Miracle-dz/UniFAR-FTUs huggingface dataset:
Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults ≥ 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial

Background Ketone bodies have been proposed as an “energy rescue” for the Alzheimer’s disease (AD) brain, which underutilizes glucose. Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology-reducing properties in animal models of AD. However, human evidence that KME may enhance brain ketone metabolism, improve cognitive performance and engage AD pathogenic cascades is scarce. Objectives To investigate the effects of ketone monoester (KME) on brain metabolism, cognitive performance and AD pathogenic cascades in cognitively normal older adults with metabolic syndrome and therefore at higher risk for AD. DESIGN: Double-blinded randomized placebo-controlled clinical trial. Setting Clinical Unit of the National Institute on Aging, Baltimore, US. Participants Fifty cognitively intact adults ≥ 55 years old, with metabolic syndrome. Intervention Drinks containing 25 g of KME or isocaloric placebo consumed three times daily for 28 days. Outcomes Primary: concentration of beta-hydroxybutyrate (BHB) in precuneus measured with Magnetic Resonance Spectroscopy (MRS). Exploratory: plasma and urine BHB, multiple brain and muscle metabolites detected with MRS, cognition assessed with the PACC and NIH toolbox, biomarkers of AD and metabolic mediators in plasma extracellular vesicles, and stool microbiome. Discussion This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis, and animal studies indicate that it can modify AD pathology. By conducting a study of KME in a population at risk for AD, we hope to bridge the existing gap between pre-clinical evidence and the potential for brain-metabolic, pro-cognitive, and anti-Alzheimer’s effects in humans.
Valuation and optimal surrender of variable annuities with guaranteed minimum benefits and periodic fees

This work studies the valuation and optimal surrender of variable (equity-linked) annuities under a Lévy-driven equity market with mortality risk. We consider a practical periodic fee structure which can vary over time and is assessed as a proportion of the fund value. At maturity, the fund value is returned to the policyholder according to a guaranteed minimum accumulation benefit (GMAB). Mortality risk is also modeled discretely, and the contract offers a guaranteed minimum death benefit (GMBD) prior to maturity. The benefits accommodate caps on the growth of funds (in addition to the rising floor) to reduce the fee level and as a disincentive to early surrender. Interest rates are modeled via a deterministic discounting term structure, which can be calibrated (bootstrapped) to the rates market, according to market convention. An efficient and accurate valuation framework is developed, along with closed form pricing formulas in the case where policy surrender is not permitted. Numerous experiments are conducted to illustrate the interplay between contract parameters and the decision to surrender, and we provide an extensive analysis that investigates how to structure contracts to disincentivize early surrender.
Comparison of Physiological Variables to Perceived Exertion During Aerobic and Anaerobic Exercise

The purpose of this study was to compare the relationship of RPE to HR, BLA, and VO2 during aerobic and resistance maximal tests as well as during resistance exercise at varying intensities. Twelve volunteers took part in three maximal tests; a treadmill VO2max, a back squat 1RM, and a squat protocol involving six sets of 50%, 70%, and 90% of 1RM to a predetermined number of repetitions as well as to failure. VO2, HR, BLA, and RPE were measured throughout each test. RPE was found to significantly relate to resistance exercise intensity only when performing sets to a predetermined number of repetitions, but not when performing to failure; it also had no significant relationship to any physiological variable in resistance exercise. HR showed a trend similar to RPE when performing sets to a predetermined number of repetitions, but no significant difference to failure. VO2 related to repetitions during the squat protocol. BLA showed no significant effect to repetitions or intensity. RPE relates to resistance exercise intensity during a 1RM protocol and during sets to a predetermined number of repetitions. There is no relationship between RPE and intensity when performing sets to failure or to any physiological variable during either protocol.
A Two-Stage Deep Neuroevolutionary Technique for Self-Adaptive Speech Enhancement

This paper presents a novel self-adaptive approach for speech enhancement in the context of highly nonstationary noise. A two-stage deep neuroevolutionary technique for speech enhancement is proposed. The first stage is composed of a deep neural network (DNN) method for speech enhancement. Two DNN methods were tested at this stage, namely, both a deep complex convolution recurrent network (DCCRN) and a residual long short-term memory neural network (ResLSTM). The ResLSTM method was combined with a minimum mean-square error method to perform a preliminary enhancement. The ResLSTM network is used as an a priori signal-to-noise ratio (SNR) estimator. The second stage implements a self-adaptive multiband spectral subtraction enhancement method using tuning optimization based on a genetic algorithm. The proposed two-stage technique is evaluated using objective measures of speech quality and intelligibility. The experiments are carried out using the NOIZEUS noisy speech corpus using conditions of real-world stationary, colored, and nonstationary noise sources at multiple SNR levels. These experiments demonstrate the advantage of building a cooperative approach using evolutionary and deep learning-based techniques that are capable of achieving robust speech enhancement in adverse conditions. Indeed, the experimental tests show that the proposed two-stage technique outperformed a baseline implementation using a state-of-the-art deep learning approach by an average 13% and 6% improvement for six noise conditions at a −5 dB and a 0 dB input SNR, respectively.
A Methodological Quality Evaluation of Meta-Analyses on Nursing Home Research: Overview and Suggestions for Future Directions

