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A P0 system is used in hybrid automobiles to improve engine economy and performance. An essential element of the P0 system for effectively transmitting power to the drive train is the belt drive system (BDS). The features of electric machine (EM) and internal combustion engines (ICE) are taken into account by standard energy management systems, such as the equivalent consumption minimization strategy (ECMS). In order to maximize the effectiveness of the P0 system, this work provides a novel formulation of the ECMS, which considers the power loss map of the BDS in addition to the characteristic maps of EM and ICE. A test bench is built up to characterize the BDS, and it is verified using an open-loop Hardware in the Loop (HIL) in the WLTP driving cycle. To find the most appropriate equivalence factors for the ECMS, which would ordinarily be tuned through trial and error, a genetic algorithm (GA) is used. With regard to the standard ECMS, the proposed methodology intends to reduce fuel usage and CO2 emissions. Two belts in BDS were tested in the WLTP to achieve CO2 savings of 1.1 and 0.9 [g/km], indicating the enhancement of system performance by using the BDS power loss maps in ECMS. [ABSTRACT FROM AUTHOR]

Preexisting neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) pose a major, unresolved challenge that restricts patient enrollment in gene therapy clinical trials using recombinant AAV vectors. Structural studies suggest that despite a high degree of sequence variability, antibody recognition sites or antigenic hotspots on AAVs and other related parvoviruses might be evolutionarily conserved. To test this hypothesis, we developed a structure-guided evolution approach that does not require selective pressure exerted by NAbs. This strategy yielded highly divergent antigenic footprints that do not exist in natural AAV isolates. Specifically, synthetic variants obtained by evolving murine antigenic epitopes on an AAV serotype 1 capsid template can evade NAbs without compromising titer, transduction efficiency, or tissue tropism. One lead AAV variant generated by combining multiple evolved antigenic sites effectively evades polyclonal anti-AAV1 neutralizing sera from immunized mice and rhesus macaques. Furthermore, this variant displays robust immune evasion in nonhuman primate and human serum samples at dilution factors as high as 1:5, currently mandated by several clinical trials. Our results provide evidence that antibody recognition of AAV capsids is conserved across species. This approach can be applied to any AAV strain to evade NAbs in prospective patients for human gene therapy. [ABSTRACT FROM AUTHOR]

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Renin-expressing cells are crucial in the control of blood pressure and fluid-electrolyte homeostasis. Notch receptors convey cell-cell signals that may regulate the renin cell phenotype. Because the common downstream effector for all Notch receptors is the transcription factor RBP-J, we used a conditional knockout approach to delete RBP-J in cells of the renin lineage. The resultant RBP-J conditional knockout (cKO) mice displayed a severe reduction in the number of renin-positive juxtaglomerular apparatuses (JGA) and a reduction in the total number of renin positive cells per JGA and along the afferent arterioles. This reduction in renin protein was accompanied by a decrease in renin mRNA expression, decreased circulating renin, and low blood pressure. To investigate whether deletion of RBP-J altered the ability of mice to increase the number of renin cells normally elicited by a physiological threat, we treated RBP-J cKO mice with captopril and sodium depletion for 10 days. The resultant treated RBP-J cKO mice had a 65% reduction in renin mRNA levels (compared with treated controls) and were unable to increase circulating renin. Although these mice attempted to increase the number of renin cells, the cells were unusually thin and had few granules and barely detectable amounts of immunoreactive renin. As a consequence, the cells were incapable of fully adopting the endocrine phenotype of a renin cell. We conclude that RBP-J is required to maintain basal renin expression and the ability of smooth muscle cells along the kidney vasculature to regain the renin phenotype, a fundamental mechanism to preserve homeostasis. [ABSTRACT FROM AUTHOR]

Waders (Charadriiformes) undergo particularly long migratory flights, making them ideal vectors for long-distance dispersal. We present a study of dispersal of plant seeds by migratory waders in the Odiel saltworks in south-west Spain. This is the first field study to demonstrate excretion of viable seeds by waders. Viable seeds of Mesembryanthemum nodiflorum (Aizoaceae), Sonchus oleraceus (Asteraceae) and Arthrocnemum macrostachyum (Chenopodiaceae) were frequent in pellets and faeces of redshank Tringa totanus, spotted redshank Tringa erythropus, and black-tailed godwit Limosa limosa during spring and autumn migrations, but less frequent during winter. Another 11 seed types were recorded at low density. More intact M. nodiflorum seeds were present in redshank faeces than in their pellets, but seeds extracted from pellets were more likely to germinate. More S. oleraceus seeds were transported per redshank pellet in spring, but more redshank migrated through the area in autumn. The distributions of the plants transported are consistent with an important role for long-distance dispersal by waders. M. nodiflorum and S. oleraceus are introduced weeds in the Americas and Australasia, and dispersal by birds may contribute to their rapid spread. Although S. oleraceus is generally thought to be wind-dispersed, birds may be responsible for longer distance dispersal events. [ABSTRACT FROM AUTHOR]

Spartina species tend to exhibit a range of phenotypes, often with short and tall growth forms. Such differences have been attributed variously to environmentally induced phenotypic plasticity and genetic differentiation between populations. This work examines the basis of height variation in Spartina maritima (Curtis) Fernald at Odiel salt marshes, southwest Spain. Populations from sites with lower sediment redox potentials tended to have significantly taller shoots. Thirty-four natural populations with an 8-fold range of shoot height were transplanted to a common environment on an unvegetated, intertidal plain and shoot height was measured annually for 3 yr. There was a striking convergence in height across populations after transplantation and the change in height in each year of a population was linearly related to its initial height. Most populations grew taller after transplantation, suggesting environmental limitation in their natural habitats. Populations that were originally tall tended to become shorter. The change in shoot height was negatively related to the difference in surface sediment redox potential between their natural sites and the common transplant site. Hypoxic sediments may stimulate stem growth, resulting in improved photosynthetic gas exchange and internal aeration of roots and rhizomes. Although height variation in S. maritima appears mainly to be a result of phenotypic plasticity, a genetic component cannot be ruled out. This study emphasizes the importance of long-term studies, preferably longer than turnover time of shoot populations. The highly plastic growth form of S. maritima allows it to colonize a wide range of habitats in environmentally heterogeneous salt marshes. [ABSTRACT FROM AUTHOR]

Background and Purpose: Factors that determine the benefit of stroke units (SU) are unknown. The aim of our study was to analyze whether semi-intensive monitoring during the acute phase of stroke reduces mortality and dependency at long term. Methods: We studied patients with an ischemic stroke or intracerebral hemorrhage, consecutively admitted to our SU within 24 h of symptoms onset. Based on bed availability, patients were allocated to either a conventional care stroke unit (C-SU, n = 209) or a semi-intensive stroke unit (SI-SU, n = 321) with continuous monitoring of cardiac, respiratory, metabolic and neurological functions during the first 72 h. Both groups were treated following the same medical and nursing protocols. Criteria for exclusion were patients with stupor/coma, previously dependent (Barthel score <85) and with TIA. Using logistic regression models, we analyzed the influence of semi-intensive care on mortality and dependency at one year. Results: Baseline characteristics were similar between patients admitted to the SI-SU and the C-SU, except for a higher frequency of more severe stroke and intracerebral hemorrhage in the SI-SU. Twenty-six percent of patients in the SI-SU and 4% in the C-SU were randomized in acute clinical trials (p < 0.01), and 61% and 39% were seen by a neurologist in less than 6 h from the onset of symptoms (p < 0.01). At 1 year, mortality and combined mortality and dependency were not significantly different between the two groups. However, due to the presence of a significant interaction between the type of unit and stroke severity, the OR of mortality for SI-SU allocation was 0.19 (95% CI, 0.07–0.54) in patients with severe stroke (CSS ≤4), whereas it was 0.64 (95% CI, 0.37–1.11) in those with mild-to-moderate stroke. Conclusions: This study suggests that semi-intensive monitoring in a stroke unit reduces mortality at 1 year in patients with severe stroke, with no influence over dependency.Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This review assesses molecular aspects of the rescue of disease-causing mutations in genodermatoses by means of naturally occurring secondary genetic phenomena. Such data have important implications for the design of gene therapy approaches for inherited skin diseases. Reversal of the phenotype depends on three elements: the number of cells involved; the degree of gene reversal; and the specific timing of the reversion. If reversion occurs in somatic cells, revertant mosaicism may occur. This is the situation in which a patient's skin is generally affected by the genodermatosis, but islands of normal skin stand out. These reflect the presence of revertant cells that are sufficient to restore a normal local skin phenotype. Reversion of the original mutation may also be partial, in which case the phenotype may display no, or only limited, improvement. Nevertheless, the phenotype may ameliorate with age if the reverted cells preferentially expand in time or if the time of onset of reversion is after birth. In essence, the complexities of naturally occurring rescue processes are important to understand because the inherent mechanisms may provide clues and insight into optimal therapeutic gene manipulation, and the possibility of mimicking nature in the management of patients with diverse genodermatoses. [ABSTRACT FROM AUTHOR]

Background and Aims Atriplex (Halimione) portulacoides is a halophytic, C3 shrub. It is virtually confined to coastal salt marshes, where it often dominates the vegetation. The aim of this study was to investigate its growth responses to salinity and the extent to which these could be explained by photosynthetic physiology. Methods The responses of young plants to salinity in the range 0–700 mol m−3 NaCl were investigated in a glasshouse experiment. The performance of plants was examined using classical growth analysis, measurements of gas exchange (infrared gas analysis), determination of chlorophyll fluorescence characteristics (modulated fluorimeter) and photosynthetic pigment concentrations; total ash, sodium, potassium and nitrogen concentrations, and relative water content were also determined. Key Results Plants accumulated Na approximately in proportion to external salinity. Salt stimulated growth up to an external concentration of 200 mol m−3 NaCl and some growth was maintained at higher salinities. The main determinant of growth response to salinity was unit leaf rate. This was itself reflected in rates of CO2 assimilation, which were not affected by 200 mol m−3 but were reduced at higher salinities. Reductions in net photosynthetic rate could be accounted for largely by lower stomatal conductance and intercellular CO2 concentration. Apart from possible effects of osmotic shock at the beginning of the experiment, salinity did not have any adverse effect on photosystem II (PSII). Neither the quantum efficiency of PSII (ΦPSII) nor the chlorophyll fluorescence ratio (Fv/Fm) were reduced by salinity, and lower mid-day values recovered by dawn. Mid-day Fv/Fm was in fact depressed more at low external sodium concentration, by the end of the experiment. Conclusions The growth responses of the hygro-halophyte A. portulacoides to salinity appear largely to depend on changes in its rate of photosynthetic gas exchange. Photosynthesis appears to be limited mainly through stomatal conductance and hence intercellular CO2 concentration, rather than by effects on PSII; moderate salinity might stimulate carboxylation capacity. This is in contrast to more extreme halophytes, for which an ability to maintain leaf area can partially offset declining rates of carbon assimilation at high salinity. [ABSTRACT FROM AUTHOR]