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The authors state that they have no conflicts of interest.
Ultrastructural Properties in Cortical Bone Vary Greatly in Two Inbred Strains of Mice as Assessed by Synchrotron Light Based Micro- and Nano-CT †‡
Article first published online: 2 JUL 2007
DOI: 10.1359/jbmr.070703
Copyright © 2007 ASBMR
Journal of Bone and Mineral Research
Volume 22, Issue 10, pages 1557–1570, October 2007
Additional Information
How to Cite
Schneider, P., Stauber, M., Voide, R., Stampanoni, M., Donahue, L. R. and Müller, R. (2007), Ultrastructural Properties in Cortical Bone Vary Greatly in Two Inbred Strains of Mice as Assessed by Synchrotron Light Based Micro- and Nano-CT . J Bone Miner Res, 22: 1557–1570. doi: 10.1359/jbmr.070703
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Published online on July 2, 2007
Publication History
- Issue published online: 4 DEC 2009
- Article first published online: 2 JUL 2007
- Manuscript Accepted: 26 JUN 2007
- Manuscript Revised: 12 JUN 2007
- Manuscript Received: 19 DEC 2006
- Abstract
- Article
- References
- Cited By
- bone ultrastructure;
- canal network;
- osteocyte lacunae;
- μCT;
- nano-CT;
- synchrotron radiation;
- negative imaging;
- biomechanics
Nondestructive SR-based μCT and nano-CT methods have been designed for 3D quantification and morphometric analysis of ultrastructural phenotypes within murine cortical bone, namely the canal network and the osteocyte lacunar system. Results in two different mouse strains, C57BL/6J-Ghrhrlit/J and C3.B6-Ghrhrlit/J, showed that the cannular and lacunar morphometry and their bone mechanics were fundamentally different.
Introduction: To describe the different aspects of bone quality, we followed a hierarchical approach and assessed bone tissue properties in different regimens of spatial resolution, beginning at the organ level and going down to cellular dimensions. For these purposes, we developed different synchrotron radiation (SR)-based CT methods to assess ultrastructural phenotypes of murine bone.
Materials and Methods: The femoral mid-diaphyses of 12 C57BL/6J-Ghrhrlit/J (B6-lit/lit) and 12 homozygous mutants C3.B6-Ghrhrlit/J (C3.B6-lit/lit) were measured with global SR μCT and local SR nano-CT (nCT) at nominal resolutions ranging from 3.5 μm to 700 nm, respectively. For volumetric quantification, morphometric indices were determined for the cortical bone, the canal network, and the osteocyte lacunar system using negative imaging. Moreover, the biomechanics of B6-lit/lit and C3.B6-lit/lit mice was determined by three-point bending.
Results: The femoral mid-diaphysis of C3.B6-lit/lit was larger compared with B6-lit/lit mice. On an ultrastructural level, the cannular indices for C3.B6-lit/lit were generally bigger in comparison with B6-lit/lit mice. Accordingly, we derived and showed a scaling rule, saying that overall cannular indices scaled with bone size, whereas indices describing basic elements of cannular and lacunar morphometry did not. Although in C3.B6-lit/lit, the mean canal volume was larger than in B6-lit/lit, canal number density was proportionally smaller in C3.B6-lit/lit, so that lacuna volume density was found to be constant and therefore independent of mouse strain and sex. The mechanical properties in C3.B6-lit/lit were generally improved compared with B6-lit/lit specimens. For C3.B6-lit/lit, we observed a sex specificity of the mechanical parameters, which could not be explained by bone morphometry on an organ level. However, there is evidence that for C3.B6-lit/lit, the larger cortical bone mass is counterbalanced or even outweighed by the larger canal network in the female mice.
Conclusions: We established a strategy to subdivide murine intracortical porosity into ultrastructural phenotypes, namely the canal network and the osteocyte lacunar system. Nondestructive global and local SR-based CT methods have been designed for 3D quantification and subsequent morphometric analysis of these phenotypes. Results in the two different mouse strains C57BL/6J-Ghrhrlit/J and C3.B6-Ghrhrlit/J showed that the cannular and lacunar morphometry and the biomechanical properties were fundamentally different.
Osteoporosis is primarily a disease of bone fragility resulting from decreased bone mass. In addition, altered architectural arrangement of bone tissue and impaired bone quality leads to decreased skeletal strength and increased fracture risk.(1) BMD, a measure of bone mass, has been identified in several epidemiological studies as being the most important risk factor for osteoporotic fractures.(2,3) Nevertheless, the idea that BMD is the best predictor of fracture risk has become a controversial issue.(4) On an individual basis, density alone accounts for 10–90% of the variation in strength of trabecular bone.(5) This also means that 90–10% of the variation in strength cannot be explained by BMD.(6) Recent data have shown that predicting trabecular bone strength can be greatly improved by including microarchitectural parameters in the analysis.(7,8)
Further improvement in predicting bone strength can be achieved by considering additionally the cortical bone compartment. Whereas the focal point of hip fracture studies was on trabecular bone for the last decades, cortical bone contributes significantly to the mechanical strength of bone.(9,10) Moreover, regarding the stiffness of cortical bone, the influence of small changes in the amount or density of bone tissue is even more pronounced than similar changes would exert in trabecular bone.(11) Eventually, loss of cortical rather than loss of trabecular bone predominates in cases of proximal femur fracture,(12) which is among the most devastating of all osteoporotic fractures.(1) On this account, cortical bone tissue has been studied in more detail and cortical bone strength has been related primarily to BMD and other parameters, which describe cortical geometry.(13,14) However, BMD was reported to be related only weakly to the mechanical properties of cortical bone.(15) On the other hand, cortical geometry and particularly intracortical porosity has been shown already before to be linked to stiffness and strength of cortical bone specimens from human donors(16–18) and from different vertebrates.(16,19,20) Furthermore, intracortical porosity has been associated with fracture risk of patients with femoral neck fractures.(21) Changes in human femoral intracortical porosity have accounted for 76% of the reduction in bone strength,(22) and several other studies revealed the negative influence of increased intracortical porosity on fracture resistance.(23–25)
We therefore suggest studying cortical bone morphology in more detail as an important aspect of bone quality. To this end, we followed a hierarchical approach and assessed cortical bone tissue properties in different regimens of spatial resolution, beginning at the organ level and going down to the cellular domain. We especially focused on the porosity within cortical bone using synchrotron radiation (SR)-based μCT and nano-CT (nCT). In general, μCT is a convenient technique to study trabecular bone architecture and modeling because it allows nondestructive measurement of bone microstructure and quantitative evaluation of its 3D morphometric parameters.(26,27) With the advent of third-generation SR sources, CT in the micrometer range has become feasible and has been used to analyze trabecular architecture and local bone tissue properties.(28–30) Recent results show that the canal network is a major contributor to local tissue porosity,(31–33) and therefore, can directly be linked to measures of bone tissue quality and thus, to the mechanical properties of bone. Additionally, osteocyte lacunae are believed to act as stress concentrators within tissue of compact bone.(34)
The purpose of this study was to establish a strategy to subdivide murine intracortical porosity into 3D ultrastructural phenotypes, namely the canal network and the osteocyte lacunar system, and to provide methods to volumetrically quantify these phenotypes for subsequent morphometric analysis. In a second step, we applied this framework to the femoral mid-diaphyses of two genetically distinct mouse strains. Moreover, Beamer et al.(35) showed that there is a significant difference in BMD and BMC between the two inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H). Finally, these two mouse strains showed differences in several skeletal characteristics(35,36) and in response to mechanical loading.(37,38) On this account, B6 and C3H inbred mouse strains offer a good model for the analysis of the different phenotypes of bone and their influence on bone quality. Based on this knowledge, we performed mechanical tests on our mouse model to determine potential mouse strain and, for the first time, sex differences. This also allowed studying the relations between bone mechanics and morphometry on an organ and ultrastructural level.
In the long run, we believe that the morphometric analysis of the ultrastructural phenotypes and the study of bone phenotypes at different hierarchy levels, in conjunction with bone mechanics, will provide new insights in the assessment of bone quality.
Mouse model
To partition bone quality into its regulatory pathways, we chose a mouse model called little (C57BL/6J-Ghrhrlit/J), wherein regulation of bone morphometry is independent of growth hormone (GH) and insulin-like growth factor-I (IGF-I).(39) More precisely, the little mouse strain carries a mutation in the growth hormone–releasing hormone receptor (Ghrhr), resulting in undetectable circulating GH and serum IGF-I that is fixed at low, but detectable levels. For this study, we used homozygous mutant mice from the inbred strain C57BL/6J-Ghrhrlit/J (B6-lit/lit) and the congenic strain C3.B6-Ghrhrlit/J (C3.B6-lit/lit) that was created by backcrossing the little mutation from the original B6 background to C3H. The result of introgressing the little mutation onto the C3H background is that C3.B6-lit/lit mice have higher BMD than B6-lit/lit.(39) All mice were raised at The Jackson Laboratory, and all animal procedures were approved by the local authorities. On necropsy, femora were dissected and were stored in ethanol for further analysis.
Hierarchical bone model
Within this study, we followed a hierarchical description of the cortical bone matrix. For these purposes, we distinguished three levels on different length scales. On the organ level, cortical bone was considered to be compact and was characterized by its radial extension and volume distribution. On the tissue level and cellular level, we described the ultrastructure of the intracortical porosity. Whereas the tissue level was described by the cannular network, the osteocyte lacunar system constituted the cellular level. The cannular network will be introduced and defined properly in the subsection 3D quantitative morphometry that follows.
To acquire cortical bone tissue properties in distinct regimens of length scale (organ, tissue, and cellular level), different CT techniques were applied. In general, the organ and the tissue level encompasses the wide range of cortical and trabecular bone structure, which can be assessed by commercially available desktop μCT scanners at a spatial resolution in the order of 10 μm. Whereas the resolution of desktop μCT systems is sufficient to acquire the microstructure of trabecular bone, the ultrastructure of cortical bone is currently not accessible with this technique. For this reason, SR-based CT was adapted and further developed to assess the cortical bone matrix on the organ, the tissue, and the cellular level. Although it would be sufficient to assess the organ level by conventional desktop μCT systems, we restricted our study to the technique of SR CT to guarantee optimal conditions for comparison between the different hierarchy levels.
To study the organ and tissue level of the cortical bone, we scanned femoral mid-diaphyses from 12 B6-lit/lit (6 female and 6 male) and 12 C3.B6-lit/lit (6 female and 6 male) 4-mo-old mice using a conventional (i.e., global) SR μCT setup at a nominal resolution of 3.5 μm (Fig. 1). This cortical compartment started at 56% of the whole femur length (calculated from the greater trochanter) and contained 388 slices resulting in a stack height of 1.56 mm (Table 1). To study the cellular level, we applied local SR CT at a submicron resolution (700-nm nominal resolution); a technique we call nano-CT (nCT). In a local CT setup, the specimen is bigger than the recorded field of view (FOV) perpendicular to the rotation axis and therefore only a portion of the whole sample is assessed. This allows for high-resolution CT without destruction of the specimen. Because of the limited access to SR facilities, only two B6-lit/lit (one female and one male) and two C3.B6-lit/lit (one female and one male) femora were scanned locally, each at the anterior, posterior, lateral, and medial site of the mid-diaphysis. The FOV within the cortical bone assessed by the local SR nCT measurements was a subset of the FOV of the global SR μCT setup, so that the same cortical regions were imaged and corresponding ultrastructural morphometric parameters could be assessed.
The SR μCT and nCT measurements were performed in air at the X-ray Tomographic Microscopy (XTM) station of the Materials Science (MS) beamline at the Swiss Light Source (SLS).(40,41) For both setups, in total, 1001 projections were acquired over a range of 180° at a photon energy of 17.5 keV. The data were reconstructed using filtered backprojection. The parameters of the different CT techniques applied are summarized in Table 1.
Image processing
A new sinogram-based algorithm was devised to eliminate ring artifacts, which arose from defects on the scintillator of the optical system at the XTM station and which were clearly visible in the reconstructed slices. To partially suppress noise within the reconstructed tomograms, a Gaussian filter was applied. Subsequent iterative global thresholding(42) provided binarized data sets separating bone matrix from soft tissue and air.
For quantitative analysis of the bone tissue on the organ level, component labeling and morphologic operations were applied to the binarized data to obtain a solid representation of the mid-diaphysis. The technique of negative imaging was applied in this study to assess the porosity within cortical bone on the tissue and on the cellular level. In this context, negative imaging denotes the technique to first measure the matrix of a porous structure using CT, and subsequently, to extract the enclosed porosity as a negative imprint of the surrounding matrix. In this study, the extraction of the cortical void spaces comprised different image processing procedures (IPL; Scanco Medical, Bassersdorf, Switzerland), including morphological operators. They were optimized to extract the canal network and the osteocyte lacunar system within cortical bone as two separate phases. Additionally, the data sets of the canal network as assessed by global SR μCT was divided into four sections, corresponding to four main anatomical sites, the anterior, posterior, lateral, and medial quadrant of the mid-diaphysis, to analyze potential site-dependencies of the morphometric indices describing the canal network. Furthermore, this supplementary partition was essential for correlation analysis between the canal network obtained from global SR μCT measurements, which contained the entire cortical shaft and the osteocyte lacunar system acquired from local SR nCT measurements, which were restricted to a single anatomical site, because of the limited experimental FOV (Table 1).
3D quantitative morphometry
Organ level:
For morphometry on the organ level, standard 3D algorithms were used(43) to compute total tissue volume (TV) enclosing both the medullary cavity and the cortical bone tissue, cortical bone volume (Ct.BV), cortical bone volume density (Ct.BV/TV), cortical thickness (Ct.Th), and polar area moment (J).
Tissue level:
On the tissue level, the void spaces within cortical bone obtained by negative imaging formed cannular structures (Fig. 2). We believe that these cannular elements represent the living space of the vasculature and/or bone remodeling units (including osteoclast lacunae) within cortical bone. We name this phenotype canal network and we precede each corresponding parameter the designation canal or cannular. For quantification of the canal network, we introduced cannular indices, corresponding to standard nomenclature of bone morphometry(44) for trabecular bone and similar to the naming of cannular parameters motivated by Cooper et al.(33) Hence, we defined number of canals (N.Ca), canal number density (N.Ca/Ct.TV), canal volume (Ca.V), canal volume density (Ca.V/Ct.TV), and canal spacing (Ca.Sp), where Ct.TV designates the cortical total volume. These parameters describe the overall canal network and were quantified by standard morphometry as introduced for 3D trabecular bone analysis.(43) Moreover, the canal network was spatially decomposed into single elements and analyzed subsequently by using element-based morphometry as recently introduced.(45) For this reason, we further defined corresponding element-based indices, which are given as mean values over the total number of elements (marked with brackets 〈 〉). Among those averaged indices were mean canal volume (〈Ca.V〉), mean canal diameter (〈Ca.Dm〉), mean canal length (〈Ca.Le〉), and mean canal orientation (〈Ca.θ〉) in relation to the femoral long axis. An illustration on how these parameters are defined is given in Fig. 3. All cannular indices were computed in 3D space without any model assumptions. In addition to the analysis for the complete mid-diaphyseal cortex, the cannular indices were computed separately for the anterior, posterior, lateral, and medial sites as well. These data were a requisite for later correlation analysis between the cannular and lacunar morphometric outcome.
Cellular level:
On the cellular level, the negative imprint of the cortical bone formed—additionally to the canal network—a cellular system (Fig. 4). Figure 4 identifies the cellular void spaces as osteocyte lacunar system. A number of osteocyte lacunar indices were introduced in analogy to standard morphometry, including number of lacunae (N.Lc), lacuna number density (N.Lc/Ct.TV), lacuna volume (Lc.V), and lacuna volume density (Lc.V/Ct.TV). Moreover, we introduced the element-based mean lacuna volume as the ratio 〈Lc.V〉 = Lc.V/N.Lc.
Biomechanical tests
For mechanical testing, we included an additional set of femoral mid-diaphyses from 12 B6-lit/lit (6 female and 6 male) and 12 C3.B6-lit/lit (6 female and 6 male) 4-mo-old mice. Before testing, the bones were rehydrated for 24 h in PBS. After a preload of 1 N, the mouse femora were loaded to failure in the anterior-posterior direction by three-point bending, using a custom-made loading device with a support distance of 5 mm, which was integrated in a materials testing machine (1456; Zwick, Ulm, Germany). The femora were positioned so that the load was applied at 56% of the whole femur length (calculated from the greater trochanter), which corresponds to the femoral height where the SR CT measurements were performed. During three-point bending, the femora were lying freely and load-displacement curves were recorded at a cross-head speed of 0.5 mm/s.(36) Ultimate force (Fu), work to failure (U), and stiffness (S) were calculated from the load-displacement curve as described elsewhere.(46)Fu indicates the strength of the bone, whereas S reflects resistance to elastic deformation, and U is the required energy to initiate a fracture.