(1) Background: The nursing home (NH) research field lacks quality reporting about meta-analyses (MAs), and most gradings of MA evidence are biased on analyzing the effectiveness of independent variables in randomized control trials. (2) Objectives: This study aimed to perform a critical methodological review of MAs in the NH research field. (3) Methods: We searched the articles from four databases (PubMed, MEDLINE, CINAHL, and PsycINFO) until 15th January 2021. We reviewed a total of 41 published review articles in the NH research field. (4) Results: The studies primarily fell into the following categories: medicine (17/41), nursing (7/41), and psychiatry or psychology (6/41); 36.6% of the reviewed studies did not use any validated MA guidelines. The lowest correctly reported PRISMA 2000 guideline item was protocol and registration (14.6%), and more than 50% of articles did not report risk of bias. Moreover, 78.0% of studies did not describe missing reports of effect size formula. (5) Discussion: NH researchers must follow appropriate and updated guidelines for their MAs in order to provide validated reviews, as well as consider statistical issues such as the complexity of interventions, proper grouping, and scientific effect-size calculations to improve the quality of their study. Future quality review studies should investigate more diverse studies.
The Relationship between Globalization-Public Expenditure on the Basis of the Compensation and Efficiency Hypotheses

The study, which deals with the changes created by the globalization indicators on the public sector, is shaped on the basis of the compensation and efficiency hypothesis. In this context, it has been investigated how the government size is affected due to the fact that the effects of globalization are felt more with the shift of transition countries from centrally planned economy to free market economy. According to panel OLS and causality test results, increases in economic freedom index, one of the globalization indicators, decrease public consumption expenditure. In this context, the efficiency hypothesis is valid for Albania, Bulgaria, Czechia, Estonia, Romania and Slovakia for the period 1995-2019.
Single-Molecule Force Spectroscopy of a Tetraaryl Succinonitrile Mechanophore

Fluorescent damage reporters that use mechanochemical activation of a covalent bond to elicit an optical signal are emerging tools in material mechanics as a means to access the nanoscale distribution of forces inside materials under stress. A promising class of damage reporters are tetraaryl succinonitriles (TASN), whose mechanical activation results in stable fluorescent radical species. However, in-depth insights into the molecular mechanics of TASN activation are absent, precluding their use as quantitative mechanoprobes. Here we perform single-molecule force spectroscopy experiments to provide these insights. We use a bridged version of the TASN unit, embedded in multi-mechanophore polymer, to enable multiplexed mechanochemical measurements at the single-molecule level. Our experiments reveal that TASN activates at surprisingly low forces and short time scales compared to other covalent mechanophores. These results establish TASN as a promising candidate for reporting the lower end of relevant forces in material mechanics.
Quantum Theory of Gravity and Arthur Eddingtons Fundamental Theory

For the first time, the article presents the Quantum Theory of Gravity, covering not only the microcosm of elementary particles, but also the macrocosm of planets, stars and black holes. This relational approach to gravity was consistently presented in Arthur Eddington's monograph “Fundamental Theory”. In the theory of quantum gravity proposes to consider instead of gravity holes in the curved space-time of Einstein's general relativity, gravitational funnels formed by the rotation of planets, stars and galaxies in a dark matter halo. The change in the gravitational potential in the funnels occurs instantly in all areas of the gravitational funnel space in accordance with the pressure gradient described by the Euler-Bernoulli equation for superfluid continuous media. The new cosmological theory represents the evolution of the universe and dark holes without a singularity. The disordered alternation of the processes of contraction and expansion of individual regions of the infinite Universe realizes the circulation of baryonic and dark matter, which allows it to exist indefinitely, bypassing the state of equilibrium. Numerical modeling allows us to assert that the theory of quantum gravity is the most reliable of the three generally accepted theories of gravity.
Research on Network Security Defense Model Based on Combination Strategy of Firewall and IPS

Firewall and intrusion detection system are widely used network security protection equipment, which plays a vital role in preventing network attack and intrusion. However, they have inevitable defects, which reduces the protection function provided in actual use. Therefore, in order to further improve network security, this paper designs a new network security protection technology which can integrate the advantages of multiple security technologies and make up for their shortcomings. This paper proposes a network security defense model based on the combination strategy of firewall and IPS. The purpose of policy based intrusion prevention system (pb-ips) is to realize the real combination of security management and network management system. This can take the network management system as the intermediary, integrate the firewall technology and intrusion detection technology, and realize a new network security protection measures.
Performances de récepteurs multi-utilisateurs dans un système OFDM avec synchronisation et estimation du canal

To increase the throughput of transmission systems, MIMO transmission have become a natural path. Two different MIMO schemes can be envisioned: point to point communications and multi-point to point communications. We propose in this paper to study the performances of multi-point to point communication (also referred to as multi-user transmissions) for different receivers and with or without channel estimation. The proposed channel estimator is a multi-user maximum likelihood estimator achieving both synchronization and the channel estimates. Linear (MMSE, ZF) and non-linear (MLSE, MAP) egaliseur will be compare with 2 or 4 symboles in the preambule. This work is partially supported by the IST project STRIKE (FP5 IST-2001-38354).
Critical Success Factors in Hotel Companies: A Managerial Perspective

Literature shows several studies which identify CSFs in hotel companies, examining their role in developing competitive advantage or in supporting the development of the business. Based on prior literature, this study identifies Critical Success Factors (CSFs) which are the most suitable for supporting hotel managers in strategic, management and operational decisions. The managerial approach followed in this research allows to propose three sets of CSFs,each pertaining to one of the three hierarchical levels of the Anthony’s pyramid, andopens the way to further research on the correlation between CSFs and performance management systems.
Multi-Exemplar Learning Particle Swarm Optimization for Regional Traffic Signal Timing Optimization with Multi-Intersections

Traffic congestion has become one of the major problems of smart travel. The application of evolutionary computation (EC) for traffic signal timing optimization (TSTO) can effectively alleviate traffic congestion at a single intersection. However, while in more complicated regional traffic signal timing optimization (RTSTO) problems, the canonical EC algorithm such as particle swarm optimization (PSO) still has limitation due to population prematurity. In this paper, a multi-exemplar learning (MEL) strategy is adopted to improve the diversity of the population, so that the particles can have more opportunities to explore the search space. Furthermore, multiple traffic indicators are used in this paper to measure the comprehensive performance of the solution. Moreover, the microsimulation software is adopted to evaluate the solution to simulate the real-world intersection, making the obtained solution more practical in real-world application. Experiments are conducted to investigate the effectiveness and efficiency of MEL-PSO. The results show that the MEL-PSO algorithm is more effective and efficient than the compared algorithms on RTSTO problems.
Metabolomic Alteration in the Plasma of Wild Rodents Environmentally Exposed to Lead: A Preliminary Study

Lead poisoning is often considered a traditional disease; however, the specific mechanism of toxicity remains unclear. The study of Pb-induced alterations in cellular metabolic pathways is important to understand the biological response and disorders associated with environmental exposure to lead. Metabolomics studies have recently been paid considerable attention to understand in detail the biological response to lead exposure and the associated toxicity mechanisms. In the present study, wild rodents collected from an area contaminated with lead (N = 18) and a control area (N = 10) were investigated. This was the first ever experimental metabolomic study of wildlife exposed to lead in the field. While the levels of plasma phenylalanine and isoleucine were significantly higher in a lead-contaminated area versus the control area, hydroxybutyric acid was marginally significantly higher in the contaminated area, suggesting the possibility of enhancement of lipid metabolism. In the interregional least-absolute shrinkage and selection operator (lasso) regression model analysis, phenylalanine and isoleucine were identified as possible biomarkers, which is in agreement with the random forest model. In addition, in the random forest model, glutaric acid, glutamine, and hydroxybutyric acid were selected. In agreement with previous studies, enrichment analysis showed alterations in the urea cycle and ATP-binding cassette transporter pathways. Although regional rodent species bias was observed in this study, and the relatively small sample size should be taken into account, the present results are to some extent consistent with those of previous studies on humans and laboratory animals.
Dynamics of actin filaments of MC3T3-E1 cells during adhesion process to substrate

In order to determine how cells change their morphology during adhesion process to a substrate, we focused on the actin cytoskeleton and investigated its morphological change along with that of the whole cell during adhesion process. An osteoblastic cell line MC3T3-E1 was used as the test model. We plated cells whose cell cycle had been synchronized by serum starvation on fibronectin-coated glass plate and cultured them for 10 min to 24 h. We then stained their F-actin and nucleus and observed them with a fluorescent microscope for cell area and shape index and 2D parameters for actin morphology, and with a laser scanning microscope for 3D morphology of actin and nucleus. In the beginning of adhesion, the trypsinized cells were round and their nuclei were surrounded uniformly by thick layer of actin. The actin layer in the upper side became actin aggregate (AA) and lower side dense peripheral band (DPB) in 30 min. The upper AA then became smaller and finally to actin filaments (AFs) spanning the cell top. The DPB expanded and finally became AFs on cell bottom by 1 h. The nucleus becomes flattened possibly due to compression by the cell membrane caused by the expansion of the DPB in the early stage of adhesion. In the later stage of adhesion, the number of AFs continuously increased and nucleus became flattened more and more until 12 h. This may be caused by the increase in the top AFs that may compress the nucleus. Cells become more elongated in response to further alignment of AFs until 12 h. These results indicate that change in AFs during adhesion process is complicated not only temporally but also spatially.
Why did the Wolbachia transinfection cross the road? drift, deterministic dynamics, and disease control

Maternally inherited Wolbachia transinfections are being introduced into natural mosquito populations to reduce the transmission of dengue, Zika, and other arboviruses. Wolbachia‐induced cytoplasmic incompatibility provides a frequency‐dependent reproductive advantage to infected females that can spread transinfections within and among populations. However, because transinfections generally reduce host fitness, they tend to spread within populations only after their frequency exceeds a critical threshold. This produces bistability with stable equilibrium frequencies at both 0 and 1, analogous to the bistability produced by underdominance between alleles or karyotypes and by population dynamics under Allee effects. Here, we analyze how stochastic frequency variation produced by finite population size can facilitate the local spread of variants with bistable dynamics into areas where invasion is unexpected from deterministic models. Our exemplar is the establishment of wMel Wolbachia in the Aedes aegypti population of Pyramid Estates (PE), a small community in far north Queensland, Australia. In 2011, wMel was stably introduced into Gordonvale, separated from PE by barriers to A. aegypti dispersal. After nearly 6 years during which wMel was observed only at low frequencies in PE, corresponding to an apparent equilibrium between immigration and selection, wMel rose to fixation by 2018. Using analytic approximations and statistical analyses, we demonstrate that the observed fixation of wMel at PE is consistent with both stochastic transition past an unstable threshold frequency and deterministic transformation produced by steady immigration at a rate just above the threshold required for deterministic invasion. The indeterminacy results from a delicate balance of parameters needed to produce the delayed transition observed. Our analyses suggest that once Wolbachia transinfections are established locally through systematic introductions, stochastic “threshold crossing” is likely to only minimally enhance spatial spread, providing a local ratchet that slightly—but systematically—aids area‐wide transformation of disease‐vector populations in heterogeneous landscapes.
Parasite inversion for determining the coefficients and time‐validity of Philip's two‐term infiltration equation

Many different equations have been proposed to describe quantitatively one‐dimensional soil water infiltration. The unknown coefficients of these equations characterize soil hydraulic properties and may be estimated from a n record, {t∼i,I∼i}i=1n$\{ {\tilde t_i},{\tilde I_i}\} _{i = 1}^n$ , of cumulative infiltration measurements using curve fitting techniques. The two‐term infiltration equation, I(t)=St+cKst$I(t) = S\sqrt t + c{K_{\rm{s}}}t$ , of Philip has been widely used to describe measured infiltration data. This function enjoys a solid mathematical–physical underpinning and admits a closed‐form solution for the soil sorptivity, S [L T−1/2], and multiple, c [−], of the saturated hydraulic conductivity, Ks [L T−1]. However, Philip's two‐term equation has a limited time validity, tvalid [T], and thus cumulative infiltration data, I∼(t∼)$\tilde I(\tilde t)$ , beyond t=tvalid$t = {t_{{\rm{valid}}}}$ will corrupt the estimates of S and Ks. This paper introduces a novel method for estimating S, c, Ks, and tvalid of Philip's two‐term infiltration equation. This method, coined parasite inversion, use as vehicle Parlange's three‐parameter infiltration equation. As prerequisite to our method, we present as secondary contribution an exact, robust and efficient numerical solution of Parlange's infiltration equation. This solution admits Bayesian parameter estimation with the DiffeRential Evolution Adaptive Metropolis (DREAM) algorithm and yields as byproduct the marginal distribution of Parlange's β parameter. We evaluate our method for 12 USDA soil types using synthetic infiltration data simulated with HYDRUS‐1D. An excellent match is observed between the inferred values of S and Ks and their “true” values known beforehand. Furthermore, our estimates of c and tvalid correlate well with soil texture, corroborate linearity of the c(β)$c({{\beta}})$ relationship for 0≤t≤tvalid$0 \le t \le {t_{{\rm{valid}}}}$ , and fall within reported ranges. A cumulative vertical infiltration of about 2.5 cm may serve as guideline for the time‐validity of Philip's two‐term infiltration equation.