Improving the outcome of patients with castration-resistant prostate cancer through rational drug development

Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Although docetaxel has recently been shown to extend the survival of patients with CRPC in two large randomised phase III studies, subsequent treatment options remain limited for these patients. A greater understanding of the molecular causes of castration resistance is allowing a more rational approach to the development of new drugs and many new agents are now in clinical development. Therapeutic targets include the adrenal steroid synthesis pathway, androgen receptor signalling, the epidermal growth factor receptor family, insulin growth factor-1 receptor, histone deacetylase, heat shock protein 90 and the tumour vasculature. Drugs against these targets are giving an insight into the molecular pathogenesis of this disease and promise to improve patient quality of life and survival. Finally, the recent discovery of chromosomal translocations resulting in the upregulation of one of at least 3 ETS genes (ERG, ETV1, ETV4) may lead to novel agents for the treatment of this disease

The Electromagnetic Counterpart of the Binary Neutron Star Merger LIGO/Virgo GW170817. II. UV, Optical, and Near-infrared Light Curves and Comparison to Kilonova Models

We present UV, optical, and NIR photometry of the first electromagnetic counterpart to a gravitational wave source from Advanced LIGO/Virgo, the binary neutron star merger GW170817. Our data set extends from the discovery of the optical counterpart at $0.47$ days to $18.5$ days post-merger, and includes observations with the Dark Energy Camera (DECam), Gemini-South/FLAMINGOS-2 (GS/F2), and the {\it Hubble Space Telescope} ({\it HST}). The spectral energy distribution (SED) inferred from this photometry at $0.6$ days is well described by a blackbody model with $T\approx 8300$ K, a radius of $R\approx 4.5\times 10^{14}$ cm (corresponding to an expansion velocity of $v\approx 0.3c$), and a bolometric luminosity of $L_{\rm bol}\approx 5\times10^{41}$ erg s$^{-1}$. At $1.5$ days we find a multi-component SED across the optical and NIR, and subsequently we observe rapid fading in the UV and blue optical bands and significant reddening of the optical/NIR colors. Modeling the entire data set we find that models with heating from radioactive decay of $^{56}$Ni, or those with only a single component of opacity from $r$-process elements, fail to capture the rapid optical decline and red optical/NIR colors. Instead, models with two components consistent with lanthanide-poor and lanthanide-rich ejecta provide a good fit to the data, the resulting "blue" component has $M_\mathrm{ej}^\mathrm{blue}\approx 0.01$ M$_\odot$ and $v_\mathrm{ej}^\mathrm{blue}\approx 0.3$c, and the "red" component has $M_\mathrm{ej}^\mathrm{red}\approx 0.04$ M$_\odot$ and $v_\mathrm{ej}^\mathrm{red}\approx 0.1$c. These ejecta masses are broadly consistent with the estimated $r$-process production rate required to explain the Milky Way $r$-process abundances, providing the first evidence that BNS mergers can be a dominant site of $r$-process enrichment

Isotopic paleobiology of some tertiary larger foraminifera from Kutch, India

The paleobiology of some Tertiary larger foraminifera from Kutch is inferred using oxygen and carbon isotopic data, Spiroclypeus and Heterostegina (having chamber-lets) show lower delta(13)C values than Nummulites and Assilina (having undivided chambers). This difference is attributed to algal endosymbionts for whom division of chambers is functionally advantageous, The isotopic data also support the view that pustules on the surface of some larger foraminifera developed to concentrate light for the benefit of endosymbionts. Isotopic variability is greater in megalospheric than in microspheric farms, indicating that the megalospheric forms are more tolerant of ecological variation than the microspheric ones, and this could be one of the reasons why they are more common in the geologic record, Similarly, variability in delta(18)O and delta(13)C isotopic values indicate that the family Nummulitidae is more stenotopic, whereas Lepidocyclinidae and Miogypsinidae appear to be more eurytopic. The order of extinction of the genera Assilina, Nummulites and Spiroclypeus also parallels the progressive decline in delta(13)C in their skeletal carbonates, This parallelism possibly indicates a greater role for endosymbionts in the evolution of larger foraminifera