Investigating Biomarkers for USH2A Retinopathy Using Multimodal Retinal Imaging

Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography underlying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diameter. Thirty-two eyes from 16 patients (mean age ± SD, 36.0 ± 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial alignment was observed between IR-EZ and OR-ELM diameters/widths (p < 0.001). The IMPM border occurred just lateral to EZ loss (p < 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 μm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p < 0.001). As the strongest correlate of cone density (p < 0.001) and best-corrected visual acuity (p < 0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint.     

Dietary flaxseed lignan or oil combined with tamoxifen treatment affects MCF‐7 tumor growth through estrogen receptor‐ and growth factor‐signaling pathways

This study aimed to elucidate which component of flaxseed, i.e. secoisolariciresinol diglucoside (SDG) lignan or flaxseed oil (FO), makes tamoxifen (TAM) more effective in reducing growth of established estrogen receptor positive breast tumors (MCF‐7) at low circulating estrogen levels, and potential mechanisms of action. In a 2×2 factorial design, ovariectomized athymic mice with established tumors were treated for 8 wk with TAM together with basal diet (control), or basal diet supplemented with SDG (1 g/kg diet), FO (38.5 g/kg diet), or combined SDG and FO. SDG and FO were at levels in 10% flaxseed diet. Palpable tumors were monitored and after animal sacrifice, analyzed for cell proliferation, apoptosis, ER‐mediated (ER‐α, ER‐β, trefoil factor 1, cyclin D1, progesterone receptor, AIBI), growth factor‐mediated (epidermal growth factor receptor, human epidermal growth factor receptor‐2, insulin‐like growth factor receptor‐1, phosphorylated mitogen activated protein kinase, PAKT, BCL2) signaling pathways and angiogenesis (vascular endothelial growth factor). All treatments reduced the growth of TAM‐treated tumors by reducing cell proliferation, expression of genes, and proteins involved in the ER‐ and growth factor‐mediated signaling pathways with FO having the greatest effect in increasing apoptosis compared with TAM treatment alone. SDG and FO reduced the growth of TAM‐treated tumors but FO was more effective. The mechanisms involve both the ER‐ and growth factor‐signaling pathways.     

Poly(vinyl alcohol) foams reinforced with carbon nanotubes for stapedial annular ligament applications

This study aims to develop carbon nanotubes (CNTs) reinforced poly(vinyl alcohol) (PVA) foams as a possible material for stapedial annular ligament (SAL) application. As-grown (AG) and purified CNTs are used as reinforcing fillers for PVA foams. Uniaxial and cyclic compression tests reveal that specific modulus and energy dissipation behavior improve after reinforcing foam with CNTs. A relatively higher improvement in specific modulus is recorded for purified CNTs as they tend to produce stiffer cell walls. Thermogravimetric analysis shows thermal stability improves after addition of CNTs in PVA foams. The 50 wt % degradation temperature is higher for PVA_AG foam in comparison to neat PVA foam. Under dynamic loading storage, modulus is found to be higher for CNT doped foams with higher relative improvement with purified CNTs than AG CNTs. It is shown that reinforcing PVA foams with purified CNTs is a feasible strategy to improve their average mechanical properties and microstructure for SAL application. While the specific elastic modulus of neat PVA foam found to be in range of 0.05–0.06 MPa gcc⁻¹ with almost zero porosity. The addition of CNTs provides a wide range of specific elastic modulus 0.1–1.3 MPa gcc⁻¹ with an average pores size of about 300 μm. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48736.     

Catalytic-free growth of VACNTs for energy harvesting

Abstract

The present study introduces a process to grow micro-honeycomb (µ-HC) vertically aligned carbon nanotubes (VACNTs) using thermal chemical vapor deposition technique. Methane is used as a source of carbon and hydrogen gas as a reducing agent. Where, the fabricated µ-HC structure reported in literature involves complex synthesis process and requires a catalyst layer, the novelty of the process used here lies in the fact that no catalyst layer is used for the growth of CNT network, rather copper foil is used as a substrate. The in-situ cracking of CNTs due to water treatment leads to the formation of µ-HC CNT network, which is confirmed by Raman spectroscopy. Further scanning electron microscopy analysis shows that the length of developed µ-HC CNT is ～5?µm. Hexagonal µ-HC network shows more than 94% absorption in UV-Vis-NIR wavelength region. The designed process provides high-yield with a low-cost synthesis of vertically aligned CNTs having 3?D microarchitecture. The fabricated CNT network can be used as an electrode for supercapacitor, as an active layer in a photovoltaic cell and most of the energy harvesting devices.     

Optimization of Reactive Dividing‐Wall Distillation Column for Ethyl t‐Butyl Ether Synthesis

Ethyl t‐butyl ether (ETBE) was synthesized via reaction of ethanol and isobutene by means of a reactive dividing‐wall distillation column (RDWC). The RDWC was simulated using the RADFRAC model of Aspen Plus. Multi‐response optimization by response surface methodology (RSM) with desirability function approach was applied for maximizing product purities and minimizing energy requirements and CO₂ emissions simultaneously with a constraint that the difference in pressure drop across the dividing wall should be zero. The prediction from the RSM optimization agrees well with the simulation. The optimized RDWC provided an excellent purity of 99.99 mol % of the product ETBE with about one‐third reduction in energy requirements and CO₂ emissions as compared to reactive distillation.     

Effect of Isothermal Annealing on Microstructural Morphology of Martensite in a Super-Martensitic Stainless Steel Subjected to Different Prior Conditions

A super-martensitic stainless steel of the Fe–Cr–Ni family was investigated for morphological changes during isothermal annealing after subjecting it to different prior conditions. The key issues during thermomechanical treatment included determination of conditions for austenite stability and reversibility and deciding the appropriate prior treatments for the cold worked alloy before subjecting it to isothermal annealing. The study evaluated the effect of isothermal annealing on the recrystallization kinetics, phase reversion, and microstructural changes in the alloy. Intercritical isothermal annealing was carried out on samples in the range 750–900 °C for short time periods in the range of 1–2.5 min. The recrystallization behavior and microstructural changes were studied by electron backscatter diffraction, X-ray diffraction, and Vickers's hardness measurements. Martensite morphology showed significant changes during the isothermal annealing process with dependence on prior matrix substrate. The tensile properties were also evaluated. The cold rolled (CR) and isothermally annealed samples provided an improved combination of strength and ductility at the optimum heat treatment parameters.     

Experimental Investigation into a Novel Modular PEMFC Fuel Cell Stack

The polymer electrolyte membrane fuel cell (PEMFC), despite being regarded as an ideal replacement to the internal combustion engine, is still not an economically attractive prime‐mover due to a number of key challenges that have yet to be fully resolved; such as degradation to cell components resulting in inadequate lifetimes, specialized manufacturing processes, and poor gravimetric/volumetric energy densities. This paper presents a stack concept which replaces the conventional bipolar plate (BPP), a component that is responsible for a large proportion of stack cost and volume in traditional fuel cell stack designs. The stack architecture compromises of active and passive components which are suited to mass manufacture and maintain functionality that the BPP fulfilled. Furthermore, the design allows the implementation of a fault tolerant system (FTS) which can bypass faulty cells while still ensuring electrical output. The stack architecture is presented and characterized over a number of operating scenarios. The experimental studies suggest that the performance of the new design is similar to that of traditional stacks over a number of operating conditions despite the removal of the BPP and the FTS continued to operate at a desired operating criterion despite the loss of a cell within the stack     

Label-free ultra-sensitive detection of atrazine based on nanomechanics

The alarming increase in the amount of dangerous pesticides such as atrazine in agricultural fields and drinking water is driving the growth of new technologies to detect these toxins well below their threat level. The recent elucidation of microcantilever nanomechanical bending in response to chemical and biomolecular interactions has added another significant facet to biochemical engineering research and has fostered the development of a variety of signal detection paradigms, at both the microscale and the nanoscale. We report the label-free detection of highly specific atrazine antibody-antigen interactions at the nanometer scale on microcantilevers, with 1?ppt (past per trillion) sensitivity. The chemical interaction-induced deflection of the cantilever beam reflects the interplay between the strain energy increase of the cantilever and the free energy reduction of the reaction, providing a unique system for investigating the connection between the nanomechanics and the chemistry of antibody-antigen interaction at picomolar concentration with nanometer resolution. Cantilevers were functionalized with highly specific and site-directed anti-atrazine antibodies and exposed to target antigen over a wide range of concentration from 4.65?pM to 46.5?μM of varying sequence in static and flow conditions. Antibody-antigen interaction of atrazine with the specific antibody resulted in net negative deflection of the cantilever. The results show that high specificity and site-directed antibody immobilization lead to ultra-high sensitivity detection of atrazine. The measurements provide results within minutes at the picomolar level, and exhibit high target specificity. This qualifies the technology as a rapid method to validate organic toxins and its progression.