Rigorous Determination of the Stoichiometry of Protein Phosphorylation Using Mass Spectrometry

Quantification of the stoichiometry of phosphorylation is usually achieved using a mixture of phosphatase treatment and differential isotopic labeling. Here, we introduce a new approach to the concomitant determination of absolute protein concentration and the stoichiometry of phosphorylation at predefined sites. The method exploits QconCAT to quantify levels of phosphorylated and nonphosphorylated peptide sequences in a phosphoprotein. The nonphosphorylated sequence is used to determine the absolute protein quantity and serves as a reference to calculate the extent of phosphorylation at the second peptide. Thus, the stoichiometry of phosphorylation and the absolute protein concentration can be determined accurately in a single experiment

A tutorial task and tertiary courseware model for collaborative learning communities

RAED provides a computerised infrastructure to support the development and administration of Vicarious Learning in collaborative learning communities spread across multiple universities and workplaces. The system is based on the OASIS middleware for Role-based Access Control. This paper describes the origins of the model and the approach to implementation and outlines some of its benefits to collaborative teachers and learners

CamFlow: Managed Data-sharing for Cloud Services

A model of cloud services is emerging whereby a few trusted providers manage the underlying hardware and communications whereas many companies build on this infrastructure to offer higher level, cloud-hosted PaaS services and/or SaaS applications. From the start, strong isolation between cloud tenants was seen to be of paramount importance, provided first by virtual machines (VM) and later by containers, which share the operating system (OS) kernel. Increasingly it is the case that applications also require facilities to effect isolation and protection of data managed by those applications. They also require flexible data sharing with other applications, often across the traditional cloud-isolation boundaries; for example, when government provides many related services for its citizens on a common platform. Similar considerations apply to the end-users of applications. But in particular, the incorporation of cloud services within `Internet of Things' architectures is driving the requirements for both protection and cross-application data sharing. These concerns relate to the management of data. Traditional access control is application and principal/role specific, applied at policy enforcement points, after which there is no subsequent control over where data flows; a crucial issue once data has left its owner's control by cloud-hosted applications and within cloud-services. Information Flow Control (IFC), in addition, offers system-wide, end-to-end, flow control based on the properties of the data. We discuss the potential of cloud-deployed IFC for enforcing owners' dataflow policy with regard to protection and sharing, as well as safeguarding against malicious or buggy software. In addition, the audit log associated with IFC provides transparency, giving configurable system-wide visibility over data flows. [...]Comment: 14 pages, 8 figure

Data-centric access control for cloud computing

© 2016 ACM. The usual approach to security for cloud-hosted applications is strong separation. However, it is often the case that the same data is used by different applications, particularly given the increase in data-driven (big data' and IoT) applications. We argue that access control for the cloud should no longer be application-specific but should be data-centric, associated with the data that can ow between applications. Indeed, the data may originate outside cloud services from diverse sources such as medical monitoring, environmental sensing etc. Information Flow Control (IFC) potentially offers data-centric, system-wide data access control. It has been shown that IFC can be provided at operating system level as part of a PaaS offering, with an acceptable overhead. In this paper we consider how IFC can be integrated with application-specific access control, transparently from application developers, while building from simple IFC primitives, access control policies that align with the data management obligations of cloud providers and tenants.This work was supported by the UK EPSRC grant EP/ K011510 CloudSafetyNet. We acknowledge the support of Microsoft through the Microsoft Cloud Computing Research Centre

Information flow audit for PaaS clouds

© 2016 IEEE. With the rapid increase in uptake of cloud services, issues of data management are becoming increasingly prominent. There is a clear, outstanding need for the ability for specified policy to control and track data as it flows throughout cloud infrastructure, to ensure that those responsible for data are meeting their obligations. This paper introduces Information Flow Audit, an approach for tracking information flows within cloud infrastructure. This builds upon CamFlow (Cambridge Flow Control Architecture), a prototype implementation of our model for data-centric security in PaaS clouds. CamFlow enforces Information Flow Control policy both intra-machine at the kernel-level, and inter-machine, on message exchange. Here we demonstrate how CamFlow can be extended to provide data-centric audit logs akin to provenance metadata in a format in which analyses can easily be automated through the use of standard graph processing tools. This allows detailed understanding of the overall system. Combining a continuously enforced data-centric security mechanism with meaningful audit empowers tenants and providers to both meet and demonstrate compliance with their data management obligations.This work was supported by UK Engineering and Physical Sciences Research Council grant EP/K011510 CloudSafetyNet: End-to-End Application Security in the Cloud. We acknowledge the support of Microsoft through the Microsoft Cloud Computing Research Centre

