Towards Additive Manufacture of Next Generation Prosthetics, Assessing Emerging CAD Strategies for Improving the Existing CAD Process

The research project that this work comes from aims to address the issues and inefficiencies of current CAD systems in regards to working on multiple scales, with a particular focus on improving prosthetic design. Working from the micron scale to the macro scale and following on from work that defined a criteria of necessary material properties, this paper is a continuation of previous work that attempts to answer the research question ‘How can new CAD strategies be applied to improve the efficiency of producing parts with these necessary material properties?’ A selection of emerging CAD strategies from the last five years have been selected with a view of improving the hybrid process order created in the previous study. Each of these processes is introduced, and their pros and cons compared before identifying the areas of the CAD criteria that they can improve efficiency. Testing was performed using the software if it is available to see areas of improvement first-hand

Rapid and Accurate Assessment of GPCR-Ligand Interactions Using the Fragment Molecular Orbital-Based Density-Functional Tight-Binding Method

The reliable and precise evaluation of receptor–ligand interactions and pair-interaction energy is an essential element of rational drug design. While quantum mechanical (QM) methods have been a promising means by which to achieve this, traditional QM is not applicable for large biological systems due to its high computational cost. Here, the fragment molecular orbital (FMO) method has been used to accelerate QM calculations, and by combining FMO with the density-functional tight-binding (DFTB) method we are able to decrease computational cost 1000 times, achieving results in seconds, instead of hours. We have applied FMO-DFTB to three different GPCR–ligand systems. Our results correlate well with site directed mutagenesis data and findings presented in the published literature, demonstrating that FMO-DFTB is a rapid and accurate means of GPCR–ligand interactions

On Muddled Methods and Their Meaning

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68431/2/10.1177_048661346900100105.pd

Nonlinear Reaction–Diffusion Process Models Improve Inference for Population Dynamics

Partial differential equations (PDEs) are a useful tool for modeling spatiotemporal dynamics of ecological processes. However, as an ecological process evolves, we need statistical models that can adapt to changing dynamics as new data are collected. We developed a model that combines an ecological diffusion equation and logistic growth to characterize colonization processes of a population that establishes long‐term equilibrium over a heterogeneous environment. We also developed a homogenization strategy to statistically upscale the PDE for faster computation and adopted a hierarchical framework to accommodate multiple data sources collected at different spatial scales. We highlighted the advantages of using a logistic reaction component instead of a Malthusian component when population growth demonstrates asymptotic behavior. As a case study, we demonstrated that our model improves spatiotemporal abundance forecasts of sea otters in Glacier Bay, Alaska. Furthermore, we predicted spatially varying local equilibrium abundances as a result of environmentally driven diffusion and density‐regulated growth. Integrating equilibrium abundances over the study area in our application enabled us to infer the overall carrying capacity of sea otters in Glacier Bay, Alaska

Loftid Aeroshell Engineering Development Unit Structural Testing

NASAs Hypersonic Inflatable Aerodynamic Decelerator (HIAD) technology was selected for a Technology Demonstration Mission under the Space Technology Mission Directorate in 2017. HIAD is an enabling technology that can facilitate atmospheric entry of heavy payloads to planets such as Earth and Mars using a deployable aeroshell. The deployable nature of the HIAD technology allows it to avoid the size constraints imposed on current rigid aeroshell entry systems. This enables use of larger aeroshells resulting in increased entry system performance (e.g. higher pay-load mass and/or volume, higher landing altitude at Mars). The Low Earth Orbit Flight Test of an Inflatable Decelerator (LOFTID) is currently scheduled for late-2021. LOFTID will be launched out of Vandenberg Air Force Base as a secondary payload on an Atlas V rocket. The flight test features a 6m diameter, 70-deg sphere-cone aeroshell and will provide invaluable high-energy orbital re-entry flight data. This data will be essential in supporting the HIAD team to mature the technology to diameters of 10m and greater. Aeroshells of this scale are applicable to potential near-term commercial applications and future NASA missions. Currently the LOFTID project has completed fabrication of the engineering design unit (EDU) inflatable structure (IS) and the flexible thermal protection system (F-TPS). These two components along with the rigid nose and center body comprise the HIAD aeroshell system. This EDU aeroshell is the precursor to the LOFTID aeroshell that will be used for flight. The EDU was built to verify the design given the subtle differences between the LOFTID aeroshell and past aeroshell designs that have been fabricated under the NASA HIAD project. To characterize the structural performance of the LOFTID aeroshell design, three structural tests will be performed. The first test to be conducted is static load testing, which will induce a uniform load across the forward surface of the aeroshell to simulate the expected pressure forces during atmospheric entry. The IS integrated with the rigid center body will first be tested alone to provide data for analytical model correlation, and then the F-TPS will be integrated for a second series of static load testing of the full aeroshell system. Instrumentation will be employed during the test series to measure component loads during testing, and a laser scanner will be used to generate a 3D map of the aeroshell surface to verify that the shape of the structure is acceptable at the simulated flight loads. After static load testing, pack and deployment testing will be conducted multiple times on the integrated system to demonstrate the aeroshells ability to fit within the required packed volume for the LOFTID mission without experiencing significant damage. Finally, the aeroshell will undergo modal testing to characterize its structural response. This presentation will discuss the setup and execution of each of the three tests that the EDU aeroshell will undergo. In addition, initial results of the testing will be presented outlining key findings as LOFTID moves for-ward with fabrication of the flight aeroshell

Assessment of Hydration Thermodynamics at Protein Interfaces with Grid Cell Theory

Molecular dynamics simulations have been analyzed with the Grid Cell Theory (GCT) method to spatially resolve the binding enthalpies and entropies of water molecules at the interface of 17 structurally diverse proteins. Correlations between computed energetics and structural descriptors have been sought to facilitate the development of simple models of protein hydration. Little correlation was found between GCT-computed binding enthalpies and continuum electrostatics calculations. A simple count of contacts with functional groups in charged amino acids correlates well with enhanced water stabilization, but the stability of water near hydrophobic and polar residues depends markedly on its coordination environment. The positions of X-ray-resolved water molecules correlate with computed high-density hydration sites, but many unresolved waters are significantly stabilized at the protein surfaces. A defining characteristic of ligand-binding pockets compared to nonbinding pockets was a greater solvent-accessible volume, but average water thermodynamic properties were not distinctive from other interfacial regions. Interfacial water molecules are frequently stabilized by enthalpy and destabilized entropy with respect to bulk, but counter-examples occasionally occur. Overall detailed inspection of the local coordinating environment appears necessary to gauge the thermodynamic stability of water in protein structures

Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner

BACKGROUND: The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. METHODS: Mono-arthritis was induced by unilateral intra-articular injection of complete Freund’s adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK(1)) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP(8–37)). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. RESULTS: Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. CONCLUSIONS: We provide evidence that environmental cold exposure enhances pain and increases blood flow in a mono-arthritis model. These changes are dependent on TRPA1. Thus, TRPA1 may act locally within the joint to influence blood flow via sensory nerves, in addition to its established nociceptive actions

Indigenous Peoples and the Australian census: value, trust, and participation

In this commentary we, as a group of Indigenous academics, trace the relationship between the Australian census and Indigenous peoples, addressing historical and present dimensions through the dual lens of value and trust. Although we come from various disciplines including statistics, public health, social science, and human geography, our approach and analysis is firmly rooted in, and builds upon, postcolonial demography that Kukutai & Taylor (2012 p. 14) state, “highlights the epistemological and methodological shortcomings of applied demographic research on Indigenous peoples, and generates calls for more innovative approaches.

The Union of Hearts Depicted: Gladstone, Home Rule and United Ireland

First paragraph: William Ewart Gladstone detested political cartoons. They embodied caricature, the exaggeration of a particular feature into a deformity to excite ridicule or hatred. Cartoons, Gladstone once pointed out, had not existed in ancient Greece. There the ideal of human beauty was so deeply cherished that its distortion was not tolerated. Yet cartoons did the statesman powerful service during his long career. Their very frequency consolidated his image as a popular politician, bringing out qualities such as courage and tenacity that he was happy to have publicised. Nowhere, however, did they advance his cause more than in Ireland after the introduction of Home Rule. The nationalist journal United Ireland, as the illustrations in this paper will show, gave currency to striking depictions of Gladstone; and they vividly portrayed the union of hearts between England and Ireland that he preached so persistently in the late 1880s. The purpose of this article is to examine a sample of the cartoons, but first they need to be placed in their context