Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease

Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), represent a major social and economic burden for worldwide health systems. During recent years, increasing attention has been directed to the role of small airways in respiratory diseases, and their exact contribution to the pathophysiology of asthma and COPD continues to be clarified. Indeed, it has been suggested that small airways play a distinct role in specific disease phenotypes. Besides providing information on small airways structure and diagnostic procedures, this review therefore aims to present updated and evidence-based findings on the role of small airways in the pathophysiology of asthma and COPD. Most of the available information derives from either pathological studies or review articles and there are few data on the natural history of small airways disease in the onset or progression of asthma and COPD. Comparisons between studies on the role of small airways are hard to draw because both asthma and COPD are highly heterogeneous conditions. Most studies have been performed in small population samples, and different techniques to characterize aspects of small airways function have been employed in order to assess inflammation and remodelling. Most methods of assessing small airways dysfunction have been largely confined to research purposes, but some data are encouraging, supporting the utilization of certain techniques into daily clinical practice, particularly for early-stage diseases, when subjects are often asymptomatic and routine pulmonary function tests may be within normal ranges. In this context further clinical trials and real-life feedback on large populations are desirable.
Proteasome inhibition induces apoptosis in primary human natural killer cells and suppresses NKp46-mediated cytotoxicity

Bortezomib is a synthetic small molecule inhibitor of the chymotryptic activity of the 26S proteasome. Effects of bortezomib on normal immune cells have also been previously reported. This study adds to observations on the effects of bortezomib on natural killer (NK) cells. Effects include induction of apoptosis in resting NK cells, together with suppression of NK-mediated cytotoxicity via the NKp46 pathway. The concern is raised that treatment with bortezomib could interfere with NK cell-mediated attack on tumor cells, or on infected cells. Background Bortezomib is a selective and potent inhibitor of the proteasome and has prominent effects in vitro and in vivo against tumors. Very recently, cytotoxic effects of bortezomib on immune-competent cells such as T cells and dendritic cells were also revealed. The aim of the study was to investigate the effects of this agent on natural killer cell survival and function. Design and Methods We investigated cytotoxic properties of bortezomib on natural killer cell apoptosis and function. Primary resting natural killer cells were purified from peripheral blood mononuclear cells of healthy donors by negative selection. The apoptotic cells were quantified by dual labeling of recombinant annexin V and propidium iodide. Mitochondrial membrane potential and expression of natural killer cell activating receptors were also quantified by flow cytometry. Natural killer cell cytotoxicity against murine and human tumor cells was tested by chromium 51 release assay. Results Our results demonstrate that bortezomib induces apoptosis in resting natural killer cells in a dose- and time-dependent manner. Glutathione, a reactive oxygen species scavenger, prevented the loss of mitochondrial membrane potential and conferred protection against bortezomib-induced apoptosis in resting natural killer cells, indicating a role for oxidative stress. Additionally, bortezomib significantly decreased expression of the natural killer activating receptor NKp46 in non-apoptotic resting natural killer cells in a dose-dependent manner, and as a result the redirected cytotoxicity mediated via NKp46 activation was diminished. Bay 11-7082, a pharmacological inhibitor of NF-κB activation, also reduced NKp46 expression and suppressed redirected cytotoxicity. Conclusions Bortezomib induces apoptosis in primary resting natural killer cells in a dose- and time-dependent manner, and reduces NKp46 receptor expression as well as natural killer cell cytotoxicity mediated by the NKp46 activation pathway, suggesting that bortezomib may disrupt natural killer cell-mediated immunity through at least two different mechanisms: induction of natural killer cell apoptosis, and suppression of NKp46 receptor-mediated cytotoxicity.
Altered nuclear cofactor switching in retinoic‐resistant variants of the PML‐RARα oncoprotein of acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) results from a reciprocal translocation that fuses the gene for the PML tumor suppressor to that encoding the retinoic acid receptor alpha (RARα). The resulting PML‐RARα oncogene product interferes with multiple regulatory pathways associated with myeloid differentiation, including normal PML and RARα functions. The standard treatment for APL includes anthracycline‐based chemotherapeutic agents plus the RARα agonist all‐trans retinoic acid (ATRA). Relapse, which is often accompanied by ATRA resistance, occurs in an appreciable frequency of treated patients. One potential mechanism suggested by model experiments featuring the selection of ATRA‐resistant APL cell lines involves ATRA‐resistant versions of the PML‐RARα oncogene, where the relevant mutations localize to the RARα ligand‐binding domain (LBD). Such mutations may act by compromising agonist binding, but other mechanisms are possible. Here, we studied the molecular consequence of ATRA resistance by use of circular dichroism, protease resistance, and fluorescence anisotropy assays employing peptides derived from the NCOR nuclear corepressor and the ACTR nuclear coactivator. The consequences of the mutations on global structure and cofactor interaction functions were assessed quantitatively, providing insights into the basis of agonist resistance. Attenuated cofactor switching and increased protease resistance represent features of the LBDs of ATRA‐resistant PML‐RARα, and these properties may be recapitulated in the full‐length oncoproteins. Proteins 2012; © 2011 Wiley Periodicals, Inc.
Real-time plane segmentation in a ROS-based navigation system for the visually impaired

This paper provides a real-time plane segmentation method which can be used in navigation systems for the visually impaired to avoid indoor obstacles. The proposed method is based on surface normal estimation in range images. Efficiency and overall accuracy are considered as two main challenges in plane segmentation algorithms which use depth information. Our method exploits integral images to enhance the efficiency of normal estimation. A dynamic determination for smoothing region is proposed in our method to improve the overall accuracy. Compared to the methods in Point Cloud Library (PCL), our method consumes less time and has better performance in a wide range of depth (1∼8m). The proposed method is implemented on Robot Operating System (ROS) at 30fps. Our method makes it possible to obtain a robust and real-time indoor navigation system integrated with commercial Time-of-flight (TOF) sensors.
The peculiar economics of english professional football

The literature on the economics of professional team sports has grown rapidly since articles first started to appear in the 1950s. Most of the literature has been generated in North America and deals mainly with issues of restriction of competition in the product and labour markets that characterize American football, basketball, ice-hockey and baseball. Much of the analysis developed in North America has also been applied to UK professional team sports, in particular to football and cricket. The economics of professional team sports has become particularly relevant over the last decade because of the changes that have taken place in both UK and European professional team sports: the setting up of the Premier League in English professional football in 1992; the move to Super League in rugby league in 1996; the professionalization of rugby union in 1996; and the restructuring of the European Champions' League in football in 1999. The strength of this trend is such that it is likely to continue to be a defining feature of sport in general, and football in particular, in the twenty-first century. This essay will focus particularly on English professional football. Firstly, however, it will analyse the 'peculiar' economics of professional team sports as developed in North America leading to a definition of 'the American model' of a professional sports league. Secondly, it will discuss the extent to which English football reflects this American model. Finally, it will examine the hypothesis put forward by T Hoehn and S. Szymanski that the present structure of English professional football is unsustainable and that the natural equilibrium for the English and other European countries' league systems would be the formation of an American-style European Superleague.
Endoscopic Skull Base/Sinonasal Adenocarcinoma Surgery: What Evidence Exists?

Background This study reviewed the published outcomes literature on endoscopic or endoscopic-assisted treatment of sinonasal and skull base adenocarcinoma (SSBA). A systematic literature review was performed. Methods A PubMed search of English language articles on endoscopic or endoscopic-assisted SSBA was performed. Each article was examined for patient data and outcomes for analysis. Results Sixteen articles (150 retrospective cases) using endoscopic or endoscopic-assisted SSBA were identified. Three (19%) reported at least15 cases of adenocarcinoma with 5-year survival ranging from 53 to 83%. In all identified studies, five (31%) reported adenocarcinoma-specific survival statistics and eight (50%) provided complete patient information. Adjuvant therapy was used in 12 studies (75%), with details outlined in 6 (38%) articles, accounting for 52 of 74 cases (70% of those patients and 35% overall). Adenocarcinoma-specific follow-up was reported in only nine studies (56%); four of these nine articles had a median/mean follow-up time of <3 years. Six articles (38%) used American Joint Committee on Cancer guidelines and four articles (25%) used International Union Against Cancer guidelines. The remaining six articles (38%) did not report on the stage of treated tumors. Four articles (25%) reported length of hospital stay and eight (50%) reported complication data. Three studies comprising 61 cases (41% of overall patients) recorded disease status, tumor stage, site involvement, and complication rates for each patient. Conclusion From the existing body of data, one can not conclude that endoscopic methods are superior or inferior to open methods, but there is growing evidence that this is an efficacious technique. Future studies should have emphasis on detailed, prospective reporting.
An Approach to Quantifying the Conversion of Carbohydrate to Fat in Humans

Using stable isotopes in metabolic research with an emphasis on C, N or deuterated compounds offers a safe and reliable tool for metabolic profiling. Isotopic tracer studies coupled with the use of LC/MS, GC/MS and NMR allows researchers to investigate specific pathways involving glucose, fatty acids, amino acids and proteins. Doubly labeled water also continues as a valuable tool in energy expenditure and nutrition-related research. ISOTEC offers a wide range of products with high enrichment and purity to meet the researcher's needs.
Cognitive and Motivational Functions of the Human Prefrontal Cortex

ical observation of countless patients with varying degrees of damage to frontal regions of cortex, Luria was able to differentiate between three broad regions of the frontal lobes with clearly distinguishable contributions to human cognition: the premotor division, the prefrontal. convex division, and the mediobasal or orbital division (Figure 4-I). According to Luria, the central features of damage to these three regions are, respectively, "disturbance of skilled movement and a disintegration of complex kinetic melodies. , lack of continuous compar-
Calculation of shape anisotropy for micropatterned thin Fe-Ni films for on-chip RF applications

We present a self-consistent calculation of the effective anisotropy of patterned, integrated ferromagnetic films. For comparison, experimental data were obtained from electroplated thin (0.5 /spl mu/m) Ni-Fe films with different patterns. The effective anisotropy of patterned samples was increased by shape demagnetizing effects from just 10 Oe up to 100 Oe. The samples with suitable characteristics were subsequently used as cores for on-chip inductors and microstrips.
Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease.

AT THE meeting of the Mid-Western Society for Pediatric Research in 1962, I reported on nine patients with remarkably similar facies with a previously unrecognized syndrome of valvular pulmonary stenosis and multiple extra cardiac anomalies.1Review of the literature at that time showed that several males resembling these patients had been reported under several different headings, most commonly under the designation of, "the male Turner syndrome. "2-5There were no definite reports of similarly affected female patients. In that report I spoke in terms of a "new syndrome" in order to stress that this condition could affect not only males but also females, and that it was also clinically and etiologically different from the true Turner6syndrome. Since that time, a further eight patients, five males and three females, with valvular pulmonary stenosis and similar associated lesions have been studied. An additional two patients, one of each sex,
Philopatry and migration of Pacific white sharks

Advances in electronic tagging and genetic research are making it possible to discern population structure for pelagic marine predators once thought to be panmictic. However, reconciling migration patterns and gene flow to define the resolution of discrete population management units remains a major challenge, and a vital conservation priority for threatened species such as oceanic sharks. Many such species have been flagged for international protection, yet effective population assessments and management actions are hindered by lack of knowledge about the geographical extent and size of distinct populations. Combining satellite tagging, passive acoustic monitoring and genetics, we reveal how eastern Pacific white sharks (Carcharodon carcharias) adhere to a highly predictable migratory cycle. Individuals persistently return to the same network of coastal hotspots following distant oceanic migrations and comprise a population genetically distinct from previously identified phylogenetic clades. We hypothesize that this strong homing behaviour has maintained the separation of a northeastern Pacific population following a historical introduction from Australia/New Zealand migrants during the Late Pleistocene. Concordance between contemporary movement and genetic divergence based on mitochondrial DNA demonstrates a demographically independent management unit not previously recognized. This population's fidelity to discrete and predictable locations offers clear population assessment, monitoring and management options.
Regulation mechanisms in mixed and pure culture microbial fermentation

Mixed‐culture fermentation is a key central process to enable next generation biofuels and biocommodity production due to economic and process advantages over application of pure cultures. However, a key limitation to the application of mixed‐culture fermentation is predicting culture product response, related to metabolic regulation mechanisms. This is also a limitation in pure culture bacterial fermentation. This review evaluates recent literature in both pure and mixed culture studies with a focus on understanding how regulation and signaling mechanisms interact with metabolic routes and activity. In particular, we focus on how microorganisms balance electron sinking while maximizing catabolic energy generation. Analysis of these mechanisms and their effect on metabolism dynamics is absent in current models of mixed‐culture fermentation. This limits process prediction and control, which in turn limits industrial application of mixed‐culture fermentation. A key mechanism appears to be the role of internal electron mediating cofactors, and related regulatory signaling. This may determine direction of electrons towards either hydrogen or reduced organics as end‐products and may form the basis for future mechanistic models. Biotechnol. Bioeng. 2014;111: 2139–2154. © 2014 Wiley Periodicals, Inc.
Simulating the effect of a social robot on moving pedestrian crowds

We investigate the interaction between a pedestrian crowd and a social robot-a relevant human-robot interaction scenario observed in train stations and entrances to public places. We use a popular agent-based social force model to simulate a pedestrian crowd as it passes near a stationary robot. The modelling framework permits analysis of difficult-to-test situations such as high density crowds and the effects of contagion whereby more people are likely to interact with the robot if it is already surrounded by an audience. Accordingly, we augment the modelling framework to account for varying crowd densities, human-robot interaction, and social influence, and inform the parameter values from empirical studies in literature. Our results show that while the rate-of-interaction, defined as the number of agents located within an interacting distance per minute, increases with flow density, the average interaction-time is independent of the same. We find that inducing social influence through contagion does not have a significant effect on the rate at which agents engage with the robot in dense crowd scenarios, and has a marginal effect at low densities. The interaction-time was found to depend on the interaction-speed at which agents engage with the robot. These results indicate that at normally witnessed flow densities crowding near the robot is unlikely to take place, and the effect of robot design choices supersede the effects of social force or contagion.
Effective Current Model for Inverter-Transmission Gate Structure and Its Application in Circuit Design

In this paper, we present an effective switching current model (<inline-formula> <tex-math notation="LaTeX">${I}_{\textsf {eff}}$ </tex-math></inline-formula>) for inverter followed by a transmission gate structure (Inv-Tx) based on its switching trajectory. Unlike an inverter or NAND/NOR gates, where <inline-formula> <tex-math notation="LaTeX">${I}_{\textsf {eff}}$ </tex-math></inline-formula> depends only on nMOSFET (pMOSFET) current for a falling (rising) transition, it is a function of both nMOSFET and pMOSFET currents for an Inv-Tx cell. The proposed model is verified against HSPICE simulations for a wide range of supply voltages and fan-outs at different technology nodes (e.g., 180, 130, and 65 nm). The model predicts the transition delay values with an average (maximum) error of 7% (11%) compared with HSPICE simulations. Synopsys TCAD Sentaurus simulations at 32-nm technology node are also used to validate the basic model assumptions. To demonstrate the utility of our model, design of some representative circuits while incorporating layout-dependent effects and inverse-narrow-width effect is presented. Finally, we show that a 256X1 multiplexer and a static D-flip-flop, with their transistor sizes and layout, optimized using the proposed model improves the performance of these circuits significantly over the conventional design methodologies.
Cannabinoid–serotonin interactions in alcohol‐preferring vs. alcohol‐avoiding mice

Because cannabinoid and serotonin (5‐HT) systems have been proposed to play an important role in drug craving, we investigated whether cannabinoid 1 (CB1) and 5‐HT1A receptor ligands could affect voluntary alcohol intake in two mouse strains, C57BL/6 J and DBA/2 J, with marked differences in native alcohol preference. When offered progressively (3–10% ethanol) in drinking water, in a free‐choice procedure, alcohol intake was markedly lower (∼ 70%) in DBA/2 J than in C57BL/6 J mice. In DBA/2 J mice, chronic treatment with the cannabinoid receptor agonist WIN 55,212–2 increased alcohol intake. WIN 55,212–2 effect was prevented by concomitant, chronic CB1 receptor blockade by rimonabant or chronic 5‐HT1A receptor stimulation by 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin, which, on their own, did not affect alcohol intake. In C57BL/6 J mice, chronic treatment with WIN 55,212–2 had no effect but chronic CB1 receptor blockade or chronic 5‐HT1A receptor stimulation significantly decreased alcohol intake. Parallel autoradiographic investigations showed that chronic treatment with WIN 55,212–2 significantly decreased 5‐HT1A‐mediated [35S]guanosine triphosphate‐γ‐S binding in the hippocampus of both mouse strains. Conversely, chronic rimonabant increased this binding in C57BL/6 J mice. These results show that cannabinoid neurotransmission can exert a permissive control on alcohol intake, possibly through CB1–5–HT1A interactions. However, the differences between C57BL/6 J and DBA/2 J mice indicate that such modulations of alcohol intake are under genetic control.
Consensual clustering for land cover mapping

In this article we propose to illustrate the ability of consensual clustering to provide mining tools in the context of land cover unsupervised classification. The proposed algorithm is based on individual co-association matrices related to several input clusterings that are combined using a Mean Shift optimization procedure. This provides valuable clusters in terms of interpretation and also information about the data to be clustered, which could be useful to discriminate between easily classified pixels and the other ones, requiring human expertise. The interest of our approach is demonstrated using the Boumerdes dataset provided by SERTIT and CNES, in the context of the 2003 earthquake.
Emotions elicited by political negative messages

In a sample composed of 176 left-wing students we analyzed experimentally (23 factorial design) emotional reactions to negative campaign messages as a function of political ir/relevance of the content, in/civility of the tone, and source’s political affiliation). We found a tri-dimensional structure of emotional responses (enthusiasm, anxiety, and aversion). Messages stemming from an ingroup source elicited enthusiasm when relevant and aversion when irrelevant, while messages stemming from an outgroup source elicited anxiety.