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A novel macrocyclic peptide strategy utilizing a glutamic acid analog that can work as an alkylated histidine replacement.
Meiotic chromosome segregation relies on synapsis and crossover (CO) recombination between homologous chromosomes. These processes require multiple steps that are coordinated by the meiotic cell cycle and monitored by surveillance mechanisms. In diverse species, failures in chromosome synapsis can trigger a cell cycle delay and/or lead to apoptosis. How this key step in ‘homolog engagement’ is sensed and transduced by meiotic cells is unknown. Here we report that in C. elegans , recruitment of the Polo-like kinase PLK-2 to the synaptonemal complex triggers phosphorylation and inactivation of CHK-2, an early meiotic kinase required for pairing, synapsis, and double-strand break (DSB) induction. Inactivation of CHK-2 terminates DSB formation and enables CO designation and cell cycle progression. These findings illuminate how meiotic cells ensure CO formation and accurate chromosome segregation.
A major goal for NASA's human spaceflight program is to send astronauts to near-Earth asteroids (NEAs) in the coming decades. Missions to NEAs would undoubtedly provide a great deal of technical and engineering data on spacecraft operations for future human space exploration while conducting in-depth scientific examinations of these primitive objects. However, prior to sending human explorers to NEAs, robotic investigations of these bodies would be required in order to maximize operational efficiency and reduce mission risk. These precursor missions to NEAs would fill crucial strategic knowledge gaps concerning their physical characteristics that are relevant for human exploration of these relatively unknown destinations. Therefore robotic investigations of NEAs, such as ESA's Marco Polo-R sample return mission to 2008 EV5, would allow NASA and its international partners to gain critical operational experience in performing complex tasks (e.g., close proximity operations, surface sample collection, etc.) under microgravity conditions at or near the surface of a potential human destination. This would provide an important synergy between the worldwide Science and Exploration communities, which will be crucial for development of future international deep space exploration architectures and has potential benefits for future exploration of other destinations beyond low-Earth orbit.
This project stems from the Exploration, Research, and Technology Directorate (UB) Projects Division, and one of their main initiatives is the "Journey to Mars". Landing on the surface of Mars which is millions of miles away is an incredibly large challenge. The terrain is covered in boulders, deep canyons, volcanic mountains, and spotted with sand dunes. The robotic lander is a kind of spacecraft with multiple purposes. One purpose is to be the protective shell for the Martian rover and absorb the impact from the landing forces; another purpose is to be a place where the rovers can come back to, actively communicate with, and recharge their batteries from. Rovers have been instrumental to the Journey to Mars initiative. They have been performing key research on the terrain of the red planet, trying to unlock the mysteries of the land for over a decade. The rovers that will need charging will not all have the same kind of internal battery either. RASSOR batteries may differ from the PbAC batteries inside Red Rover's chassis. NASA has invested heavily in the exploration of the surface of Mars. A driving force behind further exploration is the need for a more efficient operation of Martian rovers. One way is to reduce the weight as much as possible to reduce power consumption given the same mission parameters. In order to reduce the mass of the rovers, power generation, communication, and sample analysis systems currently onboard Martian rovers can be moved to a stationary lander deck. Positioning these systems from the rover to the Lander deck allows a taskforce of smaller, lighter rovers to perform the same tasks currently performed by or planned for larger rovers. A major task in transferring these systems to a stationary lander deck is ensuring that power can be transferred to the rovers.
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Curve of growth for atmospheric absorption bands of molecular oxygen
We report the results of a survey test conducted in advance of a series of community response tests (CRTs) to evaluate response to noise from NASA’s X-59 aircraft. The CRTs will require a substantial number of observations to generate a dose response curve for noise exposure and related annoyance levels and the timeframe is limited due to resource and scheduling constraints with an experimental aircraft. Respondents will be asked to fill out the surveys either on the web or as part of an application they are able to download onto their mobile phones. Respondents will be asked to fill out a survey each time the plane flies over the targeted area. The sample will be drawn targeting households within a specific ‘fly-over’ area. However, respondents may travel during the day, sometimes outside the targeted area. For the observations to be useful respondents need to be within a target area during flights. To collect the location data, respondents will be asked to identify where they were at the time of the flyover. The survey test followed the proposed methodology of the CRTs. We will describe how location data was collected using Google Maps API and evaluate reported rates of location at home, work or other places and whether these were inside or outside the target area. We will also compare how these rates varied across web and app respondents. We will use the results of this work to confirm or improve the design of the CRTs, ensuring the collection of data needed by NASA to evaluate the impact of this innovative technology.
Here we report further progress in the development of the MARCO POLO-Mars Pathfinder Atmospheric Processing Module (APM). The APM is designed to demonstrate in situ resource utilization (ISRU) of the Martian atmosphere, which primarily consists of carbon dioxide (CO2). The APM is part of a larger project with the overall goal of collecting and utilizing CO2 found in the atmosphere and water in the regolith of Mars to produce methane and oxygen to be used as rocket propellant, eliminating the need to import those to Mars for human missions, thus significantly reducing costs. The initial focus of NASA's new ISRU Project is modeling of key ISRU components, such as the CO2 Freezers and the Sabatier reactor of the APM. We have designed models of those components and verified the models with the APM by gathering additional data for the Sabatier reactor. Future efforts will be focused on simultaneous operations of the APM and other MARCO POLO-Mars Pathfinder modules.
Here we report further progress in the development of the MARCO POLO-Mars Pathfinder Atmospheric Processing Module (APM). The APM is designed to demonstrate in situ resource utilization (ISRU) of the Martian atmosphere, which primarily consists of carbon dioxide (CO2). The APM is part of a larger project with the overall goal of collecting and utilizing CO2 found in the atmosphere and water in the regolith of Mars to produce methane and oxygen to be used as rocket propellant, eliminating the need to import those to Mars for human missions, thus significantly reducing costs. The initial focus of NASA's new ISRU Project is modeling of key ISRU components, such as the CO2 Freezers and the Sabatier reactor of the APM. We have designed models of those components and verified the models with the APM by gathering additional data for the Sabatier reactor. Future efforts will be focused on simultaneous operations of the APM and other MARCO POLO-Mars Pathfinder modules.
Over the past decade, silicon solar cells with carrier-selective passivating contacts based on polysilicon capping an ultra-thin silicon oxide (commonly known as TOPCon or POLO) have demonstrated promising efficiency potentials and are regarded as an evolutionary upgrade to the PERC (passivated emitter and rear contact) cells in manufacturing. The polysilicon-based passivating contacts also exhibit excellent gettering effects that relax the wafer and cleanroom requirements to some extent. Here, in this work, we experimentally explore the impact of bulk iron contamination and polysilicon gettering on the passivation quality of the polysilicon/oxide structure and the resulting solar cells performance. Results show that both n- and p-type polysilicon/oxide passivating contacts are not affected by iron gettering, demonstrating robust and stable passivation quality. However, for a very high bulk iron contamination (1 × 10 13 cm −3 ), the accumulated iron in the p-type lightly boron-doped emitter in crystalline silicon would degrade the emitter saturation current density. This can cause a reduction in both open-circuit voltage and short-circuit current. Meanwhile, this very high iron content (1 × 10 13 cm −3 ) can further degrade the fill factor and temperature coefficient of the cells. On the other hand, for an initial iron content of 2 × 10 12 cm −3 , which should be well above the iron level in the current industrial Czochralski silicon wafers, the resulting cells demonstrate similar performance as the control group with no intentional iron contamination. This work brings attention to both the benefits of polysilicon gettering effects as well as the potential degradation due to the accumulation of metal impurities in the p-type emitter region.
Polo-like kinase 1 (PLK1) is a protein kinase that is overexpressed in breast cancer and may represent an attractive target for breast cancer treatment. However, few studies have investigated the relationship between PLK1 and radiosensitivity in breast cancer. Here, we attempted to explore whether PLK1 inhibition could sensitize breast cancer cells to radiation.
Highlights: • Several oncogenic viral proteins bind to tumor suppressor pRB via LxCxE motif. • LxCxE present in many cellular proteins that interact with pRB. • APC/C interacts with pRB via this motif in its FZR1 subunit. • FZR1 LxCxE-like LxCxD critical for FZR1-pRB direct binding and SKP2 ubiquitylation. • Mutation of FZR1 LxCxD alters cell cycle. Retinoblastoma protein (pRB) regulates cell cycle by utilizing different regions of its pocket domain for interacting with E2F family of transcription factors and with cellular and viral proteins containing an LxCxE motif. An LxCxE-like motif, LxCxD, is present in FZR1, an adaptor protein of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C). The APC/C{sup FZR1} complex regulates the timely degradation of multiple cell cycle proteins for mitotic exit and maintains G1 state. We report that FZR1 interacts with pRB via its LxCxD motif. By using point mutations, we found that the cysteine residue in the FZR1 LxCxD motif is critical for direct interaction with pRb. The direct binding of the LxCxD motif of FZR1 to the pRB LxCxE binding pocket is confirmed by using human papillomavirus protein E7 as a competitor, both in vitro and in vivo. While mutation of the cysteine residue significantly disrupts FZR1 interaction with pRB, this motif does not affect FZR1 and core APC/C association. Expression of the FZR1 point mutant results in accumulation of S-phase kinase-associated protein 2 (SKP2) and Polo-like kinase 1 (PLK1), while p27{sup Kip1} and p21{sup Cip1} proteins are downregulated, indicating a G1 cell cycle defect. Consistently, cells containing point mutant FZR1 enter the S phase prematurely. Together our results suggest that the LxCxD motif of FZR1 is a critical determinant for the interaction between FZR1 and pRB and is important for G1 restriction.
Abstract Sepsis and sepsis‐induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell‐based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo‐like kinase 1 (PLK1) and phosphorylated protein kinase B (p‐AKT) was decreased. Overexpression of PLK1 partly rescued LPS‐induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS‐induced atrophy in PLK1‐overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1‐AKT pathway. These findings enhance understanding of the mechanism of sepsis‐induced skeletal muscle atrophy.
This letter shows that the Apollo lunar-surface Suprathermal Ion Detection Experiment (SIDE) instruments lack the sensitivity to detect even large emissions of radiogenic gases from the moon if the venting of these gases occurs primarily at a few-well-defined sites of lunar transient phenomena (LTPs). It is suggested that specific flight instruments for the proposed ESA Polar Orbiting Lunar Observatory (POLO) mission, which could detect active venting, would help determine the energy source for LTPs and would increase knowledge of lunar geophysics. A critical-velocity model for the LTP energy source is briefly discussed.
A two axis thrust measuring system was analyzed by using a finite a element computer program to determine the sensitivities of the thrust vectoring nozzle system to misalignment of the load cells and applied loads, and the stiffness of the structural members. Three models were evaluated: (1) the basic measuring element and its internal calibration load cells; (2) the basic measuring element and its external load calibration equipment; and (3) the basic measuring element, external calibration load frame and the altitude facility support structure. Alignment of calibration loads was the greatest source of error for multiaxis thrust measuring systems. Uniform increases or decreases in stiffness of the members, which might be caused by the selection of the materials, have little effect on the accuracy of the measurements. It is found that the POLO-FINITE program is a viable tool for designing and analyzing multiaxis thrust measurement systems. The response of the test stand to step inputs that might be encountered with thrust vectoring tests was determined. The dynamic analysis show a potential problem for measuring the dynamic response characteristics of thrust vectoring systems because of the inherently light damping of the test stand.
The effect of weight bearing activity on the bone density was investigated in athletes by comparing the measures of bone density of athletes engaged in weight-training programs with those of polo players and nonexercising subjects. All subjects had measurements of spinal trabecular and integral bone density by quantitative tomography, as well as determinations of hip bone density by dual photon absorptiometry. Results confirmed previous findings by Block et al. (1987) of significantly greater bone density among highly trained athletes compared with nonexercising subjects of similar age. Results also indicated that athletes engaged in non-weight-bearing forms of rigorous exercise had greater levels of bone density. However, as the participants in this study were exceptional athletes, engaged in a strenuous sport with both aerobic and heavy resistance components, a confirmation of these data is needed, using larger samples of individuals.
The ALTEA project investigates the risks of functional brain damage induced by particle radiation in space. A modular facility (the ALTEA facility) is being implemented and will be operated in the International Space Station (ISS) to record electrophysiological and behavioral descriptors of brain function and to monitor their time dynamics and correlation with particles and space environment. The focus of the program will be on abnormal visual perceptions (often reported as "light flashes" by astronauts) and the impact on retinal and brain visual structures of particle in microgravity conditions. The facility will be made available to the international scientific community for human neurophysiological, electrophysiological and psychophysics experiments, studies on particle fluxes, and dosimetry. A precursor of ALTEA (the 'Alteino' project) helps set the experimental baseline for the ALTEA experiments, while providing novel information on the radiation environment onboard the ISS and on the brain electrophysiology of the astronauts during orbital flights. Alteino was flown to the ISS on the Soyuz TM34 as part of mission Marco Polo. Controlled ground experiments using mice and accelerator beams complete the experimental strategy of ALTEA. We present here the status of progress of the ALTEA project and preliminary results of the Alteino study on brain dynamics, particle fluxes and abnormal visual perceptions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.
The multi-NASA center Mars Atmosphere and Regolith COllector/PrOcessor for Lander Operations (MARCO POLO) project was established to build and demonstrate a methane/oxygen propellant production system in a Mars analog environment. Work at the Kennedy Space Center (KSC) Applied Chemistry Laboratory is focused on the Atmospheric Processing Module (APM). The purpose of the APM is to freeze carbon dioxide from a simulated Martian atmosphere containing the minor components nitrogen, argon, carbon monoxide, and water vapor at Martian pressures (approx.8 torr) by using dual cryocoolers with alternating cycles of freezing and sublimation. The resulting pressurized CO2 is fed to a methanation subsystem where it is catalytically combined with hydrogen in a Sabatier reactor supplied by the Johnson Space Center (JSC) to make methane and water vapor. We first used a simplified once-through setup and later employed a HiCO2 recycling system to improve process efficiency. This presentation and paper will cover (1) the design and selection of major hardware items, such as the cryocoolers, pumps, tanks, chillers, and membrane separators, (2) the determination of the optimal cold head design and flow rates needed to meet the collection requirement of 88 g CO2/hr for 14 hr, (3) the testing of the CO2 freezer subsystem, and (4) the integration and testing of the two subsystems to verify the desired production rate of 31.7 g CH4/hr and 71.3 g H2O/hr along with verification of their purity. The resulting 2.22 kg of CH4/O2 propellant per 14 hr day (including O2 from electrolysis of water recovered from regolith, which also supplies the H2 for methanation) is of the scale needed for a Mars Sample Return mission. In addition, the significance of the project to NASA's new Mars exploration plans will be discussed.