Reconstructing gene regulatory networks from gene expression data has received tremendous attention in functional genomics following advancements in microarray technology. These networks provide the framework for medical diagnosis, drug design, disease treatment and biological research. Several approaches from simple clustering to highly complex hybrid techniques have been proposed in literature to understand the regulatory roles of genes and proteins. The nature of the data from microarray experiments however poses a huge informatics challenge for accurate network identification. In this paper, we present the least absolute shrinkage and selection operator vector autoregressive (Lasso-VAR) technique that incorporates stability constraints through Geršgorin's theorem for inferring stable, sparse and causal genetic networks from steady-state data.
Robot-assisted laparoscopic partial nephrectomies (RALPN) are performed to treat patients with locally confined renal carcinoma. However, there are challenges in identifying tumor margins and critical benign structures in this time-critical procedure. The primary objective of this effort is to couple multiple image and data streams together to augment visual information currently provided to surgeons performing RALPN and ultimately ensure complete tumor resection and minimal damage to functional structures. Our framework involves registering high-resolution anatomic images with intra-operative ultrasound (US) and optical-based surface mapping using EM tracking. We have currently implemented methods for surface reconstructions from MR, US, and the stereo-endoscope, US-to- MR registration, and deformation registration using control points. These components have been evaluated through phantom studies to demonstrate protocol feasibility.
Arrhythmia generation post ischemia has been linked to loss of cell-to-cell electrical interaction. Arrhythmias like ventricular fibrillation and tachycardia manifest as reentrant circuits at the tissue level. In this paper, a discrete venticular myocyte network of 100×100 cells interconnected using gap junction conductances is simulated along with an ischemic inclusion to study the wave patterns that arise from the ischemic zone due to varied coupling intervals of the stimulus. It is observed from the simulations that premature excitation of the tissue in presence of an ischemic zone can act as a substrate to induce sustained reentrant arrhythmias. Also, these reentrant wave patterns are generated only within a limited window of reduced coupling intervals.
Traditional rehabilitation in the United States has been ineffective mainly due to the lack of patients fulfilling their program requirements. The PiP Virtual Rehabilitation System offers patients an engaging and customizable rehabilitation program. The PiP system is able to quantify improvement in balance by using the Nintendo Wii Balance Board (WBB) to measure the patient's center of pressure (CoP). Microsoft's Kinect for Windows (KW) is used in conjunction with the WBB to render a virtual environment for patient engagement. While the patient performs tasks in the virtual setting, their progress is monitored and displayed for the user via a graphical user interface (GUI). The anterior/posterior (A/P) maximum excursion range is calculated by identifying the largest range on the y-axis between the plotted CoP positional data. Similarly, the medial/lateral (M/L) maximum excursion range is calculated using the x-axis. Plots depicting a decrease in maximum excursion values in either the A/P or M/L directions are indicative of an improvement in balance. The PiP system is an improvement on prior rehabilitation systems.
This research aims to develop an injectable polymer-based platform to enable minimally-invasive targeted delivery of drug-loaded nano particles. Studies have shown that polymer-stabilized gas microbubbles are effective in enhancing an ultrasound image, especially those involving cancerous tumors. These contrast agents can serve a dual purpose when designed to encapsulate a drug within the shell, providing both diagnostic and therapeutic applications. The current gold standard treatment of non-resectable pancreatic ductal adenocarcinoma (PDA) is gemcitabine (GEM), which is administered systemically. However, response rates are low because the tumor environment inhibits the drug, especially the stroma surrounding the tumor. We hypothesize that GEM-loaded microbubbles injected intravenously will pass through the stroma and, when exposed to ultrasound (US), will burst to form nanoshards (n-Sh) which will lodge within the pancreatic tumor tissue, undergo sustained release of encapsulated GEM, and lead to cancer cell death through targeted therapy.
Advances in biosensor sensitivity, specificity, and accessibility are required for the development of next generation diagnostic tools. Solid-state nanopores consisting of sub-10 nm in diameter pores drilled into an insulating material show promise as single-molecule biosensors for detecting both nucleic acid and protein targets. However, this technology is limited by rapid analyte translocation speeds and complex and/or inconsistent device assemblies. To address these limitations, we have developed two orthogonally tunable solid-state nanopore modifications which slow nucleic acid translocation speeds and streamline device assembly and manipulation through the use of a 3-dimensional polymeric nanofiber mesh (NFM) coating and the development of a novel microfluidic device, respectively. A range of translocation speeds from 1x to >100x slower than a bare nanopore were achieved by tuning the chemical composition of the NFM coating. In addition, a microfluidic device was designed to streamline nanopore assembly enabling facile integration of both sample purification protocols and single-molecule detection using optical and electronic readouts simultaneously.
Silicon Dioxide (SiO 2 ) and Titanium Dioxide (TiO 2 ) are engineered nanoparticles often ingested from food and food packaging. SiO 2 is a common additive, where it is used as a flow agent or to absorb extra water [1]. TiO 2 is commonly used as a pigment for foods including candy and medications, and is often found in cosmetic skin care products [2]. The effects of ingesting these materials, however, is not yet fully understood. The purpose of this study is to characterize the size and surface chemistry of 30 nm SiO 2 and TiO 2 nanoparticles following digestion and to determine how nanoparticle ingestion affects small intestinal alkaline phosphatase activity.
Current approaches for studying tumor activity in patients involve molecular characterization in excised tissue or biopsied samples. Recognizing that tumors are composed of heterogeneous arrays of cells and their environment, there is a compelling rationale to explore the macroscopic organization of tumor tissue. We present a novel methodology for probing the micro-structural constituents of tumors in vivo utilizing generalized Q-space MRI. This approach employs varying magnetic field gradients and diffusion sensitivities to yield voxel-scale probability distribution functions of proton diffusivity, and then maps multi-voxel cellular alignment with tractography. Using this methodology, we describe the presence of macroscopic organizational features in patients with head and neck cancers, specifically depicting regional differences between the geometrically coherent periphery and incoherent core region. Such methods may comprise a method for assessing attributes of tumor biology in vivo and for predicting the response of such tumors to various drugs and interventions.
Extracellular matrix (ECM) architecture can play a critical role in cell motility during disease pathogenesis, including that of cancer. Aligned collagen fibers have previously been used to study the effect of ECM architecture on cancer cell motility. Due in part to the stasis of such in vitro model systems, the relationship between changes in ECM architecture and cell motility remains poorly understood. The goal of the present study was to establish a model system to study the effect of change in fiber alignment on cell motility. We present a model system that employs a programmable shape memory electrospun scaffold and automated cell tracking and show that changes in fiber alignment can direct cell motility.
Summary form only given. Our goal here was to develop an Escherichia coli based sensing and actuation system. Here we divided the genetic circuitry required for actuation and sensing into two strains of E. coli and linked the two strains via a cell-cell communication signal. We targeted a quorum-sensing (QS) signaling molecule to control the motility response of our actuator strain. We demonstrated that the actuator cells showed signaling molecule dependent motility. Further, we developed a mathematical model that describes our engineered actuator system to provide insight into the key parameters controlling behavior of the system. As a model sensing system, we built an isopropyl β-D-1-thiogalactopyranoside (IPTG) sensor in E. coli. The sensor was designed to produce the QS signaling molecule in response to IPTG. We then demonstrated that the actuator cells respond to signaling molecule produced by this sensor strain. The sensing and actuation system engineered here can be used to build synthetic networks where motility is tightly regulated and controlled by cell-cell communication.
An elastic spectrin network surrounding erythrocytes has been well characterized. Evidence suggests that a similar spectrin network may exist in the nucleus of nonerythrocytes. This work involves mechanically testing cells to determine if a spectrin network may provide elasticity to the cell nucleus.
Damage to the central nervous system caused by injury or disease effects millions of people yearly. Neural stem and progenitor cell mediated therapies are a promising method of treatment for this damage. Before these therapies can be considered for clinical use, however, a deeper understanding of direction of in vivo neural progenitor cell (NPC) fate must be gained. In this study, a model of one site of active neurogenesis in the adult brain, the subventricular zone, is created utilizing flow and static stimulated conditioned media and extracellular matrix from microvascular endothelial cells in combination with primary NPCs. With this model we have demonstrated that flow and static EC-ECM has differential effects on NPC survival and differentiation.
Spinal Cord Injury is a devastating and debilitating condition. To assess the extent of recovery after rehabilitation, cell transplantation and pharmacological interventions, array of behavioral, electrophysiological and histological techniques are needed. Functional recovery is often assessed using behavior, gait and kinetic testing. While behavior and kinematic testing are possible, kinetic testing often poses several limitations in small animal model. In this paper, we present details of a custom-built body weight support treadmill device with integrated kinetic setup. Data obtained from preliminary testing validates the kinetic outcomes during walking on a treadmill in animals.
In this paper, the design of a low power heterogeneous wearable multi-sensor system, built with Zynq System-on-Chip (SoC), for human activity evaluation is presented. The powerful data processing capability and flexibility of this SoC represent significant improvements over our previous ARM based system designs. The new system captures and compresses multiple color images and sensor data simultaneously. Several strategies are adopted to minimize power consumption. Our wearable system provides a new tool for the evaluation of human activity, including diet, physical activity and lifestyle.
This paper presents an image-based indoor localization system for tracking older individuals' movement at home. In this system, images are acquired at a low frame rate by a miniature camera worn conveniently at the chest position. The correspondence between adjacent frames is first established by matching the SIFT (scale-invariant feature transform) based key points in a pair of images. The location changes of these points are then used to estimate the position of the wearer based on use of the pinhole camera model. A preliminary study conducted in an indoor environment indicates that the location of the wearer can be estimated with an adequate accuracy.
In this paper, an efficient field-programmable gate array (FPGA) implementation of the JPEG baseline image compression encoder is presented for wearable devices in health and wellness applications. In order to gain flexibility in developing FPGA-specific software and balance between real-time performance and resources utilization, A High Level Synthesis (HLS) tool is utilized in our system design. An optimized dataflow configuration with a padding scheme simplifies the timing control for data transfer. Our experiments with a system-on-chip multi-sensor system have verified our FPGA implementation with respect to real-time performance, computational efficiency, and FPGA resource utilization.
Traditional EEG systems are limited when utilized in point-of-care applications due to its immobility and tedious preparation procedures. We are designing a novel device named single-unit wireless EEG sensor to solve these problems. The sensor has a size similar to a U.S. penny. Four electrodes are installed within a 20mm diameter cylinder. It can be applied to scalp in seconds to amplify, digitize and wirelessly transmit EEG. Before the design and construction of an actual sensor, in this paper, we perform a set of simulations to quantitatively study: 1) can the sensor acquire EEG reliably? 2) will the selection of sensor orientation be an important factor to influence signal strength? Our results demonstrate positive answers to these questions. Moreover, the signal sensor acquired appears to be comparable to the signal from the standard 10-20 system. These results warrant the further design and construction of a single-unit wireless EEG sensor.
This study investigates the use of a chest-worn wearable computer, the eButton, to assess physical performance of older adults. The Short Physical Performance Battery (SPPB), a standard cliniucal test, is first conducted on older human subjects. Then, a triaxial accelerometer and a triaxial gyroscope within the eButton are utilized to record acceleration and angular velocity of body motion on the same subjects for one week. The sensor data corresponding to walking episodes are segmented and features in the time and frequency domains are extracted. Comparison between these features and the total SPPB scores shows that the sensor data acquired in free-living conditions can be used as indicators of the subjects physical performance.
Gene therapies have emerged as a promising treatment for congestive heart failure, yet they lack a method for minimally invasive, uniform delivery. To address this need we developed Cerberus, a minimally invasive parallel wire robot for cardiac interventions. Prior work on controlling the movement of Cerberus required accurate knowledge of device geometry. In order to determine the geometry of the device in vivo, this paper presents work on developing an auto-calibration procedure to measure the geometry of the robot using force sensors to move injector. The presented auto-calibration routine is able to identify the shape of the device to within 0.5 mm and 0.9°.
Progress in bio-printing techniques has accentuated the need for non-invasive imaging modalities with high sensitivity, high resolution, and imaging depth of a few millimeters. Mesoscopic Fluorescence Molecular Tomography (MFMT) is a promising imaging modality for 3D localization and quantification of fluorescent labeled cells in thick scaffolds. Here we report on the characterization of our second generation MFMT system which uses an Electron-Multiplying charge coupled device (EMCCD). More precisely, we report on the effects of EM gain and deep cooling of the camera on signal-to-noise ratio (SNR) and hence the sensitivity. Experimental results showed that these parameters, when used in conjunction, increased SNR by at least 3 fold.
