34 research outputs found
Umbilical Deployment Device
The landing scheme for NASA's next-generation Mars rover will encompass a novel landing technique (see figure). The rover will be lowered from a rocket-powered descent stage and then placed onto the surface while hanging from three bridles. Communication between the rover and descent stage will be maintained through an electrical umbilical cable, which will be deployed in parallel with structural bridles. The -inch (13-mm) umbilical cable contains a Kevlar rope core, around which wires are wrapped to create a cable. This cable is helically coiled between two concentric truncated cones. It is deployed by pulling one end of the cable from the cone. A retractable mechanism maintains tension on the cable after deployment. A break-tie tethers the umbilical end attached to the rover even after the cable is cut after touchdown. This break-tie allows the descent stage to develop some velocity away from the rover prior to the cable releasing from the rover deck, then breaks away once the cable is fully extended. The descent stage pulls the cable up so that recontact is not made. The packaging and deployment technique can store a long length of cable in a relatively small volume while maintaining compliance with the minimum bend radius requirement for the cable being deployed. While the packaging technique could be implemented without the use of break-ties, they were needed in this design due to the vibratory environment and the retraction required by the cable. The break-ties used created a series of load-spikes in the deployment signature. The load spikes during the deployment of the initial three coils of umbilical showed no increase between the different temperature trials. The cold deployment did show an increased load requirement for cable extraction in the region where no break-ties were used. This increase in cable drag was superimposed on the loads required to rupture the last set of break-ties, and as such, these loads saw significant increase when compared to their ambient counterparts. While the loads showed spikes of high magnitude, they were of short duration. Because of this, neither the deployment of the rover, nor the motion of the descent stage, would be adversely affected. In addition, the umbilical was found to have a maximum of 1.2 percent chance for recontact with the ultra-high frequency antenna due to the large margin of safety built in
Pyrotechnic Actuator for Retracting Tubes Between MSL Subsystems
An apparatus, denoted the "retractuator" (a contraction of "retracting actuator"), was designed to help ensure clean separation between the cruise stage and the entry-vehicle subsystem of the Mars Science Laboratory (MSL) mission. The retractuator or an equivalent mechanism is needed because of tubes that (1) transport a heat-transfer fluid between the stages during flight and (2) are cut immediately prior to separation of the stages retractuator. The role of the retractuator is to retract the tubes, after they are cut and before separation of the subsystem, so that cut ends of the tubes do not damage thermal-protection coats on the entry vehicle and do not contribute to uncertainty of drag and consequent uncertainty in separation velocity
PI5P4Kα supports prostate cancer metabolism and exposes a survival vulnerability during androgen receptor inhibition.
Phosphatidylinositol (PI)regulating enzymes are frequently altered in cancer and have become a focus for drug development. Here, we explore the phosphatidylinositol-5-phosphate 4-kinases (PI5P4K), a family of lipid kinases that regulate pools of intracellular PI, and demonstrate that the PI5P4Kα isoform influences androgen receptor (AR) signaling, which supports prostate cancer (PCa) cell survival. The regulation of PI becomes increasingly important in the setting of metabolic stress adaptation of PCa during androgen deprivation (AD), as we show that AD influences PI abundance and enhances intracellular pools of PI-4,5-P2. We suggest that this PI5P4Kα-AR relationship is mitigated through mTORC1 dysregulation and show that PI5P4Kα colocalizes to the lysosome, the intracellular site of mTORC1 complex activation. Notably, this relationship becomes prominent in mouse prostate tissue following surgical castration. Finally, multiple PCa cell models demonstrate marked survival vulnerability following stable PI5P4Kα inhibition. These results nominate PI5P4Kα as a target to disrupt PCa metabolic adaptation to castrate resistance
GEOTRACES IC1 (BATS) contamination-prone trace element isotopes Cd, Fe, Pb, Zn, Cu, and Mo intercalibration
International audienceWe report data on the isotopic composition of cadmium, copper, iron, lead, zinc, and molybdenum at the GEOTRACES IC1 BATS Atlantic intercalibration station. In general, the between lab and within-lab precisions are adequate to resolve global gradients and vertical gradients at this station for Cd, Fe, Pb, and Zn. Cd and Zn isotopes show clear variations in the upper water column and more subtle variations in the deep water; these variations are attributable, in part, to progressive mass fractionation of isotopes by Rayleigh distillation from biogenic uptake and/or adsorption. Fe isotope variability is attributed to heavier crustal dust and hydrothermal sources and light Fe from reducing sediments. Pb isotope variability results from temporal changes in anthropogenic source isotopic compositions and the relative contributions of U.S. and European Pb sources. Cu and Mo isotope variability is more subtle and close to analytical precision. Although the present situation is adequate for proceeding with GEOTRACES, it should be possible to improve the within-lab and between-lab precisions for some of these properties
GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers.
Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is lethal to the cell, have been successfully exploited to treat cancer. GATA3 is frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset of patients with poor response to hormonal therapy and poor prognosis. However, GATA3 is not yet targetable. Here we show that GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. Depletion and pharmacological inhibition of MDM2 significantly impaired tumor growth in GATA3-deficient models in vitro, in vivo and in patient-derived organoids/xenograft (PDOs/PDX) harboring GATA3 somatic mutations. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. Our results present MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy
Author Correction: GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers.
Nutrition and cancer: A review of the evidence for an anti-cancer diet
It has been estimated that 30–40 percent of all cancers can be prevented by lifestyle and dietary measures alone. Obesity, nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes), low fiber intake, consumption of red meat, and imbalance of omega 3 and omega 6 fats all contribute to excess cancer risk. Intake of flax seed, especially its lignan fraction, and abundant portions of fruits and vegetables will lower cancer risk. Allium and cruciferous vegetables are especially beneficial, with broccoli sprouts being the densest source of sulforophane. Protective elements in a cancer prevention diet include selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids (α-carotene, β-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited benefits orally, but could be very beneficial intravenously. Supplementary use of oral digestive enzymes and probiotics also has merit as anticancer dietary measures. When a diet is compiled according to the guidelines here it is likely that there would be at least a 60–70 percent decrease in breast, colorectal, and prostate cancers, and even a 40–50 percent decrease in lung cancer, along with similar reductions in cancers at other sites. Such a diet would be conducive to preventing cancer and would favor recovery from cancer as well
Verification and Validation Testing of the Parachute Decelerator System Prior to the First Supersonic Flight Dynamics Test for the Low Density Supersonic Decelerator Program
The Parachute Decelerator System (PDS) is comprised of all components associated with the supersonic parachute and its associated deployment. During the Supersonic Flight Dynamics Test (SFDT), for the Low Density Supersonic Decelerators Program, the PDS was required to deploy the supersonic parachute in a defined fashion. The PDS hardware includes three major subsystems that must function together. The first subsystem is the Parachute Deployment Device (PDD), which acts as a modified pilot deployment system. It is comprised of a pyrotechnic mortar, a Kevlar ballute, a lanyard actuated pyrotechnic inflation aid, and rigging with its associated thermal protection material (TPS). The second subsystem is the supersonic parachute deployment hardware. This includes all of the parachute specific rigging that includes the parachute stowage can and the rigging including TPS and bridle stiffeners for bridle management during deployment. The third subsystem is the Supersonic Parachute itself, which includes the main parachute and deployment bags. This paper summarizes the verification and validation of the deployment process, from the initialization of the PDS system through parachute bag strip that was done prior to the first SFDT
Parachute Decelerator System Performance During the Low Density Supersonic Decelerator Program's First Supersonic Flight Dynamics Test
During the first Supersonic Flight Dynamics Test (SFDT-1) for NASA's Low Density Supersonic Decelerator (LDSD) Program, the Parachute Decelerator System (PDS) was successfully tested. The main parachute in the PDS was a 30.5-meter supersonic Disksail parachute. The term Disksail is derived from the canopy's constructional geometry, as it combined the aspects of a ringsail and a flat circular round (disk) canopy. The crown area of the canopy contained the disk feature, as a large flat circular disk that extended from the canopy's vent down to the upper gap. From this upper gap to the skirt-band the canopy was constructed with characteristics of sails seen in a ringsail. There was a second lower gap present in this sail region. The canopy maintained a nearly 10x forebody diameter trailing distance with 1.7 Do suspension line lengths. During the test, the parachute was deployed at the targeted Mach and dynamic pressure. Although the supersonic Disksail parachute experienced an anomaly during the inflation process, the system was tested successfully in the environment it was designed to operate within. The nature of the failure seen originated in the disk portion of the canopy. High-speed and high-resolution imagery of the anomaly was captured and has been used to aid in the forensics of the failure cause. In addition to the imagery, an inertial measurement unit (IMU) recorded test vehicle dynamics and loadcells captured the bridle termination forces. In reviewing the imagery and load data a number of hypothesizes have been generated in an attempt to explain the cause of the anomaly