Role of the N-terminal region in G protein-coupled receptor functions : negative modulation revealed by 5-HT2B receptor polymorphisms

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family

Secure modular password authentication for the web using channel bindings

Secure protocols for password-based user authentication are well-studied in the cryptographic literature but have failed to see wide-spread adoption on the Internet; most proposals to date require extensive modifications to the Transport Layer Security (TLS) protocol, making deployment challenging. Recently, a few modular designs have been proposed in which a cryptographically secure password-based mutual authentication protocol is run inside a confidential (but not necessarily authenticated) channel such as TLS; the password protocol is bound to the established channel to prevent active attacks. Such protocols are useful in practice for a variety of reasons: security no longer relies on users' ability to validate server certificates and can potentially be implemented with no modifications to the secure channel protocol library. We provide a systematic study of such authentication protocols. Building on recent advances in modelling TLS, we give a formal definition of the intended security goal, which we call password-authenticated and confidential channel establishment (PACCE). We show generically that combining a secure channel protocol, such as TLS, with a password authentication protocol, where the two protocols are bound together using either the transcript of the secure channel's handshake or the server's certificate, results in a secure PACCE protocol. Our prototype based on TLS is available as a cross-platform client-side Firefox browser extension and a server-side web application which can easily be installed on deployed web browsers and servers.

NADPH oxidases as regulators of tumor angiogenesis : current and emerging concepts

Significance Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and peroxynitrite are generated ubiquitously by all mammalian cells and have been understood for many decades as inflicting cell damage and as causing cancer by oxidation and nitration of macromolecules, including DNA, RNA, proteins, and lipids. Recent Advances A current concept suggests that ROS can also promote cell signaling pathways triggered by growth factors and transcription factors that ultimately regulate cell proliferation, differentiation, and apoptosis, all of which are important hallmarks of tumor cell proliferation and angiogenesis. Moreover, an emerging concept indicates that ROS regulate the functions of immune cells that infiltrate the tumor environment and stimulate angiogenesis, such as macrophages and specific regulatory T cells. Critical Issues In this article, we highlight that the NADPH oxidase family of ROS-generating enzymes are the key sources of ROS and, thus, play an important role in redox signaling within tumor, endothelial, and immune cells thereby promoting tumor angiogenesis. Future Directions Knowledge of these intricate ROS signaling pathways and identification of the culprit NADPH oxidases is likely to reveal novel therapeutic opportunities to prevent angiogenesis that occurs during cancer and which is responsible for the revascularization after current antiangiogenic treatment.

The paradigm shift in realising the right to read : how ebook libraries are enabling in the university sector

Millions of people with print disabilities are denied the right to read. While some important efforts have been made to convert standard books to accessible formats and create accessible repositories, these have so far only addressed this crisis in an ad hoc way. This article argues that universally designed ebook libraries have the potential of substantially enabling persons with print disabilities. As a case study of what is possible, we analyse 12 academic ebook libraries to map their levels of accessibility. The positive results from this study indicate that universally designed ebooks are more than possible; they exist. While results are positive, however, we also found that most ebook libraries have some features that frustrate full accessibility, and some ebook libraries present critical barriers for people with disabilities. Based on these findings, we consider that some combination of private pressure and public law is both possible and necessary to advance the right-to-read cause. With access improving and recent advances in international law, now is the time to push for universal design and equality.

Sex work and health in a rural context: results of qualitative study undertaken in New South Wales

The paper reports health related findings of the first study undertaken of rural sex workers in an income-rich nation. In-depth interviews were conducted with eighteen purposively selected women who work in the rural sex industry. Rural sex services have a unique structure which informs the experiences of sex workers. Recent advances in telecommunications technology have impacted upon the organisation and structure of the sex industry in rural environments. Notable has been the growth of escort services in rural areas, which has diversified the rural sex industry from its traditional base of brothel operations. The general absence of street prostitution in rural settings has meant that the profile of rural sex workers tends to resemble that of escorts or call girls in urban settings, with workers having a relatively high level of control over working conditions and compliance with public health initiatives. Important issues which impact upon the rural sex industry include confidentiality and the more limited market for sexual services likely to be encountered in rural settings. These issues may impact on the sexual health of rural sex workers in terms of risk practices and access to health services.

Acoustic identification of 12 species of echolocating bat by discriminant function analysis and artificial neural networks

We recorded echolocation calls from 14 sympatric species of bat in Britain. Once digitised, one temporal and four spectral features were measured from each call. The frequency-time course of each call was approximated by fitting eight mathematical functions, and the goodness of fit, represented by the mean-squared error, was calculated. Measurements were taken using an automated process that extracted a single call from background noise and measured all variables without intervention. Two species of Rhinolophus were easily identified from call duration and spectral measurements. For the remaining 12 species, discriminant function analysis and multilayer back-propagation perceptrons were used to classify calls to species level. Analyses were carried out with and without the inclusion of curve-fitting data to evaluate its usefulness in distinguishing among species. Discriminant function analysis achieved an overall correct classification rate of 79% with curve-fitting data included, while an artificial neural network achieved 87%. The removal of curve-fitting data improved the performance of the discriminant function analysis by 2 %, while the performance of a perceptron decreased by 2 %. However, an increase in correct identification rates when curve-fitting information was included was not found for all species. The use of a hierarchical classification system, whereby calls were first classified to genus level and then to species level, had little effect on correct classification rates by discriminant function analysis but did improve rates achieved by perceptrons. This is the first published study to use artificial neural networks to classify the echolocation calls of bats to species level. Our findings are discussed in terms of recent advances in recording and analysis technologies, and are related to factors causing convergence and divergence of echolocation call design in bats.

Editorial Preface

This special volume of Procedia Engineering contains papers presented at the 12th Global Congress on Manufacturing and Management (GCMM - 2014), held during 8-10 December 2014 at VIT University, Vellore, India. A total of 258 papers were presented during the conference, covering the entire spectrum of Materials Processing, Manufacturing Engineering, Industrial Engineering and Management. Materials and Manufacturing field is undergoing a rapid transformation due to unexpected challenges arising from the current approach to optimization and continuous performance improvement in manufacturing processes, production of large products and development of new materials. The 12th edition of the conference has earmarked the objective to offer a common platform for professionals, researchers and educators from industry, research centers and academia to present and discuss recent advances in the field of Manufacturing Engineering.

Editorial

The 2nd International Digital Human Modeling (DHM) Symposium was held at the renowned University of Michigan Transportation Research Institute (UMTRI) in Ann Arbor, Michigan in June 11–13, 2013. The symposium was co-organised by the UMTRI and Penn State University, and endorsed by the IEA Technical Committee on Human Simulation and Virtual Environments. The conference built on the very successful inaugural event DHM2011 held in Lyon two years before; and a decade of digital human modelling conferences held under the auspices of SAE International. Practitioners and scientists from 13 countries gathered to present their state-of-the-art developments and applied research, besides discussing the most recent advances in human modelling and directions for future work in DHM...

Acoustic identification of twelve species of echolocating bat by discriminant function analysis and artificial neural networks

We recorded echolocation calls from 14 sympatric species of bat in Britain. Once digitised, one temporal and four spectral features were measured from each call. The frequency-time course of each call was approximated by fitting eight mathematical functions, and the goodness of fit, represented by the mean-squared error, was calculated. Measurements were taken using an automated process that extracted a single call from background noise and measured all variables without intervention. Two species of Rhinolophus were easily identified from call duration and spectral measurements. For the remaining 12 species, discriminant function analysis and multilayer back-propagation perceptrons were used to classify calls to species level. Analyses were carried out with and without the inclusion of curve-fitting data to evaluate its usefulness in distinguishing among species. Discriminant function analysis achieved an overall correct classification rate of 79% with curve-fitting data included, while an artificial neural network achieved 87%. The removal of curve-fitting data improved the performance of the discriminant function analysis by 2 %, while the performance of a perceptron decreased by 2 %. However, an increase in correct identification rates when curve-fitting information was included was not found for all species. The use of a hierarchical classification system, whereby calls were first classified to genus level and then to species level, had little effect on correct classification rates by discriminant function analysis but did improve rates achieved by perceptrons. This is the first published study to use artificial neural networks to classify the echolocation calls of bats to species level. Our findings are discussed in terms of recent advances in recording and analysis technologies, and are related to factors causing convergence and divergence of echolocation call design in bats.

Cryptographic Hash Functions

In the modern era of information and communication technology, cryptographic hash functions play an important role in ensuring the authenticity, integrity, and nonrepudiation goals of information security as well as efficient information processing. This entry provides an overview of the role of hash functions in information security, popular hash function designs, some important analytical results, and recent advances in this field.

Cytokine secretion in macrophages : SNAREs, Rabs and membrane trafficking

Macrophages have the capacity to rapidly secrete a wide range of inflammatory mediators that influence the development and extent of an inflammatory response. Newly synthesized and/or preformed stored cytokines and other inflammatory mediators are released upon stimulation, the timing, and volume of which is highly regulated. To finely tune this process, secretion is regulated at many levels; at the level of transcription and translation and post-translationally at the endoplasmic reticulum (ER), Golgi, and at or near the cell surface. Here, we discuss recent advances in deciphering these cytokine pathways in macrophages, focusing on recent discoveries regarding the cellular machinery and mechanisms implicated in the synthesis, trafficking, and secretion of cytokines. The specific roles of trafficking machinery including chaperones, GTPases, cytoskeletal proteins, and SNARE membrane fusion proteins will be discussed.

Some of the design considerations in power generation from offshore wind farms

The global efforts to reduce carbon emissions from power generation have favoured renewable energy resources such as wind and solar in recent years. The generation of power from the renewable energy resources has become attractive because of various incentives provided by government policies supporting green power. Among the various available renewable energy resources, the power generation from wind has seen tremendous growth in the last decade. This article discusses various advantages of the upcoming offshore wind technology and associated considerations related to their construction. The conventional configuration of the offshore wind farm is based on the alternative current internal links. With the recent advances of improved commercialised converters, voltage source converters based high voltage direct current link for offshore wind farms is gaining popularity. The planning and construction phases of offshore wind farms, including related environmental issues, are discussed here.

Model refinement through high-performance computing: an agent-based HIV example

Background Recent advances in Immunology highlighted the importance of local properties on the overall progression of HIV infection. In particular, the gastrointestinal tract is seen as a key area during early infection, and the massive cell depletion associated with it may influence subsequent disease progression. This motivated the development of a large-scale agent-based model. Results Lymph nodes are explicitly implemented, and considerations on parallel computing permit large simulations and the inclusion of local features. The results obtained show that GI tract inclusion in the model leads to an accelerated disease progression, during both the early stages and the long-term evolution, compared to a theoretical, uniform model. Conclusions These results confirm the potential of treatment policies currently under investigation, which focus on this region. They also highlight the potential of this modelling framework, incorporating both agent-based and network-based components, in the context of complex systems where scaling-up alone does not result in models providing additional insights.

High-performance computing for data analytics

One of the main challenges in data analytics is that discovering structures and patterns in complex datasets is a computer-intensive task. Recent advances in high-performance computing provide part of the solution. Multicore systems are now more affordable and more accessible. In this paper, we investigate how this can be used to develop more advanced methods for data analytics. We focus on two specific areas: model-driven analysis and data mining using optimisation techniques.

Watermarking capacity control for dynamic payload embedding

Despite significant improvements in capacity-distortion performance, a computationally efficient capacity control is still lacking in the recent watermarking schemes. In this paper, we propose an efficient capacity control framework to substantiate the notion of watermarking capacity control to be the process of maintaining “acceptable” distortion and running time, while attaining the required capacity. The necessary analysis and experimental results on the capacity control are reported to address practical aspects of the watermarking capacity problem, in dynamic (size) payload embedding.