An Australian abroad : the secret life of the brushtail possum (Trichosurus vulpecula) : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatu, New Zealand

The “superspreader” hypothesis relates disease transmission to social contacts and assumes transmission is driven by the frequency, type and distribution of contacts among infected and susceptible individuals. I investigated characteristics of brushtail possum (Trichosurus vulpecula) home ranges for six wild free-living subpopulations, (four grids were studied; all of them before possum depopulation and two of them after possum depopulation) constructing social networks relevant to bovine tuberculosis (TB) transmission before and after depopulation. I also experimentally infected possums with a novel strain of TB to monitor secondary case infections in relation to these contact and other factors, including population density and sex ratio. Before depopulation home range estimates showed adult males had larger home ranges than female and younger possums. Home range overlap and area of overlap differed between subpopulations, and possum sex and age; with adult males having more and larger overlaps with other possums. Possums were fitted with proximity-logging collars and contacts registered between April and October, 2012. The number of connections an individual has with others and the probability of the distribution of contacts it has within the population, or node degree and betweenness, also known as the shortest distance between individuals, were associated with sex, with males having higher values for each. Males also contacted more possums than females. Post-depopulation results showed an influx of male possums, higher population density, and smaller home range sizes than before depopulation. Possums post-depopulation also lacked an apparent ‘routine’ in contact networks, interacting with other possums haphazardly. The greater level of contact among adult males, than before depopulation, and their effects on recovering populations post-depopulation, was likely the cause of more TB infection in adults and males. This thesis provides empirical evidence that adult male possums have home range and contact network characteristics that are likely to enhance their involvement in the transmission and persistence of TB, relative to female and younger possums. Observations of experimentally infected individuals showed that infected males survived longer than females and that, as a consequence, those males potentially acted as a “supershedding” subgroup. I therefore provide evidence that adult male possums are the most important drivers of TB transmission and persistence of infection in populations, and could be targeted for control measures

Cybernetic Implications for the U.C.C.

In the following iBrief, the authors assess the impact of recent a recent decision from the 9th Circuit assessing whether the patent system\u27s filing mechanism preempts the U.C.C. Article 9 requirement that creditors perfect their security interests in patents offered as collateral by their debtors

Josiah Parsons Cooke Jr.: Epistemology in the Service of Science, Pedagogy, and Natural Theology

Josiah Parsons Cooke established chemistry education at Harvard University, initiated an atomic weight research program, and broadly impacted American chemical education through his students, the introduction of laboratory instruction, textbooks, and influence on Harvard's admissions requirements. The devoutly Unitarian Cooke also articulated and defended a biogeochemical natural theology, which he defended by arguing for commonalities between the epistemologies of science and religion. Cooke's pre-Mendeleev classification scheme for the elements and atomic weight research were motivated by his interest in numerical order in nature, which reflected his belief in a divine lawgive

BACKWARD IMPLICIT CONTRACTS, PRE-COMMITMENT AND MARKET POWER IN THE INTERNATIONAL DURUM WHEAT MARKET

We devise a formal test of market power that is applied to the international durum market. The model captures the asymmetric cost structure brought about the initial payment system of the Canadian Wheat Board. The model generates testable hypotheses about market conduct and optimal strategic positioning.Crop Production/Industries, Industrial Organization,

A Structural Perspective of Antibody Neutralization of Dengue Virus

The four dengue viruses: DENV) are mosquito-borne flaviviruses and are considered the world\u27s most significant arboviruses in terms of worldwide disease burden. Symptoms of dengue disease are classified into dengue fever, a mild, febrile illness, and the potentially fatal severe dengue, which can include hemorrhaging and shock. Antibody protection against DENV correlates with the production of neutralizing antibodies against the envelope: E) glycoprotein. To understand the role of antibodies in DENV infection, we sought to dissect the relationship between epitope and function. Virologic studies had identified that the most potently neutralizing antibodies are against domain III: DIII) of the E protein. We have identified five epitopes within DENV DIII. Our data suggests that the most potently neutralizing antibodies are specific for a single serotype, while cross-reactive antibodies are relatively poorly neutralizing. Additionally, we were surprised to define neutralizing epitopes that were shown to be inaccessible on the surface of the virion in cryo-electron microscopy studies. Fine epitope mapping was used to define the epitopes of a panel of existing DENV-2 antibodies. Antibodies against the lateral ridge were the most potently neutralizing antibodies and reacted only with the DENV-2 serotype. The second epitope was centered on the DIII A-strand, and antibodies against this epitope reacted with several serotypes of DENV. Several poorly neutralizing antibodies reacted to all four DENV serotypes, as well as West Nile virus, a related flavivirus, mapped to the highly conserved AB loop of DIII. We expanded our studies of DIII-specific antibodies to the DENV-1 serotype. One antibody, E106, potently neutralized the five DENV-1 strains representing the five genotypes, and bound a composite epitope of the lateral ridge and A-strand epitopes. Despite the potency of E106-mediated neutralization, a combination of structural, biophysical, virologic data suggest that potent DENV-1 neutralization by E106 is coincident with bivalent engagement of the virus. Additionally, we determined the crystal structures of E111 bound to a novel fifth CC\u27 loop epitope on domain III: DIII) of the E protein from two different DENV-1 genotypes. The available atomic models of DENV virions revealed that the E111 epitope was inaccessible, suggesting that it recognizes an uncharacterized virus conformation. While the affinity of binding between E111 and DIII varied by genotype, we observed limited correlation with inhibitory activity. Instead, our results support the conclusion that potent neutralization depends on genotype-dependent exposure of the CC\u27 loop epitope. These findings establish new structural complexity of the DENV virion, which may be relevant for the choice of DENV strain for induction or analysis of neutralizing antibodies in the context of vaccine development

Patent Amendments and Prosecution History Estoppel Under Festo

On November 29, 2000, the Federal Circuit retroactively reduced the value of nearly 1.2 million unexpired United States patents by announcing a new rule for the somewhat obscure doctrine of prosecution history estoppel. Designed to foster clarity in patent applications, this new pronouncement in Festo Corp v. Shoketsu Kinzoku Kogyo Kabushiki Co. allows for easy copying of some patented inventions and reduces patent owner\u27s ability to prove infringement. This article outlines the change in the law and discusses the positive and negative consequences of the decision

The Saccharomyces cerevisiae Srs2 Helicase Regulates Homologous Recombination through the Disassembly of Recombination Intermediates

Life on Earth relies on a set of instructions encoded within an organism’s genome that is passed along from one generation to the next. Inherent to this mechanism of propagation is the need to copy the genetic material before passing it along to the progeny. Errors in this process coupled with stochastic damage will inevitably lead to changes in these instructions and may result in a reduction of fitness or even death of an individual. Yet, these same changes are also responsible for the adaptation mandated by our dynamic environment. Thus, there exists a delicate balance between maintenance and alteration of genetic material that is embodied to a large part at the various intersections of DNA replication, recombination and repair. Homologous recombination (HR) has been well studied and found to play vital roles in many cellular processes from the repair of the harrowing double-stranded break, the restart of a stalled or collapsed replication fork, as well as proper chromosome segregation during meiosis, all with the goal of striking this delicate balance. And yet, while HR is incumbent for the fitness of an organism, if left unchecked this same process can become detrimental by preventing better suited DNA repair pathways, permanently arresting cell cycle progression and creating some of the very problems it was meant to address such as aneuploidy or cancer. Despite a wealth of knowledge, the precise regulatory mechanisms remain an active area of research as they provide likely targets to combat these persistent diseases. Motor proteins that translocate along DNA have been particularly compelling and elusive due to their transitory nature, as well as the inevitability of collisions with bound protein(s) or nucleic acid structures that are likely regulated intermediates in the process. The yeast Srs2 helicase/translocase has long been regarded as the prototypical “anti-recombinase” as it has been shown to dismantle the Rad51 presynaptic filament, but also displays contradictory pro-recombinase functions. In vivo studies of Srs2 have been hampered by its involvement in multiple bioprocesses beyond recombination, while bulk in vitro approaches often produce conflicting results. Recent single molecule imaging of these players has shed light onto their involvement in the regulation of the various stages of the canonical pathway of HR. The Greene laboratory has developed ssDNA curtains to study the pre-synaptic filament and shown that Rad51-ssDNA filaments can create bonafide D-loop intermediates that would be incapable of repair and thus represent a toxic intermediate. These structures persist far longer than the entire process of DSBR in vivo and led us to hypothesize that motor proteins would be a key regulatory element to dismantle improperly paired intermediates for redistribution of the bound proteins and reengagement of the homology search process. Here I extend the use of ssDNA curtains to study Srs2 as it assembles into multimeric complexes to perform long-range disruption of various pre- and post-synaptic filament assemblies that include replication protein A (RPA), Rad51, Rad52, and D-loops. For the first time, direct observation of Srs2 translocating over RPA filaments is provided and shows these proteins are efficiently removed by Srs2. By including Rad52 on the RPA filament, I offer a refined model of the contradictory pro- and anti-recombinase activities of Srs2 through its antagonism of the single-strand annealing pathway in favor of HR. Additionally, Srs2 was found to initiate Rad51 disruption at breaks in the continuity of the filament marked by the persistence of replication protein A (RPA), Rad52, or the presence of an improper D-loop intermediate, the latter of which is efficiently disrupted before continuing translocation. In contrast to the prevailing model, we demonstrate that direct interaction between Srs2 and Rad51 is not necessary for long-range Rad51 clearance. These findings offer insights into the dynamic regulation of crucial HR intermediates by Srs2 and demonstrate that sub-nuclear concentrations of these proteins may be a likely driver for their activities

Who’s Afraid of amazon.com v. barnesandnoble.com?

On October 2, 2000, the Court of Appeals for the Federal Circuit heard the appeal in the case of Amazon.com, Inc. v. Barnesandnoble.com, Inc. This appeal revolves around the alleged infringement by Barnesandnoble.com of a one-click web-shopping system patented by Amazon.com. The one-click system is among a series of recent controversial business method patents. According to some, business methods are legitimate inventions that deserve the protection of the US Patent and Trademark Office (PTO). According to others, business methods are unworthy of patent protection and may inhibit innovation in e-commerce. The outcome of this case has been widely anticipated by both sides of the business method patent debate as a signal that these patents will or will not be upheld by courts

Oligopsony Power: Evidence from the U.S. Beef Packing Industry

Replaced with revised version of paper 08/24/09.Margin, Beef Packing, Fed Cattle Prices, Markov Regime Switching, Industrial Organization,