A comprehensive integrated drug similarity resource for in-silico drug repositioning and beyond.

Drug similarity studies are driven by the hypothesis that similar drugs should display similar therapeutic actions and thus can potentially treat a similar constellation of diseases. Drug-drug similarity has been derived by variety of direct and indirect sources of evidence and frequently shown high predictive power in discovering validated repositioning candidates as well as other in-silico drug development applications. Yet, existing resources either have limited coverage or rely on an individual source of evidence, overlooking the wealth and diversity of drug-related data sources. Hence, there has been an unmet need for a comprehensive resource integrating diverse drug-related information to derive multi-evidenced drug-drug similarities. We addressed this resource gap by compiling heterogenous information for an exhaustive set of small-molecule drugs (total of 10 367 in the current version) and systematically integrated multiple sources of evidence to derive a multi-modal drug-drug similarity network. The resulting database, 'DrugSimDB' currently includes 238 635 drug pairs with significant aggregated similarity, complemented with an interactive user-friendly web interface (http://vafaeelab.com/drugSimDB.html), which not only enables database ease of access, search, filtration and export, but also provides a variety of complementary information on queried drugs and interactions. The integration approach can flexibly incorporate further drug information into the similarity network, providing an easily extendable platform. The database compilation and construction source-code has been well-documented and semi-automated for any-time upgrade to account for new drugs and up-to-date drug information

Human papilloma virus is associated with breast cancer

Background: There is increasing evidence that high-risk human papilloma virus (HPV) is involved in cancers in addition to cervical cancer. For example, it is generally accepted that HPV has a role in a significant proportion of head and neck tumours, and it has long been hypothesised that hormone dependent oncogenic viruses, such as HPV may have causal roles in some human breast cancers. A number of reports have identified HPV DNA in breast tissue and breast cancer specimens, but these rely on standard polymerase chain reaction (PCR), which is criticised for its propensity for contamination. Methods: We have used two different technologies, in situ and standard PCR (with sequencing), and histology based on light microscopy. Results: We unambiguously demonstrate the presence of high-risk HPV in the cells of breast cancer specimens and breast cancer cell lines. In addition, we also show that the oncogenic characteristics of HPV associated breast cancer are very similar to HPV-associated cervical cancer. Specifically, that putative koilocytes are present in some HPV associated breast cancers. Interpretation: The above observations indicate a likely causal role for high-risk HPV in human breast cancer and offer the possibility of primary prevention of some breast cancers by vaccination against HPV.6 page(s

Increased risk of venous thromboembolism in patients with acute leukaemia

Patients with malignancies have an increased risk for venous thromboembolisms (VTE), but data on patients with acute leukaemia are very limited so far. We found VTE in 12% of 455 patients with acute leukaemia, half of which occurred in association with central venous catheters, with equal risk of ALL and AML

Rethinking naive realism

Perceptions are externally-directed - they present us with a mind-independent reality, and thus contribute to our abilities to think about this reality, and to know what is objectively the case. But perceptions are also internally-dependent - their phenomenal characters depend on the neuro-computational properties of the subject. A good theory of perception must account for both these facts. But Naive realism has been criticized for failing to accommodate the latter one. This paper evaluates and responds to this criticism. It first argues that a certain version of naive realism, often called “selectionism”, does indeed struggle with the internal-dependence of perceptions. It then develops an alternate version of naive realism which does not. This alternate version, inspired by an idea of Martin's, accommodates the internal-dependence of perceptions by recognizing the role that the subject's neuro-computational properties play in shaping perceptual phenomenology. At the same time, it retains the distinctive naive realist account of the external-directedness of perceptions

Sur les solutions périodiques du mouvement plan de libration des satellites et des planètes

Ce papier présente une étude analytique du mouvement plan de rotation des satellites (et des planètes) dans leurs mouvements orbitaux. Les trois familles des solution périodiques sont obtenues par la méthode du prolongement analytique de Poincaré. Ensuite, la stabilité de ces solutions périodiques est discutée, et les équations approchées des courbes limites de stabilité sont données jusqu'au quatrième ordre. This paper presents an analytical study of the rotational motion of the satellites (and the planets) in their orbital planes. The three families of periodic solutions are obtained by the method of analytical continuation as formulated by Poincaré. The stability of these solutions are analyzed, and the approximate equations of the transition curves are obtained to the fourth order.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42563/1/10569_2005_Article_BF01227807.pd

The Miocene – Pliocene boundary and the Messinian Salinity Crisis in the easternmost Mediterranean: insights from the Hatay Graben (Southern Turkey).

The Hatay Graben is one of three easternmost basins in the Mediterranean that preserve sediments that span the Miocene-Pliocene boundary, including gypsums from the Messinian Salinity Crisis (MSC). Here we integrate existing data and present new sedimentological and micropalaeontological data to investigate the palaeoenvironments of late Miocene to early Pliocene deposits and place this important area into a regional stratigraphic framework. Six sections are described along a ~ W – E transect illustrating the key features of this time period. Late Miocene (Pre-MSC) sediments are characterised by open marine marls with a benthic foraminiferal fauna suggestive of water depths of 100 – 200 m or less. Primary lower gypsum deposits are determined to be absent from the graben as sedimentological and strontium isotopes are characteristic of the resedimented lower gypsums. The intervening Messinian erosion surface is preserved near the basin margins as an unconformity but appears to be a correlative conformity in the basin depocentre. No Upper Gypsums or ‘Lago–Mare’ facies have been identified but available data do tentatively suggest a return to marine conditions in the basin prior to the Zanclean boundary. Sediments stratigraphically overlying the Messinian gypsums and marls are coarse-grained sandstones from coastal and Gilbert-type delta depositional environments. The Hatay Graben is not only strikingly similar to Messinian basins on nearby Cyprus but also to the overall model for the MSC, demonstrating the remarkable consistency of palaeoenvironments found in marginal basins across the region at this time