Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis.

Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors.

Are assumptions about the model type necessary in reaction-diffusion modeling? A FRAP application.

At present, fluorescence recovery after photobleaching (FRAP) data are interpreted using various types of reaction-diffusion (RD) models: the model type is usually fixed first, and corresponding model parameters are inferred subsequently. In this article, we describe what we believe to be a novel approach for RD modeling without using any assumptions of model type or parameters. To the best of our knowledge, this is the first attempt to address both model-type and parameter uncertainties in inverting FRAP data.

A meta method for image matching.

This paper presents a novel system for image matching in optical endoscopy. The proposed metamatching system approaches the challenge of matching images in a complex scene by incorporating multiple matchers and a decision function. Experiments are presented for Crohn's disease lesion matching in capsule endoscopy with a metamatcher consisting of five independent matchers.

High-Accuracy 3D Image-Based Registration of Endoscopic Video to C-Arm Cone-Beam CT for Image-Guided Skull Base Surgery.

Registration of endoscopic video to preoperative CT facilitates high-precision surgery of the head, neck, and skull-base. Conventional video-CT registration is limited by the accuracy of the tracker and does not use the underlying video or CT image data. A new image-based video registration method has been developed to overcome the limitations of conventional tracker-based registration.

Chromatin accessibility pre-determines glucocorticoid receptor binding patterns.

Development, differentiation and response to environmental stimuli are characterized by sequential changes in cellular state initiated by the de novo binding of regulated transcriptional factors to their cognate genomic sites. The mechanism whereby a given regulatory factor selects a limited number of in vivo targets from a myriad of potential genomic binding sites is undetermined. Here we show that up to 95% of de novo genomic binding by the glucocorticoid receptor, a paradigmatic ligand-activated transcription factor, is targeted to preexisting foci of accessible chromatin.

Dynamic interaction of HDAC1 with a glucocorticoid receptor-regulated gene is modulated by the activity state of the promoter.

Although histone deacetylases (HDACs) are normally considered as co-repressors, HDAC1 has been identified as a coactivator for the glucocorticoid receptor (GR) (Qiu, Y., Zhao, Y., Becker, M.

Motion generation of robotic surgical tasks: learning from expert demonstrations.

Robotic surgical assistants offer the possibility of automating portions of a task that are time consuming and tedious in order to reduce the cognitive workload of a surgeon. This paper proposes using programming by demonstration to build generative models and generate smooth trajectories that capture the underlying structure of the motion data recorded from expert demonstrations. Specifically, motion data from Intuitive Surgical's da Vinci Surgical System of a panel of expert surgeons performing three surgical tasks are recorded.

Retinal vessel cannulation with an image-guided handheld robot.

Cannulation of small retinal vessels is often prohibitively difficult for surgeons, since physiological tremor often exceeds the narrow diameter of the vessel (40-120 microm). Using an active handheld micromanipulator, we introduce an image-guided robotic system that reduces tremor and provides smooth, scaled motion during the procedure. The micromanipulator assists the surgeon during the approach, puncture, and injection stages of the procedure by tracking the pipette and anatomy viewed under the microscope.

Intra-operative ultrasound elasticity imaging for monitoring of hepatic tumour thermal ablation.

Background: Thermal ablation is an accepted therapy for selected hepatic malignancies. However, the reliability of thermal ablation is limited by the inability to accurately monitor and confirm completeness of tumour destruction in real time. We investigated the ability of ultrasound elasticity imaging (USEI) to monitor thermal ablation.

Real-time regularized ultrasound elastography.

This paper introduces two real-time elastography techniques based on analytic minimization (AM) of regularized cost functions. The first method (1D AM) produces axial strain and integer lateral displacement, while the second method (2D AM) produces both axial and lateral strains. The cost functions incorporate similarity of radio-frequency (RF) data intensity and displacement continuity, making both AM methods robust to small decorrelations present throughout the image.

Adaptive multispectral illumination for retinal microsurgery.

It has been shown that excessive white light exposure during retinal microsurgery can induce retinal damage. To address this problem, one can illuminate the retina with a device that alternates between white, and less damaging limited-spectrum light. The surgeon is then presented with a fully colored video by recoloring the limited-spectrum light frames, using information from the white-light frames.

Surgical task and skill classification from eye tracking and tool motion in minimally invasive surgery.

In the context of minimally invasive surgery, clinical risks are highly associated with surgeons' skill in manipulating surgical tools and their knowledge of the closed anatomy. A quantitative surgical skill assessment can reduce faulty procedures and prevent some surgical risks. In this paper focusing on sinus surgery, we present two methods to identify both skill level and task type by recording motion data of surgical tools as well as the surgeon's eye gaze location on the screen.

Augmenting capsule endoscopy diagnosis: a similarity learning approach.

The current procedure for diagnosis of Crohn's disease (CD) from Capsule Endoscopy is a tedious manual process which requires the clinician to visually inspect large video sequences for matching and categorization of diseased areas (lesions). Automated methods for matching and classification can help improve this process by reducing diagnosis time and improving consistency of categorization. In this paper, we propose a novel SVM-based similarity learning method for distinguishing between correct and incorrect matches in Capsule Endoscopy (CE).

Tracked ultrasound elastography (TrUE).

This paper presents a robust framework for freehand ultrasound elastography to cope with uncertainties of freehand palpation using the information from an external tracker. In order to improve the quality of the elasticity images, the proposed method selects a few image pairs such that in each pair the lateral and out-of-plane motions are minimized. It controls the strain rate by choosing the axial motion to be close to a given optimum value.

Development of an image analysis screen for estrogen receptor alpha (ERα) ligands through measurement of nuclear translocation dynamics.

We have developed a robust high-content assay to screen for novel estrogen receptor alpha (ERα) agonists and antagonists by quantitation of cytoplasmic to nuclear translocation of an estrogen receptor chimera in 384-well plates. The screen utilizes a green fluorescent protein tagged-glucocorticoid/estrogen receptor (GFP-GRER) chimera which consisted of the N-terminus of the glucocorticoid receptor fused to the human ER ligand binding domain. The GFP-GRER exhibited cytoplasmic localization in the absence of ERα ligands, and translocated to the nucleus in response to stimulation with ERα agonists or antagonists.

Multi-environment model estimation for motility analysis of Caenorhabditis elegans.

The nematode Caenorhabditis elegans is a well-known model organism used to investigate fundamental questions in biology. Motility assays of this small roundworm are designed to study the relationships between genes and behavior. Commonly, motility analysis is used to classify nematode movements and characterize them quantitatively.

Expanding horizons for nuclear receptors.

The nuclear receptor joint Keystone meetings, formerly organized as 'Steroid Sisters' and 'Orphan Brothers', met this year under the banners, 'Signalling, Gene Regulation and Cancer' and 'Development, Physiology and Disease'. The change reflected both the excellent progress that has been made, as well as new directions that are now central to the field. The meeting covered all aspects of regulation by nuclear receptors and provided a good orientation for investigators new to the area, as well as a timely update for those with long tenure in the field.

Review of methods for objective surgical skill evaluation.

Background: Rising health and financial costs associated with iatrogenic errors have drawn increasing attention to the dexterity of surgeons. With the advent of new technologies, such as robotic surgical systems and medical simulators, researchers now have the tools to analyze surgical motion with the goal of differentiating the level of technical skill in surgeons.

Methods: The review for this paper is obtained from a Google Scholar and PubMed search of the key words "objective surgical skill evaluation.

3D shortcuts to gene regulation.

Recent technologies have allowed high-resolution genome-wide binding profiles of numerous transcription factors and other proteins. A widespread observation has emerged from studies in diverse mammalian systems: most binding events are located at great distances from gene promoters. It is becoming apparent that the traditional one-dimensional view of gene regulation via the proximal cis regulatory elements is over-simplified.

Histone H1 phosphorylation is associated with transcription by RNA polymerases I and II.

Histone H1 phosphorylation affects chromatin condensation and function, but little is known about how specific phosphorylations impact the function of H1 variants in higher eukaryotes. In this study, we show that specific sites in H1.2 and H1.

Circulating tumor cells in metastatic colorectal cancer: efficacy and feasibility of different enrichment methods.

Comprehensive in vitro and in vivo studies comparing EpCAM-based methods with other cytometric CTC enrichment technologies in metastatic colorectal cancer (mCRC) patients are lacking. We compare four manual cytometric methods to detect CTCs in vitro and in mCRC patients. The EpCAM-based technology, MACS HEA MicroBeads((R)), showed a significant better tumor cell recovery rate compared to other cytometric methods (p-value<0.

A generalized Kernel Consensus-based robust estimator.

In this paper, we present a new Adaptive-Scale Kernel Consensus (ASKC) robust estimator as a generalization of the popular and state-of-the-art robust estimators such as RANdom SAmple Consensus (RANSAC), Adaptive Scale Sample Consensus (ASSC), and Maximum Kernel Density Estimator (MKDE). The ASKC framework is grounded on and unifies these robust estimators using nonparametric kernel density estimation theory. In particular, we show that each of these methods is a special case of ASKC using a specific kernel.

p53 binding to nucleosomal DNA depends on the rotational positioning of DNA response element.

The sequence-specific binding to DNA is crucial for the p53 tumor suppressor function. To investigate the constraints imposed on p53-DNA recognition by nucleosomal organization, we studied binding of the p53 DNA binding domain (p53DBD) and full-length wild-type p53 protein to a single p53 response element (p53RE) placed near the nucleosomal dyad in six rotational settings. We demonstrate that the strongest p53 binding occurs when the p53RE in the nucleosome is bent in the same direction as observed for the p53-DNA complexes in solution and in co-crystals.

Trans-regulation of histone deacetylase activities through acetylation.

HDAC1 and -2 are highly conserved enzymes and often coexist in the same coregulator complexes. Understanding the regulation of histone deacetylase activities is extremely important because these enzymes play key roles in epigenetic regulation in normal and cancer cells. We previously showed that HDAC1 is required for glucocorticoid receptor-mediated transcription activation and that its activity is regulated through acetylation by p300 during the induction cycle.