Quenched Charmed Meson Spectra using Tadpole Improved Quark Action on Anisotropic Lattices

Charmed meson charmonium spectra are studied with improved quark actions on anisotropic lattices. We measured the pseudo-scalar and vector meson dispersion relations for 4 lowest lattice momentum modes with quark mass values ranging from the strange quark to charm quark with 3 different values of gauge coupling $\beta$ and 4 different values of bare speed of light $\nu$. With the bare speed of light parameter $\nu$ tuned in a mass-dependent way, we study the mass spectra of $D$, $D_s$, $\eta_c$, $D^{\ast}$, $D_s^{\ast}$ and $J/\psi$ mesons. The results extrapolated to the continuum limit are compared with the experiment and qualitative agreement is found.Comment: 8 pages, 2 figures, latex fil

Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

Activity-dependent modifications strongly influence neural development. However, molecular programs underlying their context and circuit-specific effects are not well understood. To study global transcriptional changes associated with chronic elevation of synaptic activity, we performed cell-type-specific transcriptome profiling of Drosophila ventral lateral neurons (LNvs) in the developing visual circuit and identified activity-modified transcripts that are enriched in neuron morphogenesis, circadian regulation, and lipid metabolism and trafficking. Using bioinformatics and genetic analyses, we validated activity-induced isoform-specific upregulation of Drosophila lipophorin receptors LpR1 and LpR2, the homologs of mammalian low-density lipoprotein receptor (LDLR) family proteins. Furthermore, our morphological and physiological studies uncovered critical functions of neuronal lipophorin receptors (LpRs) in maintaining the structural and functional integrities in neurons challenged by chronic elevations of activity. Together, our findings identify LpRs as molecular targets for activity-dependent transcriptional regulation and reveal the functional significance of cell-type-specific regulation of neuronal lipid uptake in experience-dependent plasticity and adaptive responses

Counterfactual communication without a trace in the transmission channel

We report an experimental realization of a modified counterfactual communication protocol that eliminates the dominant environmental trace left by photons passing through the transmission channel. Compared to Wheeler's criterion for inferring past particle paths, as used in prior protocols, our trace criterion provide stronger support for the claim of the counterfactuality of the communication. We verify the lack of trace left by transmitted photons via tagging the propagation arms of an interferometric device by distinct frequency-shifts and finding that the collected photons have no frequency shift which corresponds to the transmission channel. As a proof of principle, we counterfactually transfer a quick response code image with sufficient fidelity to be scanned with a cell phone

Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension

BACKGROUND: Renovascular hypertension (RVH) impairs cardiac structure and left ventricular (LV) function, but whether mitochondrial injury is implicated in RVH-induced myocardial damage and dysfunction has not been defined. We hypothesized that cardiac remodeling in swine RVH is partly attributable to cardiac mitochondrial injury. METHODS AND RESULTS: After 12 weeks of hypercholesterolemic (HC)-RVH or control (n=14 each), pigs were treated for another 4 weeks with vehicle or with the mitochondrial-targeted peptide (MTP), Bendavia (0.1 mg/kg subcutaneously, 5 days/week), which stabilizes mitochondrial inner-membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector-computed tomography and oxygenation by blood-oxygen-level-dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic-reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert-butyl hydroperoxide (tBHP) untreated or treated with MTP. Chronic mitoprotection in vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin-sensitive sarcoplasmic reticulum Ca(2+)-ATPase activity that declined in HC-RVH normalized in MTP-treated pigs. Mitoprotection also improved LV relaxation (E/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only in MTP-treated pigs. In tBHP-treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics. CONCLUSIONS: Chronic mitoprotection blunted myocardial hypertrophy, improved LV relaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustained HC-RVH, suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy

An i2b2-based, generalizable, open source, self-scaling chronic disease registry

Objective: Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Materials and methods Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. Results: The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. Discussion We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. Conclusions: The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases

Temporal scale‐dependence of plant–pollinator networks

The study of mutualistic interaction networks has led to valuable insights into ecological and evolutionary processes. However, our understanding of network structure may depend upon the temporal scale at which we sample and analyze network data. To date, we lack a comprehensive assessment of the temporal scale-dependence of network structure across a wide range of temporal scales and geographic locations. If network structure is temporally scale-dependent, networks constructed over different temporal scales may provide very different perspectives on the structure and composition of species interactions. Furthermore, it remains unclear how various factors – including species richness, species turnover, link rewiring and sampling effort – act in concert to shape network structure across different temporal scales. To address these issues, we used a large database of temporally-resolved plant–pollinator networks to investigate how temporal aggregation from the scale of one day to multiple years influences network structure. In addition, we used structural equation modeling to explore the direct and indirect effects of temporal scale, species richness, species turnover, link rewiring and sampling effort on network structural properties. We find that plant–pollinator network structure is strongly temporally-scale dependent. This general pattern arises because the temporal scale determines the degree to which temporal dynamics (i.e. phenological turnover of species and links) are included in the network, in addition to how much sampling effort is put into constructing the network. Ultimately, the temporal scale-dependence of our plant–pollinator networks appears to be mostly driven by species richness, which increases with sampling effort, and species turnover, which increases with temporal extent. In other words, after accounting for variation in species richness, network structure is increasingly shaped by its underlying temporal dynamics. Our results suggest that considering multiple temporal scales may be necessary to fully appreciate the causes and consequences of interaction network structure.Fil: Schwarz, Benjamin. Albert Ludwigs University of Freiburg; AlemaniaFil: Vazquez, Diego P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Cara Donna, Paul J.. Chicago Botanic Garden; Estados UnidosFil: Knight, Tiffany M.. German Centre for Integrative Biodiversity Research; AlemaniaFil: Benadi, Gita. Albert Ludwigs University of Freiburg; AlemaniaFil: Dormann, Carsten F.. Albert Ludwigs University of Freiburg; AlemaniaFil: Gauzens, Benoit. German Centre for Integrative Biodiversity Research; AlemaniaFil: Motivans, Elena. German Centre for Integrative Biodiversity Research; AlemaniaFil: Resasco, Julian. University of Colorado; Estados UnidosFil: Blüthgen, Nico. Universitat Technische Darmstadt; AlemaniaFil: Burkle, Laura A.. Montana State University; AlemaniaFil: Fang, Qiang. Henan University of Science and Technology; ChinaFil: Kaiser Bunbury, Christopher N.. University of Exeter; Reino UnidoFil: Alarcón, Ruben. California State University; Estados UnidosFil: Bain, Justin A.. Chicago Botanic Garden; Estados UnidosFil: Chacoff, Natacha Paola. Universidad Nacional de Tucumán. Instituto de Ecología Regional. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Ecología Regional; ArgentinaFil: Huang, Shuang Quan. Central China Normal University; ChinaFil: LeBuhn, Gretchen. San Francisco State University; Estados UnidosFil: MacLeod, Molly. Rutgers University; Estados UnidosFil: Petanidou, Theodora. Univversity of the Aegean; Estados UnidosFil: Rasmussen, Claus. University Aarhus; DinamarcaFil: Simanonok, Michael P.. Montana State University; Estados UnidosFil: Thompson, Amibeth H.. German Centre for Integrative Biodiversity Research; AlemaniaFil: Fründ, Jochen. Albert Ludwigs University of Freiburg; Alemani

The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study

Background Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition. Methods/Design The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years. Discussion Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure

Rapid dissection and model-based optimization of inducible enhancers in human cells using a massively parallel reporter assay

Learning to read and write the transcriptional regulatory code is of central importance to progress in genetic analysis and engineering. Here we describe a massively parallel reporter assay (MPRA) that facilitates the systematic dissection of transcriptional regulatory elements. In MPRA, microarray-synthesized DNA regulatory elements and unique sequence tags are cloned into plasmids to generate a library of reporter constructs. These constructs are transfected into cells and tag expression is assayed by high-throughput sequencing. We apply MPRA to compare >27,000 variants of two inducible enhancers in human cells: a synthetic cAMP-regulated enhancer and the virus-inducible interferon-β enhancer. We first show that the resulting data define accurate maps of functional transcription factor binding sites in both enhancers at single-nucleotide resolution. We then use the data to train quantitative sequence-activity models (QSAMs) of the two enhancers. We show that QSAMs from two cellular states can be combined to design enhancer variants that optimize potentially conflicting objectives, such as maximizing induced activity while minimizing basal activity.National Human Genome Research Institute (U.S.) (grant R01HG004037)National Science Foundation (U.S.) ((NSF) grant PHY-0957573)National Science Foundation (U.S.) (NSF grant PHY-1022140)Broad Institut

The Zwicky Transient Facility: Data Processing, Products, and Archive

The Zwicky Transient Facility (ZTF) is a new robotic time-domain survey currently in progress using the Palomar 48-inch Schmidt Telescope. ZTF uses a 47 square degree field with a 600 megapixel camera to scan the entire northern visible sky at rates of ~3760 square degrees/hour to median depths of g ~ 20.8 and r ~ 20.6 mag (AB, 5sigma in 30 sec). We describe the Science Data System that is housed at IPAC, Caltech. This comprises the data-processing pipelines, alert production system, data archive, and user interfaces for accessing and analyzing the products. The realtime pipeline employs a novel image-differencing algorithm, optimized for the detection of point source transient events. These events are vetted for reliability using a machine-learned classifier and combined with contextual information to generate data-rich alert packets. The packets become available for distribution typically within 13 minutes (95th percentile) of observation. Detected events are also linked to generate candidate moving-object tracks using a novel algorithm. Objects that move fast enough to streak in the individual exposures are also extracted and vetted. The reconstructed astrometric accuracy per science image with respect to Gaia is typically 45 to 85 milliarcsec. This is the RMS per axis on the sky for sources extracted with photometric S/N >= 10. The derived photometric precision (repeatability) at bright unsaturated fluxes varies between 8 and 25 millimag. Photometric calibration accuracy with respect to Pan-STARRS1 is generally better than 2%. The products support a broad range of scientific applications: fast and young supernovae, rare flux transients, variable stars, eclipsing binaries, variability from active galactic nuclei, counterparts to gravitational wave sources, a more complete census of Type Ia supernovae, and Solar System objects.Comment: 30 pages, 16 figures, Published in PASP Focus Issue on the Zwicky Transient Facility (doi: 10.1088/1538-3873/aae8ac