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Regrets? Phil Kessel has a few. But, like Frank Sinatra said, too few to mention.
"I don't know what else I'm supposed to do in a situation like that," the Toronto Maple Leafs winger said Wednesday, about drawing a suspension for flaying Buffalo Sabres enforcer John Scott with his stick. "Obviously, I didn't handle it the best way, but I don't know what else you can really do."
What Kessel did was give Scott a couple of whacks on the legs with his stick when the 6-foot-8, 270-pounder came after him in the third period of a preseason game last Sunday. This set off a brawl that involved every player on the ice. When Kessel was out of danger, he spun around and gave Scott another whack.
That last move prompted NHL vice-president Brendan Shanahan to suspend Kessel for the Leafs' final three preseason games (which started with Tuesday's 3-2 loss to the Ottawa Senators at the Air Canada Centre).
Kessel allowed he did regret landing the last couple of blows but challenged the critics who second-guessed his stickwork.
"Put 'em in that situation and see what they do," he said. "I think a lot of people that can criticize that. Let's see what they could do out there versus a guy like that. I think they'd all be in a lot of trouble.
"Things happen so quick out there. You can slow it down and it makes it look like it's worse, but I shouldn't have done the second whack. It happens, but things happen so quick out there that you react. Obviously, I shouldn't have done [it]."
Kessel said he wasn't happy about being suspended, but since it's well-known NHL veterans do not regard most exhibition games with affection, he didn't push the matter.
"Well, obviously, I got three preseason games, and I'm happy there's no regular-season games," he said.
Kessel got off easy compared to teammate David Clarkson. The latter received an automatic 10-game suspension in the regular season for coming off the players' bench to join the fight. He also forfeits about $269,000 (U.S.) in salary.
Since Kessel is suspended for only the preseason, it won't cost him any money and the Leafs will still have their best goal-scorer available to start the season.
"[Clarkson] was sticking up for me, and I appreciate that," Kessel said. "It's a tough situation. I don't know if you guys have seen anything like that happen before, but it's tough. Losing a guy like Clarky for 10 games, he's a great player for us and everyone's going to have to step up and contribute."
Leafs head coach Randy Carlyle said, with a nasty grin, he will make sure Kessel practises hard so he stays in shape for the opening of the regular season on Oct. 1.
"When he says that, it's probably going to be hard," Kessel said. "I'm not necessarily looking forward to his bag skates."
This has been quite a training camp for Kessel. In a preseason game on Sept. 16 against the Philadelphia Flyers, he was tagged with a few stick penalties, including one for slashing his friend and former teammate Luke Schenn, who set him off with a punch in the mouth.
"It's tough because guys are fighting – obviously, I know Luke, right?" Kessel said. "He gave me a shot. We talked after the game. Guys are trying to make a name for themselves, they're trying to get noticed.
"When you feel like you're just trying to get in to the game and stuff like that happens, you're not that happy about it. But it happened and you've got to move on."
Kessel, who has not posted more than 28 minutes in penalties in any of his seven NHL seasons, does not think this spate of stick infractions will make him a marked man for the referees.
"I think I average like under 20 penalty minutes a year or something like that or around there, so it's not like I take a lot of penalties," he said. "I don't think it's going to be a problem."
What could be a problem some time between now and next summer is a new contract. His current deal expires July 1 and as a consistent 30-goal scorer, Kessel will likely demand at least $7-million a year on a long-term contract.
"I'm not really worried about it," he said, as negotiations have not started. "Nothing's happening and we move on, right?"
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Jay-Z, Lil Wayne & Drake Turn Swag On, MJ Honored At BET Awards
Jay-Z and Lil Wayne highlighted a memorable evening of performances at last night's (June 28) BET Awards at the Shrine Auditorium in Los Angeles, a night which also payed tribute to the late King of Pop, Michael Jackson.
Weezy, who took home the statue for Best Male Hip-Hop Artist, closed the show alongside his Young Money crew with "Every Girl." YM affiliate Drake kicked off the medley with his breakthrough single "Best I Ever Had," resigning himself to a stool due to a torn ACL which prevented a more mobile performance.
Hov hit the stage earlier in the evening for the lead single from his eagerly-awaited Blueprint 3, "D.O.A. [Death of Auto-Tune]." The song's video world premiered during the awards' After Party show. Beyoncé was just one of many R&B performers on the night, most of whom Michael Jackson, including host Jamie Foxx— who wore an assortment of signature MJ outfits— New Edition, Ne-Yo, and Ciara. Towards the end of the evening, a shaken Janet Jackson, who was in attendance with her father Joseph, took the stage to represent her family and address her brother's passing.
Another notable moment included Soulja Boy's performance of his hit "Turn My Swag On." SB walked off into the audience to give Kanye West a pound during the crowd favorite.
Along with Weezy, other rappers who went home with awards included M.I.A. for Best Female Hip-Hop Artist and T.I. for Viewers' Choice for his #1 hit, "Live Your Life" featuring Rihanna.- Devin Chanda


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Clinical and Developmental Immunology
Volume 2010 (2010), Article ID 814397, 8 pages
NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines
1Vaccine Department, Center of Molecular Immunology, Havana 11600, Cuba
2Laboratory of Molecular Oncology, Quilmes National University, Roque Saenz Peña 352, Bernal B1876BXD Buenos Aires, Argentina
3Elea Laboratories, C1417AZE Buenos Aires, Argentina
4Chemo-Romikin, C1061ABC Buenos Aires, Argentina
5Division of Immunogenetics, José de San Martín Clinics Hospital, University of Buenos Aires, C1120AAF Buenos Aires, Argentina
Received 12 July 2010; Accepted 24 September 2010
Academic Editor: Taro Kawai
Copyright © 2010 Luis E. Fernandez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included.
1. Ganglioside-Based Cancer Vaccines
The field of cancer vaccines definitively changed after April 2010 when the US Food and Drug Administration (FDA) approved Provenge (sipuleucel-T), a vaccine for advanced prostate cancer patients [1]. For the first time sipuleucel-T convincingly increased overall survival by about four months in a randomized Phase III trial conducted in 512 patients. While this immunotherapeutic agent is relatively inconvenient as a personalized vaccine, it seems that selecting the recombinant version of the prostatic acid phosphatase (PAP)—expressed in 95% of prostatic tumor cells—as antigen was critical [2], reaffirming target selection as a key feature in cancer vaccine design.
Reasoning in the same way, gangliosides, a broad family of structurally related glycolipids, were firstly suggested as potential targets for cancer immunotherapy [3, 4] based on their higher abundance in tumors when compared with the matched normal tissues. Disappointingly, at the beginning of the present century the failure of the best developed ganglioside-based cancer vaccine for that time, GMK [5], irradiated an unfavorable risky perception to all the projects in the field, even those not related with the target antigen, the GM2 ganglioside.
Nevertheless, in these days ganglioside cancer vaccinologists were facing a kind of "polarization" of positions in view of new facts. Eggermont et al. reported an earlier stop of the Phase III GMK vaccine clinical trial in stage II melanoma patients because the Independent Data Monitoring Committee detected an inferior survival rate for the vaccine arm [6]. While difficult to interpret with respect to potential detrimental effects, this result was considered as a significant setback for ganglioside-based specific immunotherapy in melanoma. In the opposite side, a more optimistic outlook of gangliosides as targets for active immunotherapy of cancer came from the recent work by Cheever et al., who reported in 2009 the National Cancer Institute pilot project for prioritization of cancer antigens [7]. From the selected 75 representative antigens, 4 were gangliosides (GD2, GD3, fucosyl-GM1, and N-acetyl-GM3), ranking between positions 12 and 48.
As an overall, at the present moment only two N-glycolyl (NGc) ganglioside-based vaccines, the focus of this paper, are currently tested in Phase III clinical trials [8]. These include racotumomab (formerly known as 1E10) and NGcGM3/VSSP vaccine (Table 1). Racotumomab is an anti-idiotype murine monoclonal antibody (mAb) to NGc-containing gangliosides. An anti-idiotype mAb, such as racotumomab, is the mirror image of the original antibody formed against specific surface antigens. Thus, anti-idiotype antibodies can act as antigens, inducing a response against the original antigen. On the other hand, the NGcGM3/VSSP vaccine results from the conjugation of the ganglioside into very small size proteoliposomes (VSSP) derived from N. meningitidis.
2. NGc Gangliosides in Tumor Biology
The most common sialic acids in mammals are N-acetylneuraminic acid and N-glycolylneuraminic acid, usually found as terminal constituents of different membrane glycoconjugates such as the GM3 ganglioside. The only structural difference between them consists of a single oxygen atom at the C-5 position of N-glycolylneuraminic acid, catalyzed by the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) [9]. In contrast to most mammals, including our closest relatives: the great apes, NGc is practically undetectable in healthy human tissues and fluids [10], since human cells lack the presence of CMAH [11]. It is known that this absence is due to the loss of a 92-bp segment in the exon 6, which results in a frameshift mutation of the human gene by an Alu-mediated inactivation [12, 13] dated 2.5–3 million years ago, prior to brain expansion during human evolution [14, 15].
It is noteworthy that the monosialic acid ganglioside NGcGM3 is highly expressed in several human cancer cells [16]. Although initially it was suggested that NGc could be expressed in human tissues by an alternative metabolic pathway [17], nowadays plenty of evidence suggests that the presence of this sialic acid in human cancer is the result of the metabolic incorporation of dietary NGc [18, 19], as illustrated in Figure 1. We reported that cultured mouse tumor cells lacking CMAH expression are able to process and incorporate NGc from different sources such as bovine serum, NGc-rich mucins, or purified N-glycolylneuraminic acid, thus, promoting the metastatic phenotype [20]. Moreover, genetically modified mice expressing a human-like CMAH mutation showed no endogenous NGc, as in humans [21].
The significance of NGc overexpression in human cancer is still under investigation. Taking into consideration that an anti-NGc antibody response was detected in several cancer patients, Varki [22] recently hypothesized that antibody-mediated inflammation could facilitate tumor progression. However, it is accepted that high titers of these antibodies can kill tumor cells [22]. In addition, experimental results obtained by de León et al. indicated that growth-stimulating features of the NGc on tumor cells can be explained by immune system down modulation [23].
3. Preclinical Data
Our team analyzed the antitumor activity and the preclinical toxicity of the mAb racotumomab and the NGcGM3/VSSP vaccine using different animal models. Considering that the most important feature of an anti-idiotype mAb (Ab2) is its biological effect, racotumomab was evaluated in two syngeneic murine tumor models, the F3II mammary carcinoma (BALB/c mice) and B16 melanoma (C57BL/6 mice). Both cell lines are positive for the idiotype mAb P3 (Ab1), which specifically reacts with NGc-containing gangliosides on cell surface [24, 25]. In BALB/c mice, vaccination with several intraperitoneal doses, at 14-day intervals of racotumomab coupled to keyhole limpet hemocyanin in Freund's adjuvant, significantly reduced subcutaneous tumor growth of F3II mammary carcinoma cells and the formation of spontaneous lung metastases [24]. Similarly, intravenous administration of uncoupled racotumomab, as a biological response modifier, dramatically inhibited metastatic lung colonization by B16 melanoma cells in C57BL/6 mice [24].
Vaccination with aluminum hydroxide-precipitated racotumomab induced antimetastatic effects in the 3LL-D122 Lewis lung carcinoma, a poorly immunogenic and highly metastatic model in C57BL/6 mice [37]. The effect was associated to T cell infiltration, enhancement of tumor apoptosis, and reduction of new blood vessels formation in lung nodules. The 3LL-D122 lung carcinoma is an antigen-positive, validated model for the NGcGM3 ganglioside. The model evidenced an increased expression of such specific antigen from primary tumors to metastatic lesions [38]. Immunization with the NGcGM3/VSSP vaccine, prepared either with synthetic or natural source-derived ganglioside, showed similar immunogenicity profiles and antitumor effects in the 3LL-D122 model [38].
Racotumomab also demonstrated a potent antitumor effect in combination with chemotherapy in preclinical studies, providing a rationale for chemo-immunotherapy combinations in solid cancers. Administration of low-dose cyclophosphamide together with subcutaneous immunization with racotumomab in alum significantly reduced F3II tumor growth [25]. The antitumor response was comparable to that obtained with standard high-dose chemotherapy in such breast cancer model, but without overt signs of toxicity. Interestingly, combinatory chemo-immunotherapy promoted CD8+ lymphocyte tumor infiltration and increased tumor apoptosis [25].
Ganglioside immunotherapies with racotumomab and NGcGM3/VSSP vaccine were well tolerated in animals [24, 38]. In preclinical toxicology studies, the immunization protocol did not affect body weight gain, food and water consumption or induce other signs of overt toxicity in murine models. Subacute toxicity after continuous daily treatment was expressed by an excessive activation of extramedullary myelopoiesis in the spleen and liver in all mice and a strong inflammatory reaction in the lungs, showing dense neutrophil infiltrates in the interalveolar septa [24].
4. Expression of NGc in Human Tumors
Tumor-specific expression of NGc-containing gangliosides in some human tumors suggests that the induction of an effective immune response against these antigens may be useful for patients with antigen-positive tumors. The ganglioside NGcGM3 has been described in human neoplasms, including breast carcinoma [33, 34] and melanoma [31], but is usually not detected in normal human cells. This fact defines NGcGM3 as an interesting target for immunotherapy.
As described by Tangvoranuntakul et al. [34] using a monospecific antibody against NGc, staining showed cell type-specific reactivity in adult human tissues. The overall pattern of expression was summarized as prominent in secretory epithelia and associated secretions and present in many blood vessels. In addition, in fetal tissues NGc can be detected in epithelial cells or secretions as well as the placental villus blood vessels [34].
van Cruijsen et al. [35] assessed the possible association of NGcGM3 expression with angiogenesis in lung cancer. They examined 176 samples of nonsmall cell lung cancer (NSCLC) by immunohistochemistry in tissue microarray and found that NGcGM3 is widely expressed in more than 90% of the cases. Microvessel density, as determined by CD34 staining, was lower in NSCLC tissues with high NGcGM3 expression, suggesting that the presence of the ganglioside may favor an antiangiogenic response. Moreover, based on the expression of CD83 which is a marker of mature dendritic cells, NGcGM3 appeared to be involved in tumor-induced dendritic cell suppression [35].
More recently, Scursoni et al. [36] reported for the first time the expression of NGcGM3 in a pediatric solid tumor. They detected the ganglioside in 88% of the cases of Wilms' tumor (nephroblastoma), using the specific anti-NGcGM3 mAb 14F7 and a peroxidase-labeled polymer conjugated to secondary antibodies on postchemotherapy samples. Wilms tumor is considered an ''embryonic tumor'' of the kidney, being a mimicry of various elements in normal or abnormal nephrogenesis and presenting a diverse spectrum of histologic appearance. In this regard, Wilms tumor gives the unique opportunity to learn about the expression of NGc gangliosides in diverse transformed cell lineages, comprising epithelial, stromal, and blastemal elements [39]. The strongest expression was found in the epithelial component of Wilms' tumor, and the lower percentage of positive tumor cells was observed in the stromal subtype [36]. Similar results were obtained in a preliminary study with P3, a less-specific mAb that recognizes different NGc-containing gangliosides and sulfatides, including NGcGM3 [40]. More than 70% of Wilms tumors showed a positive staining for NeuGc residues using the P3 antibody [36].
5. Immunological Response to NGc in Humans
Targeting ganglioside antigens has been a matter of concern due to the possibility of inducing autoimmune responses. Indeed, in most neuropathies of immunological origin, endogenous gangliosides have been shown to be the target of the autoimmune reactions [41–44]. Antiganglioside antibodies may also affect nonneural tissues, as occuring in systemic lupus erythematosus [45], rheumatoid arthritis, or Sjogren's syndrome [41]. Antibodies reactive to NGc-containing glycolipids have been found to be induced in patients after repeated transfusions with sera from other species [46], in rheumatoid arthritis [47], and also in melanoma patients [32]. Melanoma cells express NGc-containing gangliosides, including NGcGM3 [31], and natural anti-NGc antibodies are increased in melanoma patients. Most interestingly, a significantly higher level of anti-NGc antibodies was demonstrated in those patients who were free of disease more than 5 years after surgery than in those who relapsed within 2 years [32].
In spite of what could be expected, no induction of detrimental autoimmune reactions have been described over decades of clinical development of cancer vaccines targeting endogenous gangliosides such as GM2, GD2, and GD3. In this respect, the heterophilic nature of NGcGM3 is considered an additional asset of this tumor antigen, since, as reviewed in the following sections, the absence of significant expression in normal tissue allows for increased immune responses to immunization while precluding self-targeted reactions.
Breast cancer patients were treated with a regime of 5 biweekly IM injections of NGcGM3/VSSP vaccine followed by monthly boosters. Anti-NGcGM3 IgM and IgG responses were detected in all patients who completed the first 5 injections, collectively termed as "induction phase". The time course of antibody production showed an overall increase across the 32-week followup, and the maximal recorded titers reached 164,000 for both IgM and IgG. The functional relevance of the induced antibodies was underscored by their capacity to react against an NeuGcGM3+ murine tumor cell line and mediated complement-dependent cytotoxicity. Further confirming their specificity for the targeted ganglioside, the induced antibodies reacted as well with human mammary ductal carcinoma cells without staining of surrounding normal tissue [26].
In a second clinical trial, 21 advanced melanoma patients received the same vaccination schedule [30]. Two dose levels were examined: 0.2 and 0.4 mg of ganglioside per dose. The immunogenicity of NGcGM3/VSSP was confirmed, with all evaluable patients eliciting IgM and IgG responses after treatment. Antibody class switching to IgA was detected as well. Delayed-type hypersensitivity (DTH) responses were also evaluated with ID injections of NGcGM3/VSSP. DTH responses were observed in 46% of patients at the 0.2 mg dose level and in 78% of patients at the 0.4 mg dose level. The ganglioside contribution to the specificity of the hypersensitivity reactions was, however, not assessed. No clear relationship could be established between immunological response and the clinical outcome, and the lower dose level was selected for future clinical development due to its safer toxicity profile [30].
The immune response elicited by the murine anti-idiotypic mAb racotumomab was monitored in greater detail and in additional clinical settings. The vaccination regime for racotumomab administration consisted of a 6-dose induction phase followed by monthly boosters. Anti-ganglioside responses were induced in 16/17 melanoma patients [48], 16/16 breast cancer patients, and 16/20 NSCLC patients [27]. The specificity of the induced Ab3 antibodies was assessed by adsorption and analysis of the reactivity of the nonadsorbed fraction. Adsorption with an isotype-matched monoclonal antibody (IgG1) abrogated a small fraction of the racotumomab-directed reactivity, which is an indication of the immunodominance of the racotumomab idiotype over the rest of the IgG1 molecule [27]. Most interestingly, adsorption of Ab3 antibodies with racotumomab preserved 50 to 90% of the reactivity for NGcGM3 in the non-adsorbed fraction, suggesting that the idiotype (Id)+/antigen (Ag)+ and Id-/Ag+ specificities are present on separate antibody molecules [48]. Such Id-/Ag+ antibodies could reflect the activation of an autologous idiotypic cascade in the patient's immune system [27]. The antibodies induced by racotumomab are NGc specific. No cross-reaction was observed to NAcGM3 [48]. The time course of NGcGM3-specific antibodies over 50 weeks in breast cancer patients under racotumomab treatment showed sustained antibody titers. Some patients had detectable ganglioside-specific IgG only by week 30, suggesting that the extended vaccination regime not only is undetrimental to the immune response, but is favorable for late responders as well [29].
As described for NGcGM3/VSSP vaccine, the antibodies induced by racotumomab treatment reacted with an NGcGM3+ murine tumor cell line. In addition, racotumomab-induced antibodies were able to react with NGcGM3+ lung carcinoma tissue sections [49]. No significant differences were found in the antibody response across the dose levels examined (0.5, 1, and 2 mg). Maximal titers reached about 10,000 in the three dose levels for both IgM and IgG, with no significant differences in the titer means between dose levels [29]. The 1 mg dose level was chosen for further clinical investigation [50].
NGcGM3-specific cellular responses were assessed in racotumomab-treated breast cancer patients. Cryopreserved peripheral blood mononuclear cells were challenged in vitro with ganglioside-loaded, CD1d+, autologous monocyte-derived dendritic cells, and the response was measured with an interferon- immunospot assay. A low frequency of ganglioside-specific interferon--secreting cells was detected in 5/13 patients. These cytokine responses were undetectable at baseline and became detectable by weeks 14 to 42, thereby confirming the convenience of an extended vaccination schedule to elicit a ganglioside-specific response [29].
6. Toxicity and Preliminary Clinical Outcomes
The main toxicities observed in stage III/IV breast cancer patients receiving the NGcGM3/VSSP vaccine (200 g per dose) were erythema and induration at the injection site, occasionally associated with mild pain and fever. In spite of the fact that this trial was not adequate for efficacy assessments, a remarkable progression-free survival time was observed in 2 patients with lung metastases [26]. Similarly, in another trial in advanced cutaneous and ocular malignant melanomas, 7 patients treated with the NGcGM3/VSSP vaccine remained alive for more than 2 years after inclusion in the study [30].
In stage III/IV melanoma patients administered with biweekly doses of the anti-idiotype mAb racotumomab (2 mg per dose), the tolerance was satisfactory and no unexpected or serious adverse events were reported. The more frequent adverse event was the local reaction with induration and erythema at the injection site [48]. In a clinical trial in patients with stage III/IV breast cancer, doses of 1 or 2 mg of racotumomab were well tolerated. There were no differences between the two levels of doses tested in toxicity [50]. In another Phase I trial, the toxicity profile of racotumomab was investigated using an extended vaccination protocol of 6 biweekly intradermal injections (induction phase), followed by 10 monthly boosters (maintenance). Nineteen patients with high-risk (stage III) or metastatic breast cancer were vaccinated with different dose levels of 0.5, 1, and 2 mg. Vaccination was relatively well tolerated; local skin reactions grades I and II represented the most common adverse event followed by mild flu-like symptoms lasting for 1 to 2 days. Similar safety results were observed with the 3 tested dose levels [29].
In a compassionate-use basis study, 34 stage IIIb and 37 stage IV NSCLC patients were vaccinated with racotumomab, after receiving standard chemotherapy and radiotherapy [28]. Patients were administered with 5 biweekly injections of 1 mg of racotumomab, other 10 doses at 28-day intervals, and later the patients who maintained a good performance status continued to be immunized at this same time interval. No evidence of unexpected or serious adverse effects was reported. The median survival time of patients, who entered the study with partial response or disease stabilization and with a performance status (PS) 1 after the first line of chemo/radiotherapy, was 11.50 months since the start of vaccination. In contrast, the median survival time calculated for patients who started vaccination with progressive disease and/or a PS2 was 6.50 months [28]. A statistically significant correlation was observed between anti-ganglioside response and survival time in a subset of 20 NSCLC patients from this study. Nonresponder patients () had a median survival time of 6.35 months (95% CI, 4.97–9.67 months), whereas patients who developed IgG and/or IgM antibodies against NGcGM3 had a median survival time of 14.26 months (95% CI, 5.95–17.3 months; , log rank) [27].
Even though NGcGM3 is a glycolipid, its heterophilic expression allowed a specific immune response when patients were immunized with either a conjugate vaccine (i.e., NGcGM3/VSSP) or an anti-idiotype mAb targeting NGc gangliosides (i.e., racotumomab). Evidence of an NGc-specific cytokine response was observed in some few patients, and its correlation with clinical outcomes remains to be established. The absence of cross-reaction with endogenous gangliosides is inline with the absence of autoimmune toxicity and overall safety profile of both conjugated vaccine and the racotumomab mAb. On the other hand, high titer ganglioside-specific antibody responses were observed in most of the patients, in correlation with survival in a group of NSCLC patients accrued after completion of first-line chemotherapy [27], as described above. The possible involvement of the induced antibodies in a protective antitumor activity is actively being pursued. Recent sequencing and modelling studies suggest that racotumomab might selectively induce Ab3 antibodies with conserved germline sequences specific for heterophilic saccharide antigens [51]. Randomized controlled trials are presently underway and are expected to provide further insight into the role of the induced immune response on the clinical outcome.
In summary, the above-mentioned studies indicate that both vaccines targeted to NGc gangliosides have acceptable safety outcomes and are able to induce specific humoral and cellular immune responses. The response to vaccination seems to be stronger in those patients with lower tumor burden, better performance status, and a good response to previous oncospecific treatment. Also, preliminary evidence suggested that these vaccines may have a positive influence on survival in patients with immune response to NGcGM3 antigen. The current Phase III trials that are being conducted at present will give a definitive answer to the potential clinical benefits offered by these therapeutic vaccines. Furthermore, studies will be required to determine the more efficient combination with chemotherapy or other immune interventions to prevail over the tumor-induced immunosuppression.
7. Perspectives
This paper deals with NGc gangliosides—and particularly NGcGM3—as a target for cancer immunotherapy. With the numerous antigens that can be used in immunotherapy, the decision-making process for researchers, hospitals, and companies, in whether or not to invest resources in a specific antigen, has been always a very complicated matter. Fortunately, in a recent work by the National Cancer Institute Translational Research Working Group, Cheever et al. developed a method for prioritization of cancer antigens paving the way to take more rational, informed decisions [7]. Such work aimed to develop a priority-ranked list of cancer vaccine target antigens based on predefined and preweighted objective criteria. An additional aim was testing a new approach for prioritizing translational research opportunities based on an analytic hierarchy process (AHP), a structured technique, and a mathematical model for dealing with complex decisions. Antigen prioritization involved developing a list of "ideal" cancer antigen criteria/characteristics, assigning relative weights to those criteria using pairwise comparisons. The result of the criteria weighting, in descending order, was as follows: (a) therapeutic function, (b) immunogenicity, (c) role of the antigen in oncogenicity, (d) specificity, (e) expression level and percent of antigen-positive cells, (f) stem cell expression, (g) number of patients with antigen-positive cancers, (h) number of antigen epitopes, and (i) cellular location of antigen expression.
Having that work as a reference, we rethought of our experimentation with NGc, and, although is neither on the scope of this paper nor our prerogative to position the antigen in the ranking, we can affirm that NGc somehow matches all of the criteria considered (Table 2), at least in some proportion—as described throughout this paper—whose relative weight should be evaluated by panels of external experts.
Some authors have recently enunciated the introduction of potential biases in the National Cancer Institute Pilot Project [52]. Lang et al. affirmed that the methodology used (AHP) is not well described and is subject to several sources of possible bias, such as participant selection, number of antigens chosen for prioritization, errors in rank order, redundancy, and internal validity. First of all, we differ with Lang et al. in the fact that AHP is not well described, due to being a very well-known technique properly used in a wide variety of settings, including cancer clinical decisions [53, 54]. Cheever et al. clearly described the method by citing the popular work of Bhushan [55] and how AHP is used in a web-based tool [56]. AHP is a powerful tool, used widely in science, and, although it has had some detractors over the years, Forman and Gass. carried out an in-depth paper discussing and rebutting the academic criticisms of AHP [57].
Furthermore, at the time of Cheever's paper publication no cancer vaccine had yet been approved by FDA. However, recent approval of sipuleucel-T for men with advanced prostate cancer, targeting PAP antigen, gave us a valuable lesson on this matter [58]. Interestingly, PAP ranked 26 out of 75 antigens in the ranking of cancer antigen pilot prioritization [7], confirming its capacity to somehow "forecast" those antigens more likely to be translated to patients. Although the ranking is dynamic, given that priorities change as knowledge accrues from new studies, we must reinforce the idea that the associated lists of weighted criteria inform investigators as to what experimental evidence is required to advance antigens to higher priority levels. In this line, those criteria helped us to evaluate that NGcGM3 ganglioside comprised most if not all relevant characteristics as a cancer antigen for vaccine development.
This work was partially supported by the National Agency of Scientific and Technological Promotion (Argentina). The support of Recombio (Spain) is also acknowledged. M. R. Gabri, L. Fainboim, D. E. Gomez and D. F. Alonso are members of the National Research Council (CONICET, Argentina). D. E. Gomez and D. F. Alonso contributed equally to this work.
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Selected for triathlon work
Dr. Stephen Flikke from St. Croix Spinal & Sports Rehabilitation in Hudson has been selected to be one of the primary care physicians for the Olympic length Triathlon in the Wisconsin Dells on Sunday, Aug 12. The event is sponsored by Rev3tri which is a nationally known Triathlon series with both pro and amateur racers. First place is $25,000 and event attracts athletes from around the world. Flikke is also a primary treating physician at Iron Man Triathlons, another major event throughout the states. He treats the athletes prior to the events and then during and after the race. The business is located at 2424 Monetary Blvd. For more information, go to www.stcroixspinalcare.com or call (715) 386-4075.


