Estimation of electronic coupling in π -stacked donor-bridge-acceptor systems: correction of the two-state model

Comparison of donor-acceptor electronic couplings calculated within two-state and three-state models suggests that the two-state treatment can provide unreliable estimates of Vda because of neglecting the multistate effects. We show that in most cases accurate values of the electronic coupling in a π stack, where donor and acceptor are separated by a bridging unit, can be obtained as Ṽ da = (E2 - E1) μ12 Rda + (2 E3 - E1 - E2) 2 μ13 μ23 Rda2, where E1, E2, and E3 are adiabatic energies of the ground, charge-transfer, and bridge states, respectively, μij is the transition dipole moments between the states i and j, and Rda is the distance between the planes of donor and acceptor. In this expression based on the generalized Mulliken-Hush approach, the first term corresponds to the coupling derived within a two-state model, whereas the second term is the superexchange correction accounting for the bridge effect. The formula is extended to bridges consisting of several subunits. The influence of the donor-acceptor energy mismatch on the excess charge distribution, adiabatic dipole and transition moments, and electronic couplings is examined. A diagnostic is developed to determine whether the two-state approach can be applied. Based on numerical results, we showed that the superexchange correction considerably improves estimates of the donor-acceptor coupling derived within a two-state approach. In most cases when the two-state scheme fails, the formula gives reliable results which are in good agreement (within 5%) with the data of the three-state generalized Mulliken-Hush model

Ultramarathon is an outstanding model for the study of adaptive responses to extreme load and stress.

ABSTRACT: Ultramarathons comprise any sporting event involving running longer than the traditional marathon length of 42.195 km (26.2 miles). Studies on ultramarathon participants can investigate the acute consequences of ultra-endurance exercise on inflammation and cardiovascular or renal consequences, as well as endocrine/energetic aspects, and examine the tissue recovery process over several days of extreme physical load. In a study published in BMC Medicine, Schütz et al. followed 44 ultramarathon runners over 4,487 km from South Italy to North Cape, Norway (the Trans Europe Foot Race 2009) and recorded daily sets of data from magnetic resonance imaging, psychometric, body composition and biological measurements. The findings will allow us to better understand the timecourse of degeneration/regeneration of some lower leg tissues such as knee joint cartilage, to differentiate running-induced from age-induced pathologies (for example, retropatelar arthritis) and finally to assess the interindividual susceptibility to injuries. Moreover, it will also provide new information about the complex interplay between cerebral adaptations/alterations and hormonal influences resulting from endurance exercise and provide data on the dose-response relationship between exercise and brain structure/function. Overall, this study represents a unique attempt to investigate the limits of the adaptive response of human bodies.Please see related article: http://www.biomedcentral.com/1741-7015/10/78.

Use of a short hPDE6b promoter for rod gene transfer in a model of severe retinal cystrophy, the Rd10 mouse

Purpose: Gene therapy of severe retinal dystrophies directly affecting photoreceptor is still a challenge in terms of clinical application. One of the main hurdles is to generate high transgene expression specifically in rods or cones. In the present study, we are investigating the possibility to drive hPDE6b expression in the Rd10 mouse retina using a specific sequence of the human PDE6b promoter. Methods: Two 5' flanking fragments of the human PDE6b gene: (-93 to +53 (146 bp) and -297 to +53 (350 bp, see Di Polo and Farber, 1995) were cloned in different plasmids in order to check their expression in vitro and in vivo. These elements drove the activity of either luciferase (pGL3 plasmids) or EGFP (AAV2/8 backbone). Then, an AAV2/8 vector carrying the PDE6b cDNA was tested with subretinal injections at P9 in the Rd10 eyes. Eye fundus, OCT, ERG recordings and histological investigations were performed to assess the efficacy of the gene transfer. Results: The short PDE6b promoter containing 146bp (-93 to +53) showed the highest activity in the Y-79 cells, as described previously (Di Polo and Farber, 1995). Subretinal administrations of AAV2/8-PDE6bpromoter-EGFP allowed a rapid expression specifically in rods and not in cones. The expression is faster than a vector containing the CMV promoter. The AAV2/8-PDE6bpromoter-PDE6b and the control vector were injected at P9 in the Rd10 mouse retina and investigated 5 weeks post-injection. Out of 14 eyes, 6 presented an increased rod sensitivity of about 300 fold, and increased a- and b-wave responses in ERG recordings. Flicker stimulations revealed that cones are also functional. OCT images and histological analyses revealed an increased ONL size in the injected area. The retina treated with the therapeutic vector presented 4-6 rows of photoreceptors with outersegments containing PDE6b. In the control eyes, only 2-4 rows of photoreceptors with almost no OS were observed . Conclusions: The 146 bp promoter sequence (-93 to + 53) is the shortest regulatory element described to date which allows to obtain efficient rod-specific expression in the context of somatic gene transfer. This first result is of great interest for AAV vector design in general allowing more space for the accommodation of transgenes of interest and good expression in rods. Moreover we showed the proof of principle of the efficacy of AAV2/8-PDE6bp-PDE6b vector in the Rd10 mouse model of severe photoreceptor degeneration without using neither AAV mutated capsids, nor self-complementary vectors.

The expressions of GABA and glutannate transporters are altered in the spared nerve injury model of neuropathic pain in the rat

Neuropathic pain is a common form of chronic pain, and is unsuccessfully alleviated by usual medications. Mounting evidence strongly point at non-neuronal glial cells in the spinal cord as key actors behind the persistence of pain. In particular, a change in the astrocytic capacity to regulate extracellular concentrations of neurotransmitters might account for the strengthened spinal nociceptive neurotransmission. Therefore, we investigated whether spinal expressions of GABA (GAT) and glutamate (EAAT) transporters were affected in the spared nerve injury (SNI) rat model of neuropathic pain. SNI was induced in male Sprague-Dawley rats by a unilateral section of tibial and common peroneal branches of the sciatic nerve, leaving the sural branch untouched. Western-blot analysis was performed to study the expression of GAT-1 and GAT-3 as well as EAAT-1 and EAAT-2, the main astrocytic GABA and glutamate transporters respectively. Seven days post-surgery, a significant increase in GAT-1, GAT-3 and EAAT-1 expressions is detected in both ipsilateral and contralateral sides of lumbar spinal cord in comparison to sham animals. No change in EAAT-2 signal could be detected. Furthermore, the astrocytic reaction parallels the glutamate and GABA transporters changes as we found an increased GFAP expression compared to the sham condition, in both spinal sides. Together, our results indicate that modifications in GABA and glutamate transport may occur along with SNI-associated painful neuropathy and identify spinal neurotransmitter reuptake machinery as a putative pharmacological target in neuropathic pain.

Estimation of the viscoelastic properties of vessel walls using a computational model and Doppler ultrasound

Human arteries affected by atherosclerosis are characterized by altered wall viscoelastic properties. The possibility of noninvasively assessing arterial viscoelasticity in vivo would significantly contribute to the early diagnosis and prevention of this disease. This paper presents a noniterative technique to estimate the viscoelastic parameters of a vascular wall Zener model. The approach requires the simultaneous measurement of flow variations and wall displacements, which can be provided by suitable ultrasound Doppler instruments. Viscoelastic parameters are estimated by fitting the theoretical constitutive equations to the experimental measurements using an ARMA parameter approach. The accuracy and sensitivity of the proposed method are tested using reference data generated by numerical simulations of arterial pulsation in which the physiological conditions and the viscoelastic parameters of the model can be suitably varied. The estimated values quantitatively agree with the reference values, showing that the only parameter affected by changing the physiological conditions is viscosity, whose relative error was about 27% even when a poor signal-to-noise ratio is simulated. Finally, the feasibility of the method is illustrated through three measurements made at different flow regimes on a cylindrical vessel phantom, yielding a parameter mean estimation error of 25%.

Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain.

Changes in expression and function of voltage-gated sodium channels (VGSC) in dorsal root ganglion (DRG) neurons may play a major role in the genesis of peripheral hyperexcitability that occurs in neuropathic pain. We present here the first description of changes induced by spared nerve injury (SNI) to Na(v)1 mRNA levels and tetrodotoxin-sensitive and -resistant (TTX-S/TTX-R) Na(+) currents in injured and adjacent non-injured small DRG neurons. VGSC transcripts were down-regulated in injured neurons except for Na(v)1.3, which increased, while they were either unchanged or increased in non-injured neurons. TTX-R current densities were reduced in injured neurons and the voltage dependence of steady-state inactivation for TTX-R was positively shifted in injured and non-injured neurons. TTX-S current densities were not affected by SNI, while the rate of recovery from inactivation was accelerated in injured neurons. Our results describe altered neuronal electrogenesis following SNI that is likely induced by a complex regulation of VGSCs.

Excuse me, but your accent is very unusual. The complexity of establishing third languages in Inglourious Basterds. Applying a model of translation analysis to dubbing

The growing multilingual trend in movie production comes with a challenge for dubbing translators since they are increasingly confronted with more than one source language. The main purpose of this master’s thesis is to provide a case study on how these third languages (see CORRIUS and ZABALBEASCOA 2011) are rendered. Another aim is to put a particular focus on their textual and narrative functions and detect possible shifts that might occur in translations. By applying a theoretical model for translation analysis (CORRIUS and ZABALBEASCOA 2011), this study describes how third languages are rendered in the German, Spanish, and Italian dubbed versions of the 2009 Tarantino movie Inglourious Basterds. A broad range of solution-types are thereby revealed and prevalent restrictions of the translation process identified. The target texts are brought in context with some sociohistorical aspects of dubbing in order to detect prevalent norms of the respective cultures andto discuss the acceptability of translations (TOURY 1995). The translatability potential of even highly complex multilingual audiovisual texts is demonstrated in this study. Moreover, proposals for further studies in multilingual audiovisual translation are outlined and the potential for future investigations in this field thereby emphasised.

PlGF-1 and VEGFR-1 pathway regulation of the external epithelial hemato-ocular barrier. A model for retinal edema.

VEGF is considered as an important factor in the pathogenesis of macular edema. VEGF induces the rupture of the blood retinal barrier and may also influence the retinal pigment epithelial (RPE) outer retinal barrier. The aim of this work was to analyze the influence of the VEGF receptor pathways in the modulation of the RPE barrier breakdown in vitro and in vivo. The ARPE19 human junctions in culture are modulated by VEGF through VEGFR-1 but not through VEGFR-2. PlGF-1, that is a pure agonist of VEGFR-1, is produced in ARPE-19 cells under hypoxic conditions and mimics VEGF effects on the external retinal barrier as measured by TER and inulin flux. In vivo, the intravitreous injection of PlGF-1 induces a rupture of the external retinal barrier together with a retinal edema. This effect is reversible within 4 days. VEGF-E, that is a pure agonist of VEGFR-2, does not induce any acute effect on the RPE barrier. These results demonstrate that PlGF-1 can reproduce alterations of the RPE barrier occurring during diabetic retinopathy.

Towards Integrated Governance of Landscape Development : The Swiss Model of Regional Nature Parks

Coherent regulation of landscape as a resource is a major challenge. How can the development interests of some actors (eg cable car operators and property developers) be reconciled with those of others (agriculture, forestry) and with conservation of biodiversity and scenic value? To help understand how the newly introduced Regional Nature Parks (RNPs) can improve the coherence of the regulation regime in Switzerland, we highlight current direct mechanisms for regulation of landscape as a resource (bans, inventories, subsidies) as well as indirect mechanisms (taking place through the regulation of the physical basis of landscapes, eg forest, land, and water planning policies). We show that RNPs are fundamentally innovative because they make it possible to manage and coordinate indirect strategies for appropriate regulation of resources at a landscape scale. In other words, RNPs enable organization of governance of landscape as a resource in a perimeter that is not necessarily restricted to administrative boundaries.

Geological transect across the Northwestern Himalaya in eastern Ladakh and Lahul (A model for the continental collision of India and Asia)

The detailed geological mapping and structural study of a complete transect across the northwestern Himalaya allow to describe the tectonic evolution of the north Indian continental margin during the Tethys ocean opening and the Himalayan Orogeny. The Late Paleozoic Tethys rifting is associated with several tectonomagmatic events. In Upper Lahul and SE Zanskar, this extensional phase is recorded by Lower Carboniferous synsedimentary transtensional faults, a Lower Permian stratigraphic unconformity, a Lower Permian granitic intrusion and middle Permian basaltic extrusions (Panjal Traps). In eastern Ladakh, a Permian listric normal fault is also related to this phase. The scarcity of synsedimentary faults and the gradual increase of the Permian syn-rift sediment thickness towards the NE suggest a flexural type margin. The collision of India and Asia is characterized by a succession of contrasting orogenic phases. South of the Suture Zone, the initiation of the SW vergent Nyimaling-Tsarap Nappe corresponds to an early phase of continental underthrusting. To the S, in Lahul, an opposite underthrusting within the Indian plate is recorded by the NE vergent Tandi Syncline. This structure is associated with the newly defined Shikar Beh Nappe, now partly eroded, which is responsible for the high grade (amphibolite facies) regional metamorphism of South Lahul. The main thrusting of the Nyimaling-Tsarap Nappe followed the formation of the Shikar Beh Nappe. The Nyimaling-Tsarap Nappe developed by ductile shear of the upper part of the subducted Indian continental margin and is responsible for the progressive regional metamorphism of SE Zanskar, reaching amphibolite facies below the frontal part of the nappe, near Sarchu. In Upper Lahul, the frontal parts of the Nyimaling-Tsarap and Shikar Beh nappes are separated by a zone of low grade metamorphic rocks (pumpellyite-actinolite facies to lower greenschist facies). At high structural level, the Nyimaling-Tsarap Nappe is characterized by imbricate structures, which grade into a large ductile shear zone with depth. The related crustal shortening is about 87 km. The root zone and the frontal part of this nappe have been subsequently affected by two zones of dextral transpression and underthrusting: the Nyimaling Shear Zone and the Sarchu Shear Zone. These shear zones are interpreted as consequences of the counterclockwise rotation of the continental underthrusting direction of India relative to Asia, which occurred some 45 and 36 Ma ago, according to plate tectonic models. Later, a phase of NE vergent `'backfolding'' developed on these two zones of dextral transpression, creating isoclinal folds in SE Zanskar and more open folds in the Nyimaling Dome and in the Indus Molasse sediments. During a late stage of the Himalayan Orogeny, the frontal part of the Nyimaling-Tsarap Nappe underwent an extension of about 15 km. This phase is represented by two types of structures, responsible for the tectonic unroofing of the amphibolite facies rocks of the Sarchu area: the Sarchu high angle Normal Fault, cutting a first set of low angle normal faults, which have been created by reactivation of older thrust planes related to the Nyimaling-Tsarap Nappe.

The use of the quality model of Parasuraman, Zeithaml and Berry in health services

This is an article about the theoretical model for assessing quality in health services proposed by Parasuraman, Zheitaml and Berry, in order to measure the degree of satisfaction of users. This model is based on the analysis of expectations and perceptions of users of health services, by means of five dimensions: tangibility, reliability, responsiveness, assurance and empathy. From the difference between what is expected by the user and the service offered, gaps or shortcomings are derived that may be the main obstacle for users to perceive the provision of such services with quality. It was observed that the use of the psychometric scale called Service Quality (SERVQUAL) in some studies about satisfaction, obtained very favorable results in the institutions in which it was employed. The analysis revealed the need to improve the existing models of evaluation, as well as the importance of measuring user satisfaction in health institutions.