Resource dedication problem in a multi-project environment

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

Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine

<p>Abstract</p> <p>Background</p> <p>There is increasing recognition that many of today's diseases are due to the "oxidative stress" that results from an imbalance between the formation and neutralization of reactive molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can be removed with antioxidants. The main objective of the present study was to evaluate the antioxidant activity of plants routinely used in the Unani system of medicine. Several plants were screened for radical scavenging activity, and the ten that showed promising results were selected for further evaluation.</p> <p>Methods</p> <p>Methanol (50%) extracts were prepared from ten Unani plants, namely <it>Cleome icosandra, Rosa damascena, Cyperus scariosus, Gardenia gummifera, Abies pindrow, Valeriana wallichii, Holarrhena antidysenterica, Anacyclus pyrethrum, Asphodelus tenuifolius </it>and <it>Cyperus scariosus</it>, and were used to determine their total phenolic, flavonoid and ascorbic acid contents, in vitro scavenging of DPPH^·, ABTS^·+, NO, ^·OH, O₂^.-and ONOO^-, and capacity to prevent oxidative DNA damage. Cytotoxic activity was also determined against the U937 cell line.</p> <p>Results</p> <p>IC₅₀values for scavenging DPPH^·, ABTS^·+, NO, ^·OH, O₂^.-and ONOO^-were in the ranges 0.007 ± 0.0001 - 2.006 ± 0.002 mg/ml, 2.54 ± 0.04 - 156.94 ± 5.28 μg/ml, 152.23 ± 3.51 - 286.59 ± 3.89 μg/ml, 18.23 ± 0.03 - 50.13 ± 0.04 μg/ml, 28.85 ± 0.23 - 537.87 ± 93 μg/ml and 0.532 ± 0.015 - 3.39 ± 0.032 mg/ml, respectively. The total phenolic, flavonoid and ascorbic acid contents were in the ranges 62.89 ± 0.43 - 166.13 ± 0.56 mg gallic acid equivalent (GAE)/g extract, 38.89 ± 0.52 - 172.23 ± 0.08 mg quercetin equivalent (QEE)/g extract and 0.14 ± 0.09 - 0.98 ± 0.21 mg AA/g extract. The activities of the different plant extracts against oxidative DNA damage were in the range 0.13-1.60 μg/ml. Of the ten selected plant extracts studied here, seven - <it>C. icosandra, R. damascena, C. scariosus, G. gummifera, A. pindrow, V. wallichii </it>and <it>H. antidysenterica - </it>showed moderate antioxidant activity. Finally, potentially significant oxidative DNA damage preventive activity and antioxidant activity were noted in three plant extracts: <it>C. icosandra, R. damascena </it>and <it>C. scariosus</it>. These three plant extracts showed no cytotoxic activity against U937 cells.</p> <p>Conclusions</p> <p>The 50% methanolic extracts obtained from different plant parts contained significant amounts of polyphenols with superior antioxidant activity as evidenced by the scavenging of DPPH^·, ABTS^·+, NO, ^·OH, O₂^.-and ONOO^-. <it>C. icosandra, R. damascena </it>and <it>C. scariosus </it>showed significant potential for preventing oxidative DNA damage and radical scavenging activity, and the <it>G. gummifera, A. pindrow, V. wallichii, H. antidysenterica, A. pyrethrum, A. tenuifolius </it>and <it>O. mascula </it>extracts showed moderate activity. The extracts of <it>C. icosandra, R. damascena </it>and <it>C. scariosus </it>showed no cytotoxicity against U937 cells. In conclusion, these routinely used Unani plants, especially <it>C. icosandra, R. damascena </it>and <it>C. scariosus</it>, which are reported to have significant activity against several human ailments, could be exploited as potential sources of natural antioxidants for plant-based pharmaceutical industries.</p

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD