Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

Silicon-based spin and charge quantum computation

Silicon-based quantum-computer architectures have attracted attention because of their promise for scalability and their potential for synergetically utilizing the available resources associated with the existing Si technology infrastructure. Electronic and nuclear spins of shallow donors (e.g. phosphorus) in Si are ideal candidates for qubits in such proposals due to the relatively long spin coherence times. For these spin qubits, donor electron charge manipulation by external gates is a key ingredient for control and read-out of single-qubit operations, while shallow donor exchange gates are frequently invoked to perform two-qubit operations. More recently, charge qubits based on tunnel coupling in P$_2^+$ substitutional molecular ions in Si have also been proposed. We discuss the feasibility of the building blocks involved in shallow donor quantum computation in silicon, taking into account the peculiarities of silicon electronic structure, in particular the six degenerate states at the conduction band edge. We show that quantum interference among these states does not significantly affect operations involving a single donor, but leads to fast oscillations in electron exchange coupling and on tunnel-coupling strength when the donor pair relative position is changed on a lattice-parameter scale. These studies illustrate the considerable potential as well as the tremendous challenges posed by donor spin and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy of Science

Computational modelling of emboli travel trajectories in cerebral arteries: Influence of microembolic particle size and density

This article has been made available through the Brunel Open Access Publishing Fund.Ischaemic stroke is responsible for up to 80 % of stroke cases. Prevention of the reoccurrence of ischaemic attack or stroke for patients who survived the first symptoms is the major treatment target. Accurate diagnosis of the emboli source for a specific infarction lesion is very important for a better treatment for the patient. However, due to the complex blood flow patterns in the cerebral arterial network, little is known so far of the embolic particle flow trajectory and its behaviour in such a complex flow field. The present study aims to study the trajectories of embolic particles released from carotid arteries and basilar artery in a cerebral arterial network and the influence of particle size, mass and release location to the particle distributions, by computational modelling. The cerebral arterial network model, which includes major arteries in the circle of Willis and several generations of branches from them, was generated from MRI images. Particles with diameters of 200, 500 and 800 μ m and densities of 800, 1,030 and 1,300 kg/m 3 were released in the vessel's central and near-wall regions. A fully coupled scheme of particle and blood flow in a computational fluid dynamics software ANASYS CFX 13 was used in the simulations. The results show that heavy particles (density large than blood or a diameter larger than 500 μ m) normally have small travel speeds in arteries; larger or lighter embolic particles are more likely to travel to large branches in cerebral arteries. In certain cases, all large particles go to the middle cerebral arteries; large particles with higher travel speeds in large arteries are likely to travel at more complex and tortuous trajectories; emboli raised from the basilar artery will only exit the model from branches of basilar artery and posterior cerebral arteries. A modified Circle of Willis configuration can have significant influence on particle distributions. The local branch patterns of internal carotid artery to middle cerebral artery and anterior communicating artery can have large impact on such distributions. © 2014 The Author(s)

Health care seeking among detained undocumented migrants: a cross-sectional study

BACKGROUND: As in many European countries, access to care is decreased for undocumented migrants in the Netherlands due to legislation. Studies on the health of undocumented migrants in Europe are scarce and focus on care-seeking migrants. Not much is known on those who do not seek care. METHODS: This cross-sectional study includes both respondents who did and did not seek care, namely undocumented migrants who have been incarcerated in a detention centre while awaiting expulsion to their country of origin. A consecutive sample of all new arrivals was studied. Data were collected through structured interviews and reviews of medical records. RESULTS: Among the 224 male migrants who arrived at the detention centre between May and July 2008, 173 persons were interviewed. 122 respondents met inclusion criteria. Only half of the undocumented migrants in this study knew how to get access to medical care in the Netherlands if in need. Forty-six percent of respondents reported to have sought medical help during their stay in the Netherlands while having no health insurance (n = 57). Care was sought most frequently for injuries and dental problems. About 25% of these care seekers reported to have been denied care by a health care provider. Asian migrants were significantly less likely to seek care when compared to other ethnic groups, independent from age, chronic health problems and length of stay in the Netherlands. CONCLUSION: The study underlines the need for a better education of undocumented patients and providers concerning the opportunities for health care in the Netherlands. Moreover, there is a need to further clarify the reasons for the denial of care to undocumented patients, as well as the barriers to health care as perceived by undocumented migrants

