fMRI Investigation of Cortical and Subcortical Networks in the Learning of Abstract and Effector-Specific Representations of Motor Sequences

A visuomotor sequence can be learned as a series of visuo-spatial cues or as a sequence of effector movements. Earlier imaging studies have revealed that a network of brain areas is activated in the course of motor sequence learning. However these studies do not address the question of the type of representation being established at various stages of visuomotor sequence learning. In an earlier behavioral study, we demonstrated that acquisition of visuo-spatial sequence representation enables rapid learning in the early stage and progressive establishment of somato-motor representation helps speedier execution by the late stage. We conducted functional magnetic resonance imaging (fMRI) experiments wherein subjects learned and practiced the same sequence alternately in normal and rotated settings. In one rotated setting (visual), subjects learned a new motor sequence in response to an identical sequence of visual cues as in normal. In another rotated setting (motor), the display sequence was altered as compared to normal, but the same sequence of effector movements were used to perform the sequence. Comparison of different rotated settings revealed analogous transitions both in the cortical and subcortical sites during visuomotor sequence learning  a transition of activity from parietal to parietal-premotor and then to premotor cortex and a concomitant shift was observed from anterior putamen to a combined activity in both anterior and posterior putamen and finally to posterior putamen. These results suggest a putative role for engagement of different cortical and subcortical networks at various stages of learning in supporting distinct sequence representations

"Evidence" Under a Magnifying Glass: Thoughts on Safety Argument Epistemology

Common definitions of "safety case" emphasize that evidence is the basis of a safety argument, yet few widely referenced works explicitly define "evidence". Their examples suggest that similar things can be regarded as evidence. But the category evidence seems to contain (1) processes for finding things out, (2) information resulting from such processes, and (3) relevant documents. Moreover, any item of evidence could be replaced by further argument. Normative models of informal argumentation do not offer clear guidance on when a safety argument should cite evidence rather than appeal to a more detailed argument. Disciplines such as the law address the problem with a practical, domain-specific epistemology. In this paper, we explore these problems associated with evidence citations in safety arguments, identify goals for a theory of safety argument evidence and a practical safety argument epistemology, propose a model of safety evidence citation that advances the identified goals, and present a related extension to the Goal Structuring Notation (GSN)

Clinical evaluation of an anatomy-based patient specific quality assurance system

The Delta4DVH Anatomy 3D quality assurance (QA) system (ScandiDos), which converts the measured detector dose into the dose distribution in the patient geometry was evaluated. It allows a direct comparison of the calculated 3D dose with the measured back-projected dose. In total, 16 static and 16 volumetric-modulated arc therapy (VMAT) fields were planned using four different energies. Isocenter dose was measured with a pinpoint chamber in homogeneous phantoms to investigate the dose prediction by the Delta4DVH Anatomy algorithm for static fields. Dose distributions of VMAT fields were measured using GAFCHROMIC film. Gravitational gantry errors up to 10° were introduced into all VMAT plans to study the potential of detecting errors. Additionally, 20 clinical treatment plans were verified. For static fields, the Delta4DVH Anatomy predicted the isocenter dose accurately, with a deviation to the measured phantom dose of 1.1% ± 0.6%. For VMAT fields the predicted Delta4DVH Anatomy dose in the isocenter plane corresponded to the measured dose in the phantom, with an average gamma agreement index (GAI) (3 mm/3%) of 96.9± 0.4%. The Delta4DVH Anatomy detected the induced systematic gantry error of 10° with a relative GAI (3 mm/3%) change of 5.8% ± 1.6%. The conventional Delta4PT QA system detected a GAI change of 4.2%± 2.0%. The conventional Delta4PT GAI (3 mm/3%) was 99.8% ± 0.4% for the clinical treatment plans. The mean body and PTV-GAI (3 mm/5%) for the Delta4DVH Anatomy were 96.4% ± 2.0% and 97.7%± 1.8%; however, this dropped to 90.8%± 3.4% and 87.1% ± 4.1% for passing criteria of 3 mm/3%. The anatomy-based patient specific quality assurance system predicts the dose distribution correctly for a homogeneous case. The limiting factor for the error detection is the large variability in the error-free plans. The dose calculation algorithm is inferior to that used in the TPS (Eclipse)

Photonic crystals of coated metallic spheres

It is shown that simple face-centered-cubic (fcc) structures of both metallic and coated metallic spheres are ideal candidates to achieve a tunable complete photonic bandgap (CPBG) for optical wavelengths using currently available experimental techniques. For coated microspheres with the coating width to plasma wavelength ratio $l_c/\lambda_p \leq 10$ and the coating and host refractive indices $n_c$ and $n_h$, respectively, between 1 and 1.47, one can always find a sphere radius $r_s$ such that the relative gap width $g_w$ (gap width to the midgap frequency ratio) is larger than 5% and, in some cases, $g_w$ can exceed 9%. Using different coatings and supporting liquids, the width and midgap frequency of a CPBG can be tuned considerably.Comment: 14 pages, plain latex, 3 ps figures, to appear in Europhys. Lett. For more info on this subject see http://www.amolf.nl/research/photonic_materials_theory/moroz/moroz.htm

A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle

Mutations in human survival motor neurons 1 (SMN1) cause spinal muscular atrophy (SMA) and are associated with defects in assembly of small nuclear ribonucleoproteins (snRNPs) in vitro. However, the etiological link between snRNPs and SMA is unclear. We have developed a Drosophila melanogaster system to model SMA in vivo. Larval-lethal Smn-null mutations show no detectable snRNP reduction, making it unlikely that these animals die from global snRNP deprivation. Hypomorphic mutations in Smn reduce dSMN protein levels in the adult thorax, causing flightlessness and acute muscular atrophy. Mutant flight muscle motoneurons display pronounced axon routing and arborization defects. Moreover, Smn mutant myofibers fail to form thin filaments and phenocopy null mutations in Act88F, which is the flight muscle–specific actin isoform. In wild-type muscles, dSMN colocalizes with sarcomeric actin and forms a complex with α-actinin, the thin filament crosslinker. The sarcomeric localization of Smn is conserved in mouse myofibrils. These observations suggest a muscle-specific function for SMN and underline the importance of this tissue in modulating SMA severity

Heat Treated NiP–SiC Composite Coatings: Elaboration and Tribocorrosion Behaviour in NaCl Solution

Tribocorrosion behaviour of heat-treated NiP and NiP–SiC composite coatings was investigated in a 0.6 M NaCl solution. The tribocorrosion tests were performed in a linear sliding tribometer with an electrochemical cell interface. It was analyzed the influence of SiC particles dispersion in the NiP matrix on current density developed, on coefficient of friction and on wear volume loss. The results showed that NiP–SiC composite coatings had a lower wear volume loss compared to NiP coatings. However, the incorporation of SiC particles into the metallic matrix affects the current density developed by the system during the tribocorrosion test. It was verified that not only the volume of co-deposited particles (SiC vol.%) but also the number of SiC particles per coating area unit (and consequently the SiC particles size) have made influence on the tribocorrosion behaviour of NiP–SiC composite coatings

The International Alcohol Control Study: Methodology and implementation.

INTRODUCTION AND AIMS: The International Alcohol Control (IAC) Study is a multi-country collaborative project to assess patterns of alcohol consumption and the impact of alcohol control policy. The aim of this paper is to report the methods and implementation of the IAC. DESIGN AND METHODS: The IAC has been implemented among drinkers 16-65 years in high- and middle-income countries: Australia, England, Scotland, New Zealand, St Kitts and Nevis, Thailand, South Africa, Peru, Mongolia and Vietnam (the latter four samples were sub-national). Two research instruments were used: the IAC survey of drinkers and the Alcohol Environmental Protocol (a protocol for policy analysis). The survey was administered via computer-assisted interview and the Alcohol Environmental Protocol data were collected via document review, administrative or commercial data and key informant interviews. RESULTS: The IAC instruments were readily adapted for cross-country use. The IAC methodology has provided cross-country survey data on key measures of alcohol consumption (quantity, frequency and volume), aspects of policy relevant behaviour and policy implementation: availability, price, purchasing, marketing and drink driving. The median response rate for all countries was 60% (range 16% to 99%). Where data on alcohol available for consumption were available the validity of survey consumption measures were assessed by calculating survey coverage found to be 86% or above. Differential response bias was handled, to the extent it could be, using post-stratification weights. DISCUSSION AND CONCLUSIONS: The IAC study will allow for cross-country analysis of drinking patterns, the relationship between alcohol use and policy relevant behaviour in different countries

Estimation of speciated and total mercury dry deposition at monitoring locations in eastern and central North America

Dry deposition of speciated mercury, i.e., gaseous oxidized mercury (GOM), particulate-bound mercury (PBM), and gaseous elemental mercury (GEM), was estimated for the year 2008–2009 at 19 monitoring locations in eastern and central North America. Dry deposition estimates were obtained by combining monitored two- to four-hourly speciated ambient concentrations with modeled hourly dry deposition velocities (<i>V</i><sub>d</sub>) calculated using forecasted meteorology. Annual dry deposition of GOM+PBM was estimated to be in the range of 0.4 to 8.1 μg m<sup>−2</sup> at these locations with GOM deposition being mostly five to ten times higher than PBM deposition, due to their different modeled <i>V</i><sub>d</sub> values. Net annual GEM dry deposition was estimated to be in the range of 5 to 26 μg m<sup>−2</sup> at 18 sites and 33 μg m<sup>−2</sup> at one site. The estimated dry deposition agrees very well with limited surrogate-surface dry deposition measurements of GOM and PBM, and also agrees with litterfall mercury measurements conducted at multiple locations in eastern and central North America. This study suggests that GEM contributes much more than GOM+PBM to the total dry deposition at the majority of the sites considered here; the only exception is at locations close to significant point sources where GEM and GOM+PBM contribute equally to the total dry deposition. The relative magnitude of the speciated dry deposition and their good comparisons with litterfall deposition suggest that mercury in litterfall originates primarily from GEM, which is consistent with the limited number of previous field studies. The study also supports previous analyses suggesting that total dry deposition of mercury is equal to, if not more important than, wet deposition of mercury on a regional scale in eastern North America

ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are highly homologous yet distinct components of signal transduction pathways known to regulate cell survival and function. Recent evidence indicates an isoform-specific role for ERK2 in pain processing and peripheral sensitization. However, the function of ERK2 in primary sensory neurons has not been directly tested. To dissect the isoform-specific function of ERK2 in sensory neurons, we used mice with Cre-loxP-mediated deletion of ERK2 in Na(v)1.8(+) sensory neurons that are predominantly nociceptors. We find that ERK2, unlike ERK1, is required for peripheral sensitization and cold sensation. We also demonstrate that ERK2, but not ERK1, is required to preserve epidermal innervation in a subset of peptidergic neurons. Additionally, deletion of both ERK isoforms in Na(v)1.8(+) sensory neurons leads to neuron loss not observed with deletion of either isoform alone, demonstrating functional redundancy in the maintenance of sensory neuron survival. Thus, ERK1 and ERK2 exhibit both functionally distinct and redundant roles in sensory neurons. SIGNIFICANCE STATEMENT ERK1/2 signaling affects sensory neuron function and survival. However, it was not clear whether ERK isoform-specific roles exist in these processes postnatally. Previous work from our laboratory suggested either functional redundancy of ERK isoforms or a predominant role for ERK2 in pain; however, the tools to discriminate between these possibilities were not available at the time. In the present study, we use new genetic knock-out lines to demonstrate that ERK2 in sensory neurons is necessary for development of inflammatory pain and for postnatal maintenance of peptidergic epidermal innervation. Interestingly, postnatal loss of both ERK isoforms leads to a profound loss of sensory neurons. Therefore, ERK1 and ERK2 display both functionally distinct and redundant roles in sensory neurons

Gas-Particle Partitioning of Atmospheric Hg(II) and Its Effect on Global Mercury Deposition

Atmospheric deposition of Hg(II) represents a major input of mercury to surface environments. The phase of Hg(II) (gas or particle) has important implications for deposition. We use long-term observations of reactive gaseous mercury (RGM, the gaseous component of Hg(II)), particle-bound mercury (PBM, the particulate component of Hg(II)), fine particulate matter (PM2.5), and temperature (T) at five sites in North America to derive an empirical gas-particle partitioning relationship log10(K−1) = (10±1)–(2500±300)/T where K = (PBM/PM2.5)/RGM with PBM and RGM in common mixing ratio units, PM2.5 in μg m−3, and T in K. This relationship is within the range of previous work but is based on far more extensive data from multiple sites. We implement this empirical relationship in the GEOS-Chem global 3-D Hg model to partition Hg(II) between the gas and particle phases. The resulting gas-phase fraction of Hg(II) ranges from over 90 % in warm air with little aerosol to less than 10 % in cold air with high aerosol. Hg deposition to high latitudes increases because of more efficient scavenging of particulate Hg(II) by precipitating snow. Model comparison to Hg observations at the North American surface sites suggests that subsidence from the free troposphere (warm air, low aerosol) is a major factor driving the seasonality of RGM, while elevated PBM is mostly associated with high aerosol loads. Simulation of RGM and PBM at these sites is improved by including fast in-plume reduction of Hg(II) emitted from coal combustion and by assuming that anthropogenic particulate Hg(p) behaves as semi-volatile Hg(II) rather than as a refractory particulate component. We improve the simulation of Hg wet deposition fluxes in the US relative to a previous version of GEOS-Chem; this largely reflects independent improvement of the washout algorithm. The observed wintertime minimum in wet deposition fluxes is attributed to inefficient snow scavenging of gas-phase Hg(II).Earth and Planetary SciencesEngineering and Applied Science