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The mitochondrial carrier protein for carnitine has been identified in Saccharomyces cerevisiae. It is encoded by the gene CRC1 and is a member of the family of mitochondrial transport proteins. The protein has been over-expressed with a C-terminal His-tag in S. cerevisiae and isolated from mitochondria by nickel affinity chromatography. The purified protein has been reconstituted into proteoliposomes and its transport characteristics established. It transports carnitine, acetylcarnitine, propionylcarnitine and to a much lower extent medium- and long-chain acylcarnitines.

Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family, including the OAC protein. The transport specificities of some family members are known, but most are not. The function of the OAC has been revealed by overproduction in Escherichia coli, reconstitution into liposomes, and demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate. Reconstituted OAC catalyzes both unidirectional transport and exchange of substrates. In S. cerevisiae, OAC is in inner mitochondrial membranes, and deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate. Mitochondria from wild-type cells swelled in isoosmotic solutions of ammonium salts of oxaloacetate, sulfate, thiosulfate, and malonate, indicating that these anions are cotransported with protons. Overexpression of OAC in the deletion strain increased greatly the [(35)S]sulfate/sulfate and [(35)S]sulfate/oxaloacetate exchanges in proteoliposomes reconstituted with digitonin extracts of mitochondria. The main physiological role of OAC appears to be to use the proton-motive force to take up into mitochondria oxaloacetate produced from pyruvate by cytoplasmic pyruvate carboxylase.

The dicarboxylate carrier (DIC) is an integral membrane protein that catalyses a dicarboxylate-phosphate exchange across the inner mitochondrial membrane. We generated a yeast mutant lacking the gene for the DIC. The deletion mutant failed to grow on acetate or ethanol as sole carbon source but was viable on glucose, galactose, pyruvate, lactate and glycerol. The growth on ethanol or acetate was largely restored by the addition of low concentrations of aspartate, glutamate, fumarate, citrate, oxoglutarate, oxaloacetate and glucose, but not of succinate, leucine and lysine. The expression of the DIC gene in wild-type yeast was repressed in media containing ethanol or acetate with or without glycerol. These results indicate that the primary function of DIC is to transport cytoplasmic dicarboxylates into the mitochondrial matrix rather than to direct carbon flux to gluconeogenesis by exporting malate from the mitochondria. The delta DIC mutant may serve as a convenient host for overexpression of DIC and for the demonstration of its correct targeting and assembly.

The protein encoded by the ACR1 gene in Saccharomyces cerevisiae belongs to a family of 35 related membrane proteins that are encoded in the fungal genome. Some of them are known to transport various substrates and products across the inner membranes of mitochondria, but the functions of 28 members of the family are unknown. The yeast ACR1 gene was introduced into Escherichia coli on an expression plasmid. The protein was over-produced as inclusion bodies, which were purified and solubilised in the presence of sarkosyl. The solubilised protein was reconstituted into liposomes and shown to transport fumarate and succinate. Its physiological role in S. cerevisiae is probably to transport cytoplasmic succinate, derived from isocitrate by the action of isocitrate lyase in the cytosol, into the mitochondrial matrix in exchange for fumarate. This exchange activity and the subsequent conversion of fumarate to oxaloacetate in the cytosol would be essential for the growth of S. cerevisiae on ethanol or acetate as the sole carbon source.

The inner membranes of mitochondria contain a family of transport proteins of related sequence and structure. The DNA sequence of the genome of Saccharomyces cerevisiae encodes at least 35 members of this family. Three of them can be recognised as known isoforms of the ADP-ATP translocase and two others as the phosphate and citrate carriers. The transport functions of the remainder cannot be identified with certainty. One of them, encoded on yeast chromosome xii, shows a fairly close sequence relationship to the known sequence of the bovine mitochondrial oxoglutarate-malate carrier. The yeast protein has been obtained by over-expression in Escherichia coli, reconstituted into phospholipid vesicles and shown to have transport properties characteristic of the mitochondrial carrier for dicarboxylate ions, such as malate, and also phosphate, previously biochemically characterised, but not sequenced, from both mammalian and yeast mitochondria. This is the first example of the biochemical identification of an unknown membrane protein encoded in the yeast genome since the completion of the genomic sequence.

The ornithine carrier from rat liver mitochondria was solubilized with Triton X-100 and purified by chromatography on hydroxyapatite, PD-10, DEAE-Sephacel and celite. The purified ornithine carrier on SDS polyacrylamide gel electrophoresis consisted of a single band with an apparent molecular mass of 33.5 kDa and, when reconstituted into liposomes, catalyzed an active ornithine/ornithine exchange. Besides ornithine, also citrulline, lysine and arginine were transported by the carrier. In the reconstituted system the maximum transport rate of external 14 C-ornithine in exchange for ornithine, citrulline or lysine was 3.0 mmol/min per g protein at 25 °C The transport affinity (Km) was 0.16 mM for ornithine, 1.2 mM for lysine and 3.6 mM for citrulline. The reconstituted ornithine/citrulline exchange was dependent on the pH gradient and not on the membrane potential suggesting that the carrier catalyzes an electroneutral exchange of ornithine + against citrulline and 1 H + . The unidirectional transport of ornithine was increased by raising the concentration of protons in the opposite compartment. This and other results obtained by using FCCP or nigericin indicate that ornithine can also be transported by the purified ornithine carrier in exchange for protons. After modification with mercurials, the reconstituted ornithine carrier catalyzed another mode of transport characterized by a unidirectional substrate flux not dependent on the pH gradient and the membrane potential and by a significantly reduced substrate specificity.

The ornithine carrier was purified from rat liver mitochondria and reconstituted into liposomes by removing the detergent from mixed micelles by hydrophobic chromatography on Amberlite XAD-2. The efficiency of reconstitution was optimized with respect to the concentration of protein and phospholipid, the Triton X-100/phospholipid ratio, the Amberlite/detergent ratio and the number of passages through a single Amberlite column. The activity of the carrier was influenced by the phospholipid composition of the liposomes, increasing in the presence of acidic phospholipids and decreasing in the presence of dioleoylphosphatidylcholine. In the reconstituted system the incorporated ornithine carrier catalyzed a first-order reaction of ornithine/ornithine or ornithine/citrulline exchange. The maximum transport rate of external [14C]ornithine was 3.2 mmol/min per g protein at 25 degrees C. This value was independent of the type of substrate present at the external or internal space of the liposomes (ornithine, citrulline and lysine). The half-saturation constant (Km) was 0.16 mM for ornithine, 1.2 mM for lysine and 3.6 mM for citrulline. The activation energy of the ornithine/ornithine exchange reaction was 89 kJ/mol. The rate of exchange had a pH optimum at 8 and was inhibited by cations.

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Planning smooth and energy-efficient paths for wheeled mobile robots is a central task for applications ranging from autonomous driving to service and intralogistic robotics. Over the past decades, several sampling-based motion-planning algorithms, extend functions and post-smoothing algorithms have been introduced for such motion-planning systems. Choosing the best combination of components for an application is a tedious exercise, even for expert users. We therefore present Bench-MR, the first open-source motion-planning benchmarking framework designed for sampling-based motion planning for nonholonomic, wheeled mobile robots. Unlike related software suites, Bench-MR is an easy-to-use and comprehensive benchmarking framework that provides a large variety of sampling-based motion-planning algorithms, extend functions, collision checkers, post-smoothing algorithms and optimization criteria. It aids practitioners and researchers in designing, testing, and evaluating motion-planning systems, and comparing them against the state of the art on complex navigation scenarios through many performance metrics. Through several experiments, we demonstrate how Bench-MR can be used to gain extensive insights from the benchmarking results it generates.

The Arabidopsis thaliana genome contains 58 membrane proteins belonging to the mitochondrial carrier family. Three members of this family, here named AtAPC1, AtAPC2, and AtAPC3, exhibit high structural similarities to the human mitochondrial ATP–Mg2 +/phosphate carriers. Under normal physiological conditions the AtAPC1 gene was expressed at least five times more than the other two AtAPC genes in flower, leaf, stem, root and seedlings. However, in stress conditions the expression levels of AtAPC1 and AtAPC3 change. Direct transport assays with recombinant and reconstituted AtAPC1, AtAPC2 and AtAPC3 showed that they transport phosphate, AMP, ADP, ATP, adenosine 5′-phosphosulfate and, to a lesser extent, other nucleotides. AtAPC2 and AtAPC3 also had the ability to transport sulfate and thiosulfate. All three AtAPCs catalyzed a counter-exchange transport that was saturable and inhibited by pyridoxal-5′-phosphate. The transport activities of AtAPCs were also inhibited by the addition of EDTA or EGTA and stimulated by the addition of Ca2 +. Given that phosphate and sulfate can be recycled via their own specific carriers, these findings indicate that AtAPCs can catalyze net transfer of adenine nucleotides across the inner mitochondrial membrane in exchange for phosphate (or sulfate), and that this transport is regulated both at the transcriptional level and by Ca2 +.

The ARG-11 gene in Saccharomyces cerevisiae encodes a protein with the characteristic features of a family of 35 related membrane proteins that are encoded in the fungal genome. Some of them are known to transport various substrates and products across the inner membranes of mitochondria, but the functions of 29 members of the family are unknown. The yeast ARG-11 protein has been over-produced as inclusion bodies in Escherichia coli. It has been solubilized in the presence of sarkosyl, re-constituted into liposomes and shown to transport ornithine in exchange for protons. Its main physiological role is probably to take ornithine synthesized from glutamate in the mitochondrial matrix to the cytosol where it is converted to arginine.

To shed light on the metabolic role of two mitochondrial transporters for basic amino acids in Arabidopsis, we compared their functional properties in liposomes and expression during germination. Recombinant and purified BAC2, as previously reported for BAC1, transported various basic l-amino acids upon reconstitution in phospholipid vesicles. Both displayed highest affinity for arginine with similar Km and Vmax. However, BAC2 transported citrulline for which BAC1 had little or no affinity. Furthermore, BAC2 was less stereospecific than BAC1, transporting d-arginine and d-lysine at significant rates, and displayed a striking alkaline pH optimum (pH 8.0) whereas BAC1 activity was unaltered from pH 7.0 to 9.0. By semi-quantitative RT-PCR BAC1 transcript levels were found to be higher than those of BAC2 in germinated seeds. However, BAC2 expression transiently increased 2 days after germination. Disruption of the Arabidopsis arginase structural genes (ARGAH1 or ARGAH2) accentuated the increases of transcript levels of BAC1 at germination and of BAC2 2 days after germination and from 6 days on. Early expression of BAC1 and BAC2 is consistent with the delivery of arginine, released from seed reserves, to mitochondrial arginase and the export of ornithine. Increase of BAC2 transcript levels later in seedling development is consistent with roles in NO, polyamine or proline metabolism—processes involving arginine, citrulline and/or ornithine.

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Background Health reporting should deliver up-to-date data and information on the population's health status, its determinants and on national (or regional) healthcare services. Establishing an information or discussion base for health policy is an important objective ('data for action'), but health reporting also addresses other target groups like scientists, the media or the general public. Depending on the needs and competencies of the respective target groups, requirements for health reporting formats will differ. At the same time, heterogeneity of health reporting practices in Member States causes, next to occasional language barriers, difficulties in facilitating access to EU-comparable information. To allow for alignment and identification of good practices, our study aims to provide a comprehensive overview of the health reporting formats in the EU. Methods A web-based desk research of health reporting formats and their target groups was conducted among EU Member States and associated InfAct partner countries. Good practice examples were identified on the basis of quality criteria derived from 'Good Practice in Health Reporting' for Germany and the Eva PHR (Evaluation of National and Regional Public Health Reports) project. Based on the findings of the desk research, a guidance document for health reports will be drafted in close cooperation with InfAct partner countries. Results The guidance should accommodate the heterogeneity of reporting practices at EU level while defining desirable and feasible good practice standards. Although the focus is on public health reports, recommendations for other formats of health reporting will also be included. It will facilitate the preparation, dissemination and access to EU-comparable and high-quality health information. Conclusions The guidance is expected to be a useful tool for making health information adequately available to the targeted groups while reducing inequalities in health reporting across the EU.

The ability to perceive and predict future positions of dynamic objects is essential for mobile robots and intelligent vehicles in dynamic environments. In this paper, we present a novel planning-based approach for long-term human motion prediction that accounts for local interactions and can accurately predict joint motion of multiple agents. Long-term predictions are handled using an MDP formulation that computes a set of stochastic motion policies. To obtain distributions over future motion trajectories, we sample the policies with a weighted random walk algorithm in which each person is locally influenced by social forces from other nearby agents. Unlike related work, the algorithm is environment-aware, can account for individual agent velocities, requires no training phase and makes joint predictions for multiple agents. Experiments in simulation and with real data show that our method makes more accurate predictions than two state-of-the-art methods in terms of probabilistic and geometrical performance measures.

Background: Health Examination Surveys (HESs) can provide essential information on the health and health determinants of a population, which is not available from other data sources. Nevertheless, only some European countries have systems of national HESs. A study conducted in 2006–2008 concluded that it is feasible to organize national HESs using standardized measurement procedures in nearly all EU countries. The feasibility study also outlined a structure for a European Health Examination Survey (EHES), which is a collaboration to organize standardized HESs in countries across Europe. To facilitate setting up national surveys and to gain experience in applying the EHES methods in different cultures, EHES Joint Action (2010–2011) planned and piloted standardized HESs in the working age population in 12 countries. This included countries with earlier national HESs and countries which were planning their first national HES. The core measurements included in all surveys were weight, height, waist circumference and blood pressure, and blood samples were taken to measure lipid profiles and glucose or glycated haemoglobin (HbA1c). These are modifiable determinants of major chronic diseases not identified in health interview surveys. There was a questionnaire to complement the data on the examination measurements. Methods: Evaluation of the pilot surveys was based on review of national manuals and evaluation reports of survey organizers; observations and discussions of survey procedures during site visits and training seminars; and other communication with the survey organizers. Results: Despite unavoidable differences in the ways HESs are organized in the various countries, high quality and comparability of the data seems achievable. The biggest challenge in each country was obtaining high participation rate. Most of the pilot countries are now ready to start their full-size national HES, and six of them have already started. Conclusions: The EHES Pilot Project has set up the structure for obtaining comparable high quality health indicators on health and important modifiable risk factors of major non-communicable diseases from the European countries. The European Union is now in a key position to make this structure sustainable. The EHES core survey can be expanded to cover other measurements., peer-reviewed

The articles in this special section focus on long term human motion prediction. This represents a key ability for advanced autonomous systems, especially if they operate in densely crowded and highly dynamic environments. In those settings understanding and anticipating human movements is fundamental for robust long-term operation of robotic systems and safe human-robot collaboration. Foreseeing how a scene with multiple agents evolves over time and incorporating predictions in a proactive manner allows for novel ways of planning and control, active perception, or humanrobot interaction. Recent planning and control approaches use predictive techniques to better cope with the dynamics of the environment, thus allowing the generation of smoother and more legible robot motion. Predictions can be provided as input to the planning or optimization algorithm (e.g. as a cost term or heuristic function), or as additional dimension to consider in the problem formulation (leading to an increased computational complexity). Recent perception techniques deeply interconnect prediction modules with detection, segmentation and tracking, to generally increase the accuracy of different inference tasks, i.e. filtering, predicting. As also indicated by some of the scientific works accepted in this special issue, novel deep learning architectures allow better interleaving of the aforementioned units.

Aims and background Informing cancer patients is an ethical, legal and deontological aspect of patient management. Patients need clear instructions in order to be able to accept or refuse medical procedures. Many reports in the literature have shown differences among physicians in informing cancer patients. The aim of this study was to assess patients’ understanding of diagnosis, planned radiotherapy and risk of early and late effects, their satisfaction with the discussion with the doctor and correlation with anxiety and depression after the disclosure of a cancer diagnosis. Methods From April to July 2000 a physician with psychiatric training conducted interviews with patients after their consultation with the radiotherapist and asked them to fill in a questionnaire. Anxiety and depression were measured by means of a scoring system [HAD(A) and HAD(D)] such as the patient's satisfaction and the physician's belief in it. Eighty-two outpatients referred to our radiotherapy department were studied. Results We did not find any correlation between HAD(A) and HAD(D) scores and comprehension scores of disease, treatment schedule, side effects and patient satisfaction, or between any scores and presumed predictive variables such as diagnosis, gender, age, treatment aims, time from diagnosis, education, marital status, profession, life habits, and the role of the doctor obtaining the informed consent. Conclusions We may conclude that informed consent does not seem to increase reactive anxiety or depression. Its quality is high in our department but must be improved.

Planning smooth trajectories is important for the safe, efficient and comfortable operation of mobile robots, such as wheeled robots moving in crowded environments or cars moving at high speed. Asymptotically optimal sampling-based motion planners can be used to generate such trajectories. However, to achieve the necessary efficiency for the realtime operation of robots, one often uses their initial feasible trajectories or the trajectories of non-optimal motion planners instead, typically after a post-smoothing step. We propose a gradient-informed post-smoothing algorithm, called GRIPS, that deforms given trajectories by locally optimizing the placement of vertices while satisfying the system's kinodynamic constraints. We show experimentally that GRIPS typically produces trajectories of significantly smaller length and higher smoothness than several existing post-smoothing algorithms.

Background Research networks offer multidisciplinary expertise and promote information exchange between researchers across Europe. They are essential for the European Union’s (EU) health information system as providers of health information and data. The aim of this mapping exercise was to identify and analyze EU research networks in terms of health data collection methods, quality assessment, availability and accessibility procedures. Methods A web-based search was performed to identify EU research networks that are not part of international organizations (e.g., WHO-Europe, OECD) and are involved in collection of data for health monitoring or health system performance assessment. General characteristics of the research networks (e.g., data sources, representativeness), quality assessment procedures, availability and accessibility of health data were collected through an ad hoc extraction form. Results Fifty-seven research networks, representative at national, international or regional level, were identified. In these networks, data are mainly collected through administrative sources, health surveys and cohort studies. Over 70% of networks provide information on quality assessment of their data collection procedures. Most networks share macrodata through articles and reports, while microdata are available from ten networks. A request for data access is required by 14 networks, of which three apply a financial charge. Few networks share data with other research networks (8/49) or specify the metadata-reporting standards used for data description (9/49). Conclusions Improving health information and availability of high quality data is a priority in Europe. Research networks could play a major role in tackling health data and information inequalities by enhancing quality, availability, and accessibility of health data and data sharing across European networks.

Background Prioritization of Health information (HI) involves the establishment of methodological standards, and the development of political momentum to reliably track health status and health determinants. This is important in order to strengthen the evidence base for public health policies and facilitate effective delivery of healthcare services. In support of the establishment of a sustainable EU-wide Health information system, this consortium explores how HI is prioritized in EU and associated countries. Methods The Robert Koch Institute is conducting an online Policy Delphi survey among InfAct project partners, stakeholders from EU-Member States and associated countries. The Delphi methodology allows for rankings and priority-setting among a group of experts. The Policy Delphi facilitates the analysis of the impact and acceptability of a proposed policy option. The survey targets experts in national public health institutes and agencies, ministries of health and research. Participants are invited to provide information regarding their national HI prioritization processes, and to rank prioritization strategies and criteria, according to their degree of “desirability”, “feasibility”, “importance” and “confidence”. Results The Delphi survey will compile and assess processes and methods used to prioritize health information at national level in the EU and associated countries. The expected outcome is a list of good-practices in health information development and prioritization within countries, which could be further integrated to a health information prioritization strategy at the European level. Conclusions Prioritizing health information ensures that the right data is collected, is used to support ongoing public health policy action, and to capture emerging public health issues. This overview of prioritization strategies and methods aims to promote evidence-based public health by structuring exchanges about national HI prioritization in Europe.

Background Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes (ischemic and hemorrhagic) are scarce. Methods High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82,881 individuals (median age 50.7 years, 49.7% men) free of stroke or myocardial infarction at baseline from nine prospective European community cohorts. Multiple imputations were used to handle missing data. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for over-optimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries. Results Over a median follow-up of 12.7 years, 3,033 individuals were diagnosed with incident non-fatal or fatal stroke (N=1,654 ischemic strokes, N=612 hemorrhagic strokes, N=767 indeterminate strokes). In multivariable regression models hsTnI concentrations were associated with overall stroke (hazard ratio (HR) per one standard deviation increase 1.16, 95% confidence interval (CI) 1.10–1.21), ischemic stroke (HR 1.15, 95% CI 1.09–1.21) and hemorrhagic stroke (HR 1.10, 95% CI 1.01–1.21). Adding hsTnI concentrations to classical cardiovascular risk factors (C-indices 0.808, 0.840 and 0.735 for overall, ischemic and hemorrhagic stroke, respectively) increased the C-index significantly, but modestly. In individuals with an intermediate ten-year risk (5–20%) the net reclassification improvement for overall stroke was 0.039 (p=0.010). Conclusions Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort, but might be of some value in individuals at an intermediate risk. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): The BiomarCaRE Project is funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no.HEALTH-F2-2011-278913. This project has received further funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 648131).

Even though mobile robots have been around for decades, trajectory optimization and continuous time collision avoidance remain subject of active research. Existing methods trade off between path quality, computational complexity, and kinodynamic feasibility. This work approaches the problem using a nonlinear model predictive control (NMPC) framework, that is based on a novel convex inner approximation of the collision avoidance constraint. The proposed Convex Inner ApprOximation (CIAO) method finds kinodynamically feasible and continuous time collision free trajectories, in few iterations, typically one. For a feasible initialization, the approach is guaranteed to find a feasible solution, i.e. it preserves feasibility. Our experimental evaluation shows that CIAO outperforms state of the art baselines in terms of planning efficiency and path quality. Experiments on a robot with 12 states show that it also scales to high-dimensional systems. Furthermore real-world experiments demonstrate its capability of unifying trajectory optimization and tracking for safe motion planning in dynamic environments., Comment: Accepted by ICRA2020. This version is extended for readability and completeness. Additional content would have exceeded page limit

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The evolution of gases, the outburst of springs of acidulous and hot water, and particularly the upheaval of the ground at Torre del Greco to a height of 1·12 metre above the sea-level, are mentioned in this communication.