In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti-Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats

BACKGROUND: Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease. HYPOTHESIS/OBJECTIVES: This study describes the design and characterization of a fully felinized anti-NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self-resolving, acute inflammation model were investigated in cats. ANIMALS: Thirty-eight cats at a research colony at Charles River Laboratories, Ireland. METHODS: Felinized anti-NGF mAb, NV-02, was produced using a complementary DNA (cDNA)-based method (PETization). Purified NV-02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin-induced inflammatory pain. RESULTS: Anti-NGF mAb, NV-02 neutralized NGF with high affinity and potency and did not bind complement. NV-02-administered SC had a plasma half-life of 7-15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV-02 SC significantly decreased signs of lameness on day 2 (P = .0027), day 3 (P = .016), day 4, (P = .0063), day 5 (P = .0085), day 6 (P = .0014), and day 7 (P = .0034) after induction of inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE: The high affinity, long plasma half-life, safety, and analgesic efficacy of felinized anti-NGF mAb (NV-02) support further investigation of the analgesic potential of this antibody in the cat

Muons as Local Probes of Three-body Correlations in the Mixed State of Type-II Superconductors

The vortex glass state formed by magnetic flux lines in a type-II superconductor is shown to possess non-trivial three-body correlations. While such correlations are usually difficult to measure in glassy systems, the magnetic fields associated with the flux vortices allow us to probe these via muon-spin rotation measurements of the local field distribution. We show via numerical simulations and analytic calculations that these observations provide detailed microscopic insight into the local order of the vortex glass and more generally validate a theoretical framework for correlations in glassy systems.Comment: 4+ pages, high-quality figures available on reques

EC04-183 Chickpea Production in the High Plains

Chickpea (Cicer arietinum L.) is an annual grainlegume or “pulse crop” that is used extensively for human consumption. The seed of this plant, when dried, is commonly used in soup. Its primary use in the United States is for salad bars, while in the Middle East and India it is more frequently cooked and blended with rice dishes. Major chickpea producers include India, Pakistan, Mexico, Turkey, Canada, and Australia. Chickpea makes up more than 20 percent of world pulse production, behind dry bean and pea. Currently, the United States imports more than 80 percent of its domestic chickpea needs. Since the 1980s, chickpea production has increased rapidly in the northwestern United States. Meanwhile, due to agronomic, processing, and marketing constraints, production in the High Plains has been sporadic and often short-lived. During the past few years, the development of new varieties and the potential for chickpea production under dryland and limited irrigation conditions has generated renewed interest among High Plains producers. With this in mind, the purpose of this publication is to provide information to enhance the potential for successful chickpea production

EC04-183 Chickpea Production in the High Plains

Chickpea (Cicer arietinum L.) is an annual grainlegume or “pulse crop” that is used extensively for human consumption. The seed of this plant, when dried, is commonly used in soup. Its primary use in the United States is for salad bars, while in the Middle East and India it is more frequently cooked and blended with rice dishes. Major chickpea producers include India, Pakistan, Mexico, Turkey, Canada, and Australia. Chickpea makes up more than 20 percent of world pulse production, behind dry bean and pea. Currently, the United States imports more than 80 percent of its domestic chickpea needs. Since the 1980s, chickpea production has increased rapidly in the northwestern United States. Meanwhile, due to agronomic, processing, and marketing constraints, production in the High Plains has been sporadic and often short-lived. During the past few years, the development of new varieties and the potential for chickpea production under dryland and limited irrigation conditions has generated renewed interest among High Plains producers. With this in mind, the purpose of this publication is to provide information to enhance the potential for successful chickpea production

A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Landscapes in transition: an analysis of sustainable policy initiatives and emerging corporate commitments in the palm oil industry

The recent Southeast Asian haze crisis has generated intense public scrutiny over the rate, methods and types of landscape change in the tropics. Debate has centred on the environmental impacts of large-scale agricultural expansion, particularly the associated loss of high carbon stock forest and forests of high conservation value. Focusing on palm oil—a versatile food crop and source of bioenergy—this paper analyses national, international and corporate policy initiatives in order to clarify the current and future direction of oil palm expansion in Malaysia and Indonesia. The policies of ‘zero burn’, ‘no deforestation’ and ‘no planting on peatlands’ are given particular emphasis in the paper. The landscape implications of corporate commitments are analysed to determine the amount of land, land types and geographies that could be affected in the future. The paper concludes by identifying key questions related to the further study of sustainable land use policy and practice

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table