Challenges and Perspectives

Agriculture is a diverse field that produces a wide array of products vital to society. As global populations continue to grow the competition for natural resources will increase pressure on agricultural production of food, fiber, energy, and various high value by-products. With elevated concerns related to environmental impacts associated with the needs of a growing population, a life cycle assessment (LCA) framework can be used to determine areas of greatest impact and compare reduction strategies for agricultural production systems. The LCA methodology was originally developed for industrial operations but has been expanded to a wider range of fields including agriculture. There are various factors that increase the complexity of determining impacts associated with agricultural production including multiple products from a single system, regional and crop specific management techniques, temporal variations (seasonally and annually), spatial variations (multilocation production of end products), and the large quantity of nonpoint emission sources. The lack of consistent methodology of some impacts that are of major concern to agriculture (e.g., land use and water usage) increases the complexity of this analysis. This paper strives to review some of these issues and give perspective to the LCA practitioner in the field of agriculture

Influence of Polymorphism on the Electronic Structure of Ga2O3

The search for new wide band gap materials is intensifying to satisfy the need for more advanced and energy efficient power electronic devices. Ga$_2$O$_3$ has emerged as an alternative to SiC and GaN, sparking a renewed interest in its fundamental properties beyond the main $\beta$-phase. Here, three polymorphs of Ga$_2$O$_3$, $\alpha$, $\beta$ and $\varepsilon$, are investigated using X-ray diffraction, X-ray photoelectron and absorption spectroscopy, and ab initio theoretical approaches to gain insights into their structure - electronic structure relationships. Valence and conduction electronic structure as well as semi-core and core states are probed, providing a complete picture of the influence of local coordination environments on the electronic structure. State-of-the-art electronic structure theory, including all-electron density functional theory and many-body perturbation theory, provide detailed understanding of the spectroscopic results. The calculated spectra provide very accurate descriptions of all experimental spectra and additionally illuminate the origin of observed spectral features. This work provides a strong basis for the exploration of the Ga$_2$O$_3$ polymorphs as materials at the heart of future electronic device generations.Comment: Updated manuscript version after peer revie

Evidence of a second-order Peierls-driven metal-insulator transition in crystalline NbO2

The metal-insulator transition of NbO2 is thought to be important for the functioning of recent niobium oxide-based memristor devices, and is often described as a Mott transition in these contexts. However, the actual transition mechanism remains unclear, as current devices actually employ electroformed NbOx that may be inherently different to crystalline NbO2. We report on our synchrotron x-ray spectroscopy and density-functional-theory study of crystalline, epitaxial NbO2 thin films grown by pulsed laser deposition and molecular beam epitaxy across the metal-insulator transition at ~810⁰C. The observed spectral changes reveal a second-order Peierls transition driven by a weakening of Nb dimerization without significant electron correlations, further supported by our density-functional-theory modeling. Our findings indicate that employing crystalline NbO2 as an active layer in memristor devices may facilitate analog control of the resistivity, whereby Joule-heating can modulate Nb-Nb dimer distance and consequently control the opening of a pseudogap

Evaluation of high-throughput genomic assays for the Fc gamma receptor locus

Cancer immunotherapy has been revolutionised by the use of monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A-158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcγR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcγR genetics in predicting response to antibody therapeutics

Genome-Wide Functional Profiling Reveals Genes Required for Tolerance to Benzene Metabolites in Yeast

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease

Biomass supply chain management in North Carolina (part 1): predictive model for cropland conversion to biomass feedstocks

Increased interest in biomass cultivation requires detailed analysis of spatial production potential of possible biorefinery locations, with emphasis on feedstock production cost minimization. Integrated assessment of publicly available spatial data on current crop production, soil type, and yield potential, coupled with techno-economic production cost estimates, can support a functional method for rapid analysis of potential biorefinery sites. A novel predictive model was developed to determine cropland conversion using a probabilistic profit based equation for multiple biomass crops: giant reed, miscanthus, switchgrass, and sorghum (with either canola or barley as a winter crop). The three primary regions of North Carolina (Mountains, Piedmont, and Coastal Plain) were used as a case study and with a single parameter uncertainty analysis was completed. According to the model, the county chosen to represent the Coastal Plain (Duplin County) had the largest potential acreage that would be converted (15,071 ha, 7.1% total land, 9.3% of cropland) primarily to sorghum with canola as a winter crop. Large portions were also predicted to convert to giant reed and switchgrass, depending on the price and yield parameters used. The Piedmont (Granville County, 7697 ha, 5.5% total land, 6.9% cropland) and Mountain (Henderson County, 2117 ha, 2.2% total land, 2.3% cropland) regions were predicted to convert primarily to switchgrass acreage for biomass production, with much less available biomass overall compared to the Coastal Plain. This model provided meaningful insight into regional cropping systems and feedstock availability, allowing for improved business planning in designated regions. Determination of cropland conversion is imperative to develop realistic biomass logistical operations, which in conjunction can assist with rapid determination of profitable biomass availability. After this rapid analysis method is conducted in-depth on-ground biorefinery feasibility analysis can occur, ensuring resource are used only in locations with a high potential for available low cost biomass feedstocks

JT002, a small molecule inhibitor of the NLRP3 inflammasome for the treatment of autoinflammatory disorders

Abstract The NLRP3 inflammasome is an intracellular, multiprotein complex that promotes the auto-catalytic activation of caspase-1 and the subsequent maturation and secretion of the pro-inflammatory cytokines, IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome has been implicated in the pathophysiology of a number of inflammatory and autoimmune diseases, including neuroinflammation, cardiovascular disease, non-alcoholic steatohepatitis, lupus nephritis and severe asthma. Here we describe the preclinical profile of JT002, a novel small molecule inhibitor of the NLRP3 inflammasome. JT002 potently reduced NLRP3-dependent proinflammatory cytokine production across a number of cellular assays and prevented pyroptosis, an inflammatory form of cell death triggered by active caspase-1. JT002 demonstrated in vivo target engagement at therapeutically relevant concentrations when orally dosed in mice and prevented body weight loss and improved inflammatory and fibrotic endpoints in a model of Muckle–Wells syndrome (MWS). In two distinct models of neutrophilic airway inflammation, JT002 treatment significantly reduced airway hyperresponsiveness and airway neutrophilia. These results provide a rationale for the therapeutic targeting of the NLRP3 inflammasome in severe asthma and point to the use of JT002 in a variety of inflammatory disorders