Rate distortion optimized graph partitioning for omnidirectional image coding

International audienceOmnidirectional images are spherical signals captured by cameras with 360-degree field of view. In order to be compressed using existing encoders, these signals are mapped to planar domain. A commonly used planar representation is the equirectangular one, which corresponds to a non uniform sampling pattern on the spherical surface. This particularity is not explored in traditional image compression schemes, which treat the input signal as a classical perspective image. In this work, we build a graph-based coder adapted to the spherical surface. We build a graph directly on the sphere. Then, to have computationally feasible graph transforms, we propose a rate-distortion optimized graph partitioning algorithm to achieve an effective trade-off between the distortion of the reconstructed signals, the smoothness of the signal on each subgraph, and the cost of coding the graph partitioning description. Experimental results demonstrate that our method outperforms JPEG coding of planar equirectangular images

Molecular basis for functional switching of GFP by two disparate non-native post-translational modifications of a phenyl azide reaction handle

Through the genetic incorporation of a single phenyl azide group into superfolder GFP (sfGFP) at residue 148 we provide a molecular description of how this highly versatile chemical handle can be used to positively switch protein function in vitro and in vivo via either photochemistry or bioconjugation. Replacement of H148 with p-azido-L-phenylalanine (azF) blue shifts the major excitation peak ∼90 nm by disrupting the H-bond and proton transfer network that defines the chromophore charged state. Bioorthogonal click modification with a simple dibenzylcyclooctyne or UV irradiation shifts the neutral-anionic chromophore equilibrium, switching fluorescence to the optimal ∼490 nm excitation. Click modification also improved quantum yield over both the unmodified and original protein. Crystal structures of both the click modified and photochemically converted forms show that functional switching is due to local conformational changes that optimise the interaction networks surrounding the chromophore. Crystal structure and mass spectrometry studies of the irradiated protein suggest that the phenyl azide converts to a dehydroazepine and/or an azepinone. Thus, protein embedded phenyl azides can be used beyond simple photocrosslinkers and passive conjugation handles, and mimic many natural post-translational modifications: modulation though changes in interaction networks

Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function

INTRODUCTION: Genome-wide association studies link susceptibility to late-onset Alzheimer's disease (LOAD) with EphA1. Sequencing identified a non-synonymous substitution P460L as a LOAD risk variant. Other Ephs regulate vascular permeability and immune cell recruitment. We hypothesized that P460L dysregulates EphA1 receptor activity and impacts neuroinflammation. METHODS: EphA1/P460L receptor activity was assayed in isogenic Human Embryonic Kidney (HEK) cells. Soluble EphA1/P460L (sEphA1/sP460L) reverse signaling in brain endothelial cells was assessed by T-cell recruitment and barrier function assays. RESULTS: EphA1 and P460L were expressed in HEK cells, but membrane and soluble P460L were significantly reduced. Ligand engagement induced Y781 phosphorylation of EphA1 but not P460L. sEphA1 primed brain endothelial cells for increased T-cell recruitment; however, sP460L was less effective. sEphA1 decreased the integrity of the brain endothelial barrier, while sP460L had no effect. DISCUSSION: These findings suggest that P460L alters EphA1-dependent forward and reverse signaling, which may impact blood-brain barrier function in LOAD. Highlights: EphA1-dependent reverse signaling controls recruitment of T cells by brain endothelial cells. EphA1-dependent reverse signaling remodels brain endothelial cell contacts. LOAD-associated P460L variant of EphA1 shows reduced membrane expression and reduced ligand responses. LOAD-associated P460L variant of EphA1 fails to reverse signal to brain endothelial cells.Neuroscience and Mental Health Research Institute (NMHRI), Cardiff University and Sir Geraint Evans Cardiovascular Fund, Cardiff University (grant to A.A. and A.J.R.), L.E.T. by UK Dementia Research Institute, Cardiff University, O.R.M. by School of Medicine, Cardiff University, S.S. and C.L.T. by Eli Lilly (grant to J.W. and A.A.), and C.C. by School of Cellular and Molecular Medicine, University of Bristol. The Bioflux 200 was funded by the Leukemia Research Appeal for Wales, and iBright 1500 was funded by the Ser Cymru II programme (grant CU209 to V.K. and Manon Pritch, which was partially funded by Cardiff University and the European Regional Development Fund through the Welsh Government (Grant CU209 to V.K. and Manon Pritchard)

Random single amino acid deletion sampling unveils structural tolerance and the benefits of helical registry shift on GFP folding and structure

Altering a protein’s backbone through amino acid deletion is a common evolutionary mutational mechanism, but is generally ignored during protein engineering primarily because its effect on the folding-structure-function relationship is difficult to predict. Using directed evolution, enhanced green fluorescent protein (EGFP) was observed to tolerate residue deletion across the breadth of the protein, particularly within short and long loops, helical elements, and at the termini of strands. A variant with G4 removed from a helix (EGFPG4Δ) conferred significantly higher cellular fluorescence. Folding analysis revealed that EGFPG4Δ retained more structure upon unfolding and refolded with almost 100% efficiency but at the expense of thermodynamic stability. The EGFPG4Δ structure revealed that G4 deletion caused a beneficial helical registry shift resulting in a new polar interaction network, which potentially stabilizes a cis proline peptide bond and links secondary structure elements. Thus, deletion mutations and registry shifts can enhance proteins through structural rearrangements not possible by substitution mutations alone

Scientific Publications on Primary Biliary Cirrhosis from 2000 through 2010: An 11-Year Survey of the Literature

BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by intrahepatic bile-duct destruction, cholestasis, and fibrosis. It can lead to cirrhosis and eventually liver failure. PBC also shows some regional differences with respect to incidence and prevalence that are becoming more pronounced each year. Recently, researchers have paid more attention to PBC. To evaluate the development of PBC research during the past 11 years, we determined the quantity and quality of articles on this subject. We also compared the contributions of scientists from the US, UK, Japan, Italy, Germany, and China. METHODS: The English-language papers covering PBC published in journals from 2000 through 2010 were retrieved from the PubMed database. We recorded the number of papers published each year, analyzed the publication type, and calculated the accumulated, average impact factors (IFs) and citations from every country. The quantity and quality of articles on PBC were compared by country. We also contrasted the level of PBC research in China and other countries. RESULTS: The total number of articles did not significantly increase during the past 11 years. The number of articles from the US exceeded those from any other country; the publications from the US also had the highest IFs and the most citations. Four other countries showed complex trends with respect to the quantity and quality of articles about PBC. CONCLUSION: The researchers from the US have contributed the most to the development of PBC research. They currently represent the highest level of research. Some high-level studies, such as RCTs, meta-analyses, and in-depth basic studies should be launched. The gap between China and the advanced level is still enormous. Chinese investigators still have a long way to go

Preventive medical care in remote Aboriginal communities in the Northern Territory: a follow-up study of the impact of clinical guidelines, computerised recall and reminder systems, and audit and feedback

Background Interventions to improve delivery of preventive medical services have been shown to be effective in North America and the UK. However, there are few studies of the extent to which the impact of such interventions has been sustained, or of the impact of such interventions in disadvantaged populations or remote settings. This paper describes the trends in delivery of preventive medical services following a multifaceted intervention in remote community health centres in the Northern Territory of Australia. Methods The intervention comprised the development and dissemination of best practice guidelines supported by an electronic client register, recall and reminder systems and associated staff training, and audit and feedback. Clinical records in seven community health centres were audited at regular intervals against best practice guidelines over a period of three years, with feedback of audit findings to health centre staff and management. Results Levels of service delivery varied between services and between communities. There was an initial improvement in service levels for most services following the intervention, but improvements were in general not fully sustained over the three year period. Conclusions Improvements in service delivery are consistent with the international experience, although baseline and follow-up levels are in many cases higher than reported for comparable studies in North America and the UK. Sustainability of improvements may be achieved by institutionalisation of relevant work practices and enhanced health centre capacity

Genetically encoded phenyl azide photochemistry drives positive and negative functional modulation of a red fluorescent protein

The photochemical properties of phenyl azide have been exploited to modulate the function of a red autofluorescent protein, mCherry. Using genetic code reprogramming, phenyl azide chemistry has been introduced at functionally strategic positions in mCherry leading to deactivation, activation or enhancement upon UV irradiatio

LMS-Verify: abstraction without regret for verified systems programming

Performance critical software is almost always developed in C, as programmers do not trust high-level languages to deliver the same reliable performance. This is bad because low-level code in unsafe languages attracts security vulnerabilities and because development is far less productive, with PL advances mostly lost on programmers operating under tight performance constraints. High-level languages provide memory safety out of the box, but they are deemed too slow and unpredictable for serious system software. Recent years have seen a surge in staging and generative programming: the key idea is to use high-level languages and their abstraction power as glorified macro systems to compose code fragments in first-order, potentially domain-specific, intermediate languages, from which fast C can be emitted. But what about security? Since the end result is still C code, the safety guarantees of the high-level host language are lost. In this paper, we extend this generative approach to emit ACSL specifications along with C code. We demonstrate that staging achieves ``abstraction without regret'' for verification: we show how high-level programming models, in particular higher-order composable contracts from dynamic languages, can be used at generation time to compose and generate first-order specifications that can be statically checked by existing tools. We also show how type classes can automatically attach invariants to data types, reducing the need for repetitive manual annotations. We evaluate our system on several case studies that varyingly exercise verification of memory safety, overflow safety, and functional correctness. We feature an HTTP parser that is (1) fast (2) high-level: implemented using staged parser combinators (3) secure: with verified memory safety. This result is significant, as input parsing is a key attack vector, and vulnerabilities related to HTTP parsing have been documented in all widely-used web servers.</jats:p

Sustainability of donor programs: evaluating and informing the transition of a large HIV prevention program in India to local ownership

Sustainability is the holy grail of many development projects, yet there is limited evidence about strategies that effectively support transition of programs from donor funding to national governments. The first phase of Avahan, the India AIDS Initiative supported by the Bill and Melinda Gates Foundation (2003&#x2013;2009), aimed to demonstrate an HIV/AIDS prevention program at scale, primarily targeted at high-risk groups. During the second phase (2009&#x2013;2013), this large-scale program will be transitioned to its natural owners: the Government of India and local communities. This paper describes the evaluation design for the Avahan transition strategy.A detailed logic model for the transition was developed. The Avahan transition strategy focuses on three activities: 1 enhancing capacities among communities, non-governmental organizations (NGOs), and government entities, in line with India&#x0027;s national AIDS control strategy; 2 aligning technical and managerial aspects of Avahan programs with government norms and standards; and 3 promoting and sustaining commitment to services for most-at-risk populations. It is anticipated that programs will then transfer smoothly to government and community ownership, become institutionalized within the government system, and support a sustained HIV/AIDS response.The research design evaluates the implementation and effectiveness of 1 activities undertaken by the program; 2 intermediate effects including the process of institutionalization and the extent to which key Avahan organizational procedures and behaviors are integrated into government systems; and 3 overarching effects namely the impact of the transition process on the sustained delivery of HIV/AIDS prevention services to high-risk groups. Both qualitative and quantitative research approaches are employed so that the evaluation will both assess outcomes and explain why they have occurred.It is unusual for donor-supported projects in low- and middle-income countries to carefully plan transition processes, and prospectively evaluate these. This evaluation is designed so as to both inform decision making throughout the transition process and answer larger questions about the transition and sustainability of donor programs