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Running Time: 138 minutes
Released: 05/2009
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|"ant elder" <ant.el...@gmail.com>
|Re: Tuscany Website Updates
|Thu, 02 Nov 2006 08:29:14 GMT
On 11/2/06, Venkata Krishnan <firstname.lastname@example.com> wrote: > > Hi, > > I am putting up some proposals for updates to our website and request > feedback on this or suggestions for the better. Right away some top > level > ones are: > > - Do away with the tabs. This is because I don't see correlation between > the Tab options and the options on the navigation pane in the left. i.e > . if > the tabs are first level navigation then the pane on the left must be > sub-options within a selected tab - I don't see such a correlation. So > let's avoid confusion to the website visitor > - There is lots of green :) and am having some difficulties to get > additional colors that gel with this. Either somebody with better colour > sense helps or we moderate the green a bit. > - The images that are used for the Navigation Optoins on the left pane and > for the titles of various boxes may need to be sharpened a bit > > All this besides the fact the the various navigations paths need to be > reviewed and set right. I shall get to these as well. > > Meanwhile I have created a JIRA > http://issues.apache.org/jira/browse/TUSCANY-703 where I have attempted to > provide a view of what's in my mind for the Navigation Pane on the left > together with some changes for the Downloads page. > > You simply have to extract the zip that is attached in that JIRA and take > a > look at /site-publish/downloads.html. > > Also, I have a diagram posted for the Java_SCA Overview in the same JIRA, > please see if you can say somethings about that as well. > > Thanks. > > - Venkat Its really good you're looking at the website Venkat, it has become a bit neglected. What you've suggested above all sounds good to me, I'd suggest just going ahead and making changes as you think appropriate as that will be much easier for you. Maybe for big ones mention on the dev list first but otherwise just dive in and send emails after the fact so others can review - just as with the code CTR not RTC :) ...ant
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Goldman's reason for the upgrade was Lowe's improved margins despite a time when "many retailers are likely to experience decelerating growth." After the news the stock gained +2% in the premarkets. The retail stock has gained +10.2% over the past month. Along with the buy recommendation, Goldman estimated that the retailer's EPS would jump 18% in the third quarter and 31% in the fourth quarter. Lowe's will release its earnings report on Nov. 15.
Wal-Mart is intensely focused on fixing the mistakes made in the U.S. over the past two quarters by adding inventory back to the assortment, reinstating Action Alley, and returning to an EDLP pricing strategy. The company's outlook for 2H10 is cautious as the health of its core customer has not improved. However, correcting the company-specific issues at Wal-Mart U.S. should yield topline improvement in 2H10, and management's emphasis on the productivity loop gives us confidence that WMT can make our 2010 EPS estimate of $4.06," Citi experts announced. Wal-Mart will release its earnings report on Nov. 16, and shareholders will discover if Citi's recommendation holds true.


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Data from: Gene similarity networks provide new tools for understanding eukaryote origins and evolution
Date Published: May 21, 2013
DOI: http://dx.doi.org/10.5061/dryad.qr81p
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|Gene similarity network
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|The folder "ConnectedComponents" contains one file for each connected component. In each file, each line represents a network edge. The file GeneAnnotations.txt contains basic information for each gene.
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Teen TalesFavorites [+]
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Running Time: 101 minutes
Released: 10/2008
Studio Name: Pandemonium
Series: Teen Tales
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This was the first time we decided to stay at Marriott's Timber Lodge and we were surprised for the spacious room, and with all of the amenities like fireplace, complete kitchen and utensils, laundry, and the bathtub separated from the shower and bathroom, our daughter said: "it looks like home"! So, it made our trip even better since she was so happy! The best, very quite room!
Our only issue, was the long way to the exits, but it made it for a long indoors walking :-D.
And it is the Gondola to go to Heavenly, (since we missed it for one day, they closed on September till the skiing season) you just walk and voila there it is the entrance to the Gondola, and to the nice shopping area, theater movies, and so on...
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From the Office of Congressman Jeb Bradley
A new radio actuality has been recorded by First District Congressman Jeb Bradley. The topic is Bradley's praise for the President's approval of the state's federal disaster declaration request . This approval now means that individuals and businesses affected by the severe flooding can begin to register for FEMA assistance. To listen to the message, follow these instructions:
1. Dial (202) 226-4766
2. Enter message number and the poundkey: 2723147 #
You can also download the message (in RealPlayer format) at:
Please contact Stephanie DuBois at (202) 225-5456 with any questions.


text:
Differences in osteogenic and apoptotic genes between osteoporotic and osteoarthritic patients
Clinical rheumatology and osteoporosis
Osteoporosis is a metabolic disorder characterized by a reduction in bone mass and deterioration in the microarchitectural structure of the bone, leading to a higher risk for spontaneous and fragility fractures.
The main aim was to study the differences between human bone from osteoporotic and osteoarthritic patients about gene expression (osteogenesis and apoptosis), bone mineral density, microstructural and biomechanic parameters.
We analyzed data from 12 subjects: 6 with osteoporotic hip fracture (OP) and 6 with hip osteoarthritis (OA), as the control group. All subjects underwent medical history, analytical determinations, densitometry, histomorphometric and biochemical study. The expression of 86 genes of osteogenesis and 86 genes of apoptosis was studied in pool of bone samples from patients with OP and OA by PCR array.
We observed that most of the genes of apoptosis and osteogenesis show a decrease in gene expression in the osteoporotic group in comparison with the osteoarthritic group. The histomorphometric study shows a lower bone quality in the group of patients with hip fractures compared to the osteoarthritic group.
The bone tissue of osteoporotic fracture patients is more fragile than the bone of OA patients. Our results showed an osteoporotic bone with a lower capacities for differentiation and osteoblastic activity as well as a lower rate of apoptosis than osteoarthritic bone. These results are related with structural and biochemical parameters.
Normal bone remodelling requires a balance between bone formation and resorption and disruption of either activity or both leads to metabolic bone disorders, being osteoporosis the most prevalent one. In the process of bone formation and resorption different regulatory systems are involved, mainly communication systems between different bone cells: osteoblasts, osteoclasts and osteocytes
Microarrays studies showed that the expression of several genes is related with BMD and with osteoporotic disease
One of the best known processes of bone regulation is OPG/RANKL/RANK that regulates directly the action of osteoblasts and osteoclasts
Apoptosis plays a critical role during embryonic limb development, skeletal maturation, adult bone turnover by modeling and remodeling processes, and during fracture healing and bone regeneration. In humans, increased osteocyte apoptosis has been correlated with sites of rapid bone turnover
As a result of the balance between bone formation and resorption, bone structure may be modified and thus the biomechanical properties which are determinant of bone strength and fracture resistance.
Therefore, in the present study, we determined the alterations in the osteogenic and apoptotic activity on bone samples from osteoporotic hip fracture patients versus hip osteoarthritis patients. Also, we studied the microstructural and biomechanical characteristics of trabecular bone in these patients.
The studied population consisted of two groups of patients. The first included 6 patients (1 man and 5 women) with osteoporotic hip fractures (OP), between 62–87 years old and the second one, 6 patients (2 men and 4 women) with hip osteoarthritis (OA), between 55–78 years old. Inclusion criteria in both groups were to be aged 55 or over, not to lead a sedentary life, to walk for 3–4 hours every week, to take more than 700 mg/day of calcium (calculated by dietetic questionnaires) and not receiving treatment with an influence on bone metabolism. The OP group was made up by patients with an osteoporotic hip fracture that required arthroplasty and the OA group by patients with osteoarthritis, admitted for elective hip arthroplasty and not having presented an osteoporotic fracture during their life. Exclusion criteria were malignant diseases, hyperthyroidism, hyperparathyroidism, osteomalacia, previous bisphosphonate or systemic steroid treatment or use of vitamin D supplements or current use of hormone replacement therapy or any other drugs with effects on bone metabolism.
Patients were included in the study in a consecutive manner as they were directed to arthroplasty by the Trauma & Orthopedics Department in the University Hospital "Virgen Macarena" of Seville, Spain.
All patients were included to participle in this study and agreed their bone samples. The study was approved by the Institutional Ethics Committee and written informed consent was obtained from all the participants in the study.
During the surgical procedure, a femoral osteotomy was performed and the femoral head and neck were removed.
Biochemical parameters
We obtained a fasting blood sample, in the first 48 h after surgery, for analytical determinations of parameters related to bone metabolism: calcium corrected for albumin levels, phosphorus, β- CrossLaps, aminoterminal propeptide of type I procollagen (PINP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D) and insulin growth factor-like (IGF-I).
Corrected serum calcium and phosphorus were measured by an autoanalyzer DAX-96.
PTH, β-CrossLaps and PINP were analyzed by immunoassay by an autoanalyzer COBAS 601 (Roche, Spain). Interassay CV <5.8%, <7.6% and <4.2% respectively.
25(OH)D were analyzed by direct competitive immunoassay by an autoanalyzer LIAISON (DiaSorin, Italy). Interassay CV < 5.5%.
Serum IGF-I was measured by immunoassay by IMMULITE (Siemens, Germany). Interassay CV < 3.9%.
Dual-energy X-ray absorptiometry (DXA)
Bone mineral density (BMD) was measured in the hip and contralateral femoral neck by dual X-ray densitometer with Hologic-DISCOVERY. CV in vivo 2.9% (femoral neck) and 2.5% (total hip).
Microstructural and biomechanic bone study
The distal femoral region was analyzed without further sample preparation by micro-CT, (SkyScan 1172) at Trabeculae® (San Cibrao das Viñas, Spain). Data sets were rebuilt using a modified Feldkamp algorithm and segmented into binary images (8-bit BMP images) using adaptive local thresholding. Trabecular bone regions were analyzed using the commercial software (Sky-Scan™ CT, 1.6.0)
To evaluate the biomechanical properties we have performed uniaxial compression tests using the IGFA system
RNA extraction and cDNA synthesis
RNA was isolated from the femurs by using Trizol, following manufacturer's instructions (Invitrogen, CA, USA).
To carry out the PCR array, total RNA from 6 different patients in each experimental group was pooled (3 μg total) and the pool was reverse-transcribed with RT2 First strand kit (SABiosciences, USA) according to manufacturer's instructions. For the study of OPG and RUNx2 genes, aliquots of RNA (250 ng) were reverse-transcribed with RT2 First strand kit (SABiosciences, USA) according to manufacturer's instructions.
PCR array and real time PCR
Human osteogenesis and Human apoptosis RT2 Profilertm PCR Arrays (SuperArray, USA) were used to screen the expression of multiple genes in human bone biopsies. They were used according to the manufacturer's protocol on an ABI Prism 7500 (Applied Biosystems,USA). Results were normalized with the less variable housekeeping gene available in the array, beta-actin, and a significant (p < 0.05). 3–fold change over control was the selected criteria for an experimental gene expression change, similarly to other studies of this kind
Duplicate plates were used.
To validate de PCR array, real time PCR was done with cDNA from each patient, and was repeated three times for each gene using SYBRGreen (Roche,) and the primers of Runx2, osteoprotegerin and beta-actin (housekeeping gene) were provided by QuantiTectPrimer Assay (Quiagen,USA). Real-time PCR were performed in the ABI PRISM 7500 system (Applied Biosystems,USA). Results were expressed in mRNA copy numbers, calculated for each sample using the cycle threshold (Ct) value, and normalized against 18S rRNA.
Results were analyzed with th RT2 Profiler™ PCR Array Data Analysis (
Variables were tested for normality of distribution using Kolmogorov-Smirnov test. To statistical significance of the differences between the means of OP and OA gene expression values in the real time PCR analysis were determined by t-Student test. We used the statistical package SPSS 18.0 (Illinois, USA). Statistical differences were set at p < 0.05. Results are presented as mean ± standard error (SEM).
We analyzed data from 12 patients: 6 with osteoporotic hip fracture (OP) and 6 with hip osteoarthritis (OA), as the control group, who fulfilled the enrolment criteria. Clinical characteristics and laboratory data of the OP and OA groups are summarized in Table
In both groups, the anthropometric and biochemical characteristics were comparable. Although patients with fractures tended to be older than those with OA, age differences did not seem to influence the results because we found no statistical significant differences between groups and also we found no correlation between age and gene expression in either group.
OP patients had lower values of total hip bone mineral density (BMD) (0.83 gHA/cm 2 ± 0.04 OP; 0.89 gHA/cm 2 ± 0.06 OA) and neck BMD (0.59 gHA/cm 2 ± 0.03 OP; 0.74 gHA/OA ± 0.08 cm 2) than the control group, and higher bone remodelling serum marker, β-CrossLaps, 0.51 ng/mL ± 0.1 (OP) vs. 0.36 ng/mL ± 0.08 (OA) without rearching statistical differences. In all patients, the levels of 25 (OH) D were < 20 ng/mL.
Histomorphometry and biomechanics results
Microstructural indices show a lower bone quality in the group of patients with hip fractures compared to the osteoarthritic group (Table
We observed significant lower number of trabeculae (Tb.N.) in the bone of hip fracture patients (1.5 mm-1 ± 0.1 vs 1.9 mm-1 ± 0.1; p = 0.049) and furthermore, these patients also have a greater separation between trabeculae (Tb.Sp) (0.55 mm ± 0.46 vs. 0.02 mm ± 0.03, P = 0.04). The thickness of the trabeculae (Tb.Th) was similar in both groups.
The trabecular pattern index (inverse of connectivity index) showed higher values in the fractured patient group. The structure model index (SMI), which implies a relative prevalence of tube-cylinder trabeculae in comparison to plate-form ones, was higher in the group of patients with hip fracture, indicating a greater number of trabeculae in tube-shaped cylinder, less resitant, in these patients.
Biomechanical studies showed that the values of Young's modulus, maximum stress and maximum deflection, after applying the compression test, were lower in patients with hip fractures compared with osteoarthritic patients, although these differences did not reach significance (Table
PCR array osteogenesis
We examined whether osteoporotic patients would have any alterations in the osteogenesis in comparison with osteoarthritic patients. If we consider biologically significant variations when the induction or repression of the gene is at least 3 times, we found that 23 genes, from 86 genes involved in osteogenesis, are altered (p <0.05). In most cases, we observed a repression of these genes in osteoporotic compared with the control bone (Table
Among the down-regulated genes, it is necessary to emphasize the osteocalcin gene (BGLAP) (− 3.39-fold), a specific gene from osteoblastic cells which function is bone mineralization, CDH11 (−3.3-fold) a typical adhesion molecule of osteoblasts, Runx2 (−2.94-fold) which is a factor of transcription essential for the maturation of osteoblastic cells and BMP6 (−3.3-fold) that encodes a protein of bone formation, also typical from osteoblastic cells. The latter four genes are characteristic of osteoblastic cells and are suppressed on the macerated OP bones.
We also showed down-regulation in several transcription factors such as NFKB1, SMAD2, SMAD3, SOX9 and TNF, which in turn modulate gene expression of several genes.
PCR array apoptosis
When analyzing array apoptosis, we observed that most of the genes show a decrease in gene expression in the osteoporotic group in comparison with the osteoarthritic group (Table
As known, apoptosis can be initiated either by the death receptor-mediated pathway or the mitochondria-mediated pathway. In our study, we found that both pathways are altered on macerated OP bones. Of the 84 genes studied, 26 have a significant lower gene expression in the OP group vs. OA, and only two of them show increased expression (p <0.05). Specifically, we observed a lower expression of TNF receptor family genes as CD40 (−7.7-fold OP vs. OA), LTBR (−3.3-fold), TNFRSF11B (−3.5-fold), CD27 (−6.6-fold) and the TNF ligand Family, TNF (−16.7-fold). At a mitochondrial level, there are repressed genes such as BAD (−5.8-fold) and slightly BAX (−1.2-fold).
Caspases are final effector enzymes of programmed cell death. In the OP group, the caspases studied also have a lower gene expression, observing a significant biologically variation for caspase 9 (−6.1-fold OP vs. OA) and caspases 4 and 5 (−5.3- fold and −5.9-fold-respectively).
We have also observed the repression of genes such as Bcl2 (−6.3-fold) and BAG1 (−3.62-fold), both of the bcl-2 family and ABL1 (−6.8-fold) involved in the damage response DNA.
In OP patients, we only observed an increased in the gene expressions of BCL2A1 (9.66-fold) and BNIP1 (2.7-fold), both from the BCL2 family of anti-apoptotic features.
To verify the results obtained in the array plates, we chose two genes, with particular relevance to the activity of bone remodelling, such as Runx2 and OPG. Runx2 is the major transcription factor involved in osteoblast differentiation, and the results of the osteogenesis array plate indicate a down-regulation in OP vs. OA bone of this gene (−2.94-fold, p <0.05) (Table
When analyzed individually OPG and Runx2 gene, we observed that the OP group has almost 2 times less expression of Runx2 and 6.9 times less OPG than the control group (p = 0.004), confirming the results of osteogenesis and apoptosis arrays (Figure
Figure 1
Normalized mRNA levels for Runx2 and OPG in human femur of patients with OP and OA
Normalized mRNA levels for Runx2 and OPG in human femur of patients with OP and OA. Results are mean ± S.E.M: (n = 3). The results reported in percentages of the variation referred to OA group. *p < 0.05 OP vs. OA.
The osteogenic activity is mediated by multiple proteins and may be altered by different circumstances. We investigated whether genes associated with this activity may have a different expression in bone tissue of osteoporotic fracture patients versus osteoarthritis patients. We have studied 86 genes related to osteogenic activity and 84 to apoptosis. Most of them have a lower expression in osteoporotic bone than in osteoarthritic bone, indicating that the bone tissue in osteoporosis is more inert, having less transcriptional activity.
Regarding osteogenic activity, the macerated OP hip bone has repressed typical genes of osteoblast cell. So BGLAP (essential for bone mineralization), CDH11 (osteoblast adhesion molecule) and Runx2 (transcription factor required for osteoblastogenesis), have a lower expression in osteoporotic than arthritic bone, which is consistent with decreased osteoblast differentiation and activity in osteoporosis bone. This finding agrees with previous results
Several TGF-β/BMP signalling pathway components and modulator genes that influence osteoblast function, bone remodelling and bone mineralization, were down-regulated in OP bone, such as TGFBR1, TGFBR2, BMP5, BMP6, SMAD 2 and SMAD3. Several authors agree with these results, and it is consistent with decreased in the bone turnover in OP bone
Previous studies demonstrated that BMP6 was more potent and consistent than BMP2 and BMP7 in inducing osteoblast differentiation in primary hMSC
With regard to genes encoding the synthesis of metalloproteinases, we have also found differences when comparing the osteoporotic and arthrosic bone. The lack of MMP8 is accompanied by synovial inflammation and bone erosion in mice arthritis model, indicating that MMP8 has a protective role in this disease. The fact of finding higher expression levels MMP8 in OP patients than OA may suggest an increased activity in inflammatory joint in OA patients
In cell cycle regulation, multiple receptors and modulators of different activation pathways are involved. Among the genes studied in this group, we obtained a decreased gene expression of EGFR, FGFR1, FGFR2 and IGF1R in the OP group macerates. On the contrary, FGF1 and VEGFA are two of the three genes with an increased expression in the OP group.
Epidermal growth factor receptor (EGFR) signalling pathway is an important bone regulator and it primarily plays an anabolic role in bone metabolism. A physiological function of osteoblastic EGFR signalling is maintaining the pool of osteoprogenitors at an undifferentiated stage in bone. It is reported that blocking EGFR activity in osteoblast lineage cells results in fewer osteoprogenitors and leads to defective bone formation
All these results taken together suggest that osteoblastic activity is decreased in osteoporotic bone and bone formation rate is lower in OP than in OA bone.
The human apoptosis PCR array profiles the expression of 84 key genes involved in apoptosis or programmed cell death. We have observed a down-regulation in 26 genes and upregulation in only two of them.
The two major pathways of apoptosis are the extrinsic (Fas and other TNFR superfamily members and ligands) and the intrinsic (mitochondria-associated) pathways
Caspases are proteases that cleave intracellular proteins and are required to carry out apoptosis
Bcl-2 proteins are a family of cytosolic proteins involved in the mitochondrial pathway of apoptotic and these can be either anti or pro-apoptotic. They act as a sensor of cellular damage. At present, regulation of apoptosis by Bcl-2 family members is complex and not fully understood because most cells express a variety of antiapoptotic and proapoptotic Bcl-2 proteins, and the regulation of their interactions dictates survival or commitment to apoptosis
OPG plays essential roles in the osteoblast cell, on the one hand it inhibits bone resorption, joining the receptor activator for nuclear factor _B ligand (RANKL)
The histomorphometry data obtained indicate that OP bone is of lower quality than OA, observing a smaller number of trabeculae, greater separation between them and poorer connectivity
Our study has some limitations. Firstly, we studied trabecular bone, which may behave differently of cortical bone and secondly we present a relatively low number of patients.
These results open a wide field of research in the treatment of osteoporotic and arthritic disease. Noting the different gene activities that are in both conditions, we can deepen the study of each of these genes looking for the best candidate as a therapeutic target. In our work, we point out the genes with differential expression and also we relate gene activity to structural and biochemical differences in bone.
In summary, our findings lead us to conclude that bone tissue of osteoporotic fracture patients presented worse microstructural characteristics which make them more fragile than the bone of OA patients, in line with other authors
OP: Osteoporosis;OA: Osteoarthritis;OPG: Osteoprotegerin;RANKL: Receptor activator for nuclear factor _B ligand;BMD: Bone mineral density;Tb.N: Number of trabeculae;Tb.Sp: Separation between trabeculae;Tb.Th: Thickness of the trabeculae;SMI: Structure model index;BGLAP: Osteocalcin gene;EGFR: Epidermal growth factor receptor;FGF: Fibroblast growth factor
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
MG carried out the molecular genetic studies, participated in the bioinformatics analysis and drafted the manuscript. MJM and MAV participated in the clinical and biochemical analysis. CM carried out the bioinformatics analysis. RPC conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
This work was supported in part by the Research Project of Excellence, Junta de Andalucía (CTS-5360/09) of Spain and co-financed with ISCIII 2013-RED 12-0043 from the (RETICEF). The authors thank the staff in the Traumatology & Orthopaedic Department, "Hospital Virgen Macarena".
Osteoporosis: now and the future
Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype
Genetic and transcriptional control of bone formation
Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study
Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair
Differential effect of FGF and PDGF on cell proliferation and migration in osteoblastic cells
Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease
Osteoblast apoptosis and bone turnover
Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis
Comparative effects of 17beta-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice
PCR arrays identify metallothionein-3 as a highly hypoxia-inducible gene in human adipocytes
Gene expression profile of the bone microenvironment in human fragility fracture bone
Osteoblastogenesis and adipogenesis are higher in osteoarthritic than in osteoporotic bone tissue
Stress decreasesthe serum level of osteocalcin
An update on primary hip osteoarthritis including altered Wnt and TGF-β associated gene expression from the bony component of the disease
Critical molecular regulators, histomorphometric indices and their correlations in the trabecular bone in primary hip osteoarthritis
Smad3 differently affects osteoblast differentiation depending upon its differentiation stage
Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor beta 1 mRNA expression
The transcription factor osterix (SP7) regulates BMP6-induced human osteoblast differentiation
BMP5 activates multiple signaling pathways and promotes chondrogenic differentiation in the ATDC5 growth plate model
Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model
The relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human osteoporotic and osteoarthritic bone tissues
EGFR signaling suppresses osteoblast differentiation and inhibits expression of master osteoblastic transcription factors Runx2 and Osterix
Immobilization and bioactivity evaluation of FGF-1 and FGF-2 on powdered silicon-doped hydroxyapatite and their scaffolds for bone tissue engineering
Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats
Study on relationship between osteoporosis and mRNA expressions of vascular endothelial growth factor and bone morphogenetic protein 2 in nontraumatic avascular necrosis of femoral head
Apoptosis: programmed cell death at a molecular level
CD40-CD40 ligand
Cell death beyond apoptosis
Apoptosis in bone for tissue engineering
The BCL-2 family reunion
Osteocyte deficiency in hip fractures
Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis
Osteoprotegerin prevents glucocorticoid-induced osteocyte apoptosis in mice
Postmenopausal women with osteoarthritis and osteoporosis show different ultrastructural characteristics of trabecular bone of the femoral head
Trabecular bone microstructure and local gene expression in iliac crest biopsies of men with idiopathic osteoporosis
Pre-publication history
The pre-publication history for this paper can be accessed here:


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Today's Golfer Magazine
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Can The Grove live up to our fourball's very high expectations?
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Our verdicts on the year's best drivers, irons, putters and balls.


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I just got done digging to the bottom of the trash can.
*Sigh.* A phrase I don't often open with… thankfully. Welp, this isn't the first time I've posted this recipe, and I didn't realize that the size of the roast was already in the instructions. I thought I had to go digging for that thin little piece of plastic wrap that had the size roast that we bought. And since I got up to my elbows in yesterday's trash to report this information to you, I will do so. Ahem, (drumroll, please)… it was 2.5 pounds. (That was pretty anti-climactic. I need a dang life.) My point, I suppose, is that the recipe calls for a 3 pound roast, but you can give or take that weight, this is a flexible and very forgiving recipe.


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9/11 Ten Years Later: The Last Novel Before the Fall
My "Closing Time" was the last novel set in downtown Manhattan published prior to Sept. 11, 2001 – on Sept. 10 to be precise. Early on the morning of 9/11, my brother, then an executive at the Bank of New York, walked to the Borders at the nearby World Trade Center to buy a copy, only to find it wasn't yet on the shelf. Come back later, he was told. By 10:30 a.m., the bookstore was gone, crushed under the weight of the fallen towers. My brother was among the hundreds of thousands of people working in downtown Manhattan who escaped injury and death. I've often wondered if the bookstore's employees did too or whether they were among the 2,700 women and men who were killed as they tended to their work.
Though it took me many years to write "Closing Time" in a manner worthy of publication, I thought not a whit about it in the aftermath of the towers' collapse. On Sept. 11, I was in Morocco; after the second plane struck the south tower, hotel security hurried me to a room for my safety. As I watched the horror on BBC, I could hear the staff cheering in the kitchen below. Later, at an airport in Marrakech, I was escorted to the front of the passport line and then stashed away in a men's room, an armed guard at the door. I escaped to Paris via a private plane secured by a French multinational company. After I arrived in the early morning hours, I was greeted by Parisian shopkeepers who knew me only as an American, the man who when visiting bought the International Herald Tribune and Coca Cola sans sucre, and whose French was so bad it was both laughable and maybe a little bit charming. Crying, they hugged me in the street; snapping out of my shock, I cried too.


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Shedd Aquarium, Chicago's most popular cultural attraction, has
rolled out a plan that will launch it as the first clean
energy-powered facility of its kind in the country.
"It's a brand new initiative," said Elise Waugh, a communications
and public relations coordinator at Shedd. "It's going to be
something that other institutions can look to as a model for their
A Master Energy Roadmap aims to cut energy consumption of the
83-year-old indoor public aquarium in half by 2020. Robert Wengel,
the aquarium's vice president of facilities, said about 10 million
kilowatt-hours, enough to power 750 houses, are expected to be
saved annually.
"It's a comprehensive strategy," Wengel said. "We're going to go
from an energy saver, which is what we are now, to an energy leader
and to an energy innovator."
Shedd has begun the journey toward energy efficiency by changing
the exhibits' lighting systems. systen.
"We've done a lot of LED lighting retrofit," Wengel said. "And
that actually produced more light and a crisper light."
Wengel said the 600 light bulbs illuminating the four chandeliers
in the main foyer were replaced with LED bulbs. That move is
expected to save $7000 a year on energy costs.
The smart energy plans also include the installation of
electricity sub meters and automation systems to audit, control and
monitor energy use. An On-site solar power system will cut more
than $100,000 annually on electricity bills and provide power in
the event of a should a blackout occur. Wengel said the flow or
pressure of pumps in the giant-size tanks, built to replicate the
natural environment of the sea creatures, will be monitored by
variable-frequency drives (VFDs). Wild Reef, the largest tank,
holds 400,000 gallons of water.
The energy roadmap was designed in partnership with the City of
Chicago, the Citizens Utility Board, the Illinois Science and
Technology Coalition, and the Institute for Sustainable Energy
"This project is a real opportunity to not only reduce energy
consumption for Shedd, but its larger implication is a model site
for sustainable energy investments," said Mark Harris, the
president and CEO of ISTC. "It's really going to provide visibility
and a better understanding of the benefits of smart energy
practices. So, it's a phenomenal effort that will help not only the
Shedd, but other institutions."
Wengel said the full cost of implementing these changes over the
next seven years is not yet known.
"If you look at what we're going to spend this year on projects,
probably just over a million dollars, but as far as how we are
going to strategize the rest of those costs throughout, we're still
kind of trying to figure that out," Wengel said.
Chicago resident and homeowner, Gerald Farinas, said he has been
greatly inspired by Shedd's conservation efforts.
"Lowering the cost I pay out of my pocket has been the main
inspiration to switch to energy-conserving appliances, electronics,
and yes, even the coiled LED bulbs," Farinas said. "Shedd's saving
enough electricity to power 750 homes. That is an incredible
amount. That's a difference that shouldn't be ignored and should be
And that's just the kind of effect Shedd hopes to have on its
visitors who number up to 2 million a year. The facility attraction
was the most visited aquarium in the U.S. in 2005. With 32,500
animals and 1500 species, it has the most diverse aquatic
collection of any aquarium in the world.
"We want to be able to make what we do relatable to people in
their homes, so when they come here we want to talk about it and
tell stories so they can leave and do some of the stuff we're
doing, just on a smaller scale," Wengel said.
Mayor Emanuel also praised the sea-life haven at 1200 S. Lake
Shore Drive. The city has its own energy reduction goals and
"Shedd's Master Energy Roadmap is an incredible step toward
achieving our 2015 goal of improving citywide energy efficiency by
five percent," Emanuel said in a statement last month.
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Alchemy Produx Limited Edition Artist Candle: Lauren Nicholson | 230 gram
Alchemy Produx is the collaboration of a Melbourne pair, who have combined their backgrounds in fashion design and chemistry to craft their handmade candles. Alchemy candles are created with 100% natural Soy Wax and carefully hand poured into laboratory glassware; which are all made to order. Alchemy Produx designer range of candles are a concoction of minimalist and industrial home wares and chemistry class nostalgia.
- 50 Hours Burn Time
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- 100% Natural Soy Wax
- 9 x 16 cm
About the Artist
Lauren Nicholson is an artist / illustrator who lives in Melbourne.
She uses traditional techniques, experimental mark making and digital media to create layered imagery that is influenced by the power of colour, personal journeys, the natural world, printed matter, memories and old stories.
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Register To Attempt Complete Test
Create Account
Practise Test 3
An initially parallel cylindrical beam travels in a medium of refractive index μ(I) = μ0 + μ2I, where μ0 and μ2 are positive constants and I is the intensity of the light beam. The intensity of the beam is decreasing with increasing radius.
The initial shape of the wave front of the beam is


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This estate necklace and earrings set looks like it has an exotic origin. The colorful striped Italian glass trade beads are one clue. The silver tone beaded metal is another. More important than where this set came from is where it's going. Around your neck and on your ears is a great place.
The necklace is a visual standout with the multi-color glass beads, the large center plaque, and the seven strands of dangles. It measures 20 inches around with a secure lobster claw clasp. The center pendant with its Italian cane glass design hangs 4 1/2 inches long.
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These stylish apartments offer a convenient base, perfect for any traveller. There is a TV lounge and a bar on the premises.Reception closes at 8 pm. The latest check-in time is 8 pm. Guests who require later check-in should call in advance and advise the hotel of their estimated time of arrival. If late check-in is not pre-arranged, they will not be able to check in after 8 pm.The aparthotel offers quality studio apartments. All guest rooms have been designed with comfort and practicality in mind and are fully equipped with a kitchen with microwave and dinner table, a TV, ironing set and Internet access.
Take the M4 towards Central London, then the A4. At the roundabout, take the 2nd exit onto the A40 ramp to The City/W End (0.3 miles). Merge onto the A40 (2.3 miles). Continue straight onto Marylebone Rd/A501 (0.9 miles). Take a slight left at Albany St (98 ft). Turn left at Albany St/A4201 (0.8 miles). Turn right at Gloucester Gate Bridge/A4201. Continue to follow the A4201 (463 ft). Continue onto Pkwy/A503 (0.2 miles). Keep left at the fork. Continue to follow the A503 (427 ft). Take a sharp right at Bayham St/A503 (0.2 miles). Keep left at the fork (43 ft) and turn left at Pratt St.


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Weather Stations Review
Why Buy a Weather Station?
Dressing appropriately or taking shelter when storms arise makes having instantaneous weather reports valuable, and built-in warning alerts are important in areas with highly variable weather. Some weather station options include the Oregon Scientific Helios, Ambient Weather WS-11 and the AcuRite 02007.
Weather Stations: What to Look For
Personal weather stations vary according to available options and cost. Knowing what you want and learning whether a particular make or model provides it allows you to choose the right weather station for you. Most measure temperature, humidity and barometric pressure, while others add parameters such as wind speed and rainfall. Some important features to consider are the following.
Atmospheric Measurements
Weather stations measure parameters such as temperature, moisture and humidity. The ability to measure these attributes accurately varies according to the instrument's design. For instance, radiation shields may be necessary to obtain a precise temperature reading. Without a shield, your result may be falsely high if the temperature sensor is in direct sunlight.
A few digital home weather stations measure the absolute humidity, which is the total water vapor in the air by volume. Most measure the relative humidity, which is a function of temperature and water content expressed as a ratio. Measuring temperature and humidity makes it possible for the personal weather station to compute parameters such as the dew point.
Wind Speed & Rainfall
Propellers or spinning cups are attachments that measure wind speed. Unless black anemometers are used, these attachments may ice over. Sonic anemometers are an advanced way to measure wind speed by measuring sound traveling between transducers. They are unaffected by adverse environmental conditions, but birds landing on the transducers may alter results, causing higher than actual wind gust measurements. Getting accurate readings is a crucial factor in picking one wireless weather station over another.
The type of rain gauge varies. Consider the depth of the rain collection gauge if you live in an area with significant precipitation. Some devices have shallow gauges, which overflow in heavy rain.
Wireless Capability & Solar Power
A wireless weather station provides measurement transmission without fussing with wires. This makes installing and using the system easier. A few devices use solar power in lieu of batteries or AC current. However, solar power may require a backup battery for less sunny days or areas.
Battery life varies and some units include an alert for when the battery strength is low. Most systems use rechargeable AA or AAA batteries.
The types of personal weather station vary by cost and available options. Some systems are easier to set up, and the display may be in color or black and white. Wireless systems have a high usability score but might be more expensive, and finding a device that achieves the option level you need and fits your budget at the same time is paramount.


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Mother charged in 2-year-old's death in Bayfield County rollover
A Bayfield woman is accused of the reckless homicide of her 2-year-old daughter and of causing great bodily harm to her 4-year-old daughter, 6-year-old son and 15-year-old sister in a one-car rollover in which she was the driver and the only person wearing a seat belt or safety restraint.
Chelsea Nicole Cadotte, 23, was charged Tuesday with second-degree reckless homicide and three counts of first-degree reckless injury.
Mariah Gordon, 2, died as a result of injuries received in the July 23 accident on Wisconsin Highway 13, north of Washburn. Myley Gordon, 4, is in a coma with a traumatic brain injury, Carter Gordon, 6, suffered a broken hip and broken leg, and Erica Gonzales, 15, the defendant's sister, sustained lacerated internal organs, two broken wrists and a broken leg.
Cadotte, who has at least two prior citations for failing to restrain children in a vehicle, was the only person in the SUV who wasn't ejected from the vehicle. She expressed no visible emotion during a brief court appearance before Bayfield County Circuit Court Judge John Anderson. She waived reading of the complaint against her.
The Wisconsin State Patrol obtained a search warrant to inspect Cadotte's vehicle on Aug. 24. An expert found no mechanical problems that would have been a contributing factor to the crash.
"The investigation further revealed that at or about the time of the crash, Ms. Cadotte had been attempting to have some type of contact with the 2-year-old girl and had turned around to look at her," Bayfield County District Attorney Craig Haukaas said during a news conference outside the courtroom after the hearing. "The vehicle she was operating traveled across the oncoming lane of traffic, into the northbound gravel shoulder of the roadway. Ms. Cadotte overcorrected her steering, causing the vehicle to roll several times resulting in the aforementioned injuries and death."
Cadotte was booked into the Bayfield County Jail and released on a $25,000 signature bond. Anderson ordered her to not leave Wisconsin, except to visit a child in a Duluth hospital. The defendant also was ordered to not operate a motor vehicle with minor children as passengers and to maintain sobriety. She will be subject to random testing for sobriety by local law enforcement.
Haukaas said Cadotte had taken at least one training session on the use of child safety restraints and had been warned many times by community members and law enforcement that her children needed to be securely seat-belted while being transported. He said the defendant has received multiple citations for safety restraint violations over the past several years.
"We believe this established the probable cause to believe that Ms. Cadotte acted recklessly by failing to properly secure her passengers and showed utter disregard for human life causing the death of one human being and great bodily harm to three others," Haukaas said.
"We have the death of a child here that could have been prevented had safety restraints been used. ... Please buckle your children."
The defendant is accused of speeding, but not driving under the influence.
"There was no alcohol that was shown in the toxicology report," Haukaas said. "Evidence of drug usage is still under investigation. She did receive medication when she arrived at the hospital. That somewhat complicates the process of being able to determine the existence of drugs in advance."
After the hearing, Assistant State Public Defender Aaron Marcoux of Ashland said he and Cadotte were declining comment on the charges. When a reporter asked the current condition of 4-year-old Myley Gordon, Marcoux went to see his client and returned with the answer: "She's still in a coma, but breathing on her own and showing signs of reflexivity," Marcoux said.
Cadotte's next court appearance is scheduled for Nov. 13.