Complexity in an Unexpected Place: Quantities in Selected Acquisition Reports

We have looked at the definition of units in numerous acquisition programs and discovered that the units reported are almost never simple; in some programs, no two units are the same, and almost invariably the units produced at the end of a long production run are substantially different from the early ones. We have identified three reasons why the units may differ. The first reason is changes over time, generally as system capabilities are improved. The second is due to mixed types, where units that are inherently dissimilar;such as CH-47F and MH-47G helicopters;are produced by the same program and each is called one unit. The final reason why units can differ is reporting accidents. We give examples of all three and discuss possible methods of improving the reporting requirement.Naval Postgraduate School Acquisition Research Progra

IL‐12‐polarized Th1 cells produce GM‐CSF and induce EAE independent of IL‐23

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115966/1/eji3410.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115966/2/eji3410-sup-0002-PRC.pd

Collaborating with Wheat Producers in Demonstrating Areawide Integrated Pest Management

Focus groups were used to initiate collaborative relationships with wheat producers while learning about their farming history and decision-making. Focus group transcripts illustrate that producers were less confident in evaluating insect management problems compared to weed management. Producers do rely on Cooperative Extension in managing insect problems. Extension educators continue to play an important role in increasing producer\u27s knowledge of simplified field scouting and insect identification technology

Interferometric Polarization Control

A signal conditioning module provides a polarimeter capability in a photometric system. The module may include multiple variable delay polarization modulators. Each modulator may include an input port, and a first arm formed to include a first reflector and first rooftop mirror arranged in opposed relationship. The first reflector may direct an input radiation signal to the first rooftop mirror. Each modulator also may include an output port and a second arm formed to include a second reflector and second rooftop mirror arranged in opposed relationship. The second reflector can guide a signal from the second rooftop mirror towards the output port to provide an output radiation signal. A beamsplitting grid may be placed between the first reflector and the first rooftop mirror, and also between the second reflector and the second rooftop mirror. A translation apparatus can provide adjustment relative to optical path length vis-a-vis the first arm, the second arm and the grid

Functional assessment of the NMDA receptor variant GluN2A (R586K)

Background: The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor that has important roles in synaptogenesis, synaptic transmission, and synaptic plasticity. Recently, a large number of rare genetic variants have been found in NMDAR subunits in people with neurodevelopmental disorders, and also in healthy individuals. One such is the GluN2AR586K variant (GRIN2AG1757A), found in a person with intellectual disability. Identifying the functional consequences, if any, of such variants allows their potential contribution to pathogenesis to be assessed. Here, we assessed the effect of the GluN2AR586K variant on NMDAR pore properties. Methods: We expressed recombinant NMDARs with and without the GluN2AR586K variant in Xenopus laevis oocytes and in primary cultured mouse neurons, and made electrophysiological recordings assessing Mg2+ block, single-channel conductance, mean open time and current density. Results: The GluN2AR586K variant was not found to influence any of the properties assessed. Conclusions: Our findings suggest it is unlikely that the GluN2AR586K variant contributes to the pathogenesis of neurodevelopmental disorder

A novel expression system of domain I of human beta2 glycoprotein I in Escherichia coli

BACKGROUND: The antiphospholipid syndrome (APS), characterised by recurrent miscarriage and thrombosis, is a significant cause of morbidity and mortality. Domain I (DI) of human beta 2 glycoprotein I (β(2)GPI) is thought to contain crucial antibody binding epitopes for antiphospholipid antibodies (aPL), which are critical to the pathogenesis of APS. Expressing this protein in bacteria could facilitate studies investigating how this molecule interacts with aPL. METHODS: Using a computer programme called Juniper, sequentially overlapping primers were designed to be used in a recursive polymerase chain reaction (PCR) to produce a synthetic DI gene. Specifically Juniper incorporates 'major' codons preferred by bacteria altering 41 codons out of 61. This was cloned into the expression plasmid pET(26b) and expressed in BL21(DE3) Escherichia coli (E. coli). By virtue of a pelB leader sequence, periplasmic localisation of DI aided disulphide bond formation and toxicity was addressed by tightly regulating expression through the high stringency T7lac promoter. RESULTS: Purified, soluble his-tagged DI in yields of 750 μg/L bacterial culture was obtained and confirmed on Western blot. Expression using the native human cDNA sequence of DI in the same construct under identical conditions yielded significantly less DI compared to the recombinant optimised sequence. This constitutes the first description of prokaryotic expression of soluble DI of β(2)GPI. Binding to murine monoclonal antibodies that recognise conformationally restricted epitopes on the surface of DI and pathogenic human monoclonal IgG aPL was confirmed by direct and indirect immunoassay. Recombinant DI also bound a series of 21 polyclonal IgG samples derived from patients with APS. CONCLUSION: By producing a synthetic gene globally optimised for expression in E. coli, tightly regulating expression and utilising periplasmic product translocation, efficient, soluble E. coli expression of the eukaryotic protein DI of β(2)GPI is possible. This novel platform of expression utilising pan-gene prokaryote codon optimisation for DI production will aid future antigenic studies. Furthermore if DI or peptide derivatives of DI are eventually used in the therapeutic setting either as toleragen or as a competitive inhibitor of pathogenic aPL, then an E. coli production system may aid cost-effective production

The Growth Response of Tropical and Sub-Tropical Forage Species to Increasing Salinity

There is currently a growing coal seam gas (CSG) industry in Queensland, Australia. The industry requires beneficial-use strategies to consume the significant volumes of water released during CSG extraction. Irrigation of tropical and sub-tropical forage species for beef production is one option, however coal seam (CS) water is of varying quality due to moderate to high salinity and alkalinity. The application of chemically amended CS water over time could potentially increase soil salinity, which is known to reduce plant biomass production. While there were studies of salinity tolerance of many tropical and sub-tropical forage species 30 years ago, there is a need to examine the tolerance of more recently released species and cultivars which are suitable for planting in the Queensland CSG area

Anti proliferative activity of ELACYT™ (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells

This study evaluated combination drug partners for CP-4055, the C18:1Δ9,trans unsaturated fatty acid ester of cytarabine in HL-60 and U937 cells. Growth inhibition was assessed by ATP assay and drug interaction by the combination index and three dimensional methods. Synergy was observed in HL-60 cells for simultaneous combinations of CP-4055 with gemcitabine, irinotecan and topotecan, while combinations with cloretazine (VNP40101M) and idarubicin were additive. In U937 cells, synergy was observed with gemcitabine and additivity for the other drugs. In HL-60, the IC50 concentration of CP-4055 could be reduced 10-fold and that of gemcitabine 3-fold in combination versus the agents alone, an interaction that was independent of drug sequence, ratio and exposure time. In contrast, interactions of CP-4055 with the topoisomerase inhibitors became antagonistic when the drugs were administered 24 h prior to CP-4055 and at certain drug ratios, particularly in U937 cells. In summary, CP-4055 produced additive to synergistic anti proliferative activity when combined simultaneously with drugs from four mechanistic classes in cell culture models of human leukemia and lymphoma. The impact of drug sequence and ratio on the interactions argues for incorporation of these parameters into the design of combination chemotherapy regimens

Functional properties of in vitro excitatory cortical neurons derived from human pluripotent stem cells

The in vitro derivation of regionally defined human neuron types from patient‐derived stem cells is now established as a resource to investigate human development and disease. Characterization of such neurons initially focused on the expression of developmentally regulated transcription factors and neural markers, in conjunction with the development of protocols to direct and chart the fate of differentiated neurons. However, crucial to the understanding and exploitation of this technology is to determine the degree to which neurons recapitulate the key functional features exhibited by their native counterparts, essential for determining their usefulness in modelling human physiology and disease in vitro. Here, we review the emerging data concerning functional properties of human pluripotent stem cell‐derived excitatory cortical neurons, in the context of both maturation and regional specificity. [Image: see text