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Supplemental Fig 7 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Table 2 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Fig 5 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplementary Figure Legends 1-6, Table 1 Legend from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Fig 3 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Data Supplement from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Fig 2 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Fibroblast growth factor (FGF) cooperates with the Wnt/β-catenin pathway to promote mammary tumorigenesis. To investigate the mechanisms involved in FGF/Wnt cooperation, we genetically engineered a model of inducible FGF receptor (iFGFR) signaling in the context of the well-established mouse mammary tumor virus–Wnt-1 transgenic mouse. In the bigenic mice, iFGFR1 activation dramatically enhanced mammary tumorigenesis. Expression microarray analysis did not show transcriptional enhancement of Wnt/β-catenin target genes but instead showed a translational gene signature that also correlated with elevated FGFR1 and FGFR2 in human breast cancer data sets. Additionally, iFGFR1 activation enhanced recruitment of RNA to polysomes, resulting in a marked increase in protein expression of several different Wnt/β-catenin target genes. FGF pathway activation stimulated extracellular signal-regulated kinase and the phosphorylation of key translation regulators both in vivo in the mouse model and in vitro in a human breast cancer cell line. Our results suggest that cooperation of the FGF and Wnt pathways in mammary tumorigenesis is based on the activation of protein translational pathways that result in, but are not limited to, increased expression of Wnt/β-catenin target genes (at the level of protein translation). Further, they reveal protein translation initiation factors as potential therapeutic targets for human breast cancers with alterations in FGF signaling. Cancer Res; 70(12); 4868–79. ©2010 AACR.

Supplemental Fig 8 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Fig 4 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Table 3 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Table 1 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

Supplemental Fig 6 from Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer

We describe the first public data release of the Dark Energy Survey, DES DR1, consisting of reduced single epoch images, coadded images, coadded source catalogs, and associated products and services assembled over the first three years of DES science operations. DES DR1 is based on optical/near-infrared imaging from 345 distinct nights (August 2013 to February 2016) by the Dark Energy Camera mounted on the 4-m Blanco telescope at Cerro Tololo Inter-American Observatory in Chile. We release data from the DES wide-area survey covering ~5,000 sq. deg. of the southern Galactic cap in five broad photometric bands, grizY. DES DR1 has a median delivered point-spread function of g = 1.12, r = 0.96, i = 0.88, z = 0.84, and Y = 0.90 arcsec FWHM, a photometric precision of < 1% in all bands, and an astrometric precision of 151 mas. The median coadded catalog depth for a 1.95" diameter aperture at S/N = 10 is g = 24.33, r = 24.08, i = 23.44, z = 22.69, and Y = 21.44 mag. DES DR1 includes nearly 400M distinct astronomical objects detected in ~10,000 coadd tiles of size 0.534 sq. deg. produced from ~39,000 individual exposures. Benchmark galaxy and stellar samples contain ~310M and ~ 80M objects, respectively, following a basic object quality selection. These data are accessible through a range of interfaces, including query web clients, image cutout servers, jupyter notebooks, and an interactive coadd image visualization tool. DES DR1 constitutes the largest photometric data set to date at the achieved depth and photometric precision., 30 pages, 20 Figures. Release page found at this url https://des.ncsa.illinois.edu/releases/dr1

The Dark Energy Survey (DES) is a five-year optical imaging campaign with the goal of understanding the origin of cosmic acceleration. DES performs a similar to 5000 deg(2) survey of the southern sky in five optical bands (g, r, i, z, Y) to a depth of similar to 24th magnitude. Contemporaneously, DES performs a deep, time-domain survey in four optical bands (g, r, i, z) over similar to 27 deg(2). DES exposures are processed nightly with an evolving data reduction pipeline and evaluated for image quality to determine if they need to be retaken. Difference imaging and transient source detection are also performed in the time domain component nightly. On a bi-annual basis, DES exposures are reprocessed with a refined pipeline and coadded to maximize imaging depth. Here we describe the DES image processing pipeline in support of DES science, as a reference for users of archival DES data, and as a guide for future astronomical surveys.

We describe the creation, content, and validation of the Dark Energy Survey (DES) internal year-one cosmology data set, Y1A1 GOLD, in support of upcoming cosmological analyses. The Y1A1 GOLD data set is assembled from multiple epochs of DES imaging and consists of calibrated photometric zero-points, object catalogs, and ancillary data products—e.g., maps of survey depth and observing conditions, star–galaxy classification, and photometric redshift estimates—that are necessary for accurate cosmological analyses. The Y1A1 GOLD wide-area object catalog consists of $\sim 137$ million objects detected in co-added images covering $\sim 1800\,{\deg }^{2}$ in the DES grizY filters. The 10σ limiting magnitude for galaxies is $g=23.4$, $r=23.2$, $i=22.5$, $z=21.8$, and $Y=20.1$. Photometric calibration of Y1A1 GOLD was performed by combining nightly zero-point solutions with stellar locus regression, and the absolute calibration accuracy is better than 2% over the survey area. DES Y1A1 GOLD is the largest photometric data set at the achieved depth to date, enabling precise measurements of cosmic acceleration at z lesssim 1., Multiple funders including STFC listed on paper.

We aggregate and summarize published equation forms for predicting diameter at breast height (d.b.h.) from stump diameters, which have rarely been compared within and between regions. Equations differ by the number and type of predictors and forms of conditioning such that predictions match expectations as stump height approaches breast height. We select four equation forms published for species common to North American cool-temperate tolerant hardwood forests and test them, using published and localized coefficients with a large independent dataset. We compare the predictive strengths of different forms using regression-based equivalence testing and the financial ramifications of selecting one form over another. Predictions of d.b.h., volume and value are made for four harvested stands using each equation with published and localized coefficients. We find that most equations that predict d.b.h. from stump diameter do so quite accurately. However, equations that include stump height as a predictor are superior. There are significant financial differences between valuation of predictions of removals made with different equation forms and predictions made with published and localized coefficients. Further gains in predicting breast height from stump dimensions may come through application of a neiloid form and a whole-tree taper equation.

This paper summarizes the output of an imputation model that simultaneously estimates multiple operational-scale forest inventory attributes in the Laurentian mixed forest type of the United States. The model was constrained by national forest inventory privacy protocols and temporal uncertainties in feature and reference data. Estimates were most accurate at the county level and more variable across smaller spatial extents. Model development and validation highlighted that performance and reliability were influenced by our approach of using publicly available remote sensing predictors and ground reference data in model building. Comprehensive validation included diagnostics of the chosen model and leveraged multiscale independent data for analysis of lack-of-fit spatially and by individual feature variables. Relatively poor performance in some forest types pointed to an impact of temporal mismatch in the estimation of forest stocking in typically even-aged stands dominated by fast-growing speci...

Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment.

Fibroblast growth factor (FGF) cooperates with the Wnt/β-catenin pathway to promote mammary tumorigenesis. To investigate the mechanisms involved in FGF/Wnt cooperation, we genetically engineered a model of inducible FGF receptor (iFGFR) signaling in the context of the well-established mouse mammary tumor virus–Wnt-1 transgenic mouse. In the bigenic mice, iFGFR1 activation dramatically enhanced mammary tumorigenesis. Expression microarray analysis did not show transcriptional enhancement of Wnt/β-catenin target genes but instead showed a translational gene signature that also correlated with elevated FGFR1 and FGFR2 in human breast cancer data sets. Additionally, iFGFR1 activation enhanced recruitment of RNA to polysomes, resulting in a marked increase in protein expression of several different Wnt/β-catenin target genes. FGF pathway activation stimulated extracellular signal-regulated kinase and the phosphorylation of key translation regulators both in vivo in the mouse model and in vitro in a human breast cancer cell line. Our results suggest that cooperation of the FGF and Wnt pathways in mammary tumorigenesis is based on the activation of protein translational pathways that result in, but are not limited to, increased expression of Wnt/β-catenin target genes (at the level of protein translation). Further, they reveal protein translation initiation factors as potential therapeutic targets for human breast cancers with alterations in FGF signaling. Cancer Res; 70(12); 4868–79. ©2010 AACR.

Introduction Despite advances in early detection and adjuvant targeted therapies, breast cancer is still the second most common cause of cancer mortality among women. Tumor recurrence is one of the major contributors to breast cancer mortality. However, the mechanisms underlying this process are not completely understood. In this study, we investigated the mechanisms of tumor dormancy and recurrence in a preclinical mouse model of breast cancer. Methods To elucidate the mechanisms driving tumor recurrence, we employed a transplantable Wnt1/inducible fibroblast growth factor receptor (FGFR) 1 mouse mammary tumor model and utilized an FGFR specific inhibitor, BGJ398, to study the recurrence after treatment. Histological staining was performed to analyze the residual tumor cells and tumor stroma. Reverse phase protein array was performed to compare primary and recurrent tumors to investigate the molecular mechanisms leading to tumor recurrence. Results Treatment with BGJ398 resulted in rapid tumor regression, leaving a nonpalpable mass of dormant tumor cells organized into a luminal and basal epithelial layer similar to the normal mammary gland, but surrounded by dense stroma with markedly reduced levels of myeloid-derived tumor suppressor cells (MDSCs) and decreased tumor vasculature. Following cessation of treatment the tumors recurred over a period of 1 to 4 months. The recurrent tumors displayed dense stroma with increased collagen, tenascin-C expression, and MDSC infiltration. Activation of the epidermal growth factor receptor (EGFR) pathway was observed in recurrent tumors, and inhibition of EGFR with lapatinib in combination with BGJ398 resulted in a significant delay in tumor recurrence accompanied by reduced stroma, yet there was no difference observed in initial tumor regression between the groups treated with BGJ398 alone or in combination with lapatinib. Conclusion These studies have revealed a correlation between tumor recurrence and changes of stromal microenvironment accompanied by altered EGFR signaling. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0649-1) contains supplementary material, which is available to authorized users.

Details on the general discussion session of the 2004 Hume-Rothery Symposium on "The Structure and Diffusional Growth Mechanisms of Irrational Interphase Boundaries" is presented. The symposium was held on Mar 17, 2004 at the Charlotte Convention Center in Charlotte NC.

Parent-martensite interfaces are modelled in this work as semi-coherent interfaces comprising coherent terraces reticulated by arrays of defects that accommodate coherency strains. It is demonstrated that such interfaces can migrate conservatively if one set of defects is an array of disconnections (transformation dislocations) that can glide along the terraces. The topological character of disconnections (Burgers vector and step height) that can glide in this way is elucidated. Experimental observations of martensitic interfaces in ZrO2, Ti-10 wt.% Mo and ferrous alloys are then examined in the light of this understanding. In the cases reviewed, it is found that the interface structures observed are consistent with the terrace/disconnection model proposed.

Three questions always arise when using liquefaction features for paleoseismic analysis: What was the strength of shaking? Where was the source region? And what was the magnitude? Credible answers to these questions have been provided by liquefaction studies in the eastern and central U.S. In addition, paleoliquefaction studies have been used in many areas to show a lack of strong shaking through much of Holocene time. A high level of confidence in interpretations depends on widespread availability of exposures containing sediments susceptible to liquefaction. Throughout large parts of the U.S. there are sufficient exposures to permit detection of effects of shaking from any nearby M > 7 earthquakes (say, centered within 30 to 50 km) that have struck. In many field settings the record of paleoliquefaction encompasses much of Holocene time. A high level of confidence in interpretations also requires an in-depth appreciation of the processes involved in liquefaction-induced ground failure, as well as an appreciation of the strengths and shortcomings of the geotechnical procedures for analysis. Geotechnical analysis of the strength of prehistoric shaking often requires recognition of the mechanism of liquefaction-induced ground failure at a site. Liquefaction-induced ground failure almost always involves at least one of three mechanisms: hydraulic fracturing, lateral spreading, or surface oscillations. Conditions favorable for formation of liquefaction features can depend strongly on the local field setting and involves factors such as properties and thicknesses of sediments, depth to the water table, and proximity to a stream bank; conditions that are most favorable differ for each mechanism of ground failure. The strength of shaking can also have a major role in determining which of the mechanisms is operative at a site. Three geotechnical methods are available for analysis of paleoliquefaction effects at individual sites. The Seed et al. method generally can establish only a lower bound value of acceleration. The two other methods, recently developed, permit making estimates of upper bound and actual accelerations. One, by Ishihara, is for sites of hydraulic fracturing and can be used to establish an upper bound estimate. The other, an energy-based solution by Pond, is primarily applicable at sites of lateral spreading and provides an estimate of actual acceleration values. Both the Ishihara and the Pond method have great usefulness for paleoseismic analysis. Back-calculated accelerations using the procedures above can be used to make an estimate of prehistoric magnitude. Also, in some tectonic situations the farthest extent of liquefaction from the energy source region can be used to estimate the magnitude. The confidence in interpretation of paleomagnitude is highest whenever different procedures yield the same value. Despite several notable and very successful paleoliquefaction studies in the past 15 years or so, misconceptions abound concerning what can be derived from a paleoliquefaction study. Much more can be deduced than is generally recognized. But, correct interpretation of a paleoliquefaction study requires major input from expertise ranging from geologic to geotechnical. A comprehensive study requires input from all these disciplines even while searching for liquefaction features in the field. Successful studies that have incorporated a wide range of expertise have been relatively common in the eastern and central U.S. A similar cooperative approach could probably bracket the strength of shaking from subduction earthquakes in the Pacific Northwest of the U.S.

The structure of a \[0001]/31.5o tilt boundary in ZnO has been investigated using high-resolution electron microscopy. In some regions the interface structure is best described by reference to the periodic dichromatic pattern corresponding to the misorientation \[0001]/32.5o ( Sigma = 13). These regions exhibit arrangements of periodic facets with localized interfacial dislocations (having primitive Burgers vectors) superimposed upon them. Other regions are better described by reference to the dichromatic pattern corresponding to \[0001]/30o which is periodic parallel to \[0001]only. These segments of interface are parallel to (0110) and (1120) in the adjacent crystals and their structure is incommensurate perpendicular to \[0001]. No localized defects were found in such segments. A model is proposed for the progressive structural transition of interfaces in the misorientation range between the two singular values. It is suggested that the observation presented is a composite of the two structural forms, ...

Bicrystals of ZnO with large interfacial areas and controlled misorientations have been prepared by the solid-phase intergrowth method. The structure of three [0001] tilt boundaries with misorientations of less than 1°, 17·8 ± 0·1° and 31·5 ± 0·1° have been studied by high-resolution electron microscopy. The low-angle boundary comprised well separated crystal dislocations and the atomic structure of the large-angle boundaries could be described in terms of sequences of [0001] tunnels coordinated fivefold, sixfold and sevenfold by atomic columns. The 17·8° asymmetric (8 17 9 0) boundary (Σ = 31) was planar, exhibiting a relatively long-period repeating structure and was occasionally interrupted by interfacial dislocations. The Burgers vector and step character of these defects were investigated using circuit mapping and found to be consistent with topological theory. The 31.5° interface was found to be extensively facetted into (2 7 5 0) and (1 3 4 0) symmetric tilt boundaries. Mirror symmetry in ...

Seismic hazards in the central United States are typically based on occurrences of earthquakes in the New Madrid Seismic Zone. However, paleoliquefaction evidence shows that large prehistoric earthquakes also occurred in the Wabash Valley region of Indiana and Illinois. A geotechnical study of the soil conditions at paleoliquefaction sites there is used to estimate both the magnitudes and accelerations of the prehistoric earthquakes. This study covers an area of the Wabash River drainage approximately 250 km north to south and 180 km east to west, in southern Indiana and Illinois. In situ soil strength parameters were measured at 22 sites. The measured strength parameters are used in conjunction with liquefaction susceptibility analyses to estimate moment magnitude ( M ) and peak surface accelerations of four separate paleoearthquakes. In addition, site response studies based on the Atkinson and Boore (1995) model of bedrock motions for eastern North American earthquakes are used to develop attenuation relations. This allows a comparison of the results of the geotechnical study with a seismological prediction of peak surface accelerations due to the paleoearthquakes. Using a regionally appropriate relationship between magnitude and maximum distance to liquefaction effects (Obermeier et al. , 1993) leads to preliminary magnitude estimates of M 6.8, M 6.9, M 7.2, and M 7.8 for the four paleoearthquakes. Also, a method we developed, an energy-stress approach, is used to estimate the peak surface accelerations at these magnitudes that would be required to induce the observed liquefaction effects. Next, the acceleration estimates are compared with peak surface motions predicted by a seismological attenuation model for various magnitudes in order to determine the best-fitting magnitude. For the four paleoearthquakes studied, the geotechnical and seismological estimates of surface accelerations most closely agree for M 6.9, M 7.1, M 7.3, and M 7.8. Thus, two different methods yield basically the same paleomagnitudes, and therefore provide our best estimates.

Slot-cut excavations have been widely used to maintain stable slopes during excavation adjacent to structures or at the toe of steep slopes. It is well known that the increased stability in slot-cut excavation is due to the contribution of out-of-plane resistance or the three-dimensional (3D) effect on slope stability. The evaluation of slot-cut stability in practice, however, is often based on a highly simplified single-block wedge analysis valid only for simple slope geometry and homogeneous soil conditions. This paper presents a more rigorous approach for slot-cut stability analysis that is applicable for slopes even with complicated geometry, stratigraphy, and surcharge loading conditions. The approach considers the 3D effect by incorporating side-panel shear resistance in the force limit-equilibrium equations. A formulation is derived for a multiple-slice failure wedge, which can be conveniently implemented using a spreadsheet, combined with a two-dimensional (2D) limit-equilibrium slope stability analysis. The input for the critical 3D multiple-slice failure wedge is obtained from the output of the 2D stability analysis. In this approach, the slot-cut excavation sequence can be simply simulated and different combinations of cut depth and width can be compared. This approach is demonstrated by successful application of slot-cut construction for removal and repair of a landslide below an existing residence. This can be readily applied to other applications in which the contribution of 3D effects is considered critical in demonstrating adequate stability in temporary excavations.

Fibroblast growth factor (FGF) signaling plays an important role in embryonic stem cells and adult tissue homeostasis, but the function of FGFs in mammary gland stem cells is less well defined. Both FGFR1 and FGFR2 are expressed in basal and luminal mammary epithelial cells (MECs), suggesting that together they might play a role in mammary gland development and stem cell dynamics. Previous studies have demonstrated that the deletion of FGFR2 resulted only in transient developmental defects in branching morphogenesis. Using a conditional deletion strategy, we investigated the consequences of FGFR1 deletion alone and then the simultaneous deletion of both FGFR1 and FGFR2 in the mammary epithelium. FGFR1 deletion using a keratin 14 promoter-driven Cre-recombinase resulted in an early, yet transient delay in development. However, no reduction in functional outgrowth potential was observed following limiting dilution transplantation analysis. In contrast, a significant reduction in outgrowth potential was observed upon the deletion of both FGFR1 and FGFR2 in MECs using adenovirus-Cre. Additionally, using a fluorescent reporter mouse model to monitor Cre-mediated recombination, we observed a competitive disadvantage following transplantation of both FGFR1/R2-null MECs, most prominently in the basal epithelial cells. This correlated with the complete loss of the mammary stem cell repopulating population in the FGFR1/R2-attenuated epithelium. FGFR1/R2-null MECs were partially rescued in chimeric outgrowths containing wild-type MECs, suggesting the potential importance of paracrine mechanisms involved in the maintenance of the basal epithelial stem cells. These studies document the requirement for functional FGFR signaling in mammary stem cells during development.

Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. While MDSC regulation is widely variable even within patients harboring the same type of malignancy, the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumor genomics and syngeneic mammary tumor models, we demonstrate that mTOR signaling in cancer cells dictates a mammary tumor’s ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (e.g., FGFR) impairs tumor progression, which is partially rescued by restoring MDSCs or G-CSF. Tumor-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumor cells, forming a feed-forward loop. Analyses of primary breast cancers and patient-derived xenografts (PDXs) corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signaling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend upon a distinct immune microenvironment.

A distributed time-slot assignment protocol is developed for a mobile multi-hop broadcast packet radio network, using time division multiple access channel access and virtual circuit switching. The protocol eliminates the single point failure mode of centralized network management and the delays of centralized processing. It is applicable to the user-to-user communications functions of such systems as the U. S. Army's enhanced position location and reporting system (EPLRS). The important functions of the distributed protocol, including time-slot assignment, virtual circuit set-up, and network synthesis, are identified, and implementing algorithms are presented and verified. The performance analysis of the protocol is divided into two parts. In this paper, Part 1 of the performance analysis, the capacity of a network using this protocol is studied and a tool is developed to design the network capacity by trading off among the network area, the transmission range, and the number of packet radio units. Since these results are not in closed form, numerical results provide insight into these parameters. In Part 2 the network set-up time and network data rate are analysed and a hierarchical architecture for the distributed protocol is proposed and analysed.

Wnt signaling is crucial for a variety of biological processes, including body axis formation, planar polarity, stem cell maintenance and cellular differentiation. Therefore, targeted manipulation of Wnt signaling in vivo would be extremely useful. By applying chemical inducer of dimerization (CID) technology, we were able to modify the Wnt co-receptor, low-density lipoprotein (LDL)-receptor-related protein 5 (LRP5), to generate the synthetic ligand inducible Wnt switch, iLRP5. We show that iLRP5 oligomerization results in its localization to disheveled-containing punctate structures and sequestration of scaffold protein Axin, leading to robust β-catenin-mediated signaling. Moreover, we identify a novel LRP5 cytoplasmic domain critical for its intracellular localization and casein kinase 1-dependent β-catenin signaling. Finally, by utilizing iLRP5 as a Wnt signaling switch, we generated the Ubiquitous Activator of β-catenin (Ubi-Cat) transgenic mouse line. The Ubi-Cat line allows for nearly ubiquitous expression of iLRP5 under control of the H-2K(b) promoter. Activation of iLRP5 in isolated prostate basal epithelial stem cells resulted in expansion of p63(+) cells and development of hyperplasia in reconstituted murine prostate grafts. Independently, iLRP5 induction in adult prostate stroma enhanced prostate tissue regeneration. Moreover, induction of iLRP5 in male Ubi-Cat mice resulted in prostate tumor progression over several months from prostate hyperplasia to adenocarcinoma. We also investigated iLRP5 activation in Ubi-Cat-derived mammary cells, observing that prolonged activation results in mammary tumor formation. Thus, in two distinct experimental mouse models, activation of iLRP5 results in disruption of tissue homeostasis, demonstrating the utility of iLRP5 as a novel research tool for determining the outcome of Wnt activation in a precise spatially and temporally determined fashion.

Can an information prescription protocol be successfully integrated into a family medicine practice seeking to enhance patient education and self-management?Milton Family Practice, an outpatient clinic and resident teaching site of the University of Vermont and Fletcher Allen Health Care, is located in a semirural area fifteen miles from main campus.The objectives were to increase physicians' knowledge and use of information prescriptions, sustain integration of information prescription use, and increase physicians' ability to provide patient education information.Methods used were promotion of the National Library of Medicine's Information Rx, physician instruction, installation of patient and provider workstations, and a collaborative approach to practice integration.A post-intervention survey showed increased physician knowledge and use of the Information Rx protocol. Support procedures were integrated at the practice.Sustainable integration of Information Rx in a primary care clinic requires not only promotion and education, but also attention to clinic organization and procedures.

We have discovered hundreds of planar, nearly vertical sand- and gravel-filled dikes that we interpret to have been caused by earthquake-induced liquefaction in the Wabash Valley of Indiana- Illinois. These dikes range in width from a few cm to as much as 2.5 m. The largest dikes are centered about the general area of Vincennes, Indiana; they decrease in size and abundance to the north and south of this area. Preliminary studies indicate the high possibility that many, if not all, of the dikes were formed by a single large earthquake that took place in the Vincennes area sometime between 2,500 and 7,500 years ago. The severity of ground shaking required to have formed the dikes far exceeds the strongest level of shaking of any earthquake in the central United States since the 1811–12 New Madrid earthquakes.

Medical news often receives intense, but distorted, media coverage, which can lead to high levels of insecurity in both patients and doctors.To elicit general practitioners' self reported behaviour regarding hormone therapy (HT) advice and prescribing, before, immediately after, and 2 years following the release of the first results of the combined oestrogen and progesterone arm of the Women's Health Initiative (WHI) study; to elicit GPs' understanding of statistical risk terminology; and to explore their personal preferences relative to the trade offs between quality and length of life in medical treatment.In October 2004, a questionnaire was sent to all 169 GPs working on the central coast of New South Wales.The response rate was 67.5%. Before the release of the WHI study, 43.8% of GPs recommended HT; 5.9% did so immediately after, and 1.8% 2 years later. When expressed as number needed to treat (NNT), 20.8% of GPs stated that they were unable to interpret the absolute risk of HT use. Half of the 84 GPs who stated that they understood the concept of NNT were not going to reconsider the advice to give HT. General practitioners with a personal preference toward length of life over quality of life proved to be significantly more likely to advise against HT use (p=0.008 in a group comparison).The sensationalising of the disease specific mortality differences in HT users had a dramatic and lasting effect on GPs' attitudes to, and prescribing of, HT. General practitioners acknowledged their poor understanding of basic statistical risk terminology. Providing absolute risk terms did not alter clinical decision making in 50% of GPs, clinical decision making may well be more powerfully influenced by a doctor's personal preferences relative to the trade off between quality and quantity of life.

Crystalline materials can act as hosts to specific types of interruption of their ordered arrangements. The topological nature of such admissible discontinuities in the bulk, or on the external surface of crystals, or at interfaces in bicrystals can be established by means of symmetry arguments. Theory indicates that dislocation, disclination and dispiration lines can arise in the bulk of crystals, and also domain boundaries can occur in non-holosymmetric crystals. On surfaces, facet junctions, steps, and demisteps can arise, and also surface dislocations and domain lines if surface relaxation occurs. At interfaces, the range of discontinuities that is permissible encompasses all the types of linear feature than can arise at external surfaces and in the bulk. The object of the present paper is to illustrate distinctive types of discontinuities in hexagonal materials, particularly h.c.p. metals and wurtzite-structure crystals.