Including the workload effect in the parallel program signature

Performance prediction and application behavior modeling have been the subject of exten- sive research that aim to estimate applications performance with an acceptable precision. A novel approach to predict the performance of parallel applications is based in the con- cept of Parallel Application Signatures that consists in extract an application most relevant parts (phases) and the number of times they repeat (weights). Executing these phases in a target machine and multiplying its exeuction time by its weight an estimation of the application total execution time can be made. One of the problems is that the performance of an application depends on the program workload. Every type of workload affects differently how an application performs in a given system and so affects the signature execution time. Since the workloads used in most scientific parallel applications have dimensions and data ranges well known and the behavior of these applications are mostly deterministic, a model of how the programs workload affect its performance can be obtained. We create a new methodology to model how a program’s workload affect the parallel application signature. Using regression analysis we are able to generalize each phase time execution and weight function to predict an application performance in a target system for any type of workload within predefined range. We validate our methodology using a synthetic program, benchmarks applications and well known real scientific applications.

Effect of a Road Safety Training Program on Drivers' Comparative Optimism

Reducing comparative optimism regarding risk perceptions in traffic accidents has been proven to be particularly difficult (Delhomme, 2000). This is unfortunate because comparative optimism is assumed to impede preventive action. The present study tested whether a road safety training course could reduce drivers' comparative optimism in high control situations. Results show that the training course efficiently reduced comparative optimism in high control, but not in low control situations. Mechanisms underlying this finding and implications for the design of road safety training courses are discussed.

Evaluation of indirect susceptibility testing of Mycobacterium tuberculosis to the first- and second-line, and alternative drugs by the newer MB/BacT system

In order to evaluate the Organon Teknika MB/BacT system used for testing indirect susceptibility to the alternative drugs ofloxacin (OFLO), amikacin (AMI), and rifabutin (RIF), and to the usual drugs of standard treatment regimes such as rifampin (RMP), isoniazid (INH), pyrazinamide (PZA), streptomycin (SM), ethambutol (EMB), and ethionamide (ETH), cultures of clinical specimens from 117 patients with pulmonary tuberculosis under multidrug-resistant investigation, admitted sequentially for examination from 2001 to 2002, were studied. Fifty of the Mycobacterium tuberculosis cultures were inoculated into the gold-standard BACTEC 460 TB (Becton Dickinson) for studying resistance to AMI, RIF, and OFLO, and the remaining 67 were inoculated into Lowenstein Jensen (LJ) medium (the gold standard currently used in Brazil) for studying resistance to RMP, INH, PZA, SM, EMB, and ETH. We observed 100% sensitivity for AMI (80.8-100), RIF (80.8-100), and OFLO (78.1-100); and 100% specificity for AMI (85.4-100), RIF (85.4-100), and OFLO (86.7-100) compared to the BACTEC system. Comparing the results obtained in LJ we observed 100% sensitivity for RMP (80-100), followed by INH - 95% (81.8-99.1), EMB - 94.7% (71.9-99.7), and 100% specificity for all drugs tested except for PZA - 98.3 (89.5-99.9) at 95% confidence interval. The results showed a high level of accuracy and demonstrated that the fully automated, non-radiometric MB/BacT system is indicated for routine use in susceptibility testing in public health laboratories.

Schistosomiasis mansoni: follow-up of control program based on parasitologic and serologic methods in a Brazilian community of low endemicity

A field survey on schistosomiais was carried out in 1998, in the municipality of Pedro de Toledo, a low endemic area in the state of São Paulo, Brazil. According to the parasitologic Kato-Katz method, the prevalence rate was 1.6%, with an infection intensity of 40.9 eggs per gram of stool. By the immunofluorescence test (IFT) for detection of IgG and IgM antibodies in the serum, IgG-IFT and IgM-IFT, respectively, prevalence indices of 33.2% and 33.5% were observed. To assess the impact of the schistosomiasis control program in the area, parasitologic and serologic data obtained in 1998, analyzed according to the age, sex, and residence zone, were compared to previous data obtained in a epidemiologic study carried out in 1980, when prevalence indices were of 22.8% and 55.5%, respectively by Kato-Katz and IgG-IFT. A significant fall of the prevalence was observed, indicating that the control measures were effective. Nonetheless, residual transmission was observed, demonstrating the need for a joint effort to include new approaches for better understanding the real situation and improving the control of the disease in low endemic areas.

