429 research outputs found
Talking Head from Speech Audio using a Pre-trained Image Generator
We propose a novel method for generating high-resolution videos of talking-heads from speech audio and a single 'identity' image. Our method is based on a convolutional neural network model that incorporates a pre-trained StyleGAN generator. We model each frame as a point in the latent space of StyleGAN so that a video corresponds to a trajectory through the latent space. Training the network is in two stages. The first stage is to model trajectories in the latent space conditioned on speech utterances. To do this, we use an existing encoder to invert the generator, mapping from each video frame into the latent space. We train a recurrent neural network to map from speech utterances to displacements in the latent space of the image generator. These displacements are relative to the back-projection into the latent space of an identity image chosen from the individuals depicted in the training dataset. In the second stage, we improve the visual quality of the generated videos by tuning the image generator on a single image or a short video of any chosen identity. We evaluate our model on standard measures (PSNR, SSIM, FID and LMD) and show that it significantly outperforms recent state-of-the-art methods on one of two commonly used datasets and gives comparable performance on the other. Finally, we report on ablation experiments that validate the components of the model. The code and videos from experiments can be found at https://mohammedalghamdi.github.io/talking-heads-acm-mm
Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice
<p>Abstract</p> <p>Background</p> <p>We reported that roflumilast, a phosphodiesterase 4 inhibitor, given orally at 5 mg/kg to mice prevented the development of emphysema in a chronic model of cigarette smoke exposure, while at 1 mg/kg was ineffective. Here we investigated the effects of roflumilast on the volume density (V<sub>V</sub>) of the inflammatory cells present in the lungs after chronic cigarette smoke exposure.</p> <p>Methods</p> <p>Slides were obtained from blocks of the previous study and V<sub>V </sub>was assessed immunohistochemically and by point counting using a grid with 48 points, a 20× objective and a computer screen for a final magnification of 580×. Neutrophils were marked with myeloperoxidase antibody, macrophages with Mac-3, dendritic cells with fascin, B-lymphocytes with B220, CD4+ T-cells with CD4+ antibody, and CD8+T-cells with CD8-α. The significance of the differences was calculated using one-way analysis of variance.</p> <p>Results</p> <p>Chronic smoke exposure increased neutrophil V<sub>V </sub>by 97%, macrophage by 107%, dendritic cell by 217%, B-lymphocyte by 436%, CD4+ by 524%, and CD8+ by 417%. The higher dose of roflumilast prevented the increase in neutrophil V<sub>V </sub>by 78%, macrophage by 82%, dendritic cell by 48%, B-lymphocyte by 100%, CD4+ by 98% and CD8+ V<sub>V </sub>by 88%. The lower dose of roflumilast did not prevent the increase in neutrophil, macrophage and B-cell V<sub>V </sub>but prevented dendritic cells by 42%, CD4+ by 55%, and CD8+ by 91%.</p> <p>Conclusion</p> <p>These results indicate (<it>i</it>) chronic exposure to cigarette smoke in mice results in a significant recruitment into the lung of inflammatory cells of both the innate and adaptive immune system; (<it>ii</it>) roflumilast at the higher dose exerts a protective effect against the recruitment of all these cells and at the lower dose against the recruitment of dendritic cells and T-lymphocytes; (<it>iii</it>) these findings underline the role of innate immunity in the development of pulmonary emphysema and (<it>iiii</it>) support previous results indicating that the inflammatory cells of the adaptive immune system do not play a central role in the development of cigarette smoke induced emphysema in mice.</p
Comparison of male reproductive success in malaria-refractory and susceptible strains of Anopheles gambiae
<p>Abstract</p> <p>Background</p> <p>In female mosquitoes that transmit malaria, the benefits of being refractory to the <it>Plasmodium </it>parasite are balanced by the immunity costs in the absence of infection. Male mosquitoes, however, gain no advantage from being refractory to blood-transmitted parasites, so that any costs associated with an enhanced immune system in the males limit the evolution of female refractoriness and has practical implications for the release of transgenic males.</p> <p>Methods</p> <p>Aspects of the male cost of carrying <it>Plasmodium</it>-refractory genes were estimated by comparing the males' immune response and reproductive success among strains of <it>Anopheles gambiae </it>that had been selected for refractoriness or extreme susceptibility to the rodent malaria parasite, <it>Plasmodium yoelii nigeriensis</it>. The refractory males had a stronger melanization response than males from the susceptible line. Four traits were used as correlates of a male's reproductive success: the proportion of females that were inseminated by a fixed number of males in a cage within a fixed time frame, the proportion of females with motile sperm in their spermathecae, the proportion of ovipositing females, and the mean number of eggs per batch.</p> <p>Results</p> <p>Although there were significant differences among groups of males in sperm motility and oviposition success, these differences in male reproductive success were not associated with the refractory or susceptible male genotypes. Contrary to expectation, females mated to early emerging refractory males laid significantly more eggs per batch than females mated to later emerging susceptible males. Sperm motility and oviposition success were strongly correlated suggesting that variation in sperm motility influences female oviposition and ultimately male reproductive success.</p> <p>Conclusion</p> <p>An increased melanization response in male <it>A. gambiae </it>does not diminish male reproductive success under the experimental protocol used in this study. That refractory males induced ovipositing females to lay more eggs than susceptible males is an interesting result for any strategy considering the release of transgenic males. That sperm motility influences female oviposition is also important for the release of transgenic males.</p
Increased levels of (class switched) memory B cells in peripheral blood of current smokers
There is increasing evidence that a specific immune response contributes to the pathogenesis of COPD. B-cell follicles are present in lung tissue and increased anti-elastin titers have been found in plasma of COPD patients. Additionally, regulatory T cells (Tregs) have been implicated in its pathogenesis as they control immunological reactions. We hypothesize that the specific immune response in COPD is smoke induced, either by a direct effect of smoking or as a result of smoke-induced lung tissue destruction (i.e. formation of neo-epitopes or auto antigens). Furthermore, we propose that Tregs are involved in the suppression of this smoke-induced specific immune response
An Analysis of Solution Properties of the Graph Coloring Problem
This paper concerns the analysis of solution properties of the Graph Coloring Problem. For this purpose, we introduce a property based on the notion of representative sets which are sets of vertices that are always colored the same in a set of solutions. Experimental results on well-studied DIMACS graphs show that many of them contain such sets and give interesting information about the diversity of the solutions. We also show how such an analysis may be used to improve a tabu search algorithm
Predominant constitutive CFTR conductance in small airways
BACKGROUND: The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. METHODS: We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. RESULTS: In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath) of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25), but when gluconate replaced luminal Cl(-), the bionic Cl(- )diffusion potentials (-58 ± 3 mV; n = 25) were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl(- )permeability was at least 5 times greater than Na(+ )permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM)+IBMX (100 μM), ATP (100 μM), or adenosine (100 μM), but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM), GlyH-101* (5–50 μM), and CFTR(Inh)-172* (5 μM). RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. CONCLUSION: These results indicate that the small airway of the pig is characterized by a constitutively active Cl(- )conductance that is most likely due to CFTR
Do clinical guidelines reduce clinician dependent costs?
Clinician dependent costs are the costs of care that are under the discretion of the healthcare provider. These costs include the costs of drugs, tests and investigations, and discretionary outpatient visits and impatient stays. The purpose of this review was to summarize recent evidence, relevant to both developed and developing countries on whether evidence based clinical guidelines can change hospitals variable costs which are clinician dependent, and the degree of financial savings achieved at hospital level. Potential studies for inclusion were identified using structured searches of Econlit, J-Stor, and Pubmed databases. Two reviewers independently evaluated retrieved studies for inclusion. The methodological quality of the selected articles was assessed using the Oxford Centre for Evidence- Based Medicine (CEBM) levels of evidence. The results suggest that 10 of the 11 interventions were successful reducing financial costs. Most of the interventions, either in modeling studies or real interventions generate significant financial saving, although the former reported higher savings because the studies assumed 100 percent compliance
Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study
<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p>
<p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p>
<p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p>
<p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p>
Adherence to Antiretroviral Treatment and Correlation with Risk of Hospitalization among Commercially Insured HIV Patients in the United States
Purpose: A lower daily pill burden may improve adherence to antiretroviral treatment (ART) and clinical outcomes in patients with human immunodeficiency virus (HIV). This study assessed differences in adherence using the number of pills taken per day, and evaluated how adherence correlated with hospitalization. Methodology: Commercially insured patients in the LifeLink database with an HIV diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification code 042.xx) between 6/1/2006 and 12/31/2008 and receipt of a complete ART regimen were selected for inclusion. Patients were grouped according to their daily pill count and remained on ART for at least 60 days. Outcomes included adherence and rates of hospitalization. Adherence was measured as the proportion of days between the start and end of the regimen in which the patient maintained supply of all initiated ART components. Logistic regressions assessed the relationship between pills per day, adherence, and hospitalization, controlling for demographics, comorbidities, and ART-naïve (vs. experienced) status. Results: 7,073 patients met the study inclusion criteria, and 33.4%, 5.8%, and 60.8 % received an ART regimen comprising one, two, or three or more pills per day, respectively. Regression analysis showed patients receiving a single pill per day were significantly more likely to reach a 95 % adherence threshold versus patients receiving three or more pills per day (odds ratio [OR] = 1.59; P,0.001). Regardless of the number of pills received per day, patients were over 40 % less likely to have
Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H Inhibitor Design
Human leukotriene A4 hydrolase (hLTA4H) is a bi-functional enzyme catalyzes the hydrolase and aminopeptidase functions upon the fatty acid and peptide substrates, respectively, utilizing the same but overlapping binding site. Particularly the hydrolase function of this enzyme catalyzes the rate-limiting step of the leukotriene (LT) cascade that converts the LTA4 to LTB4. This product is a potent pro-inflammatory activator of inflammatory responses and thus blocking this conversion provides a valuable means to design anti-inflammatory agents. Four structurally very similar chemical compounds with highly different inhibitory profile towards the hydrolase function of hLTA4H were selected from the literature. Molecular dynamics (MD) simulations of the complexes of hLTA4H with these inhibitors were performed and the results have provided valuable information explaining the reasons for the differences in their biological activities. Binding mode analysis revealed that the additional thiophene moiety of most active inhibitor helps the pyrrolidine moiety to interact the most important R563 and K565 residues. The hLTA4H complexes with the most active compound and substrate were utilized in the development of hybrid pharmacophore models. These developed pharmacophore models were used in screening chemical databases in order to identify lead candidates to design potent hLTA4H inhibitors. Final evaluation based on molecular docking and electronic parameters has identified three compounds of diverse chemical scaffolds as potential leads to be used in novel and potent hLTA4H inhibitor design
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