In this paper, we propose a sentiment-based approach to investigate the temporal and spatiotemporal effects on tourists' emotions when visiting a city's tourist destinations. Our approach consists of ...four steps: data collection and preprocessing from social media; visitor origin identification; visit sentiment identification; and temporal and spatiotemporal analysis. The temporal and spatiotemporal dimensions include day of the year, season of the year, day of the week, location sentiment progression, enjoyment measure, and multi-location sentiment progression. We apply this approach to the city of Chicago using over eight million tweets. Results show that seasonal weather, as well as special days and activities like concerts, impact tourists' emotions. In addition, our analysis suggests that tourists experience greater levels of enjoyment in places such as observatories rather than zoos. Finally, we find that local and international visitors tend to convey negative sentiment when visiting more than one attraction in a day whereas the opposite holds for out of state visitors.
Increased microRNA-10b (miR-10b) expression in the cancer cells in pancreatic ductal adenocarcinoma (PDAC) is a marker of disease aggressiveness. In the present study, we determined that plasma ...miR-10b levels are significantly increased in PDAC patients by comparison with normal controls. By gene profiling, we identified potential targets downregulated by miR-10b, including Tat-interacting protein 30 (TIP30). Immunoblotting and luciferase reporter assays confirmed that TIP30 was a direct miR-10b target. Downregulation of TIP30 by miR-10b or siRNA-mediated silencing of TIP30 enhanced epidermal growth factor (EGF)-dependent invasion. The actions of miR-10b were abrogated by expressing a modified TIP30 cDNA resistant to miR-10b. EGF-induced EGF receptor (EGFR) tyrosine phosphorylation and extracellular signal-regulated kinase phosphorylation were enhanced by miR-10b, and these effects were mimicked by TIP30 silencing. The actions of EGF in the presence of miR-10b were blocked by EGFR kinase inhibition with erlotinib and by dual inhibition of PI3K (phosphatidylinositol 3'-kinase) and MEK. Moreover, miR-10b, EGF and transforming growth factor-beta (TGF-β) combined to markedly increase cell invasion, and this effect was blocked by the combination of erlotinib and SB505124, a type I TGF-β receptor inhibitor. miR-10b also enhanced the stimulatory effects of EGF and TGF-β on cell migration and epithelial-mesenchymal transition (EMT) and decreased the expression of RAP2A, EPHB2, KLF4 and NF1. Moreover, miR-10b overexpression accelerated pancreatic cancer cell (PCC) proliferation and tumor growth in an orthotopic model. Thus, plasma miR-10b levels may serve as a diagnostic marker in PDAC, whereas intra-tumoral miR-10b promotes PCC proliferation and invasion by suppressing TIP30, which enhances EGFR signaling, facilitates EGF-TGF-β cross-talk and enhances the expression of EMT-promoting genes, whereas decreasing the expression of several metastasis-suppressing genes. Therefore, therapeutic targeting of miR-10b in PDAC may interrupt growth-promoting deleterious EGF-TGF-β interactions and antagonize the metastatic process at various levels.
The aim of this paper is to provide a Bayesian formulation of the so-called magnitude-based inference approach to quantifying and interpreting effects, and in a case study example provide accurate ...probabilistic statements that correspond to the intended magnitude-based inferences. The model is described in the context of a published small-scale athlete study which employed a magnitude-based inference approach to compare the effect of two altitude training regimens (live high-train low (LHTL), and intermittent hypoxic exposure (IHE)) on running performance and blood measurements of elite triathletes. The posterior distributions, and corresponding point and interval estimates, for the parameters and associated effects and comparisons of interest, were estimated using Markov chain Monte Carlo simulations. The Bayesian analysis was shown to provide more direct probabilistic comparisons of treatments and able to identify small effects of interest. The approach avoided asymptotic assumptions and overcame issues such as multiple testing. Bayesian analysis of unscaled effects showed a probability of 0.96 that LHTL yields a substantially greater increase in hemoglobin mass than IHE, a 0.93 probability of a substantially greater improvement in running economy and a greater than 0.96 probability that both IHE and LHTL yield a substantially greater improvement in maximum blood lactate concentration compared to a Placebo. The conclusions are consistent with those obtained using a 'magnitude-based inference' approach that has been promoted in the field. The paper demonstrates that a fully Bayesian analysis is a simple and effective way of analysing small effects, providing a rich set of results that are straightforward to interpret in terms of probabilistic statements.
