Provenance-Centered Dataset of Drug-Drug Interactions

Over the years several studies have demonstrated the ability to identify potential drug-drug interactions via data mining from the literature (MEDLINE), electronic health records, public databases (Drugbank), etc. While each one of these approaches is properly statistically validated, they do not take into consideration the overlap between them as one of their decision making variables. In this paper we present LInked Drug-Drug Interactions (LIDDI), a public nanopublication-based RDF dataset with trusty URIs that encompasses some of the most cited prediction methods and sources to provide researchers a resource for leveraging the work of others into their prediction methods. As one of the main issues to overcome the usage of external resources is their mappings between drug names and identifiers used, we also provide the set of mappings we curated to be able to compare the multiple sources we aggregate in our dataset.Comment: In Proceedings of the 14th International Semantic Web Conference (ISWC) 201

Beyond Logarithmic Corrections to Cardy Formula

As shown by Cardy modular invariance of the partition function of a given unitary non-singular 2d CFT with left and right central charges c_L and c_R, implies that the density of states in a microcanonical ensemble, at excitations Delta and Delta-bar and in the saddle point approximation, is \rho_0(\Delta,\bar\Delta;c_L, c_R)=c_L c_R \exp(2\pi\sqrt{{c_L\Delta}/{6}})\exp(2\pi\sqrt{{c_R\bar\Delta}/{6}}). In this paper, we extend Cardy's analysis and show that in the saddle point approximation and up to contributions which are exponentially suppressed compared to the leading Cardy's result, the density of states takes the form \rho(\Delta,\bar\Delta; c_L,c_R)= f(c_L\Delta) f(c_R\bar\Delta)\rho_0(\Delta,\bar\Delta; c_L, c_R), for a function f(x) which we specify. In particular, we show that (i) \rho (\Delta,\bar\Delta; c_L, c_R) is the product of contributions of left and right movers and hence, to this approximation, the partition function of any modular invariant, non-singular unitary 2d CFT is holomorphically factorizable and (ii) \rho(\Delta,\bar\Delta; c_L, c_R)/(c_Lc_R) is only a function of $c_R\bar\Delta$ and $c_L\Delta$. In addition, treating \rho(\Delta,\bar\Delta; c_L, c_R) as the density of states of a microcanonical ensemble, we compute the entropy of the system in the canonical counterpart and show that the function f(x) is such that the canonical entropy, up to exponentially suppressed contributions, is simply given by the Cardy's result \ln\rho_0(\Delta,\bar\Delta; c_L, c_R).Comment: 30 pages, no figures; v2: minor improvements, one reference added, v3: minor corrections to match the published versio

Laboratory study on the mobility of major species in fly ash–brine co-disposal systems: up-flow percolation test

Apart from the generation of fly ash, brine (hyper-saline wastewater) is also a waste material generated in South African power stations as a result of water re-use. These waste materials contain major species such as Al, Si, Na, K, Ca, Mg, Cl and SO4. The co-disposal of fly ash and brine has been practiced by some power stations in South Africa with the aim of utilizing the fly ash to capture the salts in brine. The effect of the chemical interaction of the species contained in both fly ash and brine, when co-disposed, on the mobility of species in the fly ash–brine systems is the focus of this study. The up-flow percolation test was employed to determine the mobility of some major species in the fly ash–brine systems. The results of the analysed eluates from the up-flow percolation tests revealed that some species such as Al, Ca and Na were leached from the fly ash into the brine solution while some species such as Mg, Cl and SO4 were removed to some extent from the brine solution during the interaction with fly ash. The pH of the up-flow percolation systems was observed to play a significant role on the mobility of major species from the fly ash–brine systems. The study showed that some major species such as Mg, Cl and SO4 could be removed from brine solution using fly ash when certain amount of brine percolates through the ash.Web of Scienc

Cyclic AMP signalling pathways in the regulation of uterine relaxation

Studying the mechanism(s) of uterine relaxation is important and will be helpful in the prevention of obstetric difficulties such as preterm labour, which remains a major cause of perinatal mortality and morbidity. Multiple signalling pathways regulate the balance between maintaining relative uterine quiescence during gestation, and the transition to the contractile state at the onset of parturition. Elevation of intracellular cyclic AMP promotes myometrial relaxation, and thus quiescence, via effects on multiple intracellular targets including calcium channels, potassium channels and myosin light chain kinase. A complete understanding of cAMP regulatory pathways (synthesis and hydrolysis) would assist in the development of better tocolytics to delay or inhibit preterm labour. Here we review the enzymes involved in cAMP homoeostasis (adenylyl cyclases and phosphodiesterases) and possible myometrial substrates for the cAMP dependent protein kinase. We must emphasise the need to identify novel pharmacological targets in human pregnant myometrium to achieve safe and selective uterine relaxation when this is indicated in preterm labour or other obstetric complications

SPPS: A Sequence-Based Method for Predicting Probability of Protein-Protein Interaction Partners

Background: The molecular network sustained by different types of interactions among proteins is widely manifested as the fundamental driving force of cellular operations. Many biological functions are determined by the crosstalk between proteins rather than by the characteristics of their individual components. Thus, the searches for protein partners in global networks are imperative when attempting to address the principles of biology. Results: We have developed a web-based tool ‘‘Sequence-based Protein Partners Search’ ’ (SPPS) to explore interacting partners of proteins, by searching over a large repertoire of proteins across many species. SPPS provides a database containing more than 60,000 protein sequences with annotations and a protein-partner search engine in two modes (Single Query and Multiple Query). Two interacting proteins of human FBXO6 protein have been found using the service in the study. In addition, users can refine potential protein partner hits by using annotations and possible interactive network in the SPPS web server. Conclusions: SPPS provides a new type of tool to facilitate the identification of direct or indirect protein partners which may guide scientists on the investigation of new signaling pathways. The SPPS server is available to the public a

Impaired contractile function of the supraspinatus in the acute period following a rotator cuff tear

Background: Rotator cuff (RTC) tears are a common clinical problem resulting in adverse changes to the muscle, but there is limited information comparing histopathology to contractile function. This study assessed supraspinatus force and susceptibility to injury in the rat model of RTC tear, and compared these functional changes to histopathology of the muscle. Methods: Unilateral RTC tears were induced in male rats via tenotomy of the supraspinatus and infraspinatus. Maximal tetanic force and susceptibility to injury of the supraspinatus muscle were measured in vivo at day 2 and day 15 after tenotomy. Supraspinatus muscles were weighed and harvested for histologic analysis of the neuromuscular junction (NMJ), intramuscular lipid, and collagen. Results: Tenotomy resulted in eventual atrophy and weakness. Despite no loss in muscle mass at day 2 there was a 30% reduction in contractile force, and a decrease in NMJ continuity and size. Reduced force persisted at day 15, a time point when muscle atrophy was evident but NMJ morphology was restored. At day 15, torn muscles had decreased collagen-packing density and were also more susceptible to contraction-induced injury. Conclusion: Muscle size and histopathology are not direct indicators of overall RTC contractile health. Changes in NMJ morphology and collagen organization were associated with changes in contractile function and thus may play a role in response to injury. Although our findings are limited to the acute phase after a RTC tear, the most salient finding is that RTC tenotomy results in increased susceptibility to injury of the supraspinatus

DNA glycosylases: in DNA repair and beyond

The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity