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Paris is a sprawling urban jungle and Michael Mackrodts leaves no stone unturned. The world is yours...
Some beautiful filming documents an epic trip here. These spots are so buttery it's unreal. Includes Nick Garcia, Trent McClung and rippers that are legends in their home countries but maybe new to you like Phil Zwijsen, Michael Mackrodt and Karsten Kleppan.
Madars Apse and some of the Element team explore the island of Taiwan. As seen in the September mag.
Board Reanimation #2 The Larb Mar 06 |
Vans Zio Ziegler Show Release Mill Valley, CA Mar 07 |
Rock 'N' Soul Austin, TX Mar 18 |


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US 6375945 B1 Abstract The present invention pertains to improved adjuvant compositions comprising a mixture of a saponin adjuvant such as QS21 with monophosphoryl lipid A or derivative thereof such as 3D-MPL and interleukin 12. These compositions are useful in a range of prophylactic and therapeutic applications, particularly in vaccines, including cancer vaccines.
Claims(3) 1. An adjuvant compostion comprising a saponin adjuvant selected from the group consisting of QS-21 and QS-17, further comprising 3-O-deacylated monophosphoryl lipid A and Interleukin 12.
2. An adjuvant composition as claimed in
3. A method of producing an adjuvant compostion as claimed in
Description This application is a 371 of as International Application Number PCT/EP98/03671, filed Jun. 9, 1998. Not applicable. The present invention relates to improved adjuvant compositions, for the stimulation of an immune response suitable for immunotherapy applications. In particular the present invention relates to compositions comprising mixture of a saponin adjuvant with monophosphoryl lipid A or derivative thereof and interleukin 12. In particular, the invention relates to compositions comprising 3 de-o-acylated monosphoryl lipid A, QS21, and IL12. Such compositions are particularly useful in the immunotherapy of tumours. 1. Field of the Invention Cancer is a disease developing from a single cell due to genetic changes. Clinical detection of these tumours occurs mostly in a relatively late stage of disease, when the primary tumour can be removed by surgery, and the existence of micro metastases settled in different organs has often already occurred. Chemotherapy does often not completely eliminate these cells, which then remain as a source for recurrent disease. Immune cells are able to control all different tissues (with the exception of the brain) and, due to their memory function, can also eliminate hidden cells reentering the circulation (metastasis). Therefore, an activated immune response to tumour cells is expected to be of clinical benefit. Despite their undifferentiated growth, tumour cells are in many aspects indistinguishable from normal cells, and over-expression of certain proteins or expression of mutated proteins is in most cases not sufficient to activate the immune response. This situation results in failure of immune surveillance. Thus, strategies for therapy of disseminated tumours need to specifically activate the immune response to tumour cells and to trigger migratory activity of cytotoxic T cells for example leading to elimination of most and possibly every single tumour cell. Genetic mutation in tumour cells is intense, and strong immune responses are therefore required to prevent further genetic changes of the tumour cells (escape variants) under the pressure of the immune system. It is now well established that cellular antigens which are not cell surface proteins per se can be the targets of immune rejection through their recognition by immune regulatory and cytotoxic T cells. New potential target antigens for immune-mediated tumour rejection are being identified, based on their recognition by immune T cells, rather than by antibodies. Such antigens may or may not induce antibody formation. It is now recognized that the expression of tumour antigens by a cell is in itself not sufficient for induction of an immune response to these antigens. Initiation of a tumour rejection response requires a series of immune amplification phenomena dependent on the intervention of antigen presenting cells, which are responsible for delivery of a series of activation signals which ultimately leads to the rejection of the tumour. Tumour rejection antigens which are presented on tumour cells and which are recognised by cytotoxic T cells can lead to lysis of the cell. To achieve this, in a clinical setting a vaccine composition comprising a rumour rejection antigen needs to be presented in a suitable adjuvant system to enable a suitable immune response to be mounted. However, activation of the immune systems requires activation signals which are initiated by antigen presenting cells and are not activated by the tumour cells themselves. Vaccination with isolated tumour rejection antigens has been envisaged either by recombinant proteins, by the use of live recombinant vectors or by DNA vectors. Preferably subunit antigens will be used. However, to ensure these are effective, powerful adjuvant systems are required. Accordingly, the present invention provides an adjuvant composition comprising a combination of a saponin adjuvant in combination with monophosphoryl lipid A or derivative thereof together with the cytokine Interleukin 12. 2. Description of the Related Art Immunologically active saponin fractions having adjuvant activity derived from the bark of the South American tree Quillaja Saponaria Molina are known in the art. For example QS21, also known as QA21, is an Hplc purified fraction from the Quillaja Saponaria Molina tree and it's method of its production is disclosed (as QA21) in U.S. Pat. No. 5,057,540. Quillaja saponin has also been disclosed as an adjuvant by Scott et al, Int. Archs. Allergy Appl. Immun., 1985, 77, 409. Monosphoryl lipid A and derivatives thereof are known in the art. A preferred derivative is 3 de-o-acylated monophosphoryl lipid A, and is known from British Patent No. 2220211. Interleukin 12 (IL-12) is known. For a review see Trinchieri G. Interleukin-12�A proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Immunology 13: 251.276, 1995. It is a heterodimeric cytokine produced mostly by phagocytic cells in response to bacteria, bacterial products, and intracellular parasites, and to some degree by B lymphocytes. In particular, IL-12 is produced by antigen presenting cells and instrumental in induction of TH-1 cell responses. IL-12 induces IFN-gamma from NK and T cells, acts as a growth factor for activated NK and T cells, enhances the cytotoxic activity of NK cells, and induces cytotoxic T lymphocyte generation. FIG. 1 shows the immunisation protocol whereby DBA/2 mice are immunised with peptide 198 adjuvanted or not with DQS21/3D-MPL and further adjuvanted with IL-12. One or two injections are delivered subcutaneously intra footpads, following which CTL activity was measured. FIG. 2 shows the CTL activity, as measured in lytic units per million lymphocytes, following one or two immunisations of DBA/2 mice with peptide 198 adjuvanted with DQS21/3D-MPL with or without addition of IL-12. FIG. 3 shows a modified immunisation protocol whereby DBA/2 mice are immunised with peptide 198 adjuvanted or not with DQS21/3D-MPL and with or without addition of IL-12. One to four injections are delivered subcutaneously intra footpads or in the flanks, following which CTL activity was measured. FIG. 4 shows the CTL activity, as measured in lytic units per million lymphocytes, following one to four immunisations of DBA/2 mice with peptide 198 adjuvanted or not with DQS21/3D-MPL and with or without addition of IL-12. FIG. 5 shows the immunisation protocol whereby DBA/2 mice are immunised with peptide 198 adjuvanted with DQS21/3D-MPL and with increasing doses of IL-12. One or two injections are delivered subcutaneously intra footpads, following which CTL activity (IL-12 dose curve) is measured. FIG. 6 shows the CTL activity (IL-12 dose curve), as measured in lytic units per million lymphocytes, following one to two immunisations of DBA/2 mice with peptide 198 adjuvanted with DQS21/3D-MPL-and with increasing doses of IL-12. FIG. 7 shows the immunisation protocol whereby DBA/2 mice are immunised up to four times with peptide P1A adjuvanted with DQS21/3D-MPL and with or without IL-12. The injections are delivered subcutaneously intra footpads, following which CTL activity was measured. FIG. 8 shows the CTL activity (IL-12 dose curve), as measured in lytic units per million lymphocytes, following immunisation of DBA/2 mice with peptide P1A adjuvanted with DQS21/3D-MPL and with or without IL-12. IL-12 and IL-12-induced IFN-gamma favor Th1 cell differentiation by priming CD4 (+) T cells for high IFN-gamma production. However, we surprisingly found that other cytokines, such as IFN-γ, IL-2, IL-6, IL-7, GM-CSF or MCP were unable to enhance the effect of the QS21/MPL adjuvant. Preferably the compositions of the invention contain the immunologically active saponin fraction in substantially pure form. Preferably the compositions of the invention contain QS21 in substantially pure form, that is to say, the QS21 is at least 90% pure, preferably at least 95 % pure and most preferably at least 98% pure. Other immunologically active saponin fractions useful in compositions of the invention include QA17/QS17. In a preferred embodiment the composition also comprises a sterol such as cholesterol wherein the sterol is present in an excess ratio to that of the saponin. These show decreased reactogenicity when compared to compositions in which the cholesterol is absent, while the adjuvant effect is maintained. In addition it is known that QS21 degrades under basic conditions where the pH is about 7 or greater. Thus a further advantage is that the stability of QS21 to basemediated hydrolysis is enhanced in formulations containing cholesterol. Although the adjuvant compositions can be utilised for the treatment or prophylaxis of a range of disease, they find particular utility in the field of cancer immunotherapy. In particular, the adjuvant formulation finds utility particularly with tumour rejection antigens such as those for prostrate, breast, colorectal, pancreatic, renal or melanoma cancers. Exemplary antigens include MAGE 1 and MAGE 3 or other MAGE antigens for the treatment of melanoma, BAGE or GAGE LAGE (NY-eso-1) PRAME or Her-2/neu; Robbins and Kawakami (1996), Current Opinions in Immunology 8, pps 628-636; Van den Eynde et al., International Journal of Clinical & Laboratory Research (submitted 1997); Correale et al. (1997). Journal of the National Cancer Institute 89, p293. Indeed these antigens are expressed in a wide range of tumour types such as melanoma, lung carcinoma, sarcoma and bladder carcinoma. Other classes of antigens useful in the context of the present invention include tissue specific antigens such as Prostate Specific antigen (PSA); Prostate Specific Membrane antigen (PMSA), Melan A/Mart 1, gp100, tyrosinase TRP1 or TRP2. Accordingly in one aspect of the present invention there is provided a vaccine comprising an adjuvant composition according to the invention and a tumour rejection antigen, or tissue specific antigen. Other antigens or antigenic compositions include for example, polysaccharide antigens, protein antigens or DNA encoding antigens or antigenic compositions derived from HIV-1, (such as gp120 or gp160), any of Feline Immunodeficiency virus, human or animal herpes viruses, such as gD or derivatives thereof or Immediate Early protein such as ICP27 from HSV1 of HSV2, cytomegalovirus (especially human) (such as gB or derivatives thereof), Varicella Zoster Virus (such as gpI, II or III), or from a hepatitis virus such as hepatitis B virus for example Hepatitis B Surface antigen or a derivative thereof, hepatitis A virus, hepatitis C virus and hepatitis E virus, of from other viral pathogens, such as Respiratory Syncytial virus (for example RSV F and G proteins or immunogenic fragments thereof disclosed in U.S. Pat. No. 5,149,650 or chimeric polypeptides containing immunogenic fragments from HSRV proteins F and G, eg GF glycoprotein disclosed in U.S. Pat. No. 5,194,595), antigens derived from meningitis strains such as meningitis A, B and C, Streptococcus Pneumonia, human papilloma virus, in particular from strains HPV6, 11, 16 and 18, Influenza virus, Haemophilus Influenza B (Hib), Epstein Barr Virus (EBV), or derived from bacterial pathogens such as Salmonella, Neisseria, Borrelia (for example OspA or OspB or derivatives thereof), or Chlamydia, or Bordetella for example P.69, PT and FHA, or derived from parasites such as plasmodium or toxoplasma. The P815 tumour is a mastocytoma, induced in a D BA/2 mouse with methylcholanthrene and cultured as both an in vitro tumour and cell line. This represents an excellent model system for the human. The model system described in this application is a murine system whereby a murine tumour antigen, P1A, expressed in the mouse mastocytoma P815, is being tested for its ability to stimulate CTL in the mouse with and without adjuvant. The significance of this system is that P1A is a true tumour rejection antigen in that its gene is the same in both normal and tumour cells but the gene is silent in normal cells and only expressed in tumour cells. This is in comparison to other P815 antigens that were previously found and which are created by mutation of normal alleles. These are called tum- variants or tum- antigens. Mutations in the tum-antigens create new antigenic peptides which can then be recognised by CTL. Turn- antigens are likely to be tumour-specific whereas true tumour antigens will be shared between different tumours and patients and therefore the latter will be better candidates for vaccine formulations. Human tumour rejection antigens analogous to P1A include the MAGE, BAGE, GAGE etc. families as described earlier. These genes are found in both normal and tumour tissues but the corresponding proteins are expressed only in tumours and in normal testis. As the testis is an immune privileged site it is unlikely to be affected by any vaccine. P1A is a true murine TRAs. Therefore, one can test a large number of adjuvants with a variety of different assays in mice giving a good indication as to which formulations should be used with human tumour rejection antigens in human clinical trials. Preferred compositions of the invention are those forming a liposome structure. Compositions where the sterol/immunologically active saponin fraction forms an ISCOM structure also form an aspect of the invention. The ratio of QS21: sterol will typically be in the order of 1:100 to 1:1 weight to weight. Preferably excess sterol is present, the ratio of QS21:sterol being at least 1:2 w/w. Typically for human administration QS21 and sterol will be present in a vaccine in the range of about 1 ng to about 100 μg, preferably about 10 μg to about 50 μg per dose. The liposomes preferably contain a neutral lipid, for example phosphatidylcholine, which is preferably non-crystalline at room temperature, for example eggyolk phosphatidylcholine, dioleoyl phosphatidylcholine or dilauryl phosphatidylcholine. The liposomes may also contain a charged lipid which increases the stability of the lipsome-QS21 structure for liposomes composed of saturated lipids. In these cases the amount of charged lipid is preferably 1-20% w/w, most preferably 5-10%. The ratio of sterol to phospholipid is 1-50% (mol/mol), most preferably 20-25%. The compositions of the invention also contain a 3 deacylated monophosphoryl lipid A derivative (3-de-o-acylated monophosphoryl lipid A, also known as 3D-MPL) and is manufactured by Ribi Immunochem, Montana. A preferred form is disclosed in International Patent Application 92/116556. Suitable compositions of the invention are those wherein liposomes are initially prepared without 3D-MPL, and 3D-MPL is then added, preferably as 100 nm particles. The 3D-MPL is therefore not contained within the vesicle membrane (known as 3D-MPL out). Compositions where the 3D-MPL is contained within the vesicle membrane (known as 3D-MPL in) also form an aspect of the invention. The antigen can be contained within the vesicle membrane or contained outside the vesicle membrane or encapsulated. Preferably soluble antigens are outside and hydrophobic or lipidated antigens are either contained inside or outside the membrane. The 3D-MPL will be present in the range of about 1 Ug to 100 Ug and preferably about 10 to 50 μg per dose of human vaccine. Often the vaccines of the invention will not require any specific carrier and formulated in an aqueous or other pharmaceutically acceptable buffer. In some cases it may be advantageous that the vaccines of the present invention will further contain alum. Human tumours express antigens that can be recognized by autologous CTL. These antigens constitute useful targets for cancer immunotherapy. We decided to evaluate in the P815 murine mastocytoma model the efficacy of an immunization method that could be applied to human patients. Syngeneic DBA/2 mice were injected with antigenic peptides mixed with adjuvant and murine IL12. An adjuvant composition comprising QS21, lipids (DQ) and 3 de-o-acylated monophosphoryl lipid A (3D-MPL) was prepared. Briefly a mixture of lipid (such as phosphatidylcholine either from egg-yolk or synthetic) and cholesterol in organic solvent, is dried down under vacuum (or alternatively under a stream of inert gas). An aqueous solution (such as phosphate buffered saline) is then added, and the vessel agitated until all the lipid is in suspension. This suspension is then microfluidised until the liposome size is reduced to 100 nm, and then sterile filtered through a 0.2 Um filter. Extrusion or sonication could replace this step. The cholesterol phosphatidylcholine ratio is 1:4 (w/w), and the aqueous solution is added to give a final cholesterol concentration of 5 to 50 ng/ml. The liposomes have a defined size of 100 nm and are referred to as SUV (for small unilamellar vesicles). If this solution is repeatedly frozen and thawed the vesicles fuse to form large multilamellar structures (MLV) of size ranging from 500 mn to 15 μm. QS21 in aqueous solution is added to the liposomes. This mixture is then added to 50 μg of P198 peptide (KYQAVTTTL) and 3D-MPL. DBA/2 mice were injected s.c. in the two footpads with 50 μg of P198 peptide (KYQAVTTTL), corresponding to the antigen expressed by the P198 TUM�clone (Sibille et al., J. Exp. Med., 1990: 172, 35-45), mixed with the DQS21/3D-MPL adjuvant (adjuvant) 100 μl final. For a second group of animals we added to the peptide and adjuvant solution 50 ng (500U) murine IL12. This murine IL12 was purified from the supernatant of transfected P1HTR cells as described in Gajewski et al. (J. Immunol. 