Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated serum levels of human relaxin-2 in patients with esophageal squamous cell carcinoma.

AIM To assess the prognostic value of serum human relaxin 2 (H2 RLN) level in patients with esophageal squamous cell carcinoma (ESCC). METHODS From October 1998 to September 2009, 146 patients with histopathologically confirmed ESCC were enrolled in this study. One hundred patients underwent en bloc esophagectomy, and 46 patients with unresectable tumors underwent palliative surgery. Five of the 146 patients died of surgical complications. Serum levels of H2 RLN were measured by enzyme linked immunosorbent assay. The relationship between serum H2 RLN level and each of the clinicopathological parameters was analyzed using the χ² test. Patients were classified into two groups according to their H2 RLN level (< 0.462 ng/mL vs ≥ 0.462 ng/mL). When any analysis cell had fewer than five cases, the Fisher's exact test was used. The statistical difference between groups A and B in each clinicopathological category was determined by the Student's t test (two-tailed) or analysis of variance. Survival curves were plotted using the Kaplan-Meier method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS ESCC patients tended to have significantly higher serum H2 RLN concentrations (0.48 ± 0.17 ng/mL, n = 141) compared with the healthy control group (0.342 ± 0.12 ng/mL, n = 112). There was a significant difference between patients with lymph node involvement (0.74 ± 0.15 ng/mL, n = 90), distant metastasis (0.90 ± 0.19 ng/mL, n = 32) and those without lymph node involvement (0.45 ± 0.12 ng/mL, n = 51), and distant metastasis (0.43 ± 0.14 ng/mL, n = 109), respectively (P < 0.01). Patients with high H2 RLN levels (≥ 0.462 ng/mL) had a poorer prognosis than patients with low serum H2 RLN levels (< 0.462 ng/mL; P = 0.0056). The H2 RLN level was also correlated with survival and tumor-node-metastasis staging, but not with age, tumor size, gender, lymphovascular invasion or the histological grade of tumors. Cox regression analysis showed that H2 RLN was an independent variable. CONCLUSION Serum concentrations of H2 RLN are frequently elevated in ESCC patients and are correlated with disease metastasis and survival. Serum concentrations of H2 RLN may be an important prognostic marker in ESCC patients.
Proteomic Analysis of Signaling Network Regulation in Renal Cell Carcinomas with Differential Hypoxia-Inducible Factor-2α Expression

Background The loss of von Hippel–Lindau (VHL) protein function leads to highly vascular renal tumors characterized by an aggressive course of disease and refractoriness to chemotherapy and radiotherapy. Loss of VHL in renal tumors also differs from tumors of other organs in that the oncogenic cascade is mediated by an increase in the levels of hypoxia-inducible factor-2α (HIF2α) instead of hypoxia-inducible factor-1α (HIF1α). Methods and Principal Findings We used renal carcinoma cell lines that recapitulate the differences between mutant VHL and wild-type VHL genotypes. Utilizing a method relying on extracted peptide intensities as a label-free approach for quantitation by liquid chromatography–mass spectrometry, our proteomics study revealed regulation of key proteins important for cancer cell survival, proliferation and stress-resistance, and implicated differential regulation of signaling networks in VHL-mutant renal cell carcinoma. We also observed upregulation of cellular energy pathway enzymes and the stress-responsive mitochondrial 60-kDa heat shock protein. Finding reliance on glutaminolysis in VHL-mutant renal cell carcinoma was of particular significance, given the generally predominant dependence of tumors on glycolysis. The data have been deposited to the ProteomeXchange with identifier PXD000335. Conclusions and Significance Pathway analyses provided corroborative evidence for differential regulation of molecular and cellular functions influencing cancer energetics, metabolism and cell proliferation in renal cell carcinoma with distinct VHL genotype. Collectively, the differentially regulated proteome characterized by this study can potentially guide translational research specifically aimed at effective clinical interventions for advanced VHL-mutant, HIF2α-over-expressing tumors.
The You Yangs batholith in Southeastern Australia, the sources of its magmas and inferences for local crustal architecture

Abstract The 365-Ma You Yangs batholith is a mainly I-type monzogranitic body, containing rocks with both clinopyroxene and hornblende, but with a 2–2.5 km-wide rim of S-type rocks. In places, the margins of the intrusion wedge out laterally. A laccolithic shape may explain there being only low-grade contact metamorphism of the Ordovician metasedimentary wall rocks. The chemical and isotopic characteristics of the granitic rocks suggest that the magmas formed by partial melting of a source that contained some meta-igneous rocks but was dominated by chemically immature metasedimentary types, to impart an evolved Sr isotope signature (87Sr/86Srt = 0.70877–0.71066 for the main monzogranitic rocks), combined with relatively non-radiogenic εNd t (–2.4 to –1.9). Crystal fractionation played little role in shaping the compositions of the granitic magmas, with the main variations interpreted to be source-inherited. Igneous-textured microgranular enclaves (IMEs) are prominent in the monzogranitic rocks. The IMEs probably had an ultimate enriched-mantle source, and their magmas did not mix significantly with the crustally derived granitic host magmas. The characteristics of the monzogranitic rocks hosting the enclaves suggest the possibility that an unrecognised metasediment-dominated terrane of ancient arc crust may be present beneath the Bendigo Zone.
ASSESSING TEST-RETEST RELIABILITY OF THE PORTABLE BROWER SPEED TRAP II TESTING SYSTEM

The aim of the present study was to assess the test-retest reliability of the Brower Speed Trap II running speed timing system. The test-retest reliability of the system was assessed by testing 52 physical education students aged (±SD) 21.4 (±8.9) years. All participants were tested on 30-m sprint with 10-m, 20-m and 30-m split times. All measurements were obtained on two subsequent days. The results from this investigation indicate that the variations in the students’ performance between test day one and test day two was small and the intra-class correlation indicates a high repeatability. In the examination of the system reliability, the system did not show any marked systematic bias (p<.05) assessed by the paired sample t-test. However, the systematic bias and the random variation found indicate that the Brower Speed Trap II running speed timing system was a reliable testing instrument to be used in testing physical education students, and a useful instrument for measuring running speed. However, in future studies it would be interesting to examine if the system were able to monitor the small changes in running speed that could result from increasing the training of an already elite athlete. Furthermore, we concluded that if comparison of overall values of running speed is intended, it is advisable to use the same testing system, because different systems give different results based on the errors associated with it.
Risk-Sensitive Optimal Feedback Control Accounts for Sensorimotor Behavior under Uncertainty

Many aspects of human motor behavior can be understood using optimality principles such as optimal feedback control. However, these proposed optimal control models are risk-neutral; that is, they are indifferent to the variability of the movement cost. Here, we propose the use of a risk-sensitive optimal controller that incorporates movement cost variance either as an added cost (risk-averse controller) or as an added value (risk-seeking controller) to model human motor behavior in the face of uncertainty. We use a sensorimotor task to test the hypothesis that subjects are risk-sensitive. Subjects controlled a virtual ball undergoing Brownian motion towards a target. Subjects were required to minimize an explicit cost, in points, that was a combination of the final positional error of the ball and the integrated control cost. By testing subjects on different levels of Brownian motion noise and relative weighting of the position and control cost, we could distinguish between risk-sensitive and risk-neutral control. We show that subjects change their movement strategy pessimistically in the face of increased uncertainty in accord with the predictions of a risk-averse optimal controller. Our results suggest that risk-sensitivity is a fundamental attribute that needs to be incorporated into optimal feedback control models.
Cluster detection from surface-brightness fluctuations in SDSS data

Galaxy clusters can be detected as surface brightness enhancements in smoothed optical surveys. This method does not require individual galaxies to be identiable, and enables clusters to be detected out to surpris- ingly high redshifts, as recently demonstrated by the Las Campanas Distant Cluster Survey (LCDCS). Here, we investigate redshift limits for cluster detection in the Sloan Digital Sky Survey (SDSS). Calibrating assumptions about the surface brightness prole, the mass-to-light ratio, and the spectral energy distribution of galaxy clusters using available observational data, we show that it should be possible to detect galaxy groups out to redshifts of 0.5, and massive galaxy clusters out to redshifts of1:2 in summed r 0 +i 0 +z 0 SDSS data. Redshift estimates can be derived from the SDSS magnitudes of brightest cluster members out to redshifts near unity. Over the area of sky it covers, SDSS should nd >98% of the clusters detectable by the Planck satellite through the thermal Sunyaev-Zel'dovich eect. The few Planck clusters not detected in SDSS will almost all be at z > 1:2.
Life satisfaction and health-related quality of life (SF-36) of middle-aged men and women.

OBJECTIVES To investigate life satisfaction and health-related quality of life (SF-36) in a general population sample of middle-aged women and men. The effects of menopausal status and hormone replacement therapy (HRT) use upon life satisfaction and health-related quality of life (HrQOL) were also examined for the female sample. DESIGN All men and women aged 49-55 years from the age/sex register of a large general practice in London were contacted and asked to complete a questionnaire about their health. SUBJECTS A total of 103 women (55%) and 86 men (40%) participated; of the women, 15% were premenopausal, 68% peri- or postmenopausal and 17% taking HRT. RESULTS Women and men reported similar levels of HrQOL, life satisfaction and general health, although women reported more physical problems (SF-36). The significant predictors of HrQOL were serious illness, employment and marital status, but HRT use and menopausal status were not significantly associated with life satisfaction nor HrQOL (for women). CONCLUSIONS Gender differences in health and HrQOL may be less apparent during mid-life, although there were some subtle differences between men and women in reported health concerns and reasons given for (dis)satisfaction with their lives.
Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae)

Protozoan parasites belonging to genera Leishmania and Trypanosoma are the etiological agents of severe neglected tropical diseases (NTDs) that cause enormous social and economic impact in many countries of tropical and sub-tropical areas of the world. In our screening program for new drug leads from natural sources, we found that the crude extract of the endophytic fungus Cochliobolus sp. (UFMGCB-555) could kill 90% of the amastigote-like forms of Leishmania amazonensis and inhibit by 100% Ellman's reagent reduction in the trypanothione reductase (TryR) assay, when tested at 20 µg mL−1. UFMGCB-555 was isolated from the plant Piptadenia adiantoides J.F. Macbr (Fabaceae) and identified based on the sequence of the internally transcribed spacer (ITS) regions of its ribosomal DNA. The chromatographic fractionation of the extract was guided by the TryR assay and resulted in the isolation of cochlioquinone A and isocochlioquinone A. Both compounds were active in the assay with L. amazonensis, disclosing EC50 values (effective concentrations required to kill 50% of the parasite) of 1.7 µM (95% confidence interval = 1.6 to 1.9 µM) and 4.1 µM (95% confidence interval = 3.6 to 4.7 µM), respectively. These compounds were not active against three human cancer cell lines (MCF-7, TK-10, and UACC-62), indicating some degree of selectivity towards the parasites. These results suggest that cochlioquinones are attractive lead compounds that deserve further investigation aiming at developing new drugs to treat leishmaniasis. The findings also reinforce the role of endophytic fungi as an important source of compounds with potential to enter the pipeline for drug development against NTDs.
Bioassay-guided fractionation and identification of α-amylase inhibitors from Syzygium cumini leaves

Abstract Context: Pancreatic α-amylase and α-glucosidase inhibitors serve as important strategies in the management of blood glucose. Even though Syzygium cumini (L.) Skeels (Myrtaceae) (SC) is used extensively to treat diabetes; scientific evidence on antidiabetic effects of SC leaves is scarce. Objective: SC leaf extract was investigated for α-amylase inhibitory effect and continued with isolation and identification of α-amylase inhibitors. Materials and methods: Bioassay-guided fractionation was conducted using in vitro α-amylase inhibitory assay (with 20–1000 μg/mL test material) to isolate the inhibitory compounds from ethyl acetate extract of SC leaves. Structures of the isolated inhibitory compounds were elucidated using 1H NMR and 13C NMR spectroscopic analysis and direct TLC and HPLC comparison with authentic samples. Study period was from October 2013 to October 2015. Results: An active fraction obtained with chromatographic separation of the extract inhibited porcine pancreatic α-amylase with an IC50 of 39.9 μg/mL. Furthermore, it showed a strong inhibition on α-glucosidase with an IC50 of 28.2 μg/mL. The active fraction was determined to be a 3:1 mixture of ursolic acid and oleanolic acid. Pure ursolic acid and oleanolic acid showed IC50 values of 6.7 and 57.4 μg/mL, respectively, against α-amylase and 3.1 and 44.1 μg/mL respectively, against α-glucosidase. Discussion and conclusions: The present study revealed strong α-amylase and α-glucosidase inhibitory effects of ursolic acid and oleanolic acid isolated from SC leaves for the first time validating the use of SC leaves in antidiabetic therapy.
Improved Modeling of In Vivo Kinetics of Slowly Diffusing Radiotracers for Tumor Imaging

Large-molecule tracers, such as labeled antibodies, have shown success in immuno-PET for imaging of specific cell surface biomarkers. However, previous work has shown that localization of such tracers shows high levels of heterogeneity in target tissues, due to both the slow diffusion and the high affinity of these compounds. In this work, we investigate the effects of subvoxel spatial heterogeneity on measured time–activity curves in PET imaging and the effects of ignoring diffusion limitation on parameter estimates from kinetic modeling. Methods: Partial differential equations (PDE) were built to model a radially symmetric reaction-diffusion equation describing the activity of immuno-PET tracers. The effects of slower diffusion on measured time–activity curves and parameter estimates were measured in silico, and a modified Levenberg–Marquardt algorithm with Bayesian priors was developed to accurately estimate parameters from diffusion-limited data. This algorithm was applied to immuno-PET data of mice implanted with prostate stem cell antigen–overexpressing tumors and injected with 124I-labeled A11 anti–prostate stem cell antigen minibody. Results: Slow diffusion of tracers in linear binding models resulted in heterogeneous localization in silico but no measurable differences in time–activity curves. For more realistic saturable binding models, measured time–activity curves were strongly dependent on diffusion rates of the tracers. Fitting diffusion-limited data with regular compartmental models led to parameter estimate bias in an excess of 1,000% of true values, while the new model and fitting protocol could accurately measure kinetics in silico. In vivo imaging data were also fit well by the new PDE model, with estimates of the dissociation constant (Kd) and receptor density close to in vitro measurements and with order of magnitude differences from a regular compartmental model ignoring tracer diffusion limitation. Conclusion: Heterogeneous localization of large, high-affinity compounds can lead to large differences in measured time–activity curves in immuno-PET imaging, and ignoring diffusion limitations can lead to large errors in kinetic parameter estimates. Modeling of these systems with PDE models with Bayesian priors is necessary for quantitative in vivo measurements of kinetics of slow-diffusion tracers.
Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line

This review article addresses the biological factors that influence: (i) the acquisition of alcohol intake; (ii) the maintenance of chronic alcohol intake; and (iii) alcohol relapse-like drinking behavior in animals bred for their high-ethanol intake. Data from several rat strains/lines strongly suggest that catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute requirement (up 80%–95%) for rats to display ethanol’s reinforcing effects and to initiate chronic ethanol intake. Acetaldehyde binds non-enzymatically to dopamine forming salsolinol, a compound that is self-administered. In UChB rats, salsolinol: (a) generates marked sensitization to the motivational effects of ethanol; and (b) strongly promotes binge-like drinking. The specificity of salsolinol actions is shown by the finding that only the R-salsolinol enantiomer but not S-salsolinol accounted for the latter effects. Inhibition of brain acetaldehyde synthesis does not influence the maintenance of chronic ethanol intake. However, a prolonged ethanol withdrawal partly returns the requirement for acetaldehyde synthesis/levels both on chronic ethanol intake and on alcohol relapse-like drinking. Chronic ethanol intake, involving the action of lipopolysaccharide diffusing from the gut, and likely oxygen radical generated upon catechol/salsolinol oxidation, leads to oxidative stress and neuro-inflammation, known to potentiate each other. Data show that the administration of N-acetyl cysteine (NAC) a strong antioxidant inhibits chronic ethanol maintenance by 60%–70%, without inhibiting its initial intake. Intra-cerebroventricular administration of mesenchymal stem cells (MSCs), known to release anti-inflammatory cytokines, to elevate superoxide dismutase levels and to reverse ethanol-induced hippocampal injury and cognitive deficits, also inhibited chronic ethanol maintenance; further, relapse-like ethanol drinking was inhibited up to 85% for 40 days following intracerebral stem cell administration. Thus: (i) ethanol must be metabolized intracerebrally into acetaldehyde, and further into salsolinol, which appear responsible for promoting the acquisition of the early reinforcing effects of ethanol; (ii) acetaldehyde is not responsible for the maintenance of chronic ethanol intake, while other mechanisms are indicated; (iii) the systemic administration of NAC, a strong antioxidant markedly inhibits the maintenance of chronic ethanol intake; and (iv) the intra-cerebroventricular administration of anti-inflammatory and antioxidant MSCs inhibit both the maintenance of chronic ethanol intake and relapse-like drinking.
Analysis of a sleep-dependent neuronal feedback loop: the slow-wave microcontinuity of the EEG

Increasing depth of sleep corresponds to an increasing gain in the neuronal feedback loops that generate the low-frequency (slow-wave) electroencephalogram (EEG). The authors derived the maximum-likelihood estimator of the feedback gain and applied it to quantify sleep depth. The estimator computes the fraction (0%-100%) of the current slow wave which continues in the near future (0.02 s later) EEG. Therefore, this percentage was dubbed slow-wave microconfinuity (SW%). It is not affected by anatomical parameters such as skull thickness, which can considerably bias the commonly used slow-wave power (SWP). In the authors' study, both of the estimators SW% and SWP were monitored throughout two nights in 22 subjects. Each subject took temazepam (a benzodiazepine) on one of the two nights, Both estimators detected the effects of age, temazepam, and time of night on sleep. Females were found to have twice the SWP of males, but no gender effect on SW% was found. This confirms earlier reports that gender affects SWP but not sleep depth. Subjectively assessed differences in sleep quality between the nights were correlated to differences in SW%, not in SWP. These results demonstrate that slow-wave microcontinuity, being based on a physiological model of sleep, reflects sleep depth more closely than SWP does.
A 780–950 MHz, 64–146 µW Power-Scalable Synchronized-Switching OOK Receiver for Wireless Event-Driven Applications

An on/off keying receiver has been designed in 90 nm CMOS for low-power event-driven applications. Thanks to the synchronized-switching technique and power-efficient RF gain stages, this receiver achieves -86 dBm sensitivity (10 -3 bit error rate) at 10 kbps while consuming 123 μW from a 1 V supply. The receiver is highly scalable in data rates from 1 kbps at 64 μW to 100 kbps at 146 μW power consumption. The center frequency of the receiver can be also programmed from 780 to 950 MHz, covering different sub-GHz bands worldwide. The receiver is fully integrated, although an external SAW filter can be added for better selectivity.
Sour Taste Responses in Mice Lacking PKD Channels

Background The polycystic kidney disease-like ion channel PKD2L1 and its associated partner PKD1L3 are potential candidates for sour taste receptors. PKD2L1 is expressed in type III taste cells that respond to sour stimuli and genetic elimination of cells expressing PKD2L1 substantially reduces chorda tympani nerve responses to sour taste stimuli. However, the contribution of PKD2L1 and PKD1L3 to sour taste responses remains unclear. Methodology/Principal Findings We made mice lacking PKD2L1 and/or PKD1L3 gene and investigated whole nerve responses to taste stimuli in the chorda tympani or the glossopharyngeal nerve and taste responses in type III taste cells. In mice lacking PKD2L1 gene, chorda tympani nerve responses to sour, but not sweet, salty, bitter, and umami tastants were reduced by 25–45% compared with those in wild type mice. In contrast, chorda tympani nerve responses in PKD1L3 knock-out mice and glossopharyngeal nerve responses in single- and double-knock-out mice were similar to those in wild type mice. Sour taste responses of type III fungiform taste cells (GAD67-expressing taste cells) were also reduced by 25–45% by elimination of PKD2L1. Conclusions/Significance These findings suggest that PKD2L1 partly contributes to sour taste responses in mice and that receptors other than PKDs would be involved in sour detection.