Inhibition of neuronal calcium channels by a novel peptide spider toxin, DW13.3

Peptide toxins have proved to be useful agents, both in discriminating between different components of native calcium channel currents and in the molecular isolation and designation of their cloned channel counterparts. Here, we describe the isolation and characterization of the biochemical and physiological properties of a novel 74-amino acid peptide toxin (DW13.3) extracted from the venom of the spider Filistata hibernalis. The subtype specificity of DW13.3 was investigated using calcium channel currents recorded from two separate expression systems and several different cultured mammalian cell preparations. Overall, DW13.3 potently blocked all native calcium channel currents studied, with the exception of T-type currents recorded from GH3 cells. Examination of transiently expressed calcium channels in oocytes showed that DW13.3 had the highest affinity for alpha1A, followed by alpha1B > alpha1C > alpha1E. The affinity of DW13.3 for alpha1B N-type currents varied by 10-fold between expressed channels and native currents. Although block occurred in a similar 1:1 manner for all subtypes, DW13.3 produced a partial block of both alpha1A currents and P-type currents in cerebellar Purkinje cells. Selective occlusion of the P/Q-type channel ligand omega-conotoxin MVIIC (but not omega-agatoxin IVA) from its binding site in Purkinje neurons suggests that DW13.3 binds to a site close to the pore of the channel. The inhibition of different subtypes of calcium channels by DW13.3 reflects a common "macro" binding site present on all calcium channels except T-type.     

Inconsistent heuristics in theory and practice

In the field of heuristic search it is usually assumed that admissible heuristics are consistent, implying that consistency is a desirable attribute. The term “inconsistent heuristic” has, at times, been portrayed negatively, as something to be avoided. Part of this is historical: early research discovered that inconsistency can lead to poor performance for A^? (nodes might be re-expanded many times). However, the issue has never been fully investigated, and was not re-considered after the invention of IDA^?.This paper shows that many of the preconceived notions about inconsistent heuristics are outdated. The worst-case exponential time of inconsistent heuristics is shown to only occur on contrived graphs with edge weights that are exponential in the size of the graph. Furthermore, the paper shows that rather than being something to be avoided, inconsistent heuristics often add a diversity of heuristic values into a search which can lead to a reduction in the number of node expansions. Inconsistent heuristics are easy to create, contrary to the common perception in the AI literature. To demonstrate this, a number of methods for achieving effective inconsistent heuristics are presented.Pathmax is a way of propagating inconsistent heuristic values in the search from parent to children. This technique is generalized into bidirectional pathmax (BPMX) which propagates values from a parent to a child node, and vice versa. BPMX can be integrated into IDA^? and A^?. When inconsistent heuristics are used with BPMX, experimental results show a large reduction in the search effort required by IDA^?. Positive results are also presented for A^? searches.     

High prevalence of polycystic ovaries and associated clinical, endocrine, and metabolic features in women with previous gestational diabetes mellitus

The prevalence of polycystic ovaries, according to ultrasonography, and associated clinical, endocrine, and metabolic features were investigated in women with previous gestational diabetes mellitus (GDM). Thirty-four women with GDM 3-5 yr before the investigation and 36 controls with uncomplicated pregnancies, selected for similar age, parity, and date of delivery, were investigated. The women with previous GDM showed a higher prevalence of polycystic ovaries [14 of 34 (41%) vs. 1 of 36 (3%); P < 0.0001], hirsutism (P < 0.01), irregular menstrual cycles (P < 0.01), and a higher body mass index (BMI; P < 0.001) than the controls. Five women (15%) with previous GDM had developed manifest diabetes (excluded in comparisons of metabolic variables). After dividing the women with previous GDM into subgroups according to ovarian appearance, the 2 subgroups showed similar glucose tolerance and prevalence of diabetes, whereas the women with polycystic ovaries were younger (mean +/- SD, 33.3 +/- 1.4 vs. 38.2 +/- 1.1; P < 0.01), had higher truncal-abdominal/femoral fat ratio according to skin folds (P < 0.05), had higher concentrations of androstenedione (P < 0.01) and testosterone (P < 0.01), and had a higher LH/FSH ratio (P < 0.01), lower levels of GH (P < 0.01), higher levels of triglycerides (P < 0.05) and cholesterol (P < 0.05) in very low density lipoprotein, all independent of age and BMI, and had a higher prevalence of pregnancy-induced hypertension (50% vs. 15%; P < 0.05) during the index pregnancy compared with the women with normal ovaries. The group of women with GDM showed a lower early insulin release after glucose (i.v. glucose tolerance test) for their degree of insulin resistance (euglycemic hyperinsulinemic clamp) compared with controls (P < 0.05). In the two subgroups, insulin sensitivity was lower in the polycystic ovaries group, independent of BMI (P < 0.05), than in the group with normal ovaries. In conclusion, ultrasonographic, clinical and endocrine signs of polycystic ovary syndrome were much increased in women with a history of GDM. Compared with the women with normal ovaries and previous GDM, those with polycystic ovaries formed a distinct subgroup that may be more prone to develop various features of the insulin resistance syndrome. Both groups showed a similarly disturbed balance between beta-cell activity and insulin sensitivity, but in women with polycystic ovaries, insulin resistance may be the dominant component.     

Business owners' action planning and its relationship to business success in three African countries.

A model of business success was developed with motivational resources (locus of control, self-efficacy, achievement motivation, and self-reported personal initiative) and cognitive resources (cognitive ability and human capital) as independent variables, business owners' elaborate and proactive planning as a mediator, and business size and growth as dependent variables. Three studies with a total of 408 African micro and small-scale business owners were conducted in South Africa, Zimbabwe, and Namibia. Structural equation analyses partially supported the hypotheses on the importance of psychological planning by the business owners. Elaborate and proactive planning was substantially related to business size and to an external evaluation of business success and was a (partial) mediator for the relationship between cognitive resources and business success. The model carries important implications for selection, training, and coaching of business owners. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The EuQoS system: a solution for QoS routing in heterogeneous networks [Quality of Service based Routing Algorithms for Heterogeneous Networks]

EuQoS is the acronym for "end-to-end quality of service support over heterogeneous networks", which is a European research project aimed at building an entire QoS framework, addressing all the relevant network layers, protocols, and technologies. This framework, which includes the most common access networks (xDSL, UMTS, WiFi, and LAN) is being prototyped and tested in a multidomain scenario throughout Europe, composing what we call the EuQoS system. In this article we present the novel QoS routing mechanisms that are being developed and evaluated in the framework of this project. The preliminary performance results validate the design choices of the EuQoS system, and confirm the potential impact this project is likely to have in the near future     

Optimal Pulses Robust to Carrier Frequency Offset for OFDM/QAM Systems

Optimal pulses with minimum ICI power at a given CFO point for OFDM/QAM systems are found analytically. A lower bound of the ICI power is introduced as a measure of the robustness to CFO for a given pulse. Numerical comparison verifies that the optimal pulse is more robust to CFO than previously suggested pulses at the selected CFO point.     

EuQoS: End-to-End Quality of Service over Heterogeneous Networks

The EuQoS (End-to-End QoS over Heterogeneous Networks) IST Integrated European Project aimed to define a Next Generation Network architecture that builds, uses and manages end-to-end QoS across different administrative domains and heterogeneous networks (UMTS, xDSL, Ethernet, WiFi, Satellite and IP/MPLS). The EuQoS architecture preserves the openness and the decentralized decision model of the actual Internet, runs on off-the-shelf hardware and network equipment, and allows end users to request various services without changing the Application Signaling protocol, while meeting regulators’ and users’ Net Neutrality requirements. This paper presents the key elements of the EuQoS architecture and describes the main results obtained in field trials performed on a fully-functional EuQoS system prototype developed over a pan-European testbed. Furthermore, the paper discusses the main strengths of the system and the issues related to its actually deployment on a large scale, from both technical and market points of view.