Learning to Approximate a Bregman Divergence

Bregman divergences generalize measures such as the squared Euclidean distance and the KL divergence, and arise throughout many areas of machine learning. In this paper, we focus on the problem of approximating an arbitrary Bregman divergence from supervision, and we provide a well-principled approach to analyzing such approximations. We develop a formulation and algorithm for learning arbitrary Bregman divergences based on approximating their underlying convex generating function via a piecewise linear function. We provide theoretical approximation bounds using our parameterization and show that the generalization error $O_p(m^{-1/2})$ for metric learning using our framework matches the known generalization error in the strictly less general Mahalanobis metric learning setting. We further demonstrate empirically that our method performs well in comparison to existing metric learning methods, particularly for clustering and ranking problems.Comment: 19 pages, 4 figure

Fiber-optic microarray for simultaneous detection of multiple harmful algal bloom species

Author Posting. © American Society for Microbiology, 2006. This article is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Applied and Environmental Microbiology 72 (2006): 5742-5749, doi:10.1128/AEM.00332-06.Harmful algal blooms (HABs) are a serious threat to coastal resources, causing a variety of impacts on public health, regional economies, and ecosystems. Plankton analysis is a valuable component of many HAB monitoring and research programs, but the diversity of plankton poses a problem in discriminating toxic from nontoxic species using conventional detection methods. Here we describe a sensitive and specific sandwich hybridization assay that combines fiber-optic microarrays with oligonucleotide probes to detect and enumerate the HAB species Alexandrium fundyense, Alexandrium ostenfeldii, and Pseudo-nitzschia australis. Microarrays were prepared by loading oligonucleotide probe-coupled microspheres (diameter, 3 μm) onto the distal ends of chemically etched imaging fiber bundles. Hybridization of target rRNA from HAB cells to immobilized probes on the microspheres was visualized using Cy3-labeled secondary probes in a sandwich-type assay format. We applied these microarrays to the detection and enumeration of HAB cells in both cultured and field samples. Our study demonstrated a detection limit of approximately 5 cells for all three target organisms within 45 min, without a separate amplification step, in both sample types. We also developed a multiplexed microarray to detect the three HAB species simultaneously, which successfully detected the target organisms, alone and in combination, without cross-reactivity. Our study suggests that fiber-optic microarrays can be used for rapid and sensitive detection and potential enumeration of HAB species in the environment.This work was funded by the Sea Grant Technology Program (NA16RG2273)

Development of microsatellite markers in the toxic dinoflagellate Alexandrium minutum (Dinophyceae)

Author Posting. © Blackwell, 2006. This is the author's version of the work. It is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Molecular Ecology Notes 6 (2006): 756-758, doi:10.1111/j.1471-8286.2006.01331.x.Outbreaks of paralytic shellfish poisoning caused by the toxic dinoflagellate Alexandrium minutum (Dinophyceae) are a worldwide concern from both the economic and human health points of view. For population genetic studies of A. minutum distribution and dispersal, highly polymorphic genetic markers are of great value. We isolated 12 polymorphic microsatellites from this cosmopolitan, toxic dinoflagellate species. These loci provide one class of highly variable genetic markers, as the number of alleles ranged from 4 to 12, and the estimate of gene diversity was from 0.560 to 0.862 across the 12 microsatellites; these loci have the potential to reveal genetic structure and gene flow among A. minutum populations.Support for this research provided in part (to DMA) by U.S. National Science Foundation grants OCE-0136861 and OCE-0430724, and the National Institute of Environmental Health Sciences Grant 1 P50 ES012742-01

Transcriptome profiling of a toxic dinoflagellate reveals a gene-rich protist and a potential impact on gene expression due to bacterial presence

© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 5 (2010): e9688, doi:10.1371/journal.pone.0009688.Dinoflagellates are unicellular, often photosynthetic protists that play a major role in the dynamics of the Earth's oceans and climate. Sequencing of dinoflagellate nuclear DNA is thwarted by their massive genome sizes that are often several times that in humans. However, modern transcriptomic methods offer promising approaches to tackle this challenging system. Here, we used massively parallel signature sequencing (MPSS) to understand global transcriptional regulation patterns in Alexandrium tamarense cultures that were grown under four different conditions. We generated more than 40,000 unique short expression signatures gathered from the four conditions. Of these, about 11,000 signatures did not display detectable differential expression patterns. At a p-value < 1E-10, 1,124 signatures were differentially expressed in the three treatments, xenic, nitrogen-limited, and phosphorus-limited, compared to the nutrient-replete control, with the presence of bacteria explaining the largest set of these differentially expressed signatures. Among microbial eukaryotes, dinoflagellates contain the largest number of genes in their nuclear genomes. These genes occur in complex families, many of which have evolved via recent gene duplication events. Our expression data suggest that about 73% of the Alexandrium transcriptome shows no significant change in gene expression under the experimental conditions used here and may comprise a “core” component for this species. We report a fundamental shift in expression patterns in response to the presence of bacteria, highlighting the impact of biotic interaction on gene expression in dinoflagellates.This work was primarily funded by a collaborative grant from the National Institutes of Health (R01 ES 013679-01A2) awarded to DB, DMA, and M. Bento Soares. Funding support for DMA and DLE was also provided from the Woods Hole Center for Oceans and Human Health from the NSF/NIEHS Centers for Oceans and Human Health program, NIEHS (P50 ES 012742) and (NSF OCE-043072). Additional support came from the National Science Foundation (EF-0732440) in a grant awarded to F. Gerald Plumley, DB, JDH, and DMA. AM was supported by an Institutional NRSA (T 32 GM98629)

Toxicity and pathophysiology of palytoxin congeners after intraperitoneal and aerosol administration in rats

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Toxicon 150 (2018): 235-250, doi:10.1016/j.toxicon.2018.06.067.Preparations of palytoxin (PLTX, derived from Japanese Palythoa tuberculosa) and the congeners 42-OH-PLTX (from Hawaiian P. toxica) and ovatoxin-a (isolated from a Japanese strain of Ostreopsis ovata), as well as a 50:50 mixture of PLTX and 42-OH-PLTX derived from Hawaiian P. tuberculosa were characterized as to their concentration, composition, in-vitro potency and interaction with an anti-PLTX monoclonal antibody (mAb), after which they were evaluated for lethality and pathophysiological effects by intraperitoneal (IP) and aerosol administration to rats. Once each preparation was characterized as to its toxin composition by LC-HRMS and normalized to a total PLTX/OVTX concentration using HPLC-UV, all four preparations showed similar potency towards mouse erythrocytes in the erythrocyte hemolysis assay and interactions with the anti-PLTX mAb. The IP LD50 values derived from these experiments (1-3 μg/kg for all) were consistent with published values, although some differences from the published literature were seen. The aerosol LD50 values (.03-.06 μg/kg) confirmed the exquisite potency of PLTX suggested by the literature. The pathophysiological effects of the different toxin preparations by IP and aerosol administration were similar, albeit with some differences. Most commonly affected tissues were the lungs, liver, heart, kidneys, salivary glands, and adrenal glands. Despite some differences, these results suggest commonalities in potency and mechanism of action among these PLTX congeners.This work was supported by the Defense Threat Reduction Agency, through the Joint Program Executive Office for Chemical and Biological Defense, Contract number CB10396. Additional support to DMA and DLK was provided by National Science Foundation (Grant OCE-1314642) and National Institutes of Health (NIEHS-1P50-ES021923-01) through the Woods Hole Center for Oceans and Human Health

Novel Catalysts and Processing Technologies for Production of Aerospace Fuels from Non-Petroleum Raw Materials

Transportation fuels production (including aerospace propellants) from non-traditional sources (gases, waste materials, and biomass) has been an active area of research and development for decades. Reducing terrestrial waste streams simultaneous with energy conversion, plentiful biomass, new low-cost methane sources, and/or extra-terrestrial resource harvesting and utilization present significant technological and business opportunities being realized by a new generation of visionary entrepreneurs. We examine several new approaches to catalyst fabrication and new processing technologies to enable utilization of these nontraditional raw materials. Two basic processing architectures are considered: a single-stage pyrolysis approach that seeks to basically re-cycle hydrocarbons with minimal net chemistry or a two-step paradigm that involves production of supply or synthesis gas (mainly carbon oxides and H2) followed by production of fuel(s) via Sabatier or methanation reactions and/or Fischer-Trpsch synthesis. Optimizing the fraction of product stream relevant to targeted aerospace (and other transportation) fuels via modeling, catalyst fabrication and novel reactor design are described. Energy utilization is a concern for production of fuels for either terrestrial or space operations; renewable sources based on solar energy and/or energy efficient processes may be mission enabling. Another important issue is minimizing impurities in the product stream(s), especially those potentially posing risks to personnel or operations through (catalyst) poisoning or (equipment) damage. Technologies being developed to remove (and/or recycle) heteroatom impurities are briefly discussed as well as the development of chemically robust catalysts whose activities are not diminished during operation. The potential impacts on future missions by such new approaches as well as balance of system issues are addressed

Effectiveness of the mantente REAL program for preventing alcohol use in spanish adolescents

Mantente REAL is a school-based universal program to prevent drug use and other problematic behaviors specifically designed to be implemented in schools at the beginning of adolescence. This program, which is a culturally adapted version of the Keepin’ it REAL intervention, focuses on skills training for resisting social pressure to use drugs and improving psychosocial development. This study aims to evaluate the effectiveness of Mantente REAL on alcohol use in the Spanish context. The sample was composed of 755 adolescents from 12 state secondary schools in Spain, aged 11 to 15 (M = 12.24, SD = 0.56), 47.1% females. The 12 schools were randomly assigned to control and experimental groups, six to each condition. Pre-test and post-test questionnaires data were collected to evaluate the effectiveness of the program. The results indicated that a culturally adapted version of Mantente REAL was effective in preventing alcohol use among youth from northern and southern Spain. Students participating in the program demonstrated changes in the desired direction on alcohol frequency and intoxication episodes. Implications of these results regarding intervention programs aimed at preventing substance use in adolescence are discussed“Mantente REAL” es un programa universal que utiliza la escuela para prevenir el consumo de drogas y otras conductas problemáticas diseñado específicamente para ser implementado en las escuelas al comienzo de la adolescencia. Este programa, que es una versión culturalmente adaptada de la intervención Keepin’ it REAL, se centra en el entrenamiento de habilidades para resistir la presión social para consumir drogas y mejorar el desarrollo psicosocial. Este estudio tiene como objetivo evaluar la eficacia de “Mantente REAL” en el consumo de alcohol en el contexto español. La muestra estuvo compuesta por 755 adolescentes de 12 escuelas secundarias públicas en España, de 11 a 15 años (M = 12.24, DT = 0.56), el 47.1% mujeres. Las 12 escuelas fueron asignadas aleatoriamente a grupo control y experimental, seis en cada condición. Los datos se recopilaron a través de cuestionarios antes y después de la intervención para evaluar la eficacia del programa. Los resultados indicaron que la versión culturalmente adaptada de “Mantente REAL” fue eficaz para prevenir el consumo de alcohol entre los jóvenes del norte y sur de España. Los estudiantes que participaron en el programa demostraron cambios en la dirección deseada en la frecuencia del alcohol y los episodios de intoxicación. Se discuten las implicaciones de estos resultados con respecto a los programas de intervención destinados a prevenir el consumo de sustancias en la adolescenciaThis study was funded by the Global Center for Applied Health Research (Arizona State University) and supported by the Programa de Axudas á etapa posdoutoral da Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) and by FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación (Grant PSI2015-65766-R) – under the Axuda para a consolidación e estruturación de unidades de investigación competitivas e outras accións de fomento nas universidades do SUG (GRC, 2018)S

Dihydrodinophysistoxin-1 produced by Dinophysis norvegica in the Gulf of Maine, USA and its accumulation in shellfish

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Deeds, J. R., Stutts, W. L., Celiz, M. D., MacLeod, J., Hamilton, A. E., Lewis, B. J., Miller, D. W., Kanwit, K., Smith, J. L., Kulis, D. M., McCarron, P., Rauschenberg, C. D., Burnell, C. A., Archer, S. D., Borchert, J., & Lankford, S. K. Dihydrodinophysistoxin-1 produced by Dinophysis norvegica in the Gulf of Maine, USA and its accumulation in shellfish. Toxins, 12(9), (2020): E533, doi:10.3390/toxins12090533.Dihydrodinophysistoxin-1 (dihydro-DTX1, (M-H)−m/z 819.5), described previously from a marine sponge but never identified as to its biological source or described in shellfish, was detected in multiple species of commercial shellfish collected from the central coast of the Gulf of Maine, USA in 2016 and in 2018 during blooms of the dinoflagellate Dinophysis norvegica. Toxin screening by protein phosphatase inhibition (PPIA) first detected the presence of diarrhetic shellfish poisoning-like bioactivity; however, confirmatory analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) failed to detect okadaic acid (OA, (M-H)−m/z 803.5), dinophysistoxin-1 (DTX1, (M-H)−m/z 817.5), or dinophysistoxin-2 (DTX2, (M-H)−m/z 803.5) in samples collected during the bloom. Bioactivity-guided fractionation followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) tentatively identified dihydro-DTX1 in the PPIA active fraction. LC-MS/MS measurements showed an absence of OA, DTX1, and DTX2, but confirmed the presence of dihydro-DTX1 in shellfish during blooms of D. norvegica in both years, with results correlating well with PPIA testing. Two laboratory cultures of D. norvegica isolated from the 2018 bloom were found to produce dihydro-DTX1 as the sole DSP toxin, confirming the source of this compound in shellfish. Estimated concentrations of dihydro-DTX1 were >0.16 ppm in multiple shellfish species (max. 1.1 ppm) during the blooms in 2016 and 2018. Assuming an equivalent potency and molar response to DTX1, the authority initiated precautionary shellfish harvesting closures in both years. To date, no illnesses have been associated with the presence of dihydro-DTX1 in shellfish in the Gulf of Maine region and studies are underway to determine the potency of this new toxin relative to the currently regulated DSP toxins in order to develop appropriate management guidance.Partial support for this research was received from the National Oceanic and Atmospheric Administration, National Centers for Coastal Ocean Science Competitive Research, Ecology and Oceanography of Harmful Algal Blooms Program under awards NA17NOS4780184 and NA19NOS4780182 to Juliette Smith (VIMS) and Jonathan Deeds (US FDA), and Prevention, Control, and Mitigation of Harmful Algal Blooms program award NA17NOS4780179 to Stephen Archer. This paper is ECOHAB publication number EC0956

Marine harmful algal blooms (HABs) in the united states: history, current status and future trends

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Anderson, D. M., Fensin, E., Gobler, C. J., Hoeglund, A. E., Hubbard, K. A., Kulis, D. M., Landsberg, J. H., Lefebvre, K. A., Provoost, P., Richlen, M. L., Smith, J. L., Solow, A. R., & Trainer, V. L. Marine harmful algal blooms (HABs) in the united states: history, current status and future trends. Harmful Algae, 102, (2021): 101975, https://doi.org/10.1016/j.hal.2021.101975.Harmful algal blooms (HABs) are diverse phenomena involving multiple. species and classes of algae that occupy a broad range of habitats from lakes to oceans and produce a multiplicity of toxins or bioactive compounds that impact many different resources. Here, a review of the status of this complex array of marine HAB problems in the U.S. is presented, providing historical information and trends as well as future perspectives. The study relies on thirty years (1990–2019) of data in HAEDAT - the IOC-ICES-PICES Harmful Algal Event database, but also includes many other reports. At a qualitative level, the U.S. national HAB problem is far more extensive than was the case decades ago, with more toxic species and toxins to monitor, as well as a larger range of impacted resources and areas affected. Quantitatively, no significant trend is seen for paralytic shellfish toxin (PST) events over the study interval, though there is clear evidence of the expansion of the problem into new regions and the emergence of a species that produces PSTs in Florida – Pyrodinium bahamense. Amnesic shellfish toxin (AST) events have significantly increased in the U.S., with an overall pattern of frequent outbreaks on the West Coast, emerging, recurring outbreaks on the East Coast, and sporadic incidents in the Gulf of Mexico. Despite the long historical record of neurotoxic shellfish toxin (NST) events, no significant trend is observed over the past 30 years. The recent emergence of diarrhetic shellfish toxins (DSTs) in the U.S. began along the Gulf Coast in 2008 and expanded to the West and East Coasts, though no significant trend through time is seen since then. Ciguatoxin (CTX) events caused by Gambierdiscus dinoflagellates have long impacted tropical and subtropical locations in the U.S., but due to a lack of monitoring programs as well as under-reporting of illnesses, data on these events are not available for time series analysis. Geographic expansion of Gambierdiscus into temperate and non-endemic areas (e.g., northern Gulf of Mexico) is apparent, and fostered by ocean warming. HAB-related marine wildlife morbidity and mortality events appear to be increasing, with statistically significant increasing trends observed in marine mammal poisonings caused by ASTs along the coast of California and NSTs in Florida. Since their first occurrence in 1985 in New York, brown tides resulting from high-density blooms of Aureococcus have spread south to Delaware, Maryland, and Virginia, while those caused by Aureoumbra have spread from the Gulf Coast to the east coast of Florida. Blooms of Margalefidinium polykrikoides occurred in four locations in the U.S. from 1921–2001 but have appeared in more than 15  U.S. estuaries since then, with ocean warming implicated as a causative factor. Numerous blooms of toxic cyanobacteria have been documented in all 50  U.S. states and the transport of cyanotoxins from freshwater systems into marine coastal waters is a recently identified and potentially significant threat to public and ecosystem health. Taken together, there is a significant increasing trend in all HAB events in HAEDAT over the 30-year study interval. Part of this observed HAB expansion simply reflects a better realization of the true or historic scale of the problem, long obscured by inadequate monitoring. Other contributing factors include the dispersion of species to new areas, the discovery of new HAB poisoning syndromes or impacts, and the stimulatory effects of human activities like nutrient pollution, aquaculture expansion, and ocean warming, among others. One result of this multifaceted expansion is that many regions of the U.S. now face a daunting diversity of species and toxins, representing a significant and growing challenge to resource managers and public health officials in terms of toxins, regions, and time intervals to monitor, and necessitating new approaches to monitoring and management. Mobilization of funding and resources for research, monitoring and management of HABs requires accurate information on the scale and nature of the national problem. HAEDAT and other databases can be of great value in this regard but efforts are needed to expand and sustain the collection of data regionally and nationally.Support for DMA, MLR, and DMK was provided through the Woods Hole Center for Oceans and Human Health (National Science Foundation grant OCE-1840381 and National Institutes of Health grants NIEHS‐1P01-ES028938–01) and the U.S. National Office for Harmful Algal Blooms with funding from NOAA's National Centers for Coastal Ocean Science (NCCOS) through the Cooperative Institute for the North Atlantic Region (CINAR) (NA14OAR4320158, NA19OAR4320074). Funding for KAL and DMA was provided by the National Oceanic and Atmospheric Administration National Centers for Coastal Ocean Science Competitive Research Program under award NA20NOS4780195 to the Woods Hole Oceanographic Institution and NOAA's Northwest Fisheries Science Center. We also acknowledge support for A.H. from the National Oceanic and Atmospheric Administration [NOAA] Office of Ocean and Coastal Resource Management Award NA19NOS4780183, C.J.G from NOAA-MERHAB (NA19NOS4780186) and (NA16NOS4780189) for VLT Support was also received for JLS, CJG, and VLT from NOAA-NCCOS-ECOHAB under awards NA17NOS4780184 and NA19NOS4780182. This is ECOHAB publication number ECO972

Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) has heterogeneous clinical and biological behavior. Whole-genome and -exome sequencing has contributed to the characterization of the mutational spectrum of the disease, but the underlying transcriptional profile is still poorly understood. We have performed deep RNA sequencing in different subpopulations of normal B-lymphocytes and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. We detected thousands of transcriptional elements differentially expressed between the CLL and normal B cells, including protein-coding genes, noncoding RNAs, and pseudogenes. Transposable elements are globally derepressed in CLL cells. In addition, two thousand genes-most of which are not differentially expressed-exhibit CLL-specific splicing patterns. Genes involved in metabolic pathways showed higher expression in CLL, while genes related to spliceosome, proteasome, and ribosome were among the most down-regulated in CLL. Clustering of the CLL samples according to RNA-seq derived gene expression levels unveiled two robust molecular subgroups, C1 and C2. C1/C2 subgroups and the mutational status of the immunoglobulin heavy variable (IGHV) region were the only independent variables in predicting time to treatment in a multivariate analysis with main clinico-biological features. This subdivision was validated in an independent cohort of patients monitored through DNA microarrays. Further analysis shows that B-cell receptor (BCR) activation in the microenvironment of the lymph node may be at the origin of the C1/C2 differences