High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation.

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. The objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute GVHD, TRM and OS after HCT. The preparative regimen consisted of CY 50 mg/kg/day i.v. day -6; plus fludarabine 30-40 mg/m²/day i.v. on days -6 to -2 and TBI 200 cGy on day -1. F-ara-A pharmacokinetics were carried out with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A area-under-the-curve (AUC((0-∞))) was 5.0 μg h/mL (2.0-11.0), clearance 15.3 L/h (6.2-36.6), C(min) 55 ng/mL (17-166) and concentration on day(zero) 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced OS. Patients with an AUC((0-∞)) greater than 6.5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT

Evidence and modeling of turbulence bifurcation in L-mode confinement transitions on Alcator C-Mod

© 2020 Author(s). Analysis and modeling of rotation reversal hysteresis experiments show that a single turbulent bifurcation is responsible for the Linear to Saturated Ohmic Confinement (LOC/SOC) transition and concomitant intrinsic rotation reversal on Alcator C-Mod. Plasmas on either side of the reversal exhibit different toroidal rotation profiles and therefore different turbulence characteristics despite the profiles of density and temperature, which are indistinguishable within measurement uncertainty. Elements of this bifurcation are also shown to persist for auxiliary heated L-modes. The deactivation of subdominant (in the linear growth rate and contribution to heat transport) ion temperature gradient and trapped electron mode instabilities is identified as the only possible change in turbulence within a reduced quasilinear transport model across the reversal, which is consistent with the measured profiles and inferred heat and particle fluxes. Experimental constraints on a possible change from strong to weak turbulence, outside the description of the quasilinear model, are also discussed. These results indicate an explanation for the LOC/SOC transition that provides a mechanism for the hysteresis through the dynamics of subdominant modes and changes in their relative populations and does not involve a change in the most linearly unstable ion-scale drift-wave instability

Overexpression of mitochondrial creatine kinase preserves cardiac energetics without ameliorating murine chronic heart failure

Mitochondrial creatine kinase (Mt-CK) is a major determinant of cardiac energetic status and is down-regulated in chronic heart failure, which may contribute to disease progression. We hypothesised that cardiomyocyte-specific overexpression of Mt-CK would mitigate against these changes and thereby preserve cardiac function. Male Mt-CK overexpressing mice (OE) and WT littermates were subjected to transverse aortic constriction (TAC) or sham surgery and assessed by echocardiography at 0, 3 and 6 weeks alongside a final LV haemodynamic assessment. Regardless of genotype, TAC mice developed progressive LV hypertrophy, dilatation and contractile dysfunction commensurate with pressure overload-induced chronic heart failure. There was a trend for improved survival in OE-TAC mice (90% vs 73%, P = 0.08), however, OE-TAC mice exhibited greater LV dilatation compared to WT and no functional parameters were significantly different under baseline conditions or during dobutamine stress test. CK activity was 37% higher in OE-sham versus WT-sham hearts and reduced in both TAC groups, but was maintained above normal values in the OE-TAC hearts. A separate cohort of mice received in vivo cardiac 31P-MRS to measure high-energy phosphates. There was no difference in the ratio of phosphocreatine-to-ATP in the sham mice, however, PCr/ATP was reduced in WT-TAC but preserved in OE-TAC (1.04 ± 0.10 vs 2.04 ± 0.22; P = 0.007). In conclusion, overexpression of Mt-CK activity prevented the changes in cardiac energetics that are considered hallmarks of a failing heart. This had a positive effect on early survival but was not associated with improved LV remodelling or function during the development of chronic heart failure

Demonstration of a 10 Gbit/s Long Reach Wavelength Converting Optical Access Network

This paper demonstrates a 10 Gbit/s wavelength converting access network utilising a centralised optical processing unit that consolidates multiple low cost PONs onto a DWDM backhaul. The centralised processing unit functions as an amplifier, wavelength converter, pre-chirping stage and optical burst equaliser to map legacy PONs onto a DWDM grid for efficient backhaul transmission and to ease the dynamic range requirement of the 10 Gbit/s burst-mode receiver at the optical line termination (OLT). The dispersion limited performance, wavelength tolerance, and burst-mode dynamic range are evaluated demonstrating a maximum range of 62 km for 20 nm of input wavelength variation and a dynamic range of up to 22 dB

Performance of an optical equalizer in a 10 G wavelength converting optical access network

A centralized optical processing unit (COPU) that functions both as a wavelength converter (WC) and optical burst equaliser in a 10 Gb/s wavelength-converting optical access network is proposed and experimentally characterized. This COPU is designed to consolidate drifting wavelengths generated with an uncooled laser in the upstream direction into a stable wavelength channel for WDM backhaul transmission and to equalize the optical loud/soft burst power in order to relax the burst-mode receiver dynamic range requirement. The COPU consists of an optical power equaliser composed of two cascaded SOAs followed by a WC. Using an optical packet generator and a DC-coupled PIN-based digital burst-mode receiver, the COPU is characterized in terms of payload-BER for back-to-back and backhaul transmission distances of 22, 40, and 62 km. We show that there is a compromise between the receiver sensitivity and overload points that can be optimized tuning the WC operating point for a particular backhaul fiber transmission distance. Using the optimized settings, sensitivities of −30.94, −30.17, and −27.26 dBm with overloads of −9.3, −5, and >-5 dBm were demonstrated for backhaul transmission distances of 22, 40 and 62 km, respectively

Microbial Community Responses to Vanadium Distributions in Mining Geological Environments and Bioremediation Assessment

Vanadium mining activities can cause contamination of the surrounding geological environment. Vanadium may exist in multiple matrices due to its migration and transformation, forming interactive relationships; however, the connection between vanadium distributions in multiple matrices and microbial community responses remains largely unknown. Vanadium is a redox-sensitive metal that can be microbiologically reduced and immobilized. To date, bioremediation of vanadium-contaminated environments by indigenous microorganisms has rarely been evaluated. This paper reports a systematic investigation into vanadium distributions and microbial communities in soils, water, and sediment from Panzhihua, China. Large vanadium contents of 1130.1 ± 9.8 mg/kg and 0.13 ± 0.02 mg/L were found in surface soil and groundwater. Vanadium in surface water tended to precipitate. Microbial communities isolated from similar environments were alike due to similarity in matrix chemistry whereas communities were distinct when compared to different matrices, with lower richness and diversity in groundwater. Proteobacteria was distributed widely and dominated microbial communities within groundwater. Redundancy analysis shows that vanadium and nutrients significantly affected metal-tolerant bacteria. Long-term cultivation (240 days) suggests the possibility of vanadium bioremediation by indigenous microorganisms, within acid-soluble fraction. This active fraction can potentially release mobile vanadium with shifted redox conditions. Vanadium (V) was bio-reduced to less toxic, mobile vanadium (IV) primarily by enriched Bacillus and Thauera. This study reveals the biogeochemical fate of vanadium in regional geological environments and suggests a bioremediation pathway via native vanadium-reducing microbes

Explanation of the Colour Change in Alexandrites.

Alexandrites are remarkable and rare gemstones. They display an extraordinary colour change according to the ambient lighting, from emerald green in daylight to ruby red in incandescent light from tungsten lamps or candles. While this colour change has been correctly attributed to chromium impurities and their absorption band in the yellow region of the visible light spectrum, no adequate explanation of the mechanism has been given. Here, the alexandrite effect is fully explained by considering the von Kries model of the human colour constancy mechanism. This implies that our colour constancy mechanism is real (objective) and primarily attuned to correct for the colour temperature of black-body illuminants

In-Plane Orbital Texture Switch at the Dirac Point in the Topological Insulator Bi2Se3

Topological insulators are novel macroscopic quantum-mechanical phase of matter, which hold promise for realizing some of the most exotic particles in physics as well as application towards spintronics and quantum computation. In all the known topological insulators, strong spin-orbit coupling is critical for the generation of the protected massless surface states. Consequently, a complete description of the Dirac state should include both the spin and orbital (spatial) parts of the wavefunction. For the family of materials with a single Dirac cone, theories and experiments agree qualitatively, showing the topological state has a chiral spin texture that changes handedness across the Dirac point (DP), but they differ quantitatively on how the spin is polarized. Limited existing theoretical ideas predict chiral local orbital angular momentum on the two sides of the DP. However, there have been neither direct measurements nor calculations identifying the global symmetry of the spatial wavefunction. Here we present the first results from angle-resolved photoemission experiment and first-principles calculation that both show, counter to current predictions, the in-plane orbital wavefunctions for the surface states of Bi2Se3 are asymmetric relative to the DP, switching from being tangential to the k-space constant energy surfaces above DP, to being radial to them below the DP. Because the orbital texture switch occurs exactly at the DP this effect should be intrinsic to the topological physics, constituting an essential yet missing aspect in the description of the topological Dirac state. Our results also indicate that the spin texture may be more complex than previously reported, helping to reconcile earlier conflicting spin resolved measurements

Singlet-doublet Higgs mixing and its implications on the Higgs mass in the PQ-NMSSM

We examine the implications of singlet-doublet Higgs mixing on the properties of a Standard Model (SM)-like Higgs boson within the Peccei-Quinn invariant extension of the NMSSM (PQ-NMSSM). The SM singlet added to the Higgs sector connects the PQ and visible sectors through a PQ-invariant non-renormalizable K\"ahler potential term, making the model free from the tadpole and domain-wall problems. For the case that the lightest Higgs boson is dominated by the singlet scalar, the Higgs mixing increases the mass of a SM-like Higgs boson while reducing its signal rate at collider experiments compared to the SM case. The Higgs mixing is important also in the region of parameter space where the NMSSM contribution to the Higgs mass is small, but its size is limited by the experimental constraints on the singlet-like Higgs boson and on the lightest neutralino constituted mainly by the singlino whose Majorana mass term is forbidden by the PQ symmetry. Nonetheless the Higgs mixing can increase the SM-like Higgs boson mass by a few GeV or more even when the Higgs signal rate is close to the SM prediction, and thus may be crucial for achieving a 125 GeV Higgs mass, as hinted by the recent ATLAS and CMS data. Such an effect can reduce the role of stop mixing.Comment: 26 pages, 3 figures; published in JHE