Study of Size Effect in Sheet-stringer Panels

An investigation was conducted to determine whether there are significant size effects in compressive strength of large Z-stiffened sheet-stringer panels as compared with geometrically similar smaller models and thus to ascertain whether the prediction of the strength of large panels by model tests is reliable. The specimens studied were manufactured from 7075-T6 aluminum alloy and included four representative types of panel designs, with full- and one-quarter-scale panels of each type

Haematology outreach clinics in the Free State and Northern Cape

Objective. Evaluation of haematology outreach clinics in the Northern Cape and Free State.Design. Retrospective analysis of records from March 1994 to February 1996.Setting. Central South Africa is sparsely populated. Consultants from Bloemfontein held outpatient clinics in hospitals (with laboratories) in Bethlehem, Kimberley and Kroonstad.SUbjects. 117 patients with suspected haematological disease.Main outcome measures. Input measures (population, number of clinics and costs), process measures (patient numbers, patients per clinic, new consultations per clinic, patients' domicile, how they were referred, types of diagnoses and number of patients with nonhaematologicaldisorders) and output measures (attrition, changes in attendance and savings).Main results. The 84 clinics that were held, with 636 consultations, did not cost the State anything. Only 6% of the 117 patients had no haematological problem. Sixtyeight per cent had chronic haematological neoplasms. In Kimberley most of the patients came from Kimberley Hospital, while most of the patients at the other clinics were referred via Bloemfontein. There was only a 10% attrition rate and only one-third of patients were referred to Bloemfontein. We saved paying patients an estimated R21 260 in transport costs, while saving the State R172 992 by seeing patients at secondary, instead of tertiary, hospitals.Conclusions. It is cheaper to send a doctor to an outreach clinic than to refer patients to a central facility, provided there is enough work for a doctor at the clinic. It costs the State much less for patients to be seen at a secondary than a tertiary hospital. Positive spin-offs include academic stimulation of doctors and laboratories in the periphery, with more appropriate referrals to teaching hospitals. Weaknesses include poor availability of expensive drugs at the clinics and lack of standardised records. By commuting to outreach clinics, specialists can greatly reduce health expenditure and spread it from tertiary to lower levels. At the same time more patients have access to their services

Dynamic linkages between stock markets : the effects of crises and globalization

This paper investigates changes in the dynamics of linkages between selected national stock markets during the period 1995–2009. The analysis focuses on the possible effects of globalization and differences between crisis and non-crisis periods. We model the dynamics of dependencies between the series of daily returns on selected stock indices over different time periods, and compare strength of the linkages. Our tools are dynamic copula models and a formal sequential testing procedure based on the model confidence set methodology. We consider two types of dependencies: regular dependence measured by means of the conditional Spearman’s rho, and dependencies in extremes quantified by the conditional tail dependence coefficients. The main result consists of a collection of rankings created for the considered subperiods, which show how the mean level of strength of the dependencies have been changing in time. The rankings obtained for Spearman’s rho and tail dependencies differ, which allows us to distinguish between the results of crises and the effect of globalization.info:eu-repo/semantics/publishedVersio

Portuguese and Brazilian stock market integration : a non-linear and detrended approach

Besides the historical heritage that Portugal and Brazil share, the last two decades have also shown an increase in some economic indicators, such as the percentage of imports/exports and foreign direct investment. In order to take advantage of all the benefits, the countries should increase economic integration, stock market integration being one of the possibilities. In this context, this paper analyses stock market integration between these two countries, using non-linear methodologies: detrended fluctuation analysis, detrended cross-correlation analysis and detrended moving-average cross-correlation analysis. Using the main stock indexes, and splitting the sample in six different periods, the main conclusion is that integration between these two countries increased over time. However, since 2013, the integration pattern has decreased, with the economic crisis both countries suffered being the main factor.info:eu-repo/semantics/publishedVersio

Complementarity Between a Docking and a High-Throughput Screen in Discovering New Cruzain Inhibitors†

Virtual and high-throughput screens (HTS) should have complementary strengths and weaknesses, but studies that prospectively and comprehensively compare them are rare. We undertook a parallel docking and HTS screen of 197861 compounds against cruzain, a thiol protease target for Chagas disease, looking for reversible, competitive inhibitors. On workup, 99 % of the hits were eliminated as false positives, yielding 146 well-behaved, competitive ligands. These fell into five chemotypes: two were prioritized by scoring among the top 0.1 % of the docking-ranked library, two were prioritized by behavior in the HTS and by clustering, and one chemotype was prioritized by both approaches. Determination of an inhibitor/cruzain crystal structure and comparison of the high-scoring docking hits to experiment illuminated the origins of docking false-negatives and false-positives. Prioritizing molecules that are both predicted by docking and are HTS-active yields well-behaved molecules, relatively unobscured by the false-positives to which both techniques are individually prone

Automated Docking Screens: A Feasibility Study

Molecular docking is themost practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCKBlaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCKBlaster recapitulates the crystal ligand pose within 2 A ̊ rmsd 50-60 % of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5 % of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5 % of 100 property-matched decoys while also posing within 2 A ̊ rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available a

Functional Characterization of a Newly Identified Group B Streptococcus Pullulanase Eliciting Antibodies Able to Prevent Alpha-Glucans Degradation

Streptococcal pullulanases have been recently proposed as key components of the metabolic machinery involved in bacterial adaptation to host niches. By sequence analysis of the Group B Streptococcus (GBS) genome we found a novel putative surface exposed protein with pullulanase activity. We named such a protein SAP. The sap gene is highly conserved among GBS strains and homologous genes, such as PulA and SpuA, have been described in other pathogenic streptococci. The SAP protein contains two N-terminal carbohydrate-binding motifs, followed by a catalytic domain and a C-terminal LPXTG cell wall-anchoring domain. In vitro analysis revealed that the recombinant form of SAP is able to degrade α-glucan polysaccharides, such as pullulan, glycogen and starch. Moreover, NMR analysis showed that SAP acts as a type I pullulanase. Studies performed on whole bacteria indicated that the presence of α-glucan polysaccharides in culture medium up-regulated the expression of SAP on bacterial surface as confirmed by FACS analysis and confocal imaging. Deletion of the sap gene resulted in a reduced capacity of bacteria to grow in medium containing pullulan or glycogen, but not glucose or maltose, confirming the pivotal role of SAP in GBS metabolism of α-glucans. As reported for other streptococcal pullulanases, we found specific anti-SAP antibodies in human sera from healthy volunteers. Investigation of the functional role of anti-SAP antibodies revealed that incubation of GBS in the presence of sera from animals immunized with SAP reduced the capacity of the bacterium to degrade pullulan. Of interest, anti-SAP sera, although to a lower extent, also inhibited Group A Streptococcus pullulanase activity. These data open new perspectives on the possibility to use SAP as a potential vaccine component inducing functional cross-reacting antibodies interfering with streptococcal infections