Metaheuristics for solving a multimodal home-healthcare scheduling problem

Abstract We present a general framework for solving a real-world multimodal home-healthcare scheduling (MHS) problem from a major Austrian home-healthcare provider. The goal of MHS is to assign home-care staff to customers and determine efficient multimodal tours while considering staff and customer satisfaction. Our approach is designed to be as problem-independent as possible, such that the resulting methods can be easily adapted to MHS setups of other home-healthcare providers. We chose a two-stage approach: in the first stage, we generate initial solutions either via constraint programming techniques or by a random procedure. During the second stage, the initial solutions are (iteratively) improved by applying one of four metaheuristics: variable neighborhood search, a memetic algorithm, scatter search and a simulated annealing hyper-heuristic. An extensive computational comparison shows that the approach is capable of solving real-world instances in reasonable time and produces valid solutions within only a few seconds

PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay

PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay

Ontmoetingen Met Historici

224hal.;21c

Nafsu Seorang Penulis Sejarah Sejati (Seri Informasi Aceh Thn. V No.3)

24 Ha

Partial convexification of general MIPs by Dantzig-Wolfe reformulation

Dantzig-Wolfe decomposition is well-known to provide strong dual bounds for specially structured mixed integer programs (MIPs) in practice. However, the method is not implemented in any state-of-the-art MIP solver: it needs tailoring to the particular problem; the decomposition must be determined from the typical bordered block-diagonal matrix structure; the resulting column generation subproblems must be solved efficiently; etc. We provide a computational proof-of-concept that the process can be automated in principle, and that strong dual bounds can be obtained on general MIPs for which a solution by a decomposition has not been the first choice. We perform an extensive computational study on the 0-1 dynamic knapsack problem (without block-diagonal structure) and on general MIPLIB2003 instances. Our results support that Dantzig-Wolfe reformulation may hold more promise as a generalpurpose tool than previously acknowledged by the research community