Automatic sets of rational numbers

The notion of a k-automatic set of integers is well-studied. We develop a new notion - the k-automatic set of rational numbers - and prove basic properties of these sets, including closure properties and decidability.Comment: Previous version appeared in Proc. LATA 2012 conferenc

Passive ocean acoustic tomography: theory and experiment

In this paper the Passive Ocean Acoustic Tomography (P-OAT) methodology is presented. This technique, avoiding the use of a dedicated active sound source, estimates the sea water temperature spatial distribution from the received noise emitted from ships of opportunity. The feasibility of the proposed methodology has been confirmed both by test-runs on semi-synthetic data and by the use of real acoustic and environmental data collected during INTIMATE00 experiment performed on October 2000 in the Atlantic Ocean off the Portuguese coasts

Novel complex MAD phasing and RNase H structural insights using selenium oligonucleotides

The crystal structures of protein–nucleic acid complexes are commonly determined using selenium-derivatized proteins via MAD or SAD phasing. Here, the first protein–nucleic acid complex structure determined using selenium-derivatized nucleic acids is reported. The RNase H–RNA/DNA complex is used as an example to demonstrate the proof of principle. The high-resolution crystal structure indicates that this selenium replacement results in a local subtle unwinding of the RNA/DNA substrate duplex, thereby shifting the RNA scissile phosphate closer to the transition state of the enzyme-catalyzed reaction. It was also observed that the scissile phosphate forms a hydrogen bond to the water nucleophile and helps to position the water molecule in the structure. Consistently, it was discovered that the substitution of a single O atom by a Se atom in a guide DNA sequence can largely accelerate RNase H catalysis. These structural and catalytic studies shed new light on the guide-dependent RNA cleavage

Model Order Reduction for Rotating Electrical Machines

The simulation of electric rotating machines is both computationally expensive and memory intensive. To overcome these costs, model order reduction techniques can be applied. The focus of this contribution is especially on machines that contain non-symmetric components. These are usually introduced during the mass production process and are modeled by small perturbations in the geometry (e.g., eccentricity) or the material parameters. While model order reduction for symmetric machines is clear and does not need special treatment, the non-symmetric setting adds additional challenges. An adaptive strategy based on proper orthogonal decomposition is developed to overcome these difficulties. Equipped with an a posteriori error estimator the obtained solution is certified. Numerical examples are presented to demonstrate the effectiveness of the proposed method

Derivatization of DNAs with selenium at 6-position of guanine for function and crystal structure studies

To investigate nucleic acid base pairing and stacking via atom-specific mutagenesis and crystallography, we have synthesized for the first time the 6-Se-deoxyguanosine phosphoramidite and incorporated it into DNAs via solid-phase synthesis with a coupling yield over 97%. We found that the UV absorption of the Se-DNAs red-shifts over 100 nm to 360 nm (ε = 2.3 × 104 M−1 cm−1), the Se-DNAs are yellow colored, and this Se modification is relatively stable in water and at elevated temperature. Moreover, we successfully crystallized a ternary complex of the Se-G-DNA, RNA and RNase H. The crystal structure determination and analysis reveal that the overall structures of the native and Se-modified nucleic acid duplexes are very similar, the selenium atom participates in a Se-mediated hydrogen bond (Se … H–N), and the SeG and C form a base pair similar to the natural G–C pair though the Se-modification causes the base-pair to shift (approximately 0.3 Å). Our biophysical and structural studies provide new insights into the nucleic acid flexibility, duplex recognition and stability. Furthermore, this novel selenium modification of nucleic acids can be used to investigate chemogenetics and structure of nucleic acids and their protein complexes

Proteomics identifies neddylation as a potential therapy target in small intestinal neuroendocrine tumors.

Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET

Copernicus Marine Service Ocean State Report

This is the final version. Available from Taylor & Francis via the DOI in this record