Analytic shock-fronted solutions to a reaction-diffusion equation with negative diffusivity

Reaction-diffusion equations (RDEs) model the spatiotemporal evolution of a density field $u(\vec{x},t)$ according to diffusion and net local changes. Usually, the diffusivity is positive for all values of $u$, which causes the density to disperse. However, RDEs with negative diffusivity can model aggregation, which is the preferred behaviour in some circumstances. In this paper, we consider a nonlinear RDE with quadratic diffusivity $D(u) = (u - a)(u - b)$ that is negative for $u\in(a,b)$. We use a non-classical symmetry to construct analytic receding time-dependent, colliding wave, and receding travelling wave solutions. These solutions are initially multi-valued, and we convert them to single-valued solutions by inserting a shock. We examine properties of these analytic solutions including their Stefan-like boundary condition, and perform a phase plane analysis. We also investigate the spectral stability of the $u = 0$ and $u=1$ constant solutions, and prove for certain $a$ and $b$ that receding travelling waves are spectrally stable. Additionally, we introduce an new shock condition where the diffusivity and flux are continuous across the shock. For diffusivity symmetric about the midpoint of its zeros, this condition recovers the well-known equal-area rule, but for non-symmetric diffusivity it results in a different shock position.Comment: 35 pages, 10 figure

MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension

Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology

Biodistribution and inflammatory profiles of novel penton and hexon double-mutant serotype 5 adenoviruses

The use of adenovirus serotype 5 (Ad5) vectors in the clinical setting is severely hampered by the profound liver tropism observed after intravascular delivery coupled with the pronounced inflammatory and innate immune response elicited by these vectors. Liver transduction by circulating Ad5 virions is mediated by a high-affinity interaction between the capsid hexon protein and blood coagulation factor X (FX), whilst penton-α(v)integrin interactions are thought to contribute to the induction of anti-Ad5 inflammatory and innate immune responses. To overcome these limitations, we sought to develop and characterise for the first time novel Ad5 vectors possessing mutations ablating both hexon:FX and penton:integrin interactions. As expected, intravascular administration of the FX binding-ablated Ad5HVR5*HVR7*E451Q vector (AdT*) resulted in significantly reduced liver transduction in vivo compared to Ad5. In macrophage-depleted mice, increased spleen uptake of AdT* was accompanied by an elevation in the levels of several inflammatory mediators. However ablation of the penton RGD motif in the AdT* vector background (AdT*RGE) resulted in a significant 5-fold reduction in spleen uptake and attenuated the antiviral inflammatory response. A reduction in spleen uptake and inflammatory activation was also observed in animals after intravascular administration of Ad5RGE compared to the parental Ad5 vector, with reduced co-localisation of the viral beta-galactosidase transgene with MAdCAM-1+ sinus-lining endothelial cells. Our detailed assessment of these novel adenoviruses indicates that penton base RGE mutation in combination with FX binding-ablation may be a viable strategy to attenuate the undesired liver uptake and pro-inflammatory responses to Ad5 vectors after intravascular deliver

What evidence exists for temporal variability in Arctic terrestrial and freshwater biodiversity throughout the Holocene? A systematic map protocol

Background: The Arctic tundra is subject to the greatest climate change-induced temperature rises of any biome. Both terrestrial and freshwater biota are responding to recent climate warming through variability in their distribution, abundance, and richness. However, uncertainty arises within models of future change when considering processes that operate over centennial timescales. A systematic evidence synthesis of centennial-scale variability in biodiversity does not currently exist for the Arctic biome. Here, we sought to address the primary research question: what evidence exists for temporal variability in Arctic terrestrial and freshwater biodiversity throughout the Holocene (11,650 years before present (yBP)-OyBP)? Methods: Consultation with stakeholders informed key definitions, scoping and the appropriateness of the research question. The research question was structured using a PECO framework-Arctic biota (P), a timestamped year in the Holocene (E), another year in the Holocene (C), and the dimensions of biodiversity that have been measured (O)-to inform the search strategy. Search strings were benchmarked against a test list of 100 known sources to ensure a specific and comprehensive return of literature. Searches will occur across 13 bibliographic databases. The eligibility criteria specify that sources must: (a) use 'proxy' methods to measure biodiversity; (b) fall within the spatial extent of the contemporary Arctic tundra biome; and (c) consist of a time-series that overlaps with 11,650yBP to OyBP (1950AD). Information coded from studies will include proxy-specific information to account for both temporal uncertainty (i.e., the characteristics of age-depth models and dating methods) and taxonomic uncertainty (i.e., the samples and processes used for taxonomic identification). We will assess temporal uncertainty within each source by determining the quality of dating methods and measures; this information will be used to harmonise dates onto the IntCa120 calibration curve and determine the available temporal resolution and extent of evidence through space. Key outputs of this systematic map will be: (1) a graph database containing the spatial-temporal properties of each study dataset with taxonomic harmonisation; and (2) a geographical map of the evidence base.Peer reviewe

Genetic variation for tuber mineral concentrations in accessions of the Commonwealth Potato Collection

The variation in tuber mineral concentrations amongst accessions of wild tuber-bearing Solanum species in the Commonwealth Potato Collection (CPC) was evaluated under greenhouse conditions. Selected CPC accessions, representing the eco-geographical distribution of wild potatoes, were grown to maturity in peat-based compost under controlled conditions. Tubers from five plants of each accession were harvested, bulked and their mineral composition analysed. Among the germplasm investigated, there was a greater range in tuber concentrations of some elements of nutritional significance to both plants and animals, such as (Ca, Fe and Zn; 6.7, 3.6, and 4.5-fold respectively) than others, such as (K, P and S; all <3-fold). Significant positive correlations were found between mean altitude of the species' range and tuber P, K, Cu and Mg concentrations. The amount of diversity observed in the CPC collection indicates the existence of wide differences in tuber mineral accumulation among different potato accessions. This might be useful in breeding for nutritional improvement of potato tubers

A miniaturized 4 K platform for superconducting infrared photon counting detectors

We report on a miniaturized platform for superconducting infrared photon counting detectors. We have implemented a fibre-coupled superconducting nanowire single photon detector in a Stirling/Joule–Thomson platform with a base temperature of 4.2 K. We have verified a cooling power of 4 mW at 4.7 K. We report 20% system detection efficiency at 1310 nm wavelength at a dark count rate of 1 kHz. We have carried out compelling application demonstrations in single photon depth metrology and singlet oxygen luminescence detection

Municipal water quantities and health in Nunavut households: an exploratory case study in Coral Harbour, Nunavut, Canada

Background: Access to adequate quantities of water has a protective effect on human health and well-being. Despite this, public health research and interventions are frequently focused solely on water quality, and international standards for domestic water supply minimums are often overlooked or unspecified. This trend is evident in Inuit and other Arctic communities even though numerous transmissible diseases and bacterium infections associated with inadequate domestic water quantities are prevalent. Objectives: Our objective was to explore the pathways by which the trucked water distribution systems being used in remote northern communities are impacting health at the household level, with consideration given to the underlying social and environmental determinants shaping health in the region. Methods: Using a qualitative case study design, we conducted 37 interviews (28 residents, 9 key informants) and a review of government water documents to investigate water usage practices and perspectives. These data were thematically analysed to understand potential health risks in Arctic communities and households. Results: Each resident receives an average of 110 litres of municipal water per day. Fifteen of 28 households reported experiencing water shortages at least once per month. Of those 15, most were larger households (5 people or more) with standard sized water storage tanks. Water shortages and service interruptions limit the ability of some households to adhere to public health advice. The households most resilient, or able to cope with domestic water supply shortages, were those capable of retrieving their own drinking water directly from lake and river sources. Residents with extended family and neighbours, whom they can rely on during shortages, were also less vulnerable to municipal water delays. Conclusions: The relatively low in-home water quantities observed in Coral Harbour, Nunavut, appear adequate for some families. Those living in overcrowded households, however, are accessing water in quantities more typically seen in water insecure developing countries. We recommend several practical interventions and revisions to municipal water supply systems

The Milky Way in X-rays for an outside observer: Log(N)-Log(S) and Luminosity Function of X-ray binaries from RXTE/ASM data

We study the Log(N)-Log(S) and X-ray luminosity function in the 2-10 keV energy band, and the spatial (3-D) distribution of bright, log(L_X) > 34-35 erg/s, X-ray binaries in the Milky Way. In agreement with theoretical expectations and earlier results we found significant differences between the spatial distributions of low (LMXB) and high (HMXB) mass X-ray binaries. The volume density of LMXB sources peaks strongly at the Galactic Bulge. HMXBs tend to avoid the inner 3-4 kpc of the Galaxy, HMXBs are more concentrated towards the Galactic Plane and show clear signatures of the spiral structure in their spatial distribution. LMXB sources have a flatter Log(N)-Log(S) distribution and luminosity function than HMXBs. The integrated 2-10 keV luminosities of X-ray binaries, averaged over 1996--2000, are 2-3 * 10^39 (LMXB) and 2-3 * 10^38 (HMXB) erg/s. Normalised to the stellar mass and the star formation rate, respectively, these correspond to 5 * 10^28 erg/s/M_sol for LMXBs and 5 * 10^37 erg/s/(M_sol/yr) for HMXBs. Due to the shallow slopes of the luminosity functions the integrated emission of X-ray binaries is dominated by the 5-10 most luminous sources which determine the appearance of the Milky Way in the standard X-ray band for an outside observer. In particular variability of individual sources or an outburst of a bright transient source can increase the integrated luminosity of the Milky Way by as much as a factor of ~2. Although the average LMXB luminosity function shows a break near the Eddington luminosity for a 1.4 M_sol neutron star, at least 11 sources showed episodes of super-Eddington luminosity during ASM observations. We provide the maps of distribution of X-ray binaries in the Milky Way in various projections, which can be compared to images of nearby galaxies taken by CHANDRA and XMM-Newton.Comment: 23 pages, 19 figures, accepted by A&

Can we monitor heart attack in the troponin era: evidence from a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Troponins (highly sensitive biomarkers of myocardial damage) increase counts of myocardial infarction (MI) in clinical practice, but their impact on trends in admission rates for MI in National statistics is uncertain.</p> <p>Methods</p> <p>Cases coded as MI or other cardiac diagnoses in the Hospital Morbidity Data Collection (MI-HMDC) in Western Australia in 1998 and 2003 were classified using revised criteria for MI developed by an International panel convened by the American Heart Association (AHA criteria) using information on symptoms, ECGs and cardiac biomarkers abstracted from samples of medical notes. Age-sex standardized rates of MI-HMDC were compared with rates of MI based on AHA criteria including troponins (MI-AHA) or traditional biomarkers only (MI-AHAck).</p> <p>Results</p> <p>Between 1998 and 2003, rates of MI-HMDC decreased by 3.5% whereas rates of MI-AHA increased by 17%, a difference largely due to increased false-negative cases in the HMDC associated with marked increased use of troponin tests in cardiac admissions generally, and progressively lower test thresholds. In contrast, rates of MI-AHA_ckdeclined by 18%.</p> <p>Conclusions</p> <p>Increasing misclassification of MI-AHA by the HMDC may be due to reluctance by clinicians to diagnose MI based on relatively small increases in troponin levels. These influences are likely to continue. Monitoring MI using AHA criteria will require calibration of commercially available troponin tests and agreement on lower diagnostic thresholds for epidemiological studies. Declining rates of MI-AHA_ckare consistent with long-standing trends in MI in Western Australia, suggesting that neither MI-HMDC nor MI-AHA reflect the true underlying population trends in MI.</p