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

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

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.

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

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

Isoperimetric Inequalities in Simplicial Complexes

In graph theory there are intimate connections between the expansion properties of a graph and the spectrum of its Laplacian. In this paper we define a notion of combinatorial expansion for simplicial complexes of general dimension, and prove that similar connections exist between the combinatorial expansion of a complex, and the spectrum of the high dimensional Laplacian defined by Eckmann. In particular, we present a Cheeger-type inequality, and a high-dimensional Expander Mixing Lemma. As a corollary, using the work of Pach, we obtain a connection between spectral properties of complexes and Gromov's notion of geometric overlap. Using the work of Gunder and Wagner, we give an estimate for the combinatorial expansion and geometric overlap of random Linial-Meshulam complexes

Beyond paradigm : The ‘what’ and the ‘how’ of classroom research

This article reviews studies in second language classroom research from a cross-theoretic perspective, arguing that the classroom holds the potential for bringing together researchers from opposing theoretical orientations. It shows how generative and general cognitive approaches share a view of language that implicates both implicit and explicit knowledge, and that holds a bias towards implicit knowledge. Arguing that it is implicit knowledge that should be the object of research, it proposes that classroom research would benefit from incorporating insights from a generative understanding of language. Specifically, there is a need for a more nuanced view of the complexity of language in terms of linguistic domain, and the interaction between those domains. Generative second language acquisition research that shows developmental differences in terms of both linguistic domain and interface is reviewed. The core argument is a call for more attention to the ‘what’ of language development in classroom research and, by implication, teaching practice. As such, the language classroom is seen to offer potential for research that goes beyond paradigm to address both the ‘what’ and the ‘how’ of language development

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

Greene's Residue Criterion for the Breakup of Invariant Tori of Volume-Preserving Maps

Invariant tori play a fundamental role in the dynamics of symplectic and volume-preserving maps. Codimension-one tori are particularly important as they form barriers to transport. Such tori foliate the phase space of integrable, volume-preserving maps with one action and $d$ angles. For the area-preserving case, Greene's residue criterion is often used to predict the destruction of tori from the properties of nearby periodic orbits. Even though KAM theory applies to the three-dimensional case, the robustness of tori in such systems is still poorly understood. We study a three-dimensional, reversible, volume-preserving analogue of Chirikov's standard map with one action and two angles. We investigate the preservation and destruction of tori under perturbation by computing the "residue" of nearby periodic orbits. We find tori with Diophantine rotation vectors in the "spiral mean" cubic algebraic field. The residue is used to generate the critical function of the map and find a candidate for the most robust torus.Comment: laTeX, 40 pages, 26 figure

Boundary driven zero-range processes in random media

The stationary states of boundary driven zero-range processes in random media with quenched disorder are examined, and the motion of a tagged particle is analyzed. For symmetric transition rates, also known as the random barrier model, the stationary state is found to be trivial in absence of boundary drive. Out of equilibrium, two further cases are distinguished according to the tail of the disorder distribution. For strong disorder, the fugacity profiles are found to be governed by the paths of normalized $\alpha$-stable subordinators. The expectations of integrated functions of the tagged particle position are calculated for three types of routes.Comment: 23 page