111 research outputs found
Optical bio-sensors in microfluidic chips
Direct femtosecond laser writing is used to integrate optical waveguides that intersect the microfluidic channels in a commercial optofluidic chip. With laser excitation, fluorescently labeled DNA molecules of different sizes are separated by capillary electrophoresis with high operating speed and low sample consumption (~ 600 pl). ..
The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme
Cryptococcosis is a life-threatening disease often associated with HIV infection. Three Cryptococcus species CYP51 enzymes were purified and catalyzed the 14α-demethylation of lanosterol, eburicol, and obtusifoliol. The investigational agent VT-1129 bound tightly to all three CYP51 proteins (dissociation constant [K(d)] range, 14 to 25 nM) with affinities similar to those of fluconazole, voriconazole, itraconazole, clotrimazole, and ketoconazole (K(d) range, 4 to 52 nM), whereas VT-1129 bound weakly to human CYP51 (K(d), 4.53 ÎŒM). VT-1129 was as effective as conventional triazole antifungal drugs at inhibiting cryptococcal CYP51 activity (50% inhibitory concentration [IC(50)] range, 0.14 to 0.20 ÎŒM), while it only weakly inhibited human CYP51 activity (IC(50), âŒ600 ÎŒM). Furthermore, VT-1129 weakly inhibited human CYP2C9, CYP2C19, and CYP3A4, suggesting a low drug-drug interaction potential. Finally, the cellular mode of action for VT-1129 was confirmed to be CYP51 inhibition, resulting in the depletion of ergosterol and ergosta-7-enol and the accumulation of eburicol, obtusifolione, and lanosterol/obtusifoliol in the cell membranes
Analytic models of plausible gravitational lens potentials
Gravitational lenses on galaxy scales are plausibly modelled as having
ellipsoidal symmetry and a universal dark matter density profile, with a Sersic
profile to describe the distribution of baryonic matter. Predicting all lensing
effects requires knowledge of the total lens potential: in this work we give
analytic forms for that of the above hybrid model. Emphasising that complex
lens potentials can be constructed from simpler components in linear
combination, we provide a recipe for attaining elliptical symmetry in either
projected mass or lens potential. We also provide analytic formulae for the
lens potentials of Sersic profiles for integer and half-integer index. We then
present formulae describing the gravitational lensing effects due to
smoothly-truncated universal density profiles in cold dark matter model. For
our isolated haloes the density profile falls off as radius to the minus fifth
or seventh power beyond the tidal radius, functional forms that allow all
orders of lens potential derivatives to be calculated analytically, while
ensuring a non-divergent total mass. We show how the observables predicted by
this profile differ from that of the original infinite-mass NFW profile.
Expressions for the gravitational flexion are highlighted. We show how
decreasing the tidal radius allows stripped haloes to be modelled, providing a
framework for a fuller investigation of dark matter substructure in galaxies
and clusters. Finally we remark on the need for finite mass halo profiles when
doing cosmological ray-tracing simulations, and the need for readily-calculable
higher order derivatives of the lens potential when studying catastrophes in
strong lenses.Comment: 24 pages, 10 figures, matches published versio
KiDS+GAMA:The weak lensing calibrated stellar-to-halo mass relation of central and satellite galaxies
We simultaneously present constraints on the stellar-to-halo mass relation
for central and satellite galaxies through a weak lensing analysis of
spectroscopically classified galaxies. Using overlapping data from the fourth
data release of the Kilo-Degree Survey (KiDS), and the Galaxy And Mass Assembly
survey (GAMA), we find that satellite galaxies are hosted by halo masses that
are dex (68\% confidence, detection) smaller than
those of central galaxies of the same stellar mass (for a stellar mass of
). This is consistent with galaxy formation
models, whereby infalling satellite galaxies are preferentially stripped of
their dark matter. We find consistent results with similar uncertainties when
comparing constraints from a standard azimuthally averaged galaxy-galaxy
lensing analysis and a two-dimensional likelihood analysis of the full shear
field. As the latter approach is somewhat biased due to the lens incompleteness
and as it does not provide any improvement to the precision when applied to
actual data, we conclude that stacked tangential shear measurements are
best-suited for studies of the galaxy-halo connection.Comment: 12 pages, 10 figures, accepted for publication in A&
Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial
Background
Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery.
Methods
The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery
First test of Verlinde's theory of Emergent Gravity using weak gravitational lensing measurements
Verlinde (2016) proposed that the observed excess gravity in galaxies and clusters is the consequence of Emergent Gravity (EG). In this theory the standard gravitational laws are modified on galactic and larger scales due to the displacement of dark energy by baryonic matter. EG gives an estimate of the excess gravity (described as an apparent dark matter density) in terms of the baryonic mass distribution and the Hubble parameter. In this work we present the first test of EG using weak gravitational lensing, within the regime of validity of the current model. Although there is no direct description of lensing and cosmology in EG yet, we can make a reasonable estimate of the expected lensing signal of low redshift galaxies by assuming a background LambdaCDM cosmology. We measure the (apparent) average surface mass density profiles of 33,613 isolated central galaxies, and compare them to those predicted by EG based on the galaxies' baryonic masses. To this end we employ the ~180 square degrees overlap of the Kilo-Degree Survey (KiDS) with the spectroscopic Galaxy And Mass Assembly (GAMA) survey. We find that the prediction from EG, despite requiring no free parameters, is in good agreement with the observed galaxy-galaxy lensing profiles in four different stellar mass bins. Although this performance is remarkable, this study is only a first step. Further advancements on both the theoretical framework and observational tests of EG are needed before it can be considered a fully developed and solidly tested theory
Long-term culture of genome-stable bipotent stem cells from adult human liver.
Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.This work was supported by grants to MH (EU/236954) and to HC (The United European Gastroenterology Federation
(UEGF) Research Prize 2010, EU/232814-StemCellMark and NWO/116002008). MH is
supported by The Wellcome Trust Sir Henry Dale fellowship. The Rspo cell line was kindly
provided by Dr. Calvin Kuo.This is the final published version. It first appeared at http://www.cell.com/abstract/S0092-8674%2814%2901566-9
The stellar-to-halo mass relation of GAMA galaxies from 100 deg2of KiDS weak lensing data
We study the stellar-to-halo mass relation of central galaxies in the range 9.7 5 Ă 1010h-2M&sun;, the stellar mass increases with halo mass as Ë {}M_h^{0.25}. The ratio of dark matter to stellar mass has a minimum at a halo mass of 8 Ă 1011h-1M&sun; with a value of M_h/M_*=56_{-10}^{+16} [h]. We also use the GAMA group catalogue to select centrals and satellites in groups with five or more members, which trace regions in space where the local matter density is higher than average, and determine for the first time the stellar-to-halo mass relation in these denser environments. We find no significant differences compared to the relation from the full sample, which suggests that the stellar-to-halo mass relation does not vary strongly with local density. Furthermore, we find that the stellar-to-halo mass relation of central galaxies can also be obtained by modelling the lensing signal and stellar mass function of satellite galaxies only, which shows that the assumptions to model the satellite contribution in the halo model do not significantly bias the stellar-to-halo mass relation. Finally, we show that the combination of weak lensing with the stellar mass function can be used to test the purity of group catalogues
The Swedish Version of the Ritvo Autism and Asperger Diagnostic Scale: Revised (RAADS-R). A Validation Study of a Rating Scale for Adults
There is a paucity of diagnostic instruments for adults with autism spectrum disorder (ASD). This study evaluates the psychometric properties of the Swedish version of the Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), an 80-item self-rating scale designed to assist clinicians diagnosing ASD in adults. It was administered to 75 adults with ASD and 197 comparison cases. Also, a subset completed the Autism Spectrum Quotient (AQ). Three out of four subscales had high internal consistency. Sensitivity was 91% and specificity was 93%. The ASD subjects had significantly higher mean scores on all subscales. ASD females had higher scores than ASD males on the sensory motor subscale, a dimension not included in the AQ. RAADS-R showed promising test re-test reliability
Strong detection of the CMB lensingxgalaxy weak lensingcross-correlation from ACT-DR4,PlanckLegacy and KiDS-1000
We measure the cross-correlation between galaxy weak lensing data from the
Kilo Degree Survey (KiDS-1000, DR4) and cosmic microwave background (CMB)
lensing data from the Atacama Cosmology Telescope (ACT, DR4) and the Planck
Legacy survey. We use two samples of source galaxies, selected with photometric
redshifts, and , which produce a
combined detection significance of the CMB lensing/weak galaxy lensing
cross-spectrum of . With the lower redshift galaxy sample, for which
the cross-correlation is detected at a significance of , we present
joint cosmological constraints on the matter density parameter, , and the matter fluctuation amplitude parameter, , marginalising
over three nuisance parameters that model our uncertainty in the redshift and
shear calibration, and the intrinsic alignment of galaxies. We find our
measurement to be consistent with the best-fitting flat CDM
cosmological models from both Planck and KiDS-1000. We demonstrate the capacity
of CMB-weak lensing cross-correlations to set constraints on either the
redshift or shear calibration, by analysing a previously unused high-redshift
KiDS galaxy sample , with the cross-correlation detected at
a significance of . This analysis provides an independent assessment
for the accuracy of redshift measurements in a regime that is challenging to
calibrate directly owing to known incompleteness in spectroscopic surveys.Comment: 13 pages, 9 figures, 1 tables, submitted to A&
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