Indirect Detection of Axonal Architecture With Q-Space Imaging

Evaluating axon morphology would provide insights into connectivity, maturation, and disease pathology. Conventional diffusion MRI can provide metrics that are related to axon morphology, but cannot measure specific parameters such as mean axon diameter (MAD) and intracellular fraction (ICF). Q-space imaging (QSI) is an advanced diffusion MRI technique that may be able to provide more information on axon morphology. However, QSI has several limitations that affect its implementation and accuracy. The main objective of this dissertation was to address these limitations and to evaluate the potential of QSI to accurately assess axon morphology. First, a custom-built high-amplitude gradient coil was used to address the limitations in the maximum gradient amplitude available with commercial systems. Second, to understand the relationship between axon morphology and QSI, simulations were used to investigate the effects of the presence of both extracellular and intracellular signals (ECS and ICS) as well as variation in cell size and shape. Third, three QSI-based methods were designed provide specific measures of axon morphology which have not been reported before. The maximum amplitude of the custom gradient coil was 50 T/m that, for the first time, allowed for sub-micron displacement resolution while fulfilling the short gradient approximation. This enabled near-ideal QSI experiments to be performed. QSI experiments on excised mouse spinal cords showed good correlation with histology, but overestimated MAD. Simulations showed that axon morphology was the dominant effect on QSI and suggested that the presence of ECS and ICS signals may complicate interpretation. Three methods were designed to account for signal in ECS and ICS: two relied on a two-compartment model of the displacement probability density function and the echo attenuation at low q-values, and a third varied the gradient duration to differentiate diffusion in ECS from ICS. All three methods provided estimates of MAD and ICF that showed better agreement with histology than QSI. The methods were also evaluated implementation on a clinical scanner. This dissertation demonstrated the sensitivity of QSI to axon morphology and showed the feasibility of three methods to accurately estimate MAD and ICF. Further investigation is warranted to study future applications

Hall Effect and Resistivity in High-Tc Superconductors: The Conserving Approximation

The Hall coefficient (R_H) of high-Tc cuprates in the normal state shows the striking non-Fermi liquid behavior: R_H follows a Curie-Weiss type temperature dependence, and |R_H|>>1/|ne| at low temperatures in the under-doped compounds. Moreover, R_H is positive for hole-doped compounds and is negative for electron-doped ones, although each of them has a similar hole-like Fermi surface. In this paper, we give the explanation of this long-standing problem from the standpoint of the nearly antiferromagnetic (AF) Fermi liquid. We consider seriously the vertex corrections for the current which are indispensable to satisfy the conservation laws, which are violated within the conventional Boltzmann transport approximation. The obtained total current J_k takes an enhanced value and is no more perpendicular to the Fermi surface due to the strong AF fluctuations. By virtue of this mechanism, the anomalous behavior of R_H in high-Tc cuprates is neutrally explained. We find that both the temperature and the (electron, or hole) doping dependences of R_H in high-T_c cuprates are reproduced well by numerical calculations based on the fluctuation-exchange (FLEX) approximation, applied to the single-band Hubbard model. We also discuss the temperature dependence of R_H in other nearly AF metals, e.g., V_2O_3, kappa-BEDT-TTF organic superconductors, and heavy fermion systems close to the AF phase boundary.Comment: 19 pages, to appear in Phys. Rev. B, No.59, Vol.22, 199

EXPRES I. HD~3651 an Ideal RV Benchmark

The next generation of exoplanet-hunting spectrographs should deliver up to an order of magnitude improvement in radial velocity precision over the standard 1 m/s state of the art. This advance is critical for enabling the detection of Earth-mass planets around Sun-like stars. New calibration techniques such as laser frequency combs and stabilized etalons ensure that the instrumental stability is well characterized. However, additional sources of error include stellar noise, undetected short-period planets, and telluric contamination. To understand and ultimately mitigate error sources, the contributing terms in the error budget must be isolated to the greatest extent possible. Here, we introduce a new high cadence radial velocity program, the EXPRES 100 Earths program, which aims to identify rocky planets around bright, nearby G and K dwarfs. We also present a benchmark case: the 62-d orbit of a Saturn-mass planet orbiting the chromospherically quiet star, HD 3651. The combination of high eccentricity (0.6) and a moderately long orbital period, ensures significant dynamical clearing of any inner planets. Our Keplerian model for this planetary orbit has a residual RMS of 58 cm/s over a $\sim 6$ month time baseline. By eliminating significant contributors to the radial velocity error budget, HD 3651 serves as a standard for evaluating the long term precision of extreme precision radial velocity (EPRV) programs.Comment: 11 pages, 6 figures, accepted for publication in Astronomical Journa

