The capabilities and limitations of conductance-based compartmental neuron models with reduced branched or unbranched morphologies and active dendrites

Conductance-based neuron models are frequently employed to study the dynamics of biological neural networks. For speed and ease of use, these models are often reduced in morphological complexity. Simplified dendritic branching structures may process inputs differently than full branching structures, however, and could thereby fail to reproduce important aspects of biological neural processing. It is not yet well understood which processing capabilities require detailed branching structures. Therefore, we analyzed the processing capabilities of full or partially branched reduced models. These models were created by collapsing the dendritic tree of a full morphological model of a globus pallidus (GP) neuron while preserving its total surface area and electrotonic length, as well as its passive and active parameters. Dendritic trees were either collapsed into single cables (unbranched models) or the full complement of branch points was preserved (branched models). Both reduction strategies allowed us to compare dynamics between all models using the same channel density settings. Full model responses to somatic inputs were generally preserved by both types of reduced model while dendritic input responses could be more closely preserved by branched than unbranched reduced models. However, features strongly influenced by local dendritic input resistance, such as active dendritic sodium spike generation and propagation, could not be accurately reproduced by any reduced model. Based on our analyses, we suggest that there are intrinsic differences in processing capabilities between unbranched and branched models. We also indicate suitable applications for different levels of reduction, including fast searches of full model parameter space

Contrasting Spatial Distribution and Risk Factors for Past Infection with Scrub Typhus and Murine Typhus in Vientiane City, Lao PDR

Scrub typhus and murine typhus are neglected but important treatable causes of fever, morbidity and mortality in South-East Asia. Epidemiological data suggests that scrub typhus would be more common in rural areas and murine typhus in urban areas but there are very few comparative data from places where both diseases occur, as is the case in Vientiane, the capital of the Lao PDR. We therefore determined the frequency of IgG antibody seropositivity against scrub typhus and murine typhus, as indices of prior exposure to these pathogens, in a randomly selected population of 2,002 adults living in different neighbourhoods in Vientiane. The overall prevalence of IgG against these two pathogens was ∼20%. However, within the city, the spatial distribution of IgG against these two diseases was radically different - past exposure to murine typhus being more frequent in urbanized areas while past exposure to scrub typhus more frequent in outlying areas. This study underscores the importance of ecological characteristics in improving the understanding of both scrub typhus and murine typhus transmission and epidemiology

Attitude control for satellites flying in VLEO using aerodynamic surfaces

This paper analyses the use of aerodynamic control surfaces, whether passive or active, in order to carry out very low Earth orbit (VLEO) attitude maneuver operations. Flying a satellite in a very low Earth orbit with an altitude of less than 450 km, namely VLEO, is a technological challenge. It leads to several advantages, such as increasing the resolution of optical payloads or increase signal to noise ratio, among others. The atmospheric density in VLEO is much higher than in typical low earth orbit altitudes, but still free molecular flow. This has serious consequences for the maneuverability of a satellite because significant aerodynamic torques and forces are produced. In order to guarantee the controllability of the spacecraft they have to be analyzed in depth. Moreover, at VLEO the density of atomic oxygen increases, which enables the use of air-breathing electric propulsion (ABEP). Scientists are researching in this field to use ABEP as a drag compensation system, and consequently an attitude control based on aerodynamic control could make sense. This combination of technologies may represent an opportunity to open new markets. In this work, several satellite geometric configurations were considered to analyze aerodynamic control: 3-axis control with feather configuration and 2-axis control with shuttlecock configuration. The analysis was performed by simulating the attitude of the satellite as well as the disturbances affecting the spacecraft. The models implemented to simulate the disturbances were the following: Gravitational gradient torque disturbance, magnetic dipole torque disturbance (magnetic field model IGRF12), and aerodynamic torque disturbances (aerodynamic model DTM2013 and wind model HWM14).The maneuvers analyzed were the following: detumbling or attitude stabilization, pointing and demisability. Different VLEO parameters were analyzed for every geometric configuration and spacecraft maneuver. The results determined which of the analyzed geometric configurations suits better for every maneuver

Concepts and Applications of Aerodynamic Attitude and Orbital Control for Spacecraft in Very Low Earth Orbit

Spacecraft operations below 450km, namely Very Low Earth Orbit (VLEO), can offer significant advantages over traditional low Earth orbits, for example enhanced ground resolution for Earth observation, improved communications latency and link budget, or improved signal-to-noise ratio. Recently, these lower orbits have begun to be exploited as a result of technology development, particularly component miniaturisation and cost-reduction, and concerns over the increasing debris population in commercially exploited orbits. However, the high cost of orbital launch and challenges associated with atmospheric drag, causing orbital decay and eventually re-entry are still a key barrier to their wider use for large commercial and civil spacecraft. Efforts to address the impact of aerodynamic drag are being sought through the development of novel drag-compensation propulsion systems and identification of materials which can reduce aerodynamic drag by specularly reflecting the incident gas. However, the presence of aerodynamic forces can also be utilised to augment or improve spacecraft operations at these very low altitudes by providing the capability to perform coarse pointing control and trim or internal momentum management for example. This paper presents concepts for the advantageous use of spacecraft aerodynamics developed as part of DISCOVERER, a Horizon 2020 funded project with the aim to revolutionise Earth observation satellite operations in VLEO. The combination of novel spacecraft geometries and use of aerodynamic control methods are explored, demonstrating the potential for a new generation of Earth observation satellites operating at lower altitudes

JNK2 Promotes Endothelial Cell Alignment under Flow

Endothelial cells in straight, unbranched segments of arteries elongate and align in the direction of flow, a feature which is highly correlated with reduced atherosclerosis in these regions. The mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) is activated by flow and is linked to inflammatory gene expression and apoptosis. We previously showed that JNK activation by flow is mediated by integrins and is observed in cells plated on fibronectin but not on collagen or basement membrane proteins. We now show thatJNK2 activation in response to laminar shear stress is biphasic, with an early peak and a later peak. Activated JNK localizes to focal adhesions at the ends of actin stress fibers, correlates with integrin activation and requires integrin binding to the extracellular matrix. Reducing JNK2 activation by siRNA inhibits alignment in response to shear stress. Cells on collagen, where JNK activity is low, align slowly. These data show that an inflammatory pathway facilitates adaptation to laminar flow, thereby revealing an unexpected connection between adaptation and inflammatory pathways

Discoverer - Making commercial satellite operations in very low earth orbit a reality

DISCOVERER is a €5.7M European Commission funded Horizon 2020 project developing technologies to enable commercially-viable sustained-operation of satellites in very low Earth orbits. Why operate closer to the Earth? For communications applications latency is significantly reduced and link budgets improved, and for remote sensing improved link budgets allow higher resolution or smaller instruments, all providing cost benefits. In addition, all applications benefit from increased launch mass to lower altitudes, whilst end-of-life removal is ensured due to the increased atmospheric drag. However, this drag must also be minimised and compensated for. One of the key technologies being developed by DISCOVERER are materials that encourage specular reflection of the residual atmosphere at these altitudes. Combined with appropriate geometric designs these can significantly reduce drag, provide usable lift for aerodynamic attitude and orbit control, and improve the collection efficiency of aerodynamic intakes for atmosphere breathing electric propulsion systems, all of which are being developed as part of DISCOVERER. The paper provides highlights from the developments to date, and the potential for a new class of aerodynamic commercial satellites operating at altitudes below the International Space Station

Connecting climate action with other sustainable development goals

The international community has committed to combat climate change and achieve 17 Sustainable Development Goals (SDGs). Here we explore (dis)connections in evidence and governance between these commitments. Our structured evidence review suggests that climate change can undermine 16 SDGs, while combatting climate change can reinforce all 17 SDGs but undermine efforts to achieve 12. Understanding these relationships requires wider and deeper interdisciplinary collaboration. Climate change and sustainable development governance should be better connected to maximize the effectiveness of action in both domains. The emergence around the world of new coordinating institutions and sustainable development planning represents promising progress

Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

<p>Abstract</p> <p>Background</p> <p>Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs) delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B) of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs.</p> <p>Methods</p> <p>Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels.</p> <p>Results</p> <p>Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by immunohistological examination.</p> <p>Conclusions</p> <p>Our studies consolidate the properties of lentiviral vectors as a tool for potent gene delivery and for evaluation of mRNA targets for anti-inflammatory therapy. However, in contrast to local anti-TNFα treatment, the therapeutic potential of targeting IL-12B at the RNA level in psoriasis is questioned.</p