Coumarins and other fused bicyclic heterocycles with selective tumor-associated carbonic anhydrase isoforms inhibitory activity

Herein we report for the first time a series of 2-benzamido-N-(2-oxo-4-(methyl/trifluoromethyl)-2H-chromen-7-yl) benzamide 3a–f and substituted quinazolin-4(3H)-ones and 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (5, 6, 8 and 10a–c) as selective inhibitors of the tumor associated hCA IX and XII isoforms. Among the compounds reported the trifluoromethyl derivative 3d resulted the most potent against these CA isoforms with KIs of 10.9 and 6.7 n

Synthesis of new 3-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-benzenesulfonamides with strong inhibition properties against the tumor associated carbonic anhydrases IX and XII

We report a series of novel metanilamide-based derivatives 3a–q bearing the 2-mercapto-4-oxo-4H-quinazolin-3-yl moiety as tail. All compounds were synthesized by means of straightforward condensation procedures and were investigated in vitro for their inhibition potency against the human (h) carbonic anhydrase (CA; EC 4.2.1.1.1) isoforms I, II, IX and XII. Among all compounds tested the 6-iodo 3g and the 7-fluoro 3i derivatives were the most potent inhibitors against the tumor associated CA IX and XII isoform (KIs 1.5 and 2.7 nM respectively for the hCA IX and KIs 0.57 and 1.9 nM respectively for the hCA XII). The kinetic data reported here strongly support compounds of this type for their future development as radiotracers in tumor pathologies which are strictly dependent on the enzymatic activity of the hCA IX and XII isoforms

Long-term and recent changes in sea level in the Falkland Islands

Mean sea level measurements made at Port Louis in the Falkland Islands in 1981-2, 1984 and 2009, together with values from the nearby permanent tide gauge at Port Stanley, have been compared to measurements made at Port Louis in 1842 by James Clark Ross. The long-term rate of change of sea level is estimated to have been +0.75 ± 0.35 mm/year between 1842 and the early 1980s, after correction for air pressure effects and for vertical land movement due to Glacial Isostatic Adjustment (GIA). The 2009 Port Louis data set is of particular importance due to the availability of simultaneous information from Port Stanley. The data set has been employed in two ways, by providing a short recent estimate of mean sea level itself, and by enabling the effective combination of measurements at the two sites. The rate of sea level rise observed since 1992, when the modern Stanley gauge was installed, has been larger at 2.51 ± 0.58 mm/year, after correction for air pressure and GIA. This rate compares to a value of 2.79 ± 0.42 mm/year obtained from satellite altimetry in the region over the same period. Such a relatively recent acceleration in the rate of sea level rise is consistent with findings from other locations in the southern hemisphere and globall

A Survey on Retrieval of Mathematical Knowledge

We present a short survey of the literature on indexing and retrieval of mathematical knowledge, with pointers to 72 papers and tentative taxonomies of both retrieval problems and recurring techniques.Comment: CICM 2015, 20 page

Tulsa: a tool for transforming UML to layered queueing networks for performance analysis of data intensive applications

Motivated by the problem of detecting software performance anti-patterns in data-intensive applications (DIAs), we present a tool, Tulsa, for transforming software architecture models specified through UML into Layered Queueing Networks (LQNs), which are analytical performance models used to capture contention across multiple software layers. In particular, we generalize an existing transformation based on the Epsilon framework to generate LQNs from UML models annotated with the DICE profile, which extends UML to modelling DIAs based on technologies such as Apache Storm

Anterior-inferior plating of middle-third fractures of the clavicle

© The Author(s) 2009. This article is published with open access at Springerlink.com Introduction Various techniques have been reported for the treatment of middle-third clavicle (collar bone) fractures. This prospective study was conducted to evaluate the results of anterior-inferior plating using a 3.5-mm reconstruction plate for the treatment of middle-third clavicle fractures

Prevalence, Recognition, And Management Of Mental Disorders In Primary Care

According to latest figures, 50% of individuals will have a minimum of one mental health issue in their lifetime, with at least 25% experiencing a mental condition in the previous year. primary care doctors are overwhelmingly responsible for recognition, evaluation, therapy, and referral, with at least one-third of their consultations containing a direct and obvious mental aspect Primary care physicians are the foundation of the majority of medical care programs that involve recognizing, diagnosing, treating, and referring patients to specialists for every kind of diseases, whether physical, mental, or both. Over the last two decades, there has been a greater emphasis on this position, notably in the treatment of mental problems in primary care

Using models of the ocean's mean dynamic topography to identify errors in coastal geodetic levelling

Identifying errors (blunders and systematic errors) in coastal geodetic levelling networks has often been problematic. This is because (1) mean sea level (MSL) at tide gauges cannot be directly compared to height differences from levelling because the geoid/quasigeoid and MSL are not parallel, being separated by the ocean’s mean dynamic topography (MDT) and (2) the lack of redundancy at the edge of the levelling network. This paper sets out a methodology to independently identify blunders and/or systematic errors (over long distances) in geodetic levelling using MDT models to account for the separation between the geoid/quasigeoid and MSL at tide gauges. This method is then tested in a case study using an oceanographic MDT model, MSL observations, GNSS data and a quasigeoid model. The results are significant because the errors found could not be detected by standard levelling misclosure checks alone, with supplementary data from an MDT model, with cross-validation from GNSS-quasigeoid allowing their detection. In addition, it appears that an oceanographic-only MDT is as effective as GNSS and a quasigeoid model for detecting levelling errors, which could be particularly useful for countries with coastal levelling errors in their levelling networks that cannot be identified by conventional levelling closure checks