Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.

BACKGROUND: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins. METHODS: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1. RESULTS: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins. CONCLUSIONS: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed

Defisit Anggaran Dan Implikasinya Terhadap Perkembangan Ekonomi Dan Kinerja Keuangan Kabupaten Tebo

This study aims to 1) To analyze the determinants that will influence the budget deficit in Tebo district budget. 2) To analyze whether there is a correlation between the budget deficit with Tebo regency economic development. 3) To analyze whether there is a correlation between the financial performance of the budget deficit with Tebo regency. The method used in this study is a secondary data analysis methods. Based on the results of testing the model regression shows the value of the F-count is high at 12 130. With an alpha of 0.05 df1 = 3, DF2 = 4 obtained F-table at 6:59. so the F-count> F-table. this indicates that the independent variables are jointly significant effect on the dependent variable, so that personnel expenditure, capital expenditure and spending on goods and services during the period 2004-2011 are jointly significant effect on the budget deficit in Tebo regency. Each there is an increase of 1 billion budget deficit, it will cause a reduction in personnel expenses amounted to 4.52 billion Tebo regency. Any increased capital expenditure budget of 1 billion budget deficit will increase by 5.01 billion. Any increased budget allocation of goods and services amounted to 1 billion, the budget deficit will increase by 8.17 billion. the greatest influence on the budget deficit from the budget allocation of goods and services. The results of the analysis of the budget deficit relationship with economic development in Tebo regency during 2006-2010 showed that the budget deficit by using a simple Pearson correlation test has a relationship of -0.07986. These results illustrate that the budget deficit has a negative relationship with economic development. The results of the analysis of the relationship with the budget deficit in the region\u27s financial performance during the period 2006-2010 Tebo regency showed that the budget deficit with the financial performance using tools Pearson correlation test has a relationship of -0.04703. The results illustrate that the budget deficit has a negative relationship with financial performance

Predicting cortical bone adaptation to axial loading in the mouse tibia

The development of predictive mathematical models can contribute to a deeper understanding of the specific stages of bone mechanobiology and the process by which bone adapts to mechanical forces. The objective of this work was to predict, with spatial accuracy, cortical bone adaptation to mechanical load, in order to better understand the mechanical cues that might be driving adaptation. The axial tibial loading model was used to trigger cortical bone adaptation in C57BL/6 mice and provide relevant biological and biomechanical information. A method for mapping cortical thickness in the mouse tibia diaphysis was developed, allowing for a thorough spatial description of where bone adaptation occurs. Poroelastic finite-element (FE) models were used to determine the structural response of the tibia upon axial loading and interstitial fluid velocity as the mechanical stimulus. FE models were coupled with mechanobiological governing equations, which accounted for non-static loads and assumed that bone responds instantly to local mechanical cues in an on–off manner. The presented formulation was able to simulate the areas of adaptation and accurately reproduce the distributions of cortical thickening observed in the experimental data with a statistically significant positive correlation (Kendall's τ rank coefficient τ = 0.51, p < 0.001). This work demonstrates that computational models can spatially predict cortical bone mechanoadaptation to a time variant stimulus. Such models could be used in the design of more efficient loading protocols and drug therapies that target the relevant physiological mechanisms

Quantum feedback control of a superconducting qubit: Persistent Rabi oscillations

The act of measurement bridges the quantum and classical worlds by projecting a superposition of possible states into a single, albeit probabilistic, outcome. The time-scale of this "instantaneous" process can be stretched using weak measurements so that it takes the form of a gradual random walk towards a final state. Remarkably, the interim measurement record is sufficient to continuously track and steer the quantum state using feedback. We monitor the dynamics of a resonantly driven quantum two-level system -- a superconducting quantum bit --using a near-noiseless parametric amplifier. The high-fidelity measurement output is used to actively stabilize the phase of Rabi oscillations, enabling them to persist indefinitely. This new functionality shows promise for fighting decoherence and defines a path for continuous quantum error correction.Comment: Manuscript: 5 Pages and 3 figures ; Supplementary Information: 9 pages and 3 figure

Acupuncture Point Localization Varies Among Acupuncturists

Background: Studies assessing the point-specific effect of acupuncture or the characteristics of acupuncture points (APs) tend to yield inconclusive results. In order to identify a possible confounding factor, we aimed to examine the variability in AP localization by means of a survey. Material and Methods: Attendees of the 14th ICMART (International Council of Medical Acupuncture and Related Techniques) congress as well as DAGfA (German Medical Society of Acupuncture) lecturers and students were asked to locate and mark the APs LI 10 and TH 5 on a research assistant's arm. Identified points were transferred into a coordinate system, and the respective bivariate distribution function was calculated. Additionally, participants filled out a questionnaire about their acupuncture education and experience, the acupuncture style and point localization techniques used most frequently, and their estimation of the size of an AP. Results: The areas of the ellipses, theoretically containing 95% of AP localizations, varied between 44.49 and 5.18 cm(2). The largest distance between 2 identified points was 8.45 cm for LI 10 and 5.3 cm for TH 5. Apart from being trained at the same school, no other factor could be identified that determined the variability in AP localization. Conclusion: Our results indicate that congruity of AP localization among experienced acupuncturists might be low. Although there are some limitations to our results, this possible bias should be taken into account when conducting acupuncture trials and interpreting results of previous acupuncture studies

Oxygen Diffusion Layer on Ti–6Al–4V Alloy: Scratch and Dry Wear Resistance

Ti–6Al–4V has prominent physical and mechanical properties, which nominate it for various engineering applications. A drawback of the alloy, however, is low scratch and wear resistance, which can be improved by a diffusion treatment. Oxygen diffusion layer (ODL) was produced on Ti–6Al–4V by thermal oxidation at a temperature of 850 °C for 3 and 6 h. Hardness of the samples was measured using a nano-indentation tester. Micro-scratch tests were performed under progressive and constant normal loads of 0–50 N. Dry wear behavior of the samples was studied using a ball-on-disk tribometer. The wear tests were carried out under various normal loads of 7.5, 15 and 30 N for sliding distances of 50, 100, 200 and 300 m using alumina balls as the counterface. The wear and scratch tracks were examined by scanning electron microscope and surface profilometer. The ODL samples showed higher hardness and lower plastic deformation as compared with Ti–6Al–4V. The brittle behavior of the ODL samples caused the formation of cracks and the development of large acoustic signals during scratching under normal loads of 40 and 50 N. The results also showed a higher scratch and wear resistance of the ODL samples compared with Ti–6Al–4V. However, the oxygen diffusion layer formed after 3 h of oxidation showed a sharp increase in the wear rate of the alloy under a normal load of 30 N and a sliding distance of 100 m

L-Arginine promotes gut hormone release and reduces food intake in rodents

Aims: To investigate the anorectic effect of L‐arginine (L‐Arg) in rodents. Methods: We investigated the effects of L‐Arg on food intake, and the role of the anorectic gut hormones glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), the G‐protein‐coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results: Oral gavage of L‐Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet‐induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L‐Arg stimulated GLP‐1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP‐1 and PYY receptors did not influence the anorectic effect of L‐Arg. L‐Arg‐mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L‐Arg suppressed food intake in rats. Conclusions: L‐Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L‐Arg is unlikely to be mediated by GLP‐1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L‐Arg suppressed food intake in rats, suggesting that L‐Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L‐Arg suppresses food intake and its utility in the treatment of obesity