Manipulating type-I and type-II Dirac polaritons in cavity-embedded honeycomb metasurfaces

Pseudorelativistic Dirac quasiparticles have emerged in a plethora of artificial graphene systems that mimic the underlying honeycomb symmetry of graphene. However, it is notoriously difficult to manipulate their properties without modifying the lattice structure. Here we theoretically investigate polaritons supported by honeycomb metasurfaces and, despite the trivial nature of the resonant elements, we unveil rich Dirac physics stemming from a non-trivial winding in the light-matter interaction. The metasurfaces simultaneously exhibit two distinct species of massless Dirac polaritons, namely type-I and type-II. By modifying only the photonic environment via an enclosing cavity, one can manipulate the location of the type-II Dirac points, leading to qualitatively different polariton phases. This enables one to alter the fundamental properties of the emergent Dirac polaritons while preserving the lattice structure - a unique scenario which has no analog in real or artificial graphene systems. Exploiting the photonic environment will thus give rise to unexplored Dirac physics at the subwavelength scale

HIF1A reduces acute lung injury by optimizing carbohydrate metabolism in the alveolar epithelium

Background: While acute lung injury (ALI) contributes significantly to critical illness, it resolves spontaneously in many instances. The majority of patients experiencing ALI require mechanical ventilation. Therefore, we hypothesized that mechanical ventilation and concomitant stretch-exposure of pulmonary epithelia could activate endogenous pathways important in lung protection. Methods and Findings: To examine transcriptional responses during ALI, we exposed pulmonary epithelia to cyclic mechanical stretch conditions—an in vitro model resembling mechanical ventilation. A genome-wide screen revealed a transcriptional response similar to hypoxia signaling. Surprisingly, we found that stabilization of hypoxia-inducible factor 1A (HIF1A) during stretch conditions in vitro or during ventilator-induced ALI in vivo occurs under normoxic conditions. Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function. Pharmacologic studies with HIF activator or inhibitor treatment implicated HIF1A-stabilization in attenuating pulmonary edema and lung inflammation during ALI in vivo. Systematic deletion of HIF1A in the lungs, endothelia, myeloid cells, or pulmonary epithelia linked these findings to alveolar-epithelial HIF1A. In vivo analysis of 13C-glucose metabolites utilizing liquid-chromatography tandem mass-spectrometry demonstrated that increases in glycolytic capacity, improvement of mitochondrial respiration, and concomitant attenuation of lung inflammation during ALI were specific for alveolar-epithelial expressed HIF1A. Conclusions: These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation

Expression profiling of the developing mouse lung: insights into the establishment of the extracellular matrix

We have undertaken a comprehensive gene expression profiling of the entire process of murine lung development using oligonucleotide-based microarrays. Our data reveals the expression pattern of ‫ف‬ 11,000 genes throughout the morphologic stages of lung development. This includes known genes with unappreciated pulmonary expression and novel genes with undefined functions. Traditional gene expression analysis techniques verify a high degree of confidence in the microarray data. Examination of the data confirms previously known patterns of expression for extracellular matrix genes and provides new information regarding relationships in temporal expression among groups of these genes. Large-scale cluster analysis reveals associations in the expression profile of specific genes with defined developmental processes. For instance, we identify groups of genes, which are coordinately expressed with extracellular matrix genes during lung development. These data should serve as a resource for the pulmonary research community and assist in deciphering the molecular mechanisms governing normal lung development as well as those involved in aberrant developmental pathology. Mammalian lung development is a complex morphogenetic process, which initiates near mid-gestation and continues through early postnatal life. The lung arises as two lateral buds that emerge from the ventral foregut endoderm at ‫ف‬ 9 days after fertilization (in mouse) and undergo numerous rounds of dichotomous branching to form the bronchial tree. This stage of development is referred to as the pseudoglandular phase, histologically characterized by loose mesenchyme surrounding undifferentiated epithelial tubes. Recent advances have been made in the understanding of the genetic and molecular mechanisms involved in these early processes which, in part, exhibit direct analogies to vertebrate limb development (1, 2). For instance, lung structure initiation and branching morphogenesis involve coordinated regulation of molecular pathways, including Sonic Hedgehog-, Bone Morphogenetic Protein/Transforming Growth Factor-␤ -, Fibroblast Growth Factor-and Retinoic Acidrelated signaling (3). There are at least three subsequent phases of lung development that can be distinguished morphologically; the canalicular, saccular, and alveolar stages. A detailed understanding of the physiologic processes governing these latter stages of lung development, in particular the alveolar stage that results in the development of terminal airways and airsacs capable of functional gas-exchange, remains incompletely defined. Large-scale gene expression analysis provides a powerful tool that can aid in the understanding of the molecular status of a cell, tissue, or organ (4-7). This technique has been used to discriminate static differences between cells/ tissues and to compare changes in gene expression over time. In the former case, gene expression profiling provides data that can improve the description and our comprehension of a particular specimen. For instance, certain morphologically indistinguishable tumors can be discriminated on the basis of gene expression analysis data (6). In the latter case, mathematical clustering techniques have proven useful for identifying functional inter-relationships between genes based upon their expression patterns (8-10). We have undertaken a large-scale gene expression analysis of mammalian lung development using oligonucleotidebased microarrays. We have chosen to study the mouse as our model system, based upon future applications of our current data set to genetically engineered animal models. Our analysis encompasses all recognized stages of development beginning at embryonic day 12 and continuing to adulthood. These data provide an abundance of information for gene expression during lung development, including cloned genes with previously unappreciated lung expression and expressed sequence tags (ESTs) with undefined function. Additionally, cluster analysis reveals previously unappreciated relationships between the expression patterns of genes that may have functional significance in this complex process. Materials and Methods Isolation of Lung RNA Timed-pregnant Swiss-Webster mice were purchased from Taconic (Charles River, MA). Lungs were isolated by manual dissection with the aid of a dissecting microscope, where necessary (E12-E18). Stage of embryonic lung development was confirmed by visual inspection of the embryos and histologic evaluation of littermate lung sections. RNA was isolated from individual (E18, P1, P4, P7, P10, P14, P21, and adult) or pooled (E12, E14, E16) whole lungs using a modified guanidinium:phenol extraction method (Trizol; Invitrogen, Carlsbad, CA) according to manufacturer's instructions. RNA quality and integrity was confirmed by denaturing gel electrophoresis. Generation of cRNA "Target" and Chip Hybridization Ten micrograms of total RNA was used to generate "target" cRNA for hybridization to Affymetrix Mu11K chipset subA and subB oligonucleotide microarrays. A single chip set was used for each time-point. Before target generation, individual RNA samples were pooled so that each "target" was derived from a minimum of three individual lungs. This step was performed to minimize both biologic variability and the number of microarrays necessary to generate informative data. After pooling, RNA was re-purified using Qiagen purification kits (Valencia, CA). Targe

Platform dependence of inference on gene-wise and gene-set involvement in human lung development

<p>Abstract</p> <p>Background</p> <p>With the recent development of microarray technologies, the comparability of gene expression data obtained from different platforms poses an important problem. We evaluated two widely used platforms, Affymetrix U133 Plus 2.0 and the Illumina HumanRef-8 v2 Expression Bead Chips, for comparability in a biological system in which changes may be subtle, namely fetal lung tissue as a function of gestational age.</p> <p>Results</p> <p>We performed the comparison via sequence-based probe matching between the two platforms. "Significance grouping" was defined as a measure of comparability. Using both expression correlation and significance grouping as measures of comparability, we demonstrated that despite overall cross-platform differences at the single gene level, increased correlation between the two platforms was found in genes with higher expression level, higher probe overlap, and lower p-value. We also demonstrated that biological function as determined via KEGG pathways or GO categories is more consistent across platforms than single gene analysis.</p> <p>Conclusion</p> <p>We conclude that while the comparability of the platforms at the single gene level may be increased by increasing sample size, they are highly comparable ontologically even for subtle differences in a relatively small sample size. Biologically relevant inference should therefore be reproducible across laboratories using different platforms.</p

Mitral Valve Coaptation Reserve Index:A Model to Localize Individual Resistance to Mitral Regurgitation Caused by Annular Dilation

