IMAGE: a multivariate multi-site stochastic weather generator for European weather and climate

Capturing the spatial and temporal correlation of multiple variables in a weather generator is challenging. A new massively multi-site, multivariate daily stochastic weather generator called IMAGE is presented here. It models temperature and precipitation variables as latent Gaussian variables with temporal behaviour governed by an auto-regressive model whose residuals and parameters are correlated through resampling of principle component time series of empirical orthogonal function modes. A case study using European climate data demonstrates the model’s ability to reproduce extreme events of temperature and precipitation. The ability to capture the spatial and temporal extent of extremes using a modified Climate Extremes Index is demonstrated. Importantly, the model generates events covering not observed temporal and spatial scales giving new insights for risk management purposes

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

annot8r: GO, EC and KEGG annotation of EST datasets

<p>Abstract</p> <p>Background</p> <p>The expressed sequence tag (EST) methodology is an attractive option for the generation of sequence data for species for which no completely sequenced genome is available. The annotation and comparative analysis of such datasets poses a formidable challenge for research groups that do not have the bioinformatics infrastructure of major genome sequencing centres. Therefore, there is a need for user-friendly tools to facilitate the annotation of non-model species EST datasets with well-defined ontologies that enable meaningful cross-species comparisons. To address this, we have developed annot8r, a platform for the rapid annotation of EST datasets with GO-terms, EC-numbers and KEGG-pathways.</p> <p>Results</p> <p>annot8r automatically downloads all files relevant for the annotation process and generates a reference database that stores UniProt entries, their associated Gene Ontology (GO), Enzyme Commission (EC) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotation and additional relevant data. For each of GO, EC and KEGG, annot8r extracts a specific sequence subset from the UniProt dataset based on the information stored in the reference database. These three subsets are then formatted for BLAST searches. The user provides the protein or nucleotide sequences to be annotated and annot8r runs BLAST searches against these three subsets. The BLAST results are parsed and the corresponding annotations retrieved from the reference database. The annotations are saved both as flat files and also in a relational postgreSQL results database to facilitate more advanced searches within the results. annot8r is integrated with the PartiGene suite of EST analysis tools.</p> <p>Conclusion</p> <p>annot8r is a tool that assigns GO, EC and KEGG annotations for data sets resulting from EST sequencing projects both rapidly and efficiently. The benefits of an underlying relational database, flexibility and the ease of use of the program make it ideally suited for non-model species EST-sequencing projects.</p

A markov classification model for metabolic pathways

<p>Abstract</p> <p>Background</p> <p>This paper considers the problem of identifying pathways through metabolic networks that relate to a specific biological response. Our proposed model, HME3M, first identifies frequently traversed network paths using a Markov mixture model. Then by employing a hierarchical mixture of experts, separate classifiers are built using information specific to each path and combined into an ensemble prediction for the response.</p> <p>Results</p> <p>We compared the performance of HME3M with logistic regression and support vector machines (SVM) for both simulated pathways and on two metabolic networks, glycolysis and the pentose phosphate pathway for <it>Arabidopsis thaliana</it>. We use AltGenExpress microarray data and focus on the pathway differences in the developmental stages and stress responses of <it>Arabidopsis</it>. The results clearly show that HME3M outperformed the comparison methods in the presence of increasing network complexity and pathway noise. Furthermore an analysis of the paths identified by HME3M for each metabolic network confirmed known biological responses of <it>Arabidopsis</it>.</p> <p>Conclusions</p> <p>This paper clearly shows HME3M to be an accurate and robust method for classifying metabolic pathways. HME3M is shown to outperform all comparison methods and further is capable of identifying known biologically active pathways within microarray data.</p

Primary pyogenic spondylitis following kyphoplasty: a case report

<p>Abstract</p> <p>Introduction</p> <p>Only ten cases of primary pyogenic spondylitis following vertebroplasty have been reported in the literature. To the best of our knowledge, we present the first reported case of primary pyogenic spondylitis and spondylodiscitis caused by kyphoplasty.</p> <p>Case presentation</p> <p>A 72-year old Caucasian man with an osteoporotic compression fracture of the first lumbar vertebra after kyphoplasty developed sensory incomplete paraplegia below the first lumbar vertebra. This was caused by myelon compression following pyogenic spondylitis with a psoas abscess. Computed tomography guided aspiration of the abscess cavity yielded group C <it>Streptococcus</it>. The psoas abscess was percutaneously drained and laminectomy and posterior instrumentation with an internal fixator from the eleventh thoracic vertebra to the fourth lumbar vertebra was performed. In a second operation, corpectomy of the first lumbar vertebra with cement removal and fusion from the twelfth thoracic vertebra to the second lumbar vertebra with a titanium cage was performed. Six weeks postoperatively, the patient was pain free with no neurologic deficits or signs of infection.</p> <p>Conclusion</p> <p>Pyogenic spondylitis is an extremely rare complication after kyphoplasty. When these patients develop recurrent back pain postoperatively, the diagnosis of pyogenic spondylitis must be considered.</p

From biomedicine to natural history research: EST resources for ambystomatid salamanders

BACKGROUND: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories. RESULTS: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the A. t. tigrinum ESTs were obtained primarily from a normalized library, an approximately equal number of contigs were obtained for each species, with 21,091 unique contigs identified overall. The 10,592 contigs that showed significant similarity to sequences from the human RefSeq database reflected a diverse array of molecular functions and biological processes, with many corresponding to genes expressed during spinal cord injury in rat and fin regeneration in zebrafish. To demonstrate the utility of these EST resources, we searched databases to identify probes for regeneration research, characterized intra- and interspecific nucleotide polymorphism, saturated a human – Ambystoma synteny group with marker loci, and extended PCR primer sets designed for A. mexicanum / A. t. tigrinum orthologues to a related tiger salamander species. CONCLUSIONS: Our study highlights the value of developing resources in traditional model systems where the likelihood of information transfer to multiple, closely related taxa is high, thus simultaneously enabling both laboratory and natural history research

Modelling and Verification of Energy Consumption in CNC Milling

Electrical energy consumption forms 99% of the environmental impact of machining operations. Whilst replacing existing machineries for more energy efficient ones does not deem possible in short term, process planning for machining with energy consumption in mind is a more accessible solution. The effect of cutting parameters on power consumption in CNC milling of 6082 T6 aluminum alloy was investigated in this paper. Mathematical models were developed to estimate the energy and power consumption in CNC milling machines. The analysis indicated that the two less studied parameters of axial and radial depth of cut have significant impact on the total energy consumption of machining processes. Increased axial and radial depth of cut not only increase material removal rate but also increase the portion of machine tool’s power consumption dedicated to material cutting. This study indicated that 82% reduction in energy consumption can be achieved through precise selection of cuttingparameters.<br/

Novel approaches and perspectives in allergen immunotherapy

In this review, we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments such as peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

Bringing Back a Healthy Buzz? Invertebrate Parasites and Reintroductions:A Case Study in Bumblebees

Reintroductions can play a key role in the conservation of endangered species. Parasites may impact reintroductions, both positively and negatively, but few case studies of how to manage parasites during reintroductions exist. Bumblebees are in decline at regional and global scales, and reintroductions can be used to re-establish extinct local populations. Here we report on how the risks associated with parasites are being managed in an ongoing reintroduction of the short-haired bumblebee, Bombus subterraneus, to the UK. Disease risk analysis was conducted and disease risk management plans constructed to design a capture-quarantine-release system that minimised the impacts on both the bumblebees and on their natural parasites. Given that bumblebee parasites are (i) generalists, (ii) geographically ubiquitous, and (iii) show evidence of local adaptation, the disease risk management plan was designed to limit the co-introduction of parasites from the source population in Sweden to the destination site in the UK. Results suggest that this process at best eliminated, or at least severely curtailed the co-introduction of parasites, and ongoing updates of the plan enabled minimization of impacts on natural host-parasite dynamics in the Swedish source population. This study suggests that methods designed for reintroductions of vertebrate species can be successfully applied to invertebrates. Future reintroductions of invertebrates where the parasite fauna is less well known should take advantage of next-generation barcoding and multiple survey years prior to the start of reintroductions, to develop comprehensive disease risk management plans