Ligand dissociation from estrogen receptor is mediated by receptor dimerization: Evidence from molecular dynamics simulations

Estrogen Receptor (ER) is an important target for pharmaceutical design. Like other ligand-dependent transcription factors, hormone binding regulates ER transcriptional activity. Nevertheless, the mechanisms by which ligands enter and leave ERs and other nuclear receptors remain poorly understood. Here, we report results of locally enhanced sampling molecular dynamics simulations to identify dissociation pathways of two ER ligands [the natural hormone 17 beta-estradiol (E-2) and the selective ER modulator raloxifene (RAL)] from the human ER alpha ligand-binding domain in monomeric and dimeric forms. E-2 dissociation occurs via three different pathways in ER monomers. One resembles the mousetrap mechanism (Path I), involving repositioning of helix 12 (H12), others involve the separation of H8 and H11 (Path II), and a variant of this pathway at the bottom of the ligand-binding domain (Path II`). RAL leaves the receptor through Path I and a Path I variant in which the ligand leaves the receptor through the loop region between H11 and H12 (Path I`). Remarkably, ER dimerization strongly suppresses Paths II and II` for E-2 dissociation and modifies RAL escape routes. We propose that differences in ligand release pathways detected in the simulations for ER monomers and dimers provide an explanation for previously observed effects of ER quaternary state on ligand dissociation rates and suggest that dimerization may play an important, and hitherto unexpected, role in regulation of ligand dissociation rates throughout the nuclear receptor family.

Evidence for magnetic phase separation in La(0.86)Sr(0.14)Mn(1-x)Cu(x)O(3+delta) manganites from NMR and magnetic measurements

Polycrystalline La(0.86)Sr(0.14)Mn(1-x)Cu(x)O(3+delta) (x = 0, 0.05, 0.10, 0.15, 0.20) manganites were investigated by means of magnetic measurements and zero-field (139)La and (55)Mn nuclear magnetic resonance (NMR) spectroscopy. Magnetization versus temperature measurements revealed a paramagnetic to ferromagnetic transition in most samples, with lower Curie temperatures and broader transitions for samples with higher Cu contents. The details of the magnetization measurements suggested a phase-separated scenario, with ferromagnetic clusters embedded in an antiferromagnetic matrix, especially for the samples with large Cu contents (x = 0.15 and 0.20). Zero-field (139)La NMR measurements confirmed this finding, since the spectral features remained almost unchanged for all Cu-doped samples, whereas the bulk magnetization was drastically reduced with increasing Cu content. (55)Mn NMR spectra were again typical of ferromagnetic regions, with a broadening of the resonance line caused by the disorder introduced by the Cu doping. The results indicate a coexistence of different magnetic phases in the manganites studied, with the addition of Cu contributing to the weakening of the double-exchange interaction in most parts of the material.

Sr-Nd isotopic evidence for crustal contamination in the Niquelandia complex, Goias, Central Brazil

The Niquelandia complex is a Neoproterozoic mafic-ultramafic intrusion resulting from fractional crystallization of primary picritic basalt intrusions. It consists of two layered sequences: a lower and larger one (LS), where four stratigraphic units exhibit an upward decrease of ultramafic layers and increase of gabbroic layers; an upper, smaller sequence (US), separated from LS by a high-temperature shear zone and consisting of two stratigraphic units (gabbros + anorthosites and amphibolites). Nd and Sr isotopic analyses and rare earth element (REE) profiles provide evidence that the complex suffered important crustal contamination. The LS isotopic array trends from a DM region with positive epsilon Nd and moderately positive epsilon Sr towards a field occupied by crustal xenoliths, especially abundant in the upper LS (negative epsilon Nd and large, positive E:Sr). Each LS stratigraphic unit is distinct from the next underlying unit, showing lower epsilon Nd and higher epsilon Sr, suggesting inputs of fresh magma and mixing with the contaminated, residual magma. The US is characterised by a relatively high variation of epsilon Nd and constant epsilon Sr. REE patterns vary within each unit from LREE depleted to LREE enriched in the samples having lower epsilon Nd and higher epsilon Sr. The contamination process has been modelled by using the EC-AFC algorithms from [Spera, F.J., Bohrson, W.A., 2001. Energy-constrained open-system magmatic processes 1: general model and energy-constrained assimilation and fractional crystallization (EC-AFC) formulation. J. Petrology 42, 999-1018]. The differences between the LS and US isotopic arrays are consistent with contamination by the same crustal component, provided that its melting degree was higher in LS than in US. The different degrees of anatexis are explained by the heat budget released from the magma, higher in LS (because of its larger mass) than in US. Comparison of the correlations between isotopes and incompatible trace element ratios of the models and of the gabbros shows some differences, which are demonstrably related with the variable amount of cumulus phases and trapped melt in the gabbros. (c) 2007 Elsevier Ltd. All rights reserved.

What determines the use of capital budgeting methods? : Evidence from Swedish listed companies

Purpose: This paper aims to extend and contribute to prior research on the association between company characteristics and choice of capital budgeting methods (CBMs). Design/methodology/approach: A multivariate regression analysis on questionnaire data from 2005 and 2008 is used to study which factors determine the choice of CBMs in Swedish listed companies. Findings: Our results supported hypotheses that Swedish listed companies have become more sophisticated over the years (or at least less unsophisticated) which indicates a closing of the theory-practice gap; that companies with greater leverage used payback more often; and that companies with stricter debt targets and less management ownership employed accounting rate of return more frequent. Moreover, larger companies used CBMs more often. Originality/value: The paper contributes to prior research within this field by being the first Swedish study to examine the association between use of CBMs and as many as twelve independent variables, including changes over time, by using multivariate regression analysis. The results are compared to a US and a continental European study.

Organizational design as an enabler for innovation: evidence from a German Mechanical Engineering Company

Over the past two decades there has been a profusion of empirical studies of organizational design and its relationship to efficiency, productivity and flexibility of an organization. In parallel, there has been a wide range of studies about innovation management in different kind of industries and firms. However, with some exceptions, the organizational and innovation management bodies of literature tend to examine the issues of organizational design and innovation management individually, mainly in the context of large firms operating at the technological frontier. There seems to be a scarcity of empirical studies that bring together organizational design and innovation and examine them empirically and over time in the context of small and medium sized enterprises. This dissertation seeks to provide a small contribution in that direction. This dissertation examines the dynamic relationship between organizational design and innovation. This relationship is examined on the basis of a single-case design in a medium sized mechanical engineering company in Germany. The covered time period ranges from 1958 until 2009, although the actual focus falls on the recent past. This dissertation draws on first-hand qualitative empirical evidence gathered through extensive field work. The main findings are: 1. There is always a bundle of organizational dimensions which impacts innovation. These main organizational design dimensions are: (1) Strategy & Leadership, (2) Resources & Capabilities, (3) Structure, (4) Culture, (5) Networks & Partnerships, (6) Processes and (7) Knowledge Management. However, the importance of the different organizational design dimensions changes over time. While for example for the production of simple, standardized parts, a simple organizational design was appropriate, the company needed to have a more advanced organizational design in order to be able to produce customized, complex parts with high quality. Hence the technological maturity of a company is related to its organizational maturity. 2. The introduction of innovations of the analyzed company were highly dependent on organizational conditions which enabled their introduction. The results of the long term case study show, that some innovations would not have been introduced successfully if the organizational elements like for example training and qualification, the build of network and partnerships or the acquisition of appropriate resources and capabilities, were not in place. Hence it can be concluded, that organizational design is an enabling factor for innovation. These findings contribute to advance our understanding of the complex relationship between organizational design and innovation. This highlights the growing importance of a comprehensive, innovation stimulating organizational design of companies. The results suggest to managers that innovation is not only dependent on a single organizational factor but on the appropriate, comprehensive design of the organization. Hence manager should consider to review regularly the design of their organizations in order to maintain a innovation stimulating environment.

Environmental regulation, technology adoption and structural transformation: evidence from Brazilian sugarcane industry

We estimate the effects of the adoption of mechanized agriculture led by a new environmental regulation on structural change of local labor markets within a large emerging country, Brazil. In 2002, the state of S\~{a}o Paulo passed a law outlying the timeline to end sugarcane pre-harvest burning in the state. The environmental law led to the fast adoption of mechanized harvest. We investigate if the labor intensity of sugarcane production decreases; and, if so, if it leads to structural changes in the labor market. We use satellite data containing the type of sugarcane harvesting -- manual or mechanic harvest -- paired with official labor market data.%, also geomorphometric data base for our instrumental variable correction. We find suggestive evidence that mechanization of the field led to an increase in utilization of formal workers and a reduction in formal labor intensity in the sugarcane sector. This is partially compensated by an increase in the share of workers in other agricultural crops and in the construction and services sector. Although we find a reduction in employment in the manufacturing sector, the demand generated by the new agro-industries affected positively the all sectors via an increase in workers' wage.

Octenol as Attractant to Nyssomyia neivai (Diptera: Psychodidae: Phlebotominae) in the Field

The kairomone octenol is known as attractive to hematophagous Diptera such as mosquitoes, tsetse flies, and midges. There is little evidence that traps baited with octenol are also effective in attracting phlebotomine sand flies. The present report evaluated octenol in modified Centers for Disease Control and Prevention (CDC) traps in two experiments: 1) modified CDC trap without light and 2) modified CDC trap with light. The traps were baited with octenol at concentrations of 0.5, 27, and 43 mg/h in Rifled() locality, São Paulo, Brazil. Traps without octenol were used as controls. The sand fly Nyssomyia neivai (Pinto) (=Lutzomyia neivai) (Diptera: Psychodidae: Phlebotominae) was the prevalent species (99.9%) in both experiments. The results of the experiments showed that traps baited with octenol at 27 and 43 mg/h caught significantly more N. neivai than control and octenol at 0.5 mg/h with and without light. This is the first report that shows that octenol itself is attractive to N. neivai and associated with light traps significantly increases the catches.

Field study on nematode resistance in Nelore-breed cattle

The present study evaluated Nelore cattle with different degrees of resistance to natural infections by gastrointestinal nematodes. One hundred weaned male cattle, 11-12 months of age, were kept on the same pasture and evaluated from October 2003 to February 2004. Faecal and blood samples were collected for parasitological, haematological and immunological tests. In February 2004, the 10 most resistant and the 10 most susceptible animals were selected based on individual means of nematode faecal egg counts (FEC). Such animals were slaughtered for worm burden determination and nematode species identification. The repeatability estimates for FEC (+/- S.D.), log-transformed FEC and packed-cell volume (PCV) in all animals were 0.3 (+/- 0.05), 0.26 (+/- 0.04) and 0.42 (+/- 0.05), respectively. The resistant group showed lower FEC and worm burdens than the susceptible group (P < 0.05). There were no significant differences between groups regarding mean body weight, weight gain, PCV and total serum protein values (P > 0.05). The resistant group showed higher total serum IgE levels (P < 0.05) and higher mean eosinophil blood counts. However, the latter was statistically significant only 42 days after the beginning of the study. Nematodes Cooperia punctata and Haemonchus placei were predominant and the correlation between Cooperia and Haemonchus burdens was 0.64 (P < 0.05), which indicated that animals presenting increased numbers of one of those genera probably had increased numbers of the other. The current study provides further evidence of IgE active role in nematode immunity and suggests that total serum IgE level might serve as an additional marker to select Nelore cattle that are responsive to H. placei and C. punctata infections. (C) 2007 Elsevier B.V. All rights reserved.

Does gestation or feeding affect the body temperature of the golden lancehead, Bothrops insularis (Squamata: Viperidae) under field conditions?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evidence for Neoproterozoic continental arc magmatism in the Santa Quitéria Batholith of Ceará State, NW Borborema Province, NE Brazil: Implications for the assembly of West Gondwana

Recent field investigations and geochronological studies of Neoproterozoic rocks in the northwestern part of the Borborema Province, Ceará State, NE Brazil provide important clues pertaining to the nature of convergence between the Borborema Province and the West African-São Luis craton during the assembly of West Gondwana. U-Pb zircon data indicate that the earliest evidence of convergent magmatism along the northwest margin of the Borborema Province occurred around 777 Ma, and was followed by the development of a large continental arc batholith (Santa Quitéria batholith) between ca. 665 and 591 Ma within the central part of Ceará State. These findings, along with supporting geophysical data, suggest that convergence between the Borborema Province and the West African-São Luis craton involved closure of an oceanic realm with subduction polarity to the southeast beneath the northwestern part of the province. Consequently, it seems likely that the Pharusian Ocean was continuous from the Hoggar Province in West Africa into South America during the late Neoproterozoic and additional data suggests that it may have even been connected with the Goianides Ocean of the Brasília Belt farther to the southwest.

Building sustainable values in organizations with the support of human resource management: Evidence from one firm considered as the 'best place to work' in Brazil

Researchers and other professionals unanimously agree that companies should become more sustainable, but this will not happen without the support of human resource management. Paradoxically, there is a lack of information on the support human resource management offers to organizational sustainability applied to real cases. Therefore, this research presents a case study on this topic that was carried out in a leading Brazilian company, which is considered as a model and has been selected as 'the best place to work in the country'. The results provide practical examples of how this family company has been working to guarantee an increasingly sustainable performance with the support of human resources, highlighting the achievements and challenges the company has faced. One of the main results indicates that companies seeking to achieve sustainability need the assistance of the human resource field in order to design a communication system which bridges the gap between practices and sustainable values. © 2012 Management Centre for Human Values.

Evidence for associated production of a single top quark and W Boson in pp collisions at √s=7 TeV

Evidence is presented for the associated production of a single top quark and W boson in pp collisions at √s=7 TeV with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 4.9 fb -1. The measurement is performed using events with two leptons and a jet originated from a b quark. A multivariate analysis based on kinematic properties is utilized to separate the tt̄ background from the signal. The observed signal has a significance of 4.0σ and corresponds to a cross section of 16-4+5 pb, in agreement with the standard model expectation of 15.6±0.4-1.2+1.0 pb. © 2013 CERN, for the CMS Collaboration Published by the American Physical Society under the terms of the http://creativecommons.org/licenses/by/3.0/ Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

Population genetic evidence that basidiospores play an important role in the disease cycle of rice-infecting populations of Rhizoctonia solani AG-1 IA in Iran

The fungus Rhizoctonia solani AG-1 IA causes sheath blight, one of the most important rice diseases worldwide. The first objective of this study was to analyse the genetic structure of R. solani AG-1 IA populations from three locations in the Iranian Caspian Sea rice agroecosystem. Three population samples of R. solani AG-1 IA isolates were obtained in 2006 from infected rice fields separated by 126-263km. Each field was sampled twice during the season: at the early booting stage and 45days later at the early mature grain stage. The genetic structure of these three populations was analysed using nine microsatellite loci. While the population genetic structure from Tonekabon and Amol indicated high gene flow, they were both differentiated from Rasht. The high gene flow between Tonekabon and Amol was probably due mainly to human-mediated movement of infested seeds. The second objective was to determine the importance of recombination. All three populations exhibited a mixed reproductive mode, including both sexual and asexual reproduction. No inbreeding was detected, suggesting that the pathogen is random mating. The third objective was to determine if genetic structure within a field changes over the course of a growing season. A decrease in the proportion of admixed genotypes from the early to the late season was detected. There was also a significant (P=0·002) increase in the proportion of loci under Hardy-Weinberg equilibrium. These two lines of evidence support the hypothesis that basidiospores can be a source of secondary inoculum. © 2012 BSPP.

Evidence of weak ferromagnetism in doped plasticized polyaniline (PANI-DDoESSA)0.5 from electron spin resonance measurements

X-band electron spin resonance (ESR) measurements have been performed on a conducting free-standing film of polyaniline plasticized and protonated with di-n-dodecyl ester of sulfosuccinic acid (DDoESSA). The magnetic field was applied parallel and perpendicular to the plane of the film. At around 75 K a transition is observed from Pauli susceptibility to a localized state in which the spin 1/2 polarons behave as spin 1/2 dimers. A rough estimation of the intradimer and interdimer exchange constants is obtained. Below 5 K, ESR data reveal a weak ferromagnetism with the Dzyaloshinskii-Moriya vector mainly oriented in the plane of the film. The existence of a relatively well-defined n-fold axis along the chain direction in the crystalline regions confers a symmetry compatible with such analysis. © 2013 IOP Publishing Ltd.

Field and petrographic data of 1.90 to 1.88 Ga I- and A-type granitoids from the central region of the Amazonian Craton, NE Amazonas State, Brazil

O SW do município de Presidente Figueiredo, localizado no Estado do Amazonas, Nordeste do Cráton Amazônico Central, Brasil, hospeda granitoides do tipo I de idade entre 1890 a 1898 Ma (Terra Preta Granito, Suíte Água Branca), hornblenda-sienogranitos do tipo A (Sienogranito Canoas da Suíte Mapuera), rochas vulcânicas ácidas à intermediárias (Grupo Iricoumé) e granitos rapakivi de idades entre 1883 a 1889 Ma (Granito São Gabriel da Suíte Mapuera), e rochas afins (quartzo-gabro-anortosito e diorito), além de quartzo-monzonito Castanhal, milonitos e hornfels. A fácies quartzo-diorito do granito Terra Preta foi formada por processos de mistura entre um dique quartzo-gabro sinplutônico e um granodiorito hornblenda. Glóbulos parcialmente assimilados de sienogranitos hornblenda Canoas e seus contatos com o granodiorito hornblenda Terra Preta sugerem que o sienogranito Canoas é um pouco mais jovem do que o Granito Terra Preta. Xenólitos do sienogranito Canoas no interior do Granito São Gabriel mostram que o granito é mais jovem do que o sienogranito Canoas. Novas evidências geológicas e petrográficas avançam na compreensão petrológica destas rochas e sugerem que, além de cristalização fracionada, assimilação e mistura de magma, desempenharam um papel importante, pelo menos em escala local, na evolução e variação composicionais dos plutons. Tal evidência é encontrada no Granito Terra Preta misturado com materiais quartzo-diorito, félsico associado ao sienogranito Canoas e nos enclaves microgranulares intermediários, que apresentam biotita e hornblenda primárias, além de dissolução plagioclásio, corrosão de feldspatos, mantos feldspatos alcalinos, segunda geração de apatita, e elevados teores xenocristais em enclaves intermediários formados a partir da fragmentação de intrusões máficas. Análises petrográficas mostram que um evento deformacional registrado na parte Ocidental da área de estudo (com deformação progressiva de E para W) é estimado entre o magmatismo pós-colisional de 1,90 Ga e as invasões do Granito São Gabriel e rochas afins máficas/intermediárias (intraplaca). No entanto, torna-se extremamente necessário obter idades absolutas para este evento metamórfico.