Hard-wired heterogeneity in blood stem cells revealed using a dynamic regulatory network model.

MOTIVATION: Combinatorial interactions of transcription factors with cis-regulatory elements control the dynamic progression through successive cellular states and thus underpin all metazoan development. The construction of network models of cis-regulatory elements, therefore, has the potential to generate fundamental insights into cellular fate and differentiation. Haematopoiesis has long served as a model system to study mammalian differentiation, yet modelling based on experimentally informed cis-regulatory interactions has so far been restricted to pairs of interacting factors. Here, we have generated a Boolean network model based on detailed cis-regulatory functional data connecting 11 haematopoietic stem/progenitor cell (HSPC) regulator genes. RESULTS: Despite its apparent simplicity, the model exhibits surprisingly complex behaviour that we charted using strongly connected components and shortest-path analysis in its Boolean state space. This analysis of our model predicts that HSPCs display heterogeneous expression patterns and possess many intermediate states that can act as 'stepping stones' for the HSPC to achieve a final differentiated state. Importantly, an external perturbation or 'trigger' is required to exit the stem cell state, with distinct triggers characterizing maturation into the various different lineages. By focusing on intermediate states occurring during erythrocyte differentiation, from our model we predicted a novel negative regulation of Fli1 by Gata1, which we confirmed experimentally thus validating our model. In conclusion, we demonstrate that an advanced mammalian regulatory network model based on experimentally validated cis-regulatory interactions has allowed us to make novel, experimentally testable hypotheses about transcriptional mechanisms that control differentiation of mammalian stem cells. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A polynomial algorithm for special case of the one-machine scheduling problem with time-lags

The standard one-machine scheduling problem consists in schedulinga set of jobs in one machine which can handle only one job at atime, minimizing the maximum lateness. Each job is available forprocessing at its release date, requires a known processing timeand after finishing the processing, it is delivery after a certaintime. There also can exists precedence constraints between pairsof jobs, requiring that the first jobs must be completed beforethe second job can start. An extension of this problem consistsin assigning a time interval between the processing of the jobsassociated with the precedence constrains, known by finish-starttime-lags. In presence of this constraints, the problem is NP-hardeven if preemption is allowed. In this work, we consider a specialcase of the one-machine preemption scheduling problem with time-lags, where the time-lags have a chain form, and propose apolynomial algorithm to solve it. The algorithm consist in apolynomial number of calls of the preemption version of the LongestTail Heuristic. One of the applicability of the method is to obtainlower bounds for NP-hard one-machine and job-shop schedulingproblems. We present some computational results of thisapplication, followed by some conclusions.

Metaheuristics for the bus-driver scheduling problem

We present new metaheuristics for solving real crew scheduling problemsin a public transportation bus company. Since the crews of thesecompanies are drivers, we will designate the problem by the bus-driverscheduling problem. Crew scheduling problems are well known and severalmathematical programming based techniques have been proposed to solvethem, in particular using the set-covering formulation. However, inpractice, there exists the need for improvement in terms of computationalefficiency and capacity of solving large-scale instances. Moreover, thereal bus-driver scheduling problems that we consider can present variantaspects of the set covering, as for example a different objectivefunction, implying that alternative solutions methods have to bedeveloped. We propose metaheuristics based on the following approaches:GRASP (greedy randomized adaptive search procedure), tabu search andgenetic algorithms. These metaheuristics also present some innovationfeatures based on and genetic algorithms. These metaheuristics alsopresent some innovation features based on the structure of the crewscheduling problem, that guide the search efficiently and able them tofind good solutions. Some of these new features can also be applied inthe development of heuristics to other combinatorial optimizationproblems. A summary of computational results with real-data problems ispresented.

An Improved Hybrid Model for the Generic Hoist Scheduling Problem

Peer-reviewed

Generating highly balanced sudoku problems as hard problems

Sudoku problems are some of the most known and enjoyed pastimes, with a never diminishing popularity, but, for the last few years those problems have gone from an entertainment to an interesting research area, a twofold interesting area, in fact. On the one side Sudoku problems, being a variant of Gerechte Designs and Latin Squares, are being actively used for experimental design, as in [8, 44, 39, 9]. On the other hand, Sudoku problems, as simple as they seem, are really hard structured combinatorial search problems, and thanks to their characteristics and behavior, they can be used as benchmark problems for refining and testing solving algorithms and approaches. Also, thanks to their high inner structure, their study can contribute more than studies of random problems to our goal of solving real-world problems and applications and understanding problem characteristics that make them hard to solve. In this work we use two techniques for solving and modeling Sudoku problems, namely, Constraint Satisfaction Problem (CSP) and Satisfiability Problem (SAT) approaches. To this effect we define the Generalized Sudoku Problem (GSP), where regions can be of rectangular shape, problems can be of any order, and solution existence is not guaranteed. With respect to the worst-case complexity, we prove that GSP with block regions of m rows and n columns with m = n is NP-complete. For studying the empirical hardness of GSP, we define a series of instance generators, that differ in the balancing level they guarantee between the constraints of the problem, by finely controlling how the holes are distributed in the cells of the GSP. Experimentally, we show that the more balanced are the constraints, the higher the complexity of solving the GSP instances, and that GSP is harder than the Quasigroup Completion Problem (QCP), a problem generalized by GSP. Finally, we provide a study of the correlation between backbone variables – variables with the same value in all the solutions of an instance– and hardness of GSP.

Solving Challenging Real-World Scheduling Problems

This work contains a series of studies on the optimization of three real-world scheduling problems, school timetabling, sports scheduling and staff scheduling. These challenging problems are solved to customer satisfaction using the proposed PEAST algorithm. The customer satisfaction refers to the fact that implementations of the algorithm are in industry use. The PEAST algorithm is a product of long-term research and development. The first version of it was introduced in 1998. This thesis is a result of a five-year development of the algorithm. One of the most valuable characteristics of the algorithm has proven to be the ability to solve a wide range of scheduling problems. It is likely that it can be tuned to tackle also a range of other combinatorial problems. The algorithm uses features from numerous different metaheuristics which is the main reason for its success. In addition, the implementation of the algorithm is fast enough for real-world use.

Multi-objective assembly job shop scheduling using genetic algorithm and tabu search

Assembly job shop scheduling problem (AJSP) is one of the most complicated combinatorial optimization problem that involves simultaneously scheduling the processing and assembly operations of complex structured products. The problem becomes even more complicated if a combination of two or more optimization criteria is considered. This thesis addresses an assembly job shop scheduling problem with multiple objectives. The objectives considered are to simultaneously minimizing makespan and total tardiness. In this thesis, two approaches viz., weighted approach and Pareto approach are used for solving the problem. However, it is quite difficult to achieve an optimal solution to this problem with traditional optimization approaches owing to the high computational complexity. Two metaheuristic techniques namely, genetic algorithm and tabu search are investigated in this thesis for solving the multiobjective assembly job shop scheduling problems. Three algorithms based on the two metaheuristic techniques for weighted approach and Pareto approach are proposed for the multi-objective assembly job shop scheduling problem (MOAJSP). A new pairing mechanism is developed for crossover operation in genetic algorithm which leads to improved solutions and faster convergence. The performances of the proposed algorithms are evaluated through a set of test problems and the results are reported. The results reveal that the proposed algorithms based on weighted approach are feasible and effective for solving MOAJSP instances according to the weight assigned to each objective criterion and the proposed algorithms based on Pareto approach are capable of producing a number of good Pareto optimal scheduling plans for MOAJSP instances.

BEE COLONIES APPLIED TO MULTIPROCESSOR SCHEDULING

In order to achieve the high performance, we need to have an efficient scheduling of a parallelprogram onto the processors in multiprocessor systems that minimizes the entire executiontime. This problem of multiprocessor scheduling can be stated as finding a schedule for ageneral task graph to be executed on a multiprocessor system so that the schedule length can be minimize [10]. This scheduling problem is known to be NP- Hard.In multi processor task scheduling, we have a number of CPU’s on which a number of tasksare to be scheduled that the program’s execution time is minimized. According to [10], thetasks scheduling problem is a key factor for a parallel multiprocessor system to gain betterperformance. A task can be partitioned into a group of subtasks and represented as a DAG(Directed Acyclic Graph), so the problem can be stated as finding a schedule for a DAG to beexecuted in a parallel multiprocessor system so that the schedule can be minimized. Thishelps to reduce processing time and increase processor utilization. The aim of this thesis workis to check and compare the results obtained by Bee Colony algorithm with already generatedbest known results in multi processor task scheduling domain.

Multi-population genetic algorithm to solve the synchronized and integrated two-level lot sizing and scheduling problem

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stochastic scheduling - A flow shop no wait application and solutions

Minimizing the makespan of a flow-shop no-wait (FSNW) schedule where the processing times are randomly distributed is an important NP-Complete Combinatorial Optimization Problem. In spite of this, it can be found only in very few papers in the literature. By considering the Start Interval Concept, this problem can be formulated, in a practical way, in function of the probability of the success in preserve FSNW constraints for all tasks execution. With this formulation, for the particular case with 3 machines, this paper presents different heuristics solutions: by integrating local optimization steps with insertion procedures and by using genetic algorithms for search the solution space. Computational results and performance evaluations are commented. Copyright (C) 1998 IFAC.

A heuristic algorithm based on multi-assignment procedures for nurse scheduling

This paper tackles a Nurse Scheduling Problem which consists of generating work schedules for a set of nurses while considering their shift preferences and other requirements. The objective is to maximize the satisfaction of nurses' preferences and minimize the violation of soft constraints. This paper presents a new deterministic heuristic algorithm, called MAPA (multi-assignment problem-based algorithm), which is based on successive resolutions of the assignment problem. The algorithm has two phases: a constructive phase and an improvement phase. The constructive phase builds a full schedule by solving successive assignment problems, one for each day in the planning period. The improvement phase uses a couple of procedures that re-solve assignment problems to produce a better schedule. Given the deterministic nature of this algorithm, the same schedule is obtained each time that the algorithm is applied to the same problem instance. The performance of MAPA is benchmarked against published results for almost 250,000 instances from the NSPLib dataset. In most cases, particularly on large instances of the problem, the results produced by MAPA are better when compared to best-known solutions from the literature. The experiments reported here also show that the MAPA algorithm finds more feasible solutions compared with other algorithms in the literature, which suggest that this proposed approach is effective and robust. © 2013 Springer Science+Business Media New York.

Heuristic methods for the single machine scheduling problem with different ready times and a common due date

The single machine scheduling problem with a common due date and non-identical ready times for the jobs is examined in this work. Performance is measured by the minimization of the weighted sum of earliness and tardiness penalties of the jobs. Since this problem is NP-hard, the application of constructive heuristics that exploit specific characteristics of the problem to improve their performance is investigated. The proposed approaches are examined through a computational comparative study on a set of 280 benchmark test problems with up to 1000 jobs.

Combinatorial and Robust Optimisation Models and Algorithms for Railway Applications

This thesis deals with an investigation of combinatorial and robust optimisation models to solve railway problems. Railway applications represent a challenging area for operations research. In fact, most problems in this context can be modelled as combinatorial optimisation problems, in which the number of feasible solutions is finite. Yet, despite the astonishing success in the field of combinatorial optimisation, the current state of algorithmic research faces severe difficulties with highly-complex and data-intensive applications such as those dealing with optimisation issues in large-scale transportation networks. One of the main issues concerns imperfect information. The idea of Robust Optimisation, as a way to represent and handle mathematically systems with not precisely known data, dates back to 1970s. Unfortunately, none of those techniques proved to be successfully applicable in one of the most complex and largest in scale (transportation) settings: that of railway systems. Railway optimisation deals with planning and scheduling problems over several time horizons. Disturbances are inevitable and severely affect the planning process. Here we focus on two compelling aspects of planning: robust planning and online (real-time) planning.

Hybrid Methods for Resource Allocation and Scheduling Problems in Deterministic and Stochastic Environments

This work presents exact, hybrid algorithms for mixed resource Allocation and Scheduling problems; in general terms, those consist into assigning over time finite capacity resources to a set of precedence connected activities. The proposed methods have broad applicability, but are mainly motivated by applications in the field of Embedded System Design. In particular, high-performance embedded computing recently witnessed the shift from single CPU platforms with application-specific accelerators to programmable Multi Processor Systems-on-Chip (MPSoCs). Those allow higher flexibility, real time performance and low energy consumption, but the programmer must be able to effectively exploit the platform parallelism. This raises interest in the development of algorithmic techniques to be embedded in CAD tools; in particular, given a specific application and platform, the objective if to perform optimal allocation of hardware resources and to compute an execution schedule. On this regard, since embedded systems tend to run the same set of applications for their entire lifetime, off-line, exact optimization approaches are particularly appealing. Quite surprisingly, the use of exact algorithms has not been well investigated so far; this is in part motivated by the complexity of integrated allocation and scheduling, setting tough challenges for ``pure'' combinatorial methods. The use of hybrid CP/OR approaches presents the opportunity to exploit mutual advantages of different methods, while compensating for their weaknesses. In this work, we consider in first instance an Allocation and Scheduling problem over the Cell BE processor by Sony, IBM and Toshiba; we propose three different solution methods, leveraging decomposition, cut generation and heuristic guided search. Next, we face Allocation and Scheduling of so-called Conditional Task Graphs, explicitly accounting for branches with outcome not known at design time; we extend the CP scheduling framework to effectively deal with the introduced stochastic elements. Finally, we address Allocation and Scheduling with uncertain, bounded execution times, via conflict based tree search; we introduce a simple and flexible time model to take into account duration variability and provide an efficient conflict detection method. The proposed approaches achieve good results on practical size problem, thus demonstrating the use of exact approaches for system design is feasible. Furthermore, the developed techniques bring significant contributions to combinatorial optimization methods.