Unsupervised decoding of long-term, naturalistic human neural recordings with automated video and audio annotations

Fully automated decoding of human activities and intentions from direct neural recordings is a tantalizing challenge in brain-computer interfacing. Most ongoing efforts have focused on training decoders on specific, stereotyped tasks in laboratory settings. Implementing brain-computer interfaces (BCIs) in natural settings requires adaptive strategies and scalable algorithms that require minimal supervision. Here we propose an unsupervised approach to decoding neural states from human brain recordings acquired in a naturalistic context. We demonstrate our approach on continuous long-term electrocorticographic (ECoG) data recorded over many days from the brain surface of subjects in a hospital room, with simultaneous audio and video recordings. We first discovered clusters in high-dimensional ECoG recordings and then annotated coherent clusters using speech and movement labels extracted automatically from audio and video recordings. To our knowledge, this represents the first time techniques from computer vision and speech processing have been used for natural ECoG decoding. Our results show that our unsupervised approach can discover distinct behaviors from ECoG data, including moving, speaking and resting. We verify the accuracy of our approach by comparing to manual annotations. Projecting the discovered cluster centers back onto the brain, this technique opens the door to automated functional brain mapping in natural settings

Vanadium Extraction and Recovery by Alkaline Heap Leaching of Mineralized Material from the Gibellini Project in Eureka County, Nevada

Vanadium is an important metal used in ferrous and non-ferrous alloys, industrial catalysts, pigments and dyes, and as a charge carrier in vanadium redox flow batteries. Demand for and price of vanadium have increased in recent years, primarily due to a greater global demand from China. As the need for grid-level energy storage continues to expand, the demand for vanadium to be used in redox flow batteries is expected to grow as well. Low cost methods for vanadium extraction and recovery are required to ensure a stable and economic supply of vanadium. This study demonstrates that alkaline heap leaching with sodium hydroxide may be a low-cost alternative to conventional vanadium extraction methods.Vanadium in an oxidized state is known to be soluble in alkaline solutions, and historically, vanadium has been leached from finely ground ores with solutions of soda ash or caustic soda. Alkaline heap leaching of cement agglomerated ore is a proven low-cost method that is commonly used for extraction of gold and silver. It is proposed that these two proven processes could be combined into a single low-cost and effective method for vanadium extraction. In this work, this theoretical process was simulated at a laboratory scale to extract vanadium from a vanadium-bearing sample of mineralized material from the Gibellini Hill project in Eureka county, Nevada. At a commercial scale, this process would consist of cement agglomeration of a crushed vanadium ore and stacking in a heap, irrigation with sodium hydroxide solution, neutralization of the solution to remove impurities, and solvent extraction to upgrade the solution and further reject impurities. In a commercial circuit, vanadium from this solution would then be precipitated in an insoluble form such as ammonium metavanadate; however, this final step was not tested here. When simulating this process in the laboratory by column leach testing, a 68.8% vanadium extraction was observed in 44 days of leaching and rinsing. The primary impurities observed in the leach solution were aluminum and phosphorous. Aluminum was effectively removed by neutralizing the solution pH to 10 or lower, while phosphorous was rejected during solvent extraction processing. It was demonstrated that the vanadium contained in the leach solution could readily be extracted using Aliquat 336 based solvents. An extraction of 98.6% was observed, and a highly pure strip solution was produced by stripping the loaded organic with strong caustic solution. Sulfuric acid leaching is more commonly used for extraction of vanadium from its mineral sources, but alkaline leaching can have many benefits relative to acid leaching, including improved selectivity. The improved selectivity was demonstrated in this work using multi element analysis of pregnant solutions generated from both processes. In a heap leaching circuit, alkaline leaching would also enable the use of cement during agglomeration, which increases the strength of agglomerates and in turn reduces the risk of heap “ponding”. This may allow the leaching of ores with high clay contents that would not otherwise be suitable for heap leaching. Alkaline heap leaching may be especially suitable for vanadium ores that contain significant quantities of carbonate minerals, which would not respond well to sulfuric acid heap leaching due to excessive acid consumption. Unfortunately, these benefits do not come without compromise. Overall, vanadium solubility is somewhat lower in alkaline solution than in acidic. This was also demonstrated in this work. A tradeoff analysis will be required to determine what processing method is optimum for a given vanadium resource, however, this work shows that alkaline heap leaching is an option that should be considered. It should be noted that not all mineral occurrences of vanadium are expected to be soluble in alkaline solution, so laboratory testing will always be required to evaluate the utility of this process for a given ore

Cumulative Shear In Vitro Model

The purpose of our project is to find a reliable method of Subclinical Atherosclerosis detection by measuring the pressure drop across an artery. This model is intended to display how a pressure change correlates with arterial shear rate, and how a decrease in shear rate is ultimately related to atherosclerosis wherein early detection could prove life saving for millions of patients worldwide

Investigation of the 2006 Drought and 2007 Flood Extremes at the Southern Great Plains Through an Integrative Analysis of Observations

Hydrological years 2006 (HY06, 10/2005-09/2006) and 2007 (HY07, 10/2006-09/2007) provide a unique opportunity to examine hydrological extremes in the central US because there are no other examples of two such highly contrasting precipitation extremes occurring in consecutive years at the Southern Great Plains (SGP) in recorded history. The HY06 annual precipitation in the state of Oklahoma, as observed by the Oklahoma Mesonet, is around 61% of the normal (92.84 cm, based on the 1921-2008 climatology), which results in HY06 the second-driest year in the record. In particular, the total precipitation during the winter of 2005-06 is only 27% of the normal, and this winter ranks as the driest season. On the other hand, the HY07 annual precipitation amount is 121% of the normal and HY07 ranks as the seventh-wettest year for the entire state and the wettest year for the central region of the state. Summer 2007 is the second-wettest season for the state. Large-scale dynamics play a key role in these extreme events. During the extreme dry period (10/2005-02/2006), a dipole pattern in the 500-hPa GH anomaly existed where an anomalous high was over the southwestern U.S. region and an anomalous low was over the Great Lakes. This pattern is associated with inhibited moisture transport from the Gulf of Mexico and strong sinking motion over the SGP, both contributing to the extreme dryness. The precipitation deficit over the SGP during the extreme dry period is clearly linked to significantly suppressed cyclonic activity over the southwestern U.S., which shows robust relationship with the Western Pacific (WP) teleconnection pattern. The precipitation events during the extreme wet period (May-July 2007) were initially generated by active synoptic weather patterns, linked with moisture transport from the Gulf of Mexico by the northward low level jet, and enhanced by the mesoscale convective systems. Although the drought and pluvial conditions are dominated by large-scale dynamic patterns, we have demonstrated that the two positive feedback processes during the extreme dry and wet periods found in this study play a key role to maintain and reinforce the length and severity of existing drought and flood events. For example, during the extreme dry period, with less clouds, LWP, PWV, precipitation, and thinner Cu cloud thickness, more net radiation was absorbed and used to evaporate water from the ground. The evaporated moisture, however, was removed by low-level divergence. Thus, with less precipitation and removed atmospheric moisture, more absorbed incoming solar radiation was used to increase surface temperature and to make the ground drier

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Pathway to Hope: an indigenous approach to healing child sexual abuse

BackgroundThe Alaska Native (AN) population has endured multiple historical traumatic events. This population has poorer health outcomes on nearly all factors compared with Alaska non-Natives with more than 75% reportedly being physically assaulted in their lifetime, and child sexual abuse nearly 6 times the national average.ObjectiveThis article describes the Pathway to Hope (PTH) program, which is an indigenous approach to ending silence and denial related to child sexual abuse and encourages multigenerational healing.DesignPTH was developed by ANs who believe that each community is unique, thus strategies for ending denial and support for healing must be woven from the historical context, cultural strengths of individual communities. Strengths-based solutions built on truth, honesty, compassion and shared responsibility for healing and protecting today's children have been profound and successful.The PTH curriculum addresses child sexual abuse from a historical perspective; that the higher rates of sexual abuse among certain Tribes, regions and communities is linked in part to years of victimisation, but may also be perpetuated by internalised oppression and lateral violence among Tribal members.ResultsData suggest that community-based dialogue and wisdom of Native elders and spiritual leaders paired with readiness of community service providers are necessary for sustained change. At all levels, this Indigenous model for learning, sharing, helping and healing brings hope for an end to denial and silence about child sexual abuse for Native people.ConclusionThe PTH program utilises the wisdom and values that have sustained Native people for generations. Ending silence and denial about child sexual abuse and building upon strengths have assisted many Indigenous communities begin the journey toward wellness. Through the PTH, communities have taken steps to accept the challenges associated with establishing safety for children, supporting child victims in healing and to holding offenders accountable

Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions

<p>Abstract</p> <p>Background</p> <p>Although exposure to asbestos is now regulated, patients continue to be diagnosed with mesothelioma, asbestosis, fibrosis and lung carcinoma because of the long latent period between exposure and clinical disease. Asbestosis is observed in approximately 200,000 patients annually and asbestos-related deaths are estimated at 4,000 annually<abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Although advances have been made using single gene/gene product or pathway studies, the complexity of the response to asbestos and the many unanswered questions suggested the need for a systems biology approach. The objective of this study was to generate a comprehensive view of the transcriptional changes induced by crocidolite asbestos in A549 human lung epithelial cells.</p> <p>Results</p> <p>A statistically robust, comprehensive data set documenting the crocidolite-induced changes in the A549 transcriptome was collected. A systems biology approach involving global observations from gene ontological analyses coupled with functional network analyses was used to explore the effects of crocidolite in the context of known molecular interactions. The analyses uniquely document a transcriptome with function-based networks in cell death, cancer, cell cycle, cellular growth, proliferation, and gene expression. These functional modules show signs of a complex interplay between signaling pathways consisting of both novel and previously described asbestos-related genes/gene products. These networks allowed for the identification of novel, putative crocidolite-related genes, leading to several new hypotheses regarding genes that are important for the asbestos response. The global analysis revealed a transcriptome that bears signatures of both apoptosis/cell death and cell survival/proliferation.</p> <p>Conclusion</p> <p>Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1) identify and explore relationships between genes of known importance 2) identify novel candidate genes, and 3) observe the complex interplay between genes/gene products that function in seemingly different processes. This study represents the first function-based global approach toward understanding the response of human lung epithelial cells to the carcinogen crocidolite. Importantly, our investigation paints a much broader landscape for the crocidolite response than was previously appreciated and reveals novel paths to study. Our graphical representations of the function-based global network will be a valuable resource to model new research findings.</p

Pharmacokinetics and pharmacodynamics of antifungals in children and their clinical implications

Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of the polyene amphotericin B have substantially reduced the toxicity associated with the traditional amphotericin B formulation. Monotherapy with the pyrimidine analogue flucytosine rapidly promotes the emergence of resistance and cannot be recommended. However, when used in combination with other antifungal agents, therapeutic drug monitoring of flucytosine has been shown to reduce high peak flucytosine concentrations, which are strongly associated with toxicity. The triazoles feature large inter-individual pharmacokinetic variability, although this pattern is less pronounced with fluconazole. In clinical trials, posaconazole was associated with fewer adverse effects than other members of the triazole family, though both posaconazole and itraconazole display erratic absorption that is influenced by gastric pH and the gastric emptying rate. Limited data suggest that the clinical response to therapy may be improved with higher plasma posaconazole and itraconazole concentrations. For voriconazole, pharmacokinetic studies among children have revealed that children require twice the recommended adult dose to achieve comparable blood concentrations. Voriconazole clearance is also affected by the cytochrome P450 (CYP) 2C19 genotype and hepatic impairment. Therapeutic drug monitoring is recommended as voriconazole pharmacokinetics are highly variable and small dose increases can result in marked changes in plasma concentrations. For the echinocandins, the primary source of pharmacokinetic variability stems from an age-dependent decrease in clearance with increasing age. Consequently, young children require larger doses per kilogram of body weight than older children and adults. Routine therapeutic drug monitoring for the echinocandins is not recommended. The effectiveness of many systemic antifungal agents has been correlated with pharmacodynamic targets in in vitro and in murine models of invasive candidiasis and aspergillosis. Further study is needed to translate these findings into optimal dosing regimens for children and to understand how these agents interact when multiple antifungal agents are used in combination

Community Engagement, Advocacy, and the Application of Science in the Boise River Basin

This poster was presented at the 2016 Idaho EPSCoR Annual Meeting, October 19-21, in Couer d\u27Alene Idaho