An improved engine analysis and optimization tool fo hypersonic combined cycle engines

It is widely accepted that more efficient propulsion technology needs to be developed before the re-usable 'space plane' concept for cheap and reliable access to space can become a practical reality. An engineering tool, called the HYbrid PRopulsion Optimiser, or HyPro for short, has been developed to characterise and optimise the performance of a range of hypersonic propulsion systems, with particular application to air-breathing and hybrid engines. The level of modelling embodied in the tool is particularly appropriate to the rapid parametric studies and configurational trade-offs that are usually conducted during the preliminary design of the propulsion system and the hypersonic vehicle that it is intended to propel. An algorithm, based on the Genetic Programming approach, and exploiting the highly modular structure of the engine model, has been developed to search the configurational design space for the engine geometry that is best adapted to the mission for which it is intended. In contrast to conventional optimisers which can vary only the parameters of the engine design, this tool is able to provide design solutions for the propulsion system without the actual structure of the engine having been specified a priori. Several applications serve to demonstrate the value of the tool in introducing some degree of objectivity into the process of discriminating between the many different configurations that have been proposed for space plane propulsion in the past

Robust multi-disciplinary modelling of future re-usable aerospace planes

Practical embodiment of the Single-Stage to Orbit concept has long been held as the key to unlocking a future of rapid, reliable, even scheduled access to space. The full potential of Single-Stage to Orbit will only be realised when this vehicle concept is integrated into an airline-like operational paradigm which has, as its basis, the re-usability of the individual vehicles that comprise the fleet, but in addition, extends to the long-term assuredness of operations through sustained reliability, quick turnaround, and control over recurring costs to the point where the profitability of the enterprise can be assured for its owners and investors. The purpose of this paper is to make some initial steps towards providing some quantitative answers as to how decisions that are made regarding the design of the actual hardware might impact on long-term viability of the technology through influencing the reliability of the system and eventually its cost when incorporated as part of an integrated transportation system. This is achieved through embedding a physics-based simulation of the performance of the vehicle subsystems, under operational conditions, into a Discrete Event Simulation of spaceport operations, allowing the statistical relationship between the various design characteristics of the vehicle, and the metrics that are relevant to its operational cost, to be exposed

Topoclimate effect on treeline elevation depends on the regional framework: A contrast between Southern Alps (New Zealand) and Apennines (Italy) forests

Deciphering the spatial patterns of alpine treelines is critical for understanding the ecosystem processes involved in the persistence of tree species and their altitudinal limit. Treelines are thought to be controlled by temperature, and other environmental variables but they have rarely been investigated in regions with different land-use change legacies. Here, we systematically investigated treeline elevation in the Apennines (Italy) and Southern Alps (New Zealand) with contrasting human history but similar biogeographic trajectories, intending to identify distinct drivers that affect their current elevation and highlight their respective peculiarities. Over 3622 km of Apennines, treeline elevation was assessed in 302 mountain peaks and in 294 peaks along 4504 km of Southern Alps. The major difference between the Southern Alps and Apennines treeline limit is associated with their mountain aspects. In the Southern Alps, the scarcely anthropized Nothofagus treeline elevation was higher on the warmer equator-facing slopes than on the pole-facing ones. Contrary to what would be expected based on temperature limitation, the elevation of Fagus sylvatica treelines in the Apennines was higher on colder, pole-facing slopes than on human-shaped equator-facing, warmer mountainsides. Pervasive positive correlations were found between treeline elevation and temperature in the Southern Alps but not in the Apennines. While the position of the Fagus and Nothofagus treelines converge on similar isotherms of annual average temperature, a striking isothermal difference between the temperatures of the hottest month on which the two taxonomic groups grow exists. We conclude that actual treeline elevation reflects the ecological processes driven by a combination of local-scale topoclimatic conditions, and human disturbance legacy. Predicting dynamic processes affecting current and future alpine treeline position requires further insight into the modulating influences that are currently understood at a regional scale

Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus - associated hepatocellular carcinoma.

Background: The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC. Methods: We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR)and confocal immunofluorescence. Results: Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling Pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK. Conclusions: Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets

Topography modulates near-ground microclimate in the Mediterranean Fagus sylvatica treeline

Understanding processes controlling forest dynamics has become particularly important in the context of ongoing climate change, which is altering the ecological fitness and resilience of species worldwide. However, whether forest communities would be threatened by projected macroclimate change or unaffected due to the controlling effect of local site conditions is still a matter for debate. After all, forest canopy buffer climate extremes and promote microclimatic conditions, which matters for functional plant response, and act as refugia for understory species in a changing climate. Yet precisely how microclimatic conditions change in response to climate warming will depend on the extent to which vegetation structure and local topography shape air and soil temperature. In this study, we posited that forest microclimatic buffering is sensitive to local topographic conditions and canopy cover, and using meteorological stations equipped with data-loggers we measured this effect during 1 year across a climate gradient (considering aspect as a surrogate of local topography) in a Mediterranean beech treeline growing in contrasting aspects in southern Italy. During the growing season, the below-canopy near-ground temperatures were, on average, 2.4 and 1.0 °C cooler than open-field temperatures for south and north-west aspects, respectively. Overall, the temperature offset became more negative (that is, lower under-canopy temperatures at the treeline) as the open-field temperature increased, and more positive (that is, higher under-canopy temperatures at the treeline) as the open-field temperature decreased. The buffering effect was particularly evident for the treeline on the south-facing slope, where cooling of near-ground temperature was as high as 8.6 °C for the maximum temperature (in August the offset peaked at 10 °C) and as high as 2.5 °C for the average temperature. In addition, compared to the south-facing slope, the northern site exhibited less decoupling from free-air environment conditions and low variability in microclimate trends that closely track the free-air biophysical environment. Although such a decoupling effect cannot wholly isolate forest climatic conditions from macroclimate regional variability in the south-facing treeline, it has the potential to partly offset the regional macroclimatic warming experienced in the forest understory due to anthropogenic climate change

Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men

Background and aim: Experimentally uric acid may induce cardiomyocyte growth and interstitial fibrosis of the heart. However, clinical studies exploring the relationship between serum uric acid (SUA) and left ventricular (LV) mass yielded conflicting results. The aim of our study was to evaluate the relationships between SUA and LV mass in a large group of Caucasian essential hypertensive subjects. Methods and results: We enrolled 534 hypertensive patients free of cardiovascular complications and without severe renal insufficiency. In all subjects routine blood chemistry, including SUA determination, echocardiographic examination and 24 h ambulatory blood pressure (BP) monitoring were obtained. In the overall population we observed no significant correlation of SUA with LV mass indexed for height2.7 (LVMH2.7) (r = 0.074). When the same relationship was analysed separately in men and women, we found a statistically significant correlation in female gender (r = 0.27; p < 0.001), but not in males (r = 0.042; p = NS). When we grouped the study population in sex-specific tertiles of SUA, an increase in LVMH2.7 was observed in the highest tertiles in women (44.5 \ub1 15.6 vs 47.5 16 vs 55.9 \ub1 22.2 g/m2.7; p < 0.001), but not in men. The association between SUA and LVMH2.7 in women lost statistical significance in multiple regression analyses, after adjustment for age, 24 h systolic BP, body mass index, serum creatinine and other potential confounders. Conclusions: Our findings do not support an independent association between SUA and LV mass in Caucasian men and women with arterial hypertension

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus - associated hepatocellular carcinoma

Abstract Background The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC. Methods We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR) and confocal immunofluorescence. Results Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK. Conclusions Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets