Cyclic GMP-AMP synthase expression is enhanced in systemic sclerosis-associated interstitial lung disease and stimulates inflammatory myofibroblast activation.

Objective: The lungs of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) contain inflammatory myofibroblasts that arise in association with fibrotic stimuli and perturbed innate immunity. The cytosolic DNA-binding receptor cyclic GMP-AMP synthase (cGAS) is implicated in inflammation and fibrosis, but its involvement in SSc-ILD remains unknown. We examined cGAS expression, activity and therapeutic potential in SSc-ILD using human biospecimens, cultured fibroblasts, precision-cut lung slices and a well-accepted animal model.

Damage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection.

Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA (mtDNA), which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood.

A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.

Fibrosis contributes to incurable pathologies in vital organs including the lung. Myofibroblasts are fibrogenic effector cells that accumulate via incompletely understood mechanisms. We discovered that α1-adrenoreceptor expressing myofibroblasts receive sympathetic nerve-derived noradrenergic inputs in fibrotic mouse and human lungs.

cGAS Expression is Enhanced in Systemic Sclerosis Associated Interstitial Lung Disease and Stimulates Inflammatory Myofibroblast Activation.

Objective: The lungs of patients with Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD) contain inflammatory myofibroblasts arising in association with fibrotic stimuli and perturbed innate immunity. The innate immune DNA binding receptor Cyclic GMP-AMP synthase (cGAS) is implicated in inflammation and fibrosis, but its involvement in SSc-ILD remains unknown. We examined cGAS expression, activity, and therapeutic potential in SSc-ILD using cultured fibroblasts, precision cut lung slices (PCLS), and a well-accepted animal model.

Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which current treatment options only slow clinical progression. Previously, we identified a subset of patients with IPF with an accelerated disease course associated with fibroblast expression of Toll-Like Receptor 9 (TLR9) mediated by interactions with its ligand mitochondrial DNA (mtDNA).

Objectives: We aimed to show that TLR9 activation induces fibroproliferative responses that are abrogated by its antagonism by using two commercially-available indirect inhibitors and a proprietary, selective direct small molecule inhibitor.

Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts.

Introduction: The pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation of abnormal extracellular matrix, which is partly the result of an imbalance in collagen synthesis, cross-linking and degradation. During this process, collagen fragments or neoepitopes, are released into the circulation. The significance of these circulating collagen neoepitopes in sarcoidosis remains unknown.

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably.

Damage sensing through TLR9 Regulates Inflammatory and Antiviral Responses During Influenza Infection.

Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood.

Targeting the NLRP3 inflammasome and associated cytokines in scleroderma associated interstitial lung disease.

SSc-ILD (scleroderma associated interstitial lung disease) is a complex rheumatic disease characterized in part by immune dysregulation leading to the progressive fibrotic replacement of normal lung architecture. Because improved treatment options are sorely needed, additional study of the fibroproliferative mechanisms mediating this disease has the potential to accelerate development of novel therapies. The contribution of innate immunity is an emerging area of investigation in SSc-ILD as recent work has demonstrated the mechanistic and clinical significance of the NLRP3 inflammasome and its associated cytokines of TNFα (tumor necrosis factor alpha), IL-1β (interleukin-1 beta), and IL-18 in this disease.

Use of a dental surveyor to ensure optimal seating of implant overdenture attachments.

Many implant overdenture attachments accommodate divergent abutments. However, there can be instances where the denture base resin surrounding the abutment may impede seating by binding on the axial surface(s) of the abutment. This article describes the use of a dental surveyor to aid clinicians in determining where the resin denture base might be preventing the seating of overdenture attachments.

Digital scanning to aid guiding plane and rest seat preparations for removable partial dentures.

This article describes the use of a digital intraoral scanner to aid clinicians making rest seat and guiding plane preparations, simplifying the procedure and reducing the time needed to analyze the abutment modifications. No additional equipment is required other than a diagnostic cast and a digital scanner with preparation comparison software.

Coexistence of ice clusters and liquid-like water clusters on the Ru(0001) surface.

The RAIRS spectra of water adsorbed on Ru(0001) at 85 K are recorded from 600 cm to 4000 cm. Measured at water coverages from 0.13 ML to 2.

Two-octave spanning supercontinuum generation in stoichiometric silicon nitride waveguides pumped at telecom wavelengths.

We demonstrate supercontinuum generation in stoichiometric silicon nitride (SiN in SiO) integrated optical waveguides, pumped at telecommunication wavelengths. The pump laser is a mode-locked erbium fiber laser at a wavelength of 1.56 µm with a pulse duration of 120 fs.

On-chip visible-to-infrared supercontinuum generation with more than 495 THz spectral bandwidth.

We report ultra-broadband supercontinuum generation in high-confinement Si3N4 integrated optical waveguides. The spectrum extends through the visible (from 470 nm) to the infrared spectral range (2130 nm) comprising a spectral bandwidth wider than 495 THz, which is the widest supercontinuum spectrum generated on a chip.

High confinement, high yield Si(3)N(4) waveguides for nonlinear optical applications.

In this paper we present a novel fabrication technique for silicon nitride (Si(3)N(4)) waveguides with a thickness of up to 900 nm, which are suitable for nonlinear optical applications. The fabrication method is based on etching trenches in thermally oxidized silicon and filling the trenches with Si(3)N(4). Using this technique no stress-induced cracks in the Si(3)N(4) layer were observed resulting in a high yield of devices on the wafer.

Integrated CARS source based on seeded four-wave mixing in silicon nitride.

We present a theoretical investigation of an integrated nonlinear light source for coherent anti-Stokes Raman scattering (CARS) based on silicon nitride waveguides. Wavelength tunable and temporally synchronized signal and idler pulses are obtained by using seeded four-wave mixing. We find that the calculated input pump power needed for nonlinear wavelength generation is more than one order of magnitude lower than in previously reported approaches based on optical fibers.

(44g)Sc production using a water target on a 13MeV cyclotron.

Introduction: Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t1/2=3.

The effectiveness of using a patient simulator to teach light-curing skills.

Background: The authors evaluated the effectiveness of using a patient simulator (MARC Patient Simulator [MARC PS], BlueLight analytics, Halifax, Nova Scotia, Canada), to instruct dental students (DS) on how to deliver energy optimally to a restoration from a curing light. Five months later, the authors evaluated the retention of the instruction provided to the DS.

Methods: Toward the end of the DS' first year of dental education, the authors evaluated the light-curing techniques of one-half of the class of first-year DS (Group 1) before and after receiving instruction by means of the patient simulator.

Effect of instruction on dental students’ ability to light-cure a simulated restoration.

Objective: To measure the light energy that dental students delivered to a simulated Class I restoration before training, immediately after training and 4 months after training.

Methods: Thirty-eight (38) dental students used a single light-emitting diode curing light (SmartLite iQ2, Dentsply) to cure, for 10 seconds, a simulated Class I restoration positioned in the Managing Accurate Resin Curing - Patient Simulator (BlueLight analytics inc.).

The noise-limited-resolution for stimulated emission depletion microscopy of diffusing particles.

With recent developments in microscopy, such as stimulated emission depletion (STED) microscopy, far-field imaging at resolutions better than the diffraction limit is now a commercially available technique. Here, we show that, in the special case of a diffusive regime, the noise-limited resolution of STED imaging is independent of the saturation intensity of the fluorescent label. Thermal motion limits the signal integration time, which, for a given excited-state lifetime, limits the total number of photons available for detection.

Ellipsometry with randomly varying polarization states.

We show that, under the right conditions, one can make highly accurate polarization-based measurements without knowing the absolute polarization state of the probing light field. It is shown that light, passed through a randomly varying birefringent material has a well-defined orbit on the Poincar sphere, which we term a generalized polarization state, that is preserved. Changes to the generalized polarization state can then be used in place of the absolute polarization states that make up the generalized state, to measure the change in polarization due to a sample under investigation.

Incoherently pumped continuous wave optical parametric oscillator broadened by non-collinear phasematching.

In this paper, we report on a singly resonant optical parametric oscillator (OPO) pumped by an amplified spontaneous emission (ASE) source. The pump focusing conditions allow non-collinear phasematching, which resulted in a 230 nm (190 cm(-1)) spectral bandwidth. Calculations indicate that such phasematching schemes may be used to further broaden OPO spectral bandwidths.

One-Watt level mid-IR output, singly resonant, continuous-wave optical parametric oscillator pumped by a monolithic diode laser.

We report more than 1.1 Watt of idler power at 3373 nm in a singly resonant optical parametric oscillator (SRO), directly pumped by a single-frequency monolithic tapered diode laser. The SRO is based on a periodically poled MgO:LiNbO3 crystal in a four mirror cavity and is excited by 8.

A route to sub-diffraction-limited CARS Microscopy.

We theoretically investigate a scheme to obtain sub-diffraction-limited resolution in coherent anti-Stokes Raman scattering (CARS) microscopy. We find using density matrix calculations that the rise of vibrational (Raman) coherence can be strongly suppressed, and thereby the emission of CARS signals can be significantly reduced, when pre-populating the corresponding vibrational state through an incoherent process. The effectiveness of pre-populating the vibrational state of interest is investigated by considering the excitation of a neighbouring vibrational (control) state through an intense, mid-infrared control laser.

Detection and characterization of carbon contamination on EUV multilayer mirrors.

In this paper, we detect and characterize the carbon contamination layers that are formed during the illumination of extreme ultraviolet (EUV) multilayer mirrors. The EUV induced carbon layers were characterized ex situ using spectroscopic ellipsometry (SE) and laser generated surface acoustic waves (LG-SAW). We show that both LG-SAW and SE are very sensitive for measuring carbon layers, even in the presence of the highly heterogeneous structure of the multilayer.