Unfolding and refolding of cytochrome c driven by the interaction with lipid micelles

Binding of native cyt c to L-PG micelles leads to a partially unfolded conformation of cyt c. This micelle-bound state has no stable tertiary structure, but remains as -helical as native cyt c in solution. In contrast, binding of the acid-unfolded cyt c to L-PG micelles induces folding of the polypeptide, resulting in a similar helical state to that originated from the binding of native cyt c to L-PG micelles. Far-ultraviolet (UV) circular dichroism (CD) spectra showed that this common micelle-associated helical state (HL) has a native-like -helix content, but is highly expanded without a tightly packed hydrophobic core, as revealed by tryptophan fluorescence, near-UV, and Soret CD spectroscopy. The kinetics of the interaction of native and acid-unfolded cyt c was investigated by stopped-flow tryptophan fluorescence. Formation of HL from the native state requires the disruption of the tightly packed hydrophobic core in the native protein. This micelle-induced unfolding of cyt c occurs at a rate 0.1 s1, which is remarkably faster in the lipid environment compared with the expected rate of unfolding in solution. Refolding of acid-unfolded cyt c with L-PG micelles involves an early highly helical collapsed state formed during the burst phase (<3 ms), and the observed main kinetic event reports on the opening of this early compact intermediate prior to insertion into the lipid micelle

CMOS compatible integrated all-optical radio frequency spectrum analyzer

We report an integrated all-optical radio frequency spectrum analyzer based on a ~4cm long doped silica glass waveguide, with a bandwidth greater than 2.5 THz. We use this device to characterize the intensity power spectrum of ultrahighrepetition rate mode-locked lasers at repetition rates up to 400 GHz, and observe dynamic noise related behavior not observable with other technique

The effectiveness and cost-effectiveness of a complex community sport intervention to increase physical activity: An interrupted time series design

© Author(s) (or their employer(s)) 2018. Objectives: An effectiveness and cost-effectiveness analyses of two-staged community sports interventions, taster sports sessions compared with portfolio of community sport sessions. Design: Quasi-experiment using an interrupted time series design. Setting: Community sports projects delivered by eight lead partners in London Borough of Hounslow, United Kingdom Participants: Inactive people aged 14 plus years (n=246) were recruited between May 2013–February 2014. Interventions: Community sports interventions delivered in two stages, 6-week programme of taster sport sessions (Stage1) and 6-week programme of portfolio of community sporting sessions delivered by trained coaches (Stage2). Primary and secondary outcome measures: Change in days with ≥30 min of self-reported vigorous intensity physical activity (PA), moderate intensity PA, walking, sport, subjective wellbeing, and EQ5D5L quality-adjusted life-years (QALYs) Methods: Interrupted time series analysis evaluated the effectiveness of the two sports programmes. Cost-effectiveness analysis compares Stage 2 with Stage 1 from a provider’s perspective, reporting outcomes of incremental cost per Quality Adjusted Life Year (QALY) (2015/16 price year). Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results: Compared with Stage1, counterfactual change at 21 days in PA was lower for vigorous (log odds: -0.52; 95% CI -1, -0.03), moderate PA (-0.50; CI 0.94, -0.05) and sport (-0.56; CI -1.02, -0.10). Stage 2 increased walking (0.28; CI 0.3, 0.52). Effect overtime was similar. Counterfactual change at 21 days in wellbeing was positive particularly for ‘happiness’ (0.29; CI 0.06, 0.51). Stage2 was more expensive (£101 per participant) but increased QALYs (0.001; CI -0.034, 0.036). Cost per QALY for Stage2 was £50000 and has 29% chance of being cost effective (£30000 threshold). Conclusion: Community based sport interventions could increase PA among inactive people. Less intensive sports sessions may be more effective and cost-effective

Short-term and long-term cost-effectiveness of a pedometer-based exercise intervention in primary care: a within-trial analysis and beyond-trial modelling

Abstract Objectives A short-term and long-term cost-effectiveness analysis (CEA) of two pedometer-based walking interventions compared with usual care. Design (A) Short-term CEA: parallel three-arm cluster randomised trial randomised by household. (B) Long-term CEA: Markov decision model. Setting Seven primary care practices in South London, UK. Participants (A) Short-term CEA: 1023 people (922 households) aged 45–75 years without physical activity (PA) contraindications. (b) Long-term CEA: a cohort of 100 000 people aged 59–88 years. Interventions Pedometers, 12-week walking programmes and PA diaries delivered by post or through three PA consultations with practice nurses. Primary and secondary outcome measures Accelerometer-measured change (baseline to 12 months) in average daily step count and time in 10 min bouts of moderate to vigorous PA (MVPA), and EQ-5D-5L quality-adjusted life-years (QALY). Methods Resource use costs (£2013/2014) from a National Health Service perspective, presented as incremental cost-effectiveness ratios for each outcome over a 1-year and lifetime horizon, with cost-effectiveness acceptability curves and willingness to pay per QALY. Deterministic and probabilistic sensitivity analyses evaluate uncertainty. Results (A) Short-term CEA: At 12 months, incremental cost was £3.61 (£109)/min in ≥10 min MVPA bouts for nurse support compared with control (postal group). At £20 000/QALY, the postal group had a 50% chance of being cost saving compared with control. (B) Long-term CEA: The postal group had more QALYs (+759 QALYs, 95% CI 400 to 1247) and lower costs (−£11 million, 95% CI −12 to −10) than control and nurse groups, resulting in an incremental net monetary benefit of £26 million per 100 000 population. Results were sensitive to reporting serious adverse events, excluding health service use, and including all participant costs. Conclusions Postal delivery of a pedometer intervention in primary care is cost-effective long term and has a 50% chance of being cost-effective, through resource savings, within 1 year. Further research should ascertain maintenance of the higher levels of PA, and its impact on quality of life and health service use.This research was supported by the Health Technology Assessment (HTA) Programme, National Institute for Health Research (project number HTA 10/32/02 ISRCTN42122561)

Genome-Wide Linkage Scan to Identify Loci Associated with Type 2 Diabetes and Blood Lipid Phenotypes in the Sikh Diabetes Study

In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D) and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS). A total of 870 individuals (526 male/344 female) from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using Sall statistics (implemented in Merlin) did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011) occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016) and 5p15.33 (p = 0.0031) and for LDL cholesterol at 10p11.23 (p = 0.0045). Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance

Relativistic Description of Exclusive Semileptonic Decays of Heavy Mesons

Using quasipotential approach, we have studied exclusive semileptonic decays of heavy mesons with the account of relativistic effects. Due to more complete relativistic description of the $s$ quark more precise expressions for semileptonic form factors are obtained. Various differential distributions in exclusive semileptonic decays of heavy mesons are calculated. It is argued that consistent account of relativistic effects and HQET motivated choice of the parameters of quark-antiquark potential allow to get reliable value for the ratio $A_2(0)/A_1(0)$ in the $D\to K^*l\nu_l$ decay as well as the ratio~$\Gamma(D\to K^*l\nu_l)/\Gamma(D\to Kl\nu_l)$. All calculated branching ratios are in accord with available experimental data.Comment: 18 pages, LATEX, 2 figures inclosed + 4 Postscript figure

Failure of JoAnne's Global Fit to the Wilson Coefficients in Rare B Decays: A Left-Right Model Example

In the Standard Model and many of its extensions, it is well known that all of the observables associated with the rare decays $b\to s\gamma$ and $b\to s\ell^+\ell^-$ can be expressed in terms of the three Wilson coefficients, $C_{7L,9L,10L}(\mu \sim m_b)$, together with several universal kinematic functions. In particular it has been shown that the numerical values of these coefficients can be uniquely extracted by a three parameter global fit to data obtainable at future $B$-factories given sufficient integrated luminosity. In this paper we examine if such global fits are also sensitive to new operators beyond those which correspond to the above coefficients, i.e., whether is it possible that new operators can be of sufficient importance for the three parameter fit to fail and for this to be experimentally observable. Using the Left-Right Symmetric Model as an example of a scenario with an extended operator basis, we demonstrate via Monte Carlo techniques that such a possibility can indeed be realized. In some sense this potential failure of the global fit approach can actually be one of its greatest successes in identifying the existence of new physics.Comment: 30 pages, 6 figure

P and CP violation in B physics

While the Kobayashi--Maskawa single phase origin of CP violation passed its first crucial precision test in $B\to J/\psi K_S$, the chirality of weak $b$-quark couplings has not yet been carefully tested. We discuss recent proposals for studying the chiral and CP-violating structure of these couplings in radiative and in hadronic B decays.Comment: 15 pages, talk at PASCOS'03, Tata Inst., Mumbai, Jan. 200

VLBI Observations of a Complete Sample of Radio Galaxies. 10 Years Later

A complete sample of 27 radio galaxies was selected from the B2 and 3CR catalogs, in order to study their properties on the milliarcsecond scale. In the Appendix of this paper we present new radio images for 12 of them. Thanks to the present data, all the sources in this sample have been imaged at mas resolution. We discuss the general results. In particular we stress the evidence for high velocity jets in low power radio galaxies, we compare high and low power sources, and discuss the source properties in the light of the unified scheme models. We derive that the properties of parsec scale jets are similar in sources with different total radio power and kpc scale morphology. From the core - total radio power correlation, we estimate that relativistic jets with Lorentz factor $\gamma$ in the range 3 - 10 are present in high and low power radio sources. We discuss also the possible existence of a two velocity structure in the jets (fast spine and lower velocity external shear layer).Comment: 38 pages, 18 figures with an Appendix; ApJ in press (vol. 551, Apr. 20, 2001 issue

Heavy Quark Symmetry Violation in Semileptonic Decays of D Mesons

The decays of $D$ mesons to $K l \nu$ and $K^* l \nu$ final states exhibit significant deviations from the predictions of heavy-quark symmetry, as one might expect since the strange quark's mass is of the same order as the QCD scale. Nonetheless, in order to understand where the most significant effects might lie for heavier systems (such as $B \to D l\nu$ and $B \to D^* l\nu$), the pattern of these deviations is analyzed from the standpoint of perturbative QCD and ${\cal O}(1/m_s)$ corrections. Two main effects are noted. First, the perturbative QCD corrections lead to an overall decrease of predicted rates, which can be understood in terms of production of excited kaonic states. Second, ${\cal O}(1/m_s)$ effects tend to cancel the perturbative QCD corrections in the case of $Kl\nu$ decay, while they have minimal effect in $K^*l\nu$ decay.Comment: 25 pages (LaTeX) + 7 pages of Postscript figures (included at end), EFI-92-3