The American lifestyle-induced obesity syndrome diet in male and female rodents recapitulates the clinical and transcriptomic features of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the progression to nonalcoholic steatohepatitis (NASH) and increased risk of hepatocellular carcinoma remain poorly understood. Additionally, there is increasing recognition of the extrahepatic manifestations associated with NAFLD and NASH. We demonstrate that intervention with the American lifestyle-induced obesity syndrome (ALIOS) diet in male and female mice recapitulates many of the clinical and transcriptomic features of human NAFLD and NASH. Male and female C57BL/6N mice were fed either normal chow (NC) or ALIOS from 11 to 52 wk and underwent comprehensive metabolic analysis throughout the duration of the study. From 26 wk, ALIOS-fed mice developed features of hepatic steatosis, inflammation, and fibrosis. ALIOS-fed mice also had an increased incidence of hepatic tumors at 52 wk compared with those fed NC. Hepatic transcriptomic analysis revealed alterations in multiple genes associated with inflammation and tissue repair in ALIOS-fed mice. Ingenuity Pathway Analysis confirmed dysregulation of metabolic pathways as well as those associated with liver disease and cancer. In parallel the development of a robust hepatic phenotype, ALIOS-fed mice displayed many of the extrahepatic manifestations of NAFLD, including hyperlipidemia, increased fat mass, sarcopenia, and insulin resistance. The ALIOS diet in mice recapitulates many of the clinical features of NAFLD and, therefore, represents a robust and reproducible model for investigating the pathogenesis of NAFLD and its progression.NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) affects 30% of the general population and can progress to nonalcoholic steatohepatitis (NASH) and potentially hepatocellular carcinoma. Preclinical models rely on mouse models that often display hepatic characteristics of NAFLD but rarely progress to NASH and seldom depict the multisystem effects of the disease. We have conducted comprehensive metabolic analysis of both male and female mice consuming a Western diet of trans fats and sugar, focusing on both their hepatic phenotype and extrahepatic manifestations

Tunable Fully Absorbing Metasurfaces for Efficient THz Detection

Terahertz photoconductive antennas with a nanostructured active region have been actively investigated recently with a goal to achieve high efficiency THz detectors and emitters. Here we provide a novel design of perfectly-absorbing photoconductive region without plasmonic elements using a metasurface, and provide a systematic method by which the metasurface can be designed to work optimally for varying optical gate frequencies across the GaAs band-gap. This paves the way to using metasurface devices for THz detection and other applications in a wide range of laser systems operating at different wavelengths or with different photoconductive materials

A study of top polarization in single-top production at the LHC

This paper complements the study of single top production at the LHC aiming to estimate the sensitivity of different observables to the magnitude of the effective couplings. In a previous paper the dominant $W$-gluon fusion mechanism was considered, while here we extend the analysis to the subdominant (10% with our set of experimental cuts) s-channel process. In order to distinguish left from right effective couplings it is required to consider polarized cross-sections and/or include $m_b$ effects. The spin of the top is accessible only indirectly by measuring the angular distribution of its decay products. We show that the presence of effective right-handed couplings implies necessarily that the top is not in a pure spin state. We discuss to what extent quantum interference terms can be neglected in the measurement and therefore simply multiply production and decay probabilities clasically. The coarsening involved in the measurement process makes this possible. We determine for each process the optimal spin basis where theoretical errors are minimized and, finally, discuss the sensitivity in the s-channel to the effective right-handed coupling. The results presented here are all analytical and include $m_b$ corrections. They are derived within the narrow width approximation for the top.Comment: 30 pages, 14 figure

Perfectly-absorbing photoconductive metasurfaces for THz applications

Ultrafast switching of photoconductivity is essential for many terahertz (THz) technologies, however this process is inefficient. Recently developed concepts of all-dielectric metasurfaces can improve efficiency of ultrafast switches, overcoming material limitations, reducing the thickness of the photoconductive region and lowering optical power requirements for THz devices. We will consider two types of perfectly absorbing metasurfaces compatible with the photoconductive switch architecture and discuss performance of THz detectors with integrated metasurfaces. We will show that optical power level required for optimum operation for these THz detectors is more than one order of magnitude lower in comparison to devices without metasurfaces

Sensitivity and Noise in THz Photoconductive Metasurface Detectors

Photoconductive antenna THz detectors based on highly absorbing LT-GaAs metasurfaces enable high sensitivity and high signal-to-noise ratio (> 106) at optical gate powers as low as 5 μW. By investigating the dependence of detector performance on optical gate power, we compare several metasurface detectors with standard PCAs and develop a general model for quantifying the sensitivity and optimal gate power for detector operation. We also show that the LT-GaAs metasurface can even enhance sub bandgap absorption, enabling the use of these detectors in telecom wavelength systems

Perfect absorption in GaAs metasurfaces near the bandgap edge

Perfect optical absorption occurs in a metasurface that supports two degenerate and critically-coupled modes of opposite symmetry. The challenge in designing a perfectly absorbing metasurface for a desired wavelength and material stems from the fact that satisfying these conditions requires multi-dimensional optimization often with parameters affecting optical resonances in non-trivial ways. This problem comes to the fore in semiconductor metasurfaces operating near the bandgap wavelength, where intrinsic material absorption varies significantly. Here we devise and demonstrate a systematic process by which one can achieve perfect absorption in GaAs metasurfaces for a desired wavelength at different levels of intrinsic material absorption, eliminating the need for trial and error in the design process. Using this method, we show that perfect absorption can be achieved not only at wavelengths where GaAs exhibits high absorption, but also at wavelengths near the bandgap edge. In this region, absorption is enhanced by over one order of magnitude compared a layer of unstructured GaAs of the same thickness

Nonlinear Terahertz Generation in Semiconductor Metasurfaces

We demonstrate ultra-thin semiconductor metasurfaces for generation of THz pulses. By investigating the dependence of the THz amplitude and phase on excitation field polarization and crystal orientation, we deduce that the underlying THz emission mechanism in metasurfaces differs from bulk semiconductor wafers with second order nonlinearity playing a dominant role. The metasurface enables control of the THz phase and can therefore be used to spatially structure the THz emitted field. We use this effect to design and demonstrate a metasurface which simultaneously emits and focusses THz pulses

Terahertz Generation from GaAs Metasurfaces: Role of Surface Nonlinearity

We show that a GaAs metasurface can generate THz radiation with comparable efficiency to a bulk GaAs crystal. We attribute the enhanced generation to second order nonlinearity with the surface making a strong contribution

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass