149 research outputs found
Energy Cascade in a Nonlinear Mechanistic Model of Turbulence
Energy transfer plays an essential role in many natural and engineering processes which include different scales. Understanding how the energy cascade (which refers to the energy transfer among the different scales) works is of primary importance. One notable example is the energy cascade in turbulent flow whose kinetic energy is transferred from large eddies to smaller ones. Below a threshold scale the energy is dissipated due to viscous friction. We introduce a nonlinear phenomenological mechanistic model of turbulence which consists of masses connected by springs arranged in a binary tree structure. To represent the various scales, the masses are gradually decreased in lower levels. The bottom level of the model consists of nonlinear energy sinks to provide dissipation. Based on previous research, we choose the system parameters and analyze its behavior for simple impulsive excitations. The decay of the total mechanical energy and the discrete energy spectrum of the system are compared for different impulse magnitudes. It is demonstrated that the dissipation is much more significant compared to the linear model, if the input energy is large enough. The energy spectra are compared with that of the linear model. We find that the energy spectrum of the nonlinear model better highlights the cut-off feature of the Kolmogorov spectrum
C3 deficiency ameliorates the negative effects of irradiation of the young brain on hippocampal development and learning
Radiotherapy in the treatment of pediatric brain tumors is often associated with debilitating late-appearing adverse effects, such as intellectual impairment. Areas in the brain harboring stem cells are particularly sensitive to irradiation (IR) and loss of these cells may contribute to cognitive deficits. It has been demonstrated that IR-induced inflammation negatively affects neural progenitor differentiation. In this study, we used mice lacking the third complement component (C3-/-) to investigate the role of complement in a mouse model of IR-induced injury to the granule cell layer (GCL) of the hippocampus. C3-/- and wild type (WT) mice received a single, moderate dose of 8 Gy to the brain on postnatal day 10. The C3-/- mice displayed 55 % more microglia (Iba-1+) and a trend towards increase in proliferating cells in the GCL compared to WT mice 7 days after IR. Importantly, months after IR C3-/- mice made fewer errors than WT mice in a reversal learning test indicating better learning capacity in C3-/- mice after IR. Notably, months after IR C3-/- and WT mice had similar GCL volumes, survival of newborn cells (BrdU), microglia (Iba-1) and astrocyte (S100β) numbers in the GCL. In summary, our data show that the complement system contributes to IR-induced loss of proliferating cells and maladaptive inflammatory responses in the acute phase after IR, leading to impaired learning capacity in adulthood. Targeting the complement system is hence promising for future strategies to reduce the long-term adverse consequences of IR in the young brain
Serum concentrations of the axonal injury marker neurofilament light protein are not influenced by blood-brain barrier permeability
A blood biomarker to monitor individual susceptibility to neuronal injury from cranial radiotherapy could potentially help to individualize radiation treatment and thereby reduce the incidence and severity of late effects. An important feature of such a blood biomarker is that its concentration is not confounded by varying degrees of release from the brain into the blood across the blood-brain barrier (BBB). In this study, we investigated serum neurofilament light protein (NFL) concentrations in 21-day old mice following a single dose of cranial irradiation (8 Gy). Cranial irradiation resulted in acute cell injury measured as a 12.9-fold increase in caspase activity 6 h after irradiation; activation of inflammation measured by levels of CCL2 and increased BBB permeability measured by 14C-sucrose concentration ratios in brain and cerebrospinal fluid (CSF). Serum levels of NFL peaked at 6 h after both anesthesia and cranial irradiation, but no timely correlation of serum NFL concentration with BBB permeability was found. Further, three groups of patients with different degrees of BBB impairment (measured as the CSF/serum albumin ratio) were investigated. There was no correlation between serum NFL concentration and CSF/serum albumin ratio (r = 0.139, p = 0.3513), however a strong correlation was found for NFL concentration in serum and NFL concentration in CSF (r = 0.6303, p < 0.0001). In conclusion, serum NFL appears to be a reliable blood biomarker for neuronal injury, and its concentration is not confounded by BBB permeability
Biostratigraphic Evidence Relating to the Age-Old Question of Hannibal's Invasion of Italy, I: History and Geological Reconstruction
Controversy over the alpine route that Hannibal of Carthage followed from the Rhône Basin into Italia has raged amongst classicists and ancient historians for over two millennia. The motivation for identifying the route taken by the Punic Army through the Alps lies in its potential for identifying sites of historical archaeological significance and for the resolution of one of history's most enduring quandaries. Here, we present stratigraphic, geochemical and microbiological evidence recovered from an alluvial floodplain mire located below the Col de la Traversette (~3000 m asl—above sea level) on the French/Italian border that potentially identifies the invasion route as the one originally proposed by Sir Gavin de Beer (de Beer 1974). The dated layer is termed the MAD bed (mass animal deposition) based on disrupted bedding, greatly increased organic carbon and key/specialized biological components/compounds, the latter reported in Part II of this paper. We propose that the highly abnormal churned up (bioturbated) bed was contaminated by the passage of Hannibal's animals, possibly thousands, feeding and watering at the site, during the early stage of Hannibal's invasion of Italia (218 bc)
