Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitoxantrone Inhibits HIF-1α Expression in a Topoisomerase II–Independent Pathway

Purpose: Solid tumors encounter a growth-limiting hypoxic microenvironment as they develop. Hypoxia-inducible factors (HIF) play important roles in hypoxia-associated tumor development and therapeutic resistance. Targeting the HIF pathway (especially HIF-1α) represents a promising cancer treatment strategy. Here, we report a novel class of HIF-1α inhibitors and the possible molecular basis of inhibition. Experimental Design: We analyzed the inhibitory effects of clinically used topoisomerase II (TOP2)–targeting drugs on HIF-1α expression with a primary focus on mitoxantrone. The potential role of TOP2 in mitoxantrone-inhibited HIF-1α expression was studied using pharmacologic inhibition, a knockdown approach, and TOP2 mutant cells. Moreover, involvement of mitoxantrone in proteasome-mediated degradation, transcription, and translation of HIF-1α was examined. Results: The TOP2-targeting mitoxantrone, but neither doxorubicin nor etoposide (VP-16), strongly inhibited HIF-1α expression under hypoxic conditions in a dose- and time-dependent manner. Surprisingly, the mitoxantrone-mediated inhibition of HIF-1α expression was largely independent of two TOP2 isozymes, proteasomal degradation, and transcription. Furthermore, mitoxantrone inhibited HIF-1α expression and function in a similar fashion as cycloheximide, suggesting that mitoxantrone might inhibit HIF-1α via a blockage at its translation step. In vitro translation experiments using HIF-1α mRNA further confirmed inhibition of HIF-1α translation by mitoxantrone. Interestingly, levels of the polysome-bound HIF-1α and VEGF-A mRNA were elevated and decreased after mitoxantrone treatment, respectively. Conclusions: We have identified the TOP2-targeting compound, mitoxantrone, as an HIF-1α inhibitor possibly through a translation inhibition mechanism, suggesting the possibility of an additional anticancer activity for mitoxantrone. Clin Cancer Res; 17(15); 5026–37. ©2011 AACR.
Responses of leaf nitrogen and mobile carbohydrates in different Quercus species/provenances to moderate climate changes.

Global warming and shortage of water have been evidenced in the recent past and are predicted for the future. Climate change will inevitably have considerable impact on plant physiology, growth, productivity and forest ecosystem functions. The present study determined the effects of simulated daytime air warming (+1 to 1.5 °C during the growing season), drought (-40% and -57% of mean precipitation of 728 mm during the 2007 and 2008 growing season, respectively) and their combination, on leaf nitrogen (N) and non-structural carbohydrates (NSC) of two Quercus species (Q. robur and Q. petraea) and provenances (two provenances for each species) grown in two soil types in Switzerland across two treatment years, to test the hypothesis that leaf N and NSC in the more water-sensitive species (Q. robur) and provenances (originating from water-rich locations) will more strongly respond to global warming and water deficit, compared to those in the more drought-tolerant species (Q. petraea) or provenances. No species- and provenance-specific responses in leaf N and NSC to the climate treatment were found, indicating that the results failed to support our hypothesis. The between-species variation of leaf N and NSC concentrations mainly reflected differences in biology of the two species, and the between-provenance variation of N and NSC concentrations apparently mirrored the climate of their origins. Hence, we conclude that (i) the two Quercus species studied are somewhat insensitive, due to their distribution covering a wide geographical and climate range, to moderate climate change within Switzerland, and (ii) a moderate global warming of B1 scenario (IPCC 2007) will not, or at least less, negatively affect the N and carbon physiology in Q. robur and Q. petraea.
Hypertrophic Cardiomyopathy Comparison of Dual-Chamber Pacing Versus Septal Myectomy for the Treatment of Patients With Hypertrophic Obstructive Cardiomyopathy

RESULTS Baseline symptom status, left ventricular outflow tract gradients, exercise times and maximal oxygen consumption peak were similar between the two groups. Left ventricular outflow gradient was reduced from 76 6 57 to 9 6 17 mm Hg (p 5 0.0001) after myectomy, and from 77 6 61 to 55 6 39 mm Hg (p 5 0.07) after pacing (p 5 0.02 for comparison with myectomy). Ninety percent of myectomy patients experienced symptomatic improvement as compared with 47% in the pacing group. Exercise duration increased significantly from 6.6 6 2.8 to 8.7 6 3.0 min (p 5 0.0003) after myectomy compared with a change from 6.4 6 2.1 to 7.0 6 2.2 min (p 5 NS) in the pacing group. Maximal oxygen consumption increased from 19.4 6 6.4 to 22.2 6 6.5 ml/kg/min after myectomy (p 5 0.004), whereas the pacing group did not experience any significant change (19.6 6 6.5 vs. 20.1 6 6.5 ml/kg/min, p 5 NS).
Health at Birth, Parental Investments, and Academic Outcomes

This paper explores the relationship among health at birth, academic outcomes, and the potential role of parental investments using administrative panel data from Chile. Using detailed data on parental investments, we find that investments are compensatory regarding initial health, but not across twins. Twins fixed effects models estimate a persistent effect of birth weight on academic achievement, while ordinary least squares and siblings fixed effects models find this relationship to decline over time. We view these findings in the context of a model of human capital accumulation where parental investments respond to initial endowments and spill over to siblings.
Rotavirus in children with diarrhea in Tripoli, Libya

The most common cause of acute diarrhea in young children in developed and developing countries are rotaviruses. In developing countries, it is estimated that 20-70% of hospitalizations and close to one million children below the age of five die annually because of rotavirus infections. Of the seven groups (A-G) of rotaviruses, group A is usually the cause of rotavirus-associated diarrhea. Infections due to rotaviruses occur via the fecal-oral route. Previous studies from Libya showed that rotavirus is the leading cause of infectious diarrhea. However, these studies were carried out more than a decade ago. (Published: 18 February 2011) Citation: Libyan J Med 2011, 6 : 6041 - DOI: 10.3402/ljm.v6i0. 6041
Congestive heart failure as an initial manifestation of reninoma

Abstract Reninoma or juxtaglomerular cell tumor (JCT) of the kidney is a rare but curable cause of severe hypertension. We report a case of reninoma in an 18-year-old woman. Interestingly, she initially presented with dilated cardiomyopathy, without any relevant history or signs of hypertension. Malignant hypertension, one of the cardinal signs of JCT, did not become apparent in the patient until several months later. Following a thorough evaluation, we detected a small mass in the left renal cortex as well as elevated plasma renin activity, which suggested the presence of a renin-producing tumor in the kidney. The patient’s blood pressure and plasma renin activity rapidly declined after a successful laparoscopic partial nephrectomy. We postulate that hyperreninemic-hyperaldosteronism followed by fluid retention caused a sudden severe increase in ventricular afterload and subsequent congestive heart failure in this patient.
Diabetes and advanced glycation endproducts

Abstract. Vlassara H, Palace MR (Department of Geriatrics, Division of Experimental Diabetes and Ageing, Mount Sinai School of Medicine, and Department of Medicine, Division of Endocrinology, Mount Sinai School of Medicine, NY, USA). Diabetes and Advanced Glycation Endproducts. J Intern Med 2002; 251: 87–101.
Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial.

BACKGROUND Substantial loss of muscle mass occurs among men with AIDS wasting. OBJECTIVE To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting. DESIGN Randomized, controlled trial. SETTING University hospital. PATIENTS 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%). INTERVENTION In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks. MEASUREMENTS Cross-sectional muscle area and other indices of muscle mass. RESULTS Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052). CONCLUSIONS In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting.
Benzene Exposures Associated with Tasks Performed on Marine Vessels (Circa 1975 to 2000)

In this article, we assemble and synthesize the available industrial hygiene data that describe exposure during the marine transport of benzene-containing products in the United States and abroad. A total of 25 studies were identified and summarized. The measured airborne concentrations of benzene on marine vessels were found to vary depending on several key factors, including the job task, vessel characteristics, cargo type, and sample type and duration. Despite the differences in sampling strategies and benzene content of the liquids being transported, personal time-weighted-average benzene air concentrations typically ranged from 0.2–2.0 ppm during closed loading and 2–10 ppm during open loading operations. Benzene exposures during these activities are likely due to specific short-term tasks, such as connecting and disconnecting hoses and tank gauging and sampling. Similar concentrations of benzene have been reported in the pump room during marine loading operations and during tank cleaning activities in various settings. When compared with contemporaneous occupational health standards, our review indicates that most activities performed on marine vessels from the 1970s to 1990s usually did not result in benzene exposures that exceeded these standards. The information and data presented here may be useful for quantitatively estimating or reconstructing historical exposures during the marine transport of benzene-containing cargo if details about individual's work histories in the maritime industry are available.
Diet Mixing: Do Animals Integrate Growth or Resources across Temporal Heterogeneity?

Animals commonly experience spatial and temporal variation in resource quality, thus experiencing temporally variable diets. Methods for scaling up growth in component patches to long‐term growth across heterogeneity are seldom explicitly considered. Long‐term growth is sometimes considered to be a weighted average of growth rates on component diets (growth integration). However, if animals integrate resources across high‐ and low‐quality diets, their long‐term growth may be greater than predicted from diet‐specific growth rates (resource integration). We measured biomass growth rates of seven Daphnia species exposed to different types of diel variation in algal phosphorus (P) content. Support for resource integration was found for four of the seven species, which achieved near maximal growth when high‐P food was available for at least 12 h. In contrast, no support for resource integration was found for the other three species. These three species achieved only one‐half maximal growth rate under the same conditions and could be considered growth integrators. The type of integration could be predicted from the degree of stoichiometric homeostasis. Species with weak homeostatic regulation exhibited a capacity for resource integration. Resource integrators should have an advantage in heterogeneous environments.
Genetic drift of influenza A(H3N2) viruses during two consecutive seasons in 2011–2013 in Corsica, France

The 2011–2012 and 2012–2013 post‐pandemic influenza outbreaks were characterized by variability in the A(H3N2) influenza viruses, resulting in low to moderate vaccine effectiveness (VE). The aim of this study was to investigate the molecular evolution and vaccine strain match of the A(H3N2) influenza viruses, having been circulated throughout the population of the French Corsica Island in 2011–2012 and again in 2012–2013. Clinical samples from 31 patients with confirmed A(H3N2) influenza viruses were collected by general practitioners (GPs) over these two consecutive seasons. An analysis of genetic distance and antigenic drift was conducted. Based on a hemagglutinin (HA) aminoacid sequence analysis, the Corsican A(H3N2) viruses fell into the A/Victoria/208/2009 genetic clade, group 3. All influenza viruses were characterized by at least four fixed amino acid mutations which were: N145S (epitope A); Q156H and V186G (epitope B) Y219S (epitope D), with respect to the A/Perth/16/2009 (reference vaccine strain for the 2011–2012) and the A/Victoria/361/2011 (reference vaccine strain for the 2012–2013). Using the pepitope model, the percentages of the perfect match VE estimated against circulated strains declined within and between seasons, with estimations of <50%. Overall, these results seem to indicate an antigenic drift of the A(H3N2) influenza viruses which were circulated in Corsica. These findings highlight the importance of the continuous and careful surveillance of genetic changes in the HA domain during seasonal influenza epidemics, in order to provide information on newly emerging genetic variants. J. Med. Virol. 86:585–591, 2014. © 2013 Wiley Periodicals, Inc.
Blood-based assays to detect Mycobacterium bovis-infected cattle missed by tuberculin skin testing

BOVINE tuberculosis (tb) caused by the bacterial pathogen Mycobacterium bovis is a disease of economic and zoonotic importance. The control of bovine tb in the uk has primarily relied on the application of the single intradermal comparative tuberculin test (sictt) and the subsequent slaughter of
The validity of the Performance Environment Perception Scales : Environmental predictors of citizenship performance

This research examined the validity of the Performance Environment Perception Scales (PEPS), a new instrument designed to assess performance-relevant aspects of the work environment. A sample of 156 employees of an Australian university completed the PEPS and their supervisors rated their task and citizenship performance. Confirmatory Factor Analysis showed the PEPS to have a valid factor structure, and the PEPS were found to be significantly correlated with citizenship performance, but not with task performance. Although this finding is consistent with theoretical predictions, the PEPS are apparently the first measures of work environment perceptions that have confirmed this. Thus the PEPS show promise as measures for use in future research and organizational development projects that focus on relationships between the work environment and performance. Limitations of the research and implications for the validity of the PEPS, as well as for future research and practice, are discussed.
Linear FM chirp filters in pulse compression radars

Using a complex Fresnel integral algorithm, the authors extend results of other authors from a time-bandwidth product of 50 up to 720. They analyze a rectangular linear FM filter having a 300-MHz center frequency, 120-MHz bandwidth, and 6-μs dispersion time T. Two different methods of rectangular FM cosine square tapering are compared. In the first method, the tapers are of length T/12 at the two edges inside the dispersion time T, while in the second, tapers of length αT are added to the duration T (α=0.05 and 0.1). The results show that the skirt steepness, the sidelobe rejection, and the Gibbs ripples of the wave spectrum, as well as the reduction of insertion loss and the suppression of Fresnel ripples, are best at α=0.1.
Interleukin-6 potentiates neutrophil priming with platelet-activating factor.

BACKGROUND Polymorphonuclear neutrophil (PMN) priming appears to be an important event in the pathogenesis of hyperinflammatory states, resulting in adult respiratory distress syndrome or multiple organ failure. Interleukin-6 (IL-6) is an integral mediator of the acute stress response to injury and infection, but excessive and prolonged systemic levels have been associated with morbidity and mortality following trauma, burns, and elective surgery. We hypothesized that IL-6 primed PMNs for exaggerated cytotoxicity. However, we have been unable to directly prime PMNs for superoxide release with IL-6. OBJECTIVE To determine whether IL-6 acted in concert with another inflammatory mediator (platelet-activating factor [PAF]) to prime PMNs. METHODS Polymorphonuclear neutrophils isolated from healthy human donors were incubated for varying times with IL-6 (0.01 to 100 ng/mL), PAF (0.01 to 100 ng/mL), or a combination of IL-6 and PAF. Superoxide production was then measured with and without the addition of the PMN-activating formylpeptide formyl-methionyleucylphenylalanine. RESULTS Over the range of times (5 to 90 minutes) and doses tested, IL-6 did not prime PMNs, while PAF primed PMNs in a dose- and time-dependent manner. Interleukin 6 (10 ng/mL) combined with a nonpriming concentration of PAF (0.1 ng/mL) primed PMNs for superoxide production over a range of incubation times. CONCLUSION The inflammatory mediators IL-6 and PAF act synergistically to prime PMNs in vitro. This observation may begin to elucidate the mechanistic role of IL-6 in pathologic clinical states.
Evaluating Instantaneous Perfusion Responses of Parotid Glands to Gustatory Stimulation Using High-Temporal-Resolution Echo-Planar Diffusion-Weighted Imaging

BACKGROUND AND PURPOSE: Parotid glands secrete and empty saliva into the oral cavity rapidly after gustatory stimulation. However, the role of the temporal resolution of DWI in investigating parotid gland function remains uncertain. Our aim was to design a high-temporal-resolution echo-planar DWI pulse sequence and to evaluate the instantaneous MR perfusion responses of the parotid glands to gustatory stimulation. MATERIALS AND METHODS: This prospective study enrolled 21 healthy volunteers (M/F = 2:1; mean age, 45.2 ± 12.9 years). All participants underwent echo-planar DWI (total scan time, 304 seconds; temporal resolution, 4 s/scan) on a 1.5T MR imaging scanner. T2WI (b = 0 s/mm2) and DWI (b = 200 s/mm2) were qualitatively assessed. Signal intensity of the parotid glands on T2WI, DWI, and ADC was quantitatively analyzed. One-way ANOVA with post hoc group comparisons with Bonferroni correction was used for statistical analysis. P < . 05 was statistically significant. RESULTS: Almost perfect interobserver agreement was achieved (κ ≥ 0.656). The parotid glands had magnetic susceptibility artifacts in 14.3% (3 of 21) of volunteers during swallowing on DWI but were free from perceptible artifacts at the baseline and at the end of scans on all images. Increased ADC and reduced signal intensity of the parotid glands on T2WI and DWI occurred immediately after oral administration of lemon juice. Maximal signal change of ADC (24.8% ± 10.8%) was significantly higher than that of T2WI (−10.1% ± 5.2%, P < .001). The recovery ratio of ADC (100.71% ± 42.34%) was also significantly higher than that of T2WI (22.36% ± 15.54%, P < .001). CONCLUSIONS: Instantaneous parotid perfusion responses to gustatory stimulation can be quantified by ADC by using high-temporal-resolution echo-planar DWI.
Degree of ERK activation influences both positive and negative thymocyte selection

Considerable evidence suggests that the ERK pathway is required for positive but not negative thymocyte selection. Here, we report that ERK is highly activated in double‐positive (DP) thymocytes expressing an MHC class I‐restricted TCR (P14) in response to negatively selecting conditions, whereas ligands that trigger positive selection induced weaker ERK activation. Biochemical evidence also shows that death by neglect is associated with a further reduction in ERK activation. These findings are consistent with the affinity / avidity model of thymocyte selection. To further examine the role of ERK in negative selection we used the MEK‐1 inhitibor, PD98059, a specific pharmacological inhibitor of the ERK pathway. Biochemical data demonstrated a reduction of ERK activity by PD98059 in the presence of the negatively selecting ligand. Analysis of P14 TCR‐transgenic fetal thymic lobes cultured with PD98059 under negatively selecting conditions showed impaired clonal deletion of DP thymocytes and a concomitant increase in positive selection of functional mature, TCRhi transgenic T cells. This demonstrates that altering ERK activity switched negative to positive selection. Contrary to previous reports that show an exclusive role for ERK signaling in positive selection, our data demonstrate that negative selection is also sensitive to the degree of ERK activation.
Offense Trajectories, the Unfolding of Sexual and Non-Sexual Criminal Activity, and Sex Offense Characteristics of Adolescent Sex Offenders

The current study examines offending trajectories of adolescent sexual offenders (ASOs). Until recently, classification frameworks have not been designed to account for the heterogeneity of offending patterns in adolescence, how these are associated with the unfolding of sexual and non-sexual criminal activity, and whether and to what extent they are related to the characteristics of sex offenses in adolescence. The current study takes a longitudinal view of offending in adolescence by examining retrospective longitudinal data of 217 ASOs referred for treatment to a clinical service between 2001 and 2009 in Australia. General offending trajectories in adolescence were examined using semi-parametric group-based modeling, and compared according to non-violent non-sexual, violent-non-sexual, and sex offending criminal activity parameters (e.g., participation, onset, frequency, specialization/versatility) and the characteristics of the referral sexual offense. The results show distinct differences in the unfolding of sexual and non-sexual criminal activity along different offending trajectories of ASOs, and further, that these trajectories were differentially associated with the characteristics of the sexual offenses they committed.
Using Probabilistic Models of Document Retrieval without Relevance Information

Most probabilistic retrieval models incorporate information about the occurrence of index terms in relevant and non‐relevant documents. In this paper we consider the situation where no relevance information is available, that is, at the start of the search. Based on a probabilistic model, strategies are proposed for the initial search and an intermediate search. Retrieval experiments with the Cranfield collection of 1,400 documents show that this initial search strategy is better than conventional search strategies both in terms of retrieval effectiveness and in terms of the number of queries that retrieve relevant documents. The intermediate search is shown to be a useful substitute for a relevance feedback search. Experiments with queries that do not retrieve relevant documents at high rank positions indicate that a cluster search would be an effective alternative strategy.