Towards Intelligent Databases

This article is a presentation of the objectives and techniques of deductive databases. The deductive approach to databases aims at extending with intensional definitions other database paradigms that describe applications extensionaUy. We first show how constructive specifications can be expressed with deduction rules, and how normative conditions can be defined using integrity constraints. We outline the principles of bottom-up and top-down query answering procedures and present the techniques used for integrity checking. We then argue that it is often desirable to manage with a database system not only database applications, but also specifications of system components. We present such meta-level specifications and discuss their advantages over conventional approaches

Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure

<p>Abstract</p> <p>Background</p> <p>Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance.</p> <p>Methods</p> <p>In this study, an existing <it>P. falciparum </it>infection model is modified to incorporate the hypothesis of dormancy. Published <it>in vitro </it>data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment.</p> <p>Results</p> <p>The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials.</p> <p>Conclusions</p> <p>Although further studies are required to confirm dormancy <it>in vivo</it>, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.</p

Reduction-cleavable desferrioxamine B pulldown system enriches Ni( ii )-superoxide dismutase from a Streptomyces proteome

Two resins with the hydroxamic acid siderophore desferrioxamine B (DFOB) immobilised as a free ligand or its Fe(iii) complex were prepared to screen the Streptomyces pilosus proteome for proteins involved in siderophore-mediated Fe(iii) uptake. The resin design included a disulfide bond to enable the release of bound proteins under mild reducing conditions. Proteomics analysis of the bound fractions did not identify proteins associated with siderophore-mediated Fe(iii) uptake, but identified nickel superoxide dismutase (NiSOD), which was enriched on the apo-DFOB-resin but not the Fe(iii)-DFOB-resin or the control resin. While DFOB is unable to sequester Fe(iii) from sites deeply buried in metalloproteins, the coordinatively unsaturated Ni(ii) ion in NiSOD is present in a surface-exposed loop region at the N-terminus, which might enable partial chelation. The results were consistent with the notion that the apo-DFOB-resin formed a ternary complex with NiSOD, which was not possible for either the coordinatively saturated Fe(iii)-DFOB-resin or the non-coordinating control resin systems. In support, ESI-TOF-MS measurements from a solution of a model Ni(ii)-SOD peptide and DFOB showed signals that correlated with a ternary Ni(ii)-SOD peptide–DFOB complex. Although any biological implications of a DFOB–NiSOD complex are unclear, the work shows that the metal coordination properties of siderophores might influence an array of metal-dependent biological processes beyond those established in iron uptake

A complementary view on the growth of directory trees

Trees are a special sub-class of networks with unique properties, such as the level distribution which has often been overlooked. We analyse a general tree growth model proposed by Klemm {\em et. al.} (2005) to explain the growth of user-generated directory structures in computers. The model has a single parameter $q$ which interpolates between preferential attachment and random growth. Our analysis results in three contributions: First, we propose a more efficient estimation method for $q$ based on the degree distribution, which is one specific representation of the model. Next, we introduce the concept of a level distribution and analytically solve the model for this representation. This allows for an alternative and independent measure of $q$. We argue that, to capture real growth processes, the $q$ estimations from the degree and the level distributions should coincide. Thus, we finally apply both representations to validate the model with synthetically generated tree structures, as well as with collected data of user directories. In the case of real directory structures, we show that $q$ measured from the level distribution are incompatible with $q$ measured from the degree distribution. In contrast to this, we find perfect agreement in the case of simulated data. Thus, we conclude that the model is an incomplete description of the growth of real directory structures as it fails to reproduce the level distribution. This insight can be generalised to point out the importance of the level distribution for modeling tree growth.Comment: 16 pages, 7 figure

PNAS plus: plasmodium falciparum responds to amino acid starvation by entering into a hibernatory state

The human malaria parasite Plasmodium falciparum is auxotrophic for most amino acids. Its amino acid needs are met largely through the degradation of host erythrocyte hemoglobin; however the parasite must acquire isoleucine exogenously, because this amino acid is not present in adult human hemoglobin. We report that when isoleucine is withdrawn from the culture medium of intraerythrocytic P. falciparum, the parasite slows its metabolism and progresses through its developmental cycle at a reduced rate. Isoleucine-starved parasites remain viable for 72 h and resume rapid growth upon resupplementation. Protein degradation during starvation is important for maintenance of this hibernatory state. Microarray analysis of starved parasites revealed a 60% decrease in the rate of progression through the normal transcriptional program but no other apparent stress response. Plasmodium parasites do not possess a TOR nutrient-sensing pathway and have only a rudimentary amino acid starvation-sensing eukaryotic initiation factor 2α (eIF2α) stress response. Isoleucine deprivation results in GCN2-mediated phosphorylation of eIF2α, but kinase-knockout clones still are able to hibernate and recover, indicating that this pathway does not directly promote survival during isoleucine starvation. We conclude that P. falciparum, in the absence of canonical eukaryotic nutrient stress-response pathways, can cope with an inconsistent bloodstream amino acid supply by hibernating and waiting for more nutrient to be provided

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated&nbsp;burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated&nbsp;chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals

‘It was just like we were a family again’: play as a means to maintain family ties for children visiting an imprisoned parent

Children can find the process of visiting a prison traumatic and as a result of parental incarceration may experience a range of adverse outcomes. When children stay in contact with their imprisoned parent through prison visiting, however, this seems to be a protective factor. This paper reports on a play visits service based at Her Majesty's Prison Leeds, UK. The service provides supervised play work provision for children visiting their father. Data were derived from prisoners and prisoners' families and were triangulated as a means of achieving a level of validity. The findings reveal that play visits do produce positive outcomes for children and play visits are effective in maintaining and strengthening family ties. These effects may be stronger when compared to standard prison visits, but further research is needed to confirm this