Proteostasis and ageing: insights from long-lived mutant mice

The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age-related disease, and thus improving late-life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis- where proteostasis is defined here as the maintenance of the proteome- appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)-induced unfolded protein response (UPR), the ubiquitin-proteasome system (UPS) and autophagy, all appear indispensable for longevity in many long-lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long-lived mouse mutants have been described, many of which carry single-gene mutations within the growth-hormone, insulin/IGF-1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long-lived mouse mutants

Termination-insensitive noninterference leaks more than just a bit

Current tools for analysing information flow in programs build upon ideas going back to Denning's work from the 70's. These systems enforce an imperfect notion of information flow which has become known as termination-insensitive noninterference. Under this version of noninterference, information leaks are permitted if they are transmitted purely by the program's termination behaviour (i.e., whether it terminates or not). This imperfection is the price to pay for having a security condition which is relatively liberal (e.g. allowing while-loops whose termination may depend on the value of a secret) and easy to check. But what is the price exactly? We argue that, in the presence of output, the price is higher than the “one bit” often claimed informally in the literature, and effectively such programs can leak all of their secrets. In this paper we develop a definition of termination-insensitive noninterference suitable for reasoning about programs with outputs. We show that the definition generalises “batch-job” style definitions from the literature and that it is indeed satisfied by a Denning-style program analysis with output. Although more than a bit of information can be leaked by programs satisfying this condition, we show that the best an attacker can do is a brute-force attack, which means that the attacker cannot reliably (in a technical sense) learn the secret in polynomial time in the size of the secret. If we further assume that secrets are uniformly distributed, we show that the advantage the attacker gains when guessing the secret after observing a polynomial amount of output is negligible in the size of the secret

Cultural Influences on Education: students’ journeys between FE and HE

This research project explores the relationship between culture and education, in order to inform teachers about the nature of cultural influences, and the effect of these on different stages of students’ education. The particular focus is on examining students’ choices regarding progression from Further Education to Higher Education. Teaching at City and Islington Sixth Form College requires a constant dialogue between a diverse range of cultures and student experience; this study will address a need to understand factors that affect students’ experience in order to maintain and widen participation in inner city institutions. A small number of students from City and Islington Sixth Form and University College London will be interviewed and their experiences analysed in a qualitative manner; this will allow discussion of the detailed information students provide. Hence the advantages and disadvantages of students’ educational journeys and their choices regarding progression to Higher Education can be evaluated in the context of their cultural experience, and with reference to the previous body of research in this area. For confidentiality all names in this study have been changed

Additive decompositions for rings of modular forms

We study rings of integral modular forms for congruence subgroups as modules over the ring of integral modular forms for the full modular group. In many cases these modules are free or decompose at least into well-understood pieces. We apply this to characterize which rings of modular forms are Cohen--Macaulay and to prove finite generation results. These theorems are based on decomposition results about vector bundles on the compactified moduli stack of elliptic curves.Comment: Complete revision. Comments welcome. arXiv admin note: text overlap with arXiv:1609.0926

Chemical effects in ion mixing of a ternary system (metal-SiO_2)

The mixing of Ti, Cr, and Ni thin films with SiO_2 by low‐temperature (−196–25 °C) irradiation with 290 keV Xe has been investigated. Comparison of the morphology of the intermixed region and the dose dependences of net metal transport into SiO_2 reveals that long range motion and phase formation probably occur as separate and sequential processes. Kinetic limitations suppress chemical effects in these systems during the initial transport process. Chemical interactions influence the subsequent phase formation

Civil Procedure—Availability of Class Actions to Consumers for Fraudulent Misrepresentation by Seller

Vasquez v. Superior Court of San Joaquin County, 4 Cal. 3d 800, 484 P.2d 964, 94 Cal. Rptr. 796 (1971)

Chenango United Way Community Partners\u27 Performance Measurement Data: Utilization, Challenges,and Practices

The following study focuses on Chenango United Way community partners\u27 utilization of data from performance measurements. It answers two research questions: 1) what the Chenango United Way community partners are doing with the data they collect from their program outcome measurements and 2) how the Chenango United Way can help community partners utilize the data collected from their program outcome measurements to improve programs