Miracle-dz/UniFAR-FTUs huggingface dataset:
Vasopressors Do Not Influence Cerebral Critical Closing Pressure During Systemic Inflammation Evoked by Experimental Endotoxemia and Sepsis in Humans

Aim: The aim of this study was to investigate the effects of different vasopressors on the cerebral vasculature during experimental human endotoxemia and sepsis. We used the critical closing pressure (CrCP) as a measure of cerebral vascular tone. Methods: We performed a prospective pilot study, at the intensive care department (ICU) of a tertiary care university hospital in the Netherlands, in 40 healthy male subjects during experimental human endotoxemia (administration of bacterial lipopolysaccharide [LPS]) and in 10 patients with severe sepsis or septic shock. Subjects in the endotoxemia study were randomized to receive a 5 h infusion of either 0.05 &mgr;g/kg/min noradrenaline (n = 10, “LPS-nor”), 0.5 &mgr;g/kg/min phenylephrine (n = 10, “LPS-phenyl”), 0.04 IU/min vasopressin (n = 10, “LPS-AVP”), or saline (n = 10, “LPS-placebo”) starting 1 h before intravenous administration of 2 ng/kg LPS. In patients with sepsis, fluid resuscitation and vasopressor use was at the discretion of the medical team, aiming at normovolemia and a mean arterial pressure (MAP) > 65 mm Hg, using noradrenaline. The mean flow velocity in the middle cerebral artery (MFVMCA) was measured by transcranial Doppler (TCD) with simultaneously recording of heart rate, arterial blood pressure, respiratory rate, and oxygen saturation. CrCP was estimated using the cerebrovascular impedance model. Results: The CrCP decreased in the LPS-placebo group from 52.6 [46.6–55.5] mm Hg at baseline to 44.1 [41.2–51.3] mm Hg at 270 min post-LPS (P = 0.03). Infusion of phenylephrine increased the CrCP in the period before LPS administration from 46.9 [38.8–53.4] to 53.8 [52.9–60.2] mm Hg (P = 0.02), but after LPS administration, a similar decrease was observed compared with the LPS-placebo group. Noradrenaline or vasopressin prior to LPS did not affect the CrCP. The decrease in CrCP after LPS bolus was similar in all treatment groups. The CrCP in the sepsis patients equaled 35.7 [34.4–42.0] mm Hg, and was lower compared with that in the LPS-placebo subjects from baseline until 90 min after LPS (P < 0.01). Conclusions: Experimental human endotoxemia results in a decreased CrCP due to a loss of vascular resistance of the arterial bed. Vasopressors did not prevent this decrease in CrCP. Findings in patients with sepsis are comparable to those found in subjects after LPS administration. Patients with sepsis, despite treatment with vasopressors, have a risk for low cerebral blood flow and ischemia.
Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates

Significance Functional MRI (fMRI) is 25 years old, yet surprisingly its most common statistical methods have not been validated using real data. Here, we used resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses. Using this null data with different experimental designs, we estimate the incidence of significant results. In theory, we should find 5% false positives (for a significance threshold of 5%), but instead we found that the most common software packages for fMRI analysis (SPM, FSL, AFNI) can result in false-positive rates of up to 70%. These results question the validity of a number of fMRI studies and may have a large impact on the interpretation of weakly significant neuroimaging results. The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software packages SPM, FSL, and AFNI, as well as a nonparametric permutation method. For a nominal familywise error rate of 5%, the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference. Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape. By comparison, the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference. These findings speak to the need of validating the statistical methods being used in the field of neuroimaging.
Targeting RNA-Polymerase I in Both Chemosensitive and Chemoresistant Populations in Epithelial Ovarian Cancer

Purpose: A hallmark of neoplasia is increased ribosome biogenesis, and targeting this process with RNA polymerase I (Pol I) inhibitors has shown some efficacy. We examined the contribution and potential targeting of ribosomal machinery in chemotherapy-resistant and -sensitive models of ovarian cancer. Experimental Design: Pol I machinery expression was examined, and subsequently targeted with the Pol I inhibitor CX-5461, in ovarian cancer cell lines, an immortalized surface epithelial line, and patient-derived xenograft (PDX) models with and without chemotherapy. Effects on viability, Pol I occupancy of rDNA, ribosomal content, and chemosensitivity were examined. Results: In PDX models, ribosomal machinery components were increased in chemotherapy-treated tumors compared with controls. Thirteen cell lines were sensitive to CX-5461, with IC50s 25 nmol/L–2 μmol/L. Interestingly, two chemoresistant lines were 10.5- and 5.5-fold more sensitive than parental lines. CX-5461 induced DNA damage checkpoint activation and G2–M arrest with increased γH2AX staining. Chemoresistant cells had 2- to 4-fold increased rDNA Pol I occupancy and increased rRNA synthesis, despite having slower proliferation rates, whereas ribosome abundance and translational efficiency were not impaired. In five PDX models treated with CX-5461, one showed a complete response, one a 55% reduction in tumor volume, and one maintained stable disease for 45 days. Conclusions: Pol I inhibition with CX-5461 shows high activity in ovarian cancer cell lines and PDX models, with an enhanced effect on chemoresistant cells. Effects occur independent of proliferation rates or dormancy. This represents a novel therapeutic approach that may have preferential activity in chemoresistant populations. Clin Cancer Res; 23(21); 6529–40. ©2017 AACR.
Event-Based Fault Detection Filtering for Complex Networked Jump Systems

This paper is concerned with the fault detection filtering for complex systems over communication networks subject to nonhomogeneous Markovian parameters. A residual signal is generated that gives a satisfactory estimation of the fault, and an event-triggered scheme is proposed to determine whether the networks should be updated at the trigger instants decided by the event-threshold. Moreover, a random process is employed to model the phenomenon of malicious packet losses. Consequently, a novel method is presented to address the stochastically stability analysis and satisfies a given $H_{2}$ performance index simultaneously. The condition of the existence of the filter design algorithm is derived by a convex optimization approach to estimate the faults and to generate a residual. Finally, the proposed fault detection filtering method is then applied to an industrial nonisothermal continuous stirred tank reactor under realistic network conditions. Simulation results are given to show the effectiveness of the proposed design method and the designed filter.
Tuning the Size of Poly(lactic‐co‐glycolic Acid) (PLGA) Nanoparticles Fabricated by Nanoprecipitation

Polymeric nanoparticles (PNPs) are promising drug carriers in cancer treatment. Size of the particles has a significant impact on drug loading, in vivo distribution, extravasation, intratumor diffusion and cell uptake, and thus is critical for the successful development of a drug delivery regime. However, methods for manufacturing PNPs of defined size are yet to be established. The goal of this study is to establish a method that can be used to fabricate PNPs with controlled size. The factors that could impact the size of PNPs fabricated by nano‐precipitation are systematically investigated. The factors studied include polymer concentration, organic solvent, temperature, aqueous phase ionic strength, organic phase injection rate, aqueous phase agitation rate, gauge of the needles, and final polymer concentration. Polymer concentration, the choice of organic solvent, temperature, and the ionic strength of the aqueous phase are shown to have a significant impact on the size of PNPs, and the effect of these factors can be attributed to a single parameter, the diffusion coefficient of the solvent in water, Dpw. It is possible that by tightly control these four parameters, nanoparticles with highly predictable and desirable size with narrow size distribution can be fabricated.
Discrete Roughness Transition for Hypersonic Flight Vehicles

The importance of discrete roughness and the correlations developed to predict the onset of boundary layer transition on hypersonic flight vehicles are discussed. The paper is organized by hypersonic vehicle applications characterized in a general sense by the boundary layer: slender with hypersonic conditions at the edge of the boundary layer, moderately blunt with supersonic, and blunt with subsonic. This paper is intended to be a review of recent discrete roughness transition work completed at NASA Langley Research Center in support of agency flight test programs. First, a review is provided of discrete roughness wind tunnel data and the resulting correlations that were developed. Then, results obtained from flight vehicles, in particular the recently flown Hyper-X and Shuttle missions, are discussed and compared to the ground-based correlations.
Turbulence in an Auto-Oscillating Complex Plasma

We present an experiment on the development of turbulence in a microparticle cloud in a low-temperature plasma laboratory onboard the International Space Station. First, the complex plasma cloud was stabilized with an alternating electric field. Once the stabilization was switched OFF, a so-called heartbeat instability developed in which the microparticles are oscillating radially. We show that the kinetic energy spectra develop a double cascade once the cloud becomes unstable. A double cascade has been predicted by Kraichnan and Leith for forced 2-D turbulence, but has only seldomly been observed in experiments. We also show that the reduced rates of energy and enstrophy transfer can be used to infer the excitation wavenumber <inline-formula> <tex-math notation="LaTeX">$k_{\text {exc}}$ </tex-math></inline-formula>, in good agreement with <inline-formula> <tex-math notation="LaTeX">$k_{\text {exc}}$ </tex-math></inline-formula> obtained from the energy spectrum.
Global survey of concentric gravity waves in AIRS images and ECMWF analysis

Concentric gravity waves (CGWs) are atmospheric phenomena with ring‐shape perturbations originating in the troposphere. They can propagate up to the ionosphere and thermosphere and dynamically couple the lower and upper atmosphere. In this study we developed a novel ring detection algorithm to extract CGWs from the Atmosphere Infrared Sounder (AIRS) radiance data and the European Center for Medium‐Range Weather Forecasting (ECMWF) analysis temperature in the stratosphere to produce the first global maps of such phenomena. The algorithm is capable of estimating wave amplitude, wavelength, propagation direction, and source location. Both AIRS and ECMWF data show a significant diurnal variation in wave propagation direction and generation, in addition to strong seasonal variations in wavelength and amplitude. Occurrence of these ring waves is associated not only with tropical deep convections but also with summertime midlatitude convection, wintertime extratropical jets, and topography such as islands. The high‐resolution ECMWF analysis data capture most of the CGW features, but the wave amplitude is significantly weaker than AIRS observations, showing few convectively generated CGWs.
Factors influencing the educational impact of Mini-CEX and DOPS: A qualitative synthesis

Abstract Introduction: The educational impact of Mini-CEX and DOPS varies greatly and can be influenced by several factors. However, there is no comprehensive analysis and synthesis of the described influencing factors. Methods: To fill this gap, we chose a two-step approach. First, we performed a systematic literature review and selected articles describing influencing factors on the educational impact of Mini-CEX and DOPS. Second, we performed a qualitative synthesis of these factors. Results: Twelve articles were included, which revealed a model consisting of four themes and nine subthemes as influencing factors. The theme context comprises “time for Mini-CEX/DOPS” and “usability of the tools”, and influences the users. The theme users comprises “supervisors’ knowledge about how to use Mini-CEX/DOPS”, “supervisors’ attitude to Mini-CEX/DOPS”, “trainees’ knowledge about Mini-CEX/DOPS”, and “trainees’ perception of Mini-CEX/DOPS”. These influence the implementation of Mini-CEX and DOPS, including “observation” and “feedback”. The theme implementation directly influences the theme outcome, which, in addition to the educational impact, encompasses “trainees’ appraisal of feedback”. Conclusions: Our model of influencing factors might help to further improve the use of Mini-CEX and DOPS and serve as basis for future research.
Bioavailability of strawberry antioxidants in human subjects

Strawberries contain many antioxidant phytochemicals such as vitamin C, carotenoids and phenolic compounds including anthocyanins (ACN). In the present study, antioxidant composition of fresh strawberries (FS) and stored strawberries (SS) and the bioavailability of the main strawberry bioactive compounds were determined in human subjects. Thirteen healthy volunteers consumed 300 g of FS and SS on two separate occasions. Blood, before and at different time points from meal consumption, as well as 24 h urine, was collected, and parent compounds and metabolites of the different compounds were determined by HPLC or LC/MS/MS. A reduction in α-carotene plasma concentrations v. baseline values was recorded after the consumption of FS, although the amount of this carotenoid was higher in the SS. On the contrary, a significant increase of plasma vitamin C after 2, 3 and 5 h (P < 0·05) of FS and SS consumption was recorded. No quercetin and ACN were found in plasma, while coumaric acid, 4-hydroxybenzoic acid (4HBA, 56 and 54 % of pelargonidin-3-glucoside (Pel-glc) ingested with FS and SS, respectively) and protocatechuic acid (59 and 34 % of cyanidin-3-glucoside ingested with FS and SS, respectively) over 8 h from strawberry consumption were retrieved in the plasma. Pelargonidin glucuronide, pelargonidin glucoside and pelargonidin aglycone peaked in urine within 2 h of strawberry consumption, and the 24 h amount excreted was always approximately 0·9 % of the Pel-glc dose ingested. The data indicated that the content of phytochemicals in strawberries may influence the bioavailability of individual compounds. Furthermore, in the present study, the metabolism of Pel-glc was elucidated, and, for the first time, 4HBA was suggested to be a major human metabolite of Pel-glc.
Transcriptome and Secretome Analyses of the Wood Decay Fungus Wolfiporia cocos Support Alternative Mechanisms of Lignocellulose Conversion

ABSTRACT Certain wood decay basidiomycetes, collectively referred to as brown rot fungi, rapidly depolymerize cellulose while leaving behind the bulk of cell wall lignin as a modified residue. The mechanism(s) employed is unclear, but considerable evidence implicates the involvement of diffusible oxidants generated via Fenton-like chemistry. Toward a better understanding of this process, we have examined the transcriptome and secretome of Wolfiporia cocos when cultivated on media containing glucose, purified crystalline cellulose, aspen (Populus grandidentata), or lodgepole pine (Pinus contorta) as the sole carbon source. Compared to the results obtained with glucose, 30, 183, and 207 genes exhibited 4-fold increases in transcript levels in cellulose, aspen, and lodgepole pine, respectively. Mass spectrometry identified peptides corresponding to 64 glycoside hydrolase (GH) proteins, and of these, 17 corresponded to transcripts upregulated on one or both woody substrates. Most of these genes were broadly categorized as hemicellulases or chitinases. Consistent with an important role for hydroxyl radical in cellulose depolymerization, high transcript levels and upregulation were observed for genes involved in iron homeostasis, iron reduction, and extracellular peroxide generation. These patterns of regulation differ markedly from those of the closely related brown rot fungus Postia placenta and expand the number of enzymes potentially involved in the oxidative depolymerization of cellulose. IMPORTANCE The decomposition of wood is an essential component of nutrient cycling in forest ecosystems. Few microbes have the capacity to efficiently degrade woody substrates, and the mechanism(s) is poorly understood. Toward a better understanding of these processes, we show that when grown on wood as a sole carbon source the brown rot fungus W. cocos expresses a unique repertoire of genes involved in oxidative and hydrolytic conversions of cell walls.
Group invariance principles for causal generative models

The postulate of independence of cause and mechanism (ICM) has recently led to several new causal discovery algorithms. The interpretation of independence and the way it is utilized, however, varies across these methods. Our aim in this paper is to propose a group theoretic framework for ICM to unify and generalize these approaches. In our setting, the cause-mechanism relationship is assessed by comparing it against a null hypothesis through the application of random generic group transformations. We show that the group theoretic view provides a very general tool to study the structure of data generating mechanisms with direct applications to machine learning.
Dissecting functional components of reproductive isolation among closely related sympatric species of the Anopheles gambiae complex

Explaining how and why reproductive isolation evolves and determining which forms of reproductive isolation have the largest impact on the process of population divergence are major goals in the study of speciation. By studying recent adaptive radiations in incompletely isolated taxa, it is possible to identify barriers involved at early divergence before other confounding barriers emerge after speciation is complete. Sibling species of the Anopheles gambiae complex offer opportunities to provide insights into speciation mechanisms. Here, we studied patterns of reproductive isolation among three taxa, Anopheles coluzzii, An. gambiae s.s. and Anopheles arabiensis, to compare its strength at different spatial scales, to dissect the relative contribution of pre‐ versus postmating isolation, and to infer the involvement of ecological divergence on hybridization. Because F1 hybrids are viable, fertile and not uncommon, understanding the dynamics of hybridization in this trio of major malaria vectors has important implications for how adaptations arise and spread across the group, and in planning studies of the safety and efficacy of gene drive as a means of malaria control. We first performed a systematic review and meta‐analysis of published surveys reporting on hybrid prevalence, showing strong reproductive isolation at a continental scale despite geographically restricted exceptions. Second, we exploited our own extensive field data sets collected at a regional scale in two contrasting environmental settings, to assess: (i) levels of premating isolation; (ii) spatio/temporal and frequency‐dependent dynamics of hybridization, (iii) relationship between reproductive isolation and ecological divergence and (iv) hybrid viability penalty. Results are in accordance with ecological speciation theory predicting a positive association between the strength of reproductive isolation and degree of ecological divergence, and indicate that postmating isolation does contribute to reproductive isolation among these species. Specifically, only postmating isolation was positively associated with ecological divergence, whereas premating isolation was correlated with phylogenetic distance.
Event chronology and prospectivity of the mafic magmatic systems in the Arunta province

As part of the National Geoscience Agreement with the Northern Territory Geological Survey (NTGS), Geoscience Australia is evaluating mafic-ultramafic intrusions in the Arunta Province of central Australia. The major aims of this regional study are to constrain the various maficultramafic magmatic systems within the event chronology of the Arunta, and to provide a geoscientific framework for assessing the resource potential of the intrusions. Sixteen bodies were sampled from a 90 000 km area (Figure 1). SHRIMP U-Pb zircon ages were obtained for thirteen bodies by targeting fractionated mafic rocks with relatively high abundances of Zr (80 to 220 ppm). Our 100% success rate in finding large quantities of zircon in samples targeted by field and chemical criteria opens the way to dating mafic magmatism more routinely elsewhere.
Is there any difference between the iodine statuses of breast-fed and formula-fed infants and their mothers in an area with iodine sufficiency?

Abstract Despite substantial progress in the global elimination of iodine deficiency, lactating mothers and their infants remain susceptible to insufficient iodine intake. This cross-sectional study was conducted to compare iodine statuses of breast-fed and formula-fed infants and their mothers at four randomly selected health care centres in Tehran. Healthy infants <3 months old and their mothers were randomly selected for inclusion in this study. Iodine was measured in urine and breast milk samples from each infant and mother as well as commercially available infant formula. The study included 124 postpartum mothers (29·2 (sd 4·9) years old) and their infants (2·0 (sd 0·23) months old). The iodine concentrations were 50–184 µg/l for infant formula, compared with a median breast milk iodine concentration (BMIC) of 100 µg/l in the exclusive breast-feeding group and 122 µg/l in the partial formula feeding group. The median values for urinary iodine concentration in the exclusive breast-feeding group were 183 µg/l (interquartile range (IQR) 76–285) for infants and 78 µg/l (IQR 42–145) for mothers, compared with 140 µg/l (IQR 68–290) for infants and 87 µg/l (IQR 44–159) for mothers in the formula feeding group. These differences were not statistically significant. After adjustment for BMIC, ANCOVA revealed that feeding type (exclusive breast-feeding v. partial formula feeding) did not significantly affect the infants’ or mother’s urinary iodine levels. Thus, in an area with iodine sufficiency, there was no difference in the iodine statuses of infants and mothers according to their feeding type.