R&D Investment Level and Environment as Predictors of Firm Acquisition

R&D investments contribute to the development of firm technology resources, and the possession of such resources often increases a firm’s attractiveness as a potential acquisition target. However, the value ascribed to a firm’s technology resources by would-be acquirers may be moderated by its industry’s environmental characteristics. Using data from 2886 firms, we find that investments in R&D predict acquisition likelihood and that R&D investments are most strongly associated with acquisition of firms under conditions of high environmental munificence and dynamism. Theoretical and managerial implications are discussed

Salinity gradient energy: Assessment of pressure retarded osmosis and osmotic heat engines for energy generation from low-grade heat sources

Development of clean energy technologies that maximize efficiency and minimize resource consumption is a necessary component for a clean and secure energy future. The osmotic heat engine (OHE) is a closed-loop, membrane based process that utilizes low-grade heat and salinity-gradient energy between two streams for electrical energy generation. The OHE couples pressure retarded osmosis (PRO), an osmotically driven membrane process, with membrane distillation (MD), a thermally driven membrane process. In PRO, water permeates via osmosis through a semi-permeable membrane from a low concentration feed stream into a higher concentration brine (draw solution). The permeate stream becomes pressurized on the high concentration side of the membrane and a mechanical device (e.g., turbine generator set) is used to convert the hydraulic pressure to electrical energy. The MD process utilizes low-grade heat to reconcentrate the diluted brine from the PRO process and to produce a deionized water stream; these streams are then resupplied to the PRO process in the OHE. High power-density (power generated per unit area of membrane) of the PRO membrane is essential to maximize the efficiency and minimize the capital and operating costs of the OHE. Likewise, high separation efficiency is needed in the MD process to effectively reconcentrate the diluted draw solution. Thus, robust PRO membranes that can support high pressure, have high water flux, low reverse salt flux, low structural parameter, and a good membrane support structure are essential. The MD process must also be able to withstand high operating temperatures (\u3e 60 ºC) and feed water concentrations, and have low pore wetting propensity. Additionally, the use of highly soluble ionic organic and inorganic draw solutions can increase PRO power densities while achieving high MD water fluxes, thus increasing efficiencies and decreasing costs of OHE. Please click Additional Files below to see the full abstract

Orientation uncertainty reduces perceived obliquity

The influence of prejudice on perception should be greatest when certainty about stimulus identity is least. We exploited this relationship to reveal visual biases for the cardinal orientations: vertical and horizontal. Specifically, when we increased the variance of orientations in an array of grating patches, estimates of the mean became less oblique. This result is consistent with a stable prior, or prejudice, for those orientations most prevalent in natural scenes

A Computational Model of Visual Anisotropy

Visual anisotropy has been demonstrated in multiple tasks where performance differs between vertical, horizontal, and oblique orientations of the stimuli. We explain some principles of visual anisotropy by anisotropic smoothing, which is based on a variation on Koenderink's approach in [1]. We tested the theory by presenting Gaussian elongated luminance profiles and measuring the perceived orientations by means of an adjustment task. Our framework is based on the smoothing of the image with elliptical Gaussian kernels and it correctly predicted an illusory orientation bias towards the vertical axis. We discuss the scope of the theory in the context of other anisotropies in perception

SMARTphone-based, early cardiac REHABilitation in patients with acute coronary syndromes [SMART-REHAB Trial]: A randomized controlled trial protocol

© 2016 The Author(s). Background: There are well-documented treatment gaps in secondary prevention of coronary heart disease and no clear guidelines to assist early physical activity after acute coronary syndromes (ACS). Smartphone technology may provide an innovative platform to close these gaps. This paper describes the study design of a randomized controlled trial assessing whether a smartphone-based secondary prevention program can facilitate early physical activity and improve cardiovascular health in patients with ACS. Methods: We have developed a multi-faceted, patient-centred smartphone-based secondary prevention program emphasizing early physical activity with a graduated walking program initiated on discharge from ACS admission. The program incorporates; physical activity tracking through the smartphone's accelerometer with interactive feedback and goal setting; a dynamic dashboard to review and optimize cardiovascular risk factors; educational messages delivered twice weekly; a photographic food diary; pharmacotherapy review; and support through a short message service. The primary endpoint of the trial is change in exercise capacity, as measured by the change in six-minute walk test distance at 8-weeks when compared to baseline. Secondary endpoints include improvements in cardiovascular risk factor status, psychological well-being and quality of life, medication adherence, uptake of cardiac rehabilitation and re-hospitalizations. Discussion: This randomized controlled trial will use a smartphone-phone based secondary prevention program to emphasize early physical activity post-ACS. It will provide evidence regarding the feasibility and utility of this innovative platform in closing the treatment gaps in secondary prevention. Trial registration: The trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) on April 4, 2016. The registration number is ACTRN12616000426482

Kinetic regulation of multi-ligand binding proteins

Background: Second messengers, such as calcium, regulate the activity of multisite binding proteins in a concentration-dependent manner. For example, calcium binding has been shown to induce conformational transitions in the calcium-dependent protein calmodulin, under steady state conditions. However, intracellular concentrations of these second messengers are often subject to rapid change. The mechanisms underlying dynamic ligand-dependent regulation of multisite proteins require further elucidation. Results: In this study, a computational analysis of multisite protein kinetics in response to rapid changes in ligand concentrations is presented. Two major physiological scenarios are investigated: i) Ligand concentration is abundant and the ligand-multisite protein binding does not affect free ligand concentration, ii) Ligand concentration is of the same order of magnitude as the interacting multisite protein concentration and does not change. Therefore, buffering effects significantly influence the amounts of free ligands. For each of these scenarios the influence of the number of binding sites, the temporal effects on intermediate apo- and fully saturated conformations and the multisite regulatory effects on target proteins are investigated. Conclusions: The developed models allow for a novel and accurate interpretation of concentration and pressure jump-dependent kinetic experiments. The presented model makes predictions for the temporal distribution of multisite protein conformations in complex with variable numbers of ligands. Furthermore, it derives the characteristic time and the dynamics for the kinetic responses elicited by a ligand concentration change as a function of ligand concentration and the number of ligand binding sites. Effector proteins regulated by multisite ligand binding are shown to depend on ligand concentration in a highly nonlinear fashion

Mining Big Data for Tourist Hot Spots: Geographical Patterns of Online Footprints

Understanding the complex, and often unequal, spatiality of tourist demand in urban contexts requires other methodologies, among which the information base available online and in social networks has gained prominence. Innovation supported by Information and Communication Technologies in terms of data access and data exchange has emerged as a complementary supporting tool for the more traditional data collection techniques currently in use, particularly, in urban destinations where there is the need to more (near)real-time monitoring. The capacity to collect and analise massive amounts of data on individual and group behaviour is leading to new data-rich research approaches. This chapter addresses the potential for discovering geographical insights regarding tourists’ spatial patterns within a destination, based on the analysis of geotagged data available from two social networks. ·info:eu-repo/semantics/publishedVersio

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies

Modeling the Actin.myosin ATPase cross-bridge cycle for skeletal and cardiac muscle myosin isoforms

Modeling the complete actin.myosin ATPase cycle has always been limited by the lack of experimental data concerning key steps of the cycle, because these steps can only be defined at very low ionic strength. Here, using human ?-cardiac myosin-S1, we combine published data from transient and steady-state kinetics to model a minimal eight-state ATPase cycle. The model illustrates the occupancy of each intermediate around the cycle and how the occupancy is altered by changes in actin concentration for [actin] = 1–20Km. The cycle can be used to predict the maximal velocity of contraction (by motility assay or sarcomeric shortening) at different actin concentrations (which is consistent with experimental velocity data) and predict the effect of a 5 pN load on a single motor. The same exercise was repeated for human ?-cardiac myosin S1 and rabbit fast skeletal muscle S1. The data illustrates how the motor domain properties can alter the ATPase cycle and hence the occupancy of the key states in the cycle. These in turn alter the predicted mechanical response of the myosin independent of other factors present in a sarcomere, such as filament stiffness and regulatory proteins. We also explore the potential of this modeling approach for the study of mutations in human ?-cardiac myosin using the hypertrophic myopathy mutation R453C. Our modeling, using the transient kinetic data, predicts mechanical properties of the motor that are compatible with the single-molecule study. The modeling approach may therefore be of wide use for predicting the properties of myosin mutations