Phosphorylation and Methylation of Proteasomal Proteins of the Haloarcheon Haloferax volcanii

Proteasomes are composed of 20S core particles (CPs) of α- and β-type subunits that associate with regulatory particle AAA ATPases such as the proteasome-activating nucleotidase (PAN) complexes of archaea. In this study, the roles and additional sites of post-translational modification of proteasomes were investigated using the archaeon Haloferax volcanii as a model. Indicative of phosphorylation, phosphatase-sensitive isoforms of α1 and α2 were detected by 2-DE immunoblot. To map these and other potential sites of post-translational modification, proteasomes were purified and analyzed by tandem mass spectrometry (MS/MS). Using this approach, several phosphosites were mapped including α1 Thr147, α2 Thr13/Ser14 and PAN-A Ser340. Multiple methylation sites were also mapped to α1, thus, revealing a new type of proteasomal modification. Probing the biological role of α1 and PAN-A phosphorylation by site-directed mutagenesis revealed dominant negative phenotypes for cell viability and/or pigmentation for α1 variants including Thr147Ala, Thr158Ala and Ser58Ala. An H. volcanii Rio1p Ser/Thr kinase homolog was purified and shown to catalyze autophosphorylation and phosphotransfer to α1. The α1 variants in Thr and Ser residues that displayed dominant negative phenotypes were significantly reduced in their ability to accept phosphoryl groups from Rio1p, thus, providing an important link between cell physiology and proteasomal phosphorylation

a route towards defined surface functionalization

We investigate the surface-catalyzed dissociation of the archetypal molecular switch azobenzene on the Cu(111) surface. Based on X-ray photoelectron spectroscopy, normal incidence X-ray standing waves and density functional theory calculations a detailed picture of the coverage-induced formation of phenyl nitrene from azobenzene is presented. Furthermore, a comparison to the azobenzene/Ag(111) interface provides insight into the driving force behind the dissociation on Cu(111). The quantitative decay of azobenzene paves the way for the creation of a defect free, covalently bonded monolayer. Our work suggests a route of surface functionalization via suitable azobenzene derivatives and the on surface synthesis concept, allowing for the creation of complex immobilized molecular systems

Coherent driving of direct and indirect excitons in a quantum dot molecule

Quantum dot molecules (QDMs) are one of the few quantum light sources that promise deterministic generation of one- and two-dimensional photonic graph states. The proposed protocols rely on coherent excitation of the tunnel-coupled and spatially indirect exciton states. Here, we demonstrate power-dependent Rabi oscillations of direct excitons, spatially indirect excitons, and excitons with a hybridized electron wave function. An off-resonant detection technique based on phonon-mediated state transfer allows for spectrally filtered detection under resonant excitation. Applying a gate voltage to the QDM-device enables a continuous transition between direct and indirect excitons and, thereby, control of the overlap of the electron and hole wave function. This does not only vary the Rabi frequency of the investigated transition by a factor of $\approx3$, but also allows to optimize graph state generation in terms of optical pulse power and reduction of radiative lifetimes.Comment: 6 pages, 3 figure

Berkeley Supernova Ia Program I: Observations, Data Reduction, and Spectroscopic Sample of 582 Low-Redshift Type Ia Supernovae

In this first paper in a series we present 1298 low-redshift (z\leq0.2) optical spectra of 582 Type Ia supernovae (SNe Ia) observed from 1989 through 2008 as part of the Berkeley SN Ia Program (BSNIP). 584 spectra of 199 SNe Ia have well-calibrated light curves with measured distance moduli, and many of the spectra have been corrected for host-galaxy contamination. Most of the data were obtained using the Kast double spectrograph mounted on the Shane 3 m telescope at Lick Observatory and have a typical wavelength range of 3300-10,400 Ang., roughly twice as wide as spectra from most previously published datasets. We present our observing and reduction procedures, and we describe the resulting SN Database (SNDB), which will be an online, public, searchable database containing all of our fully reduced spectra and companion photometry. In addition, we discuss our spectral classification scheme (using the SuperNova IDentification code, SNID; Blondin & Tonry 2007), utilising our newly constructed set of SNID spectral templates. These templates allow us to accurately classify our entire dataset, and by doing so we are able to reclassify a handful of objects as bona fide SNe Ia and a few other objects as members of some of the peculiar SN Ia subtypes. In fact, our dataset includes spectra of nearly 90 spectroscopically peculiar SNe Ia. We also present spectroscopic host-galaxy redshifts of some SNe Ia where these values were previously unknown. [Abridged]Comment: 34 pages, 11 figures, 11 tables, revised version, re-submitted to MNRAS. Spectra will be released in January 2013. The SN Database homepage (http://hercules.berkeley.edu/database/index_public.html) contains the full tables, plots of all spectra, and our new SNID template

Chaotic and Clumpy Galaxy Formation in an Extremely Massive Reionization-era Halo

© 2022. The Author(s). Published by the American Astronomical Society. Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. https://creativecommons.org/licenses/by/4.0/Abstract: The SPT 0311–58 system at z = 6.900 is an extremely massive structure within the reionization epoch and offers a chance to understand the formation of galaxies at an extreme peak in the primordial density field. We present 70 mas Atacama Large Millimeter/submillimeter Array observations of the dust continuum and [C ii] 158 μm emission in the central pair of galaxies and reach physical resolutions of ∼100–350 pc, among the most detailed views of any reionization-era system to date. The observations resolve the source into at least a dozen kiloparsec-size clumps. The global kinematics and high turbulent velocity dispersion within the galaxies present a striking contrast to recent claims of dynamically cold thin-disk kinematics in some dusty galaxies just 800 Myr later at z ∼ 4. We speculate that both gravitational interactions and fragmentation from massive parent disks have likely played a role in the overall dynamics and formation of clumps in the system. Each clump individually is comparable in mass to other 6 < z < 8 galaxies identified in rest-UV/optical deep field surveys, but with star formation rates elevated by a factor of ~3-5. Internally, the clumps themselves bear close resemblance to greatly scaled-up versions of virialized cloud-scale structures identified in low-redshift galaxies. Our observations are qualitatively similar to the chaotic and clumpy assembly within massive halos seen in simulations of high-redshift galaxies.Peer reviewe

Benchmarking CMIP5 models with a subset of ESA CCI Phase 2 data using the ESMValTool

The Coupled Model Intercomparison Project (CMIP) is now moving into its sixth phase and aims at a more routine evaluation of the models as soon as the model output is published to the Earth System Grid Federation (ESGF). To meet this goal the Earth System Model Evaluation Tool (ESMValTool), a community diagnostics and performance metrics tool for the systematic evaluation of Earth system models (ESMs) in CMIP, has been developed and a first version (1.0) released as open source software in 2015. Here, an enhanced version of the ESMValTool is presented that exploits a subset of Essential Climate Variables (ECVs) from the European Space Agency's Climate Change Initiative (ESA CCI) Phase 2 and this version is used to demonstrate the value of the data for model evaluation. This subset includes consistent, long-term time series of ECVs obtained from harmonized, reprocessed products from different satellite instruments for sea surface temperature, sea ice, cloud, soil moisture, land cover, aerosol, ozone, and greenhouse gases. The ESA CCI data allow 'extending the calculation of performance metrics as summary statistics for some variables and add an important alternative data set in other cases where observations are already available. The provision of uncertainty estimates on a per grid basis for the ESA CCI data sets is used in a new extended version of the Taylor diagram and provides important additional information for a more objective evaluation of the models. In our analysis we place a specific focus on the comparability of model and satellite data both in time and space. The ESA CCI data are well suited for an evaluation of results from global climate models across ESM compartments as well as an analysis of long-term trends, variability and change in the context of a changing climate. The enhanced version of the ESMValTool is released as open source software and ready to support routine model evaluation in CMIP6 and at individual modeling centers. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Evaluation of drug loading, pharmacokinetic behavior, and toxicity of a cisplatin-containing hydrogel nanoparticle

Cisplatin is a cytotoxic drug used as a first-line therapy for a wide variety of cancers. However, significant renal and neurological toxicities limits it clinical use. It has been documented that drug toxicities can be mitigated through nanoparticle formulation, while simultaneously increasing tumor accumulation through the enhanced permeation and retention effect. Circulation persistence is a key characteristic for exploiting this effect, and to that end we have developed long-circulating, PEGylated, polymeric hydrogels using the Particle Replication In Non-wetting Templates (PRINT®) platform and complexed cisplatin into the particles (PRINT-Platin). Sustained release was demonstrated, and drug loading correlated to surface PEG density. A PEG Mushroom conformation showed the best compromise between particle pharmacokinetic (PK) parameters and drug loading (16 wt %). While the PK profile of PEG Brush was superior, the loading was poor (2 wt %). Conversely, the drug loading in non-PEGylated particles was better (20 wt %), but the PK was not desirable. We also showed comparable cytotoxicity to cisplatin in several cancer cell lines (non-small cell lung, A549; ovarian, SKOV-3; breast, MDA-MB-468) and a higher MTD in mice (10 mg/kg versus 5 mg/kg). The pharmacokinetic profiles of drug in plasma, tumor, and kidney indicate improved exposure in the blood and tumor accumulation, with concurrent renal protection, when cisplatin was formulated in a nanoparticle. PK parameters were markedly improved: a 16.4-times higher area-under-the-curve (AUC), a reduction in clearance (CL) by a factor of 11.2, and a 4.20-times increase in the volume of distribution (Vd). Additionally, non-small cell lung and ovarian tumor AUC was at least twice that of cisplatin in both models. These findings suggest the potential for PRINT-Platin to improve efficacy and reduce toxicity compared to current cisplatin therapies

What Is a Representative Brain? Neuroscience Meets Population Science

The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain–behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective—population neuroscience—that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas

JWST's TEMPLATES for Star Formation: The First Resolved Gas-phase Metallicity Maps of Dust-obscured Star-forming Galaxies at z ∼ 4

We present the first spatially resolved maps of gas-phase metallicity for two dust-obscured star-forming galaxies at z ∼ 4, from the JWST TEMPLATES Early Release Science program, derived from NIRSpec integral field unit spectroscopy of the Hα and [N ii] emission lines. Empirical optical line calibrations are used to determine that the sources are globally enriched to near-solar levels. While one source shows elevated [N ii]/Hα ratios and broad Hα emission consistent with the presence of an active galactic nucleus in a ≳1 kpc region, we argue that both systems have already undergone significant metal enrichment as a result of their extremely high star formation rates. Utilizing Atacama Large Millimeter/submillimeter Array rest-frame 380 μm continuum and [Ci](3P2–3P1) line maps we compare the spatial variation of the metallicity and gas-to-dust ratio in the two galaxies, finding the two properties to be anticorrelated on highly resolved spatial scales, consistent with various literature studies of z ∼ 0 galaxies. The data are indicative of the enormous potential of JWST to probe the enrichment of the interstellar medium on ∼kpc scales in extremely dust-obscured systems at z ∼ 4 and beyond