EarlyR: A Robust Gene Expression Signature for Predicting Outcomes of Estrogen Receptor–Positive Breast Cancer

Introduction Early stage estrogen receptor (ER)-positive breast cancer may be treated with chemotherapy in addition to hormone therapy. Currently available molecular signatures assess the risk of recurrence and the benefit of chemotherapy; however, these tests may have large intermediate risk groups, limiting their usefulness. Methods The EarlyR prognostic score was developed using integrative analysis of microarray data sets and formalin-fixed, paraffin-embedded–based quantitative real-time PCR assay and validated in Affymetrix data sets and METABRIC cohort using Cox proportional hazards models and Kaplan-Meier survival analysis. Concordance index was used to measure the probability of prognostic score agreement with outcome. Results The EarlyR score and categorical risk strata (EarlyR-Low, EarlyR-Int, EarlyR-High) derived from expression of ESPL1, MKI67, SPAG5, PLK1 and PGR was prognostic of 8-year distant recurrence-free interval in Affymetrix (categorical P = 3.5 × 10−14; continuous P = 8.8 × 10−15) and METABRIC (categorical P < 2.2 × 10−16; continuous P < 10−16) data sets of ER+ breast cancer. Similar results were observed for the breast cancer–free interval end point. At most 13% of patients were intermediate risk and at least 66% patients were low risk in both ER+ cohorts. The EarlyR score was significantly prognostic (distant recurrence-free interval; P < .001) in both lymph node–negative and lymph node–positive patients and was independent from clinical factors. EarlyR and surrogates of current molecular signatures were comparable in prognostic significance by concordance index. Conclusion The 5-gene EarlyR score is a robust prognostic assay that identified significantly fewer patients as intermediate risk and more as low risk than currently available assays. Further validation of the assay in clinical trial–derived cohorts is ongoing

Modeling sources in the FDTD formulation and their use in quantifying source and boundary condition errors

Journal ArticleThe modeling of voltage and current sources as either added or replaced sources in FDTD simulations is described and their differences discussed in terms of a transmission line analogy. An infinitesimal current element (ICE) is used to illustrate the validation of added source modeling and to study the errors involved with modeling an infinitesimal element within the finite-sized FDTD grid. This model is also used to illustrate the behavior of radiation boundary conditions as their near-field position with respect to the source is varied. We characterize the errors due to modeling and boundary conditions and give guidelines for obtaining acceptable accuracy in simulations

Dynamical spin-flip susceptibility for a strongly interacting ultracold Fermi gas

The Stoner model predicts that a two-component Fermi gas at increasing repulsive interactions undergoes a ferromagnetic transition. Using the random-phase approximation we study the dynamical properties of the interacting Fermi gas. For an atomic Fermi gas under harmonic confinement we show that the transverse (spin-flip) dynamical susceptibility displays a clear signature of the ferromagnetic phase in a magnon peak emerging from the Stoner particle-hole continuum. The dynamical spin susceptibilities could be experimentally explored via spin-dependent Bragg spectroscopy.Comment: 4 pages, 3 figure

Problem and treatment of DC offsets in FDTD simulations

Journal ArticleThis paper discusses the causes of and some solutions to the commonly observed problem of dc field offsets in finite-difference time-domain (FDTD) simulations. DC electric and magnetic field offsets are shown to be valid calculated responses of the modeled systems, resulting from interaction between the turn-on characteristics of the source and the properties of the models. The dc offsets may be avoided in the time domain by tailoring the source waveforms or in the frequency domain by post-processing the FDTD output

Polyphenols and non-alcoholic fatty liver disease: impact and mechanisms:impact and mechanisms

Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic component of the metabolic syndrome and its prevalence is rapidly increasing due to its strong association with insulin resistance and obesity. At present, given that NAFLD is highly prevalent and therapies are limited, much attention is focused on identifying effective dietary strategies for the prevention and treatment of the disease. Polyphenols are a group of plant bioactive compounds whose regular consumption have been associated with a reduction in the risk of a number of metabolic disorders associated with NAFLD. Here we review the emerging and relatively consistent evidence from cell culture and rodent studies showing that select polyphenols positively modulate a variety of contributors to the NAFLD phenotype, through diverse and complementary mechanisms of action. In particular, the reduction of de novo lipogenesis (via sterol regulatory element-binding protein 1c) and increased fatty acid β-oxidation, presumably involving AMP-activated protein kinase activation, will be discussed. The indirect antioxidant and anti-inflammatory properties of polyphenols which have been reported to contribute to the amelioration of NAFLD will also be addressed. In addition to a direct study of the liver, rodent studies have provided insight into the impact of polyphenols on adipose tissue function and whole body insulin sensitivity, which are likely to in part modulate their impact on NAFLD development. Finally an overview of the limited data from clinical trials will be given along with a discussion of the dose extrapolation from animal studies to human subjects

Ariel - Volume 4 Number 4

Editors David A. Jacoby Eugenia Miller Tom Williams Associate Editors Paul Bialas Terry Burt Michael Leo Gail Tenikat Editor Emeritus and Business Manager Richard J. Bonnano Movie Editor Robert Breckenridge Staff Richard Blutstein Mary F. Buechler Meg Brunt Steve Glinks Len Grasman Alice M. Johnson J.D. Kanofsky Tom Lehman Dave Mayer Bernie Odd

Subclinical infection of macaques and baboons with a baboon simarterivirus

Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3–10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies

Lightning Imaging Sensor (LIS) on the International Space Station (ISS): Path to Attaining Level 1 Science Requirements and Early Results in Year One

No abstract availabl

Global Lightning Statistics from Two Years of Science Observations by the Lightning Imaging Sensor (LIS) on the International Space Station (ISS)

No abstract availabl

Disorder-induced magnetic memory: Experiments and theories

Beautiful theories of magnetic hysteresis based on random microscopic disorder have been developed over the past ten years. Our goal was to directly compare these theories with precise experiments. We first developed and then applied coherent x-ray speckle metrology to a series of thin multilayer perpendicular magnetic materials. To directly observe the effects of disorder, we deliberately introduced increasing degrees of disorder into our films. We used coherent x-rays to generate highly speckled magnetic scattering patterns. The apparently random arrangement of the speckles is due to the exact configuration of the magnetic domains in the sample. In effect, each speckle pattern acts as a unique fingerprint for the magnetic domain configuration. Small changes in the domain structure change the speckles, and comparison of the different speckle patterns provides a quantitative determination of how much the domain structure has changed. How is the magnetic domain configuration at one point on the major hysteresis loop related to the configurations at the same point on the loop during subsequent cycles? The microscopic return-point memory(RPM) is partial and imperfect in the disordered samples, and completely absent when the disorder was not present. We found the complementary-point memory(CPM) is also partial and imperfect in the disordered samples and completely absent when the disorder was not present. We found that the RPM is always a little larger than the CPM. We also studied the correlations between the domains within a single ascending or descending loop. We developed new theoretical models that do fit our experiments.Comment: 26 pages, 25 figures, Accepted by Physical Review B 01/25/0