Bepridil opens the regulatory N-terminal lobe of cardiac troponin C

Cardiac troponin C (cTnC) is the calcium-dependent switch for contraction in heart muscle and a potential target for drugs in the therapy of congestive heart failure. This calmodulin-like protein consists of two lobes connected by a central linker; each lobe contains two EF-hand domains. The regulatory N-terminal lobe of cTnC, unlike that of skeletal troponin C (sTnC), contains only one functional EF-hand and does not open fully upon the binding of Ca2+. We have determined the crystal structure of cTnC, with three bound Ca2+ ions, complexed with the calcium-sensitizer bepridil, to 2.15-Å resolution. In contrast to apo- and 3Ca2+-cTnC, the drug-bound complex displays a fully open N-terminal lobe similar to the N-terminal lobes of 4Ca2+-sTnC and cTnC bound to a C-terminal fragment of cardiac troponin I (residues 147–163). The closing of the lobe is sterically hindered by one of the three bound bepridils. Our results provide a structural basis for the Ca2+-sensitizing effect of bepridil and reveal the details of a distinctive two-stage mechanism for Ca2+ regulation by troponin C in cardiac muscle.

Family firms and the great crisis: evidence from the italian case

Few studies have analyzed how family firms have acted during the global great crisis in comparison to their nonfamily counterparts. This paper tries to fill this gap on the basis of the Italian experience using a sample of almost 4,500 for 2007 and 2010. We study whether family control affects labour productivity, labour costs and competitiveness and if the adoption of performance related pay (PRP) reveals an efficacious strategy to mitigate the effects of the crisis and reduce the gap in competitiveness with respect to nonfamily firms. We use quantile regression techniques to test the heterogeneous role of PRP and pay attention for its possible endogeneity. We have observed that after the outburst of the crisis, the distance in terms of competitiveness of family firms with respect to their nonfamily counterparts has been amplified. We also find that family firms may take advantage from the adoption of incentive schemes, such as PRP, to encourage commitment and motivation from their employees more than nonfamily firms. The positive role of PRP on labour productivity, coupled with a moderate influence of these schemes on wage premiums, enable them to regain competitiveness also under hostile pressures, as those featuring the strong global crisis.

Formação de preços: uma investigação sobre os atributos envolvidos na definição de preços de produtos de vestuário

Este estudo visa compreender a relação entre os atributos intrínsecos e extrínsecos do produto calça jeans e o seu preço no varejo, tendo como objetivo específico analisar a influência separadamente dos atributos intrínsecos e extrínsecos sobre os preços. Para tanto, utiliza-se da teoria de atributos proposta por Lancaster (1966) e dos métodos de preços hedônicos propostos por Rosen (1974), por meio dos quais é possível observar a importância dos pacotes de atributos intrínsecos e extrínsecos sobre os preços, bem como observar a constituição de pacotes de atributos para diferentes perfis econômicos de consumidores. Foram analisadas 12 categorias de atributos sendo 5 de atributos intrínsecos e outras 7 de atributos extrínsecos. A coleta de dados foi realizada por meio de observação e a pesquisa foi realizada no período de 01 de julho a 31 de julho de 2015 nos maiores shoppings centers e principais lojas de ruas de São Paulo. A partir dos dados coletados, foram realizadas regressão múltipla e a regressão quantílica. A regressão múltipla apresentou o R2 de 58%, nessa análise os principais atributos que influenciam são: loja premium, venda assistida, origem da loja, tamanho da loja (megaloja), tamanho da loja (ampla), lavagem destroyed, resina, modelo flare, lavagem dirty, localização da loja (rua ou shopping), complementos, modelo skinny insumos elastano e poliéster. A regressão quantílica proporciou a análise para 10% das calças mais caras e para os 10% das calças mais baratas. Para as calças mais caras o R2 é de 45% para as calças mais caras há mais atributos extrínsecos do que atributos do produto interferindo no preço, são eles: os insumos poliéster e elastano, lavagem e resinagem, origem da marca da loja, posicionamento da marca, venda assistida, localização da loja, cartão de crédito - private label (nesse caso influenciando negativamente), e tamanho da loja, todos extrínsecos ao produto, se mostraram relevantes para o processo de precificação das calças jeans mais caras observadas nesse estudo. Já para as calças mais baratas, com R2 de 27%, parece haver um equilíbrio entre o número de variáveis intrínsecas e extrínsecas que interferem no preço das calças jeans mais baratas, pois somente a modelagem (atributo intrínseco) e cartão private label (atributo extrínseco) parecem não interferir na precificação. Concluiu-se que há mais atributos extrínsecos que influenciam o preço da calça jeans no varejo.

Steric and mass-induced sea level variations in the Mediterranean Sea revisited

The total sea level variation (SLV) is the combination of steric and mass␣induced SLV, whose exact shares are key to understanding the oceanic response to climate system changes. Total SLV can be observed by radar altimetry satellites such as TOPEX/POSEIDON and Jason 1/2. The steric SLV can be computed through temperature and salinity profiles from in situ measurements or from ocean general circulation models (OGCM), which can assimilate the said observations. The mass-induced SLV can be estimated from its time-variable gravity (TVG) signals. We revisit this problem in the Mediterranean Sea estimating the observed, steric, and mass-induced SLV, for the latter we analyze the latest TVG data set from the GRACE (Gravity Recovery and Climate Experiment) satellite mission launched in 2002, which is 3.5 times longer than in previous studies, with the application of a two-stage anisotropic filter to reduce the noise in high-degree and -order spherical harmonic coefficients. We confirm that the intra-annual total SLV are only produced by water mass changes, a fact explained in the literature as a result of the wind field around the Gibraltar Strait. The steric SLV estimated from the residual of “altimetry minus GRACE” agrees in phase with that estimated from OGCMs and in situ measurements, although showing a higher amplitude. The net water fluxes through both the straits of Gibraltar and Sicily have also been estimated accordingly.

Determination of cyclic and linear siloxanes in wastewater samples by ultrasound-assisted dispersive liquid-liquid microextraction followed by gas chromatography-mass spectrometry

A fast, simple and environmentally friendly ultrasound-assisted dispersive liquid-liquid microextraction (USA-DLLME) procedure has been developed to preconcentrate eight cyclic and linear siloxanes from wastewater samples prior to quantification by gas chromatography-mass spectrometry (GC-MS). A two-stage multivariate optimization approach has been developed employing a Plackett-Burman design for screening and selecting the significant factors involved in the USA-DLLME procedure, which was later optimized by means of a circumscribed central composite design. The optimum conditions were: extractant solvent volume, 13 µL; solvent type, chlorobenzene; sample volume, 13 mL; centrifugation speed, 2300 rpm; centrifugation time, 5 min; and sonication time, 2 min. Under the optimized experimental conditions the method gave levels of repeatability with coefficients of variation between 10 and 24% (n=7). Limits of detection were between 0.002 and 1.4 µg L−1. Calculated calibration curves gave high levels of linearity with correlation coefficient values between 0.991 and 0.9997. Finally, the proposed method was applied for the analysis of wastewater samples. Relative recovery values ranged between 71–116% showing that the matrix had a negligible effect upon extraction. To our knowledge, this is the first time that combines LLME and GC-MS for the analysis of methylsiloxanes in wastewater samples.

Using the damage from 2010 Haiti earthquake for calibrating vulnerability models of typical structures in Port-au-Prince (Haiti)

After the 2010 Haiti earthquake, that hits the city of Port-au-Prince, capital city of Haiti, a multidisciplinary working group of specialists (seismologist, geologists, engineers and architects) from different Spanish Universities and also from Haiti, joined effort under the SISMO-HAITI project (financed by the Universidad Politecnica de Madrid), with an objective: Evaluation of seismic hazard and risk in Haiti and its application to the seismic design, urban planning, emergency and resource management. In this paper, as a first step for a structural damage estimation of future earthquakes in the country, a calibration of damage functions has been carried out by means of a two-stage procedure. After compiling a database with observed damage in the city after the earthquake, the exposure model (building stock) has been classified and through an iteratively two-step calibration process, a specific set of damage functions for the country has been proposed. Additionally, Next Generation Attenuation Models (NGA) and Vs30 models have been analysed to choose the most appropriate for the seismic risk estimation in the city. Finally in a next paper, these functions will be used to estimate a seismic risk scenario for a future earthquake.

Tungsten coil atomic emission spectrometry combined with dispersive liquid–liquid microextraction: A synergistic association for chromium determination in water samples

A novel and environment friendly analytical method is reported for total chromium determination and chromium speciation in water samples, whereby tungsten coil atomic emission spectrometry (WCAES) is combined with in situ ionic liquid formation dispersive liquid–liquid microextraction (in situ IL-DLLME). A two stage multivariate optimization approach has been developed employing a Plackett–Burman design for screening and selection of the significant factor involved in the in situ IL-DLLME procedure, which was later optimized by means of a circumscribed central composite design. The optimum conditions were complexant concentration: 0.5% (or 0.1%); complexant type: DDTC; IL anion: View the MathML sourcePF6−; [Hmim][Cl] IL amount: 60 mg; ionic strength: 0% NaCl; pH: 5 (or 2); centrifugation time: 10 min; and centrifugation speed: 1000 rpm. Under the optimized experimental conditions the method was evaluated and proper linearity was obtained with a correlation coefficient of 0.991 (5 calibration standards). Limits of detection and quantification for both chromium species were 3 and 10 µg L−1, respectively. This is a 233-fold improvement when compared with chromium determination by WCAES without using preconcentration. The repeatability of the proposed method was evaluated at two different spiking levels (10 and 50 µg L−1) obtaining coefficients of variation of 11.4% and 3.6% (n=3), respectively. A certified reference material (SRM-1643e NIST) was analyzed in order to determine the accuracy of the method for total chromium determination and 112.3% and 2.5 µg L−1 were the recovery (trueness) and standard deviation values, respectively. Tap, bottled mineral and natural mineral water samples were analyzed at 60 µg L−1 spiking level of total Cr content at two Cr(VI)/Cr(III) ratios, and relative recovery values ranged between 88% and 112% showing that the matrix has a negligible effect. To our knowledge, this is the first time that combines in situ IL-DLLME and WCAES.

Applying scanning electron microscopy for the ultrastructural and clinical analysis of periprosthetic capsules in implant-based breast reconstruction

La reconstruction en deux étapes par expanseur et implant est la technique la plus répandue pour la reconstruction mammmaire post mastectomie. La formation d’une capsule périprothétique est une réponse physiologique universelle à tout corps étranger présent dans le corps humain; par contre, la formation d’une capsule pathologique mène souvent à des complications et par conséquent à des résultats esthétiques sous-optimaux. Le microscope électronique à balayage (MEB) est un outil puissant qui permet d’effectuer une évaluation sans pareille de la topographie ultrastructurelle de spécimens. Le premier objectif de cette thèse est de comparer le MEB conventionnel (Hi-Vac) à une technologie plus récente, soit le MEB environnemental (ESEM), afin de déterminer si cette dernière mène à une évaluation supérieure des tissus capsulaires du sein. Le deuxième objectif est d‘appliquer la modalité de MEB supérieure et d’étudier les modifications ultrastructurelles des capsules périprothétiques chez les femmes subissant différents protocoles d’expansion de tissus dans le contexte de reconstruction mammaire prothétique. Deux études prospectives ont été réalisées afin de répondre à nos objectifs de recherche. Dix patientes ont été incluses dans la première, et 48 dans la seconde. La modalité Hi-Vac s’est avérée supérieure pour l’analyse compréhensive de tissus capsulaires mammaires. En employant le mode Hi-Vac dans notre protocole de recherche établi, un relief 3-D plus prononcé à été observé autour des expanseurs BIOCELL® dans le groupe d’approche d’intervention retardée (6 semaines). Des changements significatifs n’ont pas été observés au niveau des capsules SILTEX® dans les groupes d’approche d’intervention précoce (2 semaines) ni retardée.

Assessment of Socio-Economic and Climate Change Effects on Water Resources and Agriculture in Southern and Eastern Mediterranean countries. MEDPRO Technical Paper No. 28/March 2013

This study aims at assessing the socio-economic and environmental effects of different societal and human development scenarios and climate change in the water-scarce southern and eastern Mediterranean. The study develops a two-stage modelling methodology that includes an econometric analysis for the southern and eastern Mediterranean region as a whole and a detailed, integrated socioecological assessment focusing on Jordan, Syria and Morocco. The results show that water resources will be under increasing stress in future years. In spite of country differences, a future path of sustainable development is possible in the region. Water withdrawals could decrease, preserving renewable water resources and reversing the negative effects on agricultural production and rural society. This, however, requires a combination across the region of technical, managerial, economic, social and institutional changes that together foster a substantive structural change. A balanced implementation of water supply-enhancing and demand-management measures along with improved governance are key to attaining a cost-effective sustainable future in which economic growth, a population increase and trade expansion are compatible with the conservation of water resources.

Centennial-scale evolution of Dansgaard-Oeschger events in sediment core MD95-2006

There is much uncertainty surrounding the mechanisms that forced the abrupt climate fluctuations found in many palaeoclimate records during Marine Isotope Stage (MIS)-3. One of the processes thought to be involved in these events is the Atlantic Meridional Overturning Circulation (MOC), which exhibited large changes in its dominant mode throughout the last glacial period. Giant piston core MD95-2006 from the northeast Atlantic Ocean records a suite of palaeoceanographic proxies related to the activity of both surface and deep water masses through a period of MIS-3 when abrupt climate fluctuations were extremely pronounced. A two-stage progression of surface water warming during interstadial warm events is proposed, with initial warming related to the northward advection of a thin warm surface layer within the North Atlantic Current, which only extended into deeper surface layers as the interstadial progressed. Benthic foraminifera isotope data also show millennial-scale oscillations but of a different structure to the abrupt surface water changes. These changes are argued to partly be related to the influence of low-salinity deepwater brines. The influence of deepwater brines over the site of MD95-2006 reached a maximum at times of rapid warming of surface waters. This observation supports the suggestion that brine formation may have helped to destabilize the accumulation of warm, saline surface waters at low latitudes, helping to force the MOC into a warm mode of operation. The contribution of deepwater brines relative to other mechanisms proposed to alter the state of the MOC needs to be examined further in future studies.

Mathematical modelling

The development of a new process model of cement grinding in two-stage mills is discussed. The new model has been used to simulate cement grinding and predicting mill performance in open and closed circuit configuration. The new model considered the two-compartment mill as perfectly mixed slices in series. The breakage rate function uses the back calculation technique to determine offline using drop weight and abrasion tests.

Implicit stochastic Runge-Kutta methods for stochastic differential equations

In this paper we construct implicit stochastic Runge-Kutta (SRK) methods for solving stochastic differential equations of Stratonovich type. Instead of using the increment of a Wiener process, modified random variables are used. We give convergence conditions of the SRK methods with these modified random variables. In particular, the truncated random variable is used. We present a two-stage stiffly accurate diagonal implicit SRK (SADISRK2) method with strong order 1.0 which has better numerical behaviour than extant methods. We also construct a five-stage diagonal implicit SRK method and a six-stage stiffly accurate diagonal implicit SRK method with strong order 1.5. The mean-square and asymptotic stability properties of the trapezoidal method and the SADISRK2 method are analysed and compared with an explicit method and a semi-implicit method. Numerical results are reported for confirming convergence properties and for comparing the numerical behaviour of these methods.

Assessing cost-effectiveness in mental health: vocational rehabilitation for schizophrenia and related conditions

Objective: Existing evidence suggests that vocational rehabilitation services, in particular individual placement and support (IPS), are effective in assisting people with schizophrenia and related conditions gain open employment. Despite this, such services are not available to all unemployed people with schizophrenia who wish to work. Existing evidence suggests that while IPS confers no clinical advantages over routine care, it does improve the proportion of people returning to employment. The objective of the current study is to investigate the net benefit of introducing IPS services into current mental health services in Australia. Method: The net benefit of IPS is assessed from a health sector perspective using cost-benefit analysis. A two-stage approach is taken to the assessment of benefit. The first stage involves a quantitative analysis of the net benefit, defined as the benefits of IPS (comprising transfer payments averted, income tax accrued and individual income earned) minus the costs. The second stage involves application of 'second-filter' criteria (including equity, strength of evidence, feasibility and acceptability to stakeholders) to results. The robustness of results is tested using the multivariate probabilistic sensitivity analysis. Results: The costs of IPS are $A10.3M (95% uncertainty interval $A7.4M-$A13.6M), the benefits are $A4.7M ($A3.1M-$A6.5M), resulting in a negative net benefit of $A5.6M ($A8.4M-$A3.4M). Conclusions: The current analysis suggests that IPS costs are greater than the monetary benefits. However, the evidence-base of the current analysis is weak. Structural conditions surrounding welfare payments in Australia create disincentives to full-time employment for people with disabilities.

Crystallization behavior of (Cu60Zr30Ti10)(99)Sn-1 bulk metallic glass

The crystallization behavior and crystallization kinetics Of (CU60Zr30Ti10)(99)Sn-1 bulk metallic glass was studied by X-ray diffractometry and differential scanning calorimetry. It was found that a two-stage crystallization took place during continuous heating of the bulk metallic glass. Both the glass transition temperature T-g and the crystallization peak temperatures T-p displayed a strong dependence on the heating rate. The activation energy was determined by the Kissinger analysis method. In the first-stage of the crystallization, the transformation of the bulk metallic glass to the phase one occurred with an activation energy of 386 kJ/mol; in the second-stage, the formation of the phase two took place at an activation energy of 381 kJ/mol.

Evaluating trends in abundance of immature green turtles, Chelonia mydas, in the Greater Caribbean

Many long-lived marine species exhibit life history traits. that make them more vulnerable to overexploitation. Accurate population trend analysis is essential for development and assessment of management plans for these species. However, because many of these species disperse over large geographic areas, have life stages inaccessible to human surveyors, and/or undergo complex developmental migrations, data on trends in abundance are often available for only one stage of the population, usually breeding adults. The green turtle (Chelonia mydas) is one of these long-lived species for which population trends are based almost exclusively on either numbers of females that emerge to nest or numbers of nests deposited each year on geographically restricted beaches. In this study, we generated estimates of annual abundance for juvenile green turtles at two foraging grounds in the Bahamas based on long-term capture-mark-recapture (CMR) studies at Union Creek (24 years) and Conception Creek (13 years), using a two-stage approach. First, we estimated recapture probabilities from CMR data using the Cormack-Jolly-Seber models in the software program MARK; second, we estimated annual abundance of green turtles. at both study sites using the recapture probabilities in a Horvitz-Thompson type estimation procedure. Green turtle abundance did not change significantly in Conception Creek, but, in Union Creek, green turtle abundance had successive phases of significant increase, significant decrease, and stability. These changes in abundance resulted from changes in immigration, not survival or emigration. The trends in abundance on the foraging grounds did not conform to the significantly increasing trend for the major nesting population at Tortuguero, Costa Rica. This disparity highlights the challenges of assessing population-wide trends of green turtles and other long-lived species. The best approach for monitoring population trends may be a combination of (1) extensive surveys to provide data for large-scale trends in relative population abundance, and (2) intensive surveys, using CMR techniques, to estimate absolute abundance and evaluate the demographic processes' driving the trends.