Brazilian Biodiesel Policy: Social and environmental considerations of sustainability

The objective of this article is to analyze the Brazilian Biodiesel Policy (PNPB) and to identify the social and environmental aspects of sustainability that are present or absent within it. Biofuels, namely alcohol and biodiesel, have been increasing in popularity on a global scale due to their potential as alternative and renewable energy sources. Brazil, a vast country blessed with abundant natural resources and agricultural land, has emerged as a global leader in the production of biofuels. This article includes a brief analysis of the concept of sustainable development, which served as a basis to evaluate the Policy documents. Although PNPB's implementation, which began in 2004, is still within its initial stage, it was possible to identify and elaborate on the environmental and social aspects of the Policy, namely: the social inclusion of family farmers; regional development; food security; influencing the carbon and energy balance of biodiesel; promoting sustainable agricultural practices and a diversity of feedstock.     

Photobiological hydrogen production from Synechocystis sp. PCC 6803 encapsulated in silica sol–gel

Hydrogen production was measured from viable wild-type and M55 mutant cells of Synechocystis sp. PCC 6803 encapsulated in silica sol–gel derived from tetraethoxysilane, tetramethoxysilane, and a mixture of tetraethoxysilane with methyltriethoxysilane. Glycerol and polyethylene glycol were used as additives in concentrations up to 14 wt.% to increase porosity and pore connectivity and to reduce stress on the encapsulated cells. Mixtures were evaluated for hydrogen production in a high-throughput screening assay, and samples were imaged with environmental scanning electron microscopy. Compositions showing improved H₂ production were selected for further study via quantitative analysis of H₂ production in GC vial assays. H₂ production activity was monitored for up to 5 days and H₂ production from encapsulated cells was observed at levels comparable to or exceeding cells suspended in liquid media.     

Peptide-Affinity Precipitation of Extracellular Vesicles and Cell-Free DNA Improves Sequencing Performance for the Detection of Pathogenic Mutations in Lung Cancer Patient Plasma

Liquid biopsy is a minimally-invasive diagnostic method that may improve access to molecular profiling for non-small cell lung cancer (NSCLC) patients. Although cell-free DNA (cf-DNA) isolation from plasma is the standard liquid biopsy method for detecting DNA mutations in cancer patients, the sensitivity can be highly variable. Vn96 is a peptide with an affinity for both extracellular vesicles (EVs) and circulating cf-DNA. In this study, we evaluated whether peptide-affinity (PA) precipitation of EVs and cf-DNA from NSCLC patient plasma improves the sensitivity of single nucleotide variants (SNVs) detection and compared observed SNVs with those reported in the matched tissue biopsy. NSCLC patient plasma was subjected to either PA precipitation or cell-free methods and total nucleic acid (TNA) was extracted; SNVs were then detected by next-generation sequencing (NGS). PA led to increased recovery of DNA as well as an improvement in NGS sequencing parameters when compared to cf-TNA. Reduced concordance with tissue was observed in PA-TNA (62%) compared to cf-TNA (81%), mainly due to identification of SNVs in PA-TNA that were not observed in tissue. EGFR mutations were detected in PA-TNA with 83% sensitivity and 100% specificity. In conclusion, PA-TNA may improve the detection limits of low-abundance alleles using NGS.     

Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy

The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the primary mechanism of action of anti-PD-1 therapy. In this study, we established a model system to test T cell functions modulated by Nivolumab using anti-CD3 monoclonal antibody (mAb)-stimulated peripheral blood mononuclear cells (PBMCs), and characterized T cell functions primarily based on the knowledge gained from retrospective observations of patients treated with anti-PD-1 immunotherapy. During a comprehensive cytokine profile assessment to identify potential biomarkers, we found that Nivolumab increases expression of T helper type 1 (Th1) associated cytokines such as interferon-γ (IFN-γ) and interleukin-2 (IL-2) in a subset of donors. Furthermore, Nivolumab increases production of Th2, Th9, and Th17 associated cytokines, as well as many proinflammatory cytokines such as IL-6 in a subset of donors. Conversely, Nivolumab treatment has no impact on T cell proliferation, expression of CD25, CD69, or Granzyme B, and only modestly increases in the expansion of regulatory T cells. Our results suggest that assessment of cytokine production using a simple PBMC-based T cell functional assay could be used as a potential predictive marker for anti-PD-1 immunotherapy.     

Untargeted metabolomics of human plasma reveal lipid markers unique to chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation and progressive airflow limitation, whereas idiopathic pulmonary fibrosis (IPF) is characterised by a restrictive pattern due to fibrosis and impaired gas exchange. We undertook metabolomic analysis of blood samples in IPF, COPD and healthy controls (HC) to determine differences in circulating molecules and identify novel pathogenic pathways. An untargeted metabolomics using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) was performed to profile plasma of patients with COPD (n = 21), and IPF (n = 24) in comparison to plasma from healthy controls (HC; n = 20). The most significant features were identified using multiple database matching. One-way ANOVA and variable importance in projection (VIP) scores were also used to highlight metabolites that influence the specific disease groups. Non-polar metabolites such as fatty acids (FA) and membrane lipids were well resolved and a total of 4805 features were identified. The most prominent metabolite composition differences in lipid mediators identified at ∼2–3 fold higher in both diseases compared to HC were palmitoleic acid, oleic acid and linoleic acid; and dihydrotestosterone was lower in both diseases. We demonstrated that COPD and IPF were characterised by systemic changes in lipid constituents such as essential FA sampled from circulating plasma.     

[18F]Flurpiridaz: Facile and Improved Precursor Synthesis for this Next-Generation Cardiac Positron Emission Tomography Imaging Agent

[¹⁸F]Flurpiridaz is a recently developed positron emission tomography tracer that is currently being investigated in phase III clinical trials to measure myocardial blood flow. The relatively long physical half-life of fluorine-18 alongside the high spatial resolution and outstanding myocardium-to-background ratio fuels its potential to be the next gold standard for the early detection of coronary artery disease. Notwithstanding the expected widespread use of [¹⁸F]flurpiridaz, the reported multistep synthesis of its precursor for radiofluorination involves a hazardous alkylation step using carcinogenic ethylene oxide, and a low overall chemical yield of 7 %. In this work, we have improved the overall yield more than fivefold and concurrently replaced the hazardous step. Specificity of binding of [¹⁸F]flurpiridaz to mitochondrial complex 1 was demonstrated by in vitro autoradiography on mouse heart tissue sections. These results thus pave the way for assessing myocardial blood flow and coronary flow reserve in mouse models of cardiovascular disease.     

Selenium in Diketopyrrolopyrrole-based Polymers: Influence on Electronic Properties and Charge Carrier Mobilities

Diketopyrrolopyrrole (DPP)-based π-conjugated copolymers with thiophene have exceptionally high electron mobilities. This paper investigates electronic properties and charge carrier mobilities of selenophene containing analogues. Two new copolymers, with alternating thiophene DPP (TDPP) and selenophene DPP (SeDPP) units, were synthesized. Two side-chains, hexyl (Hex) and triethylene glycol (TEG) were employed, yielding polymers designated as PTDPPSeDPP-Hex and PTDPPSeDPP-TEG. Selenophene systems have smaller band gaps, with concomitant enhancement of the stability of the reduced state. For both polymers, ambipolar mobilities were observed in organic field-effect transistors (OFET). Grazing incidence X-ray diffraction (GIXD) data indicates preferential edge-on orientation of PTDPPSeDPP-TEG, which leads to superior charge transport properties of the TEG substituted polymer, as compared to its Hex analogue. Time-dependent-density functional theory (TDDFT) calculations corroborate the decrease in the optical band gap with the inclusion of selenophene. Ambipolar charge transport is rationalized by exceptionally wide conduction bands. ΔSCF calculations confirm the larger electron affinity, and therefore the greater stability, of the reduced form of the selenophene-containing DPP polymer in presence of chloroform.     

Genotypic variation in cell wall composition in a diverse set of 244 accessions of Miscanthus

We report on a replicated spaced-plant trial in Wales of 244 diverse Miscanthus accessions grouped by classical taxonomy into M. sinensis, M. sacchariflorus and M. x giganteus. Large differences in cell wall composition were detected between taxonomic groups. Significantly higher concentrations of NDF (88.19, 85.59 and 85.03 %DW; S.E.D. of 0.300; P < 0.001); ADL (11.76, 10.15 and 9.07 %DW; S.E.D. of 0.087; P < 0.001) and cellulose (47.09, 42.94 and 42.50 %DW; S.E.D. of 0.255; P < 0.001); and significantly lower concentrations of hemicellulose (29.43, 32.50 and 33.46 %DW; S.E.D. of 0.130; P < 0.001) were present in the samples from M. x giganteus compared to the other groups. Growth year and the interaction between taxonomic group and growth year had smaller significant effects. Strong correlations were found between ADL and cellulose (R = 0.72), and hemicellulose (R = −0.76) in the M. x giganteus samples but correlations were weaker for M. sacchariflorus (R = 0.66 and −0.59) and M. sinensis (R = 0.46 and −0.40). Eleven genotypes had been assessed previously in the U.K. during the European Miscanthus Improvement (EMI) programme. These generally had higher concentrations of ADL and hemicellulose, and lower concentrations of cellulose than were reported for the U.K. site during the EMI study. These results suggest that cell wall composition and ADL concentration in particular, is highly stable between growth years but is affected by site location. Furthermore, there are differences in cell wall composition between Miscanthus taxonomic groups that may prove valuable for breeding new varieties that are compositionally matched to conversion process.     

ANN Analysis of a Roller Compaction Process in the Pharmaceutical Industry

Dry granulation via a roller compactor was simulated based on the artificial neural network (ANN) methodology. Two process parameters, including roll force and screw speed, were considered as input of the simulation whereas ribbon density was considered as output. Experimental work was carried out using an industrial‐scale roller compactor. The results showed an excellent agreement between simulation and experiments. The findings were compared as well with the results obtained in a previous study employing the Johanson model, which is the predominant model for the simulation of a roller compaction process. The overall deviation observed for the developed ANN model was found to be significantly improved in comparison with the deviation obtained for the Johanson model. The results demonstrated a very good capability and robustness of the developed ANN model in design and optimization of the roller compaction process.