Taking a new global approach, this unique book provides an updated review of the geology of Iberia and its continental margins from a geodynamic perspective. Owing to its location close to successive plate margins, Iberia has played a pivotal role in the geodynamic evolution of the Gondwanan, Rheic, Pangea, Tethys s. The geological record starts with the amalgamation of Gondwana in the Neoproterozoic succeeded by the rifting and spreading of the Rheic ocean; its demise, which led to the amalgamation of Pangea in the late Paleozoic; the rifting and spreading of several arms of the Neotethys ocean in the Mesozoic Era and their ongoing closure, which was responsible for the Alpine orogeny.
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The significant advances in the last 20 years have attracted international research interest in the geology of the Iberian Peninsula. This volume presents the most comprehensive, careful and updated description of the variscan cycle in Iberia.
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This volume focuses in the different geological events since the Cambrian-Early Ordovician rift until the late variscan orocline formations including magmatic and metamorphic evolution. He is a geologist and is currently collaborating at Laboratorio Nacional de Energia e Geologia, former Geological Survey of Portugal, where he acted also as Head of the Geology and Mineral Resources departments.
At the time, he had little knowledge of biological sciences, but quickly got up to speed on the basics while working in the lab. As he gained a firm foundation of biological knowledge, he was in an excellent position to apply his machine learning expertise to biological problems, choosing for his PhD thesis the project of identifying additional drivers in breast cancer. Breast cancers like many other cancers are the result of what is called a somatic copy number alteration SCNA , which is a deletion or duplication of DNA within certain regions of the genome.
The marked region on the left is duplicated in the chromosome to the right.
Such alterations to the DNA may or may not lead to cancer. SCNAs are thought to recurrently affect close to regions of the genome; almost every cancer genome will harbor a few. Not all SCNAs are harmful or significant. Many are simply random background alterations that have no ill effect. For identifying significant SCNAs, there are existing algorithms but most lack the necessary resolution to identify driver regions small enough so it becomes possible to identify the single gene responsible for a cancer. Nor do SCNA-detection algorithms take into account that the alteration rate can differ greatly among different genomic regions; most including GISTIC2 compute a null distribution across the entire genome to estimate the significance of alterations, meaning each region is independently evaluated against a global absolute.
Sanchez-Garcia suspected some regions might not score highly against the global absolute score but would nevertheless be significantly more altered than adjacent chromosomal regions. This measure of local alteration became an additional data point for identifying possible regions harboring driver genes. Those regions found by ISAR included previously known regions as well as additional ones, including several containing known oncogenes genes having the potential to cause cancer , thus providing strong evidence that the algorithm was making accurate predictions.
Standard classification approaches rely on an initial list of sample drivers and passengers to train the model. The problem here is that the list of known drivers is relatively small and strongly biased also toward kinases and extreme phenotypes. Sanchez-Garcia opted for a different approach, one that would look to the data itself to determine significant features. This more data-centric approach of course works best when data is plentiful, which is not the case for any single cancer data source. The solution was to incorporate different data sources, measuring different aspects of each cancer to obtain a range of different data types.
One data source was the primary tumor data, which is measured directly from patient tumors. From this data source Sanchez-Garcia obtained copy number, point mutations, and gene expression levels. A second data source was from cell lines, which is data originally derived from tumors but modified for lab study. For cell lines, he derived copy number, gene expression levels, and functional RNAi screening data, which provides functional information about the genome by knocking out each individual gene in a cell line.
While previous methods had also integrated different data sources, particularly patient data and functional lab cell line, they tended to look for intersection between data sources, in effect narrowing the data by omitting non-overlapping data. Using the technique of transfer learning —where information learned in one task is applied to another—Sanchez-Garcia initiates Helios with a small number of likely drivers, specifically those nearest the most frequently altered segment of an ISAR-identified region. Taking an unbiased approach, Helios learns the features of these strong drivers, and then looks for complementary patterns from the additional genetic and genomic data to discover additional features.
If evidence for a feature in one data source is weak, it may be stronger in another.
In this way, drivers with clearer signal help learn features to improve performance in cases with less obvious signal. Together the different features identify drivers that one feature by itself could not. The first iteration picks up the strongest signals, and this information gets incorporated into the next iteration.
Each iteration thus incorporates the new information the model learned in the previous iteration to pick up additional signal.
Each subsequent iteration works off slightly more refined information than did the previous iteration. Helios keeps iterating through the data, producing drivers with a weaker but still distinct signal until there is no more signal to be found. It is a statistically rigorous framework for combining multiple signals that might lack power individually.
At the end, Helios produces a list of candidate drivers, ranked according to the probability each is a true cancer driver. Validation was systematic and comprehensive. He paced back to his holdall, and there was another snap of latex, then the bunk dipped again. Three fingers, and you will keep quite still throughout. Do you understand? Do not get it wrong again or your bottom pays the price. She braced, expecting pain. Three fingers, after all. He was remarkably gentle, his digits entering her with ease.
Jenna had expected something more…brutal. Instead, he slowly, firmly, drove his fingers in and out of her pussy, each stroke deep and penetrating, his hand twisting slightly to increase the friction, then sliding back to almost exit entirely. Jenna counted the strokes. Six times he plunged his fingers forward, six times he slowly withdrew.
Coming Together Presents: C. Sanchez-Garcia on Apple Books
She heard the unmistakable yet remarkable sound of her own wetness and wanted to weep at the betrayal. But still, were it not for the circumstances, this internal caress felt really very nice…. About Ashe Barker. She is a 1 Amazon Bestseller and all her stories feature hot alpha males and sassy submissives, often with a lot to learn.
However dark and dirty the setting, love always emerges triumphant, and her stories never fail to deliver a satisfying happy ever after. Social Media Links and Newsletter sign-up. Newsletter Sign-up. Saturday, June 29, Tit for Tat. In the opening story in my new collection, Spring Fever and Other Sapphic Encounters , two women who have been circling around each other in the same small community for 25 years finally have an over-the-top but still plausible I hope confrontation which leads to consensual sex.
When conflict is based on misunderstandings rooted in stereotypes attractive blondes are always racist snobs, butch women are as bad as uncouth men , honest communication can dissolve the tension, or at least this is my hope. Or the tension of hostility can transmute into the tension of lust. How often this works in real life is very debatable, as I think we all agree after almost a full month of discussion. However, in erotica, satisfying sex often looks like the answer to every problem.
She wished she knew enough about weapons to assess its capacity for doing harm. Even then, Cee remembered, the cute blonde had a sarcastic edge and a chess-player's talent for strategy that surprised everyone who met her for the first time. In the following years, Cee had survived the ageism and racism of the bar crowd, and the butch-phobia of the lesbian-feminist crowd, by being a clown, a trickster, the funniest person at every social event.
And Cee was still around, with no visible scars.
Four great pieces of erotic writing, and why they’re so good.
She tried again. They have to keep running from the cops. Just put the gun down, and we can talk. She pulled the trigger.
The blast tore a hole in the wood, close to the central point. Friday, June 28, Opposites Inside Me. Sacchi Green. We occasionally discuss how we put something of ourselves into our writing, whether consciously or not.
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