Miracle-dz/UniFAR-FTUs huggingface dataset:
Nicotine effects on neutrophil F-actin formation and calcium release: implications for tobacco use and pulmonary diseases.

Alterations in neutrophil functions by tobacco components may play a pivotal role in pulmonary emphysema. This study examined the role of nicotine in altering F-actin formation and calcium (Ca2+) release (two early events in neutrophil motility). The effects of these alterations on the motile function of phagocytosis were also examined. Human peripheral neutrophils from medically healthy nonsmoking subjects were incubated with nicotine at concentrations normally encountered during acute exposure to cigarette smoke (10(-2) to 10(-5) M) and/or the chemotactic peptide FLPEP (10(-7) M). Relative F-actin stain was determined by NBD phallacidin staining followed by flow cytometry. Intracellular Ca2+ was determined by INDO-1 AM loading followed by emission ratio quantitation by fluorometry. Phagocytosis was determined by the % phagocytic cells with carboxylated microspheres. Incubation of neutrophils with varying concentrations of nicotine resulted in a significant elevation of the relative F-actin stain at 30 s at 10(-2) and 10(-3) M (p < .05, ANOVA) and at 30 min at 10(-2) to 10(-4) M (p < 0.05). In time course studies with 10(-7) M FLPEP stimulation, there was a approximately 325% rise in relative F-actin stain at 30-60 s, followed by a gradual decrease to near baseline levels. There was an immediate rise in Ca2+ to approximately 150% over baseline values, followed by a gradual decrease to baseline. By contrast, stimulation with nicotine demonstrated a approximately 105% increase in relative F-actin staining at 10(-2) M (p < .001, ANOVA) and a smaller increase at 10(-3) M, which remained elevated up to 600 s. Intracellular Ca2+ levels also rose in a dose-dependent manner with an increased of 700% over baseline with 10(-2) M nicotine, and remained elevated up to 600 s. Coincubation with both FLPEP and nicotine demonstrated additive effects in relative F-actin staining at both maximal and submaximal concentrations. Preincubation with 10(-2) or 10(-3) M nicotine suppressed the % phagocytic cells by 32% and 16%, respectively (p < .001, ANOVA) with only a 1-4% reduction in cell viability (trypan blue exclusion). The results demonstrate that the concentration of nicotine during acute cigarette exposure can directly stimulate neutrophil F-actin formation and intracellular Ca2+ release by a mechanism different from peptide stimulation. The alteration of these two pivotal neutrophil signaling events by nicotine may in turn alter other neutrophil functions in tobacco-related pulmonary emphysema.
Inhibition of rupture of established atherosclerotic plaques by treatment with apolipoprotein A-I.

AIMS Plasma concentrations of high-density lipoprotein (HDL)-cholesterol correlate inversely with the incidence of myocardial infarction in humans. We investigated the effect of treatment with human apolipoprotein A-I (apoA-I), the principal protein of HDL, on plaque disruption in an animal model. METHODS AND RESULTS Seventy apolipoprotein E knockout mice were induced to develop atherosclerotic lesions in the brachiocephalic artery by feeding a high-fat diet for 9 weeks. Mice then received twice-weekly treatment with human apoA-I (8 mg/kg) or vehicle, for 2 weeks. The incidence of acute plaque disruption was reduced by 65% in mice receiving apoA-I (P < 0.01). Plaques in treated mice had a more stable phenotype, with an increase in smooth muscle cell (SMC): macrophage ratio (P = 0.05), principally the consequence of an increase in the number of SMC in plaques. In the fibrous cap, there were reductions in matrix metalloproteinase-13 (-69%, P < 0.0001) and S100A4, a marker of SMC de-differentiation (-60%, P < 0.0001). These results indicate that 2 weeks of treatment with small amounts of human apoA-I produces more stable plaques in a mouse model. CONCLUSION Treatment with apoA-I has the potential to stabilize plaques and prevent plaque rupture in humans.
Differences in Swallowing between High and Low Concentration Taste Stimuli

Taste is a property that is thought to potentially modulate swallowing behavior. Whether such effects depend on taste, intensity remains unclear. This study explored differences in the amplitudes of tongue-palate pressures in swallowing as a function of taste stimulus concentration. Tongue-palate pressures were collected in 80 healthy women, in two age groups (under 40, over 60), stratified by genetic taste status (nontasters, supertasters). Liquids with different taste qualities (sweet, sour, salty, and bitter) were presented in high and low concentrations. General labeled magnitude scale ratings captured perceived taste intensity and liking/disliking of the test liquids. Path analysis explored whether factors of taste, concentration, age group, and/or genetic taste status impacted: (1) perceived intensity; (2) palatability; and (3) swallowing pressures. Higher ratings of perceived intensity were found in supertasters and with higher concentrations, which were more liked/disliked than lower concentrations. Sweet stimuli were more palatable than sour, salty, or bitter stimuli. Higher concentrations elicited stronger tongue-palate pressures independently and in association with intensity ratings. The perceived intensity of a taste stimulus varies as a function of stimulus concentration, taste quality, participant age, and genetic taste status and influences swallowing pressure amplitudes. High-concentration salty and sour stimuli elicit the greatest tongue-palate pressures.
Early application of digitalis in patients with acute myocardial infarction complicated with heart failure after PCI

The purpose of this work was to observe the effects of early application of digitalis on heart function, hemodynamics, and laboratory indexes in patients with Acute Myocardial Infarction (AMI) complicated with heart failure after Percutaneous Coronary Intervention (PCI). We recruited 54 patients with AMI complicated with heart failure after undergoing emergency PCI and randomly divided them into control and experimental groups. The experimental group was treated by digitalis preparation after reperfusion while the control group received saline injection. Left Ventricular End-Diastolic Diameter (LVEDD) increased in both groups, but there were no significant differences between the two groups. Left Ventricular Ejection Fraction (LVEF) was higher in the experimental group than in the control group. Heart Rate (HR), in the experimental group was lower than those in the control group after medication. Stroke Volume (SV) was higher in the experimental group than that in the control group 1 h after medication. The changes in Central Venous Pressure (CVP), Pulmonary Artery Systolic Pressure (PASP), and Cardiac Index (CI) were not significantly different between the two groups. The values of Brain Natriuretic Peptide (BNP), Creatine Kinase isoenzyme MB (CK-MB), and Troponin I (TnI) improved significantly in both groups after surgery. The incidence of ventricular arrhythmia and mortality rate 30 d post-surgery were similar in the two groups. Overall, the heart function and hemodynamic indexes of patients with AMI complicated with heart failure after PCI can be significantly ameliorated after intervention with digitalis drugs without increasing the adverse events.
Connectivity Analysis Reveals a Cortical Network for Eye Gaze Perception

Haxby et al. (Haxby JV, Hoffman EA, Gobbini MI. 2000. The distributed human neural system for face perception. Trends Cogn Sci. 4:223–233.) proposed that eye gaze processing results from an interaction between a “core” face-specific system involved in visual analysis and an “extended” system involved in spatial attention, more generally. However, the full gaze perception network has remained poorly specified. In the context of a functional magnetic resonance imaging study, we used psychophysiological interactions (PPIs) to identify brain regions that showed differential connectivity (correlation) with core face perception structures (posterior superior temporal sulcus [pSTS] and fusiform gyrus [FG]) when viewing gaze shifts relative to control eye movements (opening/closing the eyes). The PPIs identified altered connectivity between the pSTS and MT/V5, intraparietal sulcus, frontal eye fields, superior temporal gyrus (STG), supramarginal gyrus, and middle frontal gyrus (MFG). The FG showed altered connectivity with the same areas of the STG and MFG, demonstrating the contribution of both dorsal and ventral core face areas to gaze perception. We propose that this network provides an interactive system that alerts us to seen changes in other agents’ gaze direction, makes us aware of their altered focus of spatial attention, and prepares a corresponding shift in our own attention.
Immunology of Tuberculosis

MTB ranks as the first worldwide pathogen latently infecting one third of the population and the second leading cause of death from a single infectious agent, after the human immunodeficiency virus (HIV). The development of vigorous and apparently appropriate immune response upon infection with M. tuberculosis in humans and experimental animals conflict with failure to eradicate the pathogen itself and with its ability to undergo clinical latency from which it may exit. From a clinical standpoint, our views on MTB infection may take advantage from updating the overall perspective, that has quite changed over the last decade, following remarkable advances in our understanding of the manipulation of the immune system by M. tuberculosis and of the role of innate components of the immune response, including macrophages, neutrophils, dendritic cells and NK cells in the initial spread of MTB and its exit from latency. Scope of this review is to highlight the major mechanisms of MTB escape from immune control and to provide a supplementary translational perspective for the interpretation of innate immune mechanisms with particular impact on clinical aspects.
Analysis of Variability of Atmospheric Pollutants in Ambient Air of Metropolitan City Karachi, and Environmental Sustainability

It is well known that, air pollution is a composite phenomenon and intense air pollution events are governed by huge number of consistent factors. In this study, we considered the pollutant parameter (NO 2 , NO, NOx and CO) concentrations and were measured simultaneously during the period 21/11/2009 to 27/02/2010 in city of Karachi. The estimations were carried out to study the variability of pollutant emissions. Time Series analysis confirms the existence of variation in pollutant with mean daily concentration and the results suggest that the concentrations of pollutant over the interval are slowly declined. The relationships NO 2 with NOx, NO with NOx and NO 2 vs. CO were modeled with linear regression. The results of the linear regression detected underlying strong relationships among pollutant variables. The application of the regression approach confirmed that the NO 2 strongly correlated with other paired pollutants. The study will be helpful to the policy makers to control air pollution and the sustainable environment. It also needs to extend this research to study the nonlinear behavior of atmospheric pollutants in perspective of fractal dimension.
Online Supervisory Control of Hybrid Systems Using Embedded Simulation

This paper describes a technique for synthesizing supervisory discrete event controllers for hybrid plants. The discrete event model of the plant behaviour is assembled for a limited lookahead horizon at run time based on discrete abstractions of embedded continuous simulations. A supervisory controller for this limited horizon model is then computed as a state avoidance problem. Since the controller is valid for only a limited time/event horizon, it must be re-computed on-line periodically, in order to extend the operation to an infinite time horizon. We present a scheme for enforcing guaranteed safe and nonblocking behaviour which is rooted in standard industrial practice
Adherence to guidelines on antibiotic treatment for respiratory tract infections in various categories of physicians: a retrospective cross-sectional study of data from electronic patient records

Objective To study how prescription patterns concerning respiratory tract infections differ between interns, residents, younger general practitioners (GPs), older GPs and locums. Design Retrospective study of structured data from electronic patient records. Setting Data were obtained from 53 health centres and 3 out-of-hours units in Jönköping County, Sweden, through their common electronic medical record database. Participants All physicians working in primary care during the 2-year study period (1 November 2010 to 31 October 2012). Outcome measures Physicians’ adherence to current guidelines for respiratory tract infections regarding the use of antibiotics. Results We found considerable differences in prescribing patterns between physician categories. The recommended antibiotic, phenoxymethylpenicillin, was more often prescribed by interns, residents and younger GPs, while older GPs and locums to a higher degree prescribed broad-spectrum antibiotics. The greatest differences were seen when the recommendation in guidelines was to refrain from antibiotics, as for acute bronchitis. Interns and residents most often followed guidelines, while compliance in descending order was: young GPs, older GPs and locums. We also noticed that male doctors were somewhat overall more restrictive with antibiotics than female doctors. Conclusions In general, primary care doctors followed national guidelines on choice of antibiotics when treating respiratory tract infections in children but to a lesser degree when treating adults. Refraining from antibiotics seems harder. Adherence to national guidelines could be improved, especially for acute bronchitis and pneumonia. This was especially true for older GPs and locums whose prescription patterns were distant from the prevailing guidelines.
Combining Machine Learning and Crowdsourcing for Better Understanding Commodity Reviews

In e-commerce systems, customer reviews are important information for understanding market feedbacks on certain commodities. However, accurate analyzing reviews is challenging due to the complexity of natural language processing and informal descriptions in reviews. Existing methods mainly focus on studying efficient algorithms that cannot guarantee the accuracy for review analysis. Crowdsourcing can improve the accuracy of review analysis while it is subject to extra costs and low response time. In this work, we combine machine learning and crowdsourcing together for better understanding customer reviews. First, we collectively use multiple machine learning algorithms to pre-process review classification. Second, we select the reviews on which all machine learning algorithms cannot agree and assign them to humans to process. Third, the results from machine learning and crowdsourcing are aggregated to be the final analysis results. Finally, we perform real experiments with practical review data to confirm the effectiveness of our method.
Measured and Modeled C Flows after Land Use Change to Perennial Bioenergy Crops

In the first part of this Thesis the general concepts and state of art of the research subjects are introduced, then focusing on the impact of the land use change to perennial bioenergy crops on agricultural systems’ carbon stocks. Then, the specific objectives of the research that has been carried out are stated. In the second part, the detailed methods and results of the four experiments performed are described one by one. All four papers constitute original research. The first and second papers originate from direct field measurements investigating the carbon flows subsequent to the establishment of perennial grasses for bioenergy on, respectively, a fertile agricultural land and a marginal land resembling, since it had been cultivated with poplar for the previous thirty years, the conditions of a biomass supply district. The third and fourth papers originate from model simulations investigating the potential of perennial biomass crops to produce energy and second-generation biofuels at the regional scale and their impact on soil carbon stocks and, more generally, on greenhouse gases emissions. Finally, by converging the findings of all the four experiments, general conclusions are drawn, also underlying future perspectives, current gaps and further research needed in order to fill these gaps.
High Variability of Plasma Drug Concentrations in Dual Protease Inhibitor Regimens

ABSTRACT Ritonavir (RTV) strongly increases the concentrations of protease inhibitors (PIs) in plasma in patients given a combination of RTV and another PI. This pharmacological interaction is complex and poorly characterized and shows marked inter- and intraindividual variations. In addition, RTV interacts differently with saquinavir (SQV), indinavir (IDV), amprenavir (APV), and lopinavir (LPV). In this retrospective study on 542 human immunodeficiency virus-infected patients, we compared inter- and intraindividual variability of plasma PI concentrations and correlations between the Cmin (minimum concentration of drug in plasma) values for RTV and the coadministered PI Cmin values. Mean RTV Cmins are significantly lower in patients receiving combinations containing APV or LPV than in combinations with SQV or IDV. With the most common PI dose regimens (600 mg of IDV twice a day [BID], 800 mg of SQV BID, and 400 mg of LPV BID), the interindividual Cmin variability of patients treated with a PI and RTV seemed to be lower with APV and LPV than with IDV and SQV. As regards intraindividual variability, APV also differed from the other PIs, exhibiting lower Cmin variability than with the other combinations. Significant positive correlations between RTV Cmin and boosted PI Cmin were observed with IDV, SQV, and LPV, but not with APV. Individual dose adjustments must take into account the specificity the pharmacological interaction of each RTV/PI combination and the large inter- and intraindividual variability of plasma PI levels to avoid suboptimal plasma drug concentrations which may lead to treatment failure and too high concentrations which may induce toxicity and therefore reduce patient compliance.
Modeling Secure Architectural Connector with UML 2.0

Security is one of the most important quality attributes in software architecture. Previous modeling approaches provide insufficient support for an in-depth treatment of security. They lack the ability to model important security concepts. Also they are based on formal syntaxes such as using ADLs. This paper presents a more comprehensive treatment of an important security aspect, access control, at the architecture level. Our approach models security user, role, permission, two many-to-many relations for assigning a role to user and permission to role, and policy of architectural constituents. We base our new modeling language on UML 2.0 and try to model security concepts by extending UML. We also provide mechanisms for checking UML models to detect architectural vulnerabilities and assure correct access control at an early design stage.
The interplay of received social support and self-regulatory factors in smoking cessation

Objective: In smoking cessation, individual self-regulation and social support have both proven to be useful. However, the roles of self-regulatory processes and social support are mostly examined separately. The present study aims at examining the unique and joint interactive effects of self-regulation as specified in the health action process approach (HAPA) and social support on smoking cessation. The study tested whether social support can compensate for low levels of self-regulation or whether synergistic effects emerge. Design & Measures: Around a self-set quit date, 99 smokers completed baseline questionnaires on HAPA-variables, smoking-specific received social support and smoking cessation (continuous abstinence and point prevalence), with a follow-up Cpproximately 29 days after the quitdate. Results: Social support moderated the association between volitional self-efficacy and smoking, as well as coping planning and smoking but not between action planning and smoking. No compensatory effect of social support for lower levels of individual regulation emerged but the combination of high levels of the individual variables and social support was related to successful smoking cessation, indicating a synergistic effect. Conclusions: The results confirm the importance of examining both self-regulation and social factors in smoking cessation. This should be considered when developing future interventions for smoking cessation.
Delay-Aware Load Balancing Over Multipath Wireless Networks

The ability of mobile devices to be connected to more than one radio node at the same time enables mobile devices to transmit and receive traffic to and from multiple paths. This ability helps to increase the average mobile device data rate and to improve the network reliability. Load balancing among multiple paths become a key factor to avoid network congestion, nevertheless it requires efficient techniques to split traffic without adding more delay or generating too much packet reordering for delay-sensitive traffic. In this paper, we address two key issues in the context of uplink wireless mobile networks: 1) how to accurately split traffic among multiple paths and 2) how to minimize the end-to-end delay without increasing packet reordering. We propose delay-aware load balancing algorithm (DALBA), a novel strategy that splits traffic at the granularity of the packet. DALBA aims to minimize the splitting error (SE) and the end-to-end delay difference by effectively using all of the available paths. We analyze DALBA's performance through extensive simulations using H.264 video traffic. Numerical results demonstrate that DALBA outperforms previous algorithms in terms of SE, end-to-end delay and peak signal-to-noise ratio while keeping packet reordering to a suitable low value.
Functional characterization of human variants of the mu-opioid receptor gene

Opioids and their receptors have an important role in analgesia and alcohol and substance use disorders (ASUD). We have identified several naturally occurring amino acid changing variants of the human mu-opioid receptor (MOR), and assessed the functional consequences of these previously undescribed variants in stably expressing cell lines. Several of these variants had altered trafficking and signaling properties. We found that an L85I variant showed significant internalization in response to morphine, in contrast to the WT MOR, which did not internalize in response to morphine. Also, when L85I and WT receptor were coexpressed, WT MOR internalized with the L85I MOR, suggesting that, in the heterozygous condition, the L85I phenotype would be dominant. This finding is potentially important, because receptor internalization has been associated with development of tolerance to opiate analgesics. In contrast, an R181C variant abolished both signaling and internalization in response to saturating doses of the hydrolysis-resistant enkephalin [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO). Coexpression of the R181C and WT receptor led to independent trafficking of the 2 receptors. S42T and C192F variants showed a rightward shift in potency of both morphine and DAMGO, whereas the S147C variant displayed a subtle leftward shift in morphine potency. These data suggest that these and other such variants may have clinical relevance to opioid responsiveness to both endogenous ligands and exogenous drugs, and could influence a broad range of phenotypes, including ASUD, pain responses, and the development of tolerance to morphine.