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50 records · Page 3

The Application of Integrated Knowledge-based Systems for the Biomedical Risk Assessment Intelligent Network (BRAIN)

One of NASA's goals for long duration space flight is to maintain acceptable levels of crew health, safety, and performance. One way of meeting this goal is through the Biomedical Risk Assessment Intelligent Network (BRAIN), an integrated network of both human and computer elements. The BRAIN will function as an advisor to flight surgeons by assessing the risk of in-flight biomedical problems and recommending appropriate countermeasures. This paper describes the joint effort among various NASA elements to develop BRAIN and an Infectious Disease Risk Assessment (IDRA) prototype. The implementation of this effort addresses the technological aspects of the following: (1) knowledge acquisition; (2) integration of IDRA components; (3) use of expert systems to automate the biomedical prediction process; (4) development of a user-friendly interface; and (5) integration of the IDRA prototype and Exercise Countermeasures Intelligent System (ExerCISys). Because the C Language, CLIPS (the C Language Integrated Production System), and the X-Window System were portable and easily integrated, they were chosen as the tools for the initial IDRA prototype. The feasibility was tested by developing an IDRA prototype that predicts the individual risk of influenza. The application of knowledge-based systems to risk assessment is of great market value to the medical technology industry.

Loftin, Karin C.↗

Airing Out Anthrax

The AiroCide TiO2 is an air-purifier that kills 93.3 percent of airborne pathogens that pass through it, including Bacillus anthraci, more commonly known as anthrax. It is essentially a spinoff of KES Science & Technology, Inc.'s Bio-KES system, a highly effective device used by the produce industry for ethylene gas removal to aid in preserving the freshness of fruits, vegetables, and flowers. The TiO2-based ethylene removal technology that is incorporated into the company's AiroCide TiO2 and Bio-KES products was first integrated into a pair of plant-growth chambers known as ASTROCULTURE(TM) and ADVANCED ASTROCULTURE(TM). Both chambers have housed commercial plant growth experiments in space on either the Space Shuttle or the International Space Station. The AiroCide TiO2 also has a proven record of destroying 98 percent of other airborne pathogens, such as microscopic dust mites, molds, and fungi. Moreover, the device is a verified killer of Influenza A (flu), E. coli, Staphylococcus aureas, Streptococcus pyogenes, and Mycoplasma pneumoniae, among many other harmful viruses.

Source record↗

Peptides at Membrane Surfaces and their Role in Prebiotic Evolution

Protocells had to transport ions and organic matter across membranes separating the interior of the cell from the environment, capture and utilize energy and transduce environmental signals. In a series of detailed, molecular-level computer simulations we show how these peptides in contact with membranes can acquire ordered structures and functions. We have investigated the stability of a simple alpha-helical peptide containing Leucine (L) and Serine (S) of the form (LSLLLSL)3 in a model membrane system. The parallel in-plane state is the most stable configuration. The transmembrane state is metastable, and about 15 kcal/mol is required to insert the peptide into the membrane. We investigated dimes of both (LSLLLSL)3 and glycophorin A, and show how the free energy of helix association can, at least partially, offset the free energy of insertion. We have also investigated the transmembrane pore of the influenza M2 protein. This aggregate of four identical alpha-helices, each built of 25 amino acids, forms an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism, which can involve strands of hydrogen-bonded water through the pore or proton transfer through tautomerization of protein residues. The channel can be re-engineered to act as a simple proton pump.

Pohorille, Andrew↗

Peptides at Membrane Surfaces and their Role in the Origin of Life

All ancestors of contemporary cells (protocells) had to transport ions and organic matter across membranous walls, capture and utilize energy and transduce environmental signals. In modern organisms, all these functions are preformed by membrane proteins. We make the parsimonious assumption that in the protobiological milieu the same functions were carried out by their simple analogs - peptides. This, however, required that simple peptides could self-organize into ordered, functional structures. In a series of detailed, molecular-level computer simulations we demonstrated how this is possible. One example is the peptide (LSLLLSL)3 which forms a trameric bundle capable of transporting protons across membranes. Another example is the transmembrane pore of the influenza M2 protein. This aggregate of four identical alpha-helices, each built of 25 amino acids, forms an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism in this channel. The channel can be re-engineered into a simple proton pump.

