Design, synthesis and characterisation of a novel type II B-RAF paradox breaker inhibitor.

The mutation V600E in B-Raf leads to mitogen activated protein kinase (MAPK) pathway activation, uncontrolled cell proliferation, and tumorigenesis. ATP competitive type I B-Raf inhibitors, such as vemurafenib (1) and PLX4720 (4) efficiently block the MAPK pathways in B-Raf mutant cells, however these inhibitors induce conformational changes in the wild type B-Raf (B-Raf) kinase domain leading to heterodimerization with C-Raf, causing paradoxical hyperactivation of the MAPK pathway. This unwanted activation may be avoided by another class of inhibitors (type II) which bind the kinase in the DFG-out conformation, such as AZ628 (3) preventing heterodimerization.

Spatial organization-dependent EphA2 transcriptional responses revealed by ligand nanocalipers.

Ligand binding induces extensive spatial reorganization and clustering of the EphA2 receptor at the cell membrane. It has previously been shown that the nanoscale spatial distribution of ligands modulates EphA2 receptor reorganization, activation and the invasive properties of cancer cells. However, intracellular signaling downstream of EphA2 receptor activation by nanoscale spatially distributed ligands has not been elucidated.

Ketone Synthesis by a Nickel-Catalyzed Dehydrogenative Cross-Coupling of Primary Alcohols.

An intermolecular coupling of primary alcohols and organotriflates has been developed to provide ketones by the action of a Ni(0) catalyst. This oxidative transformation is proposed to occur by the union of three distinct catalytic cycles. Two competitive oxidation processes generate aldehyde in situ via hydrogen transfer oxidation or (pseudo)dehalogenation pathways.

Biological and chemical treatment technologies for waste amines from CO capture plants.

Amine-based carbon dioxide capture is the most mature technology for reducing flue gas CO emissions. It has been postulated and observed during commercialisation of this technology that significant quantities of waste amines are produced. Further industrial implementation of this technology requires adequate disposal or valorisation options for this waste.

Atrial Premature Depolarization-Induced Changes in QRS and T Wave Morphology on Resting Electrocardiograms in Horses.

Background: The electrocardiographic differentiation between atrial (APDs) and ventricular (VPDs) premature depolarizations is important. P wave prematurity and normal QRS and T wave morphology generally are used as discriminating criteria for APDs.

Hypothesis/objectives: The aim of this study was to determine whether P, Q, R, S, and T wave amplitude, PQ interval, QRS and P wave duration and P and T wave morphology differ between APDs and sinus beats.

Mechanisms of low temperature capture and regeneration of CO2 using diamino protic ionic liquids.

Carbon dioxide (CO2) chemical absorption and regeneration was investigated in two diamino carboxylate protic ionic liquids (PILs), dimethylethylenediamine formate (DMEDAH formate) and dimethylpropylenediamine acetate (DMPDAH acetate), using novel calorimetric techniques. The PILs under study have previously been shown to possess a CO2 absorption capacity similar to the industrial standard, 30% aqueous MEA, while requiring much lower temperatures to release the captured CO2. We show that this is in part due to the fact that the PILs exhibit enthalpies of CO2 desorption as low as 40 kJ mol(-1), significantly lower than the 85 kJ mol(-1) required for 30% aqueous MEA.

Genome-wide promoter binding profiling of protein phosphatase-1 and its major nuclear targeting subunits.

Protein phosphatase-1 (PP1) is a key regulator of transcription and is targeted to promoter regions via associated proteins. However, the chromatin binding sites of PP1 have never been studied in a systematic and genome-wide manner. Methylation-based DamID profiling in HeLa cells has enabled us to map hundreds of promoter binding sites of PP1 and three of its major nuclear interactors, i.

Influence of detomidine on atrial fibrillation cycle length measured by intracardiac electrogram recording and by colour tissue Doppler imaging in horses.

Reasons For Performing Study: Shortening of atrial fibrillation cycle length (AFCL) is a marker of atrial electrical remodelling due to atrial fibrillation (AF).

Objectives: To investigate the effect of administration of detomidine on AFCL measured invasively from an intra-atrial electrogram (AFCLEGM) and noninvasively by tissue Doppler imaging (AFCLTDI). We hypothesised that detomidine would have no effect on AFCL but would improve the ease of TDI measurements and facilitate noninvasive AFCL determination.

Atrial fibrillation cycle length and atrial size in horses with and without recurrence of atrial fibrillation after electrical cardioversion.

Background: Atrial fibrillation (AF) cycle length (CL) and atrial size have been used in humans to characterize electrical and structural remodeling to predict outcome of cardioversion of AF and risk for AF recurrence (rAF).

Hypothesis: Atrial fibrillation cycle length can be determined in horses with AF, and AFCL and atrial size are related to risk for rAF.

Animals: Eighteen horses with naturally occurring AF that were successfully converted to sinus rhythm (SR) by transvenous electrical cardioversion (TVEC).

Long-term follow-up of atrial function after cardioversion of atrial fibrillation in horses.

Atrial fibrillation (AF) causes atrial electrical and contractile remodelling in horses. The aim of this study was to quantify left atrial (LA) contractile function and its time course of recovery after cardioversion of naturally-occurring AF in horses. The study population included 42 AF horses which were successfully treated using transvenous electrical cardioversion TVEC (n=39) or quinidine sulfate (n=3), with trivial or mild mitral regurgitation present in 25 horses.

Noninvasive determination of atrial fibrillation cycle length by atrial colour tissue Doppler imaging in horses.

Reasons For Performing Study: Atrial fibrillation cycle length (AFCL) is an indicator of atrial electrical remodelling during atrial fibrillation (AF).

Objectives: To compare AFCL measured invasively from an intra-atrial electrogram (AFCLEGM ) with AFCL measured noninvasively by atrial colour tissue Doppler imaging (AFCLTDI ).

Study Design: Prospective descriptive clinical study.

Evaluation of tissue Doppler imaging for regional quantification of radial left ventricular wall motion in healthy horses.

Objective: To compare the feasibility and repeatability of tissue Doppler imaging (TDI) for quantification of radial left ventricular (LV) velocity and deformation from different imaging planes and to correlate cardiac event timing data obtained by TDI to M-mode and pulsed-wave Doppler-derived time intervals in horses.

Animals: 10 healthy adult horses.

Procedures: Repeated echocardiography was performed by 2 observers from right and left parasternal short-axis views at papillary muscle and chordal levels.

Influence of atrioventricular interaction on mitral valve closure and left ventricular isovolumic contraction measured by tissue Doppler imaging.

Background: The influence of atrioventricular (AV) interaction on mitral valve closure (MVC) and left ventricular (LV) isovolumic contraction is not fully clarified. We investigated the relationship among AV delay, MVC, and LV isovolumic contraction using a horse model because of the low heart rate and physiologically long AV delay.

Methods And Results: Six horses were evaluated during sinus rhythm, right ventricular pacing without preceding atrial contraction, and dual-chamber pacing at AV delays of 150 to 350 ms, programmed at a constant rate.

Ventricular response during lungeing exercise in horses with lone atrial fibrillation.

Reasons For Performing The Study: Atrial fibrillation (AF) is the most important dysrhythmia affecting performance in horses and has been associated with incoordination, collapse and sudden death. Limited information is available on ventricular response during exercise in horses with lone AF.

Objectives: To investigate ventricular response in horses with lone AF during a standardised lungeing exercise test.

Tissue Doppler imaging and 2-dimensional speckle tracking of left ventricular function in horses exposed to lasalocid.

Background: Tissue Doppler imaging (TDI) and 2-dimensional speckle tracking (2DST) can quantify left ventricular (LV) function in horses.

Objectives: To evaluate LV function by TDI and 2DST in horses with myocardial dysfunction after accidental ionophore intoxication.

Animals: Sixty-seven horses exposed to lasalocid in feed.

Cardiac changes in horses with atypical myopathy.

Background: Atypical myopathy (AM) is an acute, fatal rhabdomyolysis in grazing horses that mainly affects skeletal muscles. Postmortem examinations have shown that myocardial damage also occurs. Limited information is available on the effect of AM on cardiac function in affected and surviving horses.

Acute and long-term cardiomyopathy and delayed neurotoxicity after accidental lasalocid poisoning in horses.

Background: Horses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity.

Objectives: To describe accidental lasalocid poisoning on a farm in Belgium.

Two-dimensional speckle tracking for quantification of left ventricular circumferential and radial wall motion in horses.

Reasons For Performing Study: The use of two-dimensional speckle tracking (2DST) for quantification of left ventricular (LV) function has recently been described in horses using long-axis images and short-axis images at chordal but not at papillary muscle level.

Objectives: To compare the feasibility and reliability of 2DST for quantification of circumferential and radial LV function in short-axis images at papillary muscle and chordal level.

Methods: Repeated echocardiographic examinations were performed on 10 healthy trotter horses by 2 observers from a right parasternal short-axis view at papillary muscle and chordal level.

Towards commercial scale postcombustion capture of CO2 with monoethanolamine solvent: key considerations for solvent management and environmental impacts.

Chemical absorption with aqueous amine solvents is the most advanced technology for postcombustion capture (PCC) of CO(2) from coal-fired power stations and a number of pilot scale programs are evaluating novel solvents, optimizing energy efficiency, and validating engineering models. This review demonstrates that the development of commercial scale PCC also requires effective solvent management guidelines to ensure minimization of potential technical and environmental risks. Furthermore, the review reveals that while solvent degradation has been identified as a key source of solvent consumption in laboratory scale studies, it has not been validated at pilot scale.

Oesophageal electrocardiography in healthy horses.

Reasons For Performing Study: In human medicine, oesophageal electrocardiography (ECG) is a well-established technique that magnifies P waves with respect to the QRS complex.

Objectives: To investigate the feasibility of oesophageal ECG recording in horses and its ability to produce larger P waves compared with base-apex and unipolar recordings.

Methods: Bipolar and unipolar ECG were performed using oesophageal and surface electrodes.

Repo-Man coordinates chromosomal reorganization with nuclear envelope reassembly during mitotic exit.

Repo-Man targets protein phosphatase 1 γ (PP1γ) to chromatin at anaphase onset and regulates chromosome structure during mitotic exit. Here, we show that a Repo-Man:PP1 complex forms in anaphase following dephosphorylation of Repo-Man. Upon activation, the complex localizes to chromosomes and causes the dephosphorylation of histone H3 (Thr3, Ser10, and Ser28).

Quantification of left ventricular longitudinal strain, strain rate, velocity, and displacement in healthy horses by 2-dimensional speckle tracking.

Background: The quantification of equine left ventricular (LV) function is generally limited to short-axis M-mode measurements. However, LV deformation is 3-dimensional (3D) and consists of longitudinal shortening, circumferential shortening, and radial thickening. In human medicine, longitudinal motion is the best marker of subtle myocardial dysfunction.

trans-Monounsaturated Acids in a Marine Bacterial Isolate.

A sedimentary bacterial isolate has been shown to contain trans-monounsaturated fatty acids (6% of the total fatty acids). The ratio of trans- to cis-acids in this isolate was in the range 3.2 to 7.