CNN Architectures for Large-Scale Audio Classification

Convolutional Neural Networks (CNNs) have proven very effective in image classification and show promise for audio. We use various CNN architectures to classify the soundtracks of a dataset of 70M training videos (5.24 million hours) with 30,871 video-level labels. We examine fully connected Deep Neural Networks (DNNs), AlexNet [1], VGG [2], Inception [3], and ResNet [4]. We investigate varying the size of both training set and label vocabulary, finding that analogs of the CNNs used in image classification do well on our audio classification task, and larger training and label sets help up to a point. A model using embeddings from these classifiers does much better than raw features on the Audio Set [5] Acoustic Event Detection (AED) classification task.Comment: Accepted for publication at ICASSP 2017 Changes: Added definitions of mAP, AUC, and d-prime. Updated mAP/AUC/d-prime numbers for Audio Set based on changes of latest Audio Set revision. Changed wording to fit 4 page limit with new addition

White Lines and 3d-Occupancy for the 3d Transition-Metal Oxides

Electron energy-loss spectrometry was employed to measure the white lines at the L23 absorption edges of the 3d transition-metal oxides and lithium transition-metal oxides. The white-line ratio (L3/L2) was found to increase between d^0 and d^5 and decrease between d^5 and d^10, consistent with previous results for the transition metals and their oxides. The intensities of the white lines, normalized to the post-edge background, are linear for the 3d transition-metal oxides and lithium transition-metal oxides. An empirical correlation between normalized white-line intensity and 3d occupancy is established. It provides a method for measuring changes in the 3d-state occupancy. As an example, this empirical relationship is used to measure changes in the transition-metal valences of Li_{1-x}Ni_{0.8}Co_{0.2}O_2 in the range of 0 < x < 0.64. In these experiments the 3d occupancy of the nickel ion decreased upon lithium deintercalation, while the cobalt valence remained constant.Comment: 6 pages, 7 figure

No ecological opportunity signal on a continental scale?:Diversification and life-history evolution of african true toads (Anura: Bufonidae)

The niche-filling process predicted by the “ecological opportunity” (EO) model is an often-invoked mechanism for generating exceptional diversity in island colonizers. Whether the same process governs lineage accumulation and trait disparity during continental colonization events is less clear. Here, we test this prediction by investigating the rate dynamics and trait evolution of one of Africa's most widespread amphibian colonizers, the true toads (Bufonidae). By reconstructing the most complete molecular phylogeny of African Bufonidae to date, we find that the diversification of lineages in Africa best conforms to a constant rate model throughout time and across subclades, with little support for EO. Evolutionary rates of life-history traits have similarly been constant over time. However, an analysis of generalists and specialists showed a shift toward higher speciation rates associated with habitat specialization. The overall lack of EO signal can be interpreted in a number of ways and we propose several explanations. Firstly, methodological issues might preclude the detection of EO. Secondly, colonizers might not experience true EO conditions and due to the size, ecological heterogeneity and age of landmasses, the diversification processes might be more complex. Thirdly, lower speciation rates of habitat generalists may have affected overall proliferation of lineages

Ross Gyre variability modulates oceanic heat supply toward the West Antarctic continental shelf

C.J.P., G.A.M., M.R.M., L.D.T., and S.T.G. were supported by NSF PLR-1425989 and OPP-1936222 (Southern Ocean Carbon and Climate Observations and Modeling project). C.J.P. received additional support from a NOAA Climate & Global Change Postdoctoral Fellowship. G.A.M. received additional support from UKRI Grant Ref. MR/W013835/1. G.E.M. was supported by NSF OPP-2220969. R.Q.P. was supported by the High Meadows Environmental Institute Internship Program. R.M. was supported by the General Sir John Monash Foundation. A.F.T. was supported by NSF OPP-1644172 and NASA grant 80NSSC21K0916. M.R.M. also acknowledges funding from NSF awards OCE-1924388 and OPP-2319829 and NASA awards 80NSSC22K0387 and 80NSSC20K1076.West Antarctic Ice Sheet mass loss is a major source of uncertainty in sea level projections. The primary driver of this melting is oceanic heat from Circumpolar Deep Water originating offshore in the Antarctic Circumpolar Current. Yet, in assessing melt variability, open ocean processes have received considerably less attention than those governing cross-shelf exchange. Here, we use Lagrangian particle release experiments in an ocean model to investigate the pathways by which Circumpolar Deep Water moves toward the continental shelf across the Pacific sector of the Southern Ocean. We show that Ross Gyre expansion, linked to wind and sea ice variability, increases poleward heat transport along the gyre’s eastern limb and the relative fraction of transport toward the Amundsen Sea. Ross Gyre variability, therefore, influences oceanic heat supply toward the West Antarctic continental slope. Understanding remote controls on basal melt is necessary to predict the ice sheet response to anthropogenic forcing.Publisher PDFPeer reviewe

The Chagos Islands cases: the empire strikes back

Good governance requires the accommodation of multiple interests in the cause of decision making. However, undue regard for particular sectional interests can take their toll upon public faith in government administration. Historically, broad conceptions of the good of the commonwealth were employed to outweigh the interests of groups that resisted colonisation. In the decision making of the British Empire, the standard approach for justifying the marginalisation of the interests of colonised groups was that they were uncivilised and that particular hardships were the price to be paid for bringing to them the imperial dividend of industrial society. It is widely assumed that with the dismantling of the British Empire, such impulses and their accompanying jurisprudence became a thing of the past. Even as decolonisation proceeded apace after the Second World War, however, the United Kingdom maintained control of strategically important islands with a view towards sustaining its global role. In an infamous example from this twilight period of empire, in the 1960s imperial interests were used to justify the expulsion of the Chagos islanders from the British Indian Ocean Territory (BIOT). Into the twenty-first century, this forced elision of the UK’s interests with the imperial “common good” continues to take centre stage in courtroom battles over the islanders’ rights, being cited before domestic and international tribunals in order to maintain the Chagossians’ exclusion from their homeland. This article considers the new jurisprudence of imperialism which has emerged in a string of decisions which have continued to marginalise the Chagossians’ interests

Concurrent Inhibition of IGF1R and ERK Increases Pancreatic Cancer Sensitivity to Autophagy Inhibitors

The aggressive nature of pancreatic ductal adenocarcinoma (PDAC) mandates the development of improved therapies. As KRAS mutations are found in 95% of PDAC and are critical for tumor maintenance, one promising strategy involves exploiting KRAS-dependent metabolic perturbations. The macrometabolic process of autophagy is upregulated in KRAS-mutant PDAC, and PDAC growth is reliant on autophagy. However, inhibition of autophagy as monotherapy using the lysosomal inhibitor hydroxychloroquine (HCQ) has shown limited clinical efficacy. To identify strategies that can improve PDAC sensitivity to HCQ, we applied a CRISPR-Cas9 loss-of-function screen and found that a top sensitizer was the receptor tyrosine kinase (RTK) insulin-like growth factor 1 receptor (IGF1R). Additionally, reverse phase protein array pathway activation mapping profiled the signaling pathways altered by chloroquine (CQ) treatment. Activating phosphorylation of RTKs, including IGF1R, was a common compensatory increase in response to CQ. Inhibition of IGF1R increased autophagic flux and sensitivity to CQ-mediated growth suppression both in vitro and in vivo. Cotargeting both IGF1R and pathways that antagonize autophagy, such as ERK-MAPK axis, was strongly synergistic. IGF1R and ERK inhibition converged on suppression of glycolysis, leading to enhanced dependence on autophagy. Accordingly, concurrent inhibition of IGF1R, ERK, and autophagy induced cytotoxicity in PDAC cell lines and decreased viability in human PDAC organoids. In conclusion, targeting IGF1R together with ERK enhances the effectiveness of autophagy inhibitors in PDAC. Significance: Compensatory upregulation of IGF1R and ERK- MAPK signaling limits the efficacy of autophagy inhibitors chloroquine and hydroxychloroquine, and their concurrent inhibition synergistically increases autophagy dependence and chloroquine sensitivity in pancreatic ductal adenocarcinoma.Peer reviewe

M-Ras/R-Ras3, a Transforming Ras Protein Regulated by Sos1, GRF1, and p120 Ras GTPase-activating Protein, Interacts with the Putative Ras Effector AF6

M-Ras is a Ras-related protein that shares approximately 55% identity with K-Ras and TC21. The M-Ras message was widely expressed but was most predominant in ovary and brain. Similarly to Ha-Ras, expression of mutationally activated M-Ras in NIH 3T3 mouse fibroblasts or C2 myoblasts resulted in cellular transformation or inhibition of differentiation, respectively. M-Ras only weakly activated extracellular signal-regulated kinase 2 (ERK2), but it cooperated with Raf, Rac, and Rho to induce transforming foci in NIH 3T3 cells, suggesting that M-Ras signaled via alternate pathways to these effectors. Although the mitogen-activated protein kinase/ERK kinase inhibitor, PD98059, blocked M-Ras-induced transformation, M-Ras was more effective than an activated mitogen-activated protein kinase/ERK kinase mutant at inducing focus formation. These data indicate that multiple pathways must contribute to M-Ras-induced transformation. M-Ras interacted poorly in a yeast two-hybrid assay with multiple Ras effectors, including c-Raf-1, A-Raf, B-Raf, phosphoinositol-3 kinase delta, RalGDS, and Rin1. Although M-Ras coimmunoprecipitated with AF6, a putative regulator of cell junction formation, overexpression of AF6 did not contribute to fibroblast transformation, suggesting the possibility of novel effector proteins. The M-Ras GTP/GDP cycle was sensitive to the Ras GEFs, Sos1, and GRF1 and to p120 Ras GAP. Together, these findings suggest that while M-Ras is regulated by similar upstream stimuli to Ha-Ras, novel targets may be responsible for its effects on cellular transformation and differentiation

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

Ras-Related Small GTPases RalA and RalB Regulate Cellular Survival After Ionizing Radiation

Oncogenic activation of Ras renders cancer cells resistant to ionizing radiation (IR), but the mechanisms have not been fully characterized. The Ras-like small GTPases, RalA and RalB, are downstream effectors of Ras function and are critical for both tumor growth and survival. The Ral effector RalBP1/RLIP76 mediates survival of mice after whole body irradiation but the role of the Ral GTPases themselves in response to IR is unknown. We have investigated the role of RalA and RalB in cellular responses to IR