The Effects of Choice on Assignment Completion and Percent Correct by a High School Student with a Learning Disability

The effects of choosing between two academic assignments on task completion and percent correct by a ninth grade student with a learning disability was investigated. This case study extended the efficacy of antecedent based intervention as an instructional modification. Further, the study extends previous research by investigating the effect of choice on academic achievement. The withdrawal design showed that percent completed and correct were highest when the participant was given a choice between two assignments when compared to baseline conditions. Results are discussed in term of efficacy of choice as an antecedent intervention, choice selection, and future research directions

Dual positive and negative regulation of GPCR signaling by GTP hydrolysis

G protein-coupled receptors (GPCRs) regulate a variety of intracellular pathways through their ability to promote the binding of GTP to heterotrimeric G proteins. Regulator of G protein signaling (RGS) proteins increase the intrinsic GTPase activity of G-subunits and are widely regarded as negative regulators of G protein signaling. Using yeast we demonstrate that GTP hydrolysis is not only required for desensitization, but is essential for achieving a high maximal (saturated level) response. Thus RGS-mediated GTP hydrolysis acts as both a negative (low stimulation) and positive (high stimulation) regulator of signaling. To account for this we generated a new kinetic model of the G protein cycle where GGTP enters an inactive GTP-bound state following effector activation. Furthermore, in vivo and in silico experimentation demonstrates that maximum signaling output first increases and then decreases with RGS concentration. This unimodal, non-monotone dependence on RGS concentration is novel. Analysis of the kinetic model has revealed a dynamic network motif that shows precisely how inclusion of the inactive GTP-bound state for the G produces this unimodal relationship

Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation

© 2017 The Author(s). The 'acidic patch' is a highly electronegative cleft on the histone H2A-H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis. In vitro, the compounds induce misfolding of chromatin fibre and block the binding of the regulator of chromatin condensation 1 (RCC1) acidic patch-binding protein. This family of chromatin-modifying molecules has potential for applications in drug development and as tools for chromatin research

Serum calcium and risk of migraine : a Mendelian randomization study

Migraine affects similar to 14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sampleMendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine headache. Co-morbidity was evaluated using electronic health records obtained from the PennOmics database comprising>1 million patient entries. Genetic co-heritability and causality via MR was assessed using data from the International Headache Consortium (23,285 cases, 95,425 controls) and circulating serum calcium levels (39,400 subjects). We observed co-occurrence of migraine and hypercalcaemia ICD-9 diagnoses (OR = 1.58, P = 4 x 10-(13)), even after inclusion of additional risk factors for migraine (OR = 1.23, P = 2 x 10 -(3)). Second, we observed co-heritability (r(g) =0.191, P = 0.03) between serum calcium and migraine headache, indicating that these traits have a genetic basis in common. Finally, we found that elevation of serum calcium levels by 1 mg/dl resulting from our genetic score was associated with an increase in risk of migraine (OR = 1.80, 95% CI: 1.31-2.46, P = 2.5 x 10 -(4)), evidence supporting a causal hypothesis. We also present multiple MR sensitivity analyses in support of this central finding. Our results provide evidence that hypercalcaemia is comorbid with migraine headache diagnoses, and that genetically elevated serum calcium over lifetime appears to increase risk for migraine. Further studies will be required to understand the biologicalmechanism, pathways, and clinical implication for riskmanagement.Peer reviewe

Modelling the vertical gradient of nitrogen dioxide in an urban area

Introduction Land use regression models environmental predictors to estimate ground-floor air pollution concentration surfaces of a study area. While many cities are expanding vertically, such models typically ignore the vertical dimension. Methods We took integrated measurements of NO 2 at up to three different floors on the facades of 25 buildings in the mid-sized European city of Basel, Switzerland. We quantified the decrease in NO 2 concentration with increasing height at each facade over two 14-day periods in different seasons. Using predictors of traffic load, population density and street configuration, we built conventional land use regression (LUR) models which predicted ground floor concentrations. We further evaluated which predictors best explained the vertical decay rate . Ultimately, we combined ground floor and decay models to explain the measured concentrations at all heights. Results We found a clear decrease in mean nitrogen dioxide concentrations between measurements at ground level and those at higher floors for both seasons. The median concentration decrease was 8.1% at 10 m above street level in winter and 10.4% in summer. The decrease with height was sharper at buildings where high concentrations were measured on the ground and in canyon-like street configurations. While the conventional ground floor model was able to explain ground floor concentrations with a model R 2 of 0.84 (RMSE 4.1 μg/m 3 ), it predicted measured concentrations at all heights with an R 2 of 0.79 (RMSE 4.5 μg/m 3 ), systematically overpredicting concentrations at higher floors. The LUR model considering vertical decay was able to predict ground floor and higher floor concentrations with a model R 2 of 0.84 (RMSE 3.8 μg/m 3 ) and without systematic bias. Discussion Height above the ground is a relevant determinant of outdoor residential exposure, even in medium-sized European cities without much high-rise. It is likely that conventional LUR models overestimate exposure for residences at higher floors near major roads. This overestimation can be minimized by considering decay with height

