Scrum for product innovation : a longitudinal embedded case study

This article describes the innovation processes used in a partnership between Add Latent Ltd., an asset integrity and maintenance management consulting services provider in the energy sector and University of Salford. The challenge faced by the company is to make their in-house expertise more readily available to a worldwide audience. A longitudinal embedded case study has been used to investigate how installable desktop software applications have been redesigned to create a new set of cloud hosted software services. The innovation team adapted an agile scrum process to include exploratory prototyping and manage the geographical distribution of the team members. A minimum viable product was developed that integrated functional elements of previous software tools into an end-to-end data collection, analysis and visualisation product called AimHi which uses a cloud-hosted web services approach. Field trials were conducted using the software at the Uniper, Isle of Grain power station in Kent, UK. Enhancements were made to the AimHi product which was adopted for use at the Uniper site. The product emerged from a Knwledge Transfer Partnership whci was evaluated on cmplettion by InnovateUK and awarded the highest possible “outstanding” grade. The article illustrates how the scrum software development method was tailored for a product innovation context. Extended periods of evaluation and reflection, prototyping and requirement refinement were combined with periods of incremental feature development using sprints. The AimHi product emerged from a technology transfer and innovation project that has successfully reconciled conflicting demands from customers, universities, partner companies and project staff members

Structural insights into RNA processing by the human RISC-loading complex.

Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2

Engineering robust polar chiral clathrate crystals

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Royal Society of Chemistry 2013.The R-(+)-enantiomeric form of Dianin's compound and the S-(+)-enantiomeric form of its direct thiachroman analogue both obtained chromatographically employing a cellulose tris(3,5-dimethylphenylcarbamate) column, are shown to undergo supramolecular assembly to form a polar clathrate lattice which is stable even in the absence of a consolidating guest component

Year in review in Intensive Care Medicine 2012. II: Pneumonia and infection, sepsis, coagulation, hemodynamics, cardiovascular and microcirculation, critical care organization, imaging, ethics and legal issues.

Journal ArticleSCOPUS: re.jSCOPUS: re.jinfo:eu-repo/semantics/publishe

Partisan Profiles in Presidential Policies: an Extension of Presidential Preferences for Inflation versus Unemployment

In a recent article, Zaleski does not find any clear difference between the political preferences of Republican and Democratic administrations with respect to the choice between unemployment and inflation. This paper provides empirical support for the opposite conclusion in a generalization of Zaleski's approach allowing for instrument costs

Impact of age norms and stereotypes on managers' hiring decisions of retirees

Purpose -Our study investigates the role of managers in the re-employment of early retirees and asks what the effect is of managers’ age norms and stereotypes on managers’ employment decisions. Design/methodology/approach- A combination of a factorial study and a survey was conducted. First, information on the age norms and stereotypes was collected. Secondly, profiles of hypothetical retired job applicants were presented to the employers, who were asked to make a specific hiring decision. The information collected during both studies was combined in the analysis and multilevel models were estimated. Findings -The results indicate that higher age norms result in a higher propensity to hire an early retiree. Stereotypes, by contrast, do not influence managers’ decisions. Early retirees’ chances for re-employment are also related to their own circumstances (physical appearance and relevant experience) and organisational forces, as they are hired when organisations face labour force shortages. Research limitation / implications – with the use of vignettes study we deal with hypothetical hiring situation. Originality value- Although the effect of age norms and age stereotypes has been often suggested, not much empirical evidence was presented to support this notion. Our study estimates the effect of age norms and stereotypes on hiring decision. key words: bridge employment; early retirees; age norms; age stereotypes; multilevel models.

Regularizing Portfolio Optimization

The optimization of large portfolios displays an inherent instability to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification "pressure". This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade-off between the two, depending on the size of the available data set

The eye contact effect: mechanisms and development

The ‘eye contact effect’ is the phenomenon that perceived eye contact with another human face modulates certain aspects of the concurrent and/or immediately following cognitive processing. In addition, functional imaging studies in adults have revealed that eye contact can modulate activity in structures in the social brain network, and developmental studies show evidence for preferential orienting towards, and processing of, faces with direct gaze from early in life. We review different theories of the eye contact effect and advance a ‘fast-track modulator’ model. Specifically, we hypothesize that perceived eye contact is initially detected by a subcortical route, which then modulates the activation of the social brain as it processes the accompanying detailed sensory information

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Lysosomal dysfunction and impaired autophagy underlie the pathogenesis of amyloidogenic light chain-mediated cardiotoxicity

AL amyloidosis is the consequence of clonal production of amyloidogenic immunoglobulin light chain (LC) proteins, often resulting in a rapidly progressive and fatal amyloid cardiomyopathy. Recent work has found that amyloidogenic LC directly initiate a cardio-toxic response underlying the pathogenesis of the cardiomyopathy; however, the mechanisms that contribute to this proteotoxicity remain unknown. Using human amyloidogenic LC isolated from patients with amyloid cardiomyopathy, we reveal that dysregulation of autophagic flux is critical for mediating amyloidogenic LC proteotoxicity. Restoration of autophagic flux by pharmacological intervention using rapamycin protected against amyloidogenic light chain protein-induced pathologies including contractile dysfunction and cell death at the cellular and organ level and also prolonged survival in an in vivo zebrafish model of amyloid cardiotoxicity. Mechanistically, we identify impaired lysosomal function to be the major cause of defective autophagy and amyloidogenic LC-induced proteotoxicity. Collectively, these findings detail the downstream molecular mechanisms underlying AL amyloid cardiomyopathy and highlight potential targeting of autophagy and lysosomal dysfunction in patients with amyloid cardiomyopathy