248 research outputs found
Local synthesis of sex hormones:are there consequences for the ocular surface and dry eye?
Sex hormones are associated with the physiology and pathophysiology of almost all organs in the body, as well as most diseases. Interest in the associations between sex hormones and ocular tissues has increased in recent years. Androgens may have a positive effect on dry eye, whereas the effects of oestrogen on ocular conditions remain unclear. Intracrinology, the local synthesis and metabolism of hormones that is unique to humans, is of relevance to the eye and may help to explain why studies of the relationship between oestrogens and dry eye signs and symptoms are inconclusive. Knowledge of the pathways of hormone formation and metabolism is crucial to understanding the pathogenesis of ocular disease including dry eye. This review examines the mechanisms of steroidal sex hormone biosynthesis and reviews the significance of locally produced sex hormones, with a focus on ocular surface tissues. Much of the current literature is based on animal studies, which may not be transferable to humans due to the absence of intracrine production in animals. A large proportion of the human studies investigate systemic hormone levels rather than local levels. There is subsequently a need for additional studies to provide a better understanding of the local production of sex hormones within the human eye and ocular surface and to clarify the relationships between ocular levels of sex hormones and conditions including dry eye
Blink rate measured in situ decreases while reading from printed text or digital devices, regardless of task duration, difficulty or viewing distance
Purpose: To compare blinking measured in situ during various tasks and examine relationships with ocular surface symptoms. The day-to-day repeatability of the blink rate and interblink interval was assessed
Detailed clay mineralogy of the TriassicJurassic boundary section at Kendlbachgraben (Northern Calcareous Alps, Austria)
The Triassic-Jurassic boundary (TJB) is marked by one of the five largest
Phanerozoic mass extinctions. To constrain existing models for TJB events, we obtained a
stratigraphically highly resolved dataset from a marine section at Kendlbachgraben, Austria.
The topmost Triassic Košssen Formation contains low to medium-charged smectite and vermiculite
as alteration products of mafic-ultramafic minerals. The clay minerals in the boundary mudstone are
kaolinite 5 illite + muscovite >> smectite > chlorite. Predominant kaolinite suggests humid climate
and abundant terrigenous input. In the lowermost Jurassic, the clay mineral pattern changes to illite +
muscovite >> kaolinite >> smectite, which reflects change to less humid and more moderate climate.
The topmost Košssen Formation also contains clay spherules. Their composition, shape and size
indicate that they are alteration products of airborne volcanic glass droplets solidified in the air,
settled in the sea and altered rapidly with negligible transport in terrestrial or marine environments.
Our data are consistent with sudden climatic change at the TJB, as a result of large-scale volcanic
activity of the Central Atlantic Magmatic Province which produced distal airfall volcanic ash
Atomistic QM/MM simulations of the strength of covalent interfaces in carbon nanotubeâpolymer composites
We investigate the failure of carbon-nanotube/polymer composites by using a recently-developed hybrid quantum-mechanical/molecular-mechanical (QM/MM) approach to simulate nanotube pull-out from a cross-linked polyethene matrix. Our study focuses on the strength and failure modes of covalently-bonded nanotubeâpolymer interfaces based on amine, carbene and carboxyl functional groups and a [2+1] cycloaddition. We find that the choice of the functional group linking the polymer matrix to the nanotube determines the effective strength of the interface, which can be increased by up to 50% (up to the limit dictated by the strength of the polymer backbone itself) by choosing groups with higher interfacial binding energy. We rank the functional groups presented in this work based on the strength of the resulting interface and suggest broad guidelines for the rational design of nanotube functionalisation for nanotubeâpolymer composites
Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation
Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses
Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability
Peer reviewedPublisher PD
SUBARU prime focus spectrograph: integration, testing and performance for the first spectrograph
The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and
Redshifts (SuMIRe) project for Subaru telescope consists in four identical
spectrographs fed by 600 fibers each. Each spectrograph is composed by an
optical entrance unit that creates a collimated beam and distributes the light
to three channels, two visibles and one near infrared. This paper presents the
on-going effort for the tests & integration process for the first spectrograph
channel: we have developed a detailed Assembly Integration and Test (AIT) plan,
as well as the methods, detailed processes and I&T tools. We describe the tools
we designed to assemble the parts and to test the performance of the
spectrograph. We also report on the thermal acceptance tests we performed on
the first visible camera unit. We also report on and discuss the technical
difficulties that did appear during this integration phase. Finally, we detail
the important logistic process that is require to transport the components from
other country to Marseille
Fast automated placement of polar hydrogen atoms in protein-ligand complexes
<p>Abstract</p> <p>Background</p> <p>Hydrogen bonds play a major role in the stabilization of protein-ligand complexes. The ability of a functional group to form them depends on the position of its hydrogen atoms. An accurate knowledge of the positions of hydrogen atoms in proteins is therefore important to correctly identify hydrogen bonds and their properties. The high mobility of hydrogen atoms introduces several degrees of freedom: Tautomeric states, where a hydrogen atom alters its binding partner, torsional changes where the position of the hydrogen atom is rotated around the last heavy-atom bond in a residue, and protonation states, where the number of hydrogen atoms at a functional group may change. Also, side-chain flips in glutamine and asparagine and histidine residues, which are common crystallographic ambiguities must be identified before structure-based calculations can be conducted.</p> <p>Results</p> <p>We have implemented a method to determine the most probable hydrogen atom positions in a given protein-ligand complex. Optimality of hydrogen bond geometries is determined by an empirical scoring function which is used in molecular docking. This allows to evaluate protein-ligand interactions with an established model. Also, our method allows to resolve common crystallographic ambiguities such as as flipped amide groups and histidine residues. To ensure high speed, we make use of a dynamic programming approach.</p> <p>Conclusion</p> <p>Our results were checked against selected high-resolution structures from an external dataset, for which the positions of the hydrogen atoms have been validated manually. The quality of our results is comparable to that of other programs, with the advantage of being fast enough to be applied on-the-fly for interactive usage or during score evaluation.</p
Smell and taste changes are early indicators of the COVID-19 pandemic and political decision effectiveness
In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population
Current status of the Spectrograph System for the SuMIRe/PFS
The Prime Focus Spectrograph (PFS) is a new facility instrument for Subaru
Telescope which will be installed in around 2017. It is a multi-object
spectrograph fed by about 2400 fibers placed at the prime focus covering a
hexagonal field-of-view with 1.35 deg diagonals and capable of simultaneously
obtaining data of spectra with wavelengths ranging from 0.38 um to 1.26 um. The
spectrograph system is composed of four identical modules each receiving the
light from 600 fibers. Each module incorporates three channels covering the
wavelength ranges 0.38-0.65 mu ("Blue"), 0.63-0.97 mu ("Red"), and 0.94-1.26 mu
("NIR") respectively; with resolving power which progresses fairly smoothly
from about 2000 in the blue to about 4000 in the infrared. An additional
spectral mode allows reaching a spectral resolution of 5000 at 0.8mu (red). The
proposed optical design is based on a Schmidt collimator facing three Schmidt
cameras (one per spectral channel). This architecture is very robust, well
known and documented. It allows for high image quality with only few simple
elements (high throughput) at the expense of the central obscuration, which
leads to larger optics. Each module has to be modular in its design to allow
for integration and tests and for its safe transport up to the telescope: this
is the main driver for the mechanical design. In particular, each module will
be firstly fully integrated and validated at LAM (France) before it is shipped
to Hawaii. All sub-assemblies will be indexed on the bench to allow for their
accurate repositioning. This paper will give an overview of the spectrograph
system which has successfully passed the Critical Design Review (CDR) in 2014
March and which is now in the construction phase.Comment: 9 pages, 7 figures, submitted to "Ground-based and Airborne
Instrumentation for Astronomy V, Suzanne K. Ramsay, Ian S. McLean, Hideki
Takami, Editors, Proc. SPIE 9147 (2014)
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