Variational-Correlations Approach to Quantum Many-body Problems

We investigate an approach for studying the ground state of a quantum many-body Hamiltonian that is based on treating the correlation functions as variational parameters. In this approach, the challenge set by the exponentially-large Hilbert space is circumvented by approximating the positivity of the density matrix, order-by-order, in a way that keeps track of a limited set of correlation functions. In particular, the density-matrix description is replaced by a correlation matrix whose dimension is kept linear in system size, to all orders of the approximation. Unlike the conventional variational principle which provides an upper bound on the ground-state energy, in this approach one obtains a lower bound instead. By treating several one-dimensional spin 1/2 Hamiltonians, we demonstrate the ability of this approach to produce long-range correlations, and a ground-state energy that converges to the exact result. Possible extensions, including to higher-excited states are discussed

Variational-Correlations Approach to Quantum Many-body Problems

We investigate an approach for studying the ground state of a quantum many-body Hamiltonian that is based on treating the correlation functions as variational parameters. In this approach, the challenge set by the exponentially-large Hilbert space is circumvented by approximating the positivity of the density matrix, order-by-order, in a way that keeps track of a limited set of correlation functions. In particular, the density-matrix description is replaced by a correlation matrix whose dimension is kept linear in system size, to all orders of the approximation. Unlike the conventional variational principle which provides an upper bound on the ground-state energy, in this approach one obtains a lower bound instead. By treating several one-dimensional spin 1/2 Hamiltonians, we demonstrate the ability of this approach to produce long-range correlations, and a ground-state energy that converges to the exact result. Possible extensions, including to higher-excited states are discussed

Phonon-induced Floquet topological phases protected by space-time symmetries

For systems with spatial and nonspatial symmetries, the topological classification depends not only on these symmetries but also on the commutation/anticommutation relations between spatial and nonspatial symmetries. The coexistence of spatial and nonspatial symmetries together with appropriate commutation/anticommutation relations between them can give rise to crystalline and higher-order topological phases, which host gapless boundary modes. Alternatively, space-time symmetries in a Floquet system can take the role of spatial symmetries in deciding the topological classification. Promoting a spatial symmetry to a space-time symmetry can alter the commutation relations, which in turn can modify the topological properties of the system. We show how a coherently excited phonon mode can be used to promote a spatial symmetry with which the static system is always trivial to a space-time symmetry which supports a nontrivial Floquet topological phase. We demonstrate this effect by considering two systems: The first is a second-order topological superconductor, and the second is a first-order crystalline topological insulator. In both these cases, a coherently excited phonon mode is responsible for promoting the reflection symmetry to a time-glide symmetry. This newly introduced symmetry allows the previously trivial system to host gapless modes. In the first case, these are protected corner modes, while in the second case, these are gapless edge modes

Floquet Majorana bound states in voltage-biased Planar Josephson Junctions

We study a planar Josephson junction under an applied DC voltage bias in the presence of an in-plane magnetic field. Upon tuning the bias voltage across the junction, V_J, the two ends of the junction are shown to simultaneously host both 0- and π-Majorana modes. These modes can be probed using either a Scanning-Tunneling-Microscopy measurement or through resonant Andreev tunneling from a lead coupled to the junction. While these modes are mostly bound to the junction's ends, they can hybridize with the bulk by absorbing or emitting photons. We analyze this process both numerically and analytically, demonstrating that it can become negligible under typical experimental conditions. Transport signatures of the 0- and π-Majorana states are shown to be robust to moderate disorder

Phonon-induced Floquet topological phases protected by space-time symmetries

For systems with spatial and nonspatial symmetries, the topological classification depends not only on these symmetries but also on the commutation/anticommutation relations between spatial and nonspatial symmetries. The coexistence of spatial and nonspatial symmetries together with appropriate commutation/anticommutation relations between them can give rise to crystalline and higher-order topological phases, which host gapless boundary modes. Alternatively, space-time symmetries in a Floquet system can take the role of spatial symmetries in deciding the topological classification. Promoting a spatial symmetry to a space-time symmetry can alter the commutation relations, which in turn can modify the topological properties of the system. We show how a coherently excited phonon mode can be used to promote a spatial symmetry with which the static system is always trivial to a space-time symmetry which supports a nontrivial Floquet topological phase. We demonstrate this effect by considering two systems: The first is a second-order topological superconductor, and the second is a first-order crystalline topological insulator. In both these cases, a coherently excited phonon mode is responsible for promoting the reflection symmetry to a time-glide symmetry. This newly introduced symmetry allows the previously trivial system to host gapless modes. In the first case, these are protected corner modes, while in the second case, these are gapless edge modes