An alternative technique to reveal polysaccharides in Toxoplasma gondii tissue cysts

Ultrathin sections of tissue cysts isolated from the brain of Toxoplasma gondii infected mice were submitted to two different methodologies derived from the periodic acid - Schiff's reagent (PAS) technique. The use of osmium tetroxide vapor as a developing agent of the aldehyde oxidation to reveal polysaccharides with periodic acid resulted in positive reaction in amylopectin granules in bradyzoites, as well as in the wall and matrix of the cysts, with excellent increment of the ultrastructural morphology. This technique can be used for study of T. gondii-host cell intracellular cycle, the differentiation tachyzoite-bradyzoite, and also for the formation of cysts into the host cells.

Is the GraftConnector a valid alternative to running suture in end-to-side coronary arteries anastomoses?

BACKGROUND: An animal study was carried out to compare long-term patency rates of coronary anastomoses performed with the GraftConnector versus running suture technique. METHODS: 10 sheep, 45 to 55 kg, underwent off-pump coronary artery bypass grafting (right internal mammary artery to left anterior descending artery). In 5 animals, the anastomosis was performed with a GraftConnector and in 5 animals with 7-0 running suture. Intraoperative fluoroscopy and a fluoroscopic control at 6 months were performed. After 6 months, the animals were sacrificed and the anastomoses were examined histologically. RESULTS: All animals survived at 6 months with 100% anastomosis patency rates in both groups. In the GraftConnector group, the anastomosis diameter at 6 months fluoroscopy was 118% of native left anterior descending artery versus 97% of the control group. Luminal anastomotic width at histology was 1.7 +/- 0.2 mm in the device group versus 1.6 +/- 0.1 mm in the control group. Mean intimal hyperplasia thickness was 0.21 +/- 0.1 mm in the device group versus 0.01 mm in the control group. CONCLUSIONS: The GraftConnector provides a consistent and reproducible coronary artery anastomosis and reduces technical demand and manual dexterity in coronary operations. Long-term results demonstrate that off-pump coronary artery bypass grafting performed with the GraftConnector had the same patency rate and luminal width as those performed with running suture.

Ku-deficient yeast strains exhibit alternative states of silencing competence.

In Saccharomyces cerevisiae, efficient silencer function requires telomere proximity, i.e. compartments of the nucleoplasm enriched in silencing factors. Accordingly, silencers located far from telomeres function inefficiently. We show here that cells lacking yKu balance between two mitotically stable states of silencing competence. In one, a partial delocalization of telomeres and silencing factors throughout the nucleoplasm correlates with enhanced silencing at a non-telomeric locus, while in the other, telomeres retain their focal pattern of distribution and there is no repression at the non-telomeric locus, as observed in wild-type cells. The two states also differ in their level of residual telomeric silencing. These findings indicate the existence of a yKu-independent pathway of telomere clustering and Sir localization. Interestingly, this pathway appears to be under epigenetic control.

Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels

Background: The imatinib trough plasma concentration (C(min)) correlates with clinical response in cancer patients. Therapeutic drug monitoring (TDM) of plasma C(min) is therefore suggested. In practice, however, blood sampling for TDM is often not performed at trough. The corresponding measurement is thus only remotely informative about C(min) exposure. Objectives: The objectives of this study were to improve the interpretation of randomly measured concentrations by using a Bayesian approach for the prediction of C(min), incorporating correlation between pharmacokinetic parameters, and to compare the predictive performance of this method with alternative approaches, by comparing predictions with actual measured trough levels, and with predictions obtained by a reference method, respectively. Methods: A Bayesian maximum a posteriori (MAP) estimation method accounting for correlation (MAP-ρ) between pharmacokinetic parameters was developed on the basis of a population pharmacokinetic model, which was validated on external data. Thirty-one paired random and trough levels, observed in gastrointestinal stromal tumour patients, were then used for the evaluation of the Bayesian MAP-ρ method: individual C(min) predictions, derived from single random observations, were compared with actual measured trough levels for assessment of predictive performance (accuracy and precision). The method was also compared with alternative approaches: classical Bayesian MAP estimation assuming uncorrelated pharmacokinetic parameters, linear extrapolation along the typical elimination constant of imatinib, and non-linear mixed-effects modelling (NONMEM) first-order conditional estimation (FOCE) with interaction. Predictions of all methods were finally compared with 'best-possible' predictions obtained by a reference method (NONMEM FOCE, using both random and trough observations for individual C(min) prediction). Results: The developed Bayesian MAP-ρ method accounting for correlation between pharmacokinetic parameters allowed non-biased prediction of imatinib C(min) with a precision of ±30.7%. This predictive performance was similar for the alternative methods that were applied. The range of relative prediction errors was, however, smallest for the Bayesian MAP-ρ method and largest for the linear extrapolation method. When compared with the reference method, predictive performance was comparable for all methods. The time interval between random and trough sampling did not influence the precision of Bayesian MAP-ρ predictions. Conclusion: Clinical interpretation of randomly measured imatinib plasma concentrations can be assisted by Bayesian TDM. Classical Bayesian MAP estimation can be applied even without consideration of the correlation between pharmacokinetic parameters. Individual C(min) predictions are expected to vary less through Bayesian TDM than linear extrapolation. Bayesian TDM could be developed in the future for other targeted anticancer drugs and for the prediction of other pharmacokinetic parameters that have been correlated with clinical outcomes.

Fast subplasma membrane Ca2+ transients control exo-endocytosis of synaptic-like microvesicles in astrocytes

Astrocytes are the most abundant glial cell type in the brain. Although not apposite for long-range rapid electrical communication, astrocytes share with neurons the capacity of chemical signaling via Ca(2+)-dependent transmitter exocytosis. Despite this recent finding, little is known about the specific properties of regulated secretion and vesicle recycling in astrocytes. Important differences may exist with the neuronal exocytosis, starting from the fact that stimulus-secretion coupling in astrocytes is voltage independent, mediated by G-protein-coupled receptors and the release of Ca(2+) from internal stores. Elucidating the spatiotemporal properties of astrocytic exo-endocytosis is, therefore, of primary importance for understanding the mode of communication of these cells and their role in brain signaling. We here take advantage of fluorescent tools recently developed for studying recycling of glutamatergic vesicles at synapses (Voglmaier et al., 2006; Balaji and Ryan, 2007); we combine epifluorescence and total internal reflection fluorescence imaging to investigate with unprecedented temporal and spatial resolution, the stimulus-secretion coupling underlying exo-endocytosis of glutamatergic synaptic-like microvesicles (SLMVs) in astrocytes. Our main findings indicate that (1) exo-endocytosis in astrocytes proceeds with a time course on the millisecond time scale (tau(exocytosis) = 0.24 +/- 0.017 s; tau(endocytosis) = 0.26 +/- 0.03 s) and (2) exocytosis is controlled by local Ca(2+) microdomains. We identified submicrometer cytosolic compartments delimited by endoplasmic reticulum tubuli reaching beneath the plasma membrane and containing SLMVs at which fast (time-to-peak, approximately 50 ms) Ca(2+) events occurred in precise spatial-temporal correlation with exocytic fusion events. Overall, the above characteristics of transmitter exocytosis from astrocytes support a role of this process in fast synaptic modulation.

The UniProtKB/Swiss-Prot Tox-Prot program: A central hub of integrated venom protein data.