Anomalous Heat Conduction and Anomalous Diffusion in Low Dimensional Nanoscale Systems

Thermal transport is an important energy transfer process in nature. Phonon is the major energy carrier for heat in semiconductor and dielectric materials. In analogy to Ohm's law for electrical conductivity, Fourier's law is a fundamental rule of heat transfer in solids. It states that the thermal conductivity is independent of sample scale and geometry. Although Fourier's law has received great success in describing macroscopic thermal transport in the past two hundreds years, its validity in low dimensional systems is still an open question. Here we give a brief review of the recent developments in experimental, theoretical and numerical studies of heat transport in low dimensional systems, include lattice models, nanowires, nanotubes and graphenes. We will demonstrate that the phonon transports in low dimensional systems super-diffusively, which leads to a size dependent thermal conductivity. In other words, Fourier's law is breakdown in low dimensional structures

Workgroup report: Public health strategies for reducing aflatoxin exposure in developing countries

10.1289/ehp.9302Environmental Health Perspectives114121898-190

Atomic force microscopy analysis of nanoparticles in non-ideal conditions

Nanoparticles are often measured using atomic force microscopy or other scanning probe microscopy methods. For isolated nanoparticles on flat substrates, this is a relatively easy task. However, in real situations, we often need to analyze nanoparticles on rough substrates or nanoparticles that are not isolated. In this article, we present a simple model for realistic simulations of nanoparticle deposition and we employ this model for modeling nanoparticles on rough substrates. Different modeling conditions (coverage, relaxation after deposition) and convolution with different tip shapes are used to obtain a wide spectrum of virtual AFM nanoparticle images similar to those known from practice. Statistical parameters of nanoparticles are then analyzed using different data processing algorithms in order to show their systematic errors and to estimate uncertainties for atomic force microscopy analysis of nanoparticles under non-ideal conditions. It is shown that the elimination of user influence on the data processing algorithm is a key step for obtaining accurate results while analyzing nanoparticles measured in non-ideal conditions

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Evaluating the extent of reusability of CYP2C19 genotype data among patients genotyped for antiplatelet therapy selection

Purpose Genotype-guided antiplatelet therapy is increasingly being incorporated into clinical care. The purpose of this study is to determine the extent to which patients initially genotyped for CYP2C19 to guide antiplatelet therapy were prescribed additional medications affected by CYP2C19. Methods We assembled a cohort of patients from eight sites performing CYP2C19 genotyping to inform antiplatelet therapy. Medication orders were evaluated from time of genotyping through one year. The primary endpoint was the proportion of patients prescribed two or more CYP2C19 substrates. Secondary endpoints were the proportion of patients with a drug–genotype interaction and time to receiving a CYP2C19 substrate. Results Nine thousand one hundred ninety-one genotyped patients (17% nonwhite) with a mean age of 68 ± 3 years were evaluated; 4701 (51%) of patients received two or more CYP2C19 substrates and 3835 (42%) of patients had a drug–genotype interaction. The average time between genotyping and CYP2C19 substrate other than antiplatelet therapy was 25 ± 10 days. Conclusions More than half of patients genotyped in the setting of CYP2C19-guided antiplatelet therapy received another medication impacted by CYP2C19 in the following year. Given that genotype is stable for a patient’s lifetime, this finding has implications for cost effectiveness, patient care, and treatment outcomes beyond the indication for which it was originally performed

Apoptosis assays with lymphoma cell lines: problems and pitfalls

Much attention has been focused on the manner in which tumour cells die after treatment with cytotoxic agents. The basic question is whether cells die via apoptosis or via direct damage from the toxic agent. Various assays have been used to make this distinction. However, we show herein that some of the widely used assays for apoptosis do not in fact distinguish between apoptosis and other forms of cell death. More specifically: (1) A sub-G1 DNA content, identified by propidium iodide staining, does not distinguish between apoptotic and necrotic cells; (2) loss of mitochondrial membrane potential does not distinguish between apoptotic and necrotic cells, unless combined with an assay for an intact cell membrane; (3) subcellular fragments that arise from dead cells or from apoptotic bodies can interfere with some assays for apoptosis such as annexin V staining, as they may be close to the size of intact cells, making it difficult to decide where to set the size threshold; (4) irradiated cells display a large increase in nonspecific Ab binding. This may be partly due to an increase in cell size, but, regardless of the cause, it can lead to a mistaken conclusion that there is an increase in a particular antigen if appropriate control reagents are not tested; and (5) experiments utilising Ab crosslinking have neglected the role of cell aggregation, which can cause multiple problems including death from mechanical stress when cells are handled. Consideration of these factors will improve our ability to determine the mode of cell death