Dynamics of T-cell receptor repertoire in patients with ankylosing spondylitis after biologic therapy.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease in which T-cell immune responses play important roles. AS has been characterized by altered T-cell receptor (TCR) repertoire profiles, which are thought to be caused by expansion of disease-related TCR clonotypes. However, how biological agents affect the TCR repertoire status and whether their therapeutic outcomes are associated with certain features or dynamic patterns of the TCR repertoire are still elusive. MATERIAL AND METHODS: We collected clinical samples from AS patients pre- and post-treatment with biologics. TCR repertoire sequencing was conducted to investigate associations of TCRα and TCRß repertoire characteristics with disease activity and inflammatory indicators/cytokines. RESULTS: Our results showed that good responders were associated with an increase in the TCR repertoire diversity with higher proportions of contracted TCR clonotypes. Additionally, we further identified a positive correlation between TCR repertoire diversity and interleukin (IL)-23 levels in AS patients. A network analysis revealed that contracted AS-associated TCR clonotypes with the same complementary-determining region 3 (CDR3) motifs, which represented high probabilities of sharing TCR specificities to AS-related antigens, were dominant in good responders of AS after treatment with biologic therapies. CONCLUSIONS: Our findings suggested an important connection between TCR repertoire changes and therapeutic outcomes in biologic-treated AS patients. The status and dynamics of TCR repertoire profiles are useful for assessing the prognosis of biologic treatments in AS patients.

Obliquely Deposited Gold Nanohelices on Lithography-Free Prepared Nanoseeded Surfaces.

A substrate surface on which gold particles are distributed is prepared by annealing an ultra-thin gold film to enable glancing angle deposition. By cooling the substrate and controlling its spin rate, two spiral-like and one screw-like gold nanohelix arrays are grown upon the seeded surfaces. The mean helix radius and pitch length are reduced to 17 and 55 nm, respectively. The g-factor of the three nanohelix arrays is measured here and associated circular dichroism peak blue shifts occur as the gold helices shrink.

Design and deposition of a metal-like and admittance-matching metamaterial as an ultra-thin perfect absorber.

A stratiform metamaterial, comprising metal and dielectric thin films, exhibits both near-perfect antireflection and strong light extinction to function as a perfect and ultra-thin light absorber. The equivalent admittance and extinction coefficient of the metamaterial are tailored using a visual method that is based on an admittance diagram. A five-layered metamaterial was designed and deposited with a total thickness of 260 nm on a mirror to exhibit strong and wide angle absorption over wavelengths from 400 nm to 2000 nm. A seven-layered metamaterial with a total thickness of less than 200 nm was designed and deposited to have equivalent admittance around unity and an extinction coefficient that is comparable to that of metal. Such a metal-like metamaterial exhibits low reflectivity so couples most visible light energy into the films and dissipates energy with an equivalent skin depth of less than 55 nm over visible wavelengths.

Densely packed aluminum-silver nanohelices as an ultra-thin perfect light absorber.

Metals have been formed into nanostructures to absorb light with high efficiency through surface plasmon resonances. An ultra-thin plasmonic structure that exhibits strong absorption over wide ranges of wavelengths and angles of incidence is sought. In this work, a nearly perfect plasmonic nanostructure is fabricated using glancing angle deposition. The difference between the morphologies of obliquely deposited aluminum and silver nanohelices is exploited to form a novel three-dimensional structure, which is an aluminum-silver nanohelix array on a pattern-free substrate. With a thickness of only 470 nm, densely distributed nanohelices support rod-to-rod localized surface plasmons for broadband and polarization-independent light extinction. The extinctance remains high over wavelengths from 400 nm to 2000 nm and angles of incidence from 0° to 70°.

Immunological and biochemical characterizations of coxsackievirus A6 and A10 viral particles.

Childhood exanthema caused by different serotypes of coxsackievirus (CV-A) and enterovirus A71 (EV-A71) has become a serious global health problem; it is commonly known as hand, foot, and mouth disease (HFMD). Current EV-A71 vaccine clinical trials have demonstrated that human antibody responses generated by EV-A71 vaccinations do not cross-neutralize coxsackievirus A16 (CV-A16). An effective multivalent HFMD vaccine is urgently needed. From molecular epidemiological studies in Southeast Asia, CV-A6 and CV-A10 are commonly found in HFMD outbreaks. In this study, CV-A6 and CV-A10 were individually cultured in rhabdomyosarcoma (RD) cells grown in medium containing serum, harvested and concentrated. In viral downstream purification, two viral fractions were separated by sucrose gradient zonal ultracentrifugation and detected using a SDS-PAGE analysis and a virus infectivity assay. These two viral fractions were formalin-inactivated, and only the infectious particle fraction was found to be capable of inducing CV-A serotype-specific neutralizing antibody responses in animal immunogenicity studies. These mouse and rabbit antisera also failed to cross-neutralize EV-A71 and CV-A16 infections. Only a combination of formalin-inactivated EV-A71, CV-A6, CV-A10 and CV-A16 multivalent vaccine candidates elicited cross-neutralizing antibody responses in both mouse and rabbit immunogenicity studies. The current results certainly provide important information for multivalent HFMD vaccine development.

Self-Shadowing Deposited Pure Metal Nanohelix Arrays and SERS Application.

In this work, one-step glancing angle deposition is utilized to fabricate gold and silver nanohelix arrays (NHAs) on smooth glass substrates. During deposition, the substrate is cooled using liquid nitrogen and rotated with a tunable spin rate. The substrate spin rate is tuned to match the deposition rate to yield a spiral-like helix structure. The morphologies and optical properties of spiral-like Ag and Au NHAs are measured and compared. The polarization-dependent reflectance of Au NHA leads to a strong g-factor. The three-dimensional nanohelical structures are demonstrated to be a highly sensitive surface-enhanced Raman scattering (SERS) substrate.

Strong light coupling effect for a glancing-deposited silver nanorod array in the Kretschmann configuration.

In this work, three slanted silver nanorod arrays (NRAs) with different thicknesses are fabricated using the glancing angle deposition method. Each silver NRA in the Kretschmann configuration is arranged to form a prism/NRA/air system. Attenuated total reflection occurs over the visible wavelengths and wide incident angles of both s- and p-polarization states. The extinctance is inversely proportional to the thickness of the Ag NRA. The thinnest NRA, with a thickness of 169 nm, exhibits strong extinctance of more than 80% over the visible wavelengths. The associated forward scatterings from the three NRAs are measured and compared under illumination with a laser beam with a wavelength of 632.8 nm.

Fluorescence enhancements of fiber-optic biosensor with metallic nanoparticles.

The mechanism of fluorescence enhancements of fiber-optic biosensor with metallic nanoparticles is studied using scattering theory of evanescent waves by a metallic nanoparticle in dilute solution approximation. High local-field enhancement in the vicinity of metallic nanoparticles resulting from localized surface plasmon excitation and the fluorescence enhancement is estimated by calculating averaged local-field enhancement and radiative-rate enhancement of fluorophores in the presence of metallic anoparticles. The metallic nanoparticles not only provide strong local field to enhance the fluorescence signal of fluorophores, but also help to scatter the fluorescence signal and to increase the far-field detectable signals of the fiber-optic biosensor. The effects of the radius of gold nanoparticles, fluorophore-particle separation, and fiber-particle separation on the fluorescence enhancement are discussed in detail.

Localized surface plasmon coupled fluorescence fiber-optic biosensor with gold nanoparticles.

A novel fiber-optic biosensor based on a localized surface plasmon coupled fluorescence (LSPCF) system is proposed and developed. This biosensor consists of a biomolecular complex in a sandwich format of . It is immobilized on the surface of an optical fiber where a complex forms the fluorescence probe and is produced by mixing Cy5-labeled antibody and protein A conjugated gold nanoparticles (Au-PA). The LSPCF is excited by localized surface plasmon on the GNP surface where the evanescent field is applied near the core surface of the optical fiber. At the same time, the fluorescence signal is detected by a photomultiplier tube located beside the unclad optical fiber with high collection efficiency. Experimentally, this novel LSPCF biosensor is able to detect mouse immunoglobulin G (IgG) at a minimum concentration of 1 pg/mL (7 fM) during the biomolecular interaction of the IgG with anti-mouse IgG. The analysis is expanded by a discussion of the amplification of the LSPCF intensity by GNP coupling, and overall, this LSPCF biosensor is confirmed experimentally as a biosensor with very high sensitivity.

Readout contrast beyond diffraction limit by a slab of random nanostructures.

A simplified Fourier optics approach is applied to study how near-field optical disks retrieve evanescent signals through random nanostructure. The statistical properties of the random nanostructures are used to realize the general behavior of near-field optical disks. The mechanism of its super-resolution capability and an analytical expression of the readout contrast of near-field optical disks with random apertures are derived. The resolution of near-field optical disk is determined by the size of the random nanostructure.

Double reflection in the concave reflective blazed grating.

The miniature spectrometer has many applications in integrated optics and photonics. The blazed grating with the Rowland circle structure has the advantage of self-focusing and is chosen as the major component in the spectrometer chip. In the simulations for the blaze angle design in the visible spectrum, we discover the phenomenon of the double reflection diffraction. Its cause and parameter space are discussed. The spectrometer utilizing the phenomenon has similar performance to the standard blazed grating and is easier to manufacture in microelectromechanical systems (MEMS) technology. The discovery will greatly ease the design of the spectrometer chip.

Local-field confinement in three-pair arrays of metallic nanocylinders.

Confinement of light in nano-scale region of three silver nanocylinder pairs is studied by finite-difference time-domain simulations. Light is confined in gaps between nanocylinders due to localized plasmon excitation and the strongest local-field enhancement exhibits in the gap of the second pair. The surface plasmon resonance has red-shift for nanocylinders of larger radius. The resonance wavelength and local-field enhancement are nearly proportional to the radius of nanocylinders in visible light region, i.e., the plasmon resonance of nanocylinder pairs is predictable and controllable. An open cavity model is proposed to understand the linear relation between the resonant wavelength and the radius of nanocylinders.

Super-resolution and frequency-dependent efficiency of near-field optical disks with silver nanoparticles.

The super-resolution capability of the AgOx-type super-resolution near-field structure disk with silver nanoparticles was studied using finite-difference time-domain method at different incident light frequencies. The near fields exhibited strongly local field enhancement around silver nanoparticles in the AgOx layer due to localized surface plasmon. The subwavelength recording marks smaller than lambda/10 were distinguishable since the metallic nanoparticles with high localized fields transferred evanescent waves to detectable signals in the far field. The far-field signals from random silver nanoparticles displayed similar behaviors as those from single nanoparticle and red-shifts of peak frequencies from particle-particle interaction.

High sensitivity of surface plasmon of weakly-distorted metallic surfaces.

Effects of nano-scale surface geometry on surface plasmon are studied by the coordinate-transformation differential method to numerically calculate surface plasmon modes on a weakly disordered metallic surface. An air-silver surface profile with a subwavelength period and a nano-scale height at wavelength of 650 nm are chosen and it is found that the Bloch wave numbers and the surface plasmon modes are highly sensitive with distortions of only a few nanometers for periods much less than wavelength. On the contrary, distortions of long periods which are comparable to wavelength have little impact. Three typical surface profiles exhibit surface plasmon modes of wide variations.

Probing the focused laser spot of the apodized light source.

This paper deals with both theoretical and experimental studies of near-field imaging of the focused laser spot. In theoretical simulation, we calculate the intensity distribution in the focal region of the apodized light source. Size reduction of the focusing spot of an annular light beam is found to be related with various epsilon, which is the ratio of the obstruction radius to the radius of lens aperture. The experimental setup is based on a near-field scanning optical microscope (NSOM) system. An opaque disk is used to make an annular beam. A high numerical aperture objective lens (NA = 0.8) is used to focus incident lights of different annular light beams, and a tapered near-field optical fiber probe of the NSOM system is used to collect the intensity of the focal field. Results demonstrate that a better transverse resolution can be obtained from the reduction of the focusing spot. The intensity profile of an annular beam may have a significant influence on the size reduction of the focusing spot.

Imaging near-field transverse modes of vertical-cavity surface-emitting lasers by near-field scanning optical microscopy.

We have characterized the oxide-confined vertical-cavity surface-emitting laser (VCSEL) using short-tip, tapping-mode tuning fork near-field scanning optical microscopy (TMTF-NSOM). The near-field radiation patterns of the VCSEL were measured. By comparing the topographic and optical images, we attribute the asymmetric transverse modes to the geometric defect outside the oxide aperture. We also performed spatially resolved spectroscopic imaging over the surface of the VCSEL by coupling NSOM to a spectrometer.

Evanescent signal detection and enhanced resolution with random silver nanoparticles.

Inspired by the subwavelength resolution capability of the super-resolution near-field structure, a simplified optical structure was proposed to investigate the complicated near-field optical interactions between random silver nanoparticles and evanescent waves from a zeroth-order grating. The simplified structure consisted of a glass thin film embedded with random silver nanoparticles on a zeroth-order glass grating. The near-field and far-field optical properties of this structure were investigated by the finite-difference time-domain (FDTD) numerical simulations and the optical resolution beyond diffraction limit was demonstrated.

Enhanced resolution of AgOx-type super-RENS disks with periodic silver nanoclusters.

The super-resolution near-field structure (super-RENS) of the AgOx-type can perform the task of the high-density near-field optical recording in a more feasible way and has demonstrated better signal-to-noise ratio. For further exploration of the optical resolution and controllability of the super-RENS disks, we studied the near-field and far-field optical properties of the AgOx-type super-RENS embedded with periodic silver nanoparticles or nanoclusters with finite-difference time-domain (FDTD) simulations. It was found that the period of nanoclusters could selectively manipulate the resolution of the super-RENS disk.

Study of optical transmittance of AgOx nano thin film in super-resolution near-field structure.

The AgOx-type super-resolution near-field structure (super-RENS) is one of the nano thin films that can give a nonlinear optical effect similar to that of the optical probe of the scanning near-field optical microscope. Structural variations of different thicknesses of the AgOx thin film are observed and studied using a field-emission scanning electron microscope (FE-SEM). For single AgOx nano thin film, the critical temperature and threshold of the evaporation temperature are 154 degrees and 600 degrees, respectively. Results show that the sandwiched AgOx nano thin film has a higher critical temperature, that is, about 280 degrees. For the sandwiched AgOx nano thin film, the transmittance peak is dependent on the thickness of the AgOx thin film. The interesting properties of the AgOx nano thin film of the super-resolution structure indicate a great potential for photonic applications.

Near- and far-field optical properties of embedded scatters in AgOx-type super-resolution near-field structures.

In recent near-field optical recording techniques, the super-resolution near-field structures (super-RENS) have been successfully demonstrated to overcome the diffraction limit. To realize the possibility of replacing the conventional near-field optical probe by the super-RENS, and to understand the relations between the near-field enhancements and detectable far-field signals, we use the two-dimensional finite-difference time-domain (FDTD) method to study the near-field and far-field properties of different types of embedded scatters in the AgOx-type super-RENS.