476 research outputs found
Prototype Flight Management Capabilities to Explore Temporal RNP Concepts
Next Generation Air Transportation System (NextGen) concepts of operation may require aircraft to fly planned trajectories in four dimensions three spatial dimensions and time. A prototype 4D flight management capability is being developed by NASA to facilitate the development of these concepts. New trajectory generation functions extend today's flight management system (FMS) capabilities that meet a single Required Time of Arrival (RTA) to trajectory solutions that comply with multiple RTA constraints. When a solution is not possible, a constraint management capability relaxes constraints to achieve a trajectory solution that meets the most important constraints as specified by candidate NextGen concepts. New flight guidance functions provide continuous guidance to the aircraft s flight control system to enable it to fly specified 4D trajectories. Guidance options developed for research investigations include a moving time window with varying tolerances that are a function of proximity to imposed constraints, and guidance that recalculates the aircraft s planned trajectory as a function of the estimation of current compliance. Compliance tolerances are related to required navigation performance (RNP) through the extension of existing RNP concepts for lateral containment. A conceptual temporal RNP implementation and prototype display symbology are proposed
A solid-phase transfection platform for arrayed CRISPR screens
Arrayed CRISPRâbased screens emerge as a powerful alternative to pooled screens making it possible to investigate a wide range of cellular phenotypes that are typically not amenable to pooled screens. Here, we describe a solidâphase transfection platform that enables CRISPRâbased genetic screens in arrayed format with flexible readouts. We demonstrate efficient gene knockout upon delivery of guide RNAs and Cas9/guide RNA ribonucleoprotein complexes into untransformed and cancer cell lines. In addition, we provide evidence that our platform can be easily adapted to highâthroughput screens and we use this approach to study oncogene addiction in tumor cells. Finally demonstrating that the human primary cells can also be edited using this method, we pave the way for rapid testing of potential targeted therapies
A solidâphase transfection platform for arrayed CRISPR screens [Corrigendum]
Since the publication of this study, it has come to our attention that a citation to the study by Bulkescher et al (2017) was omitted from the Introduction. The following sentence should have been included in the introduction: âA previously reported solidâphase reverse transfection method for proteins (Bulkescher et al , 2017) was used for the delivery of RNPs for three endogenous genes suggesting the potential of solidâphase reverse transfection for CRISPR/Cas9âbased gene editing, despite its low efficiencyâ.
We apologise for any inconvenience this omission may have caused
Characterization of a K+-induced conformational switch in a human telomeric DNA oligonucleotide using 2-aminopurine fluorescence
Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucletotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a âbasketâ topology of four antiparallel strands; in contrast, Tel22 in K(+) solutions consists of a mixture of unknown topologies. Our previous studies on the mechanism of folding of Tel22 and similar telomere analogs utilized changes in UV absorption between 270 and 325 nm that report primarily on G-quartet formation and stacking showed that quadruplex formation occurs within milliseconds upon mixing with an appropriate cation. In the current study, we assessed the dynamics and equilibria of folding of specific loops by using Tel22 derivatives in which the dA residues were serially substituted with the fluorescent reporter base, 2-aminopurine (2-AP). Tel22 folding induced by Na(+) or K(+) assessed by changes in 2-AP fluorescence consists of at least three kinetic steps with time constants spanning a range of ms to several hundred seconds. Na(+)-dependent equilibrium titrations of Tel22 folding could be approximated as a cooperative two-state process. In contrast, K(+)-dependent folding curves were biphasic, revealing that different conformational ensembles are present in 1 mM and 30 mM K(+). This conclusion was confirmed by (1)H NMR. Molecular dynamics simulations revealed a K(+) binding pocket in Tel22 located near dA1 that is specific for the so-called hybrid-1 conformation in which strand 1 is in a parallel arrangement. The possible presence of this topologically specific binding site suggests that K(+) may play an allosteric role in regulating telomere conformation and function by modulating quadruplex tertiary structure
Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV
A search for new physics is presented based on an event signature of at least
three jets accompanied by large missing transverse momentum, using a data
sample corresponding to an integrated luminosity of 36 inverse picobarns
collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector
at the LHC. No excess of events is observed above the expected standard model
backgrounds, which are all estimated from the data. Exclusion limits are
presented for the constrained minimal supersymmetric extension of the standard
model. Cross section limits are also presented using simplified models with new
particles decaying to an undetected particle and one or two jets
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
X-ray emission from the Sombrero galaxy: discrete sources
We present a study of discrete X-ray sources in and around the
bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival
Chandra observations with a total exposure of ~200 ks. With a detection limit
of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30
kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler
et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS
observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray
binaries (LMXBs). We quantify the differential luminosity functions (LFs) for
both the detected GC and field LMXBs, whose power-low indices (~1.1 for the
GC-LF and ~1.6 for field-LF) are consistent with previous studies for
elliptical galaxies. With precise sky positions of the GCs without a detected
X-ray source, we further quantify, through a fluctuation analysis, the GC LF at
fainter luminosities down to 1E35 erg/s. The derived index rules out a
faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent
findings in several elliptical galaxies and the bulge of M31. On the other
hand, the 2-6 keV unresolved emission places a tight constraint on the field
LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101
sources in the halo of Sombrero. The presence of these sources cannot be
interpreted as galactic LMXBs whose spatial distribution empirically follows
the starlight. Their number is also higher than the expected number of cosmic
AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray
surveys. We suggest that either the cosmic X-ray background is unusually high
in the direction of Sombrero, or a distinct population of X-ray sources is
present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres
Autonomous aircraft operations using RTCA guidelines for airborne conflict management
Abstract A human-in-the-loop experiment was performed at the NASA Langley Research Center to study the feasibility of DAG-TM autonomous aircraft operations in highly constrained airspace. The airspace was constrained by a pair of special-use airspace (SUA) regions on either side of the pilot's planned route. Traffic flow management (TFM) constraints were imposed as a required time of arrival and crossing altitude at an en route fix. Key guidelines from the RTCA Airborne Conflict Management (ACM) concept were applied to autonomous aircraft operations for this experiment. These concepts included the RTCA ACM definitions of distinct conflict detection and collision avoidance zones, and the use of a graded system of conflict alerts for the flight crew. Three studies were conducted in the course of the experiment. The first study investigated the effect of hazard proximity upon pilot ability to meet constraints and solve conflict situations. The second study investigated pilot use of the airborne tools when faced with an unexpected loss of separation (LOS). The third study explored pilot interactions in an over-constrained conflict situation, with and without priority rules dictating who should move first. Detailed results from these studies were presented at the 5 th USA/Europe Air Traffic Management R&D Seminar (ATM2003). This overview paper focuses on the integration of the RTCA ACM concept into autonomous aircraft operations in highly constrained situations, and provides an overview of the results presented at the ATM2003 seminar. These results, together with previously reported studies, continue to support the feasibility of autonomous aircraft operations
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