Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin.

Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor alphavbeta5 for particle binding. Here, we tested RPE phagocytosis and retinal function in beta5 integrin--deficient mice, which specifically lack alphavbeta5 receptors. Retinal photoresponses severely declined with age in beta5-/- mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. beta5-/- RPE in culture failed to take up isolated photoreceptor particles. beta5-/- RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in beta5-/- retina. These results demonstrate an essential role for alphavbeta5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the beta5-/- integrin mouse strain as a new animal model of age-related retinal dysfunction

Functional Cellular Anti-Tumor Mechanisms are Augmented by Genetic Proteoglycan Targeting.

While recent research points to the importance of glycans in cancer immunity, knowledge on functional mechanisms is lacking. In lung carcinoma among other tumors, anti-tumor immunity is suppressed; and while some recent therapies boost T-cell mediated immunity by targeting immune-checkpoint pathways, robust responses are uncommon. Augmenting tumor antigen-specific immune responses by endogenous dendritic cells (DCs) is appealing from a specificity standpoint, but challenging. Here, we show that restricting a heparan sulfate (HS) loss-of-function mutation in the HS sulfating enzyme Ndst1 to predominantly conventional DCs (Ndst1f/f CD11cCre+ mutation) results in marked inhibition of Lewis lung carcinoma growth along with increased tumor-associated CD8+ T cells. In mice deficient in a major DC HS proteoglycan (syndecan-4), splenic CD8+ T cells showed increased anti-tumor cytotoxic responses relative to controls. Studies examining Ndst1f/f CD11cCre + mutants revealed that mutation was associated with an increase in anti-tumor cytolysis using either splenic CD8+ T cells or tumor-infiltrating (TIL) CD8+ T cells purified ex-vivo, and tested in pooled effector-to-target cytolytic assays against tumor cells from respective animals. On glycan compositional analysis, HS purified from Ndst1f/f CD11cCre + mutant DCs had reduced overall sulfation, including reduced sulfation of a tri-sulfated disaccharide species that was intriguingly abundant on wildtype DC HS. Interestingly, antigen presentation in the context of major histocompatibility complex class-I (MHC-I) was enhanced in mutant DCs, with more striking effects in the setting of HS under-sulfation, pointing to a likely regulatory role by sulfated glycans at the antigen/MHC-I - T-cell interface; and possibly future opportunities to improve antigen-specific T cell responses by immunologic targeting of HS proteoglycans in cancer

15-04 Travel Behavior of Blind Individuals before and after Receiving Orientation and Mobility Training

In this pilot study, we devised, tested, and refined a protocol for evaluating the travel behavior of blind individuals. Preliminary analyses of our pilot study data suggest that our new method involving Global Positioning Systems (GPS), accelerometers, and Geographic Information Systems (GIS), will enable us to collect objective, quantitative, and valid measures of blind individuals’ travel behavior and Orientation and Mobility (O&M) training’s effectiveness. Preliminary analysis results from a small sample of blind travelers describe the individuals’ trip distances, trip frequencies, trip destinations, trip modes, travel times, whether assisted or not, and perceived ability to get around. With the completion of the full-scale study (proposed for FY 2016-18), we may be able to recommend changes to current O&M training to allow more active, confident, and safe travel by blind individuals in their communities. We may also discover characteristics of the physical environment that inhibit access by blind pedestrians and are more amenable to mitigation through good transportation planning (e.g., geometric design of intersections) than through O&M training

Virtual Testbed for Monocular Visual Navigation of Small Unmanned Aircraft Systems

Monocular visual navigation methods have seen significant advances in the last decade, recently producing several real-time solutions for autonomously navigating small unmanned aircraft systems without relying on GPS. This is critical for military operations which may involve environments where GPS signals are degraded or denied. However, testing and comparing visual navigation algorithms remains a challenge since visual data is expensive to gather. Conducting flight tests in a virtual environment is an attractive solution prior to committing to outdoor testing. This work presents a virtual testbed for conducting simulated flight tests over real-world terrain and analyzing the real-time performance of visual navigation algorithms at 31 Hz. This tool was created to ultimately find a visual odometry algorithm appropriate for further GPS-denied navigation research on fixed-wing aircraft, even though all of the algorithms were designed for other modalities. This testbed was used to evaluate three current state-of-the-art, open-source monocular visual odometry algorithms on a fixed-wing platform: Direct Sparse Odometry, Semi-Direct Visual Odometry, and ORB-SLAM2 (with loop closures disabled)

THE RELATIONSHIP BETWEEN MUSCULOSKELETAL STRENGTH, PHYSIOLOGICAL CHARACTERISTICS, AND KNEE KINESTHESIA FOLLOWING FATIGUING EXERCISE

Fatiguing exercise may result in impaired functional joint stability and increased risk of unintentional injury. While there are several musculoskeletal and physiological characteristics related to fatigue onset, their relationship with proprioceptive changes following fatigue has not been examined. The purpose of this study was to establish the relationship between musculoskeletal and physiological characteristics and changes in proprioception, measured by threshold to detect passive motion (TTDPM), following fatiguing exercise. Twenty, physically active females participated (age: 28.65 ± 5.6 years, height: 165.6 ± 4.3 cm, weight: 61.8 ± 8.0 kg, BMI: 22.5± 2.3 kg/m2, BF: 23.3 ± 5.4%). During Visit 1, subjects completed an exercise history and 24-hour dietary questionnaire, and body composition, TTDPM familiarization, isokinetic knee strength, and maximal oxygen uptake/lactate threshold assessments. During Visit 2, subjects completed TTDPM and isometric knee strength testing prior to and following a fatiguing exercise protocol. Wilcoxon signed rank tests determined TTDPM and isometric knee strength changes from pre- to post- fatigue. Spearman’s rho correlation coefficients determined the relationship between strength and physiological variables with pre- to post-fatigue changes in TTDPM and with pre-fatigue and post-fatigue TTDPM in extension and flexion (α=0.05). No significant differences were demonstrated from pre-fatigue to post-fatigue TTDPM despite a significant decrease in isometric knee flexion strength (P<0.01) and flexion/extension ratio (P<0.05) following fatigue. No significant correlations were observed between strength or physiological variables and changes in TTDPM from pre- to post-fatigue in extension or flexion. Flexion/extension ratio was significantly correlated with pre-fatigue TTDPM in extension (r=-0.231, P<0.05). Peak oxygen uptake was significantly correlated with pre-fatigue (r=-0.500, P<0.01) and post-fatigue (r=-0.520, P<0.05) TTDPM in extension. No significant relationships were demonstrated between musculoskeletal and physiological characteristics and changes in TTDPM following fatigue. The results suggest that highly trained individuals may have better proprioception, and that the high fitness level of subjects in this investigation may have contributed to absence of TTDPM deficits following fatigue despite reaching a high level of perceptual and physiological fatigue. Future studies should consider various subject populations, other musculoskeletal strength characteristics, and different modalities of proprioception to determine the most important contributions to proprioceptive changes following fatigue

BASEBAND RADIO MODEM DESIGN USING GRAPHICS PROCESSING UNITS

A modern radio or wireless communications transceiver is programmed via software and firmware to change its functionalities at the baseband. However, the actual implementation of the radio circuits relies on dedicated hardware, and the design and implementation of such devices are time consuming and challenging. Due to the need for real-time operation, dedicated hardware is preferred in order to meet stringent requirements on throughput and latency. With increasing need for higher throughput and shorter latency, while supporting increasing bandwidth across a fragmented spectrum, dedicated subsystems are developed in order to service individual frequency bands and specifications. Such a dedicated-hardware-intensive approach leads to high resource costs, including costs due to multiple instantiations of mixers, filters, and samplers. Such increases in hardware requirements in turn increases device size, power consumption, weight, and financial cost. If it can meet the required real-time constraints, a more flexible and reconfigurable design approach, such as a software-based solution, is often more desirable over a dedicated hardware solution. However, significant challenges must be overcome in order to meet constraints on throughput and latency while servicing different frequency bands and bandwidths. Graphics processing unit (GPU) technology provides a promising class of platforms for addressing these challenges. GPUs, which were originally designed for rendering images and video sequences, have been adapted as general purpose high-throughput computation engines for a wide variety of application areas beyond their original target domains. Linear algebra and signal processing acceleration are examples of such application areas. In this thesis, we apply GPUs as software-based, baseband radios and demonstrate novel, software-based implementations of key subsystems in modern wireless transceivers. In our work, we develop novel implementation techniques that allow communication system designers to use GPUs as accelerators for baseband processing functions, including real-time filtering and signal transformations. More specifically, we apply GPUs to accelerate several computationally-intensive, frontend radio subsystems, including filtering, signal mixing, sample rate conversion, and synchronization. These are critical subsystems that must operate in real-time to reliably receive waveforms. The contributions of this thesis can be broadly organized into 3 major areas: (1) channelization, (2) arbitrary resampling, and (3) synchronization. 1. Channelization: a wideband signal is shared between different users and channels, and a channelizer is used to separate the components of the shared signal in the different channels. A channelizer is often used as a pre-processing step in selecting a specific channel-of-interest. A typical channelization process involves signal conversion, resampling, and filtering to reject adjacent channels. We investigate GPU acceleration for a particularly efficient form of channelizer called a polyphase filterbank channelizer, and demonstrate a real-time implementation of our novel channelizer design. 2. Arbitrary resampling: following a channelization process, a signal is often resampled to at least twice the data rate in order to further condition the signal. Since different communication standards require different resampling ratios, it is desirable for a resampling subsystem to support a variety of different ratios. We investigate optimized, GPU-based methods for resampling using polyphase filter structures that are mapped efficiently into GPU hardware. We investigate these GPU implementation techniques in the context of interpolation (integer-factor increases in sampling rate), decimation (integer-factor decreases in sampling rate), and rational resampling. Finally, we demonstrate an efficient implementation of arbitrary resampling using GPUs. This implementation exploits specialized hardware units within the GPU to enable efficient and accurate resampling processes involving arbitrary changes in sample rate. 3. Synchronization: incoming signals in a wireless communications transceiver must be synchronized in order to recover the transmitted data properly from complex channel effects such as thermal noise, fading, and multipath propagation. We investigate timing recovery in GPUs to accelerate the most computationally intensive part of the synchronization process, and correctly align the incoming data symbols in the receiver. Furthermore, we implement fully-parallel timing error detection to accelerate maximum likelihood estimation

Biological survey of Eagle County, Colorado: 2000 final report

Prepared for: Eagle Valley Land Trust.March 2000.Includes bibliographical references

Polarity control of carrier injection at ferroelectric/metal interfaces for electrically switchable diode and photovoltaic effects

We investigated a switchable ferroelectric diode effect and its physical mechanism in Pt/BiFeO3/SrRuO3 thin-film capacitors. Our results of electrical measurements support that, near the Pt/BiFeO3 interface of as-grown samples, a defective layer (possibly, an oxygen-vacancy-rich layer) becomes formed and disturbs carrier injection. We therefore used an electrical training process to obtain ferroelectric control of the diode polarity where, by changing the polarization direction using an external bias, we could switch the transport characteristics between forward and reverse diodes. Our system is characterized with a rectangular polarization hysteresis loop, with which we confirmed that the diode polarity switching occurred at the ferroelectric coercive voltage. Moreover, we observed a simultaneous switching of the diode polarity and the associated photovoltaic response dependent on the ferroelectric domain configurations. Our detailed study suggests that the polarization charge can affect the Schottky barrier at the ferroelectric/metal interfaces, resulting in a modulation of the interfacial carrier injection. The amount of polarization-modulated carrier injection can affect the transition voltage value at which a space-charge-limited bulk current-voltage (J-V) behavior is changed from Ohmic (i.e., J ~ V) to nonlinear (i.e., J ~ V^n with n \geq 2). This combination of bulk conduction and polarization-modulated carrier injection explains the detailed physical mechanism underlying the switchable diode effect in ferroelectric capacitors.Comment: Accepted for publication in Phys. Rev.

Comparative Measurements of Earth and Martian Entry Environments in the NASA Langley HYMETS Facility

Arc-jet facilities play a major role in the development of heat shield materials for entry vehicles because they are capable of producing representative high-enthalpy flow environments. Arc-jet test data is used to certify material performance for a particular mission and to validate or calibrate models of material response during atmospheric entry. Materials used on missions entering Earth s atmosphere are certified in an arc-jet using a simulated air entry environment. Materials used on missions entering the Martian atmosphere should be certified in an arc-jet using a simulated Martian atmosphere entry environment, which requires the use of carbon dioxide. Carbon dioxide has not been used as a test gas in a United States arc-jet facility since the early 1970 s during the certification of materials for the Viking Missions. Materials certified for the Viking missions have been used on every entry mission to Mars since that time. The use of carbon dioxide as a test gas in an arc-jet is again of interest to the thermal protection system community for certification of new heat shield materials that can increase the landed mass capability for Mars bound missions beyond that of Viking and Pathfinder. This paper describes the modification, operation, and performance of the Hypersonic Materials Environmental Test System (HYMETS) arc-jet facility with carbon dioxide as a test gas. A basic comparison of heat fluxes, various bulk properties, and performance characteristics for various Earth and Martian entry environments in HYMETS is provided. The Earth and Martian entry environments consist of a standard Earth atmosphere, an oxygen-rich Earth atmosphere, and a simulated Martian atmosphere. Finally, a preliminary comparison of the HYMETS arc-jet facility to several European plasma facilities is made to place the HYMETS facility in a more global context of arc-jet testing capability