Separation of breast cancer and organ microenvironment transcriptomes in metastases

Background: The seed and soil hypothesis was proposed over a century ago to describe why cancer cells (seeds) grow in certain organs (soil). Since then, the genetic properties that define the cancer cells have been heavily investigated; however, genomic mediators within the organ microenvironment that mediate successful metastatic growth are less understood. These studies sought to identify cancer- and organ-specific genomic programs that mediate metastasis. Methods: In these studies, a set of 14 human breast cancer patient-derived xenograft (PDX) metastasis models was developed and then tested for metastatic tropism with two approaches: spontaneous metastases from mammary tumors and intravenous injection of PDX cells. The transcriptomes of the cancer cells when growing as tumors or metastases were separated from the transcriptomes of the microenvironment via species-specific separation of the genomes. Drug treatment of PDX spheroids was performed to determine if genes activated in metastases may identify targetable mediators of viability. Results: The experimental approaches that generated metastases in PDX models were identified. RNA sequencing of 134 tumors, metastases, and normal non-metastatic organs identified cancer- and organ-specific genomic properties that mediated metastasis. A common genomic response of the liver microenvironment was found to occur in reaction to the invading PDX cells. Genes within the cancer cells were found to be either transiently regulated by the microenvironment or permanently altered due to clonal selection of metastatic sublines. Gene Set Enrichment Analyses identified more than 400 gene signatures that were commonly activated in metastases across basal-like PDXs. A Src signaling signature was found to be extensively upregulated in metastases, and Src inhibitors were found to be cytotoxic to PDX spheroids. Conclusions: These studies identified that during the growth of breast cancer metastases, there were genomic changes that occurred within both the cancer cells and the organ microenvironment. We hypothesize that pathways upregulated in metastases are mediators of viability and that simultaneously targeting changes within different cancer cell pathways and/or different tissue compartments may be needed for inhibition of disease progression

Can forest management based on natural disturbances maintain ecological resilience?

Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance

A multiwavelength study of the supernova remnant G296.8-0.3

We report XMM-Newton observations of the Galactic supernova remnant G296.8-0.3, together with complementary radio and infrared data. The spatial and spectral properties of the X-ray emission, detected towards G296.8-0.3, was investigated in order to explore the possible evolutionary scenarios and the physical connexion with its unusual morphology detected at radio frequencies. G296.8-0.3 displays diffuse X-ray emission correlated with the peculiar radio morphology detected in the interior of the remnant and with the shell-like radio structure observed to the northwest side of the object. The X-ray emission peaks in the soft/medium energy range (0.5-3.0 keV). The X-ray spectral analysis confirms that the column density is high (NH \sim 0.64 x 10^{22} cm^{-2}) which supports a distant location (d>9 kpc) for the SNR. Its X-ray spectrum can be well represented by a thermal (PSHOCK) model, with kT \sim 0.86 keV, an ionization timescale of 6.1 x 10^{10} cm^{-3} s, and low abundance (0.12 Z_sun). The 24 microns observations show shell-like emission correlated with part of the northwest and southeast boundaries of the SNR. In addition a point-like X-ray source is also detected close to the geometrical center of the radio SNR. The object presents some characteristics of the so-called compact central objects (CCO). Its X-ray spectrum is consistent with those found at other CCOs and the value of NH is consistent with that of G296.8-0.3, which suggests a physical connexion with the SNR.Comment: Accepted for publication in Astrophysics & Space Scienc

Scaling anomaly in cosmic string background

We show that the classical scale symmetry of a particle moving in cosmic string background is broken upon inequivalent quantization of the classical system, leading to anomaly. The consequence of this anomaly is the formation of single bound state in the coupling interval \gamma\in(-1,1). The inequivalent quantization is characterized by a 1-parameter family of self-adjoint extension parameter \omega. It has been conjectured that the formation of loosely bound state in cosmic string background may lead to the so called anomalous scattering cross section for the particles, which is usually seen in molecular physics.Comment: 4 pages,1 figur

Interacting New Agegraphic Dark Energy in a Cyclic Universe

The main goal of this work is investigation of NADE in the cyclic universe scenario. Since, cyclic universe is explained by a phantom phase ($\omega<-1$), it is shown when there is no interaction between matter and dark energy, ADE and NADE do not produce a phantom phase, then can not describe cyclic universe. Therefore, we study interacting models of ADE and NADE in the modified Friedmann equation. We find out that, in the high energy regime, which it is a necessary part of cyclic universe evolution, only NADE can describe this phantom phase era for cyclic universe. Considering deceleration parameter tells us that the universe has a deceleration phase after an acceleration phase, and NADE is able to produce a cyclic universe. Also it is found valuable to study generalized second law of thermodynamics. Since the loop quantum correction is taken account in high energy regime, it may not be suitable to use standard treatment of thermodynamics, so we turn our attention to the result of \citep{29}, which the authors have studied thermodynamics in loop quantum gravity, and we show that which condition can satisfy generalized second law of thermodynamics.Comment: 8 pages, 3 figure

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported