New ΔR for the southwest Pacific Ocean

ΔR results of known-age shells from the Solomon and Coral Seas and the northwest coast of New Ireland are presented. The results are too few to be conclusive but indicate that ΔR in this region is variable. An average ΔR value of 370 ± 25 yr is recorded for a range of shell species from Kavieng Harbor, New Ireland, and is primarily attributed to weak equatorial upwelling of depleted 14C due to seasonal current reversals. In contrast, values from the Solomon and Coral Seas are lower (average ΔR = 45 ± 19 yr). Higher ΔR values for some shellfish from these 2 seas is attributed to ingestion of 14Cdepleted sediment by deposit-feeding species

A DSMC investigation of gas flows in micro-channels with bends

Pressure-driven, implicit boundary conditions are implemented in an open source direct simulation Monte Carlo (DSMC) solver, and benchmarked against simple micro-channel flow cases found in the literature. DSMC simulations are then carried out of gas flows for varying degrees of rarefaction along micro-channels with both one and two ninety-degree bends. The results are compared to those from the equivalent straight micro-channel geometry. Away from the immediate bend regions, the pressure and Mach number profiles do not differ greatly from those in straight channels, indicating that there are no significant losses introduced when a bend is added to a micro-channel geometry. It is found that the inclusion of a bend in a micro-channel can increase the amount of mass that a channel can carry, and that adding a second bend produces a greater mass flux enhancement. This increase happens within a small range of Knudsen number (0.02 Knin 0.08). Velocity slip and shear stress profiles at the channel walls are presented for the Knudsen showing the largest mass flux enhancement

The identification of mitochondrial DNA variants in glioblastoma multiforme

Background: Mitochondrial DNA (mtDNA) encodes key proteins of the electron transfer chain (ETC), which produces ATP through oxidative phosphorylation (OXPHOS) and is essential for cells to perform specialised functions. Tumor-initiating cells use aerobic glycolysis, a combination of glycolysis and low levels of OXPHOS, to promote rapid cell proliferation and tumor growth. Glioblastoma multiforme (GBM) is an aggressively malignant brain tumor and mitochondria have been proposed to play a vital role in GBM tumorigenesis. Results: Using next generation sequencing and high resolution melt analysis, we identified a large number of mtDNA variants within coding and non-coding regions of GBM cell lines and predicted their disease-causing potential through in silico modeling. The frequency of variants was greatest in the D-loop and origin of light strand replication in non-coding regions. ND6 was the most susceptible coding gene to mutation whilst ND4 had the highest frequency of mutation. Both genes encode subunits of complex I of the ETC. These variants were not detected in unaffected brain samples and many have not been previously reported. Depletion of HSR-GBM1 cells to varying degrees of their mtDNA followed by transplantation into immunedeficient mice resulted in the repopulation of the same variants during tumorigenesis. Likewise, de novo variants identified in other GBM cell lines were also incorporated. Nevertheless, ND4 and ND6 were still the most affected genes. We confirmed the presence of these variants in high grade gliomas. Conclusions: These novel variants contribute to GBM by rendering the ETC. partially dysfunctional. This restricts metabolism to anaerobic glycolysis and promotes cell proliferation

The Physical Effects of Progenitor Rotation: Comparing Two Long-Duration 3D Core-Collapse Supernova Simulations

We analyse and determine the effects of modest progenitor rotation in the context of core-collapse supernovae by comparing two separate long-duration three-dimensional simulations of 9 M$_{\odot}$ progenitors, one rotating with an initial spin period of $\sim$60 seconds and the other non-rotating. We determine that both models explode early, though the rotating model explodes a bit earlier. Despite this difference, the asymptotic explosion energies ($\sim$10$^{50}$ ergs) and residual neutron star baryon masses ($\sim$1.3 M$_{\odot}$) are similar. We find that the proto-neutron star (PNS) core can deleptonize and cool significantly more quickly. Soon into the evolution of the rotating model, we witness more vigorous and extended PNS core convection that early in its evolution envelopes the entire inner sphere, not just a shell. Moreover, we see a corresponding excursion in both the $\nu_e$ luminosity and gravitational-wave strain that may be diagnostic of this observed dramatic phenomenon. In addition, after bounce the innermost region of the rotating model seems to execute meridional circulation. The rotationally-induced growth of the convective PNS region may facilitate the growth of core B-fields by the dynamo mechanism by facilitating the achievement of the critical Rossby number condition for substantial growth of a dipole field, obviating the need for rapid rotation rates to create dipole fields of significance. The next step is to explore the progenitor-mass and spin dependencies across the progenitor continuum of the supernova explosion, dynamics, and evolution of PNS convection and its potential role in the generation of magnetar and pulsar magnetic fields.Comment: Withdrawn pending further calculation

Reduced habituation of auditory evoked potentials indicate cortical hyper-excitability in Fragile X Syndrome

Sensory hypersensitivities are common, clinically distressing features of Fragile X Syndrome (FXS). Preclinical evidence suggests this abnormality may result from synaptic hyper-excitability in sensory systems. This model predicts reduced sensory habituation to repeated stimulus presentation. Fourteen adolescents and adults with FXS and 15 age-matched controls participated in a modified auditory gating task using trains of 4 identical tones during dense array electroencephalography (EEG). Event-related potential and single trial time–frequency analyses revealed decreased habituation of the N1 event-related potential response in FXS, and increased gamma power coupled with decreases in gamma phase-locking during the early-stimulus registration period. EEG abnormalities in FXS were associated with parent reports of heightened sensory sensitivities and social communication deficits. Reduced habituation and altered gamma power and phase-locking to auditory cues demonstrated here in FXS patients parallels preclinical findings with Fmr1 KO mice. Thus, the EEG abnormalities seen in FXS patients support the model of neocortical hyper-excitability in FXS, and may provide useful translational biomarkers for evaluating novel treatment strategies targeting its neural substrate

A Molecular Toolbox for Rapid Generation of Viral Vectors to Up- or Down-Regulate Neuronal Gene Expression in vivo

We introduce a molecular toolbox for manipulation of neuronal gene expression in vivo. The toolbox includes promoters, ion channels, optogenetic tools, fluorescent proteins, and intronic artificial microRNAs. The components are easily assembled into adeno-associated virus (AAV) or lentivirus vectors using recombination cloning. We demonstrate assembly of toolbox components into lentivirus and AAV vectors and use these vectors for in vivo expression of inwardly rectifying potassium channels (Kir2.1, Kir3.1, and Kir3.2) and an artificial microRNA targeted against the ion channel HCN1 (HCN1 miRNA). We show that AAV assembled to express HCN1 miRNA produces efficacious and specific in vivo knockdown of HCN1 channels. Comparison of in vivo viral transduction using HCN1 miRNA with mice containing a germ line deletion of HCN1 reveals similar physiological phenotypes in cerebellar Purkinje cells. The easy assembly and re-usability of the toolbox components, together with the ability to up- or down-regulate neuronal gene expression in vivo, may be useful for applications in many areas of neuroscience

An experimental investigation into quantifying CO2 leakage in aqueous environments using chemical tracers

Chemical tracers can be an effective means of detecting, attributing and quantifying any leaks to the surface from geological CO2 stores. CO2 release experiments have found it difficult to ascertain the fate, or quantify the volume of CO2 without the application of tracers. However, a significant proportion of global CO2 storage capacity is located offshore, and the marine environment poses constraints that could limit the success of using tracers. These constraints include uncertainties in the behaviour of tracers in marine sediments and the water column and sampling challenges. However, to date there have been few experimental investigations to address these uncertainties. Here, we used a benchtop experimental setup to explore how effectively methane, a common constituent of captured CO2 and of reservoir fluids, can aid the quantitation of CO2 leakage in aqueous environments. The experiment simulated gas leakage into sediments that mimic the seabed, and we measured the partitioning of co-released gases under different environmental conditions and injection rates. We find that the style of seepage and the fate of the CO2 are affected by the presence of a sand layer and the injection rate. We discuss the implications for leak monitoring approaches, including how tracers may be used to quantify the leak rates and fate of CO2 in aqueous environments. Our work contributes to ongoing efforts to develop robust offshore monitoring system that will assure operators, regulatory bodies and the public of CO2 storage integrity

Updates in the chronic kidney disease-mineral bone disorder show the role of osteocytic proteins, a potential mechanism of the bone-vascular paradox, a therapeutic target, and a biomarker

The chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex multi-component syndrome occurring during kidney disease and its progression. Here, we update progress in the components of the syndrome, and synthesize recent investigations, which suggest a potential mechanism of the bone-vascular paradox. The discovery that calcified arteries in chronic kidney disease inhibit bone remodeling lead to the identification of factors produced by the vasculature that inhibit the skeleton, thus providing a potential explanation for the bone-vascular paradox. Among the factors produced by calcifying arteries, sclerostin secretion is especially enlightening. Sclerostin is a potent inhibitor of bone remodeling and an osteocyte specific protein. Its production by the vasculature in chronic kidney disease identifies the key role of vascular cell osteoblastic/osteocytic transdifferentiation in vascular calcification and renal osteodystrophy. Subsequent studies showing that inhibition of sclerostin activity by a monoclonal antibody improved bone remodeling as expected, but stimulated vascular calcification, demonstrate that vascular sclerostin functions to brake the Wnt stimulation of the calcification milieu. Thus, the target of therapy in the chronic kidney disease-mineral bone disorder is not inhibition of sclerostin function, which would intensify vascular calcification. Rather, decreasing sclerostin production by decreasing the vascular osteoblastic/osteocytic transdifferentiation is the goal. This might decrease vascular calcification, decrease vascular stiffness, decrease cardiac hypertrophy, decrease sclerostin production, reduce serum sclerostin and improve skeletal remodeling. Thus, the therapeutic target of the chronic kidney disease-mineral bone disorder may be vascular osteoblastic transdifferentiation, and sclerostin levels may be a useful biomarker for the diagnosis of the chronic kidney disease-mineral bone disorder and the progress of its therapy

Polymerisable octahedral rhenium cluster complexes as precursors for photo/electroluminescent polymers

New polymerisable photoluminescent octahedral rhenium cluster complexes trans-[{Re₆Q₈}(TBP)₄VB)₂] (Q = S or Se; TBP – p-tert-butylpyridine; VB – vinyl benzoate) have been synthesised, characterised and used to construct rhe-nium cluster-organic polymer hybrid materials. These novel polymer systems are solution-processable and the rhenium clusters retain their photoluminescent properties within the polymer environment. Notably, when the rhenium cluster complexes are incorporated into the matrix of the electroluminescent polymer poly(N-vinylcarbazole), the resultant cluster polymer hybrid combined properties of both components and was used successfully in the construc-tion of a polymer light emitting diode (PLED). These prototype devices are the first PLEDs to incorporate octahedral rhenium clusters and provide the first direct evidence of the electroluminescent properties of rhenium clusters and indeed, to the best of our knowledge, of any member of the family of 24-electron hexanuclear cluster complexes of molybdenum, tungsten or rhenium