Miracle-dz/UniFAR-FTUs huggingface dataset:
International Journal of Copd Dovepress Suppression of Il-8 Production from Airway Cells by Tiotropium Bromide in Vitro

Background: COPD is characterized by persistent and progressive airway inflammation. Although neutrophilic airway inflammation is generally accepted to be a major factor in the pathogenesis of COPD, the influence of the agents used for the treatment of COPD on neutrophil functions such as chemotaxis is not fully understood. Purpose: The present study aimed to examine the influence of tiotropium bromide on the production of interleukin (IL)-8 from human airway epithelial cells and lung fibroblasts (LFs) after lipopolysaccharide (LPS) stimulation in vitro. of 5 × 10 5 cells/mL, were stimulated with LPS in the presence of various concentrations of tiotropium bromide. IL-8 in culture supernatants was examined by enzyme-linked immuno-sorbent assay (ELISA). IL-8 messenger ribonucleic acid (mRNA) expression was examined by real-time polymerase chain reaction. The influence of tiotropium bromide on LPS-induced signaling pathways was also analyzed by examining nuclear factor-kappa (NF-κ)B activation and signaling protein phosphorylation by ELISA. Results: Tiotropium bromide at . 15 pg/mL inhibited IL-8 production from both BEAS-2B cells and LFs after LPS stimulation. Tiotropium bromide also suppressed IL-8 mRNA expression through the inhibition of NF-κB activation and signaling protein, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase, phosphorylation. Conclusion: The present results strongly suggest that tiotropium bromide exerts the inhibitory effect on neutrophilic inflammation through the suppression of IL-8 production from epithelial cells and LFs by interfering with LPS-mediated signaling pathways and thus may contribute to lower cellular inflammation in COPD, which is responsible for favorable modification of the disease.
Multivariate models for prediction of rheological characteristics of filamentous fermentation broth from the size distribution

The main purpose of this article is to demonstrate that principal component analysis (PCA) and partial least squares regression (PLSR) can be used to extract information from particle size distribution data and predict rheological properties. Samples from commercially relevant Aspergillus oryzae fermentations conducted in 550 L pilot scale tanks were characterized with respect to particle size distribution, biomass concentration, and rheological properties. The rheological properties were described using the Herschel–Bulkley model. Estimation of all three parameters in the Herschel–Bulkley model (yield stress (τy), consistency index (K), and flow behavior index (n)) resulted in a large standard deviation of the parameter estimates. The flow behavior index was not found to be correlated with any of the other measured variables and previous studies have suggested a constant value of the flow behavior index in filamentous fermentations. It was therefore chosen to fix this parameter to the average value thereby decreasing the standard deviation of the estimates of the remaining rheological parameters significantly. Using a PLSR model, a reasonable prediction of apparent viscosity (µapp), yield stress (τy), and consistency index (K), could be made from the size distributions, biomass concentration, and process information. This provides a predictive method with a high predictive power for the rheology of fermentation broth, and with the advantages over previous models that τy and K can be predicted as well as µapp. Validation on an independent test set yielded a root mean square error of 1.21 Pa for τy, 0.209 Pa sn for K, and 0.0288 Pa s for µapp, corresponding to R2 = 0.95, R2 = 0.94, and R2 = 0.95 respectively. Biotechnol. Bioeng. 2008;100: 61–71. © 2007 Wiley Periodicals, Inc.
Contribution of Early Weight Gain to Childhood Overweight and Metabolic Health: A Longitudinal Study (EarlyBird 36)

BACKGROUND. Early weight gain (0–5 years) is thought to be an important contributor to childhood obesity and consequently metabolic risk. There is a scarcity of longitudinal studies in contemporary children reporting the impact of early weight gain on metabolic health. OBJECTIVE. We aimed to assess the impact of early weight gain on metabolic health at 9 years of age. METHOD. Two hundred thirty-three children (134 boys, 99 girls) with a gestational age of >37 weeks were assessed at birth, 5 years of age, and 9 years of age. Measures included weight SD scores at each time point and excess weight gained (Δ weight SD score) between them. The outcome measure included composite metabolic score (sum of internally derived z scores of insulin resistance, mean blood pressure, triglyceride level, and total cholesterol/high-density lipoprotein cholesterol ratio). RESULTS. Weight SD score increased by 0.29 SD score in girls and 0.26 SD score in boys from 0 to 5 years of age and by 0.03 SD score in girls and 0.11 SD score in boys from 5 to 9 years of age. Weight SD score correlated poorly to moderately before 5 years of age but strongly after 5 years of age. Birth weight SD score predicted (girls/boys) 2.4%/0% of the variability in composite metabolic score at 9 years of age. Adding Δ weight SD score (0–5 years old) contributed (girls/boys) 11.2%/7.0% to the score, and adding Δ weight SD score (5–9 years old) additionally contributed (girls/boys) 26.4%/16.5%. Importantly, once weight SD score at 9 years of age was known, predictive strength was changed little by adding Δ weight SD score. CONCLUSIONS. Most excess weight before puberty is gained before 5 years of age. Weight at 5 years of age bears little relation to birth weight but closely predicts weight at 9 years of age. Single measures of current weight are predictive of metabolic health, whereas weight gain within a specific period adds little. A single measure of weight at 5 years of age provides a pointer to future health for the individual. If metabolic status at 9 years of age means future risk, diabetes/cardiovascular prevention strategies might better focus on preschool-aged children, because the die seems to be largely cast by 5 years of age, and a healthy weight early in childhood may be maintained at least into puberty.
Differences in Epitope Restriction of Autoantibodies to Native Human Insulin (IAA) and Antibodies to Heterologous Insulin (IA)

The binding profiles of insulin autoantibodies (IAA) and insulin antibodies (IA) to highly purified species variants and fragments of insulin were studied in direct immunospecific enzyme-linked immunosorbent assay (ELISA) and indirect absorption experiments with insulins covalently coupled to Sepharose beads. Five of 10 lAA-containing sera from insulin-naive nondiabetics that bound whole human (H) insulin did not bind whole porcine (P) or whole bovine (B) insulins. These sera bound H insulin B-chain but not P B-chain or desalanated P insulin, suggesting they were dependent on the presence of threonine B30. The other 5 IAA-containing sera bound H, P, B, and desalanated porcine insulins, but only 1 bound isolated B-chains. All 10 IA-containing sera from insulin-treated diabetics bound H, P, B, and desalanated P insulins, but only 1 bound to human (and porcine) B-chain. Further binding studies with ovine, rabbit, rat, and guinea pig insulins confirmed the H (threonine B30) specificity of the 5 IAA-containing sera. B30 residues do not appear to be dominant, however, when insulin is administered exogenously. Instead, IA bind predominantly to Achain or conformational determinants involving both chains. Scatchard analysis of a representative H insulin-specific IAA serum suggested that it contained a single binding affinity, whereas analysis of a representative IA-diabetic serum suggested it contained several different affinities.
Operative Time and Outcome of Enhanced Recovery After Surgery After Laparoscopic Colorectal Surgery

Background and Objectives: Combining laparoscopy and enhanced recovery provides benefit to short-term outcomes after colorectal surgery. Advances in training and techniques have allowed surgeons to operate on cases that are technically challenging and associated with prolonged operative time. Laparoscopic techniques improve the outcome of enhanced recovery after colorectal surgery; however, there are no specifications on the effect of prolonged operations on the outcome. The objective was to elucidate the impact of prolonged surgery and blood loss on the outcome of enhanced recovery after surgery after laparoscopic colorectal surgery. Methods: Four-hundred patients who underwent elective colorectal resection on enhanced recovery after surgery in Yeovil District Hospital between 2002 and 2009 were retrospectively reviewed. Delayed discharge was defined as a prolonged length of stay beyond the mean in this series (≥8 days). Results: Three-hundred eighty-five patients were included. Median operative time was 180 minutes with a median blood loss of 100 mL. Conversion was not associated with a prolonged length of stay. Operative time and blood loss correlated with length of stay in a stepwise fashion. There were 2 cutoff points of operative time at 160 minutes and 300 minutes (5 hours), where risk of prolonged stay increased significantly (odds ratio [OR] = 2.02; 95% confidence interval [CI], 1.05–3.90; P = .027), and blood loss of >500 mL (OR = 3.114; 95% CI, 1.501–6.462, P = .002). Conclusions: Total operative timing impacts negatively on the outcome of enhanced recovery after laparoscopic colorectal resections with increased risk of delayed discharge seen after ∼2.5 hours and 5-hour duration.
A portable digitally controlled oscillator using novel varactors

This work presents a portable digitally controlled oscillator (DCO) by using two-input NOR gates as a digitally controlled varactor (DCV) in fine-tuning delay cell design. This novel varactor uses the gate capacitance difference of NOR gates under different digital control inputs to establish a DCV. Thus proposed DCO can improve delay resolution 256 times better than a single buffer design. This study also examines different types of NOR/NAND gates (2-input or 3-input) for DCV. The proposed DCO with novel DCV can be implemented with standard cells, and thus it can be ported to different processes in short time. Furthermore, the final circuit layout can be generated using an auto placement and routing (APR) tools. A test chip demonstrates that LSB resolution of the DCO can be improved to 1.55 ps with standard 0.35-/spl mu/m 2P4M CMOS digital cell library. The proposed DCO has good performance in terms of fine resolution, high portability, and short design turnaround cycle compared with conventional DCO designs.
Pulse pressure variation and prediction of fluid responsiveness in patients ventilated with low tidal volumes

OBJECTIVE: To determine the utility of pulse pressure variation (ΔRESPPP) in predicting fluid responsiveness in patients ventilated with low tidal volumes (VT) and to investigate whether a lower ΔRESPPP cut-off value should be used when patients are ventilated with low tidal volumes. METHOD: This cross-sectional observational study included 37 critically ill patients with acute circulatory failure who required fluid challenge. The patients were sedated and mechanically ventilated with a VT of 6-7 ml/kg ideal body weight, which was monitored with a pulmonary artery catheter and an arterial line. The mechanical ventilation and hemodynamic parameters, including ΔRESPPP, were measured before and after fluid challenge with 1,000 ml crystalloids or 500 ml colloids. Fluid responsiveness was defined as an increase in the cardiac index of at least 15%. ClinicalTrial.gov: NCT01569308. RESULTS: A total of 17 patients were classified as responders. Analysis of the area under the ROC curve (AUC) showed that the optimal cut-off point for ΔRESPPP to predict fluid responsiveness was 10% (AUC = 0.74). Adjustment of the ΔRESPPP to account for driving pressure did not improve the accuracy (AUC = 0.76). A ΔRESPPP≥10% was a better predictor of fluid responsiveness than central venous pressure (AUC = 0.57) or pulmonary wedge pressure (AUC = 051). Of the 37 patients, 25 were in septic shock. The AUC for ΔRESPPP≥10% to predict responsiveness in patients with septic shock was 0.84 (sensitivity, 78%; specificity, 93%). CONCLUSION: The parameter ΔRESPPP has limited value in predicting fluid responsiveness in patients who are ventilated with low tidal volumes, but a ΔRESPPP>10% is a significant improvement over static parameters. A ΔRESPPP≥10% may be particularly useful for identifying responders in patients with septic shock.
The Significance of Shifts in Precipitation Patterns: Modelling the Impacts of Climate Change and Glacier Retreat on Extreme Flood Events in Denali National Park, Alaska

In glacier-fed systems climate change may have various effects over a range of time scales, including increasing river discharge, flood frequency and magnitude. This study uses a combination of empirical monitoring and modelling to project the impacts of climate change on the glacial-fed Middle Fork Toklat River, Denali National Park, Alaska. We use a regional calibration of the model HBV to account for a paucity of long term observed flow data, validating a local application using glacial mass balance data and summer flow records. Two Global Climate Models (HADCM3 and CGCM2) and two IPCC scenarios (A2 and B2) are used to ascertain potential changes in meteorological conditions, river discharge, flood frequency and flood magnitude. Using remote sensing methods this study refines existing estimates of glacial recession rates, finding that since 2000, rates have increased from 24m per year to 68.5m per year, with associated increases in ablation zone ice loss. GCM projections indicate that over the 21st century these rates will increase still further, most extensively under the CGCM2 model, and A2 scenarios. Due to greater winter precipitation and ice and snow accumulation, glaciers release increasing meltwater quantities throughout the 21st century. Despite increases in glacial melt, results indicate that it is predominantly precipitation that affects river discharge. Three of the four IPCC scenarios project increases in flood frequency and magnitude, events which were primarily associated with changing precipitation patterns, rather than extreme temperature increases or meltwater release. Results suggest that although increasing temperatures will significantly increase glacial melt and winter baseflow, meltwater alone does not pose a significant flood hazard to the Toklat River catchment. Projected changes in precipitation are the primary concern, both through changing snow volumes available for melt, and more directly through increasing catchment runoff.
Design and characterization of Pin fed microstrip patch antennae

The ever-increasing need for mobile communication and the emergence of newer technologies require an efficient design of antennae of smaller size for wider frequency range applications such as Wi-MAX. It is an enormous challenge. Microstrip patch antennae have found extensive application in compact wireless communication system. They have advantages of low-profile, conformability, low-cost fabrication and ease of integration with feed networks. This research analyses different feeding techniques and the effect of dielectric constant used for microstrip patch design. The main objective is to design and characterize pin-fed rectangular microstrip patch antenna. The characterization includes the effect of antennae dimensions (length and width), substrate dielectric constant (εr) and substrate thickness (t) on the radiation parameters of gain, return loss and bandwidth. The simulations have been carried out on high frequency simulation software. Two different materials of Teflon (dielectric constant 2.2) and glass epoxy (dielectric constant 4.4) are analyzed for substrate design. The simulated results are compared for analysis. The compact rectangular microstrip patch antenna design procedure for cellular phones (Wi-Max) is illustrated.
Prolonged PR Interval Predicts Clinical Recurrence of Atrial Fibrillation After Catheter Ablation

Background A prolonged PR interval is known to be a poor prognostic factor in cardiovascular disease. The aim of this study was to investigate the association between PR interval and clinical outcome in patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Methods and Results We prospectively included 576 patients with AF (75.5% male, 57.8±11.6 years old, 68.8% paroxysmal AF) who underwent RFCA. We analyzed preprocedural sinus rhythm ECGs obtained in the absence of antiarrhythmic drug, and all enrolled patients were categorized into 4 groups based on the quartile values of the PR interval (166, 182, and 202 ms), and were analyzed according to the left atrium (LA) volume (CT; Computed tomography), LA voltage (NavX), and clinical outcome of AF ablation. Based on quartile value of PR interval, the highest quartile of PR interval (Q4; PR ≥202 ms) was oldest (P<0.001), and most likely to have persistent AF (P<0.001) and hypertension (P=0.013) compared with the other groups. However, there was no significant difference in LA conduction velocity and atrial effective refractory period. Q4 had the greatest LA dimension (P<0.001) and volume index (P<0.001), and lowest LA appendage‐emptying velocity (P<0.032) and LA voltage (P<0.001) compared with the others. For 13.1±7.5 months, the classification based on the PR interval was a significant predictor of AF recurrence after RFCA of AF (HR=1.969, 95% CI 1.343 to 2.886, P=0.001). Conclusions The PR interval was closely associated with advanced LA remodeling due to AF, and had a noninvasive significant predictive value of clinical recurrence of AF after RFCA.
The mutual information: Detecting and evaluating dependencies between variables

MOTIVATION Clustering co-expressed genes usually requires the definition of 'distance' or 'similarity' between measured datasets, the most common choices being Pearson correlation or Euclidean distance. With the size of available datasets steadily increasing, it has become feasible to consider other, more general, definitions as well. One alternative, based on information theory, is the mutual information, providing a general measure of dependencies between variables. While the use of mutual information in cluster analysis and visualization of large-scale gene expression data has been suggested previously, the earlier studies did not focus on comparing different algorithms to estimate the mutual information from finite data. RESULTS Here we describe and review several approaches to estimate the mutual information from finite datasets. Our findings show that the algorithms used so far may be quite substantially improved upon. In particular when dealing with small datasets, finite sample effects and other sources of potentially misleading results have to be taken into account.
Corrigendum: [Novel functional roles for PERIANTHIA and SEUSS during floral organ identity specification, floral meristem termination and gynoecial development]

*Correspondence: Robert G. Franks, Department of Plant and Microbial Biology, North Carolina State University, 2548 Thomas Hall, Campus Box 7614, Raleigh, NC 27695-7614, USA e-mail: rgfranks@ncsu.edu The gynoecium is the female reproductive structure of angiosperm flowers. In Arabidopsis thaliana the gynoecium is composed of two carpels that are fused into a tube-like structure. As the gynoecial primordium arises from the floral meristem, a specialized meristematic structure, the carpel margin meristem (CMM), develops from portions of the medial gynoecial domain. The CMM is critical for reproductive competence because it gives rise to the ovules, the precursors of the seeds. Here we report a functional role for the transcription factor PERIANTHIA (PAN) in the development of the gynoecial medial domain and the formation of ovule primordia. This function of PAN is revealed in pan aintegumenta (ant) as well as seuss (seu) pan double mutants that form reduced numbers of ovules. Previously, PAN was identified as a regulator of perianth organ number and as a direct activator of AGAMOUS (AG) expression in floral whorl four. However, the seu pan double mutants display enhanced ectopic AG expression in developing sepals and the partial transformation of sepals to petals indicating a novel role for PAN in the repression of AG in floral whorl one. These results indicate that PAN functions as an activator or repressor of AG expression in a whorl-specific fashion. The seu pan double mutants also display enhanced floral indeterminacy, resulting in the formation of “fifth whorl” structures and disruption of WUSCHEL (WUS) expression patterns revealing a novel role for SEU in floral meristem termination.
Review of Cerebral Aneurysm Formation, Growth, and Rupture

Cerebral aneurysms (CAs) occur in 3% to 5% of the general population and are characterized by localized structural deterioration of the arterial wall, with loss of the internal elastic lamina and disruption of the media.1 The most dreaded complication of CAs is rupture, the likelihood of which is related to several modifiable and nonmodifiable risk factors. Despite advances in surgical techniques and perioperative management, the mortality and morbidity associated with aneurysm rupture remain high.2 Current therapeutic options are limited to invasive therapies, namely microsurgical clipping and endovascular treatment, both of which carry a non-negligible risk of procedural morbidity. In recent years, it has become obvious that CAs are not passively enlarging vascular structures but exhibit prominent features of inflammation and tissue degeneration. Other factors mainly hemodynamic, genetic, hormonal, and environmental may also play an important role. Knowledge of the pathogenic pathways of CAs may pave the way for the development of noninvasive therapies. The purpose of this review is to summarize the most relevant data on the molecular mechanisms, genetics, and risk factors for aneurysm formation, growth, and rupture. Although there are different forms of CAs, the present discussion focuses on saccular aneurysms, which represent the most common type of CAs and are also the most common cause of subarachnoid hemorrhage (SAH). ### Cerebral Aneurysms: an Inflammatory Disease Increasing evidence points to inflammation as the leading factor in the pathogenesis of CAs. The inflammatory process is initiated by a hemodynamic insult and leads to matrix metalloproteinases (MMPs)–mediated degradation of the extracellular matrix and apoptosis of smooth muscle cells (SMCs), which are the predominant matrix-synthesizing cells of the vascular wall. These processes act in concert to weaken the arterial wall progressively, resulting in dilatation, aneurysm formation, and ultimately rupture (Figure; Table 1). The data supporting a major role for inflammation in CA pathogenesis are …