Objectives: The objective of this study was to develop a mathematical model for mitral annular dilatation simulation and determine its effects on the individualized mitral valve (MV) coaptation reserve index (CRI). Design: A retrospective analysis of intraoperative transesophageal 3-dimensionalechocardiographic MV datasets was performed. A mathematical model was created to assess the mitral CRI for each leaflet segment (A1-P1, A2-P2, A3-P3). Mitral CRI was defined as the ratio between the coaptation reserve (measured coaptation length along the closure line) and an individualized correction factor. Indexing was chosen to correct for MV sphericity and area of largest valve opening. Mathematical models were created to simulate progressive mitral annular dilatation and to predict the effect on the individual mitral CRI. Setting: At a single-center academic hospital. Participants: Twenty-five patients with normally functioning MVs undergoing cardiac surgery. Interventions: None. Measurements and Main Results: Direct measurement of leaflet coaptation along the closure line showed the lowest amount of coaptation (reserve) near the commissures (A1-P1 0.21 ± 0.05 cm and A3-P3 0.22 ± 0.06 cm), and the highest amount of coaptation (reserve) at region A2 to P2 0.25 ± 0.06 cm. After indexing, the A2-to-P2 region was the area with the lowest CRI in the majority of patients, and also the area with the least resistance to mitral regurgitation (MR) occurrence after simulation of progressive annular dilation. Conclusions: Quantification and indexing of mitral coaptation reserve along the closure line are feasible. Indexing and mathematical simulation of progressive annular dilatation consistently showed that indexed coaptation reserve was lowest in the A2-to-P2 region. These results may explain why this area is prone to lose coaptation and is often affected in MR

Real-time kinetic binding studies at attomolar concentrations in solution phase using a single-stage opto-biosensing platform based upon infrared surface plasmons

Here we present a new generic opto-bio-sensing platform combining immobilised aptamers on an infrared plasmonic sensing device generated by nano-structured thin film that demonstrates amongst the highest index spectral sensitivities of any optical fibre sensor yielding on average 3.4 × 104 nm/RIU in the aqueous index regime (with a figure of merit of 330) This offers a single stage, solution phase, atto-molar detection capability, whilst delivering real-time data for kinetic studies in water-based chemistry. The sensing platform is based upon optical fibre and has the potential to be multiplexed and used in remote sensing applications. As an example of the highly versatile capabilities of aptamer based detection using our platform, purified thrombin is detected down to 50 attomolar concentration using a volume of 1mm3 of solution without the use of any form of enhancement technique. Moreover, the device can detect nanomolar levels of thrombin in a flow cell, in the presence of 4.5% w/v albumin solution. These results are important, covering all concentrations in the human thrombin generation curve, including the problematic initial phase. Finally, selectivity is confirmed using complementary and non-complementary DNA sequences that yield performances similar to those obtained with thrombin

Feasibility of a Monitoring Mechanism Supporting a Watch List under the Water Framework Directive

This report describes work conducted by the European Commission’s Joint Research Centre in the context of its support to the implementation of the Water Framework Directive 2000/60/EC. The work aimed at the feasibility assessment of an experimental monitoring exercise in support to a so-called Watch List Mechanism in a collaborative design involving EU Member States laboratories and some 200 official monitoring station operated by the Member States. The report includes all details on sampling stations, performance of analytical methods as well as the results of the analyses of all samples with regard to the occurrence and levels of 20 compounds of concern. In total, 219 whole water samples originating from 25 EU Member States and 2 other European countries, were assessed for contents of acesulfame, glyphosate and its metabolite AMPA, 1H-Benzotriazole and tolyltriazoles, bisphenol A, triclosan and triclocarban, carbamazepine and its metabolite 10,11-dihydro-10,11-dihydroxycarbamazepine, sulfamethoxazole, perfluoropropionic acid, tris-2-chloropropyl phosphate, methyl tert-butyl ether, silver, boron and chloride (Cl-) in water. Furthermore, 23 sediment samples were analysed for decabromodiphenylethane and decabromodiphenyl ether. The underlying analytical methods are carefully documented with regards to their performance characteristics. Obtained results are assessed statistically and where possible compared to other findings. Although the analysed single samples are insufficient to make any statement on the performance of the treatment processes leading to the compost, the collective of data allows having a glance at the pan-European situation as regards the studies compounds. Background information from literature describing the situation before the survey is included, too. The report is divided into a core part and two annexes. For practical reasons, the report is split into two volumes: Volume 1 contains the report and the single analytical results; volume 2 contains the documentation of the sampling stations.JRC.H.1-Water Resource