Mixed-mode fracture characteristics of metal-to-metal adhesively bonded joints: experimental and simulation methods.

Fracture behavior of adhesively bonded joints subjected to mixed-mode (i.e. mode I+II) loading conditions is of importance in many industrial applications. This research therefore aims to characterise the failure behaviour of metal-to-metal (i.e. both aluminium adherends) adhesive joints using the mixed mode bending test (MMB), adapted from ASTM D6671/D6671M standard, along with instrumentation using acoustic emission (AE) sensor. Twenty-four adhesively bonded specimens were prepared using two types of adhesive bond materials (acrylic, cyanoacrylate) with two different bonded area 65% and 100%. To understand the effect of mixed-mode loading conditions on the failure behavior, two different mixity ratios were achieved through the design of the MMB test fixture and tested for each bonded joint. The AE results during mechanical testing shows that the time domain signals were spread over the loading phase with distinct features for different mixity ratios. They successfully identified the moment of adhesive fracture during every test. Also, the fracture behavior of the bonded joints was simulated using virtual crack closure technique (VCCT) method using finite element method to understand the loading dynamics in specimen when considering a combination of various design parameters. In addition, an analytical method (e.g. corrected beam theory or CBT) was used to determine strain energy release rates of each specimen. The results show that both the brittle and ductile specimens exhibited higher energy release rates when mode II proportion of loading was increased during the crack initiation phase. The proposed measurement can be useful to assess the overall structural health of bonded systems

Specification of the near-Earth space environment with SHIELDS

Predicting variations in the near-Earth space environment that can lead to spacecraft damage and failure is one example of “space weather” and a big space physics challenge. A project recently funded through the Los Alamos National Laboratory (LANL) Directed Research and Development (LDRD) program aims at developing a new capability to understand, model, and predict Space Hazards Induced near Earth by Large Dynamic Storms, the SHIELDS framework. The project goals are to understand the dynamics of the surface charging environment (SCE), the hot (keV) electrons representing the source and seed populations for the radiation belts, on both macro- and micro-scale. Important physics questions related to particle injection and acceleration associated with magnetospheric storms and substorms, as well as plasma waves, are investigated. These challenging problems are addressed using a team of world-class experts in the fields of space science and computational plasma physics, and state-of-the-art models and computational facilities. A full two-way coupling of physics-based models across multiple scales, including a global MHD (BATS-R-US) embedding a particle-in-cell (iPIC3D) and an inner magnetosphere (RAM-SCB) codes, is achieved. New data assimilation techniques employing in situ satellite data are developed; these provide an order of magnitude improvement in the accuracy in the simulation of the SCE. SHIELDS also includes a post-processing tool designed to calculate the surface charging for specific spacecraft geometry using the Curvilinear Particle-In-Cell (CPIC) code that can be used for reanalysis of satellite failures or for satellite design

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

Energetic particle influence on the Earth's atmosphere

This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

BACKGROUND: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. METHODS: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. RESULTS: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. CONCLUSIONS: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity

Critical role of effector macrophages in mediating CD4-dependent alloimmune injury of transplanted liver parenchymal cells

Despite the recognition that humoral rejection is an important cause of allograft injury, the mechanism of antibody-mediated injury to allograft parenchyma is not well understood. We used a well-characterized murine hepatocellular allograft model to determine the mechanism of antibody-mediated destruction of transplanted liver parenchymal cells. In this model allogeneic hepatocytes are transplanted into CD8-deficient hosts in order to focus on CD4-dependent, alloantibody-mediated rejection. Host serum alloantibody levels correlated with in vivo allospecific cytotoxic activity in CD8 KO hepatocyte rejector mice. Host macrophage depletion, but not CD4(+) T cell, NK cell, neutrophil, or complement depletion, inhibited in vivo allocytotoxicity. Recipient macrophage deficiency delayed CD4-dependent hepatocyte rejection and inhibited in vivo allocytotoxicity without influencing alloantibody production. Furthermore, hepatocyte coincubation with alloantibody and macrophages resulted in antibody-dependent hepatocellular cytotoxicity in vitro. These studies are consistent with a paradigm of acute humoral rejection in which CD4(+) T cell-dependent alloantibody production results in the targeting of transplanted allogeneic parenchymal cells for macrophage-mediated cytotoxic immune damage. Consequently, strategies to eliminate recipient macrophages during CD4-dependent rejection pathway may prolong allograft survival