Boosted Beta regression.

Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1). Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures

THE KNEE INJURIES IN SKIING: MECHANISMS AND ASSESSMENT

The purpose of this study is to describe the main mechanisms of knee injuries in skiing, and especially the dominant role of anterior cruciate ligament in these injuries. To complete classical clinical tests of ligamentous laxity and help defining the appropriate time to return to sports after an anterior cruciate ligament reconstruction, accurate 3D kinematic assessment of the weight-bearing knee joint is essential. Current limits of such an assessment are described. Then recent studies of patients with anterior cruciate ligament deficient and reconstructed, using a tibio femoral tracking device specially designed to analyse the kinematics of the knee, are presented

Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation

Objective Mitochondrial disturbances of energy-generating systems in childhood are a heterogeneous group of disorders. The aim of this multi-site survey was to characterise the natural course of a novel mitochondrial disease with ATP synthase deficiency and mutation in the TMEM70 gene. Methods Retrospective clinical data and metabolic profiles were collected and evaluated in 25 patients (14 boys, 11 girls) from seven European countries with a c. 317-2A -> G mutation in the TMEM70 gene. Results Severe muscular hypotonia (in 92% of newborns), apnoic spells (92%), hypertrophic cardiomyopathy (HCMP; 76%) and profound lactic acidosis (lactate 5-36 mmol/l; 92%) with hyperammonaemia (100-520 mu mol/l; 86%) were present from birth. Ten patients died within the first 6 weeks of life. Most patients surviving the neonatal period had persisting muscular hypotonia and developed psychomotor delay. HCMP was non-progressive and even disappeared in some children. Hypospadia was present in 54% of the boys and cryptorchidism in 67%. Increased excretion of lactate and 3-methylglutaconic acid (3-MGC) was observed in all patients. In four surviving patients, life-threatening hyperammonaemia occurred during childhood, triggered by acute gastroenteritis and prolonged fasting. Conclusions ATP synthase deficiency with mutation in TMEM70 should be considered in the diagnosis and management of critically ill neonates with early neonatal onset of muscular hypotonia, HCMP and hypospadias in boys accompanied by lactic acidosis, hyperammonaemia and 3-MGC-uria. However, phenotype severity may vary significantly. The disease occurs frequently in the Roma population and molecular-genetic analysis of the TMEM70 gene is sufficient for diagnosis without need of muscle biopsy in affected children

System-wide Perturbation Analysis with Nearly Complete Coverage of the Yeast Proteome by Single-shot Ultra HPLC Runs on a Bench Top Orbitrap

Yeast remains an important model for systems biology and for evaluating proteomics strategies. In-depth shotgun proteomics studies have reached nearly comprehensive coverage, and rapid, targeted approaches have been developed for this organism. Recently, we demonstrated that single LC-MS/MS analysis using long columns and gradients coupled to a linear ion trap Orbitrap instrument had an unexpectedly large dynamic range of protein identification (Thakur, S. S., Geiger, T., Chatterjee, B., Bandilla, P., Frohlich, F., Cox, J., and Mann, M. (2011) Deep and highly sensitive proteome coverage by LC-MS/MS without prefractionation. Mol. Cell Proteomics 10, 10.1074/mcp.M110.003699). Here we couple an ultra high pressure liquid chromatography system to a novel bench top Orbitrap mass spectrometer (Q Exactive) with the goal of nearly complete, rapid, and robust analysis of the yeast proteome. Single runs of filter-aided sample preparation (FASP)-prepared and LysC-digested yeast cell lysates identified an average of 3923 proteins. Combined analysis of six single runs improved these values to more than 4000 identified proteins/run, close to the total number of proteins expressed under standard conditions, with median sequence coverage of 23%. Because of the absence of fractionation steps, only minuscule amounts of sample are required. Thus the yeast model proteome can now largely be covered within a few hours of measurement time and at high sensitivity. Median coverage of proteins in Kyoto Encyclopedia of Genes and Genomes pathways with at least 10 members was 88%, and pathways not covered were not expected to be active under the conditions used. To study perturbations of the yeast proteome, we developed an external, heavy lysine-labeled SILAC yeast standard representing different proteome states. This spike-in standard was employed to measure the heat shock response of the yeast proteome. Bioinformatic analysis of the heat shock response revealed that translation-related functions were down-regulated prominently, including nucleolar processes. Conversely, stress-related pathways were up-regulated. The proteomic technology described here is straightforward, rapid, and robust, potentially enabling widespread use in the yeast and other biological research communities

An algal enzyme required for biosynthesis of the most abundant marine carotenoids.

Fucoxanthin and its derivatives are the main light-harvesting pigments in the photosynthetic apparatus of many chromalveolate algae and represent the most abundant carotenoids in the world's oceans, thus being major facilitators of marine primary production. A central step in fucoxanthin biosynthesis that has been elusive so far is the conversion of violaxanthin to neoxanthin. Here, we show that in chromalveolates, this reaction is catalyzed by violaxanthin de-epoxidase-like (VDL) proteins and that VDL is also involved in the formation of other light-harvesting carotenoids such as peridinin or vaucheriaxanthin. VDL is closely related to the photoprotective enzyme violaxanthin de-epoxidase that operates in plants and most algae, revealing that in major phyla of marine algae, an ancient gene duplication triggered the evolution of carotenoid functions beyond photoprotection toward light harvesting

Kaluza-Klein Thresholds and Regularization (In)dependence

We present a method to control the regularization scheme dependence in the running of couplings in Kaluza-Klein theories. Specifically we consider the scalar theory in five dimensions, assuming that one dimension is compactified and we study various regularization schemes in order to analyze concretely the regularization scheme dependence of the Kaluza-Klein threshold effects. We find that in one-loop order, although the $\beta$-functions are different for the different schemes, the net difference in the running of the coupling among the different schemes is very small for the entire range of energies. Our results have been extended to include more than one radii, and the gauge coupling unification is re-examined. Strings are also used as a regulator. We obtain a particular regularization of effective field theory which can accurately describe the string Kaluza-Klein threshold effects.Comment: 39 pages, 12 figures uses epsf.st

Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results

Background: Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. Methods: We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. Results: After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). Conclusions: LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therap

Theory, Politics... and History? Early post-war Soviet Control Engineering

A fascinating feature of post-war control engineering in the former Soviet Union was the rôle played by the study of the history of the discipline. Even before and during World War II some Soviet control scientists were actively researching the history of their subject; while after the war, historical studies played an important part both in technical developments and in legitimating a native Russian tradition. Two of the most important figures in this historical activity were A. A. Andronov and I. N. Voznesenskii, whose contributions are briefly considered

Brane/Flux Annihilation and the String Dual of a Non-Supersymmetric Field Theory

We consider the dynamics of p anti-D3 branes inside the Klebanov-Strassler geometry, the deformed conifold with M units of RR 3-form flux around the S^3. We find that for p<<M the system relaxes to a nonsupersymmetric NS 5-brane ``giant graviton'' configuration, which is classically stable, but quantum mechanically can tunnel to a nearby supersymmetric vacuum with M-p D3 branes. This decay mode is exponentially suppressed and proceeds via the nucleation of an NS 5-brane bubble wall. We propose a dual field theory interpretation of the decay as the transition between a nonsupersymmetric ``baryonic'' branch and a supersymmetric ``mesonic'' branch of the corresponding SU(2M-p)x SU(M-p) low energy gauge theory. The NS 5-brane tunneling process also provides a simple explanation of the geometric transition by which D3-branes can dissolve into 3-form flux.Comment: 27 pages, 4 figures, typo correcte