Lack of an HSP70 heat shock response in two Antarctic marine invertebrates

Members of the HSP70 gene family comprising the inducible (HSP70) genes and GRP78 (glucose-regulated protein 78 kDa) were identified in an Antarctic sea star (Odontaster validus) and an Antarctic gammarid (Paraceradocus gibber). These genes were surveyed for expression levels via Q-PCR after an acute 2-hour heat shock experiment in both animals and a time course assay in O. validus. No significant up-regulation was detected for any of the genes in either of the animals during the acute heat shock. The time course experiment in O. validus produced slightly different results with an initial down regulation in these genes at 2°C, but no significant up-regulation of the genes either at 2 or 6°C. Therefore, the classical heat shock response is absent in both species. The data is discussed in the context of the organisms’ thermal tolerance and the applicability of HSP70 to monitor thermal stress in Antarctic marine organisms

An Entailment Relation for Reasoning on the Web

Reasoning on the Web is receiving an increasing attention because of emerging fields such as Web adaption and Semantic Web. Indeed, the advanced functionalities striven for in these fields call for reasoning capabilities. Reasoning on the Web, however, is usually done using existing techniques rarely fitting the Web. As a consequence, additional data processing like data conversion from Web formats (e.g. XML or HTML) into some other formats (e.g. classical logic terms and formulas) is often needed and aspects of the Web (e.g. its inherent inconsistency) are neglected. This article first gives requirements for an entailment tuned to reasoning on the Web. Then, it describes how classical logic’s entailment can be modified so as to enforce these requirements. Finally, it discusses how the proposed entailment can be used in applying logic programming to reasoning on the Web

Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF

Background To develop antibacterial agents having novel modes of action against bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala) and the cell wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm) with the concomitant hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl-pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme. Results Screening of a phage display 12-mer library using purified P. aeruginosa MurF yielded to the identification of the MurFp1 peptide. The MurF substrate UDP-MurNAc-Ala-Glumeso-A2pm was synthesized and used to develop a sensitive spectrophotometric assay to quantify MurF kinetics and inhibition. MurFp1 acted as a weak, time-dependent inhibitor of MurF activity but was a potent inhibitor when MurF was pre-incubated with UDP-MurNAc-Ala-Glu-meso-A2pm or ATP. In contrast, adding the substrate D-Ala-D-Ala during the pre-incubation nullified the inhibition. The IC50 value of MurFp1 was evaluated at 250 μM, and the Ki was established at 420 μM with respect to the mixed type of inhibition against D-Ala-D-Ala. Conclusion MurFp1 exerts its inhibitory action by interfering with the utilization of D-Ala-D-Ala by the MurF amide ligase enzyme. We propose that MurFp1 exploits UDP-MurNAc-Ala-Glu-meso-A2pm-induced structural changes for better interaction with the enzyme. We present the first peptide inhibitor of MurF, an enzyme that should be exploited as a target for antimicrobial drug development

Estimating local car ownership models

Many studies in the transport demand literature have shown that income is an important factor in determining how many cars a household owns. When the models used to measure the strength of this relationship are estimated on cross-sectional data, they typically yield one overall value as the estimate. Local circumstances will, however, vary. This paper illustrates the use of the Geographically Weighted Regression technique to estimate the individual strength of this relationship for each of the United Kingdom electoral wards. Use of this type of model enables a wards’ income elasticity to be based on both the local estimate of the strength of this relationship and the current local level of car ownership. How the use of this local elasticity changes future forecasts of the size of the vehicle fleet is illustrated

Transcriptomic response to shell damage in the Antarctic clam, Laternula elliptica: time scales and spatial localisation

Mollusc shell is built up by secretion from the mantle and is the result of a controlled biological process termed biomineralisation. In general mollusc shells are well characterised however, the molecular mechanisms used by molluscs to produce shell remain largely unknown. One tractable method to study molecular biomineralisation mechanisms are shell damage-repair experiments, which stimulate calcification pathways. The present study used the Antarctic clam (Laternula elliptica) as a model to better understand when and where molecular biomineralisation events occur in the mantle. Two approaches were used: one experiment used high-throughput RNA-sequencing to study molecular damage-repair responses over a 2 month time series, and a second experiment used targeted semi-quantitative PCR to investigate the spatial location of molecular mechanisms in response to damage. Shell repair in L. elliptica was slow, lasting at least 2 months, and expression results revealed different biological processes were important at varying time scales during repair. A spatial pattern in relation to a single drilled hole was revealed for some, but not all, candidate genes suggesting the mantle may be functionally zoned and can respond to damage both locally and ubiquitously across the mantle. Valuable data on the temporal and spatial response of shell damage-repair provide a baseline not only for future studies in L. elliptica, but also other mollusc

Measuring Coverage of Prolog Programs Using Mutation Testing

Testing is an important aspect in professional software development, both to avoid and identify bugs as well as to increase maintainability. However, increasing the number of tests beyond a reasonable amount hinders development progress. To decide on the completeness of a test suite, many approaches to assert test coverage have been suggested. Yet, frameworks for logic programs remain scarce. In this paper, we introduce a framework for Prolog programs measuring test coverage using mutations. We elaborate the main ideas of mutation testing and transfer them to logic programs. To do so, we discuss the usefulness of different mutations in the context of Prolog and empirically evaluate them in a new mutation testing framework on different examples.Comment: 16 pages, Accepted for presentation in WFLP 201

A Denotational Semantics for First-Order Logic

In Apt and Bezem [AB99] (see cs.LO/9811017) we provided a computational interpretation of first-order formulas over arbitrary interpretations. Here we complement this work by introducing a denotational semantics for first-order logic. Additionally, by allowing an assignment of a non-ground term to a variable we introduce in this framework logical variables. The semantics combines a number of well-known ideas from the areas of semantics of imperative programming languages and logic programming. In the resulting computational view conjunction corresponds to sequential composition, disjunction to ``don't know'' nondeterminism, existential quantification to declaration of a local variable, and negation to the ``negation as finite failure'' rule. The soundness result shows correctness of the semantics with respect to the notion of truth. The proof resembles in some aspects the proof of the soundness of the SLDNF-resolution.Comment: 17 pages. Invited talk at the Computational Logic Conference (CL 2000). To appear in Springer-Verlag Lecture Notes in Computer Scienc

Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO