A framework for traversing dense annotation lattices

Pattern matching, or querying, over annotations is a general purpose paradigm for inspecting, navigating, mining, and transforming annotation repositories—the common representation basis for modern pipelined text processing architectures. The open-ended nature of these architectures and expressiveness of feature structure-based annotation schemes account for the natural tendency of such annotation repositories to become very dense, as multiple levels of analysis get encoded as layered annotations. This particular characteristic presents challenges for the design of a pattern matching framework capable of interpreting ‘flat’ patterns over arbitrarily dense annotation lattices. We present an approach where a finite state device applies (compiled) pattern grammars over what is, in effect, a linearized ‘projection’ of a particular route through the lattice. The route is derived by a mix of static grammar analysis and runtime interpretation of navigational directives within an extended grammar formalism; it selects just the annotations sequence appropriate for the patterns at hand. For expressive and efficient pattern matching in dense annotations stores, our implemented approach achieves a mix of lattice traversal and finite state scanning by exposing a language which, to its user, provides constructs for specifying sequential, structural, and configurational constraints among annotations.     

Evidence for differential binding of isoniazid by Mycobacterium tuberculosis KatG and the isoniazid-resistant mutant KatG(S315T)

Isoniazid is a mainstay of antibiotic therapy for the treatment of tuberculosis, but its molecular mechanism of action is unclear. Previous investigators have hypothesized that isoniazid is a prodrug that requires in vivo activation by KatG, the catalase-peroxidase of Mycobacterium tuberculosis, and that resistance to isoniazid strongly correlates with deletions or point mutations in KatG. One such mutation, KatG(S315T), is found in approximately 50% of clinical isolates exhibiting isoniazid resistance. In this work, 1H nuclear magnetic resonance T1 relaxation measurements indicate that KatG and KatG(S315T) each bind isoniazid at a position approximately 12 A from the active site heme iron. Electron paramagnetic resonance spectroscopy revealed heterogeneous populations of high-spin ferric heme in both wild-type KatG and KatG(S315T) with the ratios of each species differing between the two enzymes. Small changes in the proportions of these high-spin species upon addition of isoniazid support the finding that isoniazid binds near the heme periphery of both enzymes. Titration of wild-type KatG with isoniazid resulted in the appearance of a "type I" substrate-induced difference spectrum analogous to those seen upon substrate binding to the cytochromes P450. The difference spectrum may result from an isoniazid-induced change in a portion of the KatG heme iron from 6- to 5-coordinate. Titration of KatG(S315T) with isoniazid failed to produce a measurable difference spectrum indicating an altered active site configuration. These results suggest that KatG(S315T) confers resistance to isoniazid through subtle changes in the isoniazid binding site.     

Building co-operative bibliographic databases in European bioethics: a contribution from EU New Member States

The paper presents a web-based application, developed as a part of the Eurethnet database network, which is being used by project partners from EU New Member States to collect bibliographic records from bioethics domains. The application development was focused mainly on records compatibility with other Eurethnet databases, support for all European character sets, minimalisation of network traffic, and security issues. The time window available for the system development was very small and this problem was solved with our own software for automatic application generation.     

GEOCHEMICAL CHARACTERISTICS OF CRUDE OILS FROM THE SHARARA-C OIL FIELD,MURZUQ BASIN,SOUTHWESTERN LIBYA

Crude oil samples from the Sharara-C oil field (Concession NC-115, Murzuq Basin, SW Libya) were analysed by organic geochemical methods in order to infer the geochemical characteristics of their respective source rocks. Aromatic hydrocarbons were analysed by gas chromatography – mass spectrometry (GC-MS), and gas chromatography – tandem mass spectrometry (GC-MS-MS) was used to analyse saturated biomarkers. The Sharara-C oils are interpreted to have been generated by marine shales containing mixed terrigenous and marine organic materials deposited in an intermediate (suboxic) environment. Age-specific biomarker ratios indicated that the oils are older than Cretaceous, and maturation-related parameters pointed to their high thermal maturity. Consistent with previous studies, source rocks are inferred to be “hot” shales in the Lower Silurian Tanezzuft Formation. Almost all the parameter ratios calculated varied over a very narrow range, indicating that the investigated oils were compositionally similar. The only significant difference that was noted concerned the sterane/hopane ratios whose variation suggested that there was some variability in the composition of the source organic material. The organic geochemical parameters determined for the Sharara-C crude oils were compared with published data on other crude oils from Concession NC-115. Almost all the parameters agreed well with previously published data on oils from this part of the Murzuq Basin. The greatest deviation concerned the values of some of the maturity parameters. This tended to confirm the conclusions of previous studies concerning the presence of a number of distinct oil families and sub-families in the Sharara oil field area which are genetically related but which have different maturities.     

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.     

Enantioselective blockade of T-type Ca2+ current in adult rat sensory neurons by a steroid that lacks gamma-aminobutyric acid-modulatory activity

A number of steroids seem to have anesthetic effects resulting primarily from their ability to potentiate currents gated by gamma-aminobutyric acidA (GABAA) receptor activation. One such compound is (3alpha,5alpha, 17beta)-3-hydroxyandrostane-17-carbonitrile [(+)-ACN]. We were interested in whether carbonitrile substitution at other ring positions might result in other pharmacological consequences. Here we examine effects of (3beta,5alpha, 17beta)-17-hydroxyestrane-3-carbonitrile [(+)-ECN] on GABAA receptors and Ca2+ channels. In contrast to (+)-ACN, (+)-ECN does not potentiate GABAA-receptor activated currents, nor does it directly gate GABAA-receptor mediated currents. However, both steroids produce an enantioselective reduction of T-type current. (+)-ECN blocked T current with an IC50 value of 0.3 microM with a maximal block of 41%. (+)-ACN produced a partial block of T current (44% maximal block) with an IC50 value of 0.4 microM. Block of T current showed mild use- and voltage-dependence. The (-)-ECN enantiomer was about 33 times less potent than (+)-ECN, with an IC50 value of 10 microM and an amount of maximal block comparable to (+)-ECN. (+)-ECN was less effective at blocking high-voltage-activated Ca2+ current in DRG neurons (IC50 value of 9. 3 microM with maximal block of about 27%) and hippocampal neurons. (+)-ECN (10 microM) had minimal effects on voltage-gated sodium and potassium currents in rat chromaffin cells. The results identify a steroid with no effects on GABAA receptors that produces a partial inhibition of T-type Ca2+ current with reasonably high affinity and selectivity. Further study of steroid actions on T currents may lead to even more selective and potent agents.     

Failure analysis of the combat jet aircraft rudder shaft

This paper analyzes failure causes of the combat jet aircraft rudder shaft (RS) which occurred during the flight mission. A finite element method (FEM), utilized to determine the stress state of the RS subjected to hinge moment ultimate load, resulted in the high stress concentration sites around the rivet holes. The longitudinal crack was initiated from the corrosion pit in the zone of the rivet hole, where the fatigue beach marks were observed. The inner surface of the RS was heavily corroded. Moreover, pitting corrosion has destroyed approximately 50% of the wall thickness. Based on the presented results it was concluded that the failure of the RS had a character of fatigue combined with heavy corrosion. Therefore, it is recommended that the RS should be redesigned; the material changed into more corrosion resistant one and the maintenance procedure changed in order to avoid future similar failures.     

Correlated micro-photoluminescence and electron microscopy studies of the same individual heterostructured semiconductor nanowires

To correlate optical properties to structural characteristics, we developed a robust strategy for characterizing the same individual heterostructured semiconductor nanowires (NWs) by alternating low temperature micro-photoluminescence (μ-PL), low voltage scanning (transmission) electron microscopy and conventional transmission electron microscopy. The NWs used in this work were wurtzite GaAs core with zinc blende GaAsSb axial insert and AlGaAs radial shell grown by molecular beam epitaxy. The series of experiments demonstrated that high energy (200 kV) electrons are detrimental for the optical properties, whereas medium energy (5-30 kV) electrons do not affect the PL response. Thus, such medium energy electrons can be used to select NWs for correlated optical-structural studies prior to μ-PL or in NW device processing. The correlation between the three main μ-PL bands and crystal phases of different compositions, present in this heterostructure, is demonstrated for selected NWs. The positions where a NW fractures during specimen preparation can considerably affect the PL spectra of the NW. The effects of crystal-phase variations and lattice defects on the optical properties are discussed. The established strategy can be applied to other nanosized electro-optical materials, and other characterization tools can be incorporated into this routine.     

Noncoherent multistage multiuser detection of M-ary orthogonal signals

In recent years, a great deal of research has been performed on methods of alleviating the performance degradations suffered by code division multiple access (CDMA) systems due to multiple access interference. In this paper, we consider a multistage detector for noncoherent CDMA using M-ary orthogonal signals. Using a decorrelating detector as its first stage, the detector iteratively estimates the multiple access interference affecting the desired signal, subtracts the estimated interference, and forms symbol estimates for each of K users. Through numerical examples, the bit error performance of the proposed detector is demonstrated to be superior to that of previous detectors for the same signalling scheme. This revised version was published online in June 2006 with corrections to the Cover Date.