Loss of Akt activity increases circulating soluble endoglin release in preeclampsia:identification of inter-dependency between Akt-1 and heme oxygenase-1

Aims - Endothelial dysfunction is a hallmark of preeclampsia. Desensitization of the phosphoinositide 3-kinase (PI3K)/Akt pathway underlies endothelial dysfunction and haeme oxygenase-1 (HO-1) is decreased in preeclampsia. To identify therapeutic targets, we sought to assess whether these two regulators act to suppress soluble endoglin (sEng), an antagonist of transforming growth factor-ß (TGF-ß) signalling, which is known to be elevated in preeclampsia. Methods and results - Vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), angiopoietin-1 (Ang-1), and insulin, which all activate the PI3K/Akt pathway, inhibited the release of sEng from endothelial cells. Inhibition of the PI3K/Akt pathway, by overexpression of phosphatase and tensin homolog (PTEN) or a dominant-negative isoform of Akt (Aktdn) induced sEng release from endothelial cells and prevented the inhibitory effect of VEGF-A. Conversely, overexpression of a constitutively active Akt (Aktmyr) inhibited PTEN and cytokine-induced sEng release. Systemic delivery of Aktmyr to mice significantly reduced circulating sEng, whereas Aktdn promoted sEng release. Phosphorylation of Akt was reduced in preeclamptic placenta and this correlated with the elevated level of circulating sEng. Knock-down of Akt using siRNA prevented HO-1-mediated inhibition of sEng release and reduced HO-1 expression. Furthermore, HO-1 null mice have reduced phosphorylated Akt in their organs and overexpression of Aktmyr failed to suppress the elevated levels of sEng detected in HO-1 null mice, indicating that HO-1 is required for the Akt-mediated inhibition of sEng. Conclusion - The loss of PI3K/Akt and/or HO-1 activity promotes sEng release and positive manipulation of these pathways offers a strategy to circumvent endothelial dysfunction.

Accountability changes in an NGO institutional and resource dependency perspectives on BRAC

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

When is an image a health claim? A false-recollection method to detect implicit inferences about products' health benefits

Objective: Images on food and dietary supplement packaging might lead people to infer (appropriately or inappropriately) certain health benefits of those products. Research on this issue largely involves direct questions, which could (a) elicit inferences that would not be made unprompted, and (b) fail to capture inferences made implicitly. Using a novel memory-based method, in the present research, we explored whether packaging imagery elicits health inferences without prompting, and the extent to which these inferences are made implicitly. Method: In 3 experiments, participants saw fictional product packages accompanied by written claims. Some packages contained an image that implied a health-related function (e.g., a brain), and some contained no image. Participants studied these packages and claims, and subsequently their memory for seen and unseen claims were tested. Results: When a health image was featured on a package, participants often subsequently recognized health claims that—despite being implied by the image—were not truly presented. In Experiment 2, these recognition errors persisted despite an explicit warning against treating the images as informative. In Experiment 3, these findings were replicated in a large consumer sample from 5 European countries, and with a cued-recall test. Conclusion: These findings confirm that images can act as health claims, by leading people to infer health benefits without prompting. These inferences appear often to be implicit, and could therefore be highly pervasive. The data underscore the importance of regulating imagery on product packaging; memory-based methods represent innovative ways to measure how leading (or misleading) specific images can be. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Magyarország aszimmetrikus kereskedelmi függősége az integrációs profil szemszögéből (Hungary’s assimetric trade dependency)

A tanulmány az integrációs profil szempontjából fontos külkereskedelmi aszimmetrikus függőség kérdését járja körbe Németország vonatkozásában. A tanulmány célja azon kérdések megválaszolása, hogy a Németországhoz fűződő kereskedelmi függőség földrajzi eloszlása – és ezzel Magyarország integrációs profilja – változott-e jelentősen a 2004-es teljes jogú tagsággal, illetve a jelen gazdasági válság következtében előtérbe kerülő és láthatóan átalakuló EU-n belüli centrum-periféria viszony módosulásának van-e bármi jele a magyar külkereskedelem földrajzi aspektusában? _____ The short study analyses the Hungarian trade-related asymmetric dependency regarding the German economy. The paper seeks to analyse how the foreign trade related Hungarian integration profile was affected by the EU-accession back in 2004, and whether the dependency detected in the country’s trade relations reveals any signs of the emergence of a centre-periphery within the European Union.

Fatty acids and stable isotopes as indicators of early-life feeding and potential maternal resource dependency in the bull shark Carcharhinus leucas

The degree of reliance of newborn sharks on energy reserves from maternal resource allocation and the timescales over which these animals develop foraging skills are critical factors towards understanding the ecological role of top predators in marine ecosystems. We used muscle tissue stable carbon isotopic composition and fatty acid analysis of bull sharks Carcharhinus leucas to investigate early-life feeding ecology in conjunction with maternal resource dependency. Values of δ13C of some young-of-the-year sharks were highly enriched, reflecting inputs from the marine-based diet and foraging locations of their mothers. This group of sharks also contained high levels of the 20:3ω9 fatty acid, which accumulates during periods of essential fatty acid deficiency, suggesting inadequate or undeveloped foraging skills and possible reliance on maternal provisioning. A loss of maternal signal in δ13C values occurred at a length of approximately 100 cm, with muscle tissue δ13C values reflecting a transition from more freshwater/estuarine-based diets to marine-based diets with increasing length. Similarly, fatty acids from sharks >100 cm indicated no signs of essential fatty acid deficiency, implying adequate foraging. By combining stable carbon isotopes and fatty acids, our results provided important constraints on the timing of the loss of maternal isotopic signal and the development of foraging skills in relation to shark size and imply that molecular markers such as fatty acids are useful for the determination of maternal resource dependency.

Leakage temperature dependency aware real-time scheduling for power and thermal optimization

Catering to society's demand for high performance computing, billions of transistors are now integrated on IC chips to deliver unprecedented performances. With increasing transistor density, the power consumption/density is growing exponentially. The increasing power consumption directly translates to the high chip temperature, which not only raises the packaging/cooling costs, but also degrades the performance/reliability and life span of the computing systems. Moreover, high chip temperature also greatly increases the leakage power consumption, which is becoming more and more significant with the continuous scaling of the transistor size. As the semiconductor industry continues to evolve, power and thermal challenges have become the most critical challenges in the design of new generations of computing systems. ^ In this dissertation, we addressed the power/thermal issues from the system-level perspective. Specifically, we sought to employ real-time scheduling methods to optimize the power/thermal efficiency of the real-time computing systems, with leakage/ temperature dependency taken into consideration. In our research, we first explored the fundamental principles on how to employ dynamic voltage scaling (DVS) techniques to reduce the peak operating temperature when running a real-time application on a single core platform. We further proposed a novel real-time scheduling method, “M-Oscillations” to reduce the peak temperature when scheduling a hard real-time periodic task set. We also developed three checking methods to guarantee the feasibility of a periodic real-time schedule under peak temperature constraint. We further extended our research from single core platform to multi-core platform. We investigated the energy estimation problem on the multi-core platforms and developed a light weight and accurate method to calculate the energy consumption for a given voltage schedule on a multi-core platform. Finally, we concluded the dissertation with elaborated discussions of future extensions of our research. ^

The effect of randomness for dependency map on the robustness of interdependent lattices

ACKNOWLEDGMENTS This paper is supported by the National Natural Science Foundation of China (Grant Nos. 61573067 and 61472045), the Beijing Higher Education Young Elite Teacher Project (Grant No. YETP0449), the Asia Foresight Program under NSFC Grant (Grant No. 61411146001), and the Beijing Natural Science Foundation (Grant No. 4142016).

Tales from a small island: applying the ‘path-dependency’ thesis to explore migration to a remote rural community

Peer reviewed

Predictors of functional dependency in Parkinson’s disease

Financial disclosures/conflicts of interest: Dr Macleod was funded by a Clinical Academic Fellowship from the Chief Scientist Office of the Scottish Government and received grant funding from Parkinson’s UK, the Wellcome Trust, University of Aberdeen, and NHS Grampian endowments relating to this research. Dr Counsell received grant funding from Parkinson’s UK, National Institute for Health Research, the Scottish Chief Scientist Office, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, NHS Grampian endowments and SPRING relating to this research. We declare we have no conflicts of interest. Financial support: This study was funded by Parkinson’s UK, the Scottish Chief Scientist Office, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, and SPRING.  

Predictors of functional dependency in Parkinson’s disease

Financial disclosures/conflicts of interest: Dr Macleod was funded by a Clinical Academic Fellowship from the Chief Scientist Office of the Scottish Government and received grant funding from Parkinson’s UK, the Wellcome Trust, University of Aberdeen, and NHS Grampian endowments relating to this research. Dr Counsell received grant funding from Parkinson’s UK, National Institute for Health Research, the Scottish Chief Scientist Office, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, NHS Grampian endowments and SPRING relating to this research. We declare we have no conflicts of interest. Financial support: This study was funded by Parkinson’s UK, the Scottish Chief Scientist Office, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, and SPRING.  

Bayesian Learning with Dependency Structures via Latent Factors, Mixtures, and Copulas

Bayesian methods offer a flexible and convenient probabilistic learning framework to extract interpretable knowledge from complex and structured data. Such methods can characterize dependencies among multiple levels of hidden variables and share statistical strength across heterogeneous sources. In the first part of this dissertation, we develop two dependent variational inference methods for full posterior approximation in non-conjugate Bayesian models through hierarchical mixture- and copula-based variational proposals, respectively. The proposed methods move beyond the widely used factorized approximation to the posterior and provide generic applicability to a broad class of probabilistic models with minimal model-specific derivations. In the second part of this dissertation, we design probabilistic graphical models to accommodate multimodal data, describe dynamical behaviors and account for task heterogeneity. In particular, the sparse latent factor model is able to reveal common low-dimensional structures from high-dimensional data. We demonstrate the effectiveness of the proposed statistical learning methods on both synthetic and real-world data.

Time-dependency of Rocks and Implications Associated with Tunnelling

The formulation of a geotechnical model and the associated prediction of the mechanical behaviour is a challenge engineers need to overcome in order to optimize tunnel design and meet project requirements. Special challenges arise in cases where rocks and rockmasses are susceptible to time-effects and time-dependent processes govern. Progressive rockmass deformation and instability, time-dependent overloading of support and delayed failures are commonly the result of time-dependent phenomena. The research work presented in this thesis serves as an attempt to provide more insight into the time-dependent behaviour of rocks. Emphasis is given on investigating and analyzing creep deformation and time-dependent stress relaxation phenomenon at the laboratory scale and in-depth analyses are presented. This thesis further develops the understanding of these phenomena and practical yet scientific tools for estimating and predicting the long-term strength and the maximum stress relaxation of rock materials are proposed. The identification of the existence of three distinct behavioural stages during stress relaxation is presented and discussed. The main observations associated with time-dependent behaviour are employed in numerical analyses and applied at the tunnel scale. A new approach for simulating and capturing the time-dependent behaviour coupled with the tunnel advancement effect is also developed and analyzed. Guidance is provided to increase the understanding of the support-rockmass interaction and the main implications and significance of time-dependent behaviour associated with rock tunnelling are discussed. The work presented in this thesis advances the scientific understanding of time-dependent rock and rockmass behaviour, increases the awareness of how such phenomena are captured numerically, and lays out a framework for dealing with such deformations when predicting tunnel deformations. Practical aspects of this thesis are also presented, which will increase their usage in the associated industries and close the gap between the scientific and industry communities.

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques.

Persons : their identity and individuation

This study is about the nature of persons and personal identity. It belongs to a tradition that maintains that in order to understand what it is to be a person we must clarify what personal identity consists in. In this pursuit, I differentiate between the problems (i) How do persons persist? and (ii) What facts, if any, does personal identity consist in? Concerning the first question, I argue that persons persist three-dimensionally (the endurance view), and not four-dimensionally (the perdurarne view), on the ground that objects must always fall under some substance sortal concept S (the sortal dependency of individuation), and that the concept person entails that objects falling under it are three-dimensional. Concerning the second question, I differentiate between Criterianists, who maintain that it is possible to specify a non-circular and informative criterion for personal identity, and Non-Criterianists, who deny that such a specification is possible. I argue against Criterianist accounts of personal identity on the ground that they are either (i) circular, (ii) violate the intrinsicality of identity or (iii) do not adequately represent what we are essentially. I further criticise three Psychological Non-Criterianist accounts of personal identity on the ground that they wrongly assume that 'person' refers to mental entities. Instead I formulate the Revised Animal Attribute View where person is understood as a basic sortal concept which picks out a biological sort of enduring animals. In this, I claim that the real essence of a person is determined by the real essence of the kind of animal he is, without thereby denying that persons have a real essence as persons.

Vestibular and oculomotor influences on visual dependency

The degree to which a person relies on visual stimuli for spatial orientation is termed visual dependency (VD). VD is considered a perceptual trait or cognitive style influenced by psychological factors and mediated by central re-weighting of the sensory inputs involved in spatial orientation. VD is often measured using the rod-and-disk test, wherein participants align a central rod to the subjective visual vertical (SVV) in the presence of a background that is either stationary or rotating around the line of sight - dynamic SVV. Although this task has been employed to assess VD in health and vestibular disease, it is unknown what effect torsional nystagmic eye movements may have on individual performance. Using caloric ear irrigation, 3D video-oculography and the rod-and-disk test, we show that caloric torsional nystagmus modulates measures of visual dependency and demonstrate that increases in tilt after irrigation are positively correlated with changes in ocular torsional eye movements. When the direction of the slow phase of the torsional eye movement induced by the caloric is congruent with that induced by the rotating visual stimulus, there is a significant increase in tilt. When these two torsional components are in opposition there is a decrease. These findings show that measures of visual dependence can be influenced by oculomotor responses induced by caloric stimulation. The findings are of significance for clinical studies as they indicate that VD, which often increases in vestibular disorders, is not only modulated by changes in cognitive style but also by eye movements, in particular nystagmus.