An application of lean principles within a semiconductor manufacturing environment

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering; in conjunction with the Leaders for Manufacturing Program at MIT, 2005.Includes bibliographical references (p. 65-66).Intel Corporation's Fab 23 is committed to implementing lean manufacturing to reduce their production cycle times and cost. This thesis is focused around the development of the principles of lean that are most relevant to Intel's complex manufacturing flow and then the application of these principles to improve the operations in a focused area, the Sorting floor. Direct examination of the work in Sort raises the awareness of inefficiencies from overproduction and inventory; viewing this work as a series of structured activities, customer-supplier connections, and simplified flows further crystallizes the need for a structured approach towards WIP management. A pilot implementation of a CONWIP control of inventory demonstrates reductions in cycle time variability and provides a foundation for further improvements. In conclusion, the challenges experienced with changing the manufacturing systems in Sort were largely organizational and likely to be seen in many other operational areas at Fab 23.by Roy C. Wildeman, Jr.S.M.M.B.A

NK Cells in HIV-1 Infection: From Basic Science to Vaccine Strategies

NK cells play a key role in immune response against HIV infection. These cells can destroy infected cells and contribute to adequate and strong adaptive immune responses, by acting on dendritic, T, B, and even epithelial cells. Increased NK cell activity reflected by higher cytotoxic capacity, IFN-γ and chemokines (CCL3, CCL4, and CCL5) production, has been associated with resistance to HIV infection and delayed AIDS progression, demonstrating the importance of these cells in the antiviral response. Recently, a subpopulation of NK cells with adaptive characteristics has been described and associated with lower HIV viremia and control of infection. These evidences, together with some degree of protection shown in vaccine trials based on boosting NK cell activity, suggest that these cells can be a feasible option for new treatment and vaccination strategies to overcome limitations that, classical vaccination approaches, might have for this virus. This review is focus on the NK cells role during the immune response against HIV, including all the effector mechanisms associated to these cells; in addition, changes including phenotypic, functional and frequency modifications during HIV infection will be pointed, highlighting opportunities to vaccine development based in NK cells effector functions

Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

A specific structure and high richness characterize intestinal microbiota of HIVexposed seronegative individuals

Intestinal microbiota facilitates food breakdown for energy metabolism and influences the im-mune response and maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, to date, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha and beta diversity compared to HC, but similar to HIV+. A lower Treg percentage was observed in HESN than HC and HIV+, with enrichment of the genus Butyrivibrio being characteristic of this profile. Interestingly, an increase in Succinivibrio and Prevotella and a re-duction in Bacteroides genus were observed in HESN compared to HC, which is typical of HIV-infected individuals. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.Intestinal microbiota facilitates food breakdown for energy metabolism and influences the im-mune response and maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, to date, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha and beta diversity compared to HC, but similar to HIV+. A lower Treg percentage was observed in HESN than HC and HIV+, with enrichment of the genus Butyrivibrio being characteristic of this profile. Interestingly, an increase in Succinivibrio and Prevotella and a re-duction in Bacteroides genus were observed in HESN compared to HC, which is typical of HIV-infected individuals. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.https://scienti.minciencias.gov.co/cvlac/EnProdArticulo/query.do?cod_producto=73&cod_rh=0000157775https://scholar.google.com.co/citations?hl=en&user=VLZxl1UAAAAJCOL0112548https://orcid.org/0000-0002-7351-873

Approximation algorithms and hardness results for the joint replenishment Problepm with constant demands

19th Annual European Symposium, Saarbrücken, Germany, September 5-9, 2011. ProceedingsIn the Joint Replenishment Problem (JRP), the goal is to coordinate the replenishments of a collection of goods over time so that continuous demands are satisfied with minimum overall ordering and holding costs. We consider the case when demand rates are constant. Our main contribution is the first hardness result for any variant of JRP with constant demands. When replenishments per commodity are required to be periodic and the time horizon is infinite (which corresponds to the so-called general integer model with correction factor), we show that finding an optimal replenishment policy is at least as hard as integer factorization. This result provides the first theoretical evidence that the JRP with constant demands may have no polynomial-time algorithm and that relaxations and heuristics are called for. We then show that a simple modification of an algorithm by Wildeman et al. (1997) for the JRP gives a fully polynomial-time approximation scheme for the general integer model (without correction factor). We also extend their algorithm to the finite horizon case, achieving an approximation guarantee asymptotically equal to √9/8

Large-Scale Modeling of Epileptic Seizures: Scaling Properties of Two Parallel Neuronal Network Simulation Algorithms

Our limited understanding of the relationship between the behavior of individual neurons and large neuronal networks is an important limitation in current epilepsy research and may be one of the main causes of our inadequate ability to treat it. Addressing this problem directly via experiments is impossibly complex; thus, we have been developing and studying medium-large-scale simulations of detailed neuronal networks to guide us. Flexibility in the connection schemas and a complete description of the cortical tissue seem necessary for this purpose. In this paper we examine some of the basic issues encountered in these multiscale simulations. We have determined the detailed behavior of two such simulators on parallel computer systems. The observed memory and computation-time scaling behavior for a distributed memory implementation were very good over the range studied, both in terms of network sizes (2,000 to 400,000 neurons) and processor pool sizes (1 to 256 processors). Our simulations required between a few megabytes and about 150 gigabytes of RAM and lasted between a few minutes and about a week, well within the capability of most multinode clusters. Therefore, simulations of epileptic seizures on networks with millions of cells should be feasible on current supercomputers

Can an online clinical data management service help in improving data collection and data quality in a developing country setting?

Background: Data collection by Electronic Medical Record (EMR) systems have been proven to be helpful in data collection for scientific research and in improving healthcare. For a multi-centre trial in Indonesia and the Netherlands a web based system was selected to enable all participating centres to easily access data. This study assesses whether the introduction of a Clinical Trial Data Management service (CTDMS) composed of electronic Case Report Forms (eCRF) can result in effective data collection and treatment monitoring. Methods: Data items entered were checked for inconsistencies automatically when submitted online. The data were divided into primary and secondary data items. We analysed both the total number of errors and the change in error rate, for both Primary and Secondary items, over the first five month of the trial. Results: In the first five months 51 patients were entered. The Primary data error rate was 1.6%, whilst that for Secondary data was 2.7% against acceptable error rates for analysis of 1% and 2.5% respectively. Conclusion: The presented analysis shows that after five months since the introduction of the CTDMS the Primary and Secondary data error rates reflect acceptable levels of data quality. Furthermore, these error rates were decreasing over time. The digital nature of the CTDMS, as well as the online availability of that data, gives fast and easy insight in adherence to treatment protocols. As such, the CTDMS can serve as a tool to train and educate medical doctors and can improve treatment protocols.Maarten A Wildeman, Jeroen Zandbergen, Andrew Vincent, Camelia Herdini, Jaap M Middeldorp, Renske Fles, Otilia Dalesio, Emile van der Donk, I Bing Ta

Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2

Introduction: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARSCoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited.Objective: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection.Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay.Results: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin.Conclusion: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells couldbe associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección.Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2.Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa.Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia.Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia