546 research outputs found
Discontinuities of the integrated density of states for random operators on Delone sets
Despite all the analogies with "usual random" models, tight binding operators
for quasicrystals exhibit a feature which clearly distinguishes them from the
former: the integrated density of states may be discontinuous. This phenomenon
is identified as a local effect, due to occurrence of eigenfunctions with
bounded support.Comment: 9 pages, 2 figure
Digital analysis of cDNA abundance; expression profiling by means of restriction fragment fingerprinting
BACKGROUND: Gene expression profiling among different tissues is of paramount interest in various areas of biomedical research. We have developed a novel method (DADA, Digital Analysis of cDNA Abundance), that calculates the relative abundance of genes in cDNA libraries. RESULTS: DADA is based upon multiple restriction fragment length analysis of pools of clones from cDNA libraries and the identification of gene-specific restriction fingerprints in the resulting complex fragment mixtures. A specific cDNA cloning vector had to be constructed that governed missing or incomplete cDNA inserts which would generate misleading fingerprints in standard cloning vectors. Double stranded cDNA was synthesized using an anchored oligo dT primer, uni-directionally inserted into the DADA vector and cDNA libraries were constructed in E. coli. The cDNA fingerprints were generated in a PCR-free procedure that allows for parallel plasmid preparation, labeling, restriction digest and fragment separation of pools of 96 colonies each. This multiplexing significantly enhanced the throughput in comparison to sequence-based methods (e.g. EST approach). The data of the fragment mixtures were integrated into a relational database system and queried with fingerprints experimentally produced by analyzing single colonies. Due to limited predictability of the position of DNA fragments on the polyacrylamid gels of a given size, fingerprints derived solely from cDNA sequences were not accurate enough to be used for the analysis. We applied DADA to the analysis of gene expression profiles in a model for impaired wound healing (treatment of mice with dexamethasone). CONCLUSIONS: The method proved to be capable of identifying pharmacologically relevant target genes that had not been identified by other standard methods routinely used to find differentially expressed genes. Due to the above mentioned limited predictability of the fingerprints, the method was yet tested only with a limited number of experimentally determined fingerprints and was able to detect differences in gene expression of transcripts representing 0.05% of the total mRNA population (e.g. medium abundant gene transcripts)
Additive Manufacturing of Glass Components - Exploring the Potential of Glass Connections by Fused Deposition Modeling
Glass is an indispensable material in the building industry. The combination of transparency, strength and durability makes it to an unparalleled and desirable material. The technology additive manufacturing (AM) has a potential in the building industry, based on a relatively small amount of repetitions of particular building components and the tendency of applying technology innovations for buildings. Therefore, there is an interest for additive manufacturing with glass. This paper presents and summarizes the results of the preliminary research regarding additive manufacturing of glass components for joining methods for flat glass structures. Different types of glass (borosilicate glass, quartz glass and soda lime silicate glass) are discussed. Experimental investigations of joints are intended to illustrate the performance and potential of AM glass components in case of structural use. Load bearing tests were carried out to quantify the strength and load bearing capacity level of an AM structural component. The thermal residual stresses were examined by photo-elastic tests with polarized lights and scattered light method. The investigations show in principle that load transfer via fused glass joints is possible. The performed research activity is a first step towards the Additive Manufacturing of glass structures on flat glass
Crystal structure of 7,8-dihydroneopterin triphosphate epimerase
AbstractBackground: Dihydroneopterin triphosphate (H2NTP) is the central substrate in the biosynthesis of folate and tetrahydrobiopterin. Folate serves as a cofactor in amino acid and purine biosynthesis and tetrahydrobiopterin is used as a cofactor in amino acid hydroxylation and nitric oxide synthesis. In bacteria, H2NTP enters the folate biosynthetic pathway after nonenzymatic dephosphorylation; in vertebrates, H2NTP is used to synthesize tetrahydrobiopterin. The dihydroneopterin triphosphate epimerase of Escherichia coli catalyzes the inversion of carbon 2′ of H2NTP.Results: The crystal structure of the homo-octameric protein has been solved by a combination of multiple isomorphous replacement, Patterson search techniques and cyclic averaging and has been refined to a crystallographic R factor of 18.8% at 2.9 Å resolution. The enzyme is a torus-shaped, D4 symmetric homo-octamer with approximate dimensions of 65 × 65 Å. Four epimerase monomers form an unusual 16-stranded antiparallel β barrel by tight association between the N- and C-terminal β strands of two adjacent subunits. Two tetramers associate in a head-to-head fashion to form the active enzyme complex.Conclusions: The folding topology, quaternary structure and amino acid sequence of epimerase is similar to that of the dihydroneopterin aldolase involved in the biosynthesis of the vitamin folic acid. The monomer fold of epimerase is also topologically similar to that of GTP cyclohydrolase I (GTP CH-1), 6-pyrovoyl tetrahydropterin synthase (PTPS) and uroate oxidase (UO). Despite a lack of significant sequence homology these proteins share a common subunit fold and oligomerize to form central β barrel structures employing different cyclic symmetry elements, D4, D5, D3 and D2, respectively. Moreover, these enzymes have a topologically equivalent acceptor site for the 2-amino-4-oxo pyrimidine (2-oxo-4-oxo pyrimidine in uroate oxidase) moiety of their respective substrates
Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells
High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPs; particles < 0.1 μm). Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 μm) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential
Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer
<p>Abstract</p> <p>Introduction</p> <p>To evaluate efficacy and secondary resectability in patients with locally advanced pancreatic cancer (LAPC) treated with neoadjuvant chemoradiotherapy (CRT).</p> <p>Patients and methods</p> <p>A total of 215 patients with locally advanced pancreatic cancer were treated with chemoradiation at a single institution. Radiotherapy was delivered with a median dose of 52.2 Gy in single fractions of 1.8 Gy. Chemotherapy was applied concomitantly as gemcitabine (GEM) at a dose of 300 mg/m<sup>2 </sup>weekly, followed by adjuvant cycles of full-dose GEM (1000 mg/m<sup>2</sup>). After neoadjuvant CRT restaging was done to evaluate secondary resectability. Overall and disease-free survival were calculated and prognostic factors were estimated.</p> <p>Results</p> <p>After CRT a total of 26% of all patients with primary unresectable LAPC were chosen to undergo secondary resection. Tumour free resection margins could be achieved in 39.2% (R0-resection), R1-resections were seen in 41.2%, residual macroscopic tumour in 11.8% (R2) and in 7.8% resection were classified as Rx. Patients with complete resection after CRT showed a significantly increased median overall survival (OS) with 22.1 compared to 11.9 months in non-resected patients. Median OS and disease-free survival (DFS) of all patients were 12.3 and 8.1 months respectively. In most cases the first site of disease progression was systemic with hepatic (52%) and peritoneal (36%) metastases.</p> <p>Discussion</p> <p>A high percentage of patients with locally advanced pancreatic cancer can undergo secondary resection after gemcitabine-based chemoradiation and has a relative long-term prognosis after complete resection.</p
Functional MRI for Treatment Evaluation in Patients with Head and Neck Squamous Cell Carcinoma:A Review of the Literature from a Radiologist Perspective
Purpose of review: To show the role of functional MRI in patients treated for head and neck squamous cell carcinoma. Recent findings: MRI is commonly used for treatment evaluation in patients with head and neck tumors. However, anatomical MRI has its limits in differentiating between post-treatment effects and tumor recurrence. Recent studies showed promising results of functional MRI for response evaluation. Summary: This review analyzes possibilities and limitations of functional MRI sequences separately to obtain insight in the post-therapy setting. Diffusion, perfusion and spectroscopy show promise, especially when utilized complimentary to each other. These functional MRI sequences aid in the early detection which might improve survival by increasing effectiveness of salvage therapy. Future multicenter longitudinal prospective studies are needed to provide standardized guidelines for the use of functional MRI in daily clinical practice
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