1995, 154: 5637-5648). On d1 and 2, we injected locally an additional dose of IL12 100 ng (1000U) or PBS. On day 16, the mice were bled and stimulation of blood lymphocytes was performed by mixing 3�105 Ficoll purified lymphocytes with 1 irradiated stimulating cells (100 Gy) and 2�106 irradiated normal syngeneic spleen cells (30 Gy) as feeder cells. The stimulating cells were P1983 cells, an azaguanine-resistant variant derived from the P198 TUM-clone. The cells were incubated in 48-well plates in a final volume of 0,8 ml MLTC medium described in Warnier et al. (Int. J. Cancer, 1996, 67, 303-310). Seven days later, CTL activity was measured in a standard chromium-release assay using 1,000 51Cr-labelled targets. Two targets were used:the P1983 cells or the P511 cells (azaguanine-resistant variant derived from the P815 TUM+cells) not expressing the P198 antigen. To eliminate non-specific lysis, 105 cold P511 cells were added as competitors. On day 26, the mice received a second injection of peptide, adjuvant and IL12 or PBS, followed by two local injections of 100 ng (1000U) IL12 or PBS. A second bleeding of the mice was performed on day 41 to estimate CTL activity after two injections. Data are expressed in lytic units (LU)/106 lymphocytes as described in Brichard et al. (Eur. J. Immunol., 1995, 25: 664-671). Specific lytic units were calculated by subtracting the values obtained with the negative targets (usually less than 0,3 LU) from those obtained with the positive target. Mice were scored as � when the LU detected were comprised between 0,1 and 1; + when LU were comprised between 1 and 10; and ++ above 10 LU. After the first injection, no CTL activity was detected in the mice injected with the peptide and the adjuvant. When IL12 was added significant CTL activity was detected in all the animals. For the majority of the mice (13/15) the response was moderate since we measured less than 1 LU/106 PBL. After the second immunization, two mice out of 15, injected with the peptide and adjuvant alone were positive. In the group injected with IL12, CTL activity had increased and half of the mice showed a very high response. The addition of IL12 to the peptide and the adjuvant increased strongly the number of responding mice and the level of CTL activity observed after only a few injections. In this second experiment, we applied the immunisation protocol described before (FIG. 1) with some modifications. To determine the relative contribution of IL12 and adjuvant in CTL induction, we injected one group of mice in the footpads with P198 peptide and IL12 without adjuvant. To test a s.c. injection site that is applicable to humans, we also injected 2 groups of mice s.c. in the flank instead of the footpads; the first one receiving the peptide, the adjuvant and the IL12 and the second receiving only the peptide and the adjuvant. Four injections were performed and mice were bled after the first, the second and the fourth injection for CTL activity determinations. After the first immunisation, we observed that 4 mice out of 10 injected with peptide, the adjuvant and IL12 in the footpads showed a significant CTL activity. In the group injected without adjuvant 3 mice also showed CTL activity but the response was lower. Nearly no response was obtained after injection into the flanks since only 2 mice receiving the peptide, the adjuvant and IL12 showed a weak CTL activity. After the second immunisation, all the mice receiving the peptide, the adjuvant and IL12 combination in the footpads exhibited high CTL activity. All the mice injected with the peptide and the IL12 without adjuvant also showed a specific CTL activity, but much weaker. The same situation is observed for the mice injected in the flank with the peptide, the adjuvant and the IL12 while in the absence of IL12 no response is observed after injection in the flank. After the fourth injection, all the mice that received peptide. adjuvant and IL12 in the footpads had a CTL activity located in the high values. We also observed an increase in the average of CTL activity for the mice injected without adjuvant or receiving the peptide, the adjuvant and the IL12 in the flank. Even after 4 injections we did not observe any response in the mice injected in the flank without IL12. We confirm in this experiment the potent effect of IL12 on the generation of CTL activity after immunisation with the P198 peptide. This effect is enhanced by the combination with the DQS21/3D-MPL adjuvant since the response is obtained earlier in all the mice and since the average level of response is higher. The effect of IL12 is also required to obtain CTL activity when the antigen is injected in the flank instead of in the footpads. Mice were injected with the P198 peptide mixed with the DQS21/3D-MPL adjuvant. Different doses of murine IL12 3 ng (30U), 10 ng (100U), 30 ng (300U), 100 ng (1000U) were mixed with the peptide and the adjuvant and also repeated locally the two following days. The control group received the peptide and the adjuvant but no IL12. Mice were bled after each of the two immunisations to monitor the appearance and level of CTL activity. In the two preceding experiments we used a high dose of IL12 (1 μg/mouse/day). Even if the IL12 was injected locally we saw a systemic toxicity with symptoms similar to those observed in a LPS shock. We decided to try decreasing doses of IL12. The effect of IL12 was nearly fully maintained when the dose/mouse/day was decreased to 10 ng (100U). It disappeared when the mice were injected with only 30 ng IL12. At that dose, the systemic toxicity of IL12 was largely reduced but not totally absent. After several experiments with the peptide P198 showing that high CTL activity were induced by injections of a combination of peptide, adjuvant and IL12, we decided to apply this protocol to the P1A peptide. This peptide presented by the Ld molecule constitutes the P815A antigen that is a major target for the immune rejection in vivo (Uyttenhove et al. J. Exp. Med., 1983, 157:1040-1052). Gene P1A, which code for the P815A antigen is expressed in several mastocytoma tumour lines (Van den Eynde et al. J. Exp. Med., 1991, 173: 1373-1384). Like the MAGE, BAGE and GAGE genes, it is not expressed in adult normal tissues, with the exception of spermatogonia in the testis (Van den Eynde et al, 1991 and Uyttenhove et al, Int. J. Cancer, 1997, 70: 349-356). Accordingly, the P815A antigen represents a good mouse model for the human MAGE, BAGE and GAGE antigens. Mice were injected s.c. in the two footpads with 50 μg of P1A peptide (LPYLGWLVF described in Leth� et al. Eur. J. Immunol. 1992, 22: 2283-2288) mixed with the adjuvant DQS21/3D-MPL. For one group, 100 ng (1000U) of IL-12 was added to the peptide and the adjuvant. These mice received additional doses of 100 ng (1000U) IL-12 injected locally the two following days. This injection scheme was repeated four times and the mice were bled after the second and the fourth injection. The lymphocytes were restimulated in vitro for 7 days and the CTL activity was measured in a conventional51 Cr assay. We used L1210. P1A cells as stimulating cells. The syngeneic L1210 P1A transfectant cells expressing the antigen P815AB were generated as described in Uyttenhove et al. Int. J. Cancer (1997) 70: 349-356. As target cells we used P511 cells expressing all the P815 antigens and P1-204 cells, an antigen-loss variant not expressing the P815 AB antigen described in Uyttenhove et al (J. Exp. Med., 157, 1040-1052, 1983). To avoid problems of non specific lysis, cold P1-204 were added as competitors. After two injections, 9 mice out of ten showed significant CTL activity specific for the P815A antigen when IL12 was added to the peptide and adjuvant. Half of those mice exhibited high CTL activity levels. In the group injected without IL12, a positive response was detected only in one mouse and this activity was rather low. After the fourth injection, all the mice receiving IL12 were positive and the average of lytic units had increased. Without IL12 we detected a good CTL activity in four mice, one addition al mouse showed a very low response at the limit of the significance threshold. In this system again, the addition of L12 increased the number of responding mice and diminished the number of injections needed to obtain high and specific CTL activity. In this experiment we injected a high dose of IL12 (100 ng (1000U)/mouse/day). Like in the previous experiments using the P198 peptide we observed systemic toxic effects of the IL12. The addition of IL12 to peptide and adjuvant combination is very effective at increasing the number of mice displaying high CTL responses after immunisation. In addition, CTL responses appear earlier in the presence of IL12. Patent Citations
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shuddh desi romance is so cute movie plus romantic.
Looking forward to shuddh desi romance. All the best to Sushant, Parineeti and Vaani for the film.
Edited on:05 September 2013 at 12:15pm
Looking forward to Shuddh Desi Romance on September 6...Sushant...Love ya...wish you all the very best...you and Parineeti are going to rock it!
Phata Poster Nikhla Hero < 3
20 september cant wait too see it :D
All the best Sushant n the whole team of SDR.
ME too eagerly waiting for shudh desi romance and Grand masti... Masti in 2004 was a big hit and i guess this too would be the same...
eagerly waiting for shuddh desi...
A string of Bollywood celebrities including Abhishek Bachchan, Akshay ...
Spending a colourful day with family and friends and gorging on ...
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Josh Groban collaborates with creators of 'Kid History' in new video
The Utah-based YouTube channel Bored Shorts TV, home to the "Kid History" series, has once again collaborated with musician Josh Groban.
In the latest installment in the channel's "Kid Snippets" series, which was posted April 28, Groban tries to order a pizza, flaunting his credentials as a way to speed up the process.
Groban's collaboration with Bored Shorts TV began in December 2012, after he shared one of the group's videos on Twitter. The creators of the "Bored Shorts TV" YouTube channel quickly reached out to Groban, requesting to work with the singer-songwriter.
This is the second installment of the YouTube channel's pairing with Groban. The first video was released in December 2013.
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NEW YORK (CNNMoney.com) -- General Electric reported quarterly earnings and revenue Friday that fell from year-earlier results, but the company said it expects an improving economy will help its profit rise throughout the rest of the year.
The Fairfield, Conn.-based conglomerate said its first-quarter sales fell 5% to $36.6 billion, missing the forecast of analysts polled by Thomson Reuters of $37.1 billion.
Net income fell 31% to $1.9 billion after GE took a loss of $390 million from discontinued operations. Earnings from GE's continuing operations fell 18% to $2.3 billion, or 21 cents per share, for the period ended March 31. Analysts forecasted earnings of 16 cents per share.
Shares of GE (GE, Fortune 500) fell nearly 3% to $18.90. Before the markets opened Friday morning, shares had topped $20 for the first time since October 2008, before falling below the mark again.
"GE's environment continued to improve in the first quarter of 2010," said Jeff Immelt, GE's chief executive, on a conference call with analysts. "We are expanding industrial margins and realizing benefits from over two years of restructuring, while increasing investment in [research and development] to drive profitable organic growth."
Immelt said the company expects earnings to grow for the rest of 2010, but GE may take more cost-cutting measures to improve profit growth even more. The company did not give any specific guidance, but said improvements at its finance arm, GE Capital, might help GE outperform its previously dislcosed broad "framework" for the year.
As the economy improved, GE said orders rose in its health care and energy businesses, and the company increased spending on research and development by 16% in the quarter. Overall, orders fell 8% to $17.1 billion, but orders outside the United States are picking up, and the company's equipment and services backlog held at a robust $174 billion, suggesting sales will rise in future quarters.
GE is also continuing to increase its cash reserves to give the company more financial flexibility. In the first quarter, GE set aside another $19.5 billion, putting the company's reserves very close to a historic high. The company said it may use the cash for stock repurchases or strategic acquisitions.
The CEO reiterated his statement from the prior quarter that the company expects to increase its dividend in 2011. GE had slashed its dividend 68% to just 10 cents per share in February 2009 as the recession cut into the conglomerate's financial results.
One analyst said the signs were pointing in the right direction, but GE should be cautious about its outlook.
"For the past ten years, it's been a constant case of 'We didn't do well in this quarter, but we'll do better in the future,' and the stock has been cut in half because of it," said Peter Cohan, a venture capitalist, management consultant and GE shareholder. "GE has to be very careful. If it over-promises and under-delivers, the stock is going to get killed again."
The improving economic environment and credit markets also helped GE Capital, which continued to stabilize in the quarter. GE Capital's mortgage-related losses continued to decline and the division turned a profit. Immelt said the finance unit is on track for earnings growth for the foreseeable future.
Sales at GE Capital, which account for more than a third of the company's overall revenue, fell 10% to $12.3 billion in the quarter. The unit was again profitable in the fourth quarter, earning $607 million. That was down 41% from the same period last year but up nearly 80% from the previous quarter.
The company's commercial real estate business continued to get slammed, losing another $403 million in the quarter. GE's management said those losses would continue for the foreseeable future but said GE would have no problem absorbing them.
"GE Capital losses seem to have peaked," Immelt said. "We are originating new business at attractive margins and our funding costs have declined. Commercial real estate continues to be challenging, but the risks are understood and we expect them to be manageable."
Sales fell modestly in most of the company's segments last quarter, though profits largely tumbled.
The exception was the company's energy infrastructure business, which continued to grow more profitable, as it had even throughout the recession. While sales fell 5% to $8.7 billion, profit rose 12% to $1.5 billion.
The other business that buoyed GE through the recession, the technology infrastructure unit, didn't fare quite as well. Sales fell 9% to $8.7 billion and earnings dropped 18% to $1.4 billion. Almost all of those declines were due to GE's aviation business, which struggled in the quarter.
The small home and business division - formerly called the consumer and industrial division - posted a 58% surge in profit to $71 million as sales grew 1% to $1.9 billion.
NBC Universal's revenue rose 23% to $4.3 billion, but profit declined 49% to $199 million after taking a hefty loss from its coverage of the Winter Olympics in February. The network also had to paid former "Tonight Show" host Conan O'Brien and his staff $45 million in a widely publicized settlement.
GE is set to sell a majority stake in NBC Universal to cable giant Comcast (CMCSA, Fortune 500), pending regulatory approval.
After a miserable 2009 in which GE was the second-worst performer in the Dow Jones industrial average, shares of GE have been on a tear in 2010, rising 29% this year, compared to the Dow's 7% rise.
GE's stock is the third best Dow performer of the year, just behind Boeing (BA, Fortune 500) and Bank of America (BAC, Fortune 500), which also reported its financial results Friday.
Index | Last | Change | % Change |
Dow | 18,132.70 | -81.72 | -0.45% |
Nasdaq | 4,963.53 | -24.36 | -0.49% |
Treasuries | 2.00 | -0.01 | -0.69% |
Company | Price | Change | % Change |
Bank of America Corp... | 15.81 | -0.23 | -1.43% |
Apple Inc | 128.46 | -1.96 | -1.50% |
General Electric Co | 25.99 | 0.10 | 0.39% |
Microsoft Corp | 43.85 | -0.20 | -0.47% |
Chesapeake Energy Co... | 16.68 | -0.52 | -3.02% |
Bus drivers for Apple, Yahoo, Amtrak, eBay, Genentech and Zynga have unionized, following in the footsteps of drivers who shuttle Facebook employees. More |
The specter of deflation has settled over vast tracks of the global economy, forcing large and small countries alike to examine the cost of falling prices. More |
A recent study found that heavy Facebook users can experience envy, which can lead to depression. More |
Self-described 'Last of the Mohicans' is still fixing typewriters after 55 years. More |
The top 5 consumer complaints have to do with identity theft, debt collectors, imposters, telephone companies and banks. More |


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Featured news
Linux users: welcome to the world of malware
Linux users are often smug about the state of their computer security, rightly criticizing Windows for its numerous security holes, but overlooking their own vulnerabilities.
Now it's their turn to suffer.
Over the last several days, Linux users have been targeted by a phony email claiming to be from the Red Hat Security Team, claiming that a vulnerability in fileutils-1.0.6 could "allow a remote attacker to execute arbitrary code with root privileges." The email tells people to download a patch to fix the problem.
By Preston Gralla at ONLamp.
[ Read more ]
Black hole routing: Not a silver bullet for DDoS protection
As ISPs, hosting providers and online enterprises around the world continue suffering the effects of DDoS attacks, often the discussions that follow are, What is the best way to defend our networks and our customers against an attack?
Compromised cPanel "Account Suspended" pages redirect to exploit kit
The code redirects visitors to another URL where the Fiesta exploit kit is hosted, which then tries to detect and exploit several vulnerabilities in various software. If it succeeds, the visitors are saddled with a banking Trojan.
Real MITM attacks enabled by Komodia's software might have already happened
EFF researchers showed that MITM attacks taking advantage of software using Komodia's encryption libraries have probably been executed in the wild.
How safe are Android-based childrens tablets?
Looking for an Android-based tablet for your child but don't know which one to choose? If you are concerned about the device's protection against random hackers, Bluebox Security has just released a review of the nine most popular Android tablet models aimed specifically at children.
Mobile apps left vulnerable for months
McAfee Labs researchers found that mobile app providers have been slow to address the most basic SSL vulnerabilities: improper digital certificate chain validation.
Reading our newsletter every Monday will keep you up-to-date with security news.
Receive a daily digest of the latest security news.


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TD-Complete Submission
What to expect when you're expecting (an acceptance letter)
4.15 / 5.00 4,366 Viewsme
u think u got it bad!!
i didnt get an action steve for x-mas, i got a barbie........ *sniff* (kidding) gd work tho
You may have my Old Action Steve...
...he is missing one green boot. But his Belt will still r0x0r your b0x0rz!


