The Computational Philosophy: Simulation as a Core Philosophical Method

Modeling and computer simulations, we claim, should be considered core philosophical methods. More precisely, we will defend two theses. First, philosophers should use simulations for many of the same reasons we currently use thought experiments. In fact, simulations are superior to thought experiments in achieving some philosophical goals. Second, devising and coding computational models instill good philosophical habits of mind. Throughout the paper, we respond to the often implicit objection that computer modeling is "not philosophical.

Balancing end-to-end budgets of the Georges Bank ecosystem

Author Posting. © Elsevier, 2007. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Progress In Oceanography 74 (2007): 423-448, doi:10.1016/j.pocean.2007.05.003.Oceanographic regimes on the continental shelf display a great range in the time scales of physical exchange, biochemical processes and trophic transfers. The close surface-to-seabed physical coupling at intermediate scales of weeks to months means that the open ocean simplification to a purely pelagic food web is inadequate. Top-down trophic depictions, starting from the fish populations, are insufficient to constrain a system involving extensive nutrient recycling at lower trophic levels and subject to physical forcing as well as fishing. These pelagic-benthic interactions are found on all continental shelves but are particularly important on the relatively shallow Georges Bank in the northwest Atlantic. We have generated budgets for the lower food web for three physical regimes (well mixed, transitional and stratified) and for three seasons (spring, summer and fall/winter). The calculations show that vertical mixing and lateral exchange between the three regimes are important for zooplankton production as well as for nutrient input. Benthic suspension feeders are an additional critical pathway for transfers to higher trophic levels. Estimates of production by mesozooplankton, benthic suspension feeders and deposit feeders, derived primarily from data collected during the GLOBEC years of 1995-1999, provide input to an upper food web. Diets of commercial fish populations are used to calculate food requirements in three fish categories, planktivores, benthivores and piscivores, for four decades, 1963-2002, between which there were major changes in the fish communities. Comparisons of inputs from the lower web with fish energetic requirements for plankton and benthos indicate that we obtained reasonable agreement for the last three decades, 1973 to 2002. However, for the first decade, the fish food requirements were significantly less than the inputs. This decade, 1963-1972, corresponds to a period characterized by a strong Labrador Current and lower nitrate levels at the shelf edge, demonstrating how strong bottom-up physical forcing may determine overall fish yields.The research was done under the aegis of the U.S.-GLOBEC Northwest Atlantic Georges Bank Study, a program sponsored jointly by the U.S. National Science Foundation and the U.S. National Oceanic and Atmospheric Administration. We acknowledge NOAA-CICOR award NA17RJ1233 (J.H. Steele), NSF awards OCE0217399 (D.J. Gifford), OCE0217122 (J.J. Bisagni) and OCE0217257 (M.E. Sieracki). W.T. Stockhausen was supported by the NOAA Sponsored Coastal Ocean Research Program

Observing Supermassive Black Holes across cosmic time: from phenomenology to physics

In the last decade, a combination of high sensitivity, high spatial resolution observations and of coordinated multi-wavelength surveys has revolutionized our view of extra-galactic black hole (BH) astrophysics. We now know that supermassive black holes reside in the nuclei of almost every galaxy, grow over cosmological times by accreting matter, interact and merge with each other, and in the process liberate enormous amounts of energy that influence dramatically the evolution of the surrounding gas and stars, providing a powerful self-regulatory mechanism for galaxy formation. The different energetic phenomena associated to growing black holes and Active Galactic Nuclei (AGN), their cosmological evolution and the observational techniques used to unveil them, are the subject of this chapter. In particular, I will focus my attention on the connection between the theory of high-energy astrophysical processes giving rise to the observed emission in AGN, the observable imprints they leave at different wavelengths, and the methods used to uncover them in a statistically robust way. I will show how such a combined effort of theorists and observers have led us to unveil most of the SMBH growth over a large fraction of the age of the Universe, but that nagging uncertainties remain, preventing us from fully understating the exact role of black holes in the complex process of galaxy and large-scale structure formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and Treves A. (Eds), 2015, Springer International Publishing AG, Cha

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL-1 ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.info:eu-repo/semantics/publishedVersio

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy