A human carboxypeptidase E/NF-alpha 1 gene mutation in an Alzheimer's disease patient leads to dementia and depression in mice

Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-alpha 1 (NF-alpha 1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ. Expression of CPE-QQ in Neuro2a cells demonstrated that it was not secreted, but accumulated in the endoplasmic reticulum and was subsequently degraded by proteasomes. Expression of CPE-QQ in rat hippocampal neurons resulted in cell death, through increased ER stress and decreased expression of pro-survival protein, BCL-2. Transgenic mice expressing CPE-QQ did not show any difference in the processing enzyme activity of CPE compared with wild-type mice. However, the transgenic mice exhibited poor memory, depressive-like behavior, severely decreased dendrites in the hippocampal CA3 region and medial prefrontal cortex indicative of neurodegeneration, hyperphosphorylation of tau at Ser(396), and diminished neurogenesis in the dentate gyrus at 50 weeks old. All these pathologies are associated with AD and the latter with depression and were observed in 50-week-old mice. Interestingly, the younger CPE-QQ mice (11 weeks old) did not show deficits in dendrite outgrowth and neurogenesis. This study has uncovered a human CPE/NF-alpha 1 gene mutation that could lead to comorbidity of dementia and depression, emphasizing the importance of this gene in cognitive function

SmartTrack: Efficient Predictive Race Detection

Widely used data race detectors, including the state-of-the-art FastTrack algorithm, incur performance costs that are acceptable for regular in-house testing, but miss races detectable from the analyzed execution. Predictive analyses detect more data races in an analyzed execution than FastTrack detects, but at significantly higher performance cost. This paper presents SmartTrack, an algorithm that optimizes predictive race detection analyses, including two analyses from prior work and a new analysis introduced in this paper. SmartTrack's algorithm incorporates two main optimizations: (1) epoch and ownership optimizations from prior work, applied to predictive analysis for the first time; and (2) novel conflicting critical section optimizations introduced by this paper. Our evaluation shows that SmartTrack achieves performance competitive with FastTrack-a qualitative improvement in the state of the art for data race detection.Comment: Extended arXiv version of PLDI 2020 paper (adds Appendices A-E) #228 SmartTrack: Efficient Predictive Race Detectio

THE COMPARATIVE ANALYSIS ON THE OVERVIEW OF HAIR GOAT BREEDINGS TO SUSTAINABLE FOREST RESOURCES MANAGEMENT

Goat breedings in Turkey is a traditional profession dating back centuries which is carried out in and around forests of rural regions. The purpose of this study was to determine the factors with an impact on sustainable natural resource management based on the opinions of goat breeders and to put forth the contributions that may be provided to establish a sustainable management. The study will contribute to establishing a sustainable goat breeding system in Turkey as well as the management of sustainable forest resources. In this scope, the study was carried out in two different areas in the Mediterranean region of Turkey where goat breeding is widespread. The opinions of goat breeders on demographics, socioeconomic, hair goat breeding and sustainable forest resources management were acquired via survey method and used as the primary data of the study. Descriptive statistics such as frequency, percentage and crosstab values along with Mann-Whitney U Test, Chi-Square Test of Independence and Multivariate Linear Regression Analysis were used as the method. It was determined based on the study results that grazing in forest area is the most important problem for goat breeders and various other problems were also observed related to cooperation with the forest administration. It was observed that goat breeding is carried out via traditional methods by families that are above middle age. The findings indicate that the number of goat breeders decrease as a result of increasing age due to interventions for preventing damages given to trees in the forest by goats during grazing, decrease in the education level and the duration of experience in this profession

Magnetic Tracking and Electrocardiography-Guided Tip Confirmation System Versus Fluoroscopy for Placement of Peripherally Inserted Central Catheters: A Randomized, Noninferiority Comparison

Purpose!#!To determine whether the use of a magnetic tracking and electrocardiography-guided catheter tip confirmation system (TCS) is safe and noninferior to fluoroscopy concerning positioning accuracy of a peripheral inserted central catheter (PICC).!##!Methods!#!In this prospective, randomized, single-center study, adult patients scheduled for PICC insertion were assigned 1:1 either to TCS or fluoroscopy. The primary objective was a noninferiority comparison of correct PICC tip position confirmed by X-ray obtained immediately after catheter insertion. Time needed for PICC insertion and insertion-related complications up to 14 days after the procedure were secondary outcomes to be assessed for superiority.!##!Results!#!A total of 210 patients (62.3 ± 14.4 years, 63.8% male) were included at a single German center between June 2016 and October 2017. Correct PICC tip position was achieved in 84 of 103 TCS (82.4%) and 103 of 104 fluoroscopy patients (99.0%). One-sided 95% lower confidence limit on the difference between proportions was -23.1%. Thus, noninferiority of TCS was not established (p > 0.99). Insertion of PICC took longer with TCS compared to fluoroscopy (8.4 ± 3.7 min vs. 5.0 ± 2.7 min, p < 0.001). Incidence of complications within a mean follow-up of 5.0 ± 2.3 days did not differ significantly between groups.!##!Conclusion!#!Noninferiority of TCS to fluoroscopy in the incidence of correct PICC tip position was not reached. Ancillary benefit of TCS over fluoroscopy including less radiation exposure and lower resource requirements may nonetheless justify the use of TCS. The study is registered with Clinical.Trials.gov (Identifier: NCT02929368)

Simultaneous EEG/fMRI Analysis of the Resonance Phenomena in Steady-State Visual Evoked Responses

The stability of the steady-state visual evoked potentials (SSVEPs) across trials and subjects makes them a suitable tool for the investigation of the visual system. The reproducible pattern of the frequency characteristics of SSVEPs shows a global amplitude maximum around 10 Hz and additional local maxima around 20 and 40 Hz, which have been argued to represent resonant behavior of damped neuronal oscillators

Simultaneous EEG/fMRI Analysis of the Resonance Phenomena in Steady-State Visual Evoked Responses

The stability of the steady-state visual evoked potentials (SSVEPs) across trials and subjects makes them a suitable tool for the investigation of the visual system. The reproducible pattern of the frequency characteristics of SSVEPs shows a global amplitude maximum around 10 Hz and additional local maxima around 20 and 40 Hz, which have been argued to represent resonant behavior of damped neuronal oscillators. Simultaneous electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) measurement allows testing of the resonance hypothesis about the frequency-selective increases in SSVEP amplitudes in human subjects, because the total synaptic activity that is represented in the fMRI-Blood Oxygen Level Dependent (fMRI-BOLD) response would not increase but get synchronized at the resonance frequency. For this purpose, 40 healthy volunteers were visually stimulated with flickering light at systematically varying frequencies between 6 and 46 Hz, and the correlations between SSVEP amplitudes and the BOLD responses were computed. The SSVEP frequency characteristics of all subjects showed 3 frequency ranges with an amplitude maximum in each of them, which roughly correspond to alpha, beta and gamma bands of the EEG. The correlation maps between BOLD responses and SSVEP amplitude changes across the different stimulation frequencies within each frequency band showed no significant correlation in the alpha range, while significant correlations were obtained in the primary visual area for the beta and gamma bands. This non-linear relationship between the surface recorded SSVEP amplitudes and the BOLD responses of the visual cortex at stimulation frequencies around the alpha band supports the view that a resonance at the tuning frequency of the thalamo-cortical alpha oscillator in the visual system is responsible for the global amplitude maximum of the SSVEP around 10 Hz. Information gained from the SSVEP/fMRI analyses in the present study might be extrapolated to the EEG/fMRI analysis of the transient event-related potentials (ERPs) in terms of expecting more reliable and consistent correlations between EEG and fMRI responses, when the analyses are carried out on evoked or induced oscillations (spectral perturbations) in separate frequency bands instead of the time-domain ERP peaks