Testing slim-disk models on the thermal spectra of LMC X-3

Slim-disk models describe accretion flows at high luminosities, while reducing to the standard thin disk form in the low luminosity limit. We have developed a new spectral model, slimbb, within the framework of XSPEC, which describes fully relativistic slim-disk accretion and includes photon ray-tracing that starts from the disk photosphere, rather than the equatorial plane. We demonstrate the features of this model by applying it to RXTE spectra of the persistent black-hole X-ray binary LMC X-3. LMC X-3 has the virtues of exhibiting large intensity variations while maintaining itself in soft spectral states which are well described using accretion-disk models, making it an ideal candidate to test the aptness of slimbb. Our results demonstrate consistency between the low-luminosity (thin-disk) and high luminosity (slim-disk) regimes. We also show that X-ray continuum-fitting in the high accretion rate regime can powerfully test black-hole accretion disk models.Comment: 6 pages, 5 figures, submitted to A&

Coronary bypass surgery with or without surgical ventricular reconstruction

Coronary bypass surgery with or without surgical ventricular reconstruction. Jones RH, Velazquez EJ, Michler RE, Sopko G, Oh JK, O'Connor CM, Hill JA, Menicanti L, Sadowski Z, Desvigne-Nickens P, Rouleau JL, Lee KL; STICH Hypothesis 2 Investigators. Collaborators (379)Bochenek A, Krejca M, Trusz-Gluza M, Wita K, Zembala M, Przybylski R, Kukulski T, Cherniavsky A, Marchenko A, Romanov A, Wos S, Deja M, Golba K, Kot J, Rao V, Iwanochko M, Renton J, Hemeon S, Rogowski J, Rynkiewicz A, Betlejewski P, Sun B, Crestanello J, Binkley P, Chang J, Ferrazzi P, Gavazzi A, Senni M, Sadowski J, Kapelak B, Sobczyk D, Wrobel K, Pirk J, Jandova R, Velazquez E, Smith P, Milano C, Adams P, Menicanti L, Di Donato M, Castelvecchio S, Dagenais F, Dussault G, Dupree C, Sheridan B, Schuler C, Yii M, Prior D, Mack J, Racine N, Bouchard D, Ducharme A, Lavoignat J, Maurer G, Grimm M, Lang I, Adlbrecht C, Religa Z, Biederman A, Szwed H, Sadowski Z, Rajda M, Ali I, Howlett J, MacFarlane M, Siepe M, Beyersdorf F, Cuerten C, Wiechowski S, Mokrzycki K, Hill J, Beaver T, Olitsky D, Bernstein V, Janusz M, O'Neill V, Grayburn P, Hebeler R, Hamman B, Aston S, Gradinac S, Vukovic M, Djokovic L, Benetis R, Jankauskiene L, Friedrich I, Buerke M, Paraforos A, Quaini E, Cirillo M, Chua L, Lim C, Kwok B, Kong S, Stefanelli G, Labia C, Bergh C, Gustafsson C, Daly R, Rodeheffer R, Nelson S, Maitland A, Isaac D, Holland M, Di Benedetto G, Attisano T, Sievers H, Schunkert H, Stierle U, Haddad H, Hendry P, Donaldson J, Birjiniuk V, Harrington M, Nawarawong W, Woragidpunpol S, Kuanprasert S, Mekara W, Konda S, Neva C, Hathaway W, Groh M, Blakely J, Lamy A, Demers C, Rizzo T, Drazner M, DiMaio J, Joy J, Benedik J, Marketa K, Beghi C, De Blasi M, Helou J, Dallaire S, Kron I, Kern J, Bergin J, Phillips J, Aldea G, Verrier E, Harrison L, Piegas L, Paulista P, Farsky P, Veiga-Kantorowitz C, Philippides G, Shemin R, Thompson J, White H, Alison P, Stewart R, Clapham T, Rich J, Herre J, Pine L, Kalil R, Nesralla I, Santos M, Pereira de Moraes M, Michler R, Swayze R, Arnold M, McKenzie N, Smith J, Nicolau J, Oliveira S, Stolf N, Ferraz M, Filgueira J, Batlle C, Rocha A, Gurgel Camara A, Huynh T, Cecere R, Finkenbine S, St-Jacques B, Ilton M, Wittstein I, Conte J, Breton E, Panza J, Boyce S, McNulty M, Starnes V, Lopez B, Biederman R, Magovern J, Dean D, Grant S, Hammon J, Wells G, De Pasquale C, Knight J, Healy H, Maia L, Souza A, McRae R, Pierson M, Gullestad L, Sorensen G, Murphy E, Ravichandran P, Avalos K, Horowitz J, Owen E, Ascheim D, Naka Y, Yushak M, Gerometta P, Arena V, Borghini E, Johnsson P, Ekmehag B, Engels K, Rosenblum W, Swayze R, Amanullah A, Krzeminska-Pakula M, Drozdz J, Larbalestier R, Wang X, Busmann C, Horkay F, Szekely L, Keltai M, Hetzer R, Knosalla C, Nienkarken T, Chiariello L, Nardi P, Arom K, Ruengsakulrach P, Hayward C, Jansz P, Stuart S, Oto O, Sariomanoglu O, Dignan R, French J, Gonzalez M, Edes I, Szathmarine V, Yakub M, Sarip S, Alotti N, Lupkovics G, Smedira N, Pryce J, Cokkinos D, Palatianos G, Kremastinos D, Stewart R, Rinkes L, Esrig B, Baptiste M, Booth D, Ramaiah C, Ferraris V, Menon S, Martin L, Couper G, Rosborough D, Vanhaecke J, Strijckmans A, Carson P, Dupree C, Miller A, Pina I, Selzman C, Wertheimer J, Goldstein S, Cohn F, Hlatky M, Kennedy K, Rankin S, Robbins R, Zaret B, Rouleau J, Desvigne-Nickens P, Jones R, Lee K, Michler R, O'Connor C, Oh J, Rankin G, Velazquez E, Hill J, Beyersdorf F, Bonow R, Desvigne-Nickens P, Jones R, Lee K, Oh J, Panza J, Rouleau J, Sadowski Z, Velazquez E, White H, Jones R, Velazquez E, O'Connor C, Rankin G, Sellers M, Sparrow-Parker B, McCormick A, Albright J, Dandridge R, Rittenhouse L, Wagstaff D, Wakeley N, Burns S, Williams M, Bailey D, Parrish L, Daniels H, Grissom G, Medlin K, Lee K, She L, McDaniel A, Lokhnygina Y, Greene D, Moore V, Pohost G, Agarwal S, Apte P, Bahukha P, Chow M, Chu X, Doyle M, Forder J, Ocon M, Reddy V, Santos N, Tripathi R, Varadarajan P, Oh J, Blahnik F, Bruce C, Lin G, Manahan B, Miller D, Miller F, Pellikka P, Springer R, Welper J, Wiste H, Mark D, Anstrom K, Baloch K, Burnette A, Clapp-Channing N, Cowper P, Davidson-Ray N, Drew L, Harding T, Hunt V, Knight D, Patterson A, Redick T, Sanderford B, Feldman A, Bristow M, Chan T, Diamond M, Maisel A, Mann D, McNamara D, Bonow R, Berman D, Helmer D, Holly T, Leonard S, Woods M, Panza J, McNulty M, Grayburn P, Aston S. SourceDuke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. [email protected] Abstract BACKGROUND: Surgical ventricular reconstruction is a specific procedure designed to reduce left ventricular volume in patients with heart failure caused by coronary artery disease. We conducted a trial to address the question of whether surgical ventricular reconstruction added to coronary-artery bypass grafting (CABG) would decrease the rate of death or hospitalization for cardiac causes, as compared with CABG alone. METHODS: Between September 2002 and January 2006, a total of 1000 patients with an ejection fraction of 35% or less, coronary artery disease that was amenable to CABG, and dominant anterior left ventricular dysfunction that was amenable to surgical ventricular reconstruction were randomly assigned to undergo either CABG alone (499 patients) or CABG with surgical ventricular reconstruction (501 patients). The primary outcome was a composite of death from any cause and hospitalization for cardiac causes. The median follow-up was 48 months. RESULTS: Surgical ventricular reconstruction reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone. Cardiac symptoms and exercise tolerance improved from baseline to a similar degree in the two study groups. However, no significant difference was observed in the primary outcome, which occurred in 292 patients (59%) who were assigned to undergo CABG alone and in 289 patients (58%) who were assigned to undergo CABG with surgical ventricular reconstruction (hazard ratio for the combined approach, 0.99; 95% confidence interval, 0.84 to 1.17; P=0.90). CONCLUSIONS: Adding surgical ventricular reconstruction to CABG reduced the left ventricular volume, as compared with CABG alone. However, this anatomical change was not associated with a greater improvement in symptoms or exercise tolerance or with a reduction in the rate of death or hospitalization for cardiac causes. (ClinicalTrials.gov number, NCT00023595.

Dense Plasma Focus: physics and applications (radiation material science, single-shot disclosure of hidden illegal objects, radiation biology and medicine, etc.)

The paper presents some outcomes obtained during the year of 2013 of the activity in the frame of the International Atomic Energy Agency Co-ordinated research project "Investigations of Materials under High Repetition and Intense Fusion-Relevant Pulses". The main results are related to the effects created at the interaction of powerful pulses of different types of radiation (soft and hard X-rays, hot plasma and fast ion streams, neutrons, etc. generated in Dense Plasma Focus (DPF) facilities) with various materials including those that are counted as perspective ones for their use in future thermonuclear reactors. Besides we discuss phenomena observed at the irradiation of biological test objects. We examine possible applications of nanosecond powerful pulses of neutrons to the aims of nuclear medicine and for disclosure of hidden illegal objects. Special attention is devoted to discussions of a possibility to create extremely large and enormously diminutive DPF devices and probabilities of their use in energetics, medicine and modern electronics

Analytic Markovian Rates for Generalized Protein Structure Evolution

A general understanding of the complex phenomenon of protein evolution requires the accurate description of the constraints that define the sub-space of proteins with mutations that do not appreciably reduce the fitness of the organism. Such constraints can have multiple origins, in this work we present a model for constrained evolutionary trajectories represented by a Markovian process throughout a set of protein-like structures artificially constructed to be topological intermediates between the structure of two natural occurring proteins. The number and type of intermediate steps defines how constrained the total evolutionary process is. By using a coarse-grained representation for the protein structures, we derive an analytic formulation of the transition rates between each of the intermediate structures. The results indicate that compact structures with a high number of hydrogen bonds are more probable and have a higher likelihood to arise during evolution. Knowledge of the transition rates allows for the study of complex evolutionary pathways represented by trajectories through a set of intermediate structures

Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions.

The family of hexokinases (HKs) catalyzes the first step of glycolysis, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, the less well-studied HK3 is primarily expressed in hematopoietic cells and tissues and is highly upregulated during terminal differentiation of some acute myeloid leukemia (AML) cell line models. Here we show that expression of HK3 is predominantly originating from myeloid cells and that the upregulation of this glycolytic enzyme is not restricted to differentiation of leukemic cells but also occurs during ex vivo myeloid differentiation of healthy CD34+ hematopoietic stem and progenitor cells. Within the hematopoietic system, we show that HK3 is predominantly expressed in cells of myeloid origin. CRISPR/Cas9 mediated gene disruption revealed that loss of HK3 has no effect on glycolytic activity in AML cell lines while knocking out HK2 significantly reduced basal glycolysis and glycolytic capacity. Instead, loss of HK3 but not HK2 led to increased sensitivity to ATRA-induced cell death in AML cell lines. We found that HK3 knockout (HK3-null) AML cells showed an accumulation of reactive oxygen species (ROS) as well as DNA damage during ATRA-induced differentiation. RNA sequencing analysis confirmed pathway enrichment for programmed cell death, oxidative stress, and DNA damage response in HK3-null AML cells. These signatures were confirmed in ATAC sequencing, showing that loss of HK3 leads to changes in chromatin configuration and increases the accessibility of genes involved in apoptosis and stress response. Through isoform-specific pulldowns, we furthermore identified a direct interaction between HK3 and the proapoptotic BCL-2 family member BIM, which has previously been shown to shorten myeloid life span. Our findings provide evidence that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Impact of Age on the Cerebrovascular Proteomes of Wild-Type and Tg-SwDI Mice

The structural integrity of cerebral vessels is compromised during ageing. Abnormal amyloid (Aβ) deposition in the vasculature can accelerate age-related pathologies. The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis. Over 650 proteins were quantified in vessel-enriched fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice. Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty-one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent. Only six shared proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related proteomic response in the cerebrovasculature was distinctly different in the presence of microvascular Aβ deposition. Proteins found differentially expressed within the WT and Tg-SwDI animals give greater insight to the mechanisms behind age-related cerebrovascular dysfunction and pathologies and may provide novel therapeutic targets

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease