Regularizing Face Verification Nets For Pain Intensity Regression

Limited labeled data are available for the research of estimating facial expression intensities. For instance, the ability to train deep networks for automated pain assessment is limited by small datasets with labels of patient-reported pain intensities. Fortunately, fine-tuning from a data-extensive pre-trained domain, such as face verification, can alleviate this problem. In this paper, we propose a network that fine-tunes a state-of-the-art face verification network using a regularized regression loss and additional data with expression labels. In this way, the expression intensity regression task can benefit from the rich feature representations trained on a huge amount of data for face verification. The proposed regularized deep regressor is applied to estimate the pain expression intensity and verified on the widely-used UNBC-McMaster Shoulder-Pain dataset, achieving the state-of-the-art performance. A weighted evaluation metric is also proposed to address the imbalance issue of different pain intensities.Comment: 5 pages, 3 figure; Camera-ready version to appear at IEEE ICIP 201

PERT: A Method for Expression Deconvolution of Human Blood Samples from Varied Microenvironmental and Developmental Conditions

The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells). Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity

ISOpureR: an R implementation of a computational purification algorithm of mixed tumour profiles

Background Tumour samples containing distinct sub-populations of cancer and normal cells present challenges in the development of reproducible biomarkers, as these biomarkers are based on bulk signals from mixed tumour profiles. ISOpure is the only mRNA computational purification method to date that does not require a paired tumour-normal sample, provides a personalized cancer profile for each patient, and has been tested on clinical data. Replacing mixed tumour profiles with ISOpure-preprocessed cancer profiles led to better prognostic gene signatures for lung and prostate cancer. Results To simplify the integration of ISOpure into standard R-based bioinformatics analysis pipelines, the algorithm has been implemented as an R package. The ISOpureR package performs analogously to the original code in estimating the fraction of cancer cells and the patient cancer mRNA abundance profile from tumour samples in four cancer datasets. Conclusions The ISOpureR package estimates the fraction of cancer cells and personalized patient cancer mRNA abundance profile from a mixed tumour profile. This open-source R implementation enables integration into existing computational pipelines, as well as easy testing, modification and extension of the model.Prostate Cancer CanadaMovember Foundation (Grant RS2014-01

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Carbon nanotubes (CNTs) are at present being considered as potential nanovectors with the ability to deliver therapeutic cargoes into living cells. Previous studies established the ability of CNTs to enter cells and their therapeutic utility, but an appreciation of global intracellular trafficking associated with their cellular distribution has yet to be described. Despite the many aspects of the uptake mechanism of CNTs being studied, only a few studies have investigated internalization and fate of CNTs inside cells in detail. In the present study, intracellular localization and trafficking of RNA-wrapped, oxidized double-walled CNTs (oxDWNT–RNA) is presented. Fixed cells, previously exposed to oxDWNT–RNA, were subjected to immunocytochemical analysis using antibodies specific to proteins implicated in endocytosis; moreover cell compartment markers and pharmacological inhibitory conditions were also employed in this study. Our results revealed that an endocytic pathway is involved in the internalization of oxDWNT–RNA. The nanotubes were found in clathrin-coated vesicles, after which they appear to be sorted in early endosomes, followed by vesicular maturation, become located in lysosomes. Furthermore, we observed co-localization of oxDWNT–RNA with the small GTP-binding protein (Rab 11), involved in their recycling back to the plasma membrane via endosomes from the trans-golgi network

Case Report: Dual nebulised antibiotics among adults with cystic fibrosis and chronic Pseudomonas infection [version 2; referees: 1 approved, 2 approved with reservations]

Pulmonary exacerbations in adults with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (Psae) infection are usually treated with dual intravenous antibiotics for 14 days, despite the lack of evidence for best practice. Intravenous antibiotics are commonly associated with various systemic adverse effects, including renal failure and ototoxicity. Inhaled antibiotics are less likely to cause systematic adverse effects, yet can achieve airway concentrations well above conventional minimum inhibitory concentrations. Typically one inhaled antibiotic is used at a time, but dual inhaled antibiotics (i.e. concomitant use of two different inhaled antibiotics) may have synergistic effect and achieve better results in the treatment of exacerbations. We presented anecdotal evidence for the use of dual inhaled antibiotics as an acute treatment for exacerbations, in the form of a case report. A female in her early thirties with CF and chronic Psae infection improved her FEV1 by 5% and 2% with two courses of dual inhaled antibiotics to treat exacerbations in 2016. In contrast, her FEV1 changed by 2%, –2%, 0% and 2%, respectively, with four courses of dual intravenous antibiotics in 2016. Baseline FEV1 was similar prior to all six courses of treatments. The greater FEV1 improvements with dual inhaled antibiotics compared to dual intravenous antibiotics suggest the potential role of using dual inhaled antibiotics to treat exacerbations among adults with CF and chronic Psae infection, especially since a greater choice of inhaled anti-pseudomonal antibiotics is now available. A previous study in 1985 has looked at the concomitant administration of inhaled tobramycin and carbenicillin, by reconstituting antibiotics designed for parenteral administration. To our knowledge, this is the first literature to describe the concomitant use of two different antibiotics specifically developed for delivery via the inhaled route

Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger

Background: Cardiac hypertrophy is central to the etiology of heart failure. Understanding the molecular pathways promoting cardiac hypertrophy may identify new targets for therapeutic intervention. Sodium-proton exchanger (NHE1) activity and expression levels in the heart are elevated in many models of hypertrophy through protein kinase C (PKC)/MAPK/ERK/p90RSK pathway stimulation. Sustained NHE1 activity, however, requires an acid-loading pathway. Evidence suggests that the Cl-/HCO3- exchanger, AE3, provides this acid load. Here we explored the role of AE3 in the hypertrophic growth cascade of cardiomyocytes.Methods: AE3-deficient (ae3-/-) mice were compared to wildtype (WT) littermates to examine the role of AE3 protein in the development of cardiomyocyte hypertrophy. Mouse hearts were assessed by echocardiography. As well, responses of cultured cardiomyocytes to hypertrophic stimuli were measured. pH regulation capacity of ae3-/- and WT cardiomyocytes was assessed in cultured cells loaded with the pH-sensitive dye, BCECF-AM.Results: ae3-/- mice were indistinguishable from wild type (WT) mice in terms of cardiovascular performance. Stimulation of ae3-/- cardiomyocytes with hypertrophic agonists did not increase cardiac growth or reactivate the fetal gene program. ae3-/- mice are thus protected from pro-hypertrophic stimulation. Steady state intracellular pH (pHi) in ae3-/- cardiomyocytes was not significantly different from WT, but the rate of recovery of pHi from imposed alkalosis was significantly slower in ae3-/- cardiomyocytes.Conclusions: These data reveal the importance of AE3-mediated Cl-/HCO3- exchange in cardiovascular pH regulation and the development of cardiomyocyte hypertrophy. Pharmacological antagonism of AE3 is an attractive approach in the treatment of cardiac hypertrophy.Centro de Investigaciones Cardiovasculare

In the Margins: How Mainstream Legal Advocacy Strategies Fail to Fully Assist Asian American, Native Hawaiian, and Pacific Islander LGBT Youth

This Article will discuss and critique the tenuous relationship between the law and APA LGBT youth. APA LGBT youth stand as a compelling example of a vulnerable community—one that faces exposure to racism, homophobia, and mental health battles—that, for unknown reasons, are markedly disassociated from using the courts. This Article traces this estrangement to a slew of practical barriers that make legal relief improbable for an APA LGBT. Such obstacles range from the tremendous difficulty in contacting a lawyer, to an inadequate body of substantive legal protection. As a result, unless steps are taken to address this problem, APA LGBT youth community will remain largely excluded from the possibility of legal justice.</p

Influence of packing density and surface roughness of vertically-aligned carbon nanotubes on adhesive properties of gecko-inspired mimetics.

We have systematically studied the macroscopic adhesive properties of vertically aligned nanotube arrays with various packing density and roughness. Using a tensile setup in shear and normal adhesion, we find that there exists a maximum packing density for nanotube arrays to have adhesive properties. Too highly packed tubes do not offer intertube space for tube bending and side-wall contact to surfaces, thus exhibiting no adhesive properties. Likewise, we also show that the surface roughness of the arrays strongly influences the adhesion properties and the reusability of the tubes. Increasing the surface roughness of the array strengthens the adhesion in the normal direction, but weakens it in the shear direction. Altogether, these results allow progress toward mimicking the gecko's vertical mobility.The authors acknowledge funding from the EC project Technotubes.This is the accepted manuscript. The final version is available at http://pubs.acs.org/doi/abs/10.1021/am507822b

Regulatory (pan-)genome of an obligate intracellular pathogen in the PVC superphylum.

Like other obligate intracellular bacteria, the Chlamydiae feature a compact regulatory genome that remains uncharted owing to poor genetic tractability. Exploiting the reduced number of transcription factors (TFs) encoded in the chlamydial (pan-)genome as a model for TF control supporting the intracellular lifestyle, we determined the conserved landscape of TF specificities by ChIP-Seq (chromatin immunoprecipitation-sequencing) in the chlamydial pathogen Waddlia chondrophila. Among 10 conserved TFs, Euo emerged as a master TF targeting &gt;100 promoters through conserved residues in a DNA excisionase-like winged helix-turn-helix-like (wHTH) fold. Minimal target (Euo) boxes were found in conserved developmentally-regulated genes governing vertical genome transmission (cytokinesis and DNA replication) and genome plasticity (transposases). Our ChIP-Seq analysis with intracellular bacteria not only reveals that global TF regulation is maintained in the reduced regulatory genomes of Chlamydiae, but also predicts that master TFs interpret genomic information in the obligate intracellular α-proteobacteria, including the rickettsiae, from which modern day mitochondria evolved

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.Postprint (published version