Experimental determination and thermodynamic modelling of phase diagrams for high temperature materials

The phase equilibria of the Ta-Al-Co, and Ti-Fe-Mo systems were investigated and modelled in order to explore their potential as base systems for disordered BCC_A2 (β) matrix - ordered BCC_B2, D03, or L21 (β’) precipitate strengthened alloys. A detailed experimental investigation into the phase equilibria of the Ta-Al-Co system was performed, followed by the production of ternary isothermal sections at temperatures of 1000⁰C and 1150⁰C. This system does not contain a disordered BCC_A2 Ta to ordered BCC intermetallic two phase field. In contrast, recent work has established that the Ti-Fe-Mo system does contain a BCC_A2 + BCC_B2 two phase region, which allows the production of β/β’ precipitate strengthened alloys. CALPHAD assessments were performed, producing thermodynamic databases for these two systems. Models were selected to describe the Gibbs energy of each phase in the systems, which were then fitted to experimental phase diagram, and thermodynamic data, to produce a complete thermodynamic description for each system. Phase diagrams calculated from these databases were in good agreement with those plotted based on experimental data. These ternary CALPHAD databases could potentially be adapted and incorporated into existing alloy databases, in order to improve the accuracy of modelling calculations for alloy design and processing applications

Is a Positive Relationship Between Fertility and Economic Development Emerging at the Sub-National Regional Level? : Theoretical Considerations and Evidence from Europe

Peer reviewe

Gamma-Ray Bursts Trace UV Metrics of Star Formation over 3 < z < 5

We present the first uniform treatment of long duration gamma-ray burst (GRB) host galaxy detections and upper limits over the redshift range 3<z<5, a key epoch for observational and theoretical efforts to understand the processes, environments, and consequences of early cosmic star formation. We contribute deep imaging observations of 13 GRB positions yielding the discovery of eight new host galaxies. We use this dataset in tandem with previously published observations of 31 further GRB positions to estimate or constrain the host galaxy rest-frame ultraviolet (UV; 1600 A) absolute magnitudes M_UV. We then use the combined set of 44 M_UV estimates and limits to construct the M_UV luminosity function (LF) for GRB host galaxies over 3<z<5 and compare it to expectations from Lyman break galaxy (LBG) photometric surveys with the Hubble Space Telescope. Adopting standard prescriptions for the luminosity dependence of galaxy dust obscuration (and hence, total star formation rate), we find that our LF is compatible with LBG observations over a factor of 600x in host luminosity, from M_UV = -22.5 mag to >-15.6 mag, and with extrapolations of the assumed Schechter-type LF well beyond this range. We review proposed astrophysical and observational biases for our sample, and find they are for the most part minimal. We therefore conclude, as the simplest interpretation of our results, that GRBs successfully trace UV metrics of cosmic star formation over the range 3<z<5. Our findings suggest GRBs are providing an accurate picture of star formation processes from z ~3 out to the highest redshifts.Comment: publ. ApJ 809 (2015) 76; 14 figures; replacement to reflect changes to v1 (rounding effects, diff. LF from Bouwens

PLCζ is the physiological trigger of the Ca2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence

Activation of the egg by the sperm is the first, vital stage of embryogenesis. The sperm protein PLC zeta has been proposed as the physiological agent that triggers the Ca2+ oscillations that normally initiate embryogenesis. Consistent with this, recombinant PLC zeta induces Ca2+ oscillations in eggs and debilitating mutations in the PLCZ1 gene are associated with infertility in men. However, there has been no evidence that knockout of the gene encoding PLC. abolishes the ability of sperm to induce Ca2+ oscillations in eggs. Here, we show that sperm derived from Plcz1(-/-) male mice fail to trigger Ca2+ oscillations in eggs, cause polyspermy and thus demonstrate that PLC zeta is the physiological trigger of these Ca2+ oscillations. Remarkably, some eggs fertilized by PLC zeta-null sperm can develop, albeit at greatly reduced efficiency, and after a significant time-delay. In addition, Plcz1(-/-) males are subfertile but not sterile, suggesting that in the absence of PLC zeta, spontaneous egg activation can eventually occur via an alternative route. This is the first demonstration that in vivo fertilization without the normal physiological trigger of egg activation can result in offspring. PLC zeta-null sperm now make it possible to resolve long-standing questions in fertilization biology, and to test the efficacy and safety of procedures used to treat human infertility

Molecular envelopes derived from protein powder diffraction Molecular envelopes derived from protein powder diffraction data

The preparation of single crystals suitable for X-ray analysis is frequently the most difficult step in structural studies of proteins.With the aid of two examples, it is shown that de novo solution of the crystallographic phase problem can be achieved at low resolution using microcrystalline powder samples via the single isomorphous replacement method. With synchrotron radiation and optimized instrumentation, high-quality powder patterns have been recorded, from which it was possible to generate phase information for structure factors up to 6 A resolution. pH- and radiation-induced anisotropic lattice changes were exploited to reduce the problem of overlapping reflections, which is a major challenge in protein powder diffraction. The resulting data were of sufficient quality to compute molecular envelopes of the protein molecule and to map out the solvent channels in the crystals. The results show that protein powder diffraction can yield low-resolution data that are potentially useful for the characterization of microcrystalline proteins as novel micro- and mesoporous materials as well as for structural studies of biologically important macromolecules

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging.

Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi-shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD-related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning

Amyloid ? influences the relationship between cortical thickness and vascular load.

INTRODUCTION: Cortical thickness has been proposed as a biomarker of Alzheimer's disease (AD)- related neurodegeneration, but the nature of its relationship with amyloid beta (A?) deposition and white matter hyperintensity volume (WMHV) in cognitively normal adults is unclear. METHODS: We investigated the influences of A? status (negative/positive) and WMHV on cortical thickness in 408 cognitively normal adults aged 69.2 to 71.9 years who underwent 18F-Florbetapir positron emission tomography (PET) and structural magnetic resonance imaging (MRI). Two previously defined Alzheimer's disease (AD) cortical signature regions and the major cortical lobes were selected as regions of interest (ROIs) for cortical thickness. RESULTS: Higher WMHV, but not A? status, predicted lower cortical thickness across all participants, in all ROIs. Conversely, when A?-positive participants were considered alone, higher WMHV predicted higher cortical thickness in a temporal AD-signature region. DISCUSSION: WMHV may differentially influence cortical thickness depending on the presence or absence of A?, potentially reflecting different pathological mechanisms

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve

Associations of β-Amyloid and Vascular Burden With Rates of Neurodegeneration in Cognitively Normal Members of the 1946 British Birth Cohort

OBJECTIVE: To quantify the independent and interactive associations of amyloid-β (Aβ) and white matter hyperintensity volume (WMHV) - a marker of presumed cerebrovascular disease (CVD) - with rates of neurodegeneration, and to examine the contributions of APOE ε4 and vascular risk measured at different stages of adulthood in cognitively normal members of the 1946 British birth cohort. METHODS: Participants underwent brain MRI and florbetapir-Aβ positron emission tomography as part of Insight 46, an observational population-based study. Changes in whole brain, ventricular and hippocampal volume were directly measured from baseline and repeat volumetric T1 MRI using the Boundary Shift Integral. Linear regression was used to test associations with: baseline Aβ deposition; baseline WMHV; APOE ε4; and office-based Framingham heart study-cardiovascular risk scores (FHS-CVS) and systolic blood pressure (BP) at ages 36, 53 and 69 years. RESULTS: 346 cognitively normal participants (mean [SD] age at baseline scan 70.5 [0.6] years; 48% female) had high-quality T1 MRI data from both time-points (mean [SD] scan interval 2.4 [0.2] years). Being Aβ positive at baseline was associated with 0.87 ml/year faster whole brain atrophy (95% CI 0.03, 1.72), 0.39 ml/year greater ventricular expansion (95% CI 0.16, 0.64) and 0.016 ml/year faster hippocampal atrophy (95% CI 0.004, 0.027), while each 10 ml additional WMHV at baseline was associated with 1.07 ml/year faster whole brain atrophy (95% CI 0.47, 1.67), 0.31 ml/year greater ventricular expansion (95% CI 0.13, 0.60) and 0.014 ml/year faster hippocampal atrophy (95% CI 0.006, 0.022). These contributions were independent and there was no evidence that Aβ and WMHV interacted in their effects. There were no independent associations of APOE ε4 with rates of neurodegeneration after adjusting for Aβ status and WMHV, and no clear relationships between FHS-CVS or systolic BP and rates of neurodegeneration when assessed across the whole sample, nor any evidence that they acted synergistically with Aβ. CONCLUSIONS: Aβ and presumed CVD have distinct and additive effects on rates of neurodegeneration in cognitively normal elderly. These findings have implications for the use of MRI measures as biomarkers of neurodegeneration and emphasize the importance of risk management and early intervention targeting both pathways