Examination of Edge Effects with Different Storage Conditions of Preplated Dimethyl Sulfoxide Nanospots in ChemLib 1,536- and 3,456-Well Assay-Ready Plates

For ultra-high-throughput screening, 10–30 nl of compound dissolved in 75% dimethyl sulfoxide (DMSO)/25% water (vol/vol) is spotted into 1,536- and 3,456-well ChemLib™ plates (Aurora Biotechnologies, Carlsbad, CA) and stored appropriately for a short time before screening. Although this practice eliminates the compound plating bottleneck, plated volumes of DMSO slowly evaporate from assay wells if plates are not properly stored in the interim. Since many assays are sensitive to DMSO concentrations, even slight evaporation may cause intra-plate variation and thus decrease assay quality. Using a cytochrome P450 3A4 Vivid® Blue assay (Invitrogen, Carlsbad), we investigated the rate, pattern, and quantity of evaporation over a 1-year time frame to identify best practices for long-term (i.e., 6 months or greater) storage of assay-ready compound plates. Our findings regarding evaporation at plate edges indicate that nanospots preplated in ChemLib 1,536- or 3,456-well plates are best stored at −80°C, in a bag, with or without the outer evaporation wells filled or at −20°C, in a bag, with evaporation wells filled.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63203/1/adt.2008.169.pd

The evolution of substructure II: linking dynamics to environment

We present results from a series of high-resolution N-body simulations that focus on the formation and evolution of eight dark matter halos, each of order a million particles within the virial radius. We follow the time evolution of hundreds of satellite galaxies with unprecedented time resolution, relating their physical properties to the differing halo environmental conditions. The self-consistent cosmological framework in which our analysis was undertaken allows us to explore satellite disruption within live host potentials, a natural complement to earlier work conducted within static potentials. Our host halos were chosen to sample a variety of formation histories, ages, and triaxialities; despite their obvious differences, we find striking similarities within the associated substructure populations. Namely, all satellite orbits follow nearly the same eccentricity distribution with a correlation between eccentricity and pericentre. We also find that the destruction rate of the substructure population is nearly independent of the mass, age, and triaxiality of the host halo. There are, however, subtle differences in the velocity anisotropy of the satellite distribution. We find that the local velocity bias at all radii is greater than unity for all halos and this increases as we move closer to the halo centre, where it varies from 1.1 to 1.4. For the global velocity bias we find a small but slightly positive bias, although when we restrict the global velocity bias calculation to satellites that have had at least one orbit, the bias is essentially removed.Comment: 14 pages, 14 figures, MNRAS in pres

The Grizzly, April 15, 1983

Second Attack: Improvements Sought for Security • New Senior Fund • Seminar Planned • The A\u27s Come to Helfferich Hall • Letter to the Editor: Most Abominable Act • Faculty Promotions Approved • President\u27s Corner • Sexual Assault in Quad • Security Tips • Nuclear Freeze Concert • Ursinus Representatives at UN • Ice Cream Night at Bear\u27s Den • Final Exam Schedule • Republicans for Rock! • Escape From Ursinus • Bear Batsmen Drop Slugfest • Men\u27s Track Evens Up • Men\u27s Tennis Nets Two Wins • Girls\u27 Nets Optimistic • Men\u27s Lacrosse Victorioushttps://digitalcommons.ursinus.edu/grizzlynews/1098/thumbnail.jp

Early Infrared Spectral Development of V1187 Scorpii (Nova Scorpii 2004 No. 2)

We report on an unprecedented infrared time series of spectra of V1187 Sco, a very fast ONeMg nova. The observations covered a 56 day period (2004 August 6-September 30) starting 2 days after the nova's peak brightness. Time evolution of the spectra revealed changing line strengths and profiles on timescales of less than a day to weeks as the nova evolved from early postmaximum to early coronal phases. When our ground-based optical and Spitzer Space Telescope data were combined, the wavelength coverage of 0.38-36 μm allowed an accurate spectral energy distribution to be derived when it was about 6 weeks after outburst. Developing double structure in the He I lines showed them changing from narrow to broad in only a few days. Using the O I lines in combination with the optical spectra, we derived a reddening of E(B - V) = 1.56 ± 0.08 and a distance of 4.9 ± 0.5 kpc. Modeling of the ejected material strongly suggested that it was geometrically thick with ΔR/R = 0.8-0.9 (more of a wind than a shell) and a low filling factor of order a few percent. The line shapes were consistent with a cylindrical jet, bipolar, or spherical Hubble flow expansion with a maximum speed of about -3000 km s-1. The central peak appeared to be more associated with the spherical component, while the two peaks (especially in Hβ) suggested a ring with either a lower velocity component or with its axis inclined to the line of sight

A molecular phylogeny of the genus Alloteropsis (Panicoideae, Poaceae) suggests an evolutionary reversion from C4 to C3 photosynthesis

The grass Alloteropsis semialata is the only plant species with both C(3) and C(4) subspecies. It therefore offers excellent potential as a model system for investigating the genetics, physiology and ecological significance of the C(4) photosynthetic pathway. Here, a molecular phylogeny of the genus Alloteropsis is constructed to: (a) confirm the close relationship between the C(3) and C(4) subspecies of A. semialata; and (b) infer evolutionary relationships between species within the Alloteropsis genus

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Systematic Conservation Planning in the Face of Climate Change: Bet-Hedging on the Columbia Plateau

Systematic conservation planning efforts typically focus on protecting current patterns of biodiversity. Climate change is poised to shift species distributions, reshuffle communities, and alter ecosystem functioning. In such a dynamic environment, lands selected to protect today's biodiversity may fail to do so in the future. One proposed approach to designing reserve networks that are robust to climate change involves protecting the diversity of abiotic conditions that in part determine species distributions and ecological processes. A set of abiotically diverse areas will likely support a diversity of ecological systems both today and into the future, although those two sets of systems might be dramatically different. Here, we demonstrate a conservation planning approach based on representing unique combinations of abiotic factors. We prioritize sites that represent the diversity of soils, topographies, and current climates of the Columbia Plateau. We then compare these sites to sites prioritized to protect current biodiversity. This comparison highlights places that are important for protecting both today's biodiversity and the diversity of abiotic factors that will likely determine biodiversity patterns in the future. It also highlights places where a reserve network designed solely to protect today's biodiversity would fail to capture the diversity of abiotic conditions and where such a network could be augmented to be more robust to climate-change impacts

Views and experiences of people with intellectual disabilities regarding intimate relationships: a qualitative metasynthesis

The aims of this review were to systematically identify, critically appraise and synthesize the results of existing qualitative literature exploring the views and experiences of intimate relationships amongst people with intellectual disabilities. Fourteen peer-reviewed articles were identified through a systematic search of eight databases, reference lists, citations, and relevant journals. The identified articles were appraised for quality, then synthesized using a metaethnography approach. No study met all quality criteria and references to ethical approval were often lacking. Interpretation of the findings suggested three key themes: the meaning of intimate relationships, external constraints and facilitators, and managing external constraints. Though many people with intellectual disabilities desire and benefit from intimate relationships, they experience restrictions that others do not, which can lead to isolation and loneliness. Intimate relationships are not always necessarily linked with sexual behavior; therefore, intimate relationships warrant their own focus in future research, as well as in education and training for people with intellectual disabilities and their caregivers. Within this, a commitment to transparency over research processes is needed, in particular with reference to how ethical approval was obtained, since this has been a shortcoming of research with this focus to date

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860