Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

BACKGROUND Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17. CONCLUSIONS/SIGNIFICANCE The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.This work was funded by a project grant (490031) from the National Health and Medical Research Council of Australia (http://www.nhmrc.gov.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Dark Energy Survey Year 1 Clusters are Consistent with Planck

The recent Dark Energy Survey Year 1 (DES-Y1) analysis of galaxy cluster abundances and weak lensing produced $\Omega_{\rm m}$ and $\sigma_8$ constraints in 5.6$\sigma$ tension with Planck. It is suggested in that work that this tension is driven by unmodelled systematics in optical cluster selection. We present a novel simulation-based forward modeling framework that explicitly incorporates cluster selection into its model predictions. Applying this framework to the DES-Y1 data we find consistency with Planck, resolving the tension found in the DES-Y1 analysis. An extension of this approach to the final DES data set will produce robust constraints on $\Lambda$CDM parameters and correspondingly strong tests of cosmological models.Comment: 6 pages, 2 figures, 1 table, Supplemental material with 2 figures. Submitted to Physical Review Letter

Buzzard to Cardinal: Improved Mock Catalogs for Large Galaxy Surveys

We present the Cardinal mock galaxy catalogs, a new version of the Buzzard simulation that has been updated to support ongoing and future cosmological surveys, including the Dark Energy Survey (DES), DESI, and LSST. These catalogs are based on a one-quarter sky simulation populated with galaxies out to a redshift of z = 2.35 to a depth of mr = 27. Compared to the Buzzard mocks, the Cardinal mocks include an updated subhalo abundance matching model that considers orphan galaxies and includes mass-dependent scatter between galaxy luminosity and halo properties. This model can simultaneously fit galaxy clustering and group–galaxy cross-correlations measured in three different luminosity threshold samples. The Cardinal mocks also feature a new color assignment model that can simultaneously fit color-dependent galaxy clustering in three different luminosity bins. We have developed an algorithm that uses photometric data to further improve the color assignment model and have also developed a novel method to improve small-scale lensing below the ray-tracing resolution. These improvements enable the Cardinal mocks to accurately reproduce the abundance of galaxy clusters and the properties of lens galaxies in the DES data. As such, these simulations will be a valuable tool for future cosmological analyses based on large sky surveys

Exploiting Non-Linear Scales in Galaxy–Galaxy Lensing and Galaxy Clustering: A Forecast for the Dark Energy Survey

The combination of galaxy-galaxy lensing (GGL) and galaxy clustering is a powerful probe of low redshift matter clustering, especially if it is extended to the non-linear regime. To this end, we extend the N-body and halo occupation distribution (HOD) emulator method of arxiv:1907.06293 to model the redMaGiC sample of colour-selected passive galaxies in the Dark Energy Survey (DES), adding parameters that describe central galaxy incompleteness, galaxy assembly bias, and a scale-independent multiplicative lensing bias $A_{lens}$. We use this emulator to forecast cosmological constraints attainable from the GGL surface density profile $\Delta\Sigma(r_p)$ and the projected galaxy correlation function $w_{p,gg}(r_p)$ in the final (Year 6) DES data set over scales $r_p=0.3-30h^{-1}$ Mpc. For a $3\%$ prior on $A_{lens}$ we forecast precisions of $1.9\%$, $2.0\%$, and $1.9\%$ on $\Omega_m$, $\sigma_8$, and $S_8 \equiv \sigma_8\Omega_m^{0.5}$, marginalized over all halo occupation distribution (HOD) parameters as well as $A_{lens}$ and a point-mass contribution to $\Delta\Sigma$. Adding scales $r_p=0.3-3h^{-1}$ Mpc improves the $S_8$ precision by a factor of $\sim1.6$ relative to a large scale ($3.0-30.0h^{-1}$ Mpc) analysis, equivalent to increasing the survey area by a factor of ${\sim}2.6$. Sharpening the $A_{lens}$ prior to $1\%$ further improves the $S_8$ precision by a factor of $1.7$ (to $1.1\%$), and it amplifies the gain from including non-linear scales. Our emulator achieves percent-level accuracy similar to the projected DES statistical uncertainties, demonstrating the feasibility of a fully non-linear analysis. Obtaining precise parameter constraints from multiple galaxy types and from measurements that span linear and non-linear clustering offers many opportunities for internal cross-checks, which can diagnose systematics and demonstrate the robustness of cosmological results.Comment: 17 pages, 7 figures, to be submitted to MNRA

A Low Temperature Nonlinear Optical Rotational Anisotropy Spectrometer for the Determination of Crystallographic and Electronic Symmetries

Nonlinear optical generation from a crystalline material can reveal the symmetries of both its lattice structure and underlying ordered electronic phases and can therefore be exploited as a complementary technique to diffraction based scattering probes. Although this technique has been successfully used to study the lattice and magnetic structures of systems such as semiconductor surfaces, multiferroic crystals, magnetic thin films and multilayers, challenging technical requirements have prevented its application to the plethora of complex electronic phases found in strongly correlated electron systems. These requirements include an ability to probe small bulk single crystals at the micron length scale, a need for sensitivity to the entire nonlinear optical susceptibility tensor, oblique light incidence reflection geometry and incident light frequency tunability among others. These measurements are further complicated by the need for extreme sample environments such as ultra low temperatures, high magnetic fields or high pressures. In this review we present a novel experimental construction using a rotating light scattering plane that meets all the aforementioned requirements. We demonstrate the efficacy of our scheme by making symmetry measurements on a micron scale facet of a small bulk single crystal of Sr$_2$IrO$_4$ using optical second and third harmonic generation.Comment: 8 pages, 5 figure

Deciphering baryonic feedback with galaxy clusters

Upcoming cosmic shear analyses will precisely measure the cosmic matter distribution at low redshifts. At these redshifts, the matter distribution is affected by galaxy formation physics, primarily baryonic feedback from star formation and active galactic nuclei. Employing measurements from the Magneticum and IllustrisTNG simulations and a dark matter + baryon (DMB) halo model, this paper demonstrates that Sunyaev-Zel'dovich (SZ) effect observations of galaxy clusters, whose masses have been calibrated using weak gravitational lensing, can constrain the baryonic impact on cosmic shear with statistical and systematic errors subdominant to the measurement errors of DES-Y3 and LSST-Y1. We further dissect the contributions from different scales and halos with different masses to cosmic shear, highlighting the dominant role of SZ clusters at scales critical for cosmic shear analyses. These findings suggest a promising avenue for future joint analyses of Cosmic Microwave Background (CMB) and lensing surveys.Comment: To be submitted to JCAP. Comments are welcome

Central Neurocytoma: A Review of Clinical Management and Histopathologic Features.

Central neurocytoma (CN) is a rare, benign brain tumor often located in the lateral ventricles. CN may cause obstructive hydrocephalus and manifest as signs of increased intracranial pressure. The goal of treatment for CN is a gross total resection (GTR), which often yields excellent prognosis with a very high rate of tumor control and survival. Adjuvant radiosurgery and radiotherapy may be considered to improve tumor control when GTR cannot be achieved. Chemotherapy is also not considered a primary treatment, but has been used as a salvage therapy. The radiological features of CN are indistinguishable from those of other brain tumors; therefore, many histological markers, such as synaptophysin, can be very useful for diagnosing CNs. Furthermore, the MIB-1 Labeling Index seems to be correlated with the prognosis of CN. We also discuss oncogenes associated with these elusive tumors. Further studies may improve our ability to accurately diagnose CNs and to design the optimal treatment regimens for patients with CNs

Investigating the Essential of Meaningful Automated Formative Feedback for Programming Assignments

This study investigated the essential of meaningful automated feedback for programming assignments. Three different types of feedback were tested, including (a) What's wrong - what test cases were testing and which failed, (b) Gap - comparisons between expected and actual outputs, and (c) Hint - hints on how to fix problems if test cases failed. 46 students taking a CS2 participated in this study. They were divided into three groups, and the feedback configurations for each group were different: (1) Group One - What's wrong, (2) Group Two - What's wrong + Gap, (3) Group Three - What's wrong + Gap + Hint. This study found that simply knowing what failed did not help students sufficiently, and might stimulate system gaming behavior. Hints were not found to be impactful on student performance or their usage of automated feedback. Based on the findings, this study provides practical guidance on the design of automated feedback