RECENT ADVANCES IN VETERINARY ENTOMOLOGY1

The advances during the last 15 years in our knowledge of the biology and control of arthropod pests of livestock and vectors of animal disease agents exceed those made in any similar period in past history. Before 1942 we relied mainly on rotenone, pyrethrum, the thiocyanates, and the arseni­cals for control of lice, ticks, mites, biting flies, and cattle grubs. While ef­fective against some pests under certain conditions, these materials were not practical for wide-scale use and did not meet the public demand for better insecticides. Today we have highly effective and low-cost insecticides such as DDT, lindane, TDE, toxaphene, methoxychlor, chlordane, and syner­gized pyrethrum for control of livestock insects. Their use has saved the live­ stock grower many millions of dollars annually and has benefited the con­ sumer by making more and better animal products available. Of almost equal importance to the development of the new insecticides are the contributions made to our knowledge of the biology and habits of several livestock insects and their transmission of agents of animal diseases. Many new ideas and approaches to studies on insect biology and control have been developed during the last few years. A good example of this is the unique method for the control of screw-worms by release of sterilized male flies over an area. The sterile males mate with the native females, but the eggs are infertile and thus reduce the numbers of screw-worms. Another ex­ ample of new trends is the promising research with insecticides that can be given internally to livestock for destruction of external pests. These studies will be discussed in detail in the following pages. Although great progress has been made in the use of insecticides, two disturbing factors have arisen to cause worry as to the future efficiency of chemical means of control. The first is the increasing and widespread de­velopment of resistance of insects to insecticides, particularly to the chlo­rinated hydrocarbons. House flies have developed such a high degree of re­sistance to DDT and related materials that satisfactory control is impossible in most areas. Organic phosphorus insecticides have so far performed in a creditable manner in controlling house flies, but there are indications that these chemicals may eventually fail. As yet no reports on resistance of horn flies, horse flies, deer flies, stable flies, sheep keds, or lice of livestock have appeared

Discrete adjoint approximations with shocks

This paper is concerned with the formulation and discretisation of adjoint equations when there are shocks in the underlying solution to the original nonlinear hyperbolic p.d.e. For the model problem of a scalar unsteady one-dimensional p.d.e. with a convex flux function, it is shown that the analytic formulation of the adjoint equations requires the imposition of an interior boundary condition along any shock. A 'discrete adjoint' discretisation is defined by requiring the adjoint equations to give the same value for the linearised functional as a linearisation of the original nonlinear discretisation. It is demonstrated that convergence requires increasing numerical smoothing of any shocks. Without this, any consistent discretisation of the adjoint equations without the inclusion of the shock boundary condition may yield incorrect values for the adjoint solution

Dihydropyrimidine-thiones and clioquinol synergize to target beta-amyloid cellular pathologies through a metal-dependent mechanism

The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of predictive model systems. It is critical that we develop approaches to identify novel targets and lead compounds. Here, a phenotypic screen of yeast proteinopathy models identified dihydropyrimidine-thiones (DHPM-thiones) that selectively rescued the toxicity caused by β-amyloid (Aβ), the peptide implicated in Alzheimer’s disease. Rescue of Aβ toxicity by DHPM-thiones occurred through a metal-dependent mechanism of action. The bioactivity was distinct, however, from that of the 8-hydroxyquinoline clioquinol (CQ). These structurally dissimilar compounds strongly synergized at concentrations otherwise not competent to reduce toxicity. Cotreatment ameliorated Aβ toxicity by reducing Aβ levels and restoring functional vesicle trafficking. Notably, these low doses significantly reduced deleterious off-target effects caused by CQ on mitochondria at higher concentrations. Both single and combinatorial treatments also reduced death of neurons expressing Aβ in a nematode, indicating that DHPM-thiones target a conserved protective mechanism. Furthermore, this conserved activity suggests that expression of the Aβ peptide causes similar cellular pathologies from yeast to neurons. Our identification of a new cytoprotective scaffold that requires metal-binding underscores the critical role of metal phenomenology in mediating Aβ toxicity. Additionally, our findings demonstrate the valuable potential of synergistic compounds to enhance on-target activities, while mitigating deleterious off-target effects. The identification and prosecution of synergistic compounds could prove useful for developing AD therapeutics where combination therapies may be required to antagonize diverse pathologies.D.F.T was funded by NRSA Fellowship NIH 5F32NS061419. D.F.T. and S.L. were supported by WIBR funds in support of research on Regenerative Disease, the Picower/JPB Foundation, and the Edward N. and Della L. Thome Foundation. G.A.C. and S.L. were funded by a Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award. L.E.B., R.T., and S.E.S. were funded by NIH GM086180, NIH GM067041, and NIH GM111625. (5F32NS061419 - NRSA Fellowship NIH; WIBR funds in support of research on Regenerative Disease; Picower/JPB Foundation; Edward N. and Della L. Thome Foundation; Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award; GM086180 - NIH; NIH GM067041 - NIH; NIH GM111625 - NIH)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705239/Accepted manuscrip

Traversable Wormholes in Geometries of Charged Shells

We construct a static axisymmetric wormhole from the gravitational field of two charged shells which are kept in equilibrium by their electromagnetic repulsion. For large separations the exterior tends to the Majumdar-Papapetrou spacetime of two charged particles. The interior of the wormhole is a Reissner-Nordstr\"om black hole matching to the two shells. The wormhole is traversable and connects to the same asymptotics without violation of energy conditions. However, every point in the Majumdar-Papapetrou region lies on a closed timelike curve.Comment: 9 pages, LaTeX, 1 figur

Evolution of Protoneutron Stars

We study the thermal and chemical evolution during the Kelvin-Helmholtz phase of the birth of a neutron star, employing neutrino opacities that are consistently calculated with the underlying equation of state (EOS). Expressions for the diffusion coefficients appropriate for general relativistic neutrino transport in the equilibrium diffusion approximation are derived. The diffusion coefficients are evaluated using a field-theoretical finite temperature EOS that includes the possible presence of hyperons. The variation of the diffusion coefficients is studied as a function of EOS and compositional parameters. We present results from numerical simulations of protoneutron star cooling for internal stellar properties as well as emitted neutrino energies and luminosities. We discuss the influence of the initial stellar model, the total mass, the underlying EOS, and the addition of hyperons on the evolution of the protoneutron star and upon the expected signal in terrestrial detectors.Comment: 67 pages, 25 figure

Cryptic Variation in Morphological Evolution: HSP90 as a Capacitor for Loss of Eyes in Cavefish

In the process of morphological evolution, the extent to which cryptic, preexisting variation provides a substrate for natural selection has been controversial. We provide evidence that heat shock protein 90 (HSP90) phenotypically masks standing eye-size variation in surface populations of the cavefish Astyanax mexicanus. This variation is exposed by HSP90 inhibition and can be selected for, ultimately yielding a reduced-eye phenotype even in the presence of full HSP90 activity. Raising surface fish under conditions found in caves taxes the HSP90 system, unmasking the same phenotypic variation as does direct inhibition of HSP90. These results suggest that cryptic variation played a role in the evolution of eye loss in cavefish and provide the first evidence for HSP90 as a capacitor for morphological evolution in a natural setting

Edge-Based Compartmental Modeling for Infectious Disease Spread Part III: Disease and Population Structure

We consider the edge-based compartmental models for infectious disease spread introduced in Part I. These models allow us to consider standard SIR diseases spreading in random populations. In this paper we show how to handle deviations of the disease or population from the simplistic assumptions of Part I. We allow the population to have structure due to effects such as demographic detail or multiple types of risk behavior the disease to have more complicated natural history. We introduce these modifications in the static network context, though it is straightforward to incorporate them into dynamic networks. We also consider serosorting, which requires using the dynamic network models. The basic methods we use to derive these generalizations are widely applicable, and so it is straightforward to introduce many other generalizations not considered here