Single particle tracking in systems showing anomalous diffusion: the role of weak ergodicity breaking

Anomalous diffusion has been widely observed by single particle tracking microscopy in complex systems such as biological cells. The resulting time series are usually evaluated in terms of time averages. Often anomalous diffusion is connected with non-ergodic behaviour. In such cases the time averages remain random variables and hence irreproducible. Here we present a detailed analysis of the time averaged mean squared displacement for systems governed by anomalous diffusion, considering both unconfined and restricted (corralled) motion. We discuss the behaviour of the time averaged mean squared displacement for two prominent stochastic processes, namely, continuous time random walks and fractional Brownian motion. We also study the distribution of the time averaged mean squared displacement around its ensemble mean, and show that this distribution preserves typical process characteristic even for short time series. Recently, velocity correlation functions were suggested to distinguish between these processes. We here present analytucal expressions for the velocity correlation functions. Knowledge of the results presented here are expected to be relevant for the correct interpretation of single particle trajectory data in complex systems.Comment: 15 pages, 15 figures; References adde

Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant

RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination

A Standardized Morpho-Functional Classification of the Planet’s Humipedons

It was time to take stock. We modified the humipedon classification key published in 2018 to make it easier and more practical. This morpho-functional taxonomy of the topsoil (humipedon) was only available in English; we also translated it into French and Italian. A standardized morphofunctional classification of humipedons (roughly the top 30–40 cm of soil: organic and organomineral surface horizons) would allow for a better understanding of the functioning of the soil ecosystem. This paper provides the founding principles of the classification of humipedon into humus systems and forms. With the recognition of a few diagnostic horizons, all humus systems can be determined. The humus forms that make up these humus systems are revealed by measuring the thicknesses of the diagnostic horizons. In the final part of the article, several figures represent the screenshots of a mobile phone or tablet application that allows for a fast recall of the diagnostic elements of the classification in the field. The article attempts to promote a standardized classification of humipedons for a global and shared management of soil at planet level

A standardized morpho-functional classification of the planet’s humipedons

It was time to take stock. We modified the humipedon classification key published in 2018 to make it easier and more practical. This morpho-functional taxonomy of the topsoil (humipedon) was only available in English; we also translated it into French and Italian. A standardized morphofunctional classification of humipedons (roughly the top 30–40 cm of soil: organic and organomineral surface horizons) would allow for a better understanding of the functioning of the soil ecosystem. This paper provides the founding principles of the classification of humipedon into humus systems and forms. With the recognition of a few diagnostic horizons, all humus systems can be determined. The humus forms that make up these humus systems are revealed by measuring the thicknesses of the diagnostic horizons. In the final part of the article, several figures represent the screenshots of a mobile phone or tablet application that allows for a fast recall of the diagnostic elements of the classification in the field. The article attempts to promote a standardized classification of humipedons for a global and shared management of soil at planet level

Global diversity of enterococci and description of 18 novel species

Bacteria of the genus Enterococcus colonize the guts of diverse animals. Some species have acquired multiple antibiotic resistances on top of a high level of intrinsic resistance and have emerged as leading causes of hospital-associated infection. Although clinical isolates of enterococcal species E. faecalis and E. faecium have been studied with respect to their antibiotic resistances and infection pathogenesis, comparatively little is known about the biology of enterococci in their natural context of the guts of humans and other land animals, including arthropods and other invertebrates. Importantly, little is also known about the global pool of genes already optimized for expression in an enterococcal background with the potential to be readily acquired by hospital adapted strains of E. faecalis and E. faecium , known facile exchangers of mobile genetic elements. We therefore undertook a global study designed to reach into maximally diverse habitats, to establish a first approximation of the genetic diversity of enterococci on Earth. Presumptive enterococci from over 900 diverse specimens were initially screened by PCR using a specific reporter gene that we found to accurately reflect genomic diversity. The genomes of isolates exceeding an operationally set threshold for diversity were then sequenced in their entirety and analyzed. This provided us with data on the global occurrence of many known enterococcal species and their association with various hosts and ecologies and identified 18 novel species expanding the diversity of the genus Enterococcus by over 25%. The 18 novel enterococcal species harbor a diverse array of genes associated with toxins, detoxification, and resource acquisition that highlight the capacity of the enterococci to acquire and adapt novel functions from diverse gut environments. In addition to the discovery and characterization of new species, this expanded diversity permitted a higher resolution analysis of the phylogenetic structure of the Enterococcus genus, including identification of distinguishing features of its 4 deeply rooted clades and genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility. Collectively, this work provides an unprecedentedly broad and deep view of the genus Enterococcus , along with new insights into their potential threat to human health

Clonal dynamics of BRAF-driven drug resistance in EGFR-mutant lung cancer

Activation of MAPK signaling via BRAF mutations may limit the activity of EGFR inhibitors in EGFR-mutant lung cancer patients. However, the impact of BRAF mutations on the selection and fitness of emerging resistant clones during anti-EGFR therapy remains elusive. We tracked the evolution of subclonal mutations by whole-exome sequencing and performed clonal analyses of individual metastases during therapy. Complementary functional analyses of polyclonal EGFR-mutant cell pools showed a dose-dependent enrichment of BRAF(V600E) and a loss of EGFR inhibitor susceptibility. The clones remain stable and become vulnerable to combined EGFR, RAF, and MEK inhibition. Moreover, only osimertinib/trametinib combination treatment, but not monotherapy with either of these drugs, leads to robust tumor shrinkage in EGFR-driven xenograft models harboring BRAF mutations. These data provide insights into the dynamics of clonal evolution of EGFR-mutant tumors and the therapeutic implications of BRAF(V600E) co-mutations that may facilitate the development of treatment strategies to improve the prognosis of these patients

Practical whole-system provenance capture

Data provenance describes how data came to be in its present form. It includes data sources and the transformations that have been applied to them. Data provenance has many uses, from forensics and security to aiding the reproducibility of scientific experiments. We present CamFlow, a whole-system provenance capture mechanism that integrates easily into a PaaS offering. While there have been several prior whole-system provenance systems that captured a comprehensive, systemic and ubiquitous record of a system’s behavior, none have been widely adopted. They either A) impose too much overhead, B) are designed for long-outdated kernel releases and are hard to port to current systems, C) generate too much data, or D) are designed for a single system. CamFlow addresses these shortcoming by: 1) leveraging the latest kernel design advances to achieve efficiency; 2) using a self-contained, easily maintainable implementation relying on a Linux Security Module, NetFilter, and other existing kernel facilities; 3) providing a mechanism to tailor the captured provenance data to the needs of the application; and 4) making it easy to integrate provenance across distributed systems. The provenance we capture is streamed and consumed by tenant-built auditor applications. We illustrate the usability of our implementation by describing three such applications: demonstrating compliance with data regulations; performing fault/intrusion detection; and implementing data loss prevention. We also show how CamFlow can be leveraged to capture meaningful provenance without modifying existing applications.Engineering and Applied Science