Stocator: A High Performance Object Store Connector for Spark

We present Stocator, a high performance object store connector for Apache Spark, that takes advantage of object store semantics. Previous connectors have assumed file system semantics, in particular, achieving fault tolerance and allowing speculative execution by creating temporary files to avoid interference between worker threads executing the same task and then renaming these files. Rename is not a native object store operation; not only is it not atomic, but it is implemented using a costly copy operation and a delete. Instead our connector leverages the inherent atomicity of object creation, and by avoiding the rename paradigm it greatly decreases the number of operations on the object store as well as enabling a much simpler approach to dealing with the eventually consistent semantics typical of object stores. We have implemented Stocator and shared it in open source. Performance testing shows that it is as much as 18 times faster for write intensive workloads and performs as much as 30 times fewer operations on the object store than the legacy Hadoop connectors, reducing costs both for the client and the object storage service provider

An N-terminal clamp restrains the motor domains of the bacterial transcription-repair coupling factor Mfd

Motor proteins that translocate on nucleic acids are key players in gene expression and maintenance. While the function of these proteins is diverse, they are driven by highly conserved core motor domains. In transcription-coupled DNA repair, motor activity serves to remove RNA polymerase stalled on damaged DNA, making the lesion accessible for repair. Structural and biochemical data on the bacterial transcription-repair coupling factor Mfd suggest that this enzyme undergoes large conformational changes from a dormant state to an active state upon substrate binding. Mfd can be functionally dissected into an N-terminal part instrumental in recruiting DNA repair proteins (domains 1–3, MfdN), and a C-terminal part harboring motor activity (domains 4–7, MfdC). We show that isolated MfdC has elevated ATPase and motor activities compared to the full length protein. While MfdN has large effects on MfdC activity and thermostability in cis, these effects are not observed in trans. The structure of MfdN is independent of interactions with MfdC, implying that MfdN acts as a clamp that restrains motions of the motor domains in the dormant state. We conclude that releasing MfdN:MfdC interactions serves as a central molecular switch that upregulates Mfd functions during transcription-coupled DNA repair

Requirement of transcription factor NFAT in developing atrial myocardium

Nuclear factor of activated T cell (NFAT) is a ubiquitous regulator involved in multiple biological processes. Here, we demonstrate that NFAT is temporally required in the developing atrial myocardium between embryonic day 14 and P0 (birth). Inhibition of NFAT activity by conditional expression of dominant-negative NFAT causes thinning of the atrial myocardium. The thin myocardium exhibits severe sarcomere disorganization and reduced expression of cardiac troponin-I (cTnI) and cardiac troponin-T (cTnT). Promoter analysis indicates that NFAT binds to and regulates transcription of the cTnI and the cTnT genes. Thus, regulation of cytoskeletal protein gene expression by NFAT may be important for the structural architecture of the developing atrial myocardium

How to Constrain Your M Dwarf. II. The Mass–Luminosity–Metallicity Relation from 0.075 to 0.70 Solar Masse

The mass-luminosity relation for late-type stars has long been a critical tool for estimating stellar masses. However, there is growing need for both a higher-precision relation and a better understanding of systematic effects (e.g., metallicity). Here we present an empirical relationship between Mks and mass spanning $0.075M_\odot<M<0.70M_\odot$. The relation is derived from 62 nearby binaries, whose orbits we determine using a combination of Keck/NIRC2 imaging, archival adaptive optics data, and literature astrometry. From their orbital parameters, we determine the total mass of each system, with a precision better than 1% in the best cases. We use these total masses, in combination with resolved Ks magnitudes and system parallaxes, to calibrate the mass-Mks relation. The result can be used to determine masses of single stars with a precision of 2-3%, which we confirm by a comparison to dynamical masses from the literature. The precision is limited by scatter around the best-fit relation beyond mass uncertainties, perhaps driven by intrinsic variation in the mass-Mks relation or underestimated measurement errors. We find the effect of [Fe/H] on the mass-Mks relation is likely negligible for metallicities in the Solar neighborhood (0.0+/-2.2% change in mass per dex change in [Fe/H]). This weak effect is consistent with predictions from the Dartmouth Stellar Evolution Database, but inconsistent with those from MESA Isochrones and Stellar Tracks. A sample of binaries with a wider range of abundances will be required to discern the importance of metallicity in extreme populations (e.g., in the Galactic Halo or thick disk).Comment: Published in ApJ/AAS Journals. Comments welcome. Code for computing mass posteriors from Ks+distance at https://github.com/awmann/M_-M_K

Development of a "Survival" Guide for Substance Users in Harlem, New York City

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40382/2/Factor_Development of a Survival Guide_2002.pd

Association between essential tremor and blood lead concentration

Lead is a ubiquitous toxicant that causes tremor and cerebellar damage. Essential tremor (ET) is a highly prevalent neurologic disease associated with cerebellar involvement. Although environmental toxicants may play a role in ET etiology and their identification is a critical step in disease prevention, these toxicants have received little attention. Our objective was to test the hypothesis that ET is associated with lead exposure. Therefore, blood lead (BPb) concentrations were measured and a lifetime occupational history was assessed in ET patients and in controls. We frequency matched 100 ET patients and 143 controls on age, sex, and ethnicity. BPb concentrations were analyzed using graphite furnace atomic absorption spectrophotometry. A lifetime occupational history was reviewed by an industrial hygienist. BPb concentrations were higher in ET patients than in controls (mean ± SD, 3.3 ± 2.4 and 2.6 ± 1.6 µg/dL, respectively; median, 2.7 and 2.3 µg/dL; p = 0.038). In a logistic regression model, BPb concentration was associated with diagnosis [control vs. ET patient, odds ratio (OR) per unit increase = 1.21; 95% confidence interval (CI), 1.05-1.39; p = 0.007]. BPb concentration was associated with diagnosis (OR per unit increase = 1.19; 95% CI, 1.03-1.37; p = 0.02) after adjusting for potential confounders. Prevalence of lifetime occupational lead exposure was similar in ET patients and controls. We report an association between BPb concentration and ET. Determining whether this association is due to increased exposure to lead or a difference in lead kinetics in ET patients requires further investigation

How to Constrain Your M Dwarf. II. the Mass-Luminosity-Metallicity Relation from 0.075 to 0.70 Solar Masses

The mass–luminosity relation for late-type stars has long been a critical tool for estimating stellar masses. However, there is growing need for both a higher-precision relation and a better understanding of systematic effects (e.g., metallicity). Here we present an empirical relationship between MKS and M* spanning 0.075 Me < M* < 0.70 Me. The relation is derived from 62 nearby binaries, whose orbits we determine using a combination of Keck/NIRC2 imaging, archival adaptive optics data, and literature astrometry. From their orbital parameters, we determine the total mass of each system, with a precision better than 1% in the best cases. We use these total masses, in combination with resolved KS magnitudes and system parallaxes, to calibrate the MKS–M* relation. The resulting posteriors can be used to determine masses of single stars with a precision of 2%–3%, which we confirm by testing the relation on stars with individual dynamical masses from the literature. The precision is limited by scatter around the best-fit relation beyond measured M* uncertainties, perhaps driven by intrinsic variation in the MKS–M* relation or underestimated uncertainties in the input parallaxes. We find that the effect of [Fe/H] on the MKS–M* relation is likely negligible for metallicities in the solar neighborhood (0.0% ± 2.2% change in mass per dex change in [Fe/H]). This weak effect is consistent with predictions from the Dartmouth Stellar Evolution Database, but inconsistent with those from MESA Isochrones and Stellar Tracks (at 5σ). A sample of binaries with a wider range of abundances will be required to discern the importance of metallicity in extreme populations (e.g., in the Galactic halo or thick disk).A.W.M. was supported through Hubble Fellowship grant 51364 awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS 5-26555. T.J.D. acknowledges research support from Gemini Observatory. This work was supported by a NASA Keck PI Data Award (award nos. 1554237, 1544189, 1535910, and 1521162), administered by the NASA Exoplanet Science Institut

A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral

The CHR promoter element controls cell cycle-dependent gene transcription and binds the DREAM and MMB complexes

Cell cycle-dependent gene expression is often controlled on the transcriptional level. Genes like cyclin B, CDC2 and CDC25C are regulated by cell cycle-dependent element (CDE) and cell cycle genes homology region (CHR) promoter elements mainly through repression in G0/G1. It had been suggested that E2F4 binding to CDE sites is central to transcriptional regulation. However, some promoters are only controlled by a CHR. We identify the DREAM complex binding to the CHR of mouse and human cyclin B2 promoters in G0. Association of DREAM and cell cycle-dependent regulation is abrogated when the CHR is mutated. Although E2f4 is part of the complex, a CDE is not essential but can enhance binding of DREAM. We show that the CHR element is not only necessary for repression of gene transcription in G0/G1, but also for activation in S, G2 and M phases. In proliferating cells, the B-myb-containing MMB complex binds the CHR of both promoters independently of the CDE. Bioinformatic analyses identify many genes which contain conserved CHR elements in promoters binding the DREAM complex. With Ube2c as an example from that screen, we show that inverse CHR sites are functional promoter elements that can bind DREAM and MMB. Our findings indicate that the CHR is central to DREAM/MMB-dependent transcriptional control during the cell cycle