Tau Aggregation Inhibitor Therapy : An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease

ACKNOWLEDGMENTS We thank patients and their caregivers for their participation in the study and are indebted to all the investigators involved in the study, particularly Drs. Douglas Fowlie and Donald Mowat for their helpful contributions to the clinical execution of the study in Scotland. We thank Sharon Eastwood, Parexel, for assistance in preparing initial drafts of the manuscript. We acknowledge constructive comments provided by Professors G. Wilcock and S. Gauthier on drafts of the article. CMW, CRH, and JMDS are officers of, and hold beneficial interests in, TauRx Therapeutics. RTS, PB, KK, and DJW are paid consultants to TauRx Therapeutics. The study was financed entirely by TauRx TherapeuticsPeer reviewedPublisher PD

High resolution angle resolved photoemission studies on quasi-particle dynamics in graphite

We obtained the spectral function of the graphite H point using high resolution angle resolved photoelectron spectroscopy (ARPES). The extracted width of the spectral function (inverse of the photo-hole lifetime) near the H point is approximately proportional to the energy as expected from the linearly increasing density of states (DOS) near the Fermi energy. This is well accounted by our electron-phonon coupling theory considering the peculiar electronic DOS near the Fermi level. And we also investigated the temperature dependence of the peak widths both experimentally and theoretically. The upper bound for the electron-phonon coupling parameter is ~0.23, nearly the same value as previously reported at the K point. Our analysis of temperature dependent ARPES data at K shows that the energy of phonon mode of graphite has much higher energy scale than 125K which is dominant in electron-phonon coupling.Comment: 9 pages, 8 figures, accepted for publication in Phys. Rev.

Site-selective mapping of metastable states using electron-beam induced luminescence microscopy

Metastable states created by electron or hole capture in crystal defects are widely used in dosimetry and photonic applications. Feldspar, the most abundant mineral in the Earth crust (>50%), generates metastable states with lifetimes of millions of years upon exposure to ionizing radiation. Although feldspar is widely used in dosimetry and geochronometry, the creation of metastable states and charge transfer across them is poorly understood. Understanding such phenomena requires next-generation methods based on high-resolution, site-selective probing of the metastable states. Recent studies using site-selective techniques such as photoluminescence (PL), and radioluminescence (RL) at 7 K have revealed that feldspar exhibits two near-infrared (NIR) emission bands peaking at 880 nm and 955 nm, which are believed to arise from the principal electron-trapping states. Here, we map for the first time the electron-trapping states in potassium-rich feldspar using spectrally-resolved cathodoluminescence microscopy at a spatial resolution of around 6 to 22 micrometer. Each pixel probed by a scanning electron microscope provides us a cathodoluminescence spectrum (SEM-CL) in the range 600-1000 nm, and elemental data from energy-dispersive x-ray (EDX) spectroscopy. We conclude that the two NIR emissions are spatially variable and, therefore, originate from different sites. This conclusion contradicts the existing model that the two emissions arise from two different excited states of a principal trap. Moreover, we are able to link the individual NIR emission peaks with the geochemical variations (K, Na and Fe concentration), and propose a cluster model that explains the quenching of the NIR emission by Fe4+

Comparisons of physique, body composition, and somatotype by weight division between male and female collegiate taekwondo athletes

The aim of the study was to compare the physique, body composition and somatotype between male and female collegiate taekwondo athletes and specially focus on differences by weight division. 60 collegiate taekwondo athletes (male: 29, female: 31) voluntarily participated in the study. They were divided into four Olympic weight divisions (male for -58 kg, -68 kg, -80 kg, +80 kg, female for -49 kg, -57 kg, -67 kg, +67 kg). Anthropometric measurements included body weight, height, sitting height, body circumferences (relaxed arm, flexed arm, chest, waist, hip, thigh, and calf), bone widths (humerus and femur), and skinfold thicknesses (triceps, subscapular, suprailiac, thigh, and calf) were measured. The three somatotype components were assessed by Heath-Carter anthropometric method (Carter & Heath, 1990). Independent t-test and one-way ANOVA were applied to analyze difference of dependent variables. Significant level was set at .05. Male athletes were taller and heavier than female athletes. However, sum of skinfold thickness was significantly higher in female athletes than male athletes. The three somatotype components for male athletes were 3.4-3.5-3.1 and characterized with balanced mesomorphy. On the other hand, the somatotype of female athletes were 6.1-3.4-2.6 and characterized with mesomorphic endomorph. In male athletes -80 kg and +80 kg weight divisions were higher mesomorphy, but lower ectomorphy than -58 kg and -68 kg weight divisions. In female, -57 kg, -67 kg and +67 kg weight divisions were higher endomorphy and mesomorphy, but lower ectomorphy than -49 kg weight divisions. In conclusion, male athletes had higher anthropometric characteristics than female athletes except for the skinfold thickness. Female athletes had higher endomorphy, whereas male athletes had higher ectomorphy. Physique and somatotype were different between weight divisions both male and female athletes. This study provides a reference data of morphological characteristics of collegiate elite taekwondo athletes

