Mathematical Modeling Links Pregnancy-Associated Changes and Breast Cancer Risk

Recent debate has concentrated on the contribution of bad luck to cancer development. The tight correlation between the number of tissue-specific stem cell divisions and cancer risk of the same tissue suggests that bad luck has an important role to play in tumor development, but the full extent of this contribution remains an open question. Improved understanding of the interplay between extrinsic and intrinsic factors at the molecular level is one promising route to identifying the limits on extrinsic control of tumor initiation, which is highly relevant to cancer prevention. Here, we use a simple mathematical model to show that recent data on the variation in numbers of breast epithelial cells with progenitor features due to pregnancy are sufficient to explain the known protective effect of full-term pregnancy in early adulthood for estrogen receptor-positive (ER+) breast cancer later in life. Our work provides a mechanism for this previously ill-understood effect and illuminates the complex influence of extrinsic factors at the molecular level in breast cancer. These findings represent an important contribution to the ongoing research into the role of bad luck in human tumorigenesis

NMF-Based Spectral Analysis for Acoustic Event Classification Tasks

Proceedings of: 6th International Conference The Non-Linear Speech Processing (NOLISP 2013). Mons, Belgium, June 19-21, 2013.In this paper, we propose a new front-end for Acoustic Event Classification tasks (AEC). First, we study the spectral contents of different acoustic events by applying Non-Negative Matrix Factorization (NMF) on their spectral magnitude and compare them with the structure of speech spectra. Second, from the findings of this study, we propose a new parameterization for AEC, which is an extension of the conventional Mel Frequency Cepstrum Coefficients (MFCC) and is based on the high pass filtering of acoustic event spectra. Also, the influence of different frequency scales on the classification rate of the whole system is studied. The evaluation of the proposed features for AEC shows that relative error reductions about 12% at segment level and about 11% at target event level with respect to the conventional MFCC are achieved.This work has been partially supported by the Spanish Government grants TSI-020110-2009-103, IPT-120000-2010-24 and TEC2011-26807. Financial support from the Fundaci´on Carolina and Universidad Católica San Pablo, Arequipa.Publicad

Analysis of dissolved benzene plumes and methyl tertiary butyl ether (MTBE) plumes in ground water at leaking underground fuel tank (LUFT) sites

The 1990 Clean Air Act Amendments mandate the addition of oxygenates to gasoline products to abate air pollution. Currently, many areas of the country utilize oxygenated or reformulated fuel containing 15- percent and I I-percent MTBE by volume, respectively. This increased use of MTBE in gasoline products has resulted in accidental point source releases of MTBE containing gasoline products to ground water. Recent studies have shown MTBE to be frequently detected in samples of shallow ground water from urban areas throughout the United States (Squillace et al., 1995). Knowledge of the subsurface fate and transport of MTBE in ground water at leaking underground fuel tank (LUFT) sites and the spatial extent of MTBE plumes is needed to address these releases. The goal of this research is to utilize data from a large number of LUFT sites to gain insights into the fate, transport, and spatial extent of MTBE plumes. Specific goals include defining the spatial configuration of dissolved MTBE plumes, evaluating plume stability or degradation over time, evaluating the impact of point source releases of MTBE to ground water, and attempting to identify the controlling factors influencing the magnitude and extent of the MTBE plumes. We are examining the relationships between dissolved TPH, BTEX, and MTBE plumes at LUFT sites using parallel approaches of best professional judgment and a computer-aided plume model fitting procedure to determine plume parameters. Here we present our initial results comparing dissolved benzene and MTBE plumes lengths, the statistical significance of these results, and configuration of benzene and MTBE plumes at individual LUFT sites

JAK-STAT signaling in inflammatory breast cancer enables chemotherapy-resistant cell states

Inflammatory breast cancer (IBC) is a difficult-to-treat disease with poor clinical outcomes due to high risk of metastasis and resistance to treatment. In breast cancer, CD44+CD24- cells possess stem cell-like features and contribute to disease progression, and we previously described a CD44+CD24-pSTAT3+ breast cancer cell subpopulation that is dependent on JAK2/STAT3 signaling. Here we report that CD44+CD24- cells are the most frequent cell-type in IBC and are commonly pSTAT3+. Combination of JAK2/STAT3 inhibition with paclitaxel decreased IBC xenograft growth more than either agent alone. IBC cell lines resistant to paclitaxel and doxorubicin were developed and characterized to mimic therapeutic resistance in patients. Multi-omic profiling of parental and resistant cells revealed enrichment of genes associated with lineage identity and inflammation in chemotherapy resistant derivatives. Integrated pSTAT3 ChIP-seq and RNA-seq analyses showed pSTAT3 regulates genes related to inflammation and epithelial to mesenchymal transition (EMT) in resistant cells, as well as PDE4A, a cAMP-specific phosphodiesterase. Metabolomic characterization identified elevated cAMP signaling and CREB as a candidate therapeutic target in IBC. Investigation of cellular dynamics and heterogeneity at the single cell level during chemotherapy and acquired resistance by CyTOF and single cell RNA-seq identified mechanisms of resistance including a shift from luminal to basal/mesenchymal cell states through selection for rare pre-existing subpopulations or an acquired change. Lastly, combination treatment with paclitaxel and JAK2/STAT3 inhibition prevented the emergence of the mesenchymal chemo-resistant subpopulation. These results provide mechanistic rational for combination of chemotherapy with inhibition of JAK2/STAT3 signaling as a more effective therapeutic strategy in IBC

Influence of GaAs Substrate Orientation on InAs Quantum Dots: Surface Morphology, Critical Thickness, and Optical Properties

InAs/GaAs heterostructures have been simultaneously grown by molecular beam epitaxy on GaAs (100), GaAs (100) with a 2° misorientation angle towards [01−1], and GaAs (n11)B (n = 9, 7, 5) substrates. While the substrate misorientation angle increased from 0° to 15.8°, a clear evolution from quantum dots to quantum well was evident by the surface morphology, the photoluminescence, and the time-resolved photoluminescence, respectively. This evolution revealed an increased critical thickness and a delayed formation of InAs quantum dots as the surface orientation departed from GaAs (100), which was explained by the thermal-equilibrium model due to the less efficient of strain relaxation on misoriented substrate surfaces

Pharmacological prevention of type 2 diabetes.

audience: researcher, professional, studen

A survey of tagging techniques for music, speech and environmental sound

Sound tagging has been studied for years. Among all sound types, music, speech, and environmental sound are three hottest research areas. This survey aims to provide an overview about the state-of-the-art development in these areas.We discuss about the meaning of tagging in different sound areas at the beginning of the journey. Some examples of sound tagging applications are introduced in order to illustrate the significance of this research. Typical tagging techniques include manual, automatic, and semi-automatic approaches.After reviewing work in music, speech and environmental sound tagging, we compare them and state the research progress to date. Research gaps are identified for each research area and the common features and discriminations between three areas are discovered as well. Published datasets, tools used by researchers, and evaluation measures frequently applied in the analysis are listed. In the end, we summarise the worldwide distribution of countries dedicated to sound tagging research for years

The effects of mutational processes and selection on driver mutations across cancer types

Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data from 11,336 cancers of various types to infer the independent effects of mutation and selection on the set of driver mutations in a cancer type. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes have a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates