The morphological representation of channel-forming flow in arroyos

This thesis presents a study of three similar, yet contrasting, arroyos: the Rio Puerco, New Mexico and the Santa Cruz and San Simon Rivers in Arizona. Arroyo systems have been subject to several periods of cut and fill within recent geologic time. The most recent incision phase occurred during the mid- to late-19th Century, enabling subsequent morphological changes to be observed. Observations indicate that these systems have developed distinct geomorphological reaches, which evolve at different rates within the constraints of the specific controlling variables, most importantly discharge, sediment load and artificial alteration. Thus, location-for-time substitution cannot be assumed. Within the continuum of morphological change, six stages were identified, enabling a general model of arroyo evolution to be developed. Precipitation has increased in the south-western USA. However, within the arroyos studied, some gauges have seen a concurrent increase in discharge, whereas others have experienced a decline. It was discovered that the different responses were explained by the interaction between discharge and morphology at different stages of evolution. The first four stages of arroyo evolution differ little from those proposed previously. However, this study has emphasised the necessity of recognising the event-driven nature of morphological change within the system during these stages. Since some change occurs during each flood, the arroyo morphology is controlled by a combination of the flow variability and channel-deforming events. As aggradation predominates, the arroyo develops a quasi-stable form, creating a feedback between discharge and morphology. High-magnitude flows are suppressed and aggradation is promoted, permitting continued stabilisation until a quasi-equilibrium form is attained, typified by a trapezoidal active channel and densely vegetated inner floodplain. These morphological changes alter the discharge regime sufficiently that lower-magnitude flows assume greater relative effectiveness. It is not until a quasi-equilibrium morphology becomes adjusted to the effective discharge, at which point the effective discharge becomes a truly channel-forming and maintaining flow

Properties of the ultraviolet flux of type Ia supernovae: an analysis with synthetic spectra of SN 2001ep and SN 2001eh

The spectral properties of type Ia supernovae in the ultraviolet (UV) are investigated using the early-time spectra of SN 2001ep and SN 2001eh obtained using the Hubble Space Telescope (HST). A series of spectral models is computed with a Monte Carlo spectral synthesis code, and the dependence of the UV flux on the elemental abundances and the density gradient in the outer layers of the ejecta is tested. A large fraction of the UV flux is formed by reverse fluorescence scattering of photons from red to blue wavelengths. This process, combined with ionization shifts due to enhanced line blocking, can lead to a stronger UV flux as the iron-group abundance in the outer layers is increased, contrary to previous claims.Comment: 14 pages, 13 figures. Replaced with revised version accepted for publication in MNRA

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

The UV/optical spectra of the Type Ia supernova SN 2010jn: a bright supernova with outer layers rich in iron-group elements

Radiative transfer studies of Type Ia supernovae (SNe Ia) hold the promise of constraining both the time-dependent density profile of the SN ejecta and its stratification by element abundance which, in turn, may discriminate between different explosion mechanisms and progenitor classes. Here we present a detailed analysis of Hubble Space Telescope ultraviolet (UV) and ground-based optical spectra and light curves of the SN Ia SN 2010jn (PTF10ygu). SN 2010jn was discovered by the Palomar Transient Factory (PTF) 15 days before maximum light, allowing us to secure a time-series of four UV spectra at epochs from -11 to +5 days relative to B-band maximum. The photospheric UV spectra are excellent diagnostics of the iron-group abundances in the outer layers of the ejecta, particularly those at very early times. Using the method of 'Abundance Tomography' we have derived iron-group abundances in SN 2010jn with a precision better than in any previously studied SN Ia. Optimum fits to the data can be obtained if burned material is present even at high velocities, including significant mass fractions of iron-group elements. This is consistent with the slow decline rate (or high 'stretch') of the light curve of SN 2010jn, and consistent with the results of delayed-detonation models. Early-phase UV spectra and detailed time-dependent series of further SNe Ia offer a promising probe of the nature of the SN Ia mechanism.Comment: 17 pages, 9 figures (v3: several small updates to content including models; v2: metadata fixed), MNRAS, in pres

Hubble Space Telescope studies of low-redshift Type Ia supernovae: Evolution with redshift and ultraviolet spectral trends

We present an analysis of the maximum light, near ultraviolet (NUV; 2900-5500 A) spectra of 32 low redshift (0.001<z<0.08) Type Ia supernovae (SNe Ia), obtained with the Hubble Space Telescope (HST). We combine this spectroscopic sample with high-quality gri light curves obtained with robotic telescopes to measure photometric parameters, such as stretch, optical colour, and brightness. By comparing our data to a comparable sample of SNe Ia at intermediate-z (0.4<z<0.9), we detect modest spectral evolution (3-sigma), in the sense that our mean low-z NUV spectrum has a depressed flux compared to its intermediate-z counterpart. We also see a strongly increased dispersion about the mean with decreasing wavelength, confirming the results of earlier surveys. These trends are consistent with changes in metallicity as predicted by contemporary SN Ia spectral models. We also examine the properties of various NUV spectral diagnostics in the individual spectra. We find a general correlation between stretch and the velocity (or position) of many NUV spectral features. In particular, we observe that higher stretch SNe have larger Ca II H&K velocities, that also correlate with host galaxy stellar mass. This latter trend is probably driven by the well-established correlation between stretch and stellar mass. We find no trends between UV spectral features and optical colour. Mean spectra constructed according to whether the SN has a positive or negative Hubble residual show very little difference at NUV wavelengths, indicating that the NUV evolution and variation we identify do not directly correlate with Hubble residuals. Our work confirms and strengthens earlier conclusions regarding the complex behaviour of SNe Ia in the NUV spectral region, but suggests the correlations we find are more useful in constraining progenitor models than improving the use of SNe Ia as cosmological probes.Comment: 22 pages, 14 figures, accepted in MNRAS with minor changes - Spectra are available on WISeREP, http://www.weizmann.ac.il/astrophysics/wiserep

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

Background: Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria.Methods and Results: Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention.Conclusions: Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.<br/

A Minimal Functional Complex of Cytochrome P450 and FBD of Cytochrome P450 Reductase in Nanodiscs

Structural interactions that enable electron transfer to cytochromeâ P450 (CYP450) from its redox partner CYP450â reductase (CPR) are a vital prerequisite for its catalytic mechanism. The first structural model for the membraneâ bound functional complex to reveal interactions between the fullâ length CYP450 and a minimal domain of CPR is now reported. The results suggest that anchorage of the proteins in a lipid bilayer is a minimal requirement for CYP450 catalytic function. Akin to cytochromeâ b5 (cytâ b5), Argâ 125 on the Câ helix of CYP450s is found to be important for effective electron transfer, thus supporting the competitive behavior of redox partners for CYP450s. A general approach is presented to study proteinâ protein interactions combining the use of nanodiscs with NMR spectroscopy and SAXS. Linking structural details to the mechanism will help unravel the xenobiotic metabolism of diverse microsomal CYP450s in their native environment and facilitate the design of new drug entities.Auf der Grundlage einer Strukturanalyse von Cytochrom P450 (CYP450) im Komplex mit seinem Redoxpartner kann der Pfad des selektiven Elektronentransfers verstanden werden. Strukturelle Wechselwirkungen in einem solchen Komplex, verankert in einer Lipidmembran, sind eine Grundvoraussetzung für diese Funktion. Der Stoffwechsel von Wirkâ und Fremdstoffen durch diverse mikrosomale CYPs in ihrem nativen Membranumfeld wird aufgeklärt.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144609/1/ange201802210.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144609/2/ange201802210-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144609/3/ange201802210_am.pd

A Case Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic and Tractable Biomarkers in Male Breast Cancer

Purpose: Breast cancer (BC) affects both genders, but is understudied in men. Although still rare, male BC is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental design: A transcriptomic investigation of male and female BC was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n=477, training; n=220, validation set) and quantified in pre- and post-treatment samples from a male BC patient receiving Everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were up-regulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (Log rank; p=0.013; HR=1.77, 1.12-2.8 and p=0.035; HR=1.68, 1.03-2.74, respectively), or when co-expressed (p=0.01; HR=2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis (eIF4E p=0.016; HR 2.38 (1.18-4.8), eIF5 p=0.022; HR 2.55 (1.14-5.7); co-expression p=0.001; HR=7.04 (2.22-22.26)). Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/Everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in male BC patients overexpressing eIF4E and eIF5. With mTOR inhibitors which target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required

Hubble Space Telescope spectra of the Type Ia supernova SN 2011fe: a tail of low-density, high-velocity material with Z < Z⊙

Hubble Space Telescope spectroscopic observations of the nearby Type Ia supernova (SN Ia) SN 2011fe, taken on 10 epochs from −13.1 to +40.8 d relative to B-band maximum light, and spanning the far-ultraviolet (UV) to the near-infrared (IR) are presented. This spectroscopic coverage makes SN 2011fe the best-studied local SN Ia to date. SN 2011fe is a typical moderately luminous SN Ia with no evidence for dust extinction. Its near-UV spectral properties are representative of a larger sample of local events (Maguire et al.). The near-UV to optical spectra of SN 2011fe are modelled with a Monte Carlo radiative transfer code using the technique of ‘abundance tomography’, constraining the density structure and the abundance stratification in the SN ejecta. SN 2011fe was a relatively weak explosion, with moderate Fe-group yields. The density structures of the classical model W7 and of a delayed detonation model were tested. Both have shortcomings. An ad hoc density distribution was developed which yields improved fits and is characterized by a high-velocity tail, which is absent in W7. However, this tail contains less mass than delayed detonation models. This improved model has a lower energy than one-dimensional explosion models matching typical SNe Ia (e.g. W7, WDD1; Iwamoto et al.). The derived Fe abundance in the outermost layer is consistent with the metallicity at the SN explosion site in M101 (∼0.5 Z⊙). The spectroscopic rise-time (∼19 d) is significantly longer than that measured from the early optical light curve, implying a ‘dark phase’ of ∼1 d. A longer rise-time has significant implications when deducing the properties of the white dwarf and binary system from the early photometric behaviour