Calcium Handling in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

BACKGROUND: The ability to establish human induced pluripotent stem cells (hiPSCs) by reprogramming of adult fibroblasts and to coax their differentiation into cardiomyocytes opens unique opportunities for cardiovascular regenerative and personalized medicine. In the current study, we investigated the Ca(2+)-handling properties of hiPSCs derived-cardiomyocytes (hiPSC-CMs). METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and immunocytochemistry experiments identified the expression of key Ca(2+)-handling proteins. Detailed laser confocal Ca(2+) imaging demonstrated spontaneous whole-cell [Ca(2+)](i) transients. These transients required Ca(2+) influx via L-type Ca(2+) channels, as demonstrated by their elimination in the absence of extracellular Ca(2+) or by administration of the L-type Ca(2+) channel blocker nifedipine. The presence of a functional ryanodine receptor (RyR)-mediated sarcoplasmic reticulum (SR) Ca(2+) store, contributing to [Ca(2+)](i) transients, was established by application of caffeine (triggering a rapid increase in cytosolic Ca(2+)) and ryanodine (decreasing [Ca(2+)](i)). Similarly, the importance of Ca(2+) reuptake into the SR via the SR Ca(2+) ATPase (SERCA) pump was demonstrated by the inhibiting effect of its blocker (thapsigargin), which led to [Ca(2+)](i) transients elimination. Finally, the presence of an IP3-releasable Ca(2+) pool in hiPSC-CMs and its contribution to whole-cell [Ca(2+)](i) transients was demonstrated by the inhibitory effects induced by the IP3-receptor blocker 2-Aminoethoxydiphenyl borate (2-APB) and the phospholipase C inhibitor U73122. CONCLUSIONS/SIGNIFICANCE: Our study establishes the presence of a functional, SERCA-sequestering, RyR-mediated SR Ca(2+) store in hiPSC-CMs. Furthermore, it demonstrates the dependency of whole-cell [Ca(2+)](i) transients in hiPSC-CMs on both sarcolemmal Ca(2+) entry via L-type Ca(2+) channels and intracellular store Ca(2+) release

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice

Vascular dysregulation and cholinergic basal forebrain degeneration are both early pathological events in the development of Alzheimer’s disease (AD). Acetylcholine contributes to localised arterial dilatation and increased cerebral blood flow (CBF) during neurovascular coupling via activation of endothelial nitric oxide synthase (eNOS). Decreased vascular reactivity is suggested to contribute to impaired clearance of β-amyloid (Aβ) along intramural periarterial drainage (IPAD) pathways of the brain, leading to the development of cerebral amyloid angiopathy (CAA). However, the possible relationship between loss of cholinergic innervation, impaired vasoreactivity and reduced clearance of Aβ from the brain has not been previously investigated. In the present study, intracerebroventricular administration of mu-saporin resulted in significant death of cholinergic neurons and fibres in the medial septum, cortex and hippocampus of C57BL/6 mice. Arterial spin labelling MRI revealed a loss of CBF response to stimulation of eNOS by the Rho-kinase inhibitor fasudil hydrochloride in the cortex of denervated mice. By contrast, the hippocampus remained responsive to drug treatment, in association with altered eNOS expression. Fasudil hydrochloride significantly increased IPAD in the hippocampus of both control and saporin-treated mice, while increased clearance from the cortex was only observed in control animals. Administration of mu-saporin in the TetOAPPSweInd mouse model of AD was associated with a significant and selective increase in Aβ40-positive CAA. These findings support the importance of the interrelationship between cholinergic innervation and vascular function in the aetiology and/or progression of CAA and suggest that combined eNOS/cholinergic therapies may improve the efficiency of Aβ removal from the brain and reduce its deposition as CAA