Investigating Flexibility as a Performance Dimension of a Manufacturing Value Modeling Methodology (MVMM): A Framework for Identifying Flexibility Types in Manufacturing Systems☆

Abstract In recent years manufacturing companies have been faced with various challenges related to volatile demand and changing requirements from customer as well as suppliers. This trend is now even accelerating with a direct impact on the value chain. New technological roadmaps and suggested interventions in manufacturing systems try to solve these challenges and solutions such as the German high tech strategy "Industrie 4.0" or the Italian cluster "Fabbrica Intelligente" which often aimed at enhancing the flexibility of manufacturing systems among many other competitive dimensions. However, these approaches often do not provide a detailed definition of flexibility and its different manifestations. Therefore, the question rises if different types of flexibility, that have an impact on the complete manufacturing system, can be better identified with the existing Manufacturing Value Modeling Methodology (MVMM). This question becomes even more important when considering the potential that smart machines interacting with humans, such as cyber-physical systems (CPS), and the possibility to increase connectivity and data access through technologies, such as the internet of things (IoT), offer for increasing flexibility. Especially due to the various possibilities it becomes even more important to understand, which kind of flexibility is needed for a given problem. Implementing flexibility into the MVMM requires a 'catalog' that makes use of the MVMM framework presenting an overview of internal and external influence factors in order to support the identification of correct solutions and improvements related to functional areas in the manufacturing environment. Starting from a qualitative literature review on manufacturing flexibility, a 'flexibility catalog' is designed, which provides a structural definition of existing flexibility types and their composition as well as providing decision support. In conclusion, the scope of the 'flexibility catalog' is to verify that the flexibility demand fits into the market trends and is aligned to the manufacturing and company strategy, in order to help firms to take decisions and delivering value

Standardization and performance evaluation of mononuclear cell cytokine secretion assays in a multicenter study

BACKGROUND: Cryopreservation of peripheral blood mononuclear cells has been used to preserve and standardize immunologic measurements for multicenter studies, however, effects of cryopreservation on cytokine responses are incompletely understood. In designing immunologic studies for a new multicenter birth cohort study of childhood asthma, we performed a series of experiments to determine the effects of two different methods of cryopreservation on the cytokine responses of cord and peripheral blood mononuclear cells. RESULTS: Paired samples of PBMC were processed freshly, or after cryopreservation in a Nalgene container (NC) or a controlled-rate freezer (CRF). Although there were some differences between the methods, cryopreservation inhibited PHA-induced IL-10 secretion and Der f 1-induced IL-2 secretion, and augmented PHA-induced IL-2 secretion and spontaneous secretion of TNF-α. In separate experiments, NC cryopreservation inhibited secretion of several cytokines (IL-13, IL-10, IFN-γ, TNF-α) by PHA-stimulated cord blood mononuclear cells. With the exception of PHA-induced IL-13, results from fresh and cryopreserved cord blood samples were not significantly correlated. Finally, in reproducibility studies involving processing of identical cell samples in up to 4 separate laboratories, variances in cytokine responses of fresh cells stimulated at separate sites did not exceed those in cryopreserved cells stimulated at a central site. CONCLUSION: Collectively, these studies indicate that cryopreservation can affect mononuclear cell cytokine response profiles, and that IL-10 secretion and antigen-induced responses may be especially vulnerable. These studies also demonstrate that mononuclear cell responses can be standardized for performance in a small number of laboratories for multicenter studies, and underscore the importance of measuring reproducibility and of testing whether cryopreservation techniques alter specific immunologic outcomes

Cosmopolitan Species As Models for Ecophysiological Responses to Global Change: The Common Reed \u3cem\u3ePhragmites australis\u3c/em\u3e

Phragmites australis is a cosmopolitan grass and often the dominant species in the ecosystems it inhabits. Due to high intraspecific diversity and phenotypic plasticity, P. australis has an extensive ecological amplitude and a great capacity to acclimate to adverse environmental conditions; it can therefore offer valuable insights into plant responses to global change. Here we review the ecology and ecophysiology of prominent P. australis lineages and their responses to multiple forms of global change. Key findings of our review are that: (1) P. australis lineages are well-adapted to regions of their phylogeographic origin and therefore respond differently to changes in climatic conditions such as temperature or atmospheric CO2; (2) each lineage consists of populations that may occur in geographically different habitats and contain multiple genotypes; (3) the phenotypic plasticity of functional and fitness-related traits of a genotype determine the responses to global change factors; (4) genotypes with high plasticity to environmental drivers may acclimate or even vastly expand their ranges, genotypes of medium plasticity must acclimate or experience range-shifts, and those with low plasticity may face local extinction; (5) responses to ancillary types of global change, like shifting levels of soil salinity, flooding, and drought, are not consistent within lineages and depend on adaptation of individual genotypes. These patterns suggest that the diverse lineages of P. australis will undergo intense selective pressure in the face of global change such that the distributions and interactions of co-occurring lineages, as well as those of genotypes within-lineages, are very likely to be altered. We propose that the strong latitudinal clines within and between P. australis lineages can be a useful tool for predicting plant responses to climate change in general and present a conceptual framework for using P. australis lineages to predict plant responses to global change and its consequences

Rethinking Sustainability to Meet the Climate Change Challenge

A group of environmental law professors formed the Environmental Law Collaborative with the goal of engaging environmental law scholars in the thorny issues of the day. The members of the Collaborative gathered in the summer of 2012 to produce an intensive and collective assessment of sustainability in the age of climate change. Their writings examine the process of adapting the principles and application of sustainability to the demands of climate change, including framing the term sustainability in climate change discussions; coordinating sustainable practices across disciplines such as law, economics, ethics, and the hard sciences; and conceptualizing the role of sustainability in formulating adaptation and resiliency strategies. Their work also contemplates the role of law and legal systems in crafting effective climate change adaptation strategies and considers feasible strategies in the context of specific examples

A multi-decade record of high quality fCO2 data in version 3 of the Surface Ocean CO2 Atlas (SOCAT)

The Surface Ocean CO2 Atlas (SOCAT) is a synthesis of quality-controlled fCO2 (fugacity of carbon dioxide) values for the global surface oceans and coastal seas with regular updates. Version 3 of SOCAT has 14.7 million fCO2 values from 3646 data sets covering the years 1957 to 2014. This latest version has an additional 4.6 million fCO2 values relative to version 2 and extends the record from 2011 to 2014. Version 3 also significantly increases the data availability for 2005 to 2013. SOCAT has an average of approximately 1.2 million surface water fCO2 values per year for the years 2006 to 2012. Quality and documentation of the data has improved. A new feature is the data set quality control (QC) flag of E for data from alternative sensors and platforms. The accuracy of surface water fCO2 has been defined for all data set QC flags. Automated range checking has been carried out for all data sets during their upload into SOCAT. The upgrade of the interactive Data Set Viewer (previously known as the Cruise Data Viewer) allows better interrogation of the SOCAT data collection and rapid creation of high-quality figures for scientific presentations. Automated data upload has been launched for version 4 and will enable more frequent SOCAT releases in the future. High-profile scientific applications of SOCAT include quantification of the ocean sink for atmospheric carbon dioxide and its long-term variation, detection of ocean acidification, as well as evaluation of coupled-climate and ocean-only biogeochemical models. Users of SOCAT data products are urged to acknowledge the contribution of data providers, as stated in the SOCAT Fair Data Use Statement. This ESSD (Earth System Science Data) “living data” publication documents the methods and data sets used for the assembly of this new version of the SOCAT data collection and compares these with those used for earlier versions of the data collection (Pfeil et al., 2013; Sabine et al., 2013; Bakker et al., 2014). Individual data set files, included in the synthesis product, can be downloaded here: doi:10.1594/PANGAEA.849770. The gridded products are available here: doi:10.3334/CDIAC/OTG.SOCAT_V3_GRID

Nomogram for Predicting Individual Survival After Recurrence of Advanced-Stage, High-Grade Ovarian Carcinoma.

ObjectiveTo analyze clinical prognostic factors for survival after recurrence of high-grade, advanced-stage ovarian-peritoneal-tubal carcinoma and to develop a nomogram to predict individual survival after recurrence.MethodsWe retrospectively analyzed patients treated in multicenter Gynecologic Oncology Group protocols for stage III and IV ovarian-peritoneal-tubal carcinoma who underwent primary debulking surgery, received chemotherapy with paclitaxel and a platinum compound, and subsequently developed recurrence. Prognostic factors affecting survival were identified and used to develop a nomogram, which was both internally and externally validated.ResultsThere were 4,739 patients included in this analysis, of whom, 84% had stage III and 16% had stage IV ovarian carcinoma. At a median follow-up of 88.8 months (95% CI 86.2-92.0 months), the vast majority of patients (89.4%) had died. The median survival after recurrence was 21.4 months (95% CI 20.5-21.9 months). Time to recurrence after initial chemotherapy, clear cell or mucinous histology, performance status, stage IV disease, and age were significant variables used to develop a nomogram for survival after recurrence, which had a concordance index of 0.67. The time to recurrence alone accounted for 85% of the prognostic information. Similar results were found for patients who underwent second look laparotomy and had a complete pathologic response or received intraperitoneal chemotherapy.ConclusionFor individuals with advanced-stage ovarian carcinoma who recur after standard first-line therapy, estimated survivals after recurrence are closely related to the time to recurrence after chemotherapy and prognostic variables can be used to predict subsequent survival.Clinical trial registrationClinialTrials.gov, NCT00002568, NCT00837993, NCT00002717, NCT01074398, and NCT00011986

The Degree of Segmental Aneuploidy Measured by Total Copy Number Abnormalities Predicts Survival and Recurrence in Superficial Gastroesophageal Adenocarcinoma

Abstract Background: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC

Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study

BACKGROUND: Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy. METHODS: We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth. RESULTS: At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by ~90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points. CONCLUSION: HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months

Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis

<p>Abstract</p> <p>Background</p> <p>The Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells.</p> <p>Methods</p> <p>Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed.</p> <p>Results</p> <p>In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration <it>in vitro</it>.</p> <p>Conclusion</p> <p>Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.</p