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9201 Dametopp by Dale Design
Welcome! You are browsing as a guestWould you like to see projects made from this pattern and much more? create a free account What am I missing?
9201 Dametopp
A simple lace tank top knit in the round with a crocheted edge at the armholes and neckline.
Sizes: Five sizes are offered with a finished chest width of 48, 50, 52, 54, 56 centimeters. a schematic provides other useful measurements.
Information is from the Norwegian language edition of the pattern.


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A chameleon with identity crisis is appointed as a sheriff, coming to rescue without proper plan and skills.
Paramount Pictures has released a new trailer for their forthcoming animation "Rango" via Yahoo! Movies. Straighter to the point than the previously released full trailer, this video follows a chameleon named Rango which is honored as a sheriff after accidentally killing a giant eagle which apparently threatened the villagers.
Hailed a hero, Rango which initially went on an adventure to discover its true self is now expected to come to rescue whenever a critical situation emerges. Without real skills of an official, Rango's plan to escape the danger is often surprising yet funny to watch.
Johnny Depp provides the voice of Rango, joined by the likes of Isla Fisher, Abigail Breslin and Bill Nighy as other voice cast. Gore Verbinski serves behind the lens for the comedy, which is scheduled to open wide in the U.S. on March 4, 2011.


text: Hello:I'm relatively new to Cassandra, but I've been searching around, and it looks like Cassandra 0.8.x has improved support for bulk importing of data. I keep finding references to the json2sstable command, and I've read about that on the Datastax and Apache documentation pages.There's a lot of detail here if you want it, otherwise please skip to the end. json2sstable seems to run successfully, but I cannot see the data in the new CF using the CLI.My goal is extract data from various sources, munge it together in some manner, and then bulk load it into Cassandra. That is as opposed to using Hector to programmatically insert the data. I'd like to deploy these files to the cloud (Puppet) and then instruct Cassndra to bulk load them, and then inform the application that new data exists. This is for a period content update of certain column families of curated, read-only, data that occurs on a monthly basis. I'm thinking of using JMX to signal the application to switch to a new set of CFs and keep running w/o downtime. At a later time, I'll delete the old CFs.I'm using Cassandra 0.8.2 and I'm just playing with this concept. I create a test CF using the CLI[default@Ingenuity] use Test;Authenticated to keyspace: Test[default@Test] create column family TestCF with comparator = UTF8Type and column_metadata = [{column_name: nodeId, validation_class: UTF8Type}];28991070-b9f9-11e0-0000-242d50cf1fb5Waiting for schema agreement...... schemas agree across the cluster[default@Test] update column family TestCF with key_validation_class=UTF8Type;2af88440-b9f9-11e0-0000-242d50cf1fb5Waiting for schema agreement...... schemas agree across the cluster[default@Test] set TestCF['SID|123']['nodeId'] = 'ING:001';Value inserted.[default@Test] set TestCF['EG|3030']['nodeId'] = 'ING:002';Value inserted.[default@Test] set TestCF['EG|3031']['nodeId'] = 'ING:003';Value inserted.[default@Test] list TestCF;Using default limit of 100-------------------RowKey: EG|3030=> (column=nodeId, value=ING:002, timestamp=1311954072252000)-------------------RowKey: EG|3031=> (column=nodeId, value=ING:003, timestamp=1311954073631000)-------------------RowKey: SID|123=> (column=nodeId, value=ING:001, timestamp=1311954072249000)3 Rows Returned.[default@Test]Now, cassandra.yaml is stock, except I changed it to place the data in a non-default location:# directories where Cassandra should store data on disk.data_file_directories:- /usr/local/ingenuity/isec/cassandra/datastore/data# commit logcommitlog_directory: /usr/local/ingenuity/isec/cassandra/datastore/commitlog# saved cachessaved_caches_directory: /usr/local/ingenuity/isec/cassandra/datastore/saved_cachesIn that data directory:[imac:datastore/data/Test] jas% pwd/usr/local/ingenuity/isec/cassandra/datastore/data/Test[imac:datastore/data/Test] jas% ls[imac:datastore/data/Test] jas%There is nothing there. Perhaps Cassandra has not yet felt the need to write the SSTables. So, since I need to reference in actual data file with sstable2json, I ran nodetool flush:[imac:isec/cassandra/apache-cassandra-0.8.2] jas% bin/nodetool -h localhost flush Test TestCF[imac:isec/cassandra/apache-cassandra-0.8.2] jas%Now, I have files![imac:datastore/data/Test] jas% pwd/usr/local/ingenuity/isec/cassandra/datastore/data/Test[imac:datastore/data/Test] jas% lsTestCF-g-1-Data.db TestCF-g-1-Index.dbTestCF-g-1-Filter.db TestCF-g-1-Statistics.db[imac:datastore/data/Test] jas%Given that, I'm able run sstable2json and I can see I'm getting what's in that CF:[imac:isec/cassandra/apache-cassandra-0.8.2] jas% bin/sstable2json /usr/local/ingenuity/isec/cassandra/datastore/data/Test/TestCF-g-1-Data.db > testcf.jason[imac:isec/cassandra/apache-cassandra-0.8.2] jas% cat testcf.jason{"45477c33303330": [["nodeId","ING:002",1311954072252000]],"45477c33303331": [["nodeId","ING:003",1311954073631000]],"5349447c313233": [["nodeId","ING:001",1311954072249000]]}[imac:isec/cassandra/apache-cassandra-0.8.2] jas%Oops, okay, that file extension should be json not jason, but oh well... :)Okay, so I now I have data in the proper format for importing with json2sstable. Like I said, I want to import this data into a new CF. Let's call it TestCF2 (in the same keyspace):[default@Test] create column family TestCF2 with comparator = UTF8Type and column_metadata = [{column_name: nodeId, validation_class: UTF8Type}];4dcc44b0-b9fa-11e0-0000-242d50cf1fb5Waiting for schema agreement...... schemas agree across the cluster[default@Test] update column family TestCF2 with key_validation_class=UTF8Type;5092dec0-b9fa-11e0-0000-242d50cf1fb5Waiting for schema agreement...... schemas agree across the cluster[default@Test]Again there are no files created in the data directory, so I do a flush for the new CF:[imac:isec/cassandra/apache-cassandra-0.8.2] jas% bin/nodetool -h localhost flush Test TestCF2[imac:isec/cassandra/apache-cassandra-0.8.2] jas%Well, that did not help, still no files for TestCF2. There is no actual data yet, so I'm guessing the system tables have what they need. So, I go ahead and import the data using json2sstable:[imac:isec/cassandra/apache-cassandra-0.8.2] jas% bin/json2sstable -K Test -c TestCF2 testcf.jason /usr/local/ingenuity/isec/cassandra/datastore/data/Test/TestCF2-g-1-Data.dbImporting 3 keys...3 keys imported successfully.[imac:isec/cassandra/apache-cassandra-0.8.2] jas%Okay, and the files did show up:[imac:datastore/data/Test] jas% pwd/usr/local/ingenuity/isec/cassandra/datastore/data/Test[imac:datastore/data/Test] jas% lsTestCF-g-1-Data.db TestCF2-g-1-Data.dbTestCF-g-1-Filter.db TestCF2-g-1-Filter.dbTestCF-g-1-Index.db TestCF2-g-1-Index.dbTestCF-g-1-Statistics.db TestCF2-g-1-Statistics.db[imac:datastore/data/Test] jas%Back in the CLI:[default@Test] list TestCF2;Using default limit of 1000 Row Returned.[default@Test]However, if I edit TestCF-g-1-Data.db, I can sort of see the data is present. Quitting and starting the CLI has no affect. What gets the the CF data into the MemTables so it's accessible to a Cassandra client? I tried various nodetool commands (repair, compact, cleanup, flush, invalidatekeycache, invalidaterowcache) and I don't see any rows for TestCF2 in the CLI.Anyway, it seems this procedure works as I'd expect, well except for not seeing the new data. :)What am I missing here?Thanks,Jeff


