MOONS: a Multi-Object Optical and Near-infrared Spectrograph for the VLT

MOONS is a new conceptual design for a Multi-Object Optical and Near-infrared Spectrograph for the Very Large Telescope (VLT), selected by ESO for a Phase A study. The baseline design consists of 1000 fibers deployable over a field of view of 500 square arcmin, the largest patrol field offered by the Nasmyth focus at the VLT. The total wavelength coverage is 0.8um-1.8um and two resolution modes: medium resolution and high resolution. In the medium resolution mode (R=4,000-6,000) the entire wavelength range 0.8um-1.8um is observed simultaneously, while the high resolution mode covers simultaneously three selected spectral regions: one around the CaII triplet (at R=8,000) to measure radial velocities, and two regions at R=20,000 one in the J-band and one in the H-band, for detailed measurements of chemical abundances. The grasp of the 8.2m Very Large Telescope (VLT) combined with the large multiplex and wavelength coverage of MOONS - extending into the near-IR - will provide the observational power necessary to study galaxy formation and evolution over the entire history of the Universe, from our Milky Way, through the redshift desert and up to the epoch of re-ionization at z>8-9. At the same time, the high spectral resolution mode will allow astronomers to study chemical abundances of stars in our Galaxy, in particular in the highly obscured regions of the Bulge, and provide the necessary follow-up of the Gaia mission. Such characteristics and versatility make MOONS the long-awaited workhorse near-IR MOS for the VLT, which will perfectly complement optical spectroscopy performed by FLAMES and VIMOS.Comment: 9 pages, 5 figures. To appear in the proceedings of the SPIE Astronomical Instrumentation + Telescopes conference, Amsterdam, 201

MOONS: the Multi-Object Optical and Near-infrared Spectrograph for the VLT

Instrumentatio

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Molecular polarity in tropomyosin-troponin T co-crystals

New features of the structure and interactions of troponin T and tropomyosin have been revealed by electron microscopy of so-called double-diamond co-crystals. These co-crystals were formed using rabbit alpha2 tropomyosin complexed with troponin T from either skeletal or cardiac muscle, which have different lengths in the amino-terminal region, as well as a bacterially expressed skeletal muscle troponin T fragment of 190 residues that lacks the amino-terminal region. Differences in the images of the co-crystals have allowed us to establish the polarities of both the troponin T subunit and tropomyosin in the projected lattice. Moreover, in agreement with their sequences, the amino-terminal region of a bovine cardiac muscle troponin T isoform appears to be longer than that from the rabbit skeletal muscle troponin T isoform and to span more of the amino terminus of tropomyosin at the head-to-tail filament joints. Images of crystals tilted relative to the electron beam also reveal the supercoiling of the tropomyosin filaments in this lattice. Based on these results, a three-dimensional model of the double-diamond lattice has been constructed

Orientation of cholera toxin bound to model membranes

The orientation of cholera toxin bound to its cell-surface receptor, ganglioside GM1, in a supporting lipid membrane was determined by electron microscopy of negatively stained toxin-lipid samples. Image analysis of two dimensional crystalline arrays has shown previously that the B-subunits of cholera toxin orient at the membrane surface as a pentameric ring with a central channel (Reed, R. A., J. Mattai, and G.G. Shipley. 1987. Biochemistry. 26:824–832; Ribi, H. O., D. S. Ludwig, K. L. Mercer, G. K. Schoolnik, and R. D. Kornberg. 1988. Science (Wash, DC). 239:1272–1276). We recorded images of negatively stained cholera toxin and isolated B-pentamers oriented perpendicular to the lipid surface so that the pentamer ring is viewed from the side. The pentamer dimensions, estimated from the average of 100 molecules, are approximately 60 by 30 A. Images of side views of whole cholera toxin clearly show density above the pentamer ring away from the lipid layer. On the basis of difference maps between averages of side views of whole toxin and B-pentamers, this density above the pentamer has been identified as a portion of the A-subunit. The A-subunit may also extend into the pore of the pentamer. In addition, Fab fragments from a monoclonal antibody to the A-subunit were mixed with the toxin prior to binding to GM1. Density from the Fab was localized to the region of toxin above the pentamer ring confirming the location of the A-subunit.(ABSTRACT TRUNCATED AT 250 WORDS

Structural studies of tropomyosin by cryoelectron microscopy and x-ray diffraction

A comparison has been made between cryoelectron microscope images and the x-ray structure of one projection of the Bailey tropomyosin crystal. The computed transforms of the electron micrographs extend to a resolution of approximately 18 A compared with the reflections from x-ray crystallography which extend to 15 A. After correction of the images for lattice distortions and the contrast transfer function, the structure factors were constrained to the plane group (pmg) symmetry of this projection. Amplitude and phase data for five images were compared with the corresponding view from the three-dimensional x-ray diffraction data (Phillips, G.N., Jr., J.P. Fillers, and C. Cohen. 1986. J. Mol. Biol. 192: 111–131). The average R factor between the electron microscopy and x-ray amplitudes was 15%, with an amplitude-weighted mean phase difference of 4.8 degrees. The density maps derived from cryoelectron microscopy contain structural features similar to those from x-ray diffraction: these include the width and run of the filaments and their woven appearance at the crossover regions. Preliminary images obtained from frozen-hydrated tropomyosin/troponin cocrystals suggest that this approach may provide structural details not readily obtainable from x-ray diffraction studies

Quantitative Whole Body Autoradiography (QWBA) Analysis Reveals That CPX-351 Shifts the Exposure of Cytarabine (Cyt) and Daunorubicin (Daun) Away from Many Tissues While Providing Prolonged Exposure to Cytotoxic Drug Concentrations in the Bone Marrow Compared to Conventional Free Drug Administration

Abstract Background: CPX-351 is a liposomal formulation co-encapsulating Cyt and Daun, that delivers the drugs in vivo at a 5:1 molar ratio shown to be synergistic preclinically. Clinically, CPX-351 has provided evidence of promising improvements in patient outcomes, most notably in elderly newly diagnosed high risk (secondary) AML and in unfavorable risk first relapse adult AML where statistically significant increases in overall survival where observed in two randomized, controlled Phase 2 studies. In patients, CPX-351 displays a volume of distribution equal to the plasma volume and first order elimination with a half-life of &gt; 24h for both drugs while maintaining the circulating Cyt:Daun molar ratio near 5:1. This is in contrast to the two drugs as conventionally administered in non-liposomal (NL) aqueous solution form where very rapid drug elimination is observed. Comparison of tissue distribution over time between CPX-351 and NL Cyt:Daun was performed in rats to better understand the pharmacodynamic relationships for CPX-351 in the context of what is known for the non-liposomal (NL) drugs, particularly as it relates to tissues relevant to efficacy and drug toxicity. Methods: Duplicate batches utilizing either [14C]Daun or [14C]Cyt CPX-351 or saline solutions of like labeled Cyt+Daun were prepared. Long-Evans rats received single IV bolus doses of either 15 units/kg (15 mg/kg Cyt + 6.64 mg/kg Daun) CPX-351, or a saline solution of 300 mg/kg Cyt + 10 mg/kg Daun. These doses were selected based on allometric scaling to reflect the respective clinical doses of CPX-351 and non-infusional Cyt:Daun treatment regimens. Animals were sacrificed at the designated time points post-dose and were frozen in a dry-ice/hexane bath in preparation for QWBA procedures. The tissue distribution of test article-derived radioactivity was determined using QWBA. Exposure of Cyt and Daun to a wide range of tissues was estimated based on the tissue density of [14C]Cyt-derived or [14C]Daun-derived radioactivity from QWBA section images. Tissue drug exposure comparisons between CPX-351 and NL Cyt:Daun were performed using Cmax and AUC0-t values. Results: The rapid tissue distribution of Cyt and Daun following injection of the NL form of the combination was reflected by the recovery of &lt;5% of either drug in the plasma 15 minutes after injection and tissue/plasma AUC0-t ratios that were &gt;1 and &gt;10 for [14C]Cyt and [14C]Daun, respectively, for the majority of tissues studied. In contrast, for CPX-351 virtually all of the injected Cyt and Daun was present in the plasma between 0.25-1.0 hours and corresponding tissue/plasma AUC0-t ratios in the majority of tissues were &lt;0.05 and &lt;0.2 for [14C]Cyt and [14C]Daun, respectively. These differences were readily apparent in the QWBA section images. For the NL form of the combination, [14C]Cyt and [14C]Daun were widely distributed throughout the body shortly after injection. Following CPX-351 administration, radioactivity was more limited to discreet tissues and organs. Distribution of Cyt into tissues after CPX-351 administration was reduced as well as much slower than after NL Cyt injection as reflected by markedly lower Cmax values in all non-vascular tissues as well as lower AUC values in a majority of tissues. Comparing [14C]Daun distribution for CPX-351 vs NL Daun revealed a slower removal from the blood/plasma compartment and gradual distribution to tissues for CPX-351 with a similar general tissue profile as for NL drug with the notable increases in exposure to spleen, liver, testis and bone marrow. Bone marrow levels of Cyt and Daun peaked at 24h post CPX-351 injection and persisted for several days at anti-leukemic concentrations; drug levels present in the marrow at 96h were well above the CPX-351 IC50 values previously observed with fresh AML patient blast samples. In contrast, bone marrow Cyt concentrations fell below detectable limits within 24h after administration of NL drug. Conclusions: CPX-351 shifts the exposure of Cyt and Daun away from most non-hematologic tissues compared to NL drug treatment. Importantly, CPX-351 accumulates and persists in the bone marrow for over 4 days at concentrations known to have anti-leukemic activity against AML blasts. Taken together, these results provide additional biologic rationale that support the clinical improvements in both efficacy and safety seen for CPX-351 in randomized trials compared to conventional Cyt + Daun treatment. Disclosures Mayer: Celator: Employment, Equity Ownership, Patents &amp; Royalties. Sadowski:Xenobiotic Laboratories: Employment. Tardi:Celator Pharmaceuticals: Employment, Equity Ownership. Xie:Celator Pharmaceuticals: Employment, Equity Ownership. Cabral-Lilly:Ceator Pharmaceuticals: Employment, Equity Ownership. Heller:Xenobiotic Laboratories: Employment, Research Funding. </jats:sec