This paper provides an overview of the Curiosity rover's exploration at Vera Rubin ridge (VRR) and summarizes the science results. VRR is a distinct geomorphic feature on lower Aeolis Mons ...(informally known as Mount Sharp) that was identified in orbital data based on its distinct texture, topographic expression, and association with a hematite spectral signature. Curiosity conducted extensive remote sensing observations, acquired data on dozens of contact science targets, and drilled three outcrop samples from the ridge, as well as one outcrop sample immediately below the ridge. Our observations indicate that strata composing VRR were deposited in a predominantly lacustrine setting and are part of the Murray formation. The rocks within the ridge are chemically in family with underlying Murray formation strata. Red hematite is dispersed throughout much of the VRR bedrock, and this is the source of the orbital spectral detection. Gray hematite is also present in isolated, gray‐colored patches concentrated toward the upper elevations of VRR, and these gray patches also contain small, dark Fe‐rich nodules. We propose that VRR formed when diagenetic event(s) preferentially hardened rocks, which were subsequently eroded into a ridge by wind. Diagenesis also led to enhanced crystallization and/or cementation that deepened the ferric‐related spectral absorptions on the ridge, which helped make them readily distinguishable from orbit. Results add to existing evidence of protracted aqueous environments at Gale crater and give new insight into how diagenesis shaped Mars' rock record.
Plain Language Summary
Vera Rubin ridge is a feature at the base of Mount Sharp with a distinct texture and topography. Orbiter observations showed hematite, a mineral that sometimes forms by chemical reactions in water environments, was present atop the ridge. The presence of both water and chemical activity suggested the area preserved a past habitable environment. In this paper, we detail how the Curiosity science team tested this and other orbital‐based hypotheses. Curiosity data suggested that most ridge rocks were lain down in an ancient lake and had similar compositions to other Mount Sharp rocks. Curiosity confirmed that hematite was present in the ridge but no more abundantly than elsewhere. Larger grain size or higher crystallinity probably account for the ridge's hematite being more visible from orbit. We conclude Vera Rubin ridge formed because groundwater recrystallized and hardened the rocks that now make up the ridge. Wind subsequently sculpted and eroded Mount Sharp, leaving the harder ridge rocks standing because they resisted erosion compared with surrounding rocks. The implication of these results is that liquid water was present at Mount Sharp for a very long time, not only when the crater held a lake but also much later, likely as groundwater.
Key Points
We summarize Curiosity's campaign at Vera Rubin ridge (Sols 1726–2302) and the high‐level results from articles in this special issue
Vera Rubin ridge formed when diagenesis hardened rocks along the base of Aeolis Mons; wind subsequently etched the feature into a ridge
Results add evidence for protracted aqueous environments at Gale crater and give new insight into how diagenesis shaped Mars' rock record
Abstract
Objective
This study sought to evaluate whether synthetic data derived from a national coronavirus disease 2019 (COVID-19) dataset could be used for geospatial and temporal epidemic ...analyses.
Materials and Methods
Using an original dataset (n = 1 854 968 severe acute respiratory syndrome coronavirus 2 tests) and its synthetic derivative, we compared key indicators of COVID-19 community spread through analysis of aggregate and zip code-level epidemic curves, patient characteristics and outcomes, distribution of tests by zip code, and indicator counts stratified by month and zip code. Similarity between the data was statistically and qualitatively evaluated.
Results
In general, synthetic data closely matched original data for epidemic curves, patient characteristics, and outcomes. Synthetic data suppressed labels of zip codes with few total tests (mean = 2.9 ± 2.4; max = 16 tests; 66% reduction of unique zip codes). Epidemic curves and monthly indicator counts were similar between synthetic and original data in a random sample of the most tested (top 1%; n = 171) and for all unsuppressed zip codes (n = 5819), respectively. In small sample sizes, synthetic data utility was notably decreased.
Discussion
Analyses on the population-level and of densely tested zip codes (which contained most of the data) were similar between original and synthetically derived datasets. Analyses of sparsely tested populations were less similar and had more data suppression.
Conclusion
In general, synthetic data were successfully used to analyze geospatial and temporal trends. Analyses using small sample sizes or populations were limited, in part due to purposeful data label suppression—an attribute disclosure countermeasure. Users should consider data fitness for use in these cases.
The Earth surface Mineral dust source InvesTigation (EMIT) is a remote visible to shortwave infrared (VSWIR) imaging spectrometer that has been operating onboard the International Space Station since ...July 2022. This article describes EMIT's on-orbit spectroradiometric calibration and validation. Accurate spectroscopy is vital to achieve consistent mapping results with orbital imaging spectrometers. EMIT takes a unique approach to this challenge, with just six optical elements, no shutter, and no onboard calibration systems. Its simple design focuses on uniformity and stability to enable vicarious spectroradiometric calibration. Our experiments demonstrate that this approach is successful, approaching the fidelity of manual field spectroscopy in some cases, and enabling new and more accurate products across diverse Earth science disciplines. EMIT achieves several notable firsts for an instrument of its class. It demonstrates successful on-orbit adjustments of Focal Plane Array (FPA) alignment with sub-micron precision. It offers spectral uniformity better than 98%. Optical artifacts in the measurement channels are at least three orders of magnitude below the primary solar-reflected surface signals. Its noise performance enables percent-level discrimination in the depths of mineral absorption features. In these aspects, EMIT satisfies the stringent performance needs for the next generation of VSWIR imaging spectrometers to observe the Earth's ecosystems, geology, and water resources.
•The EMIT imaging spectrometer a VSWIR imaging spectrometer onboard the International Space Station.•We assess instrument performance and calibration accuracy.•EMIT offers 98% spatial uniformity and high radiometric precision.
Using the HIV-1 protease binding mode of MK-8718 and PL-100 as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease ...inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral activity relative to MK-8718.
Abstract
Brain-derived neurotrophic factor (BDNF) plays an important role in brain development and function. Substantial amounts of BDNF are present in peripheral blood, and may serve as biomarkers ...for Alzheimer’s disease incidence as well as targets for intervention to reduce Alzheimer’s disease risk. With the exception of the genetic polymorphism in the BDNF gene, Val66Met, which has been extensively studied with regard to neurodegenerative diseases, the genetic variation that influences circulating BDNF levels is unknown. We aimed to explore the genetic determinants of circulating BDNF levels in order to clarify its mechanistic involvement in brain structure and function and Alzheimer’s disease pathophysiology in middle-aged and old adults. Thus, we conducted a meta-analysis of genome-wide association study of circulating BDNF in 11 785 middle- and old-aged individuals of European ancestry from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES), the Framingham Heart Study (FHS), the Rotterdam Study and the Study of Health in Pomerania (SHIP-Trend). Furthermore, we performed functional annotation analysis and related the genetic polymorphism influencing circulating BDNF to common Alzheimer’s disease pathologies from brain autopsies. Mendelian randomization was conducted to examine the possible causal role of circulating BDNF levels with various phenotypes including cognitive function, stroke, diabetes, cardiovascular disease, physical activity and diet patterns. Gene interaction networks analysis was also performed. The estimated heritability of BDNF levels was 30% (standard error = 0.0246, P-value = 4 × 10−48). We identified seven novel independent loci mapped near the BDNF gene and in BRD3, CSRNP1, KDELC2, RUNX1 (two single-nucleotide polymorphisms) and BDNF-AS. The expression of BDNF was associated with neurofibrillary tangles in brain tissues from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP). Seven additional genes (ACAT1, ATM, NPAT, WDR48, TTC21A, SCN114 and COX7B) were identified through expression and protein quantitative trait loci analyses. Mendelian randomization analyses indicated a potential causal role of BDNF in cardioembolism. Lastly, Ingenuity Pathway Analysis placed circulating BDNF levels in four major networks. Our study provides novel insights into genes and molecular pathways associated with circulating BDNF levels and highlights the possible involvement of plaque instability as an underlying mechanism linking BDNF with brain neurodegeneration. These findings provide a foundation for a better understanding of BDNF regulation and function in the context of brain aging and neurodegenerative pathophysiology.
Thirty per cent of variation in circulating BDNF levels appears heritable. Loci adjacent to the BDNF gene and in BRD3, CSRNP1, KDELC2, RUNX1 and BDNF-AS influence levels. Using Ingenuity Pathway Analysis, these genes implicate major networks. Mendelian randomization suggests a role for BDNF in cardioembolism and BDNF expression associates with fewer neurofibrillary tangles.
Graphical Abstract
Graphical Abstract
Abstract
Background
Genetic analyses of cognitive endophenotypes have led to discoveries of novel loci contributing to Alzheimer’s disease (AD) risk. Sex differences are present in cognitive ...trajectories in aging and AD, and these may vary across cognitive domain. However, genetic drivers that may contribute to sex differences in cognitive trajectories have yet to be explored. Thus, we sought to investigate the sex‐specific genetic architecture of cognition.
Method
We leveraged 10 cohorts of cognitive aging and AD to complete this sex‐aware genetic study (N = 31,800; mean age = 73 yrs.; 55% female). Harmonized cognitive scores for memory, executive functioning, and language were derived using confirmatory factor analysis models. We calculated change in cognitive scores over time using a mixed effects model, to facilitate analysis on cognitive decline. We performed GWAS of baseline score and of estimated rate of decline in each domain and in each cohort separately among non‐Hispanic white (NHW) individuals, adjusting for baseline age and genetic principal components. Then we meta‐analyzed the results.
Result
In addition to the well‐characterized
APOE
locus, we identified a genome‐wide significant chromosome 2 locus that was associated with language decline among NHW women (rs13387871: MAF = 0.20; β
women
= 2.97×10
−3
; P
women
= 2.65×10
−9
), but not among male counterparts (β
men
= ‐3.14×10
−4
, P
men
= 0.60). This locus contains multiple eQTLs for
VRK2
, a serine/threonine kinase that has been previously linked to neuropsychiatric disorders, including schizophrenia. Furthermore, the top variant in this locus (rs13387871) was nominally significant for memory decline (β
women
= 1.74×10
−3
, P
women
= 0.01) and for executive functioning decline (β
women
= 7.58×10
−4
, P
women
= 0.02) in meta‐analyses among NHW women.
Conclusion
Our genetic analysis suggests that there may be some genetic drivers of language performance that differ by sex, and that these drivers may be shared to an extent across domains. Our future sex‐aware meta‐analyses will also include 1) non‐Hispanic black (NHB) within ancestry (N = 4,200), 2) cross‐ancestry (NHW + NHB), 3) diagnosis‐stratified, and 4) analysis of X‐chromosome. Planned follow‐up analyses will include gene‐set analyses, heritability tests, and genetic correlation tests. Through our preliminary analysis, we identified a promising locus for further exploration, and this is the first of many steps in elucidating the sex‐specific genetic architecture of cognition across ancestry groups.
Abstract
Background
A recently recognized subset of older individuals are an anomaly of cognitive decline; the “SuperAgers”, unsurprisingly named, achieve cognitive scores equivalent to much younger ...cognitively normal (CN) middle‐aged adults. Using longitudinal cognitive data harmonized across eight cohorts of aging and Alzheimer’s Dementia (AD), we investigated the genetic drivers of SuperAging.
Method
Harmonized memory, executive function, and language scores were estimated leveraging latent variable modeling and made available through the ADSP Phenotype Harmonization Consortium. SuperAgers (N = 1,095) were defined as individuals over 80 years with a mean sex‐adjusted memory score equal or exceeding CN individuals aged 50‐60, score within one age and sex‐adjusted standard deviation in the other two cognitive domains, and remain CN for all longitudinal visits. Young Cases (N = 1,906) were defined as individuals aged 50‐75 with a clinical diagnosis of AD. Old Controls (N = 3,247) were defined as CN individuals over 80, scoring within one age‐ and sex‐adjusted standard deviation in all three domains. We performed a GWAS on non‐Hispanic Whites using logistic regression comparing SuperAgers and their counterparts (Young Cases and Old Controls) with covaried adjustment for age, sex, education, and principal components for population substructure.
Result
Comparing SuperAgers with Young Cases (Figure 1), only variants in the well‐established APOE region were associated with genome‐wide significance (GWAS; P<510
−8
). Additionally, we observed a locus on chromosome 13 approach GWS (rs138699163, P = 6.5610
−8
). The locus centered on a relatively uncharacterized ncRNA, MIR4500. Analyses comparing SuperAgers to Old Controls did not find any GWS associations, with the strongest association observed at rs116535931 on chromosome 5 (P = 1.5210
−6
).
Conclusion
Our extreme‐phenotype GWAS comparing SuperAgers to Young Cases identified established and novel loci for AD. However, larger sample sizes may allow better characterization of the genetic architecture of SuperAging. Future analyses will extend to Case comparison groups to include Old Cases (age>80 years) and All Cases (age>50 years) and Control comparison groups to include Young Controls (age between 50‐60) and Agnostic Controls (age>50 years) with similar criteria.
Abstract
Background
Alzheimer’s disease (AD) is clinically characterized by disabling cognitive impairment, though substantial variability in cognitive symptoms and trajectories is observed in AD ...individuals. However, genetic predictors of domain‐specific cognitive performance remain undiscovered. We investigated cross‐sectional and longitudinal genetic architecture of harmonized memory, executive function, and language scores within and across ancestry groups.
Method
Using data from 7 cohorts of cognitive aging and AD, individuals >60 years at baseline were included (mean age at baseline = 71.2). Cognitive scores for memory, executive function, and language were harmonized using latent variable models. Slopes for cognitive scores were calculated for each domain with linear mixed‐effects models. GWAS was performed on each cognitive domain for individual cohorts, both at baseline and longitudinally. Models covaried for baseline age, sex, and the first three genetic principal components. Individual models were assessed among non‐Hispanic Whites (NHW) (N = 26,455), non‐Hispanic Blacks (NHB) (N = 3,410), and cross‐ancestry (NHW + NHB) (N = 29,865). Results were meta‐analyzed across cohorts.
Result
We identified six genetic loci showing a genome‐wide significant effect on cognition, in addition to well‐established associations between cognition and APOE: three loci in NHW, one locus in NHB, and two loci in cross‐ancestry results. In NHW, a chromosome 2 locus (rs6733839) near BIN1, a previously reported AD risk gene, was associated with longitudinal memory performance (MAF = 0.40, p = 3.36E‐08). Additionally, in NHW, two chromosome 2 loci (rs2940785 and rs2972059) were associated with memory decline (MAF = 0.05, = 3.92E‐09; MAF = 0.05, p = 5.06E‐09, respectively). Despite the small sample size, a chromosome 10 locus (rs77595416) was associated with longitudinal executive function in NHB (MAF = 0.01, p = 7.68E‐09). When analyzing cross‐ancestry results, two chromosome 2 loci near BIN1 (rs4663105 and rs6733839) were associated with memory decline (MAF = 0.44, p = 2.65E‐08; MAF = 0.40, p = 9.48E‐10, respectively).
Conclusion
We elucidate novel and replicate known genetic predictors of domain‐specific cognition in older adults. Furthermore, we show that genetic architecture of multiple cognitive domains in older adults differs by ancestry, highlighting SNPs observed in longitudinal memory (NHW and cross‐ancestry) and executive function (NHB). While replication is warranted, our results underscore the contribution of genetic predictors beyond APOE to cognitive decline and suggest the importance of ancestry‐specific analyses of cognition.
What is already known about this topic? The SARS-CoV-2 B.1.617.2 (Delta) variant is highly transmissible; however, whether it causes more severe disease in adults has been uncertain. What is added by ...this report? Analysis of COVID-NET data from 14 states found no significant increases in the proportion of hospitalized COVID-19 patients with severe outcomes during the Delta period. The proportion of hospitalized unvaccinated COVID-19 patients aged 18–49 years significantly increased during the Delta period. What are the implications for public health practice? Lower vaccination coverage in adults aged 18–49 years likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including adults aged <50 years who have relatively low vaccination rates compared with older adults.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Purpose: To assess the feasibility and effectiveness of a newly developed assistive technology system, Lee Silverman Voice Treatment Companion (LSVTR CompanionTM, hereafter referred to as ..."Companion"), to support the delivery of LSVTRLOUD, an efficacious speech intervention for individuals with Parkinson disease (PD). Method: Sixteen individuals with PD were randomized to an immediate ( n = 8) or a delayed ( n = 8) treatment group. They participated in 9 LSVT LOUD sessions and 7 Companion sessions, independently administered at home. Acoustic, listener perception, and voice and speech rating data were obtained immediately before (pre), immediately after (post), and at 6 months post treatment (follow-up). System usability ratings were collected immediately post treatment. Changes in vocal sound pressure level were compared to data from a historical treatment group of individuals with PD treated with standard, in-person LSVT LOUD. Results: All 16 participants were able to independently use the Companion. These individuals had therapeutic gains in sound pressure level, pre to post and pre to follow-up, similar to those of the historical treatment group. Conclusions: This study supports the use of the Companion as an aid in treatment of hypokinetic dysarthria in individuals with PD. Advantages and disadvantages of the Companion, as well as limitations of the present study and directions for future studies, are discussed. (Contains 1 figure and 4 tables.)
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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