Unstable Nonradial Oscillations on Helium Burning Neutron Stars

Material accreted onto a neutron star can stably burn in steady state only when the accretion rate is high (typically super-Eddington) or if a large flux from the neutron star crust permeates the outer atmosphere. For such situations we have analyzed the stability of nonradial oscillations, finding one unstable mode for pure helium accretion. This is a shallow surface wave which resides in the helium atmosphere above the heavier ashes of the ocean. It is excited by the increase in the nuclear reaction rate during the oscillations, and it grows on the timescale of a second. For a slowly rotating star, this mode has a frequency of approximately 20-30 Hz (for l=1), and we calculate the full spectrum that a rapidly rotating (>>30 Hz) neutron star would support. The short period X-ray binary 4U 1820--30 is accreting helium rich material and is the system most likely to show this unstable mode,especially when it is not exhibiting X-ray bursts. Our discovery of an unstable mode in a thermally stable atmosphere shows that nonradial perturbations have a different stability criterion than the spherically symmetric thermal perturbations that generate type I X-ray bursts.Comment: Accepted for publication in Astrophysical Journal, 22 pages, 14 figure

Core-Clickable PEG-Branch-Azide Bivalent-Bottle-Brush Polymers by ROMP: Grafting-Through and Clicking-To

The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic tructures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle. We demonstrate copper-catalyzed azide-alkre cycloaddition (CuAAC) "click-to" coupling of a photocleavable doxorubicin (DOX)-alkyne derivative to the azide core. The CuAAC coupling was quantitative across a wide range of nanoscopic sizes (similar to 6-similar to 50 nrn); UV photolysis of the resulting DOX-loaded materials yielded free DOX that was therapeutically effective against human cancer cells

TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy

Significance Alzheimer’s disease (AD) is the most common cause of dementia and is a major public health problem for which there is currently no disease-modifying treatment. There is an urgent need for greater understanding of the molecular mechanisms underlying neurodegeneration in patients to create better therapeutic options. Recently, genetic studies uncovered novel AD risk variants in the microglial receptor, triggering receptor expressed on myeloid cells 2 (TREM2). Previous studies suggested that loss of TREM2 function worsens amyloid-β (Aβ) plaque-related toxicity. In contrast, we observe TREM2 deficiency mitigates neuroinflammation and protects against brain atrophy in the context of tau pathology. These findings indicate dual roles for TREM2 and microglia in the context of amyloid versus tau pathology, which are important to consider for potential treatments targeting TREM2.</jats:p

Aperture synthesis for gravitational-wave data analysis: Deterministic Sources

Gravitational wave detectors now under construction are sensitive to the phase of the incident gravitational waves. Correspondingly, the signals from the different detectors can be combined, in the analysis, to simulate a single detector of greater amplitude and directional sensitivity: in short, aperture synthesis. Here we consider the problem of aperture synthesis in the special case of a search for a source whose waveform is known in detail: \textit{e.g.,} compact binary inspiral. We derive the likelihood function for joint output of several detectors as a function of the parameters that describe the signal and find the optimal matched filter for the detection of the known signal. Our results allow for the presence of noise that is correlated between the several detectors. While their derivation is specialized to the case of Gaussian noise we show that the results obtained are, in fact, appropriate in a well-defined, information-theoretic sense even when the noise is non-Gaussian in character. The analysis described here stands in distinction to ``coincidence analyses'', wherein the data from each of several detectors is studied in isolation to produce a list of candidate events, which are then compared to search for coincidences that might indicate common origin in a gravitational wave signal. We compare these two analyses --- optimal filtering and coincidence --- in a series of numerical examples, showing that the optimal filtering analysis always yields a greater detection efficiency for given false alarm rate, even when the detector noise is strongly non-Gaussian.Comment: 39 pages, 4 figures, submitted to Phys. Rev.

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up.

PurposeIn the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P &lt; 0.001]. Herein, we report results overall and by subgroups with extended follow-up.MethodsIn this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).ResultsAfter a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P &lt; 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained.ConclusionsWith approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427

Heterotic Strings in Two Dimensions and New Stringy Phase Transitions

We discuss heterotic string theories in two dimensions with gauge groups Spin(24) and Spin(8) x E_8. After compactification the theories exhibit a rich spectrum of states with both winding and momentum. At special points some of these stringy states become massless, leading to new first order phase transitions. For example, the thermal theories exhibit standard thermodynamics below the phase transition, but novel and peculiar behavior above it. In particular, when the radius of the Euclidean circle is smaller than the phase transition point the torus partition function is not given by the thermal trace over the spacetime Hilbert space. The full moduli space of compactified theories is 13 dimensional, when Wilson lines are included; the Spin(24) and Spin(8) x E_8 theories correspond to distinct decompactification limits.Comment: 32 pages; v2: references added, minor change

Colliding black holes: how far can the close approximation go?

We study the head-on collision of two equal-mass momentarily stationary black holes, using black hole perturbation theory up to second order. Compared to first-order results, this significantly improves agreement with numerically computed waveforms and energy. Much more important, second-order results correctly indicate the range of validity of perturbation theory. This use of second-order, to provide ``error bars,'' makes perturbation theory a viable tool for providing benchmarks for numerical relativity in more generic collisions and, in some range of collision parameters, for supplying waveform templates for gravitational wave detection.Comment: 6 pages, RevTeX, 2 figures included with eps

Hierarchical search strategy for the detection of gravitational waves from coalescing binaries: Extension to post-Newtonian wave forms

The detection of gravitational waves from coalescing compact binaries would be a computationally intensive process if a single bank of template wave forms (i.e., a one step search) is used. In an earlier paper we had presented a detection strategy, called a two step search}, that utilizes a hierarchy of template banks. It was shown that in the simple case of a family of Newtonian signals, an on-line two step search was about 8 times faster than an on-line one step search (for initial LIGO). In this paper we extend the two step search to the more realistic case of zero spin 1.5 post-Newtonian wave forms. We also present formulas for detection and false alarm probabilities which take statistical correlations into account. We find that for the case of a 1.5 post-Newtonian family of templates and signals, an on-line two step search requires about 1/21 the computing power that would be required for the corresponding on-line one step search. This reduction is achieved when signals having strength S = 10.34 are required to be detected with a probability of 0.95, at an average of one false event per year, and the noise power spectral density used is that of advanced LIGO. For initial LIGO, the reduction achieved in computing power is about 1/27 for S = 9.98 and the same probabilities for detection and false alarm as above.Comment: 30 page RevTeX file and 17 figures (postscript). Submitted to PRD Feb 21, 199

A landscape classification map of Ireland and its potential use in national land use monitoring

peer-reviewedThe associated data file for this article is available at http://hdl.handle.net/11019/2790This study presents a novel landscape classification map of the Republic of Ireland and is the first to identify broad landscape classes by incorporating physiographic and land cover data. The landscape classification responds to commitments to identify and classify the Irish landscape as a signatory to the European Landscape Convention. The methodology applied a series of clustering iterations to determine an objective multivariate classification of physiographic landscape units and land cover datasets. The classification results determined nine statistically significant landscape classes and the development of a landscape classification map at a national scale. A statistical breakdown of land cover area and diversity of each class was interpreted, and a comparison was extended using independent descriptive variables including farmland use intensity, elevation, and dominant soil type. Each class depicts unique spatial and composition characteristics, from coastal, lowland and elevated, to distinct and dominating land cover types, further explained by the descriptive variables. The significance of individual classes and success of the classification is discussed with particular reference to the wider applicability of the map. The transferability of the methodology to other existing physiographic maps and environmental datasets to generate new landscape classifications is also considered. This novel work facilitates the development of a strategic framework to efficiently monitor, compare and analyse ecological and other land use data that is spatially representative of the distribution and extent of land cover in the Irish countryside.Department of Agriculture Food and the Marin

Phase transitions in nanosystems caused by interface motion: The Ising bi-pyramid with competing surface fields

The phase behavior of a large but finite Ising ferromagnet in the presence of competing surface magnetic fields +/- H_s is studied by Monte Carlo simulations and by phenomenological theory. Specifically, the geometry of a double pyramid of height 2L is considered, such that the surface field is positive on the four upper triangular surfaces of the bi-pyramid and negative on the lower ones. It is shown that the total spontaneous magnetization vanishes (for L -> infinity) at the temperature T_f(H), related to the "filling transition" of a semi-infinite pyramid, which can be well below the critical temperature of the bulk. The discontinuous vanishing of the magnetization is accompanied by a susceptibility that diverges with a Curie-Weiss power law, when the transition is approached from either side. A Landau theory with size-dependent critical amplitudes is proposed to explain these observations, and confirmed by finite size scaling analysis of the simulation results. The extension of these results to other nanosystems (gas-liquid systems, binary mixtures, etc.) is briefly discussed