Managing configuration options for build-to-order highly customized products with application to specialty vehicles

Thesis (S.M. in Engineering and Management)--Massachusetts Institute of Technology, Engineering Systems Division, System Design and Management Program, June 2010."May 2010." Cataloged from PDF version of thesis.Includes bibliographical references (p. 134-137).In the past decades there has been a shift in customer expectations that has had a significant effect in the business models of manufacturing companies. Customer requirements have shifted from accepting standardized products to demanding highly customized products that satisfy their specific requirements. To cope with this change companies have quickly increased the variety of products that they offer in the market place. Unfortunately, often this variety is provided without understanding the implications of the added complexity on the different internal processes. This thesis research focuses on analyzing this fundamental conflict that exists in manufacturing and tries to answer the question: Is there a middle way? A compromise that will balance variety and complexity with the need for efficient production processes. A large data set containing more than 27,000 records was obtained from a software product configuration tool in use by a specialty vehicle company. This data was evaluated utilizing several methods including statistical and network analysis. It was observed that option proliferation was common during the vehicle configuration process which had an option approval rate of more than 50%. In addition, options tended not to be shared among vehicles and reused in vehicle designs. Overall there were 6,848 dormant options out of a total of 17,007. This complexity resulted in low and often negative margins for the vehicles manufactured. An option strategy model was created to aid firms in managing complexity. The model was tested using the available data and it was observed that in general improvements in option management were obtained.by Jorge Enrique Amador Gallardo.S.M.in Engineering and Managemen

Polycomb regulation is coupled to cell cycle transition in pluripotent stem cells

When self-renewing pluripotent cells receive a differentiation signal, ongoing cell duplication needs to be coordinated with entry into a differentiation program. Accordingly, transcriptional activation of lineage specifier genes and cell differentiation is confined to the G1 phase of the cell cycle by unknown mechanisms. We found that Polycomb repressive complex 2 (PRC2) subunits are differentially recruited to lineage specifier gene promoters across cell cycle in mouse embryonic stem cells (mESCs). Jarid2 and the catalytic subunit Ezh2 are markedly accumulated at target promoters during S and G2 phases, while the transcriptionally activating subunits EPOP and EloB are enriched during G1 phase. Fluctuations in the recruitment of PRC2 subunits promote changes in RNA synthesis and RNA polymerase II binding that are compromised in Jarid2 −/− mESCs. Overall, we show that differential recruitment of PRC2 subunits across cell cycle enables the establishment of a chromatin state that facilitates the induction of cell differentiation in G1 phase.This study was supported by the Spanish Ministry of Economy and Competitiveness (SAF2013-40891-R and BFU2016-75233-P) and the Andalusian Regional Government (PC-0246-2017). D.L. is a Ramón y Cajal researcher of the Spanish Ministry of Economy and Competitiveness (RYC-2012-10019)

The students of the Degree on Primary Education as voluntary in learning communities

Este trabajo ha sido elaborado por tres alumnas de la Licenciatura de Psicopedagogía bajo la tutela de la profesora que coordina la actividad de innovación docente que se presenta. En él se recoge la valoración de los estudiantes de la experiencia desarrollada en la asignatura Psicología de la Educación del Grado de Educación Primaria. Desde que se constituyeron las primeras Comunidades de Aprendizaje en la provincia de Sevilla (año 2007), la Universidad Hispalense viene facilitando la colaboración de estudiantes como voluntarios/as. Se presenta aquí la valoración de esta experiencia por parte de los voluntarios que durante el curso 2011/2012 han colaborado en las prácticas educativas de éxito que se llevan a cabo en estos centros. Se analizan los cuestionarios cumplimentados por los mismos para valorar la experiencia al finalizarla. Como se verá en los resultados los/as alumnos/as estiman esta actividad como muy positiva y útil de cara a su formación

The molecular clock protein Bmal1 regulates cell differentiation in mouse embryonic stem cells

Mammals optimize their physiology to the light–dark cycle by synchronization of the master circadian clock in the brain with peripheral clocks in the rest of the tissues of the body. Circadian oscillations rely on a negative feedback loop exerted by the molecular clock that is composed by transcriptional activators Bmal1 and Clock, and their negative regulators Period and Cryptochrome. Components of the molecular clock are expressed during early development, but onset of robust circadian oscillations is only detected later during embryogenesis. Here, we have used na¨ıve pluripotent mouse embryonic stem cells (mESCs) to study the role of Bmal1 during early development. We found that, compared to wild-type cells, Bmal12/2 mESCs express higher levels of Nanog protein and altered expression of pluripotencyassociated signalling pathways. Importantly, Bmal12/2 mESCs display deficient multi-lineage cell differentiation capacity during the formation of teratomas and gastrula-like organoids. Overall, we reveal that Bmal1 regulates pluripotent cell differentiation and propose that the molecular clock is an hitherto unrecognized regulator of mammalian development.Ramon y Cajal grant of the Spanish ministry of economy and competitiveness RYC2012-10019Spanish ministry of economy and competitiveness BFU2016-75233-PAndalusian regional government PC-0246-2017Fundacion Progreso y Salud (FPS)Instituto de Salud Carlos III European Union (EU) CPII17/00032 PI17/01574University of Granad

Intervención de enfermería sobre conocimientos de sexualidad en adultos mayores.

La sexualidad es una de las áreas del comportamiento humano más desconocida, especialmente en personas de edad avanzada. Objetivo: Evaluar el efecto de una intervención educativa de enfermería sobre sexualidad en adulto mayor. Método: Se desarrolló un estudio cuasiexperimental de intervención. El universo estuvo conformado por 30 ancianos pertenecientes a la casa de abuelo de Bahía Honda, durante el 2018, se tomó una muestra de 25 ancianos según criterios de exclusión e inclusión. A los mismos se les aplicó una encuesta que recogió las variables del estudio. Una vez realizado el diagnóstico se implementó una intervención educativa, encaminada a resolver las deficiencias encontradas. Siete semanas después se aplicó la encuesta, los datos fueron procesados mediante estadística descriptiva e inferencial. Resultado: Predominó en el 56% de los abuelos estudiados el estado civil viudo, el 68 % de ellos presentó una percepción inadecuada sobre sexualidad, el 60% de estos casos afirman haber recibido poca información sobre el tema, y el 52% tienen pocos conocimientos sobre sexualidad manifestando creencias y actitudes erróneas frente a la misma después de la intervención se modificaron estos conocimientos en un 84%. Conclusiones: Con la intervención diseñada se modificaron los conocimientos considerablemente, la mayoría de los abuelos asumieron su sexualidad, modificando creencias erróneas sobre el tema y manifestando una postura adecuada frente a ella, mejorando su calidad de vida. Por lo que una vez más, se hace necesario diseñar intervenciones para complementar la sexualidad en el adulto mayor

Intervención de enfermería sobre conocimientos de sexualidad en adultos mayores.

La sexualidad es una de las áreas del comportamiento humano más desconocida, especialmente en personas de edad avanzada. Objetivo: Evaluar el efecto de una intervención educativa de enfermería sobre sexualidad en adulto mayor. Método: Se desarrolló un estudio cuasiexperimental de intervención. El universo estuvo conformado por 30 ancianos pertenecientes a la casa de abuelo de Bahía Honda, durante el 2018, se tomó una muestra de 25 ancianos según criterios de exclusión e inclusión. A los mismos se les aplicó una encuesta que recogió las variables del estudio. Una vez realizado el diagnóstico se implementó una intervención educativa, encaminada a resolver las deficiencias encontradas. Siete semanas después se aplicó la encuesta, los datos fueron procesados mediante estadística descriptiva e inferencial. Resultado: Predominó en el 56% de los abuelos estudiados el estado civil viudo, el 68 % de ellos presentó una percepción inadecuada sobre sexualidad, el 60% de estos casos afirman haber recibido poca información sobre el tema, y el 52% tienen pocos conocimientos sobre sexualidad manifestando creencias y actitudes erróneas frente a la misma después de la intervención se modificaron estos conocimientos en un 84%. Conclusiones: Con la intervención diseñada se modificaron los conocimientos considerablemente, la mayoría de los abuelos asumieron su sexualidad, modificando creencias erróneas sobre el tema y manifestando una postura adecuada frente a ella, mejorando su calidad de vida. Por lo que una vez más, se hace necesario diseñar intervenciones para complementar la sexualidad en el adulto mayor

Changes in PRC1 activity during interphase modulate lineage transition in pluripotent cells

We thank the core facilities at GENYO for excellent technical support. We also thank the genomics unit at the CRG for assistance with RNA-seq and ChIP-seq experiments. The Landeira lab is supported by the Spanish ministry of science and innovation (PID2019-108108-100, EUR2021- 122005), the Andalusian regional government (PIER-0211-2019, PY20_00681) and the University of Granada (A-BIO-6-UGR20) grants. Research in the Klose lab is supported by the Wellcome Trust (209400/ Z/17/Z) and the European Research Council (681440). A.F. was sup- ported by a Sir Henry Wellcome Post-doctoral fellowship (110286/Z/15/ Z). Work in the Rada-Iglesias lab is funded by the Ministerio de Ciencia e Innovación, the Agencia Española de Investigación and the European Regional Development Fund (PGC2018-095301-B-I00 and RED2018- 102553-T); by the European Research Council (862022); and by the European Commission (H2020-MSCA-ITN-2019-860002).The online version contains supplementary material available at https://doi.org/10.1038/s41467-023-35859-9The potential of pluripotent cells to respond to developmental cues and trigger cell differentiation is enhanced during the G1 phase of the cell cycle, but the molecular mechanisms involved are poorly understood. Variations in polycomb activity during interphase progression have been hypothesized to regulate the cell-cycle-phase-dependent transcriptional activation of differentiation genes during lineage transition in pluripotent cells. Here, we show that recruitment of Polycomb Repressive Complex 1 (PRC1) and associated molecular functions, ubiquitination of H2AK119 and three-dimensional chromatin interactions, are enhanced during S and G2 phases compared to the G1 phase. In agreement with the accumulation of PRC1 at target promoters upon G1 phase exit, cells in S and G2 phases show firmer transcriptional repression of developmental regulator genes that is drastically perturbed upon genetic ablation of the PRC1 catalytic subunit RING1B. Importantly, depletion of RING1B during retinoic acid stimu- lation interferes with the preference of mouse embryonic stem cells (mESCs) to induce the transcriptional activation of differentiation genes in G1 phase. We propose that incremental enrolment of polycomb repressive activity during interphase progression reduces the tendency of cells to respond to develop- mental cues during S and G2 phases, facilitating activation of cell differentiation in the G1 phase of the pluripotent cell cycle.Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2019-108108-100, EUR2021-122005Andalusian regional government PIER-0211-2019, PY20_00681University of Granada A-BIO-6-UGR20Wellcome Trust 209400/Z/17/ZEuropean Research Council (ERC) European Commission 862022Wellcome Trust PGC2018-095301-B-I00Ministry of Science and Innovation, Spain (MICINN) Instituto de Salud Carlos III Spanish GovernmentEuropean Commission RED2018-102553-T, H2020-MSCA-ITN-2019-860002European Commission European Commission Joint Research Centre 681440Agencia Española de Investigación110286/Z/15/

Changes in PRC1 activity during interphase modulate lineage transition in pluripotent cells

The potential of pluripotent cells to respond to developmental cues and trigger cell differentiation is enhanced during the G1 phase of the cell cycle, but the molecular mechanisms involved are poorly understood. Variations in polycomb activity during interphase progression have been hypothesized to regulate the cell-cycle-phase-dependent transcriptional activation of differentiation genes during lineage transition in pluripotent cells. Here, we show that recruitment of Polycomb Repressive Complex 1 (PRC1) and associated molecular functions, ubiquitination of H2AK119 and three-dimensional chromatin interactions, are enhanced during S and G2 phases compared to the G1 phase. In agreement with the accumulation of PRC1 at target promoters upon G1 phase exit, cells in S and G2 phases show firmer transcriptional repression of developmental regulator genes that is drastically perturbed upon genetic ablation of the PRC1 catalytic subunit RING1B. Importantly, depletion of RING1B during retinoic acid stimulation interferes with the preference of mouse embryonic stem cells (mESCs) to induce the transcriptional activation of differentiation genes in G1 phase. We propose that incremental enrolment of polycomb repressive activity during interphase progression reduces the tendency of cells to respond to developmental cues during S and G2 phases, facilitating activation of cell differentiation in the G1 phase of the pluripotent cell cycle

EZH2 endorses cell plasticity to non-small cell lung cancer cells facilitating mesenchymal to epithelial transition and tumour colonization

CGL was funded by the Consejería de Salud y Familias, Junta de Andalucía (RH-0139-2020) and SG-P is funded by Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533). JAM is supported by RTI2018.101309B-C22 funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” and by the Chair “Doctors Galera-Requena in cancer stem cell research”. PCS is funded by Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00) and FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20). The Landeira lab is supported by the Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005), the Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681) and the University of Granada (A-BIO-6-UGR20) grants.Reversible transition between the epithelial and mesenchymal states are key aspects of carcinoma cell dissemination and the metastatic disease, and thus, characterizing the molecular basis of the epithelial to mesenchymal transition (EMT) is crucial to find druggable targets and more effective therapeutic approaches in cancer. Emerging studies suggest that epigenetic regulators might endorse cancer cells with the cell plasticity required to conduct dynamic changes in cell state during EMT. However, epigenetic mechanisms involved remain mostly unknown. Polycomb Repressive Complexes (PRCs) proteins are well-established epigenetic regulators of development and stem cell differentiation, but their role in different cancer systems is inconsistent and sometimes paradoxical. In this study, we have analysed the role of the PRC2 protein EZH2 in lung carcinoma cells. We found that besides its described role in CDKN2A-dependent cell proliferation, EZH2 upholds the epithelial state of cancer cells by repressing the transcription of hundreds of mesenchymal genes. Chemical inhibition or genetic removal of EZH2 promotes the residence of cancer cells in the mesenchymal state during reversible epithelial–mesenchymal transition. In fitting, analysis of human patient samples and tumour xenograft models indicate that EZH2 is required to efficiently repress mesenchymal genes and facilitate tumour colonization in vivo. Overall, this study discloses a novel role of PRC2 as a master regulator of EMT in carcinoma cells. This finding has important implications for the design of therapies based on EZH2 inhibitors in human cancer patients.Junta de Andalucía (RH-0139-2020)Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533)MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” RTI2018.101309B-C22Chair “Doctors Galera-Requena in cancer stem cell research”Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00)FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20)Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005)Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681)University of Granada (A-BIO-6-UGR20