Developing a strategic controller with haptic and audio feedback for autonomous driving

Traffic accidents cause over 1.2 million deaths, and tens of millions of people are injured or disabled every year. Advanced driver assistant systems and other safety features have the possibility to reduce traffic accidents but do not account for human errors. Studies show that over 90% of all traffic accidents are caused by human errors. One way to reduce human errors is to introduce automation, and several major car manufacturers predict that autonomous vehicles will be available on the consumer marker as early as 2020. In theory automated cars could reduce deaths and injuries caused by traffic accidents, but there are several issues which need to be solved before it can be realized. One of these issues is how to keep the driver in the loop while the car is in autonomous mode. A human-machine interface of a strategic controller for autonomous driving was developed. Multimodal feedback consisting of auditory and haptic signals was developed for the strategic controller using an iterative design process. A user study was carried out in order to evaluate the multimodal feedback and identify usability issues, and a simulator study was carried out in order to benchmark the concept’s usability. The strategic controller prototype developed in this thesis allows the driver to take part of the driving process and control of the car by inputting commands. The controller also provides the driver with multimodal feedback based on an analysis of mock-up sensor/image data from the vehicle. User input is either denied or accepted depending on the analysed data, and on demand feedback is also provided related to the general state of the autonomous system. Multimodal feedback was found to be promising for communicating complex information in humanmachine interactions. Although users had little to no experience of autonomous driving, they found the developed concept to be attractive and would use it for daily commuting. As it is difficult to mirror reality in simulators, test subjects may have had a more positive attitude towards the concept. However, the issue of keeping the user in the loop still persists. Feedback needs to be designed thoroughly and should not be limited to two modalities. Instead, information should be distributed through several modalities in order to reduce cognitive load and increase the user’s situational awareness. The benchmark of the developed concept showed promising results, although the results may have suffered due to hardware limitations

Challenges and Trajectories of Fiscal Policy and PFM Reform in CEE/CIS

The purpose of this study is to provide an overview of fiscal policies and PFM reforms in 7 countries in the Western Balkans and 12 countries in the CIS, including major macroeconomic and poverty trends, fiscal policy, the size and role of the public sector, public expenditure management and its linkage to policy development, the organization of budget processes on the central and local levels, the role of various actors and tools in PFM, including civil society and the international donor community. The period of 2003-2007 was characterized by an extraordinary high rate of economic growth, both worldwide and in the CEE/CIS region. This created macroeconomic room for meeting numerous development challenges: reducing poverty and inequality, improving the quality and coverage of public services, upgrading infrastructure, and advancing various reforms, including those related to PFM. However, the economic situation deteriorated dramatically in 2008 as a result of the global financial crisis, with deep recession hitting most of the countries in 2009 and bleak perspectives for subsequent years. It remains to be seen whether the crisis situation will force governments to speed up necessary reforms. In the PFM area major tasks concern lengthening fiscal planning horizon and gradual movement toward performance oriented budgeting the measure which can allow better expenditure targeting and decrease volatility in expenditure allocation), increasing budget transparency and creating real room for civil society involvement into a budget process. However, the reforms must also involve a broadly defined governance sphere, i.e. improving transparency and accountability of government, modernization of civil service, decentralization, including building a genuine system of local and regional self-government, and other similar measures to improve quality of public services and social policy interventions.public finance management, fiscal policy, Central and Eastern Europe, Western Balkans, Commonwealth of Independent States, social policies, social services, children and families

