Inferred Influence of Human Lateral Profile on Limb Load Asymmetry during a Quiet Standing Balance Test

Although the identification and characterisation of a participant's lateral profile during quiet standing have not received much research attention, they have the potential to greatly extend our understanding of upright stance stability control. This study further examines limb load asymmetries during quiet bipedal stance. During voluntary frontal-plane weight shifting for 2 min, 300 centre-of-pressure displacements on 14 blindfolded right-handed young adults were recorded. Four biomechanical indices were used to assess postural behaviour. These were the bias of time and the magnitude of the partial ground reaction forces from both legs, and the bias in the number and magnitude of microshifts influencing stability. Our study identifies a significant level of asymmetry in the quiet bipedal stance of right-handed people. This asymmetry is associated with the right-sided bias of the ground reaction force and the angle of inclination to the upright (vertical) centroidal line. We found that the initial lateralisation of the partial ground reaction forces from both feet, as well as the period of ground reaction force bias, are important elements in any clinical tests involving quiet bipedal stance.</p

Multi-Core Unit Propagation in Functional Languages

Answer Set Programming is a declarative modeling paradigm enabling specialists in diverse disciplines to describe and solve complicated problems. Growth in high performance computing is driving ever smarter and more scalable parallel answer set solvers. To improve on today\u27s cutting-edge, researchers need to develop increasingly intelligent methods for analysis of a solver\u27s runtime information. Reflecting on the solver\u27s search state typically pauses its progress until the analysis is complete. This work introduces methods from the domain of parallel functional programming and immutable type theory to construct a representation of the search state that is both amenable to introspection and efficiently scalable across multiple processor cores

Macroeconomic effects of fiscal incentives to promote electric vehicles in Iceland: Implications for government and consumer costs

Post-print (lokagerð höfundar)Iceland as an island country with abundant renewable energy resources has been totally dependent on imported petroleum fuels to meet its transport fuel demand. Transition to electric vehicles (EVs) is of particular interest for Iceland as electricity can be supplied from low-cost renewable energy resources. To evaluate how the transition to EVs can be achieved through fiscal policy incentives, a dynamic simulation modelling of the integrated energy-transport system with a detailed representation of energy technologies and vehicle fleets is implemented. The model is used for a scenario analysis by incorporating key fiscal parameters including different taxes and subsidies on vehicles and fuels. The fiscal policies to induce EVs, which are applied to both vehicle usage pattern and upfront purchase cost, include petroleum fuel tax levies, vehicle tax exemption, extra fees and subsidies. Five fiscal-induced scenarios to promote EVs, including different subsidy and feebate schemes coupled with fuel tax incentives, are compared with a BAU case. The scenario analysis reveals the impact of different fiscal policy incentives on consumer decision behaviour and the implications of fiscal-induced EV promotion for vehicle ownership costs, government tax revenues/expenditure, and overall economic benefits.The preparation of this paper has been supported by: i) the Norden Top-level Research Initiative sub-programme “Effect Studies and Adaptation to Climate Change” through the Nordic Centre of Excellence for Strategic Adaptation Research (NORD-STAR), project number 36780, ii) The Icelandic research council (RANNIS) through grant number 163464-051, iii) The National energy company (Landsvirkjun), and iv) the Icelandic Road and Coastal Administration (Vegagerdin).Peer Reviewe

Simulation-based appraisal of tax-induced electro-mobility promotion in Iceland and prospects for energy-economic development

Post-print (lokagerð höfundar)Transition to electric vehicles (EVs) requires multidimensional policy measures incorporating vehicle fleets, energy systems, consumer behaviours, and socio-economic developments. The main objective of this paper is to evaluate the implications of a tax-induced EV transition in Iceland for GHG mitigation, energy security, and economic benefits. The analytical tools include a techno-economic simulation model of the integrated energy-transport system which is linked to an Icelandic macroeconomic general equilibrium model. The impact of a new tax reform proposal by the government is compared with the current vehicle tax policy. The government proposal scenario is also examined under further inducements for EVs incorporating a value added tax exemption and banning the sale of new petroleum fuel vehicles. All scenarios are examined under a wide range of future changes in petroleum fuel prices and EV cost reduction. The results indicate that the overall macroeconomic benefits will be negligible, but they are expected to be positive in the long term as road electrification is deepened. The results show that although the tax-induced technological solution aimed at encouraging the adoption of EVs will enable a deep GHG emissions reduction in the long term, it will not be enough to meet the short-term climate targets.The preparation of this paper has been supported by: i) Samorka, Iceland, ii) The Icelandic research council (RANNIS) through grant number 163464-051, iii) The national energy company (Landsvirkjun), Iceland, iv) Reykjavik Energy, v) Iceland's Ministry of Industry and Innovation, vi) Icelandic New Energy, and vii) Landsnet, Iceland.Peer Reviewe

Computationally Designed Bispecific Antibodies using Negative State Repertoires

A challenge in the structure-based design of specificity is modeling the negative states, i.e., the complexes that you do not want to form. This is a difficult problem because mutations predicted to destabilize the negative state might be accommodated by small conformational rearrangements. To overcome this challenge, we employ an iterative strategy that cycles between sequence design and protein docking in order to build up an ensemble of alternative negative state conformations for use in specificity prediction. We have applied our technique to the design of heterodimeric CH3 interfaces in the Fc region of antibodies. Combining computationally and rationally designed mutations produced unique designs with heterodimer purities greater than 90%. Asymmetric Fc crystallization was able to resolve the interface mutations; the heterodimer structures confirmed that the interfaces formed as designed. With these CH3 mutations, and those made at the heavy-/light-chain interface, we demonstrate one-step synthesis of four fully IgG-bispecific antibodies

The spectrum of quantum black holes and quasinormal modes

The spectrum of multiple level transitions of the quantum black hole is considered, and the line widths calculated. Initial evidence is found for these higher order transitions in the spectrum of quasinormal modes for Schwarzschild and Kerr black holes, further bolstering the idea that there exists a correspondence principle between quantum transitions and classical ``ringing modes''. Several puzzles are noted, including a fine-tuning problem between the line width and the level degeneracy. A more general explanation is provided for why setting the Immirzi parameter of loop quantum gravity from the black hole spectrum necessarily gives the correct value for the black hole entropy.Comment: 5 pages, 5 figures, version to appear in Phys. Rev.

Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP : a case study using protein-loaded liposomes

Nanomedicines are well recognised for their ability to improve therapeutic outcomes. Yet, due to their complexity, nanomedicines are challenging and costly to produce using traditional manufacturing methods. For nanomedicines to be widely exploited, new manufacturing technologies must be adopted to reduce development costs and provide a consistent product. Within this study, we investigate microfluidic manufacture of nanomedicines. Using protein-loaded liposomes as a case study, we manufacture liposomes with tightly defined physico-chemical attributes (size, PDI, protein loading and release) from small-scale (1 mL) through to GMP volume production (200 mL/min). To achieve this, we investigate two different laminar flow microfluidic cartridge designs (based on a staggered herringbone design and a novel toroidal mixer design); for the first time we demonstrate the use of a new microfluidic cartridge design which delivers seamless scale-up production from bench-scale (12 mL/min) through GMP production requirements of over 20 L/h using the same standardised normal operating parameters. We also outline the application of tangential flow filtration for down-stream processing and high product yield. This work confirms that defined liposome products can be manufactured rapidly and reproducibly using a scale-independent production process, thereby de-risking the journey from bench to approved product

Functional Desaturase Fads1 (Δ5) and Fads2 (Δ6) Orthologues Evolved before the Origin of Jawed Vertebrates

Long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are essential components of biomembranes, particularly in neural tissues. Endogenous synthesis of ARA, EPA and DHA occurs from precursor dietary essential fatty acids such as linoleic and α-linolenic acid through elongation and Δ5 and Δ6 desaturations. With respect to desaturation activities some noteworthy differences have been noted in vertebrate classes. In mammals, the Δ5 activity is allocated to the Fads1 gene, while Fads2 is a Δ6 desaturase. In contrast, teleosts show distinct combinations of desaturase activities (e.g. bifunctional or separate Δ5 and Δ6 desaturases) apparently allocated to Fads2-type genes. To determine the timing of Fads1-Δ5 and Fads2-Δ6 evolution in vertebrates we used a combination of comparative and functional genomics with the analysis of key phylogenetic species. Our data show that Fads1 and Fads2 genes with Δ5 and Δ6 activities respectively, evolved before gnathostome radiation, since the catshark Scyliorhinus canicula has functional orthologues of both gene families. Consequently, the loss of Fads1 in teleosts is a secondary episode, while the existence of Δ5 activities in the same group most likely occurred through independent mutations into Fads2 type genes. Unexpectedly, we also establish that events of Fads1 gene expansion have taken place in birds and reptiles. Finally, a fourth Fads gene (Fads4) was found with an exclusive occurrence in mammalian genomes. Our findings enlighten the history of a crucially important gene family in vertebrate fatty acid metabolism and physiology and provide an explanation of how observed lineage-specific gene duplications, losses and diversifications might be linked to habitat-specific food web structures in different environments and over geological timescales

The effect of HIV on morbidity and mortality in children with severe malarial anaemia

<p>Abstract</p> <p>Background</p> <p>Malaria and HIV are common causes of mortality in sub-Saharan Africa. The effect of HIV infection on morbidity and mortality in children with severe malarial anaemia was assessed.</p> <p>Methods</p> <p>Children <5 years old were followed as part of a prospective cohort study to assess the transfusion-associated transmission of blood-borne pathogens at Mulago Hospital, Kampala, Uganda. All children were hospitalized with a diagnosis of severe malarial anaemia requiring blood transfusion. Survival to different time points post-transfusion was compared between HIV-infected and uninfected children. Generalized estimating equations were used to analyse repeated measurement outcomes of morbidity, adjusting for confounders.</p> <p>Findings</p> <p>Of 847 children, 78 (9.2%) were HIV-infected. Median follow-up time was 162 days (inter-quartile range: 111, 169). HIV-infected children were more likely to die within 7 days (Hazard ratio [HR] = 2.86, 95% Confidence interval [CI] 1.30–6.29, P = 0.009) and within 28 days (HR = 3.70, 95% CI 1.91–7.17, P < 0.001) of an episode of severe malarial anaemia, and were more likely to die in the 6 months post-transfusion (HR = 5.70, 95% CI 3.54–9.16, P < 0.001) compared to HIV-uninfected children. HIV-infected children had more frequent re-admissions due to malaria within 28 days (Incidence rate ratio (IRR) = 3.74, 95% CI 1.41–9.90, P = 0.008) and within 6 months (IRR = 2.66, 95% CI 1.17 – 6.07, P = 0.02) post-transfusion than HIV-uninfected children.</p> <p>Conclusion</p> <p>HIV-infected children with severe malarial anaemia suffered higher all-cause mortality and malaria-related mortality than HIV-uninfected children. Children with HIV and malaria should receive aggressive treatment and further evaluation of their HIV disease, particularly with regard to cotrimoxazole prophylaxis and antiretroviral therapy.</p