An area-based matrix model for uneven-aged forests

In this paper a new concept for modeling uneven-aged forests (UEAF) is presented. The term UEAF in this article encloses all forests that deviate from the even-aged structure. The matrix model is area-based, in that the forest under study is described by a distribution of areas over fixed state-spaces spanned by stem number and volume per hectare classes. Dynamics is introduced as transitions of areas inside the state-space during the simulation. Harvesting activities and the occurrence of calamities are explicitly handled. The model is designed to be suitable for large-scale analyses. The concept was tested in an application to Austrian National Forest Inventory (NFI) data. Results shown, including a comparison to older inventory data, indicate that it is worth further elaborating on the concept and the model. The work will be continued and in the next step the model concept will be applied in several other countries.JRC.H.3-Forest Resources and Climat

The European Forestry Dynamics Model: Concept, design and results of first case studies

The European Forestry Dynamics Model (EFDM) is a joint effort between the European Commission Joint Research Centre and partners in the EU Member States for the development of a forestry dynamics model. The model is expected to project the state of Europe’s forests given different climatic, economic and management scenarios. EFDM was designed as a flexible system to facilitate the different types of data input that are available from the diverse National Forest Inventories. The model captures different typologies such as site productivity, ownership and the probability of natural disturbances. Specifically, EFDM is able to process detailed national-level input data such as National Forest Inventories (NFI) outputs, as well as related national-level expertise in social and economic domains. In this way, the system supports effective utilization of the collaborative expertise in the parameterization of scenarios. This document is intended as a general introduction to the EFDM. Experiences gained from the EFDM test applications by five NFI teams (Austria, Finland, France, Portugal and Sweden) are also summarized in this report.JRC.H.3-Forest Resources and Climat

Omics approaches to identify potential biomarkers of inflammatory diseases in the focal adhesion complex

Inflammatory diseases such as inflammatory bowel disease require recurrent invasive tests, including blood tests, radiology and endoscopic evaluation for diagnosis, assessment of disease activity and to determine optimal therapeutic strategies. ‘Bedside’ simple biomarkers could be used in all phases of patient management to avoid unnecessary investigation and guide further management. The focal adhesion complex has been implicated in the pathogenesis of multiple inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. Utilising ‘omics approaches has proven to be an efficient method to identify biomarkers from within the focal adhesion complex in the field of cancer medicine and predictive biomarkers are paving the way for the success of precision medicine for cancer patients, but inflammatory diseases have lagged behind in this respect. This review explores the current status of biomarker prediction for inflammatory diseases from within the focal adhesion complex using ‘omics techniques and looks forward to future potential avenues for biomarker identification

DNA Damage, Somatic Aneuploidy, and Malignant Sarcoma Susceptibility in Muscular Dystrophies

Albeit genetically highly heterogeneous, muscular dystrophies (MDs) share a convergent pathology leading to muscle wasting accompanied by proliferation of fibrous and fatty tissue, suggesting a common MD–pathomechanism. Here we show that mutations in muscular dystrophy genes (Dmd, Dysf, Capn3, Large) lead to the spontaneous formation of skeletal muscle-derived malignant tumors in mice, presenting as mixed rhabdomyo-, fibro-, and liposarcomas. Primary MD–gene defects and strain background strongly influence sarcoma incidence, latency, localization, and gender prevalence. Combined loss of dystrophin and dysferlin, as well as dystrophin and calpain-3, leads to accelerated tumor formation. Irrespective of the primary gene defects, all MD sarcomas share non-random genomic alterations including frequent losses of tumor suppressors (Cdkn2a, Nf1), amplification of oncogenes (Met, Jun), recurrent duplications of whole chromosomes 8 and 15, and DNA damage. Remarkably, these sarcoma-specific genetic lesions are already regularly present in skeletal muscles in aged MD mice even prior to sarcoma development. Accordingly, we show also that skeletal muscle from human muscular dystrophy patients is affected by gross genomic instability, represented by DNA double-strand breaks and age-related accumulation of aneusomies. These novel aspects of molecular pathologies common to muscular dystrophies and tumor biology will potentially influence the strategies to combat these diseases

Harmonised projections of future forest resources in Europe

Data PaperAbstract • Key message A dataset of forest resource projections in 23 European countries to 2040 has been prepared for fores trelated policy analysis and decision-making. Due to applying harmonised definitions, while maintaining country-specific forestry practices, the projections should be usable from national to international levels. The dataset can be accessed at https://doi.org/10.5061/dryad.4t880qh. The associated metadata are available at https://metadata-afs.nancy.inra.fr/ geonetwork/srv/eng/catalog.search#/metadata/8f93e0d6-b524-43bd-bdb8-621ad5ae6fa9info:eu-repo/semantics/publishedVersio

Efficient Algorithms for Probing the RNA Mutation Landscape

The diversity and importance of the role played by RNAs in the regulation and development of the cell are now well-known and well-documented. This broad range of functions is achieved through specific structures that have been (presumably) optimized through evolution. State-of-the-art methods, such as McCaskill's algorithm, use a statistical mechanics framework based on the computation of the partition function over the canonical ensemble of all possible secondary structures on a given sequence. Although secondary structure predictions from thermodynamics-based algorithms are not as accurate as methods employing comparative genomics, the former methods are the only available tools to investigate novel RNAs, such as the many RNAs of unknown function recently reported by the ENCODE consortium. In this paper, we generalize the McCaskill partition function algorithm to sum over the grand canonical ensemble of all secondary structures of all mutants of the given sequence. Specifically, our new program, RNAmutants, simultaneously computes for each integer k the minimum free energy structure MFE(k) and the partition function Z(k) over all secondary structures of all k-point mutants, even allowing the user to specify certain positions required not to mutate and certain positions required to base-pair or remain unpaired. This technically important extension allows us to study the resilience of an RNA molecule to pointwise mutations. By computing the mutation profile of a sequence, a novel graphical representation of the mutational tendency of nucleotide positions, we analyze the deleterious nature of mutating specific nucleotide positions or groups of positions. We have successfully applied RNAmutants to investigate deleterious mutations (mutations that radically modify the secondary structure) in the Hepatitis C virus cis-acting replication element and to evaluate the evolutionary pressure applied on different regions of the HIV trans-activation response element. In particular, we show qualitative agreement between published Hepatitis C and HIV experimental mutagenesis studies and our analysis of deleterious mutations using RNAmutants. Our work also predicts other deleterious mutations, which could be verified experimentally. Finally, we provide evidence that the 3′ UTR of the GB RNA virus C has been optimized to preserve evolutionarily conserved stem regions from a deleterious effect of pointwise mutations. We hope that there will be long-term potential applications of RNAmutants in de novo RNA design and drug design against RNA viruses. This work also suggests potential applications for large-scale exploration of the RNA sequence-structure network. Binary distributions are available at http://RNAmutants.csail.mit.edu/

Suffocating cancer: hypoxia-associated epimutations as targets for cancer therapy

Lower than normal levels of oxygen (hypoxia) is a hallmark of all solid tumours rendering them frequently resistant to both radiotherapy and chemotherapy regimes. Furthermore, tumour hypoxia and activation of the hypoxia inducible factor (HIF) transcriptional pathway is associated with poorer prognosis. Driven by both genetic and epigenetic changes, cancer cells do not only survive but thrive in hypoxic conditions. Detailed knowledge of these changes and their functional consequences is of great clinical utility and is already helping to determine phenotypic plasticity, histological tumour grading and overall prognosis and survival stratification in several cancer types. As epigenetic changes - contrary to genetic changes - are potentially reversible, they may prove to be potent therapeutic targets to add to the cancer physicians' armorarium in the future

Selective Cholinergic Depletion in Medial Septum Leads to Impaired Long Term Potentiation and Glutamatergic Synaptic Currents in the Hippocampus

Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning

Mathematical analysis of the "Fractal Tonality" by the composer T. H. Schuler

Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersDas Ziel dieser Diplomarbeit war es, die Musiktheorie "Fraktale Tona- lität", die Thomas Herwig Schuler in seiner Dissertation vorgestellt hat, auf zugrunde liegende mathematische Strukturen zu untersuchen. Ein fundamentaler Unterschied der Fraktalen Tonalität zur traditionellen Musik ist, dass die komplette Obertonreihe verwendet wird. Dadurch hat man sämtliche rationalen Intervalle zur Verfügung. Dementsprechend kommt den mikrotonalen Klängen eine große Bedeutung zu. Die Tonschritte können viel kleiner als in der traditionellen Musik werden - bis hin zur Wahrnehmungsgrenze und in der Theorie auch darüber hinaus.Da es eine größere Vielfalt von Intervallen gibt, existieren neuartige Leitöne und damit neuartige Kadenzen. Die Analyse dieser Kadenzen bildet den größten Teil der Arbeit. Zuerst wird gezeigt, wie solche Kadenzen aufgebaut sind, und dass sie von jedem Subsystem - die Subsysteme lösen in Schulers Theorie die Tonarten aus der traditionellen Musik ab - in jedes Subsystem existieren.Dann werden aus den Kadenzen Schleifen gebildet. Das sind Abfolgen von Kadenzen, die wieder zum Ausgangsakkord zurückführen und daher endlos weiterlaufen können. Sie sind ein wichtiges Element in Schulers Modell.In der Fraktalen Tonalität kann der Komponist Tonleitern nach seinen Vorstellungen konstruieren. Mit den Konstruktionsvorschriften kann man die herkömmlichen siebentönigen Tonleitern aus der reinen Stimmung erhalten, aber man muss sich nicht darauf beschränken, sondern hat eine viel größere Auswahl zur Verfügung. Die Erstellung und die Analyse einer zwölftönigen Tonleiter mit Mikrointervallen bilden den Abschluss der Arbeit.In this thesis we analyse the music theory "fractal tonality" that the composer Thomas Herwig Schuler presented in his dissertation.The goal was to find underlying mathematical structures. A main difference to the traditional music is, that all overtones are used.Thus every rational intervals are available to the composer and microtonal sounds are very important. The steps between tones can be very small - to the perception threshold and in theory even beyond that.Since there is a bigger variety of intervals, there are new leading tones and thus new cadences. The analysis of these cadences is the main part of this work. First we see how this cadences are built. There are cadences from each subsystem to each subsystem. Those subsystems replace the keys in Schuler's theory.We then build loops out of cadences. They are succesions of cadences that lead back to the starting chord. Thus they can continue endlessly.They are an important element of Schuler's model.In the fractal tonality, the composer can build scales according to his wishes. With the construction rules for the scales one can yield the usual seven-tone-scales of the just intonation, but it is not necessary to stick to them. There is a much bigger choice available. The construction and analysis of a twelve-tone-scale form the conclusion of this thesis.7