianza suficiente en el alumno para enfrentarse a un escenario real

Epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole for six Candida species as determined by the colorimetric Sensititre YeastOne method

In the absence of clinical breakpoints (CBP), epidemiological cutoff values (ECVs) are useful to separate wild-type (WT) isolates (without mechanisms of resistance) from non-WT isolates (those that can harbor some resistance mechanisms), which is the goal of susceptibility tests. Sensititre YeastOne (SYO) is a widely used method to determine susceptibility of Candida spp. to antifungal agents. The CLSI CBP have been established, but not for the SYO method. The ECVs for four azoles, obtained using MIC distributions determined by the SYO method, were calculated via five methods (three statistical methods and based on the MIC50 and modal MIC). Respectively, the median ECVs (in mg/liter) of the five methods for fluconazole, itraconazole, posaconazole, and voriconazole (in parentheses: the percentage of isolates inhibited by MICs equal to or less than the ECVs; the number of isolates tested) were as follows: 2 (94.4%; 944), 0.5 (96.7%; 942), 0.25 (97.6%; 673), and 0.06 (96.7%; 849) for Candida albicans; 4 (86.1%; 642), 0.5 (99.4%; 642), 0.12 (93.9%; 392), and 0.06 (86.9%; 559) for C. parapsilosis; 8 (94.9%; 175), 1 (93.7%; 175), 2 (93.6%; 125), and 0.25 (90.4%; 167) for C. tropicalis; 128 (98.6%; 212), 4 (95.8%; 212), 4 (96.0%; 173), and 2 (98.5; 205) for C. glabrata; 256 (100%; 53), 1 (98.1%; 53), 1 (100%; 33), and 1 (97.9%; 48) for C. krusei; 4 (89.2%; 93), 0.5 (100%; 93), 0.25 (100%; 33), and 0.06 (87.7%; 73) for C. orthopsilosis. All methods included =94% of isolates and yielded similar ECVs (within 1 dilution). These ECVs would be suitable for monitoring emergence of isolates with reduced susceptibility by using the SYO method