Intermediate Certificate Suppression in Post-Quantum TLS: An Approximate Membership Querying Approach

Quantum computing advances threaten the security of today\u27s public key infrastructure, and have led to the pending standardization of alternative, quantum-resistant key encapsulation and digital signature cryptography schemes. Unfortunately, authentication algorithms based on the new post-quantum (PQ) cryptography create significant performance bottlenecks for TLS due to larger certificate chains which introduce additional packets and round-trips. The TLS handshake slowdown will be unacceptable to many applications, and detrimental to the broader adoption of quantum safe cryptography standards. In this paper, we propose a novel framework for Intermediate Certificate Authority (ICA) certificate suppression in TLS that reduces the authentication message size and prevents excessive round-trip delays. Our approach utilizes an approximate membership query (AMQ) data structure (probabilistic filter) to advertise known ICA certs to remote TLS endpoints so that unnecessary ICA certificates are omitted from the TLS handshake exchange. We showcase the extend of the PQ authentication overhead challenge in TLS, and evaluate the feasibility of AMQ filters for ICA suppression in terms of space and computational overhead. Finally, we experimentally evaluate the potential gains form our approach and showcase a $70\%$ reduction in exchanged ICA cert data that translates to 15-50 MB of savings in PQ TLS and for certain Web-based application scenarios

ELCA: Introducing Enterprise-level Cryptographic Agility for a Post-Quantum Era

Given the importance of cryptography to modern security and privacy solutions, it is surprising how little attention has been given to the problem of \textit{cryptographic agility}, or frameworks enabling the transition from one cryptographic algorithm or implementation to another. In this paper, we argue that traditional notions of cryptographic agility fail to capture the challenges facing modern enterprises that will soon be forced to implement a disruptive migration from today’s public key algorithms (e.g., RSA, ECDH) to quantum-safe alternatives (e.g., CRYSTALS-KYBER). After discussing the challenge of real-world cryptographic transition at scale, we describe our work on enterprise-level cryptographic agility for secure communications based on orchestrated \textit{cryptographic providers}. Our policy-driven approach, prototyped in service mesh, provides a much-needed re-envisioning for cryptographic agility and highlights what’s missing today to enable disruptive cryptographic change at scale

Suppression of ovine lymphocyte activation by Teladorsagia circumcincta larval excretory-secretory products

Teladorsagia circumcincta is an important pathogenic nematode of sheep. It has been demonstrated previously that stimulation of murine T lymphocytes with excretory-secretory (ES) products derived from fourth stage larvae of T. circumcincta (Tci-L4-ES) results in de novo expression of Foxp3, a transcription factor intimately involved in regulatory T cell function. In the current study, Foxp3(+) T cell responses in the abomasum and the effects of Tci-L4-ES on ovine peripheral blood mononuclear cells (PBMC) following T. circumcincta infection were investigated. T. circumcincta infection resulted in a significant increase in numbers of abomasal Foxp3(+) T cells, but not an increase in the proportion of T cells expressing Foxp3. Unlike in mice, Tci-L4-ES was incapable of inducing T cell Foxp3 expression but instead suppressed mitogen-induced and antigen-specific activation and proliferation of ovine PBMC in vitro. This effect was heat labile, suggesting that it is mediated by protein(s). Suppression was associated with up-regulation of interleukin-10 (IL-10) mRNA, and specific monoclonal antibody neutralisation of IL-10 resulted in a 50% reduction in suppression, indicating involvement of the IL-10 signaling pathway. Suppression was significantly reduced in PBMC isolated from T. circumcincta infected vs. helminth-naïve lambs, and this reduction in suppression was associated with an increase in Tci-L4-ES antigen-specific T cells within the PBMC. In conclusion, we have identified a mechanism by which T. circumcincta may modulate the host adaptive immune response, potentially assisting survival of the parasite within the host. However, the impact of Tci-L4-ES-mediated lymphocyte suppression during T. circumcincta infection remains to be determined

Population Maintenance of the Scyphozoan Cyanea sp. Settled Planulae and the Distribution of Medusae in the Niantic River, Connecticut, USA

Scyphozoan jellyfish are seasonally conspicuous in coastal waters, but relatively little is known about the factors that control their distribution and population dynamics.Cyanea sp is a seasonally abundant medusa in the Niantic River, Connecticut, U.S. and appears to maintain a population entirely within the estuary. To better understand the factors controlling their occurrence, we examined the temporal and spatial distribution of settled scyphistomae in relation to that of the medusae. Planula settlement patterns mirrored the presence of mature female medusae. The planulae settled primarily near the bottom. After settlement, planulacysts and polyps on the settlement plates were out competed by large barnacle and ascidian larvae, resulting in a sharp decline in cyst and polyp abundance. This stage-specific mortality may represent a population bottleneck in the life cycle of scyphozoans

Multi-Morbidity in the Older Person: An Examination of Polypharmacy and Socioeconomic Status

There has been increased focus on clinically managing multi-morbidity in the older population, but it can be challenging to find appropriate paradigm that addresses the socio-economic burden and risk for polypharmacy. The Commission on Social Determinants of Health (CSDH) has examined the need for institutional change and the parallel need to address the social causes of poor health. This study explored three potential interventions namely, meaningful information from electronic health records (EHR), social prescribing, and redistributive welfare policies from a person-centered perspective using the CARE (connecting, assessing, responding, and empowering) approach. Economic instruments that immediately redistribute state welfare and reduce income disparity such as direct taxation and conditional cash transfers could be adopted to enable older people with long-term conditions have access to healthcare services. Decreased socioeconomic inequality and unorthodox prescriptive interventions that reduce polypharmacy could mitigate barriers to effectively manage the complexities of multi-morbidity

Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

peer-reviewedBackground: About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results: The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified. Conclusions: Transcriptional diversity can potentially be generated in poly-Q encoding genes by the impact of CAG repeat tracts on mRNA alternative splicing. This effect, combined with the physical interactions of the encoded proteins in large transcriptional regulatory complexes suggests that polymorphic variations of proteins in these complexes have strong potential to affect phenotype.Dairy Australia (through the Innovative Dairy Cooperative Research Center

An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701