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There is a growing awareness that lignocellulose will be a major raw material for production of both fuel and chemicals in the coming decades--most likely through various fermentation routes. Considerable attention has been given to the problem of finding efficient means of separating the major constituents in lignocellulose (i.e., lignin, hemicellulose, and cellulose) and to efficiently hydrolyze the carbohydrate parts into sugars. In these processes, by-products will inevitably form to some extent, and these will have to be dealt with in the ensuing microbial processes. One group of compounds in this category is the furaldehydes. 2-Furaldehyde (furfural) and substituted 2-furaldehydes--most importantly 5-hydroxymethyl-2-furaldehyde--are the dominant inhibitory compounds found in lignocellulosic hydrolyzates. The furaldehydes are known to have biological effects and act as inhibitors in fermentation processes. The effects of these compounds will therefore have to be considered in the design of biotechnological processes using lignocellulose. In this short review, we take a look at known metabolic effects, as well as strategies to overcome problems in biotechnological applications caused by furaldehydes.

Age-related macular degeneration (AMD) is an eye disease that can cause visual impairment and affects the elderly over 50 years of age. AMD is characterized by the presence of drusen, which causes changes in the physiological structure of the retinal pigment epithelium (RPE) and the boundaries of the Bruch’s membrane layer (BM). Optical coherence tomography is one of the main exams for the detection and monitoring of AMD, which seeks changes through the evaluation of successive sectional cuts in the search for morphological changes caused by drusen. The use of CAD (Computer-Aided Detection) systems has contributed to increasing the chances of correct detection, assisting specialists in diagnosing and monitoring disease. Thus, the objective of this work is to present a method for the segmentation of the inner limiting membrane (ILM), retinal pigment epithelium, and Bruch’s membrane in OCT images of healthy and Intermediate AMD patients. The method uses two deep neural networks, U-Net and DexiNed to perform the segmentation. The results were promising, reaching an average absolute error of 0.49 pixel for ILM, 0.57 for RPE, and 0.66 for BM.

Computational approaches in immune-oncology therapies focus on using data-driven methods to identify potential immune targets and develop novel drug candidates. In particular, the search for PD-1/PD-L1 immune checkpoint inhibitors (ICIs) has enlivened the field, leveraging the use of cheminformatics and bioinformatics tools to analyze large datasets of molecules, gene expression and protein–protein interactions. Up to now, there is still an unmet clinical need for improved ICIs and reliable predictive biomarkers. In this review, we highlight the computational methodologies applied to discovering and developing PD-1/PD-L1 ICIs for improved cancer immunotherapies with a greater focus in the last five years. The use of computer-aided drug design structure- and ligand-based virtual screening processes, molecular docking, homology modeling and molecular dynamics simulations methodologies essential for successful drug discovery campaigns focusing on antibodies, peptides or small-molecule ICIs are addressed. A list of recent databases and web tools used in the context of cancer and immunotherapy has been compilated and made available, namely regarding a general scope, cancer and immunology. In summary, computational approaches have become valuable tools for discovering and developing ICIs. Despite significant progress, there is still a need for improved ICIs and biomarkers, and recent databases and web tools have been compiled to aid in this pursuit.

Saccharomyces cerevisiae alcohol dehydrogenases responsible for NADH-, and NADPH-specific reduction of the furaldehydes 5-hydroxymethyl-furfural (HMF) and furfural have previously been identified. In the present study, strains overexpressing the corresponding genes ( mut-ADH1 and ADH6 ), together with a control strain, were compared in defined medium for anaerobic fermentation of glucose in the presence and absence of HMF. All strains showed a similar fermentation pattern in the absence of HMF. In the presence of HMF, the strain overexpressing ADH6 showed the highest HMF reduction rate and the highest specific ethanol productivity, followed by the strain overexpressing mut-ADH1 . This correlated with in vitro HMF reduction capacity observed in the ADH6 overexpressing strain. Acetate and glycerol yields per biomass increased considerably in the ADH6 strain. In the other two strains, only the overall acetate yield per biomass was affected. When compared in batch fermentation of spruce hydrolysate, strains overexpressing ADH6 and mut- ADH1 had five times higher HMF uptake rate than the control strain and improved specific ethanol productivity. Overall, our results demonstrate that (1) the cofactor usage in the HMF reduction affects the product distribution, and (2) increased HMF reduction activity results in increased specific ethanol productivity in defined mineral medium and in spruce hydrolysate.

Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these mechanisms is important to better prevent and fight the deadly diseases caused. Those used by the fungus Pneumocystis jirovecii that causes life-threatening pneumonia in immunocompromised individuals remain poorly understood. Here, though this fungus is currently not cultivable, our detailed analysis of the subtelomeric sequence motifs and genes encoding surface proteins suggests that the system involves the reassortment of the repertoire of ca. 80 non-expressed genes present in each strain, from which single genes are retrieved for mutually exclusive expression. Dispersion of the new repertoires, supposedly by healthy carrier individuals, appears very efficient because identical alleles are observed in patients from different countries. Our observations reveal a unique strategy of antigenic variation. They also highlight the possible role in genome rearrangements of small imperfect mirror sequences forming DNA triplexes. Here the authors find that surface antigenic variation of the human pathogenic fungus Pneumocystis jirovecii involves mosaicism and reassortment of the repertoire of 80 genes present in each strain, from which single genes are retrieved for mutually exclusive expression.

Brucellosis is a neglected zoonotic disease of remarkable importance worldwide. The focus of this systematic review was to investigate occupational brucellosis and to identify the main infection risks for each group exposed to the pathogen. Seven databases were used to identify papers related to occupational brucellosis: CABI, Cochrane, Pubmed, Scielo, Science Direct, Scopus and Web of Science. The search resulted in 6123 studies, of which 63 were selected using the quality assessment tools guided from National Institutes of Health (NIH) and Case Report Guidelines (CARE). Five different job-related groups were considered greatly exposed to the disease: rural workers, abattoir workers, veterinarians and veterinary assistants, laboratory workers and hunters. The main risk factors and exposure sources involved in the occupational infection observed from the analysis of the articles were direct contact with animal fluids, failure to comply with the use of personal protective equipment, accidental exposure to live attenuated anti-brucellosis vaccines and non-compliance with biosafety standards. Brucella species frequently isolated from job-related infection were Brucella melitensis, Brucella abortus, Brucella suis and Brucella canis. In addition, a meta-analysis was performed using the case-control studies and demonstrated that animal breeders, laboratory workers and abattoir workers have 3.47 [95% confidence interval (CI); 1.47-8.19] times more chance to become infected with Brucella spp. than others individuals that have no contact with the possible sources of infection. This systematic review improved the understanding of the epidemiology of brucellosis as an occupational disease. Rural workers, abattoir workers, veterinarians, laboratory workers and hunters were the groups more exposed to occupational Brucella spp. infection. Moreover, it was observed that the lack of knowledge about brucellosis among frequently exposed professionals, in addition to some behaviors, such as negligence in the use of individual and collective protective measures, increases the probability of infection.

High-resolution distributed reinforcement strain measurements can provide invaluable information for developing and evaluating numerical and analytical models of reinforced concrete structures. A recent testing campaign conducted at UCLouvain in Belgium used fiber-optic sensors embedded along several longitudinal steel rebars of three reinforced concrete U-shaped walls. The resulting experimental dataset provides an opportunity to evaluate and compare, for different types of loading, the strain measurements obtained with the fiber-optic sensors in the confined core of the structural member against more conventional and state-of-the-practice sensors that monitor surface displacements and deformations. This work highlights the need to average strain measurements from digital image correlation techniques in order to obtain coherent results with the strains measured from fiber optics, and investigates proposals to achieve this relevant goal for research and engineering practices. The longitudinal strains measured by the fiber optics also provide additional detailed information on the behavior of these wall units compared to the more conventional instrumentation, such as strain penetration into the foundation and head of the wall units, which are studied in detail.

Despite their widespread use in non-invasive studies of porous materials, conventional MRI methods yield ambiguous results for microscopically heterogeneous materials such as brain tissue. While the forward link between microstructure and MRI observables is well understood, the inverse problem of separating the signal contributions from different microscopic pores is notoriously difficult. Here, we introduce an experimental protocol where heterogeneity is resolved by establishing 6D correlations between the individual values of isotropic diffusivity, diffusion anisotropy, orientation of the diffusion tensor, and relaxation rates of distinct populations. Such procedure renders the acquired signal highly specific to the sample’s microstructure, and allows characterization of the underlying pore space without prior assumptions on the number and nature of distinct microscopic environments. The experimental feasibility of the suggested method is demonstrated on a sample designed to mimic the properties of nerve tissue. If matched to the constraints of whole body scanners, this protocol could allow for the unconstrained determination of the different types of tissue that compose the living human brain.

Damage to structural walls in the recent earthquakes in Chile (2010) and New Zealand (2011) demonstrated that modern reinforced concrete (RC) walls may not achieve the expected ductile response but could possibly be triggered by out-of-plane displacements of the wall. Following a review of the mechanisms that cause global out-of-plane buckling of RC walls, relevant international code requirements, and past experimental tests, this paper describes the findings from quasi-static cyclic tests of two thin RC walls with single layers of vertical and horizontal reinforcement. The two walls were subjected to uni-directional (in-plane) and bi-directional (in-plane and out-of-plane) loading respectively. Both walls experienced significant out-of-plane displacements and damage caused by out-of-plane deformations ultimately triggered the wall in-plane failure. The data obtained with extensive instrumentation of the test units, which included optical measurements of the 3D displacement field, yield new insights into the development of out-of-plane displacements, in particular with regard to: evolution of out-of-plane displacements with imposed in-plane displacements, portion of height and length of the wall that are involved in the out-of-plane instability, influence of both local and global tensile strains on the buckling behaviour and role of bi-directional loading on out-of-plane instability. The tests showed that very significant out-of-plane displacements—larger than half of the wall thickness—can take place without causing out-of-plane wall failure. The damage caused by these large out-of-plane displacements, however, can lead to a premature in-plane failure of the wall.

The influence of media coverage on web-based searches may hinder the role of Google Trends (GT) in monitoring coronavirus disease (COVID-19). The aim of this study was to assess whether COVID-19-related GT data, particularly those related to ageusia and anosmia, were primarily related to media coverage or to epidemic trends. We retrieved GT query data for searches on coronavirus, cough, anosmia, and ageusia and plotted them over a period of 5 years. In addition, we analyzed the trends of those queries for 17 countries throughout the year 2020 with a particular focus on the rises and peaks of the searches. For anosmia and ageusia, we assessed whether the respective GT data correlated with COVID-19 cases and deaths both throughout 2020 and specifically before March 16, 2020 (ie, the date when the media started reporting that these symptoms can be associated with COVID-19). Over the last five years, peaks for coronavirus searches in GT were only observed during the winter of 2020. Rises and peaks in coronavirus searches appeared at similar times in the 17 different assessed countries irrespective of their epidemic situations. In 15 of these countries, rises in anosmia and ageusia searches occurred in the same week or 1 week after they were identified in the media as symptoms of COVID-19. When data prior to March 16, 2020 were analyzed, anosmia and ageusia GT data were found to have variable correlations with COVID-19 cases and deaths in the different countries. Our results indicate that COVID-19-related GT data are more closely related to media coverage than to epidemic trends.