Cramer-Rao Lower Bound for Point Based Image Registration with Heteroscedastic Error Model for Application in Single Molecule Microscopy

The Cramer-Rao lower bound for the estimation of the affine transformation parameters in a multivariate heteroscedastic errors-in-variables model is derived. The model is suitable for feature-based image registration in which both sets of control points are localized with errors whose covariance matrices vary from point to point. With focus given to the registration of fluorescence microscopy images, the Cramer-Rao lower bound for the estimation of a feature's position (e.g. of a single molecule) in a registered image is also derived. In the particular case where all covariance matrices for the localization errors are scalar multiples of a common positive definite matrix (e.g. the identity matrix), as can be assumed in fluorescence microscopy, then simplified expressions for the Cramer-Rao lower bound are given. Under certain simplifying assumptions these expressions are shown to match asymptotic distributions for a previously presented set of estimators. Theoretical results are verified with simulations and experimental data

Institutions, taxation, and market relationships in ancient Athens

This paper explores the institutional and economic development in ancient Athens from around 600 BC into the fourth century, a period during which the Athenians experienced oligarchy, tyranny, a gradually evolving but eventually far-reaching male democracy, followed by a return to more influence for the elite. Concomitantly, economic life changed qualitatively and quantitatively. Self-sufficient farming gradually gave way to market relationships and there was substantial economic growth. This analysis of institutional changes in Athens emphasizes the importance of credible commitments from those in power to other groups in society. It is furthermore likely that the increasing reliance on market relationships gradually transformed individual behaviour and individual beliefs, leading to changes in the formal and informal rules in society. Taxation played an important role: it pushed people into market relationships, illustrated the need for credible commitments, and helps to explain why foreigners were so prominent in trade in ancient Athens

Infrared Spectroscopy of Fluorenyl Cations at Cryogenic Temperatures

The notion of (anti)aromaticity is a successful concept in chemistry to explain the structure and stability of polycyclic hydrocarbons. Cyclopentadienyl and fluorenyl cations are among the most studied classical antiaromatic systems. In this work, fluorenyl cations are investigated by high-resolution gas-phase infrared spectroscopy in helium droplets. Bare fluorenyl cations are generated in the gas phase by electrospray ionization. After mass-to-charge selection, ions are captured in ultracold helium nanodroplets and probed by infrared spectroscopy using a widely tunable free-electron laser in the 600–1700 cm–1 range. The highly resolved cryogenic infrared spectra confirm, in combination with DFT computations, that all cations are present in their singlet states

The Genotype and Clinical Phenotype of Korean Patients with Familial Hypokalemic Periodic Paralysis

Familial hypokalemic periodic paralysis (HOPP) is a rare autosomal-dominant disease characterized by reversible attacks of muscle weakness occurring with episodic hypokalemia. Mutations in the skeletal muscle calcium (CACNA1S) and sodium channel (SCN4A) genes have been reported to be responsible for familial HOPP. Fifty-one HOPP patients from 20 Korean families were studied to determine the relative frequency of the known mutations and to specify the clinical features associated with the identified mutations. DNA analysis identified known mutations in 12 families: 9 (75%) were linked to the CACNA1S gene and 3 (25%) to the SCN4A gene. The Arg528His mutation in the CACNA1S gene was found to be predominant in these 12 families. Additionally, we have detected one novel silent exonic mutation (1950C>T) in the SCN4A gene. As for a SCN4A Arg669His mutation, incomplete penetrance in a woman was observed. Characteristic clinical features were observed both in patients with and without mutations. This study presents comprehensive data on the genotype and phenotype of Korean families with HOPP

The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

Fabrication of Highly Ordered Polymeric Nanodot and Nanowire Arrays Templated by Supramolecular Assembly Block Copolymer Nanoporous Thin Films

Realizing the vast technological potential of patternable block copolymers requires both the precise controlling of the orientation and long-range ordering, which is still a challenging topic so far. Recently, we have demonstrated that ordered nanoporous thin film can be fabricated from a simple supramolecular assembly approach. Here we will extend this approach and provide a general route to fabricate large areas of highly ordered polymeric nanodot and nanowire arrays. We revealed that under a mixture solvent annealing atmosphere, a near-defect-free nanoporous thin film over large areas can be achieved. Under the direction of interpolymer hydrogen bonding and capillary action of nanopores, this ordered porous nanotemplate can be properly filled with phenolic resin precursor, followed by curation and pyrolysis at middle temperature to remove the nanotemplate, a perfect ordered polymer nanodot arrays replication was obtained. The orientation of the supramolecular assembly thin films can be readily re-aligned parallel to the substrate upon exposure to chloroform vapor, so this facile nanotemplate replica method can be further extend to generate large areas of polymeric nanowire arrays. Thus, we achieved a successful sub-30 nm patterns nanotemplates transfer methodology for fabricating polymeric nanopattern arrays with highly ordered structure and tunable morphologies

Unraveling the Genetic Basis of Asthma and Allergic Diseases

Asthma and allergic diseases are believed to be complex genetic diseases which may result from the interaction of multiple genetic factors and environmental stimuli. In past decades, great efforts have been exerted in unraveling their genetic basis. The strategies in discovering genes and genetic variants, confirming their importance in pathogenesis of asthma and allergic diseases, as well as their strengths and limitations are summarized comprehensively and concisely. The current consensus about the genetic basis of asthma and allergic diseases is briefly described as well

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Pharmacogenetics of asthma in children

Allergic diseases such as bronchial asthma and atopic dermatitis develop by a combination of genetic and environmental factors. Several candidate causative genes of asthma and atopy have been reported as the genetic factors. The clinical features of patients and causes of diseases vary. Therefore, personalized medicine (tailor-made medicine) is necessary for the improvement of quality of life (QOL) and for asthma cure. Pharmacogenetics is very important for personalized medicine. Here, we present the genetics and pharmacogenetics of asthma in children. Finally, we show the guideline for personalized medicine for asthma, particularly in childhood, including the pharmacogenetics of anti-asthmatic drugs, preliminarily produced by the authors