451 research outputs found
Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner-Wadsworth-Emmons-based approach
Integrin inhibitors based on the tripeptide sequence Arg-Gly-Asp (RGD) are potential therapeutics for the treatment of idiopathic pulmonary fibrosis (IPF). Herein, we describe an expeditious three-step synthetic sequence of Horner-Wadsworth-Emmons olefination, diimide reduction, and global deprotection to synthesise cores for these compounds in high yields (63-83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps
The feasibility of implementing the ICHOM Standard Set for Hip and Knee Osteoarthritis: a mixed-methods evaluation in public and private hospital settings.
Background: There is growing international momentum for standardising patient outcome assessment and using patient-reported outcome measures (PROMs) to capture outcomes that matter to patients. The International Consortium for Health Outcomes Measurement (ICHOM) Standard Sets were developed to capture the outcomes of care for costly conditions including osteoarthritis. This study evaluated the feasibility of implementing the ICHOM Standard Set for Hip and Knee Osteoarthritis in \u27real world\u27 public and private hospital settings.
Methods: A mixed-methods design was used to capture comprehensive data on patient outcomes, implementation costs, and the implementation experiences of patients, clinicians and administrative staff. The ICHOM Standard Set was implemented at two hospital sites (1 public, 1 private) in May 2016. Patients undergoing primary hip or knee replacement for osteoarthritis were recruited from pre-admission clinics and a private orthopaedic clinic. Baseline Standard Set data were collected before surgery and at pre-determined post-operative timepoints. Data on the costs of Standard Set implementation were also collected. Semi-structured interviews were conducted with key stakeholders (
Results: The cost of Standard Set implementation and ongoing data collection for 17 months totalled $AUD94,955. Preference data (collected prior to completing the Standard Set) revealed that most participants preferred paper-based (83%) or web-based questionnaire completion (14%), with only a small proportion preferring iPad-based completion (3%). Several PROMs within the Standard Set were responsive to change (effect size range 0.19-0.85), with significant improvements in important health outcomes identified 6 weeks after surgery. Patient interviews showed a variable understanding of why patient-reported data collection is undertaken; however, patients perceived that PROMs provided relevant information to treating clinicians, and that the burden of questionnaire completion was minimal. Staff interviews revealed that PROMs are considered valuable, dedicated personnel are required to support data collection, gaps in information technology resources must be addressed, and that the Standard Set offers benefits beyond what currently-used measures provide.
Conclusion: The Standard Set can be feasibly implemented in hospital settings, but with important caveats around staffing and technical support, consideration of patient preferences, and promotion of active clinician engagement
GRAVITY: the Calibration Unit
We present in this paper the design and characterisation of a new sub-system
of the VLTI 2nd generation instrument GRAVITY: the Calibration Unit. The
Calibration Unit provides all functions to test and calibrate the beam combiner
instrument: it creates two artificial stars on four beams, and dispose of four
delay lines with an internal metrology. It also includes artificial stars for
the tip-tilt and pupil guiding systems, as well as four metrology pick-up
diodes, for tests and calibration of the corresponding sub-systems. The
calibration unit also hosts the reference targets to align GRAVITY to the VLTI,
and the safety shutters to avoid the metrology light to propagate in the
VLTI-lab. We present the results of the characterisation and validtion of these
differrent sub-units.Comment: 12 pages, 11 figures. Proceeding of SPIE 9146 "Optical and Infrared
Interferometry IV
The GRAVITY metrology system: modeling a metrology in optical fibers
GRAVITY is the second generation VLT Interferometer (VLTI) instrument for
high-precision narrow-angle astrometry and phase-referenced interferometric
imaging. The laser metrology system of GRAVITY is at the heart of its
astrometric mode, which must measure the distance of 2 stars with a precision
of 10 micro-arcseconds. This means the metrology has to measure the optical
path difference between the two beam combiners of GRAVITY to a level of 5 nm.
The metrology design presents some non-common paths that have consequently to
be stable at a level of 1 nm. Otherwise they would impact the performance of
GRAVITY. The various tests we made in the past on the prototype give us hints
on the components responsible for this error, and on their respective
contribution to the total error. It is however difficult to assess their exact
origin from only OPD measurements, and therefore, to propose a solution to this
problem. In this paper, we present the results of a semi-empirical modeling of
the fibered metrology system, relying on theoretical basis, as well as on
characterisations of key components. The modeling of the metrology system
regarding various effects, e.g., temperature, waveguide heating or mechanical
stress, will help us to understand how the metrology behave. The goals of this
modeling are to 1) model the test set-ups and reproduce the measurements (as a
validation of the modeling), 2) determine the origin of the non-common path
errors, and 3) propose modifications to the current metrology design to reach
the required 1nm stability.Comment: 20 pages, 19 figures. Proceeding of SPIE 9146 "Optical and Infrared
Interferometry IV
Synthesis of arylethylamines via C(sp3)–C(sp3) palladium-catalyzed cross-coupling
Substituted arylethylamines represent a key structural motif in natural, pharmaceutical, and agrochemical compounds. Access to such scaffolds has been the subject of long-standing synthetic interest. Herein, we report the synthesis of such scaffolds via a palladium-catalyzed C(sp3)-C(sp3) coupling between (chloromethyl)aryls and air-/moisture-stable N,N-dialkylaminomethyltrifluoroborate salts. Rapid hit identification was achieved using microscale high-throughput experimentation and was followed by millimolar-scale reaction parameter optimization. A range of structurally and electronically varied arylethylamine products were obtained in moderate to excellent yields (27-96%, >60 examples). The reaction mechanism is proposed to proceed via formation of a trialkylbenzylammonium species prior to oxidative addition
Combined CO & Dust Scaling Relations of Depletion Time and Molecular Gas Fractions with Cosmic Time, Specific Star Formation Rate and Stellar Mass
We combine molecular gas masses inferred from CO emission in 500 star forming
galaxies (SFGs) between z=0 and 3, from the IRAM-COLDGASS, PHIBSS1/2 and other
surveys, with gas masses derived from Herschel far-IR dust measurements in 512
galaxy stacks over the same stellar mass/redshift range. We constrain the
scaling relations of molecular gas depletion time scale (tdepl) and gas to
stellar mass ratio (Mmolgas/M*) of SFGs near the star formation main-sequence
with redshift, specific star formation rate (sSFR) and stellar mass (M*). The
CO- and dust-based scaling relations agree remarkably well. This suggests that
the CO-H2 mass conversion factor varies little within 0.6dex of the main
sequence (sSFR(ms,z,M*)), and less than 0.3dex throughout this redshift range.
This study builds on and strengthens the results of earlier work. We find that
tdepl scales as (1+z)^-0.3 *(sSFR/sSFR(ms,z,M*))^-0.5, with little dependence
on M*. The resulting steep redshift dependence of Mmolgas/M* ~(1+z)^3 mirrors
that of the sSFR and probably reflects the gas supply rate. The decreasing gas
fractions at high M* are driven by the flattening of the SFR-M* relation.
Throughout the redshift range probed a larger sSFR at constant M* is due to a
combination of an increasing gas fraction and a decreasing depletion time
scale. As a result galaxy integrated samples of the Mmolgas-SFR rate relation
exhibit a super-linear slope, which increases with the range of sSFR. With
these new relations it is now possible to determine Mmolgas with an accuracy of
0.1dex in relative terms, and 0.2dex including systematic uncertainties.Comment: ApJ accepte
Discovery of the first potent and selective αvβ5 integrin inhibitor based on an amide-containing core
Integrins αvβ5 and αvβ3 are closely related, proangiogenic members of the wider RGD-binding integrin family. Due to their high sequence homology, the development of αvβ5-selective compounds has remained elusive to synthetic and medicinal chemists. Herein, we describe a survey of SAR around a series of amide-containing 3-aryl-succinamic acid-based RGD mimetics. This resulted in the discovery of α,α,α-trifluorotolyl 12 which exhibits 800 × selectivity for αvβ5 versus αvβ3 with a pyrrolidine amide linker that confers selectivity for αvβ5 by positioning a key aryl ring in the SDL of αvβ5 with good complementarity; binding in this mode is disfavoured in αvβ3 due to clashes with key residues in the β3-subunit. Compound 12 exhibits selective inhibition by a cell adhesion assay, high passive permeability and solubility which enables potential use of this inhibitor as an αvβ5-selective in vitro tool compound
The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns
Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research
First direct detection of an exoplanet by optical interferometry; Astrometry and K-band spectroscopy of HR8799 e
To date, infrared interferometry at best achieved contrast ratios of a few
times on bright targets. GRAVITY, with its dual-field mode, is now
capable of high contrast observations, enabling the direct observation of
exoplanets. We demonstrate the technique on HR8799, a young planetary system
composed of four known giant exoplanets. We used the GRAVITY fringe tracker to
lock the fringes on the central star, and integrated off-axis on the HR8799e
planet situated at 390 mas from the star. Data reduction included
post-processing to remove the flux leaking from the central star and to extract
the coherent flux of the planet. The inferred K band spectrum of the planet has
a spectral resolution of 500. We also derive the astrometric position of the
planet relative to the star with a precision on the order of 100as. The
GRAVITY astrometric measurement disfavors perfectly coplanar stable orbital
solutions. A small adjustment of a few degrees to the orbital inclination of HR
8799 e can resolve the tension, implying that the orbits are close to, but not
strictly coplanar. The spectrum, with a signal-to-noise ratio of
per spectral channel, is compatible with a late-type L brown dwarf. Using
Exo-REM synthetic spectra, we derive a temperature of \,K and a
surface gravity of cm/s. This corresponds to a radius
of and a mass of , which is an independent confirmation of mass estimates from evolutionary
models. Our results demonstrate the power of interferometry for the direct
detection and spectroscopic study of exoplanets at close angular separations
from their stars.Comment: published in A&
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