Miracle-dz/UniFAR-FTUs huggingface dataset:
β-Amyloid (Aβ) Oligomers Impair Brain-derived Neurotrophic Factor Retrograde Trafficking by Down-regulating Ubiquitin C-terminal Hydrolase, UCH-L1*

Background: Axonal transport deficits are part of Alzheimer disease (AD) pathobiology. Results: β-Amyloid (Aβ) impairs BDNF-dependent retrograde signaling, which is rescued by increasing cellular UCH-L1 levels. Conclusion: In AD, Aβ impairs neurotrophin-mediated retrograde signaling by disrupting ubiquitin homeostasis. Significance: Elucidating the mechanism by which Aβ causes transport deficits that compromise synaptic plasticity and neuronal survival is crucial for discovering novel therapeutics to reverse cognitive deficits in AD. We previously found that BDNF-dependent retrograde trafficking is impaired in AD transgenic mouse neurons. Utilizing a novel microfluidic culture chamber, we demonstrate that Aβ oligomers compromise BDNF-mediated retrograde transport by impairing endosomal vesicle velocities, resulting in impaired downstream signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation. Our data suggest that a key mechanism mediating the deficit involves ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin. Aβ-induced deficits in BDNF trafficking and signaling are mimicked by LDN (an inhibitor of UCH-L1) and can be reversed by increasing cellular UCH-L1 levels, demonstrated here using a transducible TAT-UCH-L1 strategy. Finally, our data reveal that UCH-L1 mRNA levels are decreased in the hippocampi of AD brains. Taken together, our data implicate that UCH-L1 is important for regulating neurotrophin receptor sorting to signaling endosomes and supporting retrograde transport. Further, our results support the idea that in AD, Aβ may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival.
THE MOST METAL-POOR STARS. III. THE METALLICITY DISTRIBUTION FUNCTION AND CARBON-ENHANCED METAL-POOR FRACTION,,

We examine the metallicity distribution function (MDF) and fraction of carbon-enhanced metal-poor (CEMP) stars in a sample that includes 86 stars with [Fe/H] ⩽ −3.0, based on high-resolution, high signal-to-noise spectroscopy, of which some 32 objects lie below [Fe/H] = −3.5. After accounting for the completeness function, the “corrected” MDF does not exhibit the sudden drop at [Fe/H] = −3.6 that was found in recent samples of dwarfs and giants from the Hamburg/ESO survey. Rather, the MDF decreases smoothly down to [Fe/H] = −4.1. Similar results are obtained from the “raw” MDF. We find that the fraction of CEMP objects below [Fe/H] = −3.0 is 23% ± 6% and 32% ± 8% when adopting the Beers & Christlieb and Aoki et al. CEMP definitions, respectively. The former value is in fair agreement with some previous measurements, which adopt the Beers & Christlieb criterion.
Validated questionnaires should not be modified

The reformatting and changes that were made to the Asthma Control Questionnaire (ACQ) 1 for the Post-cold Asthma Control and Exacerbation (PAX) study 2 raise some important concerns about modifying validated questionnaires. Just like mechanical and electrical measurement instruments, validated questionnaires are precision measurement instruments. The only difference being that they measure subjective rather than objective health status. Like any mechanical or electrical instrument, a great deal of care and expertise goes into the development of these questionnaires. Many studies have provided developers with the knowledge of how to: specify what the questionnaire is intended to measure (its construct); structure and select the right questions; formulate the responses; select the time specifications; optimise the page formulation for accurate completion; conduct validation studies (measurement properties and whether the instrument is measuring what it is meant to measure) and provide users the wherewithal to place a clinical interpretation on the data. For the same reason that one would never think of changing the numbers on the dial of a mechanical spirometer, one should never change a validated questionnaire. Even very small changes can destroy its validity. Questions are selected by well-established methods (usually either “importance” or “factor analysis”) 3 and their position in the questionnaire carefully ordered. Wording is checked for ease and accuracy of understanding (cognitive debriefing). For the analysis, each question has a weighting. For some questionnaires, this means that an algorithm must be used ( e.g. The Short Form (SF)-36 Health Survey) 4, in others ( e.g. the ACQ) questions are selected in such a way that they have equal weighting and the overall score is the mean of all the responses. The wording of questions should never be changed. Shortened versions should only be used when they have been …
Exact solutions of the aspherical axisymmetric gravo-magnetic condensation

We nd exact and explicit self-similar solutions of the axisymmetric MHD equations of a self-gravitating polytropic gas. These solutions are able to describe a flat (uniform density) subsonic internal core, contracting homologously out of a collapsing cloud with aspherical pressure, aspherical gravitational potential, magnetic eld and rotation. Two of the solutions describing the collapse of a rotating and magnetized cloud present outflow at the pole or at the equator.
The Reliability and Validity of Liu´s Self-Report Questionnaire for Screening Putative Pre-Psychotic States (BQSPS) in Adolescents

The usage of rigorous analyses based on contemporary methods to enhance psychometric properties of screening questionnaires aimed to address psychotic-like experiences (PLE) is currently being encouraged. The Brief Self-Report Questionnaire for Screening Putative Pre-psychotic States (BQSPS) is a recently created tool addressing PLE beyond attenuated positive symptoms (APS). Its psychometric properties as a screening tool for first step assessment seems to be adequate, but further research is needed to evaluate certain validity aspects, particularly its dimensionality, internal structure, and psychometric properties in different populations. We assessed the reliability, construct validity, and criterion validity of BQSPS in two samples: 727 adolescents aged 13–18 years, and 245 young adults aged 18–33 years. We used exploratory structural equation modeling (ESEM), confirmatory factor analysis (CFA), and Structural Equation Modeling (SEM). The original four-factor structure was not replicated. The best fit in adolescents was obtained by a structure of three-correlated factors: social anxiety (SA), negative symptoms (NS), and positive symptoms (PS). This structure was confirmed in young adult subjects. The three-factor model reached a predictive capability with suicidality as external criterion. PLE are represented by a three-factor structure, which is highly stable between adolescent and young-adult samples. Although the BQSPS seems to be a valid tool for screening PLE, its psychometric properties should be improved to obtain a more accurate measurement.
High-Resolution Transmission Electron Microscopy Using Negative Spherical Aberration

A novel imaging mode for high-resolution transmission electron microscopy is described. It is based on the adjustment of a negative value of the spherical aberration CS of the objective lens of a transmission electron microscope equipped with a multipole aberration corrector system. Negative spherical aberration applied together with an overfocus yields high-resolution images with bright-atom contrast. Compared to all kinds of images taken in conventional transmission electron microscopes, where the then unavoidable positive spherical aberration is combined with an underfocus, the contrast is dramatically increased. This effect can only be understood on the basis of a full nonlinear imaging theory. Calculations show that the nonlinear contrast contributions diminish the image contrast relative to the linear image for a positive-CS setting whereas they reinforce the image contrast relative to the linear image for a negative-CS setting. The application of the new mode to the imaging of oxygen in SrTiO3 and YBa2Cu3O7 demonstrates the benefit to materials science investigations. It allows us to image directly, without further image processing, strongly scattering heavy-atom columns together with weakly scattering light-atom columns.
Replication of Epstein-Barr Virus Primary Infection in Human Tonsil Tissue Explants

Epstein-Barr virus (EBV) may cause a variety of virus-associated diseases, but no antiviral agents have yet been developed against this virus. Animal models are thus indispensable for the pathological analysis of EBV-related infections and the elucidation of therapeutic methods. To establish a model system for the study of EBV infection, we tested the ability of B95–8 virus and recombinant EBV expressing enhanced green fluorescent protein (EGFP) to replicate in human lymphoid tissue. Human tonsil tissues that had been surgically removed during routine tonsillectomy were sectioned into small blocks and placed on top of collagen sponge gels in culture medium at the air-interface, then a cell-free viral suspension was directly applied to the top of each tissue block. Increasing levels of EBV DNA in culture medium were observed after 12–15 days through 24 days post-infection in tissue models infected with B95–8 and EGFP-EBV. Expression levels of eight EBV-associated genes in cells collected from culture medium were increased during culture. EBV-encoded small RNA-positive cells were detected in the interfollicular areas in paraffin-embedded sections. Flow cytometric analyses revealed that most EGFP+ cells were CD3− CD56− CD19+ HLA-DR+, and represented both naïve (immunoglobulin D+) and memory (CD27+) B cells. Moreover, EBV replication in this model was suppressed by acyclovir treatment in a dose-dependent manner. These data suggest that this model has potential for use in the pathological analysis of local tissues at the time of primary infection, as well as for screening novel antiviral agents.
Data Gathering with Compressive Sensing in Wireless Sensor Networks: A Random Walk Based Approach

In this paper, we study the problem of data gathering with compressive sensing (CS) in wireless sensor networks (WSNs). Unlike the conventional approaches, which require uniform sampling in the traditional CS theory, we propose a random walk algorithm for data gathering in WSNs. However, such an approach will conform to path constraints in networks and result in the non-uniform selection of measurements. It is still unknown whether such a non-uniform method can be used for CS to recover sparse signals in WSNs. In this paper, from the perspectives of CS theory and graph theory, we provide mathematical foundations to allow random measurements to be collected in a random walk based manner. We find that the random matrix constructed from our random walk algorithm can satisfy the expansion property of expander graphs. The theoretical analysis shows that a k-sparse signal can be recovered using `1 minimization decoding algorithm when it takes m = O(k log(n=k)) independent random walks with the length of each walk t = O(n=k) in a random geometric network with n nodes. We also carry out simulations to demonstrate the effectiveness of the proposed scheme. Simulation results show that our proposed scheme can significantly reduce communication cost compared to the conventional schemes using dense random projections and sparse random projections, indicating that our scheme can be a more practical alternative for data gathering applications in WSNs.
Categoricity from One Successor cardinal in Tame Abstract Elementary Classes

We prove that from categoricity in λ+ we can get categoricity in all cardinals ≥ λ+ in a χ-tame abstract elementary classe $\mathcal{K}$ which has arbitrarily large models and satisfies the amalgamation and joint embedding properties, provided $\lambda > {\rm LS}(\mathcal{K})$ and λ ≥ χ. For the missing case when $\lambda ={\rm LS}(\mathcal{K})$, we prove that $\mathcal{K}$ is totally categorical provided that $\mathcal{K}$ is categorical in ${\rm LS}(\mathcal{K})$ and ${\rm LS}(\mathcal{K})^+$.
Self-regulatory perseveration and the depressive self-focusing style: a self-awareness theory of reactive depression.

In this article, we apply theory and research on self-focused attention and self-regulatory processes to the problem of depression and use this framework to integrate the roles played by a variety of psychological processes emphasized by other theories of the development and maintenance of depression. We propose that depression occurs after the loss of an important source of self-worth when an individual becomes stuck in a self-regulatory cycle in which no responses to reduce the discrepancy between actual and desired states are available. Consequently, the individual falls into a pattern of virtually constant self-focus, resulting in intensified negative affect, self-derogation, further negative outcomes, and a depressive self-focusing style in which he or she self-focuses a great deal after negative outcomes but very little after positive outcomes. Eventually, these factors lead to a negative self-image, which may take on value by providing an explanation for the individual's plight and by helping the individual avoid further disappointments. The depressive self-focusing style then maintains and exacerbates the depressive disorder. We review findings from laboratory studies of mild to moderately depressed people, correlational studies of more severely depressed people, and clinical observations with respect to consistency with the theory. Recent empirical research on depression has yielded a wide array of cognitive, social, and motivational dimensions on which depressed and nondepressed individuals differ from one another. (For reviews, see Blaney, 1977; Coyne & Gotlib, 1983; Miller, 1975.) Over the years, a variety of theoretical frameworks have evolved to attempt to account for these differences. These theories have often been viewed as antagonistic to each other, competing to offer the most comprehensive explanation of depression. In the present article, we review the central concepts used in psychological theories of depression and outline a theoretical framework that attempts to integrate a variety of processes emphasized by these theories. The theory is an attempt to specify relations among a wide range of characteristics commonly associated with unipolar reactive depression and a sequence through which they emerge. To this end, we apply contemporary theory and research on self-focused attention and self-regulation (Carver & Scheier, 1981; Duval & Wicklund,
Finite approximations to Lie groups Universal Turing Machine

Stable epistemologies and model checking have garnered profound interest from both steganographers and mathematicians in the last several years. Given the current status of efficient algorithms, leading analysts clearly desire the synthesis of operating systems, which embodies the compelling principles of knowledge-base relational robotics. Here we show not only that the well-known self-learning algorithm for the exploration of multicast applications [114, 188, 62, 70, 114, 114, 179, 70, 179, 70, 68, 70, 62, 114, 95, 54, 152, 191, 59, 168] runs in Θ(n! ) time, but that the same is true for evolutionary programming.
Customer trades and extreme events in foreign exchange

Monetary History, Exchange Rates and Financial Markets is an impressive collection of original papers in honour of Charles Goodhart's outstanding contribution to monetary economics and policy. Charles Goodhart has written extensively on many of these topics and has become synonymous with his field; the chapters within this book offer a summary of current thinking on his own research subjects and include perspectives on controversies surrounding them.
Norovirus Infection and Disease in an Ecuadorian Birth Cohort: Association of Certain Norovirus Genotypes With Host FUT2 Secretor Status

Background. Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. Methods. We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. Results. Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0–12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). Conclusions. GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children.
Preemptive analgesic effectiveness of oral ketorolac plus local tramadol after impacted mandibular third molar surgery.

OBJECTIVE The aim of this study was to compare preemptive analgesia of oral ketorolac plus submucous local placebo with oral ketorolac plus submucous local tramadol after impacted mandibular third molar surgery. STUDY DESIGN A double-blind, randomized, placebo-controlled clinical trial was conducted. Patients were randomized into two treatment groups (n = 15 per group): group A, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local placebo (1 mL saline solution); group B, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local tramadol (50 mg diluted in 1 mL saline solution). We evaluated the intensity of pain, time for the first analgesic rescue medication, and total analgesic consumption. RESULTS Pain intensity, number of patients requiring analgesic rescue medication, number of patients in each group not requiring analgesic rescue medication, and total analgesic consumption showed statistical significance. CONCLUSIONS Preemptive use of oral ketorolac plus submucous local tramadol is an alternative treatment for acute pain after surgical removal of an impacted mandibular third molar.
Web 2.0 and the empowerment of the knowledge worker

Purpose – The purpose of this paper is to discuss the potential of Web 2.0 technologies for knowledge management and to explore how corporate governance models influence the adoption of Web 2.0 for organisational learning and knowledge exchange.Design/methodology/approach – The paper begins with a literature review to understand the phenomenon of Web 2.0. It introduces the opposing governance models of hierarchical pyramids and flat pancakes to assess barriers and leverage factors for the implementation of Web 2.0 technologies as a knowledge management system which is based on collaboration and the flow of information in networks; this discourse includes concepts for the nature of knowledge and decision‐making processes. Finally, the potential of Web 2.0 to drive empowerment of knowledge workers is discussed.Findings – The potential of Web 2.0 technologies to act as a lever for organisational learning and knowledge exchange depends on the degree of openness, freedom, and employee empowerment in corporate .
The Feature Selection Path in Kernel Methods

The problem of automatic feature selection/weighting in kernel methods is examined. We work on a formulation that optimizes both the weights of features and the parameters of the kernel model simultaneously, using L1 regularization for feature selection. Under quite general choices of kernels, we prove that there exists a unique regularization path for this problem, that runs from 0 to a stationary point of the non-regularized problem. We propose an ODE-based homotopy method to follow this trajectory. By following the path, our algorithm is able to automatically discard irrelevant features and to automatically go back and forth to avoid local optima. Experiments on synthetic and real datasets show that the method achieves low prediction error and is efficient in separating relevant from irrelevant features.
TRENDS IN RECOVERY OF MEDITERRANEAN SOIL CHEMICAL PROPERTIES AND MICROBIAL ACTIVITIES AFTER INFREQUENT AND FREQUENT WILDFIRES

Since the 1970s, increase in fire frequency has been observed in all European Mediterranean regions. The objectives of this study were (1) to determine the effects of wildfire frequency on the recovery at short‐ and long‐term of soil chemical and microbial properties and (2) to identify the mechanisms underlying the recovery of these sites properties. Soils from 17 plots (Maures mountains range, Var, France) were classified into 5 wildfire regimes (i.e. not burned since at least 57 years ago, infrequently and frequently burned‐with time since fire between 4 and 17 years). Soil samples from these plots were analysed for their nutrient content, chemical functions of soil organic matter (SOM) using FT‐MIR spectroscopy and microbial mineralising activities. Our results showed that the frequent wildfire regime slowed down the recovery in the short term of SOM spectroscopic properties and nutrient availability. Both low quantity and low quality (i.e. high percentage of aromatic and phenolic organic forms) of soil organic matter were found to be related to soil microbial recovery at 4 years after frequent wildfires. The frequent wildfires improved the recovery in net nitrification and nitrate content, leading to an increase in catabolic evenness and a recovery in microbial C‐substrate utilisation profiles between 4 and 17 years. However, frequent wildfires slowed down the recovery of hydrolytic enzyme pool (i.e. FDA hydrolases) and phenol oxidase activity, both involved in soil C cycling. Overall, our observations suggest that 4 fires in 50 years is a threshold beyond which soil quality may be endangered. Copyright © 2011 John Wiley & Sons, Ltd.
Payment Policy and Competition in the Medicare+Choice Program

Over the last 2 years, Medicare+Choice (M+C) plans raised premiums and reduced benefits to an unprecedented degree, arguing that these were unavoidable consequences of inadequate payments. We investigate plan premium and benefit decisions, taking advantage of a natural experiment to separate the influences of payment rates, the intensity of interplan competition, and the underlying cost of providing coverage. We find that the effects of competition are comparable in importance to the effects of payment rates, confirming empirically that it is possible for the Medicare Program to improve benefits without increasing spending or shifting additional costs to beneficiaries.