PMI: A Delta Psi(m) Independent Pharmacological Regulator of Mitophagy

Mitophagy is central to mitochondrial and cellular homeostasis and operates via the PINK1/Parkin pathway targeting mitochondria devoid of membrane potential (ΔΨm) to autophagosomes. Although mitophagy is recognized as a fundamental cellular process, selective pharmacologic modulators of mitophagy are almost nonexistent. We developed a compound that increases the expression and signaling of the autophagic adaptor molecule P62/SQSTM1 and forces mitochondria into autophagy. The compound, P62-mediated mitophagy inducer (PMI), activates mitophagy without recruiting Parkin or collapsing ΔΨm and retains activity in cells devoid of a fully functional PINK1/Parkin pathway. PMI drives mitochondria to a process of quality control without compromising the bio-energetic competence of the whole network while exposing just those organelles to be recycled. Thus, PMI circumvents the toxicity and some of the nonspecific effects associated with the abrupt dissipation of ΔΨm by ionophores routinely used to induce mitophagy and represents a prototype pharmacological tool to investigate the molecular mechanisms of mitophagy

A theory-based approach to understanding condom errors and problems reported by men attending an STI clinic

The official published version can be accessed from the link below - Copyright @ 2008 Springer VerlagWe employed the information–motivation–behavioral skills (IMB) model to guide an investigation of correlates for correct condom use among 278 adult (18–35 years old) male clients attending a sexually transmitted infection (STI) clinic. An anonymous questionnaire aided by a CD-recording of the questions was administered. Linear Structural Relations Program was used to conduct path analyses of the hypothesized IMB model. Parameter estimates showed that while information did not directly affect behavioral skills, it did have a direct (negative) effect on condom use errors. Motivation had a significant direct (positive) effect on behavioral skills and a significant indirect (positive) effect on condom use errors through behavioral skills. Behavioral skills had a direct (negative) effect on condom use errors. Among men attending a public STI clinic, these findings suggest brief, clinic-based, safer sex programs for men who have sex with women should incorporate activities to convey correct condom use information, instill motivation to use condoms correctly, and directly enhance men’s behavioral skills for correct use of condoms

Universality in solar flare and earthquake occurrence

Earthquakes and solar flares are phenomena involving huge and rapid releases of energy characterized by complex temporal occurrence. By analysing available experimental catalogs, we show that the stochastic processes underlying these apparently different phenomena have universal properties. Namely both problems exhibit the same distributions of sizes, inter-occurrence times and the same temporal clustering: we find afterflare sequences with power law temporal correlations as the Omori law for seismic sequences. The observed universality suggests a common approach to the interpretation of both phenomena in terms of the same driving physical mechanism

Adapting SAM for CDF

The CDF and D0 experiments probe the high-energy frontier and as they do so have accumulated hundreds of Terabytes of data on the way to petabytes of data over the next two years. The experiments have made a commitment to use the developing Grid based on the SAM system to handle these data. The D0 SAM has been extended for use in CDF as common patterns of design emerged to meet the similar requirements of these experiments. The process by which the merger was achieved is explained with particular emphasis on lessons learned concerning the database design patterns plus realization of the use cases.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 4 pages, pdf format, TUAT00

Diffusion entropy and waiting time statistics of hard x-ray solar flares

We analyze the waiting time distribution of time distances $\tau$ between two nearest-neighbor flares. This analysis is based on the joint use of two distinct techniques. The first is the direct evaluation of the distribution function $\psi(\tau)$, or of the probability, $\Psi(tau)$, that no time distance smaller than a given $\tau$ is found. We adopt the paradigm of the inverse power law behavior, and we focus on the determination of the inverse power index $\mu$, without ruling out different asymptotic properties that might be revealed, at larger scales, with the help of richer statistics. The second technique, called Diffusion Entropy (DE) method, rests on the evaluation of the entropy of the diffusion process generated by the time series. The details of the diffusion process depend on three different walking rules, which determine the form and the time duration of the transition to the scaling regime, as well as the scaling parameter $\delta$. With the first two rules the information contained in the time series is transmitted, to a great extent, to the transition, as well as to the scaling regime. The same information is essentially conveyed, by using the third rules, into the scaling regime, which, in fact, emerges very quickly after a fast transition process. We show that the significant information hidden within the time series concerns memory induced by the solar cycle, as well as the power index $\mu$. The scaling parameter $\delta$ becomes a simple function of $\mu$, when memory is annihilated. Thus, the three walking rules yield a unique and precise value of $\mu$ if the memory is wisely taken under control, or cancelled by shuffling the data. All this makes compelling the conclusion that $\mu = 2.138 \pm 0.01$.Comment: 23 pages, 13 figure

A methodology for the capture and analysis of hybrid data: a case study of program debugging

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Chandra and RXTE Spectra of the Burster GS 1826-238

Using simultaneous observations from Chandra and RXTE, we investigated the LMXB GS 1826-238 with the goal of studying its spectral and timing properties. The uninterrupted Chandra observation captured 6 bursts (RXTE saw 3 of the 6), yielding a recurrence time of 3.54 +/- 0.03 hr. Using the proportional counter array on board RXTE, we made a probable detection of 611 Hz burst oscillations in the decaying phases of the bursts with an average rms signal amplitude of 4.8%. The integrated persistent emission spectrum can be described as the dual Comptonization of ~ 0.3 keV soft photons by a plasma with kT_e ~ 20 keV and an optical depth of about 2.6 (interpreted as emission from the accretion disk corona), plus the Comptonization of hotter ~ 0.8 keV seed photons by a ~ 6.8 keV plasma (interpreted as emission from or near the boundary layer). We discovered evidence for a neutral Fe K\alpha emission line, and we found interstellar Fe L_II and Fe L_III absorption features. The burst spectrum can be fit by fixing the disk Comptonization parameters to the persistent emission best-fit values, and adding a blackbody. The blackbody/seed photon temperature at the peak of the burst is ~ 1.8 keV and returns to ~ 0.8 keV over 200 s. The blackbody radius is consistent with R_bb = 10.3-11.7 km assuming a distance of 6 kpc; however, by accounting for the fraction of the surface that is obscured by the disk as a function of binary inclination, we determined the source distance must actually be near 5 kpc in order for the stellar radius to lie within the commonly assumed range of 10-12 km.Comment: Accepted for publication in ApJ; 13 pages, 6 figure

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

Noise storm continua: power estimates for electron acceleration

We use a generic stochastic acceleration formalism to examine the power $L_{\rm in}$ (${\rm erg s^{-1}}$) input to nonthermal electrons that cause noise storm continuum emission. The analytical approach includes the derivation of the Green's function for a general second-order Fermi process, and its application to obtain the particular solution for the nonthermal electron distribution resulting from the acceleration of a Maxwellian source in the corona. We compare $L_{\rm in}$ with the power $L_{\rm out}$ observed in noise storm radiation. Using typical values for the various parameters, we find that $L_{\rm in} \sim 10^{23-26}$ ${\rm erg s^{-1}}$, yielding an efficiency estimate $\eta \equiv L_{\rm out}/L_{\rm in}$ in the range 10^{-10} \lsim \eta \lsim 10^{-6} for this nonthermal acceleration/radiation process. These results reflect the efficiency of the overall process, starting from electron acceleration and culminating in the observed noise storm emission.Comment: Accepted for publication in Solar Physic