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StrengthsFinder 2.0
The #1 Wall Street Journal and #1 BusinessWeek bestseller that introduced the StrengthsFinder 2.0 assessment with features that include a personalized Strengths Insight Report, an Action-Planning Guide, and a web-based Strengths Community.
Strengths Based Leadership
The bestselling book that destroys the myth of the well-rounded leader and explains why people follow leaders.
Includes a leadership version of the StrengthsFinder 2.0 program


text:
Watch @EJay_CPT Interview - Sends Warning Shots To His Competition x Talks Tweezy & His Big Jozi Move
We recently sat down with Ejay who has been making waves for a minute now. He talked about the current status of the relationship with Tweezy after their fallout, explains why he made the big move from Cape Town to Joburg and future plans. Peep the interview after the jump.


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Everybody Loves Mel!
Mel Gibson – who has not fled the country – received the support of his ex-wife Robyn last week and now his entire family is joining together to say Oksana Grigorieva "pushed" him into flinging racial slurs and punching her in the mouth. People reports:
According to the source, "Mel didn't ask Robyn for the affidavit, where she says that he never engaged in any physical abuse towards her. Robyn just felt that enough is enough and stepped in to show that she still values her marriage to Mel and that she is sick of the media portraying Mel as a heartless and abusive monster."
"Robyn feels that Mel was and is an amazing dad," the source says, "and she is still very protective of him."
A Gibson family source says the actor's family has long seen Oksana as calculating. "She pushed him over the edge," the source says. "While they do think he needs help for his anger issues, Mel's family is supportive of him."
Wow. Talk about the most ambiguous statement ever. "She made him do it, but okay, he has anger issues." Look, I have no doubt that Oksana pulled some underhanded shit solely to squeeze a giant chunk of change out of her custody agreement, but it's not like she can go inside his brain and make him fling racial slurs while threatening arson in the absence of fellatio. That's purely the magic of Mel. The only way he can come out of this unscathed is if it turns out she secretly recorded him reading lines from his new script Fire Hummer, a post-apocalyptic tale of one man's journey to overcome racism in the pursuit of the last blowjob on Earth. And now that I just typed that, there's no way that shouldn't be his next movie. (Mel, call me. — I'm white.)
Photo: Getty


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Massey Cadillac Orlando Body Shop
Featured Business
Irish Mike's World Class AutomotiveSchedule Appointment
1624 North Forsythe Rd
Orlando, FL 32807
7.5 miles away
08/15/2017 - "Excellent, Consistent service"
"Irish Mike's is a fantastic place for us to bring our vehicles. We have used them now for a few years..."
Review for Massey Cadillac Orlando Body Shop
Eleni B. on 12/13/2012
Eleni said she had a very good experience here.
Category: Collision
Service Date: 12/12/2012
Review Created: 12/13/2012
This review was collected via phone interview by Customer Research Inc.


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When his wife Manju dies suddenly, Sanjay (Karnad) is suddenly together with his three daughters. Over the next five days, between the day Manju dies to day of the funeral, the family must deal with the painful aftermath.
Sangeeta Datta can't be accused of lacking ambition with this debut study of a family coming to terms with loss. She packs in references to Shakespeare, Satyajit Ray and Ritwik Ghatak, as well as countless musical styles, to show how cosmopolitan exiled Indians have become. But, she also examines prejudices, as sisters Mukulika Banerjee, Neerja Naik and Soha Ali Khan all find love outside the norms (with an English banker, a lesbian and a Muslim) and miss their mother's (Sharmila Tagore) ability to make doctor father (Girish Karnad) see reason. Some may find the acting a little stiff, the tuneful soft-focus reveries twee and Datta's determination to discuss contentious topics a bit forced. But this is a touching and sensitively cinematic drama.
The acting isn't always up to scratch but Datta's highbrow approach to grief makes for cerebral viewing and there's plenty of pathos too. A touching, thoughtful film.


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A performance upgrade to Live Video Encoder Toolkit is available, based on graphics hardware (GPU) accelerated video encoding.
The Live Video Encoder allows simple integration of Live Encoding and Streaming into custom applications. With the flexible API for Web Applications with Javascript or Desktop Applications with ActiveX, a custom encoding application is created in minutes.
The new hardware accelerated encoder based on Intel QuickSync / SandyBridge technology provides full HD encoding with low CPU load on Intel QuickSync & HD Graphics based plaforms. Most modern Intel CPUs based on Core i3, i5 and i7 support this architecture.
Contact us for further details and a free evaluation of the pre-release!


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techfit printed 3-inch short
Regular Price 165.00 SAR Now 115.00 SAR
Product Code:
The moisture-wicking climalite® fabric in these adidas Techfit Printed 3-Inch Shorts for women keeps you dry. They have a soft, elastic waist for comfortable movement and feature built-in sun protection.
You can return your items for free within 14 days of purchase. Returns numbers must be requested within 7 days of receiving your order and you will have a further 7 days to return unsuitable items. For more information please refer to our Returns Policy page. We deliver straight to your doorstep across the UAE and GCC; if you require further information please refer to our Shipping Policy page.
If you need any assistance please use our chat.


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|Play 2 Cars | Back to Game List
|What could be easier. You're in charge of two cars - one red, the other blue. Try to drive them down the highway while avoid the square boxes, yet catching all the round ones. This is tricky, as you have to think of two things at once, but I'm sure you'll get the hang of it!


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Earlier this month, CBS announced that it was going forward with "Under The Dome," a Steven Spielberg produced adaptation of the novel with the same name by Stephen King. And with a summer debut looming, casting is picking up speed.
Natalie Martinez and Alex Koch are the two newest additions to the cast of "Under The Dome," which takes place in Chester's Mill, a small New England town that finds itself cut off from the world by a mysterious dome.
Martinez will portray a Sheriff's deputy named Linda, who is described as "young" and "ambitious" as well as "fiercely loyal to Sheriff Duke Perkins." Martinez has previously had roles in "CSI: New York," "Sons of Tucson," "Detroit 1-8-7," Death Race (pictured above), End of Watch and the upcoming film, Broken City.
Koch will play Junior Rennie, the smart and deeply disturbed son of a local politician who is "desperately in love with local girl Angie, a waitress who's desperate to get out of Chester's Mill."
Colin Ford was previously announced to be playing a teenager named Joe, who finds himself trapped inside the dome and cut off from his family.
"Lost" veteran, Brian K. Vaughan wrote the pilot episode of "Under The Dome" and The Girl With The Dragon Tattoo helmer, Niels Arden Oplev is set to direct the pilot episode as well. The 13 episode first season is slated to premiere this summer on CBS.


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Woody Woodpecker Racing Portable | 20.04MB
The nuttiest cartoon bird ever is riding into laugh-out-loud action in WOODY WOODPECKER RACING for the Sega Dreamcast. Get in your go-kart and zip down to the zany lanes in arcade-style, fuel-burning competition. Choose from a variety of beloved Walter Lantz characters like Chilly Willy, Wally Walrus, Buzz Buzzard, and Woody himself and blaze across more than 15 challenging tracks like Area 51 and Pebble Beach in exotic locales like Japan, Italy, and Brazil. There are eight different cars to choose from and you'll upgrade them as you go into flying saucers, hovercrafts, and other quirky contraptions. In Quest mode, you'll race around difficult obstacles and unlock bonus movies when you overcome them, while Challenge Mix has youracing on different tracks and in a variety of vehicles in an attempt to meet rigorous requirements. You also get a Multiplayer mode that lets you face off against your friends in kart-bumping, kooky competition. Single Race and Time Trial modes round out the feathery roadracing shenanigans.


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Multiple problems with floating bar
I am using WP 3.5 and have unfortunately had problems with this plugin.
1. It fails to position properly (mostly in Firefox and sometimes in Chrome) near the top of an article but ends up somewhere in the middle.
2. Some buttons fail to show up such as FB like when I load a page for the first time. When I refresh, they show up.
3. Refreshing also sometimes fixes the positioning problem.
The plugin is too unpredictable. I have tried everything from disabling other plugins to emptying my cache to no avail. After several frustrating hours, I was forced to change to the "AA's Digg Digg Alternative" that has much fewer features, which is a pity because I like the power and features this plugin has. I hope it is fixed so that I begin using it again.
An example page using the correctly functional alternative plugin is at: http://zambia.co.zm/news/headlines/2013/01/23/chipolopolo-still-a-threat-nigeria/
- The topic 'Multiple problems with floating bar' is closed to new replies.


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Optical micrometer for broad applications
Micro-Epsilon Eltrotec introduces the optoCONTROL 1220 series with its versatile high-precision online micrometer for edge, gap, diameter and object center measurements. Compared to the other 1200 series micrometers, the 1220 measuring range has been reduced, which significantly increases resolution. This device is designed for a wide variety of applications in mechanical engineering, automation technology, industrial research, car equipment and printing technology, and it comes with a useful LED display, teach-in feature and an integrated controller. To ensure flexibility in quality control, the optoCONTROL 1220 includes an analog and a digital interface plus a number of digital switching outputs. The included software renders measurement values graphically.


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ESCONDIDO -- When the new fiscal years starts Thursday, it will mean fewer hours at the Escondido Public Library's Pioneer Room and adjacent computer center, officials said Tuesday.
"The Pioneer Room will be reduced from 20 hours to eight hours," said Laura Mitchell, city librarian. The Pioneer Room, which specializes in acquisition of manuscripts relating to Escondido history, will be open 2 p.m. to 6 p.m. Tuesdays and Thursdays.
The computer center will close down completely, but other public computers will continue to be available at the main library, 239 S. Kalmia St. or at the East Valley Branch Library, 2245 E. Valley Parkway, Mitchell said.
Mitchell blamed state budget cuts for the closures. The library's budget for the 2004-05 was reduced from $3.65 million last year to $3.27 million in the city's $72.9 million general fund city budget.
To swallow the cuts, the library eliminated two full-time librarians and doesn't have the staff to keep the Pioneer Room and computer center open longer, Mitchell said.


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Econo Lodge North, Battleboro
- Free continental breakfast, free WiFi, and free parking
Main amenities
- 49 guestrooms
- Seasonal outdoor pool
- 24-hour front desk
- Coffee/tea in a common area
- Computer station
- Free newspapers in the lobby
- Free continental breakfast, free WiFi, and free parking
For families
- Free cribs/infant beds
- Rollaway/extra beds (surcharge)
- Microwave
- Refrigerator
- Iron/ironing board
- Hair dryer
What's around
- North Carolina Wesleyan College (5.3 mi / 8.5 km)
- Dunn Center for The Performing Arts (5.9 mi / 9.5 km)
- Golden East Crossing Mall (6.4 mi / 10.4 km)
- Hot Wheels Amusment Park LLC (6.8 mi / 10.9 km)
- Rocky Mount Sports Complex (9.7 mi / 15.6 km)
Econo Lodge North, Battleboro
Hotel Info: 866-266-9798from $70 CAD
- Standard Double Room, 2 Double Beds, Non Smoking
- Standard Double Room, 2 Double Beds, Smoking
- Standard Room, 2 Double Beds, Non Smoking
- Standard Double Room, 2 Double Beds, Smoking
More great choices
At a glance
Key facts
Hotel size
- This hotel has 49 rooms
- This hotel is arranged over 2 floors
- Check-in time starts at 1 PM
- Check-out time is 11 AM
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- Children (18 years old and younger) stay free when occupying the parent or guardian's room, using existing bedding
- Pets allowed *
- Specific rooms only *
- 3 per room
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
- RV/bus/truck parking
Nearby Two Star Battleboro hotels
In the hotel
- Free continental breakfast
- Coffee/tea in a common area
- Outdoor seasonal pool
- Computer station
- 24-hour front desk
- Free newspapers in lobby
- Number of buildings/towers - 1
- In-room accessibility
In the room
- Coffee/tea maker
- Iron/ironing board
- Hair dryer
- Cable TV channels
- Free weekday newspaper
- Free WiFi
- Free local calls
- Refrigerator
- Microwave
Top Battleboro hotels
Nearby hotels
Also popular with travellers from Canada
Econo Lodge North, Battleboro's small print
Also known as
- Econo Lodge Hotel North
- Econo Lodge North Hotel Battleboro
- Econo Lodge North Battleboro
Pet-friendly rooms can be requested by contacting the property at the number on the booking confirmation.
Optional extras
Rollaway beds are available for USD 10 per night
Pets are allowed for an extra charge of USD 10 per pet, per night
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Is the description of this hotel not correct? Tell us


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From Cambria in the south to the outskirts of Monterey, the Big Sur Coast is one of the most beautiful and breathtaking stretches of coastline in the world.
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Run the Ridges for Missing and Endangered Kids 5k Run/Walk
Van Bibber Park
Sat 04/06/2013
100 Participants
All registered participants will receive a Run the Ridges for Missing and Endangered Kids t-shirt in a size of their choice. T-shirts can be picked up at the registration table on event day. 5k FUN Run/Walk: Registration 9:30 am Start of event 10:00 am Safety Fair 10:30-12:30 am Registration fee is non- tax deductible Route – This family friendly event will be at Van Bibber Park/Trails. Is is part of Jefferson County open space and the route will be along the Van Bibber Creek wetlands on a nice concrete trail. It's a very scenic route! Water – We will have water at the start of the 5k but to avoid unnecessary landfill waste we ask that participants please bring their own water bottle to fill up. Thanks! ***All profits raised will be donated to the National Center for Missing and Exploited Children***
- Address:5575 Ward Road, Arvada
Arvada, CO 80002


