Antihyperglycemic drugs that improve cardiovascular outcomes and a model of diabetic cardiomyopathy

Recent cardiovascular outcome trials (CVOTs) have transformed the landscape for the management of type 2 diabetes mellitus. In a remarkably short period of time, national and international guidelines have been overhauled to reflect the remarkable cardiovascular benefits of sodium/glucose linked transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor analogues (GLP-1RA) in mitigating cardiovascular risk. Both SGLT2is and GLP-1RAs remain second-line to metformin, reflecting the historical importance of this biguanide antihyperglycemic. In this review, these three very different antihyperglycemics are discussed in the light of CVOT data and of the preclinical data revealing remarkable pleiotropic signaling effects of these drugs. A model of diabetic cardiomyopathy is discussed, and the points of contact that these therapeutic interventions have upon this model may of help in understanding how each can be best targeted in this complex pathophysiological disease proces

Reperfusion, conditioning and the ongoing search for the holy grail

schaemic conditioning is the phenomenon of protection against reperfusion injury via the application of brief, repeated episodes of non-lethal ischaemia. This review has three aims: 1) to briefly explain the various categories of ischaemic conditioning; 2) to explore past clinical trials and their failures; 3) to explore the future of clinical trials in the realm of ischaemic conditioning

Inexact Bayesian point pattern matching for linear transformations

PublishedArticleWe introduce a novel Bayesian inexact point pattern matching model that assumes that a linear transformation relates the two sets of points. The matching problem is inexact due to the lack of one-to-one correspondence between the point sets and the presence of noise. The algorithm is itself inexact; we use variational Bayesian approximation to estimate the posterior distributions in the face of a problematic evidence term. The method turns out to be similar in structure to the iterative closest point algorithm.This work was supported by the University of Exeter’s Bridging the Gaps initiative, which was funded by EPSRC award EP/I001433/1 and the collaboration was formed through the Exeter Imaging Network

Molecular mechanisms regulating formation, trafficking and processing of annular gap junctions

Internalization of gap junction plaques results in the formation of annular gap junction vesicles. The factors that regulate the coordinated internalization of the gap junction plaques to form annular gap junction vesicles, and the subsequent events involved in annular gap junction processing have only relatively recently been investigated in detail. However it is becoming clear that while annular gap junction vesicles have been demonstrated to be degraded by autophagosomal and endo-lysosomal pathways, they undergo a number of additional processing events. Here, we characterize the morphology of the annular gap junction vesicle and review the current knowledge of the processes involved in their formation, fission, fusion, and degradation. In addition, we address the possibility for connexin protein recycling back to the plasma membrane to contribute to gap junction formation and intercellular communication. Information on gap junction plaque removal from the plasma membrane and the subsequent processing of annular gap junction vesicles is critical to our understanding of cell-cell communication as it relates to events regulating development, cell homeostasis, unstable proliferation of cancer cells, wound healing, changes in the ischemic heart, and many other physiological and pathological cellular phenomena

Vacuum phototriodes for the CMS electromagnetic calorimeter endcap

The measurement of scintillation light from the lead tungstate crystals of the Compact Muon Solenoid (CMS) electromagnetic calorimeter (ECAL) poses a substantial technical challenge, particularly in the endcap regions, where the radiation levels are highest. The photodetectors must be fast, sensitive, radiationhard, and operate with significant internal gain in a magnetic field of 4 Tesla. The measured performance characteristics of the first batches of series production vacuum phototriodes (VPT), developed to satisfy the needs of CMS, will be described

High Energy Cosmic Rays From Supernovae

Cosmic rays are charged relativistic particles that reach the Earth with extremely high energies, providing striking evidence of the existence of effective accelerators in the Universe. Below an energy around $\sim 10^{17}$ eV cosmic rays are believed to be produced in the Milky Way while above that energy their origin is probably extragalactic. In the early '30s supernovae were already identified as possible sources for the Galactic component of cosmic rays. After the '70s this idea has gained more and more credibility thanks to the the development of the diffusive shock acceleration theory, which provides a robust theoretical framework for particle energization in astrophysical environments. Afterwards, mostly in recent years, much observational evidence has been gathered in support of this framework, converting a speculative idea in a real paradigm. In this Chapter the basic pillars of this paradigm will be illustrated. This includes the acceleration mechanism, the non linear effects produced by accelerated particles onto the shock dynamics needed to reach the highest energies, the escape process from the sources and the transportation of cosmic rays through the Galaxy. The theoretical picture will be corroborated by discussing several observations which support the idea that supernova remnants are effective cosmic ray factories.Comment: Final draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdi

Temporal influence over the Last.fm social network

In a previous result, we showed that the influence of social contacts spreads information about new artists through the Last.fm social network. We successfully decomposed influence from effects of trends, global popularity, and homophily or shared environment of friends. In this paper, we present our new experiments that use a mathematically sound formula for defining and measuring the influence in the network. We provide new baseline and influence models and evaluation measures, both batch and online, for real-time recommendations with very strong temporal aspects. Our experiments are carried over the 2-year “scrobble” history of 70,000 Last.fm users. In our results, we formally define and distil the effect of social influence. In addition, we provide new models and evaluation measures for real-time recommendations with very strong temporal aspects. © 2015, Springer-Verlag Wien