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Cheapest self catering accommodation deals for groups, multiple hire, off peak booking, last minute availability booking. Money saving discounts at family and pet friendly holidays and caravan parks in North, South, East and West Cornwall


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For the colder months ahead, Fall /Winter 2011 looks to the ice Planet Hoth for inspiration. Home to furry snow-creatures like tauntaunsand wampas, this is where the Rebel Alliance clashes with the Imperial Army in the epic battle of Hoth.
adidas have worked in a winter-sports vibe that introduces the iconic characters, creatures, vehicles and styles of Hoth to the adidas DNA. Below you can find a look at the Star Wars x adidas Fall Winter 2011 line.
adidas SW S Leather A15
The hooded adidas Star Wars Leather Down jacket will keep you warm and snug. Feature's an imposing goat leather exterior with Darth Vader embossing on the jacket's right sleeve, a large Trefoil on the back, and a zip and press-stud front.
adidas SW S Flight Jacket Militant
The adidas Flight Jacket re-styles a classic nylon flight jacket design with four front pockets, one sleeve pocket and a concealed pocket inside. Also features a Millennium Falcon graphic on the back.
adidas Stan Smith 80s Mid Vader
Features gold foil details and original sketches of Darth Vader on both sides of the upper for an imperial march all of your own.
adidas Campus 80s Wampa
Inspired the snow beast from the planet Hoth that almost made Luke Skywalker into a meal. The adidas Campus 80s Wampa dresses up these retro shoes with wampa fur uppers made from horsehair, contrast red stitching, a wampa tongue badge, and a laser cut wampa logo.
adidas Forum Mid Military
The adidas Forum Military feature a portrait of Han on the tongue badge and the words "Galactic Scoundrel" printed below a Millennium Falcon graphic.
adidas SW S M65 Field Jacket
This M65 jacket features a winter camouflage print allover, with military inspired epaulets , the Rogue Squadron insignia, and a high collar.
adidas S.W. Hoth
Built from material inspired by Luke's Planet Hoth out fit, these shoes feature a portrait of the young Jedi done in a green similar to his green tinted goggles.
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Selected fares from Portland to Gillette
Departure | Arrival | Travel dates | Round-trip |
PDX | GCC | Wed, Apr 22 - Wed, May 6 | $409 |
PDX | GCC | Wed, May 20 - Mon, May 25 | $422 |
Portland and Gillette airports and terminals
Airports in Portland OR, US
Portland International Airport (PDX)
Distance from City Center: 6.5 miles
Airports in Gillette WY, US
Campbell County (GCC)
Distance from City Center: 4.2 miles
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Highlighted price = Cheapest round-trip flights
Prices are round trip per person (conditions apply)
Featured Gillette Airport Hotels
...While staying at The BEST WESTERN Tower West Lodge, guests can also enjoy an indoor heated pool, hot tub, game room, business center, exercise facility, guest laundry, a 24-hour airport courtesy... More
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...Transportation Gillette-Campbell County Airport (7 mi/11.3 km) Attractions CCSD Science Center (1.6 mi/2.6 km).... More
Lowest roundtrip airfare in April from Portland to Gillette
Travel dates | Departure | Arrival | Stops: | Round-trip |
Leave Wed, Apr 22 | Portland (PDX) | Gillette (GCC) | United Airlines |
Return Wed, May 6 | Gillette (GCC) | Portland (PDX) | United Airlines |
Lowest roundtrip airfare in May from Portland to Gillette
Travel dates | Departure | Arrival | Stops: | Round-trip |
Leave Mon, May 18 | Portland (PDX) | Gillette (GCC) | United Airlines |
Return Wed, May 27 | Gillette (GCC) | Portland (PDX) | United Airlines |
Flights to Gillette
Portland International Airport
Flights from Portland depart from the Portland International Airport, located at 7000 NE Airport Way. The airport is approximately 22 miles south of downtown Portland and is serviced by 13 airlines, including Delta, Air Canada, Frontier and United. Orbitz.com makes it easy to book domestic and international flights from Portland. You don't have to scour the Internet to find cheap airline tickets. Orbitz.com searches all of the flights available to get you a ticket with a low fare.
Parking and Transportation
The Portland International Airport offers long-term parking for $19 per day. If you plan to leave your car at the airport for more than 90 days, you need to make prior arrangements with the airport's parking office. You can take a taxi from downtown Portland to the airport for approximately $32, so if you plan to leave your vehicle for more than two days, taking a taxi to the airport is a cheaper option. Streetcars also run from the downtown area to the airport, and streetcar tickets cost $2.40. If you need transportation when you arrive at your destination, Orbitz.com can reserve a rental car for you.
Dining at the Airport
If you want to grab a quick meal before your flight, the Portland International Airport has a variety of restaurant choices. You can stop in Starbucks or Coffee People for a quick snack. If you want a meal, you can eat at Wendy's, Sandoval's or Pizza Schmizza. Orbitz.com does more than book flights from Portland. The website has all of the tools you need to make sure your trip goes smoothly, giving you plenty of time to eat before your flight.
Gillette Airport Information
Finding cheap flights to Gillette, Wyoming, becomes a breeze when you use Orbitz.com. The website searches dozens of airlines and travel options at the same time to find the best deals on tickets. When traveling to, you will land at Gillette Campbell County Airport. It is located four miles north of Gillette, on US Highway 14-1, and is serviced by Frontier, Delta, and United airlines. Whether you are looking for domestic or international flights into the city, check Orbitz.com for bargain flights to Gillette.
Transportation from the Airport
After you plan your flights to Gillette with Orbitz.com, the website can also help you reserve a rental car, because public transportation is not available from the airport. Car rental companies Hertz and Avis are located on the south end of the airport building, directly across from baggage claim. Alternatively, you can hire a taxicab to drive you into town.
Weather in Gillette
Gillette has a semiarid climate, with an average summer temperature in the low 80s. Pack lighter clothing if you're planning to visit the city during this season, because the temperature may rise to as high 107oF in July. During the cold season that runs from December to January, temperatures average in the low teens, so you'll need some warm clothes.
Attractions in Gillette
From national parks and monuments to sports, recreation, and winter activities, there are many things to do and see in Gillette for everyone. Orbitz.com can also help you find discount tickets to the major attractions in the city when you book flights to Gillette.
Flight schedule for flights from Portland to Gillette on Sat, Mar 7, 2015
Carrier | Flight # | Departing | Arriving | Aircraft | Flight time | ||
Airport | Time | Airport | Time | ||||
United Airlines/United Airlines | UA789/UA5390 | PDX | 5:45 AM | GCC | 12:37 PM | 320/EM2 | 5hr 52min |
Promo Code Terms and Conditions
Book a qualifying 4-night flight + hotel vacation package between January 1, 2014 12:00AM CST and March 31, 2015 11:59PM CST, for $1000 or more for travel between January 1, 2014 and June 30, 2015 via Orbitz and instantly receive $150 off the hotel portion of your booking through the use of the promotion code. Limit one discount per hotel room and one promotion code per booking. Discounts are not redeemable for cash for any reason. Promotion codes cannot be resold. Any attempt at fraud will be prosecuted to the fullest extent of the law. Void where prohibited, taxed or restricted. Orbitz reserves the right to change or limit the promotion in its sole discretion. Promo code not valid for Las Vegas, NV bookings.
Fare, taxes & fees: Fares include all taxes and fees, except baggage fees. Rates shown reflect fares found by other Orbitz users over the past 48 hours. Due to rapidly changing airline prices & seat availability, these fares may no longer be available.
Refunds/changes/cancellations: Itinerary changes, if permitted for the fare, will have a $30 service fee charged by Orbitz. Additional airline charges may apply.
Other conditions: Schedules, fares and rules are subject to change without notice. Seats are limited and may not be available on all flights/dates or in all markets. Lower fares may be available. Fares will not be honored retroactively or in exchange for any wholly/partially unused ticket. Tickets are non-transferable and non-refundable. Fare rules are provided for the selected itinerary before booking.


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Snowmobiler Rescued After Scary Avalanche His friends rush to his rescue. 2/13/2015 10:25:31 AM 3,700 36
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Both the Gator and Lady Gator basketball teams notched their 10th wins of the season Friday night as Bulloch Academy swept Region 2-AA foe Memorial Day School.
ATLANTA - Even the fractious Georgia Legislature can agree on one thing: The state needs its first water management plan.
DETROIT - A jury convicted a 911 operator Friday of willful neglect of duty after authorities said she didn't take seriously a boy's calls to report his mother had collapsed. The mother was found dead three hours after the first call.
ELIZABETH, N.J. - Two inmates returned Friday to the scene of their daring Hollywood-style escape last month, which also led to the suicide of one of their guards.
LAS VEGAS - The fight for top-billing in Saturday's Nevada Democratic presidential caucus has become much like its model in Iowa: an hour-by-hour test of who has the best organization.
LAS VEGAS - The White House campaign has brought a new act to Vegas.
ATLANTA - When civil rights elders signed on to support Hillary Rodham Clinton's run for president, it was seen as a coup in the competition for the black vote, especially in the Deep South.
COLOMBO, Sri Lanka - Suspected Tamil Tiger rebels fatally shot 10 ethnic Sinhalese civilians in southern Sri Lanka, the Defense Ministry said Friday, amid escalating violence following the government's withdrawal from a cease-fire.
