Quantum correlations from local amplitudes and the resolution of the Einstein-Podolsky-Rosen nonlocality puzzle

The Einstein-Podolsky-Rosen nonlocality puzzle has been recognized as one of the most important unresolved issues in the foundational aspects of quantum mechanics. We show that the problem is resolved if the quantum correlations are calculated directly from local quantities which preserve the phase information in the quantum system. We assume strict locality for the probability amplitudes instead of local realism for the outcomes, and calculate an amplitude correlation function.Then the experimentally observed correlation of outcomes is calculated from the square of the amplitude correlation function. Locality of amplitudes implies that the measurement on one particle does not collapse the companion particle to a definite state. Apart from resolving the EPR puzzle, this approach shows that the physical interpretation of apparently `nonlocal' effects like quantum teleportation and entanglement swapping are different from what is usually assumed. Bell type measurements do not change distant states. Yet the correlations are correctly reproduced, when measured, if complex probability amplitudes are treated as the basic local quantities. As examples we discuss the quantum correlations of two-particle maximally entangled states and the three-particle GHZ entangled state.Comment: Std. Latex, 11 pages, 1 table. Prepared for presentation at the International Conference on Quantum Optics, ICQO'2000, Minsk, Belaru

Title Page Sildenafil does not prevent heart hypertrophy and fibrosis induced by cardiomyocyte AT 1 R signaling

List of non-standard abbreviations: cGMP-dependent protein kinase type I (cGKI); protein kinase G (PKG); natriuretic peptides (NPs), cyclic guanosine-3´,5´-monophosphate (cGMP); nitric oxide (NO); cyclic adenosine-3´,5´-monophosphate (cAMP); Angiotensin II (AngII); Angiotensin II receptor type 1 (AT 1 R); sildenafil (SIL); cardiomyocyte (CM), smooth muscle cell (SMC); angiotensin converting enzyme (ACE), cGKIβ rescue mice (βRM), phosphodiesterase (PDE); Förster resonance energy transfer (FRET); 3-isobutyl-1-methylxanthine (IBMX), C-type natriuretic peptide (CNP). Section assignment: Cardiovascular Number of words: 4141 (excluding abstract, material and methods, reference list and figure legends) Number of words (abstract): 250 Number of references: 67 Page count: 37 JPET#226092 3 Abstract Analyses of several mouse models imply that the phosphodiesterase 5 (PDE5) inhibitor sildenafil (SIL), via increasing cyclic guanosine-3',5'-monophosphate (cGMP), affords protection against angiotensin II (AngII) stimulated cardiac remodeling. However, it is unclear which cell types are involved in these beneficial effects, because AngII may exert its adverse effects by modulating multiple reno-vascular and cardiac functions via AngII type 1 receptors (AT 1 R). To test the hypothesis that SIL/cGMP oppose cardiac stress provoked by amplified AngII/AT 1 R directly in cardiomyocytes (CMs), we studied transgenic mice with CM-specific overexpression of the AT 1 R under the control of the α -myosin-heavy chain promoter (αMHC-AT 1 R tg/+ ). The extent of cardiac growth was assessed in absence or presence of SIL and defined by referring changes in heart-weight to body-weight or tibia length. Hypertrophic marker genes, extracellular matrix-regulating factors and expression patterns of fibrosis markers were examined in α MHC-AT 1 R tg/+ ventricles (±SIL) and corroborated by investigating different components of the natriuretic peptide (NP)/PDE5/cGMP pathway as well as cardiac functions. cGMP levels in heart lysates and intact CMs were measured by competitive immunoassays and FRET. We find higher cardiac and CM cGMP levels and up-regulation of the cGMP-dependent protein kinase I (cGKI) with AT 1 R over-expression. However, even a prolonged SIL treatment regimen did not limit the progressive CM growth, fibrosis or decline in cardiac functions in the αMHC-AT 1 R tg/+ model suggesting that SIL does not interfere with the pathogenic actions of amplified AT 1 R signaling in CMs. Hence, the cardiac/non-cardiac cells involved in the cross-talk between SIL-sensitive PDE activity and AngII/AT 1 R need to be identified

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

Diastereomeric Cyclopentane-Based Maltosides (CPMs) as tools for membrane protein study

Amphiphilic agents, called detergents, are invaluable tools for studying membrane proteins. However, membrane proteins encapsulated by conventional head-to-tail detergents tend to denature or aggregate, necessitating the development of structurally distinct molecules with improved efficacy. Here, a novel class of diastereomeric detergents with a cyclopentane core unit, designated cyclopentane-based maltosides (CPMs), were prepared and evaluated for their ability to solubilize and stabilize several model membrane proteins. A couple of CPMs displayed enhanced behavior compared with the benchmark conventional detergent, n-dodecyl-β-d-maltoside (DDM), for all the tested membrane proteins including two G-protein-coupled receptors (GPCRs). Furthermore, CPM-C12 was notable for its ability to confer enhanced membrane protein stability compared with the previously developed conformationally rigid NBMs [J. Am. Chem. Soc.2017, 139, 3072] and LMNG. The effect of the individual CPMs on protein stability varied depending on both the detergent configuration (cis/trans) and alkyl chain length, allowing us draw conclusions on the detergent structure–property–efficacy relationship. Thus, this study not only provides novel detergent tools useful for membrane protein research but also reports on structural features of the detergents critical for detergent efficacy in stabilizing membrane proteins

Association between the Perioperative Antioxidative Ability of Platelets and Early Post-Transplant Function of Kidney Allografts: A Pilot Study

BACKGROUND: Recent studies have demonstrated that the actions of platelets may unfavorably influence post-transplant function of organ allografts. In this study, the association between post-transplant graft function and the perioperative activity of platelet antioxidants was examined among kidney recipients divided into early (EGF), slow (SGF), and delayed graft function (DGF) groups. METHODOLOGY/PRINCIPAL FINDINGS: Activities of superoxide dismutase, catalase, glutathione transferase (GST), glutathione peroxidase, and glucose-6-phosphate dehydrogenase (G6P) were determined and levels of glutathione, oxidized glutathione, and isoprostane were measured in blood samples collected immediately before and during the first and fifth minutes of renal allograft reperfusion. Our results demonstrated a significant increase in isoprostane levels in all groups. Interestingly, in DGF patients, significantly lower levels of perioperative activity of catalase (p<0.02) and GST (p<0.02) were observed. Moreover, in our study, the activity of platelet antioxidants was associated with intensity of perioperative oxidative stress. For discriminating SGF/DGF from EGF, sensitivity, specificity, and positive and negative predictive values of platelet antioxidants were 81-91%, 50-58%, 32-37%, and 90-90.5%, respectively. CONCLUSIONS: During renal transplantation, significant changes occur in the activity of platelet antioxidants. These changes seem to be associated with post-transplant graft function and can be potentially used to differentiate between EGF and SGF/DGF. To the best of our knowledge, this is the first study to reveal the potential protective role of platelets in the human transplantation setting

A Buoyancy-Based Screen of Drosophila Larvae for Fat-Storage Mutants Reveals a Role for Sir2 in Coupling Fat Storage to Nutrient Availability

Obesity has a strong genetic component, but few of the genes that predispose to obesity are known. Genetic screens in invertebrates have the potential to identify genes and pathways that regulate the levels of stored fat, many of which are likely to be conserved in humans. To facilitate such screens, we have developed a simple buoyancy-based screening method for identifying mutant Drosophila larvae with increased levels of stored fat. Using this approach, we have identified 66 genes that when mutated increase organismal fat levels. Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins. However, since mammalian sirtuins function in many tissues in different ways, it has been difficult to define their role in energy homeostasis accurately under normal feeding conditions. We show that knockdown of Sir2 in the larval fat body results in increased fat levels. Moreover, using genetic mosaics, we demonstrate that Sir2 restricts fat accumulation in individual cells of the fat body in a cell-autonomous manner. Consistent with this function, changes in the expression of metabolic enzymes in Sir2 mutants point to a shift away from catabolism. Surprisingly, although Sir2 is typically upregulated under conditions of starvation, Sir2 mutant larvae survive better than wild type under conditions of amino-acid starvation as long as sugars are provided. Our findings point to a Sir2-mediated pathway that activates a catabolic response to amino-acid starvation irrespective of the sugar content of the diet

Pregnane X Receptor and Yin Yang 1 Contribute to the Differential Tissue Expression and Induction of CYP3A5 and CYP3A4

The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 site is conserved in CYP3A4, but its inhibitory effect can be offset by PXR acting on response elements such as XREM. Taken together, the loss of YY1 binding site from promoters of the CYP3A5 gene lineage during primate evolution may have enabled the utilization of CYP3A5 both in the adaptive hepato-intestinal response to xenobiotics and as a constitutively expressed gene in other organs. Our results thus constitute a first description of uncoupling induction from constitutive expression for a major detoxifying enzyme. They also suggest an explanation for the considerable tissue expression differences between CYP3A5 and CYP3A4

Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis

INTRODUCTION: Overexpression of the HER2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective. METHODS: Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model. RESULTS: VRP-neu prevented or significantly inhibited the growth of HER2/neu-expressing murine breast cancer cells injected either into mammary tissue or intravenously. Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8(+ )T lymphocytes and serum IgG. CONCLUSION: On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu(+ )breast cancer is warranted

Cataloguing functionally relevant polymorphisms in gene DNA ligase I: a computational approach

A computational approach for identifying functionally relevant SNPs in gene LIG1 has been proposed. LIG1 is a crucial gene which is involved in excision repair pathways and mutations in this gene may lead to increase sensitivity towards DNA damaging agents. A total of 792 SNPs were reported to be associated with gene LIG1 in dbSNP. Different web server namely SIFT, PolyPhen, CUPSAT, FASTSNP, MAPPER and dbSMR were used to identify potentially functional SNPs in gene LIG1. SIFT, PolyPhen and CUPSAT servers predicted eleven nsSNPs to be intolerant, thirteen nsSNP to be damaging and two nsSNPs have the potential to destabilize protein structure. The nsSNP rs11666150 was predicted to be damaging by all three servers and its mutant structure showed significant increase in overall energy. FASTSNP predicted twenty SNPs to be present in splicing modifier binding sites while rSNP module from MAPPER server predicted nine SNPs to influence the binding of transcription factors. The results from the study may provide vital clues in establishing affect of polymorphism on phenotype and in elucidating drug response