Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for Rapid Iron Kα Line Flux Variability in MCG –6-30-15

This paper employs direct spectral fitting of individual orbital data in order to measure rapid X-ray iron Kα line and continuum spectral slope variations in Seyfert 1 galaxies with unprecedented temporal resolution. Application of this technique to a long RXTE observation of MCG -6-30-15 indicates that the line flux does vary on short (≲1 day) timescales, but that these variations are not correlated with changes in the continuum flux or slope. These rapid variations indicate that the line does indeed originate close to the black hole, confirming predictions based on its very broad profile. However, the lack of a correlation with the continuum presents problems for models in which the line variations are driven by those in the continuum, modified only by light-travel time effects. Instead, it may be that the line responds according to a physical process with a different timescale, such as ionization instabilities in the disk, or perhaps that the geometry and physical picture is more complex than implied by the simplest disk-corona models. These data also indicate that the slope of the underlying power-law continuum (Γ) shows strong variability and is tightly correlated with the continuum flux in the sense that the spectrum steepens as the source brightens. All of these results have been checked with extensive simulations, which also indicated that a spurious correlation between Γ and Compton reflection fraction (R) will result if these quantities are measured from the same spectra. This casts serious doubts on previous claims of such a Γ-R correlation.
Berberine Improves Kidney Function in Diabetic Mice via AMPK Activation

Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPKα2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice.
Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57) mice caused by chronic unpredictable mild stress (CUMS), we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.
N-Ethyl-N-Nitrosourea (ENU) Mutagenesis Reveals an Intronic Residue Critical for Caenorhabditis elegans 3′ Splice Site Function in Vivo

Metazoan introns contain a polypyrimidine tract immediately upstream of the AG dinucleotide that defines the 3′ splice site. In the nematode Caenorhabditis elegans, 3′ splice sites are characterized by a highly conserved UUUUCAG/R octamer motif. While the conservation of pyrimidines in this motif is strongly suggestive of their importance in pre-mRNA splicing, in vivo evidence in support of this is lacking. In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen in Caenorhabditis elegans, we have isolated a strain containing a point mutation in the octamer motif of a 3′ splice site in the daf-12 gene. This mutation, a single base T-to-G transversion at the -5 position relative to the splice site, causes a strong daf-12 loss-of-function phenotype by abrogating splicing. The resulting transcript is predicted to encode a truncated DAF-12 protein generated by translation into the retained intron, which contains an in-frame stop codon. Other than the perfectly conserved AG dinucleotide at the site of splicing, G at the –5 position of the octamer motif is the most uncommon base in C. elegans 3′ splice sites, occurring at closely paired sites where the better match to the splicing consensus is a few bases downstream. Our results highlight both the biological importance of the highly conserved –5 uridine residue in the C. elegans 3′ splice site octamer motif as well as the utility of using ENU as a mutagen to study the function of polypyrimidine tracts and other AU- or AT-rich motifs in vivo.
Conservation of Expression and Sequence of Metabolic Genes Is Reflected by Activity Across Metabolic States

Variation in gene expression levels on a genomic scale has been detected among different strains, among closely related species, and within populations of genetically identical cells. What are the driving forces that lead to expression divergence in some genes and conserved expression in others? Here we employ flux balance analysis to address this question for metabolic genes. We consider the genome-scale metabolic model of Saccharomyces cerevisiae, and its entire space of optimal and near-optimal flux distributions. We show that this space reveals underlying evolutionary constraints on expression regulation, as well as on the conservation of the underlying gene sequences. Genes that have a high range of optimal flux levels tend to display divergent expression levels among different yeast strains and species. This suggests that gene regulation has diverged in those parts of the metabolic network that are less constrained. In addition, we show that genes that are active in a large fraction of the space of optimal solutions tend to have conserved sequences. This supports the possibility that there is less selective pressure to maintain genes that are relevant for only a small number of metabolic states.
A population study on small rodents in the tropical rain forest of Nigeria

Ecological research on African rodents in the last few years concentrated on geographical distribution, species composition, feeding preferences and reproductive biology (Delany 1972). The emphasis on these tapies has been due to the relatively small amount of research on African rodents, the enormous variety of species, and the large size and ecological diversity of the African continent. Population studies have been almost entirely neglected, although there are some recent studies on population fluctuations, age structure of populations, and mechanisms for population regu­ lation. ln the arid zone, Poulet (1972) has described the population changes of Taterillus pygargus in Senegal, and Happold (1967) gave some data on the population structure of Jaculus jaculus at diff erent times of the year in the Sudan. ln the savanna, Anadu (1973) followed the population fluctuations of Myomys daltoni and Mus musculoides in the derived savanna of Nigeria, and Neal (1970) showed how the populations of several species in Uganda changed during the course of the year in relation to annual fires. Bellier (1967) in the Ivory Coast, and Dieterlen (1967) in the highland grasslands of Kivu (Zaire) have given data on biomass and how this changes during the course of the year. The only study of rodent populations in moist evergreen forest known to me is that of Delany (1971) who related the population structure of several species in Mayanga forest Uganda (annual rainfall 1250 mm) to variations in the reproductive rate. None of these studies lasted for more than three years. An obvious gap in our knowledge is how rodent populations in Africa (whether in rain forest, savanna or arid regions) fluctuate over long periods of time, and the magnitude of population changes.
Enhanced antisaccade abilities in children with Tourette syndrome: the Gap-effect Reversal

Tourette Syndrome (TS) is a childhood onset disorder of motor and vocal tics. The neural networks underlying TS overlap with those of saccade eye movements. Thus, deviations on saccadic tasks can provide important information about psychopathology of TS. Tourette syndrome often coexists with Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD). Hence, we manipulated various components of a saccade task to measure its effects on saccades of children with TS-only, TS+ADHD, TS+ADHD+OCD and healthy controls. Children looked toward (prosaccade) or in the opposite direction (antisaccade) of a peripheral target as soon as it appeared. The prosaccade and antisaccade tasks were presented in three conditions. In the Gap200 condition, the fixation dot disappeared 200 ms prior to the appearance of the peripheral target, In the Gap800 condition, the fixation dot disappeared 800 ms prior to the appearance of the peripheral target and in Overlap200 the fixation dot disappeared 200 ms after the appearance of the peripheral target. Fixation-offset manipulations had different effects on each group's antisaccades. The TS+ADHD+OCD group's antisaccade latencies and error rates remained relatively unchanged in the three conditions and displayed a pattern of eye movements that can be interpreted as enhanced. Alternatively, the TS+ADHD group displayed an overall pattern of longer saccadic latencies. Findings corroborate the hypothesis that the combination of tic disorder and ADHD results in unique behavioral profiles. It is plausible that a subgroup of children with TS develop an adaptive ability to control their tics which generalizes to enhanced volitional control of saccadic behavior as well. Supporting evidence and other findings are discussed.
Patient Related Outcome Measures Dovepress Pragmatic Measurement of Health Satisfaction in People with Type 2 Diabetes Mellitus Using the Current Health Satisfaction Questionnaire

Background: The concept of diabetes-related health satisfaction encompasses issues specifically related to living with diabetes (eg, blood glucose, blood pressure levels, body weight). Health satisfaction is more specific than overall health-related quality of life because it considers disease-related factors, and is different from diabetes treatment satisfaction because it addresses issues not specifically related to treatment. Low levels of health satisfaction in people with type 2 diabetes mellitus (T2DM) may negatively affect self-care behaviors and treatment outcomes; however, there are currently no instruments available to assess health satisfaction in this population. This study assessed the measurement properties of a newly constructed, 14-item Current Health Satisfaction Questionnaire (CHES-Q) designed to assess diabetes-related health satisfaction and knowledge of the disease and important laboratory results. Methods: In-depth interviews were conducted in 23 adults with T2DM to confirm the content and clarity of the CHES-Q. The revised instrument was administered to 1,015 individuals with T2DM, along with supplemental questionnaires, including the Short Form-36. All subjects completed the questionnaires again 3 to 7 days later. CHES-Q test-retest reliability, construct validity, and known-groups validity were evaluated. Results: In general, respondents found the CHES-Q to be clear and comprehensive. Test-retest reliability was generally acceptable for all items ($0.70), except for three that fell just below the widely accepted cut-point of 0.70 (range 0.63–0.69). Convergent and divergent validity was demonstrated based on hypothesized correlations with the Short Form-36. Known-groups validity was confirmed for most CHES-Q items when respondents were split into groups known to differ clinically by body mass index, disease severity, or glycated hemoglobin. Conclusion: Health satisfaction is a unique and important concept to consider when developing individualized strategies for managing T2DM because health satisfaction is a key element of patient-centered care. The CHES-Q allows for the pragmatic assessment of many aspects of diabetes-related health satisfaction in a single questionnaire.
Epidemiology of noncomplex left ventricular outflow tract obstruction malformations (aortic valve stenosis, coarctation of the aorta, hypoplastic left heart syndrome) in Texas, 1999-2001.

BACKGROUND The left ventricular outflow tract (LVOT) malformations aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS) contribute significantly to infant mortality due to birth defects. Previous epidemiology data showed rate differences between male and female and white and black ethnic groups. The Texas Birth Defects Registry, an active surveillance program, enables study in a large, diverse population including Hispanics. METHODS Records of children up to 1 year old with AVS, CoA, and HLHS born in Texas from 1999 to 2001, were collected from the registry. Those including additional heart defects or a chromosomal anomaly were excluded. Multivariate analysis included: infant sex; United States-Mexico border county residence; and maternal age, race/ethnicity, birthplace, and education. RESULTS There were 910 cases among 1.08 million live births, of which 499 met inclusion criteria. Multivariate modeling of all LVOT malformations combined demonstrated lower prevalence rate ratios (PRRs) for black males (0.26) and Hispanic males (0.70). Similar results were found for CoA but not AVS or HLHS. Higher PRRs were noted for increased maternal age for LVOT (1.3 for 24-34 years; 1.7 for >34 years), AVS, and HLHS, but not CoA, and higher PRRs across all diagnoses for males (LVOT PRR, 2.4) were noted. CoA PRRs were higher in border county vs. non-border county residents (PRR, 2.1). Maternal education and birthplace were not significant factors. CONCLUSIONS There are rate differences for males among all 3 ethnic groups. Sex and ethnic differences suggest genetic etiologies, where the ethnic differences could be used to find susceptibility loci with mapping by admixture linkage disequilibrium. Increased CoA rates along the U.S.-Mexico border suggest environmental causes that will require further monitoring.
Analysis and comparison of measured DGD data on buried single-mode fibers

Temporal and spectral measurements were made on three different 95-km fibers within a slotted-core, direct buried, standard single-mode fiber-optic cable over many days to characterize DGD variability. From this data we observed that DGD varies slowly over time but rapidly over wavelength. This data showed good agreement with a Maxwellian distribution. The frequency-averaged mean DGD varied by about 10% or less during the periods that included significant temperature swings. Outage analysis showed that for system tolerances of three times the mean DGD, outages will occur typically every 3 to 8 years with mean outage durations ranging from about one to two hours. From this analysis we conclude that high-DGD episodes are spectrally localized and will be exceedingly rare and short lived.
Removal of CPR Artifacts From the Ventricular Fibrillation ECG by Adaptive Regression on Lagged Reference Signals

Removing cardiopulmonary resuscitation (CPR)-related artifacts from human ventricular fibrillation (VF) electrocardiogram (ECG) signals provides the possibility to continuously detect rhythm changes and estimate the probability of defibrillation success. This could reduce ldquohands-offrdquo analysis times which diminish the cardiac perfusion and deteriorate the chance for successful defibrillations. Our approach consists in estimating the CPR part of a corrupted signal by adaptive regression on lagged copies of a reference signal which correlate with the CPR artifact signal. The algorithm is based on a state-space model and the corresponding Kalman recursions. It allows for stochastically changing regression coefficients. The residuals of the Kalman estimation can be identified with the CPR-filtered ECG signal. In comparison with ordinary least-squares regression, the proposed algorithm shows, for low signal-to-noise ratio (SNR) corrupted signals, better SNR improvements and yields better estimates of the mean frequency and mean amplitude of the true VF ECG signal. The preliminary results from a small pool of human VF and animal asystole CPR data are slightly better than the results of comparable previous studies which, however, not only used different algorithms but also different data pools. The algorithm carries the possibility of further optimization.
Finite Common-Mode Rejection in Fully Differential Nonlinear Circuits

In this brief, it is highlighted that fully differential nonlinear circuits, even though perfectly symmetrical, can be significantly sensitive to common-mode (CM)/power-supply (PS) interference and can be affected by even-order distortion. The cross-modulation mechanism between CM and differential input components, which gives rise to such unwanted phenomena, is investigated both analytically and on the basis of computer simulations, and its impact on CM and PS rejection is compared with the effects of device mismatch.
Three‐dimensional pathways of water masses in the South China Sea: A modeling study

We conduct a numerical Eulerian analysis on the Lagrangian characteristics of South China Sea (SCS) water masses. This is the first study to investigate the water pathway and residence time in response to time-dependent, three-dimensional basin circulation in the SCS. The circulation of the SCS is largely determined by westward intrusions of the northwestern Pacific waters in the upper layer (0-750 m) and deep layer (>1500 m), and by an eastward extrusion in the intermediate layer (750-1500 m) through Luzon Strait (LS). The waters in these three layers are interlinked to sustain the three-dimensional circulation in the SCS. The upper intrusive waters flow cyclonically and have a residence time of ∼3 years before they subduct into a deeper layer or exit the SCS through surrounding straits. The intrusive denser waters in the deep layer flow along the northern slope and reside for ∼25 years in the northern basin (north of 13°N), where a strong subduction occurs. A cyclonic circulation exists in the deep layer in the southern basin (south of 13°N), where a subduction of intermediate waters occurs over its eastern side and a deep upwelling exists over its western side. The water in the deep southern basin has a residence time of ∼40 years. The upwelled deep waters and the subducted waters from the upper layer form the intermediate water, where waters circulate anti-cyclonically towards LS and have a longest residence time (∼42 years). These findings are supported by the spatial variation in the observed potential density variance.
Mutational Analysis of Quinolone Resistance Protein QnrB1

ABSTRACT Alanine substitutions and selected deletions have been used to localize amino acids in QnrB essential for its protective activity. Essential amino acids are found at positions i and i−2 in the pentapeptide repeat module and in the larger of two loops, where deletion of only a single amino acid compromises activity. Deletion of 10 amino acids at the N terminus is tolerated, but removal of 3 amino acids in the C-terminal dimerization unit destroys activity.
Structural Discrimination of Robustness in Transcriptional Feedforward Loops for Pattern Formation

Signaling pathways are interconnected to regulatory circuits for sensing the environment and expressing the appropriate genetic profile. In particular, gradients of diffusing molecules (morphogens) determine cell fate at a given position, dictating development and spatial organization. The feedforward loop (FFL) circuit is among the simplest genetic architectures able to generate one-stripe patterns by operating as an amplitude detection device, where high output levels are achieved at intermediate input ones. Here, using a heuristic optimization-based approach, we dissected the design space containing all possible topologies and parameter values of the FFL circuits. We explored the ability of being sensitive or adaptive to variations in the critical morphogen level where cell fate is switched. We found four different solutions for precision, corresponding to the four incoherent architectures, but remarkably only one mode for adaptiveness, the incoherent type 4 (I4-FFL). We further carried out a theoretical study to unveil the design principle for such structural discrimination, finding that the synergistic action and cooperative binding on the downstream promoter are instrumental to achieve absolute adaptive responses. Subsequently, we analyzed the robustness of these optimal circuits against perturbations in the kinetic parameters and molecular noise, which has allowed us to depict a scenario where adaptiveness, parameter sensitivity and noise tolerance are different, correlated facets of the robustness of the I4-FFL circuit. Strikingly, we showed a strong correlation between the input (environment-related) and the intrinsic (mutation-related) susceptibilities. Finally, we discussed the evolution of incoherent regulations in terms of multifunctionality and robustness.
Optimal Dynamic Sequence Representations

We describe a data structure that supports access, rank and select queries, as well as symbol insertions and deletions, on a string S[1, n] over alphabet [1. σ] in time O(lg n/lg lg n), which is optimal. The time is worst-case for the queries and amortized for the updates. This complexity is better than the best previous ones by a Θ(1 + lg σ/lg lg n) factor. Our structure uses nH0(S) + O(n + σ(lg σ + lg1+en)) bits, where H0(S) is the zero-order entropy of S and 0