ValiDichro: a website for validating and quality control of protein circular dichroism spectra

Circular dichroism (CD) spectroscopy is widely used in structural biology as a technique for examining the structure, folding and conformational changes of proteins. A new server, ValiDichro, has been developed for checking the quality and validity of CD spectral data and metadata, both as an aid to data collection and processing and as a validation procedure for spectra to be included in publications. ValiDichro currently includes 25 tests for data completeness, consistency and quality. For each test that is done, not only is a validation report produced, but the user is also provided with suggestions for correcting or improving the data. The ValiDichro server is freely available at http://valispec.cryst.bbk.ac.uk/circularDichroism/ValiDichro/upload.html

Assessing the UK policies for broadband adoption

Broadband technology has been introduced to the business community and the public as a rapid way of exploiting the Internet. The benefits of its use (fast reliable connections, and always on) have been widely realised and broadband diffusion is one of the items at the top of the agenda for technology related polices of governments worldwide. In this paper an examination of the impact of the UK government’s polices upon broadband adoption is undertaken. Based on institutional theory a consideration of the manipulation of supply push and demand pull forces in the diffusion of broadband is offered. Using primary and secondary data sources, an analysis of the specific institutional actions related to IT diffusion as pursued by the UK government in the case of broadband is provided. Bringing the time dimension into consideration it is revealed that the UK government has shifted its attention from supply push-only strategies to more interventional ones where the demand pull forces are also mobilised. It is believed that this research will assist in the extraction of the “success factors” in government intervention that support the diffusion of technology with a view to render favourable results if applied to other national settings

Spectral magnitude effects on the analyses of secondary structure from circular dichroism spectroscopic data

Abstract The effects of spectral magnitude on the calculated secondary structures derived from circular dichroism (CD) spectra were examined for a number of the most commonly used algorithms and reference databases. Proteins with different secondary structures, ranging from mostly helical to mostly ␤-sheet, but which were not components of existing reference databases, were used as test systems. These proteins had known crystal structures, so it was possible to ascertain the effects of magnitude on both the accuracy of determining the secondary structure and the goodness-of-fit of the calculated structures to the experimental data. It was found that most algorithms are highly sensitive to spectral magnitude, and that the goodness-of-fit parameter may be a useful tool in assessing the correct scaling of the data. This means that parameters that affect magnitude, including calibration of the instrument, the spectral cell pathlength, and the protein concentration, must be accurately determined to obtain correct secondary structural analyses of proteins from CD data using empirical methods. Keywords: circular dichroism (CD) spectroscopy; calibration; secondary structure analyses; synchrotron radiation circular dichroism (SRCD) Circular dichroism (CD) spectroscopy can be a valuable method for determining the secondary structures of proteins. However, an accurate analysis relies on (among other things) having the correct magnitude for the spectrum. The determination of the magnitude of a circular dichroism spectrum can be adversely affected by a number of factors including errors in instrument calibration, cell pathlength, and protein concentration. Often these factors are not carefully considered when spectra are reported in the literature or analyzed by empirical secondary structure calculation methods. A number of years ago we examined the effects of magnitude on constrained, unconstrained, and normalized leastsquares methods of analyses of protein secondary structures from CD data (Wallace and Teeters 1987). We demonstrated that all except the normalized methods were highly influenced by the magnitudes of the spectra. Since that time, much more sophisticated algorithms have been developed for such empirical analyses, including variable selection, neural network, and principal component methods Abbreviations: CD, circular dichroism; cCD, conventional circular dichroism; CSA, camphor sulfonic acid; NRMSD, normalized root-meansquare deviation; QAA, quantitative amino acid analysis; SRCD, synchrotron radiation circular dichroism. Article and publication are at http://www.proteinscience.org/cg

A role for planar cell polarity during early endoderm morphogenesis

The zebrafish endoderm begins to develop at gastrulation stages as a monolayer of cells. The behaviour of the endoderm during gastrulation stages is well understood. However, knowledge of the morphogenic movements of the endoderm during somitogenesis stages, as it forms a mesenchymal rod, is lacking. Here we characterise endodermal development during somitogenesis stages, and describe the morphogenic movements as the endoderm transitions from a monolayer of cells into a mesenchymal endodermal rod. We demonstrate that, unlike the overlying mesoderm, endodermal cells are not polarised during their migration to the midline at early somitogenesis stages. Specifically, we describe the stage at which endodermal cells begin to leave the monolayer, a process we have termed ‘midline aggregation’. The planar cell polarity (PCP) signalling pathway is known to regulate mesodermal and ectodermal cell convergence towards the dorsal midline. However, a role for PCP signalling in endoderm migration to the midline during somitogenesis stages has not been established. In this report, we investigate the role for PCP signalling in multiple phases of endoderm development during somitogenesis stages. Our data exclude involvement of PCP signalling in endodermal cells as they leave the monolayer.The work was supported by a project grant from the National Health and Medical Research Council (491087) to H.V

Secondary user relations in emerging mobile computing environments

Mobile technologies are enabling access to information in diverse environ.ments, and are exposing a wider group of individuals to said technology. Therefore, this paper proposes that a wider view of user relations than is usually considered in information systems research is required. Specifically, we examine the potential effects of emerging mobile technologies on end-­‐user relations with a focus on the ‘secondary user’, those who are not intended to interact directly with the technology but are intended consumers of the technology’s output. For illustration, we draw on a study of a U.K. regional Fire and Rescue Service and deconstruct mobile technology use at Fire Service incidents. Our findings provide insights, which suggest that, because of the nature of mobile technologies and their context of use, secondary user relations in such emerging mobile environments are important and need further exploration

Time resolved amplified FRET identifies protein kinase B activation state as a marker for poor prognosis in clear cell renal cell carcinoma

Purpose Clear cell Renal Cell Carcinomas (ccRCC), the largest group of renal tumours, are resistant to classical therapies. The determination of the functional state of actionable biomarkers for the assessment of these adenocarcinomas is essential. The dysregulation of the oncoprotein, PKB/Akt has been linked with poor prognoses in human cancers. Material & methods We analysed the status of the PKB/Akt pathway in a representative tumour tissue microarray obtained from the primary tumours and their metastases in 60 ccRCC with long term follow up. We sought to define the evolution of this pathway from the primary tumour to the metastatic event and to know the impact of its functional state in tumour aggressiveness and patient survival. Two-site time resolved amplified FRET (A-FRET) was utilised for assessing the activation state of PKB/Akt and this was compared to conventional immunohistochemistry measurements. Results Activation state of PKB/Akt in primary tumours defined by A-FRET correlated with poorer overall survival (hazard ratio 0.228; p = 0.002). Whereas, increased protein expression of phosphoPKB/Akt, identified using classical immunohistochemistry, yielded no significant difference (hazard ratio 1.390; p = 0.548). Conclusions Quantitative determination of PKB/Akt activation in ccRCC primary tumours alongside other diagnostics tools could prove key in taking oncologists closer to an efficient personalised therapy in ccRCC patients. General significance The quantitative imaging technology based on Amplified-FRET can rapidly analyse protein activation states and molecular interactions. It could be used for prognosis and assess drug function during the early cycles of chemotherapy. It enables evaluation of clinical efficiency of personalised cancer treatment

An optically actuated surface scanning probe

We demonstrate the use of an extended, optically trapped probe that is capable of imaging surface topography with nanometre precision, whilst applying ultra-low, femto-Newton sized forces. This degree of precision and sensitivity is acquired through three distinct strategies. First, the probe itself is shaped in such a way as to soften the trap along the sensing axis and stiffen it in transverse directions. Next, these characteristics are enhanced by selectively position clamping independent motions of the probe. Finally, force clamping is used to refine the surface contact response. Detailed analyses are presented for each of these mechanisms. To test our sensor, we scan it laterally over a calibration sample consisting of a series of graduated steps, and demonstrate a height resolution of ∼ 11 nm. Using equipartition theory, we estimate that an average force of only ∼ 140 fN is exerted on the sample during the scan, making this technique ideal for the investigation of delicate biological samples

Feasibility of Utilizing Ethnic Beauty Salons for Cervical Cancer Screening Education

The purpose of this study was to assess the feasibility of using ethnic beauty salons to reach out to Vietnamese and Korean American women for cervical cancer screening education. Participants (N = 62) were conveniently recruited from ethnic beauty salons located in Albuquerque, New Mexico. Two feasibility questionnaires were separately administered to cosmetologists and their customers. Findings support the view that ethnic beauty salons can be used as a gateway to reach out to these populations, and cosmetologists have the potential to operate as community lay health workers to deliver cervical cancer screening education aimed at reducing disparities in cervical cancer and screening to their ethnic customers.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Distribution And Recovery Trajectory Of Macondo (Mississippi Canyon 252) Oil In Louisiana Coastal Wetlands

We measured the concentration of petroleum hydrocarbons in 405 wetland sediment samples immediately before the April 2010 Deepwater Horizon disaster led to their broad-scale oiling, and on nine trips afterwards. The average concentrations of alkanes and PAHs were 604 and 186 times the pre-spill baseline values, respectively. Oil was distributed with some attenuation up to 100 m inland from the shoreline for alkanes, but increased for aromatics, and was not well-circumscribed by the rapid shoreline assessments (a.k.a. SCAT) of relative oiling. The concentrations of target alkanes and PAHs in June 2013 were about 1% and 5%, respectively, of the February 2011 concentrations, but remained at 3.7 and 33 times higher, respectively, than in May 2010. A recovery to baseline conditions suggests that the concentration of alkanes may be near baseline values by the end of 2015, but that it may take decades for the PAH concentrations to be that low. (C) 2014 The Authors. Published by Elsevier Ltd

The State of the World’s Urban Ecosystems: what can we learn from trees, fungi and bees?

Trees are a foundation for biodiversity in urban ecosystems and therefore must be able to withstand global change and biological challenges over decades and even centuries to prevent urban ecosystems from deteriorating. Tree quality and diversity should be prioritized over simply numbers to optimize resilience to these challenges. Successful establishment and renewal of trees in cities must also consider belowground (e.g., mycorrhizas) and aboveground (e.g., pollinators) interactions to ensure urban ecosystem longevity, biodiversity conservation and continued provision of the full range of ecosystem services provided by trees. Positive interactions with nature inspire people to live more sustainable lifestyles that are consistent with stopping biodiversity loss and to participate in conservation actions such as tree‐planting and supporting pollinators. Interacting with nature simultaneously provides mental and physical health benefits to people. Since most people live in cities, here we argue that urban ecosystems provide important opportunities for increasing engagement with nature and educating people about biodiversity conservation. While advocacy on biodiversity must communicate in language that is relevant to a diverse audience, over‐simplified messaging, may result in unintended negative outcomes. For example, tree planting actions typically focus on numbers rather than diversity while the call to save bees has inspired unsustainable proliferation of urban beekeeping that may damage wild bee conservation through increased competition for limited forage in cities and disease spread. Ultimately multiple ecosystem services must be considered (and measured) to optimize their delivery in urban ecosystems and messaging to promote the value of nature in cities must be made widely available and more clearly defined