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1.
Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis.  相似文献   
2.
Organic solvent nanofiltration (OSN) is gradually expanding from academic research to industrial implementation. The need for membranes with low and sharp molecular weight cutoffs that are able to operate under aggressive OSN conditions is increasing. However, the lack of comparable and uniform performance data frustrates the screening and membrane selection for processes. Here, a collaboration is presented between several academic and industrial partners analyzing the separation performance of 10 different membranes using three model process mixtures. Membrane materials range from classic polymeric and thin film composites (TFCs) to hybrid ceramic types. The model solutions were chosen to mimic cases relevant to today's industrial use: relatively low molar mass solutes (330–550 Da) in n-heptane, toluene, and anisole.  相似文献   
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The current study set out to investigate to what extent ISIS is bolstering its jihadist ideology on a ‘cut-and-paste’ or ‘cherry-picked’ version of Islam in their renowned online propaganda magazine Dabiq. The main objective was to examine in a systematic and quantitative way to what extent ISIS utilizes the Koran in an atomistic, truncated and tailored manner to bolster its religious legitimacy. A total of 15 issues of Dabiq and 700 Koranic references were scrutinized. By means of a quantitative analysis we developed an innovative taxonomy of Koranic chapters and verses (i.e. surahs and ayat, respectively) on the basis of their appearance in Dabiq. Our large-scale data analysis provide consistent empirical evidence for severe decontextualization practices of the Koran in three ways: (1) a thin, Medinan-dominated religious layer, (2) ayah mutilation, and (3) clustered versus exclusive mentions. Limitations and implications for future research, policy makers and CVE initiatives are discussed.  相似文献   
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This paper introduces an efficient algorithm for the bike request scheduling problem (BRSP). The BRSP is built around the concept of request, defined as the pickup or dropoff of a number of identical items (bikes) at a specific station, within a certain time window, and with a certain priority. The aim of the BRSP is to sequence requests on (and hence determine the routes of) a set of vehicles, in such a way that the sum of the priorities of the executed requests is maximized, all time windows are respected, and the capacity of the vehicles is not exceeded. The generation of the set of requests is explicitly not a part of the problem definition of the BRSP. The primary application of the BRSP, from which it derives its name, is to determine the routes of a set of repositioning vehicles in a bike sharing system, although other applications exist. The algorithm introduced in this paper is based on a set of related greedy randomized adaptive search procedure followed by variable neighborhood descent (GRASP + VND) operators embedded in a large neighborhood search (LNS) framework. Since this paper presents the first heuristic for the BRSP, a computational comparison to existing approaches is not possible. We therefore compare the solutions found by our LNS heuristic to those found by an exact solver (Gurobi). These experiments confirm that the proposed algorithm scales to realistic dimensions and is able to find near‐optimal solutions in seconds.  相似文献   
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A network approach was used to develop a thermofluid process model of a cross-flow primary superheater heat exchanger with complex flow arrangement in the convective pass of a coal-fired boiler. The model solves the transient one-dimensional forms of the conservation equations for mass, energy, and momentum, combined with the applicable closure relations, boundary values, and initial values. The dual-tube 12-pass superheater was discretized along the flue gas flow path as well as along the steam flow path. The model accounts for the convective thermal resistance on the steam side, the conductive thermal resistances of the tube wall, and scaling or fouling on the tube walls, as well as the convective and radiative thermal resistances on the flue gas side. The model was qualitatively validated using real plant data and for reference purposes also systematically compared to conventional lumped parameter models. The ability of the model to analyze the effect of the ramp rate during load changes on the tube metal temperature was demonstrated, as well as the ability to determine the maldistribution of flow and temperature on the steam and flue gas sides. Models such as this can be employed to study complex thermofluid process phenomena that may occur during intermittent, transient, and low-load operation of power plants. This could form the basis for improving operations and for the development of advanced tools for online process condition monitoring.  相似文献   
8.
We discuss the potential benefits, requirements, and implementation challenges of a security-by-design approach in which an integrated development environment plugin assists software developers to write code that complies with secure coding guidelines. We discuss how such a plugin can enable a company's policy-setting security experts and developers to pass their knowledge on to each other more efficiently, and to let developers more effectively put that knowledge into practice. This is achieved by letting the team members develop customized rule sets that formalize coding guidelines and by letting the plugin check the compliance of code being written to those rule sets in real time, similar to an as-you-type spell checker. Upon detected violations, the plugin suggests options to quickly fix them and offers additional information for the developer. We share our experience with proof-of-concept designs and implementations rolled out in multiple companies, and present some future research and development directions.  相似文献   
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Apple pomace can be used as resource for the extraction of phenolic compounds with antioxidant properties. Pressing of apple in juice and pomace at lab scale in open air (aerobic) and under N2 atmosphere (anaerobic) showed a recovery of phenolic compounds of 85% in juice and pomace after anaerobic pressing, compared to 43% after aerobic pressing, indicating loss of phenolic compounds by oxidation and the advantage of anaerobic over aerobic pressing. After a membrane screening and concentration test at lab scale, the commercial nanofiltration membrane NFX was selected to concentrate phenolic compounds in an ethanol : water extract of apple pomace. At pilot scale, the concencentration of 10 selected phenolic compounds and quinic acid increased from 59.5 mg/L in the ethanol : water extract to 1256.1 mg/L in the final retentate, that is, by a factor 21.1. The volume of the crude extract was reduced by a factor of 28.5 during the filtration, indicating some loss of phenolic compounds during pilot testing due to membrane fouling or oxidation of polyphenols. The pilot concentration test using a spiral‐wound membrane module showed good flux and concentration of phenolic compounds, indicating the technical feasibility of membrane technology for efficient concentration of polyphenols in an ethanol : water extraction solvent. Unfortunately, the extraction and concentration process was not economically feasible under the assumptions made.

Practical applications

The valorization of food waste for the production of high‐added value products is an increasingly hot topic. Phytochemicals are present in relatively low concentration in the fruit matrix, and concentration in the extraction solvent is necessary to develop an industrially relevant process. In this study, membrane filtration was selected for concentration due to its low energy consumption and mild processing conditions compared to other technologies. Membrane screening and testing at lab and pilot scale with techno‐economic assessment can be used by food and nutraceutical industries to evaluate membrane technology for concentration of phytochemicals extracted from agroindustrial by‐products.  相似文献   
10.
Journal of Scheduling - Employee absences are inevitable in practice due to illness, heavy workloads or accidents. These unforeseen events result in the disruption of employee shift rosters, which...  相似文献   
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