Pohorille, Andrew↗

Membrane-Based Functions in the Origin of Cellular Life

How simple membrane peptides performed such essential proto-cellular functions as transport of ions and organic matter across membranes separating the interior of the cell from the environment, capture and utilization of energy, and transduction of environmental signals, is a key question in protobiological evolution. On the basis of detailed, molecular-level computer simulations we investigate how these peptides insert into membranes, self-assemble into higher-order structures and acquire functions. We have studied the insertion of an a-helical peptide containing leucine (L) and serine (S) of the form (LSLLLSL)S into a model membrane. The transmembrane state is metastable, and approximately 15 kcal/mol is required to insert the peptide into the membrane. Investigations of dimers formed by (LSLLLSL)S and glycophorin A demonstrate how the favorable free energy of helix association can offset the unfavorable free energy of insertion, leading to self- assembly of peptide helices in the membrane. An example of a self-assembled structure is the tetrameric transmembrane pore of the influenza virus M2 protein, which is an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism and provide guidelines how to reengineering the channel to act as a simple proton pump. In general, emergence of integral membrane proteins appears to be quite feasible and may be easier to envision than the emergence of water-soluble proteins.

Wilson, Michael A.↗

Membrane peptides and their role in protobiological evolution

How simple membrane peptides performed such essential protocellular functions as transport of ions and organic matter across membranes separating the interior of the cell from the environment, capture and utilization of energy, and transduction of environmental signals, is a key question in protobiological evolution. On the basis of detailed, molecular-level computer simulations we explain how these peptides fold at water-membrane interfaces, insert into membranes, self-assemble into higher-order structures and acquire functions. We have investigated the interfacial behavior and folding of several peptides built of leucine and glutamine residues and have demonstrated that many of them tend to adopt ordered structures. Further, we have studied the insertion of an alpha-helical peptide containing leucine (L) and serine (S) of the form (LSLLLSL)3 into a model membrane. The transmembrane state is metastable, and approximately 15 kcal mol(-1) is required to insert the peptide into the membrane. Investigations of dimers formed by (LSLLLSL)3 and glycophorin A demonstrate how the favorable free energy of helix association can offset the unfavorable free energy of insertion, leading to self-assembly of peptide helices in the membrane. An example of a self-assembled structure is the tetrameric transmembrane pore of the influenza virus M2 protein, which is an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism and provide guidelines how to re-engineer the channel to act as a simple proton pump. In general, emergence of integral membrane proteins appears to be quite feasible and may be easier to envision than the emergence of water-soluble proteins.

Models, Chemical↗

Protein crystal growth and the International Space Station

Protein structural information plays a key role in understanding biological structure-function relationships and in the development of new pharmaceuticals for both chronic and infectious diseases. The Center for Macromolecular Crystallography (CMC) has devoted considerable effort studying the fundamental processes involved in macromolecular crystal growth both in a 1-g and microgravity environment. Results from experiments performed on more than 35 U.S. space shuttle flights have clearly indicated that microgravity can provide a beneficial environment for macromolecular crystal growth. This research has led to the development of a new generation of pharmaceuticals that are currently in preclinical or clinical trials for diseases such as cutaneous T-cell lymphoma, psoriasis, rheumatoid arthritis, AIDS, influenza, stroke and other cardiovascular complications. The International Space Station (ISS) provides an opportunity to have complete crystallographic capability on orbit, which was previously not possible with the space shuttle orbiter. As envisioned, the x-ray Crystallography Facility (XCF) will be a complete facility for growing protein crystals; selecting, harvesting, and mounting sample crystals for x-ray diffraction; cryo-freezing mounted crystals if necessary; performing x-ray diffraction studies; and downlinking the data for use by crystallographers on the ground. Other advantages of such a facility include crystal characterization so that iterations in the crystal growth conditions can be made, thereby optimizing the final crystals produced in a three month interval on the ISS.

STS Shuttle Project↗

Conserved gene clusters in bacterial genomes provide further support for the primacy of RNA

Five complete bacterial genome sequences have been released to the scientific community. These include four (eu)Bacteria, Haemophilus influenzae, Mycoplasma genitalium, M. pneumoniae, and Synechocystis PCC 6803, as well as one Archaeon, Methanococcus jannaschii. Features of organization shared by these genomes are likely to have arisen very early in the history of the bacteria and thus can be expected to provide further insight into the nature of early ancestors. Results of a genome comparison of these five organisms confirm earlier observations that gene order is remarkably unpreserved. There are, nevertheless, at least 16 clusters of two or more genes whose order remains the same among the four (eu)Bacteria and these are presumed to reflect conserved elements of coordinated gene expression that require gene proximity. Eight of these gene orders are essentially conserved in the Archaea as well. Many of these clusters are known to be regulated by RNA-level mechanisms in Escherichia coli, which supports the earlier suggestion that this type of regulation of gene expression may have arisen very early. We conclude that although the last common ancestor may have had a DNA genome, it likely was preceded by progenotes with an RNA genome.

Non-NASA Center↗

Alaska at the Crossroads of Migration: Space Based Ornithology

Understanding bird migration on a global scale is one of the most compelling and challenging problems of modern biology with major implications for human health and conservation biology. Revolutionary advances in remote sensing now provide us with near real-time measurements of atmospheric and land surface conditions at high spatial resolution over entire continents. We use spatially-explicit, individual based bird migration models driven by numerical weather prediction models of atmospheric conditions, dynamic habitat suitability maps derived from remotely sensed land surface conditions, biophysiological models, and biological field data to simulate migration routes, timing, energy budgets, and survival of individual birds and populations. Long-distance migratory birds travel annually between breeding grounds in Alaska and wintering grounds in Latin Amierica. Approximately 25% of these species are potential vectors of Avian Influenza. Alaska is at the crossroads of Asian and New World migratory flyways and is likely to be a point of introduction of Asian H5N1 AI into the western hemisphere. If/when an infected bird is detected, a pressing question will be where was this bird several days ago, and where is it likely to go after it was released from the survey site? Answers to such questions will increase effectiveness of AI surveillance and mitigation measures. From a conservation perspective, Alaska's diverse landscape provides breeding sites for many migrants, and climatic and land surface changes along migratory flyways in the western hemisphere may reduce bird survival and physical condition upon arrival at Alaskan breeding territories, success and migrant populations.

Deppe, Jill↗

Sensor Network Provides Environmental Data

The National Biocomputation Center, a joint partnership between the Stanford University School of Medicine's Department of Surgery and NASA's Ames Research Center, is the test bed for much of NASA's research in telemedicine, the remote delivery of medical care. In early 2005, researchers at the National Biocomputation Center formed a spinoff company, Intelesense Technologies, to use the telemedicine sensors to provide integrated global monitoring systems. Intelesense uses the systems to better understand how environments and people are linked, monitor and protect natural resources, predict and adapt to environmental changes, provide for sustainable development, reduce the costs and impacts of natural disasters, and provide an effective and intelligent response to such disasters. Current projects range from protecting the environment to tracking emerging infectious diseases like avian influenza (bird flu) and helping people from around the world connect and interact with each other to better understand their environment and themselves.

Source record↗

Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

Goodwin, Thomas J.↗

Using Earth Observations to Understand and Predict Infectious Diseases

This presentation discusses the processes from data collection and processing to analysis involved in unraveling patterns between disease outbreaks and the surrounding environment and meteorological conditions. We used these patterns to estimate when and where disease outbreaks will occur. As a case study, we will present our work on assessing the relationship between meteorological conditions and influenza in Central America. Our work represents the discovery, prescriptive and predictive aspects of data analytics.

public health↗

Moving With Parasites: Relationships Between Animal Movement and Infectious Disease Across Systems and Scales

Animal movement patterns are important for ecological processes such as population dynamics and infectious disease transmission. Because animals move in response to environmental cues like temperature and precipitation, changes to the environment – whether they are seasonal, interannual, or long-term – can change these processes, leading to changes in population sizes or infectious disease prevalence across space and time. My work uses a combination of simulation modeling and data analysis at multiple spatial and temporal scales to understand the environment-movement-disease connection in diverse animal taxa and environments. In this seminar, I will highlight the diverse ways that the environment can influence infectious disease dynamics via changes to animal movement patterns, including through a global study of migration in ungulate populations, a study of American White Ibis adapting to urban environments in South Florida, and examples of avian influenza prevalence in wild waterfowl. Together, these examples highlight that understanding environment-movement interactions can help predict how infectious disease dynamics might change in the future, as changes to climate, land use, and habitats alter animal movement patterns.

Animal movement↗

Linking Individual Variation in Movement Behavior to Infection Dynamics in Highly Mobile Species

Animal movements are linked to infectious disease dynamics in wildlife through multiple mechanisms across various spatial and temporal scales. For example, infections can impede the movement of infected individuals, but infected hosts can also disperse infectious agents as they move. Individuals inevitably vary in their responses to infections and their roles in determining infection dynamics, which means that considering variation among individuals – whether across species, across time, or within populations – is important for understanding movement-disease relationships and their implications for epidemiology. Here, I draw on studies from multiple systems to examine how variation in movement behavior links to infectious disease epidemiology. For example, a comparative study of habitat selection across multiple waterfowl species highlights that diel behavioral patterns, rather than individual or seasonal variation, is the most important driver of the risk of overlap between waterfowl and poultry farms, and therefore for the risk of avian influenza spillover. Together, these studies show that individual traits interact with the environment to influence the roles of individuals for infectious disease ecology.

Claire Stewart Teitelbaum↗