Biostratigraphic Evidence Relating to the Age-Old Question of Hannibal's Invasion of Italy, II: Chemical Biomarkers and Microbial Signatures
Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesAs discussed in Part I, a large accumulation of mammalian faeces at the mire site in the upper Guil Valley near Mt. Viso, dated to 2168 cal 14C yr., provides the first evidence of the passage of substantial but indeterminate numbers of mammals within the time frame of the Punic invasion of Italia. Specialized organic biomarkers bound up in a highly convoluted and bioturbated bed constitute an unusual anomaly in a histosol comprised of fibric and hemist horizons that are usually expected to display horizontal bedding. The presence of deoxycholic acid and ethylcoprostanol derived from faecal matter, coupled with high relative numbers of Clostridia 16S rRNA genes, suggests a substantial accumulation of mammalian faeces at the site over 2000 years ago. The results reported here constitute the first chemical and biological evidence of the passage of large numbers of mammals, possibly indicating the route of the Hannibalic army at this time. Combined with the geological analysis reported in Part I, these data provide a background supporting the need for further historical archaeological exploration in this area.Ye
Palaeoclimate inferred from δ18O and palaeobotanical indicators in freshwater tufa of Lake Äntu Sinijärv, Estonia
We investigated a 3.75-m-long lacustrine sediment record from Lake Äntu Sinijärv, northern Estonia, which has a modeled basal age >12,800 cal yr BP. Our multi-proxy approach focused on the stable oxygen isotope composition (δ18O) of freshwater tufa. Our new palaeoclimate information for the Eastern Baltic region, based on high-resolution δ18O data (219 samples), is supported by pollen and plant macrofossil data. Radiocarbon dates were used to develop a core chronology and estimate sedimentation rates. Freshwater tufa precipitation started ca. 10,700 cal yr BP, ca. 2,000 years later than suggested by previous studies on the same lake. Younger Dryas cooling is documented clearly in Lake Äntu Sinijärv sediments by abrupt appearance of diagnostic pollen (Betula nana, Dryas octopetala), highest mineral matter content in sediments (up to 90 %) and low values of δ18O (less than −12 ‰). Globally recognized 9.3- and 8.2-ka cold events are weakly defined by negative shifts in δ18O values, to −11.3 and −11.7 ‰, respectively, and low concentrations of herb pollen and charcoal particles. The Holocene thermal maximum (HTM) is palaeobotanically well documented by the first appearance and establishment of nemoral thermophilous taxa and presence of water lilies requiring warm conditions. Isotope values show an increasing trend during the HTM, from −11.5 to −10.5 ‰. Relatively stable environmental conditions, represented by only a small-scale increase in δ18O (up to 1 ‰) and high pollen concentrations between 5,000 and 3,000 cal yr BP, were followed by a decrease in δ18O, reaching the most negative value (−12.7 ‰) recorded in the freshwater tufa ca. 900 cal yr BP
Characterisation of a Desmosterol Reductase Involved in Phytosterol Dealkylation in the Silkworm, Bombyx mori
Most species of invertebrate animals cannot synthesise sterols de novo and many that feed on plants dealkylate phytosterols (mostly C29 and C28) yielding cholesterol (C27). The final step of this dealkylation pathway involves desmosterol reductase (DHCR24)-catalysed reduction of desmosterol to cholesterol. We now report the molecular characterisation in the silkworm, Bombyx mori, of such a desmosterol reductase involved in production of cholesterol from phytosterol, rather than in de novo synthesis of cholesterol. Phylogenomic analysis of putative desmosterol reductases revealed the occurrence of various clades that allowed for the identification of a strong reductase candidate gene in Bombyx mori (BGIBMGA 005735). Following PCR-based cloning of the cDNA (1.6 kb) and its heterologous expression in Saccharomyces cerevisae, the recombinant protein catalysed reduction of desmosterol to cholesterol in an NADH- and FAD- dependent reaction
A Novel Ecdysone Receptor Mediates Steroid-Regulated Developmental Events during the Mid-Third Instar of Drosophila
The larval salivary gland of Drosophila melanogaster synthesizes and secretes glue glycoproteins that cement developing animals to a solid surface during metamorphosis. The steroid hormone 20-hydroxyecdysone (20E) is an essential signaling molecule that modulates most of the physiological functions of the larval gland. At the end of larval development, it is known that 20E—signaling through a nuclear receptor heterodimer consisting of EcR and USP—induces the early and late puffing cascade of the polytene chromosomes and causes the exocytosis of stored glue granules into the lumen of the gland. It has also been reported that an earlier pulse of hormone induces the temporally and spatially specific transcriptional activation of the glue genes; however, the receptor responsible for triggering this response has not been characterized. Here we show that the coordinated expression of the glue genes midway through the third instar is mediated by 20E acting to induce genes of the Broad Complex (BRC) through a receptor that is not an EcR/USP heterodimer. This result is novel because it demonstrates for the first time that at least some 20E-mediated, mid-larval, developmental responses are controlled by an uncharacterized receptor that does not contain an RXR-like component
International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)
Background
Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment.
Methods and results
Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines).
Conclusions
The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world
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