Account Options Accedi. Nuove uscite. Per tutti. Aggiungi alla lista desideri. Tradurre la descrizione in Italiano Italia utilizzando Google Traduttore? Ritraduci la descrizione in Inglese Regno Unito Traduci. Together we created a new computer algorithm based on artificial intelligence designed to analyze all the football matches smarter and faster.
The algorithm calculates all the probabilities and offers the winning percentages based on past statistic data, team form, head to head results, goals scored, goals conceded, odds fluctuation, team profile attacking or defending , past playing formulas. Although the algorithm has been tested and proved to be a winning option we think human mind can not be fully replaced.
The artificial intelligence can estimate the percentages for the most likely outcome based on statistical data, it doesn't have access to data like injured players, weather conditions, team motivation or individual player motivation. That's where the best tipsters from Tips Alliance come in to add value.
After the algorithm analysis all the football games the expert tipsters review all the predictions and refine them in order to obtain the best betting tips at very high win rates. The Syndicate is designed to evolve and to become a bigger, stronger and better sports community. With all the good tipsters, IT specialists, artificial intelligence passionates, designers and communication experts who work under the Syndicate brand, we are convinced that we will offer high quality apps.
Terms and Conditions: This application is only an informative tool and must be used just for fun. I want to move the table under the window. It will look better there! If however you are referring to a table that is set for a meal, you would use the word tavola instead. Bambini, a tavola! Kids, come to the table! The pasta is ready!
I sat at the table and read the menu. The table is set for dinner. Mia mamma ha portato il piatto in tavola. My mum served lunch. Lit: My mum brought lunch to the table. Vorrei prenotare un tavolo per due alle sette. I would like to reserve a table for two at seven. La serata prevede una cena servita al tavolo. The evening includes a dinner with table service. Other meanings for tavola include plank , board , chart , figure or panel. Here as well, if you combine it with other nouns, you can expand your vocabulary:.
Oh, God, look at that, two perfectly shorn balls. Aveva 2 palle match nel secondo set. He took 2 catches in the latter match. The tie will always be quoted in 2 Ball betting. Now, because you're a girl, I'm gonna give you a two-ball handicap. Con lui tutto il giorno.
Gotta hang out with him all day. Un palla, 2 palle , 3 palle, 4 palle! Now you're going to see one ball, two balls Paper, paper does not hold milk. If you're thinking of making a fool of Mamma la Turca, you'll discover that under this skirt there's a pair of balls that will make yours run and hide. Control 2 different balls with 2 different actions. Bubble Elements 2 Balls of various colors come to you, but you will need to combine them so not to get locked. Ho solo dato 2 palle di cavoli. I just gave two heads.
E 2 palle degli occhi. And mo eye balls. Un alto ciclone di 2 metri, 2 palle saltono tra fulmini, il esperimento di afferare un ologramma - tutto questo succede nel EXPI a Ferlach. Look how a 2 meter high cyclone is created in front of your eyes, let flashes bounce between two balls or try to affect a hologram. In Game 2 of the Rockets' first-round playoff series against the Oklahoma City Thunder, Beverley received his first career start and went on to record 16 points, 12 rebounds, six assists, two steals and one block.
The algorithm calculates all the probabilities and offers the winning percentages based on past statistic data, team form, head to head results, goals scored, goals conceded, odds fluctuation, team profile attacking or defending , past playing formulas. Although the algorithm has been tested and proved to be a winning option we think human mind can not be fully replaced. The artificial intelligence can estimate the percentages for the most likely outcome based on statistical data, it doesn't have access to data like injured players, weather conditions, team motivation or individual player motivation.
That's where the best tipsters from Tips Alliance come in to add value. After the algorithm analysis all the football games the expert tipsters review all the predictions and refine them in order to obtain the best betting tips at very high win rates. The Syndicate is designed to evolve and to become a bigger, stronger and better sports community. With all the good tipsters, IT specialists, artificial intelligence passionates, designers and communication experts who work under the Syndicate brand, we are convinced that we will offer high quality apps.
Terms and Conditions: This application is only an informative tool and must be used just for fun. This is not a betting application, it is not related to betting or gambling and we do not encourage betting and gambling in any way. Act responsibly! Not designed for children. Sebbene l'algoritmo sia stato testato e dimostrato di essere un'opzione vincente, pensiamo che la mente umana non possa essere completamente sostituita. Dopo aver analizzato l'algoritmo di tutte le partite di calcio, i consiglieri esperti rivedono tutti i pronostici e li perfezionano per ottenere i migliori pronostici sulle scommesse a tassi di vincita molto alti.
Agisci in modo responsabile! Non progettato per i bambini.
Although MYC gene alterations are implicated in this setting and are associated with poor outcome Barrans et al, ; Cuccuini et al, ; Johnson et al, ; Savage et al, ; Visco et al, , the specific effectors of MYC dependency in DLBCL are not well characterized Aukema et al, Aberrant expression of testis specific factors, including epigenetic regulators, is increasingly described in diverse cancer types Wang et al, This appears to drive abnormal epigenome reprogramming leading to malignant transformation and the emergence of cancer cell clones.
As an example, expression of the male germ cell factor, DNMT3L, a catalytically inactive member of DNA methyl transferases, has been described in a variety of cancers. Through its ability to increase the activity of the de novo methyl transferases, it could contribute to CpG island methylation and pathological gene silencing Gokul et al, Likewise, expression of NUT nuclear protein in testis , encoded by a testis specific gene, is abnormally activated through fusion with the ubiquitously expressed BET bromodomain protein-encoding gene, BRD4 , in an aggressive subset of carcinoma known as NUT-Midline Carcinoma French, The resultant BRD4-NUT fusion gene encodes a fusion protein that behaves as a histone superacetylator, resulting in chromatin hyperacetylation that completely alters the epigenetic landscape of the affected cells Reynoird et al, Finally, gene expression profiling in malignant brain tumours derived by inactivation of the l 3 mbt tumour suppressor in Drosophila, has revealed predominant expression of germline specific transcripts some of which were found to be essential for tumour growth Janic et al, Specifically, we geared our screening procedures to identify abnormally expressed, positively-charged, nuclear factors as these were likely to bind nucleic acids and to directly or indirectly engage aberrant and potentially druggable gene regulatory pathways in lymphoma.
Remarkably, this resistance can be relieved by treatment with small molecule inhibitors of BET bromodomain-dependent chromatin signalling. Furthermore, CYCLON was identified to be an autonomous tumour growth driver that cooperates with MYC to drive aggressive lymphoma growth in vivo thus further rationalizing the value of therapeutically targeting this factor in lymphoid malignancies.
Proteomics-based discovery strategy for identification of abnormally expressed nuclear factors in lymphoma. Schematic representation of the overall experimental strategy, as indicated. NAS: nuclear acid-soluble, MS: mass spectrometry. To identify candidate nuclear factors associated with aggressive disease and treatment resistance in lymphoma, we first derived an inventory of positively charged nuclear proteins in the DLBCL line, B Indeed, our previous work on acid soluble fractions from male germ cells Govin et al, had shown that this fraction is highly enriched in nucleic acid-binding factors, since the majority of identified proteins were known or potential DNA and RNA binding factors.
This also showed that charge interaction between positively charged proteins and negatively charged nucleic acids is a prevalent determinant of protein—nucleic acid interactions in nature. Taken together, these findings validate the clinical relevance of our biomarker discovery approach and identify candidate nuclear factors of potential relevance to the pathogenesis of lymphoid malignancies. We then performed unbiased gene set enrichment analysis GSEA to identify gene signatures i.
This analysis revealed significant down-regulation by CYCLON knockdown of a proliferation gene expression signature that includes cancer testis antigens e. Genes are ordered on the x axis by their differential expression score each vertical line representing a gene. See the Materials and Methods section and supplementary material for detailed data analysis. Black and green arrows: genes cited in text. We next tested sensitivity to Rituximab-mediated, complement-dependent cytotoxicity CDC, Fig 5B and direct killing Fig 5C in a selection of these cell lines.
The observed effects were not related to differences in the cell surface expression of the Rituximab target receptor, CD20, which was broadly similar across all cell lines Fig 5D. This indicated that CYCLON overexpression directly drives tumour cell intrinsic mechanisms that specifically impact on Rituximab response. Once tumours were established, mice were treated with daily injections of either Rituximab or control antibody for a period of 14 days.
We first performed a dose-response experiment to test the effects of JQ1 on MYC levels in our panel of lymphoma cell lines. The next step was to explore the effects of JQ1 on Rituximab response in vitro. JQ1 pre-treatment alone, under these conditions, did not induce cell death in any of the cell lines tested Supporting Information Fig S7A nor did it significantly alter responses to genotoxic agents such as etoposide Supporting Information Fig S7B. The core set of commonly down-regulated genes included ZBTB2 , which encodes a negative regulator of p53 signalling Jeon et al, and POU2F2 , which encodes a homeobox transcription factor involved in the germinal centre reaction, in response to viral infection Karnowski et al, and that has recently been shown to be mutated in DLBCL Zhang et al, Fig 4D, E.
The core set of commonly up-regulated genes included a number that encode factors involved in pathways of direct relevance to normal and pathological B-cell signalling IL6st, JAK1 and PIK3R1, for example Love et al, ; Ngo et al, as well as JNK1 which has been implicated in the regulation of complement dependent cell death Gancz et al, Combination immunochemotherapy using anti-CD20 antibodies and cytotoxic drugs has led to marked improvements in treatment response and overall survival in B-NHL.
However, treatment resistance and relapse remain problematic. This is spurring the development of alternative treatment strategies, including novel therapeutic antibodies, and targeted therapy strategies aimed at curtailing oncogene dependency pathways in lymphoid neoplasia Friedberg, A major confounding factor in these efforts, however, is the lack of knowledge on the cellular and molecular mechanisms that contribute to treatment resistance.
Here, by performing a concept-driven targeted proteomics and functional analyses, based on the ectopic activation of tissue-specific genes in cancer, we have identified a Rituximab resistance mechanism that operates in aggressive B-cell lymphoma and that is mediated by MYC-driven overexpression of the nuclear factor, CYCLON.
Remarkably, this resistance mechanism could be alleviated by next generation epigenetic therapy, using the BET bromodomain small molecule inhibitor, JQ1. JQ1 functions as a specific inhibitor of BET bromodomain binding of acetylated lysines in chromatin and has demonstrated single agent efficacy in diverse cancer models Delmore et al, ; Filippakopoulos et al, ; Mertz et al, ; Ott et al, ; Zuber et al, but has not previously been tested in combination treatment with a therapeutic monoclonal antibody.
Noteworthy, is that constitutive NFKB signalling has been linked to experimental resistance to Rituximab in lymphoma cell lines Jazirehi et al, Association of Rituximab with BET bromodomain inhibitors in this setting might be an attractive therapeutic option. The CD95 pathway is also involved in maintaining B-cell homeostasis downstream of B-cell receptor signalling and in the germinal centre reaction Hao et al, In support of this notion, normal germinal center B-cell subsets, defined by either high or low MYC levels have recently been identified Calado et al, ; Dominguez-Sola et al, This would uncouple not only MYC, as previously postulated Dominguez-Sola et al, , but also CYCLON-dependent gene regulatory circuits, from normal affinity maturation, thus facilitating malignant reprogramming of the affected B cells, ultimately leading to disturbed GC dynamics and lymphomagenesis.
In this respect, it is noteworthy that CYCLON regulates gene expression signatures of direct relevance to the pathogenesis of germinal center-derived lymphoma. This works suggests that BET bromodomain inhibition could override these oncogenic signalling events. In conclusion, we have devised a proteomics-driven strategy to leverage illegitimate gene activation events for the discovery of new treatment strategies in high risk B-cell lymphoma. A remarkable result was the identification of a MYC-controlled disease progression and Rituximab resistance regulatory circuit that is autonomously controlled by the nuclear factor CYCLON.
Unless otherwise specified, all chemicals were purchased from Sigma—Aldrich. Whole cell lysates were obtained by sonication of cell pellets in Laemmli buffer. Nuclear acid soluble fractions were obtained by direct sonication of cell nuclei in 0. MS analyses were performed on three biological replicates. MS data were analysed using the Mascot 2. The variable modifications allowed are listed at the bottom of Table S1. Manually validated hits from each of the three biological replicates were transferred to a relational database.
Protein abundance was estimated using the spectral counting method Gilchrist et al, The ABL gene was used as a control for normalization of gene expression data. Fluorescence intensities were quantified using the GCOS 1. The median was calculated across all 79 normal cell or tissue types Su et al, The following data treatment options were used: Euclidian distance of dissimilarity, McQuitty's method of hierarchical clustering and multiple fragment heuristic seriation rule.
GSEA is a computational method that determines whether an a priori defined set of genes shows statistically significant, concordant differences between two biological states Subramanian et al, Analysis was performed using GSEA v2. Membrane CD20 expression was determined by direct fluorescence. Percentages of positive cells and mean fluorescence intensities MFI were recorded and analyzed with FCS express software. Cells were transduced with lentiviral particles at an MOI multiplicity of infection of All animal experiments were conducted in agreement with the Principles of Laboratory Animal Care National Institutes of Health publication no.
Raji cells 5. For follow-up of tumour engraftment and growth, 12 mice each were injected into the right and left flanks, respectively, with either shCtrl or shCYCLON-transduced Raji cells expressing luciferase.
Semi-quantitative data were obtained from the bioluminescence images by drawing regions of interest on the area to be quantified. Results were expressed as the number of relative light units RLU per pixel per second. For the latter, CYCLON values at diagnosis were defined as high above 3rd quartile or low below 1st quartile and Kaplan—Meier survival curves and the log-rank test used to estimate overall survival.
Survival analysis in lymphoma xenograft experiments was performed by the Kaplan—Meier method and the p -value calculated by log-rank test. The Wilcoxon non-parametric method or the two-sided Student t test were used for statistical analysis in gene expression and cell death analyses and in in vivo tumour growth and Rituximab response assays to assess statistical significance.
Histograms represent the average for each group and errors bars represent standard error of the mean. B-cell non-Hodgkin lymphoma B-NHL comprises a complex spectrum of lymphoid cancers that manifest heterogeneous clinical outcomes to standardized therapies tailored to well-defined subtypes.
A significant advance in treatment of aggressive B-NHL has been achieved with anti-CD20 monoclonal antibodies Rituximab both in combination with chemotherapy or alone as a maintenance treatment. However, a proportion of patients fail to respond to, or more commonly relapse, after receiving Rituximab-containing therapy.
The cellular and molecular mechanisms underlying these events are not well characterized and treatment strategies to override treatment resistance events are lacking. Using this strategy, we identified the nuclear factor CYCLON, which has not been previously connected to cancer, as a novel transcriptional regulator of the mature B-cell development program that autonomously drives tumour growth and resistance to monoclonal antibody therapy in B-cell NHL.
AE designed study, performed experiments, analyzed data and co-wrote the manuscript. SR designed study, analyzed transcriptomic and public clinical data and co-wrote the manuscript. JBC designed and performed Rituximab sensitivity assays and flow cytometry analyses. CR designed and performed animal studies. SD designed and performed shRNA cloning.
SH, PB performed lentiviral transductions and flow cytometry analyses. AD, FC analyzed transcriptomic and public clinical data. DL analyzed data. BB analyzed proteomics data. SKJ performed mass spectrometry analyses. EF performed JQ1 synthesis. CEM designed JQ1 synthesis.
CP designed study. RG analyzed clinical data. MBC and SK conceived and designed the study, analyzed data and wrote the manuscript. EF is a Chateaubriand fellow. Additional Supporting Information may be found in the online version of this article at the publisher's web-site:. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset.
Technical support issues arising from supporting information other than missing files should be addressed to the authors. Table S3. National Center for Biotechnology Information , U. Published online Jul 4. Author information Article notes Copyright and License information Disclaimer. Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.
This article has been cited by other articles in PMC. Figure S3. Figure S6. Characterization of JQ1 final compound. Figure S7. The Syndicate is designed to evolve and to become a bigger, stronger and better sports community. With all the good tipsters, IT specialists, artificial intelligence passionates, designers and communication experts who work under the Syndicate brand, we are convinced that we will offer high quality apps.
Terms and Conditions: This application is only an informative tool and must be used just for fun. This is not a betting application, it is not related to betting or gambling and we do not encourage betting and gambling in any way. Act responsibly! Not designed for children. Sebbene l'algoritmo sia stato testato e dimostrato di essere un'opzione vincente, pensiamo che la mente umana non possa essere completamente sostituita.
Dopo aver analizzato l'algoritmo di tutte le partite di calcio, i consiglieri esperti rivedono tutti i pronostici e li perfezionano per ottenere i migliori pronostici sulle scommesse a tassi di vincita molto alti. Agisci in modo responsabile! Non progettato per i bambini. Recensioni Leggi norme e informazioni.
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See Article History. Fresco on the ceiling of the Camera degli Sposi, by Andrea Mantegna, completed It demonstrates the technique of sotto in su. Learn More in these related Britannica articles:. The perspective scheme with a viewpoint below the lower frame of the composition exaggerates the apparent height of the scene with respect to the…. Giulio Romano , late Renaissance painter and architect, the principal heir of Raphael, and one of the initiators of the Mannerist style.
Correggio , most important Renaissance painter of the school of Parma, whose late works influenced the style of many Baroque and Rococo artists. His first important works are the convent ceiling of San Paolo c. History at your fingertips. Sign up here to see what happened On This Day , every day in your inbox! Email address. Typically, a point spread has odds of for either side of the bet. In the example above between the Cowboys and Giants, the point spread is 4.
A losing bet is quite simply you betting on the Cowboys You lose the money that you placed on that bet. In these cases, there may not even be a point spread available for the game and you can only bet on the moneyline. This is a very common occurrence in sports betting and sportsbooks have the full right to shift the spread or odds for any given match prior to its start.
Many factors can influence a change of the spread such as injuries, the number of bets coming in for either team or the weather, to name a few. Depending on the timing of placing the bet, the bettor can also have an advantage or a disadvantage depending on which way the spread has shifted. If bettors had wagered on Dallas on Monday, that means they would be at a disadvantage compared to bettors who waited until Thursday because the Thursday bettors now only need Dallas to win by four points instead of five.
But it can also go the other way:. Yes, in fact, sportsbooks also release spreads for different points in the match like after the first quarter or first half, which is called live betting or in-game betting. As you can see, Dallas is a 2. Look for key numbers such as five and seven because they tend to represent two- and three-possession games.
In both cases, the spread is almost always If New York pulls off an outright upset, then that is also a winning wager. Need more winning picks? The handicapping, sports odds information contained on this website is for entertainment purposes only. Please confirm the wagering regulations in your jurisdiction as they vary from state to state, province to province and country to country.
Using this information to contravene any law or statute is prohibited. The site is not associated with nor is it endorsed by any professional or collegiate league, association or team.