Paradoxes of causal loops in spacetime

There is, among some scientists and philosophers, the idea that any theory that would allow the time travel would introduce causal issues. These types of temporal paradoxes can be avoided by the Novikov self-consistency principle or by a variation in the interpretation of many worlds with interacting worlds. The world in which we live has, according to David Lewis, a Parmenidean ontology: "a manifold of events in four dimensions," and the occupants of the world are the 4-dimensional aggregates of the stages - "temporal lines". The causal loops in backwards time travel involve events that appear to "come from nowhere," paradoxical "self-existent" objects or information, resulting in a bootstrap paradox. Many believe that causality loops are not impossible or unacceptable, but only inexplicable. DOI: 10.13140/RG.2.2.28792.7040

The role of fossils in interpreting the development of the Karoo Basin

Main articleThe Permo-Carboniferous to Jurassic aged rocks off the main Karoo Basin of South Africa are world renowned for the wealth of synapsid reptile and early dinosaur fossils, which have allowed a ten-fold biostratigraphic subdivision of the Karoo Supergroup to be erected. The role of fossils in interpreting the development of the Karoo Basin is not, however, restricted to biostratigraphic studies. Recent integrated sedimentological and palaeontological studies have helped in more precisely defining a number of problematical formational contacts within the Karoo Supergroup, as well as enhancing palaeoenvironmental reconstructions, and basin development models.Non

Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats

Hypertension-induced structural remodeling of the left atrium (LA) has been suggested to involve the renin–angiotensin system. This study investigated whether treatment with an angiotensin receptor blocker, candesartan, regresses atrial remodeling in spontaneously hypertensive rats (SHR). Effects of treatment with candesartan were compared to treatment with a nonspecific vasodilatator, hydralazine. Thirty to 32-week-old adult male SHR were either untreated (n = 15) or received one of either candesartan cilexetil (n = 9; 3 mg/kg/day) or hydralazine (n = 10; 14 mg/kg/day) via their drinking water for 14 weeks prior to experiments. Untreated age- and sex-matched Wistar- Kyoto rats (WKY; n = 13) represented a normotensive control group. Untreated SHR were hypertensive, with left ventricular hypertrophy (LVH) compared to WKY, but there were no differences in systolic pressures in excised, perfused hearts. LA from SHR were hypertrophied and showed increased fibrosis compared to those from WKY, but there was no change in connexin-43 expression or phosphorylation. Treatment with candesartan reduced systolic tail artery pressures of conscious SHR below those of normotensive WKY and caused regression of both LVH and LA hypertrophy. Although hydralazine reduced SHR arterial pressures to those of WKY and led to regression of LA hypertrophy, it had no significant effect on LVH. Notably, LA fibrosis was unaffected by treatment with either agent. These data show that candesartan, at a dose sufficient to reduce blood pressure and LVH, did not cause regression of LA fibrosis in hypertensive rats. On the other hand, the data also suggest that normalization of arterial pressure can lead to the regression of LA hypertrophy

Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806

Transient outward potassium current (Ito) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of Ito may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine Ito This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular Ito Whole cell patch-clamp recordings of Ito and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10 μmol/L NS5806 increased ventricular Ito with a leftward shift in Ito activation and accelerated restitution. At higher concentrations, stimulation of Ito was followed by inhibition. The EC50 for stimulation was 1.6 μmol/L and inhibition had an IC50 of 40.7 μmol/L. NS5806 only inhibited atrial Ito (IC50 of 18 μmol/L) and produced a modest leftward shifts in Ito activation and inactivation, without an effect on restitution. 10 μmol/L NS5806 shortened ventricular action potential duration (APD) at APD20-APD90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na(+) channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial Ito NS5806 discriminates between rabbit ventricular and atrial Ito, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac Ito.</p