An Exact Fluctuating 1/2-BPS Configuration

This work explores the role of thermodynamic fluctuations in the two parameter giant and superstar configurations characterized by an ensemble of arbitrary liquid droplets or irregular shaped fuzzballs. Our analysis illustrates that the chemical and state-space geometric descriptions exhibit an intriguing set of exact pair correction functions and the global correlation lengths. The first principle of statistical mechanics shows that the possible canonical fluctuations may precisely be ascertained without any approximation. Interestingly, our intrinsic geometric study exemplifies that there exist exact fluctuating 1/2-BPS statistical configurations which involve an ensemble of microstates describing the liquid droplets or fuzzballs. The Gaussian fluctuations over an equilibrium chemical and state-space configurations accomplish a well-defined, non-degenerate, curved and regular intrinsic Riemannian manifolds for all physically admissible domains of black hole parameters. An explicit computation demonstrates that the underlying chemical correlations involve ordinary summations, whilst the state-space correlations may simply be depicted by standard polygamma functions. Our construction ascribes definite stability character to the canonical energy fluctuations and to the counting entropy associated with an arbitrary choice of excited boxes from an ensemble of ample boxes constituting a variety of Young tableaux.Comment: Minor changes, added references, 30 pages, 4 figures, PACS numbers: 04.70.-s: Physics of black holes; 04.70.-Bw: Classical black holes; 04.50.Gh Higher-dimensional black holes, black strings, and related objects; 04.60.Cf Gravitational aspects of string theory, accepted for publication in JHE

Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion

ARPES: A probe of electronic correlations

Angle-resolved photoemission spectroscopy (ARPES) is one of the most direct methods of studying the electronic structure of solids. By measuring the kinetic energy and angular distribution of the electrons photoemitted from a sample illuminated with sufficiently high-energy radiation, one can gain information on both the energy and momentum of the electrons propagating inside a material. This is of vital importance in elucidating the connection between electronic, magnetic, and chemical structure of solids, in particular for those complex systems which cannot be appropriately described within the independent-particle picture. Among the various classes of complex systems, of great interest are the transition metal oxides, which have been at the center stage in condensed matter physics for the last four decades. Following a general introduction to the topic, we will lay the theoretical basis needed to understand the pivotal role of ARPES in the study of such systems. After a brief overview on the state-of-the-art capabilities of the technique, we will review some of the most interesting and relevant case studies of the novel physics revealed by ARPES in 3d-, 4d- and 5d-based oxides.Comment: Chapter to appear in "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancini, Springer Series in Solid-State Sciences (2013). A high-resolution version can be found at: http://www.phas.ubc.ca/~quantmat/ARPES/PUBLICATIONS/Reviews/ARPES_Springer.pdf. arXiv admin note: text overlap with arXiv:cond-mat/0307085, arXiv:cond-mat/020850

One-carbon metabolism and epigenetic programming of mammalian development

One-carbon (1C) metabolism comprises a series of integrated metabolic pathways, including the linked methionine-folate cycles, that provide methyl groups for the synthesis of biomolecules and the epigenetic regulation of gene expression via chromatin methylation. Most of the research investigating the function of 1C metabolism pertains to studies undertaken in the rodent liver. Comparatively little is known about the function of 1C metabolism in reproductive and embryonic cells, particularly in domestic ruminant species. Periconceptional dietary deficiencies in 1C substrates and cofactors are known to lead to epigenetic alterations in DNA methylation in genes that regulate key developmental processes in the embryo. Such modifications can have negative implications on the subsequent development, metabolism and health of offspring. This thesis sought to improve current understanding of the regulation of 1C metabolism in the ruminant liver, ovary and preimplantation embryo through in vivo and in vitro nutritional supplementation experiments coupled with metabolomic, transcriptomic and epigenetic analyses. The first part of this thesis (Chapter 2) assessed the metabolic consequences of dietary methyl deficiency using novel mass spectrometry–based methods that were developed for the quantification of B vitamins, folates and 1C-related amines in sheep liver. This study provided the first comparison of the relative abundance of bioactive 1C metabolites in liver harvested from methyl deficient sheep relative to a control study population of abattoir derived sheep. Relevant reductions in dietary methyl availability led to significant alterations in hepatic 1C metabolite concentrations. Large natural variations in the hepatic concentrations of individual metabolites in both sheep study populations reflected the dietary and genetic variation in our chosen outbred model species. These metabolomics platforms will be useful for investigating 1C metabolism and linked biochemical pathways in order to facilitate future dietary and genetic studies of metabolic health and epigenetic regulation of gene expression. Based on the absence of methionine cycle enzyme transcripts (e.g. MAT1A and BHMT) in the bovine ovary and preimplantation embryo, the second part of this thesis (Chapter 3 and Chapter 4) addressed the hypothesis that ruminant reproductive and embryonic cells are highly sensitive to methyl group availability and, therefore, epigenetic programming during the periconceptional period. Transcript analyses confirmed MAT2A expression in the bovine liver, ovary and at each stage of preimplantation embryo development assessed to Day 8. Transcripts for BHMT isoforms (BHMT and BHMT2) were detected in the bovine ovary but were weak or absent in embryos, highlighting a key difference in methionine metabolism between hepatic and reproductive cells. Bovine embryos were produced in vitro using custom-made media containing 0 (nonphysiological), 10 (low physiological), 50 (high physiological), and 500 µmol/L (supraphysiological) added methionine (Chapter 3). Gross morphological assessments of embryo stage, grade, cell lineage allocation and primary sex ratio revealed that culture in non- and supraphysiological methionine concentrations was detrimental for embryo development, whilst culture in the high physiological concentration appeared to be best. Reduced representation bisulphite sequencing (RRBS) of inner cell mass (ICM) and trophectoderm (TE) cells immunodissected from Day 8 blastocysts demonstrated that culturing embryos in low physiological methionine led to global hypomethylation within both cell lineages. Bioinformatic analyses of differentially methylated genes included gene set enrichment analyses (GSEA). Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were enriched within the ICM were associated with protein catabolism and autophagy, and significant terms and pathways enriched within the TE were associated with cellular transport. Of particular biological interest was the loss of methylation within regulatory region (DMR2) of the paternally imprinted gene, IGF2R, in the TE following culture in low physiological methionine. Transcript analysis found no significant effect of methionine concentration on the expression of IGF2R or the antisense transcript, AIRN, in the primary cell lineages of the Day 8 bovine preimplantation embryo. Hypomethylation of IGF2R DMR2 has been associated with aberrant IGF2R expression and large offspring syndrome (LOS) in cattle and sheep that were subjected to embryo manipulation during assisted reproductive technology (ART) procedures, such as somatic cell nuclear transfer (SCNT) or non-physiological in vitro embryo culture environments. Chapter 5 sought to evaluate the effect of somatic donor cell type on epigenetic reprogramming via DNA methylation in hepatocytes isolated from cloned sheep. RRBS facilitated the comparison of methylation reprogramming between Finn Dorset (D) clone hepatocytes and their mammary epithelial (OP5) donor cell line; and, Lleyn (L) clone hepatocytes and their Lleyn fetal fibroblast (LFF4) donor cell line. Methylation was most closely correlated between D and L clone hepatocytes than between clones and their respective donor cell lines. In general, hepatocytes were hypomethylated relative to their somatic donor cell nuclei. GSEA identified genes that encoded transcription factor proteins enriched within the ‘Sequence-specific DNA binding’ term (GO:0043565) as differentially methylated between clone hepatocytes and their donor cell lines. In addition, imprinted genes, including IGF2R, were differentially methylated in clone hepatocytes relative to somatic cell nuclei. In summary, this thesis promotes and supports the importance of an optimal methyl balance to support periconceptional development in mammals. The experiments detailed herein provide an insight into the metabolic consequences of dietary methyl deficiency (and excess) in outbred populations of domestic ruminants, with a specific focus on the liver, ovary and preimplantation embryo. The results demonstrate that tissue- and species-specific features of 1C metabolism render ruminant embryonic cells sensitive to methionine inputs within a physiological range. The observation that in vitro embryo culture and manipulation techniques, such as somatic cell nuclear transfer, can cause epigenetic alterations to DNA methylation during preimplantation development provides a basis for further study into the safety and efficacy of emerging assisted reproductive technologies

Wall roughness induces asymptotic ultimate turbulence

Turbulence is omnipresent in Nature and technology, governing the transport of heat, mass, and momentum on multiple scales. For real-world applications of wall-bounded turbulence, the underlying surfaces are virtually always rough; yet characterizing and understanding the effects of wall roughness for turbulence remains a challenge, especially for rotating and thermally driven turbulence. By combining extensive experiments and numerical simulations, here, taking as example the paradigmatic Taylor-Couette system (the closed flow between two independently rotating coaxial cylinders), we show how wall roughness greatly enhances the overall transport properties and the corresponding scaling exponents. If only one of the walls is rough, we reveal that the bulk velocity is slaved to the rough side, due to the much stronger coupling to that wall by the detaching flow structures. If both walls are rough, the viscosity dependence is thoroughly eliminated in the boundary layers and we thus achieve asymptotic ultimate turbulence, i.e. the upper limit of transport, whose existence had been predicted by Robert Kraichnan in 1962 (Phys. Fluids {\bf 5}, 1374 (1962)) and in which the scalings laws can be extrapolated to arbitrarily large Reynolds numbers

Does the lateral intercondylar ridge disappear in ACL deficient patients?

The aim of this study was to determine whether there is a difference in the presence of the lateral intercondylar ridge and the lateral bifurcate ridge between patients with sub-acute and chronic ACL injuries. We hypothesized that the ridges would be present less often with chronic ACL deficiency. Twenty-five patients with a chronic ACL injury were matched for age and gender to 25 patients with a sub-acute ACL injury. The lateral intercondylar ridge and lateral bifurcate ridge were scored as either present, absent, or indeterminate due to insufficient visualization by three blinded observers. The kappa for the three observers was .61 for the lateral intercondylar ridge and .58 for the lateral bifurcate ridge. The lateral intercondylar ridge was present in 88% of the sub-acute patients and 88% of the chronic patients. The lateral bifurcate ridge was present in 48% of the sub-acute and 48% of the chronic patients. This matched-pairs case–control study was unable to show a difference in the presence of the femoral bony ridges between patients with acute and chronic ACL injuries. The authors would suggest looking for the ridges as a landmark of the native ACL insertion site during ACL reconstruction in both acute and chronic ACL injuries

Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and diet, genetic susceptibility has been reported to play a key role in the development of this disease. The x-ray repair cross-complementing group 1 (XRCC1) gene is important in DNA base excision repair. We hypothesized that two common single nucleotide polymorphisms of XRCC1 (codons 194 Arg→Trp and 399 Arg→Gln) are related to the risk of NPC and interact with tobacco smoking. METHODS: We sought to determine whether these genetic variants of the XRCC1 gene were associated with the risk of NPC among the Cantonese population in a hospital-based case control study using polymerase chain reaction-restriction fragment length polymorphism analysis. We conducted this study in 462 NPC patients and 511 healthy controls. RESULTS: After adjustment for sex and age, we found a reduced risk of developing NPC in individuals with the Trp194Trp genotype (OR = 0.48; 95% CI, 0.27–0.86) and the Arg194Trp genotype (OR = 0.79; 95% CI, 0.60–1.05) compared with those with the Arg194Arg genotype. Compared with those with the Arg399Arg genotype, the risk for NPC was not significantly different in individuals with the Arg399Gln genotype (OR = 0.82; 95% CI, 0.62–1.08) and the Gln399Gln genotype (OR = 1.20; 95% CI, 0.69–2.06). Further analyses stratified by gender and smoking status revealed a significantly reduced risk of NPC among males (OR = 0.32; 95% CI, 0.14–0.70) and smokers (OR = 0.34; 95% CI, 0.14–0.82) carrying the XRCC1 194Trp/Trp genotype compared with those carrying the Arg/Arg genotype. No association was observed between Arg399Gln variant genotypes and the risk of NPC combined with smoking and gender. CONCLUSION: Our findings suggest that the XRCC1 Trp194Trp variant genotype is associated with a reduced risk of developing NPC in Cantonese population, particularly in males and smokers. Larger studies are needed to confirm our findings and unravel the underlying mechanisms

State-space Manifold and Rotating Black Holes

We study a class of fluctuating higher dimensional black hole configurations obtained in string theory/ $M$-theory compactifications. We explore the intrinsic Riemannian geometric nature of Gaussian fluctuations arising from the Hessian of the coarse graining entropy, defined over an ensemble of brane microstates. It has been shown that the state-space geometry spanned by the set of invariant parameters is non-degenerate, regular and has a negative scalar curvature for the rotating Myers-Perry black holes, Kaluza-Klein black holes, supersymmetric $AdS_5$ black holes, $D_1$-$D_5$ configurations and the associated BMPV black holes. Interestingly, these solutions demonstrate that the principal components of the state-space metric tensor admit a positive definite form, while the off diagonal components do not. Furthermore, the ratio of diagonal components weakens relatively faster than the off diagonal components, and thus they swiftly come into an equilibrium statistical configuration. Novel aspects of the scaling property suggest that the brane-brane statistical pair correlation functions divulge an asymmetric nature, in comparison with the others. This approach indicates that all above configurations are effectively attractive and stable, on an arbitrary hyper-surface of the state-space manifolds. It is nevertheless noticed that there exists an intriguing relationship between non-ideal inter-brane statistical interactions and phase transitions. The ramifications thus described are consistent with the existing picture of the microscopic CFTs. We conclude with an extended discussion of the implications of this work for the physics of black holes in string theory.Comment: 44 pages, Keywords: Rotating Black Holes; State-space Geometry; Statistical Configurations, String Theory, M-Theory. PACS numbers: 04.70.-s Physics of black holes; 04.70.Bw Classical black holes; 04.70.Dy Quantum aspects of black holes, evaporation, thermodynamics; 04.50.Gh Higher-dimensional black holes, black strings, and related objects. Edited the bibliograph

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Forced decadal changes in the East Asian summer monsoon: the roles of greenhouse gases and anthropogenic aerosols

Since the mid-1990s precipitation trends over eastern China display a dipole pattern, characterized by positive anomalies in the south and negative anomalies in the north, named as the Southern-Flood-Northern-Drought (SFND) pattern. This work investigates the drivers of decadal changes of the East Asian summer monsoon (EASM), and the dynamical mechanisms involved, by using a coupled climate model (specifically an atmospheric general circulation model coupled to an ocean mixed layer model) forced by changes in (1) anthropogenic greenhouse gases (GHG), (2) anthropogenic aerosol (AA) and (3) the combined effects of both GHG and AA (All Forcing) between two periods across the mid-1990s. The model experiment forced by changes in All Forcing shows a dipole pattern of response in precipitation over China that is similar to the observed SFND pattern across the mid-1990s, which suggests that anthropogenic forcing changes played an important role in the observed decadal changes. Furthermore, the experiments with separate forcings indicate that GHG and AA forcing dominate different parts of the SFND pattern. In particular, changes in GHG increase precipitation over southern China, whilst changes in AA dominate in the drought conditions over northern China. Increases in GHG cause increased moisture transport convergence over eastern China, which leads to increased precipitation. The AA forcing changes weaken the EASM, which lead to divergent wind anomalies over northern China and reduced precipitation