NMDA-receptor antagonist requirements in conantokin-G

A series of variants of the neuroactive 17-residue gamma-carboxyglutamate-(Gla)-containing polypeptide, conantokin-G (con-G), were synthesized with the intention of determining those features that were important for its N-methyl-D-aspartate (NMDA) receptor-targeted antagonist activity and for adoption of its divalent cation-dependent alpha-helical conformation. Employing the binding of [3H]dizolcipine (MK-801) as an assay for open receptor ion channels in rat brain membranes, which displays inhibition by con-G (IC50 = 0.48 microM), it was found that replacement by an Ala residue of Gla4 led to complete inactivation of the peptide, whereas a similar replacement of Gla3 resulted in a 20-fold decreased potency. Ala substitutions for Gla10 and Gla14 did not substantially affect [3H]MK-801 binding. This same substitution at Gla7 appeared to slightly enhance binding. Ala replacements of non-Gla residues demonstrated that four of them, viz. Glu2, Leu5, Gln9, and Ile12, possessed at least 200-fold decreases in inhibitory potency, whereas similar replacements at Gly1, Leu11, and Arg13 resulted in peptides with 8- to 12-fold increases in the IC50 values. The remaining amino acid residues tested in the single Ala replacement series showed no significant changes in the inhibitory characteristics of wild-type con-G. Additional studies with carboxyl-terminal truncated peptides revealed that the carboxyl-terminal 4 amino acids were unimportant for this activity. There was no strict correlation of inhibition of [3H]MK-801 binding with the ability of these peptides to form cation-dependent alpha-helices. Peptides with notably low alpha-helical content in the presence of these cations were lacking at least one, or both, of Gla10 and Gla14. Con-G[Gla3,4,7,10,14E] and con-G[Gla7,10,14E] were the only peptides that remained in a completely random conformation upon metal ion addition.     

A new hybrid approach for the solution of nonconvex economic dispatch problem with valve-point effects

Economic dispatch (ED) generally formulated as convex problem using optimization techniques by approximating generator input/output characteristic curves of monotonically increasing nature results in an inaccurate dispatch. The genetic algorithm has previously been used for the solution of problem for economic dispatch but takes longer time to converge to near optimal results. The hybrid approach is one of the methodologies used to fine tune the near optimal results produced by GA. This paper proposes new hybrid approach to solve the ED problem by using the valve-point effect. The approach we propose combines the genetic algorithm (GA) with active power optimization (APO) based on the Newton's second order approach (NSO). The genetic algorithm acts as a global optimizer giving near optimal generation schedule, which becomes the input for generation buses in APO algorithm. This algorithm acting as local search technique dispatching the generated active power of units for minimization of cost and gives optimum generation schedule. Three machines 6-bus, IEEE 5-machines 14-bus, and IEEE 6-mchines 30-bus systems have been tested for validation of our approach. Results of the proposed scheme compared with results obtained from GA alone give significant improvements in the generation cost showing the promise of the proposed approach.     

Molecular modeling of immunoglobulin light chains implicates hydrophobic residues in non-amyloid light chain deposition disease

Light chain deposition disease is a severe complication of certain immunoproliferative disorders, due to the secretion of a monoclonal light chain which precipitates close to basement membranes of several tissues. A kappa isotype restriction and an unusual frequency of a variable region subgroup (VkappaIV) suggest that precise structural features govern the propensity of pathogenic light chains to precipitate in extracellular spaces. We studied primary structures of light chains from six patients with light chain deposition disease in comparison with light chains from other pathological conditions. Sequence alignment revealed the presence of certain amino acids only in light chain deposition disease, in particular non-polar replacing hydrophilic residues. To determine the role of these residues, structures of the variable domain from four kappa chains belonging to VkappaI and VkappaIV subgroups responsible for deposition disease were modeled using known immunoglobulins as templates. The most evident structural features shared by all pathogenic light chains were hydrophobic residues exposed to the solvent in complementarity determining regions 1 or 3. In contrast to immunoglobulin light chain- related amyloidosis, where deposition of organized material might be due to electrostatic interactions between light chain dimers, hydrophobic interactions could enhance amorphous precipitation in non- amyloid light chain deposition disease.      

New aspect-oriented constructs for security hardening concerns

In this paper, we present new pointcuts and primitives to Aspect-Oriented Programming (AOP) languages that are needed for systematic hardening of security concerns. The two proposed pointcuts allow to identify particular join points in a program's control-flow graph (CFG). The first one is the GAFlow, Closest Guaranteed Ancestor, which returns the closest ancestor join point to the pointcuts of interest that is on all their runtime paths. The second one is the GDFlow, Closest Guaranteed Descendant, which returns the closest child join point that can be reached by all paths starting from the pointcut of interest. The two proposed primitives are called ExportParameter and ImportParameter and are used to pass parameters between two pointcuts. They allow to analyze a program's call graph in order to determine how to change function signatures for passing the parameters associated with a given security hardening. We find these pointcuts and primitives to be necessary because they are needed to perform many security hardening practices and, to the best of our knowledge, none of the existing ones can provide their functionalities. Moreover, we show the viability and correctness of the proposed pointcuts and primitives by elaborating and implementing their algorithms and presenting the result of explanatory case studies.     

VANET QoS-OLSR: QoS-based clustering protocol for Vehicular Ad hoc Networks

In this paper, we address the problem of clustering in Vehicular Ad hoc Networks (VANETs) using Quality of Service Optimized Link State Routing (QoS-OLSR) protocol. Several clustering algorithms have been proposed for VANET and MANET. However, the mobility-based algorithms ignore the Quality of Service requirements that are important for VANET safety, emergency, and multimedia services while the QoS-based algorithms ignore the high speed mobility constraints since they are dedicated for Mobile Ad hoc Networks (MANETs). Our solution is a new QoS-based clustering algorithm that considers a tradeoff between QoS requirements and high speed mobility constraints. The goal is to form stable clusters and maintain the stability during communications and link failures while satisfying the Quality of Service requirements. This is achieved by: (1) considering the high mobility metrics while computing the QoS, (2) using Ant Colony Optimization for MPRs selection, and (3) using MPR recovery algorithm able to select alternatives and keep the network connected in case of link failures. Performance analysis and simulation results show that the proposed model can maintain the network stability, reduce the end-to-end delay, increase the packet delivery ratio, and reduce the communications overhead.     

The stability of preferences for life-sustaining care among persons with AIDS in the Boston Health Study

In 1982, the World Health Organization (WHO) identified inadequate relief from cancer pain as an international health problem. WHO recommended that governments develop and implement national policies and programs for cancer pain relief. This report evaluates national health policy and the systems of health care delivery in relation to cancer pain management in the new South Africa. This field study included multiple methods of data collection: analysis of documents, field trips with participant observation in sites of care delivery, focused interviews, and in-depth interviews of key informants. The purposive sample of key informants (n = 33) represented multiple stakeholders in a variety of settings. Strengths of the developing health policy include specific recommendations related to palliative care; the shift to universal primary care; policies to support drug availability; the inclusion of morphine and codeine as essential drug at the primary health care level; and the development of a national standard related to cancer pain management. Health services are characterized by two parallel systems of care (private and public) with numerous vestiges of the inequities of apartheid. The management of pain varies by provider and setting; major problems with access exist in the rural areas. Health services in South Africa have been plagued by inequity and inadequate resources. New health policies have set a path to ensure universal access to health care including palliative care for cancer. Their successful implementation is the next necessary step toward improving health services and alleviating the suffering of increasing numbers of individuals with cancer.     

Endovascular interventions training and credentialing for vascular surgeons

This article reviews issues concerning the training and credentialing of vascular surgeons in the use of endovascular techniques in the peripheral vascular system. These guidelines update a prior document that was published in 1993. They have been rewritten to accommodate the rapid evolution that has occurred in the field and to provide the appropriate requirements that a vascular surgeon should fulfill to be competent in the basic skills needed to safely and effectively perform all presently accepted diagnostic and therapeutic endovascular procedures.