Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a mutation in one copy of the neurofibromin gene (NF1+/-). Even though approximately 40-60% of children with NF1 meet the criteria for attention deficit hyperactivity disorder (ADHD), very few preclinical studies, if any, have investigated alterations in impulsivity and risk-taking behavior. Mice with deletion of a single NF1 gene (Nf1+/-) recapitulate many of the phenotypes of NF1 patients. METHODS: We compared wild-type (WT) and Nf1+/- mouse strains to investigate differences in impulsivity and hyperactivity using the delay discounting task (DDT), cliff avoidance reaction (CAR) test, and open field. We also investigated whether treatment with the clinically effective alpha-2A adrenergic receptor agonist, guanfacine (0.3 mg/kg, i.p.), would reverse deficits observed in behavioral inhibition. RESULTS: Nf1+/- mice chose a higher percentage of smaller rewards when both 10- and 20-s delays were administered compared to WT mice, suggesting Nf1+/- mice are more impulsive. When treated with guanfacine (0.3 mg/kg, i.p.), Nf1+/- mice exhibited decreased impulsive choice by waiting for the larger, delayed reward. Nf1+/- mice also exhibited deficits in behavioral inhibition compared to WT mice in the CAR test by repetitively entering the outer edge of the platform where they risk falling. Treatment with guanfacine ameliorated these deficits. In addition, Nf1+/- mice exhibited hyperactivity as increased distance was traveled compared to WT controls in the open field. This hyperactivity in Nf1+/- mice was reduced with guanfacine pre-treatment. CONCLUSIONS: Overall, our study confirms that Nf1+/- mice exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD, and can be used as a model system to identify alterations in neural circuitry associated with symptoms of ADHD in children with NF1

Magnetocaloric effect in nano- and polycrystalline manganite La0.7Ca0.3MnO3La_{0.7}Ca_{0.3}MnO_3

$La_{0.7}Ca_{0.3}MnO_3$ samples were prepared in nano- and polycrystalline forms by sol-gel and solid state reaction methods, respectively, and structurally characterized by synchrotron X-ray diffraction. The magnetic properties determined by ac susceptibility and dc magnetization measurements are discussed. The magnetocaloric effect in this nanocrystalline manganite is spread over a broader temperature interval than in the polycrystalline case. The relative cooling power of the poly- and nanocrystalline manganites is used to evaluate a possible application for magnetic cooling below room temperature.Comment: 6 pages, 5 (double) figures, 1 table, 16 references; submitted to Appl. Phys.

Optimization of an Alkylpolyglucoside-Based Dishwashing Detergent Formulation.

The aim of this work was to formulate and optimize the washing performance of an alkylpolyglucoside-based dishwashing detergent. The liquid detergent was formulated with five ingredients of commercial origin: anionic (linear sodium alkylbenzenesulfonate and sodium laurylethersulfate), nonionic (C12–C14 alkylpolyglucoside) and zwitterionic (a fatty acid amide derivative with a betaine structure) surfactants, and NaCl for viscosity control. In addition to the plate test, other properties were investigated including ‘‘cloud point’’, viscosity, and emulsion stability. Statistical analysis software was used to generate a central composite experimental design. Then, a second order design and analysis of experiments approach, known as the Response Surface Methodology, was set up to investigate the effects of the five components of the formulation on the studied properties in the region covering plausible component ranges. The method proved to be efficient for locating the domains of concentrations where the desired properties were met

Data protection risk modeling into business process analysis

We present a novel way to link business process model with data protection risk management. We use established body of knowledge regarding risk manager concepts and business process towards data protections. We try to contribute to the problems that today organizations should find a suitable data protection model that could be used in as a risk framework. The purpose of this document is to define a model to describe data protection in the context of risk. Our approach including the identification of the main concepts of data protection according to the scope of the with EU directive data protection regulation. We outline data protection model as a continuous way of protection valued organization information regarding personal identifiable information. Data protection encompass the preservation of personal data information from unauthorized access, use, modification, recording or destruction. Since this kind of service is offered in a continuous way, it is important to stablish a way to measure the effectiveness of awareness of data subject discloses regrading personal identifiable information.info:eu-repo/semantics/publishedVersio

Micro-CT screening of old shell collections helps to understand the distribution of viviparity in the highly diversifed clausiliid clade of land snails

Current zoological research may benefit in many ways from the study of old collections of shells. These collections may provide materials for the verification of broad zoogeographical and ecological hypotheses on the reproduction of molluscs, as they include records from many areas where sampling is currently impossible or very difficult due to political circumstances. In the present paper we present data on viviparous and embryo-retention reproductive modes in clausiliid land snails (subfamily Phaedusinae) acquired from specimens collected since the nineteenth century in the Pontic, Hyrcanian, and East and Southeast Asian regions. X-ray imaging (micro-CT) enabled relatively quick screening of more than 1,000 individuals classified within 141 taxa, among which we discovered 205 shells containing embryos or eggs. Gravid individuals were found to belong to 55 species, representing, for some of these species, the first indication of brooding reproductive strategy

Krull Dimension of Tame Generalized Multicoil Algebras

We determine the Krull dimension of the module category of finite dimensional tame generalized multicoil algebras over an algebraically closed field, which are domestic

Mutation in triangulated categories and rigid Cohen-Macaulay modules

We introduce the notion of mutation of $n$-cluster tilting subcategories in a triangulated category with Auslander-Reiten-Serre duality. Using this idea, we are able to obtain the complete classifications of rigid Cohen-Macaulay modules over certain Veronese subrings.Comment: 52 pages. To appear in Invent. Mat

Cycle-finite module categories

We describe the structure of module categories of finite dimensional algebras over an algebraically closed field for which the cycles of nonzero nonisomorphisms between indecomposable finite dimensional modules are finite (do not belong to the infinite Jacobson radical of the module category). Moreover, geometric and homological properties of these module categories are exhibited

Multi-Scalar-Singlet Extension of the Standard Model - the Case for Dark Matter and an Invisible Higgs Boson

We consider a simple extension of the Standard Model by the addition of N real scalar gauge singlets \vp that are candidates for Dark Matter. By collecting theoretical and experimental constraints we determine the space of allowed parameters of the model. The possibility of ameliorating the little hierarchy problem within the multi-singlet model is discussed. The Spergel-Steinhardt solution of the Dark Matter density cusp problem is revisited. It is shown that fitting the recent CRESST-II data for Dark Matter nucleus scattering implies that the standard Higgs boson decays predominantly into pairs of Dark Matter scalars. It that case discovery of the Higgs boson at LHC and Tevatron is impossible. The most likely mass of the dark scalars is in the range 15 GeV \lsim \mvp \lsim 50 GeV with BR(h \to \vp\vp) up to 96%.Comment: 18 pages, 15 figure

Precision of the PET activity range during irradiation with ¹⁰C, ¹¹C, and ¹²C beams

Objective. Beams of stable ions have been a well-established tool for radiotherapy for many decades. In the case of ion beam therapy with stable 12C ions, the positron emitters 10,11C are produced via projectile and target fragmentation, and their decays enable visualization of the beam via positron emission tomography (PET). However, the PET activity peak matches the Bragg peak only roughly and PET counting statistics is low. These issues can be mitigated by using a short-lived positron emitter as a therapeutic beam. Approach. An experiment studying the precision of the measurement of ranges of positron-emitting carbon isotopes by means of PET has been performed at the FRS fragment-separator facility of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany. The PET scanner used in the experiment is a dual-panel version of a Siemens Biograph mCT PET scanner. Main results. High-quality in-beam PET images and activity distributions have been measured from the in-flight produced positron emitting isotopes 11C and 10C implanted into homogeneous PMMA phantoms. Taking advantage of the high statistics obtained in this experiment, we investigated the time evolution of the uncertainty of the range determined by means of PET during the course of irradiation, and show that the uncertainty improves with the inverse square root of the number of PET counts. The uncertainty is thus fully determined by the PET counting statistics. During the delivery of 1.6 × 107 ions in 4 spills for a total duration of 19.2 s, the PET activity range uncertainty for 10C, 11C and 12C is 0.04 mm, 0.7 mm and 1.3 mm, respectively. The gain in precision related to the PET counting statistics is thus much larger when going from 11C to 10C than when going from 12C to 11C. The much better precision for 10C is due to its much shorter half-life, which, contrary to the case of 11C, also enables to include the in-spill data in the image formation. Significance. Our results can be used to estimate the contribution from PET counting statistics to the precision of range determination in a particular carbon therapy situation, taking into account the irradiation scenario, the required dose and the PET scanner characteristics.</p