New Solid State Forms of the Anti-HIV Drug Efavirenz. Conformational Flexibility and High Z ` Issues

Structural information on the solid forms of efavirenz, a non-nucleoside reverse transcriptase inhibitor, is limited, although various polymorphic forms of this drug have been patented. We report here structural studies of four new crystal forms a pure form, a cyclohexane solvate, and cocrystals with 1,4-cyclohexanedione and 4,4'-bipyridine. Temperature dependent single-crystal to single-crystal phase transitions are observed for the pure form and for the cyclohexane solvate with an increase in the number of symmetry independent molecules, Z', upon a lowering of temperature. Other issues related to these solid forms, such as thermal stability, conformational flexibility, and high Z' occurrences, are addressed by using a combined experimental and computational approach.

Systematic study of visible transitions in Ti-like high Z ions

The magnetic dipole transitions between fine structure levels in the ground term of Ti-like ions, (3d(4)) D-5(2)-D-5(3), were investigated by observation of visible and near-UV light for several elements with atomic numbers from 51 to 78. The wavelengths are compared with theoretical values we recently calculated. The differences between the present calculations and measurements are less than 0.6%. The anomalous wavelength stability predicted by Feldman, Indelicato and Sugar [J. Opt. Soc. Am. B 8, 3 (1991)] was observed. We attribute this anomalous wavelength stability to the transition from LS to JJ coupling and the asymptotic behavior of the transition energies in the intermediate coupling regime.

Variation of strand break yield for plasmid DNA irradiated with high-Z metal nanoparticles.

PURPOSE: Poly(ADP-ribose) polymerase (PARP) plays an important role in DNA repair, and PARP inhibitors can enhance the activity of DNA-damaging agents in vitro and in vivo. AG014699 is a potent PARP inhibitor in phase II clinical development. However, the range of therapeutics with which AG014699 could interact via a DNA-repair based mechanism is limited. We aimed to investigate a novel, vascular-based activity of AG014699, underlying in vivo chemosensitization, which could widen its clinical application. EXPERIMENTAL DESIGN: Temozolomide response was analyzed in vitro and in vivo. Vessel dynamics were monitored using "mismatch" following the administration of perfusion markers and real-time analysis of fluorescently labeled albumin uptake in to tumors established in dorsal window chambers. Further mechanistic investigations used ex vivo assays of vascular smooth muscle relaxation, gut motility, and myosin light chain kinase (MLCK) inhibition. RESULTS: AG014699 failed to sensitize SW620 cells to temozolomide in vitro but induced pronounced enhancement in vivo. AG014699 (1 mg/kg) improved tumor perfusion comparably with the control agents nicotinamide (1 g/kg) and AG14361 (forerunner to AG014699; 10 mg/kg). AG014699 and AG14361 relaxed preconstricted vascular smooth muscle more potently than the standard agent, hydralazine, with no impact on gut motility. AG014699 inhibited MLCK at concentrations that relaxed isolated arteries, whereas AG14361 had no effect. CONCLUSION: Increased vessel perfusion elicited by AG014699 could increase tumor drug accumulation and therapeutic response. Vasoactive concentrations of AG014699 do not cause detrimental side effects to gut motility and may increase the range of therapeutics with which AG014699 could be combined with for clinical benefi

Effects of buried high-Z layers on fast electron propagation

By extending a prior model [A. R. Bell, J.R. Davies, S. M. Guerin, Phys. Rev. E 58, 2471 (1998)], the magnetic field generated during the transport of a fast electron beam driven by an ultraintense laser in a solid target is derived analytically and applied to estimate the effect of such field on fast electron propagation through a buried high-Z layer in a lower-Z target. It is found that the effect gets weaker with the increase of the depth of the buried layer, the divergence of the fast electrons, and the laser intensity, indicating that magnetic field effects on the fast electron divergence as measured from K-a X-ray emission may need to be considered for moderate laser intensities. On the basis of the calculations, some considerations are made on how one can mitigate the effect of the magnetic field generated at the interface.

Kinematics of local and high-z galaxies through 3D modeling of emission-line datacubes

The kinematics is a fundamental tool to infer the dynamical structure of galaxies and to understand their formation and evolution. Spectroscopic observations of gas emission lines are often used to derive rotation curves and velocity dispersions. It is however difficult to disentangle these two quantities in low spatial-resolution data because of beam smearing. In this thesis, we present 3D-Barolo, a new software to derive the gas kinematics of disk galaxies from emission-line data-cubes. The code builds tilted-ring models in the 3D observational space and compares them with the actual data-cubes. 3D-Barolo works with data at a wide range of spatial resolutions without being affected by instrumental biases. We use 3D-Barolo to derive rotation curves and velocity dispersions of several galaxies in both the local and the high-redshift Universe. We run our code on HI observations of nearby galaxies and we compare our results with 2D traditional approaches. We show that a 3D approach to the derivation of the gas kinematics has to be preferred to a 2D approach whenever a galaxy is resolved with less than about 20 elements across the disk. We moreover analyze a sample of galaxies at z~1, observed in the H-alpha line with the KMOS/VLT spectrograph. Our 3D modeling reveals that the kinematics of these high-z systems is comparable to that of local disk galaxies, with steeply-rising rotation curves followed by a flat part and H-alpha velocity dispersions of 15-40 km/s over the whole disks. This evidence suggests that disk galaxies were already fully settled about 7-8 billion years ago. In summary, 3D-Barolo is a powerful and robust tool to separate physical and instrumental effects and to derive a reliable kinematics. The analysis of large samples of galaxies at different redshifts with 3D-Barolo will provide new insights on how galaxies assemble and evolve throughout cosmic time.

SHARDS: survey for high-Z absorption red & dead sources

SHARDS, an ESO/GTC Large Program, is an ultra-deep (26.5 mag) spectro-photometric survey with GTC/OSIRIS designed to select and study massive passively evolving galaxies at z=1.0-2.3 in the GOODS-N field using a set of 24 medium-band filters (FWHM ∼ 17 nm) covering the 500-950 nm spectral range. Our observing strategy has been planned to detect, for z>1 sources, the prominent Mg absorption feature (at rest-frame ∼ 280 nm), a distinctive, necessary, and sufficient feature of evolved stellar populations (older than 0.5 Gyr). These observations are being used to: (1) derive for the first time an unbiased sample of high-z quiescent galaxies, which extends to fainter magnitudes the samples selected with color techniques and spectroscopic surveys; (2) derive accurate ages and stellar masses based on robust measurements of spectral features such as the Mg_UV or D(4000) indices; (3) measure their redshift with an accuracy Δz/(1+z)<0.02; and (4) study emission-line galaxies (starbursts and AGN) up to very high redshifts. The well-sampled optical SEDs provided by SHARDS for all sources in the GOODS-N field are a valuable complement for current and future surveys carried out with other telescopes (e.g., Spitzer, HST, and Herschel).

Measuring star formation in high-z massive galaxies: a mid-infrared to submillimetre study of the GOODS NICMOS Survey sample

We present measurements of the mean mid-infrared to submillimetre flux densities of massive (M_*≳ 10^11 M_⊙) galaxies at redshifts 1.7 < z < 2.9, obtained by stacking positions of known objects taken from the GOODS NICMOS Survey (GNS) catalogue on maps at 24 μm (Spitzer/MIPS); 70, 100 and 160 μm (Herschel/PACS); 250, 350 and 500 μm (BLAST); and 870 μm (LABOCA). A modified blackbody spectrum fit to the stacked flux densities indicates a median [interquartile] star formation rate (SFR) of SFR = 63[48, 81] M_⊙ yr^−1. We note that not properly accounting for correlations between bands when fitting stacked data can significantly bias the result. The galaxies are divided into two groups, disc-like and spheroid-like, according to their Sérsic indices, n. We find evidence that most of the star formation is occurring in n≤ 2 (disc-like) galaxies, with median [interquartile] SFR = 122[100, 150] M_⊙ yr^−1, while there are indications that the n > 2 (spheroid-like) population may be forming stars at a median [interquartile] SFR = 14[9, 20] M_⊙ yr^−1, if at all. Finally, we show that star formation is a plausible mechanism for size evolution in this population as a whole, but find only marginal evidence that it is what drives the expansion of the spheroid-like galaxies.

Far-infrared constraints on the contamination by dust-obscured galaxies of high-z dropout searches

The spectral energy distributions (SED) of dusty galaxies at intermediate redshift may look similar to very high-redshift galaxies in the optical/near infrared (NIR) domain. This can lead to the contamination of high-redshift galaxy searches based on broad-band optical/NIR photometry by lower redshift dusty galaxies because both kind of galaxies cannot be distinguished. The contamination rate could be as high as 50%. This work shows how the far-infrared (FIR) domain can help to recognize likely low-z interlopers in an optical/NIR search for high-z galaxies. We analyze the FIR SEDs of two galaxies that are proposed to be very high-redshift (z > 7) dropout candidates based on deep Hawk-I/VLT observations. The FIR SEDs are sampled with PACS/Herschel at 100 and 160 μm, with SPIRE/Herschel at 250, 350 and 500 μm and with LABOCA/APEX at 870 μm. We find that redshifts > 7 would imply extreme FIR SEDs (with dust temperatures >100 K and FIR luminosities >10^13 L_⊙). At z ~ 2, instead, the SEDs of both sources would be compatible with those of typical ultra luminous infrared galaxies or submillimeter galaxies. Considering all available data for these sources from visible to FIR we re-estimate the redshifts and find z ~ 1.6–2.5. Owing to the strong spectral breaks observed in these galaxies, standard templates from the literature fail to reproduce the visible-to-near-IR part of the SEDs even when additional extinction is included. These sources strongly resemble dust-obscured galaxies selected in Spitzer observations with extreme visible-to-FIR colors, and the galaxy GN10 at z = 4. Galaxies with similar SEDs could contaminate other high-redshift surveys.

Improving the identification of high-z Herschel sources with position priors and optical/NIR and FIR/mm photometric redshifts

We present preliminary results about the detection of high redshift (U)LIRGs in the Bullet cluster field by the PACS and SPIRE instruments within the Herschel Lensing Survey (HLS) Program. We describe in detail a photometric procedure designed to recover robust fluxes and deblend faint Herschel sources near the confusion noise. The method is based on the use of the positions of Spitzer/MIPS 24 μm sources as priors. Our catalogs are able to reliably (5σ) recover galaxies with fluxes above 6 and 10 mJy in the PACS 100 and 160 μm channels, respectively, and 12 to 18 mJy in the SPIRE bands. We also obtain spectral energy distributions covering the optical through the far-infrared/millimeter spectral ranges of all the Herschel detected sources, and analyze them to obtain independent estimations of the photometric redshift based on either stellar population or dust emission models. We exemplify the potential of the combined use of Spitzer position priors plus independent optical and IR photometric redshifts to robustly assign optical/NIR counterparts to the sources detected by Herschel and other (sub-)mm instruments.

The intergalactic and circumgalactic medium surrounding star-forming galaxies at redshifts 2 < z < 3

We present measurements of the spatial distribution, kinematics, and physical properties of gas in the circumgalactic medium (CGM) of 2.0<z<2.8 UV color-selected galaxies as well as within the 2<z<3 intergalactic medium (IGM). These measurements are derived from Voigt profile decomposition of the full Lyα and Lyβ forest in 15 high-resolution, high signal-to-noise ratio QSO spectra resulting in a catalog of ∼6000 HI absorbers.

Chapter 2 of this thesis focuses on HI surrounding high-z star-forming galaxies drawn from the Keck Baryonic Structure Survey (KBSS). The KBSS is a unique spectroscopic survey of the distant universe designed to explore the details of the connection between galaxies and intergalactic baryons within the same survey volumes. The KBSS combines high-quality background QSO spectroscopy with large densely-sampled galaxy redshift surveys to probe the CGM at scales of ∼50 kpc to a few Mpc. Based on these data, Chapter 2 presents the first quantitative measurements of the distribution, column density, kinematics, and absorber line widths of neutral hydrogen surrounding high-z star-forming galaxies.

Chapter 3 focuses on the thermal properties of the diffuse IGM. This analysis relies on measurements of the ∼6000 absorber line widths to constrain the thermal and turbulent velocities of absorbing "clouds." A positive correlation between the column density of HI and the minimum line width is recovered and implies a temperature-density relation within the low-density IGM for which higher-density regions are hotter, as is predicted by simple theoretical arguments.

Chapter 4 presents new measurements of the opacity of the IGM and CGM to hydrogen-ionizing photons. The chapter begins with a revised measurement of the HI column density distribution based on this new absorption line catalog that, due to the inclusion of high-order Lyman lines, provides the first statistically robust measurement of the frequency of absorbers with HI column densities 14 ≲ log(N_HI/cm^-2) ≲ 17.2. Also presented are the first measurements of the column density distribution of HI within the CGM (50 <d < 300 pkpc) of high-z galaxies. These distributions are used to calculate the total opacity of the IGM and IGM+CGM and to revise previous measurements of the mean free path of hydrogen-ionizing photons within the IGM. This chapter also considers the effect of the surrounding CGM on the transmission of ionizing photons out of the sites of active star-formation and into the IGM.

This thesis concludes with a brief discussion of work in progress focused on understanding the distribution of metals within the CGM of KBSS galaxies. Appendix B discusses my contributions to the MOSFIRE instrumentation project.

The superluminous supernova PS1-11ap: bridging the gap between low and high redshift

We present optical photometric and spectroscopic coverage of the superluminous supernova (SLSN) PS1-11ap, discovered with the Pan-STARRS1 Medium Deep Survey at z = 0.524. This intrinsically blue transient rose slowly to reach a peak magnitude of Mu = −21.4 mag and bolometric luminosity of 8 × 1043 erg s−1 before settling on to a relatively shallow gradient of decline. The observed decline is significantly slower than those of the SLSNe-Ic which have been the focus of much recent attention. Spectroscopic similarities with the lower redshift SN2007bi and a decline rate similar to 56Co decay time-scale initially indicated that this transient could be a candidate for a pair instability supernova (PISN) explosion. Overall the transient appears quite similar to SN2007bi and the lower redshift object PTF12dam. The extensive data set, from 30 d before peak to 230 d after, allows a detailed and quantitative comparison with published models of PISN explosions. We find that the PS1-11ap data do not match these model explosion parameters well, supporting the recent claim that these SNe are not pair instability explosions. We show that PS1-11ap has many features in common with the faster declining SLSNe-Ic, and the light-curve evolution can also be quantitatively explained by the magnetar spin-down model. At a redshift of z = 0.524, the observer-frame optical coverage provides comprehensive rest-frame UV data and allows us to compare it with the SLSNe recently found at high redshifts between z = 2 and 4. While these high-z explosions are still plausible PISN candidates, they match the photometric evolution of PS1-11ap and hence could be counterparts to this lower redshift transient.