Use of fluorescent nanoparticles to investigate nutrient acquisition by developing Eimeria maxima macrogametocytes

The enteric disease coccidiosis, caused by the unicellular parasite Eimeria, is a major and reoccurring problem for the poultry industry. While the molecular machinery driving host cell invasion and oocyst wall formation has been well documented in Eimeria, relatively little is known about the host cell modifications which lead to acquisition of nutrients and parasite growth. In order to understand the mechanism(s) by which nutrients are acquired by developing intracellular gametocytes and oocysts, we have performed uptake experiments using polystyrene nanoparticles (NPs) of 40 nm and 100 nm in size, as model NPs typical of organic macromolecules. Cytochalasin D and nocodazole were used to inhibit, respectively, the polymerization of the actin and microtubules. The results indicated that NPs entered the parasite at all stages of macrogametocyte development and early oocyst maturation via an active energy dependent process. Interestingly, the smaller NPs were found throughout the parasite cytoplasm, while the larger NPs were mainly localised to the lumen of large type 1 wall forming body organelles. NP uptake was reduced after microfilament disruption and treatment with nocodazole. These observations suggest that E. maxima parasites utilize at least 2 or more uptake pathways to internalize exogenous material during the sexual stages of development

Flow equations for QED in the light front dynamics

The method of flow equations is applied to QED on the light front. Requiring that the partical number conserving terms in the Hamiltonian are considered to be diagonal and the other terms off-diagonal an effective Hamiltonian is obtained which reduces the positronium problem to a two-particle problem, since the particle number violating contributions are eliminated. No infrared divergencies appear. The ultraviolet renormalization can be performed simultaneously.Comment: 15 pages, Latex, 3 pictures, Submitted to Phys.Rev.

Whole body and hepatic insulin action in normal, starved, and diabetic rats

In normal (N), 3-days starved (S), and streptozotocin-treated (65 mg/kg) 3-days diabetic (D) rats we examined the in vivo dose-response relationship between plasma insulin levels vs. whole body glucose uptake (BGU) and inhibition of hepatic glucose production (HGP) in conscious rats, as determined with the four-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]glucose infusion. Twelve-hour fasting (basal) HGP was 3.0 +/- 0.2, 2.1 +/- 0.2, and 5.4 +/- 0.5 mg/min in N, S, and D rats, respectively. Next, all rats were clamped at matched glycemia (6 mM). Lowering plasma glucose in D rats from +/- 20 to 6.0 mM did not increase plasma norepinephrine, epinephrine, glucagon, and corticosterone levels. For BGU, insulin sensitivity was increased (70 +/- 11 microU/ml) in S and unchanged (113 +/- 21 microU/ml) in D compared with N rats (105 +/- 10 microU/ml). Insulin responsiveness was unchanged (12.4 +/- 0.8 mg/min) in S and decreased (8.5 +/- 0.8 mg/min) in D compared with N rats (12.3 +/- 0.7 mg/min). For HGP, insulin sensitivity was unchanged (68 +/- 10 microU/ml) in S and decreased (157 +/- 21 microU/ml) in D compared with N rats (71 +/- 5 microU/ml). Insulin responsiveness was identical among N, S, and D rats (complete suppression of HGP). In summary, 1) insulin resistance in D rats is caused by hepatic insensitivity and by a reduction in BGU responsiveness. 2) S rats show normal hepatic insulin action, but insulin sensitivity for BGU is increased. Therefore, S and D rats both suffering from a comparable catabolic state (10-15% body wt loss in 3 days) show opposite effects on in vivo insulin action. This indicates that in vivo insulin resistance in D rats is not caused by the catabolic state per se

Oblique Confinement and Phase Transitions in Chern-Simons Gauge Theories

We investigate non-perturbative features of a planar Chern-Simons gauge theory modeling the long distance physics of quantum Hall systems, including a finite gap M for excitations. By formulating the model on a lattice, we identify the relevant topological configurations and their interactions. For M bigger than a critical value, the model exhibits an oblique confinement phase, which we identify with Lauglin's incompressible quantum fluid. For M smaller than the critical value, we obtain a phase transition to a Coulomb phase or a confinement phase, depending on the value of the electromagnetic coupling.Comment: 8 pages, harvmac, DFUPG 91/94 and MPI-PhT/94-9

Evidence of exactness of the mean field theory in the nonextensive regime of long-range spin models

The q-state Potts model with long-range interactions that decay as 1/r^alpha subjected to an uniform magnetic field on d-dimensional lattices is analized for different values of q in the nonextensive regime (alpha between 0 and d). We also consider the two dimensional antiferromagnetic Ising model with the same type of interactions. The mean field solution and Monte Carlo calculations for the equations of state for these models are compared. We show that, using a derived scaling which properly describes the nonextensive thermodynamic behaviour, both types of calculations show an excellent agreement in all the cases here considered, except for alpha=d. These results allow us to extend to nonextensive magnetic models a previous conjecture which states that the mean field theory is exact for the Ising one.Comment: 10 pages, 4 figure

Drug development in Alzheimer’s disease: The path to 2025

The global impact of Alzheimer’s disease (AD) continues to increase, and focused efforts are needed to address this immense public health challenge. National leaders have set a goal to prevent or effectively treat AD by 2025. In this paper, we discuss the path to 2025, and what is feasible in this time frame given the realities and challenges of AD drug development, with a focus on disease-modifying therapies (DMTs). Under the current conditions, only drugs currently in late Phase 1 or later will have a chance of being approved by 2025. If pipeline attrition rates remain high, only a few compounds at best will meet this time frame. There is an opportunity to reduce the time and risk of AD drug development through an improvement in trial design; better trial infrastructure; disease registries of well-characterized participant cohorts to help with more rapid enrollment of appropriate study populations; validated biomarkers to better detect disease, determine risk and monitor disease progression as well as predict disease response; more sensitive clinical assessment tools; and faster regulatory review. To implement change requires efforts to build awareness, educate and foster engagement; increase funding for both basic and clinical research; reduce fragmented environments and systems; increase learning from successes and failures; promote data standardization and increase wider data sharing; understand AD at the basic biology level; and rapidly translate new knowledge into clinical development. Improved mechanistic understanding of disease onset and progression is central to more efficient AD drug development and will lead to improved therapeutic approaches and targets. The opportunity for more than a few new therapies by 2025 is small. Accelerating research and clinical development efforts and bringing DMTs to market sooner would have a significant impact on the future societal burden of AD. As these steps are put in place and plans come to fruition, e.g., approval of a DMT, it can be predicted that momentum will build, the process will be self-sustaining, and the path to 2025, and beyond, becomes clearer

Chern - Simons Gauge Field Theory of Two - Dimensional Ferromagnets

A Chern-Simons gauged Nonlinear Schr\"odinger Equation is derived from the continuous Heisenberg model in 2+1 dimensions. The corresponding planar magnets can be analyzed whithin the anyon theory. Thus, we show that static magnetic vortices correspond to the self-dual Chern - Simons solitons and are described by the Liouville equation. The related magnetic topological charge is associated with the electric charge of anyons. Furthermore, vortex - antivortex configurations are described by the sinh-Gordon equation and its conformally invariant extension. Physical consequences of these results are discussed.Comment: 15 pages, Plain TeX, Lecce, June 199