text:
TGF β-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7
- Esmeralda N Blaney Davidson1Email author,
- Elly L Vitters1,
- Wim B van den Berg1 and
- Peter M van der Kraan1
DOI: 10.1186/ar1931
© Blaney Davidson et al.; licensee BioMed Central Ltd. 2006
Received: 9 January 2006
Accepted: 7 March 2006
Published: 29 March 2006
Cartilage damage in osteoarthritis (OA) is considered an imbalance between catabolic and anabolic factors, favoring the catabolic side. We assessed whether adenoviral overexpression of transforming growth factor-β (TGFβ) enhanced cartilage repair and whether TGFβ-induced fibrosis was blocked by local expression of the intracellular TGFβ inhibitor Smad7. We inflicted cartilage damage by injection of interleukin-1 (IL-1) into murine knee joints. After 2 days, we injected an adenovirus encoding TGFβ. On day 4, we measured proteoglycan (PG) synthesis and content. To examine whether we could block TGFβ-induced fibrosis and stimulate cartilage repair simultaneously, we injected Ad-TGFβ and Ad-Smad7. This was performed both after IL-1-induced damage and in a model of primary OA. In addition to PG in cartilage, synovial fibrosis was measured by determining the synovial width and the number of procollagen I-expressing cells. Adenoviral overexpression of TGFβ restored the IL-1-induced reduction in PG content and increased PG synthesis. TGFβ-induced an elevation in PG content in cartilage of the OA model. TGFβ-induced synovial fibrosis was strongly diminished by simultaneous synovial overexpression of Smad7 in the synovial lining. Of great interest, overexpression of Smad7 did not reduce the repair-stimulating effect of TGFβ on cartilage. Adenoviral overexpression of TGFβ stimulated repair of IL-1- and OA-damaged cartilage. TGFβ-induced synovial fibrosis was blocked by locally inhibiting TGFβ signaling in the synovial lining by simultaneously transfecting it with an adenovirus overexpressing Smad7.
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown, synovial fibrosis, and bone spurs. An imbalance between catabolic and anabolic factors favoring the catabolic side is very likely involved in the pathological features of OA.
Currently, many attempts are being made to repair the cartilage that has been damaged in OA. One approach focuses on shifting the metabolic imbalance back by stimulating the anabolic side. Transforming growth factor-β (TGF-β) is one of the anabolic factors involved in cartilage maintenance and appears to be a good candidate for cartilage repair. TGF-β is a stimulator of extracellular matrix production, like collagen type II and proteoglycan (PG), in chondrocytes and it downregulates matrix-degrading enzymes [1]. High amounts of TGF-β are stored in healthy cartilage [2–6], whereas in OA cartilage the expression of TGF-β is reduced [7]. Injection of TGF-β into naive murine knee joints results in an increase in PG content of the articular cartilage [8]. Moreover, in murine experimental rheumatoid arthritis, injection of TGF-β protected cartilage from PG loss [9]. In addition, TGF-β counteracts the anabolic factor interleukin-1 (IL-1), which is a very potent inducer of cartilage degradation [10, 11] both in vivo and in vitro [1, 12–16]. These data indicate that TGF-β has great potential as a tool for stimulating cartilage repair.
To obtain sufficient amounts of TGF-β in the joint for a prolonged period of time, an adenovirus can be used as a vehicle. In vitro, chondrocytes that are transfected with an adenovirus encoding TGF-β responded by elevation of PG and collagen production [17]. We wanted to assess whether adenoviral overexpression of TGF-β in the synovial lining could stimulate repair of damaged cartilage in vivo.
Unfortunately, introducing high amounts of TGF-β into a knee joint has adverse effects. Administration of 20 ng TGF-β is already sufficient to result in an increased cellularity of the synovial lining, expansion of fibroblast population in the synovial connective tissue, and continued collagen deposition [18]. Injection of high amounts of TGF-β, either as a bolus injection or via adenoviral transfection, results in marked hyperplasia of the synovium and chondro-osteophyte formation [8, 18–21]. This illustrates that the use of TGF-β for cartilage repair can result in side effects that are deleterious for future therapeutic applications.
The aim of this study was to use TGF-β as a cartilage repair factor but at the same time to prevent the TGF-β-induced fibrotic side effect. Therefore, we examined the effect of adenoviral overexpression of active TGF-β on cartilage repair and additionally studied whether simultaneous Smad7 overexpression could block TGF-β-induced fibrosis. Smad7 is an intracellular molecule that inhibits the TGF-β signaling pathway. TGF-β binds to its type II receptor, which then forms a complex with the type I TGF-β receptor.
Subsequently, the intercellular signaling molecule Smad2 or Smad3 gets phosphorylated, forms a complex with common Smad, Smad4, and shuttles to the nucleus for transcription [22]. Smad7 inhibits Smad2 and Smad3 phosphorylation, thereby preventing further signaling [23, 24].
To both stimulate cartilage and block side effects, we took advantage of the fact that adenoviruses, once injected into the murine knee joint, transfect the synovial lining but do not penetrate the cartilage [25]. We co-transfected the synovial lining with an adenovirus overexpressing TGF-β and an adenovirus overexpressing Smad7. The transfected synovial lining cells will produce TGF-β but due to an intercellular signaling block caused by Smad7, will no longer respond to this factor.
We show that adenoviral overexpression of TGF-β results in increased PG content of the cartilage both after IL-1-induced damage and in a spontaneous model of experimental OA. In both cases, the TGF-β-induced fibrosis can be prevented by simultaneous Smad7 overexpression.
Materials and methods
C57Bl/6 mice (10 weeks old) and STR/ort mice (4 weeks old) were used. Mice were kept in filter-top cages with woodchip bedding under standard pathogen-free conditions. They were fed a standard diet and tap water ad libitum. The local animal committee had approved this study.
Stimulation of cartilage repair by TGF-β after IL-1 insult
To assess whether adenoviral overexpression of TGF-β could stimulate cartilage repair, we inflicted cartilage damage in 73 C57Bl/6 mice by intra-articular injection of 10 ng IL-1 (R&D Systems, Inc., Minneapolis, MN, USA). Two days after IL-1 injection, PG synthesis will have reached a low point [11]. At this time point, an adenovirus overexpressing active TGF-β (Ad-TGF-β223/225) was injected intra-articularly (plaque-forming units [pfu] 107/6 μl) and compared with a control virus (Ad-del 70-3). Four days after the primary insult, 53 mice were used for patellae isolation for PG synthesis measurement by 35SO42- incorporation. The other 20 mice were used for isolation of whole knee joints for histology.
Blocking TGF-β-induced fibrosis
To block TGF-β-induced fibrosis, 24 C57Bl/6 mice were injected intra-articularly with adenoviruses in the combinations of Ad-TGF-β223/225 + Ad-luciferase (Ad-luc), Ad-Smad7 + Ad-luc, and Ad-TGF-β223/225 + Ad-Smad7 (at a pfu of 0.5 × 107 per adenovirus in 6 μl) or Ad-luc alone (at a total pfu of 107) as a control. After 14 days, when synovial fibrosis can be observed histologically, knee joints were isolated for histology.
Simultaneously stimulating cartilage repair and blocking of fibrosis
To make sure that Smad7 did not interfere with TGF-β-stimulated PG synthesis, we assessed whether stimulation of cartilage repair was not blocked by co-transfection with Ad-Smad7, and cartilage damage was again introduced in 48 C57Bl/6 mice by intra-articular injection with 10 ng IL-1. After 2 days, mice were injected with adenoviruses in the combinations of Ad-TGF-β223/225 + Ad-luc, Ad-TGF-β223/225 + Ad-smad7, or Ad-luc alone. Four days after IL-1 injection, 24 mice were used for isolation of patellae for 35SO42- incorporation measurements. After 2 weeks, the other mice were used for isolation of knee joints for histological assessment of fibrosis.
Cartilage repair while blocking fibrosis in spontaneous OA
To test whether we could stimulate cartilage repair in a spontaneous experimental OA model while preventing fibrosis, we extended our experiment to STR/ort mice. STR/ort mice develop OA spontaneously and show pathological changes by 8 weeks of age. We injected adenoviruses intra-articularly into the knee joint of 24 4-week-old STR/ort mice and repeated this injection after 2 weeks. The adenoviruses were injected in the combinations of Ad-TGF-β223/225 + Ad-luc, Ad-smad7 + Ad-luc, and Ad-TGF-β223/225 + Ad-smad7 at a pfu of 0.5 × 107 per adenovirus or Ad-luc at a pfu of 107 alone as a control. Four weeks after the first injection, knee joints were isolated for histological analysis of synovial fibrosis and PG content of the cartilage.
Knee joints of mice were dissected and fixed in phosphate-buffered formalin for 7 days. Thereafter, they were decalcified in 10% formic acid for 1 week. Knee joints were dehydrated with an automated tissue-processing apparatus (Tissue Tek VIP, Sakura, Ramsey, MN, USA) and embedded in paraffin. Coronal whole knee joint sections of 7 μm were made. Sections were stained with Safranin O and Fast Green.
Sections were deparaffinized and washed with phosphate-buffered saline (PBS). For antigen unmasking, sections were incubated in citrate buffer (0.1 M sodium citrate + 0.1 M citric acid) for 2 hours. Endogenous peroxidase was blocked with 1% hydrogen peroxide in methanol for 30 minutes. Thereafter, sections were blocked with 5% normal serum of the species in which the secondary antibody was produced. Specific primary antibodies against procollagen type I (2 μg/ml) (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) were incubated overnight at 4°C. After extensive washing with PBS, the appropriate biotin-labeled secondary antibody was used (DakoCytomation, Glostrup, Denmark) for 30 minutes at room temperature followed by a biotin-streptavidine detection system according to manufacturer's protocol (Vector Laboratories, Burlingame, CA, USA). Bound complexes were visualized using DAB (3,3'-diaminobenzidine) reagent, counterstained with haematoxylin, dehydrated, and mounted with Permount.
PG synthesis
For measurement of PG synthesis, 35SO42- was incorporated into isolated patellae. Immediately after isolation, the patellae were placed in Dulbecco's modified Eagle's medium with gentamicin (50 mg/ml) and pyruvate. After half an hour, medium was replaced by medium containing 35SO42- (20 μCi/ml) and incubated for 3 hours at 37°C in 5% CO2. Patellae were then further prepared for measurement of 35SO42- incorporation in the articular cartilage as previously described [26].
PG content
PG content was measured in sections stained with Safranin O and Fast Green, using a computerized imaging system as previously described [27]. Briefly, Safranin O stains PGs in the cartilage red. The amount of PGs is determined by a computerized calculation of the amount of blue light passing through the red-stained cartilage. An increase in PGs leads to more intense red staining and reduced blue light passing through. The PG content of the tibia was calculated by the average of three sections per joint.
Measurement of fibrosis
Sections were stained immunohistochemically for procollagen type I as a measure of fibrosis. Subsequently, the amount of cells that stain positive in the synovial tissue was determined. A blinded observer selected the synovial tissue in three sections per knee joint. A computerized imaging system subsequently determined the amount of positive cells in the selected area. The obtained values were averaged per knee joint.
In addition, synovial hyperplasia was assessed by measurement of synovial thickness. This was determined in sections stained with Safranin O and Fast Green. The thickness of the synovial tissue was measured with a computerized imaging system again in three sections per knee joint and averaged per joint as previously described [27] (Qwin; Leica Imaging Systems Ltd., Cambridge, UK). In short, the width of the joint from bone edge to joint capsule, minus the width of the joint space itself, was determined.
Statistical analysis
Results were analyzed with a Student's t test and stated significant if the p value was lower than 0.05.
Overexpression of TGF-β stimulates cartilage repair
TGF-β induces synovial fibrosis that can be blocked with Smad7
TGF-β overexpression repairs cartilage while fibrosis is blocked with Smad7
These data show that after IL-1-induced cartilage damage, the TGF-β-induced fibrosis could still be blocked by Smad7 overexpression without interfering with the effect TGF-β elicits on cartilage.
In experimental OA, simultaneous overexpression of TGF-β and Smad7 increased PG content of cartilage and prevented synovial fibrosis
Combining overexpression of TGF-β and Smad7 managed to maintain a significantly higher PG content in cartilage than controls (p < 0.005) (Figure 5). More than half of the increased synovial thickening that had been caused by TGF-β was inhibited significantly by overexpression of Smad7 (p < 0.005). The amount of procollagen type I-positive cells had been reduced accordingly (Figure 6).
These data clearly indicate that PG synthesis can be stimulated while inhibiting an increase of synovial fibrosis in an experimental model of OA.
The cartilage damage in OA is thought to be a consequence of a misbalance between anabolic and catabolic factors, favoring the catabolic side. In this study, we used TGF-β as the anabolic factor for cartilage repair. TGF-β has been reported to enhance periosteal chondrogenesis in explants in a dose-dependent manner [28]. Morales and colleagues [4, 5] demonstrated that TGF-β increased PG synthesis and suppressed its degradation in articular cartilage organ cultures. In addition, van Beuningen and colleagues [8] showed that in vivo TGF-β injections result in prolonged elevation of PG synthesis and PG content of cartilage in mice. These studies indicate that TGF-β has good potential for repairing cartilage. We showed that adenoviral overexpression of TGF-β was indeed able to boost cartilage repair in vivo. In vitro, it had already been shown that chondrocytes exposed simultaneously to IL-1 and TGF-β could reverse the IL-1-induced suppression of PG incorporation in their extracellular matrix [15]. Supportive of our findings, van Beuningen and colleagues [13] demonstrated that, in vivo, TGF-β also counteracted deleterious effects of IL-1 on cartilage PG synthesis and PG content. In the current study, we first damaged cartilage by IL-1 injection and subsequently overexpressed TGF-β. In this way, we could assess whether TGF-β was able to restore, instead of prevent, cartilage damage. We introduced TGF-β via adenoviral overexpression, thereby gaining prolonged high expression of TGF-β, instead of via a bolus injection that results in short TGF-β exposure. This way, we were able to demonstrate increased PG synthesis and higher PG content in cartilage not only in a clean setting introducing cartilage damage with IL-1 but also in a spontaneous OA model.
The drawback of using TGF-β is that it can have adverse effects in joints. TGF-β is a known inducer of fibrosis in various tissues, and synovial tissue is no exception [8, 21]. We took advantage of the fact that adenoviruses transfect only the synovial lining. In addition, we profited from the fact that Smad7 is an intercellular inhibitor of TGF-β. Smad7 stays inside the cell that is transfected with the adenovirus encoding Smad7. Because the synovial lining is where TGF-β induces synovial fibrosis, by co-transfection with Smad7, the lining appeared to be less sensitive to TGF-β-induced fibrosis. The reduction of TGF-β-induced fibrosis was not optimal and resulted in only a partial block of the fibrosis. This is likely due to the fact that not all cells in the synovial lining will be targeted. By optimizing this, we might be able to target every single one of the synovial lining cells and thereby fully block the TGF-β-induced fibrosis.
We have previously demonstrated that blocking TGF-β with Ad-Smad7 in OA resulted in reduction of the synovial fibrosis that was induced by the OA process itself [27]. Now we combined the Smad7 adenovirus with Ad-TGF-β to block the TGF-β-induced fibrosis. We showed that the Ad-TGF-β transfection was still functional in combination with Smad7. Moreover, we demonstrated for the first time that adenoviral overexpression of TGF-β could stimulate repair of damaged cartilage and that co-expression with Smad7 could prevent a great deal of the TGF-β-induced synovial fibrosis. Combining Smad7 and TGF-β resulted in a higher PG synthesis after IL-1 insult than did TGF-β alone. This is likely due to the reduced synovial fibrosis when combined with Smad7.
Unfortunately, synovial fibrosis is not the only side effect of TGF-β overexpression in knee joints. TGF-β can induce osteophyte formation [8, 19, 20, 29–31]. In the case of OA, TGF-β can aggravate the osteophyte formation that already occurs. We show that it is possible to target synovial cells to prevent fibrosis. In a similar fashion, we could potentially target the mesenchymal stem cells that eventually form the osteophytes after TGF-β exposure. This could be an option when key players of osteophyte formation are identified and can be blocked selectively.
We demonstrated that adenoviral overexpression of TGF-β increases PG synthesis and PG content in cartilage, even in experimental OA. In addition, co-transfecting the synovial lining with Ad-Smad7 can block the fibrosis that is induced by TGF-β overexpression.
= interleukin-1
- Luc:
= luciferase
= osteoarthritits
= phosphate-buffered saline
- pfu:
= plaque-forming unit
= proteoglycan
- TGF-β:
= transforming growth factor-β
We thank Dr. C.D. Richards for the gift of the TGF-β adenovirus. ENBD and PMK were financially supported by the Dutch Arthritis Association "Reumafonds."
Authors' Affiliations
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> From: firstname.lastname@example.com
> I have been having a problem with a woodchuck/woodchucks chewing
up plenty of plants in the garden.If anyone knows a trick or
something to scare them away or stop them from chewing up my plants
I'd like to hear it
An aggressive dog running loose will encourage them to move to
another area; tethered or indoor dogs won't discourage them.
Chickenwire fence buried at least a foot in the soil, turned out away
from what you're trying to protect will stop them. Fence doesn't
have to be more than 3' tall. You might also try hot pepper spray or
one of the other nasty tasting sprays available for discouraging
wildlife. They are strict herbivores and can wreak havoc on tasty
plantings - I used to have a time with them when I grew veggies
before I fenced off the veggie garden.
Woodchucks (AKA groundhogs) have poor eyesight but excellent hearing.
They are not rocket scientists in the brain department. They are
excellent diggers but don't climb. If cornered, they can be
aggressive and bite, otherwise they are fairly mild mannered. They
dig extensive burrows with more than one entrance, generally marked
by a large mound of soil outside the main entrance. If you find a
den, you can try running a hose in it tho' that doesn't always
work...but if you do it enough, they might decide to move elsewhere.
Marge Talt, zone 7 Maryland
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Data from Jazz Pharmaceuticals' First Phase III Study of Sodium Oxybate in Patients With Fibromyalgia to be Presented at Upcoming Conferences
PALO ALTO, Calif., Oct. 14 /PRNewswire-FirstCall/ -- Jazz Pharmaceuticals, Inc. (Nasdaq: JAZZ) announced today that data from the company's first Phase III clinical trial of sodium oxybate (JZP-6) for the treatment of fibromyalgia will be presented next week during the American College of Rheumatology 2009 Annual Meeting (ACR) in Philadelphia, Pennsylvania and also in November during the US Psychiatric and Mental Health Congress (US Psych Congress) in Las Vegas, Nevada.
- At ACR on October 20, 2009, I. Jon Russell, MD, PhD, Associate Professor of Medicine in the Division of Clinical Immunology and Rheumatology and Director, University Clinical Research Center at The University of Texas Health Science Center at San Antonio, will present a poster entitled, Effect of Sodium Oxybate on Pain, Functionality, PGIc, & Composite Scores in Fibromyalgia Results from a Phase 3 Controlled Trial. The poster will be presented in the 9:00 am 11:00 am poster session.
- Also at ACR on October 20, 2009, Philip J. Mease, MD, Clinical Professor at the University of Washington School of Medicine in Seattle and Chief of Rheumatology Clinical Research at the Swedish Hospital Medical Center, will present a poster entitled, Sodium Oxybate Improves Fatigue, Sleep Disturbance, and PGIc in Fibromyalgia Results from a Phase 3, 14-Week Controlled Trial. The poster will be presented in the 9:00 am 11:00 am poster session.
- At US Psych Congress on November 2, 2009, Stephen S. Flitman, MD, Medical Director at 21st Century Neurology, a division of Xenoscience, will present a poster entitled, Efficacy and Safety of Sodium Oxybate in Fibromyalgia: A 14-week, Randomized, Double-blind, Controlled Trial". The poster will be presented in the 3:45 pm 6:45 pm poster session.
Jazz Pharmaceuticals has completed two Phase III pivotal clinical trials of JZP-6, with positive results in both studies. Jazz Pharmaceuticals is working to submit a New Drug Application for sodium oxybate for the treatment of fibromyalgia to the U.S. Food and Drug Administration by the end of 2009.
About Sodium Oxybate
Sodium oxybate is the sodium salt form of gamma-hydroxybutyrate, an endogenous neurotransmitter and metabolite of GABA. While the precise mechanism of action is unknown, the effects may be mediated in part through interaction with GABA(B) and GHB receptors. Sodium oxybate is the active ingredient in XYREM®, approved by the FDA for the treatment of excessive daytime sleepiness and cataplexy (the sudden loss of muscle tone) in adult patients with narcolepsy. The American Academy of Sleep Medicine recommends sodium oxybate as a standard of care for the U.S. Food and Drug Administration-approved indications. It is also approved by the European Medical Evaluation Agency for the treatment of narcolepsy with cataplexy in adult patients. Most commonly reported adverse drug reactions in narcolepsy patients are dizziness, nausea and headaches. Sodium oxybate has the potential to induce respiratory depression and neuropsychiatric events. Sodium oxybate has not been evaluated by regulators for the treatment of fibromyalgia and is not approved for this use.
About Fibromyalgia
Fibromyalgia, a chronic condition characterized by widespread pain, affects 0.5% - 5% of adults worldwide. Fibromyalgia is believed to be a central nervous system condition, resulting from neurological changes in how the brain perceives and responds to pain. In addition to pain, the main symptoms are fatigue, disturbed sleep and morning stiffness. The exact causes of fibromyalgia are unknown. It may be triggered by physical trauma, emotional stress, chronic pain or infection. Genetics, neurochemicals that affect pain modulation, neurohormones and sleep physiology abnormalities are thought to play a role. Research also has suggested a relationship between sleep and pain. Fibromyalgia patients experience a high prevalence of sleep problems, including a reduction in non-restorative or deep sleep.
About Jazz Pharmaceuticals, Inc.
Jazz Pharmaceuticals is a specialty pharmaceutical company that identifies, develops and commercializes innovative treatments for important, underserved markets in neurology and psychiatry. For further information please see www.jazzpharmaceuticals.com.
SOURCE Jazz Pharmaceuticals, Inc.


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Stochasticity plays an important role in many biological processes. Examples include bistable genetic switches, noise enhanced robustness of oscillations, and uctuation enhanced sensitivity or "stochastic focusing". Numerous cellular systems, including development, morphogenesis, polarization and chemotaxis rely on spatial stochastic noise for robust performance. At the same time, stochastic simulations are complex and consume large amounts of computer time. They may require the researcher to be procient in the use of one or more complex software packages. Learning to use existing simulation tools and to integrate them with other software takes considerable time. In many cases, the tools do not exist and require the expertise of mathematicians and computer scientists to develop them. Often, researchers must purchase and maintain clusters of computers to perform the large-scale computations. All of this adds costs and delays to the research process. Currently, there exists no software package that allows researchers to easily build a stochastic model of a biological system, and scale it up to increasing levels of detail and complexity. We propose to build an environment where the modeler can focus his/her attention on the biology;alleviating the burden of software installation and versions, mathematical algorithms, code optimizations, computer systems, etc. This environment will run on laptops and computer workstations (for small problems), extending on demand to high-performance compute clusters, grids, and public or private clouds;thus creating a cost-eective and energy-ecient solution for simulations of all sizes. We will equip this environment with state of the art software for key classes of problems, and make it easy for software developers to integrate new and improved algorithms without the need to develop their own software infrastructure. We will develop new algorithms and software to address key computational capabilities that have not previously been attainable: (1) fully- adaptive, hybrid solvers for sti (and nonsti) well-mixed systems (2) ecient computation of probabilities of rare events, and (3) simulation of spatial stochastic systems at speeds that are several orders of magnitude faster than previous methods. The availability of such a community resource will enable and accelerate progress in both biology and algorithm development.
Computer modeling and simulation provide critical insights necessary for the understanding of fundamental cellular systems: researchers postulate a mathematical model incorporating the relationships between key components, simulate it on a computer, and then compare the results to experiment to determine whether the model is plausible. Such an understanding, or model, of a biochemical process is important for drug targeting and therapeutic intervention. Stochasticity (randomness) plays an important role in many biological processes. Such simulations are complex and consume large amounts of computer time. We propose to build a comprehensive, state of the art software system for simulating stochastic models. The availability of such a community resource will enable and accelerate progress in biology and medicine.
|Gillespie, Daniel T; Petzold, Linda R; Seitaridou, Effrosyni (2014) Validity conditions for stochastic chemical kinetics in diffusion-limited systems. J Chem Phys 140:054111
|Wang, Siyang; Elf, Johan; Hellander, Stefan et al. (2014) Stochastic reaction-diffusion processes with embedded lower-dimensional structures. Bull Math Biol 76:819-53
|Krintz, Chandra (2013) The AppScale Cloud Platform: Enabling Portable, Scalable Web Application Deployment. IEEE Internet Comput 17:72-75
|Hellander, Stefan (2013) Single molecule simulations in complex geometries with embedded dynamic one-dimensional structures. J Chem Phys 139:014103
|Sturrock, Marc; Hellander, Andreas; Matzavinos, Anastasios et al. (2013) Spatial stochastic modelling of the Hes1 gene regulatory network: intrinsic noise can explain heterogeneity in embryonic stem cell differentiation. J R Soc Interface 10:20120988
|Lawson, Michael J; Drawert, Brian; Khammash, Mustafa et al. (2013) Spatial stochastic dynamics enable robust cell polarization. PLoS Comput Biol 9:e1003139
|Gillespie, Daniel T; Hellander, Andreas; Petzold, Linda R (2013) Perspective: Stochastic algorithms for chemical kinetics. J Chem Phys 138:170901


text:
I have to study this for my pre tomorrow, but I have no idea what is??? Help please!
Cyclonic or 'frontal' rain occurs where two air masses meet and form a 'front.' The warmer, moisture laden air rises over the colder air as a 'warm front'. As the air rises it cools, and its relative humidity increases. Clouds form as water vapor condenses, and then fall as rain.


text:
Psalm 48New International Version (NIV)
Psalm 48[a]
A song. A psalm of the Sons of Korah.
1 Great is the Lord, and most worthy of praise,
2 Beautiful in its loftiness,
4 When the kings joined forces,
8 As we have heard,
9 Within your temple, O God,
12 Walk about Zion, go around her,
14 For this God is our God for ever and ever;
Cross references:
New International Version (NIV)
Holy Bible, New International Version®, NIV® Copyright ©1973, 1978, 1984, 2011 by Biblica, Inc.® Used by permission. All rights reserved worldwide.
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Is Eng Soon Kee Satay incorrect or missing key business information? Update your Hotfrog listing today.
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Product Description
The Butte Leather & Brindled Hair Oblong Pillow by Wooded River is made from Butte Leather and Dark Brindle Hair on Hide Leather. The fringes on the ends of the oblong pillow are made from Butte Leather. The Dark Brindle Hair on Hide & Butte Leather used to make this pillow will give that extra flair to your rustic lodge, western ranch, log cabin, or use in your contemporary home for an eclectic look.
Enjoy this rugged, hair on hide pillow on your living room couch or loveseat or as an accent pillow in your bedroom retreat.
- Made from Butte Leather and Dark Brindled Hair on Hide Leather.
- Made proudly in the USA!
|12" x 18"
|Typically Ships Via
|Shipping Cost
|Free Shipping - Curbside/Tailgate Delivery
|Free Shipping Requirements
|Free Curbside/Tailgate Shipping within the Contiguous 48 States
|Usually ships in 2 - 4 weeks


text:
PHP + JQuery - Web Application with Social APIs
This project received 20 bids from talented freelancers with an average bid price of ₹ INR / hour.Get free quotes for a project like this
Project Budget₹400 - ₹750 INR / hour
Total Bids20
Project Description
Build a Web Application with support for Social Sites - FB, Twitter, Google+, Youtube API, Google Search API.
* Publish now [ or Schedule] Twitter Tweets & FaceBook Posts.
--Ex: for Twitter - Users have to use their Twitter account - to authorise the App to do publish post/ Tweet, Follow, Get Info About Followers, Following, + Other options Supported by the respective API.
* Capture Data from APIs to Store into our NOSQL DB
* Use the above & other data - to visualize - interactively.
Also Should support:
* Connect to LinkedIN -
* Connect to Google+
Should have extensive experience in JQuery, PHP, Creating FB app, Twitter app, - LinkedIN API, Google+ API.
Reports & Visualization of Data from DB - Using HighCharts / JQuery Chart
Skills Required
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- Set your budget and the timeframe
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text: The Spinning Magic Of Left-Footed PuntersJack Dickey11/04/11 10:45amFiled to: NflpuntersAfterballhang up and listenRepublishedNewstweet29EditPromoteShare to KinjaToggle Conversation toolsGo to permalink Why did the Saints, Chargers, and Ravens—three teams with above-average punters—all work out free agent punters last week? No, it's not because any of those teams is scapegoating their punter for the whole team's jaw-dropping inconsistency. Rather, they wanted to practice against left-footed punters before facing real NFL lefties in their next games. Conventional wisdom says lefties get a spin on their balls that righties don't. But author Stefan Fatsis, who knows whereof he speaks regarding NFL special teams, says there's less importance than ever in punting left-footed, as he explains on this week's excerpt from Slate's Hang Up and Listen podcast. Advertisement You can listen to the full podcast here or subscribe on iTunes.Reply29 repliesLeave a reply


text:
404 File Not Found
Host by NetBox Version 2.8 Build 4128
Don't Let the Pigeon Stay Up Late! recounts the story of a stubborn pigeon who is just not willing to go to bed. It's really dark and past bed time but this pigeon plays all kinds of tricks trying to escape.
Please choose which cart you want to add the item.
By choosing one of the above, you are able to shop for both yourself and a registrant at the same time. Once you are ready to checkout your items will be waiting for you in both your personal and registry shopping carts.
Still need assistance?
Please contact us at 1-866-YOYO-123 (1-866-969-6123)


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Courtyard By Marriott Buffalo hotels are provided below. Search for cheap and discount Courtyard By Marriott hotel rates in Buffalo, NY for your upcoming individual or group travel. We list the best Courtyard By Marriott Buffalo hotels/motels so you can review the Buffalo Courtyard By Marriott hotel list below to find the perfect place.
Our booking engine will also list Buffalo, NY hotels that are comparable to the quality of Courtyard By Marriott.Booking a group or meeting? Set up a group hotel block in Buffalo NY
How should we direct your call?
When you stay at Courtyard Buffalo Downtown / Canalside in Buffalo, you'll be on the waterfront and minutes from Canalside and Buffalo and Erie County Naval and Military Park.


text:
Annual Report 2016
Quarterly Newsletter
Our funding comes from various State and Commonwealth Government departments.
Translation Disclaimer: Translations of pages on CBCHS website are performed by Google™ Translate, a third party service, over which CBCHS has no control. Translated pages are not part of the CBCHS website. This service is an automated computer translation and, as such, will not be a perfect translation and will be prone to mistakes that a human speaker would not otherwise make. The translation should be used as a rough guide only. CBCHS in no way accepts liability for the accuracy of these translations or any loss incurred as a result of them.


text:
Back to School for Single Moms Doesn't Have to Mean Mornings Full of Temper Tantrums, Scowls and Crying!
Are there any moms out there who relish weekday school morning routines– the mad dash to get everyone fed, dressed and packed up for school? Well, I have yet to meet that mom and if you're out there- please share with us at SMW- the secret to your back-to-school morning success…
But if you're like so many of the single moms out there- who spend 8o percent of the morning battling with your kids on everything from what clothing to wear to what cereal they're going to eat for breakfast– we've got the perfect article for you this week: Tips just for single moms to eliminate the school morning rush- and make it almost –dare I say-peachy!
We've also got some really exciting things happening at single minded women…especially for single moms. We'd love to hear your stories, see photos of your little ones and hope that you'll share a few of your life's greatest pleasures and pains and what ultimately gets you through the day.
Please visit us at our brand new community and tell us about your experiences– remember we're all in this together!!
Happy Sunday-
Melissa Chapman,


text:
LRTV Profile: Genband
Light Reading
LRTV Profile: Genband
LRTV NXTcomm6/20/2007
Light Reading
Newest First | Oldest First | Threaded View ADD A COMMENT
Educational Resourcessponsor supplied content
More Blogs from LRTV NXTcomm
NXTcomm 2008 is history and the shows executive director explains what the show tried to accomplish and several attendees weighed in with their thoughts as well
ECIs president and CEO Rafi Maor explains how carriers can provide scalable services and why managed services is a tempting business for vendors
Ken Hertzler, Director, NEC Corp. of America says virtualizing the data center can save CPU cycles, power, and money.
Sun Microsystemss Greg Calhoun talks about how his company can help service providers be more energy efficient
NECs Naoki Satomi discusses IMS and its challenges
From The Founder
Flash Poll
Live Streaming Video
Charting the CSP's Future
Six different communications service providers join to debate their visions of the future CSP, following a landmark presentation from AT&T on its massive virtualization efforts and a look back on where the telecom industry has been and where it's going from two industry veterans.
Upcoming Live Events
March 21-22, 2017, The Curtis Hotel, Denver, CO
March 22, 2017, The Curtis Hotel, Denver, CO
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May 15, 2017, Austin Convention Center - Austin, TX
All Upcoming Live Events
June 6, 2017, The Joule Hotel, Dallas, TX
SlideshowsA Photo Tour of CES 2017
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Hot Topics
Uber's HR Nightmare: Company Investigates Sexual Harassment Claims Sarah Thomas, Director, Women in Comms, 2/21/2017
Broadband Has a Problem on the Pole Mari Silbey, Senior Editor, Cable/Video, 2/21/2017
Verizon to Start Fixed 5G Customer Trials in April Dan Jones, Mobile Editor, 2/22/2017
Cloud Rains on HPE Earnings Mitch Wagner, Editor, Enterprise Cloud, 2/24/2017
Telefónica's Blanco: 5G NR 'Acceleration' Is 'Big Mistake' Iain Morris, News Editor, 2/27/2017
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Understanding the SDN-Driven IP and Optical Renaissance
March 7, 2017
IoT Security - Be Battle Ready
March 15, 2017
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March 23, 2017
Cloud-Native Architectures Will Be Key to 5G NG Core
BETWEEN THE CEOs - Executive Interviews
Light Reading founder and CEO Steve Saunders chats with Sportlogiq CEO Craig Buntin about sports data analysis.
Eyal Waldman, CEO of Mellanox Technologies, speaks to Steve Saunders, CEO of Light Reading, for an exclusive interview about the 100 GB cable challenge, cybersecurity and much more.
Animals with Phones
No One Likes This Click Here Take a hint!
Live Digital Audio


text:
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- 06-15-2014, 05:29 PM Thread Author #1
My SG3 wont turn on.
Hi. Please help. my SG3 wont turn on. It is stuck on the start up screen but doesnt proceed and further than that. I continues to flash the same screen. When I put it on charge to flashes two alternative battery icons. I have taken the battery out and put it back in the phone immediately starts flashing the start up screen without the power button even being pushed. What can I do to try fix it?
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Re: My SG3 wont turn on.
Welcome to Android Central! Have you tried a replacement battery? Also try booting into the Recovery menu and clearing the system cache partition. You won't lose any personal data. [Guide] Rebooting into Recovery Mode for the Galaxy S2, S3, and Tab2.
Posted via Android Central App.
Please excuse any typos or autocorrect derps.
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[UPDATE] access cheater's sms cell download fiel [jc1b] free
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FileName: access cheater's sms cell
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04/06/2015 01:52:18
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Windows XP/Vista/7/8 (32-Bit/64-Bit)
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04/06/2015 01:52:18
Taylor Swift download license key spyware terminator 2012 Vs Frozen With just Trouble In Taylor Paradise. Swifts New Love Matt Healy Caught Cheating With Fans go nuts ...FlexiSPY lets you spy on mobile phones and tablets and has unique call interception capability. Provides SMS Tracker, Cell phone tracker, room bugging total ...TheTruthSpy Phone Spy App Can Track The Exact Position, mobile spy app, android spy, call recording, whatsapp spy, sms tracker, call tracking2/6/2014 · Spy SMS - phone text messages FREE Without Access to ... ... kopitubruxSpy Phone software for listening of room conversations, incoming and outgoing call interception,mobile phone tracking, Spy SMS messages.Mobile spy ...I want to track my girlfriends sms messages as i think she maybe cheating on me but i can never get her phone as she never leaves it out of her hand. is there anyway ...10/26/2014 · SPY SMS free! Link: Have you ever imagine how would it be to have possibility of spying sms free online? Have you ever wondered how wou. How to spy SMS …6/2/2013 · This video show you how to install the first spy software for iPhone 100% FREE at WWW.BOSSPY.COM How to spy SMS for free read whatsapp chat, text messages ...Best Monitoring Software For Parents . Best Monitoring Software For Parents. Can you spy on a cell phone even if you can't ever get access to that cell phone?The ExactSpy app includes a cell phone tracker that instantly pinpoints your missing smartphone or tablet on a familiar Google map. Just log into ExactSpy from a ...
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text:
Boy Ballets up to the Barre in Billy Elliot the Musical
Giuseppe Bausilio as Billy Elliot
Michael Brosilow
Theater Caps are bite-sized punch-packing capsule reviews by resident theater critic Elaine Liner. Use them as a reminder -- or a teaser, if you procrastinate -- of her full-length reviews in The Mixmaster's weekly sister.
If the son of a Geordie coal miner can become a ballet dancer, anyone can. That's how you'll feel after seeing the touring production of Billy Elliot the Musical, playing through June 19 at the Winspear Opera House. On opening night, people left the show singing and dancing like giddy fools across the plaza. It makes you feel that good, this story of a motherless kid in Northern England who discovers how good it feels to dance his troubles away.
Like the 2000 movie it's based on, the Tony-winning Broadway adaptation was directed by Stephen Daldry. Lee Hall wrote the musical's book and lyrics; Elton John composed the score. It's an enormous show, heaving with rapidly moving scenery, overflowing with bright-eyed tutu'd moppets and banging with John's throbby rock. It's one of the biggest, best Broadway tours to blow through here since Wicked.
The touring production rotates five boys in the role of Billy, whose dream of winning a spot in a prestigious British ballet academy is nearly thwarted by his working-class family. Swiss 13-year-old Giuseppe Bausilio performed Billy on press night and he goes from Dallas right into the Broadway cast. But another little showman in the ensemble here is Griffin Birney, who plays Billy's cross-dressing friend Michael. Their big dance number, "Express Yourself," becomes a child's fantasia as they sing and tap with a chorus of giant frocks.
Upcoming Events
Throw a Little Magic in to Your Reality
TicketsTue., Feb. 28, 7:30pm
The Illusionists
TicketsWed., Mar. 1, 7:30pm
Jazz Satin Dolls ft. Sabrina Kessee, Brittany Johnson & Amanda Curtis
TicketsFri., Mar. 3, 9:00pm
Let It Be
TicketsTue., Mar. 7, 7:30pm
TicketsThu., Mar. 9, 7:30pm
Broadway veteran Faith Prince stomps around in baggy leg-warmers as chain-smoking village ballet teacher Mrs. Wilkinson, who discovers Billy hanging back after boxing lessons. She's old-school, like Betty Buckley and Patti LuPone, with a big, expressive face and knockout voice.
Peter Darling's choreography might remind you of the story-dances in West Side Story or Carousel. The dances in Billy Elliot rise so organically from the storyline, whole scenes are expressed without dialogue. Billy's solo audition for the academy is a transcendent moment of pure dance. Hard to believe it's performed by a young teen.
Don't rush out after Billy's exit at the end of the show. The curtain call brings the whole cast back in sparkly costumes for a long, exuberant celebration of happy hoofing.
Billy Elliot the Musical continues through June 19 at the Winspear Opera House. Call 214-880-0202.
Related Location
2403 Flora St.
Dallas, TX 75201-2415
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Women's Gymnastics
Oregon St., Cal
Fri., Mar 1
Watch 3/1 at 5:30 PM PT
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Back on Track
Stanford scored a season-high 49.125 on beam to secure a 195.775-195.200 victory at Arizona State on Saturday.
Stanford's Nicolette McNair on teams' beam set: 'We can hit big routines'
Pac-12 Networks' Sam Peszek speaks with Stanford women's gymnastics' Nicolette and Danielle McNair, after the Cardinal defeated Arizona State, 195.775-195.200.
Desert Dual
Stanford leaves California for the second time this season when it takes on Arizona State on Saturday at noon (PT).
Stanford Falls at UCLA
Stanford scored a season-high 49.300 on vault but had a tough day overall, dropping a 198.125-194.175 decision at UCLA on Saturday afternoon.
All-Time Letterwinners
Stanford Letterwinners
Special Price
Elizabeth Price earned her second Pac-12 Specialist of the Week honor this season, as announced Tuesday by the conference.


text:
Maxwell Communication Corporation creditors have approved by more than 99 per cent by number and value a UK scheme of arrangement and a US Chapter 11 reorganisation plan, according to Price Waterhouse, the administrator.
The sale of assets can now go ahead, including the Official Airlines Guide to Reed Elsevier, the publishers, for dollars 425m. Creditors' claims are put at between dollars 3.2bn and dollars 3.6bn. Asset sales are expected to realise more than dollars 1bn, with the the first payouts to creditors in November.
First for Mercury
Mercury said Europe's first air-to- ground telephone service based on digital technology was scheduled to begin by the end of the year. Mercury has taken a stake in In- Flight Phone International Europe, a joint venture with a US firm, and will spend pounds 10m building 60 base stations around Europe to receive the calls and route them through existing national networks.
Krupp-Lonrho talks
Fried. Krupp Hoesch-Krupp, the German steel group, is negotiating to buy back Lonrho's 50 per cent stake in the Krupp-Lonrho trading company, which had sales of DM2bn in 1992 and employs 2,300. In London, Lonrho said James Capel would join Societe Generale Strauss Turnbull as joint broker.
Aer Lingus rescue
The Irish cabinet approved an Aer Lingus rescue plan that will see the airline shed 1,530 jobs in a drive to reduce costs by Ir pounds 50m ( pounds 47.6m) a year. The government will make a one-off Ir pounds 175m injection of new equity to restore profitability.
More Germans jobless
The number out of work in Germany reached 3.3 million in June, with the jobless rate in western Germany up from 6.9 per cent in May to 7 per cent and eastern Germany unchanged at 14.4 per cent.
BT3 registrations
British Telecommunications had 5.2 million registrations for its BT3 public share offer by the closing date on 2 July. About 2 million were with share shops while 1.4 million were new registrations.
Coffee price soars
Coffee prices rocketed to dollars 1,000 a tonne in London, up dollars 47 on the previous close and an 18-week high, as traders reacted to a plan by Latin American producers to withhold supplies from world markets.
Moran discharged
Mr Justice Harman discharged the administration order over Moran Holdings, the tea to property group, paving the way for a re-listing of the shares - the first time a listed firm has come out of administration without a voluntary arrangement.
Aerospatiale purge
Aerospatiale, the French state- owned aircraft and defence group, is expected to shed 2,250 jobs next year because of dwindling orders.
World Markets
New York: A jump in the Commodity Research Bureau index, an inflation measure, hammered blue chips. The Dow Jones Industrial Average ended down 34.04 at 3,449.93.
Tokyo: Continued slack trading ahead of the G7 meeting lifted the Nikkei average 206.72 to 19,828.78.
Hong Kong: With turnover the lowest since mid-April, the Hang Seng index fell 36.07 to 7,168.34.
Sydney: Late buying support took prices off their lows, leaving the All Ordinaries 1.7 easier at 1,764.2.
Johannesburg: The gold rally tapered off near the close but left the sector 3.6 per cent higher. The overall index gained 36 to 4,210.
Paris: Shares reversed their five- day losing trend, the CAC-40 index closing at 1,935.12, up 9.68 points.
Frankfurt: Indications of lower inflation helped the DAX index back over the 1,700 mark, ending 8.7 points better at 1,700.87.
Zurich: Heavy buying in large bank stocks supported the rest of the market, and the Swiss Performance Index closed 15.34 points to the good at 1,504.75.
Milan: Failing to respond to the cut in the discount rate, the MIB lost 1.34 per cent to 1,177.
London: Report, page 24.Reuse content


text:
move ms sql to mysql db
This project received 5 bids from talented freelancers with an average bid price of $10 USD / hour.Get free quotes for a project like this
Project Budget$2 - $8 USD / hour
Total Bids5
Project Description
We are shutting our windows 2008 server and it currently has a website we have moved to our linux box. We need someone to now move the Microsoft 2008 SQL database over to the new linux server. The website has been moved over, we just require the database to be moved. Must be completed today.
Skills Required
Looking to make some money?
- Set your budget and the timeframe
- Outline your proposal
- Get paid for your work
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text:
- Öffnungszeiten: 24 Hours / 7 Days
- Geschätzte Transferzeit zum Flughafen: 7 Minutes
- Bus-Frequenz: Every 15 Minutes
- Entfernung zum Flughafen: 2 Miles
- Ihre Schlüssel bleiben während Ihrer Abwesenheit bei dem Parkplatzanbieter.
The Highwayman Secure Parking Facility is an AA/Police Gold Award winning Car Park.
Warum sollten Sie diesen Parkplatz buchen?
- Park and Ride service at Cardiff Airport
- Drivers are friendly and courteous they will help you with loading your luggage
- We drop you at the CWL Airport Arrivals front entrance
- Vehicles are fitted with a step to enable easier access into the bus
Informationen für Menschen mit Behinderungen
No disabled information available.
Weitere Informationen
A driver will be waiting at arrivals when you return to Cardiff Airport with your car keys, we monitor the flight times - so if your flight is early or even delayed we will be waiting for you in the Arrivals Bus Compound. Highwayman Parking guarantee that vehicles will not be moved from their car parking compound at any time. They request that you submit a note of the vehicle mileage when checking-in. Luggage can be securely locked away in a safe area while you are eating at the pub either before catching the transfer bus to the airport, or on your return to the Highwayman car park.
Bei Ankunft
Upon arrival, please park your vehicle in the furthest available bay directly in front of you, without entering the main gates. Report to reception and present your confirmation or quote your reference number. Please allow at least 30 minutes for check-in and transfer to Cardiff Airport.
Bei Rückkehr
A driver will be waiting at arrivals when you return to Cardiff Airport with your car keys, Highwayman monitor the flight times - so if your flight is early or even delayed we will be waiting for you in the Arrivals Bus Compound.
Adresse für Navigationssysteme
The Highwayman Secure Parking,
Vale of Glamorgan,
If you are using SATNAV, please put in "Nurston" along with the post code CF62 3BH
From the M4:
- Exit the M4 motorway at junction 33 and follow signs for Cardiff Airport.
- Leave the A432 dual carriageway at the first junction, take the third exit off the roundabout (A4050) PC World will be on your left side.
- Zero your mileometer at PC World, It is exactly 9.5 miles to the Car Park.
- When you eventually reach the roundabout at 6.2 miles, (this has a sculpture shaped as two dragon tails), make sure you take the second exit by passing the airport.
- At the next roundabout take the third exit signposted St.Athans and Llantwit Major.
- At 8.2 miles turn left and proceed along this lane, do not take the narrow lane to the left continue round the S bend.
- There will be a small duck pond on your right side, at the next crossroads at 8.8 miles turn left.
- Carry on along this road for a further 0.8 miles and you will see the sign for Highwayman Security Park, turn left in to the car park and the reception area is on the left.


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So far, so good!
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Senior Member
Join Date: Nov 2011
Posts: 387
Have been keeping busy.
Visited home city, and more or less sorted out everything I needed to get done. Was very proud of myself. For once, I managed to juggle chores with socialising such that I didn't feel guilty when I was taking time out to see people, and also didn't feel stressed that I couldn't see everyone. I have many people I'm close to, and I sometimes feel spread too thinly. This time I picked a manageable number of people I wanted to see, and cut myself some slack. Phew - it felt good.
Ocean's got a job interview next month - in a different city in our home country. Sheesh, possible LDR coming up if he gets this job and decides to take it (he's unsure if he will as his current work situation is pretty good for his career, even though it isn't a permanent job.) I'm not thinking too far ahead about that. Minor freakouts but mostly calm.
We'll see
Finally got all my paperwork sorted to get my qualifications from my home country carried over to where I'm living now. Hooray! Now just have to pay the fees...
I've been volunteering quite a bit here but haven't captured any paid work as yet. Trying to keep my patience, positivity and productivity. A success, in the main. Grateful that Ocean and I can still afford to make ends meet with a single income at the moment.
Starting up swimming and dance again since the holidays... my body and mind has definitely missed it.
Spent some Quality Time with Ella when I was visiting. I was camping in a tent at the back of my old house (where my friends are living now with a baby! So so cute) so we could cuddle but not be too loud. The intimacy was gentle but good. She was going away for the weekend I was there, so we didn't get much time to see each other but we stole a morning here and an evening there... It's low-key but okay.
We're not
great at keeping in touch while I'm away, though. I sense it's more her than me... I've initiated online chats a wee bit but not got very far. When we e-mail, it's usually me who sends the last message in the thread. That kind of thing. I reckon I need a bit more connection if I'm going to stay on the learning curve of Getting To Know Ella. I've been thinking of writing to her along these lines... It's okay if we don't keep in touch, but that's going to mean more work the next time [when?] we see each other.
I don't feel like I know her well enough yet, for our bodies to be uncomplicated together... something like that.
Grotto's a smidge mopey at the moment. Bijou has asked for some space, and is treating him fairly platonically these days. I feel it's possibly a seasonal thing: her scoping him out, or some other reason that could pass in time. For now, he needs a hug. Hopefully will see him tonight.
I've been spending some time with my ma the last few days, as she's visiting from overseas. Our relationship has been tough - she's very conservative Catholic and we clash a lot on topics involving sexual morality/religion. Recently we've had some good times, focusing on common interests... but there's still that tense undercurrent, an electric wire we cannot touch. I hope one day to be more open with her about my personal life, but not yet. So much is still too tender.
What else? Oh, I had this weird awful pain in my body a couple of weeks back. Not sure what it was... it's mostly gone, just a dull thing now. Some of the possibilities bode ill for my reproductive bits. I was surprised how that made me feel - panicked, sad... the foreshadowing of grief?
Ocean and I have decided to talk again about having kids in the middle of the year, when things are more certain about his job. Until then, I'd like to get more of a handle on what I really feel / want in this arena. Having spent time with friends who have children, particularly younger ones, I know the value of me being aunty - and especially an aunty who isn't drained from having kids of her own. A large part of me wants to keep it that way. The other part... requires investigation.
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Simple game, low buzz factor. None the less entertaining when a good buzz is already attained. Required supplies: people, and of course, beer.
Sit in a circle. The first player says 'one,' the next player says 'two,' and so on down the line. However, when someone reaches a number that is divisible by 7, s/he says "buzz."
If the player misses a "buzz" when needed, or when an unnecessary "buzz" occurs, that player drinks.
The obvious challenge is to see how high of a number can be attained; but this also means very little drinking. The known current record is over 1200.
Variation: An honest "buzz" would change the direction of the circle. Or add '11' into the rotation and say 'Bizz' for divisibles of 11. In this case, watch out for 77.
Game source: The (Un)Official Internet Bartender's Guide
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Kumar Privie Sanctum presents Apartments designed to reflect contemporary lifestyle. Loaded with amenities and strategically located, Kumar Privie Sanctum is an address only for the privileged few. These Residential Apartments in Pune relish a magnificent view and presents a perfect example of comfort and luxury. Kumar Privie Sanctum by a renowned builder Kumar Properties in Baner guarantee a hassle free lifestyle to its inhabitants. The floor plan of Kumar Privie Sanctum enables proper ventilation in the entire house along with spacious bedrooms. Kumar Privie Sanctum offers 3 BHK and 4 BHK luxurious Apartments in Pune. The master plan of Kumar Privie Sanctum ensures that these are one of the perfectly crafted Apartments in Baner. The amenities in Kumar Privie Sanctum comprises of Rain Water Harvesting, Landscaped Garden, Swimming Pool, Gated community, Cricket Court, Tennis Court, 24Hr Backup Electricity, Club House and Play Area. Location of Kumar Privie Sanctum is perfect for the ones who desire to invest in property in Pune with many schools, colleges, hospitals, supermarkets, recreational areas, parks and many other facilities nearby Baner. Kumar Privie Sanctum assure you a well- deserved luxurious, secure and pampered living. Currently Kumar Privie Sanctum is ongoing.
The KUMAR PROPERTIES Group is a well diversified, value driven enterprise.
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KUMAR PROPERTIES is an AVERAGE builder. It has 22 on-going projects with total inventory value of N/A
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kate spade new york
Sale Red Carlyle Watch
Online Price $225.00 $134.99
Style #:1YRU0285
It's not unusual to find us tucked away at our favorite table sipping cubans at Bemelman's Bar on any given evening. After all, the luxurious Carlyle, originally designed by Dorothy Draper in the 1930s, is one of our favorite spots in New York City. It's also the muse for this gleaming, bow-bedecked timepiece crafted of gold-plated metal with a similar sensibility---equal parts classic and utterly charming.
Case Size
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Results 1 to 3 of 3
Views: 1732 | 10-12-07, 11:55 AM #1
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Rare govt records missing at National Archives
Rare government records pertaining to events leading to abolition of privileges of erstwhile rulers of Indian states appear to be missing from the National Archives here. Senior BJP leader Jaswant Singh came to know about this through an RTI application in which he had sought information on these records. The National Archives said that the documents could not be traced and they were looking for it.
Singh, represented through his Secretary Raghvendra Singh, moved his request before Home Ministry on January 17 this year. He sought an inspection of documents, including cabinet papers and notings that preceded the abolition of "privileges and privy purses" of rulers of then Indian states.
What followed thereafter was a eight-month-long hiatus wherein the records were searched in the Ministry's record office, which finally took a stand that documents and files have been transferred to the National Archives.
The Archives, after its efforts to trace out the records, could only manage to find only two amongst a total of 10 files sought by Singh, who required those documents for research and study.
NAI, however, said its efforts were on to trace out the remaining documents.
A complaint was thereafter preferred before the Central Information Commission seeking appropriate directions.
While the Ministry did not approach its Appellate Authority in relation to his RTI plea, Chief Information Commissioner Wajahat Habibullah allowed his appeal on grounds that despite Singh's repeated requests, no documents could be provided to him.
Habibullah has directed the National Archives to make "renewed efforts" to look out for the files that have by far remained untraced. The documents would have to be opened to Singh, for inspection, within 20 days.
Rare govt records missing at National Archives- Politics/Nation-News-The Economic Times
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Unable to trace privy purse files: MHA, archives to CIC
Unable to trace privy purse files: MHA, archives to CIC
As Reported by Utkarsh Anand Thursday, June 19, 2008, indianexpress.com
New Delhi, June 18: In a shocking revelation, the Ministry of Home Affairs (MHA) and the National Archives of India (NAI) have told the Central Information Commission (CIC) that they are unable to trace files pertaining to the post-Independence Government and its policies concerning privy purses.
Nehru History
The information regarding Cabinet papers, file notings, discussion notes, minutes and such other important policy records concerning the Government and rulers of former princely states was sought by Jaswant Singh, Leader of Opposition in the Rajya Sabha.
In India, the privy purse was a grant given since 1947 to the rulers of the princely states as part of their terms of accession to the new republic, which was abolished in 1971.
The BJP leader had sought the information under the Right to Information (RTI) Act and the CIC had in its order last year directed the MHA to open for inspection the relevant files transferred to it by the NAI.
However, Jaswant Singhs secretary, who was assigned the right to inspect the files as his representative, told the CIC that despite a years delay, the MHA could provide only two files which related to peripheral matters devoid of any policy implications and hence irrelevant for him.
The CIC then summoned the officials concerned from the MHA and NAI to explain things.
While the MHA contended that it could find only two files relating to abolition of the privy purses, the NAI claimed that there were many volumes of the documents and a number of files were still with the ministry and were never sent to them for custody.
The MHA official had also carried with him two files during the recent CIC hearing but Singhs representative maintained that he had already gone through them, which did not contain information on the substantive issues.
Irked by this, Chief Information Commissioner Wajahat Habibullah said, It is distressing to note that documents of such important nature in the evolution of free Indias history that will be vital for any documentation of the history of the late 20th century are not traceable either in the MHA or in the premier repository of our countrys remembrance, the NAI.
Pulling up both the public authorities, Habibullah further said it was all the more alarming that there is no record of movement of these documents which could enable tracing of these and conservation.
The Commission has now directed the MHA to look into every nook and corner of its offices and storerooms to trace the documents and the movement of the files, if any, so that they could be retrieved.
Officials responsible from both the departments have been summoned on June 28 to compare notes and devise ways of ensuring recovery of the files in question and their proper conservation, and indeed inspection by the complainant.
IndianExpress.com :: Unable to trace privy purse files: MHA, archives to CIC
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Let Jaswant Singh inspect privy purse files, says CIC
As reported by ENS in expressindia.com on 28 June 2008:
IndianExpress.com :: Let Jaswant Singh inspect privy purse files, says CIC
Let Jaswant Singh inspect privy purse files, says CIC
New Delhi, June 27: The Central Information Commission (CIC) has directed the Home Ministry to allow former external affairs minister Jaswant Singh to inspect official files relating to the abolition of privy purses to princely states.
This inspection will be allowed free of charge, in view of the fact that this access is being given well after the time period as mandated under the RTI Act, Chief Information Commissioner Wajahat Habibullah said.
The abolition was brought to effect through the 26th Constitutional Amendment in 1971.The Commission also directed the Ministry officials to complete his search for all the files related to the subject of abolition of privileges and privy purses of the erstwhile rulers of Indian states.
On June 12, the CIC had pulled up the MHA for its failure to trace records related to abolition of privy purses. It is distressing to note that documents of so important a nature in the evolution of free Indias history that will be vital for any documentation of the history of the late 20th century are not traceable, Habibullah had said.
Following a direction by the Commission, senior MHA officials had appeared before it on Thursday and submitted three files relating to the matter.
Singh, leader of Opposition in Rajya Sabha, had sought Cabinet papers, notings, discussion notes, minutes and other records, which led to the abolition of privy purses, from the Ministry.
The CIC had placed such prime importance on finding the documents, which officials claimed were untraceable, that it had directed a search in almirahs and storerooms of officers above the rank of JS who have been dealing with the subject in the Ministry of Home Affairs, so as to allay any suspicion that the documents may have been accessed in the Ministry at some earlier date but have been placed in the cupboard and forgotten about.


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Access our African American Heritage research tool for a comprehensive mix of resources, records and tools geared to African American genealogy.
Join Urban Strings Columbus for a concert at Main Library featuring the music of African-American composers. Hear the youth ensemble play selections from Pharrell Williams, Earth Wind & Fire, Prince & more at 3p.m. on Sunday, Feb. 26.
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The Central Ohio STEM Expo, a free educational outreach event for students grades K through 8, returns on February 25. Enjoy fun, interactive activities and exhibits in the Science, Technology, Engineering and Math fields.


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I've always slashed as you said anything excessively rooted. Occasionally
I've gotten something extremely potbound and just cut off the whole bottom
inch or so, adjusting top growth for the surgery. Containers that have nice
root systems with no circling roots I usually just massage or fork out the
exterior roots.
I remember your mentioning Cherry Lake b4, this is just a simplified version
for the home gardener
----- Original Message -----
From: "james singer" <firstname.lastname@example.com>
To: <email@example.com>
Sent: Saturday, October 30, 2004 5:27 PM
Subject: Re: [CHAT] divisions in bottomless containers
> Sounds a lot like the growing regimen of Cherry Lake that I reported a
> year or so ago--the nippled pots for self pruning tree roots. I think
> root pruning is an important step in transplanting without regard to
> size; I always slash root balls on four side with a box cutter when
> transplanting.
> On Saturday, October 30, 2004, at 06:04 PM, email@example.com wrote:
> > Remember when I asked you all what was meant be "divisions in
> > bottomless
> > containers"? Well, here's roughly how it was described in class.
> >
> > Some plants grown in containers may develop longer root systems than
> > the
> > depth of the pot and start traveling around in the pot, circling it.
> > For
> > plants that grow taproots, including many prairie plants, this can be a
> > problem. To alleviate the problem and to develop a more dense fibrous
> > root system, you can use bottomless containers.
> >
> > Take a standard gallon container ( or any kind) and cut most of the
> > bottom out leaving a bit of a lip. Line the bottom with a couple of
> > paper towels and fill with soil media and plant material. Water in.
> > Place the containers' edges on bricks leaving the toweled area open to
> > the air, not on any surface. When the plant's roots grow down, they'll
> > reach the towel area and air-prune themselves rather than traveling in
> > another direction. Once air-pruned they will more readily branch out
> > and
> > develop a more fibrous root system rather than a bunch of ropey roots
> > circling the inside of the container.
> >
> > This technique isn't restricted to divisions, which is one thing that
> > had me confused. I think it could be quite valuable for any kind of
> > containerized plant.
> >
> > Kitty
> >
> > ---------------------------------------------------------------------
> > Support hort.net -- join the hort.net fund drive!
> > http://www.hort.net/funds/
> >
> >
> Island Jim
> Southwest Florida
> Zone 10a
> Minimum 30 F [-1 C]
> ---------------------------------------------------------------------
> Support hort.net -- join the hort.net fund drive!
> http://www.hort.net/funds/
Support hort.net -- join the hort.net fund drive!


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Summary | Excerpt | Reading Guide | Reviews | Beyond the book | Readalikes | Genres & Themes | Author Bio
The year is 1917, America has recently joined the War in Europe.
Fun-loving Frieda is out on the town catching a few minutes downtime from her
tedious job as a "bundle wrapper" in a department store, a job she has taken
relatively recently after fleeing her mother's house to escape marriage to the
deeply unattractive and hairy-eared widower Pinchas Hersch, who is twice her age and
sees marriage to her as a cheap form of childcare for his odious children.
Young and fun-loving she might be, but she's not reckless. She knows just how far she's prepared to go for a few drinks and the occasional gift, but the balance changes when she catches sight of Private Felix Morse. A romance ensues and Frieda, believing this to be the "real thing", allows Felix to go further than she has been with any other man. As it happens her beau is not only handsome and apparently ...
The Story Behind The Book:
Charity Girl was inspired by a line in Susan Sontags AIDS and Its
Metaphors, in which she likens the incarceration of American women during
World War I to the internment of Americans of Japanese ancestry during World War
II. Lowenthal says, "The latter historical episode I had, of course, heard
about, but not the first . . . I immediately had two thoughts: (1) how awful,
and (2) what a great basis for a novel."
During World War I about 30,000 American women were rounded up on suspicion of carrying a venereal disease, of which about 15,000 were incarcerated in reformatories and detention homesoften for months at a time, with no charge of a crime, no trial, no legal recoursewhile they received forcible medical treatment for venereal disease (keep in mind that the rights of women have changed dramatically in the past 100 ...
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1-844-268-7055Contact UsCareersBlogArchitects and Engineers
Increased load carrying capacity and track life- the lower section of Tarca® track is specially rolled from high carbon billet and welded to a structural steel web and top flange. This construction of the track increases its load carrying capacity while retaining its non-peening qualities and significantly increasing track life.
peening- gradual movement of metal by the rolling action of wheels. The metal moves to one or both sides of the rail, depending on the rail design, and is the chief source of wear. Raised tread stays flat and smooth - raised tread design allows metal to flow in both directions when repeatedly subjected to a rolling load; the tread stays flat and smooth allowing for easy rolling of loaded wheels. Maximum strength, maximum rigidity, and greater safety - the high carbon alloy steel rail is joined by a carefully controlled welding process which means maximum strength and rigidity and greater safety. Standardized rail widths - the most distinguishing feature of patented rail is that a rail of uniform width can be maintained over a wide range of beam depths and carrying capacities. This uniformity provides a basis for standardization not only in trolleys and end trucks, but also in interlocks, electrification brackets, and other accessories. A better installation, faster - Overall track depth is held to close tolerances. Flange and rail are held square with the web. This accuracy eliminates time consuming shimming and fitting during erection. Systems fit neatly together for smooth, quiet operation.
We recognize that our visitors may have various operating systems and Internet browsers. Although we want every visitor to have the best possible experience on our website, please understand it is impossible to provide webpages that work identically, efficiently, and effectively with all browsers.
The Gorbel website supports Microsoft® Internet Explorer 10 and above, Chrome 25+, and Safari and any other modern web browser compatible with HTML5 and CSS3.


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- List your item for as low as $30 - Advertise your item in both print and online
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Browse: See our comprehensive list of earthmoving equipment specifications.
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You can imagine Technical Editor Ron Horner's excitement when he spotted an old 1970s-era, German-made O&K RH6 excavator in original working condition just off a Queensland...+MORE
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What is UBAA?
Founded in 2007, originally under the name "Greater Salt Lake Business Aviation Association", UBAA is an all-volunteer organization providing educational and interactive opportunities, a representative voice, and opportunities for peer to peer networking and to give back to the community for business aviation operators and support services in the state of Utah.
Learn more
Throughout the year, UBAA provides the following opportunities for the business aviation community in Utah:
Upcoming events
Recent News
Our 2016 scholarship golf event was a great success! Thank you to all of our wonderful sponsors for making it happen! The students below were each awarded an academic scholarship.
Zachary Henderson – Salt Lake Community College
Ashley Martinez – Utah State University
Jared Valdez – Utah Valley University
Robert Lindgren – Westminster College
UBAA Scholarship Press Release 2016.pdf
Become a member
In 2015, UBAA is starting our membership program to ensure we are able to continue to provide a voice and valuable opportunities for business aviation operators and support service partners in the state of Utah.