Blue Nile Incision on the Ethiopian Plateau: Pulsed Plateau Growth, Pliocene Uplift, and Hominin Evolution

The 1.6-km-deep Gorge of the Nile, a rival of the Grand Canyon, resulted from the deep incision of the Blue Nile drainage into the uplifted Ethiopian Plateau. Understanding the incision history of the plateau is crucial to unraveling the Cenozoic tectonoclimatic evolution of the region, particularly because the region has long been used as a natural laboratory to understand the geodynamics of continental rifting and the evolution of hominins. We undertake a quantitative geomorphologic approach integrating field, geographic information system (GIS), and digital elevation model (DEM) data to analyze incision (volume, long-term rates, and spatiotemporal variability) and river longitudinal profiles of the Blue Nile drainage. Previously published isotopic ages of the Cenozoic volcanic rocks are used to constrain long-term incision rates through geologic time. Our data argue that (1) the Blue Nile drainage has removed at least 93,200 km3 of rocks from the northwestern Ethiopian Plateau since ca. 29 Ma (early Oligocene) through a three-phase (ca. 29-10 Ma, ca. 10-6 Ma, and ca. 6 Ma to present) incision, where long-term incision rates increased rapidly and episodically in the late Miocene (ca. 10 Ma and ca. 6 Ma); (2) being out-of-phase with the past climatic events and in-phase with the main volcanic episodes of the region, this episodic increase of incision rate is suggestive of episodic growth of the plateau; (3) of the ~2-km rock uplift of the plateau since ca. 30 Ma, 0.3 km was due to isostatic uplift related to erosional unloading, and the rest was due to other tectonic activities; (4) the extremely rapid long-term incision rate increase, thus a rapid uplift of the plateau, ca. 6 Ma might be related to lithospheric foundering, caused by ponded plume material beneath the Ethiopian Plateau and aided by huge tectonic stresses related to the Messinian salinity crisis of the Mediterranean Sea. These events could have caused the plateau to rise \u3e1 km within a few m.y. in the early Pliocene. This uplift history of the Ethiopian Plateau can shed critical light on the geodynamics of the Afar mantle plume and the evolution of the East African hominins via climate change

Ford Highway Driving RTK Dataset: 30,000 km of North American Highways

There is a growing need for vehicle positioning information to support Advanced Driver Assistance Systems (ADAS), Connectivity (V2X), and Autonomous Driving (AD) features. These range from a need for road determination ($<$5 meters), lane determination ($<$1.5 meters), and determining where the vehicle is within the lane ($<$0.3 meters). This paper presents the Ford Highway Driving RTK (Ford-HDR) dataset. This dataset includes nearly 30,000 km of data collected primarily on North American highways during a driving campaign designed to validate driver assistance features in 2018. This includes data from a representative automotive production GNSS used primarily for turn-by-turn navigation as well as an Inertial Navigation System (INS) which couples two survey-grade GNSS receivers with a tactical grade Inertial Measurement Unit (IMU) to act as ground truth. The latter utilized networked Real-Time Kinematic (RTK) GNSS corrections delivered over a cellular modem in real-time. This dataset is being released into the public domain to spark further research in the community.Comment: 8 pages, 4 figures, ION GNSS+ 202

Does effective population size affect rates of molecular evolution : mitochondrial data for host/parasite species pairs in bees suggests not

Adaptive evolutionary theory argues that organisms with larger effective population size (Ne) should have higher rates of adaptive evolution and therefore greater capacity to win evolutionary arm races. However, in some certain cases, species with much smaller Ne may be able to survive besides their opponents for an extensive evolutionary time. Neutral theory predicts that accelerated rates of molecular evolution in organisms with exceedingly small Ne are due to the effects of genetic drift and fixation of slightly deleterious mutations. We test this prediction in two obligate social parasite species and their respective host species from the bee tribe Allodapini. The parasites (genus Inquilina) have been locked into tight coevolutionary arm races with their exclusive hosts (genus Exoneura) for ~15 million years, even though Inquilina exhibit Ne that are an order of magnitude smaller than their host. In this study, we compared rates of molecular evolution between host and parasite using nonsynonymous to synonymous substitution rate ratios (dN/dS) of eleven mitochondrial protein-coding genes sequenced from transcriptomes. Tests of selection on mitochondrial genes indicated no significant differences between host and parasite dN/dS, with evidence for purifying selection acting on all mitochondrial genes of host and parasite species. Several potential factors which could weaken the inverse relationship between Ne and rate of molecular evolution are discussed

Biomarkers of Tuberculosis Severity and Treatment Effect: A Directed Screen of 70 Host Markers in a Randomized Clinical Trial.

More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers with baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1β, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study

Fractal Patterns in the Parameter Space of Bi-stable Duffing Oscillator

We study the dissipative bi-stable Duffing oscillator with equal energy wells and observe fractal patterns in the parameter space of driving frequency, forcing amplitude, and damping ratio. Our numerical investigation reveals the Hausdorff fractal dimension of the boundaries that separate the oscillator's intra-well and inter-well behaviors. Furthermore, we categorize the inter-well behaviors as three steady-state types: switching, reverting, and vacillating. While fractal patterns in the phase space are well-known and heavily studied, our results point to a new research direction about fractal patterns in the parameter space. Another implication of this study is that the vibration of a continuous bi-stable system modeled using a single-mode approximation also manifests fractal patterns in the parameter space. In addition, our findings can guide the design of next-generation bi-stable and multi-stable mechanical metamaterials

Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis.

RationaleThe monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment.ObjectiveWe utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment. We sought to identify treatment specific signatures within patients as well as correlate the proteome signatures to various clinical markers of treatment efficacy.MethodsSerum samples were collected from 289 subjects enrolled in CDC TB Trials Consortium Study 29 at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). Serum proteins were immunoaffinity-depleted of high abundant components, digested to peptides and analyzed for data acquisition utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed models were utilized to identify serum protein changes in the host response to antibiotic treatment as well as correlations with culture status end points.ResultsA total of 10,137 peptides corresponding to 872 proteins were identified, quantified, and used for statistical analysis across the longitudinal patient cohort. In response to TB treatment, 244 proteins were significantly altered. Pathway/network comparisons helped visualize the interconnected proteins, identifying up regulated (lipid transport, coagulation cascade, endopeptidase activity) and down regulated (acute phase) processes and pathways in addition to other cross regulated networks (inflammation, cell adhesion, extracellular matrix). Detection of possible lung injury serum proteins such as HPSE, significantly downregulated upon treatment. Analyses of microbiologic data over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2) which change in response to treatment and also strongly correlate with culture status. A similar set of proteins at baseline were found to be predictive of week 6 and 8 culture status.ConclusionA comprehensive host serum protein dataset reflective of TB treatment effect is defined. A repeating set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change significantly in response to treatment, to strongly correlate with culture status, and at baseline to be predictive of future culture conversion. If validated in cohorts with long term follow-up to capture failure and relapse of TB, these protein markers could be developed for monitoring of treatment in clinical trials and in patient care

A new toolbox to distinguish the sources of spatial memory error

Studying the sources of errors in memory recall has proven invaluable for understanding the mechanisms of working memory (WM). While one-dimensional memory features (e.g. colour, orientation) can be analysed using existing mixture modelling toolboxes to separate the influence of imprecision, guessing, and misbinding (the tendency to confuse features that belong to different memoranda), such toolboxes are not currently available for two-dimensional spatial WM tasks. Here we present a method to isolate sources of spatial error in tasks where participants have to report the spatial location of an item in memory, using two-dimensional mixture models. The method recovers simulated parameters well, and is robust to the influence of response distributions and biases, and number of non-targets and trials. To demonstrate the model, we fit data from a complex spatial WM task, and show the recovered parameters correspond well with previous spatial WM findings, and with recovered parameters on a one-dimensional analogue of this task, suggesting convergent validity for this two-dimensional modelling approach. Because the extra dimension allows greater separation of memoranda and responses, spatial tasks turn out to be much better for separating misbinding from imprecision and guessing than one-dimensional tasks. Code for these models is freely available in the MemToolbox2D package and is integrated to work with the commonly used Matlab package MemToolbox

Traffic-Related Air Pollution and All-Cause Mortality during Tuberculosis Treatment in California.

BackgroundAmbient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain.ObjectiveWe determined the impact of residential traffic on mortality during treatment of active TB.MethodsFrom 2000-2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in 100- to 400-m radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests.ResultsParticipants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the 100-m buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio (HR)=1.03 [95% confidence interval (CI): 0.86, 1.25]; third quintile HR=1.14 (95% CI: 0.95, 1.37); fourth quintile HR=1.19 (95% CI: 0.99, 1.43); fifth quintile HR=1.28 (95% CI: 1.07, 1.53), respectively; p-trend=0.002].ConclusionsResidential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699

Mosaic dysfunction of mitophagy in mitochondrial muscle disease

Mitophagy is a quality control mechanism that eliminates damaged mitochondria, yet its significance in mammalian pathophysiology and aging has remained unclear. Here, we report that mitophagy contributes to mitochondrial dysfunction in skeletal muscle of aged mice and human patients. The early disease stage is characterized by muscle fibers with central nuclei, with enhanced mitophagy around these nuclei. However, progressive mitochondrial dysfunction halts mitophagy and disrupts lysosomal homeostasis. Interestingly, activated or halted mitophagy occur in a mosaic manner even in adjacent muscle fibers, indicating cell-autonomous regulation. Rapamycin restores mitochondrial turnover, indicating mTOR-dependence of mitochondrial recycling in advanced disease stage. Our evidence suggests that (1) mitophagy is a hallmark of age-related mitochondrial pathology in mammalian muscle, (2) mosaic halting of mitophagy is a mechanism explaining mosaic respiratory chain deficiency and accumulation of pathogenic mtDNA variants in adult-onset mitochondrial diseases and normal aging, and (3) augmenting mitophagy is a promising therapeutic approach for muscle mitochondrial dysfunction.Peer reviewe