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

Glia, sympathetic activity and cardiovascular disease

New Findings What is the topic of this review? In this review, we discuss recent findings that provide a novel insight into the mechanisms that link glial cell function with the pathogenesis of cardiovascular disease, including systemic arterial hypertension and chronic heart failure. What advances does it highlight? We discuss how glial cells may influence central presympathetic circuits, leading to maladaptive and detrimental increases in sympathetic activity and contributing to the development and progression of cardiovascular disease. Increased activity of the sympathetic nervous system is associated with the development of cardiovascular disease and may contribute to its progression. Vasomotor and cardiac sympathetic activities are generated by the neuronal circuits located in the hypothalamus and the brainstem. These neuronal networks receive multiple inputs from the periphery and other parts of the CNS and, at a local level, may be influenced by their non-neuronal neighbours, in particular glial cells. In this review, we discuss recent experimental evidence suggesting that astrocytes and microglial cells are able to modulate the activity of sympathoexcitatory neural networks in disparate physiological and pathophysiological conditions. We focus on the chemosensory properties of astrocytes residing in the rostral ventrolateral medulla oblongata and discuss signalling mechanisms leading to glial activation during brain hypoxia and inflammation. Alterations in these mechanisms may lead to heightened activity of sympathoexcitatory CNS circuits and contribute to maladaptive and detrimental increases in sympathetic tone associated with systemic arterial hypertension and chronic heart failure

Isorhapontigenin, a bioavailable dietary polyphenol, suppresses airway epithelial cell inflammation through a corticosteroid-independent mechanism

Background and Purpose Chronic obstructive pulmonary disease (COPD) is a corticosteroid-resistant airway inflammatory condition. Resveratrol has exhibited anti-inflammatory activities in COPD but has weak potency and poor pharmacokinetics. This study aims to evaluate the potential of isorhapontigenin, another dietary polyphenol, as a novel anti-inflammatory agent for COPD by examining its effects in vitro and its pharmacokinetics in vivo. Experimental Approach Primary human airway epithelial cells derived from healthy and COPD subjects and A549 epithelial cells were incubated with isorhapontigenin or resveratrol and stimulated with IL-1β in the presence or absence of cigarette smoke extract. Their effects on the release of IL-6 and chemokine (C-X-C motif) ligand 8 (CXCL8) were determined and the activation of NF-κB, AP-1, MAPKs and PI3K/Akt/FoxO3A pathways compared to dexamethasone were evaluated. The pharmacokinetic profiles of isorhapontigenin were assessed in Sprague-Dawley rats after respective intravenous and oral administration. Key Results Isorhapontigenin exhibited concentration-dependent inhibition of IL-6 and CXCL8 release, with IC50 values at least two-fold lower than resveratrol. These were associated with suppressed NF-κB and AP-1 activation and notably, the PI3K/Akt/FoxO3A pathway that was relatively insensitive to dexamethasone. In vivo, isorhapontigenin was rapidly absorbed with abundant plasma exposure after oral dosing. Its oral bioavailability was approximately 50% higher than resveratrol. Conclusions and Implications Isorhapontigenin, an orally bioavailable dietary polyphenol, displayed superior anti-inflammatory effects compared to resveratrol. Furthermore, it suppressed the PI3K/Akt pathway that is insensitive to corticosteroids. These favourable efficacy and pharmacokinetic properties support its further development as a novel anti-inflammatory agent for COPD

A WD-FYVE protein binds to the kinases Akt and PKCζ/λ

WD (tryptophan-aspartic acid dipeptide)-repeat proteins play a central role in signal transduction cascades by co-ordinating the interaction of key signalling molecules. We identified a novel propeller-FYVE [domain identified in Fab1p, YOTB, Vac1p and EEA1 (early endosome antigen 1)] protein, ProF, which is expressed in various cell lines and tissues and consists of seven WD-repeats and a FYVE domain. WD-repeat proteins offer a platform for protein–protein interactions by folding into a seven-bladed propeller-like structure, while the FYVE domain binds to phosphatidylinositol 3-phosphate present mainly on intracellular membranes. The ProF protein partially co-localizes with EEA1 on vesicular structures and binds to the protein kinases Akt and PKCζ/λ (protein kinase Cζ/λ) via its WD-repeat propeller. ProF interacts more strongly with the kinases after hormonal stimulation. Endogenously expressed ProF and the two kinases interact in brain and in the preadipocyte cell line 3T3-L1, suggesting a role in secretory vesicular processes. In summary, we describe a new binding partner for kinases, located on vesicular structures in specialized cells, which may play a role for the spatial organization of signalling cascades