944 research outputs found
The economic impact of the Budapest Airport on the local economy
Airports have an unquestionably dominant role in the transport of the 21st century; air transport is the heart of the modern, globalised economy. Beyond this primary function, the international literature also emphasises the considerable economic and economy development effects of airports. The significant airports of the world not only facilitate the local economy but fundamentally determine that. The aim of the analysis is not only the study of the economic impact of the Budapest Ferihegy International Airport, but also examining the economic impact of the complex system of the companies operating at the airport and complementing each other. First of all, we discuss the methods and concepts to be applied in the analysis of the economic impact of the Budapest Airport. Although the methods and the terminology is fairly uniform in the course of the general review studies, the actual pieces of research can mean something different by the same concepts or they may examine the same thing with different concepts.
Longitudinal Tomographic Reconstruction of LHC-type Bunches in the SPS
Longitudinal tomographic reconstruction on the basis of measured profiles is an important technique to measure the particle density distribution of a bunch in longitudinal phase space. This measurement technique, well established in all circular machines of the PS complex, has been applied to the SPS for the first time. Due to recent improvements of the data acquisition of the signals from the longitudinal pick-ups in the SPS and a new LHC type wall current monitor, the quality of the bunch profiles is now more appropriate for tomography. Longitudinal beam signals from the wall current pick-ups APWL-10 and WC-2 are used as input for the reconstruction algorithm. It is shown that, due to short bunches and long cables in the SPS, the correction of the signal with the transfer function of the transmission system is indispensable. The analysis of the longitudinal distribution of a batch of 48 bunches of an LHC type beam at injection into the SPS, averaged over more than ten cycles, showed that any systematic variation of the bunch parameters along the batch is shadowed by statistical errors due to the quality of the measured bunch profiles. Avoiding the long coaxial cables from the SPS tunnel to the surface is a crucial issue for improving the quality of the bunch profiles suitable for tomographic reconstruction
Serendipitous Discovery of Light-Induced \u3cem\u3e(In Situ)\u3c/em\u3e Formation of An Azo-Bridged Dimeric Sulfonated Naphthol as a Potent PTP1B Inhibito
Background Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Results Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC50 of 36 ÎŒM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 ÎŒM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. Conclusion We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds
A bacterial chloroform reductive dehalogenase: purification and biochemical characterization
© 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology. We report herein the purification of a chloroform (CF)-reducing enzyme, TmrA, from the membrane fraction of a strict anaerobe Dehalobacter sp. strain UNSWDHB to apparent homogeneity with an approximate 23-fold increase in relative purity compared to crude lysate. The membrane fraction obtained by ultracentrifugation was solubilized in Triton X-100 in the presence of glycerol, followed by purification by anion exchange chromatography. The molecular mass of the purified TmrA was determined to be 44.5 kDa by SDS-PAGE and MALDI-TOF/TOF. The purified dehalogenase reductively dechlorinated CF to dichloromethane in vitro with reduced methyl viologen as the electron donor at a specific activity of (1.27 ± 0.04) Ă 103units mg proteinâ1. The optimum temperature and pH for the activity were 45°C and 7.2, respectively. The UV-visible spectrometric analysis indicated the presence of a corrinoid and two [4Fe-4S] clusters, predicted from the amino acid sequence. This is the first report of the production, purification and biochemical characterization of a CF reductive dehalogenase
Curvature-direction measures of self-similar sets
We obtain fractal Lipschitz-Killing curvature-direction measures for a large
class of self-similar sets F in R^d. Such measures jointly describe the
distribution of normal vectors and localize curvature by analogues of the
higher order mean curvatures of differentiable submanifolds. They decouple as
independent products of the unit Hausdorff measure on F and a self-similar
fibre measure on the sphere, which can be computed by an integral formula. The
corresponding local density approach uses an ergodic dynamical system formed by
extending the code space shift by a subgroup of the orthogonal group. We then
give a remarkably simple proof for the resulting measure version under minimal
assumptions.Comment: 17 pages, 2 figures. Update for author's name chang
T160âphosphorylated CDK2 defines threshold for HGFâdependent proliferation in primary hepatocytes
Liver regeneration is a tightly controlled process mainly achieved by proliferation of usually quiescent hepatocytes. The specific molecular mechanisms ensuring cell division only in response to proliferative signals such as hepatocyte growth factor (HGF) are not fully understood. Here, we combined quantitative time-resolved analysis of primary mouse hepatocyte proliferation at the single cell and at the population level with mathematical modeling. We showed that numerous G1/S transition components are activated upon hepatocyte isolation whereas DNA replication only occurs upon additional HGF stimulation. In response to HGF, Cyclin:CDK complex formation was increased, p21 rather than p27 was regulated, and Rb expression was enhanced. Quantification of protein levels at the restriction point showed an excess of CDK2 over CDK4 and limiting amounts of the transcription factor E2F-1. Analysis with our mathematical model revealed that T160 phosphorylation of CDK2 correlated best with growth factor-dependent proliferation, which we validated experimentally on both the population and the single cell level. In conclusion, we identified CDK2 phosphorylation as a gate-keeping mechanism to maintain hepatocyte quiescence in the absence of HGF
Potato cultivar response to seasonal drought patterns
The ability to minimize potato yield and quality losses due to drought can be greatly improved by understanding the relative responses of different cultivars to seasonal variations in water supply. To address this need, we initiated a two year field experiment to determine the responses of the six potato cultivars to different seasonal drought patterns, including 1) full season irrigation at 100% ET, 2) irrigation at 100% ET terminated during late bulking , 3) full season irrigation at 70% ET , 4) irrigation at 70% ET terminated during late bulking , and 5) a gradual reduction in irrigation from 100% ET during tuber initiation through early bulking, to 70% ET during mid-bulking, and 50% ET through late bulking. GemStar Russet and Ranger Russet, two medium-late maturing cultivars, generally produced the highest yields across the range of drought treatments, but both were fairly sensitive to changes in drought severity. Alturas, a late maturing cultivar, produced relatively high yields with full irrigation, but exhibited the greatest sensitivity to increasing drought severity, particularly when severe late-season water deficits were imposed. Yields for the early maturing cultivar Russet Norkotah were relatively low overall, but it was the least sensitive to changes in drought severity, particularly when late season drought was imposed. Russet Burbank produced comparatively high total yields across the range of drought treatments, but U.S. No. 1 yields were substantially reduced by each seasonal drought pattern. However, it was less sensitive to changes in drought severity than GemStar Russet, Ranger Russet and Alturas. Total and U.S. No. 1 yields for Summit Russet were low for each drought treatment and it exhibited intermediate sensitivity to changes in drought severity. GemStar Russet had the highest water use efficiency based on U.S. No. 1 yield
Identification of inhibitors that target dual-specificity phosphatase 5 provide new insights into the binding requirements for the two phosphate pockets
Background: Dual-specificity phosphatase-5 (DUSP5) plays a central role in vascular development and disease. We present a p-nitrophenol phosphate (pNPP) based enzymatic assay to screen for inhibitors of the phosphatase domain of DUSP5.
Methods: pNPP is a mimic of the phosphorylated tyrosine on the ERK2 substrate (pERK2) and binds the DUSP5 phosphatase domain with a Km of 7.6 ± 0.4 mM. Docking followed by inhibitor verification using the pNPP assay identified a series of polysulfonated aromatic inhibitors that occupy the DUSP5 active site in the region that is likely occupied by the dual-phosphorylated ERK2 substrate tripeptide (pThr-Glu-pTyr). Secondary assays were performed with full length DUSP5 with ERK2 as substrate.
Results: The most potent inhibitor has a naphthalene trisulfonate (NTS) core. A search for similar compounds in a drug database identified suramin, a dimerized form of NTS. While suramin appears to be a potent and competitive inhibitor (25 ± 5 ÎŒM), binding to the DUSP5 phosphatase domain more tightly than the monomeric ligands of which it is comprised, it also aggregates. Further ligand-based screening, based on a pharmacophore derived from the 7 Ă
separation of sulfonates on inhibitors and on sulfates present in the DUSP5 crystal structure, identified a disulfonated and phenolic naphthalene inhibitor (CSD3 _2320) with IC50 of 33 ÎŒM that is similar to NTS and does not aggregate.
Conclusions: The new DUSP5 inhibitors we identify in this study typically have sulfonates 7 Ă
apart, likely positioning them where the two phosphates of the substrate peptide (pThr-Glu-pTyr) bind, with one inhibitor also positioning a phenolic hydroxyl where the water nucleophile may reside. Polysulfonated aromatic compounds do not commonly appear in drugs and have a tendency to aggregate. One FDA-approved polysulfonated drug, suramin, inhibits DUSP5 and also aggregates. Docking and modeling studies presented herein identify polysulfonated aromatic inhibitors that do not aggregate, and provide insights to guide future design of mimics of the dual-phosphate loops of the ERK substrates for DUSPs.
Keywords: DUSP5, Phosphatase, Drug discovery, Docking, Suramin, Vascular anomalie
Piecewise Linear Models for the Quasiperiodic Transition to Chaos
We formulate and study analytically and computationally two families of
piecewise linear degree one circle maps. These families offer the rare
advantage of being non-trivial but essentially solvable models for the
phenomenon of mode-locking and the quasi-periodic transition to chaos. For
instance, for these families, we obtain complete solutions to several questions
still largely unanswered for families of smooth circle maps. Our main results
describe (1) the sets of maps in these families having some prescribed rotation
interval; (2) the boundaries between zero and positive topological entropy and
between zero length and non-zero length rotation interval; and (3) the
structure and bifurcations of the attractors in one of these families. We
discuss the interpretation of these maps as low-order spline approximations to
the classic ``sine-circle'' map and examine more generally the implications of
our results for the case of smooth circle maps. We also mention a possible
connection to recent experiments on models of a driven Josephson junction.Comment: 75 pages, plain TeX, 47 figures (available on request
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