Dasatinib Nanoemulsion and Nanocrystal for Enhanced Oral Drug Delivery

In this work, dasatinib (DAS) nanoemulsion and nanocrystal are produced by high-gravity technology that approaches to practical mass production. The drug nanoformulations were systematically characterized and evaluated. At a low high-gravity level (β) = 47, nanoemulsion droplets were 16.15 ± 0.42 nm with a PDI of 0.122 ± 0.021. The nanoemulsion’s size and active pharmaceutical ingredient (API) content remained stable at long-term (4 months) freeze–thaw and dilution experiments. At a high β = 188, the as-prepared nanocrystal was lamellar with a short diameter of about 200 nm and a long diameter of about 750 nm. In vitro performances demonstrated the nanoemulsion displayed higher cytotoxicity on MDA-MB-231 tumor cells, Caco-2 cell permeability and drug release than that of the nanocrystal, indicating that nanoemulsion should be an ideal alternative for dasatinib oral administration.

Mental imagery of object motion in weightlessness

Mental imagery represents a potential countermeasure for sensorimotor and cognitive dysfunctions due to spaceflight. It might help train people to deal with conditions unique to spaceflight. Thus, dynamic interactions with the inertial motion of weightless objects are only experienced in weightlessness but can be simulated on Earth using mental imagery. Such training might overcome the problem of calibrating fine-grained hand forces and estimating the spatiotemporal parameters of the resulting object motion. Here, a group of astronauts grasped an imaginary ball, threw it against the ceiling or the front wall, and caught it after the bounce, during pre-flight, in-flight, and post-flight experiments. They varied the throwing speed across trials and imagined that the ball moved under Earth’s gravity or weightlessness. We found that the astronauts were able to reproduce qualitative differences between inertial and gravitational motion already on ground, and further adapted their behavior during spaceflight. Thus, they adjusted the throwing speed and the catching time, equivalent to the duration of virtual ball motion, as a function of the imaginary 0 g condition versus the imaginary 1 g condition. Arm kinematics of the frontal throws further revealed a differential processing of imagined gravity level in terms of the spatial features of the arm and virtual ball trajectories. We suggest that protocols of this kind may facilitate sensorimotor adaptation and help tuning vestibular plasticity in-flight, since mental imagery of gravitational motion is known to engage the vestibular cortex.

Gastrocnemius medialis contractile behavior during running differs between simulated Lunar and Martian gravities

The international partnership of space agencies has agreed to proceed forward to the Moon sustainably. Activities on the Lunar surface (0.16 g) will allow crewmembers to advance the exploration skills needed when expanding human presence to Mars (0.38 g). Whilst data from actual hypogravity activities are limited to the Apollo missions, simulation studies have indicated that ground reaction forces, mechanical work, muscle activation, and joint angles decrease with declining gravity level. However, these alterations in locomotion biomechanics do not necessarily scale to the gravity level, the reduction in gastrocnemius medialis activation even appears to level off around 0.2 g, while muscle activation pattern remains similar. Thus, it is difficult to predict whether gastrocnemius medialis contractile behavior during running on Moon will basically be the same as on Mars. Therefore, this study investigated lower limb joint kinematics and gastrocnemius medialis behavior during running at 1 g, simulated Martian gravity, and simulated Lunar gravity on the vertical treadmill facility. The results indicate that hypogravity-induced alterations in joint kinematics and contractile behavior still persist between simulated running on the Moon and Mars. This contrasts with the concept of a ceiling effect and should be carefully considered when evaluating exercise prescriptions and the transferability of locomotion practiced in Lunar gravity to Martian gravity.

Understanding Reduced Gravity Effects on Early Plant Development Before Attempting Life-Support Farming in the Moon and Mars

Plants are a necessary component of any system of bioregenerative life-support for human space exploration. For this purpose, plants must be capable of surviving and adapting to gravity levels different from the Earth gravity, namely microgravity, as it exists on board of spacecrafts orbiting the Earth, and partial-g, as it exists on the surface of the Moon or Mars. Gravity is a fundamental environmental factor for driving plant growth and development through gravitropism. Exposure to real or simulated microgravity produces a stress response in plants, which show cellular alterations and gene expression reprogramming. Partial-g studies have been performed in the ISS using centrifuges and in ground based facilities, by implementing adaptations in them. Seedlings and cell cultures were used in these studies. The Mars gravity level is capable of stimulating the gravitropic response of the roots and preserving the auxin polar transport. Furthermore, whereas Moon gravity produces alterations comparable, or even stronger than microgravity, the intensity of the alterations found at Mars gravity was milder. An adaptive response has been found in these experiments, showing upregulation of WRKY transcription factors involved in acclimation. This knowledge must be improved by incorporating plants to the coming projects of Moon exploration.

Research on the Performance of a Passive Gas-Liquid Separator Used in Space

Gas-liquid separation technology is one of the key technologies of environmental control and life support in manned spaceflight. In order to realize gas-liquid separation under microgravity, a prototype of a gas-liquid separator based on passive static separation technology was designed, manufactured, and studied by both ground experimental tests and computational fluid dynamics (CFD). Results show that the experimental results on earth are in good agreement with the simulation results and the internal fluid distribution directly determines the separation rate of the separator. The separation rate and internal flow field of the separator were also investigated under various flow rate conditions and gravity levels. Results show that higher liquid flow rate and lower gravity level can improve gas-liquid separation rate which attributes to the formation of a complete liquid film at the bottom of the collector. The separation rate can reach 100% within the specific ratio range, and the structure of the equipment is simple, without any power components, meeting the requirements of long life and high reliability of space equipment. It can provide a reference for gas-liquid separation in space under the microgravity environment.

Muscle in Variable Gravity: “I Do Not Know Where I Am, But I Know What to Do”

Purpose: Fascicle and sarcomere lengths are important predictors of muscle mechanical performance. However, their regulation during stretch-shortening cycle (SSC) activities in usual and challenging conditions is poorly understood. In this study, we aimed to investigate muscle fascicle and sarcomere behavior during drop jumps (a common SSC activity) in conditions of variable gravity.Methods: Fifteen volunteers performed repeated drop jumps in 1 g, hypo-gravity (0 to 1 g), and hyper-gravity (1 to 2 g) during a parabolic flight. Gastrocnemius medialis (GM) electromyographic activity and fascicle length (Lf) were measured at drop-off, ground contact (GC), minimum ankle joint angle (MAJ), and push-off. GM sarcomere number was estimated by dividing Lf, measured by ultrasound at rest, by published data on GM sarcomere length, and measured in vivo at the same joint angle. Changes in sarcomere length were estimated by dividing GM Lf in each jump phase by sarcomere number calculated individually. The sarcomere force-generating capacity in each jump phase was estimated from the sarcomere length-tension relationship previously reported in the literature.Results: The results showed that, regardless of the gravity level, GM sarcomeres operated in the ascending portion of their length-tension relationship in all the jump phases. Interestingly, although in hypo-gravity and hyper-gravity during the braking phase (GC-MAJ) GM fascicles and sarcomeres experienced a stretch (as opposed to the quasi-isometric behavior in 1 g), at MAJ they reached similar lengths as in 1 g, allowing sarcomeres to develop about the 70% of their maximum force.Conclusion: The observed fascicle behavior during drop jumping seems useful for anchoring the tendon, enabling storage of elastic energy and its release in the subsequent push-off phase for effectively re-bouncing in all gravity levels, suggesting that an innate neuromuscular wisdom enables to perform SSC movements also in challenging conditions.

Human muscle activity and lower limb biomechanics of overground walking at varying levels of simulated reduced gravity and gait speeds

Reducing the mechanical load on the human body through simulated reduced gravity can reveal important insight into locomotion biomechanics. The purpose of this study was to quantify the effects of simulated reduced gravity on muscle activation levels and lower limb biomechanics across a range of overground walking speeds. Our overall hypothesis was that muscle activation amplitudes would not decrease proportionally to gravity level. We recruited 12 participants (6 female, 6 male) to walk overground at 1.0, 0.76, 0.55, and 0.31 G for four speeds: 0.4, 0.8, 1.2, and 1.6 ms-1. We found that peak ground reaction forces, peak knee extension moment in early stance, peak hip flexion moment, and peak ankle extension moment all decreased substantially with reduced gravity. The peak knee extension moment at late stance/early swing did not change with gravity. The effect of gravity on muscle activity amplitude varied considerably with muscle and speed, often varying nonlinearly with gravity level. Quadriceps (rectus femoris, vastus lateralis, & vastus medialis) and medial gastrocnemius activity decreased in stance phase with reduced gravity. Soleus and lateral gastrocnemius activity had no statistical differences with gravity level. Tibialis anterior and biceps femoris increased with simulated reduced gravity in swing and stance phase, respectively. The uncoupled relationship between simulated gravity level and muscle activity have important implications for understanding biomechanical muscle functions during human walking and for the use of bodyweight support for gait rehabilitation after injury.

Gastrocnemius Medialis Contractile Behavior During Running Differs Between Simulated Lunar and Martian Gravities

The international partnership of space agencies has agreed to proceed forward to the Moon sustainably. Activities on the Lunar surface (0.16g) will allow crewmembers to advance the exploration skills needed when expanding human presence to Mars (0.38g). Whilst data from actual hypogravity activities are limited to the Apollo missions, simulation studies have indicated that ground reaction forces, mechanical work, muscle activation and joint angles decrease with declining gravity level. However, these alterations in locomotion biomechanics do not necessarily scale to gravity level, the reduction in gastrocnemius medialis activation even appears to level off around 0.2g, whilst muscle activation pattern remains similar. Thus, it is difficult to predict whether gastrocnemius medialis contractile behavior during running on Moon will basically be the same as on Mars. Therefore, this study investigated lower limb joint kinematics and gastrocnemius medialis behavior during running at 1g, simulated 0.38g and 0.16g on the vertical treadmill facility. The results reveal that hypogravity-induced alterations in joint kinematics and contractile behavior still persist between simulated running on Moon and Mars. This contrasts the idea of a ceiling effect and should be carefully considered when evaluating exercise prescriptions and the transferability of locomotion practiced in Lunar gravity to Martian gravity.

Application of a Magnetic Field in Saturated Film Boiling of a Magnetic Nanofluid (MNF) under Reduced Gravity

To overcome the problem of abnormally large bubbles and the large reduction of heat flux under low gravity, the computational model of magnetic nanofluid (MNF) boiling flow was used to systematically study the thermodynamic characteristics of an MNF-saturated film boiling with and without the magnetic field. This study found that in the absence of a magnetic field, the decrease of the gravity level makes the bubble size increase and the bubble departure time increase, and the lower the gravity level, the worse the boiling heat transfer. However, after applying the magnetic field, bubble size decreases significantly and the bubble departure time is shortened. As the magnetic field intensity increases, the difference in bubble size and heat transfer characteristics between different gravity levels becomes smaller and smaller, which shows that for the boiling flow of MNF under low gravity levels, applying a magnetic field can effectively avoid the appearance of abnormally large bubbles, enhance heat transfer, and improve the safety of related heat transfer equipment.