Chaos around Holographic Regge Trajectories

Using methods of Hamiltonian dynamical systems, we show analytically that a dynamical system connected to the classical spinning string solution holographically dual to the principal Regge trajectory is non-integrable. The Regge trajectories themselves form an integrable island in the total phase space of the dynamical system. Our argument applies to any gravity background dual to confining field theories and we verify it explicitly in various supergravity backgrounds: Klebanov-Strassler, Maldacena-Nunez, Witten QCD and the AdS soliton. Having established non-integrability for this general class of supergravity backgrounds, we show explicitly by direct computation of the Poincare sections and the largest Lyapunov exponent, that such strings have chaotic motion.Comment: 28 pages, 5 figures. V3: Minor changes complying to referee's suggestions. Typos correcte

Extraction of bodily features for gait recognition and gait attractiveness evaluation

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11042-012-1319-2. Copyright @ 2012 Springer.Although there has been much previous research on which bodily features are most important in gait analysis, the questions of which features should be extracted from gait, and why these features in particular should be extracted, have not been convincingly answered. The primary goal of the study reported here was to take an analytical approach to answering these questions, in the context of identifying the features that are most important for gait recognition and gait attractiveness evaluation. Using precise 3D gait motion data obtained from motion capture, we analyzed the relative motions from different body segments to a root marker (located on the lower back) of 30 males by the fixed root method, and compared them with the original motions without fixing root. Some particular features were obtained by principal component analysis (PCA). The left lower arm, lower legs and hips were identified as important features for gait recognition. For gait attractiveness evaluation, the lower legs were recognized as important features.Dorothy Hodgkin Postgraduate Award and HEFCE

A new aircraft architecture based on the ACHEON Coanda effect nozzle: flight model and energy evaluation

Purpose Aeronautic transport has an effective necessity of reducing fuel consumption and emissions to deliver efficiency and competitiveness driven by today commercial and legislative requirements. Actual aircraft configurations scenario allows envisaging the signs of a diffused technological maturity and they seem very near their limits. This scenario clearly shows the necessity of radical innovations with particular reference to propulsion systems and to aircraft architecture consequently. Methods This paper presents analyses and discusses a promising propulsive architecture based on an innovative nozzle, which allows realizing the selective adhesion of two impinging streams to two facing jets to two facing Coanda surfaces. This propulsion system is known with the acronym ACHEON (Aerial Coanda High Efficiency Orienting Nozzle). This paper investigates how the application of an all-electric ACHEONs propulsion system to a very traditional commuter aircraft can improve its relevant performances. This paper considers the constraints imposed by current state-of-the-art electric motors, drives, storage and conversion systems in terms of both power/energy density and performance and considers two different aircraft configurations: one using battery only and one adopting a more sophisticated hybrid cogeneration. The necessity of producing a very solid analysis has forced to limit the deflection of the jet in a very conservative range (±15°) with respect to the horizontal. This range can be surely produced also by not optimal configurations and allow minimizing the use of DBD. From the study of general flight dynamics equations of the aircraft in two-dimensional form it has been possible to determine with a high level of accuracy the advantages that ACHEON brings in terms of reduced stall speed and of reduced take-off and landing distances. Additionally, it includes an effective energy analysis focusing on the efficiency and environmental advantages of the electric ACHEON based propulsion by assuming the today industrial grade high capacity batteries with a power density of 207 Wh/kg. Results It has been clearly demonstrated that a short flight could be possible adopting battery energy storage, and longer duration could be possible by adopting a more sophisticated cogeneration system, which is based on cogeneration from a well-known turboprop, which is mostly used in helicopter propulsion. This electric generation system can be empowered by recovering the heat and using it to increase the temperature of the jet. It is possible to transfer this considerable amount of heat to the jet by convection and direct fluid mixing. In this way, it is possible to increase the energy of the jets of an amount that allows more than recover the pressure losses in the straitening section. In this case, it is then possible to demonstrate an adequate autonomy of flight and operative range of the aircraft. The proposed architecture, which is within the limits of the most conservative results obtained, demonstrates significant additional benefits for aircraft manoeuvrability. In conclusion, this paper has presented the implantation of ACHEON on well-known traditional aircraft, verifying the suitability and effectiveness of the proposed system both in terms of endurance with a cogeneration architecture and in terms of manoeuvrability. It has demonstrated the potential of the system in terms of both takeoff and landing space requirements. Conclusions This innovation opens interesting perspectives for the future implementation of this new vector and thrust propulsion system, especially in the area of greening the aeronautic sector. It has also demonstrated that ACHEON has the potential of renovating completely a classic old aircraft configuration such as the one of Cessna 402

Coverage, Continuity and Visual Cortical Architecture

The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin