A note on the complexity of h-cobordisms

We show that the number of double points of smoothly immersed 2-spheres representing certain homology classes of an oriented, smooth, closed, simply-connected 4-manifold X must increase with the complexity of corresponding h-cobordisms from X to X. As an application, we give results restricting the minimal number of double points of immersed spheres in manifolds homeomorphic to rational surfaces.Comment: Minor corrections, final version to appear in AG

Tumor‐stroma interactions differentially alter drug sensitivity based on the origin of stromal cells

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large‐scale coculture assay optimized to measure drug‐induced cell death, we identify tumor–stroma interactions that modulate drug sensitivity. Our data show that the chemo‐insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts. Furthermore, we find that fibroblasts influence drug responses in two distinct and divergent manners, associated with the tissue from which the fibroblasts were harvested. These divergent phenotypes occur regardless of the drug tested and result from modulation of apoptotic priming within tumor cells. Our study highlights unexpected diversity in tumor–stroma interactions, and we reveal new principles that dictate how fibroblasts alter tumor drug responses

The Thermal Properties of Solar Flares Over Three Solar Cycles Using GOES X-ray Observations

Solar flare X-ray emission results from rapidly increasing temperatures and emission measures in flaring active region loops. To date, observations from the X-Ray Sensor (XRS) onboard the Geostationary Operational Environmental Satellite (GOES) have been used to derive these properties, but have been limited by a number of factors, including the lack of a consistent background subtraction method capable of being automatically applied to large numbers of flares. In this paper, we describe an automated temperature and emission measure-based background subtraction method (TEBBS), which builds on the methods of Bornmann (1990). Our algorithm ensures that the derived temperature is always greater than the instrumental limit and the pre-flare background temperature, and that the temperature and emission measure are increasing during the flare rise phase. Additionally, TEBBS utilizes the improved estimates of GOES temperatures and emission measures from White et al. (2005). TEBBS was successfully applied to over 50,000 solar flares occurring over nearly three solar cycles (1980-2007), and used to create an extensive catalog of the solar flare thermal properties. We confirm that the peak emission measure and total radiative losses scale with background subtracted GOES X-ray flux as power-laws, while the peak temperature scales logarithmically. As expected, the peak emission measure shows an increasing trend with peak temperature, although the total radiative losses do not. While these results are comparable to previous studies, we find that flares of a given GOES class have lower peak temperatures and higher peak emission measures than previously reported. The resulting TEBBS database of thermal flare plasma properties is publicly available on Solar Monitor (www.solarmonitor.org/TEBBS/) and will be available on Heliophysics Integrated Observatory (www.helio-vo.eu)

RHESSI Microflare Statistics II. X-ray Imaging, Spectroscopy & Energy Distributions

We present X-ray imaging and spectral analysis of all microflares the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) observed between March 2002 and March 2007, a total of 25,705 events. These microflares are small flares, from low GOES C Class to below A Class (background subtracted) and are associated with active regions. They were found by searching the 6-12 keV energy range during periods when the full sensitivity of RHESSI's detectors was available (see paper I). Each microflare is automatically analyzed at the peak time of the 6-12 keV emission: the thermal source size is found by forward-fitting the complex visibilities for 4-8 keV, and the spectral parameters (temperature, emission measure, power-law index) are found by forward fitting a thermal plus non-thermal model. The combination of these parameters allows us to present the first statistical analysis of the thermal and non-thermal energy at the peak times of microflares.Comment: 17 pages, 21 figs, Ap

Exploring impulsive solar magnetic energy release and particle acceleration with focused hard X-ray imaging spectroscopy

How impulsive magnetic energy release leads to solar eruptions and how those eruptions are energized and evolve are vital unsolved problems in Heliophysics. The standard model for solar eruptions summarizes our current understanding of these events. Magnetic energy in the corona is released through drastic restructuring of the magnetic field via reconnection. Electrons and ions are then accelerated by poorly understood processes. Theories include contracting loops, merging magnetic islands, stochastic acceleration, and turbulence at shocks, among others. Although this basic model is well established, the fundamental physics is poorly understood. HXR observations using grazing-incidence focusing optics can now probe all of the key regions of the standard model. These include two above-the-looptop (ALT) sources which bookend the reconnection region and are likely the sites of particle acceleration and direct heating. The science achievable by a direct HXR imaging instrument can be summarized by the following science questions and objectives which are some of the most outstanding issues in solar physics (1) How are particles accelerated at the Sun? (1a) Where are electrons accelerated and on what time scales? (1b) What fraction of electrons is accelerated out of the ambient medium? (2) How does magnetic energy release on the Sun lead to flares and eruptions? A Focusing Optics X-ray Solar Imager (FOXSI) instrument, which can be built now using proven technology and at modest cost, would enable revolutionary advancements in our understanding of impulsive magnetic energy release and particle acceleration, a process which is known to occur at the Sun but also throughout the Universe

U.S. Natural Resources and Climate Change: Concepts and Approaches for Management Adaptation

Public lands and waters in the United States traditionally have been managed using frameworks and objectives that were established under an implicit assumption of stable climatic conditions. However, projected climatic changes render this assumption invalid. Here, we summarize general principles for management adaptations that have emerged from a major literature review. These general principles cover many topics including: (1) how to assess climate impacts to ecosystem processes that are key to management goals; (2) using management practices to support ecosystem resilience; (3) converting barriers that may inhibit management responses into opportunities for successful implementation; and (4) promoting flexible decision making that takes into account challenges of scale and thresholds. To date, the literature on management adaptations to climate change has mostly focused on strategies for bolstering the resilience of ecosystems to persist in their current states. Yet in the longer term, it is anticipated that climate change will push certain ecosystems and species beyond their capacity to recover. When managing to support resilience becomes infeasible, adaptation may require more than simply changing management practices—it may require changing management goals and managing transitions to new ecosystem states. After transitions have occurred, management will again support resilience—this time for a new ecosystem state. Thus, successful management of natural resources in the context of climate change will require recognition on the part of managers and decisions makers of the need to cycle between “managing for resilience” and “managing for change.

Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci.We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)).We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP.National Heart, Lung and Blood Institute R01-HL095393 R01-HL097163 P01-HL092870 RC2-HL101715 U01-HL089897 U01-HL089856 U01-HL108642 P50-HL089493

Microflares and the Statistics of X-ray Flares

This review surveys the statistics of solar X-ray flares, emphasising the new views that RHESSI has given us of the weaker events (the microflares). The new data reveal that these microflares strongly resemble more energetic events in most respects; they occur solely within active regions and exhibit high-temperature/nonthermal emissions in approximately the same proportion as major events. We discuss the distributions of flare parameters (e.g., peak flux) and how these parameters correlate, for instance via the Neupert effect. We also highlight the systematic biases involved in intercomparing data representing many decades of event magnitude. The intermittency of the flare/microflare occurrence, both in space and in time, argues that these discrete events do not explain general coronal heating, either in active regions or in the quiet Sun.Comment: To be published in Space Science Reviews (2011