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1,508 result(s) for "Moore, William J."
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OMERO: flexible, model-driven data management for experimental biology
The Open Microscopy Environment Remote Objects (OMERO) software platform provides a server-based system for managing and analyzing microscopy images and non-image data. Data-intensive research depends on tools that manage multidimensional, heterogeneous datasets. We built OME Remote Objects (OMERO), a software platform that enables access to and use of a wide range of biological data. OMERO uses a server-based middleware application to provide a unified interface for images, matrices and tables. OMERO's design and flexibility have enabled its use for light-microscopy, high-content-screening, electron-microscopy and even non-image-genotype data. OMERO is open-source software, available at http://openmicroscopy.org/ .
Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models
WD repeat domain 5 (WDR5) is a core scaffolding component of many multiprotein complexes that perform a variety of critical chromatin-centric processes in the nucleus. WDR5 is a component of the mixed lineage leukemia MLL/SET complex and localizes MYC to chromatin at tumor-critical target genes. As a part of these complexes, WDR5 plays a role in sustaining oncogenesis in a variety of human cancers that are often associated with poor prognoses. Thus, WDR5 has been recognized as an attractive therapeutic target for treating both solid and hematological tumors. Previously, small-molecule inhibitors of the WDR5-interaction (WIN) site and WDR5 degraders have demonstrated robust in vitro cellular efficacy in cancer cell lines and established the therapeutic potential of WDR5. However, these agents have not demonstrated significant in vivo efficacy at pharmacologically relevant doses by oral administration in animal disease models. We have discovered WDR5 WIN-site inhibitors that feature bicyclic heteroaryl P₇ units through structure-based design and address the limitations of our previous series of small-molecule inhibitors. Importantly, our lead compounds exhibit enhanced on-target potency, excellent oral pharmacokinetic (PK) profiles, and potent dose-dependent in vivo efficacy in a mouse MV4:11 subcutaneous xenograft model by oral dosing. Furthermore, these in vivo probes show excellent tolerability under a repeated high-dose regimen in rodents to demonstrate the safety of the WDR5 WIN-site inhibition mechanism. Collectively, our results provide strong support for WDR5 WIN-site inhibitors to be utilized as potential anticancer therapeutics.
Early Multicenter Experience With Imipenem-Cilastatin-Relebactam for Multidrug-Resistant Gram-Negative Infections
Abstract A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects.
Data management challenges in three-dimensional EM
This report describes the outcomes of the Data Management Challenges in 3D Electron Microscopy workshop. Key topics discussed include data models, validation and raw-data archiving. The meeting participants agreed that the EMDataBank should take the lead in addressing these issues, and concrete action points were agreed upon that will have a substantial impact on the accessibility of three-dimensional EM data in biology and medicine.
Academic Pay in the United Kingdom and the United States: The Differential Returns to Productivity and the Lifetime Earnings Gap
This paper estimates earnings functions for two samples of U.K. and U.S. academic economists. Despite significant differences in compensation schemes, a comparably specified human capital earnings model does a good job explaining earnings variations for academic economists in both countries. Our estimates suggest that rewards for research are more immediate and direct in the United States. Because of the national salary scale, the payoffs to experience and seniority are greater and the payoffs to research are lower in the United Kingdom than in the United States. After adjusting for productivity and demographic factors, we find that U.S. economists are paid approximately 40% more than otherwise equivalent economists in the United Kingdom. Simulating career age-earnings profiles for both markets, we find that the earnings gap widens with experience for relatively productive research economists and may even narrow with age for relatively less productive research economists. Nevertheless, the cumulative lifetime earnings foregone are substantial for research and nonresearch economists in the United Kingdom.
A Facile Oxidation of Alcohols Using Pyridinium Chlorochromate/Silica Gel
An efficient and convenient adaptation of the pyridinium chlorochromate (PCC) oxidation for an organic chemistry student exercise is based on the employment of reagent-grade silica gel, which simplifies workup and purification of the product. The procedures include the oxidation of 4-tert-butylcyclohexanol to 4-tert-butylcyclohexanone and d,l-menthol to d,l-menthone.
The determinants and effects of right-to-work laws: A review of the recent literature
The recent literature on the determinants and effects of right-to-work laws is reviewed. The focus is primarily on the econometric studies published since the early 1980s. Five major areas of impact are assessed: unionization, free riding, union organizing activities and successes in NLRB elections, wage structure and state industrial development. While individual findings are quite sensitive to model specification, the accumulated evidence indicates that RTW laws have at least a significant short-run impact on all of these areas except perhaps wages.
Dynamic localisation of Ran GTPase during the cell cycle
Doc number: 66 Abstract Background: Ran GTPase has multiple functions during the cell division cycle, including nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. The activity of Ran is determined by both its guanine nucleotide-bound state and its subcellular localization. Results: Here, we have characterised the localisation and mobility of Ran coupled to green fluorescent protein (GFP) during the cell cycle in live human cells. Ran-GFP is nuclear during interphase and is dispersed throughout the cell during mitosis. GFP-RanQ69L , a mutant locked in the GTP-bound state, is less highly concentrated in the nucleus and associates with nuclear pore complexes within the nuclear envelope. During mitosis, GFP-RanQ69L is excluded from chromosomes and localizes to the spindle. By contrast, GFP-RanT24N , a mutant with low affinity for nucleotides, interacts relatively stably with chromatin throughout the cell cycle and is highly concentrated on mitotic chromosomes. Conclusion: These results show that Ran interacts dynamically with chromatin, nuclear pore complexes and the mitotic spindle during the cell cycle. These interactions are dependent on the nucleotide-bound state of the protein. Our data indicate that Ran-GTP generated at chromatin is highly mobile and interacts dynamically with distal structures that are involved in nuclear transport and mitotic spindle assembly.