Statistical analysis
For statistical analysis, the GNU statistical package R (Version 2.4.1, http://www.r-project.org) was used. The SR CT measurements on the organ and tissue hierarchy level comprised B6-lit/lit (6 female and 6 male) and C3.B6-lit/lit (6 female and 6 male) mice and consequently, our experimental setup represented a 2 × 2 factorial design, implying the two-level independent variables mouse strain (B6-lit/lit, C3.B6-lit/lit) and sex (female, male). A two-way ANOVA was performed to test for significances (p < 0.05). Additionally, to examine and discuss the behavior of the cannular indices, for which the interaction of the independent variables mouse strain and sex was not clear, they were compared by interaction plots. Finally, to inspect if the cannular indices were dependent on the anatomical site, a two-way ANOVA was applied to the factors site (anterior, posterior, lateral, and medial) and sex (female, male), and Tukey's honestly significant difference (HSD) procedure was performed subsequently for pairwise comparisons among site means as a posthoc analysis. On the cellular level, two B6-lit/lit (one female and one male) and two C3.B6-lit/lit (one female and one male) femora were scanned at the anterior, posterior, lateral, and medial sites of the mid-diaphysis. The primary osteocyte lacunar indices (N.Lc, Lc.V, and corresponding Ct.TV) were summed up over all sites (anterior, posterior, lateral, and medial) for the calculation of the lacunar ratios N.Lc/Ct.TV, Lc.V/Ct.TV, and 〈Lc.V〉 = Lc.V/N.Lc. No further statistics were performed for the cellular level because only one animal per mouse strain and sex was measured on this hierarchy level. Linear regression analysis was performed between all morphometric indices to test for linear relationships. Finally, for three-point bending, the biomechanical parameters Fu, U, and S were compared between the two mouse strains (B6-lit/lit and C3.B6-lit/lit) and among the two sexes (female and male) within the mouse strains using multiple unpaired t-tests, where differences were considered statistically significant at p < 0.05 after Bonferroni correction.
3D ultrastructural imaging and quantitative morphometry
Following our hierarchical approach on different regimes of spatial resolution, we present in a first step the morphometrical results for the cortical bone compartment (Table 2), for the canal network (Tables 3 and 4), and for the osteocyte lacunae (Table 5). In a second step, correlations between the morphometric parameters on the organ, tissue, and cellular level will be discussed (Tables 6 and 7).
Organ level:
The cortical indices summarized in Table 2 represent the morphometry results on the organ level. ANOVA of these indices identified the mouse strain as the only significant effect, with p < 0.001. One exception was Ct.BV/TV, where sex had a significant influence on the absolute values. Groupwise unpaired t-tests with Bonferroni correction located a significant difference (p < 0.05) between female and male C3.B6-lit/lit, whereas Ct.BV/TV of B6-lit/lit specimens were not affected by sex. We observed that the morphometry of the two mouse strains was dissimilar already on the organ level or more precisely, that the femoral mid-diaphysis of C3.B6-lit/lit animals was larger in comparison with B6-lit/lit mice (cf. Fig. 1). This finding was supported by the fact that cortical bone volume density (Ct.BV/TV) and cortical thickness (Ct.Th) were significantly (p < 0.001) larger for C3.B6-lit/lit compared with B6-lit/lit (Table 2).
Tissue level:
On the tissue level, negative imaging allowed visualizing the canal network within cortical bone (Fig. 2). The morphometric results for the canal network are summed up in Table 3. Canal spacing (Ca.Sp) and mean canal diameter (〈Ca.Dm〉) were significantly higher in C3.B6-lit/lit compared with B6-lit/lit. In agreement with the larger Ca.Sp, canal number density (N.Ca/Ct.TV) was lower in C3.B6-lit/lit mice; however, this was not significant (p = 0.060). For these three indices, only the factor mouse strain had significant explanation power. All other cannular indices revealed a significant and disordinal interaction between mouse strain and sex (Table 3). For canal volume density (Ca.V/Ct.TV), mean canal volume (〈Ca.V〉), and mean canal length (〈Ca.Le〉), mouse strain and sex were both significant factors. On closer examination, these three indices showed the same interaction behavior, as it is exemplified for 〈Ca.V〉 in Fig. 5. In particular, Ca.V/Ct.TV, 〈Ca.V〉, and 〈Ca.Le〉 were independent of sex for B6-lit/lit mice, but were different for female and male C3.B6-lit/lit mice (cf. Fig. 5). Thus, there is no real cross-over in the interaction plots, and accordingly, the interaction shall be classified as ordinal. To abstract these results, we can state that first Ca.V/Ct.TV, 〈Ca.V〉, and 〈Ca.Le〉 were larger for C3.B6-lit/lit compared with B6-lit/lit mice, and second, that for B6-lit/lit specimens, these indices were independent of sex. In contrast, the mean canal orientation (〈Ca.θ〉), which describes the spatial arrangement of the cannular branches, was found to be dependent on mouse strain and sex (truly disordinal interaction), meaning that it must always be considered separately for mouse strain and sex. Canal branching occurred only rarely and bifurcation of the cannular network was the exception, rather than the normal case. Moreover, the canals delineated a cone around the femoral long axis described by 〈Ca.θ〉, whereas single canals running parallel or perpendicular were observed only rarely. Finally, cannular indices were calculated for the different anatomical sites (anterior, posterior, lateral, and medial) and are listed in Table 4. Because a two-way ANOVA for the factors site and sex did not show any interaction, female and male specimens were pooled for the different sites. The question if the cannular indices do depend on the anatomical site was decided by Tukey's HSD pairwise comparisons among site means for the two mouse strains B6-lit/lit and C3.B6-lit/lit. Those site means, which were significantly different (p < 0.05) from at least one other site, are printed in bold in Table 4. According to Table 4, the element-based indices 〈Ca.V〉, 〈Ca.Dm〉, and 〈Ca.Le〉 are independent of the site, whereas the mean canal orientation (〈Ca.θ〉) was site-dependent for C3.B6-lit/lit and partly for B6-lit/lit. This is shown in Fig. 6, where the canal network within the anterior (A) and posterior (B) cortical bone of a C3.B6-lit/lit mouse femur is displayed. The cannular branches are bent more toward the femurs longitudinal axis for the posterior site compared with the anterior site. With the exception of Ca.Sp for B6-lit/lit, the overall morphometric indices were all dependent on the site, including N.Ca/Ct.TV and Ca.V/Ct.TV. This is particularly pronounced for B6-lit/lit, where the maximal N.Ca/Ct.TV and Ca.V/Ct.TV identified at the anterior site were a multiple of the minimal cannular densities detected at the posterior site. In contrast, only moderate site differences in N.Ca/Ct.TV and Ca.V/Ct.TV were found for C3.B6-lit/lit.
Cellular level:
Figure 4 shows the canal network and the osteocyte lacunar system within the murine cortical femoral bone as assessed by the nCT approach. The abundance of cell spaces in the cortex deserves closer attention. These osteocyte lacunae were mostly plate-like ellipsoids, oriented mainly in the longitudinal direction of the femur. The morphometric analysis for the lacunar indices is given in Table 5. For the cell space analysis, it must be noted that in C3.B6-lit/lit, the mean lacuna volume (〈Lc.V〉) was larger than in B6-lit/lit. On the other hand, lacuna number density (N.Lc/Ct.TV) was proportionally smaller in C3.B6-lit/lit, so that there is more bone matrix per osteocyte lacuna compared with B6-lit/lit mice, whereas sex seemed to have no influence on the actual numbers. This led to a lacuna volume density (Lc.V/Ct.TV) that was constant at 1.3% for both mouse strains (and both sexes). This is in contrast to volumetric canal density (Ca.V/Ct.TV), which was much larger in C3.B6-lit/lit compared with B6-lit/lit.
Correlation (Tables 6 and 7) showed that all parameters describing the overall cannular morphometry scaled significantly with bone size, i.e., with cortical thickness (Ct.Th) and cortical bone volume (Ct.BV). Among those are canal volume (Ca.V), number of canals (N.Ca), and their corresponding densities Ca.V/Ct.TV and N.Ca/Ct.TV. On the other side, parameters describing basic structural elements such as mean canal volume (〈Ca.V〉) and mean lacuna volume (〈Lc.V〉) were unaffected by size and rather constant. Nevertheless, they were unique per mouse strain. This was corroborated by the finding that strong correlations were detected between number of lacuna (N.Lc) and lacuna volume (Lc.V) (R ≥ 0.83) as well as between N.Ca and Ca.V (R ≥ 0.89) for both B6-lit/lit and C3.B6-lit/lit mice. In general, no linear relations between the morphometric indices describing the osteocyte lacunae and bone size have been observed.
The mechanical parameters assessed from three-point bending are given in Table 8. First, Fu, U, and S were all significantly different for the two different mouse strains as is shown representatively for Fu in Fig. 7. Second, there were no significant differences found between female and male specimens for B6-lit/lit mice (Table 8). However, in the case of C3.B6-lit/lit, ultimate force (Fu) and work to failure (U) were significantly increased in male specimens compared with female mice (Fig. 7). The same trend was observed for the stiffness (S) of C3.B6-lit/lit mice, although the sex difference was not statistically significant.
3D ultrastructural imaging and quantitative morphometry
Organ level:
Femoral mid-diaphysis of C3.B6-lit/lit is larger compared with B6-lit/lit mice.
In this study, quantitative morphometry on the organ level showed that the femoral mid-diaphysis of C3.B6-lit/lit was larger compared with B6-lit/lit mice, reflecting the increased volume density (Ct.BV/TV) and cortical thickness (Ct.Th) for C3.B6-lit/lit specimens. Similar differences were previously shown by Beamer et al.(35) between the two inbred mouse strains C3H and B6, where C3H mice were reported to exhibit greater total femur density and thicker mid-diaphyseal cortex. Therefore, B6-lit/lit and C3.B6-lit/lit appear to be good models for a high and low bone mass mouse, respectively, similar to B6 and C3H. Moreover, we showed—in line with our previous work(39)—that Ct.BV/TV of females was significantly increased for C3.B6-lit/lit in comparison with males, which is in contrast to B6-lit/lit mice, where all morphometric indices on the organ level were independent of sex. In other words, we could verify a sex specificity of Ct.BV/TV for our little mouse strain, whereas for other mouse models, the direct effect of sex steroids on bone, which is independent of IGF-I, can in general not easily be discerned.(39)
Tissue level:
Cannular indices for C3.B6-lit/lit are generally larger compared with B6-lit/lit mice.
On the tissue level, the cortical bone ultrastructure has been often characterized by intracortical porosity. The intracortical femoral porosity of rats at different sites was found to be increased by several factors, such as immobilization,(47) ovariectomy,(48) and treatment with IGF-I.(49) For wildtype Swiss Webster mice, the intracortical porosity of vertebral bone has been assessed recently by bone histomorphometry(50) and accounted for 0.8–1.2% of the cortical bone extension. In this study, we showed that the canal network and the osteocyte lacunar system together (i.e., the intracortical porosity accessible with our techniques) occupied 1.5–1.8% of the cortical bone extension (Tables 3 and 5). However, we always disentangled the intracortical porosity into the canal network and the osteocyte lacunar system for the whole study and quantified these two ultrastructural phenotypes separately. To our knowledge, the canal network within cortical human bone was quantified only once in 3D by Cooper et al.,(33) using a μCT system at 10-μm nominal spatial resolution and subsequent negative imaging for the canal extraction. Using a combination of SR CT measurements, negative imaging, and direct morphometric 3D methods, Martín-Badosa et al.(51) quantified the porosity and the pore diameter within the distal femoral diaphysis of B6 and C3H mice. Because these authors fixed the nominal resolution at 6.65 μm, osteocyte lacunae were beyond the resolution limit, and the porosity was exclusively a manifestation of the canal network. Given that, according to our results, the mean canal diameter (〈Ca.Dm〉) of femoral murine bone is <10 μm (cf. Table 3), the canal network assessed in the study of Martín-Badosa et al. was partly disconnected and was reduced to bigger canals only. In this study, the cannular indices for C3.B6-lit/lit were generally larger compared with B6-lit/lit mice. Whereas for B6-lit/lit, all cannular indices were independent of sex, Ca.V/Ct.TV, 〈Ca.V〉, and 〈Ca.Le〉 each depended similarly and significantly on sex for C3.B6-lit/lit, as shown representatively for 〈Ca.V〉 in Fig. 5. It is interesting to note that, although Ct.Th and Ct.BV vary for the different anatomical sites within the diaphysis (data not shown), 〈Ca.V〉, 〈Ca.Dm〉, and 〈Ca.Le〉 describing basic elements of the canal network within the cortical bone are independent of site, and therefore, do not scale with bone size (cf. Fig. 6). This is consistent with our correlation results where parameters describing basic elements, such as mean canal volume (〈Ca.V〉) and mean lacuna volume (〈Lc.V〉), were unaffected by size. On the other hand, 〈Ca.θ〉 and the cannular densities N.Ca/Ct.TV and Ca.V/Ct.TV were site-dependent. Especially, the respective 5-fold and 4-fold difference in N.Ca/Ct.TV and Ca.V/Ct.TV between the anterior and posterior site in B6-lit/lit specimens is noteworthy. An analog site-dependency in Ca.V/Ct.TV or nonlacunar porosity was discovered by Skedros et al.(52,53) in mid-diaphyseal ulnas of immature turkeys, where no secondary osteons were detected. There, the cortical octants with the lowest nonlacunar porosity corresponded to the bone region where compression occurs during the normal wing-flapping cycle.(54) No information on habitual loading of the mouse femur diaphysis in vivo is available. Nevertheless, if we assume that the strain distributions within the femoral mid-diaphysis in mice and dogs(55) are comparable, we can conclude that for B6-lit/lit the anterior site with predominant tensile strains and the posterior site with prevalent compressive strains correspond to regions with high and low cannular densities for N.Ca/Ct.TV and Ca.V/Ct.TV, respectively.
Cellular level:
The lacuna volume density is independent of mouse strain and sex.
As for the canal network, the known facts relating to osteocytes and osteocyte lacunae are mainly based on microscopical analysis of histological bone sections and are therefore intrinsically 2D. Quantitative information respecting the 3D osteocyte lacunar system within murine cortical bone is rare and has been assessed thus far using confocal laser scanning microscopy (CLSM).(56) Nevertheless, quantitative analysis in 3D remains challenging because CLSM introduces image artifacts, such as signal attenuation with increasing depth or image distortion caused by the sample refractive index mismatch.(57) However, osteocytes and osteocyte lacunae have been characterized manifold since Frost developed the methodology for dynamic bone histomorphometry. For example, Mullender et al. estimated the cortical osteocyte number density (N.Lc/Ct.TV) in humans(58) and rats(59) to be around 10,000·mm−3 and 90,000·mm−3, respectively. In this study, which is focused on murine specimens, we located N.Lc/Ct.TV between 50,000·mm−3 and 70,000·mm−3 (Table 5). We observed that the osteocyte lacunae are mostly plate-like ellipsoids. Similarly, but based on CLSM measurements in human femoral bone tissue specimens, McCreadie et al.(60) reported that an ellipsoidal model is appropriate for modeling lacunae. The reported values we found in the literature for osteocyte lacuna size of different species are mainly interpolations of 2D data but correspond in the order of magnitude to the values of ∼200–300 μm3 for the mean lacuna volume of our murine bone specimens (Table 5). In comparison, Wang et al.(61) reported on mean lacuna volumina in the range of 200–700 μm3 within the tibial proximal diaphysis of B6 mice, where CLSM in conjunction with a prolated spheroid model for osteocyte lacunae has been used for quantitative morphometry.
In our experiments, the volumetric density of the mid-diaphyseal intracortical canal network (Ca.V/Ct.TV) was positively related with bone size (both Ct.Th and Ct.BV) for both mouse strains (Tables 6 and 7). On the other hand, lacuna volume density (Lc.V/Ct.TV) was constant at 1.3% and consequently independent of mouse strain and sex, at varying mean lacuna volume (〈Lc.V〉) and lacuna number density (N.Lc/Ct.TV) (Table 5). No consistent relation between the lacunar indices and anatomical site could be established. Because only two mice from each mouse strain were analyzed at each single site on the cellular level, we were not able to conclusively answer the question whether there were any site-dependencies of the lacunar indices. However, it is noteworthy that mice with the larger cortices (Ct.Th of C3.B6-lit/lit compared with B6-lit/lit) have a lower lacuna density, similar to findings of Jordan et al.(62) and Borton et al.(63) for mice and men, respectively. This might imply that individual osteoblasts formed more bone before being incorporated into the mineralized tissue. In general, it was proposed that bone resorption and bone remodeling maintain the cell density within a normal range(64) and that, under circumstances where cell and lacuna size and number are not well controlled, lacuna density may have a significant effect on bone matrix stiffness(65) and risk of bone fracture.(64)
Scaling rule:
Overall cannular morphometry scales with bone size and lacunar morphometry does not.
We derived a scaling rule for the canal network and the osteocyte lacunar system. To state explicitly, Ca.V, N.Ca, and their corresponding densities Ca.V/Ct.TV and N.Ca/Ct.TV, all scaled positively with bone size (Ct.Th and Ct.BV). In contrast, 〈Ca.V〉, 〈Ca.Dm〉, and 〈Ca.Le〉 characterizing basic element dimensions of the cannular network, as well as all morphometric indices quantifying the osteocyte lacunae did not scale with bone size.
In contrast to the femoral midshaft of the wildtype mouse strains B6 and C3H,(36) ultimate force (Fu), work to failure (U), and stiffness (S) of the little specimens were all reduced because of an overall reduction in bone size. Nevertheless, C3.B6-lit/lit showed statistically significant increased mechanical properties versus B6-lit/lit specimens, very similar to the increased mechanical parameters in C3H compared with B6.(36) In the same way, reduced bone size and density, represented by smaller Ct.BV, Ct.Th and Ct.BV/TV (Table 2), can account for lowered strength, rigidity, and work to failure, or in particular, can explain why B6-lit/lit specimens are mechanically inferior to C3.B6-lit/lit mid-diaphyseal femoral bones. Because for C3.B6-lit/lit mice, Ct.BV/TV was significantly reduced for males compared with females (Table 2), we would now expect decreased mechanical characteristics for male C3.B6-lit/lit. However, this could not be seen in our three-point bending results, where all mechanical parameters were found to be increased in male specimens compared with female mice. Consequently, the biomechanical results cannot be explained by considering exclusively bone phenotypes on the organ level. Here, we suggest including the tissue level, or in our case the canal network, for the discussion of the mechanical results. Where for B6-lit/lit, all cannular indices were independent of sex, the morphometric indices Ca.V/Ct.TV, 〈Ca.V〉, and 〈Ca.Le〉 were greater for females in comparison with males in the C3.B6-lit/lit mouse strain (cf. Fig. 5). Consequently, there is evidence that for C3.B6-lit/lit, the larger cortical bone mass is counterbalanced or even outweighed by the larger canal network in the female mice, leading to increased porosity and eventually to decreased mechanical parameters.
Study limitations
As a caveat for this study, it must be mentioned that rodent bones, unlike those of higher mammals, rarely undergo intracortical remodeling. Therefore, direct comparison between the canal network in mice cortices and that in human bone might be misleading. In the mouse, cortical bone is considered to be unchanged since the time the bone was originally formed, whereas in humans, cortical bone is extensively remodeled over time. Although these results showed extensive canal void spaces in the cortical diaphysis of the mouse, this model clearly fails to show osteonal structures as we can find them in humans and other larger mammals. However, we are convinced that the insight gained into the ultrastructure and biomechanics of murine bone provides the requisite framework for genetic studiess in mice dedicated to a better understanding of the hierarchical structural organization in the cortex and its contribution to the mechanical behavior of bone.
To our knowledge, this is the first study investigating quantitatively the ultrastructural cortical bone morphometry of mice in 3D and in a fully nondestructive fashion. Murine intracortical porosity has been disentangled into the canal network and the osteocyte lacunar system, as two ultrastructural phenotypes of (murine) cortical bone. Global and local SR-based CT methods have been designed for quantification and morphometric analysis of these phenotypes. The advantage of SR CT is primarily its high spatial resolution, opening the ultrastructure of bone for nondestructive and 3D assessment, currently not accessible with conventional μCT desktop systems. New morphometric indices have been devised and applied for quantitative characterization of the canal network and the osteocyte lacunar system in the mid-diaphyseal femoral cortex of the two genetically distinct mouse strains B6-lit/lit and C3.B6-lit/lit. Moreover, these little mouse strains seem to be a good model for high and low bone mass, and in addition, for sex differences independent of GH and IGF-I. Their bone mechanics has been described and successfully related to the morphometry on the organ and the ultrastructural level. We believe that the morphometric analysis of the ultrastructural phenotypes and the study of the relationships between phenotypes of bone at different hierarchy levels will provide new insights in the assessment of bone quality on all levels of bone hierarchy. In particular, we hypothesize that the prediction of bone mechanics can be improved in certain diseases and genetic predispositions by including ultrastructural bone tissue properties, such as the canal network and the osteocyte lacunar system.
The authors thank Stefan Heinzer for help during the preparation of the manuscript. This study was supported by the Swiss National Science Foundation through the SNF Professorship in Bioengineering (FP 620–58097.99 and PP-104317/1) and by the U.S. Department of the Army (DAMD 17–01–1–0808).
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The expanding world of conscious cinema where innovative films linked with interactive programs, workshops and experiences activate the senses and create action are the underpinnings of the first U.S.... (more...)
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Extracted: How the Quest for Mineral Wealth is Plundering the PlanetPaperback
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- Publisher: Chelsea Green Publishing Co
- Format: Paperback | 368 pages
- Dimensions: 152mm x 226mm x 23mm | 499g
- Publication date: 16 May 2014
- Publication City/Country: White River Junction
- Illustrations note: Black and White, 50 images
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As we dig, drill, and excavate to unearth the planet s mineral bounty, the resources we exploit from ores, veins, seams, and wells are gradually becoming exhausted. Mineral treasures that took millions, or even billions, of years to form are now being squandered in just centuries or sometimes just decades. Will there come a time when we actually run out of minerals? Debates already soar over how we are going to obtain energy without oil, coal, and gas. But what about the other mineral losses we face? Without metals, and semiconductors, how are we going to keep our industrial system running? Without mineral fertilizers and fuels, how are we going to produce the food we need?Ugo Bardi delivers a sweeping history of the mining industry, starting with its humble beginning when our early ancestors started digging underground to find the stones they needed for their tools. He traces the links between mineral riches and empires, wars, and civilizations, and shows how mining in its various forms came to be one of the largest global industries. He also illustrates how the gigantic mining machine is now starting to show signs of difficulties. The easy mineral resources, the least expensive to extract and process, have been mostly exploited and depleted. There are plenty of minerals left to extract, but at higher costs and with increasing difficulties.The effects of depletion take different forms and one may be the economic crisis that is gripping the world system. And depletion is not the only problem. Mining has a dark side pollution that takes many forms and delivers many consequences, including climate change. The world we have been accustomed to, so far, was based on cheap mineral resources and on the ability of the ecosystem to absorb pollution without generating damage to human beings. Both conditions are rapidly disappearing. Having thoroughly plundered planet Earth, we are entering a new world. Bardi draws upon the world s leading minerals experts to offer a compelling glimpse into that new world ahead."
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Although Ugo Bardi s fine book focuses on extraction, it also discusses geological formation of minerals and ores, mining, metallurgy, coinage of precious metals, debt, waste, pollution, climate change, and the dark side of mining. Interspersed are short digressions written by other experts on related topics ranging from soil fertility and plants as miners, to peak oil and coal, and the Hubbert depletion curve. The book is clearly written and insightful. Highly recommended! --Herman Daly, author of Ecological Economics;professor emeritus, School of Public Policy, University of Maryland"


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One major problem with politics -- as we've all probably figured out by now -- is that politicians view every human challenge as political in nature, meaning, particularly these last few years. Objective No. 1 in the political trade is sticking to it The Other Party.
What else could explain Democratic obstinacy and obfuscation over offshore oil drilling? The national interest certainly couldn't explain it.
A basic principle of oil exploration is that you look for oil where it is, instead of where you'd like it to be. Assuming, in the Democrats' case, there's any place they would like it to be.
When, over the weekend, Speaker Nancy Pelosi announced she was ready to let the House consider expanded offshore drilling, she had to do so in the context of whamming the Bush administration, which, she alleged, "has increased our dependence on foreign oil, damaged our economy and left consumers paying record prices at the pump."
We all may be assured of one thing: The speaker herself isn't interested in finding oil. Her recent claim -- "I'm trying to save the planet" (by keeping drillers away from offshore waters) -- has less to do with securing stable energy supplies than with helping guide the Democrats to absolute control over Washington, D.C. The nation's need for energy can wait a bit. First, we have to kick a few more Republicans in the pants.
The speaker's offer to "consider opening portions of the Outer Continental Shelf for drilling" comes to us accompanied by language about "appropriate safeguards" -- whatever "appropriate" means to a congressional committee -- and repudiation of "taxpayer subsidies to big oil." (That entire countries -- e.g., Russia, Iran, Venezuela and Saudi Arabia -- constitute "big oil" in a special and dangerous sense is a thought one guesses the speaker wouldn't utter under torture.)
The speaker's turnaround on "considering" offshore drilling likely has more to do with voter anger over high gasoline prices than with sudden recognition that, oops, it's time to increase domestic oil supplies.
Demagoguery -- note the Greek origins of the word -- has been with us always: an indestructible part of our Edenic inheritance. A self-styled leader of "the people" wants power. He -- or she -- pumps the voters up, promising to bring down the bad guys and raise up the good ones. Him -- or her -- for instance.
Unbelievable: Students Back Deporting Americans in Exchange for Illegal Immigrants | Sarah Jean Seman
MRCTV Discovers That 'Principle Is More Important' Than Fact At Black Lives Matter Rally | Matt Vespa


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Extron Announces VTG 400DVI Video and Audio Test Generator Now Shipping
Anaheim, California (April 16, 2009) – Extron Electronics is pleased to announce that the VTG 400DVI is now shipping. The VTG 400DVI is a professional quality Video and Audio Test Generator for setting up, testing, calibrating, and troubleshooting today's complex video and audio systems. lt offers DVI output for use with digital display devices, and delivers accurate, full bandwidth video signal reproduction and high performance audio test signals. In addition to DVI, analog high resolution computer-video, component video, S-video, and composite video are supported. When used with DVI devices, the VTG 400DVI will display the native resolution whenever new EDID data is received. The VTG 400DVI also offers Scope-Trigger, a patented feature that enables analysis of a specific area within the pattern image using an oscilloscope.
"The VTG 400DVI is a professional-quality reference tool with powerful capabilities that enable proof of performance for commissioning and testing A/V systems," says Lee Dodson, Vice President of Marketing for Extron Electronics. "By including the DVI output signal on the VTG 400DVI, we can now support devices and systems that use this popular digital video format."
The VTG 400DVI offers 34 video test patterns, several with adjustable levels, and seven audio test reference signals with selectable frequencies and output levels. A total of 113 output rates are pre-programmed for high resolution computer-video, HDTV, 16:9, plasma, and RGB, as well as standard definition component video, S-video, and composite video. An intuitive control panel allows for quick and easy access to video or audio test signals and settings. The VTG 400DVI can be programmed and upgraded with new test patterns and custom scan rates through the RS-232 port using the included Extron control software. Versatile and lightweight, the VTG 400DVI is appropriate for field and bench testing, or permanent installation in integrated A/V systems.
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سكس فديو نيك Many styles of Philippine music uses 8 notes or the European way of music because Philippines was colonized by Spain.Google for `open web proxy` as well. سكس فديو نيك whenever she looks at you, lick your lips constantly, that`ll make her want to kiss you even more {she`s tryin to hold back}. I never recorded them, but remembered a few jokes here and there that always made me laugh. سكس كرتون جيمي نيوترون Simply brush your lips lightly across the crown of their head.
The driver`s prediction is called the dial-in and is posted on the race car. سكس بز طيز The piston in a racing engine has a large diameter for the engine size, and it goes up and down a relatively short distance on each cycle. Lick Kiss - Just before kissing, gently run your tongue along you partners lip whether it be the top or bottom one depending on the position of your lips.
Asian music most often uses the pentatonic scale. سكس وغتصاب These tend to be the shows that are original stories, but the vast majority are pitched by the sponsors, which could be the manga publisher, who`s out to use the anime to promote merchandise or the original manga, or a media company like Media Factory or Geneon Japan or Bandai Visual, who are interested in using the TV broadcast to promote the eventual DVD release. The story of spear-wielding bodyguard Balsa`s efforts to protect a young prince from dangers both natural and supernatural has some technical flaws, but its storytelling strength is also more than enough to outweigh its weaknesses. سكس فديو نيك The grand prize winner will also receive an all expenses paid trip to Japan - home of Cosplay.


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The Narcissistic Personality Inventory
Their result for The Narcissistic Personality Inventory ...
Your Narcissism Score is 12!
According to Psychologists, the average narcissism score is 15.3 -- or 17.8 for celebrities.For more information, check out the article on Wikipedia.
Their Analysis (Vertical line = Average)
They scored 12% on Narcissism, higher than 41% of your peers.
They scored 4% on Authority, higher than 48% of your peers.
They scored 2% on Self-sufficiency, higher than 31% of your peers.
They scored 3% on Superiority, higher than 54% of your peers.
They scored 0% on Exhibitionism, higher than 20% of your peers.
They scored 1% on Exploitativeness, higher than 15% of your peers.
They scored 1% on Vanity, higher than 25% of your peers.
They scored 1% on Entitlement, higher than 16% of your peers.
All possible test results
The Super Pure One
According to Psychologists, the average narcissism score is 15.3 -- or 17.8 for celebrities.For more information, chec... Read more
Recent Results
smiling_skeptic55 / m / Straight
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Jerry Sexton, 44, former owner of Sexton Chevrolet in Manteca, was found dead in his home Tuesday morning. It is believed that he died sometime Monday night resulting from a fall. He was found at about 9 a.m. Tuesday.
As a Realtor, Marcy Hanson didn't have a whole lot of options when the housing market took a dramatic downward spiral.
It was a complete pork dinner for the senior citizen community Friday night at just $3 a plate at what is being called "Seniors Night Out."
Developing Manteca's strategies for encouraging affordable housing is the end goal of a workshop this Thursday.
Please don't play golf in the cemetery.
Devin Tailes – a.k.a Devin Starr or just plain old Dev – is a young lady on a mission.
• Charges were related to child custody: David Blancarte, 48, who was taken into custody on an outstanding warrant March 13, did not have any domestic violence charges associated with the $20,000 contempt of court warrant for his arrest as had been reported in the March 14 edition of the Bulletin.
It was a discussion about dogs in heat.
Three Manteca City Council members are trekking to Washington, D.C., next month in a bid to snare federal dollars.
Love was in the air in San Francisco at the Marines' Memorial Club on Sutter Street – the love between a husband and a wife and the many friends they had fostered during their years together.
Jesse Noble has a much-anticipated homecoming ahead.
RIPON - Eagle Scout candidate Quinn McMurtrey, 14, put together a program with the help of the Polly Klaas Foundation to collect DNA samples for families for possible emergency use in locating lost children.
Ed Adams is no stranger to most Mantecans who attend community functions.
Chris Kovacs and Teresa Beaton were by no means strangers to the world of competitive skateboarding.
Any group has "the right" to open a homeless shelter for single men in Manteca as long as they do so in a general commercial zone.
At first glance Jack Snyder's Christmas village is stunningly impressive.
The biggest threat to Manteca and Lathrop: Flood or drought?
Road work on Louise Avenue may take a little longer than expected.
The families at Manteca HOPE Shelter and Raymus Home in Manteca are getting a truck-load delivery of blankets this weekend.
Skaters in Lathrop might have a second place to shred by the time the rainy season wraps up.
You can get a peek at the latest in housing trends while casting a vote for your favorite decorated Christmas tree to benefit three Manteca non-profits.
A statement from the Manteca Unified School District was received by the Manteca Bulletin on Wednesday regarding that day's page one story about Trustee Ashley Drain of Area 2 trying to help a student at Weston Ranch High School who was suspended for five days.
The spiffy look that newly seated Councilman Mike Morowit sported at Tuesday's meeting didn't go unnoticed by Leonard Smith.
Omar Ornelas at 19-years of age thought he already had the whole world figured out.
Vince Hernandez is back in the saddle.
A holiday treat is in store for those 40 and older this Saturday.
A call for help on Tuesday morning at the America's Best Value Inn on East Yosemite Avenue quickly turned into a tense two-hour standoff with police.
Monday's nearly inch precipitation on top of last week's two inches of rain from the devastating storm was the death knell for the old towering tree along the alley near the Post Office in downtown Manteca.
Manteca could have a new councilman tonight.


text:
How to Meet a Man at the Beach Video
Four tips for meeting men while enjoying a day at the beach.
What Do You Think?
Porn Stars Wearing Ugly Christmas Sweaters Because Why Not
Don they now their horny apparel!
People Are Outraged After a Woman Gave a Rim Job to a Radio DJ Live on the Air (NSFW)
While someone took photos.
We spoke to experts to find out what's going to be hot in the new year.


text:
This Eastern Cottontail was out for its first walk/hop. It doesn't come as natural as you would expect. His tumble makes for one baby bunny belly squeeeeee...!!!!
Scottish Batman
These Six Second Videos Explain Every Reason We Hate Facebook
Ubisoft Keeps Digging Their Own Grave by Royally Messing ...
Things Not to Do at an All Boys School
That Awkward Moment When You Sell Your Truck and ISIS Terrorists ...
Dad Cares a Lot About Vitamin D
Duro y sin compasión
How Not to Load Up Your Trailer
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Por fin una buena foto
Pick Your Site Name
Tell me more


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Car rentals and cab hire services provider – Olacabs has raised series A funding from Tiger Global Management. The funds raised will be used for to scale up operations nationally and further strengthen its technology platform.
Gaming and hospital firm, Delta Corp is planning to sell its 35.6% in Advani Hotels and Resorts India and has mandated Yes Bank for the same.


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I expect some results will take place over a period of time. But this is a great training guide and I am thankful to have the many tips on how to make bathroom trips less... Read morePublished 21 days ago by Lucinda McNeill
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The potty party was the best solution for my daughter and she was fully potty trained in two... Read more
I needed to train staff on toilet training for ASD students. It allowed me the resources I needed.Published 4 months ago by Cheryl Dean
Nothing grand presented here.. didn't help us get any further down the path...Published 5 months ago by Joe Wiemann
It was well done and had great examples and stories. However, wish there was a bit more concrete program to follow. Read morePublished 6 months ago by Daniel
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This book should have pictures so we can cut them out and show the children what to do.It would help.Published 7 months ago by Avis M McCollom


text:
Contact Stop Smart Meters!
No attachments please
Search StopSmartMeters.Org
Twitter updates
Standing up to the #sleaze and rot that kills- stand up in #SF this #thursday at the CPUC http://t.co/YdaSIiFTm2 2 days ago
Stop #SmartMeters! confronts #utility officials and politicians in #SanAntonio TX and interviews the resistance http://t.co/HbPldcUGd2 3 days ago
Demonstration Thursday Dec 18th at the CA Public #Utilities Commission in #SF: Mike Peevey: Retire to San Quentin http://t.co/zqZYAaynf4 2 weeks ago
Hey #Seattle - we'll be stopping by next week to say a few words about #smartmeters come say hi http://t.co/DDdQxR9BfP 4 weeks ago
RT @miles_wilma: The FCC is a greased-up revolving a door of ex-telecom industry personnel. https://t.co/lf0a7JtKqV? 4 weeks ago
NASA simulation shows #CarbonDioxide dispersing through atmosphere. Oil coal and gas must be left in the ground. http://t.co/BQ3WXgD0SD 4 weeks ago
More questions about the safety of #SanAntonio #smartmeters and more lies from @cpsenergy http://t.co/faqkQHyH6A 4 weeks ago
Analysis of #smartmeters Shows Radiation Pulses Occur 700 Times as Often as What #SanAntonio utility CPS Claims http://t.co/R6lDbgoxUP 1 month ago
#Irish deputy prime minister trapped in car by water rights protesters http://t.co/kjh3cIpbut 1 month ago
Dear #SanAntonio city council: be a #wise city not a #smartcity - report from our visit to Texas http://t.co/TTBA8M86wk 1 month ago
Recent Posts
- Standing Up to the Sleaze and Rot that Kills
- San Antonio, TX Residents Install Analog Lockers to Defend the Elderly and Vulnerable Against CPS Smart Meters
- This Thursday: Press Conference/ Demonstration at CA Public Utilities Commission in San Francisco
- Seattle Event Added to Our National Speaking Tour
- Analysis of CPS Energy "Smart" Meters Shows Radiation Pulses Occur 700 Times as Often as What the Utility Says
Recent Comments
- Shanti on Analysis of CPS Energy "Smart" Meters Shows Radiation Pulses Occur 700 Times as Often as What the Utility Says
- S. B. on FAQ: Shielding and Measurement Issues
- Paul Serunato on "Are They Smart for You?" 3rd Edition Brochures Now Available
- Paul Serunato on "Are They Smart for You?" 3rd Edition Brochures Now Available
- Phil Arnot on This Thursday: Press Conference/ Demonstration at CA Public Utilities Commission in San Francisco
- Barking Window
- Bay Area Anti-Smart Meter Activist Site
- Beyond Nuclear
- Big Corporation Blog
- Burbank Action Against Cell Towers (and smart meters!)
- CA Sky Watch
- Cell Phone Task Force
- Cell Tower Dangers
- Center for Electrosmog Prevention
- CLOUT- Coalition for Local Oversight of Utility Technologies
- Colorado Citizens Awareness on EMF and Smart Metering
- Consumers Digest on SM's
- CPUC Meeting Videos
- Dirty Electricity Facts
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- EHS Fight Back
- EI Wellspring Smart Meter Overview
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- Electric Sense
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- Electromagnetic Radiation Group- Western Canada
- Electroplague
- Electrosensitive Society
- Electrosensitivity.org
- EMF Analysis
- EMF Guy: The Truth and Consequences of Technology
- EMF Refugee
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- EMF Safety Network
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- EMR Action Day
- Escuela sin WiFi (en espanol)
- Federal Smart Grid Site
- First Do No Harm (blog)
- Freedom Taker
- Go Off the Grid Safely!
- GQ on Cell Phone Health Dangers
- Gubbins Experiment
- Guide for Whistleblowers
- HaltMAsmartmeters
- http://wifismartmeters.com/
- Human Powered Home
- Japanese EMF Group
- Kauai Truth
- KION TV: Smart Meters Charge You More
- Maine Coalition to Stop Smart Meters
- Marti Kheel
- Maryland Residents Against Smart Meters
- Maryland Smart Meter Awareness
- Michigan Smart Meter Education Network
- michiganstopsmartmeters.com
- Microwave Factor
- Microwave News
- Naperville Smart Meter Awareness
- Nat'l Campaign to End Corporate Personhood
- National Toxic Encephalopathy Foundation
- Nevada Constitutional Alliance
- New Hampshire Against Smart Meters
- No Smart Meters Florida
- No Smart Meters San Francisco
- NoRadBlog on Smart and Radiating Meters
- Nowtopia Talk
- NY Times Opinion Piece on Cell Phones
- On the Level Blog
- Prove It Initiative
- Radiation Education- Anti wi-fi site by kids for kids
- RFID Free Schools
- Sage Reports- Analysis of Smart Meter Radiation
- Sedona Smart Meter Awareness
- Seletun Scientific Statement Video
- Shop EMF Meters at LessEMF.com
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- StopSmartMeters (UK)
- StopSmartMeters Vermont
- Tech Luck Smart Meter Page
- The Truth About Smart Grids
- Thermoguy
- True EMF Solutions, NV
- Wake Up Opt Out- VT Against Smart Meters
- Warriors for the American Revolution
- Watch live and archived CA PUC meetings
- We are Change Colorado
- WEEP Initiative- Canadian Group Opposed to EMF
- WiFi in Schools
- Wired Child
- Wireless Right to Know
- World Smart Meter Deployment Map
- www.notosmartmeters.com/
- Your Own Health and Fitness- Camp Meeker Against Smart Meters
DisclaimerUSE OF THIS SITE DEPENDS ON AGREEMENT WITH OUR DISCLAIMER: This website is intended to help advance knowledge and stimulate further research. While all reasonable precautions have been taken to ensure the validity of the information given, no warranty is given towards its accuracy. It is not intended to substitute for medical or legal advice nor as a final statement with regard to possible prevention and avoidance recommendations or potential biological effects. No liability is accepted by the authors for damages arising from its use or misuse and interpretation by others. All references to smart meters refer to digital, wireless and powerline carrier (PLC) devices, which may vary in their emissions and frequencies.
Category Archives: PG&E
Demonstrate and Speak Out at October 2nd CPUC Meeting
Demonstrate Thursday, Oct. 2 8:30am- then… Speak at CPUC Meeting 9:30am 505 Van Ness SF Rumor has it that the California Public Utilities Commission (CPUC) is preparing to make a decision in the smart meter opt out proceeding case, after … Continue reading
Method # 786: How to Get the Word Out and Bypass the Mainstream Media Blackout About Wireless Health Risks
"K" from LA writes: "Check out my new license plate! You all should get something similar.. They rejected it at first but I appealed and sent in a letter with like 20 studies. I had a long good conversation with … Continue reading
Some PG&E Customers Getting Fees Reversed as CPUC Endlessly Delays Smart Meter "Opt Out" Decision
SAN FRANCISCO- Some utility customers in California are getting utility smart meter "opt out" fees reversed in hearings at the California Public Utilities Commission, even as the Commission itself drags out a decision about the legality of such fees, having … Continue reading
Stop Smart Meters! Director Interview: Resistance to Technocracy and the Smart Grid
From James Tracy's Memory Hole Blog: This week James is joined by Josh Hart, founder and director of the California-based Stop Smart Meters, one of the foremost organizations raising public awareness on the rollout of wireless technology and the "smart … Continue reading


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Two gay Republican contenders in San Diego mayoral race
Post your comment
Comments on this article are now closed.
Reader comments
Republican, and gay… Sounds like an oxymoron to me.
Being gay does not lead to an inbuilt left-wing politics.
well it should – the tories blocked all atempts at gay rights for as long as they could – and they would now if they could get away with it
How can a gay Republican put up with the discrimination, bigotry and humiliation to which they are subjected by other Republicans like Palin, Kerry, Buchanan, and the rest…. That it is not natural, that is perverse and masochistic
It shouldn't be relevant, and one day it wont be, but at the moment it's a bit like a jewish person voting for Hitler.
They have extend "don't ask- don't tell" into their party.
As long as you keep your mouth shut and don't campaign for gay rights- you can be a candidate.
These 2 don't seem to have kept their mouths very shut, do they? Prop 8 is going to be reversed by a coalition of Republicans and Democrats in California once the ideologically pure left-wing step out of the way:
Wonder how long it will be before there are sufficient gay people in the Republican party and sufficient change in attitudes and culture so that people will disbelieve honest pro gay stances by leading republicans as unlikely due to prior Republican behaviour?
Somehow I think it might be a long time …
Some years ago our very own Conservative Party had it's share of homophobes. In the 1980's Conservative run councils would remove protection for gay employees and it was the Conservative government that introduced Section 28 although they extended legal homosexuality to Scotland in 1980 and Northern Ireland in 1982. A number of Tory MPs such as the outspoken John Carlisle called for the recriminalisation of same-sex relations. Today this would not be allowed in the party ranks.
Thats the sort of issues I was thinking of … and whilst such horrendous attitudes have no place in modern Britain and the current Conservative party – I somehow struggle to believe the Republican party can make a similar transition
Eminently possible that the GOP at the local level is no where near as hysterical and full of maniacs as the national level party. It could be that they are genuinely interested in small government and fiscal responsibility and have not picked up the social policy stump of the current GOP clown parade. Or maybe they are just suffering from cognitive dissonance…
The Republican Party is practically schizophrenic these days– The libertarian wing has no problem with gay people and is actually more gay friendly than some core constituencies in the Democrat tent, like the teamsters and black churches, which is why the president is NOT in favor of marriage equality, etc…
Sadly, the 'God Squad' republicans seem to be in the ascendency these days.
It was the black churches, coming out to vote in force for Obama in 2008, that meant Prop 8 was carried in California. Californian Republicans tend to be pretty sensible about these things (look at the 2 mentioned in the story, and also the likes of Governor Schwarzenegger and President Bush's friend Ted Olsen who united to challenge Prop 8 in the courts).
I don't care if they are loud 'n proud or if they are quiet, just so that thier voting record supports the LGBTQ community.
These comments are un-moderated and do not necessarily represent the views of PinkNews. If you believe that a comment is inappropriate or libellous, please contact us.
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Examination of Possible "Buy-In" by Garrett AiResearch
PSAD-77-73: Published: Feb 16, 1977. Publicly Released: Sep 24, 1979.
Additional Materials:
- Full Report:
(202) 512-4800
The AiResearch Division of the Garrett Corporation's practice of "buying-in" on contracts for the production of auxiliary power units was investigated. The investigation was limited to two subcontractors between Garrett and McDonnell Douglas Corporation under the F-15 contract.
Garrett submitted bids lower than their estimated costs on the F-15 subcontract. Garrett admitted making what it referred to as a $3 million "investment" in the F-15 program. Whether Garrett has followed a consistent pattern of buy-ins cannot be determined by examining two subcontracts, but a consistent pattern can be inferred from statements Garrett made in court affadavits. McDonnell officials were aware that Garrett's price was less than expected costs and suspected that Garrett was investing in the program. It is evident that McDonnell recognizes the investment concept. Before the initial procurement of the F-15 components involved in this investigation, competitive bids were solicited from many suppliers. The selection of Garrett was based on technical superiority as well as lower prices. (RRS)
Dec 15, 2014
James Webb Space Telescope:Project Facing Increased Schedule Risk with Significant Work RemainingGAO-15-100: Published: Dec 15, 2014. Publicly Released: Dec 15, 2014.
Dec 10, 2014
NASA:Human Space Exploration Programs Face ChallengesGAO-15-248T: Published: Dec 10, 2014. Publicly Released: Dec 10, 2014.
Unmanned Aerial Systems:Efforts Made toward Integration into the National Airspace Continue, but Many Actions Still RequiredGAO-15-254T: Published: Dec 10, 2014. Publicly Released: Dec 10, 2014.
Dec 9, 2014
Space Acquisitions:DOD Needs More Guidance on Decisions to Store SatellitesGAO-15-97R: Published: Dec 9, 2014. Publicly Released: Dec 9, 2014.
Jul 23, 2014
Space Launch System:Resources Need to be Matched to Requirements to Decrease Risk and Support Long Term AffordabilityGAO-14-631: Published: Jul 23, 2014. Publicly Released: Jul 23, 2014.
Jul 16, 2014
U.S. Launch Enterprise:Acquisition Best Practices Can Benefit Future EffortsGAO-14-776T: Published: Jul 16, 2014. Publicly Released: Jul 16, 2014.
Jun 20, 2014
Export Controls:NASA Management Action and Improved Oversight Needed to Reduce the Risk of Unauthorized Access to Its TechnologiesGAO-14-690T: Published: Jun 20, 2014. Publicly Released: Jun 20, 2014.
May 15, 2014
Export Controls:NASA Management Action and Improved Oversight Needed to Reduce the Risk of Unauthorized Access to Its TechnologiesGAO-14-315: Published: Apr 15, 2014. Publicly Released: May 15, 2014.
May 8, 2014
NASA:Actions Needed to Improve Transparency and Assess Long-Term Affordability of Human Exploration ProgramsGAO-14-385: Published: May 8, 2014. Publicly Released: May 8, 2014.
Apr 15, 2014
NASA:Assessments of Selected Large-Scale ProjectsGAO-14-338SP: Published: Apr 15, 2014. Publicly Released: Apr 15, 2014.
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In MOSS 2007 we use a CAML query to query the SharePoint list and in SharePoint 2010 I found the newly introduced LINQ to SharePoint (where using SPMetal utility we generate a data context class) which works fine for a SharePoint list but how do I query a form library were most of the fields are promoted to it from the Infopath form?
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I would suggest use LINQ To XML


text:
supporting actress
Kirk Douglas Charms Everyone; Melissa Leo Gets Too Excited and Drops an F-Bomb (VIDEO)
"She's gorgeous!" he said upon seeing Oscars co-host Anne Hathaway, "Where were you when I was making pictures?"
He then gave Hugh Jackman grief for laughing, saying that everyone in Australia seems to think he's funny. "Colin Firth is not laughing," he told Jackman. "He's British."
Emmy Wish List: Supporting Categories - Drama
Earlier, I shared my wish list for the Outstanding Lead Actress in a Drama nominations, and I mentioned that Chloe Sevigny from Big Love would be a deserving selection. A TV Squad reader let me know that Chloe has actually been submitted in the supporting category. Good to know, and with that in mind, I'll start my wish list by talking about that category. (Remember, there are six nominees per category.)
The Emmys: More thoughts and theories
Looking at the Emmy nominations announced this morning, one word comes to mind: BORING.
Or maybe two words, if you add "safe." I mean, come on. I don't usually watch Friday Night Lights, Dexter, or Battlestar Galactica, but even I know that those shows should have been nominated for something (beyond technical and writing awards). Instead we get...Tony Shalhoub again? He's fine, but there has to be someone else who they can plug in there. Grey's Anatomy and House for Best Drama? That's not to say that the shows nominated aren't good and solid, but when you take a look at the dramas that were left out...gah.
Beyond the major nominations (Best Comedy, Best Drama, Lead Actor and Actress, etc), there are other nominations where a lot of your favorite shows actually show up. After the jump, I'll highlight several.
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