University of Maryland, Baltimore County
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Structural Basis of HIV-1 Gag Membrane Targeting by The N-Terminal Matrix Domain
No full textAssembly of HIV-1 particles is initiated by the trafficking of viral Gag polyproteins from the cytoplasm to the plasma membrane (PM), where they co-localize and bud to form immature particles. Membrane targeting is mediated by the N-terminally myristylated matrix (MA) domain of Gag and is dependent on the PM marker phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Conversely, the mechanism of trafficking Gag molecules to specific assembly sites is unclear. In addition to PI(4,5)P2 dependent targeting, cellular proteins TIP47 and AP-3δ have been implicated to bind MA for Gag trafficking to assembly sites. In an effort to investigate the structural basis of the proposed TIP47 and AP-3δ trafficking of MA, we conducted NMR titration experiments of recombinant TIP47 and AP-3δ with MA. Our data provide new information demonstrating that (1) AP-3δ does not interact with MA and (2) Tip47 binds MA, however, was not necessary for efficient Viral Env incorporation during viral assembly in vivo. Previous in vitro membrane binding assays revealed that PI(4,5)P2 can influence membrane affinity in a concentration dependent manner. Structural studies using a water soluble form of PI(4,5)P2 [tr-PI(4,5)P2] revealed that tr-PI(4,5)P2 binds directly to MA with the 2'acyl chain unexpectedly interacting with a hydrophobic cleft on MA. This resulted in a proposed extended lipid-binding model for MA binding at the PM. Here we report that tr-PI(4,5)P2 binds non-discriminately to hydrophobic surface patches of proteins that do not bind membranes, including HIV-1 capsid (CA), which prompted us to examine MA interactions with native PI(4,5)P2 and other membrane constituents in the presence of membrane mimetic liposomes and bicelles. NMR titration experiments with detergent bicelles revealed a small subset of surface and myristate-associated residues that are sensitive to the presence of PI(4,5)P2, whereas cleft residues that bound the 2�-chains of tr-PI(4,5)P2 molecules in the absence of bicelles or liposomes were unperturbed by the addition of PI(4,5)P2. Our findings call to question extended-lipid MA:membrane binding models and suggest a targeting mechanism that includes a role for liquid disordered regions of the PM
Medical Image Quality Assessment for Stereoscopic Display Devices Using Computational Observers
No full textAs stereoscopic display devices become common, their image quality evaluation becomes increasingly important. Most studies conducted on 3D displays rely on measurements recorded through instruments or on preference experiments with humans rating their visual experience when viewing 3D content. Currently, there is no evident link that correlates physical measurements with effects on signal detection performance or perceptual issues concerning medical imaging applications. Additionally, existing human observer study results are often subjective and difficult to generalize. We designed a computational stereoscopic observer approach inspired by the mechanisms of stereopsis in human vision for task-based image quality assessment based on a set of image pairs. The stereo-observer is constrained to a left and a right image generated using a visualization operator to render 3D datasets. We analyze white noise and lumpy backgrounds using volume rendering techniques. Our simulation framework generalizes many different types of model observers including existing 2D and 3D observers as well as providing flexibility to formulate a stereo model observer approach following the principles of stereoscopic viewing. We show results quantifying the changes in performance when varying stereo angle as measured by an ideal linear stereoscopic observer. Our findings indicate that there is an increase in performance of about 13-18 for white noise and 20-46% for lumpy backgrounds, where the stereo angle is varied from 0 to 30 degrees. Additionally, different stereo devices have different performance trade-offs due to their display characteristics. Among them, crosstalk is known to affect observer perception of 3D content. We measured and report the luminance output and crosstalk characteristics for three different technologies of stereoscopic display devices. We recorded the effect of other issues on luminance profiles such as viewing angle, use of different eye wear, and screen location. Our results show that the crosstalk signature for viewing 3D content can vary considerably when using different types of 3D glasses for active stereo displays. We also show that significant differences are present in crosstalk signatures when varying the viewing angle from 0 to 20 degrees for a stereo mirror 3D display device. Combining our stereoscopic observer model and the luminance data recorded for three types of stereoscopic display devices, we quantify the effect of crosstalk on signal detection performance when using these devices linking physical device luminance data to computational trials. We found that newer version of glasses for the active stereo display device had 30% higher signal detection performance compared to the older one due to the difference in crosstalk attributed to these peripherals. As crosstalk is reduced when viewing a passive 3D display screen at varying angles, the performance of the observer increased. There was no change in performance when different screen location crosstalk data was used for assessment using the crosstalk stereo model observer. Our methodology can be extended to emulate other parameters by modifying the display model. The applicability of our observer framework extends to stereoscopic displays used for in the areas of medical, entertainment, and other demanding imaging applications
A Grammar Induction Approach for Learning and Generating Suggestions from User Interactions
No full textWith the amount of data present for research at an all-time high and growing quickly,and with the tedious and difficult process of analyzing visualizations to identify patterns and trends in data that possibly may never be found, the need for guiding a user is becoming increasingly important. Existing approaches for solving such problems typically display the history of interactions, relying on the user to identify their own missteps and find the correct path on the way to the answer [10, 11, 13, 19]. We provide an approach to assist users in obtaining answers to their research questions through the use of interaction suggestions. We outline the details of our grammar induction algorithm to generate suggestions and define the rules used to identify a lost user and to keep users on track in finding an answer, thus improving their performance. In our approach we define performance as being the accuracy of a user's answer, the total time, and the total number of actions it took to answer a given question. We claim, through an IRB approved user study, that our approach reduces the variance of the accuracy of a user and the number of actions that they take in obtaining an answer. Our results show that users accept 54% of suggestions, which is significantly greater than the random chance of providing an accurate suggestion. With those suggestions our approach produces equal or better performance in users 91% of the time. We conclude that our suggestions do not impede the user, but rather only improve their performance while guiding them along the visual analytic process
Using Machine Learning Techniques to Identify Source Code Documents
No full textThis thesis examines the application of document classification techniques to collections of source code for the purpose of semantic annotation. Typical approaches to this problem in previous research have involved static analysis, which requires an understanding of some program semantics already, dynamic analysis, which requires program execution, or learning from metadata associated with a program. The methodology of this work is unique in that it utilizes machine learning methods to identify the behavior of algorithms based solely on syntactic features of the source code. Applications include indexing source code repositories to expedite searching therein, and recognizing inconspicuous programming faults that can lead to software producing undesired results. The methodology begins with the extraction of features from source code. The performance of both decision trees and support vector machines is analyzed. In addition, a complementary approach is evaluated that uses unsupervised clustering to find natural groupings and concept descriptions in a set of source code fragments. We provide an analysis of the effects of varying n-gram degrees, feature expressiveness and feature selection on the accuracy of the classifiers, and the structure and concepts generated by the clustering approach. Even with minimally expressive features, both the support vector machine and decision tree models are able to categorize source code samples based on the algorithm they implement with high accuracy. Most classification errors tend to occur between semantically similar algorithms, but disparate algorithms are often distinguishable
Astrocyte response to 3D microenvironments
No full textNerve injuries can be catastrophic as neurons in the adult human do not divide; therefore, neurons lost due to injury cannot be replaced by innate healing processes. Current therapeutic treatments to repair traumatic brain injury consist of rehabilitative, cellular and molecular therapies. However, these approaches target only some aspects of the injury and are not completely restorative. We propose a change in direction: to induce nerve regeneration, we focus on astrocytes, support cells in the central nervous system (CNS). We aim to harness immature astrocytes to recapitulate cues that were present in the developing brain but disrupted or lost in the adult brain injury environment. We characterized newborn mouse astrocytes in two conditions, traditional two-dimensional glass coverslips and three-dimensional (3D) hydrogels. We present quantitative data supporting that 3D culture is critical for sustaining the heterogeneity of astrocytes. We also report that fibroblast growth factor induced astrocytes encapsulated in 3D hydrogels can recapitulate developmental cues and modify the hydrogel into an environment essential for neurite outgrowth and guidance. This work is a major step towards understanding key parameters that guide astrocyte development and nerve regeneration and provides a foundation to design improved strategies for CNS injury and neurodegenerative disorders
Optical Measurement on Quantum Cascade Lasers Using Femtosecond Pulses
No full textQuantum cascade lasers (QCLs) as the state-of-the-art mid-infrared (mid-IR) coherent sources have been greatly developed in aspects such as output power, energy efficiency and spectral purity. However, there are additional applications of QCLs in high demand, namely mode-locking, mid-IR modulation, etc. The inherent optical properties and ultrafast carrier dynamics can lead to solutions to these challenges. In this dissertation, we further characterize QCLs using mid-IR femtosecond (fs) pulses generated from a laser system consisting of a Ti:sapphire oscillator, a Ti:sapphire regenerative amplifier, an optical parametric amplifier and a difference frequency generator. We study the Kerr nonlinearity of QCLs by coupling resonant and off-resonant mid-IR fs pulses into an active QCL waveguide. We observe an increase in the spectral width of the transmitted fs pulses as the coupled mid-IR pulse power increases. This is explained by the self-phase modulation effect due to the large Kerr nonlinearity of QCL waveguides. We further confirm this effect by observing the intensity dependent far-field profile of the transmitted mid-IR pulses, showing the pulses undergo self-focusing as they propagate through the active QCL due to the intensity dependent refractive index. The finite-difference time-domain simulations of QCL waveguides with Kerr nonlinearity incorporated show similar behavior to the experimental results. The giant Kerr nonlinearity investigated here may be used to realize ultrafast pulse generation in QCLs. In addition, we temporally resolved the ultrafast mid-infrared transmission modulation of QCLs using a near-infrared pump/mid-infrared probe technique at room temperature. Two different femtosecond wavelength pumps are used with photon energy above and below the quantum well (QW) bandgap. The shorter wavelength pump modulates the mid-infrared probe transmission through interband transition assisted mechanisms, resulting in a high transmission modulation depth and several nanoseconds recovery lifetime. In contrast, pumping with a photon energy below the QW bandgap induces a smaller transmission modulation depth but much faster (several picoseconds) recovery lifetime, attributed to intersubband transition assisted mechanisms. The latter ultrafast modulation (>60 GHz) can provide a potential way to realize fast QCL based free space optical communication
Transcutaneous monitoring of respiratory gases in preterm neonates
No full textThe past decades have seen a widespread application of transcutaneous monitoring in neonatology. The noninvasive approach overcomes the painful nature of blood sampling. Our work focused on the technique of simultaneous noninvasive measurement of tcpO2 (transcutaneous partial pressure of oxygen) and tcpCO2 (transcutaneous partial pressure of carbon dioxide). A small sampling chamber was built connecting the carbon dioxide and oxygen sensors to measure the gases diffusing out of the skin. The measurements were based on the initial diffusion rate instead of the mass-transfer equilibrium which allows for a faster response. By using the new method, physical activities, food intake and breathing patterns were shown to have a strong effect on the amount of carbon dioxide and oxygen evolving from the human skin. The measurement parameters such as sampler area, location, position and procedure timing were optimized using design of experiments. The measurements were validated and correlated against an FDA approved commercial transcutaneous monitor (the Radiometer TCM 4.0). The experimental setup was further modified and automated, and then approved for clinical trials at the University of Maryland, School of Medicine in the Neonatal Intensive Care Unit (NICU). The results obtained from a premature baby in the NICU were correlated to the Arterial Blood Gas (ABG) analysis. The noninvasive and rate-based monitoring technique was also extended to monitoring dissolved oxygen and carbon dioxide in cell cultures. We have shown that by measuring the initial diffusion rate we were able to determine the partial pressures of the two gases in the culture. The technique could be readily automated and measurements could be made in minutes. It was tested in demonstration experiments by growing mammalian cells in a T flask and a spinner flask at 37 degree C.The results were validated using optical sensor systems. A dynamic theoretical model based on a three dimensional unit cell representation of the experimental system that includes a single blood vessel was constructed in order to gain a better fundamental understanding of the factors that determine the performance of the new approach. The model employed the finite element numerical method and accounted for the fluid mechanics, mass transfer and reaction kinetics of the system. The model was implemented using COMSOL Multiphysics engineering simulation software
THE POTENTIAL FOR GENETIC INFORMATION IN THE SOCIAL SECURITY DISABILITY PROCESS
No full textThis research effort examined the level of understanding and practices among disability claims examiners and medical and psychological consultants regarding the use of genetic information in disability determinations to help inform Social Security Administration (SSA) policy in the field of genetics. As the number of genetic tests increases, it is expected that public perception of the role of genetic information in disability determinations has evolved and the prevalence of genetic information included as part of a claimant's medical evidence has become more common-place. While SSA has specific criteria related to a limited number of medical conditions with known genetic origin, the agency does not have regulatory guidance, policies, or procedures related to the general use of genetic information in making a medical determination. In the absence of comprehensive and clear direction, SSA disability examiners and medical and psychological consultants are left to their own discretion. It is unclear what impact this discretion has, and what is needed to ensure an accurate, consistent, and timely disability determinations. The SSA disability program is a large federal program with significant expenditures and impact on individuals; therefore, changes in policies and procedures requires significant time and planning--and in many cases, involves regulatory and statutory changes. As such, it is essential that SSA anticipate the possibilities for the use of genetic information and plan accordingly. Plausible practices and beliefs among members of the public, SSA disability examiners, and SSA medical and psychological consultants in regards to use of genetic information in SSA disability determinations are discussed in this research effort. Further, insight into possible policy opportunities, knowledge gaps, and training needs are provided, as well as recommendations for future research studies
Identifying Malware Using N-Gram Clustering Metrics
No full textWe identify a new method for detecting malware within a network that can be processed in linear time. In the digital age, more files are transferred between individuals and systems that have the potential to contain malignant processes. Traditional malware detection and analysis is performed by signature based operations or by hashing current files. A malicious attacker can quickly change found signatures or change various processes to defeat hash based detection. We need a way to quickly identify malicious files to stage them for quarantine and further analysis. In this thesis we observe the previous methods used to detect malware and develop a new process to identify malware using n-gram analysis to cluster malware specimens by their similarity to each other. Specimens from a well-known malware family are used in this demonstration
Johnny Unitas: Baltimore's Cold Warrior
No full textA hero or an ideal individual is often venerated as such to fulfill a social or psychological need, and the embrace of Johnny Unitas as a symbol of the ideal Cold War common man is no different. Johnny Unitas and his identity as a suburban father and husband allowed men in the 1950's and 1960's to come to terms with the changing state of masculinity. By representing the masculine identity that developed in the post-war era while being a successful professional football player, Johnny Unitas allowed men to embrace changes to traditional masculinity by showing the possibility of maintaining traditional traits of masculinity while embracing this new lifestyle. This article examines the image of Johnny Unitas interpreted by middle and working class men and the ways in which sportswriters and advertisers promoted views of Unitas as the ideal Cold War common man