Validating an inertial measurement unit for cricket fast bowling: a first step in assessing the feasibility of diagnosing back injury risk in cricket fast bowlers during a tele-sport-and-exercise medicine consultation

This study aimed to validate an array-based inertial measurement unit to measure cricket fast bowling kinematics as a first step in assessing feasibility for tele-sport-and-exercise medicine. We concurrently captured shoulder girdle relative to the pelvis, trunk lateral flexion, and knee flexion angles at front foot contact of eight cricket medium-fast bowlers using inertial measurement unit and optical motion capture. We used one sample t-tests and 95% limits of agreement (LOA) to determine the mean difference between the two systems and Smallest Worth-while Change statistic to determine whether any differences were meaningful. A statistically significant (p < 0.001) but small mean difference of −4.7° ± 8.6° (95% Confidence Interval (CI) [−3.1° to −6.4°], LOA [−22.2 to 12.7], SWC 3.9°) in shoulder girdle relative to the pelvis angle was found between the systems. There were no statistically significant differences between the two systems in trunk lateral flexion and knee flexion with the mean differences being 0.1° ± 10.8° (95% CI [−1.9° to 2.2°], LOA [−22.5 to 22.7], SWC 1.2°) and 1.6° ± 10.1° (95% CI [−0.2° to 3.3°], LOA [−19.2 to 22.3], SWC 1.9°) respectively. The inertial measurement unit-based system tested allows for accurate measurement of specific cricket fast bowling kinematics and could be used in determining injury risk in the context of tele-sport-and-exercise-medicine

Graphene FET sensors for Alzheimer’s disease protein biomarker clusterin detection

We report on the fabrication and characterisation of Graphene field-effect transistor (GFET) Biosensors for detecting clusterin, a prominent protein biomarker of Alzheimer’s disease (AD). There are approximately 54 million people currently living with dementia worldwide and this is expected to rise to 130 million by 2050. Although there are over 400 different types of dementia, AD is the most common type, affecting between 50–75% of those diagnosed with dementia. Diagnosis of AD can take up to 2 years currently using MRI, PET, CT scans and memory tests. There is, therefore, an urgent need to develop low-cost, accurate, non-invasive and point-of-care (PoC) sensors for early diagnosis of AD. The GFET sensors we are developing to address this challenge were fabricated on Si/SiO2 substrate through processes of photolithographic patterning and metal lift-off techniques with evaporated chromium and sputtered gold contacts. Raman Spectroscopy was performed on the devices to determine the quality of the graphene. The GFETs were annealed to improve their performance before the channels were functionalized by immobilising the graphene surface with a linker molecule and anti-clusterin antibody. The detection was achieved through the binding reaction between the antibody and varying concentrations of clusterin antigen from 1 pg/mL to 1 ng/mL. The GFETs were characterized using 4-probe direct current (DC) electrical measurements which demonstrated a limit of detection of the biosensors to be below 1 pg/mL

Our evolving understanding of the role of the γδ T cell receptor in γδ T cell mediated immunity

The γδ T cell immune cell lineage has remained relatively enigmatic and under-characterised since their identification. Conversely, the insights we have, highlight their central importance in diverse immunological roles and homeostasis. Thus, γδ T cells are considered as potentially a new translational tool in the design of new therapeutics for cancer and infectious disease. Here we review our current understanding of γδ T cell biology viewed through a structural lens centred on the how the γδ T cell receptor mediates ligand recognition. We discuss the limited knowledge of antigens, the structural basis of such reactivities and discuss the emerging trends of γδ T cell reactivity and implications for γδ T cell biology