Tuberculosis interferon-gamma responses in the breast milk of human immunodeficiency virus infected mothers

Tuberculosis (TB) cellular immune responses were examined in breastmilk of HIV-infected mothers using the T-SPOT.TB interferon gamma release assay (IGRA). Positive TB IFN-γ responses were detected in 6 of 8 (75%) valid breast milk assays. Among 7 mothers with paired breastmilk and blood assays, TB IFN- γ responses were higher in breastmilk compared to blood (p=.02). The magnitude of TB IFN-γ responses in maternal breastmilk and blood were correlated. Elucidating the influence of breastmilk TB immune responses on infant TB susceptibility and immunity may inform future maternal TB vaccine strategies

Implementación de herramientas de mejora continua en el área de almacén para incrementar la rentabilidad en la empresa comercial Maquinarias Industriales Hiroki S. A. C. - 2021

El Presente trabajo presenta la implementación de herramientas de mejora continua en el área de almacén de la empresa Hiroki teniendo como objetivo aumentar la rentabilidad de esta. Para ello se hizo un diagnóstico de la empresa usando el diagrama de Ishikawa, Pareto y una matriz de indicadores. Los problemas encontrados generaron un costo a la empresa de S/. 5 190 y se planteó las siguientes herramientas de mejora: el kardex, codificación de productos, la metodología 5’s, Layout, plan de capacitación y plan de incentivos. Los indicadores evaluados en la empresa fueron los siguientes: % de productos inventariados, % de productos codificados, % de productos almacenados correctamente, % de área limpia y ordenada, % de producto ubicado correctamente, % de personal capacitado e índice de satisfacción de empleados. Obteniendo valores iniciales de 0%, 0%, 19.9%, 9.5%, 0%, 0% y 3.81 respectivamente. Se realizó la implementación del kardex, codificación de productos, la metodología 5S, Layout, plan de capacitación y plan de incentivos durante el periodo de enero y febrero del 2021, logrando mejorar los indicadores a 100%, 100%, 100%, 90% 100%, 100% y 4.25 respectivamente. Para ver la influencia de la aplicación de las herramientas en la rentabilidad de la empresa, se utilizaron los indicadores del Roe y Roa, inicialmente estos tenían los valores de 2.8% y 1.06% respectivamente; luego de la implementación los valores obtenidos fueron de 2% y 0.75%. Estos resultados no mostraron un incremento porque la evaluación se realizó durante el periodo de implementación. El beneficio que generó el trabajo fue la reducción de los costos de S/. 5 190 a S/.0

VirK Is a Periplasmic Protein Required for Efficient Secretion of Plasmid-Encoded Toxin from Enteroaggregative Escherichia coli

Despite the autotransporter (AT) moniker, AT secretion appears to involve the function of periplasmic chaperones. We identified four periplasmic proteins that specifically bound to plasmid-encoded toxin (Pet), an AT produced by enteroaggregative Escherichia coli (EAEC). These proteins include the 17-kDa Skp chaperone and the 37-kDa VirK protein. We found that the virK gene is present in different Enterobacteriaceae. VirK bound to misfolded conformations of the Pet passenger domain, but it did not bind to the folded passenger domain or to the beta domain of Pet. Assays with an EAEC Delta virK mutant and its complemented version showed that, in the absence of VirK, Pet was not secreted but was instead retained in the periplasm as proteolytic fragments. In contrast, Pet was secreted from a Delta skp mutant. VirK was not required for the insertion of porin proteins into the outer membrane but assisted with insertion of the Pet beta domain into the outer membrane. Loss of VirK function blocked the EAEC-mediated cytotoxic effect against HEp-2 cells. Thus, VirK facilitates the secretion of the AT Pet by maintaining the passenger domain in a conformation that both avoids periplasmic proteolysis and facilitates beta-domain insertion into the outer membrane

Oxidative Phosphorylation Is a Metabolic Vulnerability in Chemotherapy-Resistant Triple-Negative Breast Cance

Oxidative phosphorylation (OXPHOS) is an active metabolic pathway in many cancers. RNA from pretreatment biopsies from patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy demonstrated that the top canonical pathway associated with worse outcome was higher expression of OXPHOS signature. IACS-10759, a novel inhibitor of OXPHOS, stabilized growth in multiple TNBC patient-derived xenografts (PDX). On gene expression profiling, all of the sensitive models displayed a basal-like 1 TNBC subtype. Expression of mitochondrial genes was significantly higher in sensitive PDXs. An in vivo functional genomics screen to identify synthetic lethal targets in tumors treated with IACS-10759 found several potential targets, including CDK4. We validated the antitumor efficacy of the combination of palbociclib, a CDK4/6 inhibitor, and IACS-10759 in vitro and in vivo. In addition, the combination of IACS-10759 and multikinase inhibitor cabozantinib had improved antitumor efficacy. Taken together, our data suggest that OXPHOS is a metabolic vulnerability in TNBC that may be leveraged with novel therapeutics in combination regimens. SIGNIFICANCE: These findings suggest that triple-negative breast cancer is highly reliant on OXPHOS and that inhibiting OXPHOS may be a novel approach to enhance efficacy of several targeted therapies

Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping

To facilitate fine-scale phenotyping of whole specimens, we describe here a set of tissue fixation-embedding, detergent-clearing and staining protocols that can be used to transform excised organs and whole organisms into optically transparent samples within 1–2 weeks without compromising their cellular architecture or endogenous fluorescence. PACT (passive CLARITY technique) and PARS (perfusion-assisted agent release in situ) use tissue-hydrogel hybrids to stabilize tissue biomolecules during selective lipid extraction, resulting in enhanced clearing efficiency and sample integrity. Furthermore, the macromolecule permeability of PACT- and PARS-processed tissue hybrids supports the diffusion of immunolabels throughout intact tissue, whereas RIMS (refractive index matching solution) grants high-resolution imaging at depth by further reducing light scattering in cleared and uncleared samples alike. These methods are adaptable to difficult-to-image tissues, such as bone (PACT-deCAL), and to magnified single-cell visualization (ePACT). Together, these protocols and solutions enable phenotyping of subcellular components and tracing cellular connectivity in intact biological networks

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe