Elastic cavitation, tube hollowing, and differential growth in plants and biological tissues

Elastic cavitation is a well-known physical process by which elastic materials under stress can open cavities. Usually, cavitation is induced by applied loads on the elastic body. However, growing materials may generate stresses in the absence of applied loads and could induce cavity opening. Here, we demonstrate the possibility of spontaneous growth-induced cavitation in elastic materials and consider the implications of this phenomenon to biological tissues and in particular to the problem of schizogenous aerenchyma formation

Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by motor neuron loss, resulting in muscle wasting, paralysis and eventual death. A key pathological feature of ALS is cytoplasmically mislocalized and aggregated TDP-43 protein in >95% of cases, which is considered to have prion-like properties. Historical studies have predominantly focused on genetic forms of ALS, which represent ∼10% of cases, leaving the remaining 90% of sporadic ALS relatively understudied. Additionally, the role of astrocytes in ALS and their relationship with TDP-43 pathology is also not currently well understood. We have therefore used highly enriched human induced pluripotent stem cell (iPSC)-derived motor neurons and astrocytes to model early cell type-specific features of sporadic ALS. We first demonstrate seeded aggregation of TDP-43 by exposing human iPSC-derived motor neurons to serially passaged sporadic ALS post-mortem tissue (spALS) extracts. Next, we show that human iPSC-derived motor neurons are more vulnerable to TDP-43 aggregation and toxicity compared with their astrocyte counterparts. We demonstrate that these TDP-43 aggregates can more readily propagate from motor neurons into astrocytes in co-culture paradigms. We next found that astrocytes are neuroprotective to seeded aggregation within motor neurons by reducing (mislocalized) cytoplasmic TDP-43, TDP-43 aggregation and cell toxicity. Furthermore, we detected TDP-43 oligomers in these spALS spinal cord extracts, and as such demonstrated that highly purified recombinant TDP-43 oligomers can reproduce this observed cell-type specific toxicity, providing further support to a protein oligomer-mediated toxicity hypothesis in ALS. In summary, we have developed a human, clinically relevant, and cell-type specific modelling platform that recapitulates key aspects of sporadic ALS and uncovers both an initial neuroprotective role for astrocytes and the cell type-specific toxic effect of TDP-43 oligomers

Effects of pH_2O, pH_2 and fO_2 on the diffusion of h-bearing species in lunar basaltic liquid and an iron-free basaltic analog at 1 atm

We have experimentally determined the diffusivity of water in a representative lunar basaltic liquid composition (LG) and in an iron-free analog of a basaltic liquid (AD) at the low water concentrations and low oxygen fugacities (fO_2) relevant to the eruption of lunar basalts. Experiments were conducted at 1 atm and 1350 °C over a range of pH_2/pH_2O from near zero to ∼10 and a range in fO_2 spanning ∼9 orders of magnitude (from 2.2 log units below the iron-wüstite buffer, IW–2.2, to IW+6.7). The water concentrations measured in our quenched experimental glasses by secondary ion mass spectrometry (SIMS) and Fourier transform infrared spectroscopy (FTIR) vary from a few ppm to ∼430 ppm. Water concentration gradients in the majority of our AD experiments are well described by models in which the diffusivity of water (D*_(water)) has a constant value of ∼2×10^(–10) m^2/s, while our LG results indicate that D*_(water) in LG melt has a constant value of ∼6×10^(–10) m^2/s under the conditions of our experiments. Water concentration gradients in hydration and dehydration experiments that were run simultaneously in H_2/CO_2 gas mixtures are well described by the same D*_(water), and water concentrations measured near the melt-vapor interfaces of these experiment pairs are approximately the same. These observations strongly support an equilibrium boundary condition for our experiments containing >70 ppm H_2O. However, dehydration experiments into nominally anhydrous CO_2, N_2, and CO/CO_2 gas mixtures leave some scope for the importance of kinetics during dehydration of melts containing less than a few 10’s of ppm H_2O. Comparison of our results with the modified speciation model (Ni et al., 2013) in which both molecular water and hydroxyl are allowed to diffuse suggests that we have resolved the diffusivity of hydroxyl (D_(OH)) in AD and LG melts. Our results support a positive correlation between D_(OH) and melt depolymerization. Best-fit values of D*_(water) for our LG experiments vary within a factor of ∼2 over a range of pH_2/pH_2O from 0.007 to 9.7 and a range of logf O_2 from IW–2.2 to IW+4.9. The relative insensitivity of our best-fit values of D*_(water) to variations in pH_2 suggests that H_2 diffusion did not control the rate of degassing of H-bearing species from the lunar glasses of Saal et al. (2008); however, we cannot rule out a role for molecular H2 diffusion under lower-temperature and/or higher-pressure conditions than explored in our experiments. The value of D*_(water) chosen by Saal et al. (2008) for modeling the diffusive degassing of the lunar volcanic glasses is within a factor of ∼2 of our measured value in LG melt at 1350 °C. By coupling our LG results at 1350 °C with an activation energy of 220 kJ/mol (Zhang et al. 2017), we obtain the following Arrhenius relationship, which can be used to model syneruptive diffusive water loss from lunar melt beads: D*_(water)(m^2/s) = 7.2×10^(-3)exp(-2.6×10^4/T(K))

A simple graphical way of evaluating coverage and directional non-coverages

Evaluation of the coverage probability and, more recently, of the intervalar location of con dence intervals, is a useful procedure if exact and asymptotic methods for constructing con dence intervals are used for some populacional parameter. In this paper, a simple graphical procedure is presented to execute this kind of evaluation in con dence methods for linear combinations of k independent binomial proportions. Our proposal is based on the representation of the mesial and distal non-coverage probabilities on a plane. We carry out a simulation study to show how this graphical representation can be interpreted and used as a basis for the evaluation of intervalar location of con dence interval methods

Challenges in administrative data linkage for research

Linkage of population-based administrative data is a valuable tool for combining detailed individual-level information from different sources for research. While not a substitute for classical studies based on primary data collection, analyses of linked administrative data can answer questions that require large sample sizes or detailed data on hard-to-reach populations, and generate evidence with a high level of external validity and applicability for policy making. There are unique challenges in the appropriate research use of linked administrative data, for example with respect to bias from linkage errors where records cannot be linked or are linked together incorrectly. For confidentiality and other reasons, the separation of data linkage processes and analysis of linked data is generally regarded as best practice. However, the ‘black box’ of data linkage can make it difficult for researchers to judge the reliability of the resulting linked data for their required purposes. This article aims to provide an overview of challenges in linking administrative data for research. We aim to increase understanding of the implications of (i) the data linkage environment and privacy preservation; (ii) the linkage process itself (including data preparation, and deterministic and probabilistic linkage methods) and (iii) linkage quality and potential bias in linked data. We draw on examples from a number of countries to illustrate a range of approaches for data linkage in different contexts

Proving Determinacy of the PharOS Real-Time Operating System

International audienceExecutions in the PharOS real-time system are deterministic in the sense that the sequence of local states for every process is independent of the order in which processes are scheduled. The essential ingredient for achieving this property is that a temporal window of execution is associated with every instruction. Messages become visible to receiving processes only after the time window of the sending message has elapsed. We present a high-level model of PharOS in TLA+ and formally state and prove determinacy using the TLA+ Proof System

FroDO: From Detections to 3D Objects

Object-oriented maps are important for scene understanding since they jointly capture geometry and semantics, allow individual instantiation and meaningful reasoning about objects. We introduce FroDO, a method for accurate 3D reconstruction of object instances from RGB video that infers their location, pose and shape in a coarse to fine manner. Key to FroDO is to embed object shapes in a novel learnt shape space that allows seamless switching between sparse point cloud and dense DeepSDF decoding. Given an input sequence of localized RGB frames, FroDO first aggregates 2D detections to instantiate a 3D bounding box per object. A shape code is regressed using an encoder network before optimizing shape and pose further under the learnt shape priors using sparse or dense shape representations. The optimization uses multi-view geometric, photometric and silhouette losses. We evaluate on real-world datasets, including Pix3D, Redwood-OS, and ScanNet, for single-view, multi-view, and multi-object reconstruction

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal