Bond-Selective Intensity Diffraction Tomography

Recovering molecular information remains a grand challenge in the widely used holographic and computational imaging technologies. To address this challenge, we developed a computational mid-infrared photothermal microscope, termed Bond-selective Intensity Diffraction Tomography (BS-IDT). Based on a low-cost brightfield microscope with an add-on pulsed light source, BS-IDT recovers both infrared spectra and bond-selective 3D refractive index maps from intensity-only measurements. High-fidelity infrared fingerprint spectra extraction is validated. Volumetric chemical imaging of biological cells is demonstrated at a speed of ~20 seconds per volume, with a lateral and axial resolution of ~350 nm and ~1.1 micron, respectively. BS-IDT's application potential is investigated by chemically quantifying lipids stored in cancer cells and volumetric chemical imaging on Caenorhabditis elegans with a large field of view (~100 micron X 100 micron)

Coupling a local adaptive grid refinement technique with an interface sharpening scheme for the simulation of two-phase flow and free-surface flows using VOF methodology

This study presents the implementation of an interface sharpening scheme on the basis of the Volume of Fluid (VOF) method, as well as its application in a number of theoretical and real cases usually modelled in literature. More specifically, the solution of an additional sharpening equation along with the standard VOF model equations is proposed, offering the advantage of “restraining” interface numerical diffusion, while also keeping a quite smooth induced velocity field around the interface. This sharpening equation is solved right after volume fraction advection; however a novel method for its coupling with the momentum equation has been applied in order to save computational time. The advantages of the proposed sharpening scheme lie on the facts that a) it is mass conservative thus its application does not have a negative impact on one of the most important benefits of VOF method and b) it can be used in coarser grids as now the suppression of the numerical diffusion is grid independent. The coupling of the solved equation with an adaptive local grid refinement technique is used for further decrease of computational time, while keeping high levels of accuracy at the area of maximum interest (interface). The numerical algorithm is initially tested against two theoretical benchmark cases for interface tracking methodologies followed by its validation for the case of a free-falling water droplet accelerated by gravity, as well as the normal liquid droplet impingement onto a flat substrate. Results indicate that the coupling of the interface sharpening equation with the HRIC discretization scheme used for volume fraction flux term, not only decreases the interface numerical diffusion, but also allows the induced velocity field to be less perturbed owed to spurious velocities across the liquid–gas interface. With the use of the proposed algorithmic flow path, coarser grids can replace finer ones at the slight expense of accuracy

Low-Dimensional Palladium Nanostructures for Fast and Reliable Hydrogen Gas Detection

Palladium (Pd) has received attention as an ideal hydrogen sensor material due to its properties such as high sensitivity and selectivity to hydrogen gas, fast response, and operability at room temperature. Interestingly, various Pd nanostructures that have been realized by recent developments in nanotechnologies are known to show better performance than bulk Pd. This review highlights the characteristic properties, issues, and their possible solutions of hydrogen sensors based on the low-dimensional Pd nanostructures with more emphasis on Pd thin films and Pd nanowires. The finite size effects, relative strengths and weaknesses of the respective Pd nanostructures are discussed in terms of performance, manufacturability, and practical applicability

A review of phase change heat transfer in shape-stabilized phase change materials (ss-PCMs) based on porous supports for thermal energy storage

Latent heat thermal energy storage (LHTES) uses phase change materials (PCMs) to store and release heat, and can effectively address the mismatch between energy supply and demand. However, it suffers from low thermal conductivity and the leakage problem. One of the solutions is integrating porous supports and PCMs to fabricate shape-stabilized phase change materials (ss-PCMs). The phase change heat transfer in porous ss-PCMs is of fundamental importance for determining thermal-fluidic behaviours and evaluating LHTES system performance. This paper reviews the recent experimental and numerical investigations on phase change heat transfer in porous ss-PCMs. Materials, methods, apparatuses and significant outcomes are included in the section of experimental studies and it is found that paraffin and metal foam are the most used PCM and porous support respectively in the current researches. Numerical advances are reviewed from the aspect of different simulation methods. Compared to representative elementary volume (REV)-scale simulation, the pore-scale simulation can provide extra flow and heat transfer characteristics in pores, exhibiting great potential for the simulation of mesoporous, microporous and hierarchical porous materials. Moreover, there exists a research gap between phase change heat transfer and material preparation. Finally, this review outlooks the future research topics of phase change heat transfer in porous ss-PCMs

Requirement of NOX2 and Reactive Oxygen Species for Efficient RIG-I-Mediated Antiviral Response through Regulation of MAVS Expression

The innate immune response is essential to the host defense against viruses, through restriction of virus replication and coordination of the adaptive immune response. Induction of antiviral genes is a tightly regulated process initiated mainly through sensing of invading virus nucleic acids in the cytoplasm by RIG-I like helicases, RIG-I or Mda5, which transmit the signal through a common mitochondria-associated adaptor, MAVS. Although major breakthroughs have recently been made, much remains unknown about the mechanisms that translate virus recognition into antiviral genes expression. Beside the reputed detrimental role, reactive oxygen species (ROS) act as modulators of cellular signaling and gene regulation. NADPH oxidase (NOX) enzymes are a main source of deliberate cellular ROS production. Here, we found that NOX2 and ROS are required for the host cell to trigger an efficient RIG-I-mediated IRF-3 activation and downstream antiviral IFNβ and IFIT1 gene expression. Additionally, we provide evidence that NOX2 is critical for the expression of the central mitochondria-associated adaptor MAVS. Taken together these data reveal a new facet to the regulation of the innate host defense against viruses through the identification of an unrecognized role of NOX2 and ROS

Modular pathways for editing non-cognate amino acids by human cytoplasmic leucyl-tRNA synthetase

To prevent potential errors in protein synthesis, some aminoacyl-transfer RNA (tRNA) synthetases have evolved editing mechanisms to hydrolyze misactivated amino acids (pre-transfer editing) or misacylated tRNAs (post-transfer editing). Class Ia leucyl-tRNA synthetase (LeuRS) may misactivate various natural and non-protein amino acids and then mischarge tRNALeu. It is known that the fidelity of prokaryotic LeuRS depends on multiple editing pathways to clear the incorrect intermediates and products in the every step of aminoacylation reaction. Here, we obtained human cytoplasmic LeuRS (hcLeuRS) and tRNALeu (hctRNALeu) with high activity from Escherichia coli overproducing strains to study the synthetic and editing properties of the enzyme. We revealed that hcLeuRS could adjust its editing strategy against different non-cognate amino acids. HcLeuRS edits norvaline predominantly by post-transfer editing; however, it uses mainly pre-transfer editing to edit α-amino butyrate, although both amino acids can be charged to tRNALeu. Post-transfer editing as a final checkpoint of the reaction was very important to prevent mis-incorporation in vitro. These results provide insight into the modular editing pathways created to prevent genetic code ambiguity by evolution

FIDEL—a retrovirus-like retrotransposon and its distinct evolutionary histories in the A- and B-genome components of cultivated peanut

In this paper, we describe a Ty3-gypsy retrotransposon from allotetraploid peanut (Arachis hypogaea) and its putative diploid ancestors Arachis duranensis (A-genome) and Arachis ipaënsis (B-genome). The consensus sequence is 11,223 bp. The element, named FIDEL (Fairly long Inter-Dispersed Euchromatic LTR retrotransposon), is more frequent in the A- than in the B-genome, with copy numbers of about 3,000 (±950, A. duranensis), 820 (±480, A. ipaënsis), and 3,900 (±1,500, A. hypogaea) per haploid genome. Phylogenetic analysis of reverse transcriptase sequences showed distinct evolution of FIDEL in the ancestor species. Fluorescent in situ hybridization revealed disperse distribution in euchromatin and absence from centromeres, telomeric regions, and the nucleolar organizer region. Using paired sequences from bacterial artificial chromosomes, we showed that elements appear less likely to insert near conserved ancestral genes than near the fast evolving disease resistance gene homologs. Within the Ty3-gypsy elements, FIDEL is most closely related with the Athila/Calypso group of retrovirus-like retrotransposons. Putative transmembrane domains were identified, supporting the presence of a vestigial envelope gene. The results emphasize the importance of FIDEL in the evolution and divergence of different Arachis genomes and also may serve as an example of the role of retrotransposons in the evolution of legume genomes in general

A call for action to the biomaterial community to tackle antimicrobial resistance

The global surge of antimicrobial resistance (AMR) is a major concern for public health and proving to be a key challenge in modern disease treatment, requiring action plans at all levels. Microorganisms regularly and rapidly acquire resistance to antibiotic treatments and new drugs are continuously required. However, the inherent cost and risk to develop such molecules has resulted in a drying of the pipeline with very few compounds currently in development. Over the last two decades, efforts have been made to tackle the main sources of AMR. Nevertheless, these require the involvement of large governmental bodies, further increasing the complexity of the problem. As a group with a long innovation history, the biomaterials community is perfectly situated to push forward novel antimicrobial technologies to combat AMR. Although this involvement has been felt, it is necessary to ensure that the field offers a united front with special focus in areas that will facilitate the development and implementation of such systems. This paper reviews state of the art biomaterials strategies striving to limit AMR. Promising broad-spectrum antimicrobials and device modifications are showcased through two case studies for different applications, namely topical and implantables, demonstrating the potential for a highly efficacious physical and chemical approach. Finally, a critical review on barriers and limitations of these methods has been developed to provide a list of short and long-term focus areas in order to ensure the full potential of the biomaterials community is directed to helping tackle the AMR pandemic

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage

C/EBPβ Promotes Transition from Proliferation to Hypertrophic Differentiation of Chondrocytes through Transactivation of p57Kip2

BACKGROUND: Although transition from proliferation to hypertrophic differentiation of chondrocytes is a crucial step for endochondral ossification in physiological skeletal growth and pathological disorders like osteoarthritis, the underlying mechanism remains an enigma. This study investigated the role of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) in chondrocytes during endochondral ossification. METHODOLOGY/PRINCIPAL FINDINGS: Mouse embryos with homozygous deficiency in C/EBPbeta (C/EBPbeta-/-) exhibited dwarfism with elongated proliferative zone and delayed chondrocyte hypertrophy in the growth plate cartilage. In the cultures of primary C/EBPbeta-/- chondrocytes, cell proliferation was enhanced while hypertrophic differentiation was suppressed. Contrarily, retroviral overexpression of C/EBPbeta in chondrocytes suppressed the proliferation and enhanced the hypertrophy, suggesting the cell cycle arrest by C/EBPbeta. In fact, a DNA cell cycle histogram revealed that the C/EBPbeta overexpression caused accumulation of cells in the G0/G1 fraction. Among cell cycle factors, microarray and real-time RT-PCR analyses have identified the cyclin-dependent kinase inhibitor p57(Kip2) as the transcriptional target of C/EBPbeta. p57(Kip2) was co-localized with C/EBPbeta in late proliferative and pre-hypertrophic chondrocytes of the mouse growth plate, which was decreased by the C/EBPbeta deficiency. Luciferase-reporter and electrophoretic mobility shift assays identified the core responsive element of C/EBPbeta in the p57(Kip2) promoter between -150 and -130 bp region containing a putative C/EBP motif. The knockdown of p57(Kip2) by the siRNA inhibited the C/EBPbeta-induced chondrocyte hypertrophy. Finally, when we created the experimental osteoarthritis model by inducing instability in the knee joints of adult mice of wild-type and C/EBPbeta+/- littermates, the C/EBPbeta insufficiency caused resistance to joint cartilage destruction. CONCLUSIONS/SIGNIFICANCE: C/EBPbeta transactivates p57(Kip2) to promote transition from proliferation to hypertrophic differentiation of chondrocytes during endochondral ossification, suggesting that the C/EBPbeta-p57(Kip2) signal would be a therapeutic target of skeletal disorders like growth retardation and osteoarthritis