Tocopherol Emulsions as Functional Autoantigen Delivery Vehicles Evoke Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.molpharmaceut.8b00887.Contemporary approaches to treating autoimmune diseases like multiple sclerosis broadly modulate the immune system and leave patients susceptible to severe adverse effects. Antigen-specific immunotherapies (ASIT) offer a unique opportunity to selectively suppress autoreactive cell populations but have suffered from marginal efficacy even when employing traditional adjuvants to improve delivery. The development of immunologically active antigen delivery vehicles could potentially increase the clinical success of antigen-specific immunotherapies. An emulsion of the antioxidant tocopherol delivering an epitope of proteolipid protein autoantigen (PLP139–151) yielded significant efficacy in mice with experimental autoimmune encephalomyelitis (EAE). In vitro studies indicated tocopherol emulsions reduced oxidative stress in antigen-presenting cells. Ex vivo analysis revealed that tocopherol emulsions shifted cytokine responses in EAE splenocytes. In addition, IgG responses against PLP139–151 were increased in mice treated with tocopherol emulsions delivering the antigen, suggesting a possible skew in immunity. Overall, tocopherol emulsions provide a functional delivery vehicle for ASIT capable of ameliorating autoimmunity in a murine model

Analysis of laser radiation using the Nonlinear Fourier transform

Modern high-power lasers exhibit a rich diversity of nonlinear dynamics, often featuring nontrivial co-existence of linear dispersive waves and coherent structures. While the classical Fourier method adequately describes extended dispersive waves, the analysis of time-localised and/or non-stationary signals call for more nuanced approaches. Yet, mathematical methods that can be used for simultaneous characterisation of localized and extended fields are not yet well developed. Here, we demonstrate how the Nonlinear Fourier transform (NFT) based on the Zakharov-Shabat spectral problem can be applied as a signal processing tool for representation and analysis of coherent structures embedded into dispersive radiation. We use full-field, real-time experimental measurements of mode-locked pulses to compute the nonlinear pulse spectra. For the classification of lasing regimes, we present the concept of eigenvalue probability distributions. We present two field normalisation approaches, and show the NFT can yield an effective model of the laser radiation under appropriate signal normalisation conditions

ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1-mutant lung cancer

Inactivating mutations in LKB1/STK11 are present in roughly 20% of nonsmall cell lung cancers (NSCLC) and portend poor response to anti-PD-1 immunotherapy. Unexpectedly, we found that LKB1 deficiency correlated with elevated tumor mutational burden (TMB) in NSCLCs from nonsmokers and genetically engineered mouse models, despite the frequent association between high-TMB and anti-PD-1 treatment efficacy. However, LKB1 deficiency also suppressed antigen processing and presentation, which are associated with compromised immunoproteasome activity and increased autophagic flux. Immunoproteasome activity and antigen presentation were restored by inhibiting autophagy through targeting the ATG1/ULK1 pathway. Accordingly, ULK1 inhibition synergized with PD-1 antibody blockade, provoking effector T-cell expansion and tumor regression in Lkb1-mutant tumor models. This study reveals an interplay between the immunoproteasome and autophagic catabolism in antigen processing and immune recognition, and proposes the therapeutic potential of dual ULK1 and PD-1 inhibition in LKB1-mutant NSCLC as a strategy to enhance antigen presentation and to promote antitumor immunity

Machine Learning-based Calibration Approach for Low-cost Air Pollution Sensors MQ-7 and MQ-131

Air quality is a vital concern globally, and Sri Lanka, according to WHO statistics, faces challenges in achieving optimal air quality levels. To address this, we introduced an innovative IoT-based Air Pollution Monitoring (APM) Box. This solution incorporates readily available Commercial Off-The-Shelf (COTS) sensors, specifically MQ-7 and MQ-131, for measuring concentrations of Carbon Monoxide (CO) and Ozone (O3) ,Arduino and "ThingSpeak" platform. Yet, those COTS sensors are not factory-calibrated. Therefore, we implemented machine learning algorithms, including linear regression and deep neural network models, to enhance the accuracy of CO and O3 concentration measurements from these non-calibrated sensors. Our findings indicate promising correlations when dealing with MQ-7 and MQ-131 measurements after removing outliers

Comprehensive Management of Ectodermal Dysplasia with Interceptive Orthodontics in a Young Boy Who Was Bullied at School

Aim. The management of hypohidrotic ectodermal dysplasia with oligodontia in Class-I malocclusion in late mix dentition. Case Report. An 11-year-old boy with ED was treated and managed by means of interceptive orthodontic treatment accompanied by direct and indirect restorative methods in a successful manner. The patient was prepared to receive definitive oral rehabilitation with dental implants for the missing teeth when the patient reaches a suitable age. The patient was followed for 5 years from the beginning of treatment. Conclusion. Management of the child with ectodermal dysplasia with oligodontia was a real challenge. Early diagnosis, necessary investigation, and providing age-appropriate multidisciplinary treatment were key steps in successful outcomes. The objectives were not only just orthodontic or paedodontics but also prosthetic and psychological

EVALUATION OF RED CURRANTS (RIBES RUBRUM L.), BLACK CURRANTS (RIBES NIGRUM L.), RED AND GREEN GOOSEBERRIES (RIBES UVA-CRISPA) FOR POTENTIAL MANAGEMENT OF TYPE 2 DIABETES AND HYPERTENSION USING IN VITRO MODELS

Red currants (Ribes rubrum L.), black currants (Ribes nigrum L.), red and green gooseberries (Ribes uva-crispa) were evaluated for the total phenolics, antioxidant capacity based on 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay and functionality such as in vitro inhibition of alpha-amylase, alpha-glucosidase and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension. The total phenolics content ranged from 3.2 (green gooseberries) to 13.5 (black currants) mg/g fruit fresh weight. No correlation was found between total phenolics and antioxidant activity. The major phenolic compounds were quercetin derivatives (black currants and green gooseberries) and chlorogenic acid (red currants and red gooseberries). Red currants had the highest alpha-glucosidase, alpha-amylase and ACE inhibitory activities. Therefore red currants could be good dietary sources with potential antidiabetes and antihypertension functionality to compliment overall dietary management of early stages of type 2 diabetes.CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior

Si doped GaAs/AlGaAs terahertz detector and phonon effect on the responsivity

Abstract Terahertz detection capability of an n-type heterojunction interfacial work function internal photoemission (HEIWIP) detector is demonstrated. Threshold frequency, f 0 , of 3.2 THz (93 lm) was obtained by using n-type GaAs emitter doped to 1 · 10 18 cm À3 and Al 0.04 Ga 0.96 As single barrier structure. The detector shows a broad spectral response from 30 to 3.2 THz (10-93 lm) with peak responsivity of 6.5 A/W at 7.1 THz under a forward bias field of 0.7 kV/cm at 6 K. The peak quantum efficiency and peak detectivity are $19$5.5 · 10 8 Jones, respectively under a bias field of 0.7 kV/cm at 6 K. In addition, the detector can be operated up to 25 K

Si doped GaAs/AlGaAs terahertz detector and phonon effect on the responsivity

Abstract Terahertz detection capability of an n-type heterojunction interfacial work function internal photoemission (HEIWIP) detector is demonstrated. Threshold frequency, f 0 , of 3.2 THz (93 lm) was obtained by using n-type GaAs emitter doped to 1 · 10 18 cm À3 and Al 0.04 Ga 0.96 As single barrier structure. The detector shows a broad spectral response from 30 to 3.2 THz (10-93 lm) with peak responsivity of 6.5 A/W at 7.1 THz under a forward bias field of 0.7 kV/cm at 6 K. The peak quantum efficiency and peak detectivity are $19$5.5 · 10 8 Jones, respectively under a bias field of 0.7 kV/cm at 6 K. In addition, the detector can be operated up to 25 K

Si doped GaAs/AlGaAs terahertz detector and phonon effect on the responsivity

NRC publication: Ye