Constraints on the perturbed mutual motion in Didymos due to impact-induced deformation of its primary after the DART impact

Binary near-Earth asteroid (65803) Didymos is the target of the proposed NASA Double Asteroid Redirection Test (DART), part of the Asteroid Impact & Deflection Assessment (AIDA) mission concept. In this mission, the DART spacecraft is planned to impact the secondary body of Didymos, perturbing mutual dynamics of the system. The primary body is currently rotating at a spin period close to the spin barrier of asteroids, and materials ejected from the secondary due to the DART impact are likely to reach the primary. These conditions may cause the primary to reshape, due to landslides, or internal deformation, changing the permanent gravity field. Here, we propose that if shape deformation of the primary occurs, the mutual orbit of the system would be perturbed due to a change in the gravity field. We use a numerical simulation technique based on the full two-body problem to investigate the shape effect on the mutual dynamics in Didymos after the DART impact. The results show that under constant volume, shape deformation induces strong perturbation in the mutual motion. We find that the deformation process always causes the orbital period of the system to become shorter. If surface layers with a thickness greater than ~0.4 m on the poles of the primary move down to the equatorial region due to the DART impact, a change in the orbital period of the system and in the spin period of the primary will be detected by ground-based measurement.Comment: 8 pages, 7 figures, 2 tables, accepted for publication in MNRA

Electrophysiological properties of myocytes isolated from the mouse atrioventricular node:L-type ICa, IKr, If, and Na-Ca exchange

The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35–37°C. Hyperpolarizing voltage commands from −40 mV elicited a Ba(2+)-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, I(f), whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear I(f), which was larger than in rabbit AVN cells. On depolarization from −40 mV L-type Ca(2+) current, I(C)(a,L), was elicited with a half maximal activation voltage (V(0.5)) of −7.6 ± 1.2 mV (n = 24). I(C)(a,L) density was smaller than in rabbit AVN cells. Rapid delayed rectifier (I(K)(r)) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to −40 mV, with an activation V(0.5) of −10.7 ± 4.7 mV (n = 8). The I(K)(r) magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (−40 mV). Spontaneous APs (5.2 ± 0.5 sec(−1); n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca(2+) release by 1 μmol/L ryanodine, implicating intracellular Ca(2+) cycling in murine AVN cell electrogenesis

QTc interval and ventricular action potential prolongation in the Mecp2Null/+ murine model of Rett syndrome

Rett Syndrome (RTT) is a congenital, X‐chromosome‐linked developmental disorder characterized by developmental delay, dysautonomia, and breathing irregularities. RTT is also associated with sudden death and QT intervals are prolonged in some RTT patients. Most individuals with RTT have mutations in the MECP2 gene. Whilst there is some evidence for QT prolongation in mouse models of RTT, there is comparatively little information on how loss of Mecp2 function affects ventricular action potentials (APs) and, to‐date, none on ventricular APs from female RTT mice. Accordingly, the present study was conducted to determine ECG and ventricular AP characteristics of Mecp2 ( Null/+ ) female mice. ECG recordings from 12–13 month old female Mecp2 ( Null/+ ) mice showed prolonged rate corrected QT (QTc) intervals compared to wild‐type (WT) controls. Although Mecp2 ( Null/+ ) animals exhibited longer periods of apnoea than did controls, no correlation between apnoea length and QT(c) interval was observed. Action potentials (APs) from Mecp2 ( Null/+ ) myocytes had longer APD(90) values than those from WT myocytes and showed augmented triangulation. Application of the investigational I(Na,Late) inhibitor GS‐6615 (eleclazine; 10 μM) reduced both APD(90) and AP triangulation in Mecp2 ( Null/+ ) and WT myocytes. These results constitute the first direct demonstration of delayed repolarization in Mecp2 ( Null/+ ) myocytes and provide further evidence that GS‐6615 may have potential as an intervention against QT prolongation in RTT

Data compression using Chebyshev transform

The present invention is a method, system, and computer program product for implementation of a capable, general purpose compression algorithm that can be engaged on the fly. This invention has particular practical application with time-series data, and more particularly, time-series data obtained form a spacecraft, or similar situations where cost, size and/or power limitations are prevalent, although it is not limited to such applications. It is also particularly applicable to the compression of serial data streams and works in one, two, or three dimensions. The original input data is approximated by Chebyshev polynomials, achieving very high compression ratios on serial data streams with minimal loss of scientific information

Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome

Rett syndrome (RTT) is a severe developmental disorder that is strongly linked to mutations in the MECP2 gene. RTT has been associated with sudden unexplained death and ECG QT interval prolongation. There are mixed reports regarding QT prolongation in mouse models of RTT, with some evidence that loss of Mecp2 function enhances cardiac late Na current, I(Na,Late). The present study was undertaken in order to investigate both ECG and ventricular AP characteristics in the Mecp2(Null/Y) male murine RTT model and to interrogate both fast I(Na) and I(Na,Late) in myocytes from the model. ECG recordings from 8–10-week-old Mecp2(Null/Y) male mice revealed prolongation of the QT and rate corrected QT (QTc) intervals and QRS widening compared to wild-type (WT) controls. Action potentials (APs) from Mecp2(Null/Y) myocytes exhibited longer APD(75) and APD(90) values, increased triangulation and instability. I(Na,Late) was also significantly larger in Mecp2(Null/Y) than WT myocytes and was insensitive to the Nav1.8 inhibitor A-803467. Selective recordings of fast I(Na) revealed a decrease in peak current amplitude without significant voltage shifts in activation or inactivation V(0.5). Fast I(Na) ‘window current’ was reduced in RTT myocytes; small but significant alterations of inactivation and reactivation time-courses were detected. Effects of two I(Na,Late) inhibitors, ranolazine and GS-6615 (eleclazine), were investigated. Treatment with 30 µM ranolazine produced similar levels of inhibition of I(Na,Late) in WT and Mecp2(Null/Y) myocytes, but produced ventricular AP prolongation not abbreviation. In contrast, 10 µM GS-6615 both inhibited I(Na,Late) and shortened ventricular AP duration. The observed changes in I(Na) and I(Na,Late) can account for the corresponding ECG changes in this RTT model. GS-6615 merits further investigation as a potential treatment for QT prolongation in RTT

In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms

Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. SIGnIFICAnCE: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens

The 1990 update to strategy for exploration of the inner planets

The Committee on Planetary and Lunar Exploration (COMPLEX) has undertaken to review and revise the 1978 report Strategy for Exploration of the Inner Planets, 1977-1987. The committee has found the 1978 report to be generally still pertinent. COMPLEX therefore issues its new report in the form of an update. The committee reaffirms the basic objectives for exploration of the planets: to determine the present state of the planets and their satellites, to understand the processes active now and at the origin of the solar system, and to understand planetary evolution, including appearance of life and its relation to the chemical history of the solar system

Next Gen NEAR: Near Earth Asteroid Human Robotic Precursor Mission Concept

Asteroids have long held the attention of the planetary science community. In particular, asteroids that evolve into orbits near that of Earth, called near-Earth objects (NEO), are of high interest as potential targets for exploration due to the relative ease (in terms of delta V) to reach them. NASA's Flexible Path calls for missions and experiments to be conducted as intermediate steps towards the eventual goal of human exploration of Mars; piloted missions to NEOs are such example. A human NEO mission is a valuable exploratory step beyond the Earth-Moon system enhancing capabilities that surpass our current experience, while also developing infrastructure for future mars exploration capabilities. To prepare for a human rendezvous with an NEO, NASA is interested in pursuing a responsible program of robotic NEO precursor missions. Next Gen NEAR is such a mission, building on the NEAR Shoemaker mission experience at the JHU/APL Space Department, to provide an affordable, low risk solution with quick data return. Next Gen NEAR proposes to make measurements needed for human exploration to asteroids: to demonstrate proximity operations, to quantify hazards for human exploration and to characterize an environment at a near-Earth asteroid representative of those that may be future human destinations. The Johns Hopkins University Applied Physics Laboratory has demonstrated exploration-driven mission feasibility by developing a versatile spacecraft design concept using conventional technologies that satisfies a set of science, exploration and mission objectives defined by a concept development team in the summer of 2010. We will describe the mission concept and spacecraft architecture in detail. Configuration options were compared with the mission goals and objectives in order to select the spacecraft design concept that provides the lowest cost, lowest implementation risk, simplest operation and the most benefit for the mission implementation. The Next Gen NEAR spacecraft was designed to support rendezvous with a range of candidate asteroid targets and could easily be launched with one of several NASA launch vehicles. The Falcon 9 launch vehicle supports a Next Gen NEAR launch to target many near-Earth asteroids under consideration that could be reached with a C3 of 18 km2/sec2 or less, and the Atlas V-401 provides added capability supporting launch to NEAs that require more lift capacity while at the same time providing such excess lift capability that another payload of opportunity could be launch in conjunction with Next Gen NEAR. Next Gen NEAR will measure and interact with the target surface in ways never undertaken at an asteroid, and will prepare for first human precursor mission by demonstrating exploration science operations at an accessible NEO. This flexible mission and spacecraft design concept supports target selection based on upcoming Earth-based observations and also provides opportunities for co-manifest & international partnerships. JHU/APL has demonstrated low cost, low risk, high impact missions and this mission will help to prepare NASA for human NEO exploration by combining the best of NASA s human and robotic exploration capabilities

Mercury Orbiter: Report of the Science Working Team

The results are presented of the Mercury Orbiter Science Working Team which held three workshops in 1988 to 1989 under the auspices of the Space Physics and Planetary Exploration Divisions of NASA Headquarters. Spacecraft engineering and mission design studies at the Jet Propulsion Lab were conducted in parallel with this effort and are detailed elsewhere. The findings of the engineering study, summarized herein, indicate that spin stabilized spacecraft carrying comprehensive particles and fields experiments and key planetology instruments in high elliptical orbits can survive and function in Mercury orbit without costly sun shields and active cooling systems