A Dual-Acting Nitric Oxide Donor and Phosphodiesterase 5 Inhibitor Activates Autophagy in Primary Skin Fibroblasts

Wound healing pathologies are an increasing problem in ageing societies. Chronic, non-healing wounds, which cause high morbidity and severely reduce the quality of life of affected individuals, are frequently observed in aged individuals and people suffering from diseases affected by the Western lifestyle, such as diabetes. Causal treatments that support proper wound healing are still scarce. Here, we performed expression proteomics to study the effects of the small molecule TOP-N53 on primary human skin fibroblasts and keratinocytes. TOP-N53 is a dual-acting nitric oxide donor and phosphodiesterase-5 inhibitor increasing cGMP levels to support proper wound healing. In contrast to keratinocytes, which did not exhibit global proteome alterations, TOP-N53 had profound effects on the proteome of skin fibroblasts. In fibroblasts, TOP-N53 activated the cytoprotective, lysosomal degradation pathway autophagy and induced the expression of the selective autophagy receptor p62/SQSTM1. Thus, activation of autophagy might in part be responsible for beneficial effects of TOP-N53.     

Performance Characterization of Game Recommendation Algorithms on Online Social Network Sites

Since years,online social networks have evolved from profile and communication websites to online portals where people interact with each other,share and consume multimedia-enriched data and play different types of games.Due to the immense popularity of these online games and their huge revenue potential,the number of these games increases every day,resulting in a current offering of thousands of online social games.In this paper,the applicability of neighborhood-based collaborative filtering(CF) algorithms for the recommendation of online social games is evaluated.This evaluation is based on a large dataset of an online social gaming platform containing game ratings(explicit data) and online gaming behavior(implicit data) of millions of active users.Several similarity metrics were implemented and evaluated on the explicit data,implicit data and a combination thereof.It is shown that the neighborhood-based CF algorithms greatly outperform the content-based algorithm,currently often used on online social gaming websites.The results also show that a combined approach,i.e.,taking into account both implicit and explicit data at the same time,yields overall good results on all evaluation metrics for all scenarios,while only slightly performing worse compared to the strengths of the explicit or implicit only approaches.The best performing algorithms have been implemented in a live setup of the online game platform.     

Gas transfer properties of wheat gluten coated paper adapted to eMAP of fresh parsley

Gas transfer properties of wheat gluten (WG) coated paper and their ability to fulfil the requirements in eMAP of fresh parsley were studied. Permeation of gases through WG-paper was demonstrated to be RH-dependent and closely related to structural modification in the WG layer. Formation of micro-cracks was evidenced in dry conditions; but when increasing RH, plasticisation occurs within the protein layer and micro-fractures were reduced until disappearance. This reversible phenomenon allowed the WG-layer to recover its integrity at RH higher than 70%, and the WG character to be expressed in such conditions. When used at 20 °C and 80% RH as part of the packaging of parsley, modified atmosphere was created and a steady state of 11 kPa O₂ and 4.5 kPa CO₂ was reached after 45 h. In such conditions, the overall quality of parsley leaves remained acceptable during 8 days, with only 28% loss of chlorophyll.     

Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre-clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple-negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non-toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono-fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first-in-class therapeutic construct capable of tumor-specific reoxygenation without associated toxicities.     

Generalizable Features for Anonymizing Motion Signals Based on the Zeros of the Short-Time Fourier Transform

Journal of Signal Processing Systems - Thanks to the recent development of sensors and Internet of Things (IoT), it is now common to use mobile application to monitor health status. These...