On the Behaviour of General-Purpose Applications on Cloud Storages

Managing data over cloud infrastructures raises novel challenges with respect to existing and well studied approaches such as ACID and long running transactions. One of the main requirements is to provide availability and partition tolerance in a scenario with replicas and distributed control. This comes at the price of a weaker consistency, usually called eventual consistency. These weak memory models have proved to be suitable in a number of scenarios, such as the analysis of large data with Map-Reduce. However, due to the widespread availability of cloud infrastructures, weak storages are used not only by specialised applications but also by general purpose applications. We provide a formal approach, based on process calculi, to reason about the behaviour of programs that rely on cloud stores. For instance, one can check that the composition of a process with a cloud store ensures `strong' properties through a wise usage of asynchronous message-passing

Notch Simultaneously Orchestrates Multiple Helper T Cell Programs Independently of Cytokine Signals

SummaryTwo models are proposed to explain Notch function during helper T (Th) cell differentiation. One argues that Notch instructs one Th cell fate over the other, whereas the other posits that Notch function is dictated by cytokines. Here we provide a detailed mechanistic study investigating the role of Notch in orchestrating Th cell differentiation. Notch neither instructed Th cell differentiation nor did cytokines direct Notch activity, but instead, Notch simultaneously regulated the Th1, Th2, and Th17 cell genetic programs independently of cytokine signals. In addition to regulating these programs in both polarized and nonpolarized Th cells, we identified Ifng as a direct Notch target. Notch bound the Ifng CNS-22 enhancer, where it synergized with Tbet at the promoter. Thus, Notch acts as an unbiased amplifier of Th cell differentiation. Our data provide a paradigm for Notch in hematopoiesis, with Notch simultaneously orchestrating multiple lineage programs, rather than restricting alternate outcomes

Ujjwala at 6 crores: Impact on Cooking Energy Transition and Climate Change

The Pradhan Mantri Ujjawala Yojana (PMUY) has been praised as a landmark initiative that has empowered six crore poor rural women to buy Liquefied Petroleum Gas (LPG) as the primary source for cooking. Having an LPG stove in the kitchen has always been an aspiration, which was unaffordable to many, until the capital cost support became available through PMUY in the form of subsidies and a loan facility. However, public debate over whether the beneficiaries are purchasing enough refill cylinders has emerged. In this article we analyze aggregated LPG refill numbers of PMUY beneficiaries by state, and discuss this within the larger perspective of clean cooking transitions and climate change. The pertinent question that remains to be answered is whether the Indian rural population is making a transition towards cleaner fuels like LPG though the advent of PMUY. Therefore it is essential to understand the refill rates of PMUY beneficiaries. In section 2 we discuss inter-state differences in PMUY refill trends and suggest recommendations for policy. Moreover, it is also necessary to also examine the potential impact of LPG consumption by PMUY beneficiaries on the environment(section 3)

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Automated Validation of State-Based Client-Centric Isolation with TLA ⁺

Clear consistency guarantees on data are paramount for the design and implementation of distributed systems. When implementing distributed applications, developers require approaches to verify the data consistency guarantees of an implementation choice. Crooks et al. define a state-based and client-centric model of database isolation. This paper formalizes this state-based model in, reproduces their examples and shows how to model check runtime traces and algorithms with this formalization. The formalized model in enables semi-automatic model checking for different implementation alternatives for transactional operations and allows checking of conformance to isolation levels. We reproduce examples of the original paper and confirm the isolation guarantees of the combination of the well-known 2-phase locking and 2-phase commit algorithms. Using model checking this formalization can also help finding bugs in incorrect specifications. This improves feasibility of automated checking of isolation guarantees in synthesized synchronization implementations and it provides an environment for experimenting with new designs.</p

Scaling up gas and electric cooking in low- and middle-income countries: climate threat or mitigation strategy with co-benefits?

Nearly three billion people in low- and middle-income countries (LMICs) rely on polluting fuels, resulting in millions of avoidable deaths annually. Polluting fuels also emit short-lived climate forcers (SLCFs) and greenhouse gases (GHGs). Liquefied petroleum gas (LPG) and grid-based electricity are scalable alternatives to polluting fuels but have raised climate and health concerns. Here, we compare emissions and climate impacts of a business-as-usual household cooking fuel trajectory to four large-scale transitions to gas and/or grid electricity in 77 LMICs. We account for upstream and end-use emissions from gas and electric cooking, assuming electrical grids evolve according to the 2022 World Energy Outlook’s ‘Stated Policies’ Scenario. We input the emissions into a reduced-complexity climate model to estimate radiative forcing and temperature changes associated with each scenario. We find full transitions to LPG and/or electricity decrease emissions from both well-mixed GHG and SLCFs, resulting in a roughly 5 millikelvin global temperature reduction by 2040. Transitions to LPG and/or electricity also reduce annual emissions of PM2.5 by over 6 Mt (99%) by 2040, which would substantially lower health risks from household air pollution. Full transitions to LPG or grid electricity in LMICs improve climate impacts over BAU trajectories

Having a lot of a good thing: multiple important group memberships as a source of self-esteem.

Copyright: © 2015 Jetten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedMembership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem.This study was supported by 1. Australian Research Council Future Fellowship (FT110100238) awarded to Jolanda Jetten (see http://www.arc.gov.au) 2. Australian Research Council Linkage Grant (LP110200437) to Jolanda Jetten and Genevieve Dingle (see http://www.arc.gov.au) 3. support from the Canadian Institute for Advanced Research Social Interactions, Identity and Well-Being Program to Nyla Branscombe, S. Alexander Haslam, and Catherine Haslam (see http://www.cifar.ca)

RAD51C Germline Mutations in Breast and Ovarian Cancer Cases from High-Risk Families

BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5′ UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001). Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene