Miracle-dz/UniFAR-FTUs huggingface dataset:
The Stem Cell Marker Lgr5 Defines a Subset of Postmitotic Neurons in the Olfactory Bulb

Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5, is a bona fide biomarker for stem cells in multiple tissues. Lgr5 is also expressed in the brain, but the identities and properties of these Lgr5+ cells are still elusive. Using an Lgr5-EGFP reporter mouse line, we found that, from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial, and neuronal markers reveals that Lgr5 does not label stem cells in the OB but instead labels a heterogeneous population of neurons with preference in certain subtypes. Patch-clamp recordings in OB slices reveal that Lgr5-EGFP+ cells fire action potentials and display spontaneous excitatory postsynaptic events, indicating that these neurons are integrated into OB circuits. Interestingly, R-spondin 3, a potential ligand of Lgr5, is also expressed in the adult OB. Collectively, our data indicate that Lgr5-expressing cells in the OB are fully differentiated neurons and imply distinct roles of Lgr5 and its ligand in postmitotic cells. SIGNIFICANCE STATEMENT Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) is a bona fide stem cell marker in many body organs. Here we report that Lgr5 is also highly expressed in the olfactory bulb (OB), the first relay station in the brain for processing odor information and one of the few neural structures that undergo continuous neurogenesis. Surprisingly, Lgr5 is not expressed in the OB stem cells, but instead in a few subtypes of terminally differentiated neurons, which are incorporated into the OB circuit. This study reveals that Lgr5+ cells in the brain represent a nonstem cell lineage, implying distinct roles of Lgr5 in postmitotic neurons.
Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: An observational cohort study

Background Fifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty. Aims To determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine. Methods This was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8–11), pubertal (12–15), and post-pubertal (16–17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates. Results Models of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR −0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models (p < 0.017). Conclusion Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.
Accurate Rapid Lifetime Determination on Time-Gated FLIM Microscopy with Optical Sectioning

Time-gated fluorescence lifetime imaging microscopy (FLIM) is a powerful technique to assess the biochemistry of cells and tissues. When applied to living thick samples, it is hampered by the lack of optical sectioning and the need of acquiring many images for an accurate measurement of fluorescence lifetimes. Here, we report on the use of processing techniques to overcome these limitations, minimizing the acquisition time, while providing optical sectioning. We evaluated the application of the HiLo and the rapid lifetime determination (RLD) techniques for accurate measurement of fluorescence lifetimes with optical sectioning. HiLo provides optical sectioning by combining the high-frequency content from a standard image, obtained with uniform illumination, with the low-frequency content of a second image, acquired using structured illumination. Our results show that HiLo produces optical sectioning on thick samples without degrading the accuracy of the measured lifetimes. We also show that instrument response function (IRF) deconvolution can be applied with the RLD technique on HiLo images, improving greatly the accuracy of the measured lifetimes. These results open the possibility of using the RLD technique with pulsed diode laser sources to determine accurately fluorescence lifetimes in the subnanosecond range on thick multilayer samples, providing that offline processing is allowed.
Effect of Additional Water and Prewet Time on the Performance of Spontaneous Combustion Gangue Sand Lightweight Concrete

Porous properties of spontaneous combustion gangue coarse aggregate determines its water absorbing character,since its water absorption is much more than natural aggregate,the selection of unit water use is particularly important in the mix proportion design. First,The relation of spontaneous combustion gangue pre water adsorption time and water absorption,and the formula of additional water are introducted in the article. Next,the study of the effect of different additional water on spontaneous combustion gangue sand lightweight concrete slump and strength,and the effect of spontaneous combustion gangue coarse aggregate prewet time on concrete slump time losing and strength are introduced. The results show: in addition that spontaneous combustion gangue coarse aggregate are wetted1 h in advance and the additional water is 80% of satuated water absorption,either spontaneous combustion gangue sand lightweight concrete mixing material slump or its strength grade meets design requirements,and slump time losing is less. The results provide some reference to the mix proportion of sand lightweight concrete.
Botnets: threats and responses

Purpose – A botnet is a network of computers on the internet infected with software robots (or bots). There are numerous botnets, and some of them control millions of computers. Cyber criminals use botnets to launch spam e‐mails and denial of service attacks; and commit click fraud and data theft. Governments use botnets for political purposes or to wage cyber warfare. The purpose of this paper is to review the botnet threats and the responses to the botnet threats.Design/methodology/approach – The paper describes how botnets are created and operated. Then, the paper discusses botnets in terms of architecture, attacking behaviors, communication protocols, observable botnet activities, rally mechanisms, and evasion techniques. Finally, the paper reviews state‐of‐the‐art techniques for detecting and counteracting botnets, and also legal responses to botnet threats.Findings – Botnets have become the platform for many online threats such as spam, denial of service attacks, phishing, data thefts, and online fr.
Distinguishing Among Evolutionary Forces Acting on Genome-Wide Base Composition: Computer Simulation Analysis of Approximate Methods for Inferring Site Frequency Spectra of Derived Mutations

Inferred ancestral nucleotide states are increasingly employed in analyses of within- and between -species genome variation. Although numerous studies have focused on ancestral inference among distantly related lineages, approaches to infer ancestral states in polymorphism data have received less attention. Recently developed approaches that employ complex transition matrices allow us to infer ancestral nucleotide sequence in various evolutionary scenarios of base composition. However, the requirement of a single gene tree to calculate a likelihood is an important limitation for conducting ancestral inference using within-species variation in recombining genomes. To resolve this problem, and to extend the applicability of ancestral inference in studies of base composition evolution, we first evaluate three previously proposed methods to infer ancestral nucleotide sequences among within- and between-species sequence variation data. The methods employ a single allele, bifurcating tree, or a star tree for within-species variation data. Using simulated nucleotide sequences, we employ ancestral inference to infer fixations and polymorphisms. We find that all three methods show biased inference. We modify the bifurcating tree method to include weights to adjust for an expected site frequency spectrum, “bifurcating tree with weighting” (BTW). Our simulation analysis show that the BTW method can substantially improve the reliability and robustness of ancestral inference in a range of scenarios that include non-neutral and/or non-stationary base composition evolution.
Is frailty a relevant concept in SLE?

Objective In geriatric populations, frailty is associated with poor health outcomes, including mortality. Frailty has not been examined in lupus, although components of the phenotype seem relevant. Methods Women with lupus (n=152) participated in research visits in 2008–2009. Frailty was assessed by Fried's frailty phenotype criteria: low weight/unintentional weight loss, slow gait (4-m walk using sex and height criteria), weakness (grip strength using gender and body mass index criteria), exhaustion (2 specific questions) and inactivity (from physical activity questionnaire). Women accumulating 3+ components were classified as ‘frail’, one or two components as ‘prefrail’, and none as ‘robust’. Physical function (36-item Short Form (SF-36) Physical Functioning subscale and Valued Life Activities disability scale), cognitive function (from a 12-test battery) and mortality were examined as outcomes. Mortality was determined as of December 2015. Multiple regression analyses examined concurrent and 2-year function controlling for age, lupus duration, race/ethnicity, glucocorticoid use, obesity, self-reported disease activity and damage and, for longitudinal analyses, baseline function. Mortality analyses controlled for age, lupus duration and baseline disease damage scores. Results Mean age was 48 (±12) years, mean lupus duration was 16 (±9) years. 20% of the sample was classified as frail and 50% as prefrail. Frail women had significantly worse physical functioning than both robust and prefrail women and were more likely to have cognitive impairment. Frail women were also more likely to experience declines in functioning and onset of cognitive impairment. Mortality rates were significantly higher in the frail group (frail 19.4%; prefrail 3.9%; robust 2.3%). Odds (95% CI) of death for frail women were elevated, even after adjusting for age, lupus duration and baseline disease damage (5.9 (0.6 to 57.1)). Conclusions Prevalence of frailty in this sample of women with lupus was higher than in samples of older adults. Frailty was associated with poor physical and cognitive function, functional declines and mortality.
Snake-like robot climbs inside different pipes

Based on the application of snake-like robot as pipeline robot, this paper presents a compound climbing gait of it. By analyzing the characteristics of existing inside climbing gaits, blend various gait with sensor information, so that the robot can climb in more complex and more extensive inside pipe environment. The experimental results show that the gait is feasible and has good climbing effect.
Differentiation of mesenchymal stem cells from human amniotic fluid to cardiomyocyte-like cells

Ischemic heart disease (IHD) is a major factor influencing worldwide mortality rates. Furthermore, IHD has become a significant health problem among the Thai population. Stem cell therapy using mesenchymal stem cells (MSCs) is an alternative therapeutic method that has been applied to improve the quality of life of patients. Amniotic fluid (AF) contains a heterogeneous cell population, including MSCs, which are multipotent stem cells that have the capability to differentiate into mesenchymal lineages. The purpose of the present study was to evaluate the MSC characteristics of human (h)AF and determine its potency regarding cardiogenic differentiation. MSC characterization following flow cytometric analysis revealed that the cells expressed MSC markers, cluster of differentiation (CD)44, CD90, human leukocyte antigen-ABC and CD73. The results of the alamar blue assay demonstrated that cell proliferation rate continuously increased from the early cultivation phase up to 5-fold during days 1 to 5 of cell culturing. The highest rate of cell proliferation was observed on day 17 with a 30-fold increase compared with that on day 1. During the cardiogenic induction stage, morphological changes were observed between day 0 and day 21, and it was revealed that the hAF derived-MSCs in the cardiogenic-induced group exhibited myotube-like morphology after 7 days of cell culturing. Following cardiogenic induction, immunohistochemistry staining was performed on day 21, and reverse transcription-quantitative polymerase chain reaction on day 7 and 21. These steps were performed to detect the protein and gene expression levels of cardiac specific proteins (GATA4, cardiac troponin T, Nkx2.5 and Connexin43). The results of the present study indicated that hAF-MSCs possess the potential to differentiate into cardiomyocyte-like cells. Thus, it was concluded that hAF may be a suitable source of MSCs for stem cell therapy and tissue engineering.
Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

Significance Calcific aortic valve disease (CAVD) is a chronic inflammatory and osteogenic condition with unknown underlying mechanism and unavailable pharmacological therapy. The present study shows that lower levels of IL-37 expression in aortic valve interstitial cells (AVICs) of diseased valves play a role in the elevated valvular osteogenic activity associated with CAVD. IL-37 inhibits NF-κB and ERK1/2 to suppress AVIC osteogenic responses, and recombinant IL-37 has a greater effect on AVICs of diseased valves. Moreover, expression of IL-37 in mice attenuates aortic valve thickening following a prolonged exposure to endotoxin or high fat diet. Thus, IL-37 is antiosteogenic in human AVICs and has the potential for limitation of CAVD progression. Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease.
Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3).

Three distinct mammalian Na+/Ca2+exchangers have been cloned: NCX1, NCX2, and NCX3. We have undertaken a detailed functional comparison of these three exchangers. Each exchanger was stably expressed at high levels in the plasma membranes of BHK cells. Na+/Ca2+exchange activity was assessed using three different complementary techniques: Na+ gradient-dependent45Ca2+uptake into intact cells, Na+gradient-dependent45Ca2+uptake into membrane vesicles isolated from the transfected cells, and exchange currents measured using giant patches of excised cell membrane. Apparent affinities for the transported ions Na+ and Ca2+ were markedly similar for the three exchangers at both membrane surfaces. Likewise, generally similar responses to changes in pH, chymotrypsin treatment, and application of various inhibitors were obtained. Depletion of cellular ATP inhibited NCX1 and NCX2 but did not affect the activity of NCX3. Exchange activities of NCX1 and NCX3 were modestly increased by agents that activate protein kinases A and C. All exchangers were regulated by intracellular Ca2+. NCX1-induced exchange currents were especially large in excised patches and, like the native myocardial exchanger, were stimulated by ATP. Results may be influenced by our choice of expression system and specific splice variants, but, overall, the three exchangers appear to have very similar properties.
Are you able not to react to what you hear? Inhibition behavior measured with an auditory Go/NoGo paradigm

ABSTRACT In everyday life people have to attend to, react to, or inhibit reactions to visual and acoustic cues. These abilities are frequently measured with Go/NoGo tasks using visual stimuli. However, these abilities have rarely been examined with auditory cues. The aims of our study (N = 106) are to develop an auditory Go/NoGo paradigm and to describe brain-healthy participants’ performance. We tested convergent validity of the auditory Go/NoGo paradigm by analyzing the correlations with other neuropsychological tasks assessing attentional control and executive functions. We also analyzed the ecological validity of the task by examining correlations of self-reported impulsivity. In the first step we found that the participants are able to differentiate correctly among several sounds and also to appropriately react or inhibit a certain reaction most of the times. Convergent validity was suggested by correlations between the auditory Go/NoGo paradigm and the Color Word Interference Test, Trail Making Test, and Modified Card Sorting Test. We did not find correlations with self-reported impulsivity. Overall, the auditory Go/NoGo paradigm may be used to assess attention and inhibition in the context of auditory stimuli. Future studies may adapt the auditory Go/NoGo paradigm with specific acoustic stimuli (e.g., sound of opening a bottle) in order to address cognitive biases in particular disorders (e.g., alcohol dependence).
Objectification of people and thoughts: An attitude change perspective

Many objectification phenomena can be understood from a mind-body dualism perspective in which the more people focus on their bodies, the less they focus on their minds. Instead of viewing mind and body in opposition to each other, we advocate for a more reciprocal view in which mind and body work in conjunction. Consistent with an integrated mind-body approach, we begin our review by describing research on embodied persuasion revealing that focusing on our own body can reduce but also increase thinking (elaboration), as well as affecting the use of thoughts in forming evaluations (validation). Next, we extend our integrated view to a new domain and suggest that physical objects can influence thoughts and that one's thoughts can also be objectified. The first portion of this section focuses on research on enclothed cognition revealing that wearing physical objects can operate through the same processes of elaboration (increasing and decreasing thinking) and validation (increasing and decreasing thought usage) as the body. The second portion reveals that thoughts can be understood and treated as if they were physical objects affecting evaluative processes by influencing elaboration and validation processes. The final section provides some practical guidance relevant to campaigns designed to reduce the objectification of women and the infrahumanization of stigmatized groups.
A Task Analysis Methodology for the Development of Minimum Physical Employment Standards

Objective: The aim of this study was to develop a systematic task analysis process for determination of minimum acceptable job performance in arduous safety-related occupations. Methods: A task analysis using modifications on established methods was completed in UK firefighters. Subject-matter experts (all male) identified critical, physically arduous tasks generic to all UK firefighters and developed individual, role-specific task simulations. Video footage and blinded voting were used to determine minimum acceptable task performance. Results: Eight tasks were identified in combination with role-specific variations, task simulations suitable for use in a physical demands analysis, and corresponding minimum acceptable performance. Conclusions: The bespoke steps highlighted here allow structured identification of task-specific minimum performance standards and simulations from which physical employment standards could be based. However, including a more divergent expert panel with respect to age, sex, and race would strengthen the applicability of this framework in future practice.
Program Analysis with a Loop-Function-based Tracing Tool on Virtual Platforms

Understanding the program behavior and data dependencies are important when designing and accelerating applications. However, conventional profiling tools are insufficient for tracking functions and loops of programs due to compiler optimizations and probe effects. In order to minimize the probe effects, virtual platforms with timing simulation are used to monitor the profiled program and provide flexibility of evaluating the future platforms. Nevertheless, the profiling information is not collected in function- or looplevel for programmers to analyze and discover performance issues. This paper proposes a stack-pointer-based method with a later loop entry detection scheme to overcome the difficulties of detecting functions and loops for programs running on a virtual platform. With the detailed performance counters and memory access patterns recorded along with the loop-call context tree, this paper also presents a framework collecting traces for detailed analysis on both of control flow and data flow of a program. The experimental results demonstrated the ability of the developed tool for collecting and profiling a program in a loop-call context tree form and for enabling further analysis on thread level parallelism and data dependency between functions and loops.
An improved phase digitization mechanism for fast-locking low-power all-digital PLLs

: An improved phase digitization mechanism is designed to overcome limited lock-in range of low-power all-digital phase-locked loop (ADPLL) with phase prediction and edge snapshot circuit. The proposed mechanism including a dual-mode multiplexer-based time-to-digital converter (TDC) and accessional algorithm is veri ﬁ ed in a modelled and simulated ADPLL. Results show that the ADPLL is able to lock in 7.8 µs, i