The Gravity Probe B mission provided two new quantitative tests of Einstein's theory of gravity, general relativity (GR), by cryogenic gyroscopes in Earth's orbit. Data from four gyroscopes gave a ...geodetic drift-rate of −6601.8 18.3 marc-s yr−1 and a frame-dragging of −37.2 7.2 marc-s yr−1, to be compared with GR predictions of −6606.1 and −39.2 marc-s yr−1 (1 marc-s = 4.848 × 10−9 radians). The present paper introduces the science, engineering, data analysis, and heritage of Gravity Probe B, detailed in the accompanying 20 CQG papers.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder occurring in male and rare female carriers of a premutation expansion (55 to 200 CGG repeats) of the ...fragile X mental retardation 1 (FMR1) gene.
Volumetric MRI studies, clinical staging, cognitive testing, and molecular analysis were conducted in 15 female premutation carriers affected by FXTAS (age 59.5 +/- 10.3 years), 20 unaffected female carriers (43.3 +/- 11.2 years), 11 genetically normal female controls (51.0 +/- 10.3 years), 36 affected male carriers (65.0 +/- 5.6 years), 25 unaffected male carriers (53.5 +/- 12.5 years), and 39 male controls (58.0 +/- 15.0 years). Female and male carriers with FXTAS were matched on duration of disease.
We found less pronounced reductions of cerebellar volume and a lower incidence of involvement (symmetric high T2 signal) of the middle cerebellar peduncles (MCP sign) in females affected by FXTAS (13%) compared with affected males (58%). We found reduced brain volumes and increased white matter disease associated with the presence of FXTAS in females compared with female controls. We also observed significant associations between reduced cerebellar volume and both increased severity of FXTAS symptoms and increased length of the CGG repeat expansion in male premutation carriers, but not in females.
Females affected by fragile X-associated tremor/ataxia syndrome (FXTAS) demonstrated milder brain changes than affected males, although they showed a similar pattern of radiologic findings consistent with brain atrophy and white matter disease. FXTAS should be considered (by ordering fragile X DNA testing) in females who present with late-onset ataxia, action tremor, or neuropathy, particularly in those with a family history of mental retardation, autism, or premature ovarian failure.
Abstract
In the next decade, transient searches from the Vera C. Rubin Observatory and the Nancy Grace Roman Space Telescope will increase the sample of known Type Ia supernovae (SNe Ia) from ∼10
3
...to 10
5
. With this reduction of statistical uncertainties on cosmological measurements, new methods are needed to reduce systematic uncertainties. Characterizing the underlying spectroscopic evolution of SN Ia remains a major systematic uncertainty in current cosmological analyses, motivating a new simulation tool for the next era of SN Ia cosmology: Build Your Own Spectral Energy Distribution (
byosed
).
byosed
is used within the SNANA framework to simulate light curves by applying spectral variations to model SEDs, enabling flexible testing of possible systematic shifts in SN Ia distance measurements. We test the framework by comparing a nominal Roman SN Ia survey simulation using a baseline SED model to simulations using SEDs perturbed with
byosed
, and investigating the impact of ignoring specific SED features in the analysis. These features include semiempirical models of two possible, predicted relationships: between SN ejecta velocity and light-curve observables, and a redshift-dependent relationship between SN Hubble residuals and host-galaxy mass. We analyze each
byosed
simulation using the SALT2 and BEAMS with Bias Corrections framework, and estimate changes in the measured value of the dark-energy equation-of-state parameter,
w
. We find a difference of Δ
w
= −0.023 for SN velocity and Δ
w
= 0.021 for redshift-evolving host mass when compared to simulations without these features. By using
byosed
for SN Ia cosmology simulations, future analyses (e.g., the Rubin and Roman SN Ia samples) will have greater flexibility to constrain or reduce such SN Ia modeling uncertainties.
Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) belongs to the fibrillin-LTBP superfamily of extracellular matrix proteins. LTBPs and fibrillins are involved in the sequestration ...and storage of latent growth factors, particularly transforming growth factor β (TGF-β), in tissues. Unlike other LTBPs, LTBP-2 does not covalently bind TGF-β, and its molecular functions remain unclear. We are screening LTBP-2 for binding to other growth factors and have found very strong saturable binding to fibroblast growth factor-2 (FGF-2) (Kd = 1.1 nM). Using a series of recombinant LTBP-2 fragments a single binding site for FGF-2 was identified in a central region of LTBP-2 consisting of six tandem epidermal growth factor-like (EGF-like) motifs (EGFs 9-14). This region was also shown to contain a heparin/heparan sulphate-binding site. FGF-2 stimulation of fibroblast proliferation was completely negated by the addition of 5-fold molar excess of LTBP-2 to the assay. Confocal microscopy showed strong co-localisation of LTBP-2 and FGF-2 in fibrotic keloid tissue suggesting that the two proteins may interact in vivo. Overall the study indicates that LTBP-2 is a potent inhibitor of FGF-2 that may influence FGF-2 bioactivity during wound repair particularly in fibrotic tissues.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We combine thermal electron densities in Mars' ionosphere with magnetic topology information to investigate the sources of the nightside ionosphere. Thermal electron density is measured in situ by ...the Langmuir Probe and Waves experiment onboard Mars Atmospheric and Volatile EvolutioN, while magnetic topology is simultaneously inferred from suprathermal electron energy‐pitch angle distributions measured by the Solar Wind Electron Analyzer and the Magnetometer. Topologically closed regions inhibit electron impact ionization, allowing us to isolate the effects of plasma transport from the dayside, which exhibits a dawn‐dusk asymmetry. Pressure gradient forces on open magnetic field lines connected to the dayside ionosphere source the high‐altitude nightside ionosphere, resulting in higher densities. Regions that are topologically open to the nightside ionosphere allow us to assess in situ production by electron impact ionization, which is responsible for ~50% of the nightside ionosphere below ~160 km and ~25% above ~220 km (on average).
Plain Language Summary
Mars' dayside ionosphere is produced by ionization of the neutral atmosphere by solar extreme ultraviolet and X‐ray photons. This photoionization source is absent at night, so the nightside ionosphere must be supplied by plasma transport from day to night or created in situ by impact ionization caused by the precipitation of energetic electrons onto the neutral atmosphere. In this study, we use measurements from the Mars Atmospheric and Volatile EvolutioN spacecraft to identify these sources and estimate their contributions to the nightside ionosphere. At altitudes below ~160 km, electron impact ionization accounts for half of the nightside ionosphere, with the other half supplied by transport from the dayside via collisional coupling with neutral winds. At higher altitudes, the nightside plasma density is found to be higher when it is directly supplied by transport from the dayside ionosphere.
Key Points
At low altitudes ion motion collisionally couples to neutral winds, sourcing the nightside ionosphere asymmetrically from dawn and dusk
On open field lines connected to the dayside, the nightside ionosphere is sourced by dayside plasma via pressure gradient forces
On average, electron impact ionization produces ~50% of Mars' nightside ionospheric plasma below ~160 km and ~25% above 220 km
For much of the 20th century, the Mersey in North West England was one of the worst polluted estuaries in Europe. Water from a range of polluting industries plus domestic sewage was discharged into ...the Mersey Catchment and Estuary. Recovery came through a concerted clean-up campaign and tightening environmental regulations, partly driven by European Commission Directives, coupled with de-industrialisation from the 1970s onward. Recovery of oxygen levels in the Estuary led to the return of a productive ecosystem. This led to conservation designations, but also concerns about transfer of pollutants to higher trophic levels in fish, birds and humans. As part of urban renewal, ecosystems in disused dock basins were restored using mussel biofiltration and artificial de-stratification, facilitating commercial redevelopment and creation of a tourist destination. The degradation and recovery of the Mersey from peak-pollution in the mid-20th century is put in the context of wider environmental change and briefly compared to other systems to develop a hysteresis model of degradation and recovery, often to novel ecosystems.
Atmospheric cloud condensation nuclei (CCN) concentrations are a key uncertainty in the assessment of the effect of anthropogenic aerosol on clouds and climate. The ability of new ultrafine particles ...to grow to become CCN varies throughout the atmosphere and must be understood in order to understand CCN formation. We have developed the Probability of Ultrafine particle Growth (PUG) model to answer questions regarding which growth and sink mechanisms control this growth, how the growth varies between different parts of the atmosphere and how uncertainties with respect to the magnitude and size distribution of ultrafine emissions translates into uncertainty in CCN generation. The inputs to the PUG model are the concentrations of condensable gases, the size distribution of ambient aerosol, particle deposition timescales and physical properties of the particles and condensable gases. It was found in most cases that condensation is the dominant growth mechanism and coagulation with larger particles is the dominant sink mechanism for ultrafine particles. In this work we found that the probability of a new ultrafine particle generating a CCN varies from <0.1% to ~90% in different parts of the atmosphere, though in the boundary layer a large fraction of ultrafine particles have a probability between 1% and 40%. Some regions, such as the tropical free troposphere, are areas with high probabilities; however, variability within regions makes it difficult to predict which regions of the atmosphere are most efficient for generating CCN from ultrafine particles. For a given mass of primary ultrafine aerosol, an uncertainty of a factor of two in the modal diameter can lead to an uncertainty in the number of CCN generated as high as a factor for eight. It was found that no single moment of the primary aerosol size distribution, such as total mass or number, is a robust predictor of the number of CCN ultimately generated. Therefore, a complete description of the emissions size distribution is generally required for global aerosol microphysics models.
Novel methods of data analysis were used to interpret codling moth (Cydia pomonella) catch data from central-trap, multiple-release experiments using a standard codlemone-baited monitoring trap in ...commercial apple orchards not under mating disruption. The main objectives were to determine consistency and reliability for measures of: 1) the trapping radius, composed of the trap's behaviorally effective plume reach and the maximum dispersive distance of a responder population; and 2) the proportion of the population present in the trapping area that is caught. Two moth release designs were used: 1) moth releases at regular intervals in the four cardinal directions, and 2) evenly distributed moth releases across entire approximately 18-ha orchard blocks using both high and low codling moth populations. For both release designs, at high populations, the mean proportion catch was 0.01, and for the even release of low populations, that value was approximately 0.02. Mean maximum dispersive distance for released codling moth males was approximately 260 m. Behaviorally effective plume reach for the standard codling moth trap was < 5 m, and total trapping area for a single trap was approximately 21 ha. These estimates were consistent across three growing seasons and are supported by extraordinarily high replication for this type of field experiment. Knowing the trapping area and mean proportion caught, catch number per single monitoring trap can be translated into absolute pest density using the equation: males per trapping area = catch per trapping area/proportion caught. Thus, catches of 1, 3, 10, and 30 codling moth males per trap translate to approximately 5, 14, 48, and 143 males/ha, respectively, and reflect equal densities of females, because the codling moth sex ratio is 1:1. Combined with life-table data on codling moth fecundity and mortality, along with data on crop yield per trapping area, this fundamental knowledge of how to interpret catch numbers will enable pest managers to make considerably more precise projections of damage and therefore more precise and reliable decisions on whether insecticide applications are justified. The principles and methods established here for estimating absolute codling moth density may be broadly applicable to pests generally and thereby could set a new standard for integrated pest management decisions based on trapping.
An in vitro model of human ovarian follicles would greatly benefit the study of female reproduction. Ovarian development requires the combination of germ cells and several types of somatic cells. ...Among these, granulosa cells play a key role in follicle formation and support for oogenesis. Whereas efficient protocols exist for generating human primordial germ cell-like cells (hPGCLCs) from human induced pluripotent stem cells (hiPSCs), a method of generating granulosa cells has been elusive. Here, we report that simultaneous overexpression of two transcription factors (TFs) can direct the differentiation of hiPSCs to granulosa-like cells. We elucidate the regulatory effects of several granulosa-related TFs and establish that overexpression of NR5A1 and either RUNX1 or RUNX2 is sufficient to generate granulosa-like cells. Our granulosa-like cells have transcriptomes similar to human fetal ovarian cells and recapitulate key ovarian phenotypes including follicle formation and steroidogenesis. When aggregated with hPGCLCs, our cells form ovary-like organoids (ovaroids) and support hPGCLC development from the premigratory to the gonadal stage as measured by induction of DAZL expression. This model system will provide unique opportunities for studying human ovarian biology and may enable the development of therapies for female reproductive health.
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