Fitting a 3D Morphable Model to Edges: A Comparison Between Hard and Soft Correspondences

We propose a fully automatic method for fitting a 3D morphable model to single face images in arbitrary pose and lighting. Our approach relies on geometric features (edges and landmarks) and, inspired by the iterated closest point algorithm, is based on computing hard correspondences between model vertices and edge pixels. We demonstrate that this is superior to previous work that uses soft correspondences to form an edge-derived cost surface that is minimised by nonlinear optimisation.Comment: To appear in ACCV 2016 Workshop on Facial Informatic

The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner

The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Fast fluorescence microscopy for imaging the dynamics of embryonic development

Live imaging has gained a pivotal role in developmental biology since it increasingly allows real-time observation of cell behavior in intact organisms. Microscopes that can capture the dynamics of ever-faster biological events, fluorescent markers optimal for in vivo imaging, and, finally, adapted reconstruction and analysis programs to complete data flow all contribute to this success. Focusing on temporal resolution, we discuss how fast imaging can be achieved with minimal prejudice to spatial resolution, photon count, or to reliably and automatically analyze images. In particular, we show how integrated approaches to imaging that combine bright fluorescent probes, fast microscopes, and custom post-processing techniques can address the kinetics of biological systems at multiple scales. Finally, we discuss remaining challenges and opportunities for further advances in this field

Ochronosis of hip joint; a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Robot life: simulation and participation in the study of evolution and social behavior.

This paper explores the case of using robots to simulate evolution, in particular the case of Hamilton's Law. The uses of robots raises several questions that this paper seeks to address. The first concerns the role of the robots in biological research: do they simulate something (life, evolution, sociality) or do they participate in something? The second question concerns the physicality of the robots: what difference does embodiment make to the role of the robot in these experiments. Thirdly, how do life, embodiment and social behavior relate in contemporary biology and why is it possible for robots to illuminate this relation? These questions are provoked by a strange similarity that has not been noted before: between the problem of simulation in philosophy of science, and Deleuze's reading of Plato on the relationship of ideas, copies and simulacra

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus

The development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. The dengue virus has three structural proteins and seven non-structural (NS) proteins. NS3 is a multifunctional protein with an N-terminal protease domain (NS3pro) that is responsible for proteolytic processing of the viral polyprotein, and a C-terminal region that contains an RNA triphosphatase, RNA helicase and RNA-stimulated NTPase domain that are essential for RNA replication. The serine protease domain of NS3 plays a central role in the replicative cycle of dengue virus. This review discusses the recent structural and biological studies on the NS2B-NS3 protease-helicase and considers the prospects for the development of small molecules as antiviral drugs to target this fascinating, multifunctional protein

Predictors of Treatment Attrition Among an Outpatient Clinic Sample of Youths With Clinically Significant Anxiety

Predictors of treatment attrition were examined in a sample of 197 youths (ages 5–18) with clinically-significant symptoms of anxiety seeking psychotherapy services at a community-based outpatient mental health clinic (OMHC). Two related definitions of attrition were considered: (a) clinician-rated dropout (CR), and (b) CR dropout qualified by phase of treatment (pre, early, or late phases) (PT). Across both definitions, rates of attrition in the OMHC sample were higher than those for anxious youths treated in randomized controlled trials, and comorbid depression symptoms predicted dropout, with a higher rate of depressed youths dropping out later in treatment (after 6 sessions). Using the PT definition, minority status also predicted attrition, with more African-American youths lost pre-treatment. Other demographic (age, gender, single parent status) and clinical (externalizing symptoms, anxiety severity) characteristics were not significantly associated with attrition using either definition. Implications for services for anxious youths in public service settings are discussed. Results highlight the important role of comorbid depression in the treatment of anxious youth and the potential value of targeted retention efforts for ethnic minority families early in the treatment process

Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients

BACKGROUND: Electronic monitoring (EM) is used increasingly to measure medication non-adherence. Unbiased EM assessment requires fulfillment of assumptions. The purpose of this study was to determine assumptions needed for internal and external validity of EM measurement. To test internal validity, we examined if (1) EM equipment functioned correctly, (2) if all EM bottle openings corresponded to actual drug intake, and (3) if EM did not influence a patient's normal adherence behavior. To assess external validity, we examined if there were indications that using EM affected the sample representativeness. METHODS: We used data from the Supporting Medication Adherence in Renal Transplantation (SMART) study, which included 250 adult renal transplant patients whose adherence to immunosuppressive drugs was measured during 3 months with the Medication Event Monitoring System (MEMS). Internal validity was determined by assessing the prevalence of nonfunctioning EM systems, the prevalence of patient-reported discrepancies between cap openings and actual intakes (using contemporaneous notes and interview at the end of the study), and by exploring whether adherence was initially uncharacteristically high and decreased over time (an indication of a possible EM intervention effect). Sample representativeness was examined by screening for differences between participants and non-participants or drop outs on non-adherence. RESULTS: Our analysis revealed that some assumptions were not fulfilled: 1) one cap malfunctioned (0.4%), 2) self-reported mismatches between bottle openings and actual drug intake occurred in 62% of the patients (n = 155), and 3) adherence decreased over the first 5 weeks of the monitoring, indicating that EM had a waning intervention effect. CONCLUSION: The validity assumptions presented in this article should be checked in future studies using EM as a measure of medication non-adherence