2,151 research outputs found

    Functional Organization of Visual Cortex in the Owl Monkey

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    In this study, we compared the organization of orientation preference in visual areas V1, V2, and V3. Within these visual areas, we also quantified the relationship between orientation preference and cytochrome oxidase (CO) staining patterns. V1 maps of orientation preference contained both pinwheels and linear zones. The location of CO blobs did not relate in a systematic way to maps of orientation; although, as in other primates, there were approximately twice as many pinwheels as CO blobs. V2 contained bands of high and low orientation selectivity. The bands of high orientation selectivity were organized into pinwheels and linear zones, but iso-orientation domains were twice as large as those in V1. Quantitative comparisons between bands containing high or low orientation selectivity and CO dark and light bands suggested that at least four functional compartments exist in V2, CO dense bands with either high or low orientation selectivity, and CO light bands with either high or low selectivity. We also demonstrated that two functional compartments exist in V3, with zones of high orientation selectivity corresponding to CO dense areas and zones of low orientation selectivity corresponding to CO pale areas. Together with previous findings, these results suggest that the modular organization of V1 is similar across primates and indeed across most mammals. V2 organization in owl monkeys also appears similar to that of other simians but different from that of prosimians and other mammals. Finally, V3 of owl monkeys shows a compartmental organization for orientation selectivity that remains to be demonstrated in other primates

    Mitoparans: mitochondriotoxic cell penetrating peptides and novel inducers of apoptosis.

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    Acknowledgments The authors would like to thank Keith Holding at the University of Wolverhampton for his outstanding technical support. This work was supported in part by Samantha Dickson Brain Tumour Trust.Introduction: The amphipathic helical peptide mastoparan (MP; H-INLKALAALAKKIL-NH2) inserts into biological membranes to modulate the activity of heterotrimeric G proteins and other targets. Moreover, whilst cell free models of apoptosis demonstrate MP to facilitate mitochondrial permeability transition and release of apoptogenic cytochrome c, MP-induced death of intact cells has been attributed to its non-specific membrane destabilising properties (necrotic mechanisms). However, MP and related peptides are known to activate other signalling systems, including p42/p44 MAP kinases and could therefore, also modulate cell fate and specific apoptotic events. The ability of MP to facilitate mitochondrial permeability in cell free systems has lead to proposals that MP could be of utility in tumour therapeutics provided that it conferred features of cellular penetration and mitochondrial localization. We have recently reported that our highly potent amphipathic MP analogue mitoparan (mitP; [Lys5,8Aib10]MP; Aib = -aminoisobutyric acid) specifically promotes apoptosis of human cancer cells, as was confirmed by in situ TUNEL staining and activation of caspase-3. Moreover, we have also demonstrated that mitP penetrates plasma membranes and redistributes to co-localize with mitochondria. Complementary studies, using isolated mitochondria, further demonstrated that mitP, through co-operation with a protein of the permeability transition pore complex voltage-dependent anion channel (VDAC), induced swelling and permeabilization of mitochondria, leading to the release of the apoptogenic factor cytochrome c. An expanding field of peptide and cell penetrating peptide (CPP) research has focussed on the selective targeting of tumours by engineering constructs that incorporate cell-specific or tissue–specific address motifs. Peptidyl address motifs could enhance the selectivity of drug delivery whilst the improved cellular uptake offered by CPP enhances bioavailability. Thus and as a potential therapeutic strategy, we extended our findings to design target-specific mitP analogues. The integrin-specific address motif RGD and a Fas ligand mimetic WEWT were incorporated by N-terminal acylation of mitP to produce novel tandem-linked chimeric peptides

    The Swiss Tropical and Public Health Institute: past, present and future

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    Compared internationally, the history of the Swiss Tropical and Public Health Institute (Swiss TPH) is unusual. Founded in 1944, at a time of utmost isolation, it was a response to specific needs of the government of Switzerland during the Second World War. In 1943, the Swiss Federal Council approached universities in Switzerland and asked them to submit project proposal that had the potential to mitigate possible post-war unemployment and threatening economic isolation. Members of the University of Basel proposed to establish a Swiss Tropical Institute (today: Swiss TPH). With its harbour at the River Rhine, Basel was an important international transport hub. The city was and still is the headquarters of important pharmaceutical companies, such as Novartis Pharma AG and F. Hoffmann-La Roche AG, which were looking for new markets overseas. Last but not least, scientific expeditions to Africa were rather common in the 19(th) and the beginning of the 20(th) century for members of Basel's bourgeoisie. Initially, Swiss TPH focused primarily on basic research into diseases of poverty, but over the years it has developed into an important player in public, international and global health. This article sees the development of the institute as a reflection of the visions of its directors from the founder Professor Rudolf Geigy to Professor Jurg Utzinger, who is the current Swiss TPH director. It includes interviews with the four latest of them, discussing their experiences and attempts to adapt the institute to an ever changing global environment. From these lessons learnt we hope to gain insights that could be relevant for today's leaders of scientific institutes; foster public-private partnerships and contribute to solve some of the most pressing global health challenges

    The dissimilar chemical composition of the planet-hosting stars of the XO-2 binary system

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    Using high-quality spectra of the twin stars in the XO-2 binary system, we have detected significant differences in the chemical composition of their photospheres. The differences correlate strongly with the elements' dust condensation temperature. In XO-2N, volatiles are enhanced by about 0.015 dex and refractories are overabundant by up to 0.090 dex. On average, our error bar in relative abundance is 0.012 dex. We present an early metal-depletion scenario in which the formation of the gas giant planets known to exist around these stars is responsible for a 0.015 dex offset in the abundances of all elements while 20 M_Earth of non-detected rocky objects that formed around XO-2S explain the additional refractory-element difference. An alternative explanation involves the late accretion of at least 20 M_Earth of planet-like material by XO-2N, allegedly as a result of the migration of the hot Jupiter detected around that star. Dust cleansing by a nearby hot star as well as age or Galactic birthplace effects can be ruled out as valid explanations for this phenomenon.Comment: ApJ, in press. Complete linelist (Table 3) available in the "Other formats -> Source" downloa

    The solar, exoplanet and cosmological lithium problems

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    We review three Li problems. First, the Li problem in the Sun, for which some previous studies have argued that it may be Li-poor compared to other Suns. Second, we discuss the Li problem in planet hosting stars, which are claimed to be Li-poor when compared to field stars. Third, we discuss the cosmological Li problem, i.e. the discrepancy between the Li abundance in metal-poor stars (Spite plateau stars) and the predictions from standard Big Bang Nucleosynthesis. In all three cases we find that the "problems" are naturally explained by non-standard mixing in stars.Comment: Astrophysics and Space Science, in press. New version has one reference correcte

    Solvable model of a strongly-driven micromaser

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    We study the dynamics of a micromaser where the pumping atoms are strongly driven by a resonant classical field during their transit through the cavity mode. We derive a master equation for this strongly-driven micromaser, involving the contributions of the unitary atom-field interactions and the dissipative effects of a thermal bath. We find analytical solutions for the temporal evolution and the steady-state of this system by means of phase-space techniques, providing an unusual solvable model of an open quantum system, including pumping and decoherence. We derive closed expressions for all relevant expectation values, describing the statistics of the cavity field and the detected atomic levels. The transient regime shows the build-up of mixtures of mesoscopic fields evolving towards a superpoissonian steady-state field that, nevertheless, yields atomic correlations that exhibit stronger nonclassical features than the conventional micromaser.Comment: 9 pages, 16 figures. Submitted for publicatio

    Analysis of Stress Concentration in Functionally Graded Plates with Linearly Increasing Young’s Modulus

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    In this article, the strain and stress analyses of functionally graded plates with circular holes that are subject to a uniaxial far-field traction load are analytically considered. The Young’s modulus is assumed to vary linearly along the radial direction around the hole. The adoption of such a type of inhomogeneity variation can be justified as follows. Firstly, and among all the possible variations of stiffness, the linear one is indeed the simplest inhomogeneity distribution. Surprisingly however, according to our knowledge extent, the associated elastic fields were not yet addressed in the literature. Secondly, a linearly varying stiffness could reasonably imply a remarkable advantage from a technological point of view. In fact, unlike nonlinearly varying stiffness plates, manufacturing routes are only required to handle constant variations throughout the radial domain. After recalling the basic equations for plane stress elasticity, the displacement, strain, and stress fields around the hole were numerically tackled and discussed for different stiffness ratios. A comparison was also carried out with other Young’s modulus distributions that have been commonly employed in the literature

    A dynamic programming setting for functionally graded thick-walled cylinders

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    Material property variation in non-homogeneous internally pressurized thick-walled cylinders is investigated within the context of dynamic programming theory. The material is assumed to be linear, elastic, isotropic, and functionally graded in the radial direction. Based on the plane stress hypothesis, a state space formulation is given and the optimal control problem is stated and solved by means of Pontryagin's Principle for different objective functionals. Optimal Young's modulus distribution is found to be piecewise linear along the radial domain. A brief digression on the possible existence of switching points is addressed. Finally, a numerical example is performed within a special class of derived optimal solutions, showing promising results in terms of equivalent stress reduction with respect to the most used variations in literature
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