Cytosolic re-localization and optimization of valine synthesis and catabolism enables increased isobutanol production with the yeast Saccharomyces cerevisiae

Background: The branched chain alcohol isobutanol exhibits superior physicochemical properties as an alternative biofuel. The yeast Saccharomyces cerevisiae naturally produces low amounts of isobutanol as a by-product during fermentations, resulting from the catabolism of valine. As S. cerevisiae is widely used in industrial applications and can easily be modified by genetic engineering, this microorganism is a promising host for the fermentative production of higher amounts of isobutanol. Results: Isobutanol production could be improved by re-locating the valine biosynthesis enzymes Ilv2, Ilv5 and Ilv3 from the mitochondrial matrix into the cytosol. To prevent the import of the three enzymes into yeast mitochondria, N-terminally shortened Ilv2, Ilv5 and Ilv3 versions were constructed lacking their mitochondrial targeting sequences. SDS-PAGE and immunofluorescence analyses confirmed expression and re-localization of the truncated enzymes. Growth tests or enzyme assays confirmed enzymatic activities. Isobutanol production was only increased in the absence of valine and the simultaneous blockage of the mitochondrial valine synthesis pathway. Isobutanol production could be even more enhanced after adapting the codon usage of the truncated valine biosynthesis genes to the codon usage of highly expressed glycolytic genes. Finally, a suitable ketoisovalerate decarboxylase, Aro10, and alcohol dehydrogenase, Adh2, were selected and overexpressed. The highest isobutanol titer was 0.63 g/L at a yield of nearly 15 mg per g glucose. Conclusion: A cytosolic isobutanol production pathway was successfully established in yeast by re-localization and optimization of mitochondrial valine synthesis enzymes together with overexpression of Aro10 decarboxylase and Adh2 alcohol dehydrogenase. Driving forces were generated by blocking competition with the mitochondrial valine pathway and by omitting valine from the fermentation medium. Additional deletion of pyruvate decarboxylase genes and engineering of co-factor imbalances should lead to even higher isobutanol production

Crisis y universidad, educación y globalización

Discurso de clausura del VIII. Congreso Internacional de la Federación de Asociaciones de Germanistas en España FAGE, Sevilla 18.-21. Septiembre 201

Peridynamic Galerkin method: an attractive alternative to finite elements

This work presents a meshfree particle scheme designed for arbitrary deformations that possess the accuracy and properties of the Finite-Element-Method. The accuracy is maintained even with arbitrary particle distributions. Mesh-based methods mostly fail if requirements on the location of evaluation points are not satisfied. Hence, with this new scheme not only the range of loadings can be increased but also the pre-processing step can be facilitated compared to the FEM. The key to this new meshfree method lies in the fulfillment of essential requirements for spatial discretization schemes. The new approach is based on the correspondence theory of Peridynamics. Some modifications of this framework allows for a consistent and stable formulation. By applying the peridynamic differentiation concept, it is also shown that the equations of the correspondence theory can be derived from the weak form. Likewise, it is demonstrated that special moving least square shape functions possess the Kronecker-δ property. Thus, Dirichlet boundary conditions can be directly applied. The positive performance of this new meshfree method, especially in comparison to the Finite-Element-Method, is shown in the calculation of several test cases. In order to guarantee a fair comparison enhanced finite element formulations are also used. The test cases include the patch test, an eigenmode analysis as well as the investigation of loadings in the context of large deformations. © 2022, The Author(s)

Mixed peridynamic formulations for compressible and incompressible finite deformations

The large flexibility of meshfree solution schemes makes them attractive for many kinds of engineering applications, like Additive Manufacturing or cutting processes. While numerous meshfree methods were developed over the years, the accuracy and robustness are still challenging and critical issues. Stabilization techniques of various kinds are typically used to overcome these problems, but often require the tuning of unphysical parameters. The Peridynamic Petrov–Galerkin method is a generalization of the peridynamic theory of correspondence materials and offers a stable and robust alternative. In this work, the stabilization free approach is extended to three dimensional problems of finite elasticity. Locking-free mixed formulations for nearly incompressible and incompressible materials are developed and investigated in convergence studies. In general, an efficient implicit quasi-static framework based on Automatic Differentiation is presented. The numerical examples highlight the convergence properties and robustness of the proposed formulations. © 2020, The Author(s)

Psychosocial Development in Middle Childhood and Early Adolescence : A Handbook for Icehearts’ Educators

Christian Bode. Psychosocial Development in Middle Childhood and Early Adolescence: A Handbook for Icehearts’ Educators. Helsinki 2015, 157 pages plus appendices. Diaconia University of Applied Sciences, Helsinki. Degree Programme in Social Services. The aim of this study was to develop a handbook for Icehearts’ educators, a Finnish third sector organization for children and youth work, and for other educators and caregivers. The focus lies on major psychosocial development phases during middle childhood and adolescence. This study is a functional thesis. The thesis product is based on an adapted literature review method and on qualitative data analysis techniques for the analysis of literature. Various textbooks and scientific articles were used for the study. The handbook introduces a framework model for the psychosocial development, describes important theories and concepts, and highlights development processes per year of age. An information database developed for the literature review and the literature analyses complements the information in the handbook. The thesis product outlines various psychosocial development domains and proposes focus areas for future children and youth work. It is a platform for the development of training concepts for educators and it is a knowledge basis for further Icehearts’ studies on external influence factors during children’s and adolescents’ development

Zur Geschichte der Gerichtlichen Medizin an der Universität Jena im Zeitraum von 1901 bis 1945

Ernst Giese, Gerhard Buhtz und Friedrich Timm, die ersten drei Lehrstuhlinhaber für gerichtliche Medizin an der Universität Jena, prägten in der ersten Hälfte des 20. Jahrhunderts das Fach Gerichtliche Medizin und hatten großen Anteil an der Entwicklung des Jenaer gerichtsmedizinischen Instituts. Zielstellung der Arbeit ist es, diese Entwicklung in einem Zeitraum von 1901 bis 1945 zu analysieren

Sclerosing Epithelioid Fibrosarcoma: Case Presentation and a Systematic Review

In sclerosing epithelioid fibrosarcoma (SEF), a rare variant of low-grade fibrosarcoma, treatment results and therapeutic options are poorly characterized. We systematically analyzed the data of all 89 patients (43 female, 46 male; mean age, 47years [range, 14-87years]) reported in the literature concerning clinical presentation, histopathology, differential diagnosis, treatment, survival rates, and prognosis, and we present an additional case. Information detailing treatment, disease control, and followup was available in 60 (67%), 75 (84%), and 68 patients (76%), respectively. Case history was variable with one-third of patients reporting a painful, enlarging mass. Ten patients (13%) presented with metastases, 23 (31%) had metastases develop after diagnosis, and 28 (37%) had local recurrence. Low cellularity, mild pleomorphy, and sclerotic hyaline matrix of SEF suggest a benign clinical behavior, and cell morphology allows for the wide differential diagnosis of benign, pseudosarcomatous, and malignant proliferations. In addition to surgery, 11 patients (15%) had chemotherapy, 22 (29%) had postoperative radiation therapy, and three (4%) had a combination of both. Twenty-three patients (34%) died from their disease after a mean of 46months, 24 (35%) were alive with disease, and 20 (31%) were alive without evidence of disease. Patients with SEF of the head and neck had the worst prognosis. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidenc

Gravitational-wave detectability of equal-mass black-hole binaries with aligned spins

Binary black-hole systems with spins aligned or anti-aligned to the orbital angular momentum provide the natural ground to start detailed studies of the influence of strong-field spin effects on gravitational wave observations of coalescing binaries. Furthermore, such systems may be the preferred end-state of the inspiral of generic supermassive binary black-hole systems. In view of this, we have computed the inspiral and merger of a large set of binary systems of equal-mass black holes with spins parallel to the orbital angular momentum but otherwise arbitrary. Our attention is particularly focused on the gravitational-wave emission so as to quantify how much spin effects contribute to the signal-to-noise ratio, to the horizon distances, and to the relative event rates for the representative ranges in masses and detectors. As expected, the signal-to-noise ratio increases with the projection of the total black hole spin in the direction of the orbital momentum. We find that equal-spin binaries with maximum spin aligned with the orbital angular momentum are more than "three times as loud" as the corresponding binaries with anti-aligned spins, thus corresponding to event rates up to 30 times larger. We also consider the waveform mismatch between the different spinning configurations and find that, within our numerical accuracy, binaries with opposite spins S_1=-S_2 cannot be distinguished whereas binaries with spin S_1=S_2 have clearly distinct gravitational-wave emissions. Finally, we derive a simple expression for the energy radiated in gravitational waves and find that the binaries always have efficiencies E_rad/M > 3.6%, which can become as large as E_rad/M = 10% for maximally spinning binaries with spins aligned with the orbital angular momentum.Comment: 18 pages, 11 figures, matches published versio