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Provided herein are high energy ion beam generator systems and methods that provide low cost, high performance, robust, consistent, uniform, low gas consumption and high current/high-moderate voltage generation of neutrons and protons. Such systems and methods find use for the commercial-scale generation of neutrons and protons for a wide variety of research, medical, security, and industrial processes.
Provided herein are high energy ion beam generator systems and methods that provide low cost, high performance, robust, consistent, uniform, low gas consumption and high current/high-moderate voltage generation of neutrons and protons. Such systems and methods find use for the commercial-scale generation of neutrons and protons for a wide variety of research, medical, security, and industrial processes.
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This viewgraph presentation reviews NASA's role in medical translational research, and the importance in research for space exploration. The application of medical research for space exploration translates to health care in space medicine, and on earth.
NASA-sponsored medical R & D programs for space applications are reviewed with particular attention to the benefits of these programs to earthbound medical services and to the general public. Notable among the results of these NASA programs is an integrated medical laboratory equipped with numerous advanced systems such as digital biotelemetry and automatic visual field mapping systems, sponge electrode caps for electroencephalograms, and sophisticated respiratory analysis equipment.
SUMMARY Functional genomics is the use of systematic gene perturbation approaches to determine the contributions of genes under conditions of interest. Although functional genomic strategies have been used in bacteria for decades, recent studies have taken advantage of CRISPR (clustered regularly interspaced short palindromic repeats) technologies, such as CRISPRi (CRISPR interference), that are capable of precisely modulating expression of all genes in the genome. Here, we discuss and review the use of CRISPRi and related technologies for bacterial functional genomics. We discuss the strengths and weaknesses of CRISPRi as well as design considerations for CRISPRi genetic screens. We also review examples of how CRISPRi screens have defined relevant genetic targets for medical and industrial applications. Finally, we outline a few of the many possible directions that could be pursued using CRISPR-based functional genomics in bacteria. Our view is that the most exciting screens and discoveries are yet to come.
Introduction: The envelope glycoprotein (Env) of HIV-1 Transmitted/Founder (T/F) viruses in subtypes B and C carries distinct genetic signatures that enhance transmission fitness, augment infectivity and immune evasion. However, there is limited data on such signatures in T/F subtypes A1, D and A1D recombinants that predominate East Africa’s HIV epidemic.Methods: We used phylogenetically corrected approaches to detect distinct genetic signatures by comparing 44 contemporary HIV-1 T/F Envs with 229 historical Envs of the same subtype in East Africa.Results and Discussion: Subtype analysis based on the full-length Env gene of contemporary T/F viruses revealed a high proportion of subtype A1, followed by A1D recombinants, and fewer subtype D. Signature analysis revealed that the contemporary subtype A1 T/Fs were more likely to select distinct amino acids, including M22 in the signal peptide, R82 in gp120, A172 in the V2 loop, E230 in the glycosite 230, K275 in the D loop, Y317 in the V3 loop, K476 and N477 in the CD4 contact site, when compared with the historical Envs (q-value < 0.2). Conversely, the contemporary subtype A1 T/F Envs were less likely to carry the amino acids Q432 in the CD4 contact site, and the L784 signature within the LLP-2 (q-value < 0.2). The A1D recombinant T/Fs were more likely to select the D620 in the C-helix, but under selected the L34 in gp120, P299 in the V3 loop and Y643 in the Heptad repeat-2, compared to the historical Envs (q-value < 0.2). The distinct signature sites reported in this study may contribute to the successful establishment of acute infection as well as the persistence of long-term infection. Therefore, effective therapeutics and vaccines may target these distinct amino acid signatures especially for the East African region as it may be necessary to employ subtype-specific vaccines according to the subtype distribution.
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Introduction: Yersinia pestis is the etiological agent of plague, a disease that remains a concern as demonstrated by recent outbreaks in Madagascar. Infection with Y. pestis results in a rapidly progressing illness that can only be successfully treated with antibiotics given shortly after symptom onset. Live attenuated or whole cell inactivated vaccines confer protection against bubonic plague, but pneumonic plague has been more difficult to prevent. Novel effective subunit vaccine formulations may circumvent some of these shortfalls. Here, we compare the immunogenicity generated by an advanced subunit vaccine (F1V fusion protein) and a nanolipoprotein particle (NLP)-based vaccine. Methods: The NLP, a high-density lipoprotein mimetic, provides a nanoscale delivery platform for recombinant Y. pestis antigens LcrV (V) and F1. BALB/c mice were immunized via subcutaneous injection twice, three or four weeks apart. Four weeks later, splenocytes and sera were collected for immune profiling, and mice were challenged with aerosolized Y. pestis CO92. Results: Both formulations induced a strong IgG response against the F1 and V proteins, along with a robust memory B cell response and a balanced cell-mediated immune response as evidenced by both Th1- and Th2-related cytokines. The NLP-based vaccine induced a stronger cytokine response against F1, V, and F1V proteins relative to the F1V vaccine. As with F1V, the inclusion of Alhydrogel (Alu) in NLP vaccine formulations was critical for enhanced immunogenicity and protective efficacy. Mice that received two doses of F1:V:NLP + Alu and CpG were completely protected from a challenge with approximately eight median lethal doses of aerosolized Y. pestis CO92 and this protection confirmed the well-documented synergy between the F1 and V antigens in context of pneumonic plague. The NLPs have defined regions of polarity that facilitates the incorporation of a wide range of adjuvants and antigens with distinct physicochemical properties and are an excellent candidate platform for the development of multi-antigen vaccines.
The mission of the Exploration Medical Capability (ExMC) Element is to advance medical system design and risk-informed decision making for exploration beyond low Earth orbit to promote human health and performance in space. In order to accomplish this mission, the Element takes a progressively Earth-independent approach to three main areas: - Answering key clinical and science research questions that will help to address the challenges of providing medical care in the extreme environment of space - Applying systems engineering processes to medical system design with the goal of developing robust requirements that can be fully integrated into future space exploration vehicle designs - Developing and demonstrating novel medical technologies that will improve future medical capabilities in space This presentation will focus on selected scientific and technical conceptual drivers for the Element, the current and future research risks and gaps, and provide an overview of the Element’s progress in 2022. In particular, it will address the ongoing effort for the IMPACT trade space analysis tool suite, the closeout work on a clinical decision support prototype, potential requirements for a long-duration lunar orbit and lunar surface medical system, and an International Space Station technology demonstration of a point-of-care laboratory analysis capability.
The mission of the Exploration Medical Capability (ExMC) Element is to advance medical system design and risk-informed decision making for exploration beyond low Earth orbit to promote human health and performance in space. In order to accomplish this mission, the Element takes a progressively Earth-independent approach to three main areas: 1)answering key clinical and science research questions that will help to address the challenges of providing medical care in the extreme environment of space, 2)applying systems engineering processes to medical system design with the goal of developing robust requirements that can be fully integrated into future space exploration vehicle designs, and 3)developing and demonstrating novel medical technologies that will improve future medical capabilities in space. This presentation will focus on selected scientific and technical conceptual drivers for the Element, the current and future research risks and gaps, and provide an overview of the Element’s progress in 2020.
Management of medical and research data at NASA's Johnson Space Center has been addressed with two separate, independent systems: the Lifetime Surveillance of Astronaut Health (formerly, The Longitudinal Study of Astronaut Health) (LSAH) and the Life Sciences Data Archive (LSDA). Project management for these has been autonomous with little or no cross-over of goals, objectives or strategy. The result has been limited debate and discussion regarding how contents from one repository might impact or guide the direction of the other. It is decidedly more efficient to use existing data and information than to re-generate them. Ensuring that both clinical and research data / information are accessible for review is a central concept to the decision to unify these repositories. In the past, research data from flight and ground analogs has been held in the LSDA and medical data held in the Electronic Medical Record or in console flight surgeon logs and records. There was little cross-pollination between medical and research findings and, as a result, applicable research was not being fully incorporated into clinical, in-flight practice. Conversely, findings by the console surgeon were not being picked up by the research community. The desired life cycle for risk mitigation was not being fully realized. The goal of unifying these repositories and processes is to provide a closely knit approach to handling medical and research data, which will not only engender discussion and debate but will also ensure that both categories of data and information are used to enhance the use of medical and research data to reduce risk and promote the understanding of space physiology, countermeasures and other mitigation strategies
The mission of the Exploration Medical Capability (ExMC) Element is to advance medical system design and risk-informed decision making for exploration beyond Low Earth Orbit to promote human health and performance in space. To accomplish this mission, ExMC focuses on several key areas: • Investigating specific risks that are relevant for human exploration spaceflight, including in-flight medical conditions, degraded or toxic medications, and renal stones • Developing medical probabilistic risk analysis tools that are integrated with systems engineering processes to inform the medical system trade space and support the development of robust requirements • Demonstrating and defining requirements for a prototype clinical decision support system • Developing and demonstrating novel medical technologies that will improve future medical capabilities in space This presentation will focus on selected scientific and technical conceptual drivers for the Element and its current and future research risks and gaps while providing an overview of the Element’s progress in 2021 and areas of focus for 2022.
systems, and cutting-edge component technologies to conduct a wide range of scientific observations and measurements. These technologies are also considered for practical applications that benefit society in remarkable ways. At NASA Goddard, the technology transfer initiative promotes matching technologies from Earth and space science needs to targeted industry sectors. This requires clear knowledge of industry needs and priorities and social demands. The process entails matching mature technologies where there are known innovation challenges and good opportunities for matching technology needs. This requires creative thinking and takes commitment of time and resources. Additionally, we also look at applications for known hot industry or societal needs. Doing so has given us occasion to host discussions with representatives from industry, academia, government organizations, and societal special interest groups about the application of NASA Goddard technologies for devices used in medical monitoring and detection tools. As a result, partnerships have been established. Innovation transpired when new products were enabled because of NASA Goddard research and technology programs.
A number of medically oriented research and hardware development programs in support of manned space flights have been sponsored by NASA. Blood pressure measuring systems for use in spacecraft are considered. In some cases, complete new bioinstrumentation systems were necessary to accomplish a specific physiological study. Plans for medical research during the Skylab program are discussed along with general questions regarding space-borne health service systems and details concerning the Health Services Support Control Center.
The Exploration Laboratory Analysis (ELA) project supports the Exploration Medical Capability (ExMC) risk, which is stated as the Risk of Inability to Adequately Treat an Ill or Injured Crew Member, and ExMC Gap 4.05: Lack of minimally invasive in-flight laboratory capabilities with limited consumables required for diagnosing identified Exploration Medical Conditions. To mitigate this risk, the availability of inflight laboratory analysis instrumentation has been identified as an essential capability in future exploration missions. Mission architecture poses constraints on equipment and procedures that will be available to treat evidence-based medical conditions according to the Space Medicine Exploration Medical Conditions List (SMEMCL), and to perform human research studies on the International Space Station (ISS) that are supported by the Human Health and Countermeasures (HHC) element. Since there are significant similarities in the research and medical operational requirements, ELA hardware development has emerged as a joint effort between ExMC and HHC. In 2012, four significant accomplishments were achieved towards the development of exploration laboratory analysis for medical diagnostics. These achievements included (i) the development of high priority analytes for research and medical operations, (ii) the development of Level 1 functional requirements and concept of operations documentation, (iii) the selection and head-to-head competition of in-flight laboratory analysis instrumentation, and (iv) the phase one completion of the Small Business Innovation Research (SBIR) projects under the topic Smart Phone Driven Blood-Based Diagnostics. To utilize resources efficiently, the associated documentation and advanced technologies were integrated into a single ELA plan that encompasses ExMC and HHC development efforts. The requirements and high priority analytes was used in the selection of the four in-flight laboratory analysis performers. Based upon the competition results, a down select process will be performed in the upcoming year. Looking ahead, this unified effort has positioned each element for an in-flight lab analysis demonstration of select diagnostics measurements in the 2015 timeframe.
Microscopy with Ultraviolet Surface Excitation (MUSE) for use in the classroom to enhance life sciences education and curricula, or for other applications, including without limtiation the operating room, other medical environments, research environments, and low resource environments. MUSE's suitability is based on multiple key factors including its simplicity of use, the incorporation of inexpensive hardware including LED illumination, and very basic tissue preparation. The ultraviolet excitation acts as passive optical sectioning confining the generated fluorescence signal to only a few micrometers below the tissue surface thus eliminating the out of focus signals. This facilitates image capture of tissue microstructure and organization from specimens at the intact or sliced surface arising from varying fluorophore concentration within the different cellular compartments. Although just the tissue auto fluorescence maybe used, image quality is enhanced with brief application of nontoxic fluorescent dyes to selectively highlight cellular compartments. Sample preparation is safe, efficient and familiar to students with basic chemistry or biology lab experience. Mixed-dye powders may be used to simplify translation of this method for educational, medical, research, low resource, and other settings.
Retrospective research and medical data collected on astronauts can be a valuable resource for researchers. This data can be requested from two separate NASA Archives. The Lifetime Surveillance of Astronaut Health (LSAH) holds astronaut medical data, and the Life Sciences Data Archive (LSDA) holds research data. One condition of use of astronaut research and medical data is the requirement that all abstracts, publications and presentations using this data must be reviewed for attributability. All final versions of abstracts, presentations, posters, and manuscripts must be reviewed by LSDA/LSAH prior to submission to a conference, journal, or other entities outside the Principal Investigator (PI) laboratory [including the NASA Export Control Document Availability Authorization (DAA) system]. If material undergoes multiple revisions (e.g., journal editor comments), the new versions must also be reviewed by LSDA/LSAH prior to re-submission to the journal. The purpose of this review is to ensure that no personally identifiable information (PII) is included in materials that are presented in a public venue or posted to the public domain. The procedures for submitting materials for review will be outlined. The process that LSAH/LSDA follows for assessing attributability will be presented. Characteristics and parameter combinations that often prompt attributability concerns will be identified. A published case report for a National Football League (NFL) player will be used to demonstrate how, in a population of public interest, a combination of information can result in inadvertent release of private or sensitive information.