The aim of GRACE was to provide a large multinational registry of the full spectrum of patients with acute coronary syndromes (ACS) in order to define patient characteristics and outcomes and derive ...predictive risk scores. The study was designed and administered by an independent steering committee; data analyses were performed under the guidance of the steering committee at the Center for Outcomes Research of the University of Massachusetts. Regular feedback regarding local, regional and international guideline and performance measures was provided to individual hospitals and clusters of hospitals. Regional and international benchmark data were available to all sites. Main GRACE involved 123 hospitals in 14 countries in North and South America, Europe, Australia and New Zealand. GRACE2 (Expanded GRACE) comprised 154 hospitals in Europe, North and South America, Asia, Australasia and China. Continuous recruitment and follow-up took place between 1999 and 2009. The first 10 -20 patients per site (depending on hospital size) were enrolled each month, resulting in the recruitment of 102 341 patients, who were categorized as having ST-segment elevation myocardial infarction, non-ST-elevation myocardial infarction or unstable angina. Standardized case report forms (datafax or electronic) were completed by trained study coordinators, and included fields relating to demographic factors, comorbid conditions, treatments and in-hospital and post-discharge (6-month) events. Blood sampling, genetic analyses and longer-term follow-up were undertaken in GRACE substudies. Prospective individual patient follow-up was carried out. All sites were audited locally; 10% of individual patient records were audited in a 2-year cycle. Less than 1% of 20 key baseline fields, and less than 1% of discharge diagnosis and discharge status data, were missing. Six-month follow-up was 85% complete. Publications and risk scores are available at http://www.outcome.org/grace. Proposals for specific analyses were considered, in competition, by an independent publications committee.
To investigate the interaction between the development of peripheral locomotor muscle fatigue, muscle recruitment and performance during repeated-sprint exercise (RSE).
In a single-blind, randomised ...and cross-over design, ten male team-sport athletes performed two RSE (fifteen 5-s cycling sprints interspersed with 25 s of rest; power self-selected) in normoxia and in acute moderate hypoxia (FIO2 0.138). Mechanical work, total electromyographic intensity (summed quadriceps electromyograms, RMSsum) and muscle (vastus lateralis) and pre-fontal cortex near-infrared spectroscopy (NIRS) parameters were calculated for every sprint. Blood lactate concentration (Lac(-)) was measured throughout the protocol. Peripheral quadriceps fatigue was assessed via changes in potentiated quadriceps twitch force (ΔQtw,pot) pre- versus post-exercise in response to supra-maximal magnetic femoral nerve stimulation. The central activation ratio (QCAR) was used to quantify completeness of quadriceps activation.
Compared with normoxia, hypoxia reduced arterial oxygen saturation (-13.7%, P=0.001), quadriceps RMSsum (-13.7%, P=0.022), QCAR (-3.3%, P=0.041) and total mechanical work (-8.3%, P=0.019). However, the magnitude of quadriceps fatigue induced by RSE was similar in the two conditions (ΔQtw,pot: -53.5% and -55.1%, P=0.71). The lower cycling performance in hypoxia occurred despite similar metabolic (muscle NIRS parameters and blood Lac(-)) and functional (twitch and M-wave) muscle states.
Results suggest that the central nervous system regulates quadriceps muscle recruitment and, thereby, performance to limit the development of muscle fatigue during intermittent, short sprints. This finding highlights the complex interaction between muscular perturbations and neural adjustments during sprint exercise, and further supports the presence of pacing during intermittent sprint exercise.
Single institution series have demonstrated that obese patients have higher rates of wound infection and delayed graft function (DGF), but similar rates of graft survival. We used UNOS data to ...determine whether obesity affects outcome following renal transplantation.
From the UNOS database, we identified patients who underwent primary kidney‐only transplantation between 1997 and 1999. Recipient and donor body mass index (BMI) was categorized as underweight (BMI < 18.5), normal (BMI 18.5–24.9), overweight (BMI 25–29.9), obese (BMI 30–34.9) or morbidly obese (BMI ≥ 35). We correlated BMI with intermediate measures of graft outcome and overall graft survival, and created multivariate models to evaluate the independent effect of BMI on graft outcome, adjusting for factors known to affect graft success.
The study sample comprised 27 377 recipients. Older age, female sex, African American race and increased comorbidity were associated with obesity (p < 0.001). Compared with normal weight patients, morbid obesity was independently associated with an increased risk of DGF (p < 0.001), prolonged hospitalization (p < 0.001), acute rejection (p = 0.006) and decreased overall graft survival (p = 0.001). Donor BMI did not affect overall graft survival (p ≥ 0.07).
Recipient obesity is associated with an increased risk of DGF and decreased graft survival following renal transplantation.
For nearly a half century, cockroaches have been recognized as a major cause of asthma morbidity in the urban, inner-city environment. Several cockroach-produced allergens have been identified and ...characterized, and a few have been produced as recombinant proteins. Recent research has moved beyond clinical, patient-based investigations to a more entomological perspective that addresses the production, physiological regulation, and developmental expression of cockroach allergens, thus providing insight into their functional biology and their relationship to current cockroach control strategies. Although successful removal of cockroach allergens from the infested environment has been difficult to accomplish with remedial sanitation, large-scale reductions in cockroach allergens below clinically relevant thresholds have recently been realized through suppression of cockroach populations. Here we review the current understanding of cockroach allergen biology and the demographics associated with human exposure and sensitization. We also critically evaluate allergen mitigation studies from an entomological perspective, highlighting disparities between successful and failed attempts to lessen the cockroach allergen burden in homes.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with marked chemoresistance and a 5-year survival rate of 7%. The integrated stress response (ISR) is a cytoprotective pathway ...initiated in response to exposure to various environmental stimuli. We used pancreatic cancer cells (PCCs) that are highly resistant to gemcitabine (Gem) and an orthotopic mouse model to investigate the role of the ISR in Gem chemoresistance. Gem induced eIF2 phosphorylation and downstream transcription factors ATF4 and CHOP in PCCs, and these effects occurred in an eIF2α-S51 phosphorylation-dependent manner as determined using PANC-1 cells, and wild type and S51 mutant mouse embryo fibroblasts. Blocking the ISR pathway in PCCs with the ISR inhibitor ISRIB or siRNA-mediated depletion of ATF4 resulted in enhanced Gem-mediated apoptosis. Polyribosomal profiling revealed that Gem caused repression of global translation and this effect was reversed by ISRIB or by expressing GADD34 to facilitate eIF2 dephosphorylation. Moreover, Gem promoted preferential mRNA translation as determined in a TK-ATF4 5'UTR-Luciferase reporter assay, and this effect was also reversed by ISRIB. RNA-seq analysis revealed that Gem upregulated eIF2 and Nrf2 pathways, and that ISRIB significantly inhibited these pathways. Gem also induced the expression of the antiapoptotic factors Nupr1, BEX2, and Bcl2a1, whereas ISRIB reduced their expression. In an orthotopic tumor model using PANC-1 cells, ISRIB facilitated Gem-mediated increases in PARP cleavage, which occurred in conjunction with decreased tumor size. These findings indicate that Gem chemoresistance is enhanced by activating multiple ISR-dependent pathways, including eIF2, Nrf2, Nupr1, BEX2, and Bcl2A1. It is suggested that targeting the ISR pathway may be an efficient mechanism for enhancing therapeutic responsiveness to Gem in PDAC.
Ammonia borane (AB) is a candidate material for on-board hydrogen storage, and hydrolysis is one of the potential processes by which the hydrogen may be released. This paper presents hydrogen ...generation measurements from the hydrolysis of dilute AB aqueous solutions catalyzed by ruthenium supported on carbon. Reaction kinetics necessary for the design of hydrolysis reactors were derived from the measurements. The hydrolysis had reaction orders greater than zero but less than unity in the temperature range from 16
°C to 55
°C. A Langmuir–Hinshelwood kinetic model was adopted to interpret the data with parameters determined by a non-linear conjugate-gradient minimization algorithm. The ruthenium-catalyzed AB hydrolysis was found to have activation energy of 76
±
0.1
kJ
mol
−1 and adsorption energy of −42.3
±
0.33
kJ
mol
−1. The observed hydrogen release rates were 843
ml
H
2
min
−1 (g
catalyst)
−1 and 8327
ml
H
2
min
−1 (g
catalyst)
−1 at 25
°C and 55
°C, respectively. The hydrogen release from AB catalyzed by ruthenium supported on carbon is significantly faster than that catalyzed by cobalt supported on alumina. Finally, the kinetic rate of hydrogen release by AB hydrolysis is much faster than that of hydrogen release by base-stabilized sodium borohydride hydrolysis.
Hypoxic training techniques are increasingly used by athletes in an attempt to improve performance in normoxic environments. The 'live low-train high (LLTH)' model of hypoxic training may be of ...particular interest to athletes because LLTH protocols generally involve shorter hypoxic exposures (approximately two to five sessions per week of <3 h) than other traditional hypoxic training techniques (e.g., live high-train high or live high-train low). However, the methods employed in LLTH studies to date vary greatly with respect to exposure times, training intensities, training modalities, degrees of hypoxia and performance outcomes assessed. Whilst recent reviews provide some insight into how LLTH may be applied to enhance performance, little attention has been given to how training intensity/modality may specifically influence subsequent performance in normoxia. Therefore, this systematic review aims to evaluate the normoxic performance outcomes of the available LLTH literature, with a particular focus on training intensity and modality.
A systematic search was conducted to capture all LLTH studies with a matched normoxic (control) training group and the assessment of performance under normoxic conditions. Studies were excluded if no training was completed during the hypoxic exposures, or if these exposures exceeded 3 h per day. Four electronic databases were searched (PubMed, SPORTDiscus, EMBASE and Web of Science) during August 2013, and these searches were supplemented by additional manual searches until December 2013.
After the electronic and manual searches, 40 papers were deemed to meet the inclusion criteria, representing 31 separate studies. Within these 31 studies, four types of LLTH were identified: (1) continuous low-intensity training in hypoxia (CHT, n = 16), (2) interval hypoxic training (IHT, n = 4), (3) repeated sprint training in hypoxia (RSH, n = 3) and (4) resistance training in hypoxia (RTH, n = 4). Four studies also used a combination of CHT and IHT. The majority of studies reported no difference in normoxic performance between the hypoxic and normoxic training groups (n = 19), while nine reported greater improvements in the hypoxic group and three reported poorer outcomes compared with the control group. Selection of training intensity (including matching relative or absolute intensity between normoxic and hypoxic groups) was identified as a key factor in mediating the subsequent normoxic performance outcomes. Five studies included some form of normoxic training for the hypoxic group and 14 studies assessed performance outcomes not specific to the training intensity/modality completed during the training intervention.
Four modes of LLTH are identified in the current literature (CHT, IHT, RSH and RTH), with training mode and intensity appearing to be key factors in mediating subsequent performance responses in normoxia. Improvements in normoxic performance appear most likely following high-intensity, short-term and intermittent training (e.g., IHT, RSH). LLTH programmes should carefully apply the principles of training and testing specificity and include some high-intensity training in normoxia. For RTH, it is unclear whether the associated adaptations are greater than those of traditional (maximal) resistance training programmes.
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