WASHINGTON - The Bush administration on Friday distanced itself from one of its own officials who criticized U.S. efforts to deal with North Korea's nuclear programs.
WASHINGTON - President Bush embraced as much as $150 billion in tax relief on Friday to jump start the lackluster economy. If Congress passes an economic stimulus package, the country will be ''just fine,'' he said.
WASHINGTON - A drug manufacturer won Supreme Court review Friday of a $6.8 million verdict in the case of a woman whose arm had to be amputated after she was injected with one of its medications.
WASHINGTON - A White House chart indicates no e-mail was archived on 473 days for various units of the Executive Office of the President, a House committee chairman says.
WASHINGTON - The Supreme Court agreed Friday to a cigarette maker's request to decide whether tobacco companies can be sued under state law for allegedly deceptive advertising of ''light'' cigarettes.
WASHINGTON - The CIA has concluded that a Pakistani tribal leader's network was behind the assassination of former Pakistan Prime Minister Benazir Bhutto, according to a U.S. intelligence official.
Oscar Wilde claimed: "A pessimist is one who, when he has a choice of two evils, chooses both."
LOS ANGELES - Leonard Nimoy, the actor known and loved by generations of "Star Trek" fans as the pointy-eared, purely logical science officer Mr. Spock, has died.
The Statesboro Police Department has arrested three suspects in a homicide investigation that left a Norcross man dead.
LOS ANGELES - In 1975, Leonard Nimoy published an autobiography with the defiant title, "I Am Not Spock." Two decades later, he bowed to fate with "I Am Spock," a revisionist sequel.
Authorities are still seeking the whereabouts of a Bulloch County mother and child reported missing Wednesday.
In his first season as Georgia Southern head coach, Willie Fritz guided the Eagles to a Sun Belt Championship in their inaugural season at the FBS level. Georgia Southern finished the season with a 9-3 mark, including a perfect 8-0 run through Sun Belt competition.
Mr. Carnell Ivey Jr.
HAMPTON, Ga. - After the glitz of Daytona, it's time for the NASCAR grind.
Bulloch County sheriff's deputies are asking the public's help in finding a woman and her 2-year-old son who left their home in the far southeastern part of the county.
WASHINGTON - Internet activists declared victory over the nation's big cable companies Thursday, after the Federal Communications Commission voted to impose the toughest rules yet on broadband providers like Comcast, Verizon and AT&T to prevent them from creating paid fast lanes and slowing or blocking Web traffic.
James Nevil, a Boy Scout with Statesboro Primitive Baptist Church's Troop 342, invites the public to attend a flag retirement ceremony at 6:30 p.m. Monday in the Boy Scout Hut on East Main Street, just across from the church.
A federal judge has cleared the way for Minnesota Vikings running back Adrian Peterson to be reinstated, ruling that an NFL arbitrator "failed to meet his duty" in a child abuse case that shook the league.
If you want to install a birdhouse - and make sure it will attract birds looking for that extra something - the Averitt Center for the Arts has a workshop for you.
Bulloch Academy senior Will Marsh scored a career-high 27 points to lead the Gators to a 61-47 thrashing of Tiftarea Academy in the first round of the GISA Class AAA state boys' basketball playoffs Thursday night.
ANAHEIM, Calif. - Los Angeles Angels outfielder Josh Hamilton is meeting with Major League Baseball officials about a disciplinary issue.
It was a sad day in August 1977 for Elvis Presley fans. The iconic singer died too soon. With nothing left but his legacy, fans held on to his memory.


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Game Questions & Answers (Q&A) service lets you ask questions about video games for game consoles or PC games. So ask your The Secret Society: Hidden Mystery question for iPhone - iPod and get answers from real gamers or answer questions and share your insights and experience with the rest of the gaming community.
- Developer: G5 Entertainment
- Publisher: G5 Entertainment
- Genre: Adventure
- Release Date: Nov 21, 2012
- ESRB: Not Set
Question & Answers
Progress in game comes and goes
I lost all progress in game and have start over. Lost all friends but they have returned. What few valentine I had were lost when the valentine box returned to my board. Maybe my lost progress will return someday
Answer from: Judi
Debye, What is your code and maybe you can be added to our groups so that we can help.
Answer from: Ann
Judi, are you the one with the puppies avatar? If so, there is nothing on your wish list but I send to you anyway. Have you gotten them? I thought perhaps you quit playing!
The Secret Society: Hidden Mystery - 1.4 Update Trailer
- Oct 31, 2013, Views: 1967
The Secret Society: Hidden Mystery - 1.5 Update Trailer
- Oct 31, 2013, Views: 1492
The Secret Society: Hidden Mystery - Gameplay Review
- Apr 14, 2014, Views: 2453
The Secret Society: Hidden Mystery - Hidden Mystery Content Update
- Apr 14, 2014, Views: 1843
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Maia knew how to get access to the fiesta, she showed us her perfect perky tits and walked in ready for some action. Who can refuse a beautiful woman with athletic legs and bubble butt just right for the smacking. This multi talented freak did it all from deep throating to anal. She was simply amazing.
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Asa Akira
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text:
Lower East Side basement boîte National Underground is the spot for techno rhythms tonight, with Hidden Recordings mastermind Deepak Sharma welcoming artists from the burgeoning label's roster. Tonight's party features a guest set from the U.K.'s Chris Finke, producer of Hidden's Don't Try This at Home EP and a resident at Birmingham's "Atomic Jam" blast; his fellow Hidden artist Domingo Cava plays as well.
Rough and Tumble
Event phone: | 212-475-0611 |
Event website: | http://thenationalunderground.com |


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fear leads to anger anger leads to hate hate leads to suffering suffering leads to crying crying leads to runny mascara runny mascara leads to panda eyes and panda eyes lead to the emo side -Hayden Christiansen
Kids who can read read the Harry Potter books. Kids who can't read watch the Twilight movies. -JK Rowling


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This Catchy Jamaican Bobsled Song Is Timed to Match the Track at Sochi 'Authentic soundtrack' from Draftfcb
Have you been waiting for someone to come up with a Jamaican Bobsled Team reggae song synced with the course in Sochi, fitting the exact shape of the racetrack with all its twists and turns?
Well wait no more, because Draftfcb New York and the Jamaica Tourist Board have done just that. According to Draftfcb, "If you press play at the exact moment the Jamaican Bobsled Team starts its run down the actual racetrack in Sochi on Sunday, you'll have your very own authentic soundtrack to one of the most anticipated moments of the Winter Olympics."
The song's got a catchy groove—"To the right! To the left! It's bobsled time!"—with an appealing animated promo clip that recalls old-school video-game graphics. ("Mon" appears just once in the lyrics, in case you were wondering.)
This marks Draftfcb's second recent tuneful foray, following the Kmart/Joe Boxer "Jingle Bells" spot from the agency's Chicago office. The reggae song's cute, but that ballsy yuletide classic set an extremely high bar for inspired musical silliness. Sorry, bobsledders, I'm afraid it's all downhill from there.
