317 research outputs found
A 3d renal proximal tubule on chip model phenocopies Lowe syndrome and Dent II disease tubulopathy
Lowe syndrome and Dent II disease are Xâlinked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositolâ5âphosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in vitro models for Lowe syndrome/Dent II disease to study the underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here, we describe a proximal tubule organ on chip model combining a 3D tubule architecture with fluid flow shear stress that phenocopies hallmarks of Lowe syndrome/Dent II dis-ease. We demonstrate the high suitability of our in vitro model for drug target validation. Further-more, using this model, we demonstrate that proximal tubule cells lacking OCRL expression upregulate markers typical for epithelialâmesenchymal transition (EMT), including the transcription factor SNAI2/Slug, and show increased collagen expression and deposition, which potentially contributes to interstitial fibrosis and disease progression as observed in Lowe syndrome and Dent II disease
A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation
Cutaneous sclerosis (CS) occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life
Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope
Nearby clusters and groups of galaxies are potentially bright sources of
high-energy gamma-ray emission resulting from the pair-annihilation of dark
matter particles. However, no significant gamma-ray emission has been detected
so far from clusters in the first 11 months of observations with the Fermi
Large Area Telescope. We interpret this non-detection in terms of constraints
on dark matter particle properties. In particular for leptonic annihilation
final states and particle masses greater than ~200 GeV, gamma-ray emission from
inverse Compton scattering of CMB photons is expected to dominate the dark
matter annihilation signal from clusters, and our gamma-ray limits exclude
large regions of the parameter space that would give a good fit to the recent
anomalous Pamela and Fermi-LAT electron-positron measurements. We also present
constraints on the annihilation of more standard dark matter candidates, such
as the lightest neutralino of supersymmetric models. The constraints are
particularly strong when including the fact that clusters are known to contain
substructure at least on galaxy scales, increasing the expected gamma-ray flux
by a factor of ~5 over a smooth-halo assumption. We also explore the effect of
uncertainties in cluster dark matter density profiles, finding a systematic
uncertainty in the constraints of roughly a factor of two, but similar overall
conclusions. In this work, we focus on deriving limits on dark matter models; a
more general consideration of the Fermi-LAT data on clusters and clusters as
gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo,
minor revisions to be consistent with accepted versio
A Scholarly Review of Supply Chain Integration within the New Zealand Blueberry Industry
Ethics and credence attributes are the humanistic basis for establishing sustainable supply chain
development. It determines brand reputation, ecology and customer experience. Furthermore, good ethics and credence Attributes promote the progress of industry leadership and increase the
possibility of win-win strategies, especially in terms of negotiation. Negotiation is the premise of supply chain collaboration. The purpose of collaboration is to establish a synchronized supply chain to improve the ability of industry coordination. This is also the key to creating value, and the importance of risk management cannot be ignored. It is not only a guarantee for the smooth operation of the supply chain, but also an important measure to improve the flexibility of the supply chain. Finally, the results of supply chain integration need to rely on performance metrics and benchmarking to control and improve the overall performance of the supply chain. This publication evaluates modern theories
in all these areas and contextualise it to the New Zealand blueberry industry. It is important that the reader appreciates the scholarly origin of this publication
Human Resource Flexibility as a Mediating Variable Between High Performance Work Systems and Performance
Much of the human resource management literature has demonstrated the impact of high performance
work systems (HPWS) on organizational performance. A new generation of studies is
emerging in this literature that recommends the inclusion of mediating variables between HPWS
and organizational performance. The increasing rate of dynamism in competitive environments
suggests that measures of employee adaptability should be included as a mechanism that may
explain the relevance of HPWS to firm competitiveness. On a sample of 226 Spanish firms, the
studyâs results confirm that HPWS influences performance through its impact on the firmâs
human resource (HR) flexibility
DEVELOPMENT of the MODEL of GALACTIC INTERSTELLAR EMISSION for STANDARD POINT-SOURCE ANALYSIS of FERMI LARGE AREA TELESCOPE DATA
Most of the celestial \u3b3 rays detected by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope originate from the interstellar medium when energetic cosmic rays interact with interstellar nucleons and photons. Conventional point-source and extended-source studies rely on the modeling of this diffuse emission for accurate characterization. Here, we describe the development of the Galactic Interstellar Emission Model (GIEM), which is the standard adopted by the LAT Collaboration and is publicly available. This model is based on a linear combination of maps for interstellar gas column density in Galactocentric annuli and for the inverse-Compton emission produced in the Galaxy. In the GIEM, we also include large-scale structures like Loop I and the Fermi bubbles. The measured gas emissivity spectra confirm that the cosmic-ray proton density decreases with Galactocentric distance beyond 5 kpc from the Galactic Center. The measurements also suggest a softening of the proton spectrum with Galactocentric distance. We observe that the Fermi bubbles have boundaries with a shape similar to a catenary at latitudes below 20\ub0 and we observe an enhanced emission toward their base extending in the north and south Galactic directions and located within \u2dc4\ub0 of the Galactic Center
The On-orbit Calibrations for the Fermi Large Area Telescope
The Large Area Telescope (LAT) on--board the Fermi Gamma ray Space Telescope
began its on--orbit operations on June 23, 2008. Calibrations, defined in a
generic sense, correspond to synchronization of trigger signals, optimization
of delays for latching data, determination of detector thresholds, gains and
responses, evaluation of the perimeter of the South Atlantic Anomaly (SAA),
measurements of live time, of absolute time, and internal and spacecraft
boresight alignments. Here we describe on orbit calibration results obtained
using known astrophysical sources, galactic cosmic rays, and charge injection
into the front-end electronics of each detector. Instrument response functions
will be described in a separate publication. This paper demonstrates the
stability of calibrations and describes minor changes observed since launch.
These results have been used to calibrate the LAT datasets to be publicly
released in August 2009.Comment: 60 pages, 34 figures, submitted to Astroparticle Physic
Astronomical Distance Determination in the Space Age: Secondary Distance Indicators
The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)
Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review
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