Animal toxins are of interest to a wide range of scientists, due to their numerous applications in pharmacology, neurology, hematology, medicine, and drug research. This, and to a lesser extent the development of new performing tools in transcriptomics and proteomics, has led to an increase in toxin discovery. In this context, providing publicly available data on animal toxins has become essential. The UniProtKB/Swiss-Prot Tox-Prot program (http://www.uniprot.org/program/Toxins) plays a crucial role by providing such an access to venom protein sequences and functions from all venomous species. This program has up to now curated more than 5000 venom proteins to the high-quality standards of UniProtKB/Swiss-Prot (release 2012_02). Proteins targeted by these toxins are also available in the knowledgebase. This paper describes in details the type of information provided by UniProtKB/Swiss-Prot for toxins, as well as the structured format of the knowledgebase.

Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2002)

The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (NF-GNB) collected from Latin America region through the SENTRY Program between 1997 and 2002 was evaluated by broth microdilution according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Nearly 74% of the NF-BGN belonged to the following genera/species: Burkholderia spp. (83), Achromobacter spp. (25), Ralstonia pickettii (16), Alcaligenes spp. (12), and Cryseobacterium spp. (12). Generally, trimethoprim/sulfamethoxazole (MIC50, < 0.5 µg/ml) was the most potent drug followed by levofloxacin (MIC50, 0.5 µg/ml), and gatifloxacin (MIC50, 1 µg/ml). The highest susceptibility rates were observed for levofloxacin (78.3%), gatifloxacin (75.6%), and meropenem (72.6%). Ceftazidime (MIC50, 4 µg/ml; 83.1% susceptible) was the most active beta-lactam against B. cepacia. Against Achromobacter spp. isolates, meropenem (MIC50, 0.25 µg/ml; 88% susceptible) was more active than imipenem (MIC50, 2 µg/ml). Cefepime (MIC50, 2 µg/ml; 81.3% susceptible), and imipenem (MIC50, 2 µg/ml; 81.3% susceptible) were more active than ceftazidime (MIC50, >16 µg/ml; 18.8% susceptible) and meropenem (MIC50, 8 µg/ml; 50% susceptible) against Ralstonia pickettii. Since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the NCCLS for many of NF-GNB species, results from large multicenter studies may help to guide the best empiric therapy.

Artificial muscle to wash blood out of fibrillating atrium: an alternative to lifelong anticoagulation.

The Atripump is a motorless, volume displacement pump based on artificial muscle technology that could reproduce the pump function of normal atrium. It could help prevent blood clots due to blood stagnation and eventually avoid anticoagulation therapy in atrial fibrillation (AF). An animal study has been designed to assess mechanical effects of this pump on fibrillating atrium. The Atripump is a dome shaped silicone coated nitinol actuator. A pacemaker like control unit drives the actuator. In five adult sheep, the right atrium (RA) was exposed and dome sutured onto the epicardium. Atrial fibrillation was induced using rapid epicardial pacing (600 beats/min). Ejection fraction of the RA was obtained with intracardiac ultrasound in baseline, AF and Atripump assisted AF conditions. The dome's contraction rate was 60/min with power supply of 12V, 400 mA for 200 ms and ran for 2 hours in total. Mean temperature on the RA was 39+/-1.5 degrees C. Right atrium ejection fraction was 31% in baseline conditions, 5% and 20% in AF and assisted AF, respectively. In two animals a thrombus appeared in the right appendix and washed out once the pump was turned on. The Atripump washes blood out the RA acting as an anticoagulant device. Possible clinical implications in patients with chronic AF are prevention of embolism of cardiac origin and avoidance of hemorrhagic complication due to chronic anticoagulation.

Evaluation of rapid alternative methods for drug susceptibility testing in clinical isolates of Mycobacterium tuberculosis

A study was carried out to compare the performance of a commercial method (MGIT) and four inexpensive drug susceptibility methods: nitrate reductase assay (NRA), microscopic observation drug susceptibility (MODS) assay, MTT test, and broth microdilution method (BMM). A total of 64 clinical isolates of Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM) was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87%) whereas for streptomycin, sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM) were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety, they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8); more standardization is needed for ethambutol.