Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Optimizing Sensor Movement Planning for Energy Efficiency

Conserving the energy for motion is an important yet notwell-addressed problem in mobile sensor networks. In this paper, we study the problem of optimizing sensor movement for energy efficiency. We adopt a complete energy model to characterize the entire energy consumption in movement. Based on the model, we propose an optimal velocity schedule for minimizing energy consumption when the road condition is uniform; and a near optimal velocity schedule for the variable road condition by using continuous-state dynamic programming. Considering the variety in motion hardware, we also design one velocity schedule for simple microcontrollers, and one velocity schedule for relatively complex microcontrollers, respectively. Simulation results show that our velocity planning may have significant impact on energy conservation

Pre-Columbian jadeitite artifacts from San Salvador Island, Bahamas and comparison with jades of the eastern Caribbean and jadeitites of the greater Caribbean region

Four artifacts from San Salvador Island, Bahamas, with affinities to jadeite jade were studied by mineralogical and petrographical techniques and compared to similar studies of jadeite rock (jadeitite) from sources in the greater Caribbean region: Guatemala (both north and south Motagua mélange occurrences); the Sierra del Convento Mélange, Cuba; and the Río San Juan Complex, Dominican Republic. Three of the four artifacts are jadeite jade. The fourth is a metavolcanic rock of greenschist facies metamorphism. Each of the three jadeitite objects is distinct in terms of mineral assemblage and microscopic minerals intergrowth textures. One artifact manifests strong similarities with a variety of jadeitite known from Cuba, the closest source geographically to the Bahamas. The other two artifacts display unique characteristics of either mineral assemblage or texture that have not been observed to date in rocks from the known sources. Consequently, search must continue for greater diversity within the documented sources or new sources of jadeite jade that conform to what was observed must be found.The authors acknowledge the support of the University of the Bahamas Gerace Research Centre, San Salvador, Bahamas and Dr. Michael P. Pateman, Director, Turks & Caicos National Museum Foundation for permission to study the artifacts. Permission was granted by the Bahamas Antiquities, Monuments, and Museums Corporation to make alterations to the artifacts to benefit their archaeological interpretation. US National Science Foundation grant EAR 0851847, Dr. Lisa Park Boush, Principal Investigator, funded the North Storr's Lake site radiocarbon dates. The authors thank the anonymous reviewer for his/her useful comments