Spin vortices and vacancies: interactions and pinning on a square lattice

The study gives a decisive answer to the recently risen question about the type and origin of interaction between spin vortices and spin vacancies in 2D spin models. The approach is based on the low-temperature approximation of the 2D XY model known as the Villain model and does not involve any additional approximations, thus preserving the lattice structure. The exact form of the Hamiltonian describing a system of topological charges and a vacant site supports the attractive type of interaction between the vacancy and the charges. The quantitative difference between the characteristics of the vortex behavior in the 2D XY and Villain models due to the different energy of the vortex "cores" in the two models is pointed out. This leads to a conclusion that the interaction between a vortex and a spin vacancy and between a vortex and the antivortex differs quantitatively for small separations in the two mentioned models.Comment: 13 pages, 5 figure

Atom-specific identification of adsorbed chiral molecules by photoemission

The study of chiral adsorbed molecules is important for an analysis of enantioselectivity in heterogeneous catalysis. Here we show that such molecules can be identified through circular dichroism in core-level photoemission arising from the chiral carbon atoms in stereoisomers of 2,3-butanediol molecules adsorbed on Si(100), using circularly polarized x rays. The asymmetry in the carbon 1s intensity excited by right and left circularly polarized light is readily observed, and changes sign with the helicity of the radiation or handedness of the enantiomers; it is absent in the achiral form of the molecule. This observation demonstrates the possibility of determining molecular chirality in the adsorbed phase

Standardized high-throughput evaluation of cell-based compound screens

<p>Abstract</p> <p>Background</p> <p>High-throughput screening of pharmaceutical compound activity in tissue culture experiments requires time-consuming repeated analysis of the large amounts of data generated. Automation of the evaluation procedure and assessment of measurement accuracy can save time and improve the comparability of results.</p> <p>Results</p> <p>We present a tool for simultaneous evaluation of an arbitrary number of compound screens including a standardized statistical validation. It is provided as a novel R package with a Tcl/Tk-based GUI for convenient use in the lab and runs on usual platforms like Linux, Windows and Mac OS. In a compound screen of lung cancer cells, the tool was successfully and efficiently applied for data analysis.</p> <p>Conclusion</p> <p>The package provides an efficient and intuitive platform for automatic evaluation of compound screens, improving the performance and standardization of data analysis.</p

Planarians in pharmacology: parthenolide is a specific behavioral antagonist of cocaine in the planarian Girardia tigrina

Planarians are traditional animal models in developmental and regeneration biology. Recently, these organisms are arising as vertebrate-relevant animal models in neuropharmacology. Using an adaptation of published behavioral protocols, we have described the alleviation of cocaine-induced planarian seizure-like movements (pSLM) by a naturally-occurring sesquiterpene lactone, parthenolide. Interestingly, parthenolide does not prevent the expression of pSLM induced by amphetamines; in vertebrates, amphetamines interact with the same protein target as cocaine. Parthenolide is also unable to prevent pSLM elicited by the cholinergic compounds nicotine and cytisine or by the glutamatergic agents L- or D- glutamic acid or NMDA. Thus, we conclude that parthenolide is a specific anti-cocaine agent in this experimental organism

Mutations in Transmembrane Domains 1, 4 and 9 of the Plasmodium falciparum Chloroquine Resistance Transporter Alter Susceptibility to Chloroquine, Quinine and Quinidine

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) can result in verapamil-reversible CQ resistance and altered susceptibility to other antimalarials. PfCRT contains 10 membrane-spanning domains and is found in the digestive vacuole (DV) membrane of intraerythrocytic parasites. The mechanism by which PfCRT mediates CQ resistance is unclear although it is associated with decreased accumulation of drug within the DV. On the permissive background of the P. falciparum 106/1(K76) parasite line, we used single-step drug selection to generate isogenic clones containing unique pfcrt point mutations that resulted in amino acid changes in PfCRT transmembrane domains 1 (C72R, K76N, K76I and K76T) and 9 (Q352K, Q352R). The resulting changes of charge and hydropathy affected quantitative CQ susceptibility and accumulation as well as the stereospecific responses to quinine and quinidine. These results, together with a previously described S163R mutation in transmembrane domain 4, indicate that transmembrane segments 1, 4 and 9 of PfCRT provide important structural components of a substrate recognition and translocation domain. Charge-affecting mutations within these segments may affect the ability of PfCRT to bind different quinoline drugs and determine their net accumulation in the DV. © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Lt

The Joint Action of Sesquiterpene Lactones from Leaves as an Explanation for the Activity of Cynara cardunculus

The work described herein is a continuation of a previous study centered on the bioprospect of cardoon (Cynara cardunculus) leaf extracts through the isolation of secondary metabolites with phytotoxic activity. Chromatographic fractionations of the ethyl acetate extract and spectroscopic analysis showed that the majority of the components were sesquiterpene lactones. Of these compounds, aguerin B, grosheimin, and cynaropicrin were very active on etiolated wheat coleoptile, standard target species, and weed growth. The joint action of binary mixtures of these three active sesquiterpene lactones and one nonactive compound (11,13-dihydroxy-8-desoxygrosheimin) was studied. The activities of fixed-ratio mixtures were assessed on wheat coleoptile. The results can be interpreted with respect to a reference model by considering dose−response analyses and isobolograms with linear regression analyses. A total of 17 binary mixtures at different levels of inhibition (ED25, ED50, and ED75) were studied, and predominantly they responded additively (25). Deviations from additivity included seven synergistic responses and two antagonistic responses. The joint action of major sesquiterpene lactones isolated from C. cardunculus can explain the activities observed in extracts and fractions. The results reported here reiterate the utility of the wheat coleoptile bioassay as a quick tool to detect potential synergistic effects in binary mixtures

Case Report Diffusion Tensor Imaging Tractography in Pure Neuritic Leprosy: First Experience Report and Review of the Literature

Five years after both right ulnar and median nerve decompression for paraesthesias and palsy, a patient, coming from Nigeria but living in Italy, came to our unit claiming to have persistent pain and combined median and ulnar palsy. Under suspicion of leprosy, skin and left sural nerve biopsy were performed. Skin tests were negative, but Schwann cells resulted as positive for acid-fast bacilli (AFB), leading to the diagnosis of Pure Neuritic Leprosy (PNL). The patient was given PB multidrug therapy and recovered from pain in two months. After nine months both High Resolution Ultrasonography (HRUS) and Magnetic Resonance Imaging (MRI) were performed, revealing thickening of the nerves. Since demyelination is common in PNL, the Authors started to use Diffusion Tensor Imaging Tractography (DTIT) to get better morphological and functional data about myelination than does the traditional imaging. DTIT proved successful in showing myelin discontinuity, reorganization, and myelination, and the Authors suggest that it can give more information about the evolution of the disease, as well as further indications for surgery (nerve decompression, nerve transfers, and babysitting for distal effector protection), and should be added to traditional imaging tools in leprosy

Perifosine as a Potential Novel Anti-Cancer Agent Inhibits EGFR/MET-AKT Axis in Malignant Pleural Mesothelioma

PI3K/AKT signalling pathway is aberrantly active and plays a critical role for cell cycle progression of human malignant pleural mesothelioma (MMe) cells. AKT is one of the important cellular targets of perifosine, a novel bio-available alkylphospholipid that has displayed significant anti-proliferative activity in vitro and in vivo in several human tumour model systems and is currently being tested in clinical trials.We tested Perifosine activity on human mesothelial cells and different mesothelioma cell lines, in order to provide evidence of its efficacy as single agent and combined therapy.We demonstrate here that perifosine, currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials, caused a dose-dependent reduction of AKT activation, at concentrations causing MMe cell growth arrest. In this study we firstly describe that MMe cells express aside from AKT1 also AKT3 and that either the myristoylated, constitutively active, forms of the two proteins, abrogated perifosine-mediated cell growth inhibition. Moreover, we describe here a novel mechanism of perifosine that interferes, upstream of AKT, affecting EGFR and MET phosphorylation. Finally, we demonstrate a significant increase in cell toxicity when MMe cells were treated with perifosine in combination with cisplatin.This study provides a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe

QUEST: A New Frontiers Uranus Orbiter Mission Concept Study

The ice giant planets, Uranus and Neptune, are fundamentally different from the gas giant and terrestrial planets. Though ice giants represent the most common size of exoplanet and possess characteristics that challenge our understanding of the way our solar system formed and evolved, they remain the only class of planetary object without a dedicated spacecraft mission. The inclusion of a Uranus orbiter as the third highest priority Flagship mission in the NASA Planetary Science Decadal Survey “Vision and Voyages for Planetary Science in the Decade 2013–2022” indicates a high level of support for exploration of the ice giants by the planetary science community. However, given the substantial costs associated with a flagship mission, it is critical to explore lower cost options if we intend to visit Uranus within an ideal launch window of 2029 - 2034 when a Jupiter gravity assist becomes available. In this paper, we describe the Quest to Uranus to Explore Solar System Theories (QUEST), a New Frontiers class Uranus orbiter mission concept study performed at the 30th Annual NASA/JPL Planetary Science Summer Seminar. The proposed QUEST platform is a spin-stabilized spacecraft designed to undergo highly elliptical, polar orbits around Uranus during a notional one-year primary science mission. The proposed major science goals of the mission are (1) to use Uranus as a natural laboratory to better understand the dynamos that drive magnetospheres in the solar system and beyond and (2) to identify the energy transport mechanisms in Uranus' magnetic, atmospheric, and interior environments in contrast with the other giant planets. With substantial mass, power, and cost margins, this mission concept demonstrates a compelling, feasible option for a New Frontiers Uranus orbiter mission