Advancing Torpor Inducing Transfer Habitats for Human Stasis to Mars

SpaceWorks Enterprises, Inc. (SEI) has conducted an evaluation of an advanced habitat system designed to transportcrews between the Earth and Mars. This new and innovative habitat concept is capable of placing crew members ininactive, torpor states during transit phases of a deep space mission. This substantially reduces the mass and size ofthe habitat, which ultimately leads to significant reductions in the overall architecture size.Our approach for achieving this is based on extending the current and evolving medical practice of TherapeuticHypothermia (TH) - a proven and effective treatment for various traumatic injuries. TH is a medical treatment thatlowers a patient's body temperature by just 5 to 10 degrees Fahrenheit causing human metabolic rate to decreasesignificantly and the body to enter an unconscious state. This method avoids the intractable challenges often associatedwith cell metabolic cessation through cryogenic freezing and other highly speculative approaches.The initial results obtained from the research and analysis conducted in the Phase I effort warranted further study ofthis concept and technology. The specific objectives of the continued work include:1. Addressing critical medical aspects and risks for inducing torpor via Therapeutic Hypothermia and theapproach for providing nutrition and hydration for the crew during torpor. 2. Focusing on mitigation aspects and technology potential for solving key human spaceflight challenges. 3. Addressing critical engineering aspects of the design that may impact the initial performance and cost resultsobtained in Phase I. 4. Examining the broader extensibility and enabling capabilities of this concept through applicability toadditional exploration missions beyond Mars. 5. Establishing a technology development roadmap, addressing both medical and engineering aspects, thatindicate a logical and scientifically achievable path forward for maturation of this technology

MOLECULAR STRUCTURE OF THE EPIDERMAL EXTRACELLULAR SPACES

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65966/1/j.1365-4362.1979.tb01946.x.pd

HPK1 Associates with SKAP-HOM to Negatively Regulate Rap1-Mediated B-Lymphocyte Adhesion

BACKGROUND: Hematopoietic progenitor kinase 1 (HPK1) is a Ste20-related serine/threonine kinase activated by a range of environmental stimuli including genotoxic stress, growth factors, inflammatory cytokines and antigen receptor triggering. Being inducibly recruited to membrane-proximal signalling scaffolds to regulate NFAT, AP-1 and NFkappaB-mediated gene transcription in T-cells, the function of HPK1 in B-cells to date remains rather ill-defined. METHODOLOGY/PRINCIPAL FINDINGS: By using two loss of function models, we show that HPK1 displays a novel function in regulating B-cell integrin activity. Wehi 231 lymphoma cells lacking HPK1 after shRNA mediated knockdown exhibit increased basic activation levels of Ras-related protein 1 (Rap1), accompanied by a severe lymphocyte function-associated antigen-1 (LFA-1) dependent homotypic aggregation and increased adhesion to intercellular adhesion molecule 1 (ICAM-1). The observed phenotype of enhanced integrin activity is caused downstream of Src, by a signalling module independent of PI3K and PLC, involving HPK1, SKAP55 homologue (SKAP-HOM) and Rap1-GTP-interacting adaptor molecule (RIAM). This alters actin dynamics and renders focal adhesion kinase (FAK) constitutively phosphorylated. Bone marrow and splenic B-cell development of HPK1(-/-) mice are largely unaffected, except age-related tendencies for increased splenic cellularity and BCR downregulation. In addition, naïve splenic knockout B-cells appear hyperresponsive to a range of stimuli applied ex vivo as recently demonstrated by others for T-cells. CONCLUSIONS/SIGNIFICANCE: We therefore conclude that HPK1 exhibits a dual function in B-cells by negatively regulating integrin activity and controlling cellular activation, which makes it an interesting candidate to study in pathological settings like autoimmunity and cancer