Risk Aversion, Prudence, and the Three-Moment Decision Model for Hedging

The linear two-moment mean-variance (MV) model has been widely used in finance and economic decision analysis as an approximation of Von Neumann-Morgenstern expected utility (EU) model. The introduction of third or higher moments not only can improve the accuracy of the approximation, but is also suitable to represent investors¡¯ skewness preference (prudence) with the latter supported by empirical evidence. The goal of this paper is to develop a general MVS model and compare it and the traditional MV model against the EU model in the setting of an individual producer hedging in the futures market. Results show: 1) the derived linear MVS model maintains the analytical convenience of MV model, 2) it can generate different results as MV, 3) it approximate EU better than MV, and 4) it is more flexible than MV.Risk and Uncertainty,

A quantitative image analysis pipeline for the characterization of filamentous fungal morphologies as a tool to uncover targets for morphology engineering: a case study using aplD in Aspergillus niger

Background Fungal fermentation is used to produce a diverse repertoire of enzymes, chemicals, and drugs for various industries. During submerged cultivation, filamentous fungi form a range of macromorphologies, including dispersed mycelia, clumped aggregates, or pellets, which have critical implications for rheological aspects during fermentation, gas/nutrient transfer, and, thus, product titres. An important component of strain engineering efforts is the ability to quantitatively assess fungal growth phenotypes, which will drive novel leads for morphologically optimized production strains. Results In this study, we developed an automated image analysis pipeline to quantify the morphology of pelleted and dispersed growth (MPD) which rapidly and reproducibly measures dispersed and pelleted macromorphologies from any submerged fungal culture. It (i) enables capture and analysis of several hundred images per user/day, (ii) is designed to quantitatively assess heterogeneous cultures consisting of dispersed and pelleted forms, (iii) gives a quantitative measurement of culture heterogeneity, (iv) automatically generates key Euclidian parameters for individual fungal structures including particle diameter, aspect ratio, area, and solidity, which are also assembled into a previously described dimensionless morphology number MN, (v) has an in-built quality control check which enables end-users to easily confirm the accuracy of the automated calls, and (vi) is easily adaptable to user-specified magnifications and macromorphological definitions. To concomitantly provide proof of principle for the utility of this image analysis pipeline, and provide new leads for morphologically optimized fungal strains, we generated a morphological mutant in the cell factory Aspergillus niger based on CRISPR-Cas technology. First, we interrogated a previously published co-expression networks for A. niger to identify a putative gamma-adaptin encoding gene (aplD) that was predicted to play a role in endosome cargo trafficking. Gene editing was used to generate a conditional aplD expression mutant under control of the titratable Tet-on system. Reduced aplD expression caused a hyperbranched growth phenotype and diverse defects in pellet formation with a putative increase in protein secretion. This possible protein hypersecretion phenotype could be correlated with increased dispersed mycelia, and both decreased pellet diameter and MN. Conclusion The MPD image analysis pipeline is a simple, rapid, and flexible approach to quantify diverse fungal morphologies. As an exemplar, we have demonstrated that the putative endosomal transport gene aplD plays a crucial role in A. niger filamentous growth and pellet formation during submerged culture. This suggests that endocytic components are underexplored targets for engineering fungal cell factories.DFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli

Respiration of aged soil carbon during fall in permafrost peatlands enhanced by active layer deepening following wildfire but limited following thermokarst

Permafrost peatlands store globally significant amounts of soil organic carbon (SOC) that may be vulnerable to climate change. Permafrost thaw exposes deeper, older SOC to microbial activity, but SOC vulnerability to mineralization and release as carbon dioxide is likely influenced by the soil environmental conditions that follow thaw. Permafrost thaw in peat plateaus, the dominant type of permafrost peatlands in North America, occurs both through deepening of the active layer and through thermokarst. Active layer deepening exposes aged SOC to predominately oxic conditions, while thermokarst is associated with complete permafrost thaw which leads to ground subsidence, inundation and soil anoxic conditions. Thermokarst often follows active layer deepening, and wildfire is an important trigger of this sequence. We compared the mineralization rate of aged SOC at an intact peat plateau (∼70 cm oxic active layer), a burned peat plateau (∼120 cm oxic active layer), and a thermokarst bog (∼550 cm anoxic peat profile) by measuring respired 14C-CO2. Measurements were done in fall when surface temperatures were near-freezing while deeper soil temperatures were still close to their seasonal maxima. Aged SOC (1600 yrs BP) contributed 22.1 ± 11.3% and 3.5 ± 3.1% to soil respiration in the burned and intact peat plateau, respectively, indicating a fivefold higher rate of aged SOC mineralization in the burned than intact peat plateau (0.15 ± 0.07 versus 0.03 ± 0.03 g CO2-C m−2 d−1). None or minimal contribution of aged SOC to soil respiration was detected within the thermokarst bog, regardless of whether thaw had occurred decades or centuries ago. While more data from other sites and seasons are required, our study provides strong evidence of substantially increased respiration of aged SOC from burned peat plateaus with deepened active layer, while also suggesting inhibition of aged SOC respiration under anoxic conditions in thermokarst bogs

Functional exploration of co-expression networks identifies a nexus for modulating protein and citric acid titres in Aspergillus niger submerged culture

Background: Filamentous fungal cell factories are used to produce numerous proteins, enzymes, and organic acids. Protein secretion and filamentous growth are tightly coupled at the hyphal tip. Additionally, both these processes require ATP and amino acid precursors derived from the citric acid cycle. Despite this interconnection of organic acid production and protein secretion/filamentous growth, few studies in fungi have identified genes which may concomitantly impact all three processes. Results: We applied a novel screen of a global co-expression network in the cell factory Aspergillus niger to identify candidate genes which may concomitantly impact macromorphology, and protein/organic acid fermentation. This identified genes predicted to encode the Golgi localized ArfA GTPase activating protein (GAP, AgeB), and ArfA guanine nucleotide exchange factors (GEFs SecG and GeaB) to be co-expressed with citric acid cycle genes. Consequently, we used CRISPR-based genome editing to place the titratable Tet-on expression system upstream of ageB, secG, and geaB in A. niger. Functional analysis revealed that ageB and geaB are essential whereas secG was dispensable for early filamentous growth. Next, gene expression was titrated during submerged cultivations under conditions for either protein or organic acid production. ArfA regulators played varied and culture-dependent roles on pellet formation. Notably, ageB or geaB expression levels had major impacts on protein secretion, whereas secG was dispensable. In contrast, reduced expression of each predicted ArfA regulator resulted in an absence of citric acid in growth media. Finally, titrated expression of either GEFs resulted in an increase in oxaloacetic acid concentrations in supernatants. Conclusion: Our data suggest that the Golgi may play an underappreciated role in modulating organic acid titres during industrial applications, and that this is SecG, GeaB and AgeB dependent in A. niger. These data may lead to novel avenues for strain optimization in filamentous fungi for improved protein and organic acid titres.TU Berlin, Open-Access-Mittel - 201

Tet-on, or tet-off, that is the question: advanced conditional gene expression in Aspergillus

In Aspergillus, controlled gene expression is often achieved using the reverse tetracycline-controlled transactivator (rtTA) dependent Tet-on system, whereby transcription is activated in a titratable manner by addition of the tetracycline derivative doxycycline. The complementary Tet-off system utilises the tetracycline-controlled transactivator (tTA) component to quantitatively reduce gene expression. In this study, we utilised a synthetic biological approach to engineer highly optimised Tet-off conditional expression systems in Aspergillus niger and Aspergillus fumigatus. Steps for delivery of these tools include utilising codon optimised cassette components, testing several promoters for improved genetic stability and validating two modified luciferase reporters for highly accurate measurements of gene expression. The Tet-off cassettes developed in this study enable facile and quantitative functional analysis, as validated by Tet-off analysis of genes involved in chitin synthesis and cell wall polarity in A. niger, and para-aminobenzoic acid synthesis in A. fumigatus. We also used a racAG18V dominant allele to demonstrate that Tet-off in A. niger enables gene over-expression and downregulation in a single isolate. Additionally, we used the improved luciferase reporters to show that the Tet-off cassette in A. niger enables quantification of gene oscillations. In order to demonstrate that synthetic biological approaches developed here are broadly applicable to engineering transcriptional circuits in filamentous fungi, we used our strategy for improving cassette stability by promoter replacement in the A. niger Tet-on system, which resulted in a modified Tet-on cassette with higher stability in recipient genomes

Tunable Nanodielectric Composites

This paper presents a progress update with the development of nanodielectric composites with electric field tunability for various high energy, high power electrical applications. It is demonstrated that nonlinear electrical/dielectric properties can be achieved via the nanostructure and interface engineering. A high level summary was given on the progress achieved as well as challenges remaining in nanodielectric engineering towards high energy density capacitors for energy storage and conversion, nonlinear dielectrics for tunable device, and high voltage varistor for surge suppression

A Library of Aspergillus niger Chassis Strains for Morphology Engineering Connects Strain Fitness and Filamentous Growth With Submerged Macromorphology

Submerged fermentation using filamentous fungal cell factories is used to produce a diverse portfolio of useful molecules, including food, medicines, enzymes, and platform chemicals. Depending on strain background and abiotic culture conditions, different macromorphologies are formed during fermentation, ranging from dispersed hyphal fragments to approximately spherical pellets several millimetres in diameter. These macromorphologies are known to have a critical impact on product titres and rheological performance of the bioreactor. Pilot productivity screens in different macromorphological contexts is technically challenging, time consuming, and thus a significant limitation to achieving maximum product titres. To address this bottleneck, we developed a library of conditional expression mutants in the organic, protein, and secondary metabolite cell factory Aspergillus niger. Thirteen morphology-associated genes transcribed during fermentation were placed via CRISPR-Cas9 under control of a synthetic Tet-on gene switch. Quantitative analysis of submerged growth reveals that these strains have distinct and titratable macromorphologies for use as chassis during strain engineering programs. We also used this library as a tool to quantify how pellet formation is connected with strain fitness and filamentous growth. Using multiple linear regression modelling, we predict that pellet formation is dependent largely on strain fitness, whereas pellet Euclidian parameters depend on fitness and hyphal branching. Finally, we have shown that conditional expression of the putative kinase encoding gene pkh2 can decouple fitness, dry weight, pellet macromorphology, and culture heterogeneity. We hypothesize that further analysis of this gene product and the cell wall integrity pathway in which it is embedded will enable more precise engineering of A. niger macromorphology in future

Altered Tyrosine Phosphorylation of Cardiac Proteins Prompts Contractile Dysfunction in Hypertrophic Cardiomyopathy

Altered Serine/Threonine phosphorylation of the cardiac proteome is an established hallmark of heart failure (HF). However, the contribution of tyrosine phosphorylation to the pathogenesis of these diseases remains unclear. The cardiac proteome was explored by global mapping to discover and quantify site-specific tyrosine phosphorylation in two cardiac hypertrophic models; cardiac overexpression of ErbB2 (TgErbB2) and cardiac expression of a-Myosin heavy chain R403Q (R403Q-aMyHCTg) compared to control hearts. Phosphoproteomic changes found in R403Q-aMyHC Tg mice indicated EGFR1, Focal Adhesion, VEGF, ErbB signaling, and Chemokine signaling pathways activity were likely to be activated. On the other hand, TgErbB2 mice findings displayed significant overrepresentation of Right Ventricular Cardiomyopathy, Hypertrophic Cardiomyopathy (HCM), and dilated cardiomyopathy (DCM) KEGG Pathways. In silico kinase-substrate enrichment analysis (KSEA) highlighted a marked downregulation of canonical MAPK Pathway Activity downstream of k-Ras in TgErbB2 mice and activation of EGFR, PP2 inhibition of c-Src, and Hepatocyte growth factor stimulation. In vivo ErbB2 inhibition by AG-825 decreased cardiac fibrosis, cardiomyocyte disarray, and rescued contractile function on TgErbB2 mice. These results suggest that altered tyrosine phosphorylation may play a regulatory role in cardiac hypertrophic models, suggesting that tyrosine kinase inhibitors could be used therapeutically in Hypertrophic Cardiomyopathy

Coracoid Abnormalities and Their Relationship with Glenohumeral Deformities in Children with Obstetric Brachial Plexus Injury

<p>Abstract</p> <p>Background</p> <p>Patients with incomplete recovery from obstetric brachial plexus injury (OBPI) usually develop secondary muscle imbalances and bone deformities at the shoulder joint. Considerable efforts have been made to characterize and correct the glenohumeral deformities, and relatively less emphasis has been placed on the more subtle ones, such as those of the coracoid process. The purpose of this retrospective study is to determine the relationship between coracoid abnormalities and glenohumeral deformities in OBPI patients. We hypothesize that coracoscapular angles and distances, as well as coracohumeral distances, diminish with increasing glenohumeral deformity, whereas coracoid overlap will increase.</p> <p>Methods</p> <p>39 patients (age range: 2-13 years, average: 4.7 years), with deformities secondary to OBPI were included in this study. Parameters for quantifying coracoid abnormalities (coracoscapular angle, coracoid overlap, coracohumeral distance, and coracoscapular distance) and shoulder deformities (posterior subluxation and glenoid retroversion) were measured on CT images from these patients before any surgical intervention. Paired Student t-tests and Pearson correlations were used to analyze different parameters.</p> <p>Results</p> <p>Significant differences between affected and contralateral shoulders were found for all coracoid and shoulder deformity parameters. Percent of humeral head anterior to scapular line (PHHA), glenoid version, coracoscapular angles, and coracoscapular and coracohumeral distances were significantly lower for affected shoulders compared to contralateral ones. Coracoid overlap was significantly higher for affected sides compared to contralateral sides. Significant and positive correlations were found between coracoscapular distances and glenohumeral parameters (PHHA and version), as well as between coracoscapular angles and glenohumeral parameters, for affected shoulders. Moderate and positive correlations existed between coracoid overlap and glenohumeral parameters for affected shoulders. On the contrary, all correlations between the coracoid and glenohumeral parameters for contralateral shoulders were only moderate or relatively low.</p> <p>Conclusions</p> <p>These results indicate that the spatial orientation of the coracoid process differs significantly between affected and contralateral shoulders, and it is highly correlated with the glenohumeral deformity. With the progression of glenohumeral deformity, the coracoid process protrudes more caudally and follows the subluxation of the humeral head which may interfere with the success of repositioning the posteriorly subluxed humeral head anteriorly to articulate with the glenoid properly.</p