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Sunday, August 16, 2009 1 comments Dear Lord GOD, you are compassionate and gracious, slow to anger, abounding in love. Thank You that my soul can praise You, for You have been good to me. Amens... Read more
Saturday, August 15, 2009 4 comments The spark strategy "trouble goal" defines this as a goal that just seems to not get done, no matter how many times you plan it, or tried it. At least thats what I got about it, but to me my trouble goal is that I often write my goal and yet I d... Read more
Monday, August 03, 2009 9 comments I made plans but didn't get to follow through with any. I ended up going on a trip with my husband for the weekend and most of it was driving. I didn't watch what I ate but I know I didn't I have seconds and I drank as much water as I could. In ... Read more
Wednesday, July 22, 2009 7 comments I've decided to change small things in my lifestyle that will lead to a healthier me. 1. drink my water, 6+ cups daily 2. eat 2+ fruits and 2+veggies daily 3. exercise 15+ daily (any type) 4. take my medication on schedule, daily Altho... Read more
Sunday, July 19, 2009 4 comments I had a beautiful week with my family and friends, while we attended a really important Native American ceremony. (some info on my facebook site) and I did lots of dancing, and said prayers for the young lady who went thru the ceremony and for ... Read more
Sunday, July 12, 2009 7 comments Joanne got a message that on this day, God wants her to know...... that faith is exactly what it takes to get through uncertainty. Faith is not necessary when you know how things are going to work out, - that's knowledge. It's in the time o... Read more
Tuesday, July 07, 2009 4 comments Hey Sparkfriends, I am taking a 2 day break from the computer, only because I need to catch up on my reading and time with my family. Also just so you know I had a really great weigh in today at TOPS, not big but enough. Next Monday's weig... Read more
Thursday, July 02, 2009 3 comments Not much of anything really, since my daughter has to work tomorrow morning and then volunteered to work the concert concession stand in the evening too (with pay). My Husband is headed out of town to go visit his oldest son who is incarcerated,... Read more
Thursday, July 02, 2009 4 comments I know I am way off from my start weight for 2009, but I am not letting that stop me..... I am already on my way to my first 5% of weightloss from my highest weight. I am stress free, I am with my immediate family and enjoying each mo... Read more
Monday, June 29, 2009 13 comments My weigh in shows I am down 4.6 pounds from last week, Read more
Monday, June 29, 2009 7 comments I have things all planned for this week and even written in my planner/datebook. This also my diet journal (for diabetes) from Day-Timers, now I just need to follow through with it. You all have a great week.... Read more
Friday, June 26, 2009 2 comments Some how, todays plans did not happen but I am trying to make the most of whats left of this day. I know I need to get caught up with my bible study, also I did the cooking(all) tonight which is a first in a long, long, long, looonng time! It ... Read more
Thursday, June 25, 2009 8 comments I just heard about Michael Jackson, and I just want to cry, Why? Maybe because he was a great singer, and he was my beloved son RILEY's favorite singer. Dang, it hurts!!! GOD please give his family peace and strength to get through these t... Read more
Monday, June 22, 2009 8 comments I did ok with a 1.4 loss this past week, and I am ready for some more. Oh yes about the house work, yes it was WORK! moving furniture, lots of lifting, bending squatting, and even arm circles to get the walls clean. You know how it is to h... Read more
Sunday, June 21, 2009 6 comments I did only three days of exercise this week and that was Mon,Tue, and Wed. For the last three days I've been cleaning, re-organizing, and re-arranging my entire house and I'm still working on it. I for sure am not snacking aimlessly and my food ... Read more


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Transit system sponsoring safe ride home
POSTED: Monday, December 21, 2009 - 11:15am
UPDATED: Friday, April 13, 2012 - 8:53am
UPDATED: Friday, April 13, 2012 - 8:53am
WACO - The Waco Transit System is sponsoring a Safe Ride Home service December 31.
To use the service, the destination to and from must be within 5 miles of Waco.
The service will be free of charge.
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Tag Archives: aussiecon 4 article
On 'Kim Stanley Robinson – Guest of Honour Speech'
This article is based on Kim Stanley Robinson's Guest of Honour Speech at AussieCon 4 (audio recording here, courtesy of Gary Kemble). By the time of Kim Stanley Robinson (Stan)'s Guest of Honour Speech on the third day of the … Continue reading
On 'The Novella'
This article is based on a session at AussieCon 4. One of the panelists, dark fantasy thriller writer Alan Baxter, has his own coverage of this session on his website. Alan Baxter has provided a good introduction to this session, … Continue reading
On 'Thinking in Trilogies'
This article is based on a session at AussieCon 4. Why trilogies? It was suggested that trilogies are partially publisher driven because it's more commercially attractive to sell three novels rather than one. However, if this were the primary explanation … Continue reading
Posted in trilogies
Tagged auslit, aussiecon, aussiecon 4, aussiecon 4 article, australian authors, fantasy authors, fantasy trilogies, fiona mcintosh, glenda larke, novel writing, ozlit, russel kirkpatrick, the australian literature review, thinking in trilogies, trilogies, trudi canavan, worldcon, worldcon 2010, write a trilogy, writing a novel, writing a trilogy, writing fiction, writing trilogies
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On 'Girl Meets Boy Meets Dragon: Romance in fantasy'
This article is based on a session at AussieCon 4. The discussion was focused mainly on romance with a little on fantasy elements such as vampires and zombies. Early in the discussion one of the panelists offered a simple version … Continue reading
Mary Victoria – Author Interview
What was your highlight from AussieCon 4 and why? My highlight from the Con was meeting and speaking with fellow authors, and of course the hard-working members of my Voyager family. I'd never corresponded with my publishing editor, Stephanie Smith, … Continue reading
Posted in chronicles of the tree, mary victoria
Tagged aussiecon, aussiecon 4, aussiecon 4 article, australian fiction, australian literature, australian novel, author interview, chronicle of the tree series, chronicles of the tree, fantasy fiction, fantasy literature, fantasy novel, mary victoria, samiha's song, the australian literature review, tymon's flight, world tree, worldcon, ya fiction, ya literature, ya spec fic, young adult fiction, young adult literature
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On 'Keeping Pace: Maintaining momentum in fiction'
This article is based on a session at AussieCon 4. Pace, or story momentum, is something that can be tricky to explain or teach effectively as if you use particular techniques and a reader is familiar with those techniques the reader may … Continue reading


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"We have to dig beneath the surface and determine what the records mean. One team's 8-8 conference record might not be the same as another team's 8-8 record in the same conference. We need to clearly evaluate what each team has done."
Craig Littlepage
"It has a phenomenal record -- it's up to 49 consecutive years of dividend increases -- one of strongest records that we're aware of."
Joseph Lisanti
"He has one of the longest records, he's more a pure quant investor, ... He's got a phenomenal record."
Christine Benz
"We think it's going to be a huge impact record. It's one of the most important records of the fourth quarter, for all genres. It is the biggest release in the country format, but aside from that, it's one of the biggest records in the business."
Joe Galante
"We're going for the record. We've set a lot of records this year. We're going for that one, too."
Mike Holmgren
"Record alone doesn't tell it. Records mean something certainly in the evaluation process, but I looked far beyond just the won-lost record, for other reasons."
Marv Levy
"Iowa's record does not mean anything. You could have a horrible non-conference season and get that one win that will change the whole season around. We are concerned about playing them and after we are through with them, we will concentrate on Illinois."
Carrie Barker


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2012 Corporate Counsel Awards
- Jessica Saunders, Managing Editor
Welcome to Atlanta Business Chronicle's inaugural Corporate Counsel Awards section, created in partnership with the Association of Corporate Counsel Georgia chapter. These awards are intended to highlight the vitally important but often behind-the-scenes role of the corporate counsel. Attorneys who practice in the legal departments of corporations, associations and other private organizations play a unique role in helping their organizations succeed, from working with management on risk issues and significant transactions to managing litigation and employee-related matters.
Corporate Counsel Award Winners
Lifetime Achievement:
Outstanding General Counsel, Large:
- Winner: Loretta Cecil, McKesson Technology Solutions
- Finalist: Debra Kuper, AGCO Corp.
- Finalist: Steven W. Smith, IHG
Outstanding General Counsel, Small:
- Winner: Jim Reed, YKK Corporation of America
- Finalist: David Quillian, PrimeRevenue Inc.
- Finalist: Kristen McGuffey, Simmons Bedding Co.
Outstanding General Counsel, Solo:
Rising Star:
Diversity Champion:
- Winner: Charemon Grant, Blue Cross Blue Shield of Georgia, WellPoint
- Finalist: Dorian Denburg, AT&T Inc.
Community Champion:
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BCA Tours and Travel LLC wants to invite all North Austin Singles for a fun filled trip to Kickapoo Lucky Eagle Pass TX. We are a travel and event company that offers all types of trips throughout the US. We are giving your group a 10% discount on the next trip, July 5th 2013 from Austin, TX (Frys Electronics) location. For $36 (regularly $40) you are able to receive a round trip luxury charter bus ride with refreshments to Kickapoo! Upon arrival you will receive a $20 players credit and 6 hours of game play. First bus will be leaving at 0600 and arriving back in Austin at 2000 hrs. Second bus will be leaving at 1800 and arriving back 0800 Saturday morning. So who is ready to GAMMMBBLLLEEEE!!!! Please call[masked] or go to www.bcatours.com and click on payments to register. Payments and registration is needed by July 4th 2013 to make sure everyone is accounted for.
I started the group because there wasn't any other type of group like this. I've met some great folks in the group who have become close friends and have also met some amazing business owners.
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LiLo Plans to Sue Her Victim
We've all seen the tape, Lindsay Lohan kinda-sorta hit a guy with her Porsche last week while driving around NYC.
The victim, Jose Rodriguez, may have been released from the hospital with no real injuries, but his wallet is about to be in a whole world of hurt once Lindsay gets through with him. According to TMZ, the often incarcerated actress plans to sue Rodriguez for his comments that she was drunk when she hit him with her car.
Rodriguez claimed that Lindsay "smelled like alcohol real bad." Incorrect syntax but otherwise a wholly believable statement based on Lohan's past. Lohan and the cops that hung out with her after the accident disagree. It turns out that Lindsay is a terrible driver, but she wasn't drunk.
LiLo's had a hard time regaining the trust of the entertainment industry big-wigs and if they believe that she was drunk when she hit Jose she could lose out on future work…so she's going to sue the guy. Lohan told TMZ, "I'm tired of people lying just to score a quick paycheck."
The lesson to be learned here is to never be anywhere that Lindsay Lohan could feasibly show up and hit you with a very expensive vehicle.
–Kimberly Rae Miller, CBS Local
More Lindsay Lohan News On Fresh1027.com
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Chicken tenders get a flavor boost from fresh lemon and thyme. They are great as a main course or served on top of a big salad.
Posted: Feb. 12, 2015
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West Briton has all the Trades and Tradesmen in Cornwall listed, many with reviews and star ratings; select one of the local Tradesmen from the list below for, amongst others, good quality local electricians, roofers, locksmiths, double glazers, kitchen installers and bathroom installers in Cornwall - be sure to return to West Briton and leave a review.
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Cordray's OK, CFPB not so much, Ohio bank backer thinks
- Rick Rouan
- Staff reporter- Columbus Business First
- Email | Google+ | Twitter
Central Ohioan Richard Cordray might have a hard time winning confirmation as director of the Consumer Financial Protection Bureau, but he has at least one fan in an industry his agency is regulating.
Ohio Bankers League CEO Mike Van Buskirk told me he was "hopeful" that President Barack Obama would re-nominate Cordray, the CFPB's first director through a controversial recess appointment by the president. Cordray's term expires this year, and some think he's going to have a tough time holding his chair at the agency.
U.S. Senate Republicans already are scoffing at the idea, says a report in the American Banker trade publication, but Van Buskirk thinks the work Cordray has done as the agency's chief could swing some votes in his favor.
The league hasn't taken an official position on Cordray's appointment or performance, but Van Buskirk said the former Ohio attorney general is "well-qualified" for the job, citing his days in the state legislature and in state leadership roles. He also noted Cordray has been willing to listen to the industries he is regulating while drafting new rules to protect consumers.
But that doesn't mean he will sail through confirmation – or even that Van Buskirk doesn't have a problem with the CFPB.
"It's not about him. It's about the structure," he said. "Dodd-Frank in my judgment was all about the chairman of the two committees saying this wasn't our fault, but I think largely it was."
Van Buskirk pointed to the duration of the five-year appointment and a lack of congressional oversight as major problems with the agency. In some ways, the agency's reach doesn't go far enough, he said, noting the CFPB has no regulatory authority over insurers, securities firms and auto salespeople who close loans.
"I trust Rich Cordray, but that's not a very good basis for setting up government entities," he said.
Rick Rouan covers banking, capital markets, insurance, logistics, nonprofits, area airports and air travel for Business First.
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Gun Owners of Vermont's annual raffle is a Kimber USA Match 2.This is a .45 ACP. We're selling only 600 tickets, 5.00 each or 5 tickets for $20.00 Drawing is after all the tickets have sold or at our annual … Read More
Gun Control Supporters Concede
Gun Sense Vermont co-founder Ann Braden conceded Tuesday that her group is unlikely to achieve its goal this year of requiring near-universal background checks for gun buyers. But she expressed hope that two other provisions in a controversial gun control … Read More
GOVt Testimony for February 20, 2015 Senate Hearing
Today, The Gun Owners of Vermont submitted testimony to the Senate Committee on Health and Welfare for their Friday, February 20, 2015 meeting.
This testimony concentrates on the mental health portion of S.31.
Phone Calls Please!
Burlington Charter Changes, Thursday, 9am. Please call your Representatives.
The hearings on H.90, H.91 and H.92 on Thursday are just a walk through of the bills. No testimony.
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Written on: 17/10/2013 by Gunnergray52 (1 review written)
Excellent service, the staff even called me back to see of I was happy with the description of the garment I purchased,
And my purchase was delivered to my door as promised to within 10 minutes, there is nothing I found to be in happy about.
Written on: 29/10/2013
Hi Gunnergray52,
Thanks for taking the time to leave your feedback. We're delighted to read that you found the service you received excellent - that is exactly the level that our staff look at achieve at all times. We hope you are happy with your new garment and please don't hesitate to get in contact with us if there is anything else that we can assist with.
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All in an hour's work
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A labour of love
My fourth baby was nine days overdue when he decided to come into the world.
I was expecting things to be fairly speedy, the last three were born within two hours of established labour, but I'd always had a number of hours of niggly contractions beforehand, perfect for doing things like getting children to bed and birthing pools set up. I expected this one to be no different.
Around 8pm on February 8 I finally felt the first contraction. It was surprisingly strong and lasted about minute. Ten minutes later I felt another one, again, quite strong for the beginning of things and lasting another minute.
Some time after that they started, every three minutes, one minute long and very strong. I called my sister to give her a heads up, I called my friend who was going to photograph the birth and finally my midwife. Hubby busied himself sorting the birthing pool interspersed with settling our almost-two-year-old who was still awake.
I found myself going back and forward to the toilet, having contractions surging through me. I felt myself starting to get agitated and out of control a bit, they were coming so quickly I could hardly get into any form of rhythm at all, even just breathing was difficult.
By 9pm the contractions were two minutes apart. My waters broke in the toilet and then my sister arrived. The contractions were surging through, feeling stronger and stronger and she was encouraging me to breathe as they came. I remember telling her I couldn't and she was reassuring me that I could, that I was climbing a mountain, I just had to get to the top, a little mantra that had helped her during her last birth.
It was at that point I dropped to my knees, forget breathing, I was starting to push. My sister called hubby in and they manhandled me to some towels that my hubby had put down in the lounge (still not sure when he did that). They pulled my trackies off and then my baby's head emerged. I remember the excitement in their voices as they encouraged me and another contraction birthed the shoulders and then the rest of his body.
They passed him to me and I held him, feeling so much relief and joy that he was finally here. I looked up at my husband and said "I'm done". I took my top off and we nestled together, snuggled in a blanket with a home knitted beanie on Isaac's head to keep him warm. Isaac cried a bit and snuffled around, stretching and grimacing, showing the promise of dimples. My photographer friend came in a couple of minutes later and about 5 minutes after her, my midwife arrived.
The euphoria stayed as we talked and laughed and waited for the placenta to do its thing. Isaac was breastfeeding and we were still somewhat disbelieving that he has come so quickly with so little warning. Eventually I birthed the placenta, hubby cut the cord and Isaac was truly his own person.
Unfortunately, due to the speed of his arrival, I'd had a bit of damage done to me, so our lovely intimate time together couldn't last. We got ourselves all dressed and we went to hospital for some repair work and an overnight stay.
The name Isaac means laughter, he is a little boy who has brought us so much happiness and he has completed our family. We are done.
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CHARLOTTE, N.C. — Cam Newton says he was surprised the Panthers released veteran wide receiver Steve Smith this offseason.
Newton says "if you were in the 704 (area code), you were caught by surprise. Everybody in the Carolinas was surprised, including myself."
Newton spoke Tuesday at team headquarters during a break from offseason condition workouts, which began Monday.
Along with Smith, the Panthers also lost Brandon LaFell, Ted Gin Jr. and Domenik Hixon via free agency, meaning Newton will be without his top four receivers from last season.
Newton isn't concerned about developing chemistry with his new group of receivers, even though he'll be out until at least June following ankle surgery.
Newton says the changes mean he needs to "take more ownership of the offense."
AP NFL website: www.pro32.ap.org and http://twitter.com/AP_NFL
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Brooklyn bakery that will deliver a bday cake?
- MaineRed Nov 14, 2006 06:17 PM
- 4
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Not being from the area, can anyone recommend a bakery near (1-3 blocks) the Brooklyn Brewery (79 N 11th St) or one that will deliver a cake to the brewery on a Saturday? :)
Thank you!
There is really nothing at all right in the area.
But, you could get a very nice cake from Fortunato's at 289 Manhattan Ave in williamsburg (718 387 2281)
or Settepani Bakery. http://www.settepani.com/
Both my perhaps deliver....they are nearby but not within spitting distance.
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A Mankato man accused of assaulting 2 people with a knife over the weekend made his first appearance in court on Monday. Bail was set at $40,000 with conditions or $150,000 without for 43-year-old Ralph Griffin. He's facing one count of terroristic threats and two counts of felony assault related to the stabbing late Friday night. Officers were dispatched to a residence on East Thompson Street in Mankato at around 11:30pm and found a 26-year-old man with two knife wounds and an 18-year-old woman with minor injuries. The man was hospitalized, while the woman was treated at the scene. Authorities were forced to use a tazer when they located Griffin because he allegedly resisted arrest. He's now scheduled to be back in court on December 13th.
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