Inhibition of REV-ERBs stimulates microglial amyloid-beta clearance and reduces amyloid plaque deposition in the 5XFAD mouse model of Alzheimer\u27s disease

A promising new therapeutic target for the treatment of Alzheimer\u27s disease (AD) is the circadian system. Although patients with AD are known to have abnormal circadian rhythms and suffer sleep disturbances, the role of the molecular clock in regulating amyloid-beta (Aβ) pathology is still poorly understood. Here, we explored how the circadian repressors REV-ERBα and β affected Aβ clearance in mouse microglia. We discovered that, at Circadian time 4 (CT4), microglia expressed higher levels of the master clock protein BMAL1 and more rapidly phagocytosed fibrillary A

E-cigarette aerosols induce unfolded protein response in normal human oral keratinocytes.

Objective: Since the introduction in 2004, global usage of e-cigarettes (ECs) has risen exponentially. However, the risks of ECs on oral health are uncertain. The purpose of this study is to understand if EC aerosol exposure impacts the gene pathways of normal human oral keratinocytes (NHOKs), particularly the unfolded protein response (UPR) pathway. Materials and methods: EC aerosols were generated reproducibly with a home-made puffing device and impinged into the culture medium for NHOKs. DNA microarrays were used to profile the gene expression changes in NHOKs treated with EC aerosols, and the Ingenuity Pathway Analysis (IPA) was used to reveal signaling pathways altered by the EC aerosols. Quantitative PCR was used to validate the expression changes of significantly altered genes. Results: DNA microarray profiling followed by IPA revealed a number of signaling pathways, such as UPR, cell cycle regulation, TGF-β signaling, NRF2-mediated oxidative stress response, PI3K/AKT signaling, NF-κB signaling, and HGF signaling, activated by EC aerosols in NHOKs. The UPR pathway genes, C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), X box binding protein 1 (XBP1), and inositol-requiring enzyme 1 alpha (IRE1α) were all significantly up-regulated in EC aerosol-treated NHOKs whereas immunoglobulin heavy-chain binding protein (BIP) and PRKR-like ER kinase (PERK) were slightly up-regulated. qPCR analysis results were found to be well correlated with those from the DNA microarray analysis. The most significantly changed genes in EC aerosol-treated NHOKs versus untreated NHOKs were CHOP, ATF4, XBP1, IRE1α and BIP. Meanwhile, Western blot analysis confirmed that CHOP, GRP78 (BIP), ATF4, IRE1α and XBP1s (spliced XBP1) were significantly up-regulated in NHOKs treated with EC aerosols. Conclusion: Our results indicate that EC aerosols up-regulate the UPR pathway genes in NHOKs, and the induction of UPR response is mediated by the PERK - EIF2α - ATF4 and IRE1α - XBP1 pathways

Uniqueness of roots up to conjugacy for some affine and finite type Artin groups

Let $G$ be one of the Artin groups of finite type ${\mathbf B}_n={\mathbf C}_n$, and affine type $\tilde{\mathbf A}_{n-1}$ and $\tilde{\mathbf C}_{n-1}$. In this paper, we show that if $\alpha$ and $\beta$ are elements of $G$ such that $\alpha^k=\beta^k$ for some nonzero integer $k$, then $\alpha$ and $\beta$ are conjugate in $G$. For the Artin group of type $\mathbf A_n$, this was recently proved by J. Gonz\'alez-Meneses. In fact, we prove a stronger theorem, from which the above result follows easily by using descriptions of those Artin groups as subgroups of the braid group on $n+1$ strands. Let $P$ be a subset of $\{1,...,n\}$. An $n$-braid is said to be \emph{$P$-pure} if its induced permutation fixes each $i\in P$, and \emph{$P$-straight} if it is $P$-pure and it becomes trivial when we delete all the $i$-th strands for $i\not\in P$. Exploiting the Nielsen-Thurston classification of braids, we show that if $\alpha$ and $\beta$ are $P$-pure $n$-braids such that $\alpha^k=\beta^k$ for some nonzero integer $k$, then there exists a $P$-straight $n$-braid $\gamma$ with $\beta=\gamma\alpha\gamma^{-1}$. Moreover, if $1\in P$, the conjugating element $\gamma$ can be chosen to have the first strand algebraically unlinked with the other strands. Especially in case of $P=\{1,...,n\}$, our result implies the uniqueness of root of pure braids, which was known by V. G. Bardakov and by D. Kim and D. Rolfsen.Comment: 15 pages, 8 figures; version published by Math.

Suppression of stored-beam oscillation and observation of flux improvement during top-up injection

This paper describes a start-to-end study of the suppression of stored-beam oscillation during top-up injection at the Pohang Light Source (PLS-II) beam line. The fast counterkicker implemented in PLS-II suppresses stored-beam oscillations in the vertical plane. During top-up injection in the magnetic spectroscopy beam line of PLS-II, flux improvement due to the suppression of stored-beam oscillation was clearly observed.11Ysciescopu

The Intrinsic Shapes of Low-Surface-Brightness Dwarf Irregular Galaxies and Comparison to Other Types of Dwarf Galaxies

In this paper, we measure the ellipticities of 30 LSB dI galaxies and compare the ellipticity distribution with that of 80 dEs (Ryden & Terndrup 1994; Ryden et al. 1998) and 62 BCDs (Sung et al. 1998). We find that the ellipticity distribution of LSB dIs is very similar to that of BCDs, and marginally different from that of dEs. We then determine the distribution of intrinsic shapes of dI galaxies and compare to those of other type dwarf galaxies under various assumptions. First, we assume that LSB dIs are either all oblate or all prolate, and use non-parametric analysis to find the best-fitting distribution of intrinsic shapes. With this assumption, we find that the scarcity of nearly circular LSB dIs implies, at the 99% confidence level, that they cannot be a population of randomly oriented oblate or prolate objects. Next, we assume that dIs are triaxial, and use parametric analysis to find permissible distributions of intrinsic shapes. We find that if the intrinsic axis ratios, $\beta$ and $\gamma$, are distributed according to a Gaussian with means $\beta_0$ and $\gamma_0$ and a common standard deviation of $\sigma$, the best-fitting set of parameters for LSB dIs is $(\beta_0,\gamma_0,\sigma) = (0.66,0.50,0.15)$, and the best fit for BCDs is $(\beta_0,\gamma_0,\sigma) = (0.66,0.55,0.16)$, while the best fit for dEs is $(\beta_0,\gamma_0,\sigma) = (0.78,0.69,0.24)$. The dIs and BCDs thus have a very similar shape distribution, given this triaxial hypothesis, while the dEs peak at a somewhat more spherical shape. Our results are consistent with an evolutionary scenario in which the three types of dwarf galaxy have a close relation with each other.Comment: total 18 pages, 4 figures, and 3 Tables, submitted to Astrophysical Journal on Mar 5 199

Evidence for the decay B0->eta pi^0

We report a search for the charmless hadronic decay $B^0\to\eta \pi^0$ with a data sample corresponding to an integrated luminosity of 694 $\rm fb^{-1}$ containing $753\times10^6$ $B\bar{B}$ pairs. The data were collected by the Belle experiment running on the $\Upsilon(4S)$ resonance at the KEKB $e^+e^-$ collider. We measure a branching fraction $\mathcal{B}(B^0\to\eta\pi^0)=(4.1^{+1.7+0.5}_{-1.5-0.7})\times 10^{-7}$, where the first uncertainty is statistical and the second is systematic. Our measurement gives an upper limit of $\mathcal{B}(B^0\to\eta\pi^0)<6.5\times 10^{-7}$ at 90\% confidence level. The signal has a significance of $3.0$ standard deviations and constitutes the first evidence for this decay mode.Comment: 11 pages, 3 figures, 2 tables, submitted to Physical Review D(R

Fabrication of Coaxial Si1−xGex Heterostructure Nanowires by O2 Flow-Induced Bifurcate Reactions

We report on bifurcate reactions on the surface of well-aligned Si1−xGex nanowires that enable fabrication of two different coaxial heterostructure nanowires. The Si1−xGex nanowires were grown in a chemical vapor transport process using SiCl4 gas and Ge powder as a source. After the growth of nanowires, SiCl4 flow was terminated while O2 gas flow was introduced under vacuum. On the surface of nanowires was deposited Ge by the vapor from the Ge powder or oxidized into SiO2 by the O2 gas. The transition from deposition to oxidation occurred abruptly at 2 torr of O2 pressure without any intermediate region and enables selectively fabricated Ge/Si1−xGex or SiO2/Si1−xGex coaxial heterostructure nanowires. The rate of deposition and oxidation was dominated by interfacial reaction and diffusion of oxygen through the oxide layer, respectively

Efficacy of an Educational Material on Second Primary Cancer Screening Practice for Cancer Survivors: A Randomized Controlled Trial

<div><h3>Background</h3><p>Cancer surivors have limited knowledge about second primary cancer (SPC) screening and suboptimal rates of completion of screening practices for SPC. Our objective was to test the efficacy of an educational material on the knowledge, attitudes, and screening practices for SPC among cancer survivors.</p> <h3>Methods</h3><p>Randomized, controlled trial among 326 cancer survivors from 6 oncology care outpatient clinics in Korea. Patients were randomized to an intervention or an attention control group. The intervention was a photo-novel, culturally tailored to increase knowledge about SPC screening. Knowledge and attitudes regarding SPC screening were assessed two weeks after the intervention, and screening practices were assessed after one year.</p> <h3>Results</h3><p>At two weeks post-intervention, the average knowledge score was significantly higher in the intervention compared to the control group (0.81 vs. 0.75, P<0.01), with no significant difference in their attitude scores (2.64 vs. 2.57, P = 0.18). After 1 year of follow-up, the completion rate of all appropriate cancer screening was 47.2% in both intervention and control groups.</p> <h3>Conclusion</h3><p>While the educatinal material was effective for increasing knowledge of SPC screening, it did not promote cancer screening practice among cancer survivors. More effective interventions are needed to increase SPC screening rates in this population.</p> <h3>Trial Registration</h3><p>ClinicalTrial.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00948337">NCT00948337</a></p> </div

Validation of a Mass Spectrometry Method To Quantify Oak Ellagitannins in Wine Samples

[EN] Detection and individual quantification of oak wood ellagitannins in oak barrel aged red wine samples are difficult mainly due to their low levels and the similarity between their structures. In this work, a quantification method using mass spectrometry has been developed and validated to quantify wine ellagitannins after sample fractionation with a previously reported method. The use of an internal standard is a requirement to correct mass signal variability. (−)-Gallocatechin, among the different tested compounds, was the only one that proved to be a suitable internal standard making possible the accurate and individual quantification of the main oak wood ellagitannins. The developed methodology has been used to detect and quantify these ellagitannins in different Spanish commercial wines, proving its usefulness

Relationship between the Sensory-Determined Astringency and the Flavanolic Composition of Red Wines

[EN] The relationship between the proanthocyanidin profile and the perceived astringency was assessed in 13 commercial Tempranillo red wines. The concentration and compositional information were obtained by liquid chromatography with diode array detection coupled to electrospray ionization mass spectrometry after acid-catalyzed depolymerization of wine proanthocyanidins in the presence of excess phloroglucinol. Statistical analysis of the results showed significant correlations between sensory and chemical determinations. Astringency was more affected by the subunit composition than by the total concentration or the average degree of polymerization of wine proanthocyanidins. Higher proportions of epicatechin (EC) subunits in extension positions and gallocatechin (GC) subunits in terminal positions were shown to increase astringency. On the contrary, the amount of epigallocatechin (EGC) in both extension and terminal positions was negatively correlated with the perceived astringency