BlinkML: Efficient Maximum Likelihood Estimation with Probabilistic Guarantees

The rising volume of datasets has made training machine learning (ML) models a major computational cost in the enterprise. Given the iterative nature of model and parameter tuning, many analysts use a small sample of their entire data during their initial stage of analysis to make quick decisions (e.g., what features or hyperparameters to use) and use the entire dataset only in later stages (i.e., when they have converged to a specific model). This sampling, however, is performed in an ad-hoc fashion. Most practitioners cannot precisely capture the effect of sampling on the quality of their model, and eventually on their decision-making process during the tuning phase. Moreover, without systematic support for sampling operators, many optimizations and reuse opportunities are lost. In this paper, we introduce BlinkML, a system for fast, quality-guaranteed ML training. BlinkML allows users to make error-computation tradeoffs: instead of training a model on their full data (i.e., full model), BlinkML can quickly train an approximate model with quality guarantees using a sample. The quality guarantees ensure that, with high probability, the approximate model makes the same predictions as the full model. BlinkML currently supports any ML model that relies on maximum likelihood estimation (MLE), which includes Generalized Linear Models (e.g., linear regression, logistic regression, max entropy classifier, Poisson regression) as well as PPCA (Probabilistic Principal Component Analysis). Our experiments show that BlinkML can speed up the training of large-scale ML tasks by 6.26x-629x while guaranteeing the same predictions, with 95% probability, as the full model.Comment: 22 pages, SIGMOD 201

3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell

The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes

Kinetics of thyroxine (T-4) and triiodothyronine (T-3) transport in the isolated rat heart

The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of I-125-thyroxine (I-115-T-4) and I-125-triiodothyronine (I-125-T-3) from the extracellular space into heart cells was measured relative to the extracellular space marker H-3-mannitol. The thyroid hormone maximal uptake was 54.4 % for I-125-T-4 and 52.15 % for I-125-T-3. The thyroid hormone net uptake was 25.69 % for I-125-T-4 and 25.49 % for I-125-T-3. Backflux from the intracellular space was 53.17 % for I-125-T-4 and 61.59 % for I-125-T-3. In the presence of unlabelled thyroid hormones, I-125-T-4 and I-125-T-3 maximal uptakes were reduced from 10.1 to 59.74 % and from 34.6 to 65.3 %, respectively, depending on the concentration of the unlabelled hormone, suggesting a saturable mechanism of the thyroid hormone uptake by the heart cells, with K-m(T4) = 105.46 muM and the maximal rate of I-125-thyroid hormone flax from the extracellular space to heart cells (V-max(T4))= 177.84 nM min(-1) for I-125-T-4 uptake, and K-m(T3) = 80.0 muM and V-max(T3) = 118.5 nM min(-1) for I-125-T-3 uptake

Structural basis for HIV-1 capsid adaption to a deficiency in IP6 packaging

Inositol hexakisphosphate (IP6) promotes HIV-1 assembly by stabilizing the immature Gag lattice and becomes enriched within virions, where it is required for mature capsid assembly. Previously, we identified Gag mutants that package little IP6 yet assemble particles, though they are non-infectious due to defective capsid formation. Here, we report a compensatory mutation, G225R, in the C-terminus of capsid protein (CA) that restores capsid assembly and infectivity in these IP6-deficient mutants. G225R also enhances in vitro assembly of CA into capsid-like particles at far lower IP6 concentrations than required for wild-type CA. CryoEM structures of G225R CA hexamers and lattices at 2.7 Å resolution reveal that the otherwise disordered C-terminus becomes structured, stabilizing hexamer-hexamer interfaces. Molecular dynamics simulations support this mechanism. These findings uncover how HIV-1 can adapt to IP6 deficiency and highlight a previously unrecognized structural role of the CA C-terminus, while offering tools for capsid-related studies

New insights into the magmatic-hydrothermal system and volatile budget of Lastarria volcano, Chile: Integrated results from the 2014 IAVCEI CCVG 12th Volcanic Gas Workshop.

Recent geophysical evidence for large-scale regional crustal inflation and localized crustal magma intrusion has made Lastarria volcano (northern Chile) the target of numerous geological, geophysical, and geochemical studies. The chemical composition of volcanic gases sampled during discrete campaigns from Lastarria volcano indicated a well-developed hydrothermal system from direct fumarole samples in A.D. 2006, 2008, and 2009, and shallow magma degassing using measurements from in situ plume sampling techniques in 2012. It is unclear if the differences in measured gas compositions and resulting interpretations were due to artifacts of the different sampling methods employed, short-term excursions from baseline due to localized changes in stress, or a systematic change in Lastarria's magmatic-hydrothermal system between 2009 and 2012. Integrated results from a two-day volcanic gas sampling and measurement campaign during the 2014 International Association of Volcanology and Chemistry of the Earth's Interior (IAVCEI) Commission on the Chemistry of Volcanic Gases (CCVG) 12th Gas Workshop are used here to compare and evaluate current gas sampling and measurement techniques, refine the existing subsurface models for Lastarria volcano, and provide new constraints on its magmatic-hydrothermal system and total degassing budget. While compositional differences among sampling methods are present, distinct compositional changes are observed, which if representative of longterm trends, indicate a change in Lastarria's overall magmatic-hydrothermal system. The composition of volcanic gases measured in 2014 contained high proportions of relatively magma- and water-soluble gases consistent with degassing of shallow magma, and in agreement with the 2012 gas composition. When compared with gas compositions measured in 2006-2009, higher relative H2O/CO2 ratios combined with lower relative CO2/St and H2O/St and stable HCl/St ratios (where St is total S [SO2 + H2S]) are observed in 2012 and 2014. These compositional changes suggest variations in the magmatic-hydrothermal system between 2009 and 2012, with possible scenarios to explain these trends including: (1) decompression-induced degassing due to magma ascent within the shallow crust; (2) crystallization-induced degassing of a stalled magma body; (3) depletion of the hydrothermal system due to heating, changes in local stress, and/or minimal precipitation; and/or (4) acidification of the hydrothermal system. These scenarios are evaluated and compared against the geophysical observations of continuous shallow inflation at ~8 km depth between 1997 and 2016, and near-surface ( < 1 km) inflation between 2000 and 2008, to further refine the existing subsurface models. Higher relative H2O/CO2 observed in 2012 and 2014 is not consistent with the depletion or acidification of a hydrothermal system, while all other observations are consistent with the four proposed models. Based on these observations, we find that scenarios 1 or 2 are the most likely to explain the geochemical and geophysical observations, and propose that targeted shallow interferometric synthetic-aperture radar (InSAR) studies could help discriminate between these two scenarios. Lastly, we use an average SO2 flux of 604 \ub1 296 t/d measured on 22 November 2014, along with the average gas composition and diffuse soil CO2 flux measurements, to estimate a total volatile flux from Lastarria volcano in 2014 of ~12,400 t/d, which is similar to previous estimates from 2012

Toward visualization of nanomachines in their native cellular environment

The cellular nanocosm is made up of numerous types of macromolecular complexes or biological nanomachines. These form functional modules that are organized into complex subcellular networks. Information on the ultra-structure of these nanomachines has mainly been obtained by analyzing isolated structures, using imaging techniques such as X-ray crystallography, NMR, or single particle electron microscopy (EM). Yet there is a strong need to image biological complexes in a native state and within a cellular environment, in order to gain a better understanding of their functions. Emerging methods in EM are now making this goal reachable. Cryo-electron tomography bypasses the need for conventional fixatives, dehydration and stains, so that a close-to-native environment is retained. As this technique is approaching macromolecular resolution, it is possible to create maps of individual macromolecular complexes. X-ray and NMR data can be ‘docked’ or fitted into the lower resolution particle density maps to create a macromolecular atlas of the cell under normal and pathological conditions. The majority of cells, however, are too thick to be imaged in an intact state and therefore methods such as ‘high pressure freezing’ with ‘freeze-substitution followed by room temperature plastic sectioning’ or ‘cryo-sectioning of unperturbed vitreous fully hydrated samples’ have been introduced for electron tomography. Here, we review methodological considerations for visualizing nanomachines in a close-to-physiological, cellular context. EM is in a renaissance, and further innovations and training in this field should be fully supported