Miracle-dz/UniFAR-FTUs huggingface dataset:
Intestinal carcinogenesis of two food processing contaminants, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine and 5‐hydroxymethylfurfural, in transgenic FVB min mice expressing human sulfotransferases

Humans express sulfotransferases (SULTs) of the SULT1A subfamily in many tissues, whilst the single SULT1A gene present in rodents is mainly expressed in liver. The food processing contaminants, 5‐hydroxymethylfurfural (HMF) and 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), are bioactivated by human SULT1A1 and SULT1A2. FVB multiple intestinal neoplasia (Min) mice, which spontaneously develop tumors and flat aberrant crypt foci (ACF) in intestine, were crossed with transgenic FVB mice expressing human SULT1A1 and 1A2 (hSULT) in several tissues, giving rise to wild‐type and Min mice with and without hSULT. One‐week‐old Min mice with or without hSULT were given HMF (375 or 750 mg/kg bw) or saline by gavage three times a week for 11 wk. In another experiment, the F1 generation received subcutaneous injections of 50 mg/kg bw PhIP or saline 1 wk before birth, and 1, 2, and 3 wk after birth. HMF did not affect the formation of tumors, but may have induced some flat ACF (incidence 15–20%) in Min mice with and without hSULT. No control mouse developed any flat ACF. With the limitation that these putative effects were weak, they were unaffected by hSULT expression. The carcinogenic effect of PhIP increased in the presence of hSULT, with a significant increase in both incidence (31–80%) and number of colonic tumors (0.4–1.3 per animal). Thus, intestinal expression of human SULT1A1 and 1A2 might increase the susceptibility to compounds bioactivated via this pathway implying that humans might be more susceptible than conventional rodent models. © 2011 Wiley Periodicals, Inc.
How Much Force Is Required to Dislodge an Alternate Airway?

Abstract Introduction. Endotracheal tube (ETT) dislodgment is a potentially catastrophic adverse event. Newer alternate airway devices—esophageal-tracheal Combitube (ETC), King laryngeal tube disposable airway (King LT), and laryngeal mask airway (LMA)—are easier to insert, but their relative extubating forces remain unknown. Objective. To examine the applied forces required to dislodge an ETC, King LT, LMA, and ETT. Methods. We used five recently deceased adult unembalmed cadavers. In random order, we sequentially inserted an ETC, King LT, LMA, and standard ETT. Because commercial tube holders are not designed for all alternate airways, we secured the devices with a standard adhesive tape method. Using a precision digital force measuring device, we measured the minimum manually applied axial force (lb) that dislodged each airway device at least 4 cm. We compared required dislodgment forces between airway devices using a mixed-effects regression model, adjusting for cadaver height, weight, neck circumference, and thyromental distance. Results. Characteristics of the cadavers were as follows (median, interquartile range [IQR]): height 172 cm (167–177), weight 98 kg (84–120), neck circumference 46.5 cm (41–52), and thyromental distance 7.5 cm (7.5–8). Required axial dislodgment forces for each airway device were as follows (median, IQR): ETC 28.3 lb (19.0–28.6), King LT 12.5 lb (11.7–13.3), LMA 18.3 lb (14.0–21.9), and ETT 14.4 lb (13.5-22.1). The ETC required twice as much dislodgment force as the ETT (adjusted difference 16.7 lb, 95% confidence interval [CI]: 8.3 to 25.1). The King LT and LMA dislodgment forces were similar to that of the ETT (King LT vs. ETT adjusted difference 5.9 lb, 95% CI: –2.4 to 14.2; LMA vs. ETT 8.1 lb, 95% CI: –0.2 to 16.5). Conclusion. In a cadaver model of unintended airway dislodgment, the ETC required the most force for dislodgment. The King LT and LMA performed similarly to a standard ETT.
Dmon1 controls recruitment of Rab7 to maturing endosomes in Drosophila

Summary The small GTPases Rab5 and Rab7 are important organisers of endosome formation and maturation. In addition, they orchestrate the trafficking of cargo through the endosomal pathway. A crucial event during maturation of endosomes is the replacement of the early organiser Rab5 with the late organiser Rab7 in a process called Rab conversion. Rab conversion is a prerequisite for late events, chief among them the fusion of matured endosomes with the lysosome. Recent work identifies members of the Sand1/Mon1 protein family as crucial factors during this process. Here, we present an analysis of the function of the Drosophila ortholog of mon1/sand1, Dmon1. We found that loss of function of Dmon1 results in an enlargement of maturing endosomes and loss of their association with Rab7. The enlarged endosomes contain Notch and other trans-membrane proteins as cargo. We report the first electron microscopy analysis of Dmon1 cells in a metazoan and extend the analysis of the endosomes in mutant cells. Our results suggest that the phenotype can be explained by the loss of function of Rab7. Moreover, the endosomes of Dmon1 cells mature normally in many aspects, despite the loss of association with Rab7. Surprisingly, we did not observe overactive or ectopic signalling through receptors such as Notch and RTKs in Dmon1 mutant cells, as would have been expected because of the accumulation of receptors in the maturing endosomes of these cells. This was the case even when receptor uptake into intraluminal vesicles was suppressed.
Selective IL-2 Responsiveness of Regulatory T Cells Through Multiple Intrinsic Mechanisms Supports the Use of Low-Dose IL-2 Therapy in Type 1 Diabetes

Low-dose interleukin-2 (IL-2) inhibited unwanted immune responses in several clinical settings and is currently being tested in patients with type 1 diabetes (T1D). Low-dose IL-2 selectively targets regulatory T cells (Tregs), but the mechanisms underlying this selectivity are poorly understood. We show that IL-2–dependent STAT5 activation in Tregs from healthy individuals and patients with T1D occurred at an ∼10-fold lower concentration of IL-2 than that required by T memory (TM) cells or by in vitro–activated T cells. This selective Treg responsiveness is explained by their higher expression of IL-2 receptor subunit α (IL-2Rα) and γ chain and also endogenous serine/threonine phosphatase protein phosphates 1 and/or 2A activity. Genome-wide profiling identified an IL-2–dependent transcriptome in human Tregs. Quantitative assessment of selected targets indicated that most were optimally activated by a 100-fold lower concentration of IL-2 in Tregs versus CD4+ TM cells. Two such targets were selectively increased in Tregs from T1D patients undergoing low-dose IL-2 therapy. Thus, human Tregs possess an IL-2–dependent transcriptional amplification mechanism that widens their selective responses to low IL-2. Our findings support a model where low-dose IL-2 selectively activates Tregs to broadly induce their IL-2/IL-2R gene program and provide a molecular underpinning for low-dose IL-2 therapy to enhance Tregs for immune tolerance in T1D.
Hippocampus 5‐HT1A‐receptors attenuate cocaine‐induced hyperlocomotion and the increase in hippocampal but not nucleus accumbens 5‐HT

Cocaine induces an increase in hippocampal and nucleus accumbens (Nac) serotonin (5‐HT) concentration parallel to locomotor activation. Both effects can be modulated by systemic 5‐HT1A‐receptor agonism/antagonism. Given the contribution of the hippocampus to spontaneous behavioral activity, these observations suggest a role for hippocampal 5‐HT as well in the modulation of cocaine effects on behavior. To determine the role of hippocampal 5‐HT1A‐receptors in cocaine effects on behavior and hippocampal 5‐HT release, we used in vivo microdialysis in freely moving rats. The 5‐HT1A‐receptor agonist, 8‐OH‐DPAT (0, 0.1, 1 and 10 μM), was applied locally into the hippocampus by reversed dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The hippocampal 5‐HT1A‐receptor activation attenuated cocaine‐induced hyperlocomotion and rearing behavior dose‐dependently. Parallel to that, the cocaine‐induced 5‐HT increase was attenuated dose‐dependently in the hippocampus but was left unaffected in the Nac. The intra‐hippocampal application of 8‐OH‐DPAT affected neither behavioral activity nor 5‐HT concentration in the hippocampus and in the Nac. In accord with these findings, hippocampal 5‐HT1A‐receptors may not be directly involved in the regulation of spontaneous behavior or basal 5‐HT concentration in the hippocampus and Nac. However, the results indicate an inhibitory role of hippocampal 5‐HT1A‐receptors in cocaine‐induced hyperactivity and in the 5‐HT increase evoked by cocaine in the hippocampus but not in the Nac. © 2004 Wiley‐Liss, Inc.
Usefulness of pulsed tissue Doppler for the assessment of left ventricular myocardial function in overt hypothyroidism.

