Dynamical non-axisymmetric instabilities in rotating relativistic stars

We present new results on dynamical instabilities in rapidly rotating neutron-stars. In particular, using numerical simulations in full General Relativity, we analyse the effects that the stellar compactness has on the threshold for the onset of the dynamical bar-mode instability, as well as on the appearance of other dynamical instabilities. By using an extrapolation technique developed and tested in our previous study [1], we explicitly determine the threshold for a wide range of compactnesses using four sequences of models of constant baryonic mass comprising a total of 59 stellar models. Our calculation of the threshold is in good agreement with the Newtonian prediction and improves the previous post-Newtonian estimates. In addition, we find that for stars with sufficiently large mass and compactness, the m=3 deformation is the fastest growing one. For all of the models considered, the non-axisymmetric instability is suppressed on a dynamical timescale with an m=1 deformation dominating the final stages of the instability. These results, together with those presented in [1], suggest that an m=1 deformation represents a general and late-time feature of non-axisymmetric dynamical instabilities both in full General Relativity and in Newtonian gravity.Comment: To appear on CQG, NFNR special issue. 16 pages, 5 color figures, movies from http://www.fis.unipr.it/numrel/BarMode/ResearchBarMode.htm

Interaction of Silymarin Flavonolignans with Organic Anion-Transporting Polypeptides

Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption and elimination, including the intestine and liver. Silymarin is a popular herbal supplement often used by patients with chronic liver disease; higher oral doses than those customarily used (140 mg three times/day) are being evaluated clinically. The present study examined the effect of silymarin flavonolignans on OATP1B1-, OATP1B3-, and OATP2B1-mediated transport in cell lines stably expressing these transporters and in human hepatocytes. In overexpressing cell lines, OATP1B1- and OATP1B3-mediated estradiol-17β-glucuronide uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin flavonolignans investigated. OATP1B1-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively). Furthermore, silymarin, silybin A, and silybin B (100 µM) significantly inhibited OATP-mediated estradiol-17β-glucuronide and rosuvastatin uptake into human hepatocytes. Calculation of the maximal unbound portal vein concentrations/IC50 values indicated a low risk for silymarin-drug interactions in hepatic uptake with a customary silymarin dose. The extent of silymarin-drug interactions depends on OATP isoform specificity and concentrations of flavonolignans at the site of drug transport. Higher than customary doses of silymarin, or formulations with improved bioavailability, may increase the risk of flavonolignan interactions with OATP substrates in patients

Numerical relativity with characteristic evolution, using six angular patches

The characteristic approach to numerical relativity is a useful tool in evolving gravitational systems. In the past this has been implemented using two patches of stereographic angular coordinates. In other applications, a six-patch angular coordinate system has proved effective. Here we investigate the use of a six-patch system in characteristic numerical relativity, by comparing an existing two-patch implementation (using second-order finite differencing throughout) with a new six-patch implementation (using either second- or fourth-order finite differencing for the angular derivatives). We compare these different codes by monitoring the Einstein constraint equations, numerically evaluated independently from the evolution. We find that, compared to the (second-order) two-patch code at equivalent resolutions, the errors of the second-order six-patch code are smaller by a factor of about 2, and the errors of the fourth-order six-patch code are smaller by a factor of nearly 50.Comment: 12 pages, 5 figures, submitted to CQG (special NFNR issue

The Origin of Ina: Evidence for Inflated Lava Flows on the Moon

Ina is an enigmatic volcanic feature on the Moon known for its irregularly shaped mounds, the origin of which has been debated since the Apollo Missions. Three main units are observed on the floor of the depression (2.9 km across, < or =64 m deep) located at the summit of a low-shield volcano: irregularly shaped mounds up to 20 m tall, a lower unit 1 to 5 m in relief that surrounds the mounds, and blocky material. Analyses of Lunar Reconnaissance Orbiter Camera images and topography show that features in Ina are morphologically similar to terrestrial inflated lava flows. Comparison of these unusual lunar mounds and possible terrestrial analogs leads us to hypothesize that features in Ina were formed through lava flow inflation processes. While the source of the lava remains unclear, this new model suggests that as the mounds inflated, breakouts along their margins served as sources for surface flows that created the lower morphologic unit. Over time, mass wasting of both morphologic units has exposed fresh surfaces observed in the blocky unit. Ina is different than the terrestrial analogs presented in this study in that the lunar features formed within a depression, no vent sources are observed, and no cracks are observed on the mounds. However, lava flow inflation processes explain many of the morphologic relationships observed in Ina and are proposed to be analogous with inflated lava flows on Earth

Hepatic Metabolism and Biliary Excretion of Silymarin Flavonolignans in Isolated Perfused Rat Livers: Role of Multidrug Resistance-Associated Protein 2 (Abcc2)

Silymarin, an extract from seeds of Silybum marianum, is used by 8-33% of patients to self-treat chronic viral hepatitis C in the United States. Studies in humans and rodents suggest that biliary excretion of glucuronide and sulfate conjugates is the major route for silymarin’s elimination. To determine the role of multidrug resistance associated-protein 2, Mrp2 (Abcc2), in the biliary excretion of silymarin, the hepatobiliary disposition of the six major silymarin flavonolignans was studied using isolated perfused livers (IPRLs) from wild-type (WT) and Mrp2-deficient (TR-) Wistar rats. For all flavonolignans, approximately 96% of the dose was cleared from perfusate within 30 min in both WT and TR- livers, and < 5% of parent was recovered in bile or perfusate by the end of the perfusion. In WT livers, the percentage of dose excreted as conjugates into bile varied for each flavonolignan (silychristin, 51.6% ± 9.3; silydianin, 101.5% ± 28.3; silybin A, 21.0% ± 8.3; silybin B, 31.7% ± 13.2; isosilybin A, 50.5% ± 23.6; isosilybin B, 42.8% ± 19.3). Among the flavonolignans, only silydianin was primarily glucuronidated and almost completely recovered in bile. In TR- livers, biliary excretion of flavonolignan conjugates was reduced 80-92%, with 30-83% of each flavonolignan conjugate recovered in perfusate compared to only 5-30% at 90 min. Biliary excretion of glucuronide and sulfate conjugates of all flavonolignans were reduced by 94-98% and 73-84% respectively, in TR- IPRLs. These data indicate a primary role for Mrp2 in the biliary elimination of silymarin flavonolignan conjugates

AMR, stability and higher accuracy

Efforts to achieve better accuracy in numerical relativity have so far focused either on implementing second order accurate adaptive mesh refinement or on defining higher order accurate differences and update schemes. Here, we argue for the combination, that is a higher order accurate adaptive scheme. This combines the power that adaptive gridding techniques provide to resolve fine scales (in addition to a more efficient use of resources) together with the higher accuracy furnished by higher order schemes when the solution is adequately resolved. To define a convenient higher order adaptive mesh refinement scheme, we discuss a few different modifications of the standard, second order accurate approach of Berger and Oliger. Applying each of these methods to a simple model problem, we find these options have unstable modes. However, a novel approach to dealing with the grid boundaries introduced by the adaptivity appears stable and quite promising for the use of high order operators within an adaptive framework

EVALUATION OF THE CONTRIBUTION OF CYTOCHROME P450 3A4 TO HUMAN LIVER MICROSOMAL BUPROPION HYDROXYLATION

This paper is available online at http://dmd.aspetjournals.org ABSTRACT: The purpose of this investigation was to evaluate the role of cytochrome P450 (CYP) 3A4 in human liver microsomal bupropion (BUP) hydroxylation. Across the BUP concentration range of 0.075 to 12 mM, cDNA-expressed CYP3A4 demonstrated BUP hydroxylase activity only when incubated with concentrations &gt;4 mM. When assayed at 12 mM BUP, cDNA-expressed CYP3A4 catalyzed BUP hydroxylation at a 30-fold lower rate than cDNA-expressed CYP2B6 (0.2 versus 7 pmol/min/pmol of P450 Bupropion (BUP) 1 is a second-generation antidepressant agent that is also used in the management of smoking cessation. This drug undergoes extensive hepatic metabolism in humans via oxidative and reductive pathways Clinical pharmacokinetic studies have demonstrated 3-to 10-fold interindividual differences in HBUP C max and AUC In a prior in vitro study reported in abstract form, CYP3A4 demonstrated the second highest rate of BUP hydroxylation among a panel of cDNA-expressed P450 isozyme

The effectiveness of manual stretching in the treatment of plantar heel pain: a systematic review

Background: Plantar heel pain is a commonly occurring foot complaint. Stretching is frequently utilised as a treatment, yet a systematic review focusing only on its effectiveness has not been published. This review aimed to assess the effectiveness of stretching on pain and function in people with plantar heel pain. Methods: Medline, EMBASE, CINAHL, AMED, and The Cochrane Library were searched from inception to July 2010. Studies fulfilling the inclusion criteria were independently assessed, and their quality evaluated using the modified PEDro scale. Results: Six studies including 365 symptomatic participants were included. Two compared stretching with a control, one study compared stretching to an alternative intervention, one study compared stretching to both alternative and control interventions, and two compared different stretching techniques and durations. Quality rating on the modified Pedro scale varied from two to eight out of a maximum of ten points. The methodologies and interventions varied significantly between studies, making meta-analysis inappropriate. Most participants improved over the course of the studies, but when stretching was compared to alternative or control interventions, the changes only reached statistical significance in one study that used a combination of calf muscle stretches and plantar fascia stretches in their stretching programme. Another study comparing different stretching techniques, showed a statistically significant reduction in some aspects of pain in favour of plantar fascia stretching over calf stretches in the short term. Conclusions: There were too few studies to assess whether stretching is effective compared to control or other interventions, for either pain or function. However, there is some evidence that plantar fascia stretching may be more effective than Achilles tendon stretching alone in the short-term. Appropriately powered randomised controlled trials, utilizing validated outcome measures, blinded assessors and long-term follow up are needed to assess the efficacy of stretching

HIV non-B subtype distribution: emerging trends and risk factors for imported and local infections newly diagnosed in South Australia

Monitoring HIV subtype distribution is important for understanding transmission dynamics. Subtype B has historically been dominant in Australia, but in recent years new clades have appeared. Since 2000, clade data have been collected as part of HIV surveillance in South Australia. The aim of this study was to evaluate the prevalence of and risk factors for HIV-1 non-B subtypes. The study population was composed of newly diagnosed, genotyped HIV subjects in South Australia between 2000 and 2010. We analyzed time trends and subtype patterns in this cohort; notification data were aggregated into three time periods (2000–2003, 2004–2006, and 2007–2010). Main outcome measures were number of new non-B infections by year, exposure route, and other demographic characteristics. There were 513 new HIV diagnoses; 425 had information on subtype. The majority (262/425) were in men who have sex with men (MSM), predominantly subtype B and acquired in Australia. Infections acquired in Australia decreased from 77% (2000–2003) to 64% (2007–2010) ( p = 0.007) and correspondingly the proportion of subtype B declined from 85% to 68% ( p = 0.002). Non-B infections were predominantly (83%) heterosexual contacts, mostly acquired overseas (74%). The majority (68%) of non-B patients were born outside of Australia. There was a non-significant increase from 1.6% to 4.2% in the proportion of locally transmitted non-B cases (p = 0.3). Three non-B subtypes and two circulating recombinant forms (CRFs) were identified: CRF_AE (n = 41), C (n = 36), CRF_AG (n = 13), A (n = 9), and D (n = 2). There has been a substantial increase over the past decade in diagnosed non-B infections, primarily through cases acquired overseas