Component-aware Orchestration of Cloud-based Enterprise Applications, from TOSCA to Docker and Kubernetes

Enterprise IT is currently facing the challenge of coordinating the management of complex, multi-component applications across heterogeneous cloud platforms. Containers and container orchestrators provide a valuable solution to deploy multi-component applications over cloud platforms, by coupling the lifecycle of each application component to that of its hosting container. We hereby propose a solution for going beyond such a coupling, based on the OASIS standard TOSCA and on Docker. We indeed propose a novel approach for deploying multi-component applications on top of existing container orchestrators, which allows to manage each component independently from the container used to run it. We also present prototype tools implementing our approach, and we show how we effectively exploited them to carry out a concrete case study

Climate reconstruction from Barrow Island, Western Australia

Barrow Island ( 20.7°S) is ideally situated to register the first coastal occupations in Australia as well as peoples' responses to major changes in sea level, climate and eventual isolation from critical resources on the mainland. Its location in the arid region between monsoonal and extratropical rainfall belts also imply that Barrow Island may have experienced dramatic changes in precipitation over the period of human occupation. Boodie cave has been the focus of Barrow Island Archeological Project and records a rich record of human occupation. Also present at Boodie cave are significant quantities of water-lain cave carbonates (flowstones, stalactites, and stalagmites). Active (modern) deposition of such carbonates is limited to very small encrustations and consists primarily of stalactites that are less than 5 cm in diameter. This situation indicates that deposition of significant carbonates is indicative of wetter conditions at Barrow Island and dating of these carbonates using the U/Th method provides a record of wet intervals at Barrow Island over the last 120 thousand years. In addition to ages from flowstones, three complete speleothems were collected Ledge Cave for climatic reconstruction using stable isotopes. Ledge cave is large subterranean with high relative humidity (>98%) and abundant, but largely inactive speleothems. The wettest interval in our cave carbonate record predates stratigraphic units with cultural material, but indicates that wet intervals on Barrow Island were broadly coincidental with lake expansions on the Australian mainland. In particular, a very wet interval between 120 and 90 ka is recorded in two of the Ledge Cave speleothems. The Barrow Island speleothem record suggests that displacement of the Intertropical Convergence Zone (ITCZ) and the strength of the Indo-Australian monsoon may have been the most important influence on water balance at Barrow Island. Continued development of these climate archives will offer insights into climate that is directly applicable to the unique human occupation record also preserved at this site

Thermal stabilization of metal matrix nanocomposites by nanocarbon reinforcements

Metal matrix composites reinforced by nanocarbon materials, such as carbon nanotubes or nanodiamonds, are very promising materials for a large number of functional and structural applications. Carbon nanotubes and nanodiamonds-reinforced metal matrix nanocomposites with different concentrations of the carbon phase were processed by high-pressure torsion deformation and the evolving nanostructures were thoroughly analyzed by electron microscopy. Particular emphasis is placed on the thermal stability of the nanocarbon reinforced metal matrix composites, which is less influenced by the amount of added nanocarbon reinforcements than by the nanocarbon reinforcement type and its distribution in the metal matrix

Cloud angular momentum and effective viscosity in global SPH simulations with feedback

We examine simulations of isolated galaxies to analyse the effects of localized feedback on the formation and evolution of molecular clouds. Feedback contributes to turbulence and the destruction of clouds, leading to a population of clouds that is younger, less massive, and with more retrograde rotation. We investigate the evolution of clouds as they interact with each other and the diffuse interstellar medium, and determine that the role of cloud interactions differs strongly with the presence of feedback: in models without feedback, scattering events dramatically increase the retrograde fraction, but in models with feedback, mergers between clouds may slightly increase the prograde fraction. We also produce an estimate of the viscous time-scale due to cloud–cloud collisions, which increases with increasing strength of feedback (tν ∼ 20 Gyr versus tν ∼ 10 Gyr), but is still much smaller than previous estimates (tν ∼ 1000 Gyr); although collisions become more frequent with feedback, less energy is lost in each collision than in the models without feedback

CSF Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in PD and DLB

BACKGROUND: Molecular pathways associated with α-synuclein proteostasis have been detected in genetic studies and in cell models and include autophagy, ubiquitin-proteasome system, mitochondrial homeostasis, and synaptic plasticity. However, we lack biomarkers that are representative for these pathways in human biofluids. OBJECTIVE: The objective of this study was to evaluate CSF protein profiles of pathways related to α-synuclein proteostasis. METHODS: We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with α-synucleinopathy (385 PD patients and 67 DLB patients). We included 80 PD patients and 17 DLB patients with variants in the glucocerebrosidase gene to serve as proxy for accelerated α-synuclein pathology with pronounced clinical trajectories. RESULTS: (1) Proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy were lower in PD and DLB patients compared with healthy controls. (2) These patterns were more pronounced in DLB than in PD patients, accentuated by GBA variant status in both entities. (3) CSF levels of these proteins were positively associated with CSF levels of total α-synuclein, with lower levels of proteostasis proteins related to lower levels of total α-synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of α-synuclein longitudinally compared with PD patients with a normal proteostasis profile. CONCLUSION: CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to α-synuclein proteostasis in PD and DLB

Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson’s disease and dementia with Lewy bodies

The clinicopathological heterogeneity in Lewy-body diseases (LBD) highlights the need for pathology-driven biomarkers in-vivo. Misfolded alpha-synuclein (α-Syn) is a lead candidate based on its crucial role in disease pathophysiology. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has recently shown high sensitivity and specificity for the detection of misfolded α-Syn in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this study we performed the CSF RT-QuIC assay in 236 PD and 49 DLB patients enriched for different genetic forms with mutations in GBA, parkin, PINK1, DJ1, and LRRK2. A subgroup of 100 PD patients was also analysed longitudinally. We correlated kinetic seeding parameters of RT-QuIC with genetic status and CSF protein levels of molecular pathways linked to α-Syn proteostasis. Overall, 85% of PD and 86% of DLB patients showed positive RT-QuIC α-Syn seeding activity. Seeding profiles were significantly associated with mutation status across the spectrum of genetic LBD. In PD patients, we detected positive α-Syn seeding in 93% of patients carrying severe GBA mutations, in 78% with LRRK2 mutations, in 59% carrying heterozygous mutations in recessive genes, and in none of those with bi-allelic mutations in recessive genes. Among PD patients, those with severe GBA mutations showed the highest seeding activity based on RT-QuIC kinetic parameters and the highest proportion of samples with 4 out of 4 positive replicates. In DLB patients, 100% with GBA mutations showed positive α-Syn seeding compared to 79% of wildtype DLB. Moreover, we found an association between α-Syn seeding activity and reduced CSF levels of proteins linked to α-Syn proteostasis, specifically lysosome-associated membrane glycoprotein 2 and neurosecretory protein VGF. These findings highlight the value of α-Syn seeding activity as an in-vivo marker of Lewy-body pathology and support its use for patient stratification in clinical trials targeting α-Syn

The role of drag and gravity on dust concentration in a gravitationally unstable disc

We carry out three-dimensional smoothed particle hydrodynamics simulations to study the role of gravitational and drag forces on the concentration of large dust grains (St > 1) in the spiral arms of gravitationally unstable protoplanetary discs, and the resulting implications for planet formation. We find that both drag and gravity play an important role in the evolution of large dust grains. If we include both, grains that would otherwise be partially decoupled will become well coupled and trace the spirals. For the dust grains most influenced by drag (with Stokes numbers near unity), the dust disc quickly becomes gravitationally unstable and rapidly forms clumps with masses between 0.15–6M⊕. A large fraction of clumps are below the threshold where runaway gas accretion can occur. However, if dust self-gravity is neglected, the dust is unable to form clumps, despite still becoming trapped in the gas spirals. When large dust grains are unable to feel either gas gravity or drag, the dust is unable to trace the gas spirals. Hence, full physics is needed to properly simulate dust in gravitationally unstable discs. Dust trapping of large grains in spiral arms of discs stable to gas fragmentation could explain planet formation in very young discs by a population of planetesimals formed due to the combined roles of drag and gravity in the earliest stages of a disc’s evolution. Furthermore, it highlights that gravitationally unstable discs are not just important for forming gas giants quickly, it can also rapidly form Earth mass bodies

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy

Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient. Nowadays, optical modalities, such as optical coherence tomography (OCT) and Raman spectroscopy (RS), have proven to detect cancer in real time and can provide more detailed clinical information of a lesion, e.g. its penetration depth (stage) and the differentiation of the cells (grade). In this paper, we present an ex vivo study performed with a combined piezoelectric tube-based OCT-probe and fiber optic RS-probe imaging system that allows large field-of-view imaging of bladder biopsies, using both modalities and co-registered visualization, detection and grading of cancerous bladder lesions. In the present study, 119 examined biopsies were characterized, showing that fiber-optic based OCT provides a sensitivity of 78% and a specificity of 69% for the detection of non-muscle-invasive bladder cancer, while RS, on the other hand, provides a sensitivity of 81% and a specificity of 61% for the grading of low- and high-grade tissues. Moreover, the study shows that a piezoelectric tube-based OCT probe can have significant endurance, suitable for future long-lasting in vivo applications. These results also indicate that combined OCT and RS fiber probe-based characterization offers an exciting possibility for label-free and morpho-chemical optical biopsies for bladder cancer diagnostics. © 2020 The Royal Society of Chemistry

Transplacental Passage of Interleukins 4 and 13?

The mechanisms by which prenatal events affect development of adult disease are incompletely characterized. Based on findings in a murine model of maternal transmission of asthma risk, we sought to test the role of the pro-asthmatic cytokines interleukin IL-4 and -13. To assess transplacental passage of functional cytokines, we assayed phosphorylation of STAT-6, a marker of IL-4 and -13 signaling via heterodimeric receptor complexes which require an IL-4 receptor alpha subunit. IL-4 receptor alpha−/− females were mated to wild-type males, and pregnant females were injected with supraphysiologic doses of IL-4 or 13. One hour after injection, the receptor heterozygotic embryos were harvested and tissue nuclear proteins extracts assayed for phosphorylation of STAT-6 by Western blot. While direct injection of embryos produced a robust positive control, no phosphorylation was seen after maternal injection with either IL-4 or -13, indicating that neither crossed the placenta in detectable amounts. The data demonstrate a useful approach to assay for transplacental passage of functional maternal molecules, and indicate that molecules other than IL-4 and IL-13 may mediate transplacental effects in maternal transmission of asthma risk