Physics-Constrained Hardware-Efficient Ansatz on Quantum Computers that is Universal, Systematically Improvable, and Size-consistent

Variational wavefunction ans\"{a}tze are at the heart of solving quantum many-body problems in physics and chemistry. Here, we propose a physics-constrained approach for designing hardware-efficient ansatz (HEA) with rigorous theoretical guarantees on quantum computers by satisfying a few fundamental constraints, which is inspired by the remarkably successful way to design exchange-correlation functionals in density functional theories by satisfying exact constraints. Specifically, we require that the target HEA to be universal, systematically improvable, and size-consistent, which is an important concept in quantum many-body theories for scalability, but has been largely overlooked in previous designs of HEA by heuristics. We extend the notion of size-consistency to HEA, and present a concrete realization of HEA that satisfies all these fundamental constraints and only requires linear qubit connectivity. The developed physics-constrained HEA is superior to other heuristically designed HEA in terms of both accuracy and scalability, as demonstrated numerically for the Heisenberg model and some typical molecules. In particular, we find that restoring size-consistency can significantly reduce the number of layers needed to reach certain accuracy. In contrast, the failure of other HEA to satisfy these constraints severely limits their scalability to larger systems with more than ten qubits. Our work highlights the importance of incorporating physical constraints into the design of HEA for efficiently solving many-body problems on quantum computers.Comment: 21 pages, 4 figure

Calreticulin and calnexin in the endoplasmic reticulum are important for phagocytosis

Calreticulin and calnexin are Ca(2+)-binding proteins with chaperone activity in the endoplasmic reticulum. These proteins have been eliminated by gene replacement in Dictyostelium, the only microorganism known to harbor both proteins; family members in Dictyostelium are located at the base of phylogenetic trees. A dramatic decline in the rate of phagocytosis was observed in double mutants lacking calreticulin and calnexin, whereas only mild changes occurred in single mutants. Dictyostelium cells are professional phagocytes, capable of internalizing particles by a sequence of activities: adhesion of the particle to the cell surface, actin-dependent outgrowth of a phagocytic cup, and separation of the phagosome from the plasma membrane. In the double-null mutants, particles still adhered to the cell surface, but the outgrowth of phagocytic cups was compromised. Green fluorescent protein-tagged calreticulin and calnexin, expressed in wild-type cells, revealed a direct link of the endoplasmic reticulum to the phagocytic cup enclosing a particle, such that the Ca(2+) storage capacity of calreticulin and calnexin might directly modulate activities of the actin system during particle uptake

Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

The dynamic regulation of the cellular trafficking of human angiotensin (Ang) type 1 receptor (AT(1)R) is not well understood. Therefore, we investigated the cellular trafficking of AT(1)R–enhanced green fluorescent protein (EGFP) (AT(1)R-EGFP) heterologously expressed in HEK293 cells by determining the change in donor lifetime (AT(1)R-EGFP) in the presence or absence of acceptor(s) using fluorescence lifetime imaging–fluorescence resonance energy transfer (FRET) microscopy. The average lifetime of AT(1)R-EGFP in our donor-alone samples was ∼2.33 ns. The basal state lifetime was shortened slightly in the presence of Rab5 (2.01±0.10 ns) or Rab7 (2.11±0.11 ns) labeled with Alexa 555, as the acceptor fluorophore. A 5-min Ang II treatment markedly shortened the lifetime of AT(1)R-EGFP in the presence of Rab5-Alexa 555 (1.78±0.31 ns) but was affected minimally in the presence of Rab7-Alexa 555 (2.09±0.37 ns). A 30-min Ang II treatment further decreased the AT(1)R-EGFP lifetime in the presence of both Rab5- and Rab7-Alexa 555. Latrunculin A but not nocodazole pretreatment blocked the ability of Ang II to shorten the AT(1)R-EGFP lifetime. The occurrence of FRET between AT(1)R-EGFP (donor) and LAMP1-Alexa 555 (acceptor) with Ang II stimulation was impaired by photobleaching the acceptor. These studies demonstrate that Ang II-induced AT(1)R lysosomal degradation through its association with LAMP1 is regulated by Rab5∕7 via mechanisms that are dependent on intact actin cytoskeletons

D\u3csub\u3e5\u3c/sub\u3e dopamine receptor decreases NADPH oxidase, reactive oxygen species and blood pressure via heme oxygenase-1

D5 dopamine receptor (D5R) knock-out mice (D 5-/-) have a higher blood pressure (BP) and higher reactive oxygen species (ROS) production than their D5R wild-type littermates (D5+/+). We tested the hypothesis that the high BP and increased ROS production in D5-/- mice may be caused by decreased heme oxygenase-1 (HO-1) expression and activity. We found that renal HO-1 protein expression and HO enzyme activity were decreased (65 and 50%, respectively) in D5-/- relative to D 5+/+ mice. A 24 h of administration of hemin, an HO-1 inducer, increased HO-1 expression and HO activity (6.8- and 1.9-fold, respectively) and normalized the increased ROS production and BP in D 5-/- mice. Expression of HO-1 protein and HO activity were increased (2.3- and 1.5-fold, respectively) in HEK cells that heterologously expressed human wild-type D5R (HEK-hD5R), but not the empty vector-transfected HEK-293 cells. Fenoldopam (Fen), a D5R agonist, increased HO activity (3 h), HO-1 protein expression, HO-1 and D 5R colocalization and co-immunoprecipitation in HEK-hD5R cells. Cellular NADPH oxidase activity was decreased by 35% in HEK-hD 5R that was abrogated with silencing of the heme oxygenase 1 gene (HMOX1). HMOX1 siRNA also impaired the ability of Fen to decrease NADPH oxidase activity in HEK-hD5R cells. In summary, the D5R positively regulates HO-1 through direct protein/protein interaction in the short-term and by increasing HO-1 protein expression in the long-term. The impaired D 5R regulation of HO-1 and ROS production contributes to the pathogenesis of hypertension in D5-/- mice. © 2013 The Japanese Society of Hypertension. All rights reserved

D\u3csub\u3e3\u3c/sub\u3e dopamine receptor directly interacts with D\u3csub\u3e1\u3c/sub\u3e dopamine receptor in immortalized renal proximal tubule cells

D3 receptors act synergistically with D1 receptors to inhibit sodium transport in renal proximal tubules; however, the mechanism by which this occurs is not known. Because dopamine receptor subtypes can regulate and interact with each other, we studied the interaction of D3 and D1 receptors in rat renal proximal tubule (RPT) cells. The D 3 agonist PD128907 increased the immunoreactive expression of D 1 receptors in a concentration- and time-dependent manner; these effects were blocked by the D3 antagonist U99194A. PD128907 also transiently (15 minutes) increased the amount of cell surface membrane D 1 receptors. Laser confocal immunofluorescence microscopy showed that D3 receptor and D1 receptor colocalized in RPT cells more distinctly in Wistar-Kyoto rats than in spontaneously hypertensive rats (SHRs). In addition, D3 and D1 receptors could be coimmunoprecipitated, and this interaction was increased after D3 receptor agonist stimulation for 24 hours in Wistar-Kyoto rats but not in SHRs. We propose that the synergistic effects of D3 and D1 receptors may be caused by a D3 receptor-mediated increase in total, as well as cell surface membrane D1 receptor expression, and direct D3 and D1 receptor interaction, both of which are impaired in SHRs. © 2006 American Heart Association, Inc

Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells

NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6–14/group). Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA), effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (−45.1±3.2% vs. mock-siRNA, n=6–8) in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (−32.5±1.8%) than HT (−14.8±1.8). In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system

Upregulation of renal sodium transporters in D5 dopamine receptor-deficient mice

D5 dopamine receptor (D5R)-deficient (D 5-/-) mice have hypertension that is aggravated by an increase in sodium intake. The present experiments were designed to test the hypothesis that a dysregulation of renal sodium transporters is related to the salt sensitivity in D5-/- mice. D5R was expressed in the renal proximal tubule, thick ascending limb, distal convoluted tubule, and cortical and outer medullary collecting ducts in D5+/+ mice. On a control Na+ diet, renal protein expressions of NKCC2 (sodium-potassium-2 chloride cotransporter), sodium chloride cotransporter, and α and γ subunits of the epithelial sodium channel were greater in D5-/- than in D5+/+ mice. Renal renin abundance and urine aldosterone levels were similar but renal angiotensin II type 1 receptor (AT1R) protein expression was increased in D5-/- mice. An elevated Na+ diet increased further the elevated blood pressure of D5-/- mice but did not affect the normal blood pressure of D5+/+ mice. The increased levels of NKCC2, sodium chloride cotransporter, and α and γ subunits of the epithelial sodium channel persisted with the elevated Na+ diet and unaffected by chronic AT1R blockade (losartan) in D5-/- mice. The expressions of proximal sodium transporters NHE3 (sodium hydrogen exchanger type 3) and NaPi2 (sodium phosphate cotransporter type 2) were increased by the elevated Na diet in D 5-/- mice; the increased expression of NHE3 but not NaPi2 was abolished by AT1R blockade. Our findings suggest that the increased protein expression of sodium transporters/channels in distal nephron segments may be the direct consequence of the disruption of D5R, independent of the renin-angiotensin aldosterone system. © 2010 American Heart Association, Inc