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45 records · Page 3

Miniature Time-of-Flight Mass Spectrometer

Major advances must occur to protect astronauts from prolonged periods in near-zero gravity and high radiation associated with extended space travel. The dangers of living in space must be thoroughly understood and methods developed to reverse those effects that cannot be avoided. Six of the seven research teams established by the National Space Biomedical Research Institute (NSBRI) are studying biomedical factors for prolonged space travel to deliver effective countermeasures. To develop effective countermeasures, each of these teams require identification of and quantitation of complex pharmacological, hormonal, and growth factor compounds (biomarkers) in humans and in experimental animals to develop an in-depth knowledge of the physiological changes associated with space travel. At present, identification of each biomarker requires a separate protocol. Many of these procedures are complicated and the identification of each biomarker requires a separate protocol and associated laboratory equipment. To carry all of this equipment and chemicals on a spacecraft would require a complex clinical laboratory; and it would occupy much of the astronauts time. What is needed is a small, efficient, broadband medical diagnostic instrument to rapidly identify important biomarkers for human space exploration. The Miniature Time-Of- Flight Mass Spectrometer Project in the Technology Development Team is developing a small, high resolution, time-of-flight mass spectrometer (TOFMS) to quantitatively measure biomarkers for human space exploration. Virtues of the JHU/APL TOFMS technologies reside in the promise for a small (less than one cubic ft), lightweight (less than 5 kg), low-power (less than 50 watts), rugged device that can be used continuously with advanced signal processing diagnostics. To date, the JHU/APL program has demonstrated mass capability from under 100 to beyond 10,000 atomic mass units (amu) in a very small, low power prototype for biological analysis. Further, the electronic nature of the TOFMS output makes it ideal for rapid telemetry to earth for in-depth analysis by ground support teams.

Potember, Richard S.↗

A Novel Biomedical Device Utilizing Light Emitting Nano-Structures

This paper will discuss the development of a novel biomedical detection device that will be used to detect microorganisms with the use of infrared fluorochrome polymers attached to antibodies in fluids such as water. The fluorochrome polymers emit light in the near inferred region (NIR), approximately 805 nm, when excited by an NIR laser at 778 nm. The device could remarkably change the way laboratory testing is done today. The testing process is usually performed on a time scale of days while our device will be able to detect microorganisms in minutes. This type of time efficient analysis is ideal for use aboard the International Space Station and the Space Shuttle (ISS/SS) and has many useful commercial applications, for instance at a water treatment plant and food processing plants. With more research and experimentation the testing might also one day be used to detect bacteria and viruses in complex fluids such as blood, which would revolutionize blood analysis as it is performed today. My contribution to the project has been to develop a process which will allow an antibody/fluorescent dye pair to be conjugated to a specific bacteria or virus and than to to be separated from a sample body of water for detection. The antibody being used in this experiment is anti beta galactosidase and its complement enzyme is beta galactosidase, a non harmful derivative of E. Coli. The anti beta galactosidase has been conjugated to the fluorochrome polymer, IRDye800, which emits at approximately 806 nm. The dye when excited by the NIR laser emits a signal which is detected by a spectrometer and then is read by state of the art computer software. The state-of-the-art process includes incubating the anti beta galactosidase and beta galactosidase in a phosphate buffer solution in a test tube, allowing the antibody to bind to specific sites on the enzyme. After the antibody is bound to the enzyme, it is centrifuged in specific filters that will allow free antibody to wash away and leave the antibody-enzyme complexes on top in solution for testing and analysis. This solution is pipetted into a cuvette, a special plastic test tube, which will then be excited by the laser. The signal read will tell US that an antibody is present and since it is bound to the enzyme, that the bacteria is also present.

Varaljay, Vanessa A.↗

Sensory processing in the vestibular nuclei during active head movements

Many secondary vestibular neurons are sensitive to head on trunk rotation during reflex-induced and voluntary head movements. During passive whole body rotation the interaction of head on trunk signals related to the vestibulo-collic reflex with vestibular signals increases the rotational gain of many secondary vestibular neurons, including many that project to the spinal cord. In some units, the sensitivity to head on trunk and vestibular input is matched and the resulting interaction produces an output that is related to the trunk velocity in space. In other units the head on trunk inputs are stronger and the resulting interaction produces an output that is larger during the reflex. During voluntary head movements, inputs related to head on trunk movement combine destructively with vestibular signals, and often cancel the sensory reafferent consequences of self-generated movements. Cancellation of sensory vestibular signals was observed in all of the antidromically identified secondary vestibulospinal units, even though many of these units were not significantly affected by reflexive head on trunk movements. The results imply that the inputs to vestibular neurons related to head on trunk rotation during reflexive and voluntary movements arise from different sources. We suggest that the relative strength of reflexive head on trunk input to different vestibular neurons might reflect the different functional roles they have in controlling the posture of the neck and body.

Non-NASA Center↗

A Modular 512-Channel Neural Signal Acquisition ASIC for High-Density 4096 Channel Electrophysiology

The complexity of information processing in the brain requires the development of technologies that can provide spatial and temporal resolution by means of dense electrode arrays paired with high-channel-count signal acquisition electronics. In this work, we present an ultra-low noise modular 512-channel neural recording circuit that is scalable to up to 4096 simultaneously recording channels. The neural readout application-specific integrated circuit (ASIC) uses a dense 8.2 mm × 6.8 mm 2D layout to enable high-channel count, creating an ultra-light 350 mg flexible module. The module can be deployed on headstages for small animals like rodents and songbirds, and it can be integrated with a variety of electrode arrays. The chip was fabricated in a TSMC 0.18 µm 1.8 V CMOS technology and dissipates a total of 125 mW. Each DC-coupled channel features a gain and bandwidth programmable analog front-end along with 14 b analog-to-digital conversion at speeds up to 30 kS/s. Additionally, each front-end includes programmable electrode plating and electrode impedance measurement capability. We present both standalone and in vivo measurements results, demonstrating the readout of spikes and field potentials that are modulated by a sensory input.

47 OTHER INSTRUMENTATION↗

Differences in the hemodynamic response to event-related motor and visual paradigms as measured by near-infrared spectroscopy

Several current brain imaging techniques rest on the assumption of a tight coupling between neural activity and hemodynamic response. The nature of this neurovascular coupling, however, is not completely understood. There is some evidence for a decoupling of these processes at the onset of neural activity, which manifests itself as a momentary increase in the relative concentration of deoxyhemoglobin (HbR). The existence of this early component of the hemodynamic response function, however, is controversial, as it is inconsistently found. Near infrared spectroscopy (NIRS) allows quantification of levels of oxyhemoglobin (HbO(2)) and HbR during task performance in humans. We acquired NIRS data during performance of simple motor and visual tasks, using rapid-presentation event-related paradigms. Our results demonstrate that rapid, event-related NIRS can provide robust estimates of the hemodynamic response without artifacts due to low-frequency signal components, unlike data from blocked designs. In both the motor and visual data the onset of the increase in HbO(2) occurs before HbR decreases, and there is a poststimulus undershoot. Our results also show that total blood volume (HbT) drops before HbO(2) and undershoots baseline, raising a new issue for neurovascular models. We did not find early deoxygenation in the motor data using physiologically plausible values for the differential pathlength factor, but did find one in the visual data. We suggest that this difference, which is consistent with functional magnetic resonance imaging (fMRI) data, may be attributable to different capillary transit times in these cortices.

NASA Program Biomedical Research and Countermeasur↗

Physics-guided dual implicit neural representations for source separation

Significant challenges exist in efficient data analysis of most advanced experimental and observational techniques because the collected signals often include unwanted contributions, such as background and signal distortions, that can obscure the physically relevant information of interest. To address this, we have developed a self-supervised machine-learning approach for source separation using a dual implicit neural representation framework that jointly trains two neural networks: one for approximating distortions of the physical signal of interest and the other for learning the effective background contribution. Our method learns directly from the raw data by minimizing a reconstruction-based loss function without requiring labeled data or pre-defined dictionaries. We demonstrate the effectiveness of our framework by considering a challenging case study involving large-scale simulated, as well as experimental, momentum-energy-dependent inelastic neutron scattering data in a four-dimensional parameter space, characterized by heterogeneous background contributions and unknown distortions to the target signal. The method is found to successfully separate physically meaningful signals from a complex or structured background even when the signal characteristics vary across all four dimensions of the parameter space. An analytical approach that informs the choice of the regularization parameter is presented. Our method offers a versatile framework for addressing source separation problems across diverse domains, ranging from superimposed signals in astronomical measurements to structural features in biomedical image reconstructions.

47 OTHER INSTRUMENTATION↗

Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms

Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.

Non-NASA Center↗

Drug discovery efforts at George Mason University

With over 39,000 students, and research expenditures in excess of $200 million, George Mason University (GMU) is the largest R1 (Carnegie Classification of very high research activity) university in Virginia. Mason scientists have been involved in the discovery and development of novel diagnostics and therapeutics in areas as diverse as infectious diseases and cancer. Below are highlights of the efforts being led by Mason researchers in the drug discovery arena. To enable targeted cellular delivery, and non-biomedical applications, Veneziano and colleagues have developed a synthesis strategy that enables the design of self-assembling DNA nanoparticles (DNA origami) with prescribed shape and size in the 10 to 100 nm range. The nanoparticles can be loaded with molecules of interest such as drugs, proteins and peptides, and are a promising new addition to the drug delivery platforms currently in use. The investigators also recently used the DNA origami nanoparticles to fine tune the spatial presentation of immunogens to study the impact on B cell activation. These studies are an important step towards the rational design of vaccines for a variety of infectious agents. To elucidate the parameters for optimizing the delivery efficiency of lipid nanoparticles (LNPs), Buschmann, Paige and colleagues have devised methods for predicting and experimentally validating the pKa of LNPs based on the structure of the ionizable lipids used to formulate the LNPs. These studies may pave the way for the development of new LNP delivery vehicles that have reduced systemic distribution and improved endosomal release of their cargo post administration. To better understand protein-protein interactions and identify potential drug targets that disrupt such interactions, Luchini and colleagues have developed a methodology that identifies contact points between proteins using small molecule dyes. The dye molecules noncovalently bind to the accessible surfaces of a protein complex with very high affinity, but are excluded from contact regions. When the complex is denatured and digested with trypsin, the exposed regions covered by the dye do not get cleaved by the enzyme, whereas the contact points are digested. The resulting fragments can then be identified using mass spectrometry. The data generated can serve as the basis for designing small molecules and peptides that can disrupt the formation of protein complexes involved in disease processes. For example, using peptides based on the interleukin 1 receptor accessory protein (IL-1RAcP), Luchini, Liotta, Paige and colleagues disrupted the formation of IL-1/IL-R/IL-1RAcP complex and demonstrated that the inhibition of complex formation reduced the inflammatory response to IL-1B. Working on the discovery of novel antimicrobial agents, Bishop, van Hoek and colleagues have discovered a number of antimicrobial peptides from reptiles and other species. DRGN-1, is a synthetic peptide based on a histone H1-derived peptide that they had identified from Komodo Dragon plasma. DRGN-1 was shown to disrupt bacterial biofilms and promote wound healing in an animal model. The peptide, along with others, is being developed and tested in preclinical studies. Other research by van Hoek and colleagues focuses on in silico antimicrobial peptide discovery, screening of small molecules for antibacterial properties, as well as assessment of diffusible signal factors (DFS) as future therapeutics. The above examples provide insight into the cutting-edge studies undertaken by GMU scientists to develop novel methodologies and platform technologies important to drug discovery.

59 BASIC BIOLOGICAL SCIENCES↗

Freestanding BaTiO 3 ‐Au Vertically Aligned Nanocomposite toward Flexible Multi‐Sensing Platform

Abstract Flexible and wearable sensors show enormous potential for personalized healthcare devices by real‐time monitoring of an individual's health. Typically, a single functional material is selected for one sensor to sense a particular physical signal while multiple materials will be selected for multi‐mode sensing. Vertically aligned nanocomposites (VANs) have recently demonstrated various material combinations and novel coupled multifunctionalities that are hard to achieve in any single‐phase material alone, including multiphase multiferroics, magneto‐optic coupling, and strong magnetic and optical anisotropy. Integrating these novel VANs into wearable sensors shows enormous potential in multi‐mode sensing owing to their multifunctional nature. In this work, the transfer of VANs onto polydimethylsiloxane as a novel flexible chemical and pressure sensor is demonstrated. For this demonstration, the classical BaTiO 3 ‐Au VAN with combined plasmonic and piezoelectric properties is used to demonstrate a multi‐sensing mechanism. A thin water‐soluble buffer of Sr 3 Al 2 O 6 serves as a buffer layer for the epitaxial growth and transfer process. The electrical output based on the piezoelectric responses and identifying 4‐mercaptobenzoic acid by surface‐enhanced Raman spectroscopy reveal great potential for free‐standing VANs in a wearable multifunctional sensing platform.

Tsai, Benson Kunhung [School of Materials Engineer↗