BACKGROUND The aim of this study was to assess the role of tissue Doppler (TD) in the identification of left ventricular (LV) myocardial regionl abnormalities in overt hypothyroidism. METHODS Fourteen women with newly diagnosed, never treated overt hypothyroidism and 14 healthy women, matched for age, underwent standard echocardiography and pulsed TD, by placing the sample volume at the basal posterior septum and lateral mitral annulus, in the apical 4-chamber view. The myocardial systolic (SM) and diastolic velocities (Em, Am and their ratio) and time intervals (relaxation time [RTm], pre-contraction time [PCTm], contraction time) were measured. RESULTS The two groups were comparable for body surface area, blood pressure and heart rate. At standard echocardiography, patients with overt hypothyroidism had a significantly greater septal thickness and LV mass index, a longer LV pre-ejection period (PEP), deceleration time and isovolumic relaxation time (IVRT) and a lower E peak velocity and E/A ratio. TD showed a significantly longer PCTm and RTm and a lower Em and Em/Am ratio of both the septum and mitral annulus in overt hypothyroidism. The ratio of the standard Doppler E to Em of the mitral annulus was 5.5 +/- 1.2 in controls and 5.3 +/- 1.7 in overt hypothyroidism (p = NS). In the overall population, PEP, IVRT, PCTm and RTm were correlated negatively with FT3 and FT4, and positively with thyroid-stimulating hormone. After adjusting for age, body surface area and heart rate in separate multivariate analyses, the associations of TD PCTm with the thyroid hormones and thyroid-stimulating hormone were greater than the homologous associations of standard Doppler PEP. CONCLUSIONS Standard echocardiography confirms itself as a satisfactory diagnostic technique for the identification of LV global dysfunction in overt hypothyroidism. Pulsed TD may be useful to determine the severity of LV myocardial dysfunction in relation to the degree of hormonal impairment.
Robust Serial Nanocommunication With QCA

We present a serial communication system implemented as quantum-dot cellular automata (QCA). QCA is a promising alternative to the current CMOS technology. It can be implemented at the nanoscale, reaching ultra-low power consumption and high clock rate. Communication systems are important in current computer systems and it is expected to be even more important in near future. Although QCA has been widely studied in the development of logic circuits, there are few studies applying this promising technology to the design of communication systems. In a bottom-up approach, we describe the parallel-to-serial and serial-to-parallel converters, which are essential to the serial communication. We also propose and present components for robust communication, such as QCA circuits for Hamming code and parity checker. We demonstrate the functionality, test and validate the proposed architectures using QCADesigner simulator. Due to the importance of communication systems, this study is central in consolidating QCA as a possible CMOS substitute.
Outbreaks of infection caused by community-acquired methicillin-resistant Staphylococcus aureus in a Canadian correctional facility.

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) has been identified in prison settings in the United States. The present study investigated two clusters of skin and soft tissue infection caused by community-acquired (CA) MRSA in a correctional facility in southern Ontario. METHODS Outbreak investigations were conducted by the responsible public health authority. Strain relatedness was assessed through comparison of pulsed-field gel electrophoresis and antibiograms. RESULTS Two distinct outbreaks of CAMRSA-associated disease occurred in 2002 and 2004. Most patients presented with abscesses in the lower extremities. All isolates had identical DNA banding patterns on pulsed-field gel electrophoresis. One-half of the affected inmates resided in a cellblock with one other affected inmate. No other risk factors were identified. CONCLUSIONS One of the first outbreaks of CAMRSA infections in a correctional facility in Canada is documented. Taken in conjunction with outbreaks elsewhere, this suggests that residence in correctional facilities may be a risk factor for CAMRSA infection.
Radiological scoring methods for ankylosing spondylitis: a comparison between the Bath Ankylosing Spondylitis Radiology Index and the modified Stoke Ankylosing Spondylitis Spine Score.

OBJECTIVE The main objective of the present study was to test the interobserver reliability, truth, discrimination and feasibility of two scoring methods available in ankylosing spondylitis (AS) over a follow-up period of 3 years. METHODS Two blinded trained observers scored 95 AS radiographs from a cohort of AS patients. Each radiograph was scored by two scoring methods, the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), and the Bath Ankylosing Spondylitis Radiology Index--spine (BASRI-spine). Interobserver agreement was analyzed by intraclass correlation coefficients (ICC). The construct validity was assessed by examining the correlation of the scoring methods with measures of spinal mobility (Bath Ankylosing Spondylitis Metronomy Index--BASMI), functional limitation (Bath Ankylosing Spondylitis Functional Index--BASFI) and disease duration. Bland and Altman's 95% limits of agreement method and effect size (ES) analysis were used to estimate the smallest detectable difference (SDD) of radiological progression and responsiveness. RESULTS The BASRI-spine reached intra- and interobserver ICC of 0.755 and 0.831, respectively. The mSASSS scores were more reliable, with ICC of 0.874 and 0.941, respectively. Both scoring systems correlated significantly with BASMI (p = 0.01), while only the mSASSS showed a significant correlation (p = 0.02) with BASFI. With regards to sensitivity to change, it was found that mSASSS classified the highest percentage of patients with more changes than the BASRI-spine (mSASSS: 35.8% vs. BASRI-spine: 15.8%). The ES analysis also suggested that the mSASSS was more responsive than BASRI-spine. Concerning feasibility, the BASRI-spine takes less time for scoring. CONCLUSION We have shown that the mSASSS offers advantages in measurement properties and is the most appropriate method by which to assess progression of structural damage in AS.
Assessment of Clinical Symptoms and Multichannel Intraluminal Impedance and pH Monitoring in Children After Thoracoscopic Repair of Esophageal Atresia and Distal Tracheoesophageal Fistula.

BACKGROUND Motility disturbances of the esophagus and gastroesophageal reflux disease (GERD) are observed frequently in children after repair of congenital esophageal atresia with distal tracheoesophageal fistula (EA/TEF). Recently, in many pediatric surgical centers, thoracoscopic repair was introduced, which theoretically would change the postoperative course. OBJECTIVES The goal of the study was to assess physical development, disease symptoms, and GERD symptom frequency in children who underwent thoracoscopic surgery of congenital EA/TEF. MATERIAL AND METHODS The study comprised 22 children (14 boys and 8 girls), aged 16 to 79 months (average age 47.3 months) after surgery of EA/TEF. Clinical symptoms and physical development were analyzed. In 19 children, multichannel intraluminal esophageal impedance connected with pH-metry (MII/pH) was performed. In 11 patients, esophagogastroduodenoscopy with a histological study of mucosa samples was done. RESULTS The most frequent symptoms were dysphagia, belching, cough and recurrent bronchitis. In 31.5% of the children, body mass deficiency was observed and in 28.6%, low body mass and short stature. Prematurity was present in half of the patients. Depending on the result of the MII/pH study, the children were divided into two groups: 10 children with GERD and 9 children without diagnosis of gastroesophageal reflux. In the 10 with GERD, acid reflux was diagnosed in 9 and non-acid reflux was diagnosed in one. MII/pH demonstrated statistically significant differences in the number of reflux episodes, reflux index, bolus exposure index, mean time of esophageal exposure and acid exposure and mean acid clearance time in children with GERD in comparison to children without this disease. In 36.4% of children who underwent endoscopy, esophagitis was diagnosed, esophageal stricture in 18% and gastric metaplasia in 9.1%. CONCLUSIONS In children who underwent corrective thoracoscopic surgery of EA/TEF, GERD caused by motility disorders of the esophagus was frequently observed. These children require constant monitoring and early treatment of the complication.
Self-assessment of communication skills preparedness: adult versus pediatric skills.

PURPOSE To characterize and compare incoming residents' self-reported 1) amount and sufficiency of medical school training in clinical communication for patients of different ages, and 2) training experience and anticipated comfort level when breaking news of serious diagnoses with patients of different ages. METHOD A self-assessment tool was voluntarily completed by residents entering Brown- and Dartmouth-affiliated residencies. Descriptive statistics were generated and 2-tailed t tests were used to compare mean responses for patient age categories within each area of questioning. RESULTS A total of 143 (78%) of 184 residents completed self-assessments. Estimates of training time with adult patients were greater than any other patient age category and were rated most sufficient. Twelve percent and 11% of respondents reported no formal training in pediatric and adolescent skills, respectively, and more than half reported that they had never observed a pediatric or adolescent "bad news" interaction. Half of the respondents had personally informed a patient or family of a serious diagnosis, most often concerning middle-aged or elderly patients. Respondents anticipated greatest discomfort discussing serious illness in younger patients and least discomfort discussing serious illness in adult and elderly patients. CONCLUSIONS Residents feel less prepared for and receive less training in general communication skills, particularly skills required for delivering bad news, in pediatric clinical interactions as compared with interactions with adult patients. Additional formalized training in communication skills and strategies for breaking bad news to pediatric and adolescent patients may be warranted.
Trade and Geography in the Spread of Islam

In this study we explore the historical determinants of contemporary Muslim representation. Motivated by a plethora of case studies and historical accounts among Islamicists stressing the role of trade for the adoption of Islam, we construct detailed data on pre-Islamic trade routes, harbors, and ports to determine the empirical regularity of this argument. Our analysis - conducted across countries and across ethnic groups within countries - establishes that proximity to the pre-600 CE trade network is a robust predictor of today's Muslim adherence in the Old World. We also show that Islam spread successfully in regions that are ecologically similar to the birthplace of the religion, the Arabian Peninsula. Namely, territories characterized by a large share of arid and semiarid regions dotted with few pockets of fertile land are more likely to host Muslim communities. We discuss the various mechanisms that may give rise to the observed pattern.
Agonist-stimulated β-Adrenergic Receptor Internalization Requires Dynamic Cytoskeletal Actin Turnover*

Stimulation of β-adrenergic receptors (βARs) leads to sequential recruitment of β-arrestin, AP-2 adaptor protein, clathrin, and dynamin to the receptor complex, resulting in endocytosis. Whether a dynamic actin cytoskeleton is required for βAR endocytosis is not known. In this study, we have used β1- and β2 ARs, two ubiquitously expressed members of the βAR family, to comprehensively evaluate the requirement of the actin cytoskeleton in receptor internalization. The integrity of the actin cytoskeleton was manipulated with the agent latrunculin B (LB) and mutants of cofilin to depolymerize actin filaments. Treatment of cells with LB resulted in dose-dependent depolymerization of the cortical actin cytoskeleton that was associated with significant attenuation in internalization of β2ARs, β1ARs, and mutants of β1ARs that internalize via either clathrin- or caveolin-dependent pathways. Importantly, LB treatment did not inhibit β-arrestin translocation or dynamin recruitment to the agonist-stimulated receptor. To unequivocally demonstrate the requirement of the actin cytoskeleton for β2AR endocytosis, we used an actin-binding protein cofilin that biochemically depolymerizes and severs actin filaments. Isoproterenol-mediated internalization of β2AR was completely blocked in the presence of wild type cofilin, which could be rescued by a mutant of cofilin that mimics a constitutive phosphorylated state and leads to normal agonist-stimulated β2AR endocytosis. Finally, treatment with jasplakinolide, an inhibitor of actin turnover, resulted in dose-dependent inhibition of β2AR internalization, suggesting that turnover of actin filaments at the receptor complex is required for endocytosis. Taken together, these data demonstrate that intact and functional dynamic actin cytoskeleton is required for normal βAR internalization.
Study of Transient Spark Discharge Properties Using Kinetic Modeling

The kinetic model simulating plasma chemistry induced by Transient Spark (TS) discharge in air is presented in this paper. TS is a dc-driven self-pulsing discharge of streamer-to-spark transition type. The presented kinetic model defines the temporal evolution of reduced electric field strength E/N, gas temperature, and density of neutrals N during the evolution of TS discharge, so that calculated electron density is in agreement with experimental results. We studied the mechanism of the streamer-to-spark transition and breakdown in TS using this model. We assume that the breakdown mechanism in TS is based on the gas density decrease and can be summarized as follows: heating of the channel → increase in the pressure → hydrodynamic expansion → decrease in N in the core of the channel → increase in E/N → acceleration of ionization processes. However, this mechanism is influenced by species accumulated due to previous TS pulses at higher TS repetition frequencies. Sensitivity analysis focused on major electron loss and production processes indicates an important role of the amount of O2 dissociated by the previous pulses. A lower density of O2 means a lower rate of electron attachment, while accumulated atomic oxygen atoms lead to acceleration of electron detachment processes.