The purinergic P2Y14 receptor axis is a molecular determinant for organism survival under in utero radiation toxicity

In utero exposure of the embryo and fetus to radiation has been implicated in malformations or fetal death, and often produces lifelong health consequences such as cancers and mental retardation. Here we demonstrate that deletion of a G-protein-coupled purinergic receptor, P2Y14, confers potent resistance to in utero radiation. Intriguingly, a putative P2Y14 receptor ligand, UDP-glucose, phenocopies the effect of P2Y14 deficiency. These data indicate that P2Y14 is a receptor governing in utero tolerance to genotoxic stress that may be pharmacologically targeted to mitigate radiation toxicity in pregnancy

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but \u3e95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity

CANDELS Sheds Light on the Environmental Quenching of Low-mass Galaxies

We investigate the environmental quenching of galaxies, especially those with stellar masses (M*)$<10^{9.5} M_\odot$, beyond the local universe. Essentially all local low-mass quenched galaxies (QGs) are believed to live close to massive central galaxies, which is a demonstration of environmental quenching. We use CANDELS data to test {\it whether or not} such a dwarf QG--massive central galaxy connection exists beyond the local universe. To this purpose, we only need a statistically representative, rather than a complete, sample of low-mass galaxies, which enables our study to $z\gtrsim1.5$. For each low-mass galaxy, we measure the projected distance ($d_{proj}$) to its nearest massive neighbor (M*$>10^{10.5} M_\odot$) within a redshift range. At a given redshift and M*, the environmental quenching effect is considered to be observed if the $d_{proj}$ distribution of QGs ($d_{proj}^Q$) is significantly skewed toward lower values than that of star-forming galaxies ($d_{proj}^{SF}$). For galaxies with $10^{8} M_\odot < M* < 10^{10} M_\odot$, such a difference between $d_{proj}^Q$ and $d_{proj}^{SF}$ is detected up to $z\sim1$. Also, about 10\% of the quenched galaxies in our sample are located between two and four virial radii ($R_{Vir}$) of the massive halos. The median projected distance from low-mass QGs to their massive neighbors, $d_{proj}^Q / R_{Vir}$, decreases with satellite M* at $M* \lesssim 10^{9.5} M_\odot$, but increases with satellite M* at $M* \gtrsim 10^{9.5} M_\odot$. This trend suggests a smooth, if any, transition of the quenching timescale around $M* \sim 10^{9.5} M_\odot$ at $0.5<z<1.0$.Comment: 8 pages, 5 figures. ApJL accepted. Typos correcte

Transcriptional regulation of the urokinase receptor (u-PAR) - A central molecule of invasion and metastasis

The phenomenon of tumor-associated proteolysis has been acknowledged as a decisive step in the progression of cancer. This short review focuses on the urokinase receptor (u-PAR), a central molecule involved in tumor-associated invasion and metastasis, and summarizes the transcriptional regulation of u-PAR. The urokinase receptor (u-PAR) is a heavily glycosylated cell surface protein and binds the serine protease urokinase specifically and with high affinity. It consists of three similar cysteine-rich repeats and is anchored to the cell membrane via a GPI-anchor. The u-PAR gene comprises 7 exons and is located on chromosome 19q13. Transcriptional activation of the u-PAR promoter region can be induced by binding of transcription factors (Sp1, AP-1, AP-2, NF-kappaB). One current study gives an example for transcriptional downregulation of u-PAR through a PEA3/ets transcriptional silencing element. Knowledge of the molecular regulation of this molecule in tumor cells could be very important for diagnosis and therapy in the near future