The 2016 Reactivations of Main-Belt Comets 238P/Read and 288P/(300163) 2006 VW139

We report observations of the reactivations of main-belt comets 238P/Read and 288P/(300163) 2006 VW139, that also track the evolution of each object's activity over several months in 2016 and 2017. We additionally identify and analyze archival SDSS data showing 288P to be active in 2000, meaning that both 238P and 288P have now each been confirmed to be active near perihelion on three separate occasions. From data obtained of 288P from 2012-2015 when it appeared inactive, we find best-fit R-band H,G phase function parameters of H_R=16.80+/-0.12 mag and G_R=0.18+/-0.11, corresponding to effective component radii of r_c=0.80+/-0.04 km, assuming a binary system with equally-sized components. Fitting linear functions to ejected dust masses inferred for 238P and 288P soon after their observed reactivations in 2016, we find an initial average net dust production rate of 0.7+/-0.3 kg/s and a best-fit start date of 2016 March 11 (when the object was at a true anomaly of -63 deg) for 238P, and an initial average net dust production rate of 5.6+/-0.7 kg/s and a best-fit start date of 2016 August 5 (when the object was at a true anomaly of -27 deg) for 288P. Applying similar analyses to archival data, we find similar start points for previous active episodes for both objects, suggesting that minimal mantle growth or ice recession occurred between the active episodes in question. Some changes in dust production rates between active episodes are detected, however. More detailed dust modeling is suggested to further clarify the process of activity evolution in main-belt comets.Comment: 21 pages, 9 figures, accepted by A

Observational and Dynamical Characterization of Main-Belt Comet P/2010 R2 (La Sagra)

We present observations of comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS 1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed from August 2010 through February 2011, while a dust trail aligned with the object's orbit plane is also observed from December 2010 through August 2011. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between August 2010 and December 2010, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of H_R=17.9+/-0.2 mag, corresponding to a nucleus radius of ~0.7 km, assuming an albedo of p=0.05. Using optical spectroscopy, we find no evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q_CN<6x10^23 mol/s, from which we infer an H2O production rate of Q_H2O<10^26 mol/s. Numerical simulations indicate that P/La Sagra is dynamically stable for >100 Myr, suggesting that it is likely native to its current location and that its composition is likely representative of other objects in the same region of the main belt, though the relatively close proximity of the 13:6 mean-motion resonance with Jupiter and the (3,-2,-1) three-body mean-motion resonance with Jupiter and Saturn mean that dynamical instability on larger timescales cannot be ruled out.Comment: 23 pages, 13 figures, accepted for publication in A

Directing Neuronal Signaling through Cell-Surface Glycan Engineering

The ability to tailor plasma membranes with specific glycans may enable the control of signaling events that are critical for proper development and function. We report a method to modify cell surfaces with specific sulfated chondroitin sulfate (CS) glycosaminoglycans using chemically modified liposomes. Neurons engineered to display CS-E-enriched polysaccharides exhibited increased activation of neurotrophin-mediated signaling pathways and enhanced axonal growth. This approach provides a facile, general route to tailor cell membranes with biologically active glycans and demonstrates the potential to direct important cellular events through cell-surface glycan engineering

Sulfated glycans engage the Ang–Tie pathway to regulate vascular development

The angiopoietin (Ang)–Tie pathway is essential for the proper maturation and remodeling of the vasculature. Despite its importance in disease, the mechanisms that control signal transduction through this pathway are poorly understood. Here, we demonstrate that heparan sulfate glycosaminoglycans (HS GAGs) regulate Ang–Tie signaling through direct interactions with both Ang ligands and Tie1 receptors. HS GAGs formed ternary complexes with Ang1 or Ang4 and Tie2 receptors, resulting in potentiation of endothelial survival signaling. In addition, HS GAGs served as ligands for the orphan receptor Tie1. The HS–Tie1 interaction promoted Tie1–Tie2 heterodimerization and enhanced Tie1 stability within the mature vasculature. Loss of HS–Tie1 binding using CRISPR–Cas9-mediated mutagenesis in vivo led to decreased Tie protein levels, pathway suppression and aberrant retinal vascularization. Together, these results reveal that sulfated glycans use dual mechanisms to regulate Ang–Tie signaling and are important for the development and maintenance of the vasculature

Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC)

The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). High IRS-2 expression was significantly associated with decreased overall survival in adenocarcinoma (ADC) patients, whereas low IRS-1 cytoplasmic expression showed a trend toward association with decreased overall survival in squamous cell carcinoma (SCC) patients. Tumors with low IRS-1 and high IRS-2 expression were found to be associated with poor outcomes in ADC and SCC, indicating a potential role for IRS-2 in the aggressive behavior of NSCLC. Our results suggest distinct contributions of IRS-1 and IRS-2 to the biology of ADC and SCC that impact disease progression

Addenbrooke’s Cognitive Examination III: Psychometric Characteristics and Relations to Functional Ability in Dementia

Objectives: The Addenbrooke’s Cognitive Examination (ACE) is a common cognitive screening test for dementia. Here, we examined the relationship between the most recent version (ACE-III) and its predecessor (ACE-R), determined ACE- III cutoff scores for the detection of dementia, and explored its relationship with functional ability. Methods: Study 1 included 199 dementia patients and 52 healthy controls who completed the ACE-III and ACE-R. ACE-III total and domain scores were regressed on their corresponding ACE-R values to obtain conversion formulae. Study 2 included 331 mixed dementia patients and 87 controls to establish the optimal ACE-III cutoff scores for the detection of dementia using receiver operator curve analysis. Study 3 included 194 dementia patients and their carers to investigate the relationship between ACE-III total score and functional ability. Results: Study 1: ACE-III and ACE-R scores differed by ≤1 point overall, the magnitude varying according to dementia type. Study 2: a new lower bound cutoff ACE-III score of 84/100 to detect dementia was identified (compared with 82 for the ACE-R). The upper bound cutoff score of 88/100 was retained. Study 3: ACE-III scores were significantly related to functional ability on the Clinical Dementia Rating Scale across all dementia syndromes, except for semantic dementia. Conclusions: This study represents one of the largest and most clini- cally diverse investigations of the ACE-III. Our results demonstrate that the ACE-III is an acceptable alternative to the ACE-R. In addition, ACE-III performance has broader clinical implications in that it relates to carer reports of functional impairment in most common dementias. (JINS, 2018, 24, 854–863

Encoding a qubit into multilevel subspaces

We present a formalism for encoding the logical basis of a qubit into subspaces of multiple physical levels. The need for this multilevel encoding arises naturally in situations where the speed of quantum operations exceeds the limits imposed by the addressability of individual energy levels of the qubit physical system. A basic feature of the multilevel encoding formalism is the logical equivalence of different physical states and correspondingly, of different physical transformations. This logical equivalence is a source of a significant flexibility in designing logical operations, while the multilevel structure inherently accommodates fast and intense broadband controls thereby facilitating faster quantum operations. Another important practical advantage of multilevel encoding is the ability to maintain full quantum-computational fidelity in the presence of mixing and decoherence within encoding subspaces. The formalism is developed in detail for single-qubit operations and generalized for multiple qubits. As an illustrative example, we perform a simulation of closed-loop optimal control of single-qubit operations for a model multilevel system, and subsequently apply these operations at finite temperatures to investigate the effect of decoherence on operational fidelity.Comment: IOPart LaTeX, 2 figures, 31 pages; addition of a numerical simulatio