Remote sensing of sediment characteristics by optimized echo-envelope matching

A sediment geoacoustic parameter estimation technique is described which compares bottom returns, measured by a calibrated monostatic sonar oriented within 15° of vertical and having a 10°–21° beamwidth, with an echo envelope model based on high-frequency (10–100 kHz) incoherent backscattertheory and sediment properties such as: mean grain size, strength, and exponent of the power law characterizing the interface roughness energy density spectrum, and volume scattering coefficient. An average echo envelope matching procedure iterates on the reflection coefficient to match the peak echo amplitude and separate coarse from fine-grain sediments, followed by a global optimization using a combination of simulated annealing and downhill simplex searches over mean grain size, interface roughness spectral strength, and sediment volume scattering coefficient. Error analyses using Monte Carlo simulations validate this optimization procedure. Moderate frequencies (33 kHz) and orientations normal with the interface are best suited for this application. Distinction between sands and fine-grain sediments is demonstrated based on acoustic estimation of mean grain size alone. The creation of feature vectors from estimates of mean grain size and interface roughness spectral strength shows promise for intraclass separation of silt and clay. The correlation between estimated parameters is consistent with what is observed in situ

Time dependent seafloor acoustic backscatter (10-100kHz)

A time-dependent model of the acoustic intensity backscattered by the seafloor is described and compared with data from a calibrated, vertically oriented, echo-sounder operating at 33 and 93 kHz. The model incorporates the characteristics of the echo-sounder and transmitted pulse, and the water column spreading and absorption losses. Scattering from the water–sediment interface is predicted using Helmholtz–Kirchhoff theory, parametrized by the mean grain size, the coherent reflection coefficient, and the strength and exponent of a power-law roughness spectrum. The composite roughness approach of Jackson et al. [J. Acoust. Soc. Am. 79, 1410–1422 (1986)], modified for the finite duration of the transmitted signal, is used to predict backscatter from subbottom inhomogeneities. It depends on the sediment’s volume scattering and attenuation coefficients, as well as the interface characteristics governing sound transmission into the sediment. Estimation of model parameters (mean grain size, roughness spectrum strength and exponent, volume scattering coefficient) reveals ambiguous ranges for the two spectral components. Analyses of model outputs and of physical measurements reported in the literature yield practical constraints on roughness spectrum parameter settings appropriate for echo-envelope-based sediment classification procedures

Near bottom sediment characterization offshore SW San Clemente Island

Normal incidence, 23.5 kHz seafloor acoustic backscatter data and bottom video were measured with the Deep Tow instrument package of the Scripps Institution of Oceanography in 100 meter water depth south of San Clemente Island, CA. The collected data were processed using an echo envelopesediment characterization method, to derive geoacoustic parameters such as particle mean grain size and the strength of the power law characterizing the roughness energy density spectrum of thesediment-water interface. Two regions, sand and silt, were selected based on available ground truth, perceived along-track sediment homogeneity, data quality and tow fish stability. Distinction between sand and fine grain sediments can be accomplished by creation of feature vectors comprised of mean grain size (MΦ) and interface roughness spectral strength (w2). Estimates for mean grain size and roughness spectral strength (MΦ, w2) were (1.5, 0.0095) for sand, and (6.7, 0.0033) for silt, where MΦ is expressed in PHI units, and w2 has units cm4. These results are consistent with local ground truth measurements and illustrate the potential of this sediment characterization method in survey mode

Key stages in mammary gland development: The cues that regulate ductal branching morphogenesis

Part of how the mammary gland fulfills its function of producing and delivering adequate amounts of milk is by forming an extensive tree-like network of branched ducts from a rudimentary epithelial bud. This process, termed branching morphogenesis, begins in fetal development, pauses after birth, resumes in response to estrogens at puberty, and is refined in response to cyclic ovarian stimulation once the margins of the mammary fat pad are met. Thus it is driven by systemic hormonal stimuli that elicit local paracrine interactions between the developing epithelial ducts and their adjacent embryonic mesenchyme or postnatal stroma. This local cellular cross-talk, in turn, orchestrates the tissue remodeling that ultimately produces a mature ductal tree. Although the precise mechanisms are still unclear, our understanding of branching in the mammary gland and elsewhere is rapidly improving. Moreover, many of these mechanisms are hijacked, bypassed, or corrupted during the development and progression of cancer. Thus a clearer understanding of the underlying endocrine and paracrine pathways that regulate mammary branching may shed light on how they contribute to cancer and how their ill effects might be overcome or entirely avoided

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Amphiregulin Mediates Estrogen, Progesterone, and EGFR Signaling in the Normal Rat Mammary Gland and in Hormone-Dependent Rat Mammary Cancers

Both estrogen (E) and progesterone (P) are implicated in the etiology of human breast cancer. Defining their mechanisms of action, particularly in vivo, is relevant to the prevention and therapy of breast cancer. We investigated the molecular and cellular mechanisms of E and/or P-induced in vivo proliferation, in the normal rat mammary gland and in hormone-dependent rat mammary cancers which share many characteristics with the normal human breast and hormone-dependent breast cancers. We show that E+P treatment induced significantly greater proliferation in both the normal gland and mammary cancers compared to E alone. In both the normal gland and tumors, E+P-induced proliferation was mediated through the increased production of amphiregulin (Areg), an epidermal growth factor receptor (EGFR) ligand, and the activation of intracellular signaling pathways (Erk, Akt, JNK) downstream of EGFR that regulate proliferation. In vitro experiments using rat primary mammary organoids or T47D breast cancer cells confirmed that Areg and the synthetic progestin, R5020, synergize to promote cell proliferation through EGFR signaling. Iressa, an EGFR inhibitor, effectively blocked this proliferation. These results indicate that mediators of cross talk between E, P, and EGFR pathways may be considered as relevant molecular targets for the therapy of hormone-dependent breast cancers, especially in premenopausal women

Myoepithelial cells: good fences make good neighbors

The mammary gland consists of an extensively branched ductal network contained within a distinctive basement membrane and encompassed by a stromal compartment. During lactation, production of milk depends on the action of the two epithelial cell types that make up the ductal network: luminal cells, which secrete the milk components into the ductal lumen; and myoepithelial cells, which contract to aid in the ejection of milk. There is increasing evidence that the myoepithelial cells also play a key role in the organizational development of the mammary gland, and that the loss and/or change of myoepithelial cell function is a key step in the development of breast cancer. In this review we briefly address the characteristics of breast myoepithelial cells from human breast and mouse mammary gland, how they function in normal mammary gland development, and their recently appreciated role in tumor suppression

Stromal Fibroblasts in Digestive Cancer

The normal gastrointestinal stroma consists of extra-cellular matrix and a community of stromal cells including fibroblasts, myofibroblasts, smooth muscle cells, pericytes, endothelium and inflammatory cells. α-smooth muscle actin (α-SMA) positive stromal fibroblasts, often referred to as myofibroblasts or activated fibroblasts, are critical in the development of digestive cancer and help to create an environment that is permissive of tumor growth, angiogenesis and invasion. This review focusses on the contribution of activated fibroblasts in carcinogenesis and where possible directly applies this to, and draws on examples from, gastrointestinal cancer. In particular, the review expands on the definition, types and origins of activated fibroblasts. It examines the molecular biology of stromal fibroblasts and their contribution to the peritumoral microenvironment and concludes by exploring some of the potential clinical applications of this exciting branch of cancer research. Understanding the origin and biology of activated fibroblasts will help in the development of an integrated epithelial-stromal sequence to cancer that will ultimately inform cancer pathogenesis, natural history and future therapeutics

Inflammation and breast cancer. Metalloproteinases as common effectors of inflammation and extracellular matrix breakdown in breast cancer

Two rapidly evolving fields are converging to impact breast cancer: one has identified novel substrates of metalloproteinases that alter immune cell function, and the other has revealed a role for inflammation in human cancers. Evidence now shows that the mechanisms underlying these two fields interact in the context of breast cancer, providing new opportunities to understand this disease and uncover novel therapeutic strategies. The metalloproteinase class of enzymes is well studied in mammary gland development and physiology, but mostly in the context of extracellular matrix modification. Aberrant metalloproteinase expression has also been implicated in breast cancer progression, where these genes act as tumor modifiers. Here, we review how the metalloproteinase axis impacts mammary physiology and tumorigenesis and is associated with inflammatory cell influx in human breast cancer, and evaluate its potential as a regulator of inflammation in the mammary gland