Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of the epidermal growth factor receptor in epithelial repair in asthma

Epithelial damage and airway remodeling are consistent features of bronchial asthma and are correlated with disease chronicity, severity, and bronchial hyperreactivity. To examine the mechanisms that control bronchial epithelial repair, we investigated expression of the epidermal growth factor receptor (c‐erbB1, EGFR) in asthmatic bronchial mucosa and studied repair responses in vitro. In biopsies from asthmatic subjects, areas of epithelial damage were frequently observed and exhibited strong EGFR immunostaining. EGFR expression was also high in morphologically intact asthmatic epithelium. Using image analysis, EGFR immunoreactivity (% of total epithelial area, median (range) was found to increase from 9.4 (4.1‐20.4) in normal subjects (n=10) to 18.4 (9.3‐28.9) in mild asthmatics (P<0.01, n=13) and 25.4 (15.4‐31.8) in severe asthmatics (P<0.00, n=5). Epithelial EGFR immunoreactivity remained elevated in patients treated with corticosteroids and was positively correlated with subepithelial reticular membrane thickening. Using 16HBE 14o‐ bronchial epithelial cells, we found that EGF accelerated repair of scrape‐wounded monolayers and that the EGFR‐selective inhibitor, tyrphostin AG1478, inhibited both EGF‐stimulated and basal wound closure whereas dexamethasone was without effect. Intrinsic activation of the EGFR was confirmed by analysis of tyrosine phosphorylated proteins, which revealed a rapid, damage‐induced phosphorylation of the EGFR, irrespective of the presence of exogenous EGF. To assess the relationship between EGFR‐mediated repair and tissue remodeling, release of the profibrogenic mediator TGF‐β2 was also measured. Scrape wounding increased release of TGF‐β2 from epithelial monolayers and EGF had no additional stimulatory effect. However, when repair was retarded with AG1478, the amount of TGF‐β2 increased significantly. These data indicate that the EGFR may play an important role in bronchial epithelial repair in asthma and that impairment of this function may augment airway remodeling. —Puddicombe, S. M. , Polosa, R. , Richter, A. , Krishna, M. T. , Howarth, P. H. , Holgate, S. T. , Davies, D. E. Involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J. 14, 1362–1374 (2000)
Resource Contention in Multiagent Systems

The dynamics of resource contention in multiagent systems with imperfect information can be extremely complex, ranging from nonlinear oscillations to chaotic behavior. It was shown by Hogg and Huberman that it is possible to stabilize such systems by allowing agents to follow different strategies. We now show that there is a wide range of possible strategies consistent with the existing equilibrium. As time progresses, agents explore different strategy mixes, resulting in bursts of momentary instability. These bursts eventually relax into a stable equilibrium. This mechanism of stability punctuated by bursts of erratic activity appears to be quite general in systems where agents explore strategies in search of local improvements.
Adverse drug reactions to antiretroviral therapy: prospective study in children in sikasso (mali).

OBJECTIVES Adverse events during antiretroviral treatment are frequent and various. Their diagnosis incurs some various difficulties according to the geographic context. Our aim was to describe the frequency, nature, and preventability of adverse drug reactions (ADRs) due to antiretroviral treatment in Malian outpatient children. METHODS The study was a 6-month (June 1 to November 30, 2010) prospective, observational study of 92 children admitted to a pediatric hospital in Sikasso, Mali. The patients were treated with a generic drug and/or drug combinations. Prior to treatment initiation, demographic characteristics, clinical history, and biologic parameters, including CD4 cell counts, were collected for each patient. The World Health Organization's adverse drug reactions classification was used to characterize the side effects. Adverse effects and toxicities were graded 1, 2, and 3. Analysis of data was performed using SPSS Version 17.0 software. RESULTS Ninety-two human immunodeficiency virus-infected children met the criteria of inclusion. After 24 weeks of treatment, we observed that 14.1% of children had at least one side effect during our study. Side effects were many and varied, with the most frequent being cutaneous rash, nausea, vomiting, and diarrhea (38.5%, 23.1%, 15.4%, and 15.4%, respectively). Side effects were grade 1 in most cases. One case of grade 2 and one case of grade 3 were observed with rash. We observed one case of grade 3 side effects during our study. The treatment regimen was changed in 15.2% of cases, including one case because of side effects. CONCLUSION ADRs are not rare in Mali, particularly in children. These ADRs have an impact on quality of life for patients. We recommend a pharmacovigilance system for sustainable management of side effects in patients infected with human immunodeficiency virus in Mali.
Integrating Crop Growth Models with Whole Genome Prediction through Approximate Bayesian Computation

Genomic selection, enabled by whole genome prediction (WGP) methods, is revolutionizing plant breeding. Existing WGP methods have been shown to deliver accurate predictions in the most common settings, such as prediction of across environment performance for traits with additive gene effects. However, prediction of traits with non-additive gene effects and prediction of genotype by environment interaction (G×E), continues to be challenging. Previous attempts to increase prediction accuracy for these particularly difficult tasks employed prediction methods that are purely statistical in nature. Augmenting the statistical methods with biological knowledge has been largely overlooked thus far. Crop growth models (CGMs) attempt to represent the functional relationships between plant physiology and the environment in the formation of yield and similar output traits of interest. Thus, they can explain the impact of G×E and certain types of non-additive gene effects on the expressed phenotype. Approximate Bayesian computation (ABC), a novel and powerful computational procedure, allows the incorporation of CGMs directly into the estimation of whole genome marker effects in WGP. Here we provide a proof of concept study for this novel approach and demonstrate its use with a simulated data set. We show that this novel approach can be considerably more accurate than the benchmark WGP method GBLUP in predicting performance in environments represented in the estimation set as well as in previously unobserved environments for traits determined by non-additive gene effects. We conclude that this proof of concept demonstrates that using ABC for incorporating biological knowledge in the form of CGMs into WGP is a very promising novel approach to improving prediction accuracy for some of the most challenging scenarios of interest to applied geneticists.
Where should I send my post?: the concept of discourse quality in online forums and its dependency on membership size

Today's Web users are faced with a large number of available online communities for every domain. While there are rules-of-thumb for the choice of a specific community, the validity of these heuristics has hardly been tested empirically. Furthermore, there is a lack of well-founded measures that allow for a systematic comparison of different online forum communities. In this contribution, we propose the concept of discourse quality as a means to this end. This measure is conceptualized from a user perspective and combines quantitative as well as qualitative parts, including a codebook for content analysis. To show the applicability and the usefulness of this measure, we systematically compare 34 online forums with varying degrees of membership size. We are able to show that the forums with the most members online consistently show high discourse quality. Finally, we discuss the potential of benchmark measures for future online community research.
Genomic correlates of response to CTLA-4 blockade in metastatic melanoma

Is cancer immunotherapy a private affair? Immune checkpoint blockade, a relatively new cancer treatment, substantially extends the survival of a subset of patients. Previous work has shown that patients whose tumors harbor the largest number of mutations—and thus produce a large number of “neoantigens” recognized as foreign by the immune system—are most likely to benefit. Expanding on these earlier studies, Van Allen et al. studied over 100 patients with melanoma and found a similar correlation (see the Perspective by Gubin and Schreiber). There was no evidence, however, that specific neoantigen sequences were shared by patients who responded. Science, this issue p. 207, see also p. 158 Melanoma patients who respond to immunotherapy do not appear to share common tumor neoantigens. [Also see Perspective by Gubin and Schreiber ] Monoclonal antibodies directed against cytotoxic T lymphocyte–associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab, we analyzed whole exomes from pretreatment melanoma tumor biopsies and matching germline tissue samples from 110 patients. For 40 of these patients, we also obtained and analyzed transcriptome data from the pretreatment tumor samples. Overall mutational load, neoantigen load, and expression of cytolytic markers in the immune microenvironment were significantly associated with clinical benefit. However, no recurrent neoantigen peptide sequences predicted responder patient populations. Thus, detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.
Bilateral Maps for Partial Matching

Feature‐driven analysis forms the basis of many shape processing tasks, where detected feature points are characterized by local shape descriptors. Such descriptors have so far been defined to capture regions of interest centred at individual points. Using such regions to compare feature points can be problematic when performing partial shape matching, because the region of interest is typically defined as an isotropic neighbourhood around a point, which does not adapt to the geometry of the shape parts. We introduce the bilateral map, a local shape descriptor whose region of interest is defined by two feature points. Compared to the classical descriptor definition using a single point, the bilateral approach exploits the use of a second point to place more constraints on the selection of the spatial context for feature analysis. This leads to a descriptor where the shape of the region of interest adapts to the context of the two points, making it more refined for shape matching. In particular, we show that our new descriptor is more effective for partial matching, because potentially extraneous regions of the models are selectively ignored owing to the adaptive nature of the bilateral map. This property also renders the bilateral map partially insensitive to topological changes. We demonstrate the effectiveness of the bilateral map for partial matching via several correspondence and retrieval experiments and evaluate the results both qualitatively and quantitatively.
Isolating and Reconstructing Key Components of North Atlantic Ocean Variability From a Sclerochronological Spatial Network

Our understanding of North Atlantic Ocean variability within the coupled climate system is limited by the brevity of instrumental records and a deficiency of absolutely dated marine proxies. Here we demonstrate that a spatial network of marine stable oxygen isotope series derived from molluscan sclerochronologies (δ18Oshell) can provide skillful annually resolved reconstructions of key components of North Atlantic Ocean variability with absolute dating precision. Analyses of the common δ18Oshell variability, using principal component analysis, highlight strong connections with tropical North Atlantic and subpolar gyre (SPG) sea surface temperatures and sea surface salinity in the North Atlantic Current (NAC) region. These analyses suggest that low‐frequency variability is dominated by the tropical Atlantic signal while decadal variability is dominated by variability in the SPG and salinity transport in the NAC. Split calibration and verification statistics indicate that the composite series produced using the principal component analysis can provide skillful quantitative reconstructions of tropical North Atlantic and SPG sea surface temperatures and NAC sea surface salinities over the industrial period (1864–2000). The application of these techniques with extended individual δ18Oshell series provides powerful baseline records of past North Atlantic variability into the unobserved preindustrial period. Such records are essential for developing our understanding of natural climate variability in the North Atlantic Ocean and the role it plays in the wider climate system, especially on multidecadal to centennial time scales, potentially enabling reduction of uncertainties in future climate predictions.
A 115-mW, 0.5-μm CMOS GPS receiver with wide dynamic-range active filters

This paper presents a 115-mW Global Positioning System radio receiver that is implemented in a 0.5-/spl mu/m CMOS technology. The receiver includes the complete analog signal path, comprising a low-noise amplifier, I-Q mixers, on-chip active filters, and 1-bit analog-digital converters. In addition, it includes a low-power phase-locked loop that synthesizes the first local oscillator. The receiver achieves a 2.8-dB noise figure (prelimiter), a 56-dB spurious-free dynamic range, and a 17-dB signal-to-noise ratio for a noncoherent digital back-end implementation when detecting a signal power of -130 dBm at the radio-frequency input.
Structural insights on the translation initiation complex: ghosts of a universal initiation complex

All living organisms utilize ribosomes to translate messenger RNA into proteins. Initiation of translation, the process of bringing together mRNA, initiator transfer RNA, and the ribosome, is therefore of critical importance to all living things. Two protein factors, IF1 (a/eIF1A) and IF2 (a/eIF5B), are conserved among all three kingdoms of life and have been called universal initiation factors (Roll‐Mecak et al., 2001). Recent X‐ray, NMR and cryo‐EM structures of the universal factors, alone and in complex with eubacterial ribosomes, point to the structural homology among the initiation factors and initiation complexes. Taken together with genomic and functional evidence, the structural studies allow us to predict some features of eukaryotic and archaeal initiation complexes. Although initiation of translation in eukaryotes and archaea requires more initiation factors than in eubacteria we propose the existence of a common denominator initiation complex with structural and functional homology across all kingdoms of life.
Past, Present, and Future of the Pathophysiological Model of the Basal Ganglia

The current model of basal ganglia (BG) was introduced two decades ago and has settled most of our current understanding of BG function and dysfunction. Extensive research efforts have been carried out in recent years leading to further refinement and understanding of the normal and diseased BG. Several questions, however, are yet to be resolved. This short review provides a synopsis of the evolution of thought regarding the pathophysiological model of the BG and summarizes the main recent findings and additions to this field of research. We have also tried to identify major challenges that need to be addressed and resolved in the near future. Detailed accounts and state-of-the-art developments concerning research on the BG are provided in the articles that make up this Special Issue.
Feasibility and Quit Rates of the Tobacco Status Project: A Facebook Smoking Cessation Intervention for Young Adults

Background Young adult smokers are a challenging group to engage in smoking cessation interventions. With wide reach and engagement among users, Facebook offers opportunity to engage young people in socially supportive communities for quitting smoking and sustaining abstinence. Objective We developed and tested initial efficacy, engagement, and acceptability of the Tobacco Status Project, a smoking cessation intervention for young adults delivered within Facebook. Methods The intervention was based on the US Public Health Service Clinical Practice Guidelines and the Transtheoretical Model and enrolled participants into study-run 3-month secret Facebook groups matched on readiness to quit smoking. Cigarette smokers (N=79) aged 18-25, who used Facebook on most days, were recruited via Facebook. All participants received the intervention and were randomized to one of three monetary incentive groups tied to engagement (commenting in groups). Assessments were completed at baseline, 3-, 6-, and 12-months follow-up. Analyses examined retention, smoking outcomes over 12 months (7-day point prevalence abstinence, ≥50% reduction in cigarettes smoked, quit attempts and strategies used, readiness to quit), engagement, and satisfaction with the intervention. Results Retention was 82% (65/79) at 6 months and 72% (57/79) at 12 months. From baseline to 12-months follow-up, there was a significant increase in the proportion prepared to quit (10/79, 13%; 36/79, 46%, P<.001). Over a third (28/79, 35%) reduced their cigarette consumption by 50% or greater, and 66% (52/79) made at least one 24-hour quit attempt during the study. In an intent-to-treat analysis, 13% (10/79) self-reported 7-day abstinence (6/79, 8% verified biochemically) at 12-months follow-up. In their quit attempts, 11% (9/79) used a nicotine replacement therapy approved by the Food and Drug Administration, while 18% (14/79) used an electronic nicotine delivery system to quit (eg, electronic cigarette). A majority (48/79, 61%) commented on at least one Facebook post, with more commenting among those with biochemically verified abstinence at 3 months (P=.036) and those randomized to receive a personal monetary incentive (P=.015). Over a third of participants (28/79, 35%) reported reading most or all of the Facebook posts. Highest acceptability ratings of the intervention were for post ease (57/79, 72%) and thinking about what they read (52/79, 66%); 71% (56/79) recommended the program to others. Only 5 participants attended the optional cognitive-behavioral counseling sessions, though their attendance was high (6/7 sessions overall) and the sessions were rated as easy to understand, useful, and helpful (all 90-100% agreed). Conclusions A Facebook quit smoking intervention is attractive and feasible to deliver, and early efficacy data are encouraging. However, the 1.5-fold greater use of electronic cigarettes over nicotine replacement products for quitting is concerning.
Location, location: using functional magnetic resonance imaging to pinpoint brain differences relevant to stimulant use.

AIMS The purpose of this review is to summarize the neural substrate dysfunctions and disrupted cognitive, affective and experiential processes observed in methamphetamine and cocaine-dependent individuals. METHODS We reviewed all publications in PubMed that conducted comparison studies between healthy volunteers and cocaine-, amphetamine- or methamphetamine-dependent individuals using functional magnetic resonance imaging. RESULTS Stimulant dependence is characterized by a distributed alteration of functional activation to a number of experimental paradigms. Attenuated anterior and posterior cingulate activation, reduced inferior frontal and dorsolateral prefrontal cortex activation and altered posterior parietal activation point towards an inadequate demand-specific processing of information. Processes reported most consistently to be deficient in these functional neuroimaging studies include inhibitory control, executive functioning and decision-making. CONCLUSION One emerging theme is that stimulant-dependent individuals show specific, rather than generic, brain activation differences, i.e. instead of showing more or less brain activation regardless of task, they exhibit process-related brain activation differences that are consistent with a shift from context-specific, effortful processing to more stereotyped, habitual response generation.
Anaerobic bacterial populations on normal and diseased human biopsy tissue obtained at colonoscopy

Human epithelium was cultured to characterize differences in microbial populations between regions of normal colon and between polyps, inflammatory bowel disease, and cancer and their respective adjacent normal mucosa. Twenty-one patients (12 polyps, 5 inflammatory bowel disease, 4 cancer) underwent colonoscopy with anaerobic culture of mucosal biopsies from normal and diseased ascending, transverse, descending, and sigmoid colon. No differences for total number of organisms and recovery of species between ascending colon and other normal regions were seen except for sigmoid colon. Significant differences between polyps and adjacent normal tissue were seen for total number of organisms and recovery of genera and species. No significant differences in total number of organisms and recovery of genera were seen between cancer and inflammatory bowel disease and their respective adjacent normal tissue. The recovery of genera from polyps and normal tissue was Bacteroides greater than Fusobacterium greater than Clostridium greater than Eubacterium greater than Peptostreptococcus. These data suggest that (i) the total number of anaerobic organisms and species remained relatively constant, except for lower numbers in normal distal colon which were probably a result of the preparation for colonoscopy; (ii) polyp formation favored increased microbial colonization; and (iii) the increased number of organisms generally reflected those genera and species seen on adjacent normal mucosa.
An architecture for rapid decoding of large vocabulary conversational speech

This paper addresses the question of how to design a large vocabulary recognition system so that it can simultaneously handle a sophisticated language model, perform state-ofthe-art speaker adaptation, and run in one times real time1 (1 RT). The architecture we propose is based on classical HMM Viterbi decoding, but uses an extremely fast initial speaker-independent decoding to estimate VTL warp factors, feature-space and model-space MLLR transformations that are used in a final speaker-adapted decoding. We present results on past Switchboard evaluation data that indicate that this strategy compares favorably to published unlimited-time systems (running in several hundred times real-time). Coincidentally, this is the system that IBM fielded in the 2003 EARS Rich Transcription evaluation.
Joint pilot sequence design and power control for Max-Min fairness in uplink massive MIMO

This paper optimizes the pilot assignment and pilot transmit powers to mitigate pilot contamination in Massive MIMO (multiple-input multiple-output) systems. While prior works have treated pilot assignment as a combinatorial problem, we achieve a more tractable problem formulation by directly optimizing the pilot sequences. To this end, we compute a lower bound on the uplink (UL) spectral efficiency (SE), for Rayleigh fading channels with maximum ratio (MR) detection and arbitrary pilot sequences. We optimize the max-min SE with respect to the pilot sequences and pilot powers, under power budget constraints. This becomes an NP-hard signomial problem, but we propose an efficient algorithm to obtain a local optimum with polynomial complexity. Numerical results manifest the near optimality of the proposed algorithm and show significant gains over existing suboptimal algorithms.