Metformin Reduces Potassium Currents and Prolongs Repolarization in Non-Diabetic Heart

Metformin is the first choice drug for the treatment of type 2 diabetes due to positive results in reducing hyperglycaemia and insulin resistance. However, diabetic patients have higher risk of ventricular arrhythmia and sudden cardiac death, and metformin failed to reduce ventricular arrhythmia in clinical trials. In order to explore the mechanisms responsible for the lack of protective effect, we investigated in vivo the effect of metformin on cardiac electrical activity in non-diabetic rats; and in vitro in isolated ventricular myocytes, HEK293 cells expressing the hERG channel and human induced pluripotent stem cells derived cardiomyocytes (hIPS-CMs). Surface electrocardiograms showed that long-term metformin treatment (7 weeks) at therapeutic doses prolonged cardiac repolarization, reflected as QT and QTc interval duration, and increased ventricular arrhythmia during the caffeine/dobutamine challenge. Patch-clamp recordings in ventricular myocytes isolated from treated animals showed that the cellular mechanism is a reduction in the cardiac transient outward potassium current (I_to). In vitro, incubation with metformin for 24 h also reduced I_to, prolonged action potential duration, and increased spontaneous contractions in ventricular myocytes isolated from control rats. Metformin incubation also reduced I_hERG in HEK293 cells. Finally, metformin incubation prolonged action potential duration at 30% and 90% of repolarization in hIPS-CMs, which is compatible with the reduction of I_to and I_hERG. Our results show that metformin directly modifies the electrical behavior of the normal heart. The mechanism consists in the inhibition of repolarizing currents and the subsequent decrease in repolarization capacity, which prolongs AP and QTc duration.     

Microstructure of diffusional zirconia–titanium and zirconia–(Ti–6 wt% Al–4 wt% V) alloy joints

Zirconia–titanium and zirconia–titanium alloy joints were made by diffusion bonding under an inert atmosphere at temperatures in the 1162–1494°C range. To inhibit the strong oxygen uptake by the titanium member a platinum insert was alternatively used. The microstructures and elemental profiles across the joints were investigated by scanning electron microscopy imaging and energy-dispersive spectroscopy or wavelength-dispersive spectroscopy microanalysis. It was found that direct ZrO2–Ti joining produces oxygen saturation in the Ti member and the formation of (Ti,Zr)2O at the interface. ZrO2/Pt/Ti joints present a complex layer sequence which at lower temperatures can be described on the basis of the Pt–Ti binary, except near the ceramic where a (Pt,Zr)-rich layer forms; at higher temperatures these joints develop an oxide layer of composition Ti2O3, this oxide probably resulting from local decomposition of the ceramic and reaction of oxygen with the incoming titanium. When Ti is replaced by the Ti–6 wt% Al–4 wt% V alloy in joints where Pt is present, the main consequences are the presence of liquid at lower joining temperatures and the earlier development of the oxide layer, now of nominal composition TiO. In all Pt-containing joints a phase of nominal composition Ti3Pt2 forms; it is advanced that this may be an equilibrium phase not predicted by the Pt–Ti diagrams available. All joints are weak, the fracture path running through the metal in the case of direct ZrO2–Ti joints and through the interface between the ceramic and the (Pt,Zr)-rich layer in joints where Pt is present.     

Future technologies for very high throughput satellite systems

In this paper, we investigate the possible satellite's role and technical solutions required for providing broadband services complementing the terrestrial fifth generation wireless standards. First, we review the satellite networks use cases, services, and system requirements. Then we investigate the satellite potential purpose for broadband service provision and the associated challenges with focus on the system and space/ground technological aspects. Different architectural satellite network solutions are illustrated jointly with the key system design trade‐offs. Particular emphasis is dedicated to the payload architecture. Finally, we illustrate the space and ground segment technologies enabling the successful satellite contribution to broadband services provision.     

The Strength of Desires: A Logical Approach

The aim of this paper is to propose a formal approach to reasoning about desires, understood as logical propositions which we would be pleased to make true, also acknowledging the fact that desire is a matter of degree. It is first shown that, at the static level, desires should satisfy certain principles that differ from those to which beliefs obey. In this sense, from a static perspective, the logic of desires is different from the logic of beliefs. While the accumulation of beliefs tend to reduce the remaining possible worlds they point at, the accumulation of desires tends to increase the set of states of affairs tentatively considered as satisfactory. Indeed beliefs are expected to be closed under conjunctions, while, in the positive view of desires developed here, one can argue that endorsing \(\varphi \vee \psi\) as a desire means to desire \(\varphi\) and to desire \(\psi\). However, desiring \(\varphi\) and \(\lnot \varphi\) at the same time is not usually regarded as rational, since it does not make much sense to desire one thing and its contrary at the same time. Thus when a new desire is added to the set of desires of an agent, a revision process may be necessary. Just as belief revision relies on an epistemic entrenchment relation, desire revision is based on a hedonic entrenchment relation satisfying other properties, due to the different natures of belief and desire. While epistemic entrenchment relations are known to be qualitative necessity relations (in the sense of possibility theory), hedonic relations obeying a set of reasonable postulates correspond to another set-function in possibility theory, called guaranteed possibility, that drive well-behaved desire revision operations. Then the general framework of possibilistic logic provides a syntactic setting for encoding desire change. The paper also insists that desires should be carefully distinguished from goals.     

DOGeye: Controlling your home with eye interaction

Nowadays home automation, with its increased availability, reliability and with its ever reducing costs is gaining momentum and is starting to become a viable solution for enabling people with disabilities to autonomously interact with their homes and to better communicate with other people. However, especially for people with severe mobility impairments, there is still a lack of tools and interfaces for effective control and interaction with home automation systems, and general-purpose solutions are seldom applicable due to the complexity, asynchronicity, time dependent behavior, and safety concerns typical of the home environment. This paper focuses on user-environment interfaces based on the eye tracking technology, which often is the only viable interaction modality for users as such. We propose an eye-based interface tackling the specific requirements of smart environments, already outlined in a public Recommendation issued by the COGAIN European Network of Excellence. The proposed interface has been implemented as a software prototype based on the ETU universal driver, thus being potentially able to run on a variety of eye trackers, and it is compatible with a wide set of smart home technologies, handled by the Domotic OSGi Gateway. A first interface evaluation, with user testing sessions, has been carried and results show that the interface is quite effective and usable without discomfort by people with almost regular eye movement control.     

The Rise of People-Centric Sensing

Technological advances in sensing, computation, storage, and communications will turn the near-ubiquitous mobile phone into a global mobile sensing device. People-centric sensing will help drive this trend by enabling a different way to sense, learn, visualize, and share information about ourselves, friends, communities, the way we live, and the world we live in. It juxtaposes the traditional view of mesh sensor networks with one in which people, carrying mobile devices, enable opportunistic sensing coverage. In the MetroSense Project's vision of people-centric sensing, users are the key architectural system component, enabling a host of new application areas such as personal, public, and social sensing.     

A new ligand for immunoglobulin g subdomains by screening of a synthetic peptide library

By screening a synthetic peptide library of general formula (NH(2)-Cys1-X2-X3-X4)(2)-Lys-Gly-OH, a disulfide-bridged cyclic peptide, where X2-X3-X4 is the tripeptide Phe-His-His, has been selected as a ligand for immunoglobulin G (IgG). The peptide, after a preliminary chromatographic characterization, has proved useful as a new affinity ligand for the purification of polyclonal as well as monoclonal antibodies from biological fluids, with recovery yields of up to 90% (90% purity). The ligand is able to bind antibody fragments containing both Fab and Fc from different antibody isotypes, a fact suggesting the presence of at least two different antibody-binding sites. While the recognition site on Fab is unknown, comparative binding studies with Fc, in association with the striking similarities of the peptide (named Fc-receptor mimetic, FcRM) with a region of the human FcgammaRIII receptor, strongly indicate that the peptide could recognize a short amino acid stretch of the lower hinge region, which has a key role in autoimmune disease triggering. The unique properties make the ligand attractive for both the purification of antibody fragments and as a lead for the generation of Fc-receptor antagonists.