Intrinsic Dimension of Path Integrals: Data-Mining Quantum Criticality and Emergent Simplicity

Quantum many-body systems are characterized by patterns of correlations defining highly nontrivial manifolds when interpreted as data structures. Physical properties of phases and phase transitions are typically retrieved via correlation functions, that are related to observable response functions. Recent experiments have demonstrated capabilities to fully characterize quantum many-body systems via wave-function snapshots, opening new possibilities to analyze quantum phenomena. Here, we introduce a method to data mine the correlation structure of quantum partition functions via their path integral (or equivalently, stochastic series expansion) manifold. We characterize path-integral manifolds generated via state-of-the-art quantum Monte Carlo methods utilizing the intrinsic dimension (ID) and the variance of distances between nearest-neighbor (NN) configurations: the former is related to data-set complexity, while the latter is able to diagnose connectivity features of points in configuration space. We show how these properties feature universal patterns in the vicinity of quantum criticality, that reveal how data structures simplify systematically at quantum phase transitions. This is further reflected by the fact that both ID and variance of NN distances exhibit universal scaling behavior in the vicinity of second-order and Berezinskii-Kosterlitz-Thouless critical points. Finally, we show how non-Abelian symmetries dramatically influence quantum data sets, due to the nature of (noncommuting) conserved charges in the quantum case. Complementary to neural-network representations, our approach represents a first elementary step towards a systematic characterization of path-integral manifolds before any dimensional reduction is taken, that is informative about universal behavior and complexity, and can find immediate application to both experiments and Monte Carlo simulations

pGlu-serpinin protects the normotensive and hypertensive heart from ischemic injury

Serpinin peptides derive from proteolytic cleavage of Chromogranin-A at C-terminus. Serpinin and the more potent pyroglutaminated-Serpinin (pGlu-Serp) are positive cardiac beta-adrenergic-like modulators, acting through β1-AR/AC/cAMP/PKA pathway. Since in some conditions this pathway and/or other pro-survival pathways, activated by other Chromogranin-A fragments, may cross-talk and may be protective, here we explored whether pGlu-Serp cardioprotects against ischemia/reperfusion injury under normotensive and hypertensive conditions. In the latter condition cardioprotection is often blunted because of the limitations on pro-survival Reperfusion-Injury-Salvage-Kinases (RISK) pathway activation. The effects of pGlu-Serp were evaluated on infarct size (IS) and cardiac function by using the isolated and Langendorff perfused heart of normotensive (WKY) and spontaneously hypertensive (SHR) rats exposed to ischemic pre-conditioning (PreC) and post-conditioning (PostC). In both WKY and SHR rat, pGlu-Serp induced mild cardioprotection in both PreC and in PostC. pGlu-Serp administered at the reperfusion (Serp-PostC) significantly reduced IS, being more protective in SHR than in WKY. Conversely, developed Left Ventricular Pressure (LVDevP) post-ischemic recovery was greater in WKY than in SHR. pGlu-Serp-PostC reduced contracture in both strains. Co-infusion with specific RISK inhibitors (PI3K/AkT, MitoK(ATP) channels, and PKC) blocked the pGlu-Serp-PostC protective effects. To show direct effect on cardiomyocytes, we pre-treated H9c2 with pGlu-Serp which were thus protected against hypoxia/reoxygenation. These results suggest pGlu-Serp as a potential modulatory agent implicated in the protective processes which can limit infarct size and overcome the hypertension-induced failure of PostC

Carbazole and simplified derivatives: Novel tools toward β-adrenergic receptors targeting

β-Adrenergic receptors (β-ARs) are G protein-coupled receptors involved in important physiological and pathological processes related to blood pressure and cardiac activity. The inhibition of cardiac β1-ARs could be beneficial in myocardial hypertrophy, ischemia and failure. Several carbazole-based compounds have been described as promising β-blockers. Herein, we investigate the capability of a carbazole derivative and three simplified indole analogs to interact with the active binding site of β1-AR by molecular docking studies. In the light of the obtained results, our compounds were tested by biological assays in H9c2 cardiomyocytes exposed to isoproterenol (ISO) to confirm their potential as β1-blockers agents, and two of them (8 and 10) showed interesting and promising properties. In particular, these compounds were effective against ISO-dependent in vitro cardiac hypertrophy, even at concentrations lower than the known β-AR antagonist propranolol. Overall, the data suggest that the indole derivatives 8 and 10 could act as potent β1-blockers and, active at low doses, could elicit limited side effects

Catestatin Increases the Expression of Anti-Apoptotic and Pro-Angiogenetic Factors in the Post-Ischemic Hypertrophied Heart of SHR.

BACKGROUND:In the presence of comorbidities the effectiveness of many cardioprotective strategies is blunted. The goal of this study was to assess in a hypertensive rat model if the early reperfusion with anti-hypertensive and pro-angiogenic Chromogranin A-derived peptide, Catestatin (CST:hCgA352-372; CST-Post), protects the heart via Reperfusion-Injury-Salvage-Kinases (RISK)-pathway activation, limiting infarct-size and apoptosis, and promoting angiogenetic factors (e.g., hypoxia inducible factor, HIF-1α, and endothelial nitric oxide synthase, eNOS, expression). METHODS AND RESULTS:The effects of CST-Post on infarct-size, apoptosis and pro-angiogenetic factors were studied in isolated hearts of spontaneously hypertensive rats (SHR), which underwent the following protocols: (a) 30-min ischemia and 120-min reperfusion (I/R); (b) 30-min ischemia and 20-min reperfusion (I/R-short), both with and without CST-Post (75 nM for 20-min at the beginning of reperfusion). In unprotected Wistar-Kyoto hearts, used as normal counterpart, infarct-size resulted smaller than in SHR. CST-Post reduced significantly infarct-size and improved post-ischemic cardiac function in both strains. After 20-min reperfusion, CST-Post induced S-nitrosylation of calcium channels and phosphorylation of RISK-pathway in WKY and SHR hearts. Yet specific inhibitors of the RISK pathway blocked the CST-Post protective effects against infarct in the 120-min reperfusion groups. Moreover, apoptosis (evaluated by TUNEL, ARC and cleaved caspase) was reduced by CST-Post. Importantly, CST-Post increased expression of pro-angiogenetic factors (i.e., HIF-1α and eNOS expression) after two-hour reperfusion. CONCLUSIONS:CST-Post limits reperfusion damages and reverses the hypertension-induced increase of I/R susceptibility. Moreover, CST-Post triggers antiapoptotic and pro-angiogenetic factors suggesting that CST-Post can be used as an anti-maladaptive remodeling treatment