The infrared imaging spectrograph (IRIS) for TMT: spectrograph design

The Infra-Red Imaging Spectrograph (IRIS) is one of the three first light instruments for the Thirty Meter Telescope (TMT) and is the only one to directly sample the diffraction limit. The instrument consists of a parallel imager and off-axis Integral Field Spectrograph (IFS) for optimum use of the near infrared (0.84um-2.4um) Adaptive Optics corrected focal surface. We present an overview of the IRIS spectrograph that is designed to probe a range of scientific targets from the dynamics and morphology of high-z galaxies to studying the atmospheres and surfaces of solar system objects, the latter requiring a narrow field and high Strehl performance. The IRIS spectrograph is a hybrid system consisting of two state of the art IFS technologies providing four plate scales (4mas, 9mas, 25mas, 50mas spaxel sizes). We present the design of the unique hybrid system that combines the power of a lenslet spectrograph and image slicer spectrograph in a configuration where major hardware is shared. The result is a powerful yet economical solution to what would otherwise require two separate 30m-class instruments.Comment: 15 pages, 11 figure

Revascularization of Chronic Hibernating Myocardium Stimulates Myocyte Proliferation and Partially Reverses Chronic Adaptations to Ischemia

AbstractBackgroundThe time course and extent of recovery after revascularization of viable dysfunctional myocardium are variable. Although fibrosis is a major determinant, myocyte structural and molecular remodeling may also play important roles.ObjectivesThis study sought to determine whether persistent myocyte loss and/or irreversibility of protein changes that develop in hibernating myocardium have an impact on functional recovery in the absence of infarction.MethodsSwine implanted with a chronic left anterior descending artery (LAD) stenosis to produce hibernating myocardium underwent percutaneous revascularization, with serial functional recovery evaluated for 1 month (n = 12). Myocardial tissue was evaluated to assess myocyte size, nuclear density, and proliferation indexes in comparison with those of normal animals and nonrevascularized controls. Proteomic analysis by 2-dimensional differential in-gel electrophoresis was used to determine the reversibility of molecular adaptations of hibernating myocytes.ResultsAt 3 months, physiological features of hibernating myocardium were confirmed, with depressed LAD wall thickening and no significant infarction. Revascularization normalized LAD flow reserve, with no immediate change in LAD wall thickening. Regional LAD wall thickening slowly improved but remained depressed 1 month post–percutaneous coronary intervention. Surprisingly, revascularization was associated with histological evidence of myocytes re-entering the growth phase of the cell cycle and increases in the number of c-Kit+ cells. Myocyte nuclear density returned to normal, whereas regional myocyte hypertrophy regressed. Proteomic analysis demonstrated heterogeneous effects of revascularization. Up-regulated stress and cytoskeletal proteins normalized, whereas reduced contractile and metabolic proteins persisted.ConclusionsDelayed recovery of hibernating myocardium in the absence of scar may reflect persistent reductions in the amounts of contractile and metabolic proteins. Although revascularization appeared to stimulate myocyte proliferation, the persistence of small immature myocytes may have contributed to delayed functional recovery

Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans mutants with resistance to known anthelmintic drugs such as ivermectin are equally or more susceptible to these three drugs, suggesting that they may act on novel targets to kill worms. Sertraline, paroxetine, and chlorpromazine have long histories of use clinically as antidepressant or antipsychotic medicines. They may represent new classes of anthelmintic drug that could be used in combination with existing front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance

New Asian and Nearctic Hypechiniscus species (Heterotardigrada: Echiniscidae) signalize a pseudocryptic horn of plenty

The cosmopolitan echiniscid genus Hypechiniscus contains exclusively rare species. In this contribution, by combining statistical morphometry and molecular phylogeny, we present qualitative and quantitative aspects of Hypechiniscus diversity, which remained hidden under the two purportedly cosmopolitan species: H. gladiator and H. exarmatus. A neotype is designated for H. gladiator from Creag Meagaidh (Scotland), and an informal re-description is provided for H. exarmatus based on animals from Creag Meagaidh and the Isle of Skye (Inner Hebrides). Subspecies/forms of H. gladiator are suppressed due to the high developmental variability of the cirrus dorsalis. At the same time, four species of the genus are described: H. daedalus sp. nov. from Roan Mountain and the Great Smoky Mountains (Southern Appalachian Mountains, USA), H. flavus sp. nov. and H. geminus sp. nov. from the Yatsugatake Mountains (Honshu, Japan), and H. cataractus sp. nov. from the Malay Archipelago (Borneo and the Moluccas). Dorsal and ventral sculpturing, together with morphometric traits, are shown to be the key characters that allow for the phenotypic discrimination of species within the genus. Furthermore, the morphology of Hypechiniscus is discussed and compared to that of the most similar genera, Pseudechiniscus and Stellariscus. Finally, a diagnostic key to all recognized Hypechiniscus species is provided

4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.

BackgroundChagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice.Methodology/principal findingsBoth acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart.Conclusions/significanceThe positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life

Properties of the Strange Axial Mesons in the Relativized Quark Model

We studied properties of the strange axial mesons in the relativized quark model. We calculated the $K_1$ decay constant in the quark model and showed how it can be used to extract the $K_1 (^3P_1) - K_1 (^1P_1)$ mixing angle ($\theta_K$) from the weak decay $\tau \to K_1 \nu_\tau$. The ratio $BR(\tau \to \nu_\tau K_1 (1270))/BR(\tau\to \nu_\tau K_1(1400))$ is the most sensitive measurement and also the most reliable since the largest of the theoretical uncertainties factor out. However the current bounds extracted from the TPC/Two-Gamma collaboration measurements are rather weak: we typically obtain $-30^o \lesssim \theta_K \lesssim 50^o$ at 68\% C.L. We also calculated the strong OZI-allowed decays in the pseudoscalar emission model and the flux-tube breaking model and extracted a $^3P_1 - ^1P_1$ mixing angle of $\theta_K \simeq 45^o$. Our analysis also indicates that the heavy quark limit does not give a good description of the strange mesons.Comment: Revised version to be published in Phys. Rev. D. Minor changes. Latex file uses revtex version 3 and epsfig, 4 postcript figures are attached. The full postcript version with embedded figures is available at ftp://ftp.physics.carleton.ca/pub/theory/godfrey/ocipc9512.ps.

Observation of interstellar lithium in the low-metallicity Small Magellanic Cloud

The primordial abundances of light elements produced in the standard theory of Big Bang nucleosynthesis (BBN) depend only on the cosmic ratio of baryons to photons, a quantity inferred from observations of the microwave background. The predicted primordial 7Li abundance is four times that measured in the atmospheres of Galactic halo stars. This discrepancy could be caused by modification of surface lithium abundances during the stars' lifetimes or by physics beyond the Standard Model that affects early nucleosynthesis. The lithium abundance of low-metallicity gas provides an alternative constraint on the primordial abundance and cosmic evolution of lithium that is not susceptible to the in situ modifications that may affect stellar atmospheres. Here we report observations of interstellar 7Li in the low-metallicity gas of the Small Magellanic Cloud, a nearby galaxy with a quarter the Sun's metallicity. The present-day 7Li abundance of the Small Magellanic Cloud is nearly equal to the BBN predictions, severely constraining the amount of possible subsequent enrichment of the gas by stellar and cosmic-ray nucleosynthesis. Our measurements can be reconciled with standard BBN with an extremely fine-tuned depletion of stellar Li with metallicity. They are also consistent with non-standard BBN.Comment: Published in Nature. Includes main text and Supplementary Information. Replaced with final title and abstrac

The Infrared Imaging Spectrograph (IRIS) for TMT: Instrument Overview

We present an overview of the design of IRIS, an infrared (0.84 - 2.4 micron) integral field spectrograph and imaging camera for the Thirty Meter Telescope (TMT). With extremely low wavefront error (<30 nm) and on-board wavefront sensors, IRIS will take advantage of the high angular resolution of the narrow field infrared adaptive optics system (NFIRAOS) to dissect the sky at the diffraction limit of the 30-meter aperture. With a primary spectral resolution of 4000 and spatial sampling starting at 4 milliarcseconds, the instrument will create an unparalleled ability to explore high redshift galaxies, the Galactic center, star forming regions and virtually any astrophysical object. This paper summarizes the entire design and basic capabilities. Among the design innovations is the combination of lenslet and slicer integral field units, new 4Kx4k detectors, extremely precise atmospheric dispersion correction, infrared wavefront sensors, and a very large vacuum cryogenic system.Comment: Proceedings of the SPIE, 9147-76 (2014