669 research outputs found
Improved spacecraft radio science using an on-board atomic clock: application to gravitational wave searches
Recent advances in space-qualified atomic clocks (low-mass, low
power-consumption, frequency stability comparable to that of ground-based
clocks) can enable interplanetary spacecraft radio science experiments at
unprecedented Doppler sensitivities. The addition of an on-board digital
receiver would allow the up- and down-link Doppler frequencies to be measured
separately. Such separate, high-quality measurements allow optimal data
combinations that suppress the currently-leading noise sources: phase
scintillation noise from the Earth's atmosphere and Doppler noise caused by
mechanical vibrations of the ground antenna. Here we provide a general
expression for the optimal combination of ground and on-board Doppler data and
compute the sensitivity such a system would have to low-frequency gravitational
waves (GWs). Assuming a plasma scintillation noise calibration comparable to
that already demonstrated with the multi-link CASSINI radio system, the
space-clock/digital-receiver instrumentation enhancements would give GW strain
sensitivity of for randomly polarized, monochromatic GW
signals over a two-decade ( Hz) region of the low-frequency
band. This is about an order of magnitude better than currently achieved with
traditional two-way coherent Doppler experiments. The utility of optimally
combining simultaneous up- and down-link observations is not limited to GW
searches. The Doppler tracking technique discussed here could be performed at
minimal incremental cost to also improve other radio science experiments (i.e.
tests of relativistic gravity, planetary and satellite gravity field
measurements, atmospheric and ring occultations) on future interplanetary
missions.Comment: 21 pages, 5 figures. Submitted to Phys. Rev.
The meaning of life in a developing universe
The evolution of life on Earth has produced an organism that is beginning to model and understand its own evolution and the possible future evolution of life in the universe. These models and associated evidence show that evolution on Earth has a trajectory. The scale over which living processes are organized cooperatively has increased progressively, as has its evolvability. Recent theoretical advances raise the possibility that this trajectory is itself part of a wider developmental process. According to these theories, the developmental process has been shaped by a larger evolutionary process that involves the reproduction of universes. This evolutionary process has tuned the key parameters of the universe to increase the likelihood that life will emerge and develop to produce outcomes that are successful in the larger process (e.g. a key outcome may be to produce life and intelligence that intentionally reproduces the universe and tunes the parameters of âoffspringâ universes). Theory suggests that when life emerges on a planet, it moves along this trajectory of its own accord. However, at a particular point evolution will continue to advance only if organisms emerge that decide to advance the evolutionary process intentionally. The organisms must be prepared to make this commitment even though the ultimate nature and destination of the process is uncertain, and may forever remain unknown. Organisms that complete this transition to intentional evolution will drive the further development of life and intelligence in the universe. Humanityâs increasing understanding of the evolution of life in the universe is rapidly bringing it to the threshold of this major evolutionary transition
Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins
Bioinorganic canon states that active-site
thiolate coordination promotes rapid electron transfer (ET)
to and from type 1 copper proteins. In recent work, we have
found that copper ET sites in proteins also can be constructed
without thiolate ligation (called âtype zeroâ sites). Here we
report multifrequency electron paramagnetic resonance
(EPR), magnetic circular dichroism (MCD), and nuclear
magnetic resonance (NMR) spectroscopic data together with
density functional theory (DFT) and spectroscopy-oriented
configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type
zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers
relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1
centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the
orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding
Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study.
Frontotemporal dementia (FTD) is a highly heritable condition with multiple genetic causes. In this study, similarities and differences of gray matter (GM) atrophy patterns were assessed among 3 common forms of genetic FTD (mutations in C9orf72, GRN, and MAPT). Participants from the Genetic FTD Initiative (GENFI) cohort with a suitable volumetric T1 magnetic resonance imaging scan were included (319): 144 nonmutation carriers, 128 presymptomatic mutation carriers, and 47 clinically affected mutation carriers. Cross-sectional differences in GM volume between noncarriers and carriers were analyzed using voxel-based morphometry. In the affected carriers, each genetic mutation group exhibited unique areas of atrophy but also a shared network involving the insula, orbitofrontal lobe, and anterior cingulate. Presymptomatic GM atrophy was observed particularly in the thalamus and cerebellum in the C9orf72 group, the anterior and medial temporal lobes in MAPT, and the posterior frontal and parietal lobes as well as striatum in GRN. Across all presymptomatic carriers, there were significant decreases in the anterior insula. These results suggest that although there are important differences in atrophy patterns for each group (which can be seen presymptomatically), there are also similarities (a fronto-insula-anterior cingulate network) that help explain the clinical commonalities of the disease
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Using polygenic scores for identifying individuals at increased risk of substance use disorders in clinical and population samples
Genome-wide, polygenic risk scores (PRS) have emerged as a useful way to characterize genetic liability. There is growing evidence that PRS may prove useful for early identification of those at increased risk for certain diseases. The current potential of PRS for alcohol use disorders (AUD) remains an open question. Using data from both a population-based sample [the FinnTwin12 (FT12) study] and a high-risk sample [the Collaborative Study on the Genetics of Alcoholism (COGA)], we examined the association between PRSs derived from genome-wide association studies (GWASs) of (1) alcohol dependence/alcohol problems, (2) alcohol consumption, and (3) risky behaviors with AUD and other substance use disorder (SUD) criteria. These PRSs explain similar to 2.5-3.5% of the variance in AUD (across FT12 and COGA) when all PRSs are included in the same model. Calculations of area under the curve (AUC) show PRS provide only a slight improvement over a model with age, sex, and ancestral principal components as covariates. While individuals in the top 20, 10, and 5% of the PRS distribution had greater odds of having an AUD compared to the lower end of the continuum in both COGA and FT12, the point estimates at each threshold were statistically indistinguishable. Those in the top 5% reported greater levels of licit (alcohol and nicotine) and illicit (cannabis and opioid) SUD criteria. PRSs are associated with risk for SUD in independent samples. However, usefulness for identifying those at increased risk in their current form is modest, at best. Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples.Peer reviewe
Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood
Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18-31 (beta coefficients ranged from 0.02-0.06, p-values ranged from 10-6-10-12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective
'To live and die [for] Dixie': Irish civilians and the Confederate States of America
Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism
[O2â01â06]: FRONTOâSUBCORTICAL HYPOPERFUSION IN PRESYMPTOMATIC FTD IS ASSOCIATED WITH BEHAVIORAL MEASURES, BUT NOT COGNITIVE DEFICITS: THE GENFI STUDY
Tectonic structure, evolution, and the nature of oceanic core complexes and their detachment fault zones (13°20âČN and 13°30âČN, Mid Atlantic Ridge)
Microbathymetry data, in situ observations, and sampling along the 138200N and 138200N oceanic
core complexes (OCCs) reveal mechanisms of detachment fault denudation at the seafloor, links between tectonic
extension and mass wasting, and expose the nature of corrugations, ubiquitous at OCCs. In the initial
stages of detachment faulting and high-angle fault, scarps show extensive mass wasting that reduces their
slope. Flexural rotation further lowers scarp slope, hinders mass wasting, resulting in morphologically complex
chaotic terrain between the breakaway and the denuded corrugated surface. Extension and drag along the fault
plane uplifts a wedge of hangingwall material (apron). The detachment surface emerges along a continuous
moat that sheds rocks and covers it with unconsolidated rubble, while local slumping emplaces rubble ridges
overlying corrugations. The detachment fault zone is a set of anostomosed slip planes, elongated in the alongextension
direction. Slip planes bind fault rock bodies defining the corrugations observed in microbathymetry
and sonar. Fault planes with extension-parallel stria are exposed along corrugation flanks, where the rubble cover
is shed. Detachment fault rocks are primarily basalt fault breccia at 138200N OCC, and gabbro and peridotite
at 138300N, demonstrating that brittle strain localization in shallow lithosphere form corrugations, regardless of
lithologies in the detachment zone. Finally, faulting and volcanism dismember the 138300N OCC, with widespread
present and past hydrothermal activity (Semenov fields), while the Irinovskoe hydrothermal field at the
138200N core complex suggests a magmatic source within the footwall. These results confirm the ubiquitous
relationship between hydrothermal activity and oceanic detachment formation and evolution
Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales.
BACKGROUND: In patients with frontotemporal dementia, it has been shown that brain atrophy occurs earliest in the anterior cingulate, insula and frontal lobes. We used visual rating scales to investigate whether identifying atrophy in these areas may be helpful in distinguishing symptomatic patients carrying different causal mutations in the microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame (C9ORF72) genes. We also analysed asymptomatic carriers to see whether it was possible to visually identify brain atrophy before the appearance of symptoms. METHODS: Magnetic resonance imaging of 343 subjects (63 symptomatic mutation carriers, 132 presymptomatic mutation carriers and 148 control subjects) from the Genetic Frontotemporal Dementia Initiative study were analysed by two trained raters using a protocol of six visual rating scales that identified atrophy in key regions of the brain (orbitofrontal, anterior cingulate, frontoinsula, anterior and medial temporal lobes and posterior cortical areas). RESULTS: Intra- and interrater agreement were greater than 0.73 for all the scales. Voxel-based morphometric analysis demonstrated a strong correlation between the visual rating scale scores and grey matter atrophy in the same region for each of the scales. Typical patterns of atrophy were identified: symmetric anterior and medial temporal lobe involvement for MAPT, asymmetric frontal and parietal loss for GRN, and a more widespread pattern for C9ORF72. Presymptomatic MAPT carriers showed greater atrophy in the medial temporal region than control subjects, but the visual rating scales could not identify presymptomatic atrophy in GRN or C9ORF72 carriers. CONCLUSIONS: These simple-to-use and reproducible scales may be useful tools in the clinical setting for the discrimination of different mutations of frontotemporal dementia, and they may even help to identify atrophy prior to onset in those with MAPT mutations
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