Residential energy efficiency interventions: A meta-analysis of effectiveness studies

BACKGROUND: The residential sector releases around 17% of global greenhouse gas emissions and making residential buildings more energy efficient can help mitigate climate change. Engineering models are often used to predict the effects of residential energy efficiency interventions (REEI) on energy consumption, but empirical studies find that these models often over-estimate the actual impact of REEI installation. Different empirical studies often estimate different impacts for the same REEI, possibly due to variations in implementation, climate and population. Funding for this systematic review was provided by the evaluation function at the European Investment Bank Group. OBJECTIVES: The review aims to assess the effectiveness of installing REEIs on the following primary outcomes: energy consumption, energy affordability, CO2 emissions and air quality indices and pollution levels. SEARCH METHODS: We searched CAB Abst, Econlit, Greenfile, Repec, Academic Search Complete, WB e-lib, WoS (SCI and SSCI) and other 42 databases in November 2020. In addition, we searched for grey literature on websites, checked the reference lists of included studies and relevant reviews, used Google Scholar to identify studies citing included studies, and contacted the authors of studies for any ongoing and unpublished studies. We retrieved a total of 13,629 studies that we screened at title and abstract level, followed by full-text screening and data extraction. SELECTION CRITERIA: We included randomised control trials, and quasi-experimental studies that evaluated the impact of installing REEIs anywhere in the world and with any comparison. DATA COLLECTION AND ANALYSIS: Two independent reviewers screened studies for eligibility, extracted data and assessed risk of bias. When more than one included study examined the same installation of the same type of REEI for a similar outcome, we conducted a meta-analysis. We also performed subgroup analyses. MAIN RESULTS: A total of 16 studies were eligible and included in the review: two studies evaluated the installation of efficient lighting, three studies the installation of attic/loft insulation, two studies the installation of efficient heat pumps, eight studies the installation of a bundle of energy efficiency measures (EEMs), and one study evaluated other EEMs. Two studies, neither appraised as having a low risk of bias, find that lighting interventions lead to a significant reduction in electricity energy consumption (Hedges' g = −0.29; 95% confidence interval [CI]: −0.48, −0.10). All the other interventions involved heating or cooling, and effects were synthesizised by warmer or colder climate and then across climates. Four studies examined the impact of attic/loft insulation on energy consumption, and two of these studies were appraised as having a low risk of bias. Three studies took place in colder climates with gas consumption as an outcome, and one study took place in a warmer climate, with the electricity consumption (air conditioning) as the outcome. The average impact across all climates was small (Hedges' g = 0.04; 95% CI: −0.09, 0.01) and statistically insignificant. However, two of the studies appear to have evaluated the effect of installing small amounts (less than 75 mm) of insulation. The other two studies, one of which was appraised as low risk of bias and the other involving air conditioning, found significant reductions in consumption. Two studies examined the impact of installing electric heat pumps. The average impact across studies was not statistically significant (Hedges' g = −0.11; 95% CI: −0.41, 0.20). However, there was substantial variation between the two studies. Replacing older pumps with more efficient versions significantly reduced electricity consumption in a colder climate (Hedges' g = −0.36; 95% CI, −0.57, −0.14) in a high risk of bias study. However, a low risk of bias study found a significant increase in electricity consumption from installing new heat pumps (Hedges' g = 0.09; 95% CI, 0.06, 0.12). Supplemental analyses in the latter study indicate that households also used the heat pumps for cooling and that the installed heat pumps most likely reduced overall energy consumption across all sources—that is, households used more electricity but less gas, wood and coal. Seven studies examined bundled REEIs where the households chose which EEMs to install (in five studies the installation occurred after an energy audit that recommended which EEMs to install). Overall, the studies estimated that installing an REEI bundle is associated with a significant reduction in energy consumption (Hedges' g = −0.36; 95% CI, −0.52, −0.19). In the two low risk of bias studies, conducted with mostly low-income households, installed bundles reduced energy consumption by a statistically significant amount (Hedges' g = −0.16; 95% CI, −0.13, −0.18). AUTHORS' CONCLUSIONS: The 16 included studies indicate that installing REEIs can significantly reduce energy consumption. However, the same type of REEI installed in different studies caused different effects, indicating that effects are conditional on implementation and context. Exploring causes of this variation is usually not feasible because existing research often does not clearly report the features of installed interventions. Additional high quality impact evaluations should be commissioned in more diverse contexts (only one study was conducted in either Asia or Africa—both involved lighting interventions—and no studies were conducted in South America or Southern Europe)

Peptide scrambling during collision-induced dissociation is influenced by N-terminal residue basicity

‘Bottom up’ proteomic studies typically use tandem mass spectrometry data to infer peptide ion sequence, enabling identification of the protein whence they derive. The majority of such studies employ collision-induced dissociation (CID) to induce fragmentation of the peptide structure giving diagnostic b-, y-, and a- ions. Recently, rearrangement processes that result in scrambling of the original peptide sequence during CID have been reported for these ions. Such processes have the potential to adversely affect ion accounting (and thus scores from automated search algorithms) in tandem mass spectra, and in extreme cases could lead to false peptide identification. Here, analysis of peptide species produced by Lys-N proteolysis of standard proteins is performed and sequences that exhibit such rearrangement processes identified. The effect of increasing the gas-phase basicity of the N-terminal lysine residue through derivatization to homoarginine toward such sequence scrambling is then assessed. The presence of a highly basic homoarginine (or arginine) residue at the N-terminus is found to disfavor/inhibit sequence scrambling with a coincident increase in the formation of b(n-1)+H2O product ions. Finally, further analysis of a sequence produced by Lys-C proteolysis provides evidence toward a potential mechanism for the apparent inhibition of sequence scrambling during resonance excitation CID

Framework synthesis to inform the ideation and design of a paper-based health information system (PHISICC)

Background: Health information systems (HIS) are meant to support decision-making at all levels of the system, including frontline health workers. In field studies in Côte d’Ivoire, Mozambique and Nigeria, we observed health workers' interactions with the HIS and identified twelve decision-making components of HIS. The objective of this framework synthesis is to portray these components in HIS research, in order to inform the ideation of a paper-based HIS intervention (PHISICC). Methods: We searched studies in the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Epistemonikos, Medline, in-Process on the Ovid platform, OpenGrey, PDQ Evidence (“pretty darnd quick” Evidence), the World Health Organization (WHO) Global Health Library and included studies focussing on HIS interventions, data quality, information support tools and data use for decision-making in the context of the governmental health care sector. We assessed the methodological quality of studies using the Critical Appraisal Skills Programme tool. We synthesised the findings based on the decision-making components of HIS and thematic areas. Results: The search identified 6784 studies; 50 were included. Most of the 50 studies had quality concerns. All studies included at least one of the decision-making components: the most prominent were the technical aspects of ‘recording’ and ‘reporting’. Data use for decision-making was much less represented. Conclusion: HIS research focuses on the more technical aspects of HIS. Further research on HIS, given the strong push towards HIS digitalisation, should consider putting at the centre the human experience of decision-making and data use, in order to make HIS relevant for quality of care

Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS

Glycans functionalised with hydrophobic trityl groups were synthesised and adsorbed onto polystyrene and glass slides in an array format. The adsorbed glycans could be analysed directly on these minimally conducting surfaces by MALDI-TOF mass spectrometry analysis after aluminium tape was attached to the underside of the slides. Furthermore, the trityl group appeared to act as an internal matrix and no additional matrix was necessary for the MS analysis. Thus, trityl groups can be used as simple hydrophobic, noncovalently linked anchors for ligands on surfaces and at the same time facilitate the in situ mass spectrometric analysis of such ligands