Practical Lattice-Based Digital Signature Schemes

Digital signatures are an important primitive for building secure systems and are used in most real-world security protocols. However, almost all popular signature schemes are either based on the factoring assumption (RSA) or the hardness of the discrete logarithm problem (DSA/ECDSA). In the case of classical cryptanalytic advances or progress on the development of quantum computers, the hardness of these closely related problems might be seriously weakened. A potential alternative approach is the construction of signature schemes based on the hardness of certain lattice problems that are assumed to be intractable by quantum computers. Due to significant research advancements in recent years, lattice-based schemes have now become practical and appear to be a very viable alternative to number-theoretic cryptography. In this article, we focus on recent developments and the current state of the art in lattice-based digital signatures and provide a comprehensive survey discussing signature schemes with respect to practicality. Additionally, we discuss future research areas that are essential for the continued development of lattice-based cryptography.

Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months' streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the molecular and functional expression of TRPV4 channels in retinal microvascular endothelial cells. These changes may contribute to diabetes induced endothelial dysfunction and retinopathy.

Development of an app to support learning in A-level maths

This project involved producing an app for smart devices to enable modernised learning for A-level maths students. Research in a stakeholder school showed that 94% of pupils surveyed within the upper-secondary level owned a smartphone and most owned a tablet also, emphasising the opportunity for using apps to support learning. The app was developed using iBuildApp, an online app-creation programme which requires no programming. Past exam questions and solutions, notes and video tutorials were included and the topic was vectors, identified by teachers as problematic. Pupils generally found the app easy to use and wanted further development. The videos were popular despite this not ranking highly as a preferred method of revision previously. Teachers were happy for pupils to use the app to supplement their learning, both in the classroom and outside.

Research in Progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK)

The UK Refractory Asthma Stratification Programme(RASP-UK) will explore novel biomarker stratificationstrategies in severe asthma to improve clinicalmanagement and accelerate development of newtherapies. Prior asthma mechanistic studies have notstratified on inflammatory phenotype and theunderstanding of pathophysiological mechanisms inasthma without Type 2 cytokine inflammation is limited.RASP-UK will objectively assess adherence tocorticosteroids (CS) and examine a novel compositebiomarker strategy to optimise CS dose; this will alsoaddress what proportion of patients with severe asthmahave persistent symptoms without eosinophilic airwaysinflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies.

Evidence supporting a role for N-epsilon-(3-formyl-3,4-dehydropiperidino)lysine accumulation in Muller glia dysfunction and death in diabetic retinopathy

Purpose: Recent evidence suggests that neuroglial dysfunction and degeneration contributes to the etiology and progression of diabetic retinopathy. Advanced lipoxidation end products (ALEs) have been implicated in the pathology of various diseases, including diabetes and several neurodegenerative disorders. The purpose of the present study was to investigate the possible link between the accumulation of ALEs and neuroretinal changes in diabetic retinopathy.

Methods: Retinal sections obtained from diabetic rats and age-matched controls were processed for immunohistochemistry using antibodies against several well defined ALEs. In vitro experiments were also performed using a human Muller (Moorfields/Institute of Ophthalmology-Muller 1 [ MIO-M1]) glia cell line. Western blot analysis was used to measure the accumulation of the acrolein-derived ALE adduct N epsilon-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) in Muller cells preincubated with FDP-lysine-modified human serum albumin (FDP-lysine-HSA). Responses of Muller cells to FDP-lysine accumulation were investigated by analyzing changes in the protein expression of heme oxygenase-1 (HO-1), glial fibrillary acidic protein (GFAP), and the inwardly rectifying potassium channel Kir4.1. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) were determined by reverse transcriptase PCR (RT-PCR). Apoptotic cell death was evaluated by fluorescence-activated cell sorting (FACS) analysis after staining with fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide.

Results: No significant differences in the levels of malondialdehyde-, 4-hydroxy-2-nonenal-, and 4-hydroxyhexenal-derived ALEs were evident between control and diabetic retinas after 4 months of diabetes. By contrast, FDP-lysine immunoreactivity was markedly increased in the Muller glia of diabetic rats. Time-course studies revealed that FDP-lysine initially accumulated within Muller glial end feet after only a few months of diabetes and thereafter spread distally throughout their inner radial processes. Exposure of human Muller glia to FDP-lysine-HSA led to a concentration-dependent accumulation of FDP-lysine-modified proteins across a broad molecular mass range. FDP-lysine accumulation was associated with the induction of HO-1, no change in GFAP, a decrease in protein levels of the potassium channel subunit Kir4.1, and upregulation of transcripts for VEGF, IL-6, and TNF-alpha. Incubation of Muller glia with FDP-lysine-HSA also caused apoptosis at high concentrations.

Conclusions: Collectively, these data strongly suggest that FDP-lysine accumulation could be a major factor contributing to the Muller glial abnormalities occurring in the early stages of diabetic retinopathy.

CaV3.1 T-Type Ca2+ Channels Contribute to Myogenic Signalling in Rat Retinal Arterioles

Purpose: Although L-type Ca2+ channels are known to play a key role in the myogenic reactivity of retinal arterial vessels, the involvement of other types of voltage-gated Ca2+ channels in this process remains unknown. In the present study we have investigated the contribution of T-type Ca2+ channels to myogenic signalling in arterioles of the rat retinal microcirculation.

Methods: Confocal immunolabelling of wholemount preparations was used to investigate the localisation of CaV3.1-3 channels in retinal arteriolar smooth muscle cells. T-type currents and the contribution of T-type channels to myogenic signalling were assessed by whole-cell patch-clamp recording and pressure myography of isolated retinal arteriole segments.

Results: Strong immunolabelling for CaV3.1 was observed on the plasma membrane of retinal arteriolar smooth muscle cells. In contrast, no expression of CaV3.2 or CaV3.3 could be detected in retinal arterioles, although these channels were present on glial cell end feet surrounding the vessels and retinal ganglion cells, respectively. TTA-A2 sensitive T-type currents were recorded in retinal arteriolar myocytes with biophysical properties distinct from those of the L-type currents present in these cells. Inhibition of T-type channels using TTA-A2 or ML-218 dilated isolated, myogenically active, retinal arterioles.

Conclusions: CaV3.1 T-type Ca2+ channels are functionally expressed on arteriolar smooth muscle cells of retinal arterioles and play an important role in myogenic signalling in these vessels. The work has important implications concerning our understanding of the mechanisms controlling blood flow autoregulation in the retina and its disruption during ocular disease.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Contemporary Politics in the Middle East (Cambridge: Polity, 2011 – third edition)

The third edition of this dynamic book has been fully revised and updated to provide a comprehensive introduction to contemporary politics in the Middle East. Purposefully employing a clear thematic structure and including a wide range of case studies, data, visuals and further reading guidance the book explores and analyses the major issues which define the politics of this region of the globe.
Milton-Edwards begins by introducing and explaining key concepts and debates and goes on to outline the impact of colonialism and its legacy, the rise of Arab nationalism and anti-colonial politics. She then examines major political issues affecting the region, such as American foreign policy, political Islam, war and conflict, political economy, democratization, ethnicity and the role of women. The book concludes by highlighting the politics of the region in the twenty-first century and the future challenges it faces. This is a perfect introduction for undergraduates, covering key political, economic and social debates and providing updates and guidance for further reading.

"The genius of this book is that it integrates together the different themes which run through Middle Eastern politics. The coherence of the approach which the author has adopted is indicated by the manner in which she has updated the work in this second edition. Despite the substantial changes which the East has undergone since 9/11 and the 2003 Gulf War, the original line of analysis retains all its force. It remains a key reference for all those who are seeking to understand the region's politics, whether undergraduates, postgraduates or lay readers."
Tim Niblock, Exeter University
"I welcome the new edition of this comprehensive guide to the politics of such an important region of the world. It combines sensible generalizations with useful case studies of particularly important subjects. It is a must for all those who want to understand the complex politics of the modern Middle East."
Roger Owen, Harvard University
"Beverley Milton-Edwards has produced an excellent book, which is both wide-ranging in its coverage and punchy in its arguments. As such, its functions are dual. It works well as a text book, introducing the general reader to key themes in the contemporary region, from oil politics to ethnicity, to women and nationalism. But it also works as a running commentary on key debates, such as the rile of colonialism and the relationship between Islam and democracy. In short, this is a book with attitude."
Philip Robins, St Antony's College, Oxford

Gender, religion, and sociopolitical issues in cross-cultural online education

Cross-cultural education is thought to develop critical consciousness of how unequal distributions of power and privilege affect people’s health. Learners in different sociopolitical settings can join together in developing critical consciousness – awareness of power and privilege dynamics in society – by means of communication technology. The aim of this research was to define strengths and limitations of existing cross-cultural discussions in generating critical consciousness. The setting was the FAIMER international fellowship program for mid-career interdisciplinary health faculty, whose goal is to foster global advancement of health professions education. Fellows take part in participant-led, online, written, task-focused discussions on topics like professionalism, community health, and leadership. We reflexively identified text that brought sociopolitical topics into the online environment during the years 2011 and 2012 and used a discourse analysis toolset to make our content analysis relevant to critical consciousness. While references to participants’ cultures and backgrounds were infrequent, narratives of political-, gender-, religion-, and other culture-related topics did emerge. When participants gave accounts of their experiences and exchanged cross-cultural stories, they were more likely to develop ad hoc networks to support one another in facing those issues than explore issues relating to the development of critical consciousness. We suggest that cross-cultural discussions need to be facilitated actively to transform learners’ frames of reference, create critical consciousness, and develop cultural competence. Further research is needed into how to provide a safe environment for such learning and provide faculty development for the skills needed to facilitate these exchanges.

The progress in understanding and treatment of diabetic retinopathy

In most countries, diabetic retinopathy is the most frequently occurring complication of diabetes mellitus and remains a leading cause of vision loss globally. Its etiology and pathology have been extensively studied for half a century, yet there are disappointingly few therapeutic options. Although some new treatments have been introduced for diabetic macular edema (DME) (e.g. intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') and new steroids), up to 50% of patients fail to respond. Furthermore, for people with proliferative diabetic retinopathy (PDR), laser photocoagulation remains a mainstay therapy, even though it is inherently a destructive procedure. This review summarizes the clinical features of diabetic retinopathy and its risk factors. It describes details of retinal pathology and the cell culture approaches and animal models that are used to mimic its key components, advance understanding of its pathogenesis, and enable identification of new therapeutic targets. We emphasise that although there have been significant advances, there is still a pressing need for a better understanding basic mechanisms to enable development of reliable and robust means to identify patients at highest risk, and to intervene effectively before vision loss occurs.