Industry strategies for the promotion of E-mobility under alternative policy and economic scenarios

Purpose: In this study, we consider the European electro-mobility market from an industrial perspective, and focus on effects of market conditions and manufacturer strategies, with the objective to gain insight on what could inhibit the successful market penetration of electric powertrain vehicles. Methods: We use the EC-JRC Powertrain Technology Transition Market Agent Model (PTTMAM), a system dynamics model based around the interactions of conceptual market agent groups in the EU. We assess strategies employed by automobile manufacturers towards the development and market penetration of electric vehicles. Results: Impacts on electric powertrain sales shares (up to 2050) related to industrial strategies, represented by learning effect, marketing effort and R&D funding, are presented under different scenarios related to policy, regulation and market conditions. Conclusion: It is concluded from the results presented here that competition between electrical powertrain options may be more inhibitive than competition against conventional counterparts, with both monetary and non-monetary industry support for immature powertrains key to their long-term success when supportive policies are designed to be technology neutral

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

The Mutational Profile of Unicystic Ameloblastoma

BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM ( n = 39) and to compare it to conventional AM ( n = 39). The associations between mutation status and recurrence probability were also analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8 intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs, only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate high frequency of activating BRAF V600E mutations in both UAM and AM of the mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be lower as was shown for AM previously. It could therefore be argued that UAM and AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations were associated with an increased rate of local recurrence ( P = 0.0003), which might indicate that routine mutation testing also has an impact on prognosis

HERC6 is the main E3 ligase for global ISG15 conjugation in mouse cells

Type I interferon (IFN) stimulates expression and conjugation of the ubiquitin-like modifier IFN-stimulated gene 15 (ISG15), thereby restricting replication of a wide variety of viruses. Conjugation of ISG15 is critical for its antiviral activity in mice. HECT domain and RCC1-like domain containing protein 5 (HerC5) mediates global ISGylation in human cells, whereas its closest relative, HerC6, does not. So far, the requirement of HerC5 for ISG15-mediated antiviral activity has remained unclear. One of the main obstacles to address this issue has been that no HerC5 homologue exists in mice, hampering the generation of a good knock-out model. However, mice do express a homologue of HerC6 that, in contrast to human HerC6, can mediate ISGylation. Here we report that the mouse HerC6 N-terminal RCC1-like domain (RLD) allows ISG15 conjugation when replacing the corresponding domain in the human HerC6 homologue. In addition, sequences in the C-terminal HECT domain of mouse HerC6 also appear to facilitate efficient ISGylation. Mouse HerC6 paralleled human HerC5 in localization and IFN-inducibility. Moreover, HerC6 knock-down in mouse cells abolished global ISGylation, whereas its over expression enhanced the IFNβ promoter and conferred antiviral activity against vesicular stomatitis virus and Newcastle disease virus. Together these data indicate that HerC6 is likely the functional counterpart of human HerC5 in mouse cells, suggesting that HerC6-/-mice may provide a feasible model to study the role of human HerC5 in antiviral responses

Direction and magnitude of nicotine effects on the fMRI BOLD response are related to nicotine effects on behavioral performance

Considerable variability across individuals has been reported in both the behavioral and fMRI blood oxygen level-dependent (BOLD) response to nicotine. We aimed to investigate (1) whether there is a heterogeneous effect of nicotine on behavioral and BOLD responses across participants and (2) if heterogeneous BOLD responses are associated with behavioral performance measures. In this double-blind, placebo-controlled, cross-over study, 41 healthy participants (19 smokers)—drawn from a larger population-based sample—performed a visual oddball task after acute challenge with 1 mg nasal nicotine. fMRI data and reaction time were recorded during performance of the task. Across the entire group of subjects, we found increased activation in the anterior cingulate cortex, middle frontal gyrus, superior temporal gyrus, post-central gyrus, planum temporal and frontal pole in the nicotine condition compared with the placebo condition. However, follow-up analyses of this difference in activation between the placebo and nicotine conditions revealed that some participants showed an increase in activation while others showed a decrease in BOLD activation from the placebo to the nicotine condition. A reduction of BOLD activation from placebo to nicotine was associated with a decrease in reaction time and reaction time variability and vice versa, suggesting that it is the direction of BOLD response to nicotine which is related to task performance. We conclude that the BOLD response to nicotine is heterogeneous and that the direction of response to nicotine should be taken into account in future pharmaco-fMRI research on the central action of nicotine

Revealing the Functional Neuroanatomy of Intrinsic Alertness Using fMRI: Methodological Peculiarities

Clinical observations and neuroimaging data revealed a right-hemisphere fronto-parietal-thalamic-brainstem network for intrinsic alertness, and additional left fronto-parietal activity during phasic alertness. The primary objective of this fMRI study was to map the functional neuroanatomy of intrinsic alertness as precisely as possible in healthy participants, using a novel assessment paradigm already employed in clinical settings. Both the paradigm and the experimental design were optimized to specifically assess intrinsic alertness, while at the same time controlling for sensory-motor processing. The present results suggest that the processing of intrinsic alertness is accompanied by increased activity within the brainstem, thalamus, anterior cingulate gyrus, right insula, and right parietal cortex. Additionally, we found increased activation in the left hemisphere around the middle frontal gyrus (BA 9), the insula, the supplementary motor area, and the cerebellum. Our results further suggest that rather minute aspects of the experimental design may induce aspects of phasic alertness, which in turn might lead to additional brain activation in left-frontal areas not normally involved in intrinsic alertness. Accordingly, left BA 9 activation may be related to co-activation of the phasic alertness network due to the switch between rest and task conditions functioning as an external warning cue triggering the phasic alertness network. Furthermore, activation of the intrinsic alertness network during fixation blocks due to enhanced expectancy shortly before the switch to the task block might, when subtracted from the task block, lead to diminished activation in the typical right hemisphere intrinsic alertness network. Thus, we cautiously suggest that – as a methodological artifact – left frontal activations might show up due to phasic alertness involvement and intrinsic alertness activations might be weakened due to contrasting with fixation blocks, when assessing the functional neuroanatomy of intrinsic alertness with a block design in fMRI studies

The German Young Olympic Athletes' Lifestyle and Health Management Study (GOAL Study): design of a mixed-method study

<p>Abstract</p> <p>Background</p> <p>In order to perform at top levels, elite athletes have to both protect and risk their health at the same time. Adolescent elite athletes have the additional challenge of coping with substantial physical, psychological and social transformations. The contradictory phenomenon of protecting and risking the adolescent athletes' health in sports challenges the development of health promotion and protection strategies. The GOAL Study (German Young Olympic Athletes' Lifestyle and Health Management Study) analyzes the individual and organizational management of health in adolescent elite sports.</p> <p>Methods/design</p> <p>We combine quantitative and qualitative approaches in a mixed-method study. This allows us to gather a broad range of representative information on squad athletes from all Olympic disciplines as well as in-depth information on four selected Olympic disciplines (artistic gymnastics, biathlon, handball and wrestling). Within the quantitative section we attempt to identify the young athletes' health and nutrition behavior, their subjective health state and their lay health representations, health-related social networks, and structures of medical attendance. 1138 national team level athletes born between 1992 and 1995 from 51 Olympic disciplines responded to the questionnaire (response rate: 61,75%). The qualitative section investigates the meaning and relevance of health and nutrition within the athletes' sports specific surroundings, the impact of biographic backgrounds on individual health behavior, and sports specific cultures of health, nutrition and risk. We interviewed 24 athletes and 28 coaching and medical experts, and carried out 14 multi-day participant observations at training sessions and competitions.</p> <p>Conclusions</p> <p>The studies' results will serve as the basis for developing tailored health promotion strategies to be in cooperation with German elite sports associations.</p

Luminescence Dating in Fluvial Settings: Overcoming the Challenge of Partial Bleaching

Optically stimulated luminescence (OSL) dating is a versatile technique that utilises the two most ubiquitous minerals on Earth (quartz or K-feldspar) for constraining the timing of sediment deposition. It has provided accurate ages in agreement with independent age control in many fluvial settings, but is often characterised by partial bleaching of individual grains. Partial bleaching can occur where sunlight exposure is limited and so only a portion of the grains in the sample was exposed to sunlight prior to burial, especially in sediment-laden, turbulent or deep water columns. OSL analysis on multiple grains can provide accurate ages for partially bleached sediments where the OSL signal intensity is dominated by a single brighter grain, but will overestimate the age where the OSL signal intensity is equally as bright (often typical of K-feldspar) or as dim (sometimes typical of quartz). In such settings, it is important to identify partial bleaching and the minimum dose population, preferably by analysing single grains, and applying the appropriate statistical age model to the dose population obtained for each sample. To determine accurate OSL ages using these age models, it is important to quantify the amount of scatter (or overdispersion) in the well-bleached part of the partially bleached dose distribution, which can vary between sediment samples depending upon the bedrock sources and transport histories of grains. Here, we discuss how the effects of partial bleaching can be easily identified and overcome to determine accurate ages. This discussion will therefore focus entirely on the burial dose determination for OSL dating, rather than the dose-rate, as only the burial doses are impacted by the effects of partial bleaching

Fingertip force control during bimanual object lifting in hemiplegic cerebral palsy

In the present study we examined unimanual and bimanual fingertip force control during grasping in children with hemiplegic cerebral palsy (CP). Participants lifted, transported and released an object with one hand or both hands together in order to examine the effect on fingertip force control for each hand separately and to determine whether any benefit exists for the affected hand when it performed the task concurrently with the less-affected hand. Seven children with hemiplegic CP performed the task while their movement and fingertip force control were measured. In the bimanual conditions, the weight of the instrumented objects was equal or unequal. The durations of the all temporal phases for the less-affected hand were prolonged during bimanual control compared to unimanual control. We observed close synchrony of both hands when the task was performed with both hands, despite large differences in duration between both hands when they performed separately. There was a marginal benefit for two of the five force related variables for the affected hand (grip force at onset of load force, and peak grip force) when it transported the object simultaneously with the less-affected hand. Collectively, these results corroborate earlier findings of reaching studies that showed slowing down of the less-affected hand when it moved together with the affected hand. A new finding that extends these studies is that bimanual tasks may have the potential to facilitate force control of the affected hand. The implications of these findings for recent rehabilitative therapies in children with CP that make use of bimanual training are discussed

Pharmacological inhibition of Akt and downstream pathways modulates the expression of COX-2 and mPGES-1 in activated microglia

<p>Abstract</p> <p>Background</p> <p>Microglia are considered a major target for modulating neuroinflammatory and neurodegenerative disease processes. Upon activation, microglia secrete inflammatory mediators that contribute to the resolution or to further enhancement of damage in the central nervous system (CNS). Therefore, it is important to study the intracellular pathways that are involved in the expression of the inflammatory mediators. Particularly, the role of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and glycogen synthase kinase-3 (GSK-3) pathways in activated microglia is unclear. Thus, in the present study we investigated the role of Akt and its downstream pathways, GSK-3 and mTOR, in lipopolysaccharide (LPS)-activated primary rat microglia by pharmacological inhibition of these pathways in regard to the expression of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1) and to the production of prostaglandin (PG) E₂and PGD₂.</p> <p>Findings</p> <p>We show that inhibition of Akt by the Akt inhibitor X enhanced the production of PGE₂and PGD₂without affecting the expression of COX-2, mPGES-1, mPGES-2 and cytosolic prostaglandin E synthase (cPGES). Moreover, inhibition of GSK-3 reduced the expression of both COX-2 and mPGES-1. In contrast, the mTOR inhibitor rapamycin enhanced both COX-2 and mPGES-1 immunoreactivity and the release of PGE₂and PGD₂. Interestingly, NVP-BEZ235, a dual PI3K/mTOR inhibitor, enhanced COX-2 and reduced mPGES-1 immunoreactivity, albeit PGE₂and PGD₂levels were enhanced in LPS-stimulated microglia. However, this compound also increased PGE₂in non-stimulated microglia.</p> <p>Conclusion</p> <p>Taken together, we demonstrate that blockade of mTOR and/or PI3K/Akt enhances prostanoid production and that PI3K/Akt, GSK-3 and mTOR differently regulate the expression of mPGES-1 and COX-2 in activated primary microglia. Therefore, these pathways are potential targets for the development of novel strategies to modulate neuroinflammation.</p