A test matrix sequencer for research test facility automation

The hardware and software configuration of a Test Matrix Sequencer, a general purpose test matrix profiler that was developed for research test facility automation at the NASA Lewis Research Center, is described. The system provides set points to controllers and contact closures to data systems during the course of a test. The Test Matrix Sequencer consists of a microprocessor controlled system which is operated from a personal computer. The software program, which is the main element of the overall system is interactive and menu driven with pop-up windows and help screens. Analog and digital input/output channels can be controlled from a personal computer using the software program. The Test Matrix Sequencer provides more efficient use of aeronautics test facilities by automating repetitive tasks that were once done manually

Dental measurements do not diagnose modern artiodactyl species: Implications for the systematics of Merycoidodontoidea

Though dental measurements are frequently used to diagnose the fossil species of Merycoidodontoidea and other extinct artiodactyls, the effective diagnosis of modern artiodactyl taxa via dental measurements has not been extensively tested. Our study finds that variation in artiodactyl dentition is generally higher than in primates, carnivores, rodents and even elephants, with molar coefficients of variation ranging up to 18% (Camelus bactrianus), and that dental measurements poorly diagnose modern artiodactyls via discriminant function analysis, adjusted t -tests on coefficients of variation, or finite mixture analysis. The higher-than-expected coefficients of variation for artiodactyls imply that some fossil taxa may be over-split, but the low utility of dental measurements in separating sympatric species of duikers also suggests that dental measurements are not effective for fully diagnosing certain artiodactyl groups. We advocate a systematic revision of Merycoidodontoidea and many other fossil artiodactyl groups with lower emphasis on dental measurements and better accounting for the ways selenodont dentition varies

Abatacept in the treatment of rheumatoid arthritis

T-cell biology has regained importance in the pathogenesis of rheumatoid arthritis. Despite the significant improvements associated with the introduction of tumor necrosis factor-α blockade, reasonable proportions of failures and suboptimal responses have been reported, necessitating a search for alternative targeted therapies. This has included drug therapy designed to interrupt T-cell activation via the co-stimulation pathway. Abatacept is a recombinant fusion protein that blocks the co-stimulatory signal mediated by the CD28-CD80/86 pathway, which is required for T-cell activation. Several clinical trials have confirmed the safety and efficacy of this drug in the treatment of rheumatoid arthritis. This review summarizes the clinical data supporting this line of treatment and considers the safety and efficacy data from phase II and III trials

Intergenerational transfers in European families

This research examines the financial assistance given by parents to their adult children and the extent to which it is influenced by social policy. In recent years these intergenerational financial transfers have been the subject of much research and a great deal has been learnt about when and why parents make the decision to provide financial assistance (Cox, 1987; Kohli, 1999; Albertini & Kohli, 2012). Furthermore, there has been considerable research on apparent differences in such financial assistance across countries and the extent to which this is attributable to differences in the social policies of these countries (Albertini, Kohli, & Vogel, 2007; Schenk, Dykstra, & Maas, 2010; Brandt & Deindl, 2013). The aim of this research is to further this understanding by considering transfers from different perspectives, first by considering the receipt of transfers rather than the giving of transfers and then by exploring the transfer decision in the context of multi-child families. Through these approaches and by using new data sources and analytical methods, the research estimates the association between social policy and intergenerational financial transfers. Furthermore, it was the specific aim of this research to consider whether such an association would explain cross-national variation in transfer behaviour and the importance of social policies relative to other determinants of transfer behaviour. To achieve these aims a variety of quantitative methods were used to model the giving and receiving of transfers using data from the Survey for Health, Ageing and Retirement in Europe (SHARE) and the European Union’s Statistics on Income and Living Conditions (EU-SILC). The analysis of this latter dataset represents an important contribution in itself as it allows for the exploration of the receipt of transfers in a comparative perspective for the first time. To incorporate the complex and rich nature of these two datasets, multilevel models are used to model households over time and children within families. The results of these analyses suggest that there is a small association between certain policies and parents providing financial assistance to their adult children. Those in receipt of larger public pensions are marginally more likely to provide financial assistance to their adult children than those with smaller public pensions. As for adult children themselves, those receiving financial assistance from the state in the form of child benefit, housing benefits, social exclusion benefits and educational benefits are fractionally more likely to receive from their parents as well. The estimated coefficients and maximum effect size of such social policies are very small compared to time invariant factors which include the parent’s financial resources and the number of siblings the child has. In addition, the cross-national variation in transfer behaviour identified within the analyses is considerably smaller than in previous research. The research concludes that social policies are of less importance with regards to transfer behaviour than previous research has suggested. Whilst the research identifies a clear association between social policies and transfer behaviour, it is relatively weak compared to other factors. However the research stops short of concluding that social policies do not matter, instead suggesting that future research should critically assess the importance of intergenerational transfers in determining the adult child’s outcomes

Next Generation Universal Ground Control System HMI Design

The existing Human Machine Interface (HMI) for the Army’s Universal Ground Control Station (UGCS) represents a 1980s, windows-based technology which is neither intuitive nor scalable for operators. It creates high levels of cognitive load on the operators, and its closed architecture limits its adaptability for UAS missions as technologies evolve. This research presents a methodology for creating and evaluating next generation HMI designs while leveraging GNU Image Manipulation Program (GIMP) and TELLUS flight simulation software in the creation of five HMI prototype designs. A proof of concept approach in the evaluation of prototypes was performed with five UAS Aircraft Operators (15W MOS) and five USMA cadets; examination of the impact of age and experience on the perceived value of new HMI designs will influence recommendations on full experimental design. The value-focused approach to design presented in this paper and prototype designs provide a basis for full prototype development and experimental testing through PM UAS with the Intelligence and Maneuver Centers of Excellence. Results include a trade space and sensitivity analysis towards development of improved HMI designs. The methodology and high performing prototypes for HMI design will be integrated by the PM UAS CSI Project Office for further development and full experimental analysis

Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells.

It has long been speculated that metabolites, produced by gut microbiota, influence host metabolism in health and diseases. Here, we reveal that indole, a metabolite produced from the dissimilation of tryptophan, is able to modulate the secretion of glucagon-like peptide-1 (GLP-1) from immortalized and primary mouse colonic L cells. Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods. These effects were attributed to the ability of indole to affect two key molecular mechanisms in L cells. On the one hand, indole inhibited voltage-gated K(+) channels, increased the temporal width of action potentials fired by L cells, and led to enhanced Ca(2+) entry, thereby acutely stimulating GLP-1 secretion. On the other hand, indole slowed ATP production by blocking NADH dehydrogenase, thus leading to a prolonged reduction of GLP-1 secretion. Our results identify indole as a signaling molecule by which gut microbiota communicate with L cells and influence host metabolism.This is the final version. It was first published by Elsevier at http://www.cell.com/cell-reports/abstract/S2211-1247%2814%2900901-2

Novel SCN9A mutations underlying extreme pain phenotypes: unexpected electrophysiological and clinical phenotype correlations.

The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is exemplified by the heterogeneity of clinical phenotypes associated with its mutation. Gain-of-function mutations are typically pain-causing and have been associated with inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). IEM is usually caused by enhanced NaV1.7 channel activation, whereas mutations that alter steady-state fast inactivation often lead to PEPD. In contrast, nonfunctional mutations in SCN9A are known to underlie congenital insensitivity to pain (CIP). Although well documented, the correlation between SCN9A genotypes and clinical phenotypes is still unclear. Here we report three families with novel SCN9A mutations. In a multiaffected dominant family with IEM, we found the heterozygous change L245 V. Electrophysiological characterization showed that this mutation did not affect channel activation but instead resulted in incomplete fast inactivation and a small hyperpolarizing shift in steady-state slow inactivation, characteristics more commonly associated with PEPD. In two compound heterozygous CIP patients, we found mutations that still retained functionality of the channels, with two C-terminal mutations (W1775R and L1831X) exhibiting a depolarizing shift in channel activation. Two mutations (A1236E and L1831X) resulted in a hyperpolarizing shift in steady-state fast inactivation. To our knowledge, these are the first descriptions of mutations with some retained channel function causing CIP. This study emphasizes the complex genotype-phenotype correlations that exist for SCN9A and highlights the C-terminal cytoplasmic region of NaV1.7 as a critical region for channel function, potentially facilitating analgesic drug development studies.J.J.C. and A.M.H. were supported by an MRC Research Career Development fellowship. F.M.G., F.R., and E.C.E. were supported by Wellcome Trust Senior Fellowships WT088357/Z/09/Z and WT084210/Z/07/Z and MRC Grant MC_UU_12012/3. C.G.W. was supported by the Cambridge Biomedical Research Campus.This is the final published version. It first appeared at http://www.jneurosci.org/content/35/20/7674.short

Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate

Background Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors. Objective To assess structural damage progression through 2 years. Methods Intention-to-treat patients with one post-baseline radiograph (rituximab n = 281; placebo n = 187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received >= 1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104. Results At week 104, significantly lower changes in TSS (1.14 vs 2.81; p < 0.0001), erosion score (0.72 vs 1.80; p < 0.0001) and joint space narrowing scores (0.42 vs 1.00; p < 0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years. Conclusions Rituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitor