QSAR Modeling of a Set of Pyrazinoate Esters as Antituberculosis Prodrugs

Tuberculosis is an infection caused mainly by Mycobacterium tuberculosis. A first-line antimycobacterial drug is pyrazinamide (PZA), which acts partially as a prodrug activated by a pyrazinamidase releasing the active agent, pyrazinoic acid (POA). As pyrazinoic acid presents some difficulty to cross the mycobacterial cell wall, and also the pyrazinamide-resistant strains do not express the pyrazinamidase, a set of pyrazinoic acid esters have been evaluated as antimycobacterial agents. In this work, a QSAR approach was applied to a set of forty-three pyrazinoates against M. tuberculosis ATCC 27294, using genetic algorithm function and partial least squares regression (WOLF 5.5 program). The independent variables selected were the Balaban index (I), calculated n-octanol/water partition coefficient (ClogP), van-der-Waals surface area, dipole moment, and stretching-energy contribution. The final QSAR model (N = 32, r(2) = 0.68, q(2) = 0.59, LOF = 0.25, and LSE = 0.19) was fully validated employing leave-N-out cross-validation and y-scrambling techniques. The test set (N = 11) presented an external prediction power of 73%. In conclusion, the QSAR model generated can be used as a valuable tool to optimize the activity of future pyrazinoic acid esters in the designing of new antituberculosis agents.

The 2008 update of the Aspergillus nidulans genome annotation: A community effort

The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.

Prosody of tone Sandhi in Vietnamese reduplications

In this paper we take advantage of the segmental control afforded by full and partial Vietnamese reduplication on a constant carrier phrase to obtain acoustic evidence of assymetrical prominence relations (van der Hulst 2005), in support of a hypothesis that Vietnamese reduplications are phonetically right headed and that tone sandhi is a reduction phenomenon occurring on prosodically weak positions (Shih 2005). Acoustic parameters of syllable duration (onset, nucleus and coda), F0 range, F0 contour, vowel intensity, spectral tilt and vowel formant structure are analyzed to determine: (1) which syllable of the two (base or reduplicant) is more prominent and (2) how the tone sandhi forms differ from their full reduplicated counterparts. Comparison of full and partial reduplicant syllables in tone sandhi forms provide additional support for this analysis.

BIO Logical Agents: Norms, Beliefs, Intentions in Defeasible Logic

In this paper we follow the BOID (Belief, Obligation, Intention, Desire) architecture to describe agents and agent types in Defeasible Logic. We argue, in particular, that the introduction of obligations can provide a new reading of the concepts of intention and intentionality. Then we examine the notion of social agent (i.e., an agent where obligations prevail over intentions) and discuss some computational and philosophical issues related to it. We show that the notion of social agent either requires more complex computations or has some philosophical drawbacks.

Interaction between Normative Systems and Cognitive Agents in Temporal Modal Defeasible Logic

While some recent frameworks on cognitive agents addressed the combination of mental attitudes with deontic concepts, they commonly ignore the representation of time. An exception is [1]that manages also some temporal aspects both with respect to cognition and normative provisions. We propose in this paper an extension of the logic presented in [1]with temporal intervals.

Contextual Deliberation of Cognitive Agents in Defeasible Logic

This article extends Defeasible Logic to deal with the contextual deliberation process of cognitive agents. First, we introduce meta-rules to reason with rules. Meta-rules are rules that have as a consequent rules for motivational components, such as obligations, intentions and desires. In other words, they include nested rules. Second, we introduce explicit preferences among rules. They deal with complex structures where nested rules can be involved.

(FAB12_1_002) 'Would you know the new, you must search the old': William Lethaby's 'Architecture, Mysticism and Myth' (1891) and the 'Hypnerotomachia Poliphili' (1499)

Published in the final months of 1891, Architecture, Mysticism and Myth was the first architectural treatise written by the late nineteenth-century English architect and theorist William Richard Lethaby (1857-1931).' Documenting the characteristic attributes of the architectural myth of the "temple idea", and its presence amongst architectures of multiple ancient cultures, the text was endowed with a distinctly historical tone. In examining the motives behind myth, which Lethaby defined as the interaction and reaction between the natural universe and the built environment, Lethaby also injected a series of theoretical considerations into the text. It is clear that Lethaby's interest in the temple idea was not limited to its curious, prolific presence in past architectures, hut also embraced a consideration of what lessons the temple idea may contribute to the struggle of the late nineteenth-century English architect to define an "art of the future".

Increased expression of mitochondrial genes in human alcoholic brain revealed by differential display

Polymerase chain reaction (PCR)-based differential display was used to screen for alterations in gene expression in the mesolimbic system of the human alcoholic brain. Total RNA was extracted from the nucleus accumbens of five alcoholic and five control brains. A selected subpopulation of mRNA was reverse-transcribed to cDNA and amplified by PCR. A differentially expressed cDNA fragment was recovered, cloned, and sequenced. Full sequence analysis of this 467 bp fragment revealed 98.2% homology with the human mitochondrial 12S rRNA gene. Dot-blot analysis showed increased expression of this gem in nucleus accumbens and hippocampus, but not in the superior frontal cortex, primary motor cortex, caudate, and pallidus/putamen In a total of eight human alcoholic brains, compared with seven control brains. A similar increased expression was observed by dot-blot analysis, using RNA from the cerebral cortex of rats chronically treated with alcohol vapor. Hybridization of a 16S rRNA oligonucleotide probe indicated that the expression of both rRNAs genes was significantly increased in nucleus accumbens. These results indicate that chronic alcohol consumption induces alteration in expression of mitochondrial genes in selected brain regions. The altered gene expression may reflect mitochondrial dysfunction In the alcohol-affected brain.

Late Quaternary cycles of mangrove development and decline on the north Australian continental shelf

Mangrove communities in the Australian tropics presently occur as narrow belts of vegetation in estuaries and on sheltered, muddy coasts. Palynological data from continental shelf and deep-sea cores indicate a long-term cyclical component of mangrove development and decline at a regional scale, which can be linked to specific phases of late Quaternary sealevel change. Extensive mangrove development, relative to today, occurs during periods of marine transgression, whereas very diminished mangrove occurs during marine regressions and during rarer periods of relative sea-level stability. Episodes of flourishing mangrove cannot be linked to phases of humid climate, as has been suggested in studies elsewhere. Rather, the cycle of expansion and decline of mangrove communities on a grand scale is explained in terms of contrasting physiographic settings characteristic of continental-shelf coasts during transgressive and regressive phases, in particular by the existence, or lack, of well-developed tidal estuaries. Copyright (C) 1999 John Wiley & Sons, Ltd.

Overseas visitors admitted to Queensland hospitals for water-related injuries

Objective: To determine the number of overseas visitors admitted to Queensland hospitals for water-related injuries over three years, the causes of their injuries, the resulting conditions treated, and the type of hospitals to which they were admitted. Design: Retrospective analysis of admissions of overseas visitors to Queensland hospitals over the three financial years 1995/96, 1996/97 and 1997/98. Patients: 296 overseas visitors admitted for water-related injuries, identified from hospital records by their usual place of residence. Main outcome measures: Number of admissions, causes of injuries, conditions treated. and bed days occupied by these patients at different types of hospitals (metropolitan, regional and rural public hospitals, and private hospitals). Results: The 296 overseas visitors accounted for a total of 596 separate admissions, many of these the result of patients with decompression illness being admitted several times to a regional hospital hyperbaric chamber for treatment as day patients. The largest number of injuries involved the use of diving equipment. The main conditions treated were decompression illness (54.7%), fractures and dislocations (15.5%), and drowning and non-fatal submersion (14.9%). Overall, overseas visitors admitted to hospital following a water-related incident occupied 1215 bed days; 90% of these admissions were to regional hospitals. Conclusions: The main reason for admission of overseas visitors is for decompression illness, suggesting that the prevention of injuries among scuba divers requires further coordinated efforts by health and tourism authorities.

Causes and consequences of long-term climatic variability on the Australian continent

1. Ice-volume forced glacial-interglacial cyclicity is the major cause of global climate variation within the late Quaternary period. Within the Australian region, this variation is expressed predominantly as oscillations in moisture availability. Glacial periods were substantially drier than today with restricted distribution of mesic plant communities, shallow or ephemeral water bodies and extensive aeolian dune activity. 2. Superimposed on this cyclicity in Australia is a trend towards drier and/or more variable climates within the last 350 000 years. This trend may have been initiated by changes in atmospheric and ocean circulation resulting from Australia's continued movement into the Southeast Asian region and involving the onset or intensification of the El Nino-Southern Oscillation system and a reduction in summer monsoon activity. 3. Increased biomass burning, stemming originally from increased climatic variability and later enhanced by activities of indigenous people, resulted in a more open and sclerophyllous vegetation, increased salinity and a further reduction in water availability. 4. Past records combined with recent observations suggest that the degree of environmental variability will increase and the drying trend will be enhanced in the foreseeable future, regardless of the extent or nature of human intervention.

Late Quaternary Milankovitch-scale climatic change and variability and its impact on monsoonal Australasia

Four pollen and charcoal records derived from marine cores around the northern perimeter of Australia are examined to provide a regional picture of patterns, causes and impacts of climate change over the last 100-300 ka. The availability of radiocarbon dates and oxygen isotope records for the cores provides primary chronological control. Spectral analysis of components of these records demonstrates an overall importance of Milankovitch frequencies with clear glacial-interglacial cyclicity dominated by variation in precipitation. In addition, a number of pollen taxa, as well as charcoal particles, exhibit a 30 ka frequency that is considered, from its relationship with biomass burning and with results of past modelling, to reflect changes in the intensity of El Nino-Southern Oscillation (ENSO) variability. Pollen components of all records show a decline, frequently stepwise, in more fire-sensitive vegetation and its replacement with more fire-tolerant vegetation. There is some evidence that this trend is linked to an onset or general increase in ENSO activity and perhaps also to variation in monsoon activity dating from about 300 ka BP that was caused by changes to oceanic circulation within the Indonesian region. The trend may have accelerated within the last 45 ka due to burning by indigenous people. (C) 2003 Elsevier B.V. All rights reserved.