A Feedback System for the Motor Learning of Skills in Golf

AbstractThis paper presents a feedback GUI to improve the motor skills of a subject performing a golf putt. In this paper inertial sensors (gyroscopes) and video were used to capture the swing. Feedback was provided by a graphical user interface created in Matlab and displayed the video of the putt and quantitative values such as the putt tempo (ratio Backswing duration: Downswing duration) and score which gives an indication of how close the putt tempo is to the ideal rato of (2:1). A zero-crossing method was used to determine the swing phases and durations from the rotational velocity.The effectiveness of the feedback GUI was tested using 10 participants (4 experienced and 6 inexperienced). Each participant executed two sets of 15 putts over distances of 3m, 6m and 9m on an artificial turf putting surface with feedback provided by the GUI between the two sets of putts. The results indicated that overall tempo ratio of experienced and inexperienced participants became closer to 2:1 after the feedback. The standard deviation also decreased which meant that participants also improved their putting consistency. The results indicate that the participants were able to improve their skill in terms of putting performance indicators after using the feedback GUI

miRNA-140-5p: new avenue for pulmonary arterial hypertension drug development?

Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Pathologically, PAH is characterised by sustained vasoconstriction and progressive obliteration of small pulmonary arteries through a process of medial thickening, intimal fibrosis and the formation of angioproliferative lesions. Current treatments target the sustained vasoconstriction via either the prostacyclin, endothelin or nitric oxide pathway but do little to address the underlying progressive proliferative vascular disease. Dysregulated expression of microRNA (miR) has been identified in PAH and we have recently highlighted reduced miR-140-5p in patients with PAH. Replacement of miR-140-5p attenuated disease in animal models with the regulation of Smurf1, a E3 ubiquitin ligase targeting BMPR2 as one identified mechanism. These data highlight Smurf1 inhibition as a treatment for PAH

Effectiveness of stratospheric solar-radiation management as a function of climate sensitivity

If implementation of proposals to engineer the climate through solar-radiation management (SRM) ever occurs, it is likely to be contingent on climate sensitivity. However, modelling studies examining the effectiveness of SRM as a strategy to offset anthropogenic climate change have used only the standard parameterizations of atmosphere–ocean general circulation models that yield climate sensitivities close to the Coupled Model Intercomparison Project mean. Here, we use a perturbed-physics ensemble modelling experiment to examine how the response of the climate to SRM implemented in the stratosphere (SRM-S) varies under different greenhouse-gas climate sensitivities. When SRM-S is used to compensate for rising atmospheric concentrations of greenhouse gases, its effectiveness in stabilizing regional climates diminishes with increasing climate sensitivity. However, the potential of SRM-S to slow down unmitigated climate change, even regionally, increases with climate sensitivity. On average, in variants of the model with higher sensitivity, SRM-S reduces regional rates of temperature change by more than 90% and rates of precipitation change by more than 50%.Engineering and Applied Science

NS2 is dispensable for efficient assembly of hepatitis C virus-like particles in a bipartite trans-encapsidation system.

Infectious hepatitis C virus (HCV) particle production in the genotype 2a JFH-1-based cell culture system involves non-structural proteins in addition to canonical virion components. NS2 has been proposed to act as a protein adaptor, co-ordinating the early stages of virion assembly. However, other studies have identified late-acting roles for this protein, making its precise involvement in infectious particle production unclear. Using a robust, bipartite trans-encapsidation system based upon baculovirus expression of HCV structural proteins, we have generated HCV-like particles (HCV-LP) in the absence of NS2 with overt similarity to wild-type virions. HCV-LP could transduce naive cells with trans-encapsidated subgenomic replicon RNAs and shared similar biochemical and biophysical properties with JFH-1 HCV. Both genotype 1b and JFH-1 intracellular HCV-LP were produced in the absence of NS2, whereas restoring NS2 to the JFH-1 system dramatically enhanced secreted infectivity, consistent with a late-acting role. Our system recapitulated authentic HCV particle assembly via trans-complementation of bicistronic, NS2-deleted, chimeric HCV, which is otherwise deficient in particle production. This closely resembled replicon-mediated NS2 trans-complementation, confirming that baculovirus expression of HCV proteins did not unduly affect particle production. Furthermore, this suggests that separation of structural protein expression from replicating HCV RNAs that are destined to be packaged alleviates an early stage requirement for NS2 during particle formation. This highlights our current lack of understanding of how NS2 mediates assembly, yet comparison of full-length and bipartite systems may provide further insight into this process

Equine Rhinitis A Virus and Its Low pH Empty Particle: Clues Towards an Aphthovirus Entry Mechanism?

Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease virus (FMDV), belonging to the genus Aphthovirus of the Picornaviridae. How picornaviruses introduce their RNA genome into the cytoplasm of the host cell to initiate replication is unclear since they have no lipid envelope to facilitate fusion with cellular membranes. It has been thought that the dissociation of the FMDV particle into pentameric subunits at acidic pH is the mechanism for genome release during cell entry, but this raises the problem of how transfer across the endosome membrane of the genome might be facilitated. In contrast, most other picornaviruses form ‘altered’ particle intermediates (not reported for aphthoviruses) thought to induce membrane pores through which the genome can be transferred. Here we show that ERAV, like FMDV, dissociates into pentamers at mildly acidic pH but demonstrate that dissociation is preceded by the transient formation of empty 80S particles which have released their genome and may represent novel biologically relevant intermediates in the aphthovirus cell entry process. The crystal structures of the native ERAV virus and a low pH form have been determined via highly efficient crystallization and data collection strategies, required due to low virus yields. ERAV is closely similar to FMDV for VP2, VP3 and part of VP4 but VP1 diverges, to give a particle with a pitted surface, as seen in cardioviruses. The low pH particle has internal structure consistent with it representing a pre-dissociation cell entry intermediate. These results suggest a unified mechanism of picornavirus cell entry

Viral Internal Ribosome Entry Site Structures Segregate into Two Distinct Morphologies

An increasing number of viruses have been shown to initiate protein synthesis by a cap-independent mechanism involving internal ribosome entry sites (IRESs). Predictions of the folding patterns of these RNA motifs have been based primarily on sequence and biochemical analyses. Biophysical confirmation of the models has been achieved only for the IRES of hepatitis C virus (HCV), which adopts an open structure consisting of two major stems. We have conducted an extensive comparison of flavivirus and picornavirus IRES elements by negative stain transmission electron microscopy. All of the flavivirus IRESs we examined (those of GB virus-B, GB virus-C, and classical swine fever virus) fold to give a structure similar to that of the HCV IRES, as does an IRES recently found on mRNA encoded by human herpesvirus 8. The larger picornavirus IRESs (those of foot-and-mouth disease virus, rhinovirus, encephalomyocarditis virus, and hepatitis A virus) are morphologically similar, comprising a backbone with two protruding stems, and distinct from the flavivirus IRESs

Employing transposon mutagenesis to investigate foot-and-mouth disease virus replication

Probing the molecular interactions within the foot-and-mouth disease virus (FMDV) RNA replication complex has been restricted in part to the lack of suitable reagents. Random insertional mutagenesis has proven an excellent method to reveal domains of proteins essential for viral replication as well as locations that can tolerate small genetic insertions. Such insertion sites can be subsequently adapted by the incorporation of commonly used epitope tags and so facilitate their detection with commercial available reagents. In this study, we use random transposon-mediated mutagenesis to produce a library of 15 nucleotide insertions in the FMDV nonstructural polyprotein. Using a replicon-based assay we isolated multiple replication-competent as well as replication-defective insertions. We have adapted the replication competent insertion sites for the successful incorporation of epitope tags within FMDV non-structural proteins, for the use in a variety of downstream assays. Additionally, we show that replication of some of the replication-defective insertion mutants can be rescued by co-transfection of a 'helper' replicon, demonstrating a novel use of random mutagenesis to identify inter-genomic trans-complementation. Both the epitope tags and replication-defective insertions identified here will be valuable tools for probing interactions within picornaviral replication complexes

Sex-dependent influence of endogenous estrogen in pulmonary hypertension

Rationale: The incidence of pulmonary arterial hypertension (PAH) is greater in women suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males exogenously administered estrogen can protect against PH; however in models that display female susceptibility estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and gender in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH; the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of gender on pulmonary expression of aromatase in these models and in lungs from PAH patients. Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was due to reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor alpha also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased BMPR2 and Id1 expression compared to male. Anastrozole treatment reversed the impaired BMPR2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared to male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential

Recovery of Bennu's Orientation for the OSIRIS-REx Mission: Implications for the Spin State Accuracy and Geolocation Errors

The goal of the OSIRIS-REx mission is to return a sample of asteroid material from Near-Earth Asteroid (101955) Bennu. The role of the navigation and fight dynamics team is critical for the spacecraft to execute a precisely planned sampling maneuver over a specifically-selected landing site. In particular, the orientation of Bennu needs to be recovered with good accuracy during orbital operations to contribute as small an error as possible to the landing error budget. Although Bennu is well characterized from Earth-based radar observations, its orientation dynamics are not sufficiently known to exclude the presence of a small wobble. To better understand this contingency and evaluate how well the orientation can be recovered in the presence of a large 1 degree wobble, we conduct a comprehensive simulation with the NASA GSFC GEODYN orbit determination and geodetic parameter estimation software. We describe the dynamic orientation modeling implemented in GEODYN in support of OSIRIS-REx operations, and show how both altimetry and imagery data can be used as either undifferenced (landmark, direct altimetry) or differenced (image crossover, altimetry crossover) measurements. We find that these two different types of data contribute differently to the recovery of instrument pointing or planetary orientation. When upweighted, the absolute measurements help reduce the geolocation errors, despite poorer astrometric (inertial) performance. We find that with no wobble present, all the geolocation requirements are met. While the presence of a large wobble is detrimental, the recovery is still reliable thanks to the combined use of altimetry and imagery data

High-resolution Local Gravity Model of the South Pole of the Moon from GRAIL Extended Mission Data

We estimated a high-resolution local gravity field model over the south pole of the Moon using data from the Gravity Recovery and Interior Laboratory's extended mission. Our solution consists of adjustments with respect to a global model expressed in spherical harmonics. The adjustments are expressed as gridded gravity anomalies with a resolution of 1/6deg by 1/6deg (equivalent to that of a degree and order 1080 model in spherical harmonics), covering a cap over the south pole with a radius of 40deg. The gravity anomalies have been estimated from a short-arc analysis using only Ka-band range-rate (KBRR) data over the area of interest. We apply a neighbor-smoothing constraint to our solution. Our local model removes striping present in the global model; it reduces the misfit to the KBRR data and improves correlations with topography to higher degrees than current global models