Tracking a hysteretic and disorder-broadened phase transition via the electromagnon response in improper ferroelectrics

We demonstrate that electromagnons can be used to directly probe the nature of a phase transition between magnetically ordered phases in an improper ferroelectric. The antiferromagnetic/paraelectric to antiferromagnetic/ferroelectric phase transition in Cu1-xZnxO (x=0, 0.05) alloys was tracked via the electromagnon response using terahertz time-domain spectroscopy, on heating and cooling through the phase transition. The transition was found to exhibit thermal hysteresis, confirming its first-order nature, and to broaden under the influence of spin-disorder upon Zn substitution. The energy of the electromagnon increases upon alloying, as a result of the non-magnetic ions modifying the magnetic interactions that give rise to the multiferroic phase and electromagnons. We describe our findings in the context of recent theoretical work that examined improper ferroelectricity and electromagnons in CuO from phenomenological and first-principles approaches

Colossal terahertz magnetoresistance at room temperature in epitaxial La0.7Sr0.3MnO3 nanocomposites and single-phase thin films

Colossal magnetoresistance (CMR) is demonstrated at terahertz (THz) frequencies by using terahertz time-domain magnetospectroscopy to examine vertically-aligned nanocomposites (VANs) and planar thin films of La_0.7Sr_0.3MnO_3. At the Curie temperature (room temperature) the THz conductivity of the VAN was dramatically enhanced by over 2 orders of magnitude under the application of a magnetic field, with a non-Drude THz conductivity that increased with frequency. The dc CMR of the VAN is controlled by extrinsic magnetotransport mechanisms such as spin-polarized tunneling between nano-grains. In contrast, we find that THz CMR is dominated by intrinsic, intragrain transport: the mean free path was smaller than the nanocolumn size, and the planar thin-film exhibited similar THz CMR to the VAN. Surprisingly, the observed colossal THz magnetoresistance suggests that the magnetoresistance can be large for ac motion on nanometre length scales, even when the magnetoresistance is negligible on the macroscopic length scales probed by dc transport. This suggests that colossal magnetoresistance at THz frequencies may find use in nanoelectronics and in THz optical components controlled by magnetic fields. The VAN can be scaled in thickness while retaining a high structural quality, and offers a larger THz CMR at room temperature than the planar film

Single-Nucleotide Polymorphisms in LPA Explain Most of the Ancestry-Specific Variation in Lp(a) Levels in African Americans

Lipoprotein(a) (Lp(a)) is an important causal cardiovascular risk factor, with serum Lp(a) levels predicting atherosclerotic heart disease and genetic determinants of Lp(a) levels showing association with myocardial infarction. Lp(a) levels vary widely between populations, with African-derived populations having nearly 2-fold higher Lp(a) levels than European Americans. We investigated the genetic basis of this difference in 4464 African Americans from the Jackson Heart Study (JHS) using a panel of up to 1447 ancestry informative markers, allowing us to accurately estimate the African ancestry proportion of each individual at each position in the genome. In an unbiased genome-wide admixture scan for frequency-differentiated genetic determinants of Lp(a) level, we found a convincing peak (LOD = 13.6) at 6q25.3, which spans the LPA locus. Dense fine-mapping of the LPA locus identified a number of strongly associated, common biallelic SNPs, a subset of which can account for up to 7% of the variation in Lp(a) level, as well as >70% of the African-European population differences in Lp(a) level. We replicated the association of the most strongly associated SNP, rs9457951 (p = 6×10−22, 27% change in Lp(a) per allele, ∼5% of Lp(a) variance explained in JHS), in 1,726 African Americans from the Dallas Heart Study and found an even stronger association after adjustment for the kringle(IV) repeat copy number. Despite the strong association with Lp(a) levels, we find no association of any LPA SNP with incident coronary heart disease in 3,225 African Americans from the Atherosclerosis Risk in Communities Study

Evaluation of microarray-based DNA methylation measurement using technical replicates: the Atherosclerosis Risk In Communities (ARIC) Study

Background: DNA methylation is a widely studied epigenetic phenomenon; alterations in methylation patterns influence human phenotypes and risk of disease. As part of the Atherosclerosis Risk in Communities (ARIC) study, the Illumina Infinium HumanMethylation450 (HM450) BeadChip was used to measure DNA methylation in peripheral blood obtained from ~3000 African American study participants. Over 480,000 cytosine-guanine (CpG) dinucleotide sites were surveyed on the HM450 BeadChip. To evaluate the impact of technical variation, 265 technical replicates from 130 participants were included in the study. Results: For each CpG site, we calculated the intraclass correlation coefficient (ICC) to compare variation of methylation levels within- and between-replicate pairs, ranging between 0 and 1. We modeled the distribution of ICC as a mixture of censored or truncated normal and normal distributions using an EM algorithm. The CpG sites were clustered into low- and high-reliability groups, according to the calculated posterior probabilities. We also demonstrated the performance of this clustering when applied to a study of association between methylation levels and smoking status of individuals. For the CpG sites showing genome-wide significant association with smoking status, most (~96%) were seen from sites in the high reliability cluster. Conclusions: We suggest that CpG sites with low ICC may be excluded from subsequent association analyses, or extra caution needs to be taken for associations at such sites

Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues

Human immunodeficiency virus theranostics facilitates the development of long acting (LA) antiretroviral drugs (ARVs) by defining drug-particle cell depots. Optimal drug formulations are made possible based on precise particle composition, structure, shape and size. Through the creation of rod-shaped particles of defined sizes reflective of native LA drugs, theranostic probes can be deployed to measure particle-cell and tissue biodistribution, antiretroviral activities and drug retention. Methods: Herein, we created multimodal rilpivirine (RPV) 177lutetium labeled bismuth sulfide nanorods (177LuBSNRs) then evaluated their structure, morphology, configuration, chemical composition, biological responses and adverse reactions. Particle biodistribution was analyzed by single photon emission computed tomography (SPECT/CT) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging. Results: Nanoformulated RPV and BSNRs-RPV particles showed comparable physicochemical and cell biological properties. Drug-particle pharmacokinetics (PK) and biodistribution in lymphoid tissue macrophages proved equivalent, one with the other. Rapid particle uptake and tissue distribution were observed, without adverse reactions, in primary blood-derived and tissue macrophages. The latter was seen within the marginal zones of spleen. Conclusions: These data, taken together, support the use of 177LuBSNRs as theranostic probes as a rapid assessment tool for PK LA ARV measurements

The Third wave in globalization theory

This essay examines a proposition made in the literature that there are three waves in globalization theory—the globalist, skeptical, and postskeptical or transformational waves—and argues that this division requires a new look. The essay is a critique of the third of these waves and its relationship with the second wave. Contributors to the third wave not only defend the idea of globalization from criticism by the skeptics but also try to construct a more complex and qualified theory of globalization than provided by first-wave accounts. The argument made here is that third-wave authors come to conclusions that try to defend globalization yet include qualifications that in practice reaffirm skeptical claims. This feature of the literature has been overlooked in debates and the aim of this essay is to revisit the literature and identify as well as discuss this problem. Such a presentation has political implications. Third wavers propose globalist cosmopolitan democracy when the substance of their arguments does more in practice to bolster the skeptical view of politics based on inequality and conflict, nation-states and regional blocs, and alliances of common interest or ideology rather than cosmopolitan global structures

Evaluation of microarray-based DNA methylation measurement using technical replicates: the Atherosclerosis Risk In Communities (ARIC) Study

Abstract Background DNA methylation is a widely studied epigenetic phenomenon; alterations in methylation patterns influence human phenotypes and risk of disease. As part of the Atherosclerosis Risk in Communities (ARIC) study, the Illumina Infinium HumanMethylation450 (HM450) BeadChip was used to measure DNA methylation in peripheral blood obtained from ~3000 African American study participants. Over 480,000 cytosine-guanine (CpG) dinucleotide sites were surveyed on the HM450 BeadChip. To evaluate the impact of technical variation, 265 technical replicates from 130 participants were included in the study. Results For each CpG site, we calculated the intraclass correlation coefficient (ICC) to compare variation of methylation levels within- and between-replicate pairs, ranging between 0 and 1. We modeled the distribution of ICC as a mixture of censored or truncated normal and normal distributions using an EM algorithm. The CpG sites were clustered into low- and high-reliability groups, according to the calculated posterior probabilities. We also demonstrated the performance of this clustering when applied to a study of association between methylation levels and smoking status of individuals. For the CpG sites showing genome-wide significant association with smoking status, most (~96%) were seen from sites in the high reliability cluster. Conclusions We suggest that CpG sites with low ICC may be excluded from subsequent association analyses, or extra caution needs to be taken for associations at such sites

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genome-Wide Association Study of Coronary Heart Disease and Its Risk Factors in 8,090 African Americans: The NHLBI CARe Project

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia