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Non-Hodgkin's lymphoma (NHL) is a heterogeneous and highly disseminated disease, but the mechanisms of its growth and dissemination are not well understood. Using a mouse model of this disease, we employed multimodal imaging, including intravital microscopy (IVM) combined with bioluminescence, as a powerful tool to better elucidate NHL progression. We injected EGFP and luciferase-expressing Eμ-Myc/Arf−/− (Cdkn2a−/−) mouse lymphoma cells (EL-Arf−/−) into C57BL/6NCrl mice intravenously. Long-term observation inside a peripheral lymph node was enabled by a novel lymph node internal window chamber (LNIWC) technique that allows chronic, sequential lymph node imaging under in vivo physiological conditions. Interestingly, during early stages of tumor progression we found that few if any lymphoma cells homed initially to the inguinal lymph node, despite clear evidence of lymphoma cells in the bone marrow and spleen. Unexpectedly, we detected a reproducible efflux of lymphoma cells from spleen and bone marrow, concomitant with a massive and synchronous influx of lymphoma cells into the inguinal lymph node, several days after injection. We confirmed a coordinated efflux/influx of tumor cells by injecting EL-Arf−/− lymphoma cells directly into the spleen and observing a burst of lymphoma cells, validating that the burst originated in organs remote from the lymph nodes. Our findings argue that in NHL an efflux of tumor cells from one disease site to another, distant site where they become established occurs in discrete bursts.
Human Non-Hodgkin's Lymphoma (NHL) is a heterogeneous and highly disseminated disease that includes very aggressive subtypes which display explosive growth, such as Burkitt's lymphoma(1). The mechanisms and microscale details of lymphoma growth and dissemination are not yet well-understood. Yet such knowledge could greatly improve strategies for early detection and management of lymphoma patients. Reliable approaches for longitudinal monitoring of lymph nodes in animal models are thus critical to help elucidate biological phenomena occurring in lymph nodes.
To directly address the mechanisms of lymphoma progression, we focused on the murine inguinal lymph node and imaged cancer progression using intravital microscopy (IVM) combined with bioluminescence imaging in living mice. We employed the Eμ-myc transgenic mouse model, which expresses the Myc oncogene in the B cell compartment, resulting in mice with transplantable lymphomas. This orthotopic mouse lymphoma model was chosen because it captures critical genetic and pathological features of the human disease (2, 3). IVM has long been a useful tool to address unknown biological mechanisms in diverse fields including immunology(4-6), cancer biology(7-11), nanoparticle delivery(12-14), drug discovery(15) and biomarker research(16), etc in animal models. Though lymph nodes have been imaged in mice using IVM for over a decade(17, 18), current techniques to directly and chronically image a lymph node microscopically are still lacking. Because of the lack of a chronic microscale lymph node imaging technique reported in the literature, we established one for the serial visualization of lymphoma development under physiological conditionsand combined it with bioluminescence imaging in order to reveal the mechanisms by which lymphoma actually forms.
Normal lymphocyte trafficking is essential for the regulation of systemic immune processes, as well as lymphocyte differentiation and development. Most mature lymphocytes recirculate continuously from blood to tissue and back to the blood again(19). This recirculation is regulated by lymphocyte-endothelial interactions mediated by adhesion molecules (e.g., L-selectin, CD44, integrin, VLA-4, and LFA-1) and select chemokines(20, 21). Such interactions may be maintained in lymphoma trafficking patterns; it is believed that unlike the metastasis of other cancers, lymphoma dissemination likely reflects conserved physiologic behavior - normal lymphocyte homing and recirculation molecules have been implicated in lymphoma dissemination and invasion(20, 21). However, the precise mechanisms and time frame of lymphoma trafficking are not well-understood. Improved methods and targets for detection and therapy of the disease could likely result from understanding the time course and mechanisms(20, 21), particularly unpredictable characteristics of disease that diverge from normal trafficking patterns.
In this study, we developed a novel lymph node internal window chamber (LNIWC) and with bioluminescence examined lymphoma growth and dissemination in spatial and temporal detail. We made surprising observations that appear to constitute processes distinct from normal lymphocyte homing patterns: for instance, within a 12 hour period identified via chronic serial imaging, we reproducibly observed a large, rapid efflux from the bone marrow and spleen, with a concomitant influx of lymphoma cells into the inguinal lymph node (ILN) region.
Eμ-myc/Arf−/− lymphoma cells which harbor loss-of-function regions in the Arf gene were derived by intercrossing Eμ-myc transgenic mice with Arf-null mice, all in the C57BL/6 background as described previously(2). Eμ-myc/Arf−/− Lymphoma cells and EL-Arf−/− lymphoma cells were cultured in a mixed medium including Dulbecco's modified Eagle medium (DMEM) and Iscove's Modified Dulbecco's Medium (IMDM) with 10% fetal bovine serum (FBS) and 1% penicillin G-streptomycin on irradiated Mouse Embryonic Fibroblast (MEFs) feeder cells. Eμ-myc/Arf−/− and Eμ-myc/p53−/− cells were obtained from Dr. Scott Lowe's Laboratory (Cold Spring Harbor) in 2009. These cell lines were authenticated, showing that the Arf and p53 genes were deleted, respectively, and that these murine cells overexpress the myc gene. PCR was used for detection with a specific primer. In 2010, we confirmed that the Arf−/− gene is deleted using PCR. Also in 2010 we confirmed that either Arf or p53 was deleted in the respective cell lines via western blotting.
Firefly Luciferase (Luc2)-eGFP (LG), linked by "gcctctgctgcctctgcc" which encodes 6 amino acids (VSAVSA), was kindly provided by Dr. Christopher Contag (Stanford University). This vector contains the Ubiquitin C promoter sequence. The details can be found in Supplementary methods.
C57BL/6 mice were purchased from Charles River Laboratories (Wilmington, Massachusetts). All animal studies were approved by The Stanford University Institutional Animal Care and Use Committee. 1 × 106 EL-Arf−/− Lymphoma cells were diluted with 200 μl of PBS and injected intravenously via the tail vein as described (2). Control mice were injected with 200 μl of PBS.
Animals were anesthetized with isoflurane, hair was removed from mice using hair clippers and depilatory cream. An incision was made on the peritoneal skin and the left ILN was located on the internal side of the mouse skin by reference to the intersection of three large blood vessels on the interior after the tissue has been opened (see Figs. 1c). From the interior, our custom-made titanium frames were placed onto the ILN region and fixed in place using surgical sutures (Blue Polypropylene, 5-0, FS-2) (Med Rep Express, Patricia Brafford, MA). Thus this window chamber resides within the living animal with tissues above and surrounding it in this novel strategy. The skin was closed with surgical staples (Braintree Scientific, Inc., Braintree, MA). The details of the surgical procedure can be viewed online (Supplementary Movie 1).
Images were collected with an intravital laser scanning microscope (IV-100, Olympus Corporation, Tokyo, Japan) using Olympus UplanFL objectives and Olympus FluoView FV300 version 4.3 software. ImageJ (NIH) and Olympus software was employed for image processing. Regions of the lymph nodes were excited with a set of lasers at 488 and 748 nm to detect EL-Arf−/− lymphoma cells and outline the blood vessels. The details can be found in Supplementary methods.
For bioluminescence imaging, 0.2 ml of 15 mg/ml D-Luciferin (Biosynth AG, Switzerland) was injected intraperitoneally into C57BL/6 mice under 1-2% inhaled isoflurane anesthesia. Bioluminescence signal was monitored using the IVIS system 200 series (Xenogen, Alameda, CA, USA), consisting of a highly-sensitive, cooled CCD camera. Living Image software (Xenogen, Alameda, CA, USA) was used to grid the imaging data and integrate the total bioluminescence signal in each region-of-interest (ROI). All bioluminescence images were acquired with a 1 s exposure. Data were analyzed using total photon flux emission (photons/second) in the ROIs. Data was normalized using the background signal.
To assess EGFP+ cells in murine tissues, the BM, ILN, and spleen were isolated from C57BL/6 mice on day 7 and 14 after EL-Arf−/− cell inoculation. All tissues were minced and filtered with a 100 μm cell strainer (BD Falcon, Bedford, MA). The cells were analyzed by a FACScan flow cytometer (Becton Dickinson, San Jose, CA, USA).
Results were expressed as mean ± standard error of the mean. An unpaired, 2-tailed Student's t test was used to calculate P-values (except for Fig. 2d, in which a Wilcoxon test was employed). P-values of 0.05 or less were considered statistically significant.
In order to image and analyze lymphoma development in detail, we applied a multimodal intravital fluorescence and bioluminescence imaging approach to an established lymphoma model(2)by transfecting a lentiviral vector containing firefly luciferase and EGFP sequences into the parental (Eμ-myc Arf−/− cells) line to generate EGFP/luc2 ("EL-Arf−/−") cells. To ensure that expression of firefly luciferase and EGFP protein does not induce abnormal biological function, we compared the cell growth patterns and the apoptosis sensitivity between the parental (Eμ-myc Arf−/− cells) and the lentivirus-transfected lymphoma cells (EL-Arf−/− cells). We confirmed there is no significant difference in cell growth and apoptosis sensitivity between the two sets of cells (Supplementary Fig. S1), which indicates that the reporter genes we inserted do not modify these lymphoma cell properties; furthermore, our results are consistent with results generated from the parental cell line(2, 22).
Previous studies on this lymphoma model have not elucidated tumor and angiogenesis development in the ILN. In initial experiments, we analyzed tumor development patterns using isosulfan blue to localize the lymph node and analyzed angiogenesis development using IVM. With IVM, we identified that microvascular number and circulating dye intensity was significantly higher in EL-Arf−/− lymphoma cell injected-mice compared to control mice from day 14 onward (Supplementary Fig. S2). Using macroscopic observation, we observed significant tumor development after day 14 compared with PBS-injected control mice (p<0.05) (Fig. 1 b-c).
In order to understand cell proliferation patterns in mice at the whole-body level, we performed frequent (daily) bioluminescence imaging on living mice (N=12 per group) after injection of either EL-Arf−/− cells or PBS. On day 7 (and earlier), we detected bioluminescence signal in the BM and spleen but not in the ILN (Fig. 2a). We performed further analysis to validate our imaging results: we isolated the BM, ILN, and spleen from mice 7 days after EL-Arf−/− lymphoma cell- or PBS-injection, then the EGFP+ cell population was analyzed using flow cytometry. We detected a significant number of EGFP+ cells in the BM and spleen, but not in the ILN (Fig.2 b-c). PCR data also showed that less than 100 EL-Arf−/− lymphoma cells (if any) are located in the ILN by day 3 (Fig. 2d). Furthermore, we confirmed these results using ex vivo bioluminescence analysis on days 7 and 14 (Supplementary Fig. S3). These data collectively indicate that EL-Arf−/− cells proliferated in both the BM and the spleen, but not in the ILN in the early stage of cancer progression.
In the early stage of lymphoma dissemination, frequent bioluminescence imaging displayed an increasing signal in the BM and spleen (i.e., proliferation of EL-Arf−/− cells) but not the ILN. Yet interestingly, toward the middle stage (after day 8), we observed decreased bioluminescence signal in the BM (66.5±8.7, day 8 vs. day 8.5) and spleen (36.0±3.6, day 8 vs. day 8.5) with a concomitant increase in signal in the ILN (215.0±57.0, day 8 vs. day 9) (N=12 EL-Arf−/− injected group, N=5 control mice) (Fig.3 a-b). The phenomenon observed is thus highly reproducible and the timepoint at which it occurs post-injection is rather specific. Moreover, when we increased the initial injection cell number five-fold (to 5×106 EL-Arf−/− cells), we reproducibly observed a much earlier efflux of EL-Arf−/− lymphoma cells around day 5 (Supplementary Fig. S4). This result may reveal a dependence of the efflux on local cell concentration. Furthermore, even when injecting EL-Arf−/− lymphoma cells directly into the spleen (rather than via tail vein, so that no cells could have initially seeded the periphery), importantly we observed the same phenomenon: efflux from spleen and influx to ILN (Supplementary Fig. S5). These results strongly indicate that EL-Arf−/− lymphoma cells proliferate in the spleen and BM, then flow out from these sites to the periphery. Importantly, we also observed the same efflux/influx phenomenon using a different lymphoma cell type (p53−/− crossed with Eμ-myc and transfected with EGFP/luc2, termed EL-p53−/−) via bioluminescence imaging (Supplementary Fig. S6).
In order to sequentially image the genesis of lymphoma in the ILN at the microscale, we developed a novel LNIWC. It consisted of a titanium frame (9.0 mm diameter, 2.0 mm thickness and 0.35 g). An incision was made on the peritoneal skin, and the ILN was located visually by the vascular pattern (Supplementary Movie 1). The LNIWC was then implanted over the ILN. The LNIWC was fixed in place with sutures and the peritoneal region was closed with surgical clips (Fig. 4a-c and Supplementary Movie 1). Surgical clips were removed and access to the window was obtained every time IVM was performed, then the clips were replaced each time. This approach enables us to serially obtain IVM images for up to two weeks, and we validated the technique's utility against two other methods for visualizing the ILN sequentially on the microscale (see Supplementary Table 1). These two other methods are similar to techniques which have been employed for imaging other abdominal organs such as liver and other "body windows," but they suffered from difficulties due primarily to the unique challenges of serially imaging the lymph node in living subjects (as a result of the intimate vascular connections between lymph node and adjacent tissue, these techniques suffered from tissue adhesions and fibrosis, see Supplementary Information). We chose to employ the LNIWC method in our experiments due to its ability to considerably decrease autofluorescence in serial imaging sessions and because it provided a fiduciary marker for us to consistently return to precisely the same sites to image them longitudinally (see Supplementary Information). We observed neither loss in body weight (p=0.67) nor any unusual mouse behavior throughout the observation period in both the LNIWC and non-LNIWC groups (Fig. 4e, Supplementary movie 2). We were also able to observe macroscopic tumor growth in the LNIWC (Fig. 4f). In accordance with our PCR and bioluminescence data, we were unable to detect EGFP-expressing cells in the inguinal lymph node until day 9±1 day after injection of the EL-Arf−/− cell group (N=7 mice) using IVM; on the other hand, we never detected EGFP signal from the control (PBS-injected) mice (N=4) (Fig. 5a-b) (Supplementary Fig. S7). We also observed the same reproducible phenomena in our other lymphoma model, the EL-p53−/− injected mice, using IVM (Supplementary Fig. S8). Furthermore, using the LNIWC with IVM high-resolution imaging, we observed a single circulating EL-Arf−/− lymphoma cell in the vasculature feeding the ILN on day 10 (Supplementary Movie 3), while we never observed tumor cells in vasculature on other days. This suggests that effluxed lymphoma cells likely reach and seed the periphery via blood circulation. FACS and PCR analyses validated that no tumor cells were present in ILN both 3 days and 1 week after EL-Arf−/− injection (Fig. 2b-d). Because we were able to image the same mouse at the same site every 2-3 days, we observed a relatively sudden EL-Arf−/− cell influx into the ILN between day 8-10 post-injection. In order to focus on this time period, we obtained IVM-images every 12 hours from 8-10 days post-injection of cells. Intriguingly, we observed a sudden large influx of EL-Arf−/− cells into the ILN within a 12 h time period reproducibly across N=7 mice (Fig. 5b-c). Therefore, the LNIWC, which has not been previously described for intravital imaging, enabled us to visualize the ILN longitudinally and observe the "burst effect" of cells into the ILN.
Using immunohistochemistry we then showed that after these cells arrive, the EL-Arf−/− lymphoma cells establish a rapidly proliferating tumor in the ILN (Supplementary Fig. S9). These results together indicate that EL-Arf−/− lymphoma cells flow out from the spleen/BM to the periphery via the circulation in the middle stage and then proliferate to form a tumor in peripheral lymph nodes (including the ILN and superficial cervical lymph nodes, see Fig. 3). Further, these results suggest the spleen must be somehow conditioned for efflux and underscore the utility of multimodal IVM and bioluminescence imaging to visualize tumor cell trafficking in live mice.
Malignant transformation of normal lymphocytes results in lymphoma, and many lymphoma subtypes migrate and disseminate. This dissemination may reflect conserved physiologic behavior unlike the metastasis of other cancers, considering that normal lymphocyte homing and recirculation molecules have been implicated in lymphoma dissemination and invasion. Since the time course and mechanisms of lymphoma trafficking are not well-understood, we developed a multimodal imaging platform to sequentially image lymphoma cells; we combined a novel LNIWC technique for IVM with bioluminescence imaging to derive time course and basic mechanistic information on lymphoma development.
The LNIWC, which represents a modification of previous window chamber techniques(23), was developed to obtain sequential images. The LNIWC method can be used to serially image (up to two weeks for 6-7 independent imaging sessions) the ILN to observe lymphoma progression in an orthotopic mouse lymphoma model under physiological conditions. Critically, the method also enabled us to easily find and image the same location during each imaging session because of the ability to use the LNIWC as a spatial point-of-reference, including suture holes and the chamber itself for spatial orientation. To our knowledge, this technique enables the first instance of serial imaging of a lymph node in a living mouse.
Using multimodal (intravital/bioluminescence) imaging, we discovered a key, novel feature of the EL-Arf−/− lymphoma model: tumor cell initiation and expansion in the bone marrow and spleen, followed by a burst into peripheral lymph nodes and progression in the ILN. It is notable that this cell line is not unique in this respect - we observed that the EL-p53−/− cell line also displayed a similar, reproducible pattern of efflux/influx (Supplementary Figs. S6 and S8), suggesting the mechanism we observed is not model-dependent and is likely to be a more general feature of lymphoma dissemination. The insights achieved with these models could prove invaluable in understanding how different genetic alterations can influence migration of lymphoid cells to different lymphoid sites as these models are in many ways similar to human lymphoma (2, 3).
We note that prior to this work, the lymph node tumors in these murine models were evaluated primarily via palpation and whole-body fluorescence imaging, which are not sensitive to low numbers of tumor cells and thus do not provide detailed information particularly at the earlier time points. Therefore, it was previously presumed that in the Eμ-myc lymphoma model tumors began forming within the lymph node immediately after the intravenous injection of cells(2). Given the previous assumptions, we were initially surprised to find a lack of lymphoma cells in the ILN during the first ~9 days after injection using IVM. Our findings using the LNIWC, which were further validated by bioluminescence, FACS, and PCR analyses, collectively demonstrate that around day 9 tumor cells exit the spleen and BM and at least some fraction of these cells very reproducibly and robustly reach the ILN. It was surprising to us that lymphoma cells do not gradually depart from the spleen and BM into the ILN, but instead they arrive rapidly in a burst into the ILN. While the murine lymphoma model differs in several aspects from human lymphoma, our pre-clinical findings do mirror distribution patterns in human lymphoma such as splenic marginal zone lymphoma (SMZL) and chronic lymphocytic leukemia (CLL) in the later stages. Early in these diseases, lymphoma cells appear in the bone marrow and spleen, without significant peripheral node involvement. In later stages, lymphoma cells can often be found in other organs(24-27) with increasing tumor burden and even after successful treatment, lymphoma cells may "re-seed" the original lymph nodes/lymphoma(28). This re-seeding can critically accelerate tumor growth, angiogenesis, and the recruitment of stromal elements(28). Our model may be applicable to these and other Non-Hodgkin's and Hodgkin's Lymphomas, where the BM and spleen could serve as reservoirs for cells that seed and re-seed recurrent sites of disease. Understanding the pattern and mechanisms of lymphoma progression could unlock new ways to detect and treat this disease. More generally, our model may help answer key questions about the interplay of host factors and microenvironment that allow malignant cells to home to, proliferate at, and exit from specific sites of disease in a wide range of hematologic and solid tumors. Therefore, with the advent of biologic therapies and immune modulation for treatment of cancer, understanding what triggers this efflux, and critically finding ways to delay or even stop it, may enable physicians to interfere with disease spreading, re-seeding, or further metastasizing.
In conclusion, our multimodal intravital (LNIWC) and bioluminescence approach enabled us to explore how a lymphoma mass truly evolves within the lymph node; this led us to discover lymphoma cell efflux from the spleen and BM and a concomitant influx into the ILN within a surprisingly short time period. This finding has implications for understanding and developing novel treatment regimens for human lymphoma and potentially other cancers.
This work was supported in part by NCI PS-OC MC-START U54 CA143907 and NCI U54 CA119367. We gratefully acknowledge Dr. Alice Fan and Dr. Laurence Marton for their assistance in paper review. We are also grateful to Professor Chen Yuan Dong for discussions on window chambers.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Contribution: K.I. and B.R.S. designed the study, conducted experiments, and wrote the manuscript. N.P. edited the manuscript and contributed to the IVM study. J.Y. and S.S. conducted experiments. C.M. and S.L. established lymphoma cells and edited the manuscript. S.S.G. organized the study and edited the manuscript.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers. |


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Tech Support Executive ( 1 - 2 yrs)
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12 bungalows for sale in CR0
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- Alternatively enter another alternative location or adjust your search criteria.
- If 'no results' continues to show, we may not have any properties for sale in your desired location.
4 Bedroom Detached Bungalow For Sale
Wickham Road, Croydon, CR0Detached chalet style bungalow, which has been extended to provide spacious and versatile living accommodation, which is idea for entertaining the family and friends. Comprises of four double bedrooms, two bathrooms, plus separate w.c. Three reception rooms and a good...
3 Bedroom Detached Bungalow For Sale
Woodmere Close, Croydon, CR0Coming Soon In 2017A rare opportunity to acquire this unique brand new three bedroom detached bungalow situated in in the ever popular Shirley area. Woodmere Close is on a cul-de-sac located off Woodmere Avenue and is within easy access of local buses on Orchard...
4 Bedroom Bungalow For Sale
Larcombe Close, Croydon, CR0A detached chalet style bungalow with 4 bedrooms, sitting/dining room, garage, private parking and westerly facing garden close to transport links.
6 Bedroom Bungalow For Sale
The Glade, Croydon, CR0A detached chalet bungalow located in a popular residential road. The accommodation briefly comprises; six bedrooms, four bathrooms, 19' reception room, 18' conservatory 15' kitchen and a cloakroom. (contd...)
6 Bedroom Detached Bungalow For Sale
The Glade, Croydon, CR0This detached chalet style bungalow offers spacious and versatile living accommodation and currently comprises of six bedrooms, three bathrooms, an en-suites, plus separate cloak room. Generous size lounge, kitchen and conservatory. The property features double glazed...
3 Bedroom Detached Bungalow For Sale
Shirley Road, Croydon, CR0Occupying a substantial plot is this detached bungalow consisting of three double bedrooms, 18'2 wide reception room with separate 11'7 x 10'10 kitchen both of which overlook the well maintained rear garden, family bathroom and W.C and utility cupboard accessed via the
3 Bedroom Detached Bungalow For Sale
The Glade, Croydon, CR0OPEN HOUSE 1st & 2nd April- please call for viewing arrangements.Detached bungalow set back from the road and offering versatile living accommodation of two/three bedrooms or one/two reception rooms. Having just undergone a programme of refurbishment to include, a...
3 Bedroom Detached Bungalow For Sale
Coombe Avenue, Croydon, CR0Exceptionally spacious detached bungalow located in a private road on the east side of Croydon just a short walk from Lloyd Park and tram link. The accommodation benefits from having gas central heating and briefly comprises entrance hall, cloakroom, 'L' shaped living...
2 Bedroom Bungalow For Sale
Devonshire Way, Croydon, CR0Deceptively spacious well presented two bedroom bungalow. (contd...)
2 Bedroom Semi-Detached Bungalow For Sale
Shirley, Croydon, CR0A well presented and spacious two double bedroom semi-detached bungalow situated in a popular residential area of Shirley within close proximity of mainline, tram link stations and local amenities. The accommodation comprises of a spacious lounge with featured...
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No boring historical pageant this, Warner Bros.' is a fast-paced, often hilarious romantic romp. Her Mexican accent held in check, the ravishingly beautiful Dolores Del Rio plays 18th-century French courtesan DuBarry like a 20th-century golddigger on the make. Brought to Versailles as the companion of courtier D'Aigullon (Victor Jory), former street waif DuBarry charms her way...more
All Madame Du Barry cast + crew photos


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Sarah Brightman: Ticket Package
Verizon Theatre at Grand Prairie • Grand Prairie, TX
Saturday, October 12
What you get
- Choice of Ticket or Ticket Package
- Broadway Star & World-Renowned Soprano -- One Night Only!
As the star of West End and Broadway classics including Cats and The Phantom of the Opera, Sarah Brightman quickly earned a reputation as one of the most amazing singers to ever take the stage. Since then, she's sold more than 6 million albums worldwide and had the honor of being the first artist invited twice to perform at the Olympic Games. Now, catch this worldwide sensation when she lands at Verizon Theatre at Grand Prairie on Saturday, October 12 in support of her new album, Dreamchaser.
Choose from the following offers:
• $40 for one 400-Level ticket
• $85 for a ticket package including one 400-Level Center ticket, one Mazda Club pass, and general parking
Find out more about Sarah Brightman
Fine print
REFUND POLICY: This event is nonrefundable. No full or partial refunds are given to customers who miss an event. In the event of a cancellation, your voucher will be fully refunded • Each voucher is good for 1 person • The deal is valid on event date only • Purchaser must pick up ticket(s) at Will Call prior to show • Purchaser may change the name of the individual retrieving tickets up to 24 hours in advance of event via the LivingSocial website event details section; no name-changes or alternate pick-ups permitted without notice at venue • Event is rain or shine • LivingSocial is pleased to offer you the opportunity to purchase this deal to be fulfilled by the entity indicated on the voucher and/or by Anschutz Entertainment Group, Inc., its subsidiaries and affiliates ("AEG"). By purchasing this deal, you agree that your name, email, zip code and other information related to the deal you purchased will be used by LivingSocial as well as provided by LivingSocial to AEG and/or the entity indicated on the voucher to assist in fulfilling the deal you purchased and, subject to LivingSocial's privacy policy [livingsocial.com/privacy_policy] as wellOther conditions apply
Except where noted in the fine print:
• Cannot be combined with any other offer or promotion
• Tax and gratuity are not included
• Merchant is responsible for the quality of the products or services provided to you at redemption
• LivingSocial Terms and Conditions - https://m.livingsocial.com/terms
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text: The Pink Camo Wedding Rings For Her also develop 12 months by year. If the outdated folks find only gold, silver, platinum ring, now folks simply find the blended material ring. Such because the blended ring between gold and platinum, or other material. The marriage ring designers find that the blended material is nearly as good as the unique material. Many individuals ask the designer to design and make them a gorgeous wedding ceremony ring. They might bring their own design and select what material that they need of their ring. Typically, there are some bride and groom put their blood inside their wedding ceremony rings. It's the symbol of eternal life for each of them. The fabric needs totally different time, value, and price, it depends on the weight of the ring and likewise the design of the ring.


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Pay-Per-Minute Viewing
You can now enjoy this movie on your iPhone®, iPad®, or compatible Smart TV & Android devices.
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Coriole Shiraz Mclaren Vale the Soloist Single Vineyard (2006)
Winery: | Coriole Pty Ltd |
Region: | Australia » South Australia » Mclaren Vale |
Varietal: | Syrah |
Type: | Table Wines |
You're a member of the 'Rhône Ranger' band. Your groupies think you're 'hot', even when you're boozy and "strung out"...
"King of the Red Wine Grapes." The colonizer of the vineyards, pushing native wine grapes into its shadows. The Caber...
Prounounced "San-joh-vay-say," this Italian wine varietal is Tuscany's #1 red wine grape. It's the pistol of Central ...
Sauvignon Blanc is widely grown in California -- at over 15,000 acres, it's now the third most planted variety -- and...
History of the grape: Modern day French oenologist Pierre Galet states Chenin Blanc has been in France at least since...
The irony here is that Syrah's origins could give Carmen Sandiego a run for her international wallet. Syrah's deepest...
Be the first follower of this winery and get updates on your profile.
August 2010
Nose: blackcurrant, plum, rich dark fruit, spice, christmas cake. Palate: plum, blackcurrant, spice, rich dark fruit. Moderate tannins, fresh sharp acidity. Rich, complex, intense and long on the palate. Read More
February 2010
Nose: bitter cherry, blackberry, spice, chocolate. Palate: bitter cherry, blackberry, chocolate, earthy, chocolate. Long, with intense tannic finish. Firm tannins, which softened as the wine aired. The wine seems fairly young, and would probably age well. Read More
December 2009
Nose of dark fruits, cranberry, spice, earth, leather and tobacco leaves. Palate rich, generous and ripe with dark fruits, cranberry, plum and firm tannins. Long on the palate, complex and intense. An interesting wine that is great value for the price. Read More
November 2009
Colour: a beautiful strawberry pink. Nose: Rich, sweet and intense, with cherry, rose petal and meaty strawberry. Palate: Cherry, rose petal, strawberry. Sharp acid, with refreshing minerallity on back palate. Initial sweetness from juicy fruit flavours, but quite dry. Read More
Oct 17, 2009
Description added for this page.
Oct 17, 2009
New image uploaded to this page.
September 2009
An interesting, complex wine. Nose of gooseberries, quite sweet. Palate initially almost sweet, but with very dry, sharp acid. Taste of gooseberries and grass/fresh herbs, with a nutty roasted almost taste too. Finishes with a complex acidic, minerally edge. Read More
September 2009
Well balanced medium bodied wine. Nose of cherries and other red fruit. Tastes of cherries & red fruit, rich but with little sweetness to the fruit. Read More
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21 items found |
You can send New Year Gifts to Ecuador in the following cities.
What our Customers Say about our Service |
"It is in difficult times that you really know the character and quality of people. The same applies to business and companies.
There we were. Living in Australia and wanting to send a gift basket to our uncle in the US, celebrating his amazing 100th birthday. We did it through Gift Basket Overseas and were happy with the user friendly site. Simple process. Short and efficient. To our surprise, the basket didn't arrive at the date promised. We began an investigation, compounded by an 18 hour time difference between Sydney, Australia and Scottsdale, AZ. From day one, every single customer representative we corresponded with only had one thing in mind: to resolve the problem. Through many iterations we found out I had a typo on the street name and although the zip code was correct, the courier delivered to an address that was not our uncle's. GBO sent a replacement basket at their cost and still that didn't make it to him. After a lot of investigations and the personal involvement of their customer service director, we finally had the gifts arrive at their destination. A very big thank you and we can assure you that you now have a customer for life and I will be recommending you to my friends. You showed us what customer service is all about. Thanks!" Andre T - North Ryde NSW, Australia - Apr 11, 2014 "I cannot thank Gift Baskets Overseas enough for ensuring that our son's 21st birthday was exceptional! He is currently in the Czech Republic and we wanted to send him something that had to be delivered on this actual birthday. I worked with Gift Baskets Overseas and he did indeed receive his surprise and on his birthday! I cannot tell you how important that was to us. They even sent me updates as to when they had contacted him and the time of delivery! Unbelievable customer service and total commitment of providing the very best. This is highly unusual in today's world. I will continue to use them and I would suggest anyone who wants to send the very best and have knowledge that it will actually be delivered and arrive on time - use Gift Baskets Overseas! Thank you for making his day so memorable!" Paola L. - Menlo Park CA, USA - May 11, 2010 "I had ordered the 'Spa day for him' gift basket to be delivered to my fiance on his birthday in Germany. I wanted it to be a surprise for him. It was delivered on time and he was totally taken by surprise! :) Everything from placing me the order to him receiving it on time was hassle free! Thank you giftbasketsoverseas.com! Will surely recommened this! :)" Shreya - India - Oct 2, 2015 "Last night I got a confirmation that the recipient received the cake and greeting card. I'm so glad that you solved the problem. I was considering for the next year to look for another company, but as you took care about the reported issue, surely I will come back to you for your services. Thanks a lot. Keep doing a good service, and take care of this kind of issues for future customers." Gabriela A - Guadalajara, Mexico - Sep 21, 2015 Read more testimonials or leave your feedback here. |


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The Rob Roy Guest House
3227 Dover Rd ,, Folkestone, CT19 6NH
Price From
View Rooms- Good
- 3 guest reviews
About the hotel
The Rob Roy is a traditional 6 bedroom bed & breakfast Guest House, with 4 bedrooms en suite plus free WiFi. We are situated only 10 to 15 minutes down hill walk to Folkestone Harbour, beaches, the town centre & restaurants etc. It is only 10 drive minutes from the Channel Tunnel and 20 minutes from the Dover ferries and the Eurostar passenger trains at Ashford.
We are also perfectly positioned to explore the Garden of England and its many attractions, for example: beautiful beaches and promenades, historic castles, coastal parks, The North Downs Way, wild life parks, The Battle of Britain Memorial and Museum, Dover Castle and much more!
A warm welcome awaits you from Sarah and Jim who offer you a comfortable cosy stay, with a fine choice of breakfasts to see you on your way. Cooked breakfast weekdays is from 8-9am, weekends from 8. 30-9. 30am, but early cooked breakfasts from 7. 30am (8am weekends) can be booked on arrival. An extensive buffet breakfast is supplied for those guests leaving earlier.
We operate a no smoking policy, however smoking is allowed outside on the first floor verandah.
Dogs are welcome by prior arrangement in Room 1 ONLY, a fully refurbished ground floor ensuite room with door leading to the Rob Roy owner's private garden where you may sit outside in your own patio area. Dogs can use the garden while supervised. Other pets are welcome in the remaining rooms.
Accommodation is available throughout the year,with the exception of Christmas (24th - 26th December) and other publicised times.
Check-in time: From 4:00 pm or telephone if earlier ETA. Check-out time: 10:00 am.
WHEN BOOKING, please enter an approximate time of arrival under 'SPECIAL REQUIREMENTS' to ensure we are available to meet you!
Our Family room sleeps up to 6, in a double bed, bunk-beds and a Z-bed or cot. The top bunk beds is not appropriate for children over the age of 12.
Read MoreLess
Facilities Show/hide
- Main
- Hotel Non-Smoking Throughout, Babysitting services, Iron And Board In Each Room, Pets Allowed
- Parking
- Car parking available onsite, Car Parking Available Offsite
- Business
- Wi-Fi Available In Public Areas
- Dining
- Bar
Can't find the facilities you're looking for?
- Call us on 0333 300 1007 and we'll help find the perfect hotel for you
- Call
Useful Info Show/hide
- Between 16:00 and 22:00
- By 10:00 hours
- Up to 17 years old
- The price shown is based on the occupancy and dates you have searched for. Prices and availability are subject to change based on the arrival date, number of nights and occupancy searched for. All prices are inclusive of all local taxes.
- Pets are allowed
Customer Reviews
Our reviews are from genuine LateRooms.com customers. We verify that the customer has stayed before leaving a review.
67% would recommend it to a friend
Customer service
Food quality
Room quality
Very basic.
As they say don't judge a book by its cover . But we were made welcome by the owner.
Read More Less
Very nice with good friendly service....


text:
Model Description: Longway 3FM8 Compatible Battery
Compatibility: 3FM8 (6V 8Ah battery with F1 Terminals)
Condition: New, Fresh Stock
Includes: (1) battery, a compatible replacement for the LongWay 3FM8
Warranty: 1 year full replacement warranty included, additional warranty is available
Life time expectancy: 3-5 years
Manufacturer: UPS Battery Center Ltd.
The LongWay 3FM8 replacement battery is a high quality rechargeable sealed lead acid battery that is designed to provide excellent performance, durability and long life. This battery meets or exceeds original manufacturer specifications.
Our batteries are new and always fresh stock. The LongWay 3FM8 replacement battery is covered by our industry leading 1 year replacement warranty. Extended warranty of up to 3 years is available for your convenience. Our warranty is inclusive of shipping costs and is hassle free, the only warranty of this kind in the marketplace.
Physical Dimensions:
Nominal Voltage: 6V
Nominal Capacity: 8Ah
Terminal Type: F1
Weight: 3.09 Lbs
Length: 98mm (3.86")
Width: 56mm (2.20")
Height: 115mm (4.53")
The LongWay 3FM8 replacement battery consists of (1) High Quality 6V 8Ah battery.


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Country Inn & Suites By Carlson, Wilson, NC places you within a 15-minute drive of Country Doctor Museum and Edna Boykin Cultural Center. This 73-room, 3-star hotel welcomes guests with conveniences like an indoor pool, free in-room WiFi, and free self parking. Oliver Nestus Freeman Round House Museum and Imagination Station are also within a 15-minute drive of this Wilson hotel.
Free hot/cold buffet breakfast is included with your stay.
All 73 air-conditioned rooms feature microwaves, refrigerators, and coffee makers. 32-inch flat-screen TVs come with cable channels, and guests can stay connected with free WiFi and wired Internet. Beds sport premium bedding and bathrooms offer hair dryers and free toiletries. Other standard amenities include free newspapers, free long-distance calls, and free local calls.
Property features
At Country Inn & Suites By Carlson, Wilson, NC, guests enjoy an indoor pool, a fitness center, and free WiFi in public areas. If you decide to drive, there's free parking. Staff members can answer questions about accommodations, and also provide a safe deposit box at the front desk. Additional amenities include conference space, a business center, and a library.
- Free hot/cold buffet breakfast
- Free WiFi in rooms and public areas
- Free parking
- Indoor pool
Country Inn & Suites By Carlson, Wilson, NC
Hotel Amenities
Hotel Amenities
Country Inn & Suites By Carlson, Wilson, NC features an indoor pool and a fitness center. Public areas are equipped with complimentary high-speed wireless Internet access. A business center is on site at this 3-star property. A complimentary breakfast is offered. This business-friendly hotel also offers a library, express check-out, and a safe deposit box at the front desk. Complimentary self parking is available on site.
Country Inn & Suites By Carlson, Wilson, NC is a smoke-free property.
- Total number of rooms - 73
- Number of floors - 4
- Business center
- Free breakfast
- Conference space
- Elevator/lift
- Express check-out
- Fitness facilities
- Free WiFi
- Library
- Safe-deposit box at front desk
- Free self parking
- Year Built 2008
- Smoke-free property
- Indoor pool
- Wedding services
Family Friendly Amenities
- Family Hotel
- Indoor pool
- Free Wi-Fi
- Refrigerator
- Microwave
- Cribs/infant beds (complimentary)
Available in all rooms: Free WiFi , Free wired high-speed Internet
Available in some public areas: Free WiFi
Free self parking
Room Amenities
Country Inn & Suites By Carlson, Wilson, NC offers 73 air-conditioned accommodations with complimentary newspapers and coffee/tea makers. Beds feature premium bedding. 32-inch flat-screen televisions come with premium cable channels. Refrigerators and microwaves are provided. Bathrooms include shower/tub combinations, complimentary toiletries, and hair dryers.
This Wilson hotel provides complimentary wired and wireless high-speed Internet access. Business-friendly amenities include desks and phones; local and long-distance calls are complimentary (restrictions may apply). Additionally, rooms include irons/ironing boards and blackout drapes/curtains. Housekeeping is provided daily.
- Free long-distance calls
- Premium TV channels
- Premium bedding
- Air conditioning
- Free newspaper
- In-room climate control (air conditioning)
- Phone
- Free local calls
- Refrigerator
- Coffee/tea maker
- Microwave
- Daily housekeeping
- Private bathroom
- Free toiletries
- Hair dryer
- Shower/tub combination
- Iron/ironing board
- Desk
- Blackout drapes/curtains
- Cable TV service
- Flat-panel TV
- Free WiFi
- Free wired high-speed Internet
- Connecting/adjoining rooms available
- Free cribs/infant beds
- Rollaway/extra beds (surcharge)
Where to Eat
Guests are offered a complimentary hot/cold buffet breakfast.
Nearby Things to Do
Recreational amenities at the hotel include an indoor pool and a fitness center.
The recreational activities listed below are available either on site or nearby; fees may apply.
- Golfing nearby
- Golf lessons available nearby
If you have requests for specific accessibility needs, please note them at check-out when you book your room.
- Accessible bathroom
- Roll-in shower
- In-room accessibility
Hotel Policies
Minimum check-in age is 18
Check-in time ends at 5:30 AM
Check-in time starts at 3 PM
Special check-in instructions:
Check-out time is noon
Payment types
Children and extra beds
- Children are welcome.
- Kids stay free! Children 17 years old and younger stay free when using existing bedding.
- Rollaway/extra beds are available for USD 10.00 per night.
- Free cribs (infant beds)!
- Pets allowed for an extra charge of USD 20 per pet, per night
- 2 per room
- Specific rooms only
- Pet-friendly rooms can be requested by contacting the property at the number on the booking confirmation
You need to know
Extra-person charges may apply and vary depending on property policy.
Government-issued photo identification and a credit card are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
Optional extras
- Pet fee: USD 20 per pet, per night
- Rollaway bed fee: USD 10.00 per night
Hotel Name
- Country Carlson Wilson NC
- Country Inn Carlson Wilson NC
We should mention
This property's policy is to refuse certain bookings for the purpose of group events or parties, including pre-wedding stag/bachelor and hen/bachelorette parties. Children 17 years old and younger stay free when occupying the parent or guardian's room, using existing bedding. The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation. This property allows pets in specific rooms only (surcharges apply and can be found in the Fees section). Guests can request one of these rooms by contacting the property directly, using the contact information on the booking confirmation.


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Through three quarters of Saturday's game, the Alabama defense accumulated 322 yards, scored 20 points, picked up 17 first downs and converted 5-of-11 third downs. In the fourth quarter, the gained just one-yard, picked up just one first down and missed their only third down conversion.
The Gator offense score 14 fourth quarter points, but the defense shut the Bama offense down cold.
"We knew that if we came out and made a stand then we would win the game," linebacker Brandon Spikes said. "I think our defense showed up today."
After Florida took a 24-20 lead with 9:21 left, Alabama had a chance to answer the score. The Tide had scored on their previous two drives and kept the Gator defense on the field for more than ten minutes in the third quarter.
On the first play of the drive, Bama quarterback Jon Parker Wilson tried to hit Julio Jones streaking down the sideline. To that point, Jones had five catches for 124 yards. But cornerback Joe Haden timed the play perfectly knocking the ball away with safety Major Wright hitting Jones for added insurance.
Alabama faced a 3rd-and-8 when the Gator defense then made quite possibly the biggest play of the game. Defensive end Jermaine Cunningham moved inside after the snap and sacked Wilson for a loss of 11 yards.
"It was big because it was at a point where we were up and we needed to get a third down stop," defensive coordinator Charlie Strong said. "It was a stunt. We had a four-man front and we moved the guys around and he got the sack. Dunlap actually helped the stunt because he was the one that picked and allowed Cunningham to get free."
"We knew they were going to pass the ball," Spikes said. "We just had to rush it and Jermaine is a down field rusher, so I knew he would get there."
The Gator defense made up for earlier mistakes in the fourth quarter. Haden who made the play against Jones missed the first tackle on Jones earlier in the game that resulted in a 64-yard gain and Alabama's first touchdown.
"The one big play we missed a bunch of tackles," Strong said. "Jones is a big physical player, but when it was time to lock him down, our guys did a good job."
By the time the fourth quarter rolled around, the Gator defense stayed disciplined and rendered the Bama offense as ineffective.
"They started running the same plays, so it was just up to us to stop them," Spikes said. "Our defense is based on a gap-scheme. If one guy gets out of their gap, that's when they run the ball like they were. We just got it together and we started controlling the line."
All week long, the Gators had to hear how tough and physical the Alabama offensive line was and how hard running back Glen Coffee ran. But the Florida defense minimized the early blows and came through in the end.
"That was a really physical game for us, but we knew that it was going to be physical," Strong said.
Just like most years, the Gators proved that defense wins championships. Now they hope that defense will lead them to another national championship.
"You do have to play defense," Strong said. "They have a great defense, and at the end our defense came through. You look at it and both offenses moved the ball. In the end we were able to stop them, but they made some big stops, too."


text:
In an offer to help the sagging exports sector , Union Commerce and Industries Minister Nirmala Sitharaman today asked the business to "effectively engage" with the administration and talk about the issues exporters are confronting.
"Indo – Pak Border Will Be Sealed By 2018"says Rajnath Singh
currency volatility, internationally, the demand is not catching up and the WTO (World Trade Organisation) itself is revising the estimates for the second time on global exporters. Of course, there are concerns which I would voice I would want the industry to interact with the government much more," Sitharaman said at a function here organised by the Federation of Indian Export Organisations (FIEO).
"I would definitely ask the FIEO to be able to provide platform for the government and the exporters need to talk about what kind of relief measures were needed and also suggest sectoral issues that need to be addressed," she said, after handing over the Exports Excellence Awards organised by the FIEO, Southern Region.
She said the exporters were searching for the markets that were "still sustainable for exports".


text:
Location: Stateline, NV | Tickets: 0 | RSVP Tweet
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Lake Tahoe Outdoor Arena At Harveys Hwy. 50 Stateline, NV 89449
"A Summer's Day" festival, Royal Western India Turf Club, Mumbai, India AP Photo / Rafiq Maqbool
March 3, 2013 |
Bridge School Benefit, Shoreline Amphitheatre, Mountain View, Calif. John Davisson
October 22, 2011 |
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Purpose: This Announcement notifies contractors to real property and their vendors that the Department of Revenue Services (DRS) has issued a new certificate, CERT-141, Contractors Exempt Purchase Certificate, to replace the old Contractors Exempt Purchase Certificate when making exempt purchases of materials. Effective Date: Upon issuance. Statutory Authority: Conn. Gen. Stat. §12-412(1), (2), (5), (8), (84), (90), (92), (93), and (95); Conn. Gen. Stat. §§7-273mm and 16-344; and Conn. Agencies Regs. §12-426-18. Definitions Wherever the term contractor is used in this Announcement, it includes subcontractors of the contractor performing a contract with an exempt entity. Exempt entity means any of the following persons entitled to make purchases of tangible personal property exempt from sales and use taxes: · Governmental entities: Use of CERT-141: Contractors for the repair, alteration, improvement, remodeling, or construction of real property use CERT-141 to make exempt purchases of materials and supplies to be installed or placed in a project being performed under contract with an exempt entity. The materials and supplies must remain in the project after its completion including tangible personal property that remains tangible personal property after its installation or placement. Examples of items in these contracts that are likely to be exempt are bathroom partitions, metal lockers, theater seats, and other items nailed, bolted, or screwed into the real property, as well as appliances and furniture not permanently affixed to the property but that remain on the property after the contract is completed. If a contractor is unable to designate the exact amount of materials or supplies to be installed or placed in a project being performed under contract with an exempt entity, the contractor must estimate the amount of the purchases. The contractor will be held strictly accountable for any use tax due the state on the purchases in the event of any use other than the permanent installation or placement of the purchases in the exempt project identified in the CERT-141. If the tangible personal property is not used in the manner described above, a contractor who claimed an exemption owes use tax on the total price of the tangible personal property. Upon completion of the project, the contractor must report and pay use tax on any materials still in inventory that were purchased exempt from tax. If materials or supplies are installed or placed in a project for an exempt entity and the contractor has already paid tax on the materials or supplies, the purchase price of the materials or supplies may be deducted on the next return as an adjustment. Contractors are the consumers of all the tools, supplies consumed, and equipment used in fulfilling a construction contract. Contractors must pay tax on the purchase of these items because they do not become incorporated or placed in the exempt job even if they are used up during the job. Blanket Certificate: Besides being used for individual purchases, CERT-141 may also be used for a continuing line of exempt purchases. In either case, the contractor must provide a separate CERT-141 for each project with an exempt entity. A blanket certificate remains in effect for three years unless the purchaser revokes it in writing before the period expires. Recordkeeping: For at least six years from the date it is issued, a contractor who issued a CERT-141 must keep a copy of it and records that substantiate the information entered on it including records to support the contractors use of the certificate and to show the disposition of all materials or supplies purchased. For at least six years from the date of purchase, a seller must keep CERT-141 and bills or invoices to the purchaser. The bills, invoices, or records covering the purchase made under the CERT-141 must be marked to indicate an exempt purchase was made. The words Exempt under CERT-141 satisfy the requirement. Old Contractors Exempt Purchase Certificate Is Withdrawn: Contractors making purchases of materials exempted under one of the statutory provisions listed above should no longer use the old Contractors Exempt Purchase Certificate. Any unused blank copies of the old certificate should be discarded. In addition, CERT-141 as originally issued in June 2008 has been revised in March 2009. Unused blank copies of the June 2008 version of the CERT-141 should be discarded. Effect of This Document: Announcements alert taxpayers to new developments (other than newly enacted or amended Connecticut or federal laws or newly released judicial decisions), including new administrative positions, policies, or practices. For Further Information: Call DRS during business hours, Monday through Friday:
Select Option 6 to speak to a representative. TTY, TDD, and Text Telephone users only may transmit inquiries anytime by calling 860-297-4911. Forms and Publications: Forms and publications are available anytime by:
Paperless Filing/Payment Methods (fast, easy, free, and confidential): Business and individual taxpayers can use the Taxpayer Service Center (TSC) to file a variety of tax returns and extensions, as well as to pay taxes or bills over the Internet. Visit the DRS website at www.ct.gov/DRS and select an option from the list on the TSC image. DRS E-Alerts Service: Get connected to the latest news from DRS. Receive notification by email of changes to legislation, policies, and procedures. DRS E-Alerts provide information for employers withholding tax, TSC-BUS Online Filing Alerts, News Press Releases, and Top 100 Delinquency List. Visit the DRS website at www.ct.gov/DRS and select e-Alerts from the left navigation bar. AN 2009(6) |
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text: Newport International Film FestivalThe Newport International Film Festival (NIFF) was founded in 1998 by Christine Schomer, Nancy Donahoe and Pami Shamir. In addition to our daily panel discussions with well-known industry professionals, NIFF schedules over 100 screenings of feature length narrative films, documentaries and shorts, as well as both international and U.S. film premieres. |


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We explore the current limits of the axial resolution of optical sectioning microscopy using a single lens, by combining the resolving power of novel 1.45 numerical aperture oil immersion lenses with superresolving binary aperture filters. We quantify the axial resolution brought about by the increase in semiaperture angle to α max =72.8° and demonstrate an absolute gain in axial resolution through binary pupil filters. Implemented in a confocalized two-photon excitation microscope, the combination of both effectively improves the axial resolution to 330 nm full-width-half-maximum, which is by 34% over that of a standard 1.4 NA system.
© 2002 Optical Society of America
Full Article | PDF ArticleOSA Recommended Articles
Karsten Bahlmann and Stefan W. Hell
Appl. Opt. 39(10) 1652-1658 (2000)
Marion Lang, Tobias Müller, Johann Engelhardt, and Stefan W. Hell
Opt. Express 15(5) 2459-2467 (2007)
Stefan W. Hell, Axel R. Utz, Martin Schrader, Pekka E. Hänninen, and Erkki Soini
J. Opt. Soc. Am. A 12(9) 2072-2076 (1995)


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Essential Guide
The CIO cloud blueprint: A strategic planning guide
A comprehensive collection of articles, videos and more, hand-picked by our editors
Take off the tech hat when contemplating cloud adoption strategy
Isn't the cloud just outsourcing, the Internet? IT strategy expert Harvey Koeppel ponders the winding (and often misleading) paths to cloud adoption.
The CIO cloud blueprint: A strategic planning guide
All roads to a cloud adoption strategy are paved with misinformation. SearchCIO IT and business strategy expert Harvey Koeppel explains why a tech POV is the worst offense of all in the first part of this two-part column on developing a cloud adoption strategy. In the second piece, Koeppel runs through 14 questions that will lead to business value -- and no, none of them start with "Isn't the cloud really just outsourcing?"
The adoption of cloud infrastructures within modern enterprise data centers provides CIOs with an opportunity to move the needle on several of the most fundamental and most-often-quoted (and often under-achieved) IT objectives: shorter time to market for new products and services, less time and money spent on developing and maintaining applications and infrastructure, enormous scalability, best-in-class reliability and all without comprising cyber or information security. Given these very compelling opportunities, why has (private and/or public) cloud adoption strategies been the subject of so much debate, deliberation and, for some, even controversy?
The challenge of the many (too many)…
Migrating to the cloud has come to mean many different things to many different people. Consider the following regarding some of the most basic of questions in the space:
What is cloud? | 1.4 billion search results |
What are the benefits of cloud? | 186 million search results |
Should we move to the cloud? | 128 million search results |
The good news: The number of search results decreases as the questions move from the more general to the more specific. The bad news: The amount of "stuff" floating around on this topic is overwhelming, it is growing, and its sheer volume presents a big data challenge (different column) to all but the most techie of techies whom, with all due respect, often need to get a life.
If you are even casually familiar with some of the fundamental principles of database design and management, your physical and/or virtual eyebrows will likely be raised because you know that "many-to-many" relationships are hard to manage. In strict relational database design, many-to-many relationships are, in fact, not supported and can only be implemented by using additional junction/join tables to map the details of these relationships.
My personal opinion (careful now, as I am a former techie myself) is that if you think about cloud as technology, you will likely get consumed in the "morass of stuff" and have a tough time following a path that will lead anywhere even vaguely resembling delivery of business value to your internal and external customers. You will find yourself bereft with even more questions, often starting with words like "Isn't cloud really just…" For example:
Isn't cloud computing really just…
- The Internet?
- Outsourcing?
- Using a package versus a custom application?
- Trading capital expense for operating expense?
- "Buying by the drink"?
- Less secure than traditional infrastructure models?
If you think about cloud as technology, you … have a tough time following a path that will lead anywhere vaguely resembling delivery of business value.
Each of these questions is clearly pertinent. How you answer each question -- most of which have multiple answers -- will likely create dependency(ies) and/or be dependent upon how you answer one or more of the other questions, individually and in combinations. What we have here is actually a complex set of (many) many-to-many relationships. And these are only a few of the likely hundreds of similar questions that could be posed on the topic should you be so inclined as to poke through the billions of search results identified above.
Rest assured that I have absolutely no intention of attempting to take on the likely impossible task of building the data model that explains how all of these cloud adoption strategy questions and answers relate to each other with respect to implementing cloud.
I should, for the record, state here that even if one were to absorb the abundance of cloud-related literature, listen attentively to all the vendor pitches and somehow construct and evaluate the data model envisioned above, the road to successful cloud implementation is still filled with challenges that may not yet be recommended for someone with a weak heart.
From a public cloud perspective, dealing with vendor contracts can be significant hurdles to overcome. The issues include lock-ins, pricing, service-level agreements, security, multi-vendor integration, adoption of standardized business processes, handling of existing equipment leases or partially depreciated assets, disaster recovery and continuity of business, etc.
Implementing private cloud infrastructures requires a keen understanding of the following (to name a few):
vendor product/service stacks;
component integration;
service management systems;
More columns by Harvey Koeppel
Extracting value from disruptive technologies
Big data changes everything in a big way
Eight means to keep pace with mobile workers
service management organizations;
user charge-back and billing systems;
network and bandwidth management;
integration with existing identity management and security platforms;
conversion from legacy applications that were not necessarily designed to be run in virtualized environments.
Harvey has laid out the problem. Go to part two for his solution: a list of 14 business questions that will help CIOs develop cloud adoption strategies that will actually lead to business value.
Let me know what you think. Post a comment or drop me a note at firstname.lastname@example.com. Discuss, debate or even argue -- let's continue the conversation.
Find more PRO+ content and other member only offers, here.


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Thread: Xtreem Jiu Jitsu in El Paso, TX
5/26/2013 2:24pm, #41
- Join Date
- May 2013
- Posts
- 6
- Style
--I wish I had seen this post but I just recently signed up for this blog and moved from the El Paso area. Interesting...
5/27/2013 4:58pm, #42
- Join Date
- Nov 2011
- Location
- Texas
- Posts
- 202
- Style
1Thank you for your response. Understand that most of us on this site merely want honesty and evidence to be revealed. Nothing more. The last thing that we want is another pissing contest. My suggestion is to read through the thread and find the specific problems people have presented and retort. Again, thanks for your response.
Lurk more and post less.
6/06/2013 4:12pm, #43
- Join Date
- Jun 2013
- Posts
- 14
--Yes but Ruben a lot of us on this site (in varying degrees) have dedicated our lives to the art of Brazilian jiu-jitsu. When someone is teaching bjj techniques and calling themselves a black belt (while only having one in some traditional form of ju-jitsu) is pretty deceiving. He talks about winning the pan ams but there is no mention that he did it at blue belt and in a senior division. There is a world of difference between a black belt gold medalist in the adult division as opposed to the say senior 3 division at blue belt. For one, most of those divisions only have like 3 competitors to begin with. All that being said no one is saying your instructor can't grapple, just that he grossly misrepresented credentials which is a big deal to most of us no matter how much you respect the guy.


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Preventive Pet Healthcare Champion Workbook |
Preventive healthcare is an important part of your commitment to quality care for your patients. But, at any busy practice, preventive pet healthcare can get lost during the non-stop action of a regular day. Sometimes it takes a talented, passionate someone to remind the practice team to keep preventive healthcare a priority in your clinic. That someone can be you! Learn new leadership skills to earn new leadership responsibilities at your practice by becoming a Champion of preventive pet healthcare today. Whether you're an old pro at leading initiatives or an enthusiastic first-timer, this workbook has everything you need. You can do this!! VHMA Members can order the Champion's Workbook for $49, non-members may order the Champion's Workbook for $89.
Webinar tutorial on How to Use This Workbook |
Webinar - Inventory 202
WEBINAR: CVPM Informational
WEBINAR: CVPM Preparation Workbook


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The BBC is missing a huge trick, you know. Forget Springwatch, Badgerwatch, Lambwatch – what they should be doing, if my experience is anything to go by, is Henwatch. I have five Welsommer hens (called Helga, Quentin, Helga, Big Ginge and Helga (you read that right, there are three we can't tell apart)) and watching them rioting around the garden now the days are longer and the sun is stronger, is one of the main pleasures of my days, now that David Mitchell has found love elsewhere. They ruin any attempts at planting, egg production is sporadic at best and they terrify the cats, but the pleasure of watching five chickens rush up the length of the garden like loose-knickered old ladies every time the back door opens is worth any amount of catkins or cubs. And their vocalisation is amazing too – we can tell by sound when one has got stuck round the back of the house or when a particularly juicy slug has met a beaky end. Hours of fun for all the family, plus bonus eggs and they even eat stale breakfast cereal!
These are two of the ladies in question, when newly acquired. Before they were released on the world and before their elastic loosened.
And now, if you'll excuse me, I have to go and sob into some gin..David, why did you forsake me! Sniff.
11 thoughts on "Jane Lovering on The joy of Hens"
The hens are gorgeous, Jane! I hope watching them makes up – to some extent, anyway – for David's utterly shameless and unjustifiable defection. But life isn't fair…
How cute – if that's the right word.
The play I went to last Saturday, The Recruiting Officer, had a real live hen on the stage. It was tucked firmly under the arm of one of the characters. The hen's emoting was impressive, and it sounds to me as if your character-full hens could well have a future treading the boards.
Liz X
They look lovely and thanks for giving me a laugh – three Helgas, brilliant!
LOL – Spooky! I have 5 hens – which I adore too, whilst the cats do not. The spookiness kind of ends though with the mention of David Mitchell X
Gorgeous hens, Jane. Which one's Helga? And which one's Helga?
Hx -
They sound as though they all have personalities, I think it comes with naming them, as our daughters used to do with ours when they were little!
Blimey, they're big, aren't hey? No wonder you can hear them. Why not send them round to Victoria Coren's house? When, they're hungry? Just a thought.
They do have very distinct personalities (although not so much that we can distinguish between Helgas). Am thinking of training them as Attack Hens, they can be quite scary en masse. And then inviting The Mitchells to tea…
I take it – seeing as you've named them – they won't end up being basted with garlic and butter, then?
Break it to me gently……who has David Mitchell got hooked up with – fool! He could have had an award-winning author…….sigh. -
No, Linda, they are strictly pet hens and for the eggs. I couldn't eat anything with a name. And David – the crazy fool – has got himself tied up with Victoria Coren! I mean, I know she's gorgeous and funny and intelligent and famous and talented and well-off, but really? What does he see in her?
Oh no! But fret not…..it will be all talk and clever words – and no do! – between them, I expect….:)


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Raymond Khoury
The Last Templar
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1291 AD, Acre. As the city burns under the onslaught of the Sultan's men, the Falcon Temple sets sail, carrying a small band of knights and a mysterious chest entrusted to them by the Order's Grand Master. But the ship vanishes without a trace... Present day New York. At the Metropolitan Museum, four horsemen dressed as Knights Templar storm the gala opening of an exhibition of Vatican treasures and, in a brutal and bloody attack, steal an arcane medieval decoder...
Category(ies): | crime, fiction, thriller |
Publisher: | Orion |
ISBN Number: | 0752880705 |


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Humoreske for piano in B flat major, Op. 20: VI. Zum Beschluss
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Vans Japan has released a new Valentine's Day 2011 Sk8 Hi. The sneaker comes in a chocolate brown patent leather colorway with a heart embroidered on the tongue. Furthermore it comes with 3 pairs of laces and features a metallic lining. The sneaker is now available from ABC-Mart.
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