This discussion paper aims to set out the key challenges and opportunities emerging from distributed manufacturing (DM). We begin by describing the concept, available definitions and consider its ...evolution where recent production technology developments (such as additive and continuous production process technologies), digitisation together with infrastructural developments (in terms of IoT and big data) provide new opportunities. To further explore the evolving nature of DM, the authors, each of whom are involved in specific applications of DM research, examine through an expert panel workshop environment emerging DM applications involving new production and supporting infrastructural technologies. This paper presents these generalisable findings on DM challenges and opportunities in terms of products, enabling production technologies and the impact on the wider production and industrial system. Industry structure and location of activities are examined in terms of the democratising impact on participating network actors. The paper concludes with a discussion on the changing nature of manufacturing as a result of DM, from the traditional centralised, large-scale, long lead-time forecast-driven production operations to a new DM paradigm where manufacturing is a decentralised, autonomous near end user-driven activity. A forward research agenda is proposed that considers the impact of DM on the industrial and urban landscape.
Open design is a catchall term for various on- and offline design and making activities. It can be used to describe a type of design process that allows for (is open to) the participation of anybody ...(novice or professional) in the collaborative development of something. As well as this, it can mean the distribution and unrestricted use of design blueprints and documentation for the use by others.
In this paper, the authors highlight various aspects of open and collaborative design and argue for the use of new terms that address what is open and when. A range of design projects and online platforms that have open attributes are then explored, whereby these terms are applied. In terms of design, the focus is specifically on the design of physical things rather than graphical, software or system design.
The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription ...factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape, we measured genome-wide RUNX1- and RUNX1/ETO-bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end, we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide redistribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal, and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML.
It is hypothesized that the extent and severity of fibrosis and cellularity found on lung biopsy determine the prognosis and response to therapy in idiopathic pulmonary fibrosis (IPF). The objective ...of this study was to determine which histopathologic features predict survival in IPF. We prospectively studied 87 patients with usual interstitial pneumonia (UIP) confirmed by surgical lung biopsy. Four pathologists independently graded the extent and severity of specific histopathologic features. We used Cox proportional-hazards models to assess the effect of histopathologic patterns on patients' survival. The effects of age, sex, and smoking were also included in the analysis. Sixty-three patients died during the 17-yr study period. Survival was longer in subjects with lesser degrees of granulation/connective tissue deposition (fibroblastic foci). The degree of alveolar space cellularity, alveolar wall fibrosis, and cellularity did not affect survival. A history of cigarette smoking, the level of dyspnea, and the degree of lung stiffness at presentation were also shown to be independent factors predicting survival. The extent of fibroblastic foci present on lung biopsy predicts survival in IPF. These findings support the hypothesis that the critical pathway to end-stage fibrosis is not "alveolitis" but rather the ongoing epithelial damage and repair process associated with persistent fibroblastic proliferation. Controlling these processes, rather than stopping inflammation, appears most important in preventing progressive disease and the fatal outcome common in IPF.
Higher diet quality scores are associated with a lower risk for many chronic diseases and all-cause mortality; however, it is unclear if diet quality is associated with aging biology.
This study ...aimed to examine the association between diet quality and a measure of biological aging known as epigenetic aging.
A cross-sectional data analysis was used to examine the association between three diet quality scores based on self-reported food frequency questionnaire data and five measures of epigenetic aging based on DNA methylation (DNAm) data from peripheral blood.
This study included 4,500 postmenopausal women recruited from multiple sites across the United States (1993-98), aged 50 to 79 years, with food frequency questionnaire and DNAm data available from the Women’s Health Initiative baseline visit.
Five established epigenetic aging measures were generated from HumanMethylation450 Beadchip DNAm data, including AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno, AgeAccelGrim, and DunedinPACE.
Linear mixed models were used to test for associations between three diet quality scores (Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores) and epigenetic aging measures, adjusted for age, race and ethnicity, education, tobacco smoking, physical activity, Women’s Health Initiative substudy from which DNAm data were obtained, and DNAm-based estimates of leukocyte proportions.
Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores were all inversely associated with AgeAccelPheno, AgeAccelGrim, and DunedinPACE (P < 0.05), with the largest effects with DunedinPACE. A one standard deviation increment in diet quality scores was associated with a decrement (β ± SE) in DunedinPACE z score of –0.097 ± 0.014 (P = 9.70 x 10-13) for Healthy Eating Index, –0.107 ± 0.014 (P = 1.53 x 10-14) for Dietary Approaches to Stop Hypertension, and –0.068 ± 0.013 (P = 2.31 x 10-07) for the alternate Mediterranean diet.
In postmenopausal women, diet quality scores were inversely associated with DNAm-based measures of biological aging, particularly DunedinPACE.
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