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This coming Sunday, September 28th, is the thirtieth anniversary of Pope John Paul I's death. Two days later we shall be marking the sixty-fifth anniversary of Pope Pius XII's historic encyclical on biblical studies, Divino Afflante Spiritu ("Inspired by the Divine Spirit").
John Paul I was the first pope in the entire history of the Church to take a double name. He also left his mark in history by being the first pope in more than a thousand years to refuse to be crowned like an emperor, with the triple tiara. (What follows is drawn largely from my book, Lives of the Popes.)
Although John Paul I was only pope for thirty-three days, his was not the shortest pontificate in history. There were at least ten other popes who served for thirty-two days or less, the shortest being Urban VII, whose pontificate in 1590 lasted only twelve days.
The conclave that gathered on August 26, 1978, twenty days after the death of Paul VI, was the largest conclave in the history of the Church: 111 cardinal-electors. But it required only four ballots, all on that day, to establish a winner: Cardinal Albino Luciani, Patriarch of Venice.
In choosing a double name, the new pope did so, he said, to honor Pope John XXIII, who ordained him a bishop and who preceded him in Venice, and Pope Paul VI, who named him a cardinal.
John Paul I struck a humble note the next day just before his Sunday papal blessing: "Be sure of this," he said to the crowd assembled below him in Saint Peter's Square, "I do not have the wisdom of heart of Pope John. I do not have the preparation and culture of Pope Paul."
In an address to the cardinals earlier that morning, the new pope pledged to continue the implementation of the Second Vatican Council, to revise the Code of Canon Law for the Latin and Oriental Churches (the new Codes were promulgated under John Paul II in 1983 and 1990 respectively), and to promote evangelization, ecumenism, dialogue with all people, and peace.
John Paul I never lived to carry out his agenda. Late in the evening of September 28th, the pope died of a heart attack while reading in bed. His light was still on when his body was discovered early the next morning.
The failure to conduct an autopsy, because of the recent custom (since Pius X in 1914) against embalming a deceased pope, and the inconsistent stories that were told regarding the question of who discovered the pope's body in his bedroom, generated a few bizarre rumors.
The Vatican claimed that it was his Irish priest-secretary, John Magee, who discovered the body when, in fact, it was Sister Vincenza, his long-time housekeeper.
Others charged that the pope had been poisoned to prevent him from exposing financial irregularities in the Vatican Bank.
The most likely truth is that John Paul I died prematurely because he needed treatment for his serious health problems and did not seek or receive it. Upon death, he was just short of his sixty-sixth birthday.
The Romans had taken an immediate liking to this humble, smiling pope and reacted more emotionally to his death than they had to Paul VI's only two months earlier.
At his funeral, the dean of the College of Cardinals, Carlo Confalonieri, said that John Paul I had "flashed like a meteor across the sky."
He was buried in the crypt of Saint Peter's just across the aisle from another short-reigned pope, Marcellus II, whose pontificate had lasted only twenty-one days in 1555.
When Cardinal Karol Wojtyla was elected to succeed John Paul I on October 16, 1978, he was the first Slavic pope in history and also the first non-Italian in over 450 years. He would also become the second-longest reigning pope in history (not counting St. Peter himself): twenty-six-and-a-half years.
The second important anniversary that the Catholic Church is about to observe is the publication of Pius XII's encyclical on biblical studies, Divino Afflante Spiritu. Biblical scholars then and since have referred to the encyclical as the Magna Carta of biblical renewal.
The encyclical directed exegetes to uncover the literal meaning of Sacred Scripture, that is, "what the writer intended to express." Biblical scholars, the pope insisted, are to use the most up-to-date scientific and historical methods to achieve this purpose. He urged scholars and preachers alike to avoid excessive use of figurative and allegorical senses of Scripture.
Despite strong opposition from some forces in the hierarchy at the time, the encyclical's directives were incorporated by Vatican II into its Dogmatic Constitution on Divine Revelation.
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text: Getty Images [ John Stamos Is Doing a Web Show Where He Reunites Stars With the People Who Took Their Virginity By Jade May 1, 2013 This show could either be really funny, or really really awkward! Read More Category: Hollywood Buzz Tags: john stamos, virginity, web series, yahoo Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


text: Hello, my name is Karina I am 16 years old, I was born in Colombia, but raised in Florida. I'm a great listener and a good friend, I like to think ;) ha ha. Well, I'm not going to say I am obsessed about Twilight, but I do like it ALOT! Seriously? A freaking love story with a vampire....Hot! ha ha. So, my life time quote I try to live by is: "yesterday was history tomorrow is a mystery, but today is a gift thats why we call it the present" -the creater is unknown. I have pretty strong oppinions, but I try to keep them to myself. My life time goal is to become an actress, but if that doesn't work out I have a back up plan ;) I would like to become a nurse partitionest. Anywho, I am a very kind person and a great listener so lets talk :D Peace


text: Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) and Active Biotech (NASDAQ OMX NORDIC: ACTI) announced today enrollment of the first patient in the CONCERTO study - the third Phase III placebo-controlled study designed to evaluate the efficacy, safety and tolerability of once-daily oral laquinimod in patients with relapsing-remitting multiple sclerosis (RRMS). The primary outcome measure of CONCERTO will be confirmed disability progression as measured by the Expanded Disability Status Scale (EDSS). "Previous Phase III studies in more than 2,400 people with RRMS suggest a unique profile of laquinimod, directly affecting the neurodegenerative processes that lead to disability progression, the main concern in the treatment of RRMS," said CONCERTO principal investigator, Dr. Timothy Vollmer, Professor of Neurology, University of Colorado Denver, Medical Director of the Rocky Mountain Multiple Sclerosis Center, and Co-Director of the RMMSC at Anschutz. "We are currently enrolling patients in this third pivotal study to further examine the clinical benefits of laquinimod on disability progression, the primary endpoint of the CONCERTO trial, and brain atrophy, at both the previously studied 0.6 mg dose, and now a higher 1.2 mg dose." The multinational, randomized, double blind placebo-controlled study will aim to enroll approximately 1,800 patients at more than 300 sites globally ( http://clinicaltrials.gov/show/NCT01707992). Along with the primary endpoint of time to confirmed disability progression, the study will also examine the impact of laquinimod on endpoints such as percent change in brain volume and other clinical and MRI markers of disease activity. "For nearly 30 years, Teva has been focused on improving the lives of people with multiple sclerosis by delivering innovative treatment options that address this complex disease," said Dr. Michael Hayden, President of Global R&D and Chief Scientific Officer at Teva Pharmaceutical Industries Ltd. "The CONCERTO study demonstrates our commitment to collaborating with MS communities worldwide to further develop laquinimod and address unmet patient needs."


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Just when Peter Bourjos thought he was out, the Angels pulled him back in, clearing a spot for the speedy center fielder Wednesday by trading designated hitter Kendrys Morales to the Seattle Mariners for left-hander Jason Vargas.
Vargas, who turns 30 on Feb. 2, will deepen the rotation — the former Long Beach State teammate of Angels ace Jered Weaver went 14-11 with a 3.85 earned-run average in 33 starts last season, striking out 141 and walking 55 in 217 1/3 innings.
The Angels paid a fair price for a durable pitcher who has a 3.83 ERA and has averaged 203 2/3 innings over the last three seasons — the switch-hitting Morales, 29, batted .273 with 22 home runs and 73 runs batted in last season.


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An absurd satire on dethroned European royalty with a neo-realistic view of the London ghetto.
An absurd satire on dethroned European royalty with a neo-realistic view of the London ghetto.
Marcello Mastroianni, the last of his line, lives in exile in a magnificent London townhouse at the end of a cul-de-sac in a black ghetto area. He is a totally ineffectual, sheltered sickly man, whose only human contacts are a flock of parasitic social magpies.
Footage on the ghetto comings and goings, as orchestrated by director John Boorman, has a gritty documentary feel.
There is a grotesquely hilarious scene of a mass nude water therapy of Mastroianni's entourage led by society doctor David de Keyser.
But the two sequences are all that work in Leo. The rest is at best silly, at worst pretentious allegory and unsuccessful social comment.
Leo the Last
United Artists. Director John Boorman; Producer Robert Chartoff, Irwin Winkler; Screenplay William Stair, John Boorman; Camera Peter Suschitzky; Editor Tom Priestley; Music Fred Myrow; Art Director Tony Wollard
(Color) Extract of a review from 1970. Running time: 103 MIN.
Marcello Mastroianni Billie Whitelaw Calvin Lockhart Glenna Forster-Jones Vladek Sheybal Gwen Ffrangcon-Davies


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On September 2, 2010 Revgear fighter Joel Mickells won his second professional Muay Thai fight at Ring Wars Omaha 8 event. For the second year
In November 2009 Joel Mickells got his Blue Belt in Brazilian Jiu Jitsu. And last weekend – February 20, 2010 – Joel competed for the
On September 26, 2009 Revgear Sponsored Joel Mickells won one Gold and 2 Bronze medals in the Best of the Best Brazilian Jiu-Jitsu Proams in
Joel Mickells, Revgear sponsored fighter, won his first professional fight on Thursday, September 3, 2009. This was a Pro Muay Thai Fight for Ring Wars
On July 10, 2009, Revgear sponsored Joel Mickells was fighting at Fight to Win Promotions in Denver, Colorado. He was fighting against Anthony Werner –
Revgear sponsored fighter Joel Mickells participated in the Best of the Best Brazilian Jiu-jitsu ProAms in Omaha, Nebraska on June 20, 2009. He placed 3rd
On June 7, 2009 Revgear Sponsored Fighter Joel Mickells defeated Nathan Ruthowski in the Thai Boxing Association Men's Class A Lightweight (135 lb) Title Belt
On April 17, 2009, VFC, the Midwest's top fighting organization made its first stop at Lincoln, Nebraska on its Road To Victory Tour with VFC:
Joel Mickells, 25 is from Omaha, Nebraska. His main passion in life is Martial Arts. He trains in various styles – Jiu-jitsu, Muay Thai, Western


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Blair: Saddam has still time to disarm
The British prime minister, Tony Blair, said Monday that he believed "passionately" that Iraqi leader, Saddam Hussein, must be stripped of his weapons of mass destruction, with or without a new UN resolution.
He said Britain must show rogue states "that when we say we intend to deal with the issue of weapons of mass destruction, we mean it". Blair conveyed there was still time for the Saddam to give up his weapons programs. But if he did not, he would have to be disarmed by force.
"I know and understand the concerns that people have," the British leader said. "The threat seems to some people to be remote but I passionately believe that we must disarm Iraq.
"I tell you honestly what my fear is: my fear is that we wake up one day and we find that either that one of these dictatorial states has used weapons of mass destruction - and Iraq has done so in the past - and we get sucked into a conflict with all the devastation that would cause.
"Or, alternatively, these weapons - which are being traded all around the world at the moment - fall into the hands of these terrorist groups, these fanatics who will stop at absolutely nothing to cause death and destruction on a mass scale. "That is what I have to worry about," he declared during his monthly press conference.
Blair said Saddam was "almost certainly" not telling the truth in his weapons report given to the UN last month.
However, he noted he wanted to walk "the UN route" in tackling Iraq and there would be further discussion there if Iraq was in breach of the UN resolution.
"But I want to make it quite clear - and I believe this to be the position of all the main security council members - if there is a breach we would expect the United Nations to honour the undertakings that were given and make sure that the will of the UN is upheld," he said. "I have no doubt at all they will do so."
The British Prime Minister added: "If there is a breach of the existing UN resolution I have no doubt at all that the right thing to do in those circumstances is disarm Saddam by force." (Albawaba.com)


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Banjul, Gambia -
Separatist rebels in Senegal's restive Casamance region have released eight hostages in an area close to the Gambian border following talks with Catholic mediators, sources said.
A delegation from the Casamance Movement of Democratic Forces (MDFC) handed over the hostages - six members of the military, a member of a paramilitary police unit and one civilian - to Gambian authorities shortly before 1.00pm (13.00 GMT), said the International Committee of the Red Cross (ICRC) in a statement.
ICRC representatives witnessed the release, Angelo Romano, a member of the Rome-based Sant'Egidio community, told AFP.
The eight had been captured in December 2011 and January 2012.
The Sant'Egidio community said seven members of the military and a firefighter had been released but checks to establish their identity were underway.
Romano said five army members who had been captured in December 2011 in an attack on an army camp at Kabeum, 60 kilometres north-west of Ziguinchor, were among those freed.
One of the MFDC's military chiefs Salif Sadio, a member of the group's most hardline wing, clad in white for the occasion, said the release was a sign of the movement's "goodwill to resolve this conflict peacefully".
But he also warned that the "release does not mean the end of our battle and even less the renunciation of our option of independence. The fight for national independence continues."
The freed hostages were to be handed over to a representative of the Senegalese embassy in Banjul before their repatriation.
The Senegalese government began peace negotiations in Rome with representatives of the Casamance rebel movement in October.
The MFDC has been fighting for independence since 1982 in a conflict that has defeated several peace initiatives.
Over the past 30 years the conflict has cost thousands of military and civilian lives and displaced thousands of people and refugees though no accurate figures exist.
The Sant'Egidio Community was founded in Rome in 1968 and got involved in sponsoring peace negotiations in the 1980s when it found that its humanitarian action in Mozambique would be largely useless without peace.
The community has close ties to the Vatican and for many years has made a speciality of parallel and discreet diplomatic activities, earning the name of the "little Trastevere United Nations" from the district of Rome where it is situated. - Sapa-AFP


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Philips Downsizes Mobile TV
las vegas royal philips electronics will release a new chip that enables much smaller tv phones, according to an announcement today at the ctia wireless trade show in las vegas.
mobile tv is a big topic at ctia, with much of the buzz around dvb-h (digital video broadcasting-handhelds), a european-driven standard for broadcasting digital tv channels to phones. while companies such as mobitv and smartvideo already bring live tv to some phones and pdas, they stream the shows over internet connections, with a separate stream going to each user who demands it. direct television broadcasts, on their own chunk of radio spectrum, are much cheaper to deliver to a mass audience because they don't clog up internet pipes or a bunch of individual cellular connections.
the major competitor for dvb-h is mediaflo, designed by u.s. firm qualcomm. verizon has pledged to use mediaflo. no u.s. carrier has yet partnered with modeo, the u.s. provider of dvb-h services, but analysts say cingular would be the most natural match. qualcomm and modeo have both said they'll launch tv services sometime in 2006.
the first dvb-h phones cropped up at trade shows last year; the current front-runner phone to launch dvb-h in the us is the nokia n92, but even that second-generation device is rather clunky. philips' new bgt216 chipset directly attacks that problem, shrinking the size of a dvb-h module from 15 by 26 mm to a mere 7 by 7 mm.
"this way, you really enable people to make smaller equipment," said joost verhoeks, international product marketing manager for philips semiconductors. of course, lcd size is also a limiting factor in tv handsets, verhoeks said. you don't want to watch lost on a screen the size of a postage stamp.
the bgt216 will be available immediately to handset manufacturers, and should make its way into phones in early 2007, according to verhoeks. although it will initially be expensive, prices should drop if and when mobile tv becomes more widely adopted.
verhoeks says trials in europe have shown that people are willing to pay about $10 per month for mobile tv. here in the u.s., that amount currently gets you several live tv channels on top of sprint's basic power vision service. per-use scenarios are also possible, verhoeks said.
"look to sports stadiums," verhoeks said. "you have 100,000 people, paying maybe $30 to $40 for a ticket. if you would offer them a service for a flat fee of maybe $10 per month where they can view different angles, where they can get replays, or watch other games going on in the same league, [mobile tv might take off.]"
|Complete CTIA Show Coverage
more ctia 2006 coverage:


text:
24th week!
No make up used.
Its been a long journey but! I did it :)
Its been a long journey but! I did it :)
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text:
A PAIR of men have been charged by police of handling stolen goods in relation to motor vehicle parts found in an industrial unit.
Shahzad Yousaf, 36, of Balfour Road, Ilford, and Graham Goodwin, 49, of The Windsors, Buckhurst Hill, were arrested in May 2013 following an investigation at the unit in Old Barn Lane, Rettendon.
Both will appear at Chelmsford Magistrates' Court on March 12 with Yousaf facing eight charges and Goodwin being charged with 14.
The duo have been released on bail until their court date.


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So, here is my idea. I wear a long t-shirt and tights. Then i wear my favorite green blazer. It looks like a dress right? Yeay.. I did it! I mix my clothes. Maybe its true, if the women like shopping. Because i love it! And it never have a reason to buy a clothes such as dresses, skirts, blazers, shoes, heels, etc. Why? Because we just love it! That why i realize today.
My theme song for today is The Time Of My Life.
I've had the time of my lifeAnd I've never felt this way beforeAnd I swear this is trueAnd I owe it all to you
-By Black Eye Peas-
-By Black Eye Peas-