79 research outputs found

    Split scheduling with uniform setup times

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    We study a scheduling problem in which jobs may be split into parts, where the parts of a split job may be processed simultaneously on more than one machine. Each part of a job requires a setup time, however, on the machine where the job part is processed. During setup, a machine cannot process or set up any other job. We concentrate on the basic case in which setup times are job-, machine- and sequence-independent. Problems of this kind were encountered when modelling practical problems in planning dis- aster relief operations. Our main algorithmic result is a polynomial-time algorithm for minimising total completion time on two parallel identical machines. We argue, why the same problem with threemachines is not an easy extension of the two-machine case, leaving the complexity of this case as a tantalising open problem. We give a constant-factor approximation algorithm for the general case with any number of machines and a polynomial-time approximation scheme for a fixed number of machines. For the version with the objective to minimise total weighted completion time, we prove NP-hardness. Finally, we conclude with an overview of the state of the art for other split scheduling problems with job-, machine- and sequence-independent setup times

    Autophagy acts through TRAF3 and RELB to regulate gene expression via antagonism of SMAD proteins

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    Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB. We show that RELB represses TGFβ target promoters independently of DNA binding at NF-κB recognition sequences, instead binding with SMAD family member(s) at SMAD-response elements. Thus, autophagy antagonises TGFβ gene expression. Finally, autophagy-deficient A549 cells regain tumorigenicity upon SMAD4 knockdown. Thus, at least in this setting, a physiologic function for autophagic regulation of gene expression is tumour growth

    Perceptions of involvement in advance care planning and emotional functioning in patients with advanced cancer

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    Purpose: Advance Care Planning (ACP) is positively associated with the quality of care, but its impact on emotional functioning is ambiguous. This study investigated the association between perceptions of ACP involvement and emotional functioning in patients with advanced cancer. Methods: This study analyzed baseline data of 1,001 patients of the eQuiPe study, a prospective, longitudinal, multicenter, observational study on quality of care and quality of life in patients with advanced cancer in the Netherlands. Patients with metastatic solid cancer were asked to participate between November 2017 and January 2020. Patients’ perceptions of ACP involvement were measured by three self-administered statements. Emotional functioning was measured by the EORTC-QLQ-C30. A linear multivariable regression analysis was performed while taking gender, age, migrant background, education, marital status, and symptom burden into account. Results: The majority of patients (87%) reported that they were as much involved as they wanted to be in decisions about their future medical treatment and care. Most patients felt that their relatives (81%) and physicians (75%) were familiar with their preferences for future medical treatment and care. A positive association was found between patients’ perceptions of ACP involvement and their emotional functioning (b=0.162, p<0.001, 95%CI[0.095;0.229]) while controlling for relevant confounders. Conclusions: Perceptions of involvement in ACP are positively associated with emotional functioning in patients with advanced cancer. Future studies are needed to further investigate the effect of ACP on emotional functioning. Trial registration number: NTR6584 Date of registration: 30 June 2017 Implications for Cancer Survivors: Patients’ emotional functioning might improve from routine discussions regarding goals of future care. Therefore, integration of ACP into palliative might be promising

    Development of an international Core Outcome Set (COS) for best care for the dying person: study protocol

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    Background: In contrast to typical measures employed to assess outcomes in healthcare such as mortality or recovery rates, it is difficult to define which specific outcomes of care are the most important in caring for dying individuals. Despite a variety of tools employed to assess different dimensions of palliative care, there is no consensus on a set of core outcomes to be measured in the last days of life. In order to optimise decision making in clinical practice and comparability of interventional studies, we aim to identify and propose a set of core outcomes for the care of the dying person. Methods: Following the COMET initiative approach, the proposed study will proceed through four stages to develop a set of core outcomes: In stage 1, a systematic review of the literature will identify outcomes measured in existing peer reviewed literature, as well as outcomes derived through qualitative studies. Grey literature, will also be included. Stage 2 will allow for the identification and determination of patient and proxy defined outcomes of care at the end of life via quantitative and qualitative methods at an international level. In stage 3, from a list of salient outcomes identified through stages 1 and 2, international experts, family members, patients, and patient advocates will be asked to score the importance of the preselected outcomes through a Delphi process. Stage 4 consists of a face-to-face consensus meeting of in

    Zuylen, Robust control of traffic networks under uncertain conditions

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    Abstract Uncertainty of traffic network operations has been a subject of lively debate in the last decade. However, little effort has been put in developing control frameworks that are not only aimed at improving the average performance of the system, but also at improving the system robustness and reliability. In fact, it can be argued that most of the current control approaches are only aimed at improving the efficiency, which can even be counterproductive from a robustness point of view. The main contributions of this article is the proposition of a new control framework based on the notion of controlled Markov processes, which explicitly takes into account the uncertainty in predicted traffic conditions and system performance. Furthermore, in contrast to traditional optimal control approaches, the objective function can include general statistic of the random system performance, such as the mean, standard deviation or 95-percentile. The contribution aims to make clear how different performance function specifications yield different control strategies. This is shown for a relatively simple case study

    The Influence of Spillback Modelling when Assessing Consequences of Blockings in a Road Network

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    Robustness of a network is a main objective for road network managers these days, and has therefore become an important study area for transportation scientists. This article discusses one specific aspect in assessing road network robustness: the consequences of the closure of a link. These spillback effects have been examined in a dedicated traffic simulator in which the representation of spillback can be switched on and off. The impacts are studied in a simulation study of a road network of a regional size in which sequentially links are blocked. Two scenarios for route choice are considered: a fixed route choice based on a daily congestion pattern and a route choice adapted to the actual congestion caused by the closure. The study has also shown the influence of information which makes travellers adapt their routes. Road network robustness and characteristics of vulnerable links are evaluated for both spillback and non-spillback cases. It is found that a valid spillback modelling is a prerequisite for correctly analysing the robustness of the network as a whole, as well as for correctly indicating the locations in the network where a closure causes the largest delays. Furthermore, without simulating spillback, it is not possible to identify correctly the most vulnerable links for the network performance.Transport & PlanningCivil Engineering and Geoscience
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