Hepatitis C virus (HCV) is a positive strand RNA virus that propagates primarily in the liver. We show here that the liver-specific microRNA-122 (miR-122), a member of a class of small cellular RNAs that mediate posttranscriptional gene regulation usually by repressing the translation of mRNAs through interaction with their 3 0 -untranslated regions (UTRs), stimulates the translation of HCV. Sequestration of miR-122 in liver cell lines strongly reduces HCV translation, whereas addition of miR-122 stimulates HCV translation in liver cell lines as well as in the non-liver HeLa cells and in rabbit reticulocyte lysate. The stimulation is conferred by direct interaction of miR-122 with two target sites in the 5 0 -UTR of the HCV genome. With a replication-defective NS5B polymerase mutant genome, we show that the translation stimulation is independent of viral RNA synthesis. miR-122 stimulates HCV translation by enhancing the association of ribosomes with the viral RNA at an early initiation stage. In conclusion, the liver-specific miR-122 may contribute to HCV liver tropism at the level of translation.

Bats are reservoir animals harboring many important pathogenic viruses and with the capability of transmitting these to humans and other animals. To establish an effective surveillance to monitor transboundary spread of bat viruses between Myanmar and China, complete organs from the thorax and abdomen from 853 bats of six species from two Myanmar counties close to Yunnan province, China, were collected and tested for their virome through metagenomics by Solexa sequencing and bioinformatic analysis. In total, 3,742,314 reads of 114 bases were generated, and over 86% were assembled into 1,649,512 contigs with an average length of 114 bp, of which 26,698 (2%) contigs were recognizable viral sequences belonging to 24 viral families. Of the viral contigs 45% (12,086/26,698) were related to vertebrate viruses, 28% (7,443/26,698) to insect viruses, 27% (7,074/26,698) to phages and 95 contigs to plant viruses. The metagenomic results were confirmed by PCR of selected viruses in all bat samples followed by phylogenetic analysis, which has led to the discovery of some novel bat viruses of the genera Mamastrovirus, Bocavirus, Circovirus, Iflavirus and Orthohepadnavirus and to their prevalence rates in two bat species. In conclusion, the present study aims to present the bat virome in Myanmar, and the results obtained further expand the spectrum of viruses harbored by bats.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.

We demonstrate a new optomechanical device system which allows highly efficient transduction of femtogram nanobeam resonators. Doubly clamped nanomechanical resonators with mass as small as 25 fg are embedded in a high-finesse two-dimensional photonic crystal nanocavity. Optical transduction of the fundamental flexural mode around 1 GHz was performed at room temperature and ambient conditions, with an observed displacement sensitivity of 0.94 fm/Hz 1/2 . Comparison of measurements from symmetric and asymmetric double-beam devices reveals hybridization of the mechanical modes where the structural symmetry is shown to be the key to obtain a high mechanical quality factor. Our novel configuration opens the way for a new category of "NEMS-in-cavity" devices based on optomechanical interaction at the nanoscale. KEYWORDS: Nanoelectromechanical system (NEMS), nanomechanics, cavity optomechanics, photonic crystal cavities, mass sensingFlexural nanomechanical resonators have consistently set records for sensitive measurements of mass, force, and displacement [1][2][3][4][5][6][7][8][9] . These resonators with an ultrasmall mass are of particular interest because they inherently operate at the ultrahigh frequency of the fundamental mechanical mode, which is advantageous for developing high-speed sensors with ultimate sensitivity. At the same time, achieving a high mechanical quality (Q) factor, particularly in ambient setting, is equally important because the transducer sensitivity and the coherence time of the mechanical vibration are proportional to the Q factor. On the other hand, although recent developments in one-dimensional (1D) photonic crystals (PhC) have enabled optomechanical transduction at high frequencies 10,11 , the resonating mode is often post-selected among many acoustic modes simultaneously supported in an optimized photonic structure. The coupling between a single optical cavity mode and commonly utilized flexural mechanical vibrational modes thus still remains challenging. Additionally, the demonstrated high-frequency modes are based on high stiffness rather than small motional mass. Furthermore, the poor heat dissipation of the 1D PhC limits the highest operating power of the cavity 12,13 . Therefore, an optomechanical system with a well-defined, ultrasmall-mass, high-Q mechanical resonator that overlaps strongly with a high-Q optical cavity with large power handling capability is highly desirable for extremely sensitive measurements involving mass, force, and displacement. Here we implement the first realization of the idea of a "NEMS-in-cavity," by embedding a femtogram doubly clamped nanomechanical double-beam resonator in a finely tuned two-dimensional (2D) PhC nanocavity. Conceptually this "nanobeam-in-cavity" configuration is analogous to cavity quantum electrodynamics (cQED) system realized by embedding a single emitter (e.g., an atom, molecule, or quantum dot) in a high-Q optical cavity. Here, we carve out a nanomechanical resonator with well-defined vibration modes (in place of the...

Abstract:We demonstrate experimentally an air-slot mode-gap photonic crystal cavity with quality factor of 15,000 and modal volume of 0.02 cubic wavelengths, based on the design of an air-slot in a width-modulated line-defect in a photonic crystal slab. The origin of the high Q air-slot cavity mode is the mode-gap effect from the slotted photonic crystal waveguide mode with negative dispersion. The high Q cavities with ultrasmall mode volume are important for applications such as cavity quantum electrodynamics, nonlinear optics and optical sensing.

Using Fano-type guided resonances (GRs) in photonic crystal (PhC) slab structures, we numerically and experimentally demonstrate optical reflectivity enhancement of high-Q SiN x membrane-type resonators used in membrane-in-the-middle optomechanical (OM) systems.Normal-incidence transmission and mechanical ringdown measurements of 50-nm-thick PhC membranes demonstrate GRs near 1064 nm, leading to a ~ 4× increase in reflectivity while preserving high mechanical Q factors of up to ~ 5 × 10 6 . The results would allow improvement of membrane-in-the-middle OM systems by virtue of increased OM coupling, presenting a path towards ground state cooling of such a membrane and observations of related quantum effects.

Solitary waves have consistently captured the imagination of scientists, ranging from fundamental breakthroughs in spectroscopy and metrology enabled by supercontinuum light, to gap solitons for dispersionless slow-light, and discrete spatial solitons in lattices, amongst others. Recent progress in strong-field atomic physics include impressive demonstrations of attosecond pulses and high-harmonic generation via photoionization of free-electrons in gases at extreme intensities of 1014 W/cm2. Here we report the first phase-resolved observations of femtosecond optical solitons in a semiconductor microchip, with multiphoton ionization at picojoule energies and 1010 W/cm2 intensities. The dramatic nonlinearity leads to picojoule observations of free-electron-induced blue-shift at 1016 cm−3 carrier densities and self-chirped femtosecond soliton acceleration. Furthermore, we evidence the time-gated dynamics of soliton splitting on-chip, and the suppression of soliton recurrence due to fast free-electron dynamics. These observations in the highly dispersive slow-light media reveal a rich set of physics governing ultralow-power nonlinear photon-plasma dynamics.

Discontinuous native protein gel electrophoresisAnalysis of the oligomeric state of a native protein usually requires analytical ultracentrifugation or repeated gel filtration to calculate the protein's size. We have developed a discontinuous native protein gel electrophoresis system that allows the separation of even basic proteins according to their size, oligomeric state, and shape. This gel system combines the addition of negative charges to the proteins by Serva Blue G with a discontinuous buffer system and gradient gels. As in SDS-PAGE, chloride constitutes the high mobility anion in the gel and anode buffer. However, for sample focusing this system employs histidine instead of glycine as the slow dipolar ion following from the cathode buffer to improve migration of basic proteins. In addition, proteins run into gel pores corresponding to their size and shape in the gradient gel. Using this gel system, we show that the polypyrimidine tract-binding protein (PTB) is a monomer.