Cluster Performance reconsidered: Structure, Linkages and Paths in the German Biotechnology Industry, 1996-2003

This paper addresses the evolution of biotechnology clusters in Germany between 1996 and 2003, paying particular attention to their respective composition in terms of venture capital, basic science institutions and biotechnology firms. Drawing upon the significance of co-location of "money and ideas", the literature stressing the importance of a cluster's openness and external linkages, and the path dependency debate, the paper aims to analyse how certain cluster characteristics correspond with its overall performance. After identifying different cluster types, we investigate their internal and external interconnectivity in comparative manner and draw on changes in cluster composition. Our results indicate that the structure, i.e. to which group the cluster belongs, and the openness towards external knowledge flows deliver merely unsystematic indications with regard to a cluster's overall success. Its ability to change composition towards a more balanced ratio of science and capital over time, on the other hand, turns out as a key explanatory factor. Hence, the dynamic perspective proves effective illuminating cluster growth and performance, where our explorative findings provide a promising avenue for further evolutionary research

Managing understory light conditions in boreal mixedwoods through variation in the intensity and spatial pattern of harvest: A modelling approach

In the context of partial harvesting, adequately managing post-harvest light conditions are essential to obtain a desired composition of tree species regeneration. The objective of this study was to determine how varying the intensity and spatial pattern of harvest would affect understory light conditions in boreal mixedwood stands of northwestern Quebec using the spatially explicit SORTIE-ND light model. The model was evaluated based on comparisons of observed and predicted light levels in both mapped and un-mapped plots. In mapped plots, reasonably accurate predictions of the overall variation in light levels were obtained, but predictions tended to lack spatial precision. In un-mapped plots, SORTIE-ND accurately predicted stand-level mean GLI (Gap Light Index) under a range of harvest intensities. The model was then used to simulate nine silvicultural treatments based on combinations of three intensities of overstory removal (30%, 45% and 60% of basal area) and three harvest patterns (uniform, narrow strips, large gaps). Simulations showed that increasing overstory removal had less impact on light conditions with uniform harvests, and a more marked effect with more aggregated harvest patterns. Whatever the harvest intensity, uniform cuts almost never created high light conditions (GLI > 50%). Gap cuts, on the other hand, resulted in up to 40% of microsites receiving GLI > 50%. Our results suggest that either a 30% strip or gap cut or a 45–60% uniform partial harvest could be used to accelerate the transition from an aspen dominated composition to a mixedwood stand because both types of cut generate the greatest proportion of moderately low light levels (e.g., 15–40% GLI). These light levels tend to favour an accelerated growth response among shade-tolerant conifers, while preventing excessive recruitment of shade-intolerant species. A better understanding of how spatial patterns of harvest interact with tree removal intensity to affect understory light conditions can provide opportunities for designing silvicultural prescriptions that are tailored to species’ traits and better suited to meet a variety of management objectives

Neutron spin echo spectroscopy under 17 T magnetic field at RESEDA

We report proof-of-principle measurements at the neutron resonance spin echo spectrometer RESEDA (MLZ) under large magnetic fields by means of Modulation of IntEnsity with Zero Effort (MIEZE). Our study demonstrates the feasibility of applying strong magnetic fields up to 17 T at the sample while maintaining unchanged sub-μeV resolution. We find that the MIEZE-spin-echo resolution curve remains essentially unchanged as a function of magnetic field up to the highest fields available, promising access to high fields without need for additional fine-tuning of the instrument. This sets the stage for the experimental investigations of subtle field dependent phenomena, such as magnetic field-driven phase transitions in hard and soft condensed matter physics

Annotating genes and genomes with DNA sequences extracted from biomedical articles

Motivation: Increasing rates of publication and DNA sequencing make the problem of finding relevant articles for a particular gene or genomic region more challenging than ever. Existing text-mining approaches focus on finding gene names or identifiers in English text. These are often not unique and do not identify the exact genomic location of a study

The permanently chaperone-active small heat shock protein Hsp17 from Caenorhabditis elegans exhibits topological separation of its N-terminal regions

Small Heat shock proteins (sHsps) are a family of molecular chaperones that bind nonnative proteins in an ATP-independent manner. Caenorhabditis elegans encodes 16 different sHsps, among them Hsp17, which is evolutionarily distinct from other sHsps in the nematode. The structure and mechanism of Hsp17 and how these may differ from other sHsps remain unclear. Here, we find that Hsp17 has a distinct expression pattern, structural organization, and chaperone function. Consistent with its presence under nonstress conditions, and in contrast to many other sHsps, we determined that Hsp17 is a mono-disperse, permanently active chaperone in vitro, which interacts with hundreds of different C. elegans proteins under physiological conditions. Additionally, our cryo-EM structure of Hsp17 reveals that in the 24-mer complex, 12 N-terminal regions are involved in its chaperone function. These flexible regions are located on the outside of the spherical oligomer, whereas the other 12 N-terminal regions are engaged in stabilizing interactions in its interior. This allows the same region in Hsp17 to perform different functions depending on the topological context. Taken together, our results reveal structural and functional features that further define the structural basis of permanently active sHsps

pubmed2ensembl: A Resource for Mining the Biological Literature on Genes

The last two decades have witnessed a dramatic acceleration in the production of genomic sequence information and publication of biomedical articles. Despite the fact that genome sequence data and publications are two of the most heavily relied-upon sources of information for many biologists, very little effort has been made to systematically integrate data from genomic sequences directly with the biological literature. For a limited number of model organisms dedicated teams manually curate publications about genes; however for species with no such dedicated staff many thousands of articles are never mapped to genes or genomic regions.To overcome the lack of integration between genomic data and biological literature, we have developed pubmed2ensembl (http://www.pubmed2ensembl.org), an extension to the BioMart system that links over 2,000,000 articles in PubMed to nearly 150,000 genes in Ensembl from 50 species. We use several sources of curated (e.g., Entrez Gene) and automatically generated (e.g., gene names extracted through text-mining on MEDLINE records) sources of gene-publication links, allowing users to filter and combine different data sources to suit their individual needs for information extraction and biological discovery. In addition to extending the Ensembl BioMart database to include published information on genes, we also implemented a scripting language for automated BioMart construction and a novel BioMart interface that allows text-based queries to be performed against PubMed and PubMed Central documents in conjunction with constraints on genomic features. Finally, we illustrate the potential of pubmed2ensembl through typical use cases that involve integrated queries across the biomedical literature and genomic data.By allowing biologists to find the relevant literature on specific genomic regions or sets of functionally related genes more easily, pubmed2ensembl offers a much-needed genome informatics inspired solution to accessing the ever-increasing biomedical literature

Contribution of CTCF binding to transcriptional activity at the HOXA locus in NPM1-mutant AML cells

Transcriptional regulation of the HOXA genes is thought to involve CTCF-mediated chromatin loops and the opposing actions of the COMPASS and Polycomb epigenetic complexes. We investigated the role of these mechanisms at the HOXA cluster in AML cells with the common NPM1c mutation, which express both HOXA and HOXB genes. CTCF binding at the HOXA locus is conserved across primary AML samples, regardless of HOXA gene expression, and defines a continuous chromatin domain marked by COMPASS-associated histone H3 trimethylation in NPM1-mutant primary AML samples. Profiling of the three-dimensional chromatin architecture in primary AML samples with the NPM1c mutation identified chromatin loops between the HOXA cluster and loci in the SNX10 and SKAP2 genes, and an intergenic region located 1.4 Mbp upstream of the HOXA locus. Deletion of CTCF binding sites in the NPM1-mutant OCI-AML3 AML cell line reduced multiple long-range interactions, but resulted in CTCF-independent loops with sequences in SKAP2 that were marked by enhancer-associated histone modifications in primary AML samples. HOXA gene expression was maintained in CTCF binding site mutants, indicating that transcriptional activity at the HOXA locus in NPM1-mutant AML cells may be sustained through persistent interactions with SKAP2 enhancers, or by intrinsic factors within the HOXA gene cluster

Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G>A and c.707T>C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dop

Viewing forests through the lens of complex systems science

Complex systems science provides a transdisciplinary framework to study systems characterized by (1) heterogeneity, (2) hierarchy, (3) self‐organization, (4) openness, (5) adaptation, (6) memory, (7) non‐linearity, and (8) uncertainty. Complex systems thinking has inspired both theory and applied strategies for improving ecosystem resilience and adaptability, but applications in forest ecology and management are just beginning to emerge. We review the properties of complex systems using four well‐studied forest biomes (temperate, boreal, tropical and Mediterranean) as examples. The lens of complex systems science yields insights into facets of forest structure and dynamics that facilitate comparisons among ecosystems. These biomes share the main properties of complex systems but differ in specific ecological properties, disturbance regimes, and human uses. We show how this approach can help forest scientists and managers to conceptualize forests as integrated social‐ecological systems and provide concrete examples of how to manage forests as complex adaptive systems

Dissecting the Transcriptional Regulatory Properties of Human Chromosome 16 Highly Conserved Non-Coding Regions

Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs) have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions