The Keck Cosmic Web Imager

We are designing the Keck Cosmic Web Imager (KCWI) as a new facility instrument for the Keck II telescope at the W. M. Keck Observatory (WMKO). KCWI is based on the Cosmic Web Imager (CWI), an instrument that has recently had first light at the Hale Telescope. KCWI is a wide-field integral-field spectrograph (IFS) optimized for precision sky limited spectroscopy of low surface brightness phenomena. KCWI will feature high throughput, and flexibility in field of view (FOV), spatial sampling, bandpass, and spectral resolution. KCWI will provide full wavelength coverage (0.35 to 1.05 μm) using optimized blue and red channels. KCWI will provide a unique and complementary capability at WMKO (optical band integral field spectroscopy) that is directly connected to one of the Observatory's strategic goals (faint object, high precision spectroscopy), at a modest cost and on a competitive time scale, made possible by its simple concept and the prior demonstration of CWI

Inhibition of VEGF and Angiopoietin-2 to Reduce Brain Metastases of Breast Cancer Burden

For metastases in the central nervous system, angiogenesis enhances metastatic potential and promotes progression. Primary factors which drive vessel growth are vascular endothelial growth factor (VEGF) and angiopoietin-2. Preclinical models show inhibition of either factor reduces metastases spread and inhibits growth. This work sets out to answer two questions in a preclinical mouse model. First, whether the combined inhibition of VEGF and angiopoietin-2, reduces passive permeability and limits drug uptake into brain metastases; and second, whether this inhibition reduces metastases burden in brain. We observed combinatorial inhibition of VEGF and angiopoietin-2, decreased (p \u3c 0.05) angiogenesis and vascular branching in an aortic ring assay and decreased (p \u3c 0.05) endothelial wound closure times. Using a brain metastases of breast cancer model (induced by intracardiac injections of brain seeking MDA-MB-231Br cells or 4T1Br cells), we observed, similar to VEGF, angiopoetin-2 expression correlates to increased angiogenesis (p \u3c 0.05) and increased lesion permeability. To determine efficacy, animals were administered bevacizumab plus L1-10 (angiopoietin inhibitor) twice per week until neurological symptoms developed. Lesion permeability significantly decreased by ∼50% (p \u3c 0.05) compared to untreated lesions, but remained ∼25% greater (p \u3c 0.0%) than brain. In subsequent experiments, animals were administered similar regimens but sacrificed on day 32. The number of metastatic lesions developed was significantly (p \u3c 0.001) reduced in the bevacizumab group (56%) and combination group (86%). Lesions’ size was reduced in bevacizumab treated lesions (∼67%) and bevacizumab and L1-10 treated lesions (∼78%) developing area \u3c 0.5 mm2. In summary, combinatorial inhibition of VEGF and angiopoietin reduces lesion permeability and brain metastatic burden

The combined effect of biological control with plant competition on the management of parthenium weed (Parthenium hysterophorus L.)

Parthenium hysterophorus L., (Asteraceae) commonly known as parthenium weed, is a highly invasive plant that has become a problematic weed of pasture lands in Australia and many other countries around the world. For the management of this weed, an integrated approach comprising biological control and plant competition strategies was tested in southern central Queensland. Two competitive pasture plant species (butterfly pea and buffel grass), selected for their high competitive ability, worked successfully with the biological control agent (Epiblema strenuana Walker) to synergistically reduce the biomass of parthenium weed, by between 62 and 69%. In the presence of biological control agent, the corresponding biomass of competitive plants, butterfly pea and buffel grass increased in comparison to when the biological control agent had been excluded, by 15 and 35%, respectively. This suggests that biological control and competitive plants can complement one another to bring about improved management of parthenium weed in Australia. Further, this approach may be adopted in countries where some of the biological control agents are already present including South Africa, Ethiopia, India, Pakistan and Nepal

Advances in instrumentation at the W. M. Keck Observatory

In this paper we describe both recently completed instrumentation projects and our current development efforts in the context of the Observatory's science driven strategic plan which seeks to address key questions in observational astronomy for extra-galactic, Galactic, and planetary science with both seeing limited capabilities and high angular resolution adaptive optics capabilities. This paper will review recently completed projects as well as new instruments in development including MOSFIRE, a near IR multi-object spectrograph nearing completion, a new seeing limited integral field spectrograph for the visible wavelength range called the Keck Cosmic Web Imager, and the Keck Next Generation Adaptive Optics facility and its first light science instrument DAVINCI

Concept for the Keck Next Generation Adaptive Optics system

The Next Generation Adaptive Optics (NGAO) system will represent a considerable advancement for high resolution astronomical imaging and spectroscopy at the W. M. Keck Observatory. The AO system will incorporate multiple laser guidestar tomography to increase the corrected field of view and remove the cone effect inherent to single laser guide star systems. The improvement will permit higher Strehl correction in the near-infrared and diffraction-limited correction down to R band. A high actuator count micro-electromechanical system (MEMS) deformable mirror will provide the on-axis wavefront correction to a number of instrument stations and additional MEMS devices will feed multiple channels of a deployable integral-field spectrograph. In this paper we present the status of the AO system design and describe its various operating modes

Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer

Abstract Background: Brain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes. Methods: Human metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of female NuNu mice. Metastases were allowed to grow for 28 days, after which animals were injected fluorescent tracers Texas Red (625 Da) or Texas Red dextran (3 kDa) or a chemotherapeutic agent 14C-paclitaxel. The accumulation of tracers and 14C-paclitaxel in BAT were determined by using quantitative fluorescent microscopy and autoradiography respectively. The effect of chemotherapy in BAT was determined by staining for activated astrocytes. Results: The mean permeability of texas Red (625 Da) within BAT region increased 1.0 to 2.5-fold when compared to normal brain, whereas, Texas Red dextran (3 kDa) demonstrated mean permeability increase ranging from 1.0 to 1.8-fold compared to normal brain. The Kin values in the BAT for both Texas Red (625 Da) and Texas Red dextran (3 kDa) were found to be 4.32 ± 0.2 × 105 mL/s/g and 1.6 ± 1.4 × 105 mL/s/g respectively and found to be significantly higher than the normal brain. We also found that there is significant increase in accumulation of 14C-Paclitaxel in BAT compared to the normal brain. We also observed animals treated with chemotherapy (paclitaxel (10 mg/kg), erubilin (1.5 mg/kg) and docetaxel (10 mg/kg)) showed activated astrocytes in BAT. Conclusions: Our data showed increased permeation of fluorescent tracers and 14C-paclitaxel in the BAT. This increased permeation lead to elevated levels of activated astrocytes in BAT region in the animals treated with chemotherapy

NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer

Background: Brain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity. Methods: Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively). Results: NKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (\u3e20 ng/g for 168 h) versus conventional irinotecan (\u3e1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals. Conclusions: Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m2 NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results

Concert recording 2018-02-20a

[Track 1]. Fünf Orchesterlieder nach Ansichtenkartentexten von Peter Altenberg, op. 4. I. Seele, wie bist du schöner... [Track 2]. II. Sahst du nach dem Gewitterregen [Track 3]. III. Über die Grenzen des All [Track 4]. IV. Nichts ist gekommen [Track 5]. V. Hier ist Friede / Alban Berg -- [Track 6]. Flowers of heaven. Three songs on Korean poetry for soprano and cello. I. The home village [Track 7]. II. Wildflowers of the mountain [Track 8]. III. Return to heaven / Robert Mueller -- [Track 9]. Buru for voice and chamber ensemble / Suhki Kang -- [Track 10]. Little sketches for soprano and flute / Ivan Elezovic -- [Track 11]. Labyrinth of love for soprano and small chamber ensemble. II. Eros (Sappho fragment 47) [Track 12]. VI. Liz\u27s lament [Track 13]. VIII. Short talk on the sensation of aeroplane takeoff / Michael Daugherty

Advances in instrumentation at the W. M. Keck Observatory

In this paper we describe both recently completed instrumentation projects and our current development efforts in the context of the Observatory's science driven strategic plan which seeks to address key questions in observational astronomy for extra-galactic, Galactic, and planetary science with both seeing limited capabilities and high angular resolution adaptive optics capabilities. This paper will review recently completed projects as well as new instruments in development including MOSFIRE, a near IR multi-object spectrograph nearing completion, a new seeing limited integral field spectrograph for the visible wavelength range called the Keck Cosmic Web Imager, and the Keck Next Generation Adaptive Optics facility and its first light science instrument DAVINCI

MAGIQ at the W. M. Keck Observatory: initial deployment of a new acquisition, guiding, and image quality monitoring system

The W. M. Keck Observatory has completed the development and initial deployment of MAGIQ, the Multi-function Acquisition, Guiding and Image Quality monitoring system. MAGIQ is an integrated system for acquisition, guiding and image quality measurement for the Keck telescopes. This system replaces the acquisition and guiding hardware and software for existing instruments at the Observatory and is now the standard for visible wavelength band acquisition cameras for future instrumentation. In this paper we report on the final design and implementation of this new system, which includes three major components: a visible wavelength band acquisition camera, image quality measurement capability, and software for acquisition, guiding and image quality monitoring. The overall performance is described, as well as the details of our approach to integrating low order wavefront sensing capability in order to provide closed loop control of telescope focus