Indiana Nonprofit Employment: Historical Trends in Arts, Entertainment and Recreation, 1995-2009

Nonprofit organizations make significant contributions to the quality of life for the residents of Indiana. In particular, arts, entertainment, and recreation organizations play an important role in preserving culture, enriching the lives of children and adults, fostering creative expression, and providing sport and entertainment. These organizations may also serve as a powerful economic force for the state by attracting not only tourists, but also a young, educated workforce that can have a major positive impact on regional output and productivity. This report from the Indiana Nonprofits: Scope and Community Dimensions project presents new data on the size, composition, and distribution of paid arts, entertainment, and recreation employment in Indiana's private nonprofit sector over the 1995-2009 time period. All dollars are adjusted for inflation and are reported in constant 2009 dollars. Note that there are too few government employees in the arts, entertainment and recreation industry to allow for separate analysis of public sector employment

Kompetenzorientierte Begleitung der Studierenden in der Studieneingangsphase

Die Öffnung des Hochschulzugangs geht mit einer heterogenen Studierendenklientel einher und verursacht Passungsprobleme zwischen studentischen Lebenslagen, Vorerfahrungen, Qualifikationen und tradierten Studienanforderungen. Das Projekt KoBeg greift diese Problematik auf. Mittels eines eigens für die Studieneingangsphase entwickelten binnendifferenzierten Lehr-/Lernkonzepts, das sich in seiner didaktisch-methodischen Ausgestaltung an eduScrum® anlehnt, soll der Erwerb studienerfolgsrelevanter Kompetenzen unterstützt werden. Im vorliegenden Beitrag wird das Konzept theoretisch fundiert skizziert, mit dem Ziel, einen hochschuldidaktischen Austausch anzuregen

Communicating serum chemical concentrations to study participants: follow up survey

<p>Abstract</p> <p>Background</p> <p>A considerable literature now supports the importance of effective communication with study participants, including how best to develop communication plans focusing on the uncertainty of health risks associated with particular environmental exposures. Strategies for communicating individual concentrations of environmental chemicals in human biological samples in the absence of clearly established safe or hazardous levels have been discussed from a conceptual basis and to a lesser extent from an empirical basis. We designed and evaluated an empirically based communication strategy for women of reproductive age who previously participated in a prospective study focusing on persistent environmental chemicals and reproductive outcomes.</p> <p>Methods</p> <p>A cohort of women followed from preconception through pregnancy or up to 12 menstrual cycles without pregnancy was given their individual serum concentrations for lead, dichloro-2,2-bis<it>p</it>-chlorophenyl ethylene, and select polychlorinated biphenyl congeners. Two versions of standardized letters were prepared depending upon women's exposure status, which was characterized as low or high. Letters included an introduction, individual concentrations, population reference values and guidance for minimizing future exposures. Participants were actively monitored for any questions or concerns following receipt of letters.</p> <p>Results</p> <p>Ninety-eight women were sent letters informing them of their individual concentrations to select study chemicals. None of the 89 (91%) participating women irrespective of exposure status contacted the research team with questions or concerns about communicated exposures despite an invitation to do so.</p> <p>Conclusions</p> <p>Our findings suggest that study participants can be informed about their individual serum concentrations without generating unnecessary concern.</p

Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair

Microcephaly with early-onset, intractable seizures and developmental delay (MCSZ) is a hereditary disease caused by mutations in polynucleotide kinase/phosphatase (PNKP), a DNA strand break repair protein with DNA 5'-kinase and DNA 3'-phosphatase activity. To investigate the molecular basis of this disease, we examined the impact of MCSZ mutations on PNKP activity in vitro and in cells. Three of the four mutations currently associated with MCSZ greatly reduce or ablate DNA kinase activity of recombinant PNKP at 30°C (L176F, T424Gfs48X and exon15Δfs4X), but only one of these mutations reduces DNA phosphatase activity under the same conditions (L176F). The fourth mutation (E326K) has little impact on either DNA kinase or DNA phosphatase activity at 30°C, but is less stable than the wild-type enzyme at physiological temperature. Critically, all of the MCSZ mutations identified to date result in ∼10-fold reduced cellular levels of PNKP protein, and reduced rates of chromosomal DNA strand break repair. Together, these data suggest that all four known MCSZ mutations reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5'-kinase activity and all of the mutations greatly reducing cellular DNA 3'-phosphatase activity

Oceanids C2: An Integrated Command, Control, and Data Infrastructure for the Over-the-Horizon Operation of Marine Autonomous Systems

Long-range Marine Autonomous Systems (MAS), operating beyond the visual line-of-sight of a human pilot or research ship, are creating unprecedented opportunities for oceanographic data collection. Able to operate for up to months at a time, periodically communicating with a remote pilot via satellite, long-range MAS vehicles significantly reduce the need for an expensive research ship presence within the operating area. Heterogeneous fleets of MAS vehicles, operating simultaneously in an area for an extended period of time, are becoming increasingly popular due to their ability to provide an improved composite picture of the marine environment. However, at present, the expansion of the size and complexity of these multi-vehicle operations is limited by a number of factors: (1) custom control-interfaces require pilots to be trained in the use of each individual vehicle, with limited cross-platform standardization; (2) the data produced by each vehicle are typically in a custom vehicle-specific format, making the automated ingestion of observational data for near-real-time analysis and assimilation into operational ocean models very difficult; (3) the majority of MAS vehicles do not provide machine-to-machine interfaces, limiting the development and usage of common piloting tools, multi-vehicle operating strategies, autonomous control algorithms and automated data delivery. In this paper, we describe a novel piloting and data management system (C2) which provides a unified web-based infrastructure for the operation of long-range MAS vehicles within the UK's National Marine Equipment Pool. The system automates the archiving, standardization and delivery of near-real-time science data and associated metadata from the vehicles to end-users and Global Data Assembly Centers mid-mission. Through the use and promotion of standard data formats and machine interfaces throughout the C2 system, we seek to enable future opportunities to collaborate with both the marine science and robotics communities to maximize the delivery of high-quality oceanographic data for world-leading science

A deep blue B,N-doped heptacene emitter that shows both thermally activated delayed fluorescence and delayed fluorescence by triplet-triplet annihilation

Authors thank the Leverhulme Trust (RPG-2016-047). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska Curie grant agreement No 838885 (NarrowbandSSL) and 812872 (TADFlife). We thank Umicore for their generous supply of catalysts. S.S. acknowledges support from the Marie Skłodowska-Curie Individual Fellowship. SB acknowledges support from the Bayrisches Staatsministerium für Wissenschaft und Kunst (Stmwk) in the framework of the initiative "SolTech", as well as from the German Science foundation (DFG) (No. 392306670). Computational resources have been provided by the Consortium des Équipements de Calcul Intensif (CÉCI), funded by the Fonds de la Recherche Scientifiques de Belgique (F.R.S.-FNRS) under Grant No. 2.5020.11, as well as the Tier-1 supercomputer of the Fédération Wallonie-Bruxelles, infrastructure funded by the Walloon Region under the grant agreement n111754.An easy-to-access, near-UV-emitting linearly extended B,N-doped heptacene with high thermal stability is designed and synthesized in good yields. This compound exhibits thermally activated delayed fluorescence (TADF) at ambient temperature from a multiresonant (MR) state and represents a rare example of a non-triangulene-based MR-TADF emitter. At lower temperatures triplet–triplet annihilation dominates. The compound simultaneously possesses narrow, deep-blue emission with CIE coordinates of (0.17, 0.01). While delayed fluorescence results mainly from triplet–triplet annihilation at lower temperatures in THF solution, where aggregates form upon cooling, the TADF mechanism takes over around room temperature in solution when the aggregates dissolve or when the compound is well dispersed in a solid matrix. The potential of our molecular design to trigger TADF in larger acenes is demonstrated through the accurate prediction of ΔEST using correlated wave-function-based calculations. On the basis of these calculations, we predicted dramatically different optoelectronic behavior in terms of both ΔEST and the optical energy gap of two constitutional isomers where only the boron and nitrogen positions change. A comprehensive structural, optoelectronic, and theoretical investigation is presented. In addition, the ability of the achiral molecule to assemble on a Au(111) surface to a highly ordered layer composed of enantiomorphic domains of racemic entities is demonstrated by scanning tunneling microscopy.PostprintPeer reviewe

Front cover - Cell Membrane Wrapping: Influence of Cell Membrane Wrapping on the Cell−Porous Silicon Nanoparticle Interactions (Adv. Healthcare Mater. 17/2020)

Biohybrid nanosystems represent the cutting‐edge research in biofunctionalization of micro‐ and nano‐systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane‐coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell‐specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage‐mediated uptake

An Information Management Framework for Environmental Digital Twins (IMFe) as a concept and pilot

Environmental science is concerned with assessing the impacts of changing environmental conditions upon the state of the natural world. Environmental Digital Twins (EDT) are a new technology that enable environmental change scenarios for real systems to be modelled and their impacts visualised. They will be particularly effective with delivering understanding of these impacts on the natural environment to non-specialist stakeholders. The UK Natural Environment Research Council (NERC) recently published its first digital strategy, which sets out a vision for digitally enabled environmental science for the next decade. This strategy places data and digital technologies at the heart of UK environmental science. EDT have been made possible by the emergence of increasingly large, diverse, static data sources, networks of dynamic environmental data from sensor networks and time-variant process modelling. Once combined with visualisation capabilities these provide the basis of the digital twin technologies to enable the environmental scientists community to make a step-change in understanding of the environment. Components may be developed separately by a network but can be combined to improve understanding provided development follows agreed standards to facilitate data exchange and integration. Replicating the behaviours of environmental systems is inevitably a multi-disciplinary activity. To enable this, an information management framework for Environmental digital twins (IMFe) is needed that establishes the components for effective information management within and across the EDT ecosystem. This must enable secure, resilient interoperability of data, and is a reference point to facilitate data use in line with security, legal, commercial, privacy and other relevant concerns. We present recommendations for developing an IMFe including the application of concepts such as an asset commons and balanced approach to standards to facilitate minimum interoperability requirements between twins while iteratively implementing an IMFe. Achieving this requires components to be developed that follow agreed standards to ensure that information can be trusted by the user, and that they are semantically interoperable so data can be shared. A digital Asset Register will be defined to provide access to and enable linking of such components. This previously conceptual project has now been enhanced into the Pilot IMFe project aiming to define the architectures, technologies, standards and hardware infrastructure to develop a fully functioned environmental digital twin. During the project lifespan this will be tested with by construction of a pilot EDT for the Haig Fras Marine Conservation Zone (MCZ) that both enables testing of the proposed IMFe concepts and will provide a clear demonstration of the power of EDT to monitor and scenario test a complex environmental system for the benefit of stakeholders

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p&lt;0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p&lt;0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p&lt;0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology