Study of the pathogenesis of Louping-Ill

Studies of the pathogenesis of louping -ill virus infection were undertaken to define the disease process in susceptible sheep and were extended to consider the influence of maternally derived antibody on the course of infection. In addition, the possible role of the red grouse in the epidemiology of louping-ill was investigated.Sheep inoculated subcutaneously with louping-ill virus developed a viraemia within 24 hours, maximum titres being reached two to three days later. In most sheep the virus titres were sufficient to infect the natural vector, Ixodes ricinus. The viraemia subsequently fell rapidly and the fall was associated with the appearance of both serum haemagglutination - inhibiting and neutralizing antibodies. Sheep surviving infection had shorter and lower viraemias and developed antibodies faster than animals that succumbed. There was, therefore, a definite association between the duration and magnitude of the viraemia and the appearance of serum antibody and survival.The antibody response of sheep to infection with loupingill virus is typical of the response of other species to infection with togaviruses. The initial serum haemagglutination -inhibiting antibody activity was primarily due to IgM which was progressively replaced by IgG; no IgM was detected after the 22nd day.The cerebrospinal fluid of sheep inoculated subcutaneously II with louping -ill virus invariably contained haemagglutination - inhibiting antibody. As with serum much of this antibody was IgM during the acute phase of infection, whereas with survivors it was entirely IgG. This pattern was reflected in the total levels of IgM and IgG in cerebrospinal fluid; IgM was present in cerebrospinal fluid during the acute phase, but could not be detected in cerebrospinal fluid from survivors or control animals. The relative proportion of antibody to louping -ill virus detected in cerebrospinal fluid of infected animals was considerably greater than that to a serum marker not involved in the disease process. It is therefore concluded that antibody specific to louping -ill virus is locally produced in the central nervous system.Serum antibody in lambs derived from colostrum was protective. Infection of lambs with high levels of antibody was completely aborted. Lambs with low levels of haemagglutination -inhibiting antibodies experienced infection in the absence of viraemia, but with the development of an immune response.Approximately 80 per cent of red grouse infected peripherally with louping -ill virus died and the levels of viraemia achieved were sufficient to infect the vector. As with sheep, the levels of virus that developed in surviving birds were lower than in birds that succumbed. The cessation of viraemia was also associated with the appearance of high titres of serum antibody to louping-ill virus.The epidemiological implications of these findings are discussed. It is concluded that throughout much of the hill grazing of Scotland where louping -ill is endemic, sheep are the principal vertebrate host; lambs that acquire colostral antibody to louping -ill virus will be protected throughout the period of tick activity in the spring, ewe hoggs in their second spring would appear to be the most important component of the sheep flock in the maintenance of louping-ill virus. Feral species probably play a very minor role.An historical appraisal indicates that louping -ill virus has been introduced to the grouse moors of Scotland in the comparative recent past due to the introduction of large scale sheep farming during the 19th century. Prior to this grouse probably did not encounter infection. The grouse - louping-ill virus, host -virus relationship has therefore only recently evolved which explains the marked susceptibility of the species to infection with virus

The lead and zinc deposits in the sedimentary rocks of East Tennessee and Southwest Virginia

In its geographic and geologic relations this area forms a part of the Appalachian province, which extends from the Atlantic Coastal plain on the East to the Mississippi lowlands on the West and from Central Alabama to Southern New York. All parts of the region thus defined have a common history recorded in its rocks, its geologic structure and its topographic features --Geography, page 1

The role of lambs in louping-ill virus amplification

In some areas of Scotland, the prevalence of louping-ill virus has not decreased despite the vaccination of replacement ewes for over 30 years. The role of unvaccinated lambs in viral persistence was examined through a combination of an empirical study of infection rates of lambs and mathematical modelling. Serological sampling revealed that most lambs were protected by colostral immunity at turnout in May/June but were fully susceptible by the end of September. Between 8 and 83% of lambs were infected over the first season, with seroconversion rates greater in late rather than early summer. The proportion of lambs that could have amplified the louping-ill virus was low, however, because high initial titres of colostral antibody on farms with a high force of infection gave protection for several months. A simple mathematical model suggested that the relationship between the force of infection and the percentage of lambs that became viraemic was not linear and that the maximum percentage of viraemic lambs occurred at moderately high infection rates. Examination of the conditions required for louping-ill persistence suggested that the virus could theoretically persist in a sheep flock with over 370 lambs, if the grazing season was longer than 130 days. In practice, however, lamb viraemia is not a general explanation for louping-ill virus persistence as these conditions are not met in most management systems and because the widespread use of acaracides in most tick-affected hill farming systems reduces the number of ticks feeding successfully

Common View Time Transfer Using Worldwide GPS and DMA Monitor Stations

Analysis of the on-orbit Navstar clocks and the Global Positioning System (GPS) monitor station reference clocks is performed by the Naval Research Laboratory using both broadcast and postprocessed precise ephemerides. The precise ephemerides are produced by the Defense Mapping Agency (DMA) for each of the GPS space vehicles from pseudo-range measurements collected at five GPS and at five DMA monitor stations spaced around the world. Recently, DMA established an additional site co-located with the US Naval Observatory precise time site. The time reference for the new DMA site is the DoD Master Clock. Now, for the first time, it is possible to transfer time every 15 minutes via common view from the DoD Master Clock to the 11 GPS and DMA monitor stations. The estimated precision of a single common-view time transfer measurement taken over a 15-minute interval was between 1.4 and 2.7 nanoseconds. Using the measurements from all Navstar space vehicles in common view during the 15-minute interval, typically 3-7 space vehicles, improved the estimate of the precision to between 0.65 and 1.13 nanoseconds. The mean phase error obtained from closure of the time transfer around the world using the 11 monitor stations and the 25 space vehicle clocks over a period of 4 months had a magnitude of 31 picoseconds. Analysis of the low noise time transfer from the DoD Master Clock to each of the monitor stations yields not only the bias in the time of the reference clock, but also focuses attention on structure in the behaviour of the reference clock not previously seen. Furthermore, the time transfer provides a a uniformly sampled database of 15-minute measurements that make possible, for the first time, the direct and exhaustive computation of the frequency stability of the monitor station reference clocks. To lend perspective to the analysis, a summary is given of the discontinuities in phase and frequency that occurred in the reference clock at the Master Control Station during the period covered by the analysis

GPS Moving Vehicle Experiment

The Naval Research Laboratory (NRL) in the development of timing systems for remote locations, had a technical requirement for a Y code (SA/AS) Global Positioning System (GPS) precise time transfer receiver (TTR) which could be used both in a stationary mode or mobile mode. A contract was awarded to the Stanford Telecommunication Corporation (STEL) to build such a device. The Eastern Range (ER) als had a requirement for such a receiver and entered into the contract with NRL for the procurement of additional receivers. The Moving Vehicle Experiment (MVE) described in this paper is the first in situ test of the STEL Model 5401C Time Transfer System in both stationary and mobile operations. The primary objective of the MVE was to test the timing accuracy of the newly developed GPS TTR aboard a moving vessel. To accomplish this objective, a joint experiment was performed with personnel from NRL and the er at the Atlantic Undersea Test and Evaluation Center (AUTEC) test range at Andros Island. Results and discussion of the test are presented in this paper