Reward and punishment: the neural correlates of reinforcement feedback during motor learning

‘By the carrot or the stick’ reward or punishment has been contemplated by instructors to motivate their pupils to learn a new motor skill. The reinforcements of reward and punishment have demonstrated dissociable effects on motor learning with punishment enhancing the learning rate and reward increasing retention of the motor task. However it is still unclear how the brain processes reward and punishment during motor learning. This study sought to investigate the role of reinforcement feedback in cortical neural activity associated with motor learning. A novel visuomotor rotation task was employed with reward punishment or null feedback as the participants adapted their movement to a 30-degree counter-clockwise rotation. We measured movement time and task accuracy throughout the task. Surface electroencephalography was utilized to record cortical neural activity throughout the learning and retention of the motor task. Event-related potentials (ERPs) were calculated to assess how the brain processes the reinforcement feedback and prepares for movement. Repeated measures ANOVAs were utilized to detect differences in the movement parameters and ERP amplitudes. This study found that reward and punishment feedback did not produce different effects on the rate of task learning. However punishment feedback impaired the retention (memory) of the motor task. These behavioral effects were accompanied by changes in the amplitude of ERPs during feedback presentation and movement preparation. These results suggest that punishment feedback alters brain processes involved in memory formation during motor learning

Analysis of structural features of peptide MHC protein complexes

To help determine possible mechanisms by which MHC molecules bind a diverse but limited range of peptides, the interactions between peptides and MHC proteins have been studied using two different systems. A predictive algorithm, based on empirical analysis of known T-cell epitopes, was used to locate determinants in the L1, E6, and E7 open reading frames (ORF) of human papilloma virus (HPV) type 16. Peptides containing putative determinants were synthesised and assayed for lymphoproliferative activity in mice. The T cells elicited were highly specific for HPV type 16, but were also found to exhibit degenerate MHC restriction, indicating that some of the peptides were able to form immunogenic complexes with different MHC proteins. The contact residues and conformational features of a panel of different peptides bound to HLA DR1Dw1 were determined by analysing the ability of analogues containing long chain biotinylated lysine substituted at each position, to bind both the MHC protein and labelled avidin. The structural and conformational features of each of the peptides when bound to the HLA molecule were unique. However, three of the peptides originally defined by HLA-DR1Dw1 restricted T cells, shared several conformational features, while the remaining three peptides defined by T cells restricted through other alleles, shared some but not all of these features. Critical contact residues identified within the determinants were used to align their sequences and revealed structural homology between the peptides at positions making contact with the MHC protein. A similar pattern of residues was found in a large number of other determinants known to bind to different MHC loci and alleles. The data suggested a common structural mechanism by which many peptides bind to MHC proteins. Knowledge of this mechanism should enable the rational design of MHC binding peptides for the development of both vaccines and autoimmune disease therapies

Principles of Christian Law

A panel of experts has produced a Statement of Principles of Christian Law, drawn from an examination of their internal regulatory instruments. These principles are offered for further examination by comparative scholars of church law, as an expression of shared ecclesiology, and in furtherance of the ecumenical endeavour

Cloud-based solutions for distributed climate modeling

ECCO in the cloud - overviewA new, cloud-based framework for climate modeling is introduced allowing to run climate models at the “click of a button”. The framework aims to simplify dissemination of climate models, increase transparency of modeling activities, expand their user base, and facilitate broader research collaboration.NASA Physical Oceanograph

Dynamic phasor modelling of multi-generator variable frequency electrical power systems

The Dynamic Phasor (DP) concept has been widely used in modelling electrical power systems. So far, the DP concept has been restricted to modelling systems with one single electrical source at a fixed fundamental frequency; either one generator or an ideal three-phase AC source. This paper aims to extend the DP modelling methodology to a wider application area. Two major achievements have been introduced: 1. application of DPs for multi-source, multi-frequency systems; 2. modelling of systems with time-varying frequencies. These two techniques enable the use of DPs to study nearly all types of Electrical Power Systems (EPS). The developed theory is validated using a twin-generator system from the More Open Electrical Technologies (MOET) project. The accuracy and effectiveness of the developed models is confirmed by comparing the simulation results of detailed switching models and DP models under both balanced and unbalanced conditions

An unexpected Prins desymmetrisation reaction driven by silyl migration

Prins desymmetrisation reactions of cyclohexa-1,4-diene derivatives have been investigated as a route to the core of the cladiellin diterpenes. During the course of this work, we observed the formation of a partially-reduced benzofuran 18, which is clearly derived from oxocarbenium ion 21. This can only be rationalised by an unexpected primary to secondary silyl group migration

Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model [v1; ref status: approved with reservations 1, http://f1000r.es/5l9]

Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF) in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or de novo germline LOF mutations, most of which truncate the DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of patients lack predisposing germline or mosaic mutations and have disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development

Maternal super-obesity (body mass index ≥ 50) and adverse pregnancy outcomes

Abstract Objective. To determine if pregnancy complications are increased in super-obese (a body mass index (BMI) of 50 or more) compared to other, less obese parturients. Design. Cross-sectional study. Setting and population. All 19,700 eligible women, including 425 (2.2%) super-obese women with singleton births between 1996 and 2007 delivering at a tertiary referral center, identified using a perinatal research database. Methods. Bivariate and trend analyses were used to assess the relation between super-obesity and various pregnancy complications compared to other well-established BMI categories. Adjusted odds ratios (ORs) were calculated using multivariable logistic regression techniques. Main outcome measures. Outcomes for adjusted and unadjusted analyses were small-for-gestational age (SGA) birth, large-for-gestational age (LGA) birth, preeclampsia, gestational diabetes mellitus (GDM), fetal death, preterm birth, placental abruption, cesarean delivery, and Apgar scores < 7. Results. Compared to all other obese and non-obese women, super-obese women had the highest rates of preeclampsia, GDM, LGA, and cesarean delivery (all p < 0.05 for trend test). Super-obesity was also associated with a 44% reduction in SGA compared to all other women (OR 0.55, 95% confidence interval (CI) 0.40–0.76) and a 25% reduction compared to other, less obese women (OR 0.75, 95% CI 0.54–1.03). Super-obesity was positively associated with LGA, GDM, preeclampsia, cesarean delivery, and a 5-minute Apgar score < 7 compared to all other women after controlling for important confounders. Conclusion. Super-obesity is associated with higher rates of pregnancy complications compared to women of all other BMI classes, including other obese women

Geographic Information System Data Analysis

Data was collected in order to further NASA Langley Research Center's Geographic Information System(GIS). Information on LaRC's communication, electrical, and facility configurations was collected. Existing data was corrected through verification, resulting in more accurate databases. In addition, Global Positioning System(GPS) points were used in order to accurately impose buildings on digitized images. Overall, this project will help the Imaging and CADD Technology Team (ICTT) prove GIS to be a valuable resource for LaRC

Utility of repeat cytological assessment of thyroid nodules initially classified as benign: clinical insights from multidisciplinary care in an Irish tertiary referral centre.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is the tool of choice for evaluating thyroid nodules with the majority classified as benign following initial assessment. However, concern remains about false negative results and some guidelines have recommended routine repeat aspirates. We aimed to assess the utility of routine repeat FNAB for nodules classified as benign on initial biopsy and to examine the impact of establishing a multidisciplinary team for the care of these patients. METHODS: We performed a retrospective review of 400 consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our hospital between July 2008 and July 2011. Data recorded included demographic, clinical, histological and radiological variables. RESULTS: Three hundred and fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of routine repeat biopsy increased significantly over the time course of the study (p for trend = 0.012). Nine Thy 2 nodules were classified differently on the basis of routine repeat biopsy; one patient was classified as malignant on repeat biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified as a follicular lesions on repeat biopsy-six diagnosed as benign following lobectomy; two declined lobectomy and were followed radiologically with no nodule size increase. CONCLUSIONS: The false negative rate of an initial benign cytology result, from a thyroid nodule aspirate, is low. In the setting of an experienced multidisciplinary thyroid team, routine repeat aspiration is not justified