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Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model
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- Eck, S.M., Hoopes, P.J., Petrella, B.L. et al. Breast Cancer Res Treat (2009) 116: 79. doi:10.1007/s10549-008-0085-3
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Matrix metalloproteinase-1 (MMP-1) is critical for mediating breast cancer metastasis to bone. We investigated the role of MMP-1 in breast cancer invasion of soft tissues and bone using human MDA MB-231 breast cancer cells stably transfected with shRNAs against MMP-1 and a novel murine model of bone invasion. MMP-1 produced by breast cancer cells with control shRNA facilitated invasion of tumors into soft tissue in vivo, which correlated with enhanced blood vessel formation at the invasive edge, compared to tumors with silenced MMP-1 expression. Tumors expressing MMP-1 were also associated with osteolysis in vivo, whereas tumors with inhibited MMP-1 levels were not. Additionally, tumor-secreted MMP-1 activated bone-resorbing osteoclasts in vitro. Together, these data suggest a mechanism for MMP-1 in the activation of osteoclasts in vivo. We conclude that breast cancer-derived MMP-1 mediates invasion through soft tissues and bone via mechanisms involving matrix degradation, angiogenesis, and osteoclast activation.
KeywordsBreast cancerBoneInvasionMetastasisMMPMurine model
American Type Culture Collection
Dartmouth-Hitchcock Medical Center
Human microvessel endothelial cells
Hematoxylin and eosin
Macrophage colony stimulating factor
Receptor activator of NF-κB ligand
Short hairpin RNA
Tartrate-resistant acid phosphatase
Breast cancer cells have a high propensity to metastasize to bone [1–3]; and 65–75% of breast cancer patients with advanced disease develop bone metastases . Once in the bone, breast cancer cells stimulate bone matrix turnover, causing the release of growth factors embedded within the mineralized matrix, thereby promoting tumor growth . High matrix turnover also results in osteolysis, and as the bone is destroyed, breast cancer patients suffer from painful fractures, hypercalcemia, and nerve compression . Although many studies have focused on breast cancer metastasis to bone, breast cancer also directly invades the soft tissues, ribs and sternum bones of the chest. Following mastectomy, 10–20% of patients develop local/regional recurrence (LRR), a recurrent tumor in the skin, subcutaneous tissue, muscle, or bone within the chest wall . The molecular mechanisms by which breast cancer cells invade interstitial tissues in LRR and induce osteolysis in patients with either metastatic disease or LRR remain unclear.
The matrix metalloproteinase (MMP) family consists of over 20 enzymes that degrade the extracellular matrix. Physiologic levels of MMPs are low, but expression is elevated in most cancers [8, 9]. Matrix metalloproteinase-1 (MMP-1) is an interstitial collagenase that is often upregulated in breast cancer, and in vitro studies demonstrate that this enzyme facilitates the invasive properties of breast cancer cells [10, 11].
Bone is predominantly comprised of mineralized fibrillar type-I collagen [12, 13], which in its soluble form, is degraded by the interstitial collagenases, namely, MMP-1 [14, 15]. Recently, Massague’s group identified an osteotropism gene set in which MMP-1 is one of four genes consistently overexpressed in breast cancer cells . Their data demonstrate that MMP-1 is essential for metastasis to bone and raise the question of whether breast cancer-derived MMP-1 also contributes to local invasion and to tumor-induced osteolysis once cancer cells colonize the bone.
Resorption of bone requires the dissolution of mineralized and soluble matrix components, a process that is accomplished primarily by multinucleated, bone-residing osteoclast cells, which require activation and differentiation. It is well established that osteoclasts are activated by the binding of receptor activator of nuclear factor kappa B ligand (RANKL) to its receptor, RANK, on osteoclasts . In vitro studies using general MMP inhibitors and synthetic collagen suggest that interstitial collagenases also aid in this process by cleaving collagen, thereby generating collagen fragments, which then activate osteoclasts . Following activation, an osteoclast attaches to the bone surface and seals a compartment, known as a lacuna, into which it secretes proteolytic enzymes [19–21], including tartrate-resistant acid phosphatase (TRAP), which degrades mineralized bone, and leaves soluble type-I collagen . The lysosomal protease, cathepsin K, functions in this acidic pH to partially degrade remaining collagen products [22, 23] and MMPs, which are active at neutral pH, degrade leftover collagen after the osteoclast has retreated in in vitro experiments [24, 25]. These studies provide evidence that MMPs may aid in bone resorption, but the role(s) of tumor-derived MMP-1 in the process of bone resorption has not been investigated. Interestingly, MMP-1 has been localized to osteoclasts and their lacunae , and bone-resorbing agents stimulate collagenase production in the bone . These findings imply that collagenases play a role in breast cancer-induced bone resorption in vivo by cleaving collagen, thereby producing collagen fragments that activate osteoclasts. To determine the function(s) of MMP-1 in the invasion and destruction of bone, we created a novel murine breast cancer xenograft model.
Several approaches have been used to study breast cancer/bone interactions and/or bone metastasis in vivo. Intra-tibial injections allow researchers to study interactions between tumors and cells in the bone microenvironment; this procedure, however, stimulates a bone remodeling response that can complicate interpretation of results . Arguello and colleagues described a model in which tumor cells are injected into the left cardiac ventricle . This technique requires cancer cells to extravasate and settle in a secondary location, such as bone; however, these injections are technically challenging  and yield a low tumor incidence (~30%) over 10–12 weeks . Pollard and Luckert described a rat model to investigate tumor induced osteolysis, in which prostate tumor cells that arose spontaneously in the dorsolateral lobes were transplanted to an area adjacent to bone, but the periosteum was scratched during innoculation to enhance tumor cell attachment to bone .
In our model, breast cancer cells are injected into the hind limb musculature, adjacent to, but not contacting, the femur. This model is technically simple, reproducible, and avoids a needle-induced bone remodeling response. Using this model and RNAi technology we investigated the role of breast tumor-secreted MMP-1 in the invasion of soft tissues and the bone. We demonstrate that MMP-1 mediates invasion of tumor cells through peritumoral soft tissues and enhances osteolysis in vivo. We propose that these events are facilitated by vasculature recruitment and osteoclast activation.
Materials and methods
Culturing of cells
MDA MB-231 breast cancer cells (American Type Culture Collection, ATCC, Rockville, MD) and human microvessel endothelial cells (HMVECs, Cascade Biologics, Portland, OR) were cultured as described . RAW264.7 cells (ATCC) were cultured in MEM, supplemented with 10% FBS, penicillin (100 units/ml)/streptomycin (100 μg/ml), and 2 mmol/l glutamine. For serum-free conditions, cells were rinsed with HBSS and cultured in their respective media, supplemented with 0.2% lactalbumin hydrolysate (LH).
Short hairpin RNA plasmids
Construction of short hairpin RNA (shRNA) plasmids were described . In this study, three different MMP-1 shRNA oligonucleotides (shRNA 5′, 153, or 305) were ligated into the pSUPER.retro.puro expression vector (OligoEngine, Seattle, WA). Each shRNA targeted a specific region of the MMP-1 mRNA sequence: starting at base 26 in the 5′ untranslated region of the MMP-1 mRNA, or at base 153 or 305 of the MMP-1 mRNA coding region. shRNA sequences used were: MMP-1 (5′): 5′-GGAAGCCATCACTTACCTTGC-3′; MMP-1 (153): 5′-GAGCAAGATGTGGACTTAG-3′; and MMP-1 (305): 5′-ACCAGATGCTGAAACCCTG-3′. MMP-1 shRNA (153) and shRNA (305) have been described [31, 32] and the 5′ MMP-1 shRNA was designed using Block-iT (Invitrogen, Carlsbad, CA). A non-specific mammalian sequence (MAMM-X, OligoEngine) was inserted into the pSuper-retro-puro vector as an shRNA control.
Each shRNA plasmid was transfected into MDA MB-231 breast cancer cells using Lipofectamine 2000 (Invitrogen), following the manufacturer’s instructions. Cells were selected with puromycin-supplemented (1.5 μg/ml) DMEM50/50-F12; surviving colonies were expanded  and analyzed for MMP-1 mRNA expression using quantitative real-time RT-PCR (see below). The three control shRNA clones that best mirrored parent MDA MB-231 MMP-1 mRNA levels and the three MMP-1 shRNA clones with >90% inhibition of MMP-1 (compared to the control group) were chosen for experiments. We measured MMP-2, -3, -9, -13 and -14 and 2′, 5′ oligoadenylate synthetase 1 (OAS1) mRNA levels in the parental cells and stably transfected derivatives as described . Clones were cultured individually, but were pooled immediately prior to experiments.
Quantitative real-time RT-PCR
Real-time PCR reactions were performed using 250 ng of input RNA per reaction as described previously [30, 31, 33, 34]. mRNA was quantified using standard curves generated using serial log dilutions of a cDNA plasmid containing the gene of interest and ranged from 1 to 1,000 pg. Data were averaged and normalized to the housekeeping gene, hypoxanthine-phosphoribosyl transferase (HPRT), and are presented as a percent of the MDA MB-231 cells or fold inhibition. Primer sequences were: MMP-1: 5′-AGCTAGCTCAGGATGACATTGATG-3′ (forward) and 5′-GCCGATGGGCTGGACAG-3′ (reverse) and HPRT: 5′-AGCTTGCTGGTGAAAAGGAC-3′ (forward) and 5′-CCAGATGTTTCCAAACTCAACTTGA-3′ (reverse). Primer sequences for other MMPs were provided previously .
Proliferation of clones
Proliferation rates of transfected cells were compared to parental cells by pooling an equal number of cells from each clone and plating 5 × 103 cells per well of a 12-well culture plate. At 24, 36, 48, 72, or 96 h, cells were detached with trypsin and viable cells were counted using trypan blue exclusion.
Collagen degradation assay
Control or MMP-1 shRNA transfected cells were serum-starved (24 h), harvested, and pooled. Cells (5 × 105 cells/ml) were suspended in neutralized type-I collagen (1 mg/ml) (Organogenesis, Canton, MA) , and 1 ml was added per well of a 6-well plate. After the collagen polymerized at 37°C, 1 ml of serum-free DMEM containing ~0.0003% trypsin to activate latent MMPs was added to each well. After 24 h at 37°C, the overlying media were removed and weighed. The medium released from a collagen gel was calculated by weighing the total media collected minus the original medium added (1 g). Assays stained for MMP-1 using immunohistochemistry (IHC) were terminated at 6 h, so that gels embedded with control shRNA cells were not entirely degraded. Collagen gels were removed from wells with a rubber spatula, fixed in 10% neutral buffered formaldehyde and processed for histological staining in the Pathology Department at Dartmouth Hitchcock Medical Center (DHMC). Goat MMP-1 antibody (R&D Systems, Minneapolis, MN) was diluted to 1:100.
In vivo tumorigenesis
In groups of eight, female nude mice (nu/nu Charles River, Wilmington, MA) were injected intramuscularly in the left hind limb with 1 × 106 cells containing pools of control shRNA or MMP-1 shRNA clones. The femurs in nu/nu mice are visible through the skin; therefore it was possible to deposit cells near to, but without contacting, this bone. Cells were suspended in 100 μl Growth Factor Reduced Matrigel (BD Biosciences, San Jose, CA). Mice were housed in the Animal Resource Center at Dartmouth Medical School until sacrificed on day 7, 14, 21, or 28 post-inoculation. Upon sacrifice, the tumor-bearing and contralateral limbs were harvested for histological analysis. A portion of each tumor (~0.25 g) obtained on day 28 was placed in RNAlater (Qiagen), flash-frozen in liquid nitrogen, and ground into powder using a mortar and pestle. RNeasy RLT lysis buffer (Qiagen) was added immediately, total RNA was harvested, DNAse-treated and analyzed as described under Quantitative real-time RT-PCR. The Dartmouth College Institutional Animal Care and Use Committee approved animal studies.
Following sacrifice, femurs were decalcified in Nitrical (Decal Chemical Corp., Tallman, NY), cut in a cross-section or longitudinal plane, and fixed in formaldehyde. Samples were processed and stained with hematoxylin and eosin (H&E). The number of invasive tumor protrusions, defined as a substantial portion of tumor (>200 μm in length) that jutted away from the round-shaped portion of the tumor, was counted per tumor. A pathologist quantified tumor invasion of the bone. A tumor was considered to have invaded the bone if tumor cells breached the outermost, or periosteal, layer of the bone. Invasion of bone was defined as a positive (1), or a null (0) event. Tumor vasculature was quantified by staining endothelial cells with a rabbit polyclonal CD31 antibody (AbCam, Cambridge, MA) diluted 1:100. Vessels were counted in three fields (20×)  per tumor.
Tube formation assay
