The application of generalized, cyclic, and modified numerical integration algorithms to problems of satellite orbit computation

Generalized, cyclic, and modified multistep numerical integration methods are developed and evaluated for application to problems of satellite orbit computation. Generalized methods are compared with the presently utilized Cowell methods; new cyclic methods are developed for special second-order differential equations; and several modified methods are developed and applied to orbit computation problems. Special computer programs were written to generate coefficients for these methods, and subroutines were written which allow use of these methods with NASA's GEOSTAR computer program

The monitoring task in automated checkout of space vehicles

Man-machine system - human monitoring tasks in automatic checkout of space vehicle

Thermalization from gauge/gravity duality: Evolution of singularities in unequal time correlators

We consider a gauge/gravity dual model of thermalization which consists of a collapsing thin matter shell in asymptotically Anti-de Sitter space. A central aspect of our model is to consider a shell moving at finite velocity as determined by its equation of motion, rather than a quasi-static approximation as considered previously in the literature. By applying a divergence matching method, we obtain the evolution of singularities in the retarded unequal time correlator $G^R(t,t')$, which probes different stages of the thermalization. We find that the number of singularities decreases from a finite number to zero as the gauge theory thermalizes. This may be interpreted as a sign of decoherence. Moreover, in a second part of the paper, we show explicitly that the thermal correlator is characterized by the existence of singularities in the complex time plane. By studying a quasi-static state, we show the singularities at real times originate from contributions of normal modes. We also investigate the possibility of obtaining complex singularities from contributions of quasi-normal modes.Comment: 35 pages, 4 figure

Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors

Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turn-over by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by SCFFbxw7. However, N-Myc protein is stabilized in neuroblastoma by Aurora-A kinase in a manner that is sensitive to certain Aurora-A-selective inhibitors. Here we identify a direct interaction between the catalytic domain of Aurora-A and a site flanking Myc Box I that also binds SCFFbxw7. We determine the crystal structure of the complex between Aurora-A and this region of N-Myc to 1.72 Å resolution. The structure indicates that the conformation of Aurora-A induced by compounds such as alisertib and CD532 is not compatible with binding of N-Myc, explaining the activity of these compounds in neuroblastoma cells and providing a rational basis for the design of cancer therapeutics optimized for destabilization of the complex. We also propose a model for the stabilization mechanism in which binding to Aurora-A alters how N-Myc interacts with SCFFbxw7 to disfavor the generation of Lys48-linked poly-Ub chains

Durable response to serial tyrosine kinase inhibitors (TKIs) in an adolescent with metastatic TFG-ROS1 fusion positive Inflammatory Myofibroblastic Tumor (IMT)

Here, we present the case of an adolescent with a rare metastatic Inflammatory myofibroblastic tumor (IMT) harboring a TFG-ROS1 fusion initially detected on tumor progression and retrospectively identified in the primary tumor after targeted RNA sequencing. The patient benefitted from sequential TKIs over a 5-year period with response to the third generation ALK/ROS inhibitor, lorlatinib leading to resection of the primary tumor. Detailed molecular analysis can identify targetable oncogenic kinase fusions that alters management in patients with unresectable disease and should be considered in all patients

¹⁸F-meta-fluorobenzylguanidine (¹⁸F-mFBG) to monitor changes in norepinephrine transporter expression in response to therapeutic intervention in neuroblastoma models

argeted radiotherapy with {13}^1I-mIBG, a substrate of the human norepinephrine transporter (NET-1), shows promising responses in heavily pre-treated neuroblastoma (NB) patients. Combinatorial approaches that enhance {13}^1I-mIBG tumour uptake are of substantial clinical interest but biomarkers of response are needed. Here, we investigate the potential of {18}^F-mFBG, a positron emission tomography (PET) analogue of the {123}^I-mIBG radiotracer, to quantify NET-1 expression levels in mouse models of NB following treatment with AZD2014, a dual mTOR inhibitor. The response to AZD2014 treatment was evaluated in MYCN amplified NB cell lines (Kelly and SK-N-BE(2)C) by Western blot (WB) and immunohistochemistry. PET quantification of {18}^F-mFBG uptake post-treatment in vivo was performed, and data correlated with NET-1 protein levels measured ex vivo. Following 72 h AZD2014 treatment, in vitro WB analysis indicated decreased mTOR signalling and enhanced NET-1 expression in both cell lines, and {18}^F-mFBG revealed a concentration-dependent increase in NET-1 function. AZD2014 treatment failed however to inhibit mTOR signalling in vivo and did not significantly modulate intratumoural NET-1 activity. Image analysis of {18}^F-mFBG PET data showed correlation to tumour NET-1 protein expression, while further studies are needed to elucidate whether NET-1 upregulation induced by blocking mTOR might be a useful adjunct to {131}^I-mIBG therapy

Degenerate Stars and Gravitational Collapse in AdS/CFT

We construct composite CFT operators from a large number of fermionic primary fields corresponding to states that are holographically dual to a zero temperature Fermi gas in AdS space. We identify a large N regime in which the fermions behave as free particles. In the hydrodynamic limit the Fermi gas forms a degenerate star with a radius determined by the Fermi level, and a mass and angular momentum that exactly matches the boundary calculations. Next we consider an interacting regime, and calculate the effect of the gravitational back-reaction on the radius and the mass of the star using the Tolman-Oppenheimer-Volkoff equations. Ignoring other interactions, we determine the "Chandrasekhar limit" beyond which the degenerate star (presumably) undergoes gravitational collapse towards a black hole. This is interpreted on the boundary as a high density phase transition from a cold baryonic phase to a hot deconfined phase.Comment: 75 page

QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field

International audienceThe open field is a classic test used to assess exploratory behavior, anxiety, and locomotor activity in rodents. Here we mapped quantitative trait loci (QTLs) underlying behaviors displayed in an open field, using a panel of 53 BXD recombinant inbred mouse strains with deep replication (10 per strain and sex). The use of these strains permits the integration and comparison of data obtained in different laboratories, and also offers the possibility to study trait covariance by exploiting powerful bioinformatics tools and resources. We quantified behavioral traits during 20 min test sessions including (1) percent time spent and distance travelled near the wall (thigmotaxis), (2) leaning against the wall, (3) rearing, (4) jumping, (5) grooming duration, (6) grooming frequency, (7) locomotion, and (8) defecation. All traits exhibit moderate heritability making them amenable to genetic analysis. We identified a significant QTL on chromosome M.m. 4 at ~104 Mb that modulates grooming duration in both males and females (LRS values of ~18, explaining 25% and 14% of the variance, respectively) and a suggestive QTL modulating locomotion that maps to the same locus. Bioinformatic analysis indicates Disabled 1 (Dab1, a key protein in the reelin signaling pathway) as a particularly strong candidate gene modulating these behaviors. We also found two highly suggestive QTLs for a sex by strain interaction for grooming duration on chromosomes 13 and 17. In addition, we identified a pairwise epistatic interaction between loci on chromosomes 12 at 36-37 Mb and 14 at 34-36 Mb that influences rearing frequency in males