La simplificación administrativa y la satisfacción de los clientes como factor de eficiencia y eficacia empresarial en la Municipalidad de Lima Metropolitana 2019

Esta investigación tiene como objetivo estudiar el cumplimiento de la simplificación administrativa que afecta a los usuarios de la Municipalidad de Lima, razón por la que los gobiernos locales no aplican procesos de simplificación administrativa para beneficiar a la ciudadanía. Diseño de investigación no experimental, transversal e investigación correlacional –cualitativo. El estudio de la población está conformado por clientes de la municipalidad, en este caso los ciudadanos que realizan diligencias en la municipalidad de Lima. Población 40 y Muestra 36 personas, instrumento de encuesta Likert. La tabulación y el procesamiento de datos se hicieron en SPSS Statistics. Los resultados indican que el 60% [de la muestra de clientes] del distrito de Lima está[n] insatisfecho[s] por el servicio brindado por la demora, poca claridad y desconfianza que trasmiten al momento de cualquier gestión demandada, también el bajo desempeño del personal perjudicando el cumplimiento de sus actividades.Campus Lima Centr

Análisis, evaluación, propuesta de mejora e implementacion en el flujo del proceso de VAS para un operador logístico

La presente tesis tiene como objetivo elevar la eficiencia y disminuir los tiempos de atención de pedidos del proceso de VAS (Valor Agregado al Servicio) del operador logístico en estudio, mediante la optimización del flujo logístico de los productos en las estaciones o zonas de trabajo, sin dejar de agregar valor a las actividades, se busca obtener mayor productividad en el desempeño del personal y operación logística. El método usado tiene alcance desde la recepción del pedido del CLIENTE hasta el despacho de los productos a los clientes finales. Primero se elaboró el diagnóstico de la situación actual del proceso, luego se determinó los Clientes con mayor participación en las operaciones de VAS mediante la ponderación de los criterios: frecuencia de pedidos, demanda de unidades y participación en la venta. Se realizó una clasificación de pareto, para luego realizar la ponderación y definir los principales Clientes que generarán mayor impacto. Se describen y se presentan las actividades de la operación de VAS mediante herramientas de análisis de procesos para cada Cliente. Se identifican y se clasifican aquellas actividades que “Agregan valor” y “No agregan valor y no son necesarias” con el fin de obtener hallazgos operativos para concretar el problema y su causa-raíz. El diagnostico evidenció que el proceso presentaba mudas, principalmente en esperas y traslados, de este modo las causas se convirtieron en oportunidades de mejora, del conjunto se realizó un análisis de criticidad y factibilidad con el objetivo de seleccionar aquellas que sean fáciles de implementar y que generen mayor impacto positivo. De las 19 propuestas de mejora se eligieron nueve que permitirán reducir tiempos y costos de operación. Por tanto, se optimizó el tiempo invertido en las actividades que “Agregan valor” y disminuir o eliminar aquellas actividades que “No agregan valor”. También se mejoró la distribución de Layout del proceso. La implementación y ejecución de la propuesta de mejora, estima disminuir los traslados en un 85.25%, reducir el tiempo de operación en un 41.44%, y elevar la eficiencia en un 37.15 % en promedio. A su vez el costo de operación se reduciría en un 26.42% anual.Tesi

Circular RNA CpG island hypermethylation-associated silencing in human cancer

Noncoding RNAs (ncRNAs), such as microRNAs and long noncoding RNAs (lncRNAs), participate in cellular transformation. Work done in the last decade has also demonstrated that ncRNAs with growth-inhibitory functions can undergo promoter CpG island hypermethylation-associated silencing in tumorigenesis. Herein, we wondered whether circular RNAs (circRNAs), a type of RNA transcripts lacking 5′-3′ ends and forming closed loops that are gaining relevance in cancer biology, are also a target of epigenetic inactivation in tumors. To tackle this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in conjuction with circRNA expression microarrays. We have found that the loss of DNA methylation provokes a release of circRNA silencing. In particular, we have identified that promoter CpG island hypermethylation of the genes TUSC3 (tumor suppressor candidate 3), POMT1 (protein O-mannosyltransferase 1), ATRNL1 (attractin-like 1) and SAMD4A (sterile alpha motif domain containing 4A) is linked to the transcriptional downregulation of both linear mRNA and the hosted circRNA. Although some circRNAs regulate the linear transcript, we did not observe changes in TUSC3 mRNA levels upon TUSC3 circ104557 overexpression. Interestingly, we found circRNA-mediated regulation of target miRNAs and an in vivo growth inhibitory effect upon TUSC3 circ104557 transduction. Data mining for 5′-end CpG island methylation of TUSC3, ATRNL1, POMT1 and SAMD4A in cancer cell lines and primary tumors showed that the epigenetic defect was commonly observed among different tumor types in association with the diminished expression of the corresponding transcript. Our findings support a role for circRNA DNA methylation-associated loss in human cancer

Gene Amplification-Associated Overexpression of the Selenoprotein tRNA Enzyme TRIT1 Confers Sensitivity to Arsenic Trioxide in Small-Cell Lung Cancer

The alteration of RNA modification patterns is emerging as a common feature of human malignancies. If these changes affect key RNA molecules for mRNA translation, such as transfer RNA, they can have important consequences for cell transformation. TRIT1 is the enzyme responsible for the hypermodification of adenosine 37 in the anticodon region of human tRNAs containing serine and selenocysteine. Herein, we show that TRIT1 undergoes gene amplification-associated overexpression in cancer cell lines and primary samples of small-cell lung cancer. From growth and functional standpoints, the induced depletion of TRIT1 expression in amplified cells reduces their tumorigenic potential and downregulates the selenoprotein transcripts. We observed that TRIT1-amplified cells are sensitive to arsenic trioxide, a compound that regulates selenoproteins, whereas reduction of TRIT1 levels confers loss of sensitivity to the drug. Overall, our results indicate a role for TRIT1 as a small-cell lung cancer-relevant gene that, when undergoing gene amplification-associated activation, can be targeted with the differentiation agent arsenic trioxide

Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer

Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNA5 (mRNA5). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology

The Breast Cancer Oncogene EMSY Represses Transcription of Antimetastatic microRNA miR-31.

Amplification of the EMSY gene in sporadic breast and ovarian cancers is a poor prognostic indicator. Although EMSY has been linked to transcriptional silencing, its mechanism of action is unknown. Here, we report that EMSY acts as an oncogene, causing the transformation of cells in vitro and potentiating tumor formation and metastatic features in vivo. We identify an inverse correlation between EMSY amplification and miR-31 expression, an antimetastatic microRNA, in the METABRIC cohort of human breast samples. Re-expression of miR-31 profoundly reduced cell migration, invasion, and colony-formation abilities of cells overexpressing EMSY or haboring EMSY amplification. We show that EMSY is recruited to the miR-31 promoter by the DNA binding factor ETS-1, and it represses miR-31 transcription by delivering the H3K4me3 demethylase JARID1b/PLU-1/KDM5B. Altogether, these results suggest a pathway underlying the role of EMSY in breast cancer and uncover potential diagnostic and therapeutic targets in sporadic breast cancer

Estandarización de marcadores moleculares microsatélites para su uso en la industria forestal de misiones, argentina

Título en ingles: Standarization of microsatellite molecular markers for Misiones (Argentina) forest industry Resumen: Provincia de Misiones posee actualmente una actividad forestal en pujante crecimiento ubicándose entre las primeras del país. Este marco de desarrollo productivo permite predecir un ámbito de crecimiento favorecido por las nuevas condiciones del mercado internacional. Por otro lado a pesar del avance de la tecnología industrial, no se ha alcanzado el nivel de desarrollo biotecnológico óptimo que conjugue la calidad genética con características fenotípicas de excelencia en las especies maderables de mayor demanda en la Provincia basándose la selección en criterios netamente fenotípicos y en la experiencia del productor, sin contarse con métodos moleculares desarrollados en la región. Este trabajo presenta los resultados del Proyecto Federal de Innovación Productiva (PFIP Mi09) cuyo objetivo principal fue estandarizar y transferir al sector productivo un conjunto de marcadores moleculares microsatélites para ser aplicado al análisis de poblaciones y forestaciones de Araucaria angustifolia y Pinus taeda provenientes de la Provincia de Misiones (Argentina). Esto permitirá conocer el perfil genético de plantaciones y poblaciones de estas especies forestales, pudiendo aplicarse a la certificación de calidad en la producción forestal o a la selección de ejemplares de especies nativas. Palabras clave: biotecnología; forestaciones; Araucaria angustifolia; Pinus taeda; microsatélites. Abstract: Misiones Province currently has the first intensive forestry activity of Argentine. This framework of productive development allows predict an area of growth favored by the new conditions of the international market. On the other side despite the progress of industrial technology, has not been reached the optimal level of biotechnological development that combining quality with genomic and phenotypic characteristics of forest species. This work presents the results of Federal Project of Productive Innovation (PFIP Mi09) whose main objective was standardize and transfer to the productive sector a set of microsatellites molecular markers to be applied to the populations analysis of Araucaria angustifolia and Pinus taeda forestation from the Misiones (Argentine). This will reveal the plantations and forest genetic profile and may be applied to genetic certification of forest production quality. Key words: technology; forestry; Araucaria angustifolia; Pinus taeda; microsatellit

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

Epigenetic Profiling and Response to CD19 Chimeric Antigen Receptor T-Cell Therapy in B-Cell Malignancies

Background: Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance of epigenetic changes in cancer immunology prompted us to determine the impact of the DNA methylation profiles of CART19 cells on the clinical course. Methods: We recruited 114 patients with B-cell malignancies, comprising 77 patients with acute lymphoblastic leukemia and 37 patients with non-Hodgkin lymphoma who were treated with CART19 cells. Using a comprehensive DNA methylation microarray, we determined the epigenomic changes that occur in the patient T cells upon transduction of the CAR vector. The effects of the identified DNA methylation sites on clinical response, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, event-free survival, and overall survival were assessed. All statistical tests were 2-sided. Results: We identified 984 genomic sites with differential DNA methylation between CAR-untransduced and CAR-transduced T cells before infusion into the patient. Eighteen of these distinct epigenetic loci were associated with complete response (CR), adjusting by multiple testing. Using the sites linked to CR, an epigenetic signature, referred to hereafter as the EPICART signature, was established in the initial discovery cohort (n = 79), which was associated with CR (Fisher exact test, P < .001) and enhanced event-free survival (hazard ratio [HR] = 0.36; 95% confidence interval [CI] = 0.19 to 0.70; P = .002; log-rank P = .003) and overall survival (HR = 0.45; 95% CI = 0.20 to 0.99; P = .047; log-rank P = .04;). Most important, the EPICART profile maintained its clinical course predictive value in the validation cohort (n = 35), where it was associated with CR (Fisher exact test, P < .001) and enhanced overall survival (HR = 0.31; 95% CI = 0.11 to 0.84; P = .02; log-rank P = .02). Conclusions: We show that the DNA methylation landscape of patient CART19 cells influences the efficacy of the cellular immunotherapy treatment in patients with B-cell malignancy.Supported by CERCA Programme/Generalitat de Catalunya, Health Department PERIS #SLT/002/16/00374, AGAUR-project #2017SGR1080; MCI/AEI/ERDF project #RTI2018-094049-B-I00; ERC EPIPHARM; Cellex Foundation; “la Caixa” Foundation (LCF/PR/GN18/51140001 and LCF/PR/GN18/50310007), RF-2016–02364388, Accelerator Award—Cancer Research UK/AIRC—INCAR Associazione Italiana Ricerca per la Ricerca sul Cancro (AIRC) Project 5 × 1000 no. 9962, AIRC IG 2018 id. 21724, AIRC MFAG id. 21769 and id. 20450; MIUR (Grant PRIN 2017); and RCR-2019–23669115