Impact micro-positioning actuator

An impact micro-positioning actuator. In one aspect of the invention, a threaded shaft is threadably received in a nut and the nut is impacted by an impacting device, causing the nut first to rotate relative to the shaft by slipping as a result of shaft inertia and subsequently to stick to the shaft as a result of the frictional force therebetween. The nut is returned to its initial position by a return force provided by a return mechanism after impact. The micro-positioning actuator is further improved by controlling at least one and preferably all of the following: the friction, the impact provided by the impacting device, the return force provided by the return mechanism, and the inertia of the shaft. In another aspect of the invention, a threaded shaft is threadably received in a nut and the shaft is impacted by an impacting device, causing the shaft to rotate relative to the nut

A cryogenic liquid-mirror telescope on the moon to study the early universe

We have studied the feasibility and scientific potential of zenith observing liquid mirror telescopes having 20 to 100 m diameters located on the moon. They would carry out deep infrared surveys to study the distant universe and follow up discoveries made with the 6 m James Webb Space Telescope (JWST), with more detailed images and spectroscopic studies. They could detect objects 100 times fainter than JWST, observing the first, high-red shift stars in the early universe and their assembly into galaxies. We explored the scientific opportunities, key technologies and optimum location of such telescopes. We have demonstrated critical technologies. For example, the primary mirror would necessitate a high-reflectivity liquid that does not evaporate in the lunar vacuum and remains liquid at less than 100K: We have made a crucial demonstration by successfully coating an ionic liquid that has negligible vapor pressure. We also successfully experimented with a liquid mirror spinning on a superconducting bearing, as will be needed for the cryogenic, vacuum environment of the telescope. We have investigated issues related to lunar locations, concluding that locations within a few km of a pole are ideal for deep sky cover and long integration times. We have located ridges and crater rims within 0.5 degrees of the North Pole that are illuminated for at least some sun angles during lunar winter, providing power and temperature control. We also have identified potential problems, like lunar dust. Issues raised by our preliminary study demand additional in-depth analyses. These issues must be fully examined as part of a scientific debate we hope to start with the present article.Comment: 35 pages, 11 figures. To appear in Astrophysical Journal June 20 200

First On-Sky High Contrast Imaging with an Apodizing Phase Plate

We present the first astronomical observations obtained with an Apodizing Phase Plate (APP). The plate is designed to suppress the stellar diffraction pattern by 5 magnitudes from 2-9 lambda/D over a 180 degree region. Stellar images were obtained in the M' band (4.85 microns) at the MMTO 6.5m telescope, with adaptive wavefront correction made with a deformable secondary mirror designed for low thermal background observations. The measured PSF shows a halo intensity of 0.1% of the stellar peak at 2 lambda/D (0.36 arcsec), tapering off as r^{-5/3} out to radius 9 lambda/D. Such a profile is consistent with residual errors predicted for servo lag in the AO system. We project a 5 sigma contrast limit, set by residual atmospheric fluctuations, of 10.2 magnitudes at 0.36 arcsec separation for a one hour exposure. This can be realised if static and quasi-static aberrations are removed by differential imaging, and is close to the sensitivity level set by thermal background photon noise for target stars with M'>3. The advantage of using the phase plate is the removal of speckle noise caused by the residuals in the diffraction pattern that remain after PSF subtraction. The APP gives higher sensitivity over the range 2-5 lambda/D compared to direct imaging techniques.Comment: 22 pages, 5 figures, 1 table, ApJ accepte

Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis.

Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues were also shown to be nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

High Resolution Images of Orbital Motion in the Trapezium Cluster: First Scientific Results from the MMT Deformable Secondary Mirror Adaptive Optics System

We present the first scientific images obtained with a deformable secondary mirror adaptive optics system. We utilized the 6.5m MMT AO system to produce high-resolution (FWHM=0.07'') near infrared (1.6 um) images of the young (~1 Myr) Orion Trapezium theta 1 Ori cluster members. A combination of high spatial resolution and high signal to noise allowed the positions of these stars to be measured to within ~0.003'' accuracies. Including previous speckle data (Weigelt et al. 1999), we analyze a six year baseline of high-resolution observations of this cluster. Over this baseline we are sensitive to relative proper motions of only ~0.002''/yr (4.2 km/s at 450 pc). At such sensitivities we detect orbital motion in the very tight theta 1 Ori B2B3 (52 AU separation) and theta 1 Ori A1A2 (94 AU separation) systems. Such motions are consistent with those independently observed by Schertl et al. (2003) with speckle interferometry, giving us confidence that these very small (~0.002''/yr) orbital motions are real. All five members of the theta 1 Ori B system appear likely gravitationally bound. The very lowest mass member of the theta 1 Ori B system (B4) has K' ~11.66 and an estimated mass of ~0.2 Msun. There was very little motion (4+/-15 km/s) detected of B4 w.r.t B1 or B2, hence B4 is possibly part of the theta 1 Ori B group. We suspect that if this very low mass member is physically associated it most likely is in an unstable (non-hierarchical) orbital position and will soon be ejected from the group. The theta 1 Ori B system appears to be a good example of a star formation ``mini-cluster'' which may eject the lowest mass members of the cluster in the near future. This ``ejection'' process could play a major role in the formation of low mass stars and brown dwarfs.Comment: To appear in the December 10, 2003 issue of the Astrophysical Journal 21 pages, 14 figures (some in color, but print OK in B&W

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Approaches to lowering the cost of large space telescopes

New development approaches, including launch vehicles and advances in sensors, computing, and software, have lowered the cost of entry into space, and have enabled a revolution in low-cost, high-risk Small Satellite (SmallSat) missions. To bring about a similar transformation in larger space telescopes, it is necessary to reconsider the full paradigm of space observatories. Here we will review the history of space telescope development and cost drivers, and describe an example conceptual design for a low cost 6.5 m optical telescope to enable new science when operated in space at room temperature. It uses a monolithic primary mirror of borosilicate glass, drawing on lessons and tools from decades of experience with ground-based observatories and instruments, as well as flagship space missions. It takes advantage, as do large launch vehicles, of increased computing power and space-worthy commercial electronics in low-cost active predictive control systems to maintain stability. We will describe an approach that incorporates science and trade study results that address driving requirements such as integration and testing costs, reliability, spacecraft jitter, and wavefront stability in this new risk-tolerant "LargeSat" context.Comment: Presented at SPIE, Optics+Photonics 2023, Astronomical Optics: Design, Manufacture, and Test of Space and Ground Systems IV in San Diego, CA, US