To condition media, clones expressing control or MMP-1 shRNAs were pooled and plated (1 × 106 cells/100 mm dish). After 24 h, 5 ml basal medium, consisting of Medium 132 (Cascade Biologics) supplemented with 2% FBS, was added to each plate and conditioned for an additional 24 h. For the tube formation assay, 50 μl Growth Factor Reduced Matrigel® (BD Biosciences) was added per well of a 96-well plate and allowed to polymerize. Then, 7.5 × 103 HMVECs in 100 μl of (1) control shRNA cell conditioned media (CM), (2) control shRNA CM with an MMP-1 neutralizing antibody (1 μg/ml, Chemicon, MAB13402) or (3) MMP-1 shRNA CM were added per well. Tube formation was quantified by averaging the number of branch points in 3 views per well, with 9 wells per condition at 20×.
To condition media, control or MMP-1 shRNA clones were pooled and plated at 1 × 106 cells/100 mm dish. After 24 h, 5 ml MEM media, supplemented with 0.2% LH, was added to each plate for 24 h. To make non-soluble, cross-linked collagen, collagen-coated plates (BD Biosciences) were subjected to ultra-violet irradiation overnight. For the osteoclastogenesis assay, murine monocytic RAW264.7 cells were resuspended (5 × 104 cells/ml), and 1 ml was plated per 24 mm-well of collagen-coated plates. After 24 h, RAW264.7 cells were left untreated in MEM with LH, or treated with (1) RANKL (50 ng/ml, R&D Systems) and M-CSF (20 ng/ml, R&D Systems), (2) control shRNA CM on soluble collagen or fixed collagen, (3) control shRNA CM with an MMP-1 neutralizing antibody (1 μg/ml, Chemicon), or a control, anti-FLAG antibody (1 μg/ml, Sigma), (4) MMP-1 shRNA CM, or (5) activated or latent recombinant MMP-1 (rMMP-1, R&D Systems). Following 3 days at 37°C, cells were stained for TRAP, using a kit as per the manufacturer’s instructions (Sigma). To examine TRAP staining, counterstaining with hematoxylin was unnecessary. To identify multinucleated cells, the hematoxylin counterstain was used, as the manufacturer directs. Mature osteoclasts (TRAP+ and multinucleated, >2 nuclei) were counted and averaged in 9 views per triplicate group using the 40× objective.
Student’s t test was used to determine statistical significance. All samples were prepared in triplicate and experiments were conducted at least three times. Statistical power at P < 0.05 was considered significant.
shRNA stable inhibition of MMP-1
To verify shRNA specificity, we measured mRNA in our clones for MMP-2, -3, -9, -13 and -14, which are associated with tumor progression . mRNA levels of these MMPs were not influenced by the MMP-1 shRNA, compared to the parental (data not shown and ). Further, MMP-1 was more highly expressed (copies per copy housekeeping gene) than other MMPs (data not shown and ). To ensure that shRNAs did not induce an interferon response , OAS1 mRNA was quantified  and was unchanged in cells stably expressing shRNAs compared to parental cells (data not shown).
MMP-1 shRNA prevented degradation of type-I collagen in vitro
Since MMP-1 contributes to breast tumor invasion by degrading type-I collagen in vivo , we recapitulated this in vitro using a functional assay [30, 31, 33]. Gels embedded with control shRNA cells were completely destroyed (Fig. 1b). Approximately 800 μl of media was liberated from these gels; however, collagen gels remained intact when containing MMP-1 shRNA cells, P < 0.0001 (Fig. 1b). Negative values on the y-axis result from evaporation, and for this reason the original 1,000 μl is not fully recovered when the entire gel has dissolved. To monitor secreted MMP-1 protein within the collagen matrix, the assay was stopped at 6 h and stained for MMP-1 using IHC. Control shRNA cells stained positively for MMP-1, while only a few MMP-1 shRNA cells stained partially, despite the equal number of cells in each gel (Fig. 1c). Importantly, collagen surrounding control shRNA cells displayed punctate MMP-1 staining throughout (arrowhead), indicating that these cells secrete MMP-1; in contrast, MMP-1 was not present in the matrix surrounding MMP-1 shRNA cells (arrowhead) (Fig. 1c). These results demonstrate that MDA MB-231 cells with silenced MMP-1 expression have significantly reduced MMP-1 mRNA levels, protein levels, and enzymatic activity, compared to cells expressing MMP-1. These data are consistent with the traditional role of MMP-1 in matrix degradation.
Tumor invasion through soft tissue was attenuated in tumors with silenced MMP-1
Eight mice from each group (control or MMP-1 shRNA) were sacrificed 7, 14, 21, or 28 days post-injection, and the hind limbs were removed for histological examination. H&E staining of the tumor/femur region revealed that by day 7, mice injected with control shRNA cells formed tumors with invasive fronds (Fig. 2b, upper left panel) and longer protrusions (>200 μm) (Fig. 2b, lower left panel). These invasive outcroppings appeared to be growing between muscle fascicles and may be positioned in parallel with the bone; however, we observed that they had a propensity to invade toward bone, rather than in any other direction (data not shown). In contrast, most MMP-1 shRNA tumors displayed a well-defined capsular space (Fig. 2b, right panels). Seven days post-injection, the number protrusive outcroppings (>200 μm) from control shRNA tumors was significantly greater than that observed in MMP-1 shRNA tumors, P = 0.014 (Fig. 2c). Although control tumors maintained a more invasive phenotype on days 14 and 21 (data not shown), the overall number of protrusions was not significantly different from MMP-1 shRNA tumors. These data allow us to conclude that silencing MMP-1 expression in breast cancer cells makes them less invasive through soft tissues.
MMP-1 shRNA tumors displayed decreased blood vessel density early in tumorigenesis
To further examine whether tumor-secreted MMP-1 increases angiogenesis, we used a standard in vitro tube formation assay [46, 47], in which activated endothelial cells plated on Matrigel differentiate to form tube-like networks, while inactive cells do not. After 2 days, we observed that the addition of control shRNA cell conditioned medium (CM) to HMVECs stimulated the formation of more tube-like structures than HMVECs treated with MMP-1 shRNA CM or with control shRNA CM containing an MMP-1 neutralizing antibody (Fig. 3c). Quantification of branch points  revealed that HMVECs exposed to control shRNA CM in the absence or presence of a control antibody formed complex networks. On the contrary, the number of branch points formed by HMVECs exposed to control shRNA CM with an MMP-1 neutralizing antibody or MMP-1 shRNA CM was significantly reduced, P < 0.05 (Fig. 3d), confirming that MDA MB-231-secreted MMP-1 induces the activation and differentiation of endothelial cells. It has been shown that MMP-1 interacts with proteinase-activated receptor 1 on endothelial cells to promote their activation [30, 48]; thus, it is feasible that breast cancer-derived MMP-1 functions likewise.
Tumors with silenced MMP-1 levels prevented osteolysis in vivo
MDA MB-231 cell-secreted MMP-1 induced the activation and differentiation of osteoclasts in the presence of soluble type-I collagen
To examine the mechanism(s) by which MMP-1 produced by the breast cancer cells facilitated osteolysis and bone invasion in vivo, we tested whether MMP-1 recruits, activates, and/or differentiates osteoclasts in vitro. To analyze recruitment, RAW264.7 osteoclast precursor cells were plated in transwells and allowed to migrate through membranes toward media conditioned by control or MMP-1 shRNA cells. We found that MMP-1 in the control shRNA conditioned media (CM) did not stimulate migration or recruitment of osteoclast precursor cells in vitro (data not shown), and therefore conclude that breast cancer cells likely did not facilitate in vivo osteolysis by recruiting osteoclast precursors to the tumor/bone interface.
Previous in vitro studies suggested that collagenase-generated collagen fragments trigger osteoclast bone resorption [18, 51]. Hence, we hypothesized that tumor-secreted MMP-1 facilitates osteoclast activation by cleaving collagen, thereby producing collagen fragments, which then trigger osteoclast activation. To test this, we cross-linked the collagen in collagen-coated plates and found that control shRNA CM-induced osteoclast maturation was significantly diminished when osteoclast precursor cells were plated on insoluble collagen, P = 0.0002, (Fig. 5e). Together, these results indicate that osteoclast maturation induced by tumor-secreted MMP-1 requires soluble collagen.
We conclude that while breast cancer-derived MMP-1 does not recruit osteoclasts, it activates osteoclast precursor cells (as seen by the expression of TRAP), and stimulates their multinucleation in the presence of soluble type-I collagen, providing one mechanism of osteoclast resorption (as defined by the presence of lacunae) at the interface of bone and MMP-1-expressing tumor cells. While our results suggest that tumor-derived MMP-1 activates osteoclasts in vitro, we cannot exclude the possibility of the tumor cells directly degrading bone in vivo. However, it is generally accepted that breast cancer cells cannot directly resorb bone [52, 53].
Breast cancer lesions in bone arise most frequently from metastasis, and also, but less commonly, by direct invasion of a primary breast tumor into the ribs and/or sternum, also known as local/regional reoccurrence (LRR). Defining the mechanisms by which breast cancer cells invade soft tissues and trigger destruction of bone is important to understanding breast cancer pathology of the bone. Given its well-established role in the invasion and degradation of type-I collagen, we studied breast cancer secreted matrix metalloproteinase-1 (MMP-1) in the invasion of interstitial tissues and bone. Using a novel murine model in which MDA MB-231 breast cancer cells harboring either control or MMP-1 shRNAs were injected near to the femur, we demonstrate the importance of tumor-derived MMP-1 in the directional invasion of interstitial tissues and the stimulation of osteolysis in vivo.
Our data show that inhibiting expression of MMP-1 suppresses tumor invasion of soft tissues (Fig. 2). Interestingly, tumors expressing MMP-1 had enhanced angiogenesis on the invasive outcroppings, compared to tumors lacking MMP-1 (Fig. 3). Thus, we propose that this invasion is associated with the ability of MMP-1-secreting tumors to recruit vasculature and consequently, chemoattractive agents, such as SDF-1. Our findings support two studies showing that (1) MMP-1 expression in invasive melanoma increases angiogenesis and (2) breast cancer-derived MMP-1 contributes to the assembly of new tumor blood vessels [30, 43].
Once in bone, factors secreted by tumors initiate pathological bone resorption by activating bone-residing osteoclasts and stimulating their differentiation [13, 24, 54–56]. Interestingly, MMP-1, which is frequently overexpressed in breast cancer, is: (1) localized to osteoclasts and their resorption lacunae , (2) upregulated by agents that stimulate bone resorption , and (3) implicated in the process of normal bone resorption during remodeling . Thus, we hypothesized that expression of MMP-1 by breast cancer cells also plays a role in tumor-induced osteolysis and we used a novel model to investigate this idea. At day 28, we observed scalloped lacunae at the interface of bone and MMP-1 expressing tumors, which were absent in bone adjacent to MMP-1 deficient tumors. Tumors secreting MMP-1 invaded the periosteum, compact bone, and the bone marrow cavity, but this was diminished by tumors lacking MMP-1 expression, suggesting a direct role for MMP-1 in mediating these events.
To investigate the molecular mechanisms behind our observations, we examined the ability of MMP-1-secreting tumor cells to recruit and/or activate osteoclasts. Although MMP-1 secreted by the tumor cells did not recruit osteoclast precursor cells, it did stimulate the activation and differentiation of these cells when plated on soluble type-I collagen, but not on insoluble type-I collagen (Fig. 5). This finding expands upon previous in vitro data that suggested collagenase-generated collagen fragments triggered osteoclast activation . Importantly, we show that inhibiting MMP-1, using a neutralizing antibody, blocks osteoclast differentiation. Because soluble type-I collagen was required for MDA MB-231-secreted MMP-1 to induce the activation and differentiation of osteoclasts, we propose that collagen fragments produced by MMP-1 are responsible for the maturation of osteoclasts. Our data demonstrate, for the first time, that breast cancer-derived MMP-1 is capable of inducing the maturation of osteoclasts and that this is accomplished only in the presence of soluble type-I collagen.
To our knowledge, an in vivo model suitable for investigating LRR, an event that affects up to 30% of breast cancer patients after mastectomy , has not been described. LRR involves the direct invasion of interstitial tissues and bones of the chest wall by residual primary breast cancer cells. Our murine model recapitulates LRR, and also allows observations of the tumor cell/bone interactions. Although these interactions are initiated at the cortex of the bone, rather than in the bone marrow cavity, we found that breast cancer cells invaded into the marrow cavity in ~30% of mice by day 28.
Our model of breast cancer invasion of bone may be especially applicable to LRR studies, but can also be used widely to study cancer-induced osteolysis and invasion, and to analyze the efficacy of potential therapeutic drugs targeting tumor/bone interactions. Our findings may be broadly relevant to tumor-driven invasion of bone by other cancers, including lung, prostate, and kidney, as these commonly metastasize to bone , and have increased MMP-1 [58–60].
We would like to extend thanks to Dr. C. Harker Rhodes for IHC consultation and Dr. Steve Fiering for thoughtful ideas. Grant support: NIH grants AR26599 and CA77267 (C. E. Brinckerhoff) and NIH grant T32-CA009658 (S. M. Eck).


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A few years ago, Bobby Campion, a Co Laois publican, paid €120 for a photograph at a Sheppard's auction. It showed Irish first World War veterans, including his granduncle Jack Moyney, attending a Remembrance Sunday church service in Co Tipperary in the 1960s.
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In today’s hyper body conscious society, it is all too easy to pick apart every flaw and minor imperfection about your body. With the barrage of airbrushed model images we are exposed to on a near daily basis, you may find yourself critiquing your body constantly. The truth is that each and every body has its own unique beauty that can’t be captured by one prototype. If you find yourself berating your body, read on to find out seven things you can do today to love your body more!
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domain: psychology


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I am Reader in Modern History here at UEA, and I research and write on minorities, migration and the state. As Britain’s leading historian of Gypsies, Roma and Travellers, my work contributes directly to histories of state expansion, migration, ideologies and violence as well as histories of empire, xenophobia and identity. As a social and medical historian I explore intersections between national, imperial and international structures in the regulation of migration, refugee movements, public health and welfare. My books, A Minority and the State: Travellers in Britain in the Twentieth Century (Manchester: MUP, 2008) and Another Darkness, Another Dawn: A History of Gypsies, Roma and Travellers (Reaktion: London, 2014), both construct a history of these communities and set them within wider historical trends and processes. With Ben Rogaly I was part of the ESRC Identities and Social Action programme with our project ‘Deprived white community? Social action in three Norwich estates, 1940-2000’, which resulted in the jointly authored Moving Histories of Class and Community: Identity, Place and Belonging in Contemporary England (Basingstoke, 2009), republished in paperback in April 2011. A Wellcome Institute Research Fellowship for my project ‘Public Health and Outsiders: British responses to refugees in the twentieth century’ has supported my growing interest in refugee histories. and how their reception in Britain sheds light onto broader historical trends, and I am currently writing a book, entitled The Britain they Entered: Refugees to Britain in the Twentieth Century, stemming from this research. This charts the arrival of different cohorts of refugees to Britain, and considers what their arrival can tell us about fundamental changes in British society over the period.
I have an interest in different methodological approaches to history, particularly combining oral histories and archival methodologies and of collaborative interdisciplinary research. I have an established track record of working with policy makers, third sector organisations and community groups and extensive online, radio, television and print media experience communicating the importance of history to general audiences.
I welcome applications from post-graduate students interested in researching histories of the modern state, and minorities, marginalised and vulnerable peoples, including Roma/ Gypsy/ Traveller populations, refugees and migrants.

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Selecting a reliable water meter is vital to controlling and measuring water drainage. As a way to install water meter the flow water should be shut off which ranges from inconvenient to get a homeowner to extremely costly for the business, municipality, or water supplier. This makes selecting a excellent, reliable water meter essential. Fortunately, there are many key indicators that produce deciding on the best meter and much easier process.
There are several solutions to measure water usage however there are several designs that have become common. Probably the most popular options is volumetric or positive displacement metering. One other popular option is electronic or magnetic metering. Usually the size of positive displacement meters cover anything from 1/2 to 2 inch sizes. Electronic cold water meters range between 50 % inch to 24 inches. This gives them to cover an array of applications including potable water, water vending, and various kinds of water treatment.
Accuracy are at the main of deciding on a dependable water meter. Probably the most common reasons a meter is definitely an accurate is because of a reverse flow of water in the outlet. A trusted meter utilizes a backwater spring valve to automatically prevent reverse rotation and effectively measure standard water consumption. Concurrently, mineral water flow is not hindered from the backwater spring valve since it will remain open as long as it flows in the nozzle over the strainer on the inlet. With electronic meters, external static magnetic fields could also cause reading inaccuracies also. When utilizing a digital meter it’s imperative that is certainly tested to be sure this not relying on external magnetic forces.
It is usually vital that you make sure the water meter is made to withstand whatever environmental factors it will face. For example, some meters perform poorly in environments where freezing or Burstein is actually a possibility. The vast majority of problematic for wet type meters. An excellent meter is designed hence the gearbox won’t let water in. This makes sure that freezing and bursting in the winter is very little possibility.
So that you can cut costs and save time, many municipalities and corporations are turning to electronic or remote readings. If this describes a technology which will potentially be deployed you should select a meter which is works with it.
Finally, the general durability of the lake meter should be researched as well. Generally, the greater, static parts aren’t after that potentially break. It’s the smaller, active pieces that are at an increased risk. To pick an excellent, reliable meter it is essential that it provides a established track record of reliability in environments similar to the way will be deployed.
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This Chocolate Caramel Banana Upside-Down Skillet Cake has all the elements you look for in a great piece of cake! Chocolate - Check -- Buttery Brown sugar caramel - Got 'em! -- Ripe bananas - Heck yeah! And this cake begins and ends in a skillet. Can't get better than that! http://www.mind-over-batter.com
Chocolate Fudge Banana Skillet Cake Recipe--You can make this healthy skillet cake from start to finish in 20 minutes!! Your dessert is waiting. :) Vegan and paleo friendly. No flour and no refined sugar!

domain: food


Understanding COVID-19 Funding For Schools: School Safety Today
With so many different federal actions providing COVID-19 funding for schools to reopen this Fall, educators, administrators, and facility managers are struggling to understand the best way to take advantage of all of this assistance and how to center their strategies in thoughtful ways.
Here to give insights on this episode of School Safety Today, a Raptor Technologies podcast is Dr. Paula Love, President, RFPMatch.com, The Funding Doctor. She talked with host Daniel Litwin, the Voice of B2B, about how to align funds to protect your school, details on grant application and submission, and how to create sustainability in your investments and maximize the use of funds.
“What I see right now is a funding frenzy because you’re trying to navigate all these funds and different fund names,” Love said. “Sometimes it’s difficult to ascertain which grants are associated with different acts.”
The CARES Act (Coronavirus Aid Relief and Economic Security) provided funds to the Department of Education called Education Stabilization Funds, which is the umbrella that oversees all funds. There are two pathways that K-12 schools can access: they are ESSER (Elementary and Secondary School Education Relief) and GEER(Governor’s Education Emergency Relief) funds.
The ARP ESSER fund has set aside $123 billion in available funds to help K-12 schools safely reopen their doors, providing dollars for health screening tools, funds for learning loss, and additional resources to address the mental well-being of students impacted by the isolation of lockdown. GEER set aside $3 billion, which will use a governor’s discretion for how they will use that money in their state.
Listen to hear Dr. Love further break down the COVID-19 funding for schools.
Follow us on social media for the latest updates in B2B!


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The Blorenge is a mountain in the southeastern corner of the Brecon Beacons (Bannau Brycheiniog) which overlooks the River Usk. From the summit of the Blorenge, walkers can enjoy stunning views of the Black Mountains, Central Beacons and the Severn Estuary.
However, a Blorenge walk can offer much more than just great views. With its abundance of heather moorland, this rounded peak is an important breeding ground for Red Grouse. The area also offers visitors sightings of polecats, weasels, badgers, foxes and adders. And for those interested in history, the Blorenge played an important role in the Industrial Revolution taking place at nearby Blaenavon.
In this guide I describe three walking routes that explore this fascinating hill.
Blorenge or the Blorenge, is a peak in the Brecon Beacons National Park. Blorenge hill, which tops out at 561m (1841ft), is also designated a Site of Special Scientific Interest due to its abundance of heather moorland. A section of the lower hill known as the Punchbowl, is a nature reserve managed by the Woodland trust.
From the summit of the Blorenge, the flat topped peak of Sugar Loaf will instantly stand out as the biggest and closest hill, standing proud to the north of Abergavenny. To the east of Abergavenny walkers will recognise the stand alone mountain of Skirrid. Finally if you are blessed with clear weather, to the east you can pick out the largest peak in the Beacons, Pen y Fan.
The Blorenge is located between Llanfoist and Blaenavon, which is a World Heritage Site. Given this location, the Blorenge is steeped in Industrial Heritage.
Blaenavon was a leading producer of iron and limestone which was distributed all over the world. A tramroad was built to connect Blaenavon to Llanfoist Wharf, which then connected to the Monmouthshire and Brecon Canal for further distribution.
This revolutionary tramroad passed around and through Blorenge mountain. The tramroad and tunnel can be viewed on a walk around the Blorenge. (Walk option number 2)
A walk of the Blorenge could easily be combined with an exploration of Blaenavon and its World Heritage attractions.
Read Related Articles
- Best Walks In The Brecon Beacons
- Waterfall walks in the Brecon Beacons
- Walks from Llanthony Priory
- Hay Bluff Walks
1. A Short Blorenge Walk
- Starting Point: Keepers Pond Car Park on the B4246
- OS Explorer Map OL13
- Distance: 6.5km/4 miles
- Time: 2 hours
- Difficulty: Moderate
This car park sits at 482m which means you have incredible views, right from the off. For me this is the best Blorenge walk as it provides amazing views for most of the route and is not too strenuous. The route is also well trodden and very easy to follow.
From the car park head to the Keepers Pond and follow the path to left, heading in a northeasterly direction. The path is well maintained and has an information board at the far end of the lake. Continue along this path until it forks into two. This junction is marked with a stone way-marker which is signed Govilon and Llanfoist.
Take the right-hand path which continues straight-on to contour the hill. Shortly after you will begin to climb slightly into a grassy gulley. Once you exit the gulley you will have fabulous views of Blorenge’s northern slopes and Skirrid mountain beyond.
Continue around to a small building, from which point you must turn right to begin the slight climb to the summit. This once boggy path has been replaced with a well laid gravel path and is obvious to follow. You will soon see the slight rocky mound that marks a Bronze Age burial chamber and Blorenge summit.
From the summit, the gravel path continues in a southerly direction towards Foxhunters carpark, which is flanked by two large radio masts. At the car park turn right and join the small tarmac road. Follow this road for just a few hundred meters and then branch off to the right, along a grassy path to return to Keepers Pond carpark.
Did you know? The Keeper’s Pond was built in the early 19th century to provide water for Garn Ddyrys Forge. The gamekeeper of the Grouse moors lived in a cottage near to the pond and that’s where the name comes from.
2. A Long Blorenge Mountain Hike
- Starting Point: Keepers Pond Car Park on the B4246
- OS Explorer Map OL13
- Distance: 11km/7 miles
- Time: 4-5 hours
- Difficulty: Moderate-challenging
This is another great Blorenge circular walk, but this one does involve a lot more “up” and is therefore more challenging than the first option.
From the carpark, again head to the pond and follow the path to the left in a clockwise direction. At the far end of the pond the path continues in a northerly direction. This time, at the fork, branch off to the left following the stone sign for Govilon and Llanfoist.
This rocky path descends briefly before it levels off and meets the old Hill Tramroad. Turn right here, staying on the tramroad as it contours around the northerly end of the Blorenge. Keep your eye out for remains of the Blorenge’s tramroad tunnel.
Continue around the eastern side of the hill until you reach a small wooded area with a lake in the middle. This glacial cwm is known as the Punchbowl, which is a Woodland Trust Nature Reserve. Take a moment to watch for a variety of birdlife at this man-made lake, before beginning the climb to the summit.
From the punchbowl take the trail to the left of the lake and ascend the lower path into the woods. Continue along this path until it joins the small road which leads to Foxhunter carpark. Turn right along the road and after 500m take a sharp right back onto a grassy path.
Climb steeply up the eastern side of the hill to reach a plateau. You are nearly at the summit! Follow the path as it turns left past a small building and climbs in a southerly direction towards the summit, on a well maintained gravel path.
A small pile of rocks marks the summit with a trig point just beyond. From the summit continue along the gravel path towards the two radio masts located to one side of Foxhunter carpark. At the carpark turn right and again walk along the country road for a few hundred meters. Branch off the road to the right, along a grassy path to return to Keepers Pond carpark and the end of this circler walk.
Did you know? Blorenge mountain is thought to have inspired the hymn “All things bright and beautiful”. The line “the purple headed mountain, the river running by” is thought to reference Blorenge mountain and the river Usk
3. A Quick Walk To Blorenge Summit
- Starting Point: Foxhunters car park
- OS Explorer Map OL13
- Distance: 3km
- Time: 1 hour
- Difficulty: Easy
If you want to enjoy a short and easy walk to the summit of the Blorenge, then this is the walk for you! Branch off the B4246 road from Blaenavon, just before the Keepers Pond and take the small country road to Foxhunters carpark.
From Foxhunters carpark there is a well maintained gravel path that heads in a northerly direction, straight to the mountain summit. The trail is around 1.5km one way and has a gradual ascent of around 45m.
A small pile of rocks marks an ancient burial chamber and a trig point signifies the summit of Blorenge. From the summit enjoy views of Sugar Loaf and the valley beyond in one direction and views of the Bristol Channel in the other.
Did you know? Foxhunter’s carpark is dedicated to the famous showjumping horse, Foxhunter, who won Britain’s only gold medal in the 1952 Summer Olympics. Foxhunter is buried just off the trail close to the carpark and is marked by a plaque.
What To Pack For A Blorenge Mountain Walk
For a complete mountain day packing list take a look at this post, but here are some of the essentials.
- Waterproofs – of course, it’s Wales!
- Water – bottles with filters are very handy for safely refilling in streams and rivers. Discover which filtered water bottle is right for you in this handy guide!
- A hat and warm layers for the top where it’s quite exposed
- Good hiking shoes/boots – some areas are often boggy and the terrain is rough in parts
- The relevant Brecon Beacons map and compass
- These paths are marked on maps.me so download the map before you go
Prefer not to walk alone? If you’re looking for a Mountain Leader to guide you on a mountain adventure, please contact me here to discuss rates and availability.
Where to Stay in the Brecon Beacons
The Brecon Beacons has several cute market towns and villages to use as a base for exploring the national park. There aren’t many large chain hotels but instead, you will find a selection of bed and breakfasts, pubs/Inns, glamping and camping opportunities.
As a central location, you can’t go far wrong with the town of Brecon. The beautiful Camden Lodge B&B offers exceptional service, with large, clean rooms that have delightful views over the hills. To experience the charm of a cosy, local pub try the Usk and Railway Inn at Sennybridge. This is a fabulous location for mountain bikers looking to get out in the hills.
If you’d prefer to be based near the Black Mountains in the east, opt for the Ty Croeso Boutique B&B which is an exquisitely renovated Victorian building located near the small town of Crickhowell. In the west, Cwtch Bach is a gorgeous stone bricked holiday home perfect for exploring The Black Mountain region.
For a luxury glamping experience try the Cuddfan, whose bell tent located along the banks of the river Grwyne offers a real escape back into nature. For more luxury glamping ideas take a look at this guide to glamping in the Brecon Beacons.
Blorenge Walk Summary
The Blorenge is a hill in the Black Mountains region of the Brecon Beacons (Bannau Brycheiniog). It is a relatively small, rounded peak located between Abergavenny and Blaenavon. Blorenge mountain offers walkers a chance to enjoy fine views, a variety of wildlife and a glimpse into the areas industrial heritage.
There are several routes to enjoy a walk of the Blorenge, with options to suit all abilities. In this guide I outline three walking routes which range in difficulty and length. I provide brief trail descriptions, distances, times and starting locations for each.

domain: geography


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An artificial foot has been discovered in a Cornish layby.
The lonesome limb somehow made its way to the side of the road, leaving some passing motorists slightly unnerved.
Cornwall Live photojournalist Greg Martin was on his way to Polperro this morning when he stumbled across the foot by the A390 this morning.
Greg said: “I think the layby was somewhere near West Taphouse.
“I was driving past, saw the foot, and didn’t want to be the guy who drives past a dismembered foot and then sees that police have made a gruesome discovery on the news later, so I turned around.”
Fortunately, there were no police appeals about severed bodies and Greg soon discovered that the foot was in fact made of rubber.
We’re a bit stumped as to why it was out and about all on its own.
There have been a few scarecrows spotted in the area so perhaps that’s where it came from.
Or maybe someone is just pulling our leg and left it there as a joke.
If you know who has left it there, get in touch.
You can email email@example.com or message us on Facebook.


The IUNI U2, a very interesting top-of-the-range smartphone from the Chinese manufacturer IUNI, has remained unfortunately the exclusive of the Chinese market due to the lack of English in the system settings. But the new IUNI U3 could change things.
IUNI is a Chinese company that has started the production of smartphones to give more possibilities to its version of Android, the IUNI OS, which offers a special design and interesting security options. Tomorrow, 26 Agosto, will unveil its new top of the range, the IUNI U3.
As you can see from the photos in this article, the IUNI U3 could have a design similar to that of the Nubia Z7. The smartphone should offer a 5.5 inch display with Quad HD 2560 x 1440 pixels resolution, Qualcomm Snapdragon 801 processor to 2.3GHz, 3GB of RAM, 32GB of internal memory, 12 mega-pixel main camera with video recording in 4K and rear camera from Mega-pixel 4 with ultra-pixel technology.
The software should also be Android 4.4.4 customized by the IUNI OS, which should finally receive the English language.
The IUNI U3 could prove to be a very interesting product. The launch event is scheduled for tomorrow, so we'll find out if the spy photos are real and if the technical specifications are confirmed.[With]


Clark County officials have notified 17 residents in the Lawrenceville area that they have until August 23rd to switch to the county's water system or rick having their water supply cut off.
Last June, the county installed a water system in the Lawrenceville area. It cost about $767,000. But 17 residents have not connected to the new system yet, according to Clark County Utility Director Alice Godsey. She says the old water system will be shut down in August and unless residents want to dig a well, they need to be connected to the new system.
The cost of connecting to the County's new water system is between $500 and $1,000, but the County Utility Office says financial assistance is available. Residents are encouraged to contact the Utility Office to discuss getting connected to the new water system.
Alice Godsey says the new system provides water that tastes and smells better and is more reliable than the old system, which was undersized and outdated.


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New American Standard Bible
Then Rabshakeh returned and found the king of Assyria fighting against Libnah, for he had heard that the king had left Lachish.
King James Bible
So Rabshakeh returned, and found the king of Assyria warring against Libnah: for he had heard that he was departed from Lachish.
Darby Bible Translation
And Rab-shakeh returned, and found the king of Assyria warring against Libnah; for he had heard that he had departed from Lachish.
World English Bible
So Rabshakeh returned, and found the king of Assyria warring against Libnah, for he had heard that he was departed from Lachish.
Young's Literal Translation
And Rabshakeh turneth back and findeth the king of Asshur fighting against Libnah, for he hath heard that he hath journeyed from Lachish.
Isaiah 37:8 Parallel
CommentaryBarnes' Notes on the Bible
So Rabshakeh returned - Returned from Jerusalem to the camp of his master. He had received no answer to his insulting message Isaiah 36:21; he saw there was no prospect that the city would surrender; and he therefore returned again to the camp.
And found the king of Assyria warring against Libnah - He had departed from Lachish. Why he had done this is unknown. It is possible that he had taken it, though this is not recorded anywhere in history. Or it is possible that he had found it impracticable to subdue it as speedily as he had desired; and had withdrawn from it for the purpose of subduing other places that would offer a more feeble resistance. Libnah was a city in the south of Judah Joshua 15:42, given to the priests, and declared a city of refuge 1 Chronicles 6:54, 1 Chronicles 6:57. Eusebius and Jerome say it was in the district of Eleutheropolis (Calmet). It was about ten miles to the northwest of Lachish. This city was taken by Joshua, and all its inhabitants put to the sword After taking this. Joshua next assaulted and took Lachish Joshua 10:29-32.
LibraryThe First Trumpet.
The first trumpet of the seventh seal begins from the final disturbance and overthrow of the Roman idolarchy at the close of the sixth seal; and as it was to bring the first plague on the empire, now beginning to fall, it lays waste the third part of the earth, with a horrible storm of hail mingled with fire and blood; that is, it depopulates the territory and people of the Roman world, (viz. the basis and ground of its universal polity) with a terrible and bloody irruption of the northern nations, …
Joseph Mede—A Key to the Apocalypse
Christ Rightly and Properly Said to have Merited Grace and Salvation for Us.
They journeyed from Rimmon-perez and camped at Libnah.
Then Joshua and all Israel with him passed on from Makkedah to Libnah, and fought against Libnah.
And Joshua and all Israel with him passed on from Libnah to Lachish, and they camped by it and fought against it.
The LORD gave Lachish into the hands of Israel; and he captured it on the second day, and struck it and every person who was in it with the edge of the sword, according to all that he had done to Libnah.
Zedekiah was twenty-one years old when he became king, and he reigned eleven years in Jerusalem; and his mother's name was Hamutal the daughter of Jeremiah of Libnah.
Jump to PreviousAssyria Commander Departed Ears Field Fighting Findeth Found Heard Journeyed Libnah Making Rabshakeh Rab'shakeh Rab-Shakeh Turneth War Warring Withdrew
Jump to NextAssyria Commander Departed Ears Field Fighting Findeth Found Heard Journeyed Libnah Making Rabshakeh Rab'shakeh Rab-Shakeh Turneth War Warring Withdrew
LinksIsaiah 37:8 NIV
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domain: history


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SAP NOW Africa 2018 wrapped up last week at the Sandton Convention Centre, with the two-day long event focusing on how local businesses can better prepare themselves for digital disruption and leverage technology to keep pace with their rivals.
The theme for the event was, “Tomorrow is already here,” posing the question to attendees and delegates as to how they will embrace the future.
It also focused on the notion of intelligent enterprises.
How they are created? What the journey involved in becoming one is? And why it’s important to be one?
Intrigued by the definition of an intelligent enterprise, we discussed the subject with SAP Africa COO Mehmood Khan, who unpacked the value that intelligent enterprises could have on the African continent.
Doing things intelligently
Khan explains that the intelligent enterprise is not simply a message that SAP wish to bring to Africa, but to the entire world.
“We find ourselves in an environment where we can create intelligent enterprises. There are a lot of technologies that are coming together like IoT and Blockchain, but an intelligent enterprise is one that can do some of the learning on its own,” says Khan.
The COO also stresses that an intelligent enterprise is one that has an intrinsic ability to adapt. Not only in the way it develops services and solutions, but also in the way it deals with employees, how it tackles security and approaches its marketing strategy to name a few.
He adds that intelligence does not extend only to certain business applications, but to the organisation as a whole.
“If you can build a technology platform that allows you to be an intelligent enterprise. One that is quick learning, fast to adapt and can automate all of those non-value adding elements, then your business can actually operate with what is going on in the industry. That’s the big change we want to drive in all business,” points out Khan.
Adaptability is key
One of the key elements that distinguishes intelligent enterprises from ones that aren’t, is adaptability, as Khan touched on earlier.
The reason why this adaptability is fundamental, however, is in how effectively an organisation is able to react to significant changes in the market.
Such a change, according to Khan, on the cusp of happening is national health insurance, as it potentially has massive ramifications for all businesses in South Africa.
“If NHI is launched, every organisation in the country will have to change,” says Khan. Adding that, “It effects your HR environment, your supply chain, your security, and so on, so you’ll need to react to it fairly quickly.”
The way our traditional IT systems currently operate will make those quick transitions far more difficult to facilitate says Khan.
Another example of an industry lacking sufficient intelligent enterprises is the finance market, with Khan noting that new solutions take six months-plus to be developed, which leaves gaps open to disruptive organisations to make an impact.
As such, organisations that were quite monolithic in their thinking and processes, need to make a change.
Stepping stone to success
As for why Africa will benefit from having more intelligent enterprises operating on the continent, Khan believes that SAP’s customers (and businesses that aren’t their customers) will only truly be successful if the region is successful.
“I think it’s a virtuous circle. Africa does have the opportunity to compete globally, as our continent has amazing talent, but we need to give people the chance,” says Khan.
“If you have an intelligent enterprise, and have a platform that allows you to be agile and adapt quickly, you have all the same things that organisations in the UK, US, Europe and Far East do, and that affords you a better chance to compete on a global level,” he adds.
Khan also stresses the importance for every organisation to want to improve the lives of its customers, and place that over financial success, which too is an aspect that an intelligent enterprise is aware of.
“If our businesses are competitive, Africa grows and we will reach our mission, which is to make people’s lives better,” concludes Khan.


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Here we go again: The U.S president is attacked on a global scale for his thinking on trade and investments. Mrs. Merkel, chancellor of Germany even announced a “new chapter in U.S. European relations” and stated that “Europe must take our fate into our own hands’’. Similar accusations had been raised in 1980 after the election of President Reagan. He was labelled a B class actor, a cowboy and an inexperienced but lucky vote gainer. The accusers were wrong then and they are wrong now!
President Trump lived up to his convictions during the tense G-7 political summit just as he had already done during and after the U.S. presidential campaign. No surprises there when he reflected on the need for more balanced trade relations and the requirement for all nations to pay a fair contribution for the benefits they obtained from the United States.
President Trump has issued a new executive order focusing on so-called “Buy American, Hire American” policies. Making the announcement at the Snap-On Tools plant in Kenosha, Wisconsin, the President’s order directs various federal agencies to produce reports and recommendations on government procurement policies, with the goal of increasing domestic employment and production.
The Executive Order (found here) covers two broad areas of government policy: numerous “Buy American” laws and regulations, which set requirements that materials purchased by the government – say, steel for building a bridge – give preference to US domestic producers; and “Hire American,” which aim to address reported abuses of H1B visas that undermine high-skilled domestic labor.


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He appreciates the gesture but retiring St George Illawarra co-captain Ben Creagh has knocked back a farewell game for the NRL club this weekend.
Creagh was surprisingly included in the team named for the final match of the season against Newcastle on Saturday but on Wednesday he ruled himself out of the match due to his chronic knee injury.
He said it was special to be named to play in a jumper he made his own for most of his career.
"The club's done a nice thing by naming me in the 12 jersey, I played a lot of games there for the Dragons. But I've trained again today and it'd be a token game if I played," he said.
A member of the club's 2010 premiership-winning team, Creagh, 31, said he wouldn't last long on the field and didn't want to stain his 16 seasons in the game with a poor performance.
"Unfortunately my knee's that bad now. It's not getting better," he said.
"It's not what I want to remember my last game on, going out there and struggling, getting run past and missing tackles.
"I won't play this weekend and that's the way it is."
Teammate Benji Marshall, who will also play his final game in the Red V against the Knights, labelled Creagh the best captain he has played under in his career.
"I can honestly say with my time here, he's probably the best leader I've ever seen or been under and probably the most-respected player that I've seen," he said.
"Just the way he carries himself and if you talk to anyone around the club, you wouldn't find a person who'd say a bad word about him.
"From my point of view, the stuff he's done for me away from football is more important than the stuff with football."
Creagh said it was imperative the team's coaching staff and playing group openly discuss the failings of a season that resulted in the club missing the finals for the fourth time in five years.
"There'll be a lot of learning to come out of this year, hopefully a lot honesty when the season ends between coaches and players, to find out where we went wrong," he said.
"Not gloss over the things that have gone wrong this year and try and fix it for 2017 because there's a very talented bunch of footy players at this club."
Creagh finishes his career on 270 games, three games short of club record holder Ben Hornby.

domain: sports


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Earlier this month, we provided a “LEED for Contractors” training for a local contractor. We discussed our hands-on approach to LEED project management and how…
Join us at IFMA World Workplace October 7-9 in Denver, Colorado! Register here and we look forward to seeing you there!
Check out how this greenhouse business in NYC is pushing the boundaries of urban agriculture.

domain: agronomy


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ROME – The United Nations World Food Programme (WFP) is launching an emergency food and nutrition operation to respond to urgent hunger needs among 3.5 million vulnerable people identified in a multi-agency food security survey that was completed in the Democratic People’s Republic of Korea (DPRK) last month.
The operation – which will include the highest standards of monitoring and control to ensure that food gets to where it is needed - will primarily focus on the nutritional needs of women and children. The recent WFP-led Rapid Food Security Assessment concluded that food shortages in DPRK have led to a serious deterioration in the health of millions of people who are already struggling to feed themselves.
“We face a critical window to get supplies into the country and reach the millions who are already hungry,” said WFP Deputy Executive Director and Chief Operating Officer, Amir Abdulla. “Our primary concern is for those who are most vulnerable to shocks in the food supply – children, mothers, the elderly and large families.”
A bitter winter, crop loss, and a lack of resources to secure cereal supplies from outside the country have left DPRK highly vulnerable to food shortages. While acute malnutrition has not reached crisis levels, widespread chronic malnutrition and the poor diet in DPRK mean that if there is any significant reduction in food intake the situation could deteriorate rapidly.
With government rations currently providing only about half of people’s daily food needs, some families are already resorting to negative survival strategies, including cutting down on the size and number of meals.
WFP will be providing both staple cereals to vulnerable groups through the Public Distribution System (PDS), as well as ingredients for the local production of nutritious food such as corn-soy milk, rice-milk blend and nutrient rich biscuits.
The new operation will be rolled out with a number of rigorous monitoring conditions, agreed with the DPRK authorities. More than 400 site visits by WFP international staff will take place every month, with only 24-hour notice required, including access to county and provincial markets. About a fifth of all international staff will be Korean-speaking.
As food supplies are needed immediately, WFP is looking to procure food in neighbouring countries, and use ports and rail entry points as close as possible to the areas where food is needed most urgently.
The new emergency operation is planned for one year, with continued assistance in the form of specialised nutritious products to selected groups continuing after the main October harvest. The cost will be just over US$200 million.
With DPRK’s continued vulnerability to natural disasters such as droughts and floods also a significant risk factor, WFP plans to have contingency stocks in available in the country to allow a rapid response to any new acute needs.
“WFP has worked in DPRK for 15 years and we will be drawing on all that experience and expertise to ensure this operation provides vital, timely food and nutrition to those who cannot support themselves through these difficult months,” Abdulla said.


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Colorado National Parks
Comanche National Grassland
Comanche National Grassland covers over 435,000 acres in the southeastern corner of Colorado. 150 million years ago, the grasslands were home to dinosaurs. In 1749 - 1805, the land was home to the Comanche Indian Tribe. After they left the land, it became grazing land for cattle ranchers until 1898. The Santa Fe Trail also ran past these grasslands from 1821 - 1880. Since 1954, the US Forest Service has managed the land, and in 1960 it was designated as a grassland. Now the land is used for livestock grazing, wildlife habitation, recreation and mineral production. This grassland is split into two different areas, the Carrizo unit south of Springfield, on the border of Oklahoma; the Timpas unit south of La Junta.
The Picture Canyon Trail is located in the Carrizo Unit of the grasslands. This moderate trail runs through the grasslands providing views of many rock cliffs, as well as, abundant wildlife. Bird sightings are common, as over 257 species of birds inhabit the area. Some of the birds you might see are Say's Phoebes, Bullock's Orioles, Rock Wrens, Western Meadowlarks, Lark Sparrows, Mourning Doves and Red Headed Woodpeckers.
Be sure to visit the Picketwire Canyonlands. At these canyonlands, you will view dinosaur tracks. Dinosaurs roamed this area millions of years ago, in an area that was once a river. As the dinosaurs waded through the mud, they left over 1,300 tracks that later were buried and turned into stone. Rangers will give tours by appointment only. Tours are offered in April, May, June, September and October.
Other activities available in the grasslands are hiking, mountain biking and horseback riding on the many trails in the grassland. Scenic driving, picnicking and viewing historic sites are also popular. Prehistoric rock art, early homesteaders' rock huts, and limestone markers from the Santa Fe Trail are some of the exciting historic sites in the grassland. Bent's Old Fort is also nearby for more history.
From Springfield: take on Highway 287 south for 17 miles. At County Road M turn right (west) and continue for 22 miles, then turn left (south) at Forest Service Road 539 and travel 1.9 miles to the parking lot.
From La Junta: take Highway 109 for 58 miles. Highway 160 east for 18 miles then County Road 3 turn right and go south for 7 miles. Turn left at County road P and travel east for 3 miles. At County Road 6 turn right and travel south for 2 miles, then turn right (west) at County Road M and continue 1-1/2 miles. Turn left (south) at Forest Service Road 539 and go 1.9 miles to the parking lot.
More Activities & Information
La Junta, Colorado includes: Bent's Old Fort National Historic Site, Branson, Las Animas

domain: travel


text:
By Grant Morrison
Read or Download Batman Incorporated (2012-) #3 PDF
Best science fiction & fantasy books
The darkish Knight struggles opposed to a deadly—yet surprisingly familiar—foe! As a mysterious determine slinks in the course of the halls of Arkham Asylum, Batman needs to struggle his method via a gauntlet of psychos, and Bruce Wayne faces the unforeseen criminal ramifications of Batman Incorporated!
Bloodshot is the world's maximum residing weapon. His blood is full of excessive tech nano-machines that allow him to heal from any harm inside mins, converse and regulate any computing device, and develop into a reproduction of a person he sees. he's hyper-reflexive, inhumanly robust and quickly, and he has the resilience of a tank.
It's a burden he has borne because the days of antiquity. A curse Peter Tomlinson notion he'd ultimately shed in Mystic Falls. yet others won't allow him get away his destiny so simply. between them a tortured relations of vampires and a tender lady with mysteries of her personal. Can he holiday the supernatural ties that bind or will he stroll by myself for one more millennia?
An outcast Starseer taught to distrust the Alliance, an ex-Alliance soldier caught on dull safeguard accountability, discovery of a strong and unsafe historic artifact… What may possibly get it wrong? happening presently after the occasions in finish video game, Artifact discovered is a thrilling area event set in Lindsay Buroker’s exciting Fallen Empire universe.
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Batman Incorporated (2012-) #3 by Grant Morrison

domain: literature


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BOUTHER DE PERTHES, Jacques. Petit Glossaire,
Paris : 1835First edition of this glossary on bureaucratic matters by French archaeologist and writer Jacques Bouther de Perthes (1788-1868), who was one of the first to establish the presence of prehistoric man in Europe.
Stock Code: 125015
ROHAULT, Jacques. Tractatus Physicus
London : 1682First London edition, following the Geneva Latin edition of 1674; originally published as Traité de physique (Paris: Charles Savreux, 1671). This edition is dedicated to the physician Thomas Short (1635-1685); Pepys owned a copy (item 1278 in the catalogue of his library). Through the English version of the theologian and philosopher Samuel Clarke... Learn More£850.00
Stock Code: 127068
DILLON, John Talbot. Travels Through Spain,
London : 1782Second London edition, third overall, of Dillon's earliest work which was first published in 1780 in London, and the following year in Dublin.
John Talbot Dillon (1734-1806) was a traveller and historian. He was also "clearly proud to be a baron of the Holy Roman empirea title conferred on his father, Francis, and passed down on his death in... Learn More£1,850.00
Stock Code: 133535
DARWIN, Charles. The Descent of Man, and selection in relation to sex.
New York : 1871First US edition, later issue without errata. First published in the UK earlier that year, it was in this work that the word "evolution" appears for the first time, preceding its appearance in the sixth edition of The Origin of Species the following year. Darwin had hoped that one of his supporters might tackle the thorny question of human evolution,... Learn More£1,250.00
Stock Code: 117907
WARD, Rowland. A Naturalist's Life Study in the Art of Taxidermy.
London : 1913First edition, first impression. Rowland Ward was the Michelangelo of Victorian taxidermy, that most Victorian of art-forms. An innovator who developed many techniques still used today, basing his work on painstaking observation he brought the techniques of naturalistic display to their high point. He was a friend of many of the greatest sportsmen of... Learn More£1,650.00
Stock Code: 132698
PEACHEY, Emma. The Little Flower Maker.
London : 1869First edition. A rare, beautifully produced work designed by 'Mrs Peachey, a first rate artist in her department... favourably known to the public, by a former work on Modelling Wax Flowers to enable her youthful friends, who have often admired specimens of her skill, to become adepts in the charming art of paper flower making'. The techniques of paper... Learn More£1,500.00
Stock Code: 136827
DARWIN, Charles & Francis. The Power of Movement in Plants.
London : 1880First edition, first issue, with 32 pp. inserted adverts dated May 1878 and with two lines of errata at the foot of page x; 1,500 copies were printed. The collaborative authorship proclaimed on the title page reflects Darwin's concern to introduce his children into the world of science. Francis Darwin had trained as a doctor but turned from medicine... Learn More£2,500.00
Stock Code: 129604
HUMBOLDT, Alexander von. Fine mezzotint portrait by Paul Sigmund Habelmann after the painting by Emma Gaggiotti Richards
Berlin : 1854Rare and very attractive half-length portrait of the great German naturalist, explorer and botanist Alexander von Humboldt (1769-1859), the finest and most impressive version from the oil by Emma Gaggiotti Richards, an oval head-and-shoulders portrait, the original of which is at the Archiv der Berlin-Brandenburgischen Akademie der Wissenschaften. It... Learn More£1,250.00
Stock Code: 131927
DARWIN, Charles. The Origin of Species by Means of Natural Selection.
London : 1872Sixth edition, second issue, printed simultaneously with the first issue, which is marked as the "eleventh thousand" on the title page. Freeman notes that the second issue is "notably less common". The sixth edition is the last lifetime edition. Darwin continually made revisions to his text; this edition featuring a new chapter, chapter VII, and a glossary... Learn More£1,875.00
Stock Code: 120358
LEVAILLANT, François. Histoire naturelle des perroquets.
Paris : 1801-05First edition in the preferred folio format of this celebrated work, which stands in the front rank of ornithological books; a quarto version was issued at the same time. The very fine colour plates are by Jacques Barraband, "a superlative bird artist" (Buchanan, p. 97-8), which, apart from their undoubted beauty, display a scientific accuracy that... Learn More£125,000.00
Stock Code: 137037
CHIZHEVSKII, Aleksandr Leonidovich. Strukturnyi analiz dvizhushcheisia krovi (The Structural Analysis of Moving Blood).
Moscow : 1959First edition, inscribed by the author on the front endpaper verso, "To big Misha for good memory. Prof. A.L. Chizhevskii. May 8, 1960". This was one of the last publications of Alexander Chizhevskii (1897-1964), the eminent Soviet interdisciplinary scientist and the founder of heliobiology and aero-ionization, and widely considered to be his magnum... Learn More£3,500.00
Stock Code: 137282
MEAD, Margaret. Coming of Age in Samoa.
New York : 1928First edition, first printing, of Mead's first and pioneering book which launched her career as an internationally recognised anthropologist. Based on Mead's immersive field work in American Samoa in 1925, Coming of Age in Samoa is one of the most widely read anthropology books ever published. Its unwavering influence during the following decades is... Learn More£2,750.00
Stock Code: 118644
DARWIN, Charles. The Origin of Species by Means of Natural Selection.
London : 1875Sixth edition, fifth issue, marked as the "fifteenth thousand" on the title page. The sixth edition is the last lifetime edition. Darwin continually made revisions to his text; this edition featuring a new chapter, chapter VII, and a glossary by W. S. Dallas. "The edition was aimed at a wider public and printed in smaller type... giving the general... Learn More£1,850.00
Stock Code: 120369
DARWIN, Charles. Letter signed by Darwin ("Ch. Darwin"), the text in the hand of his wife Emma, to William Ogle.
Down, Beckenham : [shortly after 27 November 1878]Darwin writes to thank his colleague and regular correspondent William Ogle (18271912) for his English translation of Anton Kerner's Die Schutzmittel der Bluthen gegen unberufene Gaste (The protective measures of flowers against uninvited guests, 1876), which appeared as Flowers and Their Unbidden Guests (Ogle trans. 1878). The book arrived at Down... Learn More£6,500.00
Stock Code: 146638
GENNETÉ, Claude Léopold. Nouvelle construction de cheminées,
Liège : 1760Second edition, preceded by the rare Paris edition of 1759. An important work on chimneys and their ventilation: "the latest technology on making chimneys draw properly and preventing smoke in rooms" (Deborah Howard, William Adam, Architectural Society of Scotland, 1990; who also notes that James Adam acquired a copy in Belgium "at the start of his... Learn More£325.00
Stock Code: 113696
DARWIN, Erasmus. The Poetical Works.
London : 1806First edition of this posthumous collection placing Darwin's exuberant and eccentric inquiry into the Linnaean system in rhyming couplets alongside his poetic speculations on evolution, the whole much enlivened by numerous plates including a number by Blake and Fuseli. A wide-margined, ?large paper copy in a handsome Regency binding from the library... Learn More£2,250.00
Stock Code: 141677
DARWIN, Charles. Autograph letter signed to Henry Colburn.
[late October 1837]An unrecorded early letter from Charles Darwin to his publisher Henry Colburn, regarding the proofing of his upcoming first book, the Journal of Researches (now known as Voyage of the Beagle), the seminal account of probably the most important voyage in the history of science.
Darwin completed the first draft of the book in June 1837, and in... Learn More£15,000.00
Stock Code: 142676
GREAT EXHIBITION. Exhibition of the Works of Industry of all Nations, 1851.
London : 1852Presentation edition, with a copy presented to every exhibitor at the Great Exhibition of 1851; trade editions were also produced. The book is a key contemporary document for the Exhibition, giving the jury awards and details of the thirty categories of exhibit, and was selected in Printing and the Mind of Man as the representative book for the Exhibition.... Learn More£1,750.00
Stock Code: 131571
BUNBURY, Charles James Fox. Life, Letters and Journals.
London : 1894First and sole edition of this highly uncommon memoir of the distinguished palaeobotanist Sir Charles James Fox Bunbury, eighth baronet (18091886), printed for private circulation among friends and relatives only. It includes a generous gathering of his letters and substantial selections from his journals, of which ODNB remarks, "few other journals... Learn More£1,650.00
Stock Code: 123689
HALE, Matthew. The Primitive Origination of Mankind, considered and examined According to The Light of Nature.
London : 1677First edition. The great jurist "argues for the creation of the human race by an intelligent agent; its arguments touch on numerous topics, including the impossibility of an infinite succession, the character of time and space, the demographic tendencies of modern England and of ancient Israel, and the unlikelihood of spontaneous generation in anything... Learn More£1,500.00
Stock Code: 100334
DARWIN, Charles. The Variation of Animals and Plants under Domestication.
London : 1868First edition, second issue (with the one-line erratum in volume I); 1,250 copies were published in February 1868 and the two issues have "considerable textual differences" (Freeman). "The term 'survival of the fittest' (borrowed at Wallace's insistence from Herbert Spencer's 1866 Principles of Biology) first appeared in the Variation and in the fifth... Learn More£2,000.00
Stock Code: 113772
MAUND, Benjamin. The Botanic Garden:
London : 1825-35An appealing run of one of the best known botanical periodicals of the 19th-century, comprising the first decade of the periodical's existence in its first five volumes; the entire series was eventually extended to 13 volumes and published up until 1851. Benjamin Maund (c.1790-1864) "sought to share his lifelong passion for flowers by producing an interesting... Learn More£1,250.00
Stock Code: 147430


text:
The Shawnee County Sheriff's Department is investigating allegations that a male student at Seaman High School has used nude photos of his female classmates to coerce and harass them via social media into sending him more nude photos of themselves.
Seaman Unified School District 345 superintendent Steve Noble confirmed the investigation to The Topeka Capital-Journal.
“The allegations are quite severe," Noble said. "The allegations are quite significant.”
He said the district is taking the allegations seriously.
“We are involved in an ongoing investigation," Noble said. "When allegations are brought forth that are severe and represent negative behavior, we take all of those allegations seriously. This particular instance is no different.”
Several Seaman High School students told The Capital-Journal that the student, who is a senior, obtained or attempted to obtain nude photos of between 50 and 100 female students at the school. They said they believe he began collecting photos of female classmates when he was a student at Seaman Middle School and, over the course of several years, began creating fake social media accounts to intimidate female students.
Students began to suspect the senior was behind the fake social media accounts two years ago. They say female students feel unsafe around him.
The Capital-Journal's policy is to attribute information to named sources. Students who spoke or communicated with The Capital-Journal asked that their names not be used out of fear of retaliation.
Noble said he was told that the alleged activity wasn't done on school-issued technology devices.
“It is my understanding that we don’t have any school property involved in this investigation,” he said.
Noble said Phil McKay, USD 345's director of security, filed a report with the sheriff's office in late September and that a report was filed at the same time with the Kansas Department of Children and Families.
“We have not received any word back on the results of those investigations,” Noble said.
Sheriff Herman Jones said late Tuesday the sheriff's office was working on the investigation with Seaman schools and its security.
Noble said he is aware of the allegations that a large number of female students feel unsafe around the male student but that school administrators have been following board of education-approved policies to deal with the situation since September.
“We want our parents to know and our kids to know that we try to create the safest environment for our students," Noble said. "That is our No. 1 goal. Everyone has a right to that and we expect that of ourselves.”
In a late September 2017 interview with The Capital-Journal regarding a student's threat made via social media toward the high school, McKay said social media can be a “good thing and a bad thing." He said threats made toward the school, staff or students, regardless of their nature, on social media “are looked into” by school administrators.
“Let’s not get into specifics but let’s say somebody gets something on their phone and they’re at school and then they bring it to the school,” he said. “So then the school looks into it to make sure whatever was said on social media isn’t true or, if it is, that they look into it. You know, so everybody is safe. Maybe it’s bullying or stuff like that.”
McKay said social media has made student interactions more challenging.
“It can also be a good thing because you have people who stay in contact with each other," he said. "As long as it’s used for that, that’s great. It’s when they step over the line where then we have to react on that to make sure whatever’s being said or whatever’s put out, we have a safe learning environment.”
Noble said he made the USD 345 board of education aware of the situation in early October, and the board discussed it in executive session during its Oct. 9 meeting.
Board members Fred Patton, Frank Henderson, Karl McNorton, Cherie Sage, Keith Griffin and James Adams confirmed Noble apprised them last fall of a since-deleted online petition about the student. They said Noble recently updated them, also in a group message, about since-deleted social media information referencing the situation. They said they want the investigations to progress.
Board member Christie Appelhanz said she couldn't immediately recall the initial information provided by Noble in the fall but stressed the issue needs a "swift response," given the number of students who feel unsafe at Seaman High School.
Contact reporter Angela Deines at (785) 295-1143 or @AngelaDeines on Twitter.


NP wanted to burn low-grade Rosebud coal (obtained from mines along the line) in their locomotives. This required the Yellowstone to be designed with a huge (the largest ever used on a steam locomotive) firebox (182 sq. ft.). The front half of the firebox was over the two rear pairs of drivers and the trailing truck (which was equipped with a booster).
It was the largest steam locomotive in the world (at that time) and ALCO celebrated by serving dinner to 12 people seated in the firebox! Remember, this was long before the Big Boys were even a thought. NP asked for bids for 11 more like it and in 1930 Baldwin got the job. The NP Yellowstones steamed poorly and produced less that 5,000 HP. NP found that the grates were simply too large to maintain a high temperature and complete combustion. The combustion problem was solved by blocking off The front two feet of the firebox on each locomotive. At some point the Z-5s were upgraded with roller bearings.
These were known as "Yellowstones" and gave the name to the wheel arrangement. The first engine (5000) was built by Alco-Schenectady and had works number 67578. Its adhesion weight came to 553,000 lb (2251,230 kg) and total engine weight amounted to 717,000 lb (325,226 kg). Maximum axle loading was 70,500 lb (31,978 kg). For some reason, this mostly Alco road then gave the production order to Baldwin.
Note the large firebox suitable for burning low-calorie "Rosebud coal." Valve motion limited cutoff of the 14" (356 mm) piston valves, which had a maximum travel of 7 1/2" (191 mm). When the original firebox proved too large to sustain a high-enough temperature and permit complete combustion of the fuel, the fix was installing a Gaines' wall two feet from the front of the firebox, effectively reducing the size of the grate, but increasing the interior temperature. The brick arch was to be located such that the area above the arch was at least 100% of the flue area. (For a full description of the Gaines combustion chamber's intended effect on combustion, see Locobase 4228.)
The Q&C "Nogroth" grate seems to have been a rosebud rocker design, intended "to burn sub-bituminous coal.". The 3/8" (9.5 mm) diameter hole provided air and the perforated plates rocked "both ways" with a 4 1/2" (114.5 mm) opening.
Three Nicholson thermic syphons in the firebox and two in the combustion chamber contributed 256 sq ft (23.8 sq m) to direct heating surface area. The combustion chamber itself added another 162 sq ft (15.05 sq m). The design also featured Type B Dupont Simplex stokers with a capacity of 20 short tons (18,144 kg) of coal per hour, Alco Type G power reverse gear, and a Coffin feedwater heater.
Tonnage rating over a ruling grade of 1.1% was 4,000 tons (3,636 metric tons). This class was rebuilt with Timken roller bearings in 1944, given a sturdier front frame, had steam leaks sealed, and run at a higher boiler pressure, producing 145,930 lb (66,193 kg) of tractive effort. The feed water heaters were removed in the late 1940s.
|Principal Dimensions by Steve Llanso of Sweat House Media|
|Railroad||Northern Pacific (NP)|
|Number in Class||11|
|Locomotive Length and Weight|
|Driver Wheelbase (ft / m)||16.75 / 5.11|
|Engine Wheelbase (ft / m)||66.66 / 20.32|
|Ratio of driving wheelbase to overall engine wheebase||0.25|
|Overall Wheelbase (engine & tender) (ft / m)||110.08 / 33.55|
|Axle Loading (Maximum Weight per Axle) (lbs / kg)||70,900 / 32,160|
|Weight on Drivers (lbs / kg)||558,900 / 253,513|
|Engine Weight (lbs / kg)||723,400 / 328,129|
|Tender Loaded Weight (lbs / kg)||402,000 / 182,344|
|Total Engine and Tender Weight (lbs / kg)||1,125,400 / 510,473|
|Tender Water Capacity (gals / ML)||21,200 / 80.30|
|Tender Fuel Capacity (oil/coal) (gals/tons / ML/MT)||27 / 24.50|
|Minimum weight of rail (calculated) (lb/yd / kg/m)||116 / 58|
|Geometry Relating to Tractive Effort|
|Driver Diameter (in / mm)||63 / 1600|
|Boiler Pressure (psi / kPa)||250 / 17.20|
|High Pressure Cylinders (dia x stroke) (in / mm)||26" x 32" / 660x813 (4)|
|Tractive Effort (lbs / kg)||145,930 / 66192.81|
|Factor of Adhesion (Weight on Drivers/Tractive Effort)||3.83|
|Firebox Area (sq ft / m2)||872 / 81.01|
|Grate Area (sq ft / m2)||182 / 16.91|
|Evaporative Heating Surface (sq ft / m2)||7673 / 712.84|
|Superheating Surface (sq ft / m2)||3219 / 299.05|
|Combined Heating Surface (sq ft / m2)||10,892 / 1011.89|
|Evaporative Heating Surface/Cylinder Volume||195.10|
|Computations Relating to Power Output (More Information)|
|Robert LeMassena's Power Computation||45,500|
|Same as above plus superheater percentage||59,150|
|Same as above but substitute firebox area for grate area||283,400|


text:
Band 8a Advanced Arrhythmia specialist nurse –12 month fixed term contract or secondment - 1.0 WTE (0.8 WTE would be considered for the right applicant).
This is a rare and exciting opportunity to work within the Electrophysiology (EP) team based at the Cardiac Centre, Morriston hospital, Swansea. We wish to appoint a Band 8a, advanced arrhythmia specialist nurse. We seek to appoint a dynamic and forward thinking individual who has a demonstrable history of leadership along with advanced skills and experience in managing patient cohorts who live with complex cardiac conditions.
The post holder will lead a small team of arrhythmia and cardio-genetic specialist nurses to provide high standards of care to a broad range of patients diagnosed with arrhythmias, inherited cardiac conditions and / or having complex cardiac devices. He/she will lead, inspire and evaluate innovative pathways of care and embrace diverse mediums of technology in the delivery of prudent and patient focussed care. In addition, he/she will lead on the delivery and evaluation of education programmes for patient groups, the public and professionals alike.
The successful candidate will have experience in presenting / teaching and have exceptional communication and motivational skills.
Prior to applying, applicants MUST have the agreement of their manager / Trust for secondment opportunity.
* Interview panel will include a patient / carer representative
The ability to speak Welsh is desirable for this post; Welsh and/or English speakers are equally welcome to apply.
For further details / informal visits contact:
Wendy ChurchouseBHF Clinical Nurse Specialist
Dr James Barry, Clinical lead / EP Consultant Cardiologist, or Dr Dewi Thomas / Dr Andre Margulescu, EP Consultant Cardiologists / 532969
Bank or payment details should never be provided when applying for a job. For information on how to stay safe in your job search, visit SAFERjobs.Report this job
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JACKSONVILLE, Fla. - WOKV’s oil expert tells us gas prices in Jacksonville are a little bit higher than this time last year, and he expects the upward trend to continue in the coming weeks.
“It might not be a bad idea to fill up today because I believe a week from now, prices may be very similar or slightly higher to where they are today,” says Patrick DeHaan with GasBuddy.com.
In the last week, prices have increased seven cents to today’s average of $3.45 for a gallon of gas in Jacksonville.
A report released Wednesday by the U.S. Energy Information Association says that gasoline inventories increased by 7.4 million barrels in the last week alone, which DeHaan says is significant.
“We’ll have to continue to watch that,” he says. “This is just the tip of the iceberg. But for the time being, it could mean lower prices in the next couple weeks.”
DeHaan believes we will only see slight increases in the coming week but nothing that he would deem significant.


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