Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary restriction of energy and sugar results in a reduction in human cytochrome P450 2E1 activity

Dietary habits are often considered as a pathogenic factor for fatty liver. The impact of dietary intake and steatosis on drug metabolism remains poorly investigated. Our aim was to assess the effect of dietary intake on in vivo cytochrome P450 (CYP) activities in eleven patients with abnormal liver function tests potentially due to fatty liver and associated with a high-sugar diet. Liver function tests, liver volume, aminopyrine breath test (ABT) and chlorzoxazone (CZ) pharmacokinetics (area under the curve, AUC) which are known to reflect CYP2E1 activity were evaluated before and after 2 months restriction of dietary sugar intake. Features at inclusion were an increased BMI (30·3 (sd 3·2) kg/m2), high hepatic volume (1·96 (sd 0·48) litres), hyperechogenic liver parenchyma, elevated liver enzyme activities (alanine aminotransferase (EC 2.6.1.2) 58·6 (sd 17·4) IU/l with alanine aminotransferase : aspartate aminotransferase (EC 2.6.1.1) ratio > 1), together with a normal ABT value (0·68 (sd 0·21) % specific activity of administered dose of [14C]aminopyrine in breath after 1 h) and a high CYP2E1 activity (CZ AUC 20·3 (sd 7·1) μg/ml per h). A dietary sugar restriction was prescribed. On the basis of repeated interviews by the same dietitian, unaware of any clinical and biochemical data, six patients remained compliant to the diet and exhibited reductions in BMI (P < 0·001), serum alanine aminotransferase (P = 0·008), liver volume (P = 0·002) and CYP2E1 activity (P = 0·007), a significant increase in ABT (P < 0·001) together with the disappearance of liver hyperechogenicity at ultrasound. In contrast, the five non-compliant patients did not show any significant change in any of these variables. In conclusion, CYP2E1 activity is induced in patients with perturbations of liver function tests potentially due to fatty liver. In these patients, effective dietary sugar restriction is associated with a reduction in liver volume, a reduction in CYP2E1 activity and an increased aminopyrine metabolism rate.
Detection of a circadian enhancer in the mDbp promoter using prokaryotic transposon vector-based strategy

In mammals, the expression of 5–10% of genes occurs with circadian fluctuation in various organs and tissues. This cyclic transcription is thought to be directly or indirectly regulated through circadian transcriptional/translational feedback loops consisting of a set of clock genes. Among the clock genes in mammals, expression of the Dbp mRNA robustly oscillates both in vivo and in culture cells. Here, we present circadian enhancer detection strategy using prokaryotic transposon system. The mDbp promoter drives reporter gene expression in robust circadian cycles in rat-1 fibroblasts. To identify the circadian enhancer generating this robust rhythm, we developed a prokaryotic transposon-based enhancer detecting vector for in vitro transposition. Using this system, we identified a strong circadian enhancer region containing the CATGTG sequence in the 5′ flanking region of the mDbp gene; this enhancer region is critical for the ability of the mDbp promoter to drive robust oscillation in living cells. This enhancer is classified as a CANNTG type non-canonical E-box. These findings strongly suggest that CANNTG-type non-canonical E-boxes may contribute, at least in part, to the regulation of robust circadian gene expression. Furthermore, these data may help explain the wider effects of the CLOCK/BMAL1 complex in control of clock output genes.
Patterns of central venous oxygen saturation, lactate and veno-arterial CO2 difference in patients with septic shock

Background and Aims: Tissue hypoperfusion is reflected by metabolic parameters such as lactate, central venous oxygen saturation (ScvO2) and the veno-arterial CO2 (vaCO2) difference. We studied the relation of these parameters over time and with outcome in patients with severe septic shock. Materials and Methods: In this single-center, prospective observational cohort study, adult patients (≥18 years) with circulatory shock were included. Echocardiography and simultaneous arterial and venous blood gases were done on enrolment (0 h) and at 24, 48 and 72 h. The partial pressure of CO2, lactate and ScvO2 were recorded from the central venous blood samples. The vaCO2 was calculated as the difference in CO2 between paired venous and arterial blood gas samples. Results: Of the 104 patients with circulatory shock, 79 patients (44 males) with septic shock aged 49.8 (standard deviation ± 14.6) years and with sequential organ failure assessment (SOFA) score of 11.0 ± 3.4 were included. 71 patients (89.9%) were ventilated (11.4 ± 12.3 ventilator-free days). The duration of hospitalization was 16.6 ± 12.8 days and hospital mortality 50.6%. Lactate significantly decreased over time with a greater decrement in survivors than nonsurvivors (−0.35 vs. −0.10, P < 0.001). For every l/min increase in cardiac output, vaCO2 decreased by 0.34 mmHg (P = 0.006). There was no association between ScvO2 and mortality (P = 0.930). 0 h SOFA and vaCO2 ≤6 mmHg were strongly associated (P = 0.005, P = 0.018, respectively) with higher odds of mortality. However, this association was evident only in those with ScvO2 >70% and not in ScvO2 ≤70%. Conclusion: In septic shock, vaCO2 ≤6 mmHg is independently associated with mortality, particularly in those with normalized ScvO2 consistent with metabolic microcirculatory abnormalities in these patients.
Noise Minimization in Eukaryotic Gene Expression

All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or “noise. ” Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.
Concurrent Validity of the Opcrit Diagnostic System

Background OPCRIT (a suite of computer programs that allow data entry and generate diagnoses according to 12 operational diagnostic systems) is used in a wide range of psychiatric research including both European Science Foundation and NIMH research initiatives in the molecular genetics of mental disorders. We examined its concurrent validity in 100 subjects collected for linkage studies of Bipolar Disorder and Schizophrenia. Method We compared diagnoses generated by OPCRIT from data rated by two trained clinicians with diagnoses made according to consensus, best-estimate, lifetime procedures by the same two raters according to DSM–III–R and RDC classifications. Results Good to excellent agreement was achieved between OPCRIT diagnoses and those made by consensus best-estimate procedures. Conclusions OPCRIT provides a convenient, reliable, rapid and valid approach to polydiagnostic assessment that can be used as an adjunct to conventional (but time consuming) best-estimate consensus diagnostic procedures.
LARgE Survey – I. Dead monsters: the massive end of the passive galaxy stellar mass function at cosmic noon

We introduce the largest to date survey of massive quiescent galaxies at redshift z~1.6. With these data, which cover 27.6 deg^2, we can find significant numbers of very rare objects such as ultra-massive quiescent galaxies that populate the extreme massive end of the galaxy mass function, or dense environments that are likely to become present-day massive galaxy clusters. In this paper, the first in a series, we apply our gzK adaptation of the BzK technique to select our z~1.6 galaxy catalog and then study the quiescent galaxy stellar mass function with good statistics over M_stars ~ 10^10.2 - 10^11.7 M_sun --- a factor of 30 in mass --- including 60 ultra-massive z~1.6 quiescent galaxies with M_stars > 10^11.5 M_sun. We find that the stellar mass function of quiescent galaxies at z~1.6 is well represented by the Schechter function over this large mass range. This suggests that the mass quenching mechanism observed at lower redshifts must have already been well established by this epoch, and that it is likely due to a single physical mechanism over a wide range of mass. This close adherence to the Schechter shape also suggests that neither merging nor gravitational lensing significantly affect the observed quenched population. Finally, comparing measurements of M* parameters for quiescent and star-forming populations (ours and from the literature), we find hints of an offset (M*_SF > M*_PE), that could suggest that the efficiency of the quenching process evolves with time.
MEAN VALUE THEOREMS ON MANIFOLDS

We derive several mean value formulae on manifolds, generalizing the classical one for harmonic functions on Euclidean spaces as well as later results of Schoen-Yau, Michael-Simon, etc, on curved Riemannian manifolds. For the heat equation a mean value theorem with respect to ‘heat spheres’ is proved for heat equation with respect to evolving Riemannian metrics via a space-time consideration. Some new monotonicity formulae are derived. As applications of the new local monotonicity formulae, some local regularity theorems concerning Ricci flow are proved.
Contextualized Word Embeddings Enhanced Event Temporal Relation Extraction for Story Understanding

Learning causal and temporal relationships between events is an important step towards deeper story and commonsense understanding. Though there are abundant datasets annotated with event relations for story comprehension, many have no empirical results associated with them. In this work, we establish strong baselines for event temporal relation extraction on two under-explored story narrative datasets: Richer Event Description (RED) and Causal and Temporal Relation Scheme (CaTeRS). To the best of our knowledge, these are the first results reported on these two datasets. We demonstrate that neural network-based models can outperform some strong traditional linguistic feature-based models. We also conduct comparative studies to show the contribution of adopting contextualized word embeddings (BERT) for event temporal relation extraction from stories. Detailed analyses are offered to better understand the results.
Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development

The trace metal copper (Cu) plays an essential role in biology as a cofactor for many enzymes that include Cu, Zn superoxide dismutase, cytochrome oxidase, ceruloplasmin, lysyl oxidase, and dopamine β-hydroxylase. Consequently, Cu transport at the cell surface and the delivery of Cu to intracellular compartments are critical events for a wide variety of biological processes. The components that orchestrate intracellular Cu trafficking and their roles in Cu homeostasis have been elucidated by the studies of model microorganisms and by the characterizations of molecular basis of Cu-related genetic diseases, including Menkes disease and Wilson disease. However, little is known about the mechanisms for Cu uptake at the plasma membrane and the consequences of defects in this process in mammals. Here, we show that the mouse Ctr1 gene encodes a component of the Cu transport machinery and that mice heterozygous for Ctr1 exhibit tissue-specific defects in copper accumulation and in the activities of copper-dependent enzymes. Mice completely deficient for Ctr1 exhibit profound growth and developmental defects and die in utero in mid-gestation. These results demonstrate a crucial role for Cu acquisition through the Ctr1 transporter for mammalian Cu homeostasis and embryonic development.
Combining stellar populations with orbit-superposition dynamical modelling: the formation history of the lenticular galaxy NGC 3115

We present a combination of the Schwarzschild orbit-superposition dynamical modelling technique with the spatially resolved mean stellar age and metallicity maps to uncover the formation history of galaxies. We apply this new approach to a remarkable five-pointing mosaic of VLT/MUSE observations obtained by Guérou et al. (2016) extending to a maximum galactocentric distance of ${\sim } {120}{\, {\rm arcsec}}\ \left({5.6}\, {\rm kpc}\right)$ along the major axis, corresponding to ∼2.5Re. Our method first identifies ‘families’ of orbits from the dynamical model that represent dynamically distinct structures of the galaxy. Individual ages and metallicities of these components are then fit for using the stellar-population information. Our results highlight components of the galaxy that are distinct in the combined stellar dynamics/populations space, which implies distinct formation paths. We find evidence for a dynamically cold, metal-rich disc, consistent with a gradual in situ formation. This disc is embedded in a generally old population of stars, with kinematics ranging from dispersion dominated in the centre to an old, diffuse, metal-poor stellar halo at the extremities. We find also a direct correlation between the dominant dynamical support of these components, and their associated age, akin to the relation observed in the Milky Way. This approach not only provides a powerful model for inferring the formation history of external galaxies but also paves the way to a complete population-dynamical model.
Multiparticle correlation studies in 
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The secondand third-order azimuthal anisotropy Fourier harmonics of charged particles produced in pPb collisions, at √ sNN = 8.16 TeV, are studied over a wide range of event multiplicities. Multiparticle correlations are used to isolate global properties stemming from the collision overlap geometry. The second-order “elliptic” harmonic moment is obtained with high precision through four-, six-, and eight-particle correlations and, for the first time, the third-order “triangular” harmonic moment is studied using four-particle correlations. A sample of peripheral PbPb collisions at √ sNN = 5.02 TeV that covers a similar range of event multiplicities as the pPb results is also analyzed. Model calculations of initial-state fluctuations in pPb and PbPb collisions can be directly compared to the high precision experimental results. This work provides new insight into the fluctuation-driven origin of the v3 coefficients in pPb and PbPb collisions, and into the dominating overall collision geometry in PbPb collisions at the earliest stages of heavy ion interactions. Submitted to Physical Review Letters c © 2019 CERN for the benefit of the CMS Collaboration. CC-BY-4.0 license ∗See Appendix A for the list of collaboration members ar X iv :1 90 4. 11 51 9v 1 [ he pex ] 2 5 A pr 2 01 9
Remote Sensing Techniques in Monitoring Post-Fire Effects and Patterns of Forest Recovery in Boreal Forest Regions: A Review

The frequency and severity of forest fires, coupled with changes in spatial and temporal precipitation and temperature patterns, are likely to severely affect the characteristics of forest and permafrost patterns in boreal eco-regions. Forest fires, however, are also an ecological factor in how forest ecosystems form and function, as they affect the rate and characteristics of tree recruitment. A better understanding of fire regimes and forest recovery patterns in different environmental and climatic conditions will improve the management of sustainable forests by facilitating the process of forest resilience. Remote sensing has been identified as an effective tool for preventing and monitoring forest fires, as well as being a potential tool for understanding how forest ecosystems respond to them. However, a number of challenges remain before remote sensing practitioners will be able to better understand the effects of forest fires and how vegetation responds afterward. This article attempts to provide a comprehensive review of current research with respect to remotely sensed data and methods used to model post-fire effects and forest recovery patterns in boreal forest regions. The review reveals that remote sensing-based monitoring of post-fire effects and forest recovery patterns in boreal forest regions is not only limited by the gaps in both field data and remotely sensed data, but also the complexity of far-northern fire regimes, climatic conditions and environmental conditions. We expect that the integration of different remotely sensed data coupled with field campaigns can provide an important data source to support the monitoring of post-fire effects and forest recovery patterns. Additionally, the variation and stratification of pre- and post-fire vegetation and environmental conditions should be considered to achieve a reasonable, operational model for monitoring post-fire effects and forest patterns in boreal regions.
O ct 2 01 6 1-BOUNDED ENTROPY AND REGULARITY PROBLEMS IN

We define and investigate the singular subspace Hs(N ⊆ M) of an inclusion of tracial von Neumann algebras. The singular subspace is a canonical N-N subbimodule of L(M) containing the quasinormalizer introduced in [37], the one-sided quasinormalizer introduced in [11], and the wq-normalizer introduced in [14] (following upon work in [26] and [39]). We then obtain a weak notion of regularity (called spectral regularity) by demanding that the singular subspace of N ⊆ M generates M. By abstracting Voiculescu’s original proof of absence of Cartan subalgebras in [51] we show that there can be no diffuse, hyperfinite subalgebra of L(Fn) which is spectrally regular. Our techniques are robust enough to repeat this process by transfinite induction and rule out chains of spectrally regular inclusions of algebras starting from a diffuse, hyperfinite subalgebra and ending in L(Fn). We use this to prove some conjectures made by Galatan-Popa in their study of smooth cohomology of II1-factors (see [14]). Our results may be regarded as a consistency check for the possibility of existence of a “good” cohomology theory of II1-factors. We can also use our techniques to show that if Ut is a one-parameter orthogonal group on a real Hilbert space H and the spectral measure of its generator is singular with respect to the Lebesgue measure, then the continuous core of the free Araki-Woods factor Γ(H, Ut)′′ is not isomorphic to L(Ft⊗B(l(N)) for any t ∈ (1,∞]. In particular, Γ(H, Ut)′′ 6∼= Γ(L(R, m), λt)′′ where m is Lebesgue measure and λ is the left regular representation. This was previously only know when the spectral measure of the generator of Ut had all of its convolution powers singular with respect to Lebesgue measure. We give similar applications to crossed products by free Bogoliubov actions in the spirit of [22].
Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.
NLTE modelling of integrated light spectra

Aims.We study the effects of non-local thermodynamic equilibrium (NLTE) on the abundance analysis of barium, magnesium, and manganese from integrated light spectroscopy, as typically applied to the analysis of extra-galactic star clusters and galaxies. In this paper, our reference object is a synthetic simple stellar population (SSP) representing a mono-metallicα-enhanced globular cluster with the metallicity [Fe/H] = −2.0 and the age of 11 Gyr.Methods. We used the MULTI2.3 program to compute LTE and NLTE equivalent widths of spectral lines of Mg I, Mn I, and Ba II ions, which are commonly used in abundance analyses of extra-galactic stellar populations. We used ATLAS12 model atmospheres for stellar parameters sampled from a model isochrone to represent individual stars in the model SSP. The NLTE and LTE equivalent widths calculated for the individual stars were combined to calculate the SSP NLTE corrections.Results. We find that the NLTE abundance corrections for the integrated light spectra of the metal-poor globular cluster are significant in many cases, and often exceed 0.1 dex. In particular, LTE abundances of Mn are consistently under-estimated by 0.3 dex for all optical lines of Mn I studied in this work. On the other hand, Ba II, and Mg I lines show a strong differential effect: the NLTE abundance corrections for the individual stars and integrated light spectra are close to zero for the low-excitation lines, but they amount to − 0.15 dex for the strong high-excitation lines. Our results emphasise the need to take NLTE effects into account in the analysis of spectra of individual stars and integrated light spectra of stellar populations.