Certificate Transparency with Enhancements and Short Proofs

Browsers can detect malicious websites that are provisioned with forged or fake TLS/SSL certificates. However, they are not so good at detecting malicious websites if they are provisioned with mistakenly issued certificates or certificates that have been issued by a compromised certificate authority. Google proposed certificate transparency which is an open framework to monitor and audit certificates in real time. Thereafter, a few other certificate transparency schemes have been proposed which can even handle revocation. All currently known constructions use Merkle hash trees and have proof size logarithmic in the number of certificates/domain owners. We present a new certificate transparency scheme with short (constant size) proofs. Our construction makes use of dynamic bilinear-map accumulators. The scheme has many desirable properties like efficient revocation, low verification cost and update costs comparable to the existing schemes. We provide proofs of security and evaluate the performance of our scheme.Comment: A preliminary version of the paper was published in ACISP 201

Daily L-leucine supplementation in novice trainees during a 12-week weight training program.

PURPOSE: To investigate the effects of daily oral L-leucine ingestion on strength, bone mineral-free lean tissue mass (LTM) and fat mass (FM) of free living humans during a 12-wk resistance-training program. METHODS: Twenty-six initially untrained men (n = 13 per group) ingested either 4 g/d of L-leucine (leucine group: age 28.5 ± 8.2 y, body mass index 24.9 ± 4.2 kg/m2) or a corresponding amount of lactose (placebo group: age 28.2 ± 7.3 y, body mass index 24.9 ± 4.2 kg/m2). All participants trained under supervision twice per week following a prescribed resistance training program using eight standard exercise machines. Testing took place at baseline and at the end of the supplementation period. Strength on each exercise was assessed by five repetition maximum (5-RM), and body composition was assessed by dual energy X-ray absorptiometry (DXA). RESULTS: The leucine group demonstrated significantly higher gains in total 5-RM strength (sum of 5-RM in eight exercises) and 5-RM strength in five out of the eight exercises (P < .05). The percentage total 5-RM strength gains were 40.8% (± 7.8) and 31.0% (± 4.6) for the leucine and placebo groups respectively. Significant differences did not exist between groups in either total percentage LTM gains or total percentage FM losses (LTM: 2.9% ± 2.5 vs 2.0% ± 2.1, FM: 1.6% ± 15.6 vs 1.1% ± 7.6). CONCLUSION: These results suggest that 4 g/d of L-leucine supplementation may be used as a nutritional supplement to enhance strength performance during a 12-week resistance training program of initially untrained male participants

Computational analysis of the LRRK2 interactome.

LRRK2 was identified in 2004 as the causative protein product of the Parkinson's disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson's disease, alongside one associated with cancer. It is now well established that coding changes in LRRK2 are one of the most common causes of Parkinson's. Genome-wide association studies (GWAs) have, more recently, reported single nucleotide polymorphisms (SNPs) around the LRRK2 locus to be associated with risk of developing sporadic Parkinson's disease and inflammatory bowel disorder. The functional research that has followed these genetic breakthroughs has generated an extensive literature regarding LRRK2 pathophysiology; however, there is still no consensus as to the biological function of LRRK2. To provide insight into the aspects of cell biology that are consistently related to LRRK2 activity, we analysed the plethora of candidate LRRK2 interactors available through the BioGRID and IntAct data repositories. We then performed GO terms enrichment for the LRRK2 interactome. We found that, in two different enrichment portals, the LRRK2 interactome was associated with terms referring to transport, cellular organization, vesicles and the cytoskeleton. We also verified that 21 of the LRRK2 interactors are genetically linked to risk for Parkinson's disease or inflammatory bowel disorder. The implications of these findings are discussed, with particular regard to potential novel areas of investigation

Data mining of gene arrays for biomarkers of survival in ovarian cancer

The expected five-year survival rate from a stage III ovarian cancer diagnosis is a mere 22%; this applies to the 7000 new cases diagnosed yearly in the UK. Stratification of patients with this heterogeneous disease, based on active molecular pathways, would aid a targeted treatment improving the prognosis for many cases. While hundreds of genes have been associated with ovarian cancer, few have yet been verified by peer research for clinical significance. Here, a meta-analysis approach was applied to two care fully selected gene expression microarray datasets. Artificial neural networks, Cox univariate survival analyses and T-tests identified genes whose expression was consistently and significantly associated with patient survival. The rigor of this experimental design increases confidence in the genes found to be of interest. A list of 56 genes were distilled from a potential 37,000 to be significantly related to survival in both datasets with a FDR of 1.39859 × 10−11, the identities of which both verify genes already implicated with this disease and provide novel genes and pathways to pursue. Further investigation and validation of these may lead to clinical insights and have potential to predict a patient’s response to treatment or be used as a novel target for therapy

Agent-based modeling: a systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity.

A crisis continues to brew within the pharmaceutical research and development (R&amp;D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&amp;S) methods. We suggest strategies and scenarios intended to enable new M&amp;S use cases that directly engage R&amp;D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&amp;S requirements must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&amp;S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&amp;S should be actualized within a larger information technology framework--a dynamic knowledge repository--wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline

Filtered screens and augmented Teichm\"uller space

We study a new bordification of the decorated Teichm\"uller space for a multiply punctured surface F by a space of filtered screens on the surface that arises from a natural elaboration of earlier work of McShane-Penner. We identify necessary and sufficient conditions for paths in this space of filtered screens to yield short curves having vanishing length in the underlying surface F. As a result, an appropriate quotient of this space of filtered screens on F yields a decorated augmented Teichm\"uller space which is shown to admit a CW decomposition that naturally projects to the augmented Teichm\"uller space by forgetting decorations and whose strata are indexed by a new object termed partially oriented stratum graphs.Comment: Final version to appear in Geometriae Dedicat

Point-wise mutual information-based video segmentation with high temporal consistency

In this paper, we tackle the problem of temporally consistent boundary detection and hierarchical segmentation in videos. While finding the best high-level reasoning of region assignments in videos is the focus of much recent research, temporal consistency in boundary detection has so far only rarely been tackled. We argue that temporally consistent boundaries are a key component to temporally consistent region assignment. The proposed method is based on the point-wise mutual information (PMI) of spatio-temporal voxels. Temporal consistency is established by an evaluation of PMI-based point affinities in the spectral domain over space and time. Thus, the proposed method is independent of any optical flow computation or previously learned motion models. The proposed low-level video segmentation method outperforms the learning-based state of the art in terms of standard region metrics

The relation between hemispheric lateralisation and measures of immune competence and adherence in Human Immunodeficiency Virus Type 1 (HIV-1)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright © 2012 Sumner et al

HAGE, a cancer/testis antigen expressed at the protein level in a variety of cancers

The search for novel tumour antigens that are either uniquely expressed or over-expressed in a wide variety of tumours is still ongoing. Because of their expression in a broad spectrum of cancers and limited expression in normal tissues, cancer/testis antigens are considered to be potentially reliable targets for immunotherapy of cancer in general. The helicase antigen HAGE has been identified as a cancer/testis antigen. However, little is known about its expression in normal and cancer tissues. Using a newly developed antibody against HAGE, specific staining of its expression by immunohistochemistry was validated and optimised on murine tumours transfected to express the HAGE protein. The antibody was subsequently used to determine HAGE expression in normal human and cancer tissue microarrays. HAGE protein expression was confirmed in 75% (12/16) of carcinomas as compared to normal tissues, which either did not express HAGE at all or expressed HAGE at very low levels with the exception of testis. Interestingly, discrepancies were also found between mRNA analysis by real time quantitative PCR (RT-qPCR) and protein analysis by immunohistochemistry, emphasising the need to validate the expression of cancer/testis antigens at the protein level prior to the development of new vaccine strategies. HAGE is therefore proposed to be a valid candidate for designing a broad spectrum vaccine against cancer

Impact of thiopurines and anti-tumour necrosis factor therapy on hospitalisation and long-term surgical outcomes in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the large bowel and is associated with a significant risk of both requirement for surgery and the need for hospitalisation. Thiopurines, and more recently, anti-tumour necrosis factor (aTNF) therapy have been used successfully to induce clinical remission. However, there is less data available on whether these agents prevent long-term colectomy rates or the need for hospitalisation. The focus of this article is to review the recent and pertinent literature on the long-term impact of thiopurines and aTNF on long-term surgical and hospitalisation rates in UC. Data from population based longitudinal research indicates that thiopurine therapy probably has a protective role against colectomy, if used in appropriate patients for a sufficient duration. aTNF agents appear to have a short term protective effect against colectomy, but data is limited for longer periods. Whereas there is insufficient evidence that thiopurines affect hospitalisation, evidence favours that aTNF therapy probably reduces the risk of hospitalisation within the first year of use, but it is less clear on whether this effect continues beyond this period. More structured research needs to be conducted to answer these clinically important questions