146 research outputs found

    Resource dedication problem in a multi-project environment

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    There can be different approaches to the management of resources within the context of multi-project scheduling problems. In general, approaches to multiproject scheduling problems consider the resources as a pool shared by all projects. On the other hand, when projects are distributed geographically or sharing resources between projects is not preferred, then this resource sharing policy may not be feasible. In such cases, the resources must be dedicated to individual projects throughout the project durations. This multi-project problem environment is defined here as the resource dedication problem (RDP). RDP is defined as the optimal dedication of resource capacities to different projects within the overall limits of the resources and with the objective of minimizing a predetermined objective function. The projects involved are multi-mode resource constrained project scheduling problems with finish to start zero time lag and non-preemptive activities and limited renewable and nonrenewable resources. Here, the characterization of RDP, its mathematical formulation and two different solution methodologies are presented. The first solution approach is a genetic algorithm employing a new improvement move called combinatorial auction for RDP, which is based on preferences of projects for resources. Two different methods for calculating the projects’ preferences based on linear and Lagrangian relaxation are proposed. The second solution approach is a Lagrangian relaxation based heuristic employing subgradient optimization. Numerical studies demonstrate that the proposed approaches are powerful methods for solving this problem

    S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate.

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    R-2-hydroxyglutarate accumulates to millimolar levels in cancer cells with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both metabolite enantiomers, R- and S-2-hydroxyglutarate, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that 2-hydroxyglutarate accumulates in mouse CD8+ T cells in response to T-cell receptor triggering, and accumulates to millimolar levels in physiological oxygen conditions through a hypoxia-inducible factor 1-alpha (HIF-1α)-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8+ T-cell differentiation in response to this metabolite. Modulation of histone and DNA demethylation, as well as HIF-1α stability, mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8+ T cells. Thus, S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, through a metabolic-epigenetic axis, to immune fate and function

    Who wants to talk to terrorists?

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    Interviewing terrorists or former terrorists has become an increasingly popular research method in terrorism studies. What terrorists say can shed light on motivations, decision-making processes and operational details that without first-hand testimony could only be inferred. In this chapter, a selection of these studies is reviewed alongside a consideration of global trends in terrorism and developments in terrorism research

    ATLAS detector and physics performance: Technical Design Report, 1

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    Province: Three Autopsy Cases

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    Background: Turkey is one of the richest countries in the world in terms of balneotherapy resources. Thermo-mineral water baths are preferred by the elderly because of their positive beneficial effects over regulation of musculoskeletal system functions. However, existing cardiovascular and respiratory system diseases may constitute a risk and trigger ischemic changes in the heart.Methods: In this study, 2 cases are presented who suffered sudden cardiac death while having a thermal bath and 1 drowning case that was precipitated by chronic myocardial infarction. While 1 case was 63 years old, 2 cases were above 65 years of age. Two (2) cases had atherosclerotic coronary artery disease, whereas 1 case had heart failure.Results: The success of spa treatment, which is based on stimulation/harmonization therapy, restores bodily harmony and depends on the health of organs and functions playing a role in this process.Conclusions: In the elderly, some conditions, particularly limited pulmonary and cardiovascular functionality, should be taken into consideration while applying those treatments

    Hippocampal neuron loss due to electric injury in rats: a stereological study.

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    Electric injury may cause different changes from minimal damage (e.g. small burns) to severe complications up to death. Several morphological changes of the skin and the internal organs are used for the diagnosis of electrical injury. However, macroscopic findings and histological changes of the internal organs and the skin may be absent in many cases. Furthermore, neuropsychological changes including deficits of cognitive functions may be seen in survivor victims. The aim of the present study is to examine whether electric injury causes decreasing in the number of pyramidal neurons in the rat hippocampus and whether this decreasing can be demonstrated by stereological method. The rats were separated into three groups: first group, native control group; second group, the points of electrical contact were on the back skin in this group; third group, the points of electrical contact were on the temporal region in this group. The current was the usual city current (110V, 50Hz, 100A AC). On the third day, the rats were decapitated; the brains were removed, and sectioned horizontally through the hippocampus and samples chosen according to the systematic random sampling strategy. Afterwards the samples were stained by H&E and optical fractionator method, one of the unbiased stereological methods, was used to estimate the total pyramidal neuron number. The results showed that the total number of pyramidal neurons in three subdivision of the hippocampus (CA3-2 and CA1) was 242,141+/-31,167, 193,388+/-24,795 and 187,448+/-28,300 in the first, second and third groups, respectively. The differences between first and second-third groups were statistically significant (p<0.05). There was not any significant difference between the second and the third groups. In conclusion, electrocution causes loss of the pyramidal neuronal in CA3-2 and CA1 subdivisions of the rat hippocampus in this study
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