Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman’s correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.     

Enhancing the stability and crystallinity of CsPbIBr2 through antisolvent engineering

All inorganic lead-based perovskites containing bromine-iodine alloys, such as CsPbIBr_2, have arisen as one of the most attractive candidates for absorber layers in solar cells. That said, there remains a large gap when it comes to film and crystal quality between the inorganic and hybrid perovskites. In this work, antisolvent engineering is employed as a simple and reproducible method for improving CsPbIBr₂ thin films. We found that both the antisolvent used and the conditions under which it was applied have a measurable impact on both the quality and stability of the final product. We arrived at this conclusion by characterising the samples using scanning electron microscopy, X-ray diffraction, UV–visible and photoluminescence measurements, as well as employing a novel system to quantify stability. Our findings, and the application of our novel method for quantifying stability, demonstrate the ability to significantly enhance CsPbIBr₂ samples, produced via a static one-step spin coating method, by applying isopropanol 10 s after commencing the spin programme. The antisolvent quenched CsPbIBr₂ films demonstrate both improved crystallinity and an extended lifespan.

     

A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy

Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery.     

Embedding financialization: a policy review of the English Affordable Homes Programme

Decent, affordable housing continues to be a major concern for policy-makers, providers and society at large. This paper contributes to the debate over the future of social housing in England by reviewing the Affordable Homes Programme (AHP). The AHP (2011–2015) saw the level of grant funding reduced dramatically; with the shortfall to be filled from housing associations own resources, increased rents and borrowing. To understand the implications of the AHP, this paper utilizes the concept of financialization. Financialization is a multifaceted process that seeks to explain the increased role and power of the financial markets in society. Specifically, the paper shows that the AHP leads to increased debt levels in the social housing sector, is predicated on short-termism and accumulation by dispossession. Finally, by employing financialization the paper also addresses debates about the nature of housing policy and how it can best be conceptualized.     

Optimization of environmental impact reduction and economic feasibility of solvent waste recovery using a new software tool

The environmental impact reduction and operating costs savings associated with the purification and recovery of solvent waste in the manufacture of active pharmaceutical ingredients (API's) were investigated. A software toolbox has been developed that combines Aspen Plus^® process simulation with SimaPro^® and Ecosolvent life cycle assessment (LCA) databases. A LCA approach was used in order to consider the environmental impact beyond pharmaceutical production plant boundaries. The feasibility of a relatively small flexible equipment-skid capable of recovering multiple solvent waste streams was evaluated. Distillation and pervaporation were considered to separate binary waste solvent mixtures. Optimum distillation reflux ratio and feed stage were determined to maximize the environmental impact reductions and operating cost savings. The optimum reflux ratio was significantly higher than 1.2 times the minimum reflux ratio suggested by traditional heuristics. The emissions and cost reductions obtained were as much as 49% and 56% higher, respectively, as compared to using the conventional optimum reflux ratio. A comprehensive cash flow analysis showed that the recovery of low volume solvent waste streams is economically feasible, despite traditional thinking. Three case studies from Pfizer are presented to show how our software tool can aid in green engineering decision making.     

Elastic and inelastic analysis for weld failure prediction of two adjacent steel buildings

Two adjacent buildings near the epicenter of the January 17th Northridge earthquake, one with weld fractures and one without weld fractures, are considered in this research. Both buildings are six stories in height, and their primary lateral force resisting system comprises special moment resisting frames above grade. The buildings considered are referred to herein as the East Building and the West Building. Two basic types of computer studies were performed. One was an elastic 3-D analysis using SAP90, and the other an inelastic 2-D analysis using DRAIN-2DX. Three different models were, created for the elastic analysis. Two for the East Building, designated the ‘benchmark model’, and the ‘probable model’, and one for the West Building, designated the ‘West Building model’. Two different models were created for the inelastic analysis only for the East Building, also called the benchmark model and the probable model. The East Building was unoccupied at the time of the earthquake, hence two models were created for this building. The benchmark model is representative of the design state of the building, while the probable model is representative of the state of the building at the time of the earthquake. The West Building, which was fully occupied at the time of the earthquake, was modeled similarly to the benchmark. Elastic and inelastic studies were performed on these models to determine if a correlation exists between analysis and observed behavior. The findings from the analysis showed no damage to the West Building with possible damage to the East Building. This result is corroborated by the damage survey.     

Interactions of 1 μm latex particles with pseudomonas aeruginosa biofilms

Fluorescently labelled latex microbeads were used to study the interaction of particles with Pseudomonas aeruginosa biofilms in a continuous flow annular reactor. Beads were readily distinguished and enumerated in both intact and disaggregated biofilm samples. The fraction of beads that attached to biofilm during a 24 h period ranged from 0.001 to 0.01 and was proportional to biofilm cell carbon and to the standard deviation of biofilm thickness. Microbeads added to biofilm of steady state thickness (30 μm) were observed to be located throughout the entire biofilm depth in 24 h. Many of the microbeads that attached to biofilm shortly after bacterial inoculation (thickness of 2 μm) remained near the substratum as cells grew past and covered them. Microbeads were observed near the biofilm-substratum interface for up to 5 days after bead addition. Beads formed aggregates on biofilms, but not in bulk water. Beads captured by biofilm remained in the reactor system longer than beads that never attached to biofilm.     

Sourcing faecal pollution: a combination of library-dependent and library-independent methods to identify human faecal pollution in non-sewered catchments

Library-dependent (LD) (biochemical fingerprinting of Escherichia coli and enterococci) and library-independent (LI) (PCR detection of human-specific biomarkers) methods were used to detect human faecal pollution in three non-sewered catchments. In all, 550 E. coli isolates and 700 enterococci isolates were biochemically fingerprinted from 18 water samples and compared with metabolic fingerprint libraries of 4508 E. coli and 4833 enterococci isolates. E. coli fingerprints identified human unique biochemical phenotypes (BPTs) in nine out of 18 water samples; similarly, enterococci fingerprints identified human faecal pollution in 10 water samples. Seven samples were tested by PCR for the detection of biomarkers. Human-specific HF134 Bacteroides and enterococci surface protein (esp) biomarkers were detected in five samples. Four samples were also positive for HF183 Bacteroides biomarker. The combination of biomarkers detected human faecal pollution in six out of seven water samples. Of the seven samples analysed for both the indicators/markers, at least one indicator/marker was detected in every sample. Four of the seven PCR-positive samples were also positive for one of the human-specific E. coli or enterococci BPTs. The results indicated human faecal pollution in the studied sub-catchments after storm events. LD and LI methods used in this study complimented each other and provided additional information regarding the polluting sources when one method failed to detect human faecal pollution. Therefore, it is recommended that a combination of methods should be used to identify the source(s) of faecal pollution where possible.     

Exploring,modelling and predicting spatiotemporal variations in house prices

Hedonic price modelling has long been a powerful tool to estimate house prices in the real estate market. Increasingly, traditional global hedonic price models that largely ignore spatial effects are being superseded by models that deal with spatial dependency and spatial heterogeneity. In addition, many novel methods integrating spatial economics, statistics and geographical information science (GIScience) have been developed recently to incorporate temporal effects into hedonic house price modelling. Here, a local spatial modelling technique, geographically weighted regression (GWR), which accounts for spatial heterogeneity in housing utility functions is applied to a 19-year set of house price data in London (1980–1998) in order to explore spatiotemporal variations in the determinants of house prices. Further, based on the local parameter estimates derived from GWR, a new method integrating GWR and time series (TS) forecasting techniques, GWR–TS, is proposed to predict future local parameters and thus future house prices. The results obtained from GWR demonstrate variations in local parameter estimates over both space and time. The forecasted future values of local estimates as well as house prices indicate that the proposed GWR–TS method is a useful addition to hedonic price modelling.