Spin and charge order in the vortex lattice of the cuprates: experiment and theory

I summarize recent results, obtained with E. Demler, K. Park, A. Polkovnikov, M. Vojta, and Y. Zhang, on spin and charge correlations near a magnetic quantum phase transition in the cuprates. STM experiments on slightly overdoped BSCCO (J.E. Hoffman et al., Science 295, 466 (2002)) are consistent with the nucleation of static charge order coexisting with dynamic spin correlations around vortices, and neutron scattering experiments have measured the magnetic field dependence of static spin order in the underdoped regime in LSCO (B. Lake et al., Nature 415, 299 (2002)) and LaCuO_4+y (B. Khaykovich et al., Phys. Rev. B 66, 014528 (2002)). Our predictions provide a semi-quantitative description of these observations, with only a single parameter measuring distance from the quantum critical point changing with doping level. These results suggest that a common theory of competing spin, charge and superconducting orders provides a unified description of all the cuprates.Comment: 18 pages, 7 figures; Proceedings of the Mexican Meeting on Mathematical and Experimental Physics, Mexico City, September 2001, to be published by Kluwer Academic/Plenum Press; (v2) added clarifications and updated reference

Overexpression of mitochondrial creatine kinase preserves cardiac energetics without ameliorating murine chronic heart failure

Mitochondrial creatine kinase (Mt-CK) is a major determinant of cardiac energetic status and is down-regulated in chronic heart failure, which may contribute to disease progression. We hypothesised that cardiomyocyte-specific overexpression of Mt-CK would mitigate against these changes and thereby preserve cardiac function. Male Mt-CK overexpressing mice (OE) and WT littermates were subjected to transverse aortic constriction (TAC) or sham surgery and assessed by echocardiography at 0, 3 and 6 weeks alongside a final LV haemodynamic assessment. Regardless of genotype, TAC mice developed progressive LV hypertrophy, dilatation and contractile dysfunction commensurate with pressure overload-induced chronic heart failure. There was a trend for improved survival in OE-TAC mice (90% vs 73%, P = 0.08), however, OE-TAC mice exhibited greater LV dilatation compared to WT and no functional parameters were significantly different under baseline conditions or during dobutamine stress test. CK activity was 37% higher in OE-sham versus WT-sham hearts and reduced in both TAC groups, but was maintained above normal values in the OE-TAC hearts. A separate cohort of mice received in vivo cardiac 31P-MRS to measure high-energy phosphates. There was no difference in the ratio of phosphocreatine-to-ATP in the sham mice, however, PCr/ATP was reduced in WT-TAC but preserved in OE-TAC (1.04 ± 0.10 vs 2.04 ± 0.22; P = 0.007). In conclusion, overexpression of Mt-CK activity prevented the changes in cardiac energetics that are considered hallmarks of a failing heart. This had a positive effect on early survival but was not associated with improved LV remodelling or function during the development of chronic heart failure

Silver(I) N-Heterocyclic Carbene Complexes Derived from Clotrimazole: Antiproliferative Activity and Interaction with an Artificial Membrane-Based Biosensor

With the aim of combining the potential anticancer properties of both clotrimazole, an imidazole based antifungal agent, and silver(I) N-heterocyclic carbenes, 13 novel silver(I) N-heterocyclic carbene complexes derived from clotrimazole were synthesized. The complexes were fully characterized, and the partition coefficient of each was determined to provide a measure of hydrophobicity. The antiproliferative properties of the complexes against cancerous and noncancerous cell lines found optimum cytotoxicity when the complex displays an “intermediate lipophilicity”, which describes a complex that possesses both water-soluble groups and lipophilic aromatic groups. The silver complexes were screened on a synthetic biomembrane-like device using a chip-based phospholipid-coated Pt/Hg electrode embedded in a flow cell system. The results are recorded as rapid cyclic voltammograms (RCVs), which give insight into the interactions of the complexes with a cell membrane. Interestingly the principle of “intermediate lipophilicity” also applies to the monolayer interaction to which the silver atom significantly implements an irreversibility

Transcriptional alteration of cytoskeletal genes induced by microcystins in three organs of rats

This study explored the mechanisms of toxicity of microcystins by measuring the transcription levels of nine cytoskeletal genes (actin, tubulin, vimentin, ezrin, radixin, moesin, MAP1b, tau, stathmin) in the liver, kidney and spleen of male Wistar rats treated with microcystins at a dose of 80 mu g MC-LReq kg(-1) bw. Microcystins disrupted the transcriptional homeostasis of cytoskeletal genes in these organs. Changes in the transcription of four genes (beta-actin, ezrin, radixin and tau) in liver, one gene (stathmin) in kidney, and one gene (radixin) in spleen were significantly correlated with the tissue concentration of microcystins. However, the influences on the transcription of most genes we studied were greater in the liver than in the kidney or spleen. The effects of microcystins on the transcription of cytoskeletal genes may explain some of the morphological and pathological changes observed in these organs and provide new information on the hepatotoxicity of these compounds. Additionally, transcriptional changes in tumor-associated cytoskeletal genes (ezrin, moesin and stathmin) that were observed in the present study provide a possible clue to the tumor-promoting potential of microcystins and their influences on the transcription of MAP1b and tau imply possible neurological toxicity of microcystins in vertebrates. (C) 2010 Published by Elsevier Ltd

Gravitational collapse with tachyon field and barotropic fluid

A particular class of space-time, with a tachyon field, \phi, and a barotropic fluid constituting the matter content, is considered herein as a model for gravitational collapse. For simplicity, the tachyon potential is assumed to be of inverse square form i.e., V(\phi) \sim \phi^{-2}. Our purpose, by making use of the specific kinematical features of the tachyon, which are rather different from a standard scalar field, is to establish the several types of asymptotic behavior that our matter content induces. Employing a dynamical system analysis, complemented by a thorough numerical study, we find classical solutions corresponding to a naked singularity or a black hole formation. In particular, there is a subset where the fluid and tachyon participate in an interesting tracking behaviour, depending sensitively on the initial conditions for the energy densities of the tachyon field and barotropic fluid. Two other classes of solutions are present, corresponding respectively, to either a tachyon or a barotropic fluid regime. Which of these emerges as dominant, will depend on the choice of the barotropic parameter, \gamma. Furthermore, these collapsing scenarios both have as final state the formation of a black hole.Comment: 18 pages, 7 figures. v3: minor changes. Final version to appear in GR

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

Effects of superoxide donor menadione in adult Rat myocardium are associated with increased diastolic intracellular calcium.

Superoxide anions have been associated with many aspects of cardiovascular disease. Menadione is a superoxide anion donor that alters the heart's electrical and mechanical functions. The aim of this study was to demonstrate simultaneous changes in intracellular Ca2+ ([Ca2+]i) and mechanical activity in intact adult cardiac myocytes, and mechanical activity and electrical activity in isolated whole hearts in order to provide greater insight into the mechanisms associated with the detrimental effects of menadione on the myocardium. Isolated hearts from adult male Wistar rats (n = 11, 200–250 g) were Langendorff perfused at 38°C with a Krebs–Henseleit solution. A saline-filled balloon was placed in the left ventricle (LV) in order to measure diastolic and developed pressure. Monophasic action potentials were simultaneously recorded from the epicardial surface. External stimulation at 5 Hz and intrinsic pacing were used throughout a 10 min control period and 30 min exposure to 50 μM menadione. Single LV myocytes (n = 7 from n = 4 animals) were loaded with the Ca2+-indicator Fura4-AM, stimulated at 1 Hz and exposed to 50 μM menadione. Myocyte length was simultaneously measured with [Ca2+]i using a video edge detection system. In isolated hearts, exposure to menadione significantly decreased contractility and action potential duration (with a similar time course); intrinsic heart rate and rhythmicity. Diastolic pressure was significantly increased. In single adult myocytes, menadione caused a significant increase in diastolic [Ca2+]i and a decrease in resting cell length and led to spontaneous release of [Ca2+]i. We conclude that the effects of menadione upon electrical and mechanical activity of the heart are at least in part a consequence of dysregulation of [Ca2+]i handling and the subsequent increase in diastolic [Ca2+] alterations in [Ca2+]i are consistent with the generation of delayed after depolarization arrhythmias

Analyses of associations between three positionally cloned asthma candidate genes and asthma or asthma-related phenotypes in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Six asthma candidate genes, ADAM33, NPSR1, PHF11, DPP10, HLA-G, and CYFIP2, located at different chromosome regions have been positionally cloned following the reported linkage studies. For ADAM33, NPSR1, and CYFIP2, the associations with asthma or asthma-related phenotypes have been studied in East Asian populations such as Chinese and Japanese. However, for PHF11, DPP10, and HLA-G, none of the association studies have been conducted in Asian populations. Therefore, the aim of the present study is to test the associations between these three positionally cloned genes and asthma or asthma-related phenotypes in a Chinese population.</p> <p>Methods</p> <p>Two, five, and two single nucleotide polymorphisms (SNPs) in the identified top regions of PHF11, DPP10, and HLA-G, respectively, were genotyped in 1183 independent samples. The study samples were selected based on asthma affectation status and extreme values in at least one of the following three asthma-related phenotypes: total serum immunoglobulin E levels, bronchial responsiveness test, and skin prick test. Both single SNP and haplotype analyses were performed.</p> <p>Results</p> <p>We found that DPP10 was significantly associated with bronchial hyperresponsiveness (BHR) and BHR asthma after the adjustment for multiple testing; while the associations of PHF11 with positive skin reactions to antigens and the associations of HLA-G with BHR asthma were only nominally significant.</p> <p>Conclusion</p> <p>Our study is the first one to provide additional evidence that supports the roles of DPP10 in influencing asthma or BHR in a Chinese population.</p

Human and Machine Learning

In this paper, we consider learning by human beings and machines in the light of Herbert Simon’s pioneering contributions to the theory of Human Problem Solving. Using board games of perfect information as a paradigm, we explore differences in human and machine learning in complex strategic environments. In doing so, we contrast theories of learning in classical game theory with computational game theory proposed by Simon. Among theories that invoke computation, we make a further distinction between computable and computational or machine learning theories. We argue that the modern machine learning algorithms, although impressive in terms of their performance, do not necessarily shed enough light on human learning. Instead, they seem to take us further away from Simon’s lifelong quest to understand the mechanics of actual human behaviour

Evaluation of high-throughput genomic assays for the Fc gamma receptor locus

Cancer immunotherapy has been revolutionised by the use of monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A-158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcγR